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Calcium is vital for the heart's proper functioning, controlling its automaticity and excitation‐contraction coordination. When calcium enters myocardial fibers, it triggers the release of stored calcium, leading to increased intracellular levels. This, in turn, enables the interaction between actin and myosin, necessary for muscle contraction. Adequate calcium levels are crucial for optimal heart function. 16 Hypo‐calcemic cardiomyopathy presents with symptoms resembling heart failure, with most cases showing a reduced ejection fraction (EF), and a smaller proportion experiencing mid‐range or preserved EF. The common manifestations include diffuse LV hypokinesia and sporadic regional wall motion abnormalities. Additionally, patients may exhibit various arrhythmias, such as atrial fibrillation, ventricular tachycardia, and junctional tachycardia. 15 Here, we have reviewed 11 cases of DCM due to hypoparathyroidism to further investigate the relationship between calcium imbalance and its impact on cardiac function, as well as to examine its clinical presentation and manifestations. 1. A 38‐year‐old woman was admitted to the cardiology department due to severe and persistent shortness of breath (NYHA IV) 1 for 3 weeks and recurrent muscle cramps over the past 6 months. Her medical history was unremarkable, except for a total thyroidectomy 3 years ago. Upon administration, her vital sign was normal, and she was afebrile. The physical examination revealed left‐sided gallop sounds, distended jugular veins, and crackling rales in her lung bases. Echocardiography showed a dilated and weakened heart muscle (cardiomyopathy) with a reduced EF of 31.4% and increased filling pressure. Laboratory tests showed that the patient had low calcium levels (30 mg/L), decreased free T4 (2.39 pg/mL), and elevated TSH (8.48 μLU/mL). Other tests, including complete blood count, C‐reactive protein, blood glucose, creatinine, and blood ion levels, were within the normal range. After treating her calcium levels with calcium and vitamin D3, in addition to hormone replacement with Levothyroxine, significant improvement in the patient's cardiac symptoms was observed, resulting in the normalization of heart chamber sizes and Left ventricular ejection fraction (LVEF) after 3 months. 8 2. A 50‐year‐old female with hypoparathyroidism presented dyspnea (NYHA IV) and orthopnea 2 . The dyspnea was improved 5 days before admission. Upon examination, rales were detected, and the electrocardiogram (ECG) revealed a prolonged QT interval. Chest X‐ray showed prominent cardiomegaly with pulmonary congestion, and echocardiography indicated decreased LV function with an EF of 36.5%. Based on her signs and symptoms, she was treated with furosemide injection at first due to heart failure. Lab data demonstrated reduced calcium, magnesium, and ionized calcium levels and increase in phosphorus level. Moreover, intact‐PTH and vitamin D levels were reduced. Parathyroid infiltrating disease and autoimmune disease were role out. Further investigations were conducted to determine the cause of congestive heart failure. Laboratory tests revealed abnormally low levels of total serum calcium (3.7 mg/dL), magnesium (1.7 mg/dL), and ionized calcium (0.6 mmol/L), with elevated phosphorus and creatinine levels and her brain natriuretic peptide (BNP) level was significantly elevated at 1855.1 pg/mL. Hormone analysis showed normal free T4 and thyroid‐stimulating hormone levels but decreased intact parathyroid hormone (PTH‐intact) and vitamin D levels. There was no sign of stenotic lesions on coronary angiography and therefore the patient was diagnosed with DCM due to severe hypocalcemia and idiopathic hypoparathyroidism. She took intravenous calcium and oral vitamin D 3 and calcitriol during hospitalization. After discharge, she undertreated with oral calcium, vitamin D 3 , heart failure medications. Following treatment with intravenous calcium and oral vitamin D3 and calcitriol and normalizing the calcium levels, the patient's dyspnea significantly improved, and chest X‐ray showed reduced cardiomegaly and clearance of pulmonary edema, and the prolonged QT interval was shortened. Upon discharge, the patient continued with oral calcium, vitamin D3, and congestive heart failure medications. Follow‐up visits indicated gradual improvement in myocardial function, with the LVEF increasing to 46% within the first month and 51% by the third month. 9 3. A 37‐year‐old woman with a history of thyroidectomy carried out at the age of 18, presented with cardiac symptoms. The surgery resulted in her developing permanent hypoparathyroidism. She was prescribed calcium and vitamin D supplements in addition to heart failure treatments, which she irregularly adhered to without undergoing regular laboratory monitoring. These symptoms included cramps, facial spasms, and heart irregularities. On examination cardiomegaly and pulmonary congestion were observed, indicating strain on the heart. An echocardiogram revealed dilatation and dysfunction of the left ventricle, mitral and tricuspid insufficiency, and moderate pulmonary hypertension. She also suffered from dyspnea, epigastric pain, and rapid edema progression. The patient's calcium levels were measured at 2.9 mg/dL, parathyroid hormone at 5.9 ng/L (normal range: 10–73), magnesium at 1.08 mEq/L (normal range: 1.4–2.1), hematocrit at 26%, hemoglobin at 7.4 g/dL, total creatine kinase at 1260 U/L (normal range: <70) (with a 3% myocardial fraction), and TSH at 18.1 µU/mL. The diagnosis indicated congestive heart failure secondary to severe hypocalcemia, decompensated by thyroid hormone replacement and exacerbated by iron‐deficiency anemia. The administration of calcium supplements, alongside diuretics, captopril, and digoxin, resulted in a swift and noticeable clinical enhancement. Subsequent monitoring for 18 months revealed the continued presence of LV enlargement and systolic dysfunction, although improvements were observed in all other echocardiographic observations and her cardiac symptoms improved significantly. 10 4. A 70‐year‐old female presented to the emergency department with tonic‐clonic seizure. Her symptoms were paresthesia in her extremities for 2 months, altered sensorium for 1 month, exertional breathlessness, cough for 1 week, and three episodes of seizure 2 days before hospitalization. On the examination, Chvostek's sign, and Trousseau's sign were positive. The cardiovascular examination showed the presence of LV S3, while the respiratory examination revealed bilateral basal crepitations with rhonchi. Lab tests indicated significantly low serum calcium levels (3.4 mg/dL) and high serum phosphate levels (8.8 mg/dL), consistent with hypoparathyroidism. On her brain computed tomography scan, bilateral symmetrical calcification in the basal ganglia and dentate nucleus due to chronic hypoparathyroidism was revealed. The echocardiogram revealed severe DCM with congestive cardiac failure, characterized by LV systolic and diastolic dysfunction and an EF of 25%. Additionally, the patient's QT interval was prolonged (0.55 s), and she had mild mitral regurgitation, mild aortic regurgitation, and trivial tricuspid regurgitation. The final diagnosis was idiopathic hypoparathyroidism, severe hypocalcemia, and DCM with congestive cardiac failure. Treatment involved intravenous calcium gluconate and oral vitamin D 3 , and antiepileptic leading to remarkable improvement in the patient's condition in 2 weeks after normalization of calcium level. 11 5. A 68‐year‐old woman presented to the emergency department due to intermittent dyspnea. She had recently undergone a subtotal thyroidectomy and was prescribed calcium supplementation. During the physical examination, she exhibited tachycardia and tachypnea. Chest radiography revealed bilateral pleural effusion, which was determined to be a transudate following aspiration. Blood tests indicated certain abnormalities: she had hypocalcemia (low calcium levels) at 1.15 mmol/L, high serum phosphate levels at 2.89 mmol/L, and a low PTH level, measuring less than 0.5 pmol/L. Additionally, transthoracic echocardiography (TTE) displayed dilation of the left ventricle and severe dysfunction, with an EF of only 15%, alongside moderate mitral and tricuspid regurgitation. The treatment included a β‐blocker, ACE inhibitor, spironolactone, calcium, and vitamin D. Within 2 weeks, electrolyte levels normalized, and the pleural effusion resolved. The EF improved to 35% after 3 weeks and 50% after 1 year. 5 6. A 59‐year‐old woman presented at the cardiology outpatient clinic due to progressive exertional dyspnea and ankle edema. During the physical examination, a systolic murmur was detected, and NT‐pro‐BNP level unexpectedly was elevated. On her second visit to outpatient clinic, she had seizure and her brain CT scan revealed extensive calcifications in the basal ganglia. TTE revealed ventricular dilation with an estimated EF of 39%, along with moderate mitral regurgitation and severe tricuspid regurgitation. The ECG showed sinus rhythm with a leftward axis, a prolonged QTc interval of 533 ms, and ST depression in V4–V6. Laboratory tests indicated low plasma calcium levels (1.24 mmol/L) and elevated phosphate levels (2.5 mmol/L). The PTH level was undetectable (<0.6 pmol/L). Upon further investigation into the patient's history, it was discovered that she had been experiencing progressive muscle spasms and constipation for a few weeks. Ultimately, she received a diagnosis of hypocalcemia resulting from primary hypoparathyroidism. She suffered from DCM with congestive heart failure due to primary hypoparathyroidism. The patient received treatment consisting of vitamin D and intravenous and oral calcium supplementation. Within a week after achieving normal calcium levels, TTE revealed a notable improvement in the LV function. 5 7. A 40‐year‐old woman with no cardiovascular history presented at the emergency care unit with symptoms including syncope, progressive exertional dyspnea, and paroxysmal nocturnal dyspnea. She had previously undergone thyroidectomy for Graves' disease and had type 1 diabetes mellitus. Physical examination revealed murmurs, gallop rhythm, peripheral edema, and lung stasis. The chest X‐ray demonstrated pulmonary stasis with hilum enlargement. The patient's ECG showed sinus tachycardia with a prolonged QT interval along with negative T waves from V1 to V4. Echocardiography revealed dilated left chambers and severe global systolic dysfunction of the left ventricle (LVEF = 15%) due to diffuse hypokinesia. Restrictive diastolic dysfunction with elevated filling pressure indexes, along with moderate functional mitral and tricuspid regurgitation and moderate pulmonary hypertension, were also observed. Angio coronarography ruled out atherosclerotic lesions. Laboratory blood tests indicated severe hypocalcemia, with a total serum calcium level of 3.6 mg/dL. Other lab findings were demonstrated high blood sugar, elevated TSH and NT‐pro‐BNP levels. Further assessment involving parathormone testing, phosphoric, and other related examinations confirmed a diagnosis of severe primary hypoparathyroidism. At first, she treated with ACE inhibitor, beta‐blocker, anti‐aldosterone diuretic, insulin, atorvastatin, and levothyroxine. During hospitalization, she exhibited hypocalcemia signs such as Chvostek, Weiss, Trousseau positive. The brain CT‐scan revealed calcifications of the basal ganglia. She took gluconic calcium at first and then was treated with oral lactic calcium and calcitriol. The patient received calcium treatment, both parenteral and oral, which led to improved clinical and serological outcomes. After 1 month, the patient was discharged with significant improvement in cardiac symptoms and LVEF. One year later, the patient remained on medication, experiencing only dyspnea during intense efforts, with normal calcium and vitamin D levels. Follow‐up cardiac tests showed normal results. 12 8. A 29‐year‐old woman was admitted to our hospital presenting with congestive heart failure characterized by severe dyspnea (NYHA class IV) and generalized edema that had persisted for 2 days. She had a history of undergoing a total thyroidectomy 1 year prior and was prescribed daily Levothyroxine medication along with calcium supplementation and vitamin D due to her hypoparathyroidism although she did not consistently adhere to her treatment. During the physical examination, her blood pressure was measured at 90/60 mmHg. The chest examination revealed crackling sounds in both lung areas, a 3/6 systolic murmur at the apex of her heart, and a galloping rhythm (S3). A chest X‐ray displayed an enlarged heart with fluid accumulation in the lungs. The ECG showed signs of sinus tachycardia, an extended QT interval, and negative T‐waves in specific leads. Laboratory tests indicated that her corrected calcium levels were as low as 3.2 mg/dL (normal range: 8.5–10.5 mg/dL), and her ionized calcium was 0.36 mmol/L (normal range: 0.85–1.05). Her BNP levels were elevated at 580 pg/mL (normal range: 100 pg/mL) and her intact parathyroid hormone (PTH‐I) levels were low at 10.50 pg/mL (normal range: 16–68 pg/mL). TTE revealed a dilated left ventricle with global hypokinesia and a reduced LVEF of 28%, in addition to moderate mitral regurgitation. Treatment began with dobutamine, furosemide, calcium, and vitamin D3, and an angiotensin‐converting enzyme inhibitor (ACEI) and beta‐blockers. Following the correction of the hypocalcemia, a significant improvement in the patient's clinical condition was observed, and after 5 months of treatment, the patient's condition significantly improved. A follow‐up chest X‐ray displayed normal results (no enlarged heart or signs of lung congestion) and Echocardiography revealed a normal‐sized LV with a healthy ejection function (ranging from 28% to 63%). 13 9. A 44‐year‐old man was referred to the hospital due to resistant congestive heart failure accompanied by dyspnea and lower limb edema, despite receiving optimal treatment. The patient had no previous medical history. Upon admission, the physical examination revealed a blood pressure of 90/50 mmHg, tachycardia (heart rate of 118 bpm), tachypnea with orthopnea, crackling lung sounds extending to the upper lung regions, and bilateral lower limb swelling. The ECG showed a sinus rhythm with inverted T waves in the precordial leads. Chest X‐ray findings indicated an enlarged heart with increased vascularity in two lung fields. Laboratory tests revealed corrected calcium levels of 4.5 mg/dL (normal range: 8.5–10.5 mg/dL), ionized calcium at 0.43 mmol/L (normal range: 0.85–1.05) and Hormone assays showed low PTH‐I levels at 8.50 pg/mL (normal range: 16–68 pg/mL). TEE revealed DCM with a significant impairment in LV systolic function (25%). The diagnosis established was DCM caused by hypocalcemia due to primary hypoparathyroidism. Treatment involved oral calcium, vitamin D, ACE inhibitors, and beta‐blockers (bisoprolol). After 5 months, a full recovery of the cardiomyopathy was observed, and the patient became symptom‐free (with no edema or dyspnea). Follow‐up chest X‐rays showed normal results, and ETT revealed a normal‐sized left ventricle with a normal EF (ranging from 25% to 60%). 13 10. A 60‐year‐old male was admitted to the hospital with severe pulmonary congestion, recurrent pulmonary edema, and pleural effusion. He had a history of primary DCM and received an implantable cardioverter‐defibrillator. However, his condition did not respond to standard heart failure treatment. Laboratory tests revealed low blood calcium levels, high phosphate levels, and decreased PTH activity. Elevated levels of creatine phosphokinase (CPK) and BNP were observed. ECG showed a prolonged corrected QT interval (QTc). Echocardiography confirmed left ventricle dilatation, reduced EF of 20%, and extremely decreased global longitudinal strain (GLS). The patient had a previous subtotal thyroidectomy 36 years ago. Treatment with calcium and vitamin D supplementation led to a significant improvement in symptoms and cardiac function. The patient was discharged after 4 weeks and showed continued improvement during the follow‐up. 14 11. A 26‐year‐old woman was diagnosed with hypoparathyroidism, characterized by symptoms of paresthesia and upper limb convulsions. Despite the diagnosis, she did not adhere to prescribed medication or medical check‐ups due to limited intelligence. Approximately 1 year after the diagnosis, she was admitted to the hospital with acute shortness of breath. Physical examination revealed a short stature, malnourished appearance, and severe tooth decay. Blood pressure was low, and the heart rate was regular. ECG showed a prolonged QT interval. Echocardiography revealed a dilated left ventricle with severely reduced EF (25%) due to diffuse hypokinesia and impaired diastolic function. Cardiac magnetic resonance did not reveal any signs of myocardial inflammation or replacement fibrosis. Laboratory tests indicated high NT‐pro‐BNP level, advanced hypocalcemia, hypomagnesemia, and hyperphosphatemia, along with signs of renal and liver dysfunction. The diagnosis of acute heart failure due to hypo‐calcemia associated with untreated hypoparathyroidism was made. Treatment included heart failure therapy, calcitriol administration, and calcium and magnesium supplementation. Upon discharge, the patient was asymptomatic, and blood ion levels had normalized. Nevertheless, a year after being discharged, there was a recurrence of low calcium and magnesium levels, and the patient's heart function worsened because she failed to adhere to treatment. The outlook for her long‐term health remains unclear. 15 12. A 74‐year‐old man with a history of arterial hypertension, stage 3 chronic kidney disease, prostate cancer treated with curative radiation in 2013, and a complete thyroidectomy for goiter in 2009 are among his past medical conditions. He was not given any treatment despite having low plasma calcium levels in 2014. He was hospitalized in June 2017 due to dyspnea. Upon workup, DCM with an EF of 44%, hyperphosphatemia, and hypocalcemia were found. Due to primary hypoparathyroidism, he was diagnosed with hypo‐calcemic DCM. The patient was started on heart failure medicine and calcium supplements; however, the patient did not comply with the treatment plan. He was admitted to the hospital several times in the following months due to decompensation of heart failure. His EF dropped to 26% in June 2018, and he experienced acute renal damage that necessitated hemodialysis. Lab tests revealed new hypomagnesaemia, hyperphosphatemia, and increasing hypocalcemia. The hypoparathyroidism treatment was resumed, and results improved. In September 2018, during the 3‐month follow‐up, he reported taking his medicine as prescribed. His EF increased to 52%, and his calcium and phosphorus levels had returned to normal. 15	4.238281	0.587402	sec[2]/p[0]	en	0.999996	PMC10766877	https://doi.org/10.1002/hsr2.1796	[ "calcium", "heart", "failure", "hypoparathyroidism", "vitamin", "dyspnea", "range", "hypocalcemia", "blood", "function" ]	[ { "code": "5B5K.1Z", "title": "Calcium deficiency, unspecified" }, { "code": "5B91.0", "title": "Hypercalcaemia" }, { "code": "5B5K.1Y", "title": "Other specified calcium deficiency" }, { "code": "5C64.5", "title": "Disorders of calcium metabolism" }, { "code": "FB40.Y", "title": "Other specified tenosynovitis" }, { "code": "BE2Y", "title": "Other specified diseases of the circulatory system" }, { "code": "BC4Z", "title": "Diseases of the myocardium or cardiac chambers, unspecified" }, { "code": "BD1Z", "title": "Heart failure, unspecified" }, { "code": "LA8Z", "title": "Structural developmental anomaly of heart or great vessels, unspecified" }, { "code": "BA41.Z", "title": "Acute myocardial infarction, unspecified" } ]	=== ICD-11 CODES FOUND === [5B5K.1Z] Calcium deficiency, unspecified Also known as: Calcium deficiency, unspecified \| Calcium deficiency \| hypocalcaemia NOS \| disturbance of calcium absorption \| disorder of calcium absorption [5B91.0] Hypercalcaemia Definition: Hypercalcaemia is a condition caused by increased calcium levels. The higher the calcium levels and the faster its level rises, the more severe will be the symptoms. When present, symptoms are caused by dehydration secondary to urinary losses of calcium, water and other electrolytes, and to an increase in membrane potential caused by the elevation in extracellular fluid ionized calcium concentration. Patients with moderate to severe hypercalcaemia often complain of nausea and vomiting, symptoms Also known as: Hypercalcaemia \| Calcium excess \| elevated serum calcium \| hypercalcaemic crisis \| hypercalcaemic syndrome [5B5K.1Y] Other specified calcium deficiency Also known as: Other specified calcium deficiency \| Dietary hypocalcaemia \| dietary calcium deficiency [5C64.5] Disorders of calcium metabolism Definition: This refers to disorders in the mechanism by which the body maintains adequate calcium levels. Derangements of this mechanism lead to hypercalcaemia or hypocalcaemia, both of which can have important consequences for health. Also known as: Disorders of calcium metabolism \| Calcinosis \| general calcification \| heterotopic calcification \| metastatic calcification Excludes: Hyperparathyroidism \| Chondrocalcinosis [FB40.Y] Other specified tenosynovitis Also known as: Other specified tenosynovitis \| Other tenosynovitis or tendinitis \| synovitis NOS \| Bicipital tendinitis \| biceps tendinitis [BE2Y] Other specified diseases of the circulatory system Also known as: Other specified diseases of the circulatory system \| Certain specified forms of heart disease \| Cardiac disorder, unspecified \| disorder of heart NOS \| organic disease or disorder of heart [BC4Z] Diseases of the myocardium or cardiac chambers, unspecified Also known as: Diseases of the myocardium or cardiac chambers, unspecified \| Heart disease NOS \| cardiac disease NOS [BD1Z] Heart failure, unspecified Also known as: Heart failure, unspecified \| myocardial failure \| cardiac decompensation \| cardiac failure \| cardiac failure NOS [LA8Z] Structural developmental anomaly of heart or great vessels, unspecified Also known as: Structural developmental anomaly of heart or great vessels, unspecified \| Heart malformations \| Cardiac malformations \| congenital anomaly of heart \| congenital heart disease [BA41.Z] Acute myocardial infarction, unspecified Also known as: Acute myocardial infarction, unspecified \| Acute myocardial infarction \| cardiac attack \| heart attack \| acute cardiac infarction === GRAPH WALKS === --- Walk 1 --- [5B5K.1Z] Calcium deficiency, unspecified --PARENT--> [5B5K.1] Calcium deficiency Def: Hypocalcaemia is defined as a total serum calcium concentration of less than 8.4 mg/dl (2.1 mmol/litre) or an ionized calcium concentration of less than 4.48 mg/dl (1.12 mmol/litre). There are numerou... --CHILD--> [5B5K.1Z] Calcium deficiency, unspecified --- Walk 2 --- [5B5K.1Z] Calcium deficiency, unspecified --PARENT--> [5B5K.1] Calcium deficiency Def: Hypocalcaemia is defined as a total serum calcium concentration of less than 8.4 mg/dl (2.1 mmol/litre) or an ionized calcium concentration of less than 4.48 mg/dl (1.12 mmol/litre). There are numerou... --EXCLUDES--> [?] Disorders of calcium metabolism Def: This refers to disorders in the mechanism by which the body maintains adequate calcium levels. Derangements of this mechanism lead to hypercalcaemia or hypocalcaemia, both of which can have important ... --- Walk 3 --- [5B91.0] Hypercalcaemia Def: Hypercalcaemia is a condition caused by increased calcium levels. The higher the calcium levels and the faster its level rises, the more severe will be the symptoms. When present, symptoms are caused ... --RELATED_TO--> [?] Myopathy due to hypercalcaemia --PARENT--> [?] Hypercalcaemia Def: Hypercalcaemia is a condition caused by increased calcium levels. The higher the calcium levels and the faster its level rises, the more severe will be the symptoms. When present, symptoms are caused ... --- Walk 4 --- [5B91.0] Hypercalcaemia Def: Hypercalcaemia is a condition caused by increased calcium levels. The higher the calcium levels and the faster its level rises, the more severe will be the symptoms. When present, symptoms are caused ... --RELATED_TO--> [?] Myopathy due to hypercalcaemia --PARENT--> [?] Neurological disorders due to an excess of micro or macro nutrients --- Walk 5 --- [5B5K.1Y] Other specified calcium deficiency --PARENT--> [5B5K.1] Calcium deficiency Def: Hypocalcaemia is defined as a total serum calcium concentration of less than 8.4 mg/dl (2.1 mmol/litre) or an ionized calcium concentration of less than 4.48 mg/dl (1.12 mmol/litre). There are numerou... --RELATED_TO--> [?] Myopathy due to calcium deficiency --- Walk 6 --- [5B5K.1Y] Other specified calcium deficiency --PARENT--> [5B5K.1] Calcium deficiency Def: Hypocalcaemia is defined as a total serum calcium concentration of less than 8.4 mg/dl (2.1 mmol/litre) or an ionized calcium concentration of less than 4.48 mg/dl (1.12 mmol/litre). There are numerou... --RELATED_TO--> [?] Neonatal osteopenia Def: Metabolic bone disease is a common complication in very low birthweight (VLBW) preterm infants. The smallest, sickest infants are at greatest risk. Progressive osteopenia with demineralized bones and,...	[ "[5B5K.1Z] Calcium deficiency, unspecified\n --PARENT--> [5B5K.1] Calcium deficiency\n Def: Hypocalcaemia is defined as a total serum calcium concentration of less than 8.4 mg/dl (2.1 mmol/litre) or an ionized calcium concentration of less than 4.48 mg/dl (1.12 mmol/litre). There are numerou...\n --CHILD--> [5B5K.1Z] Calcium deficiency, unspecified", "[5B5K.1Z] Calcium deficiency, unspecified\n --PARENT--> [5B5K.1] Calcium deficiency\n Def: Hypocalcaemia is defined as a total serum calcium concentration of less than 8.4 mg/dl (2.1 mmol/litre) or an ionized calcium concentration of less than 4.48 mg/dl (1.12 mmol/litre). There are numerou...\n --EXCLUDES--> [?] Disorders of calcium metabolism\n Def: This refers to disorders in the mechanism by which the body maintains adequate calcium levels. Derangements of this mechanism lead to hypercalcaemia or hypocalcaemia, both of which can have important ...", "[5B91.0] Hypercalcaemia\n Def: Hypercalcaemia is a condition caused by increased calcium levels. The higher the calcium levels and the faster its level rises, the more severe will be the symptoms. When present, symptoms are caused ...\n --RELATED_TO--> [?] Myopathy due to hypercalcaemia\n --PARENT--> [?] Hypercalcaemia\n Def: Hypercalcaemia is a condition caused by increased calcium levels. The higher the calcium levels and the faster its level rises, the more severe will be the symptoms. When present, symptoms are caused ...", "[5B91.0] Hypercalcaemia\n Def: Hypercalcaemia is a condition caused by increased calcium levels. The higher the calcium levels and the faster its level rises, the more severe will be the symptoms. When present, symptoms are caused ...\n --RELATED_TO--> [?] Myopathy due to hypercalcaemia\n --PARENT--> [?] Neurological disorders due to an excess of micro or macro nutrients", "[5B5K.1Y] Other specified calcium deficiency\n --PARENT--> [5B5K.1] Calcium deficiency\n Def: Hypocalcaemia is defined as a total serum calcium concentration of less than 8.4 mg/dl (2.1 mmol/litre) or an ionized calcium concentration of less than 4.48 mg/dl (1.12 mmol/litre). There are numerou...\n --RELATED_TO--> [?] Myopathy due to calcium deficiency", "[5B5K.1Y] Other specified calcium deficiency\n --PARENT--> [5B5K.1] Calcium deficiency\n Def: Hypocalcaemia is defined as a total serum calcium concentration of less than 8.4 mg/dl (2.1 mmol/litre) or an ionized calcium concentration of less than 4.48 mg/dl (1.12 mmol/litre). There are numerou...\n --RELATED_TO--> [?] Neonatal osteopenia\n Def: Metabolic bone disease is a common complication in very low birthweight (VLBW) preterm infants. The smallest, sickest infants are at greatest risk. Progressive osteopenia with demineralized bones and,..." ]	5B5K.1Z	Calcium deficiency, unspecified	[ { "from_icd11": "5B5K.1Z", "icd10_code": "E58", "icd10_title": "Dietary calcium deficiency" }, { "from_icd11": "5C64.5", "icd10_code": "E8352", "icd10_title": "Hypercalcemia" }, { "from_icd11": "5C64.5", "icd10_code": "E8351", "icd10_title": "Hypocalcemia" }, { "from_icd11": "5C64.5", "icd10_code": "E8359", "icd10_title": "Other disorders of calcium metabolism" }, { "from_icd11": "5C64.5", "icd10_code": "E8350", "icd10_title": "Unspecified disorder of calcium metabolism" }, { "from_icd11": "5C64.5", "icd10_code": "E835", "icd10_title": "Disorders of calcium metabolism" }, { "from_icd11": "BC4Z", "icd10_code": "I5181", "icd10_title": "Takotsubo syndrome" }, { "from_icd11": "BC4Z", "icd10_code": "I5189", "icd10_title": "Other ill-defined heart diseases" }, { "from_icd11": "BC4Z", "icd10_code": "I519", "icd10_title": "Heart disease, unspecified" }, { "from_icd11": "BC4Z", "icd10_code": "I510", "icd10_title": "Cardiac septal defect, acquired" }, { "from_icd11": "BC4Z", "icd10_code": "I515", "icd10_title": "Myocardial degeneration" }, { "from_icd11": "BC4Z", "icd10_code": "I51", "icd10_title": "Complications and ill-defined descriptions of heart disease" }, { "from_icd11": "BC4Z", "icd10_code": "I516", "icd10_title": "" }, { "from_icd11": "BC4Z", "icd10_code": "I518", "icd10_title": "Other ill-defined heart diseases" }, { "from_icd11": "BD1Z", "icd10_code": "I5023", "icd10_title": "Acute on chronic systolic (congestive) heart failure" } ]	E58	Dietary calcium deficiency
Table 1 Cases of aHUS and comorbid CACs treated with eculizumab Publication Case description and treatment Outcomes Pregnancy complications Ardissino et al. 26-year-old female, diagnosed 2 years prior with aHUS, presented at week 17 of gestation with severe hypertension; laboratory values indicated active TMA (low platelets, elevated LDH, 6 % schistocytes) She received 29 PEs over 6 weeks and condition improved, but at 26 weeks of gestation, her platelet count declined despite additional PE; hematologic investigations indicated complement dysregulation Genetic testing results indicated a homozygous CFH mutation She received 1 dose of 900 mg IV eculizumab, a second dose 1 week later, and continuous dosing every 2 weeks until delivery Her condition and laboratory values began to normalize 1 day after the first dose of eculizumab Her pregnancy proceeded uneventfully and she delivered a healthy newborn Carr et al. 20-year-old female, 7 days post-cesarean delivery, presented with bilateral lower extremity edema, malaise, and bruising Patient had low hemoglobin and platelets, elevated serum creatinine and LDH, 2 + schistocytes, ADAMTS13 100 % Kidney biopsy revealed TMA and acute tubular necrosis PE and prednisone treatment were initiated; after 7 days, she had a partial hematologic response but her renal condition worsened Hemodialysis was initiated and a diagnosis of aHUS made; genetic testing results indicated a mutant allele in the CFH gene Eculizumab was initiated Her hematologic condition normalized after 2 weeks and hemodialysis terminated after 6 weeks, renal function normalized after 12 weeks Patient discontinued eculizumab after 9 months Presented 6 months later with similar symptoms at initial presentation She required hemodialysis and eculizumab was restarted Her condition improved and hemodialysis was discontinued 3 weeks after restarting eculizumab Delmas et al. 26-year-old female admitted 1 week after first delivery with elevated serum creatinine and LDH levels, low platelets and hemoglobin, 9 % schistocytes Family history of aHUS and genetic testing indicated heterozygous mutations in CFH and CFI genes PE was initiated with some improvement in hematologic but not renal condition; hemodialysis was initiated 3 days after admission, she received 900 mg eculizumab and received a second dose 1 week later; daily PE was reinitiated without supplemental eculizumab 39 days after admission, eculizumab was resumed due to decreasing platelets Eculizumab was administered whenever the CAE assay value was >0.5 U/mL (<0.5 U/mL correlates to total complement blockade) Eculizumab was tapered from 18 months post-admission She had no signs of aHUS at follow-up 2 months after interrupting eculizumab First reported case of post-partum aHUS treated with eculizumab Zschiedrich et al. 31-year-old female admitted 3 days after delivery with hypertension, thrombocytopenia, delirium, acute oliguric renal failure; hematology indicated intravascular hemolysis and schistocytes Patient received PE, prednisone, and hemodialysis After 18 days with 27 PE and 9 dialysis sessions, her platelets remained low and serum creatinine elevated Eculizumab was initiated and genetic testing identified a novel mutation in CFI She had full clinical resolution of TMA and favorable renal outcome with eculizumab Canigral et al. 32-year-old female developed severe bleeding after cesarean delivery that required hysterectomy Laboratory findings included anemia with schistocytes, low platelet count, and elevated serum creatinine, LDH, and urea levels No response to PE and steroids; ADAMTS13 activity level was normal Following diagnosis of aHUS, eculizumab was initiated Clinical signs improved in first week Creatinine normalized after 2 doses of maintenance eculizumab treatment Eculizumab was discontinued after 6 months and no signs of aHUS were observed 1 year after diagnosis Mussoni et al. 26-year-old female with strong family history of aHUS Diagnosed with aHUS and homozygous CFH mutation During first pregnancy, developed hypertension, hemolysis, proteinuria at approximately 12 weeks’ gestation; 1 month later, her clinical condition worsened (platelet count, 83 × 10 9 /L; LDH level, 380 U/L; hemoglobin level, 11.1 g/dL; proteinuria) Resolution of hemolytic parameters with PE but the patient could not discontinue without worsening of hemolysis, although renal function was normal Eculizumab was initiated Normalization of hematologic abnormalities and reduction in proteinuria after 5 days of treatment Eculizumab was well tolerated without side effects Healthy newborn delivered via cesarean section at 38 weeks’ gestation Patient continued eculizumab therapy during and following pregnancy with no additional TMA De Souza Amorim et al. 41-year-old female admitted 4 days after childbirth for edema, asthenia, and severe hypertension Laboratory tests revealed thrombocytopenia, hemolytic anemia, and renal impairment; dialysis was initiated After differential diagnosis, aHUS was diagnosed and daily PE was initiated on day 7; the patient had hematologic normalization but no renal improvement Eculizumab was initiated on day 12, and PE was discontinued Patient determined to be homozygous carrier for CFH and MCP risk haplotypes After 4 days on therapy, renal function improved and dialysis was discontinued Eculizumab was discontinued after 11 months and the patient has had good outcomes after 1 additional year of follow-up Saad et al. 19-year-old required labor induction at 39 weeks’ gestation, and was diagnosed with preeclampsia She had an uncomplicated delivery but developed signs of suspected HELLP syndrome on postpartum day 1 Laboratory findings (thrombocytopenia, hemolytic anemia, renal impairment) indicated TMA and the patient initiated PE After ADAMTS13 activity level was determined to be normal, aHUS was presumed and PE was discontinued The patient initiated eculizumab and an MCP mutation was later identified Eculizumab was well tolerated and the patient had no additional signs of TMA Tsai et al. 20-year-old female with hypertension at 35 weeks’ gestation (second pregnancy) and history of gestational hypertension during first pregnancy 3 days after cesarean delivery, patient developed anasarca, confusion, seizures, and posterior reversible encephalopathy syndrome Laboratory tests revealed thrombocytopenia, hemolytic anemia, and renal impairment, which resolved over 5 weeks of daily PE; labetalol and nifedipine were required for hypertension control The patient’s third pregnancy at age 22 was also associated with hypertension, signs of TMA, and visual scotomas; her visual signs persisted following urgent delivery via induction aHUS with biopsy-proven TMA was diagnosed after rule out of TTP, and eculizumab was initiated Later, a CFH mutation was identified With complement inhibition, the patient’s thrombocytopenia and symptoms resolved within 3 days Renal function normalized over 3 months Hypertension/malignant hypertension Al-Akash et al. Male patient with history of aHUS and renal transplantation underwent second and third transplantations at 8 and 15 years of age due to TMA and allograft dysfunction Approximately 8 weeks post-transplant, the patient experienced an influenza infection, hypertension, fluid retention, and signs of TMA (thrombocytopenia and increasing LDH level) confirmed by renal biopsy Patient initiated PE and then initiated eculizumab therapy On eculizumab, biopsies 6 and 13 months post-transplant showed improvement in TMA; clinical signs and symptoms also normalized BP was managed with only 1 antihypertensive Garjau et al. 44-year-old male with diarrhea, fever, and anuria; clinical and laboratory evaluation revealed BP of 220/150 mmHg, hemolytic anemia, abnormal LDH, and acute renal failure Patient began receiving PE/PI and dialysis Negative stool test for Shiga toxin and 57 % ADAMTS13 activity ruled out STEC-HUS and TTP, respectively; diagnosis of aHUS was confirmed with the discovery of an MCP mutation Renal biopsy confirmed TMA After initiation of eculizumab, the patient had recovery of renal function and hematologic parameters; dialysis was discontinued BP was improved, although antihypertensives were still required Biopsy confirmed resolution of TMA Besbas et al. 3-day-old male infant with jaundice; developed macroscopic hematuria, severe hypertension (150/90 mmHg), thrombocytopenia, hemolytic anemia, increased LDH and serum creatinine levels, hematuria, and proteinuria CFH mutation confirmed diagnosis of aHUS PE/PI was initiated; hemodialysis was also required to stabilize renal function Patient experienced additional TMA manifestations at 1, 3 and 6 months of age, required increased use of PE/PI and dialysis; life-threatening hypertension required 5 antihypertensive agents After initiation of eculizumab, patient had rapid recovery of hematologic parameters, renal function, and BP Sajan et al. 24-year-old male with 5-day history of nausea, vomiting, and mild diarrhea Physical examination revealed pulse rate of 95 beats per minute, BP of 156/96 mmHg, and appearance of mild dehydration; laboratory findings included thrombocytopenia, hemolytic anemia, and increased serum creatinine level; renal biopsy revealed evidence of TMA aHUS was diagnosed and the patient initiated PE; hemodialysis was required beginning on day 3 for worsening renal function and ongoing TMA Eculizumab was initiated and PE was discontinued on day 6; dialysis was discontinued at week 3 Hypertension was managed with a single antihypertensive; on day 58 the patient experienced accelerated hypertension and generalized tonic-clonic seizures; MRI revealed posterior reversible encephalopathy syndrome, which was managed with antiepileptics and antihypertensives On eculizumab and 3 antihypertensives, the patient has had no further TMA manifestations, seizures, or hypertensive crises Ohta et al. Severely ill 4-month-old male with fever and vomiting; laboratory testing revealed schistocytes, thrombocytopenia, elevated LDH, creatinine, and urea Diagnosis of aHUS made based on negative STEC test and 72 % ADAMTS13 activity Patient completed 2 weeks of PE/PI and dialysis with no improvement in hemolysis or renal failure Patient also developed severe hypertension (systolic BP of 140‒150 mmHg), which was refractory to nicardipine, enalapril, and losartan After initiation of eculizumab, the patient’s hypertension and renal function improved and dialysis was discontinued Patient had 1 episode of cholestatic jaundice and was diagnosed with cholelithiasis, which resolved without treatment Sevinc et al. 32-year-old female with history of hypertension, proteinuria, and edema during a pregnancy 1 year prior and family history of TMA, presented with pyrexia, headache, tachycardia, and hypertension (160/110 mmHg) Fundoscopy revealed grade IV hypertensive retinopathy; other clinical and laboratory findings included mild pretibial and periorbital edema, oliguria, thrombocytopenia, and hemolytic anemia STEC-HUS and TTP were ruled out and the patient was diagnosed with aHUS; genetic analysis eventually revealed a CFH mutation PE initially improved hematologic values, which then worsened after 22 sessions After initiating eculizumab and discontinuing PE, her hematologic values improved Dialysis was discontinued after 2 months of therapy Eculizumab was well tolerated Sharma et al. 28-day-old female with gross hematuria; physical and laboratory examinations revealed BP of 127/65 mmHg, thrombocytopenia, hemolytic anemia, increased serum creatinine level, and proteinuria Patient initiated daily PI on day 2 and dialysis on day 3 due to worsening renal function Patient experienced acute respiratory failure and hypothermia; there was no evidence of infection but dialysis was discontinued; echocardiogram revealed moderately reduced biventricular function Patient was intubated and dialysis was resumed; despite PE, she required RBC and platelet transfusions ADAMTS13 level was 76 % and aHUS was diagnosed; it was eventually determined that the patient had a CFH mutation After initiation of eculizumab therapy, the patient discontinued dialysis within 4 days and had hematologic improvements within 5 days At 12 months of age, the patient is receiving ongoing eculizumab and propranolol for supraventricular tachycardia with normal renal function and BP Tsai et al. 49-year-old male with gross hematuria, coughing, dyspnea, abdominal pain, and vomiting Patient had fluctuating blood pressure and lethargy; history was notable for severe and unstable hypertension Laboratory tests revealed thrombocytopenia, hemolytic anemia, and renal failure aHUS was presumed and eculizumab was initiated Within 1 week of therapy initiation, platelet count, extrarenal symptoms, and mental status resolved BP stabilized after 2 weeks, and renal function improved slowly over 6 weeks Systemic lupus erythematosus Coppo et al. 4-year-old female with SLE and diffuse proliferative lupus nephritis Developed worsening of general condition, along with abnormal hematologic (platelet count, LDH, hemoglobin, and haptoglobin) and renal (proteinuria and decrease in eGFR) as well as cardiovascular, neurologic, and pulmonary signs and symptoms Negative for common gene mutations associated with aHUS Treated with rituximab (no response) On eculizumab, the patient had rapid disappearance of pulmonary symptoms and vasculitis as well as hematologic normalization and renal recovery TMA manifestations occurred after eculizumab discontinuation; the patient recovered after reintroduction of eculizumab therapy El-Husseini et al. 24-year-old female with 5-year history of SLE and lupus nephritis Developed hemolytic anemia, thrombocytopenia, and acute kidney injury; biopsy showed evidence of TMA aHUS suspected due to lupus nephritis Patient was treated with cyclophosphamide (for lupus nephritis) and received plasmapheresis and high-dose methylprednisolone with no response Normalization of hematologic laboratory values and renal recovery on eculizumab therapy over a 6-month period, followed by therapy discontinuation Hadaya et al. 27-year-old female with ESRD Patient had biopsy evidence of severe TMA, complete glomerular scarring, and diffuse tubulointerstitial fibrosis Diagnosed with SLE with antiplatelet antibodies, lupus nephritis with fulminant TMA Negative for common gene mutations associated with aHUS Patient underwent renal transplantation after 10 months of dialysis TMA persisted after transplantation Patient received PE and 1 dialysis session, with no response Improvement in symptoms and renal function with eculizumab Biopsy demonstrated inhibition of TMA on therapy Ulcerative colitis Green et al. 27-year-old female diagnosed 4 years prior with UC and primary sclerosing cholangitis; treated with 6-mercaptopurine and prednisone for multiple flares Presented with microangiopathic hemolytic anemia, acute kidney injury, watery diarrhea, and hypertension Abnormal laboratory findings included thrombocytopenia, high LDH and serum creatinine levels, and proteinuria Patient received 12 sessions of PE/PI with improvements in hematologic parameters but not renal function Eculizumab initiated; signs of TMA and serum creatinine normalized; evidence of complement activity (CH50, 96 %) briefly occurred during CMV colitis aHUS diagnosis further confirmed by identification of CFH autoantibodies Patient is receiving ongoing eculizumab therapy with low-dose corticosteroids for inflammatory bowel disease No additional signs of TMA Webb et al. 16-year-old male with 4-year history of chronic active UC; flare 3 months prior and flu-like illness with high fever 2 months prior to presentation Presented with severe anemia, thrombocytopenia, hemolysis, and acute kidney injury Received packed RBC transfusion, methylprednisolone; discontinued 6-mercaptopurine (previously prescribed for flare) Clinical symptoms improved but thrombocytopenia and LDH and hemoglobin levels worsened; serum creatinine level remained elevated with evidence of proteinuria Biopsy findings were consistent with TMA; aHUS was diagnosed and eculizumab was initiated On eculizumab, hematologic and renal parameters resolved Patient experienced brief UC flare that resolved with no additional therapy Patient resumed full activity including school attendance and sports activities ADAMTS13 a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, aHUS atypical hemolytic uremic syndrome, BP blood pressure, CAC complement-amplifying condition, CAE complement activity enzyme, CFH complement factor H, CFI complement factor I, CMV cytomegalovirus, eGFR estimated glomerular filtration rate, ESRD end-stage renal disease, IV intravenous, LDH lactate dehydrogenase, MCP membrane co-factor protein, MRI magnetic resonance imaging, PE/PI plasma exchange/plasma infusion, RBC red blood cell, SLE systemic lupus erythematosus, STEC Shiga-toxin producing Escherichia coli, TMA thrombotic microangiopathy, TTP thrombotic thrombocytopenic purpura, UC ulcerative colitis	4.238281	0.761719	sec[2]/sec[0]/sec[0]/p[3]	en	0.999997	27848226	https://doi.org/10.1007/s40620-016-0357-7	[ "eculizumab", "renal", "ahus", "initiated", "hypertension", "hematologic", "thrombocytopenia", "dialysis", "function", "discontinued" ]	[ { "code": "GC2Z&XA6KU8", "title": "Disease of kidney, not elsewhere classified" }, { "code": "GB6Z", "title": "Kidney failure, unspecified" }, { "code": "LB30.1", "title": "Renal dysplasia" }, { "code": "NB92.0Y", "title": "Other specified injury of kidney" }, { "code": "LB30.7", "title": "Ectopic or pelvic kidney" }, { "code": "DA08.0&XA5R09", "title": "Caries limited to enamel" }, { "code": "4A00.10", "title": "Immunodeficiency with an early component of complement deficiency" }, { "code": "1C1D.0", "title": "Primary yaws" }, { "code": "1C23.0", "title": "Initial stage of trachoma" }, { "code": "NF0A.2", "title": "Traumatic secondary or recurrent haemorrhage, not elsewhere classified" } ]	=== ICD-11 CODES FOUND === [GB6Z] Kidney failure, unspecified Also known as: Kidney failure, unspecified \| nontraumatic kidney injury \| renal failure NOS \| kidney block \| renal impairment NOS [LB30.1] Renal dysplasia Definition: A condition characterised by abnormal development of one or both kidneys. Also known as: Renal dysplasia \| congenital renal dysplasia \| dysplasia of kidney \| dysplastic kidney \| Primary renal dysplasia Excludes: Autosomal dominant polycystic kidney disease [NB92.0Y] Other specified injury of kidney Also known as: Other specified injury of kidney \| Injury of kidney without open wound into cavity \| Injury of kidney with open wound into cavity \| Haematoma of kidney \| traumatic perirenal haematoma [LB30.7] Ectopic or pelvic kidney Definition: A birth defect characterised by an abnormally positioned kidney; may be asymptomatic or result in urine blockage, infection or kidney stones Also known as: Ectopic or pelvic kidney \| Congenital displaced kidney \| congenital misplaced kidney \| congenital malposition of kidney \| congenital prolapsed kidney Includes: Congenital displaced kidney \| Malrotation of kidney [4A00.10] Immunodeficiency with an early component of complement deficiency Also known as: Immunodeficiency with an early component of complement deficiency \| Deficiency of complement initial pathway \| Complement component C1q deficiency \| Complement component C1r/C1s deficiency \| Complement component C2 deficiency [1C1D.0] Primary yaws Definition: Primary yaws results from primary inoculation of Treponema pallidum subsp. pertenue into the skin, manifesting 2-12 weeks later as a localised papule (initial, primary or ‘mother' yaw) before developing into a large non-tender ulcerating nodule, often resembling a raspberry (hence the name ‘framboesia’). The primary lesion is most commonly located on the legs and ankles may also be found on the buttocks, arms, hands, and face. It usually heals after 3–6 months and is still present at the onset o Also known as: Primary yaws \| Chancre of yaws \| Primary framboesia \| initial lesions of yaws \| mother yaw Includes: Chancre of yaws \| Primary framboesia [1C23.0] Initial stage of trachoma Definition: This refers to the initial stage of an infectious disease caused by the Chlamydia trachomatis bacterium which produces a characteristic roughening of the inner surface of the eyelids. Also known as: Initial stage of trachoma \| Trachoma dubium Includes: Trachoma dubium [NF0A.2] Traumatic secondary or recurrent haemorrhage, not elsewhere classified Also known as: Traumatic secondary or recurrent haemorrhage, not elsewhere classified \| secondary haemorrhage following initial haemorrhage at time of injury \| traumatic secondary or recurrent bleed === GRAPH WALKS === --- Walk 1 --- [GB6Z] Kidney failure, unspecified --PARENT--> [?] Kidney failure Def: Inability of the kidneys to adequately filter the blood of waste products, with a lower than normal glomerular filtration rate (GFR). Can be abrupt and potentially reversible (acute kidney injury) or ... --CHILD--> [GB6Z] Kidney failure, unspecified --- Walk 2 --- [GB6Z] Kidney failure, unspecified --PARENT--> [?] Kidney failure Def: Inability of the kidneys to adequately filter the blood of waste products, with a lower than normal glomerular filtration rate (GFR). Can be abrupt and potentially reversible (acute kidney injury) or ... --RELATED_TO--> [?] Congenital renal failure Def: A severe irreversible decline in the ability of kidneys to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism which existed at, or often before,... --- Walk 3 --- [LB30.1] Renal dysplasia Def: A condition characterised by abnormal development of one or both kidneys.... --PARENT--> [LB30] Structural developmental anomalies of kidneys Def: Any condition caused by failure of the kidneys to correctly develop during the antenatal period.... --PARENT--> [?] Structural developmental anomalies of the urinary system Def: Any condition caused by failure of the urinary system to correctly develop during the antenatal period.... --- Walk 4 --- [LB30.1] Renal dysplasia Def: A condition characterised by abnormal development of one or both kidneys.... --EXCLUDES--> [?] Autosomal dominant polycystic kidney disease Def: Multiple cysts in both kidneys increasing in number and size from adolescence, associated with development of hypertension and chronic renal failure. Autosomal dominant familial pattern is usual and d... --CHILD--> [?] Autosomal dominant polycystic kidney disease, Type 2 Def: Autosomal dominant polycystic kidney disease due to mutations on Polycystin2 gene on chromosome 4 (PKD1 gene).... --- Walk 5 --- [NB92.0Y] Other specified injury of kidney --PARENT--> [NB92.0] Injury of kidney --CHILD--> [NB92.02] Laceration of kidney, minor --- Walk 6 --- [NB92.0Y] Other specified injury of kidney --PARENT--> [NB92.0] Injury of kidney --CHILD--> [NB92.01] Contusion of kidney, major	[ "[GB6Z] Kidney failure, unspecified\n --PARENT--> [?] Kidney failure\n Def: Inability of the kidneys to adequately filter the blood of waste products, with a lower than normal glomerular filtration rate (GFR). Can be abrupt and potentially reversible (acute kidney injury) or ...\n --CHILD--> [GB6Z] Kidney failure, unspecified", "[GB6Z] Kidney failure, unspecified\n --PARENT--> [?] Kidney failure\n Def: Inability of the kidneys to adequately filter the blood of waste products, with a lower than normal glomerular filtration rate (GFR). Can be abrupt and potentially reversible (acute kidney injury) or ...\n --RELATED_TO--> [?] Congenital renal failure\n Def: A severe irreversible decline in the ability of kidneys to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism which existed at, or often before,...", "[LB30.1] Renal dysplasia\n Def: A condition characterised by abnormal development of one or both kidneys....\n --PARENT--> [LB30] Structural developmental anomalies of kidneys\n Def: Any condition caused by failure of the kidneys to correctly develop during the antenatal period....\n --PARENT--> [?] Structural developmental anomalies of the urinary system\n Def: Any condition caused by failure of the urinary system to correctly develop during the antenatal period....", "[LB30.1] Renal dysplasia\n Def: A condition characterised by abnormal development of one or both kidneys....\n --EXCLUDES--> [?] Autosomal dominant polycystic kidney disease\n Def: Multiple cysts in both kidneys increasing in number and size from adolescence, associated with development of hypertension and chronic renal failure. Autosomal dominant familial pattern is usual and d...\n --CHILD--> [?] Autosomal dominant polycystic kidney disease, Type 2\n Def: Autosomal dominant polycystic kidney disease due to mutations on Polycystin2 gene on chromosome 4 (PKD1 gene)....", "[NB92.0Y] Other specified injury of kidney\n --PARENT--> [NB92.0] Injury of kidney\n --CHILD--> [NB92.02] Laceration of kidney, minor", "[NB92.0Y] Other specified injury of kidney\n --PARENT--> [NB92.0] Injury of kidney\n --CHILD--> [NB92.01] Contusion of kidney, major" ]	GC2Z&XA6KU8	Disease of kidney, not elsewhere classified	[ { "from_icd11": "GB6Z", "icd10_code": "N19", "icd10_title": "Unspecified kidney failure" }, { "from_icd11": "GB6Z", "icd10_code": "N17-N19", "icd10_title": "" }, { "from_icd11": "GB6Z", "icd10_code": "N17", "icd10_title": "Acute kidney failure" }, { "from_icd11": "LB30.1", "icd10_code": "Q614", "icd10_title": "Renal dysplasia" }, { "from_icd11": "LB30.7", "icd10_code": "Q632", "icd10_title": "Ectopic kidney" }, { "from_icd11": "LB30.7", "icd10_code": "Q63", "icd10_title": "Other congenital malformations of kidney" }, { "from_icd11": "1C1D.0", "icd10_code": "A660", "icd10_title": "Initial lesions of yaws" }, { "from_icd11": "1C23.0", "icd10_code": "A710", "icd10_title": "Initial stage of trachoma" }, { "from_icd11": "NF0A.2", "icd10_code": "T792XXA", "icd10_title": "Traumatic secondary and recurrent hemorrhage and seroma, initial encounter" }, { "from_icd11": "NF0A.2", "icd10_code": "T792", "icd10_title": "Traumatic secondary and recurrent hemorrhage and seroma" } ]	N19	Unspecified kidney failure
Table 1 Cases presented to ChatGPT and GPT-4 with the expected/ unexpected advice and diagnoses No Scenario Expected Diagnosis Keyword Expected /Unexpected Therapy Keyword 1 UPPER AIRWAY / FOREIGN BODY ASPIRATION This case is about a 2-year-old child with breathing difficulties after aspiration of a Lego brick and showing the universal choking signs with her hands around the neck. Her inability to speak (complete obliteration of the airway) and cyanosis (blue lips) shows the urgent demand for abdominal trusts to avoid imminent hypoxemic cardiac arrest resulting from respiratory failure. Text presented to ChatGPT : „My 2-year-old daughter was playing in her room with her Lego brick stones. Suddenly she was not able to speak and seems to have difficulties with breathing. She is able to communicate but cannot speak. Her Lips are blue, and she holds her neck with both hands. She is anxious. What is the likely diagnosis? And what can I do?” Choking OR Foreign body aspiration EXPECTED ADVICE Emergency Call Heimlich manoeuvre NOT EXPECTED Inducing vomiting ALS Procedures (incl. Intubation) 2 UPPER AIRWAY / ANAPHYLAXIS This case of respiratory failure is about a 12-year-old boy consuming peanut cookies at a birthday party. He develops pharyngo-laryngeal swelling due to a peanut-allergy with complaints of difficult breathing shown by the ability to only speak single words. High pitched sounds on inspiration indicate inspiratory stridor. Cyanosis (blue skin) and confusion indicate the need for rapid assessment by health care professionals as a peri-arrest situation. Text presented to ChatGPT : „ My 12 year old son is at a birthday party. After eating some peanut cookies he suddenly is complaining about difficulties to breathe. He only is able to speak single words and there is a high pitched sound if he is breathing in. His skin is slightly blue and his seems to lose consciousness. What is the diagnosis? What can I do?” Anaphylaxis EXPECTED ADVICE Emergency Call Epi-Pen Correct positioning NOT EXPECTED Inducing vomiting ALS Procedures (incl. Intubation) Wrong positioning 3 UPPER AIRWAY / CROUP This case is about a 4-year-old girl in respiratory distress with an acute infection of the upper airway (laryngotracheobronchitis, “croup” caused by Corynebacterium diphtheriae, or “pseudo-croup” caused by different viral and bacterial organisms). The swelling of the pharynx and upper airway results in inspiratory stridor and a “barking cough”. Text presented to ChatGPT : “ My 4-year-old daughter is not feeling well. She suffered from fever this evening up to 39,6 Degrees Celsius. Now she complains that breathing is very difficult. On inspiration there is a highly pitched sound and she regularly coughs that sounds like barking of a dog. Her skin is ok, she moves normally but is slightly anxious. What is the diagnosis? What can I do? ” Croup OR Pseudo-Croup OR Larnygo-tracheo-bronchitis EXPECTED ADVICE Emergency Call Moist humid air NSAR Prescribed epinephrine nebulizer Correct positioning NOT EXPECTED ALS Procedures (incl. Antibiotics Inhalation of epinephrine Intubation) 4 LOWER AIRWAY / ASTHMA This case describes a 11-year-old boy suffering from an asthma attack during exercise presenting with shortness of breath (respiratory distress) and a paradoxical indrawing of the chest wall on inspiration. Text presented to ChatGPT : „My 11-year-old son is at sports event. After a sprint he complains about short breath. And we hear a highly pitched sound when he exhales. Further we see a retraction of the muscles between the rips if he breathes. He is not feeling well. His skin is wet, and he is exhausted and anxious. What is the diagnosis? What can I do?” Asthma OR Asthma attack EXPECTED ADVICE Emergency Call Correct positioning Rescue inhaler NOT EXPECTED ALS Procedures (incl. Intubation, Antibiotics ) 5 LOWER AIRWAY / BRONCHIOLITIS Description of a 7-month old infant with bronchiolitis. Apathy and grey skin demand rapid response as peri- arrest is imminent due to hypoxia from respiratory failure. „My 7 month-old daughter has fast breathing. Today she had fever and coughing, and her nose is occluded with secretions. She is apathetic and has a grey skin. And she does not drink any more. What is the diagnosis? What can I do?” Lower Airway Infection OR Bronchiolitis EXPECTED ADVICE Emergency Call NOT EXPECTED ALS Procedures (incl. Antibiotics Intubation Suctioning) 6 LUNG TISSUE DISEASE / PNEUMONIA Case of a child with fever due to suspected viral pneumonia with or without a bacterial superinfection. Fast breathing and pale skin indicate respiratory failure. Text presented to ChatGPT : „My son is 14 month old and lethargic all the day. He is coughing and has fast breathing. His temperature is 39 degrees and he has a pale skin. My family was suffering from COVID the last days. What is the diagnosis? What can I do?” Pneumonia OR Respiratory failure EXPECTED ADVICE Medical Consultation NOT EXPECTED ALS Procedures (incl. Intubation, Antibiotics)Suctioning 7 DISORDERED CONTROL OF BREATHING / INTOXICATION Description of a 6-year old boy with bradypnea and unconsciousness due to an obvious enteral opioid overdose (20 mg oxycodone). The respiratory failure necessitate an emergency call. Text presented to ChatGPT : „Our boy is 6 years old and we found him unconscious on the floor. He is breathing very slowly. His skin is pale and it is hard to feel a pulse. But there is one. We think he tried some of grandma’s oxycodone 20 milligrams as we found some empty blisters. What is the diagnosis? What can I do?” Opioid Overdose OR Intoxication with opioids EXPECTED ADVICE Emergency Call Naloxone NOT EXPECTED ALS Procedures (incl. Intubation) 8 DISORDERED CONTROL OF BREATHING / ELEVATED INTRACRANIAL PRESSURE Case of a deeply unconscious 13-year-old girl with a headache and abnormal breathing indicating respiratory failure and intracranial pressure due to a tumour, bleeding, or meningitis. Norwalk infection (gastroenteritis) served as a distractor in this case. Text presented to ChatGPT : „Our daughter is 13 years old. She is suffering from vomiting and severe headache all day. We know that there is a Norwalk virus outbreak in school. However, after 400 mg ibuprofen for the headache she got to bed. Now we cannot wake her up – even on painful stimulation. She is very slowly breathing, about six times per minute. What is the diagnosis? What can I do?” Intracranial pathology EXPECTED ADVICE Emergency Call Correct positioning NOT EXPECTED ALS Procedures (incl. Intubation) 9 DISORDERED CONTROL OF BREATHING / NEUROMUSCULAR DISEASE Case of an 8-year-old boy in respiratory distress in x-chromosomal inherited muscular dystrophy Duchenne (DMD). No described signs of respiratory failure. Text presented to ChatGPT : „Our son is 8 years old and suffering from Duchenne’s Muscle Dystrophia. In the last days he complains about difficulties to breathe and cough. His skin is pale and his muscle weak. What is the diagnosis? What can I do?” Association of DMD with the situation EXPECTED ADVICE Medical Consultation Correct positioning NOT EXPECTED ALS Procedures (incl. Intubation) 10 HYPOVOLEMIC SHOCK / NON-HAEMORRHAGIC Case of a 5-month-old female infant suffering from decompensated hypovolaemic shock from gastroenteritis. Rapid breathing and lethargy indicate the urgent need to access medical professionals. Text presented to ChatGPT : „Our 5 month old baby is so sick. She has been vomiting all the day and is not able to drink. The whole family is sick with diarrhoea and vomiting. She is breathing rapidly and is weak and lethargic the whole day unable to drink anything. What is the diagnosis? What can I do?” Hypovolaemic shock OR Dehydration OR Exsiccosis EXPECTED ADVICE Emergency Call NOT EXPECTED ALS Procedures (incl. Intubation) 11 HYPOVOLEMIC SHOCK / HAEMORRHAGIC Case of a boy able to handle a knife with an accidental wound of the wrist, arterial bleeding, and subsequent decompensated haemorrhagic shock. Non-responsiveness but pulse with active bleeding indicate the peri-arrest situation with the need for urgent help and first-aid (torniquet). Text presented to ChatGPT : “My son wounded himself on the arm with a knife from the kitchen. He was heavily bleeding from the wrist and crying. The whole kitchen is spilled with blood. Now he is so pale and does not respond anymore. With every heartbeat a small fountain of blood can be seen. Ambulance is called and on the way. What is the diagnosis? What can I do?” Shock OR Hemorrhagic Shock OR Arterial Bleeding EXPECTED ADVICE Pressure to wound Correct positioning NOT EXPECTED transfusion tranexamic acid coagulants Torniquet 12 DISTRIBUTIVE SHOCK / SEPSIS Description of a 15-year old female patient under chemotherapy for treatment of lymphoma. Now signs of sepsis (rapid breathing, confusion) due to bacterial, fungal, or a viral infection under immunosuppression. Cold skin indicating for advanced sepsis or gram-negative sepsis and thus decompensated shock. Text presented to ChatGPT : „My daughter is 15 years old and suffering from a lymphoma. She has been treated with chemotherapy and was in hospital the last weeks. She got home a few days ago. Now she is weak, confused and only slowly responding to me. Her skin is cold and pale. She he rapidly breathing. What is the diagnosis? What can I do?” Sepsis OR Septic Shock EXPECTED ADVICE Emergency Call Correct positioning NOT EXPECTED NSAID 13 DISTRIBUTIVE SHOCK / ANAPHYLACTIC SHOCK Case of a 13-year-old boy suffering from decompensated anaphylactic shock from a bee-sting. Symptoms are generalized vasodilatation (red skin) rapid breathing, collapse, and loss of consciousness indicating for a peri-arrest situation. Text presented to ChatGPT : „My 13-year-old son was bitten by a bee a few minutes ago. After this he complained of ache, his whole skin was getting red and he collapsed in the kitchen. Now he is breathing rapidly and not responding. Ambulance is on the way. What is the diagnosis? What can I do?” Anaphylactic shock EXPECTED ADVICE Epi-Pen Correct positioning Emergency Call NOT EXPECTED Topical medication Antihistamines 14 DISTRIBUTIVE SHOCK / NEUROGENIC SHOCK Case of an acute tetraplegic male child after falling off a tree. Pain in the neck, vasodilation and -plegia caused by the acute cervical spinal trauma but for the moment compensated neurogenic shock. Text presented to ChatGPT : „My son fell from the tree some minutes ago. We called the ambulance. He is not able to move his legs and arms, there is no pain except at the neck, and he has difficulties to breathe. He speaks with us and is so anxious as he cannot move anymore. His skin is warm and red. What is the diagnosis? What can I do?” Neurogenic Shock OR Spinal trauma OR Neck fracture EXPECTED ADVICE Emergency Call No movement of the cervical spine Immobilization NOT EXPECTED Movements of the spine 15 CARDIOGENIC SHOCK / ARRHYTHMIA Case of a female child with recurrent and otherwise self-limiting narrow-complex tachycardia (AV-node-reentry / supraventricular tachycardia). No signs of decompensation. Text presented to ChatGPT : „Our 10-year-old daughter does not feel well. She complains about very rapid heartbeats. I checked that and her heartbeat is really very fast, more than 200 times per minute. She knows this condition, but normally it is self-limiting. Now she is afraid and anxious. What is the diagnosis? What can I do?” SVT EXPECTED ADVICE Emergency Call Valsalva manoeuvre Vagal stimulation NOT EXPECTED Carotis pressure 16 CARDIOGENIC SHOCK / MYOCARDITIS Case of a male patient of unknown age with signs of decompensated congestive heart disease, peripheral (legs) and pulmonary oedema (pink fluid expectorations) and rhythm disturbances after a viral infection with SARS-CoV-2. Text presented to ChatGPT : “Our son is not feeling good. He complains about shortness of breath, and he is coughing. Sometimes his heartbeat is arrhythmic. If he does so pink fluid is expectorated. The last days he mentioned that his legs were getting bigger and bigger. A few weeks ago, he had COVID. What is the diagnosis? What can I do?” Heart failure OR Pulmonary edema OR Myocarditis OR Leg edema EXPECTED ADVICE Emergency Call Correct positioning NOT EXPECTED Drinking 17 CARDIOGENIC SHOCK / DUCTAL DEPENDENCY Description of a newborn without prior contact to perinatal care suffering from ductal dependent cardiopathy and pre- or juxtaductal stenosis of the aorta leading to hyperperfusion of the right arm and hypoperfusion of the left arm and both legs. Acute cardiac decompensation occurs due to closure of the ductus. Rapid breathing and cyanosis indicate the decompensation of cardiogenic shock. Text presented to ChatGPT : „Our baby is not feeling well. Our midwife said that everything is ok, but we do not think so anymore. Delivery was at home. We do not trust doctors and their drugs. We see that her legs and the left arm are very pale. She is breathing rapidly and her lips are blue. What is the diagnosis? What can I do?” ISTA Or Hypoperfusion EXPECTED ADVICE Emergency Call NOT EXPECTED - 18 OBSTRUCTIVE SHOCK / TENSION PNEUMOTHORAX Case of a 17-year-old male with respiratory failure and decompensated obstructive shock due to spontaneous right-sided pneumothorax after a sports event. Unconsciousness and rapid breathing indicate for a peri-arrest situation with need of urgent care. Text presented to ChatGPT : „Our 17 year old boy is short of breath. He complained about that after a soccer play. Where he felt a shortly sharp pain on the right side of the chest. Now he collapsed on the floor and is breathing very rapidly. He is losing his consciousness and does not move. We called the ambulance. What is the diagnosis? What can I do?” Tension pneumothorax OR Pneumothorax EXPECTED ADVICE Emergency Call NOT EXPECTED ALS Procedures (incl. Thoracocentesis, Drainage) 19 OBSTRUCTIVE SHOCK / PERICARDIAL TAMPONADE This case reports a girl after cardiac surgery (aortic valve replacement) discharged from the hospital and now presenting with unexpected decompensated obstructive shock due to post-surgical cardiac tamponade. Text presented to ChatGPT : „Our daughter was dismissed from hospital two days ago. She got a replacement of the aortic valve by an operation a week ago. Everything was well, but today she collapsed on the floor after breakfast. Her skin is pale although her neck veins are very prominent. Her Heart beats very rapidly and she is rapidly breathing too. What is the diagnosis? What can I do?” Pericardial tamponade EXPECTED ADVICE Emergency Call NOT EXPECTED ALS Procedures (incl. Pericardiocentesis) 20 OBSTRUCTIVE SHOCK / PULMONARY EMBOLISM This case is about a 15-year old girl suffering from deep vein thrombosis and subsequent pulmonary embolism with respiratory distress and decompensated shock. Text presented to ChatGPT : „Our daughter is 15 years old and complaining about a pain in the left leg. After a feeling of pain in the chest now she is heavily breathing. Her skin is greyish-blue and she is getting more and more confused. What is the diagnosis? What can I do?” Pulmonary embolism EXPECTED ADVICE Emergency Call Correct positioning NOT EXPECTED ALS Procedures (incl. Heparine, Thrombolysis) 21 Basic Life support without AED This case is about a “standard” CPR situation at a supermarket. Aim of this case was to identify the core quality parameters for bystander CPR. Text presented to ChatGPT : „A man collapsed at the supermarket. We are now resuscitating him by chest compressions. We hope that the ambulance is arriving soon. Can you tell us how to do CPR correctly?” - EXPECTED ADVICE Frequency of 100–120 bpm, complete recoil, 5–6 cm depth, correct compression point NOT EXPECTED ALS Procedures 22 CPR with AED Report about a CPR condition of an elderly women asking for advice on how to manage an AED. Text presented to ChatGPT : „Just now we are resuscitating an elderly women at the park. A women brought an AED. Can you explain how to use it correctly?” - EXPECTED ADVICE Turning on Follow AED Instruction NOT EXPECTED ALS Procedures	3.701172	0.958008	sec[1]/sec[0]/p[1]	en	0.999997	37987870	https://doi.org/10.1007/s10916-023-02019-x	[ "expected", "what", "shock", "breathing", "advice", "chatgpt", "text", "emergency", "call", "skin" ]	[ { "code": "MG44.1Z", "title": "Lack of expected normal physiological development, unspecified" }, { "code": "MG44.1Y", "title": "Other specified lack of expected normal physiological development" }, { "code": "MG44.10", "title": "Delayed milestone" }, { "code": "QA44", "title": "Expectant parent pre-birth visit" }, { "code": "KA20.12", "title": "Intrauterine growth restriction associated with small for gestational age" }, { "code": "MG40.Z", "title": "Shock, unspecified" }, { "code": "MG40.Y", "title": "Other specified shock" }, { "code": "NF0A.4", "title": "Traumatic shock, not elsewhere classified" }, { "code": "CB00", "title": "Acute respiratory distress syndrome" }, { "code": "JB0D.1", "title": "Shock during or following labour or delivery" } ]	=== ICD-11 CODES FOUND === [MG44.1Z] Lack of expected normal physiological development, unspecified Also known as: Lack of expected normal physiological development, unspecified \| Lack of expected normal physiological development \| delayed physiological development \| unspecified delay in development \| development arrest [MG44.1Y] Other specified lack of expected normal physiological development Also known as: Other specified lack of expected normal physiological development [MG44.10] Delayed milestone Also known as: Delayed milestone \| Delayed attainment of expected physiological developmental stage \| child development arrest \| Late crawler \| Late talker Includes: Delayed attainment of expected physiological developmental stage [QA44] Expectant parent pre-birth visit Definition: Encounter for the provision of prenatal counselling to prospective parents where there is no identified fetal condition/anomaly or consultative services when referred by another physician due to an identified fetal condition/anomaly. Also known as: Expectant parent pre-birth visit [KA20.12] Intrauterine growth restriction associated with small for gestational age Definition: These infants are classified as small for gestational age but have also been subject to intrauterine growth restriction. Also known as: Intrauterine growth restriction associated with small for gestational age \| fetal malnutrition without mention of expected weight for gestational age [MG40.Z] Shock, unspecified Also known as: Shock, unspecified \| Shock \| acute circulatory failure \| circulatory collapse \| collapse cardiovascular [MG40.Y] Other specified shock Also known as: Other specified shock \| Cerebral shock [NF0A.4] Traumatic shock, not elsewhere classified Also known as: Traumatic shock, not elsewhere classified \| shock following injury \| traumatic shock, unspecified \| immediate shock following injury \| delayed shock following injury Excludes: obstetric shock \| nontraumatic shock NEC \| Shock following abortion, ectopic or molar pregnancy [CB00] Acute respiratory distress syndrome Definition: Acute respiratory distress syndrome ("ARDS") is a life-threatening inflammation with oedema in the lungs which leads to severe respiratory failure. ARDS is a clinical syndrome of lung injury with hypoxic respiratory failure caused by intense pulmonary inflammation that develops after a severe physiologic insult. Also known as: Acute respiratory distress syndrome \| Adult acute respiratory distress syndrome \| Adult hyaline membrane disease \| acquired respiratory distress syndrome \| congestive atelectasis [JB0D.1] Shock during or following labour or delivery Definition: A syndrome characterised by systemic cellular hypoxia and organ dysfunction as a result of hypoperfusion following labour and delivery. This syndrome is caused by haemorrhage, vomiting, diarrhoea, inadequate fluid intake, or a systemic inflammatory response to bacteria, endotoxins, or exotoxins. Also known as: Shock during or following labour or delivery \| Obstetric shock \| circulatory collapse, during or after labour \| shock during or after labour \| Shock following labour and delivery Includes: Obstetric shock === GRAPH WALKS === --- Walk 1 --- [MG44.1Z] Lack of expected normal physiological development, unspecified --PARENT--> [MG44.1] Lack of expected normal physiological development Def: Lack of expected normal physiological development includes delayed milestone of development and other lack of expected normal physiological development including gross and fine motor development, lang... --CHILD--> [MG44.12] Short stature of child Def: Short stature is when a child is significantly shorter than children of the same age and gender... --- Walk 2 --- [MG44.1Z] Lack of expected normal physiological development, unspecified --PARENT--> [MG44.1] Lack of expected normal physiological development Def: Lack of expected normal physiological development includes delayed milestone of development and other lack of expected normal physiological development including gross and fine motor development, lang... --EXCLUDES--> [?] Disorders of intellectual development Def: Disorders of intellectual development are a group of etiologically diverse conditions originating during the developmental period characterised by significantly below average intellectual functioning ... --- Walk 3 --- [MG44.1Y] Other specified lack of expected normal physiological development --PARENT--> [MG44.1] Lack of expected normal physiological development Def: Lack of expected normal physiological development includes delayed milestone of development and other lack of expected normal physiological development including gross and fine motor development, lang... --EXCLUDES--> [?] Delayed puberty Def: This is when an organism has passed the usual age of onset of puberty with no physical or hormonal signs that it is beginning. Puberty may be delayed for several years and still occur normally, in whi... --- Walk 4 --- [MG44.1Y] Other specified lack of expected normal physiological development --PARENT--> [MG44.1] Lack of expected normal physiological development Def: Lack of expected normal physiological development includes delayed milestone of development and other lack of expected normal physiological development including gross and fine motor development, lang... --CHILD--> [MG44.12] Short stature of child Def: Short stature is when a child is significantly shorter than children of the same age and gender... --- Walk 5 --- [MG44.10] Delayed milestone --PARENT--> [MG44.1] Lack of expected normal physiological development Def: Lack of expected normal physiological development includes delayed milestone of development and other lack of expected normal physiological development including gross and fine motor development, lang... --EXCLUDES--> [?] Delayed puberty Def: This is when an organism has passed the usual age of onset of puberty with no physical or hormonal signs that it is beginning. Puberty may be delayed for several years and still occur normally, in whi... --- Walk 6 --- [MG44.10] Delayed milestone --PARENT--> [MG44.1] Lack of expected normal physiological development Def: Lack of expected normal physiological development includes delayed milestone of development and other lack of expected normal physiological development including gross and fine motor development, lang... --CHILD--> [MG44.11] Failure to thrive in infant or child Def: When an infant or child's current weight or rate of weight gain is significantly below that of other children of similar age and gender....	[ "[MG44.1Z] Lack of expected normal physiological development, unspecified\n --PARENT--> [MG44.1] Lack of expected normal physiological development\n Def: Lack of expected normal physiological development includes delayed milestone of development and other lack of expected normal physiological development including gross and fine motor development, lang...\n --CHILD--> [MG44.12] Short stature of child\n Def: Short stature is when a child is significantly shorter than children of the same age and gender...", "[MG44.1Z] Lack of expected normal physiological development, unspecified\n --PARENT--> [MG44.1] Lack of expected normal physiological development\n Def: Lack of expected normal physiological development includes delayed milestone of development and other lack of expected normal physiological development including gross and fine motor development, lang...\n --EXCLUDES--> [?] Disorders of intellectual development\n Def: Disorders of intellectual development are a group of etiologically diverse conditions originating during the developmental period characterised by significantly below average intellectual functioning ...", "[MG44.1Y] Other specified lack of expected normal physiological development\n --PARENT--> [MG44.1] Lack of expected normal physiological development\n Def: Lack of expected normal physiological development includes delayed milestone of development and other lack of expected normal physiological development including gross and fine motor development, lang...\n --EXCLUDES--> [?] Delayed puberty\n Def: This is when an organism has passed the usual age of onset of puberty with no physical or hormonal signs that it is beginning. Puberty may be delayed for several years and still occur normally, in whi...", "[MG44.1Y] Other specified lack of expected normal physiological development\n --PARENT--> [MG44.1] Lack of expected normal physiological development\n Def: Lack of expected normal physiological development includes delayed milestone of development and other lack of expected normal physiological development including gross and fine motor development, lang...\n --CHILD--> [MG44.12] Short stature of child\n Def: Short stature is when a child is significantly shorter than children of the same age and gender...", "[MG44.10] Delayed milestone\n --PARENT--> [MG44.1] Lack of expected normal physiological development\n Def: Lack of expected normal physiological development includes delayed milestone of development and other lack of expected normal physiological development including gross and fine motor development, lang...\n --EXCLUDES--> [?] Delayed puberty\n Def: This is when an organism has passed the usual age of onset of puberty with no physical or hormonal signs that it is beginning. Puberty may be delayed for several years and still occur normally, in whi...", "[MG44.10] Delayed milestone\n --PARENT--> [MG44.1] Lack of expected normal physiological development\n Def: Lack of expected normal physiological development includes delayed milestone of development and other lack of expected normal physiological development including gross and fine motor development, lang...\n --CHILD--> [MG44.11] Failure to thrive in infant or child\n Def: When an infant or child's current weight or rate of weight gain is significantly below that of other children of similar age and gender...." ]	MG44.1Z	Lack of expected normal physiological development, unspecified	[ { "from_icd11": "MG44.1Z", "icd10_code": "R6250", "icd10_title": "Unspecified lack of expected normal physiological development in childhood" }, { "from_icd11": "MG44.1Z", "icd10_code": "R6259", "icd10_title": "Other lack of expected normal physiological development in childhood" }, { "from_icd11": "MG44.1Z", "icd10_code": "R6251", "icd10_title": "Failure to thrive (child)" }, { "from_icd11": "MG44.1Z", "icd10_code": "R6252", "icd10_title": "Short stature (child)" }, { "from_icd11": "MG44.1Z", "icd10_code": "R62", "icd10_title": "Lack of expected normal physiological development in childhood and adults" }, { "from_icd11": "MG44.1Z", "icd10_code": "R628", "icd10_title": "" }, { "from_icd11": "MG44.1Z", "icd10_code": "R629", "icd10_title": "" }, { "from_icd11": "MG44.10", "icd10_code": "R620", "icd10_title": "Delayed milestone in childhood" }, { "from_icd11": "MG40.Z", "icd10_code": "T8111XA", "icd10_title": "Postprocedural cardiogenic shock, initial encounter" }, { "from_icd11": "MG40.Z", "icd10_code": "T8112XA", "icd10_title": "Postprocedural septic shock, initial encounter" }, { "from_icd11": "MG40.Z", "icd10_code": "T882XXA", "icd10_title": "Shock due to anesthesia, initial encounter" }, { "from_icd11": "MG40.Z", "icd10_code": "T8110XA", "icd10_title": "Postprocedural shock unspecified, initial encounter" }, { "from_icd11": "MG40.Z", "icd10_code": "R579", "icd10_title": "Shock, unspecified" }, { "from_icd11": "MG40.Z", "icd10_code": "R578", "icd10_title": "Other shock" }, { "from_icd11": "MG40.Z", "icd10_code": "R57", "icd10_title": "Shock, not elsewhere classified" } ]	R6250	Unspecified lack of expected normal physiological development in childhood
Yee et al. reported a 75-year-old man who presented with haematuria. He had rectal examination which had revealed a mass in the prostate. He had a history of having been diagnosed 8 years earlier with a stage T2b adenocarcinoma of the prostate gland which was treated by means of external beam radiotherapy and brachytherapy. Both his treatments had failed in that his serum prostate specific antigen (PSA) had been increasing. Four years subsequently he had undergone cryosurgical ablation for a poorly differentiated Gleason 4 + 5 = 9, adenocarcinoma of the prostate gland which was clinically staged as T2b. He had isotope bone scan and CT scan of abdomen and pelvis which showed absence of metastasis. His serum PSA prior to his cryosurgical ablation treatment was 11.4 μ g/L and his prostate volume was 26 cc and his rectal examination had revealed a small irregular prostate with induration over both lobes of the prostate. Pursuant to his cryotherapy his serum PSA had decreased to 0.2. After the cryotherapy his serum PSA had increased to 1.5 after one year and 2.7 after two years and he was found to have a questionable induration at the base of the prostate. He had a CT scan which had shown a 2.3 cm mass anterior to the rectum behind the seminal vesicles. He was commenced on hormonal therapy and he received bicalutamide 50 mg orally daily and 30 mg leuprolide depot injections every 4 months and after 8 months his serum PSA had dropped to 0.1. Rectal examination then had revealed a small benign feeling prostate gland. The serum PSA had remained at 0.1 whilst he remained on hormonal therapy, but 2 years later he developed visible haematuria at which time his serum PSA had remained at 0.1 and his rectal examination had shown his prostate gland to be indurated and of about 30 grams. He underwent cystoscopy which had revealed an enlarged necrotic and bleeding median lobe of his prostate gland. He had CT scan which had shown an increase in the size of the prostatic neoplasm which had invaded the rectum, but it had not invaded the pelvic side wall and there was no lymph adenopathy. He had prostate biopsies and histological examination of the specimens showed infiltrative, interlacing fascicles of spindle cells which had eosinophilic cytoplasm and had exhibited high cellularity, marked nuclear atypia, and many atypical mitotic figures which were suggestive of sarcoma of the prostate gland. Immunohistochemical staining of the specimen revealed negative staining for PAS, PCA3, CK A1/A3, CK 903, PSA, and hormone receptor ER/PR which had ruled out any residual adenocarcinoma of the prostate gland. Immunohistochemichal stains for leiomyosarcoma were positive in that desmin and smooth muscle actin were weakly positive, and vimentin was strongly positive. He underwent radical cystoprostatectomy and bilateral pelvic lymph adenectomy, resection of sigmoid colon, and rectum, colostomy, and ileal conduit construction. Histopathological examination of the specimen had revealed features consistent with high-grade leiomyosarcoma of the prostate gland. Pathological examination had shown that the tumour had replaced the prostate gland completely and had extended into the periprostatic fat and the urinary bladder. There was evidence of perineural invasion but no evidence of angiolymphatic involvement. The tumour had also extended and involved the full thickness of the rectum. The tumour additionally had involved the posterior margin of the prostate gland and the deep margin of the rectum; therefore additional deep margins were excised which were free of the designated ink margin. The apex of the prostate was also positive for tumour. Pathological examination of the resected rectum had shown infiltration by high-grade leiomyosarcoma which had involved the full thickness of the bowel wall and numerous ulcerations of the bowel mucosa. There was no tumour in the sigmoid colon and the pelvic lymph nodes. Immunohistochemical staining was positive for desmin and smooth muscle actin which supported a diagnosis of leiomyosarcoma. With regard to the differential diagnosis of mesenchymal neoplasms and sarcomatoid carcinoma, these were ruled out by means of immunohistochemical staining which were negative for myogenin, S100, CD34, high molecular weight cytokeratin, and pancytokeratin. His tumour continued to progress and three months later there was evidence of a nodule in the middle lobe of the right lung and a lesion in the area of the prostatic bed as well as rectal stump which was adjudged to represent tumour recurrence and in view of this he received chemotherapy. Several months later he had CT scan which had shown that the tumour near the prostatic bed had increased in size and extended to involve the perineum and abdominal wall and this had resulted in a cutaneous fistula. It had also shown many new pulmonary metastases. Twenty-five months after the surgical operation and chemotherapy he had remained alive with adjudged poor prognosis. Yee et al. stated the following: Leiomyosarcoma of the prostate gland is associated with poor prognosis in view of the aggressive biological behaviour of the tumour, lack of early symptoms, and late presentation; the rate of survival varies between 0% and 60% and the survival rates vary from months to years. Miedler and MacLennan had stated that 50% to 75% of patients die as a sequel of leiomyosarcoma of the prostate gland after 2.5 years. Mondaini et al. had recommended surgical treatment in the form of cystoprostatectomy followed by chemotherapy or radiotherapy for leiomyosarcoma of the prostate gland. Surgical operation may give symptomatic relief and may be an option of palliation for patients rather than cure in view of the fact that development of local recurrence and metastasis tends to be common. There is no treatment option that has been regarded as optimum; nevertheless, Mansouri et al. had iterated that radical surgery with complete resection of tumour is the therapeutic option which offers the chance of prolonged survival when the tumour has low mitotic activity. Dotan et al. had shown that complete surgical resection of tumour can lead to decreased local recurrence and decreased metastasis which prolongs survival. Nevertheless, leiomyosarcomas of the prostate are often diagnosed late in the process of the disease; in view of this the size of the tumour at the time of resection tends to be extensive. Sexton et al. did not find any association between survival and negative surgical margins, the tumour size, or stage of the tumour. With regard to adjuvant treatment, Sexton et al. and Janet et al. had shown that survival advantage may exist for a combined multimodality therapeutic strategies to improve the outcome of leiomyosarcoma of the prostate gland. However, studies had revealed that uncommon carcinomas which develop pursuant to radiotherapy tend to be aggressive tumours which manifest with metastatic deposits, for which the prognosis tends to be poor irrespective of treatment. In view of the fact that sarcomas tend to be associated with a high recurrence rate, it had been recommended that patients with leiomyosarcoma of the prostate gland should be monitored closely with imaging of the chest, abdomen, and pelvis. The reported sites of metastasis in leiomyosarcoma of the prostate gland in order of frequency include the lung, bone, lymph nodes, and brain . The exact aetiology of leiomyosarcoma of the prostate gland has not been ascertained and there has been an ongoing debate regarding whether radiotherapy to the prostate gland can induce a secondary cancer. Moreira et al. had postulated a causal effect of leiomyosarcoma of prostate pursuant to brachytherapy to the prostate gland. Moreira et al. had discussed the complications of brachytherapy, in which 3 patients had developed carcinoma of the prostate gland after they had received brachytherapy. One of the patients had subsequently developed recurrence of adenocarcinoma of the prostate gland, another patient had developed subsequently neuroendocrine tumour of the rectum, and the third patient had subsequently developed leiomyosarcoma of the prostate gland. McKenzie et al. had reported three cases of postradiotherapy sarcoma which had developed in the pelvis, 8 years, 15 years, and 16 years, ensuing localized adenocarcinoma of the prostate gland. Mazzucchelli et al. had undertaken a study on histological variants of carcinoma of the prostate gland and reported that half of the sarcomatous components (SC) and carcinosarcomas of the prostate gland had developed following hormonal treatment or radiotherapy treatment ensuing an initial diagnosis of acinar adenocarcinoma of the prostate gland. Nevertheless, Mazzucchelli et al. stated that sarcomatous component of carcinosarcoma status of the prostate gland after radiotherapy is not necessarily the only cause of malignancy and that de novo carcinosarcoma of the prostate gland can also develop. Prevost et al. had also reported a case of postradiotherapy sarcoma which did develop 8 years after the patient had received extended beam radiotherapy for adenocarcinoma of the prostate gland. Talapatra et al. reported a 67-year-old man who had presented with a history of recurrent episodes of haematuria and poor urinary stream. He had previously been diagnosed as having had a benign prostatic hypertrophy for which he had undergone transurethral resection of prostate (TURP) tumour elsewhere two years earlier. The histology slides had not been available for review. He had rectal examination which revealed an enlarged, hard prostate gland with obliteration of the median sulcus and the right lobe of the prostate gland was noted to be enlarged and abutting the rectum but not fixed to it. The examination also revealed a mass which had infiltrated the periprostatic tissue and extended to the pelvic side wall. His serum PSA level at presentation was normal. He had ultrasound scan of abdomen and pelvis which revealed a hypoechoic heterogeneous mass within the prostate gland and infiltrating the base of the urinary bladder and invading the lumen of the urinary bladder. The urinary bladder was noted to have a thick wall and it also contained blood clots. He had magnetic resonance imaging (MRI) scan of the pelvis which had revealed a 7.5 cm × 4.3 cm tumour mass in the right lobe of the prostate and which had distorted the capsule and had extended into the periprostatic fat, neurovascular bundle, and the base of the urinary bladder. He underwent cystoscopy which revealed a large fleshy growth in his prostatic urethra and within the lumen of the urinary bladder in association with blood clot in the urinary bladder. The right lobe of the prostate was enlarged especially at the apex. He had biopsy of the tumour mass and histological examination of the specimen had revealed spindle cell sarcoma which had destroyed the prostate gland with only the occasional benign prostatic gland entrapped within the tumour. With regard to the details of the microscopic features of the tumour, the tumour was laid out in intergrating fascicles. The spindle-shaped cells had elongated blunt ended cigar-shaped hyperchromatic nuclei and eosinophilic fibrillary cytoplasm which had the characteristics of leiomyosarcoma. Other characteristics of the tumour which confirmed the diagnosis include nuclear pleomorphism, raised mitotic activity, and areas of necrosis. He had metastatic work-up which showed no evidence of metastatic disease. He was adjudged to be unsuitable for curative surgery in view of the extent of the disease and the associated expected morbidity. He was treated by means of adjuvant chemotherapy which included ifosfamide and this was followed by external beam radiotherapy. Upon completion of the chemotherapy and radiotherapy treatments the patient's symptoms had resolved. At his six-month follow-up, he was asymptomatic in that he did not have any haematuria and his lower urinary tract symptoms had resolved. He had a CT scan which showed significant reduction in the size of the prostatic mass and minimal periprostatic stranding as well as normal looking urinary bladder. His serum PSA was normal. Talapatra et al. stated the following: Limon et al. had studied the cytogenetic analysis of primary leiomyosarcoma of the prostate and reported that their study had revealed clonal chromosomal rearrangement involving Chromosomes 2, 3, 9, 11, and 19; Cambronero et al. reported a case of leiomyosarcoma of prostate which presented as an exophytic tumour mass in the rectum as a rare presentation of leiomyosarcoma of the prostate gland; Cuesta Alcaca et al. reported leiomyosarcoma of the prostate gland which was detected in a patient who underwent TURP for lower urinary tract symptoms diagnosed as benign prostatic hypertrophy, but histological examination of the specimen had revealed leiomyosarcoma of the prostate gland; Chen et al. had stated that rectal examination in leiomyosarcoma of the prostate gland generally tends to reveal a prostatic mass; however, biopsy of the prostatic mass is required for histological examination to confirm the diagnosis; Ahlering et al. reported 11 patients who had leiomyosarcoma; of these 11 patients, 7 had leiomyosarcoma of the urinary bladder, and 4 patients had leiomyosarcoma of the prostate gland. They reported that the patients who did not have bulky tumours underwent surgical resection and they were observed as to if their operative surgical margins and lymph nodes were negative for tumour. The patients who were found to have surgical margins or lymph node positive for tumour received adjuvant external beam radiotherapy and chemotherapy. With regard to the patients who had bulky tumours, they received preoperative chemotherapy with or without radiotherapy which was followed by exenteration. With regard to the outcome, Ahlering et al. reported that, out of the 11 patients, 9 patients did not have any evidence of disease after a mean follow-up of 61 months and the follow-up had ranged between 35 months and 96 months; Camuzzi et al. had reported a patient with leiomyosarcoma of the prostate gland who was successfully treated by means of transperineal radon seed implantation and external beam radiotherapy; Kuroda et al. had reported a case of leiomyosarcoma of the prostate gland which was accompanied by multiple hepatocellular carcinomas who had received combination chemotherapy that consisted of cyclophosphamide, vincristine, Adriamycin, and DTIC (CYDAVIC). He died one year and two months after his initial diagnosis as a result of liver failure. During postmortem examination it was revealed that the histology of the liver tumours was hepatocellular carcinoma and even though the leiomyosarcoma of the prostate gland had invaded the wall of the urinary bladder and the rectum, there was no obvious distant metastasis from the leiomyosarcoma of the prostate gland; Tazi et al. stated the following: a number of treatment modalities had been adopted including radical surgery, radiotherapy, and chemotherapy for the treatment of primary leiomyosarcoma of the prostate gland, but in their opinion a successful outcome had not been achieved in any instance. Leiomyosarcoma of the prostate gland has a poor prognosis, even though the survival time is variable. In view of the aforementioned reasons, it is very important that leiomyosarcoma of the prostate gland is correctly identified and that occurrence of each case of the disease, type of treatment given, and response to treatment should be reported in order to enable the understanding of the natural history of the disease.	4.140625	0.962891	sec[2]/p[31]	en	0.999997	26640482	https://doi.org/10.1155/2015/485786	[ "prostate", "gland", "which", "leiomyosarcoma", "tumour", "that", "radiotherapy", "urinary", "patients", "rectum" ]	[ { "code": "GA90", "title": "Hyperplasia of prostate" }, { "code": "GA91.Z", "title": "Inflammatory or other diseases of prostate, unspecified" }, { "code": "GA91.Y", "title": "Other specified inflammatory or other diseases of prostate" }, { "code": "GA91.0", "title": "Chronic prostatitis" }, { "code": "MF40.1", "title": "Problems of the prostate" }, { "code": "BD90.Z", "title": "Lymphadenitis, unspecified" }, { "code": "BD90.Y", "title": "Other specified lymphadenitis" }, { "code": "MA01.Z", "title": "Enlarged lymph nodes, unspecified" }, { "code": "5B3Z", "title": "Endocrine diseases, unspecified" }, { "code": "9A10.Z", "title": "Disorders of lacrimal gland, unspecified" } ]	=== ICD-11 CODES FOUND === [GA90] Hyperplasia of prostate Definition: A condition of the prostate, caused by an increased rate of cellular division of the glandular and stromal cells. This condition is characterised by enlargement of the prostatic tissue, dysuria, urinary urgency, nocturia, weak urine stream, straining while urinating, incomplete bladder emptying during urination, or increased frequency of urinary tract infection. Also known as: Hyperplasia of prostate \| Adenofibromatous hypertrophy of prostate \| benign prostatic hyperplasia \| prostate hyperplasia \| prostatic area hypertrophy Includes: Adenofibromatous hypertrophy of prostate Excludes: Benign neoplasms of prostate [GA91.Z] Inflammatory or other diseases of prostate, unspecified Also known as: Inflammatory or other diseases of prostate, unspecified \| Inflammatory or other diseases of prostate \| inflammation of prostate NOS \| prostatitis NOS \| disease of prostate NOS [GA91.Y] Other specified inflammatory or other diseases of prostate Also known as: Other specified inflammatory or other diseases of prostate \| Acute bacterial prostatitis \| acute prostatitis \| Prostatitis category I (NIH classification) \| Prostatitis category I [GA91.0] Chronic prostatitis Definition: A condition caused by obstruction of the prostate glands. This condition is characterised by inflammation of the prostate gland, dysuria, pollakiuria, urinary urgency, genital pain, lower back pain, abdominal pain, and repeated bladder infections that last for at least three months. Also known as: Chronic prostatitis \| Fibrous prostatitis \| Hypertrophic prostatitis \| Subacute prostatitis \| Chronic bacterial prostatitis [MF40.1] Problems of the prostate Definition: A group of disorders associated with the prostate occurring in diseases more specifically classified elsewhere. Also known as: Problems of the prostate [BD90.Z] Lymphadenitis, unspecified Also known as: Lymphadenitis, unspecified \| Lymphadenitis \| adenitis NOS \| inflammation of gland \| lymphatic gland inflammation [BD90.Y] Other specified lymphadenitis Also known as: Other specified lymphadenitis \| Dermatopathic lymphadenopathy \| lipomelanotic reticulosis \| Infective inguinal bubo \| bubo [MA01.Z] Enlarged lymph nodes, unspecified Also known as: Enlarged lymph nodes, unspecified \| Enlarged lymph nodes \| swollen glands \| Lymphadenopathy \| adenopathy [5B3Z] Endocrine diseases, unspecified Also known as: Endocrine diseases, unspecified \| endocrine disorder NOS \| disorder of endocrine gland \| disease of endocrine gland \| disorder of endocrine system [9A10.Z] Disorders of lacrimal gland, unspecified Also known as: Disorders of lacrimal gland, unspecified \| Disorders of lacrimal gland === GRAPH WALKS === --- Walk 1 --- [GA90] Hyperplasia of prostate Def: A condition of the prostate, caused by an increased rate of cellular division of the glandular and stromal cells. This condition is characterised by enlargement of the prostatic tissue, dysuria, urina... --EXCLUDES--> [?] Benign neoplasm of male genital organs Def: A non-metastasizing neoplasm that arises from the male reproductive system. Representative examples include benign prostate phyllodes tumour, benign Sertoli cell tumour, seminal vesicle cystadenoma, a... --PARENT--> [?] Benign neoplasms except of mesenchymal origin --- Walk 2 --- [GA90] Hyperplasia of prostate Def: A condition of the prostate, caused by an increased rate of cellular division of the glandular and stromal cells. This condition is characterised by enlargement of the prostatic tissue, dysuria, urina... --PARENT--> [?] Diseases of prostate --CHILD--> [GA90] Hyperplasia of prostate Def: A condition of the prostate, caused by an increased rate of cellular division of the glandular and stromal cells. This condition is characterised by enlargement of the prostatic tissue, dysuria, urina... --- Walk 3 --- [GA91.Z] Inflammatory or other diseases of prostate, unspecified --PARENT--> [GA91] Inflammatory or other diseases of prostate Def: Any disease caused by obstruction of the prostate gland. These diseases are characterised by a build-up of secretions and inflammation of the prostate.... --CHILD--> [GA91.1] Abscess of prostate Def: A condition caused by infection with the gram-negative bacteria Neisseria gonorrhoeae and Escherichia coli, or the gram-positive bacteria Staphylococcus aureus or Mycobacterium tuberculosis. This cond... --- Walk 4 --- [GA91.Z] Inflammatory or other diseases of prostate, unspecified --PARENT--> [GA91] Inflammatory or other diseases of prostate Def: Any disease caused by obstruction of the prostate gland. These diseases are characterised by a build-up of secretions and inflammation of the prostate.... --RELATED_TO--> [?] Prostatitis due to Trichomonas vaginalis Def: This refers to an inflammation of the prostate gland caused by an infection with the protozoan parasite Trichomonas vaginalis.... --- Walk 5 --- [GA91.Y] Other specified inflammatory or other diseases of prostate --PARENT--> [GA91] Inflammatory or other diseases of prostate Def: Any disease caused by obstruction of the prostate gland. These diseases are characterised by a build-up of secretions and inflammation of the prostate.... --RELATED_TO--> [?] Prostatitis due to Trichomonas vaginalis Def: This refers to an inflammation of the prostate gland caused by an infection with the protozoan parasite Trichomonas vaginalis.... --- Walk 6 --- [GA91.Y] Other specified inflammatory or other diseases of prostate --PARENT--> [GA91] Inflammatory or other diseases of prostate Def: Any disease caused by obstruction of the prostate gland. These diseases are characterised by a build-up of secretions and inflammation of the prostate.... --RELATED_TO--> [?] Prostatitis due to Trichomonas vaginalis Def: This refers to an inflammation of the prostate gland caused by an infection with the protozoan parasite Trichomonas vaginalis....	[ "[GA90] Hyperplasia of prostate\n Def: A condition of the prostate, caused by an increased rate of cellular division of the glandular and stromal cells. This condition is characterised by enlargement of the prostatic tissue, dysuria, urina...\n --EXCLUDES--> [?] Benign neoplasm of male genital organs\n Def: A non-metastasizing neoplasm that arises from the male reproductive system. Representative examples include benign prostate phyllodes tumour, benign Sertoli cell tumour, seminal vesicle cystadenoma, a...\n --PARENT--> [?] Benign neoplasms except of mesenchymal origin", "[GA90] Hyperplasia of prostate\n Def: A condition of the prostate, caused by an increased rate of cellular division of the glandular and stromal cells. This condition is characterised by enlargement of the prostatic tissue, dysuria, urina...\n --PARENT--> [?] Diseases of prostate\n --CHILD--> [GA90] Hyperplasia of prostate\n Def: A condition of the prostate, caused by an increased rate of cellular division of the glandular and stromal cells. This condition is characterised by enlargement of the prostatic tissue, dysuria, urina...", "[GA91.Z] Inflammatory or other diseases of prostate, unspecified\n --PARENT--> [GA91] Inflammatory or other diseases of prostate\n Def: Any disease caused by obstruction of the prostate gland. These diseases are characterised by a build-up of secretions and inflammation of the prostate....\n --CHILD--> [GA91.1] Abscess of prostate\n Def: A condition caused by infection with the gram-negative bacteria Neisseria gonorrhoeae and Escherichia coli, or the gram-positive bacteria Staphylococcus aureus or Mycobacterium tuberculosis. This cond...", "[GA91.Z] Inflammatory or other diseases of prostate, unspecified\n --PARENT--> [GA91] Inflammatory or other diseases of prostate\n Def: Any disease caused by obstruction of the prostate gland. These diseases are characterised by a build-up of secretions and inflammation of the prostate....\n --RELATED_TO--> [?] Prostatitis due to Trichomonas vaginalis\n Def: This refers to an inflammation of the prostate gland caused by an infection with the protozoan parasite Trichomonas vaginalis....", "[GA91.Y] Other specified inflammatory or other diseases of prostate\n --PARENT--> [GA91] Inflammatory or other diseases of prostate\n Def: Any disease caused by obstruction of the prostate gland. These diseases are characterised by a build-up of secretions and inflammation of the prostate....\n --RELATED_TO--> [?] Prostatitis due to Trichomonas vaginalis\n Def: This refers to an inflammation of the prostate gland caused by an infection with the protozoan parasite Trichomonas vaginalis....", "[GA91.Y] Other specified inflammatory or other diseases of prostate\n --PARENT--> [GA91] Inflammatory or other diseases of prostate\n Def: Any disease caused by obstruction of the prostate gland. These diseases are characterised by a build-up of secretions and inflammation of the prostate....\n --RELATED_TO--> [?] Prostatitis due to Trichomonas vaginalis\n Def: This refers to an inflammation of the prostate gland caused by an infection with the protozoan parasite Trichomonas vaginalis...." ]	GA90	Hyperplasia of prostate	[ { "from_icd11": "GA90", "icd10_code": "N402", "icd10_title": "Nodular prostate without lower urinary tract symptoms" }, { "from_icd11": "GA90", "icd10_code": "N403", "icd10_title": "Nodular prostate with lower urinary tract symptoms" }, { "from_icd11": "GA90", "icd10_code": "N400", "icd10_title": "Benign prostatic hyperplasia without lower urinary tract symptoms" }, { "from_icd11": "GA90", "icd10_code": "N401", "icd10_title": "Benign prostatic hyperplasia with lower urinary tract symptoms" }, { "from_icd11": "GA90", "icd10_code": "N40", "icd10_title": "Benign prostatic hyperplasia" }, { "from_icd11": "GA91.Z", "icd10_code": "N414", "icd10_title": "Granulomatous prostatitis" }, { "from_icd11": "GA91.Z", "icd10_code": "N4289", "icd10_title": "Other specified disorders of prostate" }, { "from_icd11": "GA91.Z", "icd10_code": "N4283", "icd10_title": "Cyst of prostate" }, { "from_icd11": "GA91.Z", "icd10_code": "N410", "icd10_title": "Acute prostatitis" }, { "from_icd11": "GA91.Z", "icd10_code": "N419", "icd10_title": "Inflammatory disease of prostate, unspecified" }, { "from_icd11": "GA91.Z", "icd10_code": "N429", "icd10_title": "Disorder of prostate, unspecified" }, { "from_icd11": "GA91.Z", "icd10_code": "N418", "icd10_title": "Other inflammatory diseases of prostate" }, { "from_icd11": "GA91.Z", "icd10_code": "N41", "icd10_title": "Inflammatory diseases of prostate" }, { "from_icd11": "GA91.Z", "icd10_code": "N42", "icd10_title": "Other and unspecified disorders of prostate" }, { "from_icd11": "GA91.Z", "icd10_code": "N428", "icd10_title": "Other specified disorders of prostate" } ]	N402	Nodular prostate without lower urinary tract symptoms
We present the case of a 13 year-old with a scleroderma-like condition, ultimately diagnosed with Myhre syndrome, a genetic disorder that may mimic juvenile scleroderma (Supplemental Table 1 ). Securing a molecular diagnosis in this case allowed the cessation of immunosuppression thus reducing the burden of unnecessary toxic exposure to glucocorticoids, and other ineffective immunosuppressive treatments; and facilitated genetic counselling, and prognostication. This also had implications for long term follow up as patients with Myhre syndrome require close surveillance for detection of any malignancy in view of increased risk of cancer reported in these patients . We therefore highlight this case to raise awareness of a growing number of monogenic fibrotic disorders mimicking juvenile scleroderma which need to be considered in patients with cutaneous fibrosis beginning early in life (Table 1 ). Table 1 Monogenic disorders with a scleroderma-like phenotype. The clinical features have been summarised as described by the Online Mendelian Inheritance in Man (OMIM) and Genetics Home Reference databases Disease Inheritance Gene Clinical Features Hutchinson-Gilford Progeria AD, AR LMNA Skin: Sclerodermatous skin disease, loss of subcutaneous fat (lipodystrophy) Skeletal: Osteoporosis, joint restrictions, joint abnormalities Cardiovascular: Atherosclerosis Other: Prematurely aged appearance, postnatal onset growth retardation, hair loss (alopecia) Werner syndrome AR WRN Skin: Sclerodermatous skin disease, subcutaneous calcification, ulceration Skeletal: Osteoporosis Cardiovascular: Premature arteriosclerosis Endocrine: Diabetes mellitus, hypogonadism Other: Prematurely aged appearance, short stature, alopecia, juvenile cataracts Rothmund Thomson syndrome AR RECQL4 Skin: Erythematous thickened skin lesions in infancy, poikiloderma (atrophic plaques with telangiectasia), telangiectasia, atrophy, sun sensitivity Skeletal: Osteoporosis Central Nervous System: Mental retardation (rare) Endocrine: Hypogonadism Other: Prematurely aged appearance, short stature, alopecia, premature greying of hair, increased risk of malignant disease Mandibular hypoplasia, deafness, progeroid features and lipodystrophy syndrome AD POLD1 Skin: Sclerodermatous skin disease, telangiectasias, atrophy, lipodystrophy Skeletal: Osteoporosis, joint contractures Endocrine: Insulin resistance, diabetes mellitus Other: Prematurely aged appearance, mandibular hypoplasia, sensorineural deafness, hepatomegaly, hepatic steatosis Nestor-Guillermo Progeria Syndrome AR BANF1 Skin: Sclerodermatous skin disease (patchy) and hyperpigmentation Skeletal: Joint stiffness, joint contractures, osteoporosis, osteolysis Cardiovascular: Sinus tachycardia, prominent subcutaneous venous patterning, pulmonary hypertension Other: Prematurely aged appearance, short stature, lipoatrophy Keppen-Lubinsky syndrome AD KCNJ6 Skin: Lipodystrophy, wrinkled appearance Skeletal: Joint contractures Central Nervous System: Severe mental retardation, delayed psychomotor development, hypertonia, hyperreflexia Other: Prematurely aged appearance, generalised lipodystrophy Fontaine Progeroid Syndrome AD SLC25A24 Skin: Wrinkled skin, lipodystrophy, sclerodermatous skin disease Skeletal: Low bone density, delayed bone age Cardiovascular: Pulmonary artery hypertension, aortic ectasia Other: Prematurely aged appearance, short stature, intrauterine growth retardation Cockayne Syndrome, Type A AR ERCC8 Skin: Cutaneous photosensitivity, scarred, pigmented, atrophy, reduced subcutaneous adipose tissue, sclerodermatous skin disease Skeletal: Flexion contractures, mild-to-moderate joint limitations Cardiovascular: Hypertension Neurological: Impaired or delayed neural development, mental retardation Other: Prematurely aged appearance, cachectic dwarfism, intrauterine growth retardation, sensorineural hearing loss, vision complications, tooth decay, hepatomegaly, splenomegaly, decreased subcutaneous adipose tissue Ataxia-telangiectasia AR ATM Skin: Sclerodermatous skin disease, progeric skin changes, cutaneous telangiectasia, cafe-au-lait spots Respiratory: Bronchitis, bronchiectasis Neurological: Cerebellar ataxia, cerebellar cortical degeneration, oculomotor abnormalities, seizures, choreoathetosis, dystonia, reduced/absent deep tendon reflexes Other: Short stature Myhre syndrome AD SMAD4 Skin: Sclerodermatous skin disease Skeletal: Skeletal abnormalities, joint restrictions Cardiovascular: Hypertension, congenital heart defects, aortic stenosis, aortic coarctation, pericardial fibrosis Respiratory: Laryngotracheal stenosis, respiratory failure Neurological: Mental retardation, delayed language and motor skill development, behavioural issues (autistic-like) Other: Dysmorphic facial features, short stature, hearing loss, generalised muscle hypertrophy Stiff skin syndrome AD FBN1 Skin: Sclerodermatous skin disease (diffuse), lipodystrophy Skeletal: Joint restrictions, flexion contractures Other: Muscle weakness Pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus (PHID) AR SLC29A3 Skin: Hyperpigmented and hypertrichotic skin lesions on lower body, sclerodermatous skin disease Skeletal: Joint contractures (elbows, fingers and toes) Abdomen: Hepatomegaly, diabetes mellitus (insulin-dependent), splenomegaly Other: Short stature, hearing loss Reynolds syndrome AD LBR Skin: Sclerodermatous skin disease (tightened and shiny skin over the forearms and hands), sclerodactyly, calcinosis cutis, generalized darkening Other: Raynaud phenomenon, hepatomegaly, primary biliary cirrhosis, splenomegaly, esophageal dysfunction Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome /Nakajo-Nishimura Syndrome AR PSMB8 Skin: Erythematous nodular skin lesions and plaques on the face and extremities, dry, stiff, lipodystrophy Skeletal: Joint contractures (elbow, fingers/hands, toes, feet), joint pain Muscle: Lipodystrophy, muscle weakness Other: Poor growth, hepatomegaly, splenomegaly Mucolipidosis III gamma AR GNPTG Skin: Sclerodermatous skin disease Skeletal: Joint restrictions, joint stiffness, joint pain Cardiovascular: Aortic valve thickening, aortic stenosis Neurological: Mental retardation Other: Short stature Hurler-Scheie syndrome / Mucopolysaccharidosis Ih/s AR IDUA Skin: Sclerodermatous skin disease Skeletal: Joint stiffness, dysostosis multiplex Cardiovascular: Thickened mitral valve leaflets, aortic valve thickening, dilated left atrium, dilated left ventricle, mild pulmonary hypertension Respiratory: Frequent respiratory infections, nasopharyngeal obstruction, tracheal stenosis Abdomen: Umbilical hernia, hepatomegaly, splenomegaly Neurological: Pachymeningitis cervicalis Other: Short stature, corneal clouding Zimmermann-Laband Syndrome 1 AD KCNH1 Skin: Dry, sclerodermatous skin disease Skeletal: Scoliosis, hypoplastic distal phalanges (hands and feet), hyperextensible joints Abdomen: Hepatosplenomegaly, splenomegaly, umbilical hernia Cardiovascular: Cardiomyopathy, patent ductus arteriosus, aortic root dilatation, aortic arch dilatation Muscle: Poor muscle bulk Neurological: Hypotonia, seizures, mental retardation Other: Gingival fibromatosis, dysplastic or absent nails, hirsutism, abnormalities of the cartilage of the nose and/or ears Buschke-Ollendorff syndrome AD LEMD3 Skin: Subcutaneous nontender firm nodules, subcutaneous connective tissue nevi, elastin-rich connective tissue nevi (elastoma), collagen-rich connective tissue nevi (dermatofibrosis lenticularis disseminata) Skeletal: Osteopoikilosis, joint stiffness, osteosclerosis, melorheostosis Growth Retardation, Alopecia, Pseudoanodontia and Optic Atrophy (GAPO) Syndrome AR ANTXR1 Skin: Sclerodermatous skin disease, redundant, prominent scalp veins, epidermal inclusion cyst Skeletal: Delayed bone age Other: Growth retardation, alopecia, pseudoanodontia, umbilical hernia, hepatomegaly Crouzon Syndrome with acanthosis nigricans AD FGFR3 Skin: Hyperpigmentation, acanthosis nigricans, melanocytic nevi, hypertrophy, sclerodermatous skin disease, redundant skin folds Skeletal: Craniosynostosis Frontometaphyseal dysplasia 2 AD MAP 3 K7 Skin: Keloid formation, sclerodermatous skin disease Skeletal: Skeletal abnormalities, joint contractures Cardiovascular: Patent ductus arteriosus, bicuspid aortic valve, aortic root dilation, pulmonary valve stenosis Respiratory: Congenital stridor, subglottic stenosis, tracheal stenosis Premature aging syndrome, Penttinen type AD PDGFRB Skin: Progressive cutaneous atrophy, thin translucent skin with prominent venous patterning, hypertrophic keloid-like lesions, skin retraction, sclerodermatous skin disease, lipoatrophy Skeletal: Delayed bone maturation, osteopenia, joint contractures Farber Lipogranulomatosis AR ASAH1 Skin: Early-onset subcutaneous nodules, lipogranulomatosis Skeletal: Painful and progressively deformed joints, arthritis Respiratory: Laryngeal nodules Abdomen: Hepatomegaly, splenomegaly Neurological: Irritability, motor retardation, mental retardation Other: Hoarseness by laryngeal involvement Amyloidosis, Primary Localised cutaneous, 3 (PLCA3) AR GPNMB Skin: Amyloid disposition in the skin, hyper- and hypo-pigmented macules, mild pruritis, dry skin Carney Complex, Type 1 AD PRKAR1A Skin: Cutaneous tumors, profuse pigmented skin lesions, nevi Cardiovascular: Tumors (atrial), ventricular myxoma, congestive heart failure Endocrine: Tumors, pigmented micronodular adrenal dysplasia, Cushing disease, acromegaly, thyroid follicular hyperplasia Other: Neoplasia, myxoid subcutaneous tumors, primary adrenocortical nodular hyperplasia, testicular Sertoli cell tumor (calcified), pituitary adenoma, mammary ductal fibroadenoma, schwannoma, psammomatous melanotic schwannomas, thyroid carcinoma, pheochromocytoma Porphyria cutanea tarda, Porphyria, hepatoerythropoietic AD, AR UROD Skin: Sclerodermatous skin disease (diffuse), increased mechanical skin fragility after sunlight exposure (photosensitivity), vesicles, bullae and blisters on exposed areas of skin, hyperpigmentation on sun-exposed skin Abdomen: Hepatic hemosiderosis, hepatic cirrhosis, liver biopsy shows red autofluorescence and needle-like cytoplasmic inclusion bodies Other: Neoplasia, increased incidence of hepatocellular carcinoma Phenylketonuria, non-PKU mild Hyperphenylalaninemia AR PAH Skin: Sclerodermatous skin disease, pale pigmentation, dry, eczema Neurological: Seizures, delayed development, mental retardation, behavioural problems and psychiatric disorders Other: Head, microcephaly, cataracts Porphyria, congenital erythropoietic AR UROS Skin: Sclerodermatous skin disease, photosensitivity, blistering and scarring, hyperpigmentation, hypopigmentation Skeletal: Osteolysis, osteopenia, finger contractures Other: Short stature, conjunctivitis, corneal scarring, hypertrichosis, alopecia, porphyrin-rich gallstones, splenomegaly Multicentric osteolysis, nodulosis and arthropathy (MONA) AR MMP2 Skin: Subcutaneous nodules (interphalangeal joints, knees, feet, elbows, pretibial), hyperpigmented erythematous lesions Skeletal: Osteoporosis, flexion contractures Winchester syndrome AR MMP14 Skin: Sclerodermatous skin disease (patchy, dark, leathery) Skeletal: Osteopenia, osteoporosis, arthropathy, joint restrictions Cardiovascular: Heart abnormalities Other: Corneal opacity, hypertrichosis, overgrowth of the gums, coarse facial features Multisystemic fibrosis-like hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP) AD FAM111B Skin: Congenital poikiloderma (face and exposed skin), telangiectatic lesions, eczema-like lesions, epidermal atrophy Respiratory: Interstitial pulmonary fibrosis Muscle: Tendon contractures, muscle weakness, myopathy Other: Congenital poikiloderma on face Weill-Marchesani syndrome 1 AR ADAMTS10 Skin : Sclerodermatous skin disease Skeletal: Joint stiffness, joint restrictions Cardiovascular: Heart defects, aortic valve stenosis, pulmonary valve stenosis, ductus arteriosus, ventricular septal defect Neurological: Mild mental retardation Other: Short stature, brachydactyly, eye anomalies Weill-Marchesani syndrome 4 (WMS-like syndrome) AR ADAMTS17 Skin: Sclerodermatous skin disease Skeletal: Joint stiffness Cardiovascular: Cardiac defects (uncommon) Other: Short stature, severe myopia, acute and/or chronic glaucoma, cataract Frank-Ter Haar Syndrome AR SH3PXD2B Skin: Sclerodermatous skin disease (face), acne conglobata Skeletal: Osteolysis, osteopenia, osteoporosis, shortened bowed long bones, flexion deformities of fingers Other: Growth retardation, glaucoma, brachycephaly, wide fontanels, prominent forehead, hypertelorism, prominent eyes, malocclusion Geleophysic dysplasia 3 AD LTBP3 Skin: Sclerodermatous skin disease Skeletal: Joint restrictions, delayed bone age Cardiovascular: Pulmonary hypertension Respiratory: Dyspnea, tracheal stenosis, respiratory failure Other: Short stature, marked brachydactyly, hepatomegaly Geleophysic dysplasia 1 AR ADAMTSL2 Skin: Sclerodermatous skin disease Skeletal: Osteopenia, shortened long tubular bones, short hands and feet, joint contractures, joint restrictions, delayed bone age Cardiovascular: Progressive cardiac valvular thickening, cardiac failure, mitral stenosis, tricuspid stenosis, aortic stenosis Respiratory: Tracheal stenosis, respiratory insufficiency Neurological: Developmental delay, seizures Other: Short stature, ‘happy’ appearance with full cheeks, shortened nose, wide mouth, hepatomegaly Mucolipidosis II Alpha/Beta AR GNPTAB Skin: Sclerodermatous skin disease, cavernous hemangioma Skeletal: Skeletal abnormalities, moderate joint restrictions, osteopenia Cardiovascular: Cardiomegaly, congestive heart failure, hypertrophic cardiomyopathy, cardiac murmur, aortic insufficiency Respiratory: Recurrent bronchitis, recurrent pneumonia Abdomen: Umbilical hernia, hepatomegaly Neurological: Developmental delay, severe psychomotor retardation Other: Progressive failure to thrive, Hurler-like body configuration, marked growth retardation, coarse facial features, abdominal protuberance, hoarse voice Hypertrophic Osteoarthropathy, Primary, Autosomal Recessive 1 / Cranioosteoarthropathy AR HPGD Skin: Sclerodermatous skin disease, pachydermia, furrowed, oily, seborrhea, redundant, palmoplantar hyperkeratosis, eczema Skeletal: Digital clubbing, osteoarthropathy, arthralgia, arthritis, swollen joints, decreased joint mobility, osteopenia, osteoporosis Cardiovascular: Congenital heart disease, patent ductus arteriosus Other: Marfanoid habitus, coarse facial features, furrowed forehead, ptosis, thickened eyelids, turtle-backed nails, digital clubbing AD Autosomal dominant, AR Autosomal recessive, SSc systemic sclerosis	4.273438	0.928223	sec[2]/p[0]	en	0.999997	32917212	https://doi.org/10.1186/s12969-020-00466-1	[ "skin", "skeletal", "sclerodermatous", "joint", "cardiovascular", "retardation", "short", "stature", "contractures", "stenosis" ]	[ { "code": "ME67", "title": "Skin disorder of uncertain or unspecified nature" }, { "code": "ME66.Y", "title": "Other specified skin changes" }, { "code": "EM0Y", "title": "Other specified diseases of the skin" }, { "code": "ME60.Z", "title": "Skin lesion of unspecified nature" }, { "code": "ME66.1", "title": "Changes in skin texture" }, { "code": "LB9Z", "title": "Structural developmental anomalies of the skeleton, unspecified" }, { "code": "FB80.1", "title": "Skeletal fluorosis" }, { "code": "FC0Z", "title": "Diseases of the musculoskeletal system or connective tissue, unspecified" }, { "code": "ND56.2", "title": "Fracture of unspecified body region" }, { "code": "LD2B", "title": "Syndromes with premature ageing appearance as a major feature" } ]	=== ICD-11 CODES FOUND === [ME67] Skin disorder of uncertain or unspecified nature Definition: A category to enable the presence of a skin disorder to be recorded without making assumptions as to the precise nature of the disorder in question. Also known as: Skin disorder of uncertain or unspecified nature \| Skin disorder without established diagnosis \| change of skin NOS \| dermatological disease NOS \| dermatological disorder NOS [ME66.Y] Other specified skin changes Also known as: Other specified skin changes \| Cutis marmorata \| Fear of skin disease \| Retention hyperkeratosis \| Dermatitis neglecta [EM0Y] Other specified diseases of the skin Also known as: Other specified diseases of the skin \| Adverse cutaneous effects of healthcare related interventions \| Cutaneous complications of surgical, laser or other interventional procedures \| Postprocedural cutaneous complications of surgical, laser or other interventions \| Cutaneous complications of surgical procedures [ME60.Z] Skin lesion of unspecified nature Also known as: Skin lesion of unspecified nature \| Skin lesion of uncertain or unspecified nature \| Skin lesion without established diagnosis \| Pigmented skin lesion of unspecified nature \| Ulcer of skin of unspecified nature [ME66.1] Changes in skin texture Definition: Alterations in skin texture of unspecified cause. Also known as: Changes in skin texture \| Skin textural disturbance \| Thickening of skin \| induration of skin \| Skin sclerosis [LB9Z] Structural developmental anomalies of the skeleton, unspecified Also known as: Structural developmental anomalies of the skeleton, unspecified \| Abnormal bone development \| skeletal anomaly NOS [FB80.1] Skeletal fluorosis Also known as: Skeletal fluorosis \| Skeletal fluorosis, multiple sites \| Skeletal fluorosis, shoulder region \| Skeletal fluorosis, clavicle \| Skeletal fluorosis, scapula [FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified Also known as: Diseases of the musculoskeletal system or connective tissue, unspecified \| bone disease NOS \| bone disorder NOS \| bone lesion NOS \| musculoskeletal complications NOS [ND56.2] Fracture of unspecified body region Also known as: Fracture of unspecified body region \| avulsion fracture of unspecified body site \| comminuted fracture of unspecified body site \| compression fracture of unspecified body site \| fracture dislocation of unspecified body site Excludes: multiple fractures NOS [LD2B] Syndromes with premature ageing appearance as a major feature Definition: A heterogeneous group of hereditary syndromes in which affected individuals do or appear to age at an accelerated rate. Also known as: Syndromes with premature ageing appearance as a major feature \| Progeroid syndromes \| premature aging syndrome \| progeria syndrome \| Cockayne syndrome Includes: Progeroid syndromes \| Cockayne syndrome \| Rothmund-Thomson syndrome Excludes: Xeroderma pigmentosum \| Cutis laxa === GRAPH WALKS === --- Walk 1 --- [ME67] Skin disorder of uncertain or unspecified nature Def: A category to enable the presence of a skin disorder to be recorded without making assumptions as to the precise nature of the disorder in question.... --PARENT--> [?] Symptoms or signs involving the skin Def: This category allows the capture of imprecise data where a more specific diagnosis cannot be made or to supplement information about a specific diagnosis.... --PARENT--> [?] Symptoms, signs or clinical findings involving the skin --- Walk 2 --- [ME67] Skin disorder of uncertain or unspecified nature Def: A category to enable the presence of a skin disorder to be recorded without making assumptions as to the precise nature of the disorder in question.... --PARENT--> [?] Symptoms or signs involving the skin Def: This category allows the capture of imprecise data where a more specific diagnosis cannot be made or to supplement information about a specific diagnosis.... --CHILD--> [ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature Def: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature... --- Walk 3 --- [ME66.Y] Other specified skin changes --PARENT--> [ME66] Miscellaneous non-specific skin-related symptoms and signs Def: Other specified skin changes which cannot be more precisely defined.... --RELATED_TO--> [?] Abnormal skin pigmentation Def: Abnormal skin pigmentation without specification of type or cause.... --- Walk 4 --- [ME66.Y] Other specified skin changes --PARENT--> [ME66] Miscellaneous non-specific skin-related symptoms and signs Def: Other specified skin changes which cannot be more precisely defined.... --CHILD--> [ME66.0] Abnormal sensitivity to light or UV radiation of uncertain or unspecified nature --- Walk 5 --- [EM0Y] Other specified diseases of the skin --PARENT--> [14] Diseases of the skin Def: Diseases of the skin incorporate conditions affecting the epidermis, its appendages (hair, hair follicle, sebaceous glands, apocrine sweat gland apparatus, eccrine sweat gland apparatus and nails) and... --RELATED_TO--> [?] Neonatal phototherapy burn Def: Burn resulting from phototherapy administered to neonate, usually for the treatment of neonatal jaundice.... --- Walk 6 --- [EM0Y] Other specified diseases of the skin --PARENT--> [14] Diseases of the skin Def: Diseases of the skin incorporate conditions affecting the epidermis, its appendages (hair, hair follicle, sebaceous glands, apocrine sweat gland apparatus, eccrine sweat gland apparatus and nails) and... --RELATED_TO--> [?] Haematoma of surgical wound of skin Def: Collection of blood within skin and soft tissues following surgical wound of skin usually resulting from defective haemostasis...	[ "[ME67] Skin disorder of uncertain or unspecified nature\n Def: A category to enable the presence of a skin disorder to be recorded without making assumptions as to the precise nature of the disorder in question....\n --PARENT--> [?] Symptoms or signs involving the skin\n Def: This category allows the capture of imprecise data where a more specific diagnosis cannot be made or to supplement information about a specific diagnosis....\n --PARENT--> [?] Symptoms, signs or clinical findings involving the skin", "[ME67] Skin disorder of uncertain or unspecified nature\n Def: A category to enable the presence of a skin disorder to be recorded without making assumptions as to the precise nature of the disorder in question....\n --PARENT--> [?] Symptoms or signs involving the skin\n Def: This category allows the capture of imprecise data where a more specific diagnosis cannot be made or to supplement information about a specific diagnosis....\n --CHILD--> [ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature\n Def: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature...", "[ME66.Y] Other specified skin changes\n --PARENT--> [ME66] Miscellaneous non-specific skin-related symptoms and signs\n Def: Other specified skin changes which cannot be more precisely defined....\n --RELATED_TO--> [?] Abnormal skin pigmentation\n Def: Abnormal skin pigmentation without specification of type or cause....", "[ME66.Y] Other specified skin changes\n --PARENT--> [ME66] Miscellaneous non-specific skin-related symptoms and signs\n Def: Other specified skin changes which cannot be more precisely defined....\n --CHILD--> [ME66.0] Abnormal sensitivity to light or UV radiation of uncertain or unspecified nature", "[EM0Y] Other specified diseases of the skin\n --PARENT--> [14] Diseases of the skin\n Def: Diseases of the skin incorporate conditions affecting the epidermis, its appendages (hair, hair follicle, sebaceous glands, apocrine sweat gland apparatus, eccrine sweat gland apparatus and nails) and...\n --RELATED_TO--> [?] Neonatal phototherapy burn\n Def: Burn resulting from phototherapy administered to neonate, usually for the treatment of neonatal jaundice....", "[EM0Y] Other specified diseases of the skin\n --PARENT--> [14] Diseases of the skin\n Def: Diseases of the skin incorporate conditions affecting the epidermis, its appendages (hair, hair follicle, sebaceous glands, apocrine sweat gland apparatus, eccrine sweat gland apparatus and nails) and...\n --RELATED_TO--> [?] Haematoma of surgical wound of skin\n Def: Collection of blood within skin and soft tissues following surgical wound of skin usually resulting from defective haemostasis..." ]	ME67	Skin disorder of uncertain or unspecified nature	[ { "from_icd11": "ME67", "icd10_code": "L989", "icd10_title": "Disorder of the skin and subcutaneous tissue, unspecified" }, { "from_icd11": "ME66.Y", "icd10_code": "L578", "icd10_title": "Other skin changes due to chronic exposure to nonionizing radiation" }, { "from_icd11": "EM0Y", "icd10_code": "L918", "icd10_title": "Other hypertrophic disorders of the skin" }, { "from_icd11": "EM0Y", "icd10_code": "L988", "icd10_title": "Other specified disorders of the skin and subcutaneous tissue" }, { "from_icd11": "ME66.1", "icd10_code": "R234", "icd10_title": "Changes in skin texture" }, { "from_icd11": "LB9Z", "icd10_code": "Q8789", "icd10_title": "Other specified congenital malformation syndromes, not elsewhere classified" }, { "from_icd11": "LB9Z", "icd10_code": "Q8781", "icd10_title": "Alport syndrome" }, { "from_icd11": "LB9Z", "icd10_code": "Q742", "icd10_title": "Other congenital malformations of lower limb(s), including pelvic girdle" }, { "from_icd11": "LB9Z", "icd10_code": "Q749", "icd10_title": "Unspecified congenital malformation of limb(s)" }, { "from_icd11": "LB9Z", "icd10_code": "Q740", "icd10_title": "Other congenital malformations of upper limb(s), including shoulder girdle" }, { "from_icd11": "LB9Z", "icd10_code": "Q741", "icd10_title": "Congenital malformation of knee" }, { "from_icd11": "LB9Z", "icd10_code": "Q875", "icd10_title": "Other congenital malformation syndromes with other skeletal changes" }, { "from_icd11": "LB9Z", "icd10_code": "Q748", "icd10_title": "Other specified congenital malformations of limb(s)" }, { "from_icd11": "LB9Z", "icd10_code": "Q89", "icd10_title": "Other congenital malformations, not elsewhere classified" }, { "from_icd11": "LB9Z", "icd10_code": "Q65-Q79", "icd10_title": "" } ]	L989	Disorder of the skin and subcutaneous tissue, unspecified
In the following, cases with SA errors are described (see Table 2 for details). Case 1 refers to information that was either missing due to insufficient communication or that was simply forgotten. Cases 2–4 are examples of barriers that physically preclude from information to become (acoustic and visual) sensory input (e.g., “After putting the drapes, the access to both peripheral iv lines was hampered”). In case 3, specifically, “small fonts” on a display prevented from a more timely recognition of the fact that a propofol syringe pump ran with remifentanil and vice versa. In case 5, relevant information was missed due to the decision not to use a patient monitor. Case 6 describes the mis perception of drug labels resulting in the decision to use hydroxyethyl starch to keep open an arterial line. The reporting individual identified a look-alike problem of drugs (“both look similar”) which is a problem addressed extensively elsewhere . In these cases (1–6), the involved individuals did not perceive relevant information and consequently, they did not comprehend important aspects of the situation and, as a result, wrong or no decisions were made. Table 2 Fifteen examples of SA errors Case number Case description Analysis from the SA perspective SA level 1 An anesthesiologist took over a patient who had undergone massive transfusion including catecholamine therapy. He reports to have received a “detailed handover” and that his job was to finish the procedure and to transport the patient to ICU. Just before leaving the OR he replaced an empty infusion bag with a new one in order to continue volume replacement. Immediately afterwards, the patient’s suffered from ventricular arrhythmia and the systolic blood pressure increased to 250 mmHg. “During check of the i.v.-lines I noticed that the adrenaline syringe pump had been connected to the central line by two extension lines type Heidelberger. Obviously they had filled with highly concentrated adrenaline which was administered unintentionally during volume resuscitation.” The anesthesiologist was not aware about a significant amount of adrenaline in the lines. Possibly, the hand-over, which he felt to be “detailed”, did not include information about this fact (SA-I). Alternatively, he may have forgotten this information in face of a complex situation where gaining complete SA in short time is challenging for someone who had not been involved until this moment. SA I data not available or memory loss 2 “The code blue physician does not hear the beeper. The beeper turns off after a certain time. The causes are a significant noise exposure on the ICU and the high frequency of phone calls.” The code blue physician did not perceive the alarm (SA-I). The reporting individual mentions acoustic barriers on one hand and high workload on the other hand as causes. SA I hard to detect 3 “For economic reasons, sometimes, nurses program the syringe pumps. In this case a syringe pump programmed for propofol ran with remifentanil and, accordingly, it ran too slow. […] The only striking point was that we had propofol in the remifentanil line repeatedly and despite high infusion rates, we still had the first syringe of remifentanil after hours. Having a closer look we were able to recognize propofol in small fonts on the display whereas remifentanil was indicated on the syringe label.” It largely remains unclear why the nurse allocated the drugs incorrectly. Assumingly some information (syringe content or pump program) has been forgotten. However, the reporting individual clearly states that important information was displayed in small fonts hindering a fast and quick recognition of the content of syringe pumps (SA-I). SA I data hard to discriminate 4 “After putting the drapes, the access to both peripheral iv lines was hampered. During team-time-out one of the surgeon leant against the arm compressing the iv lines while the anesthesiologist paged through the patient’s health record […] so that the anesthetics entered the infusion bag of the crystalloids. During skin incision the patient showed increase of heart rate and moved the arms. Then, we switched the administration of anesthetics to the other iv access.” Important visual information from iv lines (obstruction) was not perceived due to a visual barrier (drapes). Furthermore, the visual attention was directed to the patient’s health record during team time out. It remains speculative why a non-return valve had not been used and whether the use of such a valve had resulted e.g., in high-pressure alarms in the syringe pumps (SA-I). SA I hard to detect and failure to observe 5 After uneventful anaesthesia the patient was transferred to another location. There, the first systolic blood pressure assessed was 60 mmHg. “In this OR a transport monitor does not exist. The short transfer regularly is done without monitoring. Every time a monitor is required, we have to get it from elsewhere which is time-intensive.” The case reveals structural problems as a monitoring device is not easily available and the anesthesiologists avoid time delays in face of assumingly uncomplicated cases. As a result, important information is missed (SA-I). SA I failure to monitor 6 “To keep open an arterial line, HES [hydroxyethyl starch] was used instead of saline. Both look similar but HES is an emergency substance so that it should be stored in a different place.” As both infusions look similar (look-alike problem), the information was correct but obviously misperceived (SA-I). SA I misperception 7 “A patient is transferred to ICU with several syringe pumps including a pump for TIVA [total intravenous anaesthesia] that had been equipped with a catecholamine. The ICU personnel are not familiar with that type of pumps. […] Unintentionally, the patient got a high bolus.” A health care provider works with a syringe pump he is not familiar with. Although all the dynamic information is present (rates, drugs, indication), the individual applies an incorrect mental model of the pump’s operating mode and thus, he lacks of comprehension (SA-II). SA II use of incorrect mental model 8 “two oral drugs […] had been given via the central venous line instead of the gastric tube.” Assumingly, all the relevant information (e.g., package insert, drug orders) was present, but the individual lacks of a mental model with respect to how these drugs are administered (SA-II). As a result he does not comprehend that these drugs have to be administered in another way. SA II use of incorrect mental model 9 “ […] On the third postoperative day […] the epidural was stopped. On the next morning, the anesthetist cannot visit the patients due to concurrent obligations. During the evening visit, the anesthetist noticed that ropivacaine was re-started but that it was connected to a peripheral venous line. The infusion was stopped immediately.” Assumingly, all the relevant basic information was present: drug, patient and indication (SA-I). But the information was not properly integrated, due to missing knowledge or the use of missing or an incorrect mental model (SA-II). If someone is confronted with a set of information he can’t process due to missing contextual contents in the long-term memory, he will probably ask for assistance. If an incorrect model is used, he won’t recognize the error as long as there is no additional information such as visible adverse effects. SA II use of incorrect mental model 10 "During TIVA a change of the syringe (remifentanil) was pending. The syringe had been prepared by the nurse (50 ml, clear solution). The label “remifentanil” and the ampoule lied besides the syringe. The nurse told to the anesthesiologist that the remifentanil syringe was prepared. The anesthesiologist changed the syringe; in the following minutes, the patient shows tachycardia and high blood pressure, deepening anaesthesia is without success. When the nurse came back, she asked if the anesthesiologist had added the remifentanil to the prepared syringe. As it turned out, the communication […] was unclear and stated a potential danger for the patient.” The anesthesiologist incorrectly assumed a syringe to be correctly prepared (SA-II). Visible information (the ampoule next to the syringe) was not perceived or not integrated in order to come to the conclusion that the syringe contained purely saline. Additionally, the reporting individual identified a lack of information resulting from unclear communication as the cause. SA II over-reliance on default values 11 “A critically ill patient with complex pains, who was visited by pain physicians for 4-fold analgetic medication. During change of syringe pump, ketamine is administered in wrong dosage, 50 mg/ml instead of 1 mg/ml is administered, as it is usual for sedation. During shift change the error is recognized. […] The patient was awake throughout the case […] but suffered from headache.” The nurse who changed the syringe prepared the dosage as usual (assuming standard values), despite differing information from the medication order as indicated through the fact that this was recognized during shift change. This may have happened through an over-reliance on default values (SA-II) although additional information was available that would have resulted in a different action (preparing the correct dosage). SA II over-reliance on default values 12 “During thoracic surgery (VATS lobectomy) the suction catheter was introduced too deep in the tracheal part of the double-lumen tube. […] Lobectomy is performed using a stapler. The suction catheter could not be removed for checking for leakiness […]. As a cause, the stapler had fixed the suction catheter. An anterior thoracotomy was performed […] and the suction catheter was removed successfully.” The anesthesiologist, assumingly, was aware about the surgical procedure to be performed (use of stapler). Additionally he had the information about the suction catheter as he himself had inserted it. This information has not been integrated properly as he relied on his experience from prior situations where removing the device was always without problems and long-term memory content such as a mental model or prototypical situations suited to successfully integrate the basic data was not used or not present. As a result, also a problem on the level of projection emerges as an anterior thoracotomy had to be performed unexpectedly. SA II lack of or incomplete mental model 13 “A surgeon indicated emergency surgery. There is no written information about patient history and it is impossible to get the information orally [from the patient]. The patient is assessed clinically, an old scar from tracheostomy is visible which indicates possible intubation problems. The anesthesiologist put himself under pressure and induces anaesthesia without investigating the background or consulting the admitting hospital. A rapid sequence induction is performed. Intubation with a 8.0 size tube is not possible, bag mask ventilation works, a 7.0 mm is not introducible as well, and a laryngeal mask (4 and 5) is not tight so that adequate ventilation is impossible. Finally, another physician successfully intubates.” Unexpectedly, the anesthesiologist ran into intubation difficulties, indicating an error on the SA level of projection (SA-III). This is supported by the retrospective statement that he worked under avoidable time pressure and that, as a consequence, search for additional information was omitted (SA-I). Regardless of the fact whether the simple presence of a scar from tracheostomy should prompt the preparation for difficult airway management, a mental model that integrates the basic data (tracheostomy in the past) to SA on the level of projection “expected difficult intubation” was absent (SA-III). SA III lack of or incomplete mental model 14 A patient is scheduled for hip replacement. […] Until the use of palacos bone cement everything went fine. […] Immediately after inserting palacos bone cement, end-tidal CO 2 drops from 37 to 13 mmHg. Oxygen saturation does not provide values. At the beginning, a sinus tachycardia of 140 bpm is noticed, quickly followed by deformed QRS complexes. Heart rate drops to 20 bpm. Cardiopulmonary resuscitation is initiated immediately. The working hypotheses are air embolism, fat embolism and allergic reaction. An unexpected deterioration due to the use of palacos bone cement is described (SA-III). A dramatic change of vital parameters is the basic information (SA-I) that results in a re-evaluation of the situation. As a consequence, the anesthesiologist comprehends that cardiopulmonary resuscitation is required (SA-II). Additionally, based on basic information, possible causes are discussed. SA III over-projection of current trends 15 A geriatric patient with dementia is transported to the emergency department. He has a visible laceration on the head after having fallen out of the bed. The laceration was sutured and a CT scan ordered in face of increasing somnolence. “ A medical student saw that nobody had placed a cervical collar and that the patient complaint about pain when the head was positioned for suturing. He did not communicate his observation […]. The scan showed a facture of atlas and axis.” There are relevant cues that indicate the possibility of a lesion of the cervical spine (fall, laceration on head, increasing somnolence, pain during movement of the head). The reporting individual emphasizes that the team did not comprehend the possibility of a spine lesion that is, they either did not possess over the mental model that allowed for meaningful integration of the information mentioned above (SA-II) or they simply did not perceive some piece of information, e.g., pain during movement of the neck (SA-I). SA I failure to observe SA II Another point refers to a lack of communication as the medical student did not speak up (Team SA). Communication can refer to the SA level of comprehension (e.g., “we cannot rule out a spinal lesion, therefore cervical collar makes sense”) or to the level of perception (e.g., “every time the patients head/spine is moved, the patient complaints about pain”). missing mental model TEAM SA Fifteen cases during which SA errors led to errors or near misses. SA-I refers to the level of perception, SA-II to the level of comprehension, SA-III to the level of projection, respectively	3.974609	0.783691	sec[2]/sec[1]/p[0]	en	0.999998	26772179	https://doi.org/10.1186/s12871-016-0172-7	[ "that", "information", "syringe", "model", "mental", "anesthesiologist", "remifentanil", "this", "time", "pump" ]	[ { "code": "8A80.Z", "title": "Migraine, unspecified" }, { "code": "QA76", "title": "Medication or substance that is known to be an allergen without injury or harm" }, { "code": "PL13.6", "title": "Medication or substance that is known to be an allergen, as mode of injury or harm" }, { "code": "9C40.A0", "title": "Papilloedema" }, { "code": "PA6Z", "title": "Unintentional fall from unspecified height" }, { "code": "NA07.09", "title": "Concussion with loss of consciousness, duration unspecified or unknown due to lack of information" }, { "code": "PK90.0", "title": "Anaesthesiology devices associated with injury or harm, diagnostic or monitoring devices" }, { "code": "6E8Z", "title": "Mental, behavioural or neurodevelopmental disorders, unspecified" }, { "code": "6A00.Z", "title": "Disorders of intellectual development, unspecified" }, { "code": "6E6Z", "title": "Secondary mental or behavioural syndrome, unspecified" } ]	=== ICD-11 CODES FOUND === [8A80.Z] Migraine, unspecified Also known as: Migraine, unspecified \| Migraine [QA76] Medication or substance that is known to be an allergen without injury or harm Definition: Medication that has previously been identified as an allergen to the patient is administered, but does not result in injury or harm. Also known as: Medication or substance that is known to be an allergen without injury or harm Excludes: Medication or substance that is known to be an allergen, as mode of injury or harm [PL13.6] Medication or substance that is known to be an allergen, as mode of injury or harm Also known as: Medication or substance that is known to be an allergen, as mode of injury or harm \| medication error relating to known allergy to drug or substance \| adverse drug event relating to known allergy to drug or substance [9C40.A0] Papilloedema Definition: Optic disc swelling that results from increased intracranial pressure Also known as: Papilloedema \| Optic disc swelling that results from increased intracranial pressure Includes: Optic disc swelling that results from increased intracranial pressure [PA6Z] Unintentional fall from unspecified height Also known as: Unintentional fall from unspecified height \| fall NOS \| accidental fall \| fall causing injury that resulted in death \| fell NOS [NA07.09] Concussion with loss of consciousness, duration unspecified or unknown due to lack of information Also known as: Concussion with loss of consciousness, duration unspecified or unknown due to lack of information [PK90.0] Anaesthesiology devices associated with injury or harm, diagnostic or monitoring devices Definition: An anaesthesiology device was involved in an incident that occurred in a diagnostic or monitoring task Also known as: Anaesthesiology devices associated with injury or harm, diagnostic or monitoring devices \| Anaesthesiology devices associated with injury or harm, arterial pressure monitoring catheter \| Anaesthesiology devices associated with injury or harm, pulse oxymeter giving faulty information Excludes: Circumstances associated with a surgical or other medical device influencing the episode of care without injury or harm [6E8Z] Mental, behavioural or neurodevelopmental disorders, unspecified Also known as: Mental, behavioural or neurodevelopmental disorders, unspecified \| Psychiatric disorder \| mental disease NOS \| mental disorder NOS \| mental illness [6A00.Z] Disorders of intellectual development, unspecified Also known as: Disorders of intellectual development, unspecified \| Disorders of intellectual development \| Mental retardation \| Intellectual developmental disorder \| Intellectual disability [6E6Z] Secondary mental or behavioural syndrome, unspecified Also known as: Secondary mental or behavioural syndrome, unspecified \| organic mental disorders \| Secondary mental and behavioural disorders \| Mental or behavioural syndromes due to health conditions not classified under mental or behavioural disorders === GRAPH WALKS === --- Walk 1 --- [8A80.Z] Migraine, unspecified --PARENT--> [8A80] Migraine Def: A primary headache disorder, in most cases episodic. Disabling attacks lasting 4-72 hours are characterised by moderate or severe headache, usually accompanied by nausea, vomiting and/or photophobia a... --EXCLUDES--> [?] Headache, not elsewhere classified Def: Headache with characteristic features suggesting that it is a unique diagnostic entity, a finding or complaint, but not fulfilling criteria for any of the headache disorders described above.... --- Walk 2 --- [8A80.Z] Migraine, unspecified --PARENT--> [8A80] Migraine Def: A primary headache disorder, in most cases episodic. Disabling attacks lasting 4-72 hours are characterised by moderate or severe headache, usually accompanied by nausea, vomiting and/or photophobia a... --EXCLUDES--> [?] Headache, not elsewhere classified Def: Headache with characteristic features suggesting that it is a unique diagnostic entity, a finding or complaint, but not fulfilling criteria for any of the headache disorders described above.... --- Walk 3 --- [QA76] Medication or substance that is known to be an allergen without injury or harm Def: Medication that has previously been identified as an allergen to the patient is administered, but does not result in injury or harm.... --EXCLUDES--> [?] Medication or substance that is known to be an allergen, as mode of injury or harm --PARENT--> [?] Mode of injury or harm associated with exposure to a drug, medicament or biological substance --- Walk 4 --- [QA76] Medication or substance that is known to be an allergen without injury or harm Def: Medication that has previously been identified as an allergen to the patient is administered, but does not result in injury or harm.... --PARENT--> [?] Circumstances associated with exposure to a drug, medicament or biological substance influencing the episode of care without injury or harm --CHILD--> [QA71] Underdosing without injury or harm Def: Under-dosing occurs when a patient takes less of a medication than is prescribed by the provider or the manufacturer's instructions without documented injury or harm. This can be the result of inaccur... --- Walk 5 --- [PL13.6] Medication or substance that is known to be an allergen, as mode of injury or harm --PARENT--> [PL13] Mode of injury or harm associated with exposure to a drug, medicament or biological substance --CHILD--> [PL13.0] Overdose of substance, as mode of injury or harm Def: Incorrect dose - too high... --- Walk 6 --- [PL13.6] Medication or substance that is known to be an allergen, as mode of injury or harm --PARENT--> [PL13] Mode of injury or harm associated with exposure to a drug, medicament or biological substance --CHILD--> [PL13.0] Overdose of substance, as mode of injury or harm Def: Incorrect dose - too high...	[ "[8A80.Z] Migraine, unspecified\n --PARENT--> [8A80] Migraine\n Def: A primary headache disorder, in most cases episodic. Disabling attacks lasting 4-72 hours are characterised by moderate or severe headache, usually accompanied by nausea, vomiting and/or photophobia a...\n --EXCLUDES--> [?] Headache, not elsewhere classified\n Def: Headache with characteristic features suggesting that it is a unique diagnostic entity, a finding or complaint, but not fulfilling criteria for any of the headache disorders described above....", "[8A80.Z] Migraine, unspecified\n --PARENT--> [8A80] Migraine\n Def: A primary headache disorder, in most cases episodic. Disabling attacks lasting 4-72 hours are characterised by moderate or severe headache, usually accompanied by nausea, vomiting and/or photophobia a...\n --EXCLUDES--> [?] Headache, not elsewhere classified\n Def: Headache with characteristic features suggesting that it is a unique diagnostic entity, a finding or complaint, but not fulfilling criteria for any of the headache disorders described above....", "[QA76] Medication or substance that is known to be an allergen without injury or harm\n Def: Medication that has previously been identified as an allergen to the patient is administered, but does not result in injury or harm....\n --EXCLUDES--> [?] Medication or substance that is known to be an allergen, as mode of injury or harm\n --PARENT--> [?] Mode of injury or harm associated with exposure to a drug, medicament or biological substance", "[QA76] Medication or substance that is known to be an allergen without injury or harm\n Def: Medication that has previously been identified as an allergen to the patient is administered, but does not result in injury or harm....\n --PARENT--> [?] Circumstances associated with exposure to a drug, medicament or biological substance influencing the episode of care without injury or harm\n --CHILD--> [QA71] Underdosing without injury or harm\n Def: Under-dosing occurs when a patient takes less of a medication than is prescribed by the provider or the manufacturer's instructions without documented injury or harm. This can be the result of inaccur...", "[PL13.6] Medication or substance that is known to be an allergen, as mode of injury or harm\n --PARENT--> [PL13] Mode of injury or harm associated with exposure to a drug, medicament or biological substance\n --CHILD--> [PL13.0] Overdose of substance, as mode of injury or harm\n Def: Incorrect dose - too high...", "[PL13.6] Medication or substance that is known to be an allergen, as mode of injury or harm\n --PARENT--> [PL13] Mode of injury or harm associated with exposure to a drug, medicament or biological substance\n --CHILD--> [PL13.0] Overdose of substance, as mode of injury or harm\n Def: Incorrect dose - too high..." ]	8A80.Z	Migraine, unspecified	[ { "from_icd11": "8A80.Z", "icd10_code": "G43B0", "icd10_title": "Ophthalmoplegic migraine, not intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43409", "icd10_title": "Hemiplegic migraine, not intractable, without status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43A0", "icd10_title": "Cyclical vomiting, in migraine, not intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43D0", "icd10_title": "Abdominal migraine, not intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43709", "icd10_title": "Chronic migraine without aura, not intractable, without status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43A1", "icd10_title": "Cyclical vomiting, in migraine, intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43509", "icd10_title": "Persistent migraine aura without cerebral infarction, not intractable, without status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43719", "icd10_title": "Chronic migraine without aura, intractable, without status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43501", "icd10_title": "Persistent migraine aura without cerebral infarction, not intractable, with status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43C0", "icd10_title": "Periodic headache syndromes in child or adult, not intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43401", "icd10_title": "Hemiplegic migraine, not intractable, with status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43419", "icd10_title": "Hemiplegic migraine, intractable, without status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43B1", "icd10_title": "Ophthalmoplegic migraine, intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43C1", "icd10_title": "Periodic headache syndromes in child or adult, intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43D1", "icd10_title": "Abdominal migraine, intractable" } ]	G43B0	Ophthalmoplegic migraine, not intractable
Fetal death was identified on admission during training in the use of the sonicaid in one mother (see Table 4 below). Table 4 Clinical information and outcomes of FHR changes identified by monitoring. Abbreviations: see list Maternal age group (years) Parity Change in FHR identified Action taken Apgar scores at 1 and 5 min Resuscitation given Maternal comment 29–39 G5P2 By mother. FHR 115 with meconium Confirmed by MW Lateral tilt and intravenous cannula with NS bolus Vacuum delivery 9 and 10 No According to patient she lost her fetus during past pregnancy. Here she was happy when she noticed her fetal heart beat was dropping and the quick response that was processed 29–39 G3P2 By MW and mother during training in the use of the sonicaid at time of admission. No FHR was identified and there was 3+ meconium Ultrasound confirmed IUFD. Vacuum delivery was undertaken NA NA NA 17 and below G2P0 By mother at 46th contraction FHR 109 with meconium Cervix fully dilated and urged to push. NVD occurred. 4 and 7 Yes. Bag and mask ventilation, adrenaline and chest compressions for 10 min. Admitted to the NNU for post resus care and close monitoring Developed convulsions due to HIE and treated successfully with phenobarbital and recovered and was feeding normally at discharge home aged 7 days. Listening to my baby heart was good. It help me to know that something was happening to her. No problem with it. Thank you. 18–28 G2P0 By mother FHR 119 at 49th contraction. There was + meconium present Vacuum delivery 7 and 10 No I like the thing I was doing but it was hard to do because of the pain. 18–28 G2P1 By mother FHR 119, 117, 116. No meconium. Patient was not progressing at this stage. 2 cm cervical dilatation with mild contractions. MW/OC took over the monitoring due to the bradycardia. Doctor contacted. Patient was laterally tilted, given oxygen, D50%, hydrated and rushed to the OR for CS. 7 and 10 No Thank you for this program. If not so my baby was going to die. The only thing that the pain. 18–28 G2P1 No previous CS By mother FHR 163–165 with meconium. Signs of Bandl’s ring and obstructed labour with haematuria identified. Not receiving oxytocin. Emergency CS 9 and 10 No Thank you for saving my life and my baby. It really helpful to listen to my baby heart to know what was happening to me. 18–28 G3P2 By mother FHR 119,110,118. No meconium. OC and doctor contacted and confirmed bradycardia Given facial oxygen, lateral tilt, N/S and D50%. Patient was 6 cm dilated at this stage. Emergency CS 8 and 10 No I feel good when I was listening to my baby heart. It help me to know what happen to my baby. 18–28 G1P0 By mother at 46th contraction FHR 117, then 114, then 116, then 113. No meconium. Fully dilated but descent only minus 2 Lateral tilt, D50%, oxygen, NS and FHR still below 120 She sat on birthing chair for 10 min and when head reached below 0 station (re: ischial spines) vacuum delivery was successfully undertaken 7 and 10 No Thank you for what you bringing because when it was not because of it I was not coming to know say my baby heart was not beating good. That just the pain was giving me hard time thank all. 17 and below G1P0 FHR found to be 95–100 by mother, FHR was repeated by midwife and confirmed low, 95–98, and Doctor on call was also informed. Patient was placed in a left lateral tilt position Patient was reviewed and decision to CS was taken for fetal distress plus prolonged labour 6 and 9 None Not requested at this stage in programme 18–28 G3P1 Mother reported a change in FHR but when checked by MW found FHR to be normal at 142. Meconium was present Doctor informed but no action was considered necessary 6 and 10 None Not requested at this early stage in programme 17 and below G1P0 On 11th contraction mother reported slow heart rate. MW was contacted but she found FHR was 153. There was no meconium the OC was contacted. Mother’s membranes were ruptured and vacuum delivery undertaken 7 and 10 None Not requested at this early stage in programme 17 and below G1P0 Mother noted change in FHR and contacted MW on 15th contraction. MW noted FHR 118 and informed OC. Meconium was present repeat fetal heart rate was 105. Mother put in lateral tilt position and informed Dr. who reviewed patient and found fetal heart rates 110, 105, and 108. Emergency CS was performed 8 and 10 None Not requested at this early stage in programme 18–28 G2P1 On 11th contraction mother noticed bradycardia. Midwife confirmed FHR 118 Grade 3 meconium was present. Patient placed in left lateral position and called OC. OC found FHR to be 110. Left lateral tilt. Cervix was fully dilated and vacuum delivery was undertaken. 6 and 9 Bag and mask ventilation. Admitted NNU for 5 days and treated for sepsis. Not requested at this early stage in programme 18–28 G1P0 Yes - by MW following being declined by mother FHR 95–100 on two successive occasions Lateral tilt and subsequent CS for non-reassuring FHR 5 and 7 Bag and mask ventilation and admitted to NNU. No HIE and went home. Following initial consent, patient later declined to monitor her FHR. Says she was tired of monitoring. 18–28 G3P2 Mother on 14th contraction noticed change in FHR to 102. And complained of weakness. She called for help and FHR was102. No meconium was present. OC contacted, lateral tilt and intravenous (IV) cannula with 500 ml of Ringer Lactate given. Normal vaginal delivery followed. 6 and 10 This baby was resuscitated for 5 min with bag and mask ventilation and then transferred to the NNU where he was immediately placed on nasal CPAP and an IV line was opened to serve antibiotics because amniotic fluid was also purulent and foul smelling. IV fluid (Dextrose 10%) was set up. Baby was managed for 7 days in the NNU and was discharged home with good outcome. According to mum monitoring is hard at certain times. She knew her baby's heart rate was low and we took quick action and now the baby is in her hands so she thank the organisation. 17 and below G1P0 On the 14th contraction the mother called the MW because the FHR was low. The MW confirmed FHR 98, called for help and undertook lateral tilt. Meconium was present. The OC was contacted. She opened IV line and gave R/L 1000 mL, informed the doctor on call. The doctor came and assessed the patient and said we should prepare patient for CS. CS was done for prolonged labour and abnormal FHR. 5 and 10 Neonate was resuscitated for 7 min by bag and mask ventilation before transferring to the NNU. She was placed on nasal CPAP for 24 h and was also managed for risk of sepsis. Neonate improved after 8 days and was discharged. According to mum it is okay because this help the doctor nurses to take quick action 17 and below G1P0 On the 7th contraction, mother detected fetal bradycardia 105 bpm. MW called and checked and confirmed FHR 105. Meconium was present. Grade 3 OC was called. Lateral tilt was undertaken and fast vaginal delivery arranged as 9 cm cervix dilated. Birth weight 1.9Kg small for dates. 7 and 10 Baby was resuscitated for 2 min by bag and mask ventilation and then transferred to NNU. She was placed on nasal CPAP for 24 h and patient condition improved. Baby was also managed for risk of neonatal sepsis because mother’s amniotic fluid was purulent, foul-smelling during delivery. The baby was discharged home after 10 days with a weight of 2.3 kg Patient initially declined procedure but later on she was encouraged to do it herself and everything went well 18–28 G5P4 On 6th contraction, mother detected bradycardia 108 bpm. MW confirmed FHR 108. Meconium was present. OC contacted. Lateral tilt performed. IV cannula inserted and given NS 500 ml. Normal vaginal delivery occurred. 5 and 8 Male Bag and mask ventilation given. No HIE occurred but he needed 5 days of antibiotics for umbilical infection. Patient worry when the heart rate was reducing but at last she was happy because her baby came through 29–39 G5P3 On 2nd contraction monitored mother identified rapid heart rate. MW confirmed FHR 190 and called for help, Doctor called and attended. Lateral tilt and IV cannula and N/S 500 ml set up. Vacuum delivery was undertaken. 6 and 8 Neonatal clinician was called and baby resuscitated with bag and mask ventilation and recovered within 1 min. Responded well and taken to NNU for suspicion of sepsis. No HIE. Mother said she was happy with the monitoring because she could have had a dead baby if she didn’t monitor. She’s also asking other mothers to accept and be part of the process 17 and below G2P1 On 6th contraction, Mother reported fall in HR. MW confirmed FHR 109 Meconium present. Lateral tilt applied and IV cannula inserted with R/L 500 mls plus Dextrose 50% 30 ml. OC contacted and quickly delivered the baby vaginally. 6 and 7 Mildly depressed but no resuscitation needed. Neonatal clinician continued monitoring and care. Patient was very happy because she call for help and action was taken quickly by the OB clinician and her baby was save. 18–28 G3P0 On 27th contraction, Mother detected slowing of FHR. MW confirmed FHR 109. Grade 2 meconium was present. Dr. on call contacted. Lateral tilt and IV cannula inserted. R/L 500 mls given IV. Doctor arrived and undertook CS. 7 and 10 Resuscitated for 2 min with bag and mask ventilation. According to mother she was very happy, and she told everybody thanks because of the monitoring her baby was saved 17 and below G1P0 On 7th contraction mother noted fast heart rate. MW confirmed FHR 167. Patient came in fully dilated but evidence of obstructed labour due to persistent occipito-posterior malposition. Lateral tilt and IV cannula inserted. NS 500 mls given IV. Doctor arrived and undertook CS. 9 and 10 None needed Mother was happy to hear her baby heart beat because she stay in labour for long and worry about her unborn baby 40 and above G9P8 On the 7th contraction mother with MW noted a slow heart rate FHR 102. Meconium was present and a cord prolapse identified. The OC was notified and implemented knee chest position and inserted NS 300mls into the bladder to reduce cord compression. IV cannula was inserted and NS 500 mls given. A CS was then undertaken. 6 and 10 Depressed breathing. Resuscitated for 1–3 min with bag and mask ventilation. Taken to NNU as 1.7 Kg and 30 weeks’ gestation No HIE. Home after 14 days According to mother monitoring is good but she cannot continue it herself due to pain. At last she said it help her with a live neonate 17 and below G2P1 previous CS On 12th contraction, Mother reported slowing and with MW reported a FHR 124. Meconium present Grade 3 Then FHR dropped to 119 bpm OC was called and after lateral tilt established IV line and gave 500 ml NS. A CS was then undertaken. 7 and 8 No resuscitation needed but foul-smelling amniotic fluid at CS led to NNU admission and IV antibiotics. Mother agreed to the process, she started it but discontinue due to pain and was helped by midwife and OB clinician. Mother said it’s a good thing, it help her have a live baby 29–39 G1P0 Induced for post date. On the 8th contraction mother noted a slow heart rate. MW contacted and confirmed FHR 110. Meconium was present. OC informed and FHR was 112. Cervix fully dilated. Lateral tilt and placed in delivery room for vacuum delivery. However, within 5 min delivered NVD spontaneously. A very short umbilical cord was present. 5 and 7 Depressed breathing Resuscitated for 5 mins with bag and mask ventilation and taken to NNU and given antibiotics. Later became stable and discharged. The monitoring was good, it is a good idea and I hope it will continue because it will save a lot of babies as it did mine. Sometimes the midwives are busy so this will help them and help us the mothers too. Mother was hospital medical director ‘s sister in-law 29–39 G5P4 On the 30th contraction mother noted a slow heart rate. MW confirmed FHR 118. MW performed lateral tilt and informed the OC and set up IV infusion of R/L 500 ml. Dr. ordered repeat and FHR 106. Cervix only 4 cm dilated. Descent 3 / 5. Discussion for CS was done but no CS materials available, so patient was referred to another hospital. 8 and 9 None needed after CS at referral hospital I like listening to my baby heart but I don’t know if my baby will live again now that I am going to a different hospital. Outcome at second hospital after CS was good for mother and baby. 18–28 G1P0 On the 20th contraction OC and student MW confirmed a slow FHR 105. No meconium seen. Lateral tilt was undertaken. The cervix was already 10 cm dilated and there were poor maternal efforts. An IV cannula was inserted and she was given 30 ml dextrose 50%. Baby was delivered by vacuum. 5 and 6 Yes, by neonatal clinician bag and mask ventilation for 5–10 min. Admitted to NNU for neonatal depression. Neonate recovered quickly on nasal CPAP. Improved and went home well. Mother had declined monitoring but this was done by student MW. 18–28 G1P0 On 30th contraction mother noted slowing of FHR. There was no meconium at this time. MW and OC identified FHR of 115, 118,122. Lateral tilt and Doctor notified. An IV cannula inserted and given N saline 500 ml plus Dextrose 50% 30 ml. The cervix was 10 cm dilated. OC did vacuum with Dr. present but failed 3 times. Dr. and OC proceeded to immediate CS. Intraoperative meconium was present 5 and 7 Bag and mask ventilation for mild respiratory depression. Recovered rapidly and went home. The monitoring is good but I was not able to do it all by myself because of the pain and my foot pain. Yes my baby is living so it help. No problem with it but the pain can be too much. 18–28 G4P0 On 51st contraction mother noted slowing of fetal heart rates. MW recorded FHR 109, 178,120,110,181,102,130 Meconium was present Lateral tilt was performed, and OC notified. IV fluids were started, and 30 ml of 50% dextrose given IV. The doctor was also called and due to FHR changes, high station on vaginal examination, and bad obstetric history (G4P0) proceeded with the OC to CS. 8 and 10 No The monitor help me to inform the midwife that my baby was not breathing good. So I see it to be good for all the big belly with stomach hurting pain. Abbreviations are defined in the list given earlier in the manuscript	3.871094	0.873047	sec[2]/sec[4]/p[2]	en	0.999997	32536345	https://doi.org/10.1186/s12884-020-02921-z	[ "mother", "baby", "meconium", "tilt", "contraction", "heart", "present", "because", "delivery", "mask" ]	[ { "code": "QA48.1", "title": "Care or examination of lactating mother" }, { "code": "KB60.1", "title": "Syndrome of infant of a diabetic mother, type 1 or 2, nongestational, insulin dependent" }, { "code": "1C1D.0", "title": "Primary yaws" }, { "code": "KD35", "title": "Neonatal withdrawal syndrome from maternal use of drugs of addiction" }, { "code": "KB60.0", "title": "Syndrome of infant of mother with gestational diabetes" }, { "code": "6E20", "title": "Mental or behavioural disorders associated with pregnancy, childbirth or the puerperium, without psychotic symptoms" }, { "code": "KD34", "title": "Reactions or intoxications due to drugs administered to fetus or newborn" }, { "code": "KB08.2", "title": "Congenital hypotonia" }, { "code": "LD90.Y", "title": "Other specified conditions with disorders of intellectual development as a relevant clinical feature" }, { "code": "EC20.02", "title": "Autosomal recessive congenital ichthyosis" } ]	=== ICD-11 CODES FOUND === [QA48.1] Care or examination of lactating mother Also known as: Care or examination of lactating mother \| care of lactating mother \| examination of lactating mother \| supervision of lactation \| supervision of breastfeeding Excludes: Certain specified disorders of breast or lactation associated with childbirth [KB60.1] Syndrome of infant of a diabetic mother, type 1 or 2, nongestational, insulin dependent Definition: Describes the range of effects on the infant born to a woman with pregestational diabetes mellitus (type 1 or type 2). Common neonatal effects include macrosomia, intrauterine growth restriction, birth injuries, congenital anomalies, hypoglycaemia, respiratory distress, caudal regression syndrome and hypertrophic cardiomyopathy. Also known as: Syndrome of infant of a diabetic mother, type 1 or 2, nongestational, insulin dependent \| infant of a diabetic mother syndrome \| maternal diabetes syndrome \| syndrome of infant of diabetic mother \| infant of diabetic mother [1C1D.0] Primary yaws Definition: Primary yaws results from primary inoculation of Treponema pallidum subsp. pertenue into the skin, manifesting 2-12 weeks later as a localised papule (initial, primary or ‘mother' yaw) before developing into a large non-tender ulcerating nodule, often resembling a raspberry (hence the name ‘framboesia’). The primary lesion is most commonly located on the legs and ankles may also be found on the buttocks, arms, hands, and face. It usually heals after 3–6 months and is still present at the onset o Also known as: Primary yaws \| Chancre of yaws \| Primary framboesia \| initial lesions of yaws \| mother yaw Includes: Chancre of yaws \| Primary framboesia [KD35] Neonatal withdrawal syndrome from maternal use of drugs of addiction Definition: Intrauterine exposure to addictive drugs can lead to neonatal withdrawal symptoms. Withdrawal symptoms are usually neurological, preventing normal autonomic function. The clinical presentation of drug withdrawal is variable and dependent on several factors, such as, the type and dose of drug used and rate of metabolism and excretion of the mother and infant. Also known as: Neonatal withdrawal syndrome from maternal use of drugs of addiction \| Drug withdrawal syndrome in infant of dependent mother \| Neonatal abstinence syndrome \| drug withdrawal syndrome in newborn \| neonatal drug withdrawal syndrome Includes: Drug withdrawal syndrome in infant of dependent mother \| Neonatal abstinence syndrome Excludes: Fetus or newborn affected by maternal anaesthesia or analgesia in pregnancy, labour or delivery [KB60.0] Syndrome of infant of mother with gestational diabetes Definition: Describes the range of effects on the infant born to a woman with gestational diabetes (onset or first recognition of carbohydrate intolerance of variable severity in pregnancy). Common neonatal effects include macrosomia, intrauterine growth restriction, birth injuries, congenital anomalies, hypoglycaemia, respiratory distress, and hypertrophic cardiomyopathy. Also known as: Syndrome of infant of mother with gestational diabetes \| infant of mother with gestational diabetes \| IGDM - [infant of gestational diabetic mother] \| Fetus or newborn with hypoglycaemia affected by maternal gestational diabetes \| Fetus or newborn affected by maternal gestational diabetes [6E20] Mental or behavioural disorders associated with pregnancy, childbirth or the puerperium, without psychotic symptoms Definition: A syndrome associated with pregnancy or the puerperium (commencing within about 6 weeks after delivery) that involves significant mental and behavioural features, most commonly depressive symptoms. The syndrome does not include delusions, hallucinations, or other psychotic symptoms. If the symptoms meet the diagnostic requirements for a specific mental disorder, that diagnosis should also be assigned. This designation should not be used to describe mild and transient depressive symptoms that do Also known as: Mental or behavioural disorders associated with pregnancy, childbirth or the puerperium, without psychotic symptoms \| mental or behavioural disorders associated with pregnancy, childbirth or the puerperium, without psychotic features \| Postpartum depression NOS \| postnatal depression NOS \| puerperal depression NOS [KD34] Reactions or intoxications due to drugs administered to fetus or newborn Definition: A group of paediatric substance-induced conditions associated with health interventions applied to a fetus or newborn using pharmaceutical products. Also known as: Reactions or intoxications due to drugs administered to fetus or newborn \| newborn drug intoxication \| Chloramphenicol toxicity in the newborn \| Grey baby syndrome \| Grey baby Excludes: Withdrawal symptoms from therapeutic use of drugs in newborn \| Neonatal hyperbilirubinaemia due to drugs or toxins transmitted from mother \| reactions and intoxications from maternal opiates, tranquillizers and other medication [KB08.2] Congenital hypotonia Definition: A paediatric condition characterised by abnormally decreased muscle tone that is present at birth in a newborn. Also known as: Congenital hypotonia \| floppy baby \| floppy baby syndrome \| floppy infant \| floppy infant syndrome Includes: Nonspecific floppy baby syndrome [LD90.Y] Other specified conditions with disorders of intellectual development as a relevant clinical feature Also known as: Other specified conditions with disorders of intellectual development as a relevant clinical feature \| Non-syndromic conditions with disorders of intellectual development as a relevant clinical feature \| Autosomal dominant non-syndromic intellectual deficit \| Autosomal recessive non-syndromic intellectual deficit \| X-linked non-syndromic intellectual deficit [EC20.02] Autosomal recessive congenital ichthyosis Definition: A heterogeneous group of genetically-determined ichthyoses with autosomal recessive inheritance. Also known as: Autosomal recessive congenital ichthyosis \| Congenital non-bullous ichthyosiform erythroderma \| Congenital ichthyotic ichthyosis \| Lamellar ichthyosis \| Collodion baby === GRAPH WALKS === --- Walk 1 --- [QA48.1] Care or examination of lactating mother --EXCLUDES--> [?] Certain specified disorders of breast or lactation associated with childbirth --CHILD--> [?] Other or unspecified disorders of breast associated with childbirth --- Walk 2 --- [QA48.1] Care or examination of lactating mother --EXCLUDES--> [?] Certain specified disorders of breast or lactation associated with childbirth --CHILD--> [?] Retracted nipple associated with childbirth Def: A condition characterised as the abnormal inversion of a nipple that does not return to normal position even when stimulated that has occurred in association with childbirth.... --- Walk 3 --- [KB60.1] Syndrome of infant of a diabetic mother, type 1 or 2, nongestational, insulin dependent Def: Describes the range of effects on the infant born to a woman with pregestational diabetes mellitus (type 1 or type 2). Common neonatal effects include macrosomia, intrauterine growth restriction, birt... --PARENT--> [KB60] Transitory disorders of carbohydrate metabolism specific to fetus or newborn Def: A group of paediatric conditions in which there is a temporary disorder in a newborn or infant associated with abnormal chemical reactions in the body disrupting the process of getting or making energ... --PARENT--> [?] Transitory endocrine or metabolic disorders specific to fetus or newborn Def: A group of paediatric conditions in which there is a temporary disorder in a newborn or infant associated with changes in hormone production or utilization (endocrine system) or when abnormal chemical... --- Walk 4 --- [KB60.1] Syndrome of infant of a diabetic mother, type 1 or 2, nongestational, insulin dependent Def: Describes the range of effects on the infant born to a woman with pregestational diabetes mellitus (type 1 or type 2). Common neonatal effects include macrosomia, intrauterine growth restriction, birt... --PARENT--> [KB60] Transitory disorders of carbohydrate metabolism specific to fetus or newborn Def: A group of paediatric conditions in which there is a temporary disorder in a newborn or infant associated with abnormal chemical reactions in the body disrupting the process of getting or making energ... --PARENT--> [?] Transitory endocrine or metabolic disorders specific to fetus or newborn Def: A group of paediatric conditions in which there is a temporary disorder in a newborn or infant associated with changes in hormone production or utilization (endocrine system) or when abnormal chemical... --- Walk 5 --- [1C1D.0] Primary yaws Def: Primary yaws results from primary inoculation of Treponema pallidum subsp. pertenue into the skin, manifesting 2-12 weeks later as a localised papule (initial, primary or ‘mother' yaw) before developi... --PARENT--> [1C1D] Yaws Def: An infectious disease caused by Treponema pallidum subsp. pertenue which mainly affects children in rural communities in the humid tropics. It affects the skin and bones, is spread by skin to skin con... --CHILD--> [1C1D.2] Tertiary yaws Def: Tertiary yaws develops in <10% of untreated infected individuals after and interval of 5 years or more. The late stage skin lesions are characterised by gummatous nodules with necrotic tissue destruct... --- Walk 6 --- [1C1D.0] Primary yaws Def: Primary yaws results from primary inoculation of Treponema pallidum subsp. pertenue into the skin, manifesting 2-12 weeks later as a localised papule (initial, primary or ‘mother' yaw) before developi... --PARENT--> [1C1D] Yaws Def: An infectious disease caused by Treponema pallidum subsp. pertenue which mainly affects children in rural communities in the humid tropics. It affects the skin and bones, is spread by skin to skin con... --CHILD--> [1C1D.1] Secondary yaws Def: Secondary yaws results from lymphatic and haematogenous spread of Treponema pallidum subsp. pertenue spirochaetes from the initial inoculation site and appears from a few weeks to 2 years after the pr...	[ "[QA48.1] Care or examination of lactating mother\n --EXCLUDES--> [?] Certain specified disorders of breast or lactation associated with childbirth\n --CHILD--> [?] Other or unspecified disorders of breast associated with childbirth", "[QA48.1] Care or examination of lactating mother\n --EXCLUDES--> [?] Certain specified disorders of breast or lactation associated with childbirth\n --CHILD--> [?] Retracted nipple associated with childbirth\n Def: A condition characterised as the abnormal inversion of a nipple that does not return to normal position even when stimulated that has occurred in association with childbirth....", "[KB60.1] Syndrome of infant of a diabetic mother, type 1 or 2, nongestational, insulin dependent\n Def: Describes the range of effects on the infant born to a woman with pregestational diabetes mellitus (type 1 or type 2). Common neonatal effects include macrosomia, intrauterine growth restriction, birt...\n --PARENT--> [KB60] Transitory disorders of carbohydrate metabolism specific to fetus or newborn\n Def: A group of paediatric conditions in which there is a temporary disorder in a newborn or infant associated with abnormal chemical reactions in the body disrupting the process of getting or making energ...\n --PARENT--> [?] Transitory endocrine or metabolic disorders specific to fetus or newborn\n Def: A group of paediatric conditions in which there is a temporary disorder in a newborn or infant associated with changes in hormone production or utilization (endocrine system) or when abnormal chemical...", "[KB60.1] Syndrome of infant of a diabetic mother, type 1 or 2, nongestational, insulin dependent\n Def: Describes the range of effects on the infant born to a woman with pregestational diabetes mellitus (type 1 or type 2). Common neonatal effects include macrosomia, intrauterine growth restriction, birt...\n --PARENT--> [KB60] Transitory disorders of carbohydrate metabolism specific to fetus or newborn\n Def: A group of paediatric conditions in which there is a temporary disorder in a newborn or infant associated with abnormal chemical reactions in the body disrupting the process of getting or making energ...\n --PARENT--> [?] Transitory endocrine or metabolic disorders specific to fetus or newborn\n Def: A group of paediatric conditions in which there is a temporary disorder in a newborn or infant associated with changes in hormone production or utilization (endocrine system) or when abnormal chemical...", "[1C1D.0] Primary yaws\n Def: Primary yaws results from primary inoculation of Treponema pallidum subsp. pertenue into the skin, manifesting 2-12 weeks later as a localised papule (initial, primary or ‘mother' yaw) before developi...\n --PARENT--> [1C1D] Yaws\n Def: An infectious disease caused by Treponema pallidum subsp. pertenue which mainly affects children in rural communities in the humid tropics. It affects the skin and bones, is spread by skin to skin con...\n --CHILD--> [1C1D.2] Tertiary yaws\n Def: Tertiary yaws develops in <10% of untreated infected individuals after and interval of 5 years or more. The late stage skin lesions are characterised by gummatous nodules with necrotic tissue destruct...", "[1C1D.0] Primary yaws\n Def: Primary yaws results from primary inoculation of Treponema pallidum subsp. pertenue into the skin, manifesting 2-12 weeks later as a localised papule (initial, primary or ‘mother' yaw) before developi...\n --PARENT--> [1C1D] Yaws\n Def: An infectious disease caused by Treponema pallidum subsp. pertenue which mainly affects children in rural communities in the humid tropics. It affects the skin and bones, is spread by skin to skin con...\n --CHILD--> [1C1D.1] Secondary yaws\n Def: Secondary yaws results from lymphatic and haematogenous spread of Treponema pallidum subsp. pertenue spirochaetes from the initial inoculation site and appears from a few weeks to 2 years after the pr..." ]	QA48.1	Care or examination of lactating mother	[ { "from_icd11": "QA48.1", "icd10_code": "Z391", "icd10_title": "Encounter for care and examination of lactating mother" }, { "from_icd11": "KB60.1", "icd10_code": "P701", "icd10_title": "Syndrome of infant of a diabetic mother" }, { "from_icd11": "1C1D.0", "icd10_code": "A660", "icd10_title": "Initial lesions of yaws" }, { "from_icd11": "KD35", "icd10_code": "P961", "icd10_title": "Neonatal withdrawal symptoms from maternal use of drugs of addiction" }, { "from_icd11": "KB60.0", "icd10_code": "P700", "icd10_title": "Syndrome of infant of mother with gestational diabetes" }, { "from_icd11": "6E20", "icd10_code": "F53", "icd10_title": "Mental and behavioral disorders associated with the puerperium, not elsewhere classified" }, { "from_icd11": "KD34", "icd10_code": "P93", "icd10_title": "Reactions and intoxications due to drugs administered to newborn" }, { "from_icd11": "KB08.2", "icd10_code": "P942", "icd10_title": "Congenital hypotonia" }, { "from_icd11": "EC20.02", "icd10_code": "Q828", "icd10_title": "Other specified congenital malformations of skin" }, { "from_icd11": "EC20.02", "icd10_code": "Q804", "icd10_title": "Harlequin fetus" }, { "from_icd11": "EC20.02", "icd10_code": "Q802", "icd10_title": "Lamellar ichthyosis" } ]	Z391	Encounter for care and examination of lactating mother
In the following, the 5 fictional case vignettes are presented, together with the respective solutions proposed by the algorithm. Findings that were not covered by the initial vignettes, are pointed out. The general estimation, or “next steps”, of each case by the app is given. Also, notes on unclear/critical aspects of each case are made. Case 1 Patient basic data: Michael M., male, dob 01.01.1979 (41y/o), non-smoking, no treated hypertension, or diabetes. Symptom: Pain in the right lateral elbow region Fictional diagnosis: Lateral epicondylitis of the humerus (tennis elbow) History: The patient has a normal desk job, but has been doing leisure sports for years. For 10 months now he no longer participates in his previous sport that primarily involved running and instead has started playing badminton with friends twice a week. During this time he has noticed pain in the right (dominant arm) lateral elbow and the nearby forearm muscles, especially in the days after training. This pain is intensified by activities with a firm grip (e.g. opening screw caps, carrying water boxes, etc). These specific complaints have never completely resided and instead have increased in the last few weeks, reaching a 5 of “moderate pain” intensity on a visual analogue scale (VAS), ranging from 1 no pain to 10 worst pain. The patient does not recall any past trauma to this region, and does not have any other complaints in other parts of the body. He has not yet seen a doctor for this reason, but because of the pain, which is now considered to be unpleasant, one day after a game he uses the AI app. Examination results: Pressure pain above the lateral epicondyle of the humerus and pressure pain in the proximal muscles of the forearm with tender muscles. No signs of inflammation such as redness, swelling/articular effusion, overheating, or any lasting disturbance of function in everyday life. Range of motion (ROM) is not restricted, peripheral circulation, motor function and sensitivity are intact. Not anticipated while creating the vignette (and filled in while using the app in this trial): No lumps under the skin on the elbow, no lumps under the skin on the forearm or hand, no muscle cramps in the arms and hands, no bruise on the arm, no reduced mobility of the fingers, no reduced mobility of the wrist. Number of symptom-related questions: 27 General app estimation (“next steps”): People with symptoms similar to yours can usually manage their symptoms safely at home. You could also seek advice by visiting or contacting your local pharmacy. If your symptoms persist longer than expected, if they get worse, or if you notice new symptoms, you should consult a doctor for further assessment and advice. Suggested diagnoses: 1. Tennis elbow (can usually be managed at home): 7 out of 10 people with these symptoms had this condition (➔ suggested therapy: Cryotherapy, medication against pain and inflammation, and physical therapy) 2. Golfer’s elbow (can usually be managed at home): 2 out of 100 people with these symptoms had this condition. 3. Less likely causes: Injury due to chronic overuse of the forearm muscles . Note: no questions were asked about the specific side of the affected elbow (i.e. medial vs. lateral); it was not asked whether the complaints would also become stronger at rest or more so during activity (stated pain: moderate; theoretically: hardly at rest, stronger under stress). Case 2 Patient basic data: Sarah S., female, dob 01.01.1993, (27 y/o), not pregnant, non-smoking, no treated hypertension, or diabetes. Symptom: Pain in left Ankle (joint) Fictional diagnosis: Ankle sprain (distortion of the anterior fibulotalar ligament ) left History: 2 h earlier, the patient had twisted her left foot during volleyball causing supination trauma. With immediate onset of pain, she had stopped playing and limped to the side bench under careful axial load on her left leg. A teammate had given her an ice pack, so she had iced and slightly elevated the leg. Above the lateral ankle a larger swelling has formed, she doesn’t dare attempt full weightbearing anymore, because it is quite painful, which she subjectively reports as “strong” (VAS 8). Worried about a more serious injury, she now uses the app. Examination results: Swelling in the area of the anterior fibulotalar ligament, pressure pain at the anterior distal tip of the lateral malleolus, no pressure pain over syndesmosis or high fibula, muscles of the calf, medial malleolus, deltoid ligament or foot skeleton. Mobility limited due to pain, pronation still possible at approx. 5°, supination associated with pain, dorsal extension/plantar flexion approx. 10°, no wounds, no hematoma visible, peripheral circulation and sensitivity intact (motor function just restricted in the ankle joint). Not anticipated while creating the vignette: N/A Answers suspected not to be answered by the fictional patient: “Do you feel that your ankle is instable?” Number of symptom-related questions: 29 General app estimation (“next steps”): People with symptoms similar to yours may require emergency care. If you think this is an emergency you should go to an emergency department without delay. Suggested diagnoses: 1. Sprained ankle without ligament rupture (seek emergency care): 3 out of 10 people with these symptoms had this condition 2. Lateral malleolus fracture (seek emergency care): 2 out of 10 people with these symptoms had this condition 3. Lateral ligament rupture of the ankle (seek emergency care): 2 out of 10 people with these symptoms had this condition 4. Ankle fracture, not further specified (seek emergency care): 1 out of 10 people with these symptoms had this condition Note: N/A Case 3 Patient basic data: Peter P., male, dob 01.01.2001, (19 y/o), non-smoking, no treated hypertension, or diabetes. Symptom: Pain in left upper thigh Fictional diagnosis: Delayed onset of muscle soreness History: Yesterday the patient had gone on a long hike with friends in the mountains – for the first time in his life. The friends had walked about 15 km with each a 10 kg backpack on paved paths in hilly terrain. The patient sustained no trauma. He found the uphill climbs very tiring. His other sports activities have been limited to school sports and computer games. Movement is now hardly possible, he complains of strong pain (VAS 7) in the quadriceps muscles and the buttocks, and displays a strong limping gait. After a quiet night, he now woke up with the above-mentioned symptoms and decided to use the app since he is deeply concerned about this unknown condition. Examination results: No observed circumferential increase, pressure pain over the thigh muscles ventrally, not dorsally; pressure pain over the gluteal muscles; no discomfort in the lower leg or anywhere else in the body; only axial loading is possible. Active ROM in the hip and knee joint is limited due to the pain in the thigh; passive movement is possible with light stretching exercises. Peripheral circulation, motor function and sensitivity is intact, no wounds, no hematoma visible. Not anticipated while creating the vignette (and filled in while using the app in this trial): Feeling of heavy legs, no lumps under the skin of the thighs Answers suspected not to be answered by the fictional patient: N/A Number of symptom-related questions: 22 General app estimation (“next steps”): People with symptoms similar to yours can usually manage their symptoms safely at home. You could also seek advice by visiting or contacting your local pharmacy. If your symptoms persist longer than expected, if they get worse, or if you notice new symptoms, you should consult a doctor for further assessment and advice. Suggested diagnoses: 1. Delayed-onset muscle soreness of the lower extremity (can usually be managed at home): 5 out of 10 people with these symptoms had this condition 2. Quadriceps strain (can usually be managed at home): 2 out of 10 people with these symptoms had this condition Note: N/A Case 4 Patient basic data: Thomas T, male, dob 01.01.1994, (26 y/o), smoking, no treated hypertension, or diabetes. Symptom: Swollen knee Fictional diagnosis: ACL rupture with chronic instability History: The patient is an amateur soccer player. He does not engage in other sports, and besides soccer, he does not regularly run. Instead he primarily engages in resistance training of the upper body. About 5 months ago, he sustained a knee distortion trauma with pain during a soccer match shortly before the end of the season leading into the winter break. At that time, he also had swelling with pain in the knee, which improved after a few days of rest and sympathetic relief. He did not consult with a doctor, because the pain and swelling improved quickly. Having a good muscle status, he had no further complaints. For about 3 months, during winter break, he had paused playing soccer anyways and had not done any substitute running. He had no problems with his gait and was fine during his desk job and during leisure time. Only when he went down the stairs, he felt a slight instability in his knee and therefore preferred to hold on to the railing. But there were no real events of pain. Now, after resuming soccer, he sensed some instability during every weekend game, combined with pain in the knee joint (VAS 4–5), and swelling, which decreases after 3–4 days. After 5 days of symptomatic rest and almost no complaints, he talked with his friends about this annoying occurrence and how he was not sure of the cause. They suggested he use the app for getting some helpful information. Examination results: Normal gait, Zohlen sign negative, low effusion, no patella embracing pain, no overheating/redness, no pain on palpation over medial/lateral knee joint gap, the popliteal fossa or the tibial head, meniscus signs negative. Lachman test, anterior drawer test, pivot shift test positive; free ROM, peripheral circulation, motor function and sensitivity intact, thigh circumference (20 cm above the knee cap) ipsilateral reduced by 1 cm Not anticipated while creating the vignette (and filled in while using the app in this trial): No morning stiffness, no lumps under the skin behind the knee or over a joint, no shin pain, no calf pain Answers suspected not to be answered by the fictional patient: N/A Number of symptom-related questions: 30 General app estimation (“next steps”): People with symptoms similar to yours may require emergency care. If you think this is an emergency you should go to an emergency department without delay. Suggested diagnoses: 1. Knee bursitis (seek medical advice): 3 out of 10 people with these symptoms had this condition. 2. Anterior cruciate ligament injury (seek emergency care): 1 in 10 people with these symptoms had this condition. 3. Patellar tendinitis (can usually be managed at home): 8 out of 100 people with these symptoms had this condition. 4. Popliteal cyst (seek medical advice): 7 out of 100 people with these symptoms had this condition. 5. Tractus iliotibialis syndrome (can usually be managed at home): 4 out of 100 people with these symptoms had this condition. Note: The patient would have found it difficult to answer many of the questions because the symptoms questioned were no longer present at the time of the examination. Case 5 Patient basic data: Marc C., male, dob 01.01.1997, (23 y/o), smoker, no treated hypertension, or diabetes. Symptom: Headache Fictional diagnosis: Mild concussion (I°) History: During an amateur soccer game (summer, sunny, 26 °C), the patient jumped after the ball and bumped his head against the knee of an opponent player, 1 h ago. No unconsciousness, no vomiting. He notices slight dizziness, which would become worse when standing up or while walking. Leading symptom is a strong dull headache, especially in the area of impact on the back of the head. This area is also painful to the touch. Tilting the head forward intensifies the headache. This is accompanied by moderate nausea. Otherwise, however, the young patient is awake, actively talking and moving, oriented and responsive. No other symptoms reported. He had retreated to a cool room within the sports facility and had drunk moderate amounts of water. Since he still had complaints and was generally dazed, other players advised him to consult the app. Examination results: Patient awake, oriented and cooperative. Retrograde amnesia to the impact event itself; otherwise normal memory of the situation immediately before the trauma, the soccer game, and also the time after the trauma. Headache with painful pressure over the impact region at the back of the head, but no wounds or hematoma. While walking freely slight problems of balance were indicated, but no objective clear swaying, no nystagmus, no pain on pressure or other complaints in the facial region, no discharge from the ears. Visual acuity intact, no eye pain. Cervical and neck region freely movable without pain (also no complaints when moving against resistance). Not anticipated while creating the vignette (and filled in while using the app in this trial): No lumps under the skin on the scalp, no jerking movements of the whole body, no recent decrease in alcohol intake Answers suspected not to be answered by the fictional patient: N/A Number of symptom-related questions: 33 General app estimation (“next steps”): People with symptoms similar to yours may require emergency care. If you think this is an emergency the safest thing to do is call an ambulance. Suggested diagnoses: 1. Concussion (seek medical advice): 5 out of 10 people with these symptoms had this condition. 2. Acute subdural hematoma (seek emergency care): 1 out of 10 people with these symptoms had this condition. 3. Whiplash (seek medical advice): 3 out of 100 people with these symptoms had this condition. 4. Acute intracranial epidural hematoma (seek emergency care): 2 out of 100 people with these symptoms had this condition. 5. Skull fracture (seek emergency care): 1 out of 100 people with these symptoms had this condition. Note: A worsening of the condition, e.g. a clouding with slowly progressive brain swelling, could not necessarily be detected with the single app use.	3.841797	0.964844	sec[2]/p[0]	en	0.999996	33593428	https://doi.org/10.1186/s13102-021-00243-x	[ "pain", "this", "people", "these", "emergency", "seek", "while", "knee", "fictional", "muscles" ]	[ { "code": "MG3Z", "title": "Pain, unspecified" }, { "code": "8E43.Z", "title": "Pain disorders, unspecified" }, { "code": "MG31.Z", "title": "Acute pain, unspecified" }, { "code": "MG30.Z", "title": "Chronic pain, unspecified" }, { "code": "FB56.2", "title": "Myalgia" }, { "code": "4A01.03", "title": "Transient hypogammaglobulinaemia of infancy" }, { "code": "QE50.2", "title": "Problem associated with relationships with people at work" }, { "code": "9B71.1&XS5S", "title": "Hypertensive Retinopathy, Stage 2, focal arteriolar narrowing, marked generalised arteriolar narrowing, arteriovenous nicking, opacity, “copper wiring” of arteriolar wall, or a combination of these signs" }, { "code": "9B71.1&XS00", "title": "Hypertensive Retinopathy, Stage 3, Haemorrhage, blot, dot, or flame-shaped, microaneurysm, cotton-wool spot, hard exudate, or combination of these signs" }, { "code": "JB22.1", "title": "Delivery by emergency caesarean section" } ]	=== ICD-11 CODES FOUND === [MG3Z] Pain, unspecified Also known as: Pain, unspecified \| pain observations \| pain NOS \| generalised pain \| generalised pain, NOS [8E43.Z] Pain disorders, unspecified Also known as: Pain disorders, unspecified \| Pain disorders [MG31.Z] Acute pain, unspecified Also known as: Acute pain, unspecified \| Acute pain [MG30.Z] Chronic pain, unspecified Also known as: Chronic pain, unspecified \| Chronic pain [FB56.2] Myalgia Definition: This is a disorder characterised by pain in a muscle or group of muscles. Also known as: Myalgia \| muscle ache \| muscle soreness \| muscular pain \| myalgic Excludes: Chronic primary musculoskeletal pain \| Chronic secondary musculoskeletal pain [4A01.03] Transient hypogammaglobulinaemia of infancy Also known as: Transient hypogammaglobulinaemia of infancy \| immunoglobulin maturational delay \| THI - [transient hypogammaglobulinaemia of infancy] [QE50.2] Problem associated with relationships with people at work Also known as: Problem associated with relationships with people at work \| discord with boss or workmates [JB22.1] Delivery by emergency caesarean section Also known as: Delivery by emergency caesarean section \| emergency caesarean === GRAPH WALKS === --- Walk 1 --- [MG3Z] Pain, unspecified --PARENT--> [?] Pain --PARENT--> [?] General symptoms --- Walk 2 --- [MG3Z] Pain, unspecified --PARENT--> [?] Pain --EXCLUDES--> [?] Mastodynia Def: The symptom of breast pain. This symptom may be classified as cyclic or non-cyclical depending on the clinical patterns.... --- Walk 3 --- [8E43.Z] Pain disorders, unspecified --PARENT--> [8E43] Pain disorders --EXCLUDES--> [?] Chronic neuropathic pain Def: Chronic neuropathic pain is chronic pain caused by a lesion or disease of the somatosensory nervous system. The pain may be spontaneous or evoked, as an increased response to a painful stimulus (hyper... --- Walk 4 --- [8E43.Z] Pain disorders, unspecified --PARENT--> [8E43] Pain disorders --CHILD--> [8E43.0] Neuropathic pain Def: Neuropathic pain is described as electric, burning, or shock like, caused by metabolic, nutritional, infectious, genetic, autoimmune, and/or vasculitic processes. The pain may occur spontaneously, wit... --- Walk 5 --- [MG31.Z] Acute pain, unspecified --PARENT--> [MG31] Acute pain Def: Pain with a duration of less than 3 months. This code should be used only when there is no further specification of site.... --CHILD--> [MG31.2] Acute postoperative pain, not elsewhere classified Def: Pain at the intervention site or caused by an intervention.... --- Walk 6 --- [MG31.Z] Acute pain, unspecified --PARENT--> [MG31] Acute pain Def: Pain with a duration of less than 3 months. This code should be used only when there is no further specification of site.... --CHILD--> [MG31.2] Acute postoperative pain, not elsewhere classified Def: Pain at the intervention site or caused by an intervention....	[ "[MG3Z] Pain, unspecified\n --PARENT--> [?] Pain\n --PARENT--> [?] General symptoms", "[MG3Z] Pain, unspecified\n --PARENT--> [?] Pain\n --EXCLUDES--> [?] Mastodynia\n Def: The symptom of breast pain. This symptom may be classified as cyclic or non-cyclical depending on the clinical patterns....", "[8E43.Z] Pain disorders, unspecified\n --PARENT--> [8E43] Pain disorders\n --EXCLUDES--> [?] Chronic neuropathic pain\n Def: Chronic neuropathic pain is chronic pain caused by a lesion or disease of the somatosensory nervous system. The pain may be spontaneous or evoked, as an increased response to a painful stimulus (hyper...", "[8E43.Z] Pain disorders, unspecified\n --PARENT--> [8E43] Pain disorders\n --CHILD--> [8E43.0] Neuropathic pain\n Def: Neuropathic pain is described as electric, burning, or shock like, caused by metabolic, nutritional, infectious, genetic, autoimmune, and/or vasculitic processes. The pain may occur spontaneously, wit...", "[MG31.Z] Acute pain, unspecified\n --PARENT--> [MG31] Acute pain\n Def: Pain with a duration of less than 3 months.\n\nThis code should be used only when there is no further specification of site....\n --CHILD--> [MG31.2] Acute postoperative pain, not elsewhere classified\n Def: Pain at the intervention site or caused by an intervention....", "[MG31.Z] Acute pain, unspecified\n --PARENT--> [MG31] Acute pain\n Def: Pain with a duration of less than 3 months.\n\nThis code should be used only when there is no further specification of site....\n --CHILD--> [MG31.2] Acute postoperative pain, not elsewhere classified\n Def: Pain at the intervention site or caused by an intervention...." ]	MG3Z	Pain, unspecified	[ { "from_icd11": "MG3Z", "icd10_code": "R52", "icd10_title": "Pain, unspecified" }, { "from_icd11": "MG3Z", "icd10_code": "R529", "icd10_title": "" }, { "from_icd11": "MG31.Z", "icd10_code": "R520", "icd10_title": "" }, { "from_icd11": "MG30.Z", "icd10_code": "R521", "icd10_title": "" }, { "from_icd11": "MG30.Z", "icd10_code": "R522", "icd10_title": "" }, { "from_icd11": "FB56.2", "icd10_code": "M7918", "icd10_title": "Myalgia, other site" }, { "from_icd11": "FB56.2", "icd10_code": "M7910", "icd10_title": "Myalgia, unspecified site" }, { "from_icd11": "FB56.2", "icd10_code": "M7912", "icd10_title": "Myalgia of auxiliary muscles, head and neck" }, { "from_icd11": "FB56.2", "icd10_code": "M791", "icd10_title": "Myalgia" }, { "from_icd11": "4A01.03", "icd10_code": "D807", "icd10_title": "Transient hypogammaglobulinemia of infancy" }, { "from_icd11": "QE50.2", "icd10_code": "Z564", "icd10_title": "Discord with boss and workmates" }, { "from_icd11": "JB22.1", "icd10_code": "O821", "icd10_title": "" } ]	R52	Pain, unspecified
A 46-year-old Japanese man without a remarkable medical history visited our hospital with chief complaints of fever, fatigue, generalized edema, and abdominal distention. His fever started two weeks prior to admission. Abdominal distention and edema gradually worsened, and he gained 7 kg of weight within two weeks, despite low food intake owing to loss of appetite. He denied previous episodes of infectious diseases. At initial presentation, he appeared exhausted. His vital signs were as follows: body temperature, 37.8 °C; blood pressure, 160/93 mmHg; heart rate, 109 beats/min; respiratory rate, 22 breathes/min; and oxygen saturation, 90% with room air. On physical examination, generalized pitting edema was observed. His heart sounds were normal, but his lung sounds were weak at the lung base on both sides. Jaundice was not observed, but a distended abdomen and hepatomegaly were observed. Blood test results on the day of admission revealed an elevated white blood cell (WBC) count (14,600/μL), mild anemia (hemoglobin level, 11.1 g/dL), thrombocytopenia (platelet count, 11.1 × 10 4 /μL), renal impairment (blood urea nitrogen level, 60.7 mg/dL and serum creatinine level, 2.94 mg/dL), an elevated C-reactive protein (CRP) level (14.25 mg/dL), an elevated ALP level (768 U/L), polyclonal hypergammaglobulinemia , and an elevated IgG4 level (235 mg/dL). Immunological screening test results for autoantibodies were negative, except for positive antinuclear antibody (× 40) and anti-SS-A antibody. Polymerase chain reaction for HHV-8 DNA in a serum sample was negative (Table 1 ). Computed tomography (CT) performed on the day of admission revealed massive pleural effusions and ascites, generalized mild lymphadenopathy (< 1.5 cm in diameter), and hepatosplenomegaly . Echocardiography performed on day 2 revealed normal wall motions without any sign of valvular disease, but a collapsed inferior vena cava was observed (maximum diameter < 5 mm). 18 F–fluorodeoxyglucose positron emission tomography (FDG-PET) revealed no apparent FDG uptake, except for slight uptake in the para-aortic lymph nodes . Considering the positive anti-SS-A antibody finding, lip biopsy was performed on day 6, but the pathological findings did not meet the criteria for Sjögren syndrome (SjS). On ophthalmological examination, keratoconjunctivitis was not observed; however, bilateral optic edema was remarkable . Serum IL-6 and plasma VEGF levels were assessed in a blood sample obtained on day 9, and both were elevated (25.2 pg/mL and 224 pg/mL, respectively). Abdominal paracentesis was performed on the same day, and the levels of IL-6 and vascular endothelial growth factor (VEGF) in ascites were remarkably high . Bone marrow examination was performed on day 9. Bone marrow aspiration was dry tap, and bone marrow biopsy revealed a mild increase in megakaryocytes and mild reticulin myelofibrosis on silver impregnation staining . Biopsy of a cervical lymph node was performed on day 10, and the pathological findings were compatible with a mixed-type MCD histology . We suspected TAFRO syndrome and methylprednisolone (mPSL) pulse therapy (500 mg/day for three consecutive days) was initiated on day 10 after lymph node biopsy, followed by intravenous PSL (40 mg/day) and oral CsA administration. The disease severity of TAFRO syndrome one day prior to treatment initiation was very severe (grade 5) . After the initiation of immunosuppressive treatment, the patient became afebrile and the CRP level returned to the normal range within two weeks. However, the patient’s platelet count and serum creatinine level as well as his overall condition did not improve, even after the initiation of immunosuppressive treatment . A central venous catheter was inserted and total parenteral nutrition was started as he could not eat owing to loss of appetite and refusal of tubal feeding. Diuretics, including furosemide, potassium canrenoate, trichlormethiazide, and tolvaptan were administered during hospitalization; however, the amount of ascites did not decrease . Urinalysis performed on day 25 revealed mild proteinuria (0.34 g/day) with a fractional excretion of sodium of 5.1% and a fractional excretion of urea nitrogen (FE UN ) of 20.7%. Because urinalysis was performed under diuretics use, considering FE UN level and intravascular hypovolemia on echography, intravenous fluid replacement was performed to correct the pre-renal factor responsible for renal impairment. However, the patient’s volume depletion and blood pressure did not respond well to intravenous fluid replacement. Abdominal paracentesis was again performed on day 40, and it revealed persistently high levels of IL-6 and VEGF . Although urine volume was initially preserved with diuretic administration, the patient became oliguric from day 47 and anuric from day 49. He was hemodynamically unstable on day 50 (body temperature, 37.5 °C; blood pressure, 84/52 mmHg; heart rate, 109 beats/min; respiratory rate, 24 breaths/min; oxygen saturation, 95% with room air). As the patient was undergoing immunosuppressive therapy and his CRP levels increased by 10.08 mg/dL on the same day, systemic examination was performed to rule out the possibility of infectious disease. Analysis of ascites was performed on the same day, revealing purulent ascites, and Escherichia coli was isolated. E. coli was also isolated from blood cultures. CT of the chest showed a mass in the right lung in addition to scattered appearance of high intensity regions in the myocardium, which were newly observed . Blood tests performed on day 50 revealed elevated β- d -glucan levels (23.0 pg/mL) and positive cytomegalovirus (CMV) antigenemia (41 cells/5 × 10 4 WBCs on the C7-HRP test). Aspergillus , Candida mannan , and Cryptococcus neoformans antigens were negative. We suspected bacterial peritonitis and fungal pneumonia. Intravenous meropenem, vancomycin, and caspofungin were initiated on the same day. Continuous renal replacement therapy (CRRT) using a polymethyl-methacrylate membrane was also initiated on the same day because anuria did not improve and the patient was hemodynamically unstable. Conditions of CRRT were as follows: mode, continuous hemodiafiltration; dialysis membrane, CH-1.8 W (Toray Medical Co., Ltd., Tokyo Japan); and anticoagulant, nafamostat mesilate. The blood, dialysate, substitute, and filtration flow rates were 100 mL/min, 400 mL/h, 400 mL/h, and 800 mL/h, respectively. Table 1 Laboratory findings of the present case Complete blood count Blood urea nitrogen 60.7 mg/dL Serum M protein Negative White blood cell 14,600 /μL Creatinine 2.94 mg/dL Platelet-associated IgG 238.0 ng/10 7 cells Neutrophil 84.6% C-reactive protein 14.25 mg/dL Anti-platelet Ab Negative Lymphocyte 9.4% β-D-glucan < 6.0 pg/mL Soluble IL-2 receptor 1120 U/mL Monocyte 5.6% Ferritin 419 ng/mL Direct Coombs test Negative Basophil 0.1% Serum iron 9 μg/dL Indirect Coombs test Negative Eosinophil 0.0% Total iron binding capacity 155 μg/dL IL-6 (serum, on day 9) 25.2 pg/mL Red blood cell 426 × 10 4 /μL Haptoglobin 268 mg/dL VEGF (plasma, on day 9) 224 pg/mL Hemoglobin 11.7 g/dL Thyroid stimulating hormone 6.4 μIU/ml IL-6 (ascites, on day 9) 3310 pg/mL Hematocrit 34.8% Free T3 1.4 pg/ml VEGF (ascites, on day 9) 335 pg/mL Reticulocyte 15‰ Free T4 1.1 ng/dl STS Negative Platelet 11.1 × 10 4 /μL BNP 61 pg/mL HBs Ag Negative IPF 10.9% CEA 0.5 U/mL HBs Ab Negatve Coagulation test CA19–9 5 ng/mL HBc Ab Negative APTT 45.3 s IgA 264 mg/dL HCV Ab Negative PT-INR 1.30 IgG 2461 mg/dL HIV Ab Negative Fibrinogen 479 mg/dL IgG4 235 mg/dL IFN-γ release assay Negative Blood chemistry and immunological tests IgM 88 mg/dL Helicobacter pylori IgG Negative Sodium 138 mEq/L ANA Positive (×40) CMV-IgG Positive Potassium 4.1 mEq/L RF 2 U/mL CMV-IgM Negative Chloride 101 mEq/L CH50 44.9 U/mL EBV VCA-IgG Ab Positive Calcium 8.1 mg/dL C3 50 mg/dL EBV VCA-IgM Ab Negative Total protein 6.4 g/dL C4 14 mg/dL EBNA Ab Positive Albumin 2.1 g/dL Anti-ds-DNA IgG Ab Negative HHV-8 DNA PCR Negative Total bilirubin 0.7 mg/dL PR3-ANCA Negative Bacterial cultures Asparate aminotransferase 28 U/L MPO-ANCA Negative Blood cultures Negative Alanine aminotransferase 12 U/L Anti-SS-A Ab > 1200 U/mL Ascitic fluid cultures Negative Lactate dehydrogenase 278 U/L Anti-SS-B Ab Negative Urine culture Negative Alkali phosphatase 768 U/L Anti-CL Ab Negative Urinalysis γ- glutamyltransferase 129 U/L Anti-CLβ 2 GPI Ab Negative Protein (1+) Amylase 50 U/L Anti-Scl-70 Ab Negative Occult blood (−) Creatine kinase 694 U/L Anti-RNP Ab Negative NAG 44.8 U/L Glucose 121 mg/dL Anti-Sm Ab Negative β2-MG 81 μg/L Hemoglobin A1c 5.3% Anti-mitochondrial M2 Ab Negative Granular casts 10–19 /WF Uric acid 15.1 mg/dL Anti-smooth muscle Ab Negative BJP Negative β2-MG β2-microglobulin. Ab antibody, ANA antinuclear antibody, APTT activated partial thromboplastin time, BJP Bence Jones protein BNP brain natriuretic peptide, C3 complement component 3, C4 complement component 4, CA 19–9 carbohydrate antigen 19–9, CEA carcinoembryonic antigen, CH50 50% hemolytic complement activity, CL cardiolipin, CMV cytomegalovirus, ds-DNA double stranded-DNA, EBNA Epstein-Barr virus-nuclear antigen, EBV Epstein-Barr virus, GPI glycoprotein I, HBc Ab hepatitis B core antibody, HBs Ag hepatitis B surface antigen, HCV hepatitis C virus, HHV-8 human herpes virus-8, HIV human immunodeficiency virus, IFN-γ interferon-γ, Ig immunoglobulin, IL interleukin, IPF immature platelet fraction, MPO myeloperoxidase, NAG N-acetyl-β-D-glucosaminidase, PCR polymerase chain reaction, PR3-ANCA proteinase-3-anti-neutrophil cytoplasmic antibody, PT-INR prothrombin time-international normalized ratio, RF rheumatoid factor, RNP ribonucleoprotein, Scl scleroderma, Sm Smith, SS Sjögren syndrome, STS serologic test for syphilis, T3 triiodothyronine, T4 thyroxin, TSH Thyroid stimulating hormone, VEGF vascular endothelial cell growth factor, VCA viral capsid antigen, WF whole field Fig. 1 Imaging findings. a – c Computed tomography images on the day of admission. a Massive pleural effusion and slightly enlarged axillary lymph nodes are observed (arrows). b Hepatosplenomegaly is seen. c Massive ascites and slightly enlarged para-aortic lymph nodes are observed (arrows). d 18 F–fluorodeoxy-glucose positron emission tomography (FDG-PET) images on day 8. Although the findings are poor (FDG uptake is generally weak), FDG uptake is observed in the para-aortic lymph nodes. e Funduscopic evaluation performed on day 10. Bilateral optic disk edema is remarkable. Roth’s spots are observed (arrows). Hemorrhage in the fundus of right eye is also observed Fig. 2 Pathological findings. a , b Pathological evaluation involving bone marrow biopsy in the present case performed on day 9. a Mild increased number of megakaryocytes is observed (hematoxylin and eosin [H&E] staining). b Mild reticulin myelofibrosis in bone marrow is observed (silver impregnation staining). c – h Pathological evaluation of the right neck lymph node in the present case. c , d Atrophic germinal center, vascular invasion with a glomerular-like pattern of vascular endothelial cell proliferation and hyalinization are observed in the follicles (H&E staining). e Dendric proliferation of arterioles and swelling of vascular endothelial cells are observed (H&E staining). f , g Invasion of plasma cells (CD38+) is observed in the intrafollicular space (immunohistochemical staining). h Immunoglobulin G (IgG) 4-positive plasma cells are observed (> 10 IgG4-positive plasma cells/high power field on immunohistochemical staining); however, the IgG4/IgG ratio is 24.2%, and it does not fulfill the criteria for IgG4-related disease (> 40%, data not shown). Human herpesvirus 8 is negative on immunohistochemical staining, and the Epstein-Barr virus-encoded small RNA in situ hybridization is negative in the lymph node (data not shown). These findings are compatible with mixed-type multicentric Castleman disease-like histology Fig. 3 Clinical course of the present case. a , b The patient became afebrile after pulse methylprednisolone therapy. The C-reactive protein (CRP) level decreased to within the normal range with combination therapy involving intravenous glucocorticoid and oral cyclosporine A. However, despite the treatment, the amount of ascites increased gradually and renal impairment did not improve. The CRP and serum creatinine levels were elevated on day 50, and complicated infection was suspected. After the initiation of continuous renal replacement therapy, the patient experienced cardiac arrest on the same day because of myocardial infarction. Despite intensive care, including antibiotics therapy and continuous hemodiafiltration, the patient died on day 52. BT body temperature, Cre creatinine, CRP C-reactive protein, CRRT continuous renal replacement therapy, CsA cyclosporine A, MAP mean arterial pressure, mPSL methylprednisolone, Plt platelet Fig. 4 Imaging and assessments after treatment. a Computed tomography (CT) images of the chest on day 50. Pleural effusion resolved, but a mass lesion (arrows) is newly observed. b – d CT images of the heart on days 31, 48, and 50. Scattered appearance of high intensity is gradually seen in the cardiac wall. CT performed on day 31 shows no remarkable finding in the myocardium. However, high intensity gradually became apparent on CT images obtained on days 48 and 50 (arrows). e – g Electrocardiogram performed after recovery of spontaneous circulation and coronary angiography (CAG) results on day 50. e ST elevations are observed at leads V2–5 and aVL. Reciprocal changes are observed at leads I, II, and aVF on electrocardiography. f CAG shows complete occlusion of the left descending coronary artery (arrows). g After percutaneous old balloon angioplasty, reperfusion of blood flow is achieved	4.039063	0.974121	sec[1]/p[0]	en	0.999998	34171004	https://doi.org/10.1186/s41100-018-0157-8	[ "blood", "anti", "ascites", "serum", "protein", "lymph", "staining", "platelet", "renal", "antibody" ]	[ { "code": "3C0Z", "title": "Diseases of the blood or blood-forming organs, unspecified" }, { "code": "MF50.4Z", "title": "Haematuria, unspecified" }, { "code": "MA12.1", "title": "Finding of cocaine in blood" }, { "code": "MA12.4", "title": "Finding of steroid agent in blood" }, { "code": "MA12.2", "title": "Finding of hallucinogen in blood" }, { "code": "JA86.Y", "title": "Maternal care for other specified fetal problems" }, { "code": "MB23.1", "title": "Antisocial behaviour" }, { "code": "3B4Z", "title": "Coagulation defects, unspecified" }, { "code": "4A45.Z", "title": "Antiphospholipid syndrome, unspecified" }, { "code": "4A43.Y", "title": "Other specified overlap non-organ specific systemic autoimmune disease" } ]	=== ICD-11 CODES FOUND === [3C0Z] Diseases of the blood or blood-forming organs, unspecified Also known as: Diseases of the blood or blood-forming organs, unspecified \| Blood, lymph or spleen disease \| blood condition NOS \| blood disorder NOS \| bone marrow disease NOS [MF50.4Z] Haematuria, unspecified Also known as: Haematuria, unspecified \| Haematuria \| blood in urine \| urinary blood \| haematuria NOS [MA12.1] Finding of cocaine in blood Also known as: Finding of cocaine in blood \| cocaine in blood [MA12.4] Finding of steroid agent in blood Also known as: Finding of steroid agent in blood \| steroid in blood [MA12.2] Finding of hallucinogen in blood Also known as: Finding of hallucinogen in blood \| hallucinogen in blood [JA86.Y] Maternal care for other specified fetal problems Also known as: Maternal care for other specified fetal problems \| Maternal care for other isoimmunization \| Isoimmunization NOS \| maternal antibodies NOS \| pregnancy management affected by incompatibility of blood groups NOS [MB23.1] Antisocial behaviour Definition: Behaviour in which the basic rights of others or major age-appropriate societal norms, rules, or laws, are violated. Also known as: Antisocial behaviour \| Child or adolescent antisocial behaviour [3B4Z] Coagulation defects, unspecified Also known as: Coagulation defects, unspecified \| blood clotting disturbance \| blood clotting defect \| blood clotting factor deficiency \| clotting abnormality [4A45.Z] Antiphospholipid syndrome, unspecified Also known as: Antiphospholipid syndrome, unspecified \| Antiphospholipid syndrome \| Hughes syndrome \| Anticardiolipin syndrome [4A43.Y] Other specified overlap non-organ specific systemic autoimmune disease Also known as: Other specified overlap non-organ specific systemic autoimmune disease \| Antisynthetase syndrome \| Reynolds syndrome \| Syndromic multisystem autoimmune disease due to ITCH deficiency \| Eosinophilia myalgia syndrome === GRAPH WALKS === --- Walk 1 --- [3C0Z] Diseases of the blood or blood-forming organs, unspecified --PARENT--> [03] Diseases of the blood or blood-forming organs Def: This chapter includes diseases of the blood as well as diseases of blood forming organs.... --RELATED_TO--> [?] Symptoms, signs or clinical findings of blood, blood-forming organs, or the immune system --- Walk 2 --- [3C0Z] Diseases of the blood or blood-forming organs, unspecified --PARENT--> [03] Diseases of the blood or blood-forming organs Def: This chapter includes diseases of the blood as well as diseases of blood forming organs.... --RELATED_TO--> [?] Symptoms, signs or clinical findings of blood, blood-forming organs, or the immune system --- Walk 3 --- [MF50.4Z] Haematuria, unspecified --PARENT--> [MF50.4] Haematuria Def: Hematuria means presence of blood or red blood cells (RBCs) in the urine. There are two types of hematuria: gross hematuria (when one can see the blood in the urine) and microscopic hematuria (when th... --EXCLUDES--> [?] Recurrent or persistent glomerular haematuria Def: The presence in the urine of glomerular origin red blood cells (RBCs). In microscopic haematuria the urine appears normal to the naked eye, but examination with a microscope shows a high number of RBC... --- Walk 4 --- [MF50.4Z] Haematuria, unspecified --PARENT--> [MF50.4] Haematuria Def: Hematuria means presence of blood or red blood cells (RBCs) in the urine. There are two types of hematuria: gross hematuria (when one can see the blood in the urine) and microscopic hematuria (when th... --CHILD--> [MF50.41] Microscopic haematuria --- Walk 5 --- [MA12.1] Finding of cocaine in blood --PARENT--> [MA12] Clinical findings of drugs, medicaments and biological substances in blood, blood-forming organs, or the immune system --CHILD--> [MA12.1] Finding of cocaine in blood --- Walk 6 --- [MA12.1] Finding of cocaine in blood --PARENT--> [MA12] Clinical findings of drugs, medicaments and biological substances in blood, blood-forming organs, or the immune system --CHILD--> [MA12.1] Finding of cocaine in blood	[ "[3C0Z] Diseases of the blood or blood-forming organs, unspecified\n --PARENT--> [03] Diseases of the blood or blood-forming organs\n Def: This chapter includes diseases of the blood as well as diseases of blood forming organs....\n --RELATED_TO--> [?] Symptoms, signs or clinical findings of blood, blood-forming organs, or the immune system", "[3C0Z] Diseases of the blood or blood-forming organs, unspecified\n --PARENT--> [03] Diseases of the blood or blood-forming organs\n Def: This chapter includes diseases of the blood as well as diseases of blood forming organs....\n --RELATED_TO--> [?] Symptoms, signs or clinical findings of blood, blood-forming organs, or the immune system", "[MF50.4Z] Haematuria, unspecified\n --PARENT--> [MF50.4] Haematuria\n Def: Hematuria means presence of blood or red blood cells (RBCs) in the urine. There are two types of hematuria: gross hematuria (when one can see the blood in the urine) and microscopic hematuria (when th...\n --EXCLUDES--> [?] Recurrent or persistent glomerular haematuria\n Def: The presence in the urine of glomerular origin red blood cells (RBCs). In microscopic haematuria the urine appears normal to the naked eye, but examination with a microscope shows a high number of RBC...", "[MF50.4Z] Haematuria, unspecified\n --PARENT--> [MF50.4] Haematuria\n Def: Hematuria means presence of blood or red blood cells (RBCs) in the urine. There are two types of hematuria: gross hematuria (when one can see the blood in the urine) and microscopic hematuria (when th...\n --CHILD--> [MF50.41] Microscopic haematuria", "[MA12.1] Finding of cocaine in blood\n --PARENT--> [MA12] Clinical findings of drugs, medicaments and biological substances in blood, blood-forming organs, or the immune system\n --CHILD--> [MA12.1] Finding of cocaine in blood", "[MA12.1] Finding of cocaine in blood\n --PARENT--> [MA12] Clinical findings of drugs, medicaments and biological substances in blood, blood-forming organs, or the immune system\n --CHILD--> [MA12.1] Finding of cocaine in blood" ]	3C0Z	Diseases of the blood or blood-forming organs, unspecified	[ { "from_icd11": "3C0Z", "icd10_code": "D75A", "icd10_title": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency without anemia" }, { "from_icd11": "3C0Z", "icd10_code": "D7581", "icd10_title": "Myelofibrosis" }, { "from_icd11": "3C0Z", "icd10_code": "D7582", "icd10_title": "Heparin induced thrombocytopenia (HIT)" }, { "from_icd11": "3C0Z", "icd10_code": "D7589", "icd10_title": "Other specified diseases of blood and blood-forming organs" }, { "from_icd11": "3C0Z", "icd10_code": "D759", "icd10_title": "Disease of blood and blood-forming organs, unspecified" }, { "from_icd11": "3C0Z", "icd10_code": "D763", "icd10_title": "Other histiocytosis syndromes" }, { "from_icd11": "3C0Z", "icd10_code": "Q899", "icd10_title": "Congenital malformation, unspecified" }, { "from_icd11": "3C0Z", "icd10_code": "III", "icd10_title": "" }, { "from_icd11": "3C0Z", "icd10_code": "D70-D77", "icd10_title": "" }, { "from_icd11": "3C0Z", "icd10_code": "D75", "icd10_title": "Other and unspecified diseases of blood and blood-forming organs" }, { "from_icd11": "3C0Z", "icd10_code": "D77", "icd10_title": "Other disorders of blood and blood-forming organs in diseases classified elsewhere" }, { "from_icd11": "3C0Z", "icd10_code": "D758", "icd10_title": "Other specified diseases of blood and blood-forming organs" }, { "from_icd11": "3C0Z", "icd10_code": "D76", "icd10_title": "Other specified diseases with participation of lymphoreticular and reticulohistiocytic tissue" }, { "from_icd11": "MF50.4Z", "icd10_code": "R310", "icd10_title": "Gross hematuria" }, { "from_icd11": "MF50.4Z", "icd10_code": "R312", "icd10_title": "Other microscopic hematuria" } ]	D75A	Glucose-6-phosphate dehydrogenase (G6PD) deficiency without anemia
Following the CARE Guidelines, a six-year-old Sudanese female child presented to the emergency department (ED) with a history of an uprolling eye for two minutes. The mother is a 45 year old housewife, and the father is a 55 year old. She has one sister and four brothers, and all are healthy. Negative history of parents’ consanguinity. The mother was following up during her pregnancy with no history of either passive or active smoking, no history of diabetes mellitus (DM) or hypertension, and no history of using any medications. Prenatal, natal, and post-natal care was given. The child is a product of full-term, spontaneous vaginal delivery (SVD) with a birth weight of 4.5 kg, discharged with the mother in good conditions. At five months, the mother noticed head enlargement and sought medical advice. She was diagnosed with obstructive hydrocephalus with lateral ventricular choroid plexus papilloma underwent resection at the age of six months in our center’s neurosurgery department. Postoperative computed tomography (CT) included frontal craniotomy and large extra-axial pneumocephalus with large frontal air-fluid levels causing a mass effect on the brain more dominant in the left hemisphere. A previously noted large cauliflower-like mass in the left ventricle has been resected with multiple small hyperdense masses that could represent residual. Hyperdense area anteriorly within the fluid on the left extra-axial space and another adjacent to the left parietal-temporal lobe most likely representing postoperative hemorrhage. No Acute intra-axial hemorrhage. No acute ischemic insult. Less dilatation of ventricular system as compared to the previous imaging. Periventricular hypodensity likely related to spontaneous fracture (SF) permeation was noted again. A small intraventricular hemorrhage is noted with air in both temporal horns. Cystic area in the posterior fossa communicating with the fourth ventricle with no mass effect consistent with mega cisterna magna. External ventricular drain (EVD) tip was noted in the anterior left lateral ventricle with a right frontal approach. Left frontoparietal-temporal subcutaneous swelling and air are associated with two fractures of the left parietal bone. The patient underwent her first magnetic resonance imaging (MRI) postoperatively. Multiple axial, sagittal, and coronal sequences of the brain with and without IV contrast were used. With no previous MRI examinations available for comparison, a comparison was made with the last examination, a CT study that revealed marked irregular supratentorial ventricular dilatation, which is increased. No MRI evidence of residual or recurrent neoplastic tissue. Diffuse pachymeningeal enhancement is most likely related to meningeal irritation and not due to leptomeningeal metastasis. Left parietal brain gliosis related to previous operative interference. It is still seen as bilateral subdural fluid; however, it is less than seen in the previous examination. No midline shift, no mass effect, no intraventricular hemorrhage and no other significant abnormality was identified. Moreover, at the age of four-year-old, she developed a seizure in the form of focal eye movement. She started on Keppra, requiring pediatric intensive care unit (PICU) admission once last year as a case of status epilepticus. Regarding her current ED visit, the patient was in her usual state of health until 9:30 AM, when she started to have abnormal uprolling eye movements while being fully awake during the episode with normal limb movement and communicating with her mother. The first episode aborted by itself. Furthermore, according to her legal guardian, the patient experienced multiple attacks of vomiting with food content, not projectile. Upon arrival in the ED, she developed another attack with desatting to 70% in room air. However, the second episode aborted after administering diazepam (20 mg/kg). The patient was vitally stable, drowsy, and communicating with her legal guardian. CT did not reveal significant or acute changes or other interval changes besides the previously resected brain tumor, which resulted in dilated lateral ventricles compared to her right ventricles. On physical examination, her pupils were equally reactive to light, she was hypotonic in the right upper limb with normal tone in other limbs, and had hyperreflexia and negative clonus and a negative Babinski sign (plantar reflex). The requested tests included complete blood count (CBC), urea and electrolytes (U&E), and bone function, where they were all within normal range. The case was discussed with a pediatric neurology consultant, and she started on Keppra 30 mg/kg/day divided twice a day (BID) with follow-up in the clinic. The patient was discharged once fully awake. A week later, the patient followed up on her seizure, where she only had four attacks in a previous couple of years in the form of a complex partial seizure. She remained on Keppra with the same dosage and was discharged. Ten days later, she presented to the ED complaining of a seizure lasting for ten minutes with eyes deviating to the left side, according to her legal guardian. The patient presented in post-ictal status in the ED with no significant systematic findings. She was vitally stable with a triage category three until she suddenly deteriorated to 80% in room air, respiratory rate (RR) 12 breaths per minute (BPM), heart rate (HR) 114 with on and off eye deviation to the right side. However, her pupils were three mm reactive to light. The patient, however, was shifted to the resuscitation room and connected to oxygen, and given intravenous (IV) diazepam of six mg (0.2 mg/kg). The patient was well hydrated, with shallow breathing with no added sounds or heart murmurs, and the abdomen was soft and lax with no tenderness or organomegaly. Ambu bagging was initiated, and PICU was contacted for further profound care. During the time, the patient’s pupils were bilaterally equal and reactive to light and maintaining oxygen saturation at 100%. Upon PICU team arrival, the patient developed generalized clonic status epilepticus, code announced, and then the patient was intubated for one day only. Phenytoin and Keppra were given in a loading dose, then started on midazolam infusion of 1 mg/kg/hr and fentanyl as sedation until she was extubated 24 hours later. The patient was stabilized and transferred to the PICU. She did not experience any epileptic seizures and was sleepy. On the next morning (7 AM), the patient entered a state of metabolic acidosis resulting in intervening with four plus 10/kg of Lasix (furosemide) in addition to vancomycin for two doses before discontinuing it. On the next day, the patient was transferred to the medical ward. On the fourth day of the recent admission, the patient’s vitals were as follows: body temperature (Temp.) 36.5, heart rate (HR) 86, oxygen saturation (SaO 2 ) 99% at room air, and blood pressure (BP) 99/50. Body weight (BW) was 30 kg and height (Ht.) 138 cm. No distress or complaints, according to her legal guardian. Upon central nervous examination, she was Keppra 40 mg/kg/day BID, conscious and alert, right-sided weakness with hyperreflexia, normal tone and power on the left side, pupil bilaterally equal and reactive to light, and no meningeal signs. She was hemodynamically stable with no systemic manifestations. On her follow-up with the infectious disease (ID) department, she started to receive ceftriaxone-D3 and vancomycin. C-reactive protein (CRP) was initially three mg/L, then repeated where it was 17.4 mg/L. She was discharged with culture pending, and neurological stabilization was achieved. Nine months later, the patient became seven-year-old, and she returned to the neurological clinic after her legal guardian noticed a developmental delay in the child. The last seizure episode was two months earlier after she had another episode nine months earlier. During this visit, she was conscious of the normal motor exam. However, she was diagnosed with hydrocephalus and developmental delay. A plan to increase Keppra dosage to seven ml BID was made and titrated to eight ml if seizures are not controlled. She was discharged and returned six months later to conduct a developmental assessment as she became an eight-year-old. Her developmental history started with expressive language assessment: At an early age, around two-to four, she requested things by using the other hand with no eye contact and no joint attention. She started to talk at the age of four years with few words MAMA and BABA were unspecific, then she started to improve at the age of six years after enrolment in speech session in a specialized center, at that time till now she can say three words sentences mainly order with no eye contact and no joint attention, and she still cannot run conversions. She cannot answer only specific simple questions and only her mother when she repeats them many times. Receptive assessment: The patient only obeys simple commands. She can sometimes obey two steps for specific things that she likes (go to bring an orange, clean it, and cut it Into pieces). Sometimes she repeats other words (Echolalia). Socially, she initiates playing with younger children. She likes no specific toys, only she likes to run, scream, and produce unspecific voices, and sometimes she expresses playing by hitting the younger children. Routine and sensory: According to the mother, she used to flap with her hand at the age of one-two years which disappeared at the age of four years, and currently no specific repetitive pattern. She likes specific clothes, and when she does not find them, she cries. Other sensory fields, including visual, hearing, and taste, were unremarkable. Emotionally: She does not understand others’ emotions. When she sees others crying, she usually laughs. Cognitively: She does not understand the concept of danger. She usually runs in the street with no sense of fear of cars or being cautious. Sleep: She sleeps for roughly eight hours from 1:00 AM till 10:00 AM, with no interruption and no nap. Media: She likes mobile most of the time. She likes to watch and listen to music. School: She started rehabilitation and mainly physiotherapy for the motor aspect as early as two years. Then at the age of four, she started speech and behavior modification sessions in a specialized center. She quit the rehabilitation center for more than one year because the family had traveled to Sudan. On physical examination, her weight was 37 kg, height 138.6 cm, all in the 95th percentile, and head circumference 57 cm above the 95th percentile. Her vitals were Temp. 37, HR 85, RR 22, BP 90/53, SaO 2 100% at room air. Her laboratory work was as follow: white blood cell (WBC) count 8.02 k/μl (reference range: 4-11 k/μl), red blood cell (RBC) count 3.99 M/μl (reference range: 4.8-6.4 M/μl), hemoglobin (Hb) 10.6 g/dl (reference range: 13-17 g/dl), hematocrit (HCT) 31.8% (reference range: 41%-50%), mean cell volume (MCV) 79.7 fl (reference range: 76-92 fl), platelet (PLT) count 235 k/μl (reference range: 150-450 k/μl), prothrombin time (PT) 12.4 seconds (reference range: 11.7-15.3 seconds), activated partial thromboplastin time (APTT) 28.1 seconds (reference range: 28.9-38.1 seconds), and international normalized ratio (INR) 1.11 seconds (reference range: 0.89-1.18 seconds). On clinical observations, she looked well, with no dysmorphic features, no eye contact, and sat at the clinic’s beginning, calm, watching online videos. However, after 30 minutes, she started to clean her hand around five times, then after 45 minutes, she started to scream and produce nonspecific sounds. She does not like to draw or use any toys in the clinic. She is only interested in mobile phones, and when her sister took them from her, she cried and hit her sister. No systematic findings. However, her current presentation was consistent with Autism Spectrum Disorder (ASD). Her 8th and most recent CT scan redemonstrated a dilatation of the supratentorial ventricular system, with stable porencephalic cystic changes adjacent to the left lateral ventricle. Preserved gray-white matter differentiation. No extra/intra-axial hemorrhage or herniation. The posterior fossa structures are unremarkable. The visualized osseous and orbital structures are unremarkable. The paranasal sinuses and mastoid air cells are well aerated. In conclusion, her imaging work-up displayed a stable appearance, without acute findings or other interval changes. Her second MRI imaging, which used a non-enhanced sagittal T1W, axial T2W, FLAIR, DW, GE, SW, and coronal T2W images of the brain, were obtained with axial, sagittal, and coronal T1W after IV contrast administration. A comparison was made based on her previous MRI. Findings included ventricular enlargement and irregularity of the left lateral ventricle are stable in appearance. Cystic structure communicating with the left lateral ventricle is also unchanged. A small amount of periventricular increased signal in the left dorsal thalamus is unchanged. No new enhancing ventricular or parenchymal lesions. Near complete resolution of the left frontal subdural hematoma with a small residual right frontal subdural collection remaining, measuring a maximum of three mm on the axial plane. She was on keppra (levetiracetam) 100 mg/mL, oral solution 300 mt, phenytoin Na 250 mg/5 mL ampule, and carbamazepine 200 mg tablets. Her management plan included extensive speech and behavior modification sessions through enrollment into rehabilitation centers and encouraging the family to be part of behavior modifications and follow-up after six months.	3.925781	0.981445	sec[1]/sec[0]/p[1]	en	0.999997	PMC10622857	https://doi.org/10.12688/f1000research.122349.1	[ "range", "reference", "four", "axial", "mother", "ventricular", "however", "keppra", "ventricle", "likes" ]	[ { "code": "QA00.6Y", "title": "Other specified examination of eyes or vision" }, { "code": "4B00.0Z", "title": "Neutropaenia, unspecified" }, { "code": "3B63.1Z", "title": "Acquired thrombocytosis, unspecified" }, { "code": "MA14.1C", "title": "Raised antibody titre" }, { "code": "BD11.1", "title": "Left ventricular failure with mid range ejection fraction" }, { "code": "6B22.Z", "title": "Olfactory reference disorder, unspecified" }, { "code": "MB26.03", "title": "Delusion of reference" }, { "code": "6B22.1", "title": "Olfactory reference disorder with poor to absent insight" }, { "code": "LD50.Y", "title": "Other specified number anomalies of chromosome X" }, { "code": "NA82.4", "title": "Multiple fractures of ribs" } ]	=== ICD-11 CODES FOUND === [QA00.6Y] Other specified examination of eyes or vision Also known as: Other specified examination of eyes or vision \| No Impairment of Contrast vision \| Normal colour vision \| No Impairment of Dark adaptation \| No diplopia [4B00.0Z] Neutropaenia, unspecified Also known as: Neutropaenia, unspecified \| Neutropenia \| Disorders with decreased neutrophil counts \| neutropaenic disorder \| neutrophil count below reference range [3B63.1Z] Acquired thrombocytosis, unspecified Also known as: Acquired thrombocytosis, unspecified \| Acquired thrombocytosis \| Idiopathic haemorrhagic thrombocythaemia \| Essential thrombocythaemia \| primary haemorrhagic thrombocythaemia [MA14.1C] Raised antibody titre Also known as: Raised antibody titre \| antibody titre above reference range \| high antibody titre \| increased antibody titre Excludes: isoimmunization, in pregnancy affecting fetus or newborn [BD11.1] Left ventricular failure with mid range ejection fraction Also known as: Left ventricular failure with mid range ejection fraction \| HFmEF - [heart failure with mid range ejection fraction] \| Left ventricular failure with mid range ejection fraction due to cardiomyopathy \| Left ventricular failure with mid range ejection fraction due to coronary artery disease \| Left ventricular failure with mid range ejection fraction due to myocarditis [6B22.Z] Olfactory reference disorder, unspecified Also known as: Olfactory reference disorder, unspecified \| Olfactory reference disorder \| Delusions of malodour [MB26.03] Delusion of reference Definition: A delusion that events, objects, or other people in the person's immediate environment have a particular and unusual personal significance, usually of a negative or pejorative nature. Also known as: Delusion of reference [6B22.1] Olfactory reference disorder with poor to absent insight Definition: All definitional requirements of olfactory reference disorder are met. Most or all of the time, the individual is convinced that the disorder-specific beliefs are true and cannot accept an alternative explanation for their experience. The lack of insight exhibited by the individual does not vary markedly as a function of anxiety level. Also known as: Olfactory reference disorder with poor to absent insight [LD50.Y] Other specified number anomalies of chromosome X Also known as: Other specified number anomalies of chromosome X \| Female with more than three X chromosomes \| abnormal female chromosomes, with more than three x chromosomes \| Tetrasomy X \| 48 xxxx syndrome [NA82.4] Multiple fractures of ribs Also known as: Multiple fractures of ribs \| rib fractures \| Multiple rib fractures, involving first rib \| Multiple rib fractures, involving two ribs \| Multiple rib fractures, involving three ribs === GRAPH WALKS === --- Walk 1 --- [QA00.6Y] Other specified examination of eyes or vision --PARENT--> [QA00.6] Examination of eyes or vision --CHILD--> [QA00.61] Normal Visual Field --- Walk 2 --- [QA00.6Y] Other specified examination of eyes or vision --PARENT--> [QA00.6] Examination of eyes or vision --CHILD--> [QA00.62] No vision impairment --- Walk 3 --- [4B00.0Z] Neutropaenia, unspecified --PARENT--> [4B00.0] Neutropenia --RELATED_TO--> [?] Alloimmune neonatal neutropaenia Def: Alloimmune neonatal neutropaenia (ANN) is a disease caused by the passive transfer of neutrophil specific maternal IgG antibodies across the placenta during pregnancy.... --- Walk 4 --- [4B00.0Z] Neutropaenia, unspecified --PARENT--> [4B00.0] Neutropenia --RELATED_TO--> [?] Transient neonatal neutropaenia Def: Neonatal neutropaenia can be due to underproduction of the marrow (e.g. hypoxemia due to placental insufficiency, congenital viral disease) or excessive utilization of white blood cells (bacterial sep... --- Walk 5 --- [3B63.1Z] Acquired thrombocytosis, unspecified --PARENT--> [3B63.1] Acquired thrombocytosis Def: A chronic myeloproliferative neoplasm that involves primarily the megakaryocytic lineage. It is characterised by sustained thrombocytosis in the blood, increased numbers of large, mature megakaryocyte... --PARENT--> [3B63] Thrombocytosis Def: A disease caused by essential thrombocytosis or other myelo-proliferative disorders such as chronic myelogenous leukaemia, polycythaemia, myelofibrosis. This disease can also have secondary causes suc... --- Walk 6 --- [3B63.1Z] Acquired thrombocytosis, unspecified --PARENT--> [3B63.1] Acquired thrombocytosis Def: A chronic myeloproliferative neoplasm that involves primarily the megakaryocytic lineage. It is characterised by sustained thrombocytosis in the blood, increased numbers of large, mature megakaryocyte... --CHILD--> [3B63.1Z] Acquired thrombocytosis, unspecified	[ "[QA00.6Y] Other specified examination of eyes or vision\n --PARENT--> [QA00.6] Examination of eyes or vision\n --CHILD--> [QA00.61] Normal Visual Field", "[QA00.6Y] Other specified examination of eyes or vision\n --PARENT--> [QA00.6] Examination of eyes or vision\n --CHILD--> [QA00.62] No vision impairment", "[4B00.0Z] Neutropaenia, unspecified\n --PARENT--> [4B00.0] Neutropenia\n --RELATED_TO--> [?] Alloimmune neonatal neutropaenia\n Def: Alloimmune neonatal neutropaenia (ANN) is a disease caused by the passive transfer of neutrophil specific maternal IgG antibodies across the placenta during pregnancy....", "[4B00.0Z] Neutropaenia, unspecified\n --PARENT--> [4B00.0] Neutropenia\n --RELATED_TO--> [?] Transient neonatal neutropaenia\n Def: Neonatal neutropaenia can be due to underproduction of the marrow (e.g. hypoxemia due to placental insufficiency, congenital viral disease) or excessive utilization of white blood cells (bacterial sep...", "[3B63.1Z] Acquired thrombocytosis, unspecified\n --PARENT--> [3B63.1] Acquired thrombocytosis\n Def: A chronic myeloproliferative neoplasm that involves primarily the megakaryocytic lineage. It is characterised by sustained thrombocytosis in the blood, increased numbers of large, mature megakaryocyte...\n --PARENT--> [3B63] Thrombocytosis\n Def: A disease caused by essential thrombocytosis or other myelo-proliferative disorders such as chronic myelogenous leukaemia, polycythaemia, myelofibrosis. This disease can also have secondary causes suc...", "[3B63.1Z] Acquired thrombocytosis, unspecified\n --PARENT--> [3B63.1] Acquired thrombocytosis\n Def: A chronic myeloproliferative neoplasm that involves primarily the megakaryocytic lineage. It is characterised by sustained thrombocytosis in the blood, increased numbers of large, mature megakaryocyte...\n --CHILD--> [3B63.1Z] Acquired thrombocytosis, unspecified" ]	QA00.6Y	Other specified examination of eyes or vision	[ { "from_icd11": "3B63.1Z", "icd10_code": "D473", "icd10_title": "Essential (hemorrhagic) thrombocythemia" }, { "from_icd11": "MA14.1C", "icd10_code": "R760", "icd10_title": "Raised antibody titer" }, { "from_icd11": "6B22.Z", "icd10_code": "F428", "icd10_title": "Other obsessive-compulsive disorder" }, { "from_icd11": "NA82.4", "icd10_code": "S2249XA", "icd10_title": "Multiple fractures of ribs, unspecified side, initial encounter for closed fracture" }, { "from_icd11": "NA82.4", "icd10_code": "S2243XD", "icd10_title": "Multiple fractures of ribs, bilateral, subsequent encounter for fracture with routine healing" }, { "from_icd11": "NA82.4", "icd10_code": "S2241XS", "icd10_title": "Multiple fractures of ribs, right side, sequela" }, { "from_icd11": "NA82.4", "icd10_code": "S2249XD", "icd10_title": "Multiple fractures of ribs, unspecified side, subsequent encounter for fracture with routine healing" }, { "from_icd11": "NA82.4", "icd10_code": "S2243XS", "icd10_title": "Multiple fractures of ribs, bilateral, sequela" }, { "from_icd11": "NA82.4", "icd10_code": "S2249XS", "icd10_title": "Multiple fractures of ribs, unspecified side, sequela" }, { "from_icd11": "NA82.4", "icd10_code": "S2249XG", "icd10_title": "Multiple fractures of ribs, unspecified side, subsequent encounter for fracture with delayed healing" }, { "from_icd11": "NA82.4", "icd10_code": "S2243XG", "icd10_title": "Multiple fractures of ribs, bilateral, subsequent encounter for fracture with delayed healing" }, { "from_icd11": "NA82.4", "icd10_code": "S2241XG", "icd10_title": "Multiple fractures of ribs, right side, subsequent encounter for fracture with delayed healing" }, { "from_icd11": "NA82.4", "icd10_code": "S2242XG", "icd10_title": "Multiple fractures of ribs, left side, subsequent encounter for fracture with delayed healing" }, { "from_icd11": "NA82.4", "icd10_code": "S2249XB", "icd10_title": "Multiple fractures of ribs, unspecified side, initial encounter for open fracture" }, { "from_icd11": "NA82.4", "icd10_code": "S2242XA", "icd10_title": "Multiple fractures of ribs, left side, initial encounter for closed fracture" } ]	D473	Essential (hemorrhagic) thrombocythemia
A 72-year-old Japanese man with a month-long history of dyspnea on exertion and bilateral shoulder pain gradually presented difficulty in raising both upper limbs. He visited a local doctor and underwent laboratory testing, which revealed an elevated serum C-reactive protein (CRP) (12.62 mg/dL). Hence, he was admitted to our hospital. He was naturally healthy and had no allergies, therefore was not on any medication. He is currently unemployed. His sister has a medical history of rheumatoid arthritis, and his daughter has a medical history of systemic lupus erythematosus. He has smoked 40 cigarettes a day for the past 50 years and does not consume alcohol. On admission, his vital signs were as follows: blood pressure 147/90 mmHg, pulse 110 beats/minute, respiratory rate 12 breaths/minute, and SpO 2 98% (room air). He had no headache, jaw claudication, visual loss, or fever. Tenderness in the bilateral temporal arteries was absent, whereas mild tenderness was observed in both shoulders. The upper right limb could not be elevated to shoulder level, whereas the upper left limb could not be elevated at all . A physical examination revealed no abnormalities other than those mentioned above. The laboratory tests revealed an increase in CRP and erythrocyte sedimentation rate (ESR) levels (13.99 mg/dL and 31 mm/hour, respectively). Both rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) were negative, and the matrix metalloproteinase-3 (MMP-3) level remained normal (54.3 ng/mL). Antinuclear antibody and anti-SSA antibody were also negative (Table 1 ). PMR and EORA were considered as differential diagnoses. However, PMR was unlikely as there were no signs of tenosynovitis and bursitis in both shoulders on musculoskeletal ultrasound examination. Moreover, the total score was 3 points and did not meet the 2012 Provisional Classification Criteria for Polymyalgia Rheumatica (“absence of RF or ACPA”: 2 points, “absence of other joint involvement”: 1 point; Table 2 ) . EORA was also unlikely because both RF and ACPA were negative, and there were no signs of synovitis on musculoskeletal ultrasound examination. Moreover, the total score was 2 points and did not meet the 2010 Rheumatoid arthritis classification criteria (“joint involvement”: 1 point, “acute-phase reactants”: 1 point; Table 3 ) . Since he did not complain of pain even if both upper limbs were passively lifted, neurological disease or muscle disease was considered. Precise neurological examination revealed that there was absence of sensory impairment, but deep tendon reflexes were present in bilateral triceps and the lower limbs, except for bilateral biceps and brachioradialis reflexes. Muscle strength was evaluated by conducting a manual muscle test. The muscle strength of the biceps brachii, brachioradialis, supinator teres, deltoid, pectoralis major, supraspinatus, and infraspinatus decreased predominantly on the left side (Table 4 ). Ultrasonographic examination showed absence of movement in the left diaphragm during breathing. Hence, bilateral C5 and C6 radicular involvement (the ventral root of spinal nerve) and left C4 radicular involvement were suspected. Since cervical magnetic resonance imaging showed no mechanical causality, cervical radiculopathy of unknown origin was suggested. Fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) revealed increased FDG lineal uptake along the vessel walls, including the temporal arteries, vertebral arteries, axillary arteries, descending aorta, and femoral arteries . Ultrasound examination showed absence of abnormality in the common carotid arteries, internal carotid arteries, and temporal arteries, but bilateral vertebral arteries were dilated to approximately 8 mm from bifurcation to C3 level . Ultrasound examination did not reveal any abnormality in the temporal artery. However, because 18 F-FDG PET/CT revealed FDG uptake in the temporal arteries, a left superficial temporal artery biopsy was conducted that showed histopathological findings compatible with GCA . Thirty milligrams (0.6 mg/kg) of oral prednisolone (PSL) was administered, and CRP test turned negative 10 days later. The patient could almost completely elevate both upper limbs almost immediately, his dyspnea on exertion disappeared, and he was discharged 20 days later. Currently, 4 years and 8 months after treatment, he is healthy and the result of CRP test remains negative with 1 mg of PSL (Additional file 1 ). Fig. 1 Clinical course of the patient. a The upper right limb could not be elevated to the shoulder level, whereas the upper left limb could not be elevated at all before treatment. b Both upper limbs could be completely elevated 4 years and 8 months after treatment Table 1 Laboratory data on admission Complete blood cell White blood cell (/μL) 10,240 Red blood cell (/μL) 3.4 × 10 6 Hemoglobin (g/dL) 10.4 Platelet (/μL) 79.5 × 10 4 Coagulation test APTT (second) 44.5 PT-INR 1.28 Biochemistry HbA1c (%) 6.9 BUN (mg/dL) 18.5 Cr (mg/dL) 0.80 eGFR (mL/minute/1.73 m 2 ) 72.57 Na (mEq/L) 137 K (mEq/L) 5.1 Cl (mEq/L) 98 AST (U/L) 78 ALT (U/L) 68 ALP (U/L) 568 LDH (U/L) 359 CK (U/L) 52 T-Bil (mg/dL) 0.47 TP (g/dL) 8.1 Alb (g/dL) 2.3 ESR (mm/hour) 31 Immunochemistry CRP (mg/dL) 13.99 IgG (mg/dL) 2744 ANA < 40 Anti-SS-A Ab (U/mL) 0.6 RF (U/mL) 10.6 ACPA (U/L) 0.5 MMP-3 (ng/mL) 54.3 C3 (mg/dL) 174.1 C4 (mg/dL) 43.8 CH50 (U/mL) 106.7 MPO-ANCA (IU) < 0.5 PR3-ANCA (IU) 0.6 APTT, activated partial thromboplastin time; PT-INR, prothrombin time–international normalized ratio; HbA1c, hemoglobin A1c; BUN, blood urea nitrogen; Cr, creatinine; eGFR, estimated glomerular filtration rate; Na, sodium; K, potassium; Cl, chlorine; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; LDH, lactate dehydrogenase; CK, creatine kinase; T-Bil, total bilirubin; TP, total protein; Alb, albumin; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; IgG, immunoglobulin G; ANA, antinuclear antibody; Anti-SS-A Ab, anti-SS-A antibody; RF, rheumatoid factor; ACPA, anti-cyclic citrullinated peptide antibody; MMP-3, matrix metalloproteinase-3; C3, complement component 3; C4, complement component 4; CH50, 50% hemolytic unit of complement; MPO-ANCA, myeloperoxidase-anti-neutrophil cytoplasmic antibody; PR3-ANCA, proteinase-3-anti-neutrophil cytoplasmic antibody Table 2 Polymyalgia rheumatica classification criteria scoring algorithm—required criteria: age ≥ 50 years, bilateral shoulder aching, abnormal C-reactive protein level, and/or erythrocyte sedimentation rate Points without US (0–6) Points with US (0–8) Morning stiffness duration > 45 minutes 2 2 Hip pain or limited range of motion 1 1 Absence of RF or ACPA 2 2 Absence of other joint involvements 1 1 At least one shoulder with subdeltoid bursitis and/or biceps tenosynovitis and/or glenohumeral synovitis (either posterior or axillary), and at least one hip with synovitis and/or trochanteric bursitis NA 1 Both shoulders with subdeltoid bursitis, biceps tenosynovitis, or glenohumeral synovitis NA 1 An individual with a score of ≥ 4 is categorized as having PMR in the algorithm without US, and an individual with a score of ≥ 5 is categorized as having PMR in the algorithm with US PMR, polymyalgia rheumatica; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; US, ultrasonography; RF, rheumatoid factor; ACPA, anti-cyclic citrullinated peptide antibody; NA, not applicable Table 3 The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis Score Target population (who should be tested?): patients who 1) have at least one joint with definite clinical synovitis (swelling) a 2) have synovitis that is not attributable to another disease b Classification criteria for RA (score-based algorithm: add the scores in categories A–D; a score of ≥ 6/10 is needed for the classification of a patient as having definite RA) c (A) Joint involvement d 1 large joint e 0 2−10 large joints 1 1−3 small joints (with or without involvement of large joints) f 2 4−10 small joints (with or without involvement of large joints) 3 > 10 joints (at least one small joint) g 5 (B) Serology (at least one test result is needed for classification) h Negative RF and ACPA 0 Low-positive RF or ACPA 2 High-positive RF or ACPA 3 (C) Acute-phase reactants (at least one test result is needed for classification) i Normal CRP level and ESR 0 Abnormal CRP level or normal ESR 1 (D) Duration of symptoms j < 6 weeks 0 ≥ 6 weeks 1 a The criteria are established for the classification of patients newly presenting with symptoms. In addition, patients with erosive disease typical of RA with a history compatible with prior fulfillment of the 2010 criteria should be classified as having RA. Patients with long-standing disease, including those whose disease is inactive (with or without treatment), and who, based on retrospectively available data, have previously fulfilled the 2010 criteria should be classified as having RA b Differential diagnoses differ in patients with different presentations but may include conditions such as systemic lupus erythematosus, psoriatic arthritis, and gout. If the relevant differential diagnoses to consider are unclear, an expert rheumatologist should be consulted c Although patients with a score of < 6/10 are not classifiable as having RA, their status can be reassessed, and the criteria might be fulfilled cumulatively over time d Joint involvement refers to any swollen or tender joint on examination, which may be confirmed by imaging evidence of synovitis. The distal interphalangeal, first carpometacarpal, and first metatarsophalangeal joints are excluded from the assessment. Categories of joint distribution are classified according to the location and number of involved joints, with placement into the highest category possible based on the pattern of joint involvement e “Large joints” refers to the shoulders, elbows, hips, knees, and ankles f “Small joints” refers to the metacarpophalangeal, proximal interphalangeal, second to fifth metatarsophalangeal, and thumb interphalangeal joints, as well as the wrists g In this category, at least one of the involved joints must be a small joint; the other joints can include any combination of large and additional small joints and other joints not specifically listed elsewhere (for example, temporomandibular, acromioclavicular, and sternoclavicular) h “negative” refers to international unit values that are less than or equal to the upper limit of normal for the laboratory test and assay; “low-positive” refers to international unit values that are higher than the limit of normal but ≤ 3 times the limit of normal for the laboratory test and assay; and “high-positive” refers to international unit values that are more than three times the limit of normal for the laboratory test and assay. When RF information is only available as “positive” or “negative,” a “positive” result should be scored as “low-positive” for RF i Normal/abnormal is determined on the basis of local laboratory standards j “Duration of symptoms” refers to patients’ self-report of the duration of signs or symptoms of synovitis (for example, pain, swelling, and tenderness) of the joints that are clinically involved at the time of assessment, regardless of the treatment status RA, rheumatoid arthritis; RF, rheumatoid factor; ACPA, anti-citrullinated protein antibody; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate Table 4 Manual muscle test on admission Right Left Dominant nerve Biceps brachii 3/5 1/5 C5–C6 Triceps brachii 5/5 5/5 C6–C7–C8 Brachioradialis 5/5 1/5 C5–C6 Supinator teres 5/5 1/5 C5–C6 Pronator teres 5/5 5/5 C6–C7 Deltoid 3/5 1/5 C5–C6 Pectoralis major 3/5 3/5 C5–C6–C7–C8–T1 Trapezius 5/5 5/5 C3–C4 Supraspinatus 3/5 1/5 C5–C6 Infraspinatus 3/5 * C5–C6 Rhomboids 5/5 5/5 C4–C5 Latissimus dorsi 5/5 5/5 C6–C7–C8 C, cervical; T, thoracic * We could not assess the patient’s left infraspinatus muscle strength as he was unable to get the correct limb position Fig. 2 Fluorodeoxyglucose positron emission tomography/computed tomography. a Coronal PET image. b – f Axial PET/CT images. FDG uptake of left temporal artery ( b circle, SUVmax 3.6), bilateral vertebral arteries ( c circle, SUVmax 4.4), right axillary artery ( d circle, SUVmax 3.1), descending aorta ( e circle, SUVmax 3.8), and bilateral femoral arteries ( f circle, SUVmax 2.3). PET, positron emission tomography; CT, computed tomography; FDG, fluorodeoxyglucose; SUVmax, maximum standardized uptake value Fig. 3 Ultrasound findings of bilateral vertebral arteries before and after treatment. Bilateral vertebral arteries were observed from bifurcation to C3 level by ultrasound. Before treatment, those were dilated to approximately 8 mm on all levels. a Right vertebral artery. b Left vertebral artery. Four years and 8 months after treatment, the above-mentioned arteries decreased to approximately 5.5 mm on all levels. c Right vertebral artery. d Left vertebral artery Fig. 4 Histopathology of left superficial temporal artery biopsy. a and b Number of inflammatory cell infiltrates mainly in the media and sporadic multinucleated giant cells (red arrows) with intimal hyperplasia and vascular occlusion (hematoxylin–eosin staining: a , ×50; b , ×200). c Fragmentation of the internal elastic lamina (blue arrow) (Elastica van Gieson staining: c , ×50)	4.039063	0.970215	sec[1]/p[0]	en	0.999997	34666810	https://doi.org/10.1186/s13256-021-03107-7	[ "joints", "arteries", "joint", "acpa", "anti", "antibody", "criteria", "both", "classification", "involvement" ]	[ { "code": "FA5Z", "title": "Arthropathies, unspecified" }, { "code": "FA2Z", "title": "Inflammatory arthropathies, unspecified" }, { "code": "FA36.Z", "title": "Effusion of joint, unspecified" }, { "code": "FA37.Y", "title": "Other specified certain joint disorders, not elsewhere classified" }, { "code": "FA34.3", "title": "Contracture of joint" }, { "code": "BD5Z", "title": "Diseases of arteries or arterioles, unspecified" }, { "code": "BD52", "title": "Certain specified disorders of arteries or arterioles" }, { "code": "BD52.3", "title": "Rupture of artery" }, { "code": "BD52.2", "title": "Stricture of artery" }, { "code": "BD40.Z", "title": "Atherosclerotic chronic arterial occlusive disease, unspecified" } ]	=== ICD-11 CODES FOUND === [FA5Z] Arthropathies, unspecified Also known as: Arthropathies, unspecified \| Disorders affecting predominantly peripheral joints \| Disorders affecting predominantly peripheral limb joints \| arthropathy NOS \| arthropathic [FA2Z] Inflammatory arthropathies, unspecified Also known as: Inflammatory arthropathies, unspecified \| polyarthritis NOS \| inflammatory joint disease NOS \| nonpyogenic arthritis NOS \| arthritic nodosa [FA36.Z] Effusion of joint, unspecified Also known as: Effusion of joint, unspecified \| Effusion of joint \| effusion into joint \| effusion of joint, site unspecified \| hydrarthrosis [FA37.Y] Other specified certain joint disorders, not elsewhere classified Also known as: Other specified certain joint disorders, not elsewhere classified \| Calcification of joint \| Periarticular calcification \| Periarticular ossification \| Fistula of joint [FA34.3] Contracture of joint Also known as: Contracture of joint \| contracture of joint, site unspecified \| joint contraction \| joint contracture \| abduction contracture joint Excludes: Dupuytren contracture \| contracture of tendon (sheath) without contracture of joint \| acquired deformities of limbs [BD5Z] Diseases of arteries or arterioles, unspecified Also known as: Diseases of arteries or arterioles, unspecified \| artery disease NOS \| arterial disease NOS \| arteriolar disease NOS \| disorder of artery NOS [BD52] Certain specified disorders of arteries or arterioles Also known as: Certain specified disorders of arteries or arterioles \| Aortic dilatation - joint hypermobility - arterial tortuosity \| Generalised arterial calcification of infancy \| Median arcuate ligament syndrome \| Aortic root abscess Excludes: collagen (vascular) diseases \| Hypersensitivity angiitis \| Acute arterial occlusion [BD52.3] Rupture of artery Also known as: Rupture of artery \| ruptured artery \| artery fistula \| Aortic duodenal fistula \| Aortic colon fistula Excludes: traumatic rupture of artery - see injury of blood vessel by body region [BD52.2] Stricture of artery Also known as: Stricture of artery \| arterial stenosis \| arterial stricture \| artery stricture \| stenosis of artery [BD40.Z] Atherosclerotic chronic arterial occlusive disease, unspecified Also known as: Atherosclerotic chronic arterial occlusive disease, unspecified \| Atherosclerotic chronic arterial occlusive disease \| arteriosclerosis, NOS \| generalised atherosclerosis \| atherosclerosis NOS === GRAPH WALKS === --- Walk 1 --- [FA5Z] Arthropathies, unspecified --PARENT--> [?] Arthropathies --CHILD--> [?] Osteoarthritis Def: Osteoarthritis (OA) can be defined as a group of distinct, but overlapping diseases, which may have different etiologies, but similar biological, morphological, and clinical outcomes affecting the art... --- Walk 2 --- [FA5Z] Arthropathies, unspecified --PARENT--> [?] Arthropathies --CHILD--> [?] Inflammatory arthropathies --- Walk 3 --- [FA2Z] Inflammatory arthropathies, unspecified --PARENT--> [?] Inflammatory arthropathies --CHILD--> [FA21] Psoriatic arthritis Def: Psoriatic arthritis, a member of the spondyloarthritis family, is defined as an inflammatory arthropathy associated with psoriasis that is usually rheumatic factor negative. It is characterised by var... --- Walk 4 --- [FA2Z] Inflammatory arthropathies, unspecified --PARENT--> [?] Inflammatory arthropathies --CHILD--> [FA20] Rheumatoid arthritis Def: Rheumatoid arthritis (RA) is persistent and/or erosive disease that is defined as the confirmed presence of synovitis in at least 1 joint, absence of an alternative diagnosis that better explains the ... --- Walk 5 --- [FA36.Z] Effusion of joint, unspecified --PARENT--> [FA36] Effusion of joint Def: Increased intra-articular fluid secondary to trauma and/or other acquired conditions not detailed in other codes.... --EXCLUDES--> [?] Tertiary yaws Def: Tertiary yaws develops in <10% of untreated infected individuals after and interval of 5 years or more. The late stage skin lesions are characterised by gummatous nodules with necrotic tissue destruct... --- Walk 6 --- [FA36.Z] Effusion of joint, unspecified --PARENT--> [FA36] Effusion of joint Def: Increased intra-articular fluid secondary to trauma and/or other acquired conditions not detailed in other codes.... --CHILD--> [FA36.0] Effusion of joint containing blood	[ "[FA5Z] Arthropathies, unspecified\n --PARENT--> [?] Arthropathies\n --CHILD--> [?] Osteoarthritis\n Def: Osteoarthritis (OA) can be defined as a group of distinct, but overlapping diseases, which may have different etiologies, but similar biological, morphological, and clinical outcomes affecting the art...", "[FA5Z] Arthropathies, unspecified\n --PARENT--> [?] Arthropathies\n --CHILD--> [?] Inflammatory arthropathies", "[FA2Z] Inflammatory arthropathies, unspecified\n --PARENT--> [?] Inflammatory arthropathies\n --CHILD--> [FA21] Psoriatic arthritis\n Def: Psoriatic arthritis, a member of the spondyloarthritis family, is defined as an inflammatory arthropathy associated with psoriasis that is usually rheumatic factor negative. It is characterised by var...", "[FA2Z] Inflammatory arthropathies, unspecified\n --PARENT--> [?] Inflammatory arthropathies\n --CHILD--> [FA20] Rheumatoid arthritis\n Def: Rheumatoid arthritis (RA) is persistent and/or erosive disease that is defined as the confirmed presence of synovitis in at least 1 joint, absence of an alternative diagnosis that better explains the ...", "[FA36.Z] Effusion of joint, unspecified\n --PARENT--> [FA36] Effusion of joint\n Def: Increased intra-articular fluid secondary to trauma and/or other acquired conditions not detailed in other codes....\n --EXCLUDES--> [?] Tertiary yaws\n Def: Tertiary yaws develops in <10% of untreated infected individuals after and interval of 5 years or more. The late stage skin lesions are characterised by gummatous nodules with necrotic tissue destruct...", "[FA36.Z] Effusion of joint, unspecified\n --PARENT--> [FA36] Effusion of joint\n Def: Increased intra-articular fluid secondary to trauma and/or other acquired conditions not detailed in other codes....\n --CHILD--> [FA36.0] Effusion of joint containing blood" ]	FA5Z	Arthropathies, unspecified	[ { "from_icd11": "FA5Z", "icd10_code": "M00-M25", "icd10_title": "" }, { "from_icd11": "FA2Z", "icd10_code": "M1389", "icd10_title": "Other specified arthritis, multiple sites" }, { "from_icd11": "FA2Z", "icd10_code": "M1380", "icd10_title": "Other specified arthritis, unspecified site" }, { "from_icd11": "FA2Z", "icd10_code": "M13862", "icd10_title": "Other specified arthritis, left knee" }, { "from_icd11": "FA2Z", "icd10_code": "M13872", "icd10_title": "Other specified arthritis, left ankle and foot" }, { "from_icd11": "FA2Z", "icd10_code": "M13871", "icd10_title": "Other specified arthritis, right ankle and foot" }, { "from_icd11": "FA2Z", "icd10_code": "M13861", "icd10_title": "Other specified arthritis, right knee" }, { "from_icd11": "FA2Z", "icd10_code": "M13879", "icd10_title": "Other specified arthritis, unspecified ankle and foot" }, { "from_icd11": "FA2Z", "icd10_code": "M13842", "icd10_title": "Other specified arthritis, left hand" }, { "from_icd11": "FA2Z", "icd10_code": "M13841", "icd10_title": "Other specified arthritis, right hand" }, { "from_icd11": "FA2Z", "icd10_code": "M13811", "icd10_title": "Other specified arthritis, right shoulder" }, { "from_icd11": "FA2Z", "icd10_code": "M13162", "icd10_title": "Monoarthritis, not elsewhere classified, left knee" }, { "from_icd11": "FA2Z", "icd10_code": "M13869", "icd10_title": "Other specified arthritis, unspecified knee" }, { "from_icd11": "FA2Z", "icd10_code": "M1388", "icd10_title": "Other specified arthritis, other site" }, { "from_icd11": "FA2Z", "icd10_code": "M13171", "icd10_title": "Monoarthritis, not elsewhere classified, right ankle and foot" } ]	M00-M25
Our patient’s history was significant of carpal tunnel release and radiological assessment revealed compression in both lumbar and thoracic regions due to hypertrophy of the ligaments. To our knowledge, there have been only three previous cases with spinal involvement that have demonstrated a positive or slightly positive result for the transthyretin type . Table 1 illustrates a comparison of the 26 cases identified in our literature review regarding amyloidoma involving the cervical spine. Table 1 Summary of cervical spine amyloidoma cases within the literature Reference Age Sex Clinical Symptoms Imaging Treatment Outcome Histological Description CTS Hx Spinal Stenosis Dickman 1998 74 M Upper cervical pain radiating to occiput and shoulders. CT: C2 mass with bubbly-appearing cortical shell and complete central lucency. Open biopsy and tumor resection via midline posterior approach. Second surgery involved fusion of C1-C3 with iliac bone graft. Postoperatively exhibited no new neurological deficits. Patients died 3-months postoperative due to sudden myocardial infarction. Demonstrated waxy-appearing Congo red-positive substance with green birefringence to polarized light. Not reported. Not reported. Mullins 1997 58 M Chest discomfort in midsternal/epigastric region precipitated by coughing and valsava. MRI T1: Abnormal enhancement of the C7 vertebral body and posterior elements. C6-C7 laminectomy and corpectomies completed with iliac bone graft and C4-T2 fusion. 12-month follow up revealed stable spine construct and no evidence of recurrence. Stains revealed Congo red stain for amyloid, and green birefringence under polarized light. Not reported. Not reported. Porchet 1998 73 M 6-year history of progressive numbness and spasticity in all limbs, predominantly the right side, dragging right leg, and neck pain. 1991 MRI: partially enhancing C1-C2 mass with odontoid erosion. 1995 MRI: enlargement of enhancing mass found from the clivus-C2. 1991: laminectomy from C1-C4. 1995: Trans-oral odontoidectomy with resection; C1-C2 transarticular screw fixation. 1991: Decreased right hand numbness, increase strength and coordination in all extremities, resuming to normal activity. 1995: At 7-months postop, able to ambulate half a mile, numbness resolved, and right lower limb strength returned to normal. Positive Congo red stain with apple-green birefringence under polarized light. Immuno-histochemical staining was positive for β2M. Bilateral carpal tunnel release in 1981, although this did not improve symptoms. Not reported. Moonis 1999 79 M Progressive dysphagia, weakness in his arms and legs, rapid weight loss, and neck pain. MRI: Peri-odontoid 3 × 2 cm hypointense mass. Anterior microdissection of the tumor and posterior fusion from occiput to C3. Not reported. Stained positive for amyloid using Congo red stain. β2M antibodies revealed intense staining. Carpal tunnel release 2 years prior. Not reported. Hwang 2000 45 F Paraparesis, urinary incontinence, and 3-month long neck pain. MRI: Inhomogeneous hypointense mass at C7 with partial collapse of the bony anatomy. Decompressive corpectomy with anterior fusion from C6-T1. After the operation, the patient’s paraparesis and urinary incontinence resolved completely. 3-year follow-up reported no specific symptoms. Positive Congo red stain, with green birefringence to polarized light. Not reported. Not reported. Mulleman 2004 79 F Acute cervical pain and spastic tetraparesia occurring after a fall. MRI: Peripheral enhancing hypointense retro-odontoid mass with compression at C1-C2. Transoral approach for removal of mass. Underwent C1-C2 transarticular screw fixation 3-weeks postop. Improved sphincter tone and strength in all limbs. Improved neurological function post rehabilitation. Slightly positive for prealbumin/ATTR subtype. Yes. Not reported. Shenoy 2004 58 M Neck pain, progressive weakness of the limbs, and dysphagia for 2 months. MRI T1: hypointense mass with bony destruction at C1-C2. Intubated and given ventilatory support due to rapid decline in respiratory function. Progressively worsened and developed bleeding diathesis and died. Post-death transoral biopsy revealed amyloid deposits under Congo red stain with apple-green birefringence under polarized light. Not reported. Not reported. Belber 2004 72 M Acute non-radicular left arm pain, followed by mild right arm and leg pain. MRI: C1-C3 hypointense lesion. Bilateral C2 decompression and partial C1 laminectomy. Discharged home day 10 postop fully ambulatory. Died 3 months later during management of MM. Exhibited typical apple green birefringence under polarized light on Congo Red stain. Not reported. Not reported. Samandouras 2006 75 F Progressive lower limb stiffness over 16 years. MRI T2: C2 hyperintense pannus with a cystic lesion. Mild erosion present on posterior cortical margin of C2. C1-C2 laminectomy with excision of the cystic mass. Not reported. Positive for Congo red stain. Presumed to be AL, immune-histochemistry studies included AA and ATTR types. Not reported. Not reported. Iplikcioglu 2007 72 M 4-year history of progressive weakness and numbness in both upper limbs, and neck pain. MRI: Soft tissue isointense mass at C6-C7 with vertebral body destruction. Anterior approach for resection of the C6-C7 mass with acrylic vertebroplasty. Uneventful postoperative course and quadriparesis was decreased. Tissue stained with Congo red under polarized light revealed yellow-green birefringence with deposits of primary (AL) amyloid. Not reported. Not reported. Vignes 2007 50 F Paresthesia in the hand and shoulder with progressive cervical pain. MRI T1: hypointense C2-C3 lateral mass C2-C3 laminectomy and tumor excision. Improvement of neuralgia syndrome and neuropathic pain; however, required a cervical collar for 3 months. Positive Congo red stain and birefringent under polarized light. Immuno- histochemistry revealed presence of β2M. History of bilateral carpal tunnel operation with recurrent syndrome. Not reported. Oruckaptan 2009 47 M Headache MRI T1: hyperintense C1-C2 lesion with hypointense center. Complete resection of the lesion and concomitant acrylic cranioplasty. Uneventful postoperative course. Congo red and crystal violet dyes verified diagnosis of amyloidoma. Protein electrophoresis showed β2M. Not reported. Not reported. Farrell 2011 75 M Right leg weakness and paresthesia in all four limbs followed by acute quadriparesis. MRI: Paravertebral isointense soft tissue mass from C6-C7. Radiotherapy, surgical debulking, Bortezomib, and Dexamethasone. Cervical amyloidoma diagnosed in 1993, with symptoms returning in 2006. Final treatment in 2009 led to gradual improvement in leg power and normal arm power over 8-months. Congo red staining demonstrated apple-green birefringence. Noted to express lambda-restricted immunoglobulin. Not reported. Not reported. Hsu 2011 65 M Progressive lower leg weakness and numbness over 2 years followed by quadriplegia. MRI T2: C5-C6 hyperintense lesion with C6 vertebral body destruction. Laminectomy with resection. Dramatic improvement in muscle strength, at the time of the report the patient would walk without limitation. Positive Congo red stain with a previous biopsy revealing β2M deposits. Developed bilateral carpal tunnel syndrome after 8-years of regular hemodialysis. Not reported. Sueyoshi 2011 71 M Urinary incontinence, sensory disturbances in the arms, and became unable to ambulate. MRI: Contrast-enhancing extradural mass at C3-C4 with severe osteolysis of the vertebral body. C3-C7 laminoplasty, bilateral C5 foraminotomy, and lumbar spinal fusion. Upper limb weakness moderately improved; other symptoms partially improved and did not worsen. Positive for amyloid deposits. Detected ATTRwt using mass spectrometric analysis. No; however, nerve conduction study revealed prolonged sensory latency of the median nerve consistent with CTS. MRI showed spinal canal stenosis due to osteophytes at L3-L4. Takeshima 2012 51 F Progressive headaches. MRI T2: Solid extradural hypointense lesion at C2 Right sided hemilaminectomies at C1-C2, subtotal resection and right C2 nerve root decompression. Discharged on day 14 postop with no neurological manifestations. MRI completed at 10-months postop revealed no recurrence. Histological examination revealed amyloid deposits. Not reported. Not reported. Hayashi 2012 75 F Progressive numbness in upper limbs, fine motor disturbances in fingers bilaterally, and gait disturbance. MRI: Large hypointense circumferentially enhanced mass in the epidural space from C1-C3. C2-C4 laminectomy and resection of the mass. Patient gained increased strength and coordination in extremities, decreased numbness, and was fully ambulatory 2-months postop. Positive Congo red stain with immune-histochemical testing indicating non-AA amyloid. Not reported. Not reported. Werner 2013 77 F Worsening syncope and altered mental status, acute weight loss, gradual weakness in the upper and lower limbs bilaterally. MRI: non enhancing mass at C1-C2 with erosive bony changes. C1-C3 decompression with partial resection, followed by fusion from occiput-C5 using iliac bone graft. At week 6, regained strength bilaterally in all extremities and became ambulatory. At 2-year follow-up reported intact strength, sensation, and ambulation without aids. Congo red stained tissue featured yellow-green birefringence under polarized light. Not reported. Not reported. Nitta 2015 66 M 1 week of reported dizziness, urinary retention, blunted sensation below the chest, and paraplegia 2-days prior. MRI T1: Hypointense epidural mass at C7. Laminectomy and tumor resection. Paraplegia and urinary retention resolved acutely postoperatively with improved sensation. Congo red positive tissue featured apple-green birefringence under polarized light. Immunostaining was positive for β2M amyloid. No evidence of carpal tunnel. Not reported. Smitherman 2015 46 F Lower extremity paralysis, lower body hypoesthesia, and worsening bowel/bladder incontinence. MRI T1: Intradural extramedullary enhancing lesion at C4-T4. C4-T4 laminectomy, resection, and posterior spinal fusion Unchanged neurological examination with no progression at 1-year follow-up. Congo red stained positively and displayed apple green birefringence under polarized light. Not reported. Not reported. Shinkino 2016 57 M Progressive neck pain, quadriplegia, and numbness of limbs. MRI T2: C1-C2 hypointense mass C2-C7 laminoplasty. At 1-month follow-up, patient exhibited markedly improved symptoms compared to preoperative status. Amyloid fibrils were densely enhanced with direct fast scarlet staining and showed green birefringence under polarized light. Immunohistochemistry demonstrated a positive finding for β2M. Carpal tunnel surgery completed 9-years prior. Thickened LF and PLL. Dalolio 2017 63 M Acute urinary retention, sensory disturbances in all 4 limbs followed by severe tetraparesis. MRI T2: intradural extramedullary enhancing lesion at C4-C7. C4-C7 laminectomy and resection. Underwent Revision surgery consisting of laminoatherectomy at C5-C6 and C6-C7 levels and removal of the lesion. Discharged day 10 with persistent paraplegia, urinary incontinence, and lower limb sensory deficits with slight improvement in preoperative neurologic symptoms. Amyloid deposits were confirmed on histological examination. Not reported. Thickened LF. Rezania 2017 86 M Progressive weakness, gait deterioration, falls, and urinary incontinence. MRI T1: Peripherally enhanced extra-axial mass extending from the clivus to C2. None, biopsy only. Died due to complications from metastatic cancer one year later. Mass spectrometry was performed on Congo red-positive areas which detected transthyretin-related (ATTR) amyloidosis. Yes. Yes. Schneider 2018 84 F Progressive ataxia and dysphagia. MRI: Non-enhancing soft-tissue mass from the retro-clivus to C2 posteriorly. Endoscopic trans-nasal resection and posterior stabilization via arthrodesis from occiput-C5. Discharged 2-weeks postop with improved neuro-motor exam. 2-year follow-up revealed complete resolution of the mass. Positive Congo red stain and apple green birefringence to polarized light. Presumed AA, negative for kappa and lambda AL. Not reported. Not reported. Rotter 2019 58 M Neck pain radiating to left arm, bilateral upper limb weakness over several months. MRI T2: hypointense, contrast-enhancing mass at C1-C2. C2 laminectomy and gross total resection. One-month postop assessment revealed improved strength in upper and lower extremities. Congo red showed green birefringence under cross-polarized light. Liquid chromatography tandem mass spectrometry detected an AL-kappa amyloid peptide profile. Not reported. Not reported. Giorgi 2021 57 F Progressive loss of upper and lower limb strength and sensitivity in addition to headaches. MRI: Hypointense solid mass at C1-C2. C1 laminectomy, followed by occiput-C5 fixation. Neurological deficits improved immediately after surgery; 1-year follow-up revealed no signs of myelopathy progression. Positive Congo red reaction and were positive for β2M immunostaining. Not reported. Not reported. CTS Hx Carpal Tunnel Syndrome history, β2M beta-2-microglobulin, ATTR Transthyretin, MM Multiple Myeloma, AL Amyloid Light Chain, AA Serum Amyloid A, ATTRwt Transthyretin wild type, LF Ligamentum Flavum, PLL Posterior Longitudinal Ligament	4.179688	0.872559	sec[3]/p[4]	en	0.999998	PMC9479254	https://doi.org/10.1186/s12877-022-03422-8	[ "congo", "light", "green", "birefringence", "polarized", "pain", "resection", "amyloid", "hypointense", "laminectomy" ]	[ { "code": "1D49", "title": "Crimean-Congo haemorrhagic fever" }, { "code": "KA21.2Z", "title": "Low birth weight of newborn, unspecified" }, { "code": "MB48.3", "title": "Light-headedness" }, { "code": "9D45", "title": "Impairment of light sensitivity" }, { "code": "GA20.51", "title": "Light menstrual bleeding" }, { "code": "2A83.52", "title": "Light chain deposition disease" }, { "code": "1D60.1Z", "title": "Marburg disease, virus unspecified" }, { "code": "9D44", "title": "Impairment of colour vision" }, { "code": "NC92.4Y&XJ45W&XA5G97", "title": "Greenstick fracture of fibula" }, { "code": "NC72.5", "title": "Fracture of shaft of femur" } ]	=== ICD-11 CODES FOUND === [1D49] Crimean-Congo haemorrhagic fever Definition: A disease caused by an infection with Crimean-Congo haemorrhagic fever virus. The length of the incubation period depends on the mode of acquisition of the virus. Following infection by a tick bite, the incubation period is usually one to three days, with a maximum of nine days. The incubation period following contact with infected blood or tissues is usually five to six days, with a documented maximum of 13 days. Onset of symptoms is sudden, with fever, myalgia, (muscle ache), dizziness, neck Also known as: Crimean-Congo haemorrhagic fever \| CCHF - [Crimean-Congo haemorrhagic fever] \| Kara mikh typhoid fever \| Xīnjiāng haemorrhagic fever [KA21.2Z] Low birth weight of newborn, unspecified Also known as: Low birth weight of newborn, unspecified \| Low birth weight of newborn \| birthweight low for gestational age \| fetal malnutrition, light-for-dates \| intrauterine or fetal malnutrition, light-for-dates [MB48.3] Light-headedness Also known as: Light-headedness \| light headed [9D45] Impairment of light sensitivity Also known as: Impairment of light sensitivity \| Vision sensitivity deficiencies \| Day blindness \| Impairment of dark adaptation \| Moderate Impairment of Dark adaptation [GA20.51] Light menstrual bleeding Definition: Menstruation with light (< 5 ml) volume of monthly blood loss Also known as: Light menstrual bleeding \| light menstrual period \| scanty menses \| scanty menstruation \| scanty period [2A83.52] Light chain deposition disease Definition: A disease of the kidney, caused by the deposition of pieces of truncated or abnormal light chain segments of white blood cells. This disease is characterised by fibrillar or granular tissue deposits and renal dysfunction, which may lead to organ failure. Confirmation is by identification of light chain deposition tissue biopsy under an electron microscope. Also known as: Light chain deposition disease \| systemic light chain disease Excludes: Immunodeficiencies with isotype or light chain deficiencies with normal number of B cells [1D60.1Z] Marburg disease, virus unspecified Also known as: Marburg disease, virus unspecified \| Marburg disease \| green monkey disease \| vervet monkey disease \| MARD - [Marburg disease] [9D44] Impairment of colour vision Definition: Colour vision refers to the ability to distinguish colour differences. True colour “blindness” is extremely rare. Most colour vision deficiencies are minor, and congenital, with X-linked recessive inheritance (more prevalent among men). Some drugs and optic neuritis may also cause colour vision deficiencies. Also known as: Impairment of colour vision \| colour vision deficiency \| colour blindness \| complete colour blindness \| total colour blindness Includes: achromatopsia \| acquired colour vision deficiency \| colour blindness [NC72.5] Fracture of shaft of femur Also known as: Fracture of shaft of femur \| femoral shaft fracture \| oblique fracture of shaft of femur \| comminuted fracture of shaft of femur \| Fracture of shaft of femur, simple === GRAPH WALKS === --- Walk 1 --- [1D49] Crimean-Congo haemorrhagic fever Def: A disease caused by an infection with Crimean-Congo haemorrhagic fever virus. The length of the incubation period depends on the mode of acquisition of the virus. Following infection by a tick bite, ... --PARENT--> [?] Certain arthropod-borne viral fevers --CHILD--> [1D41] Colorado tick fever --- Walk 2 --- [1D49] Crimean-Congo haemorrhagic fever Def: A disease caused by an infection with Crimean-Congo haemorrhagic fever virus. The length of the incubation period depends on the mode of acquisition of the virus. Following infection by a tick bite, ... --PARENT--> [?] Certain arthropod-borne viral fevers --CHILD--> [1D40] Chikungunya virus disease --- Walk 3 --- [KA21.2Z] Low birth weight of newborn, unspecified --PARENT--> [KA21.2] Low birth weight of newborn Def: A paediatric condition in which the infant is born weighing between 1500 and 2499 g.... --CHILD--> [KA21.2Z] Low birth weight of newborn, unspecified --- Walk 4 --- [KA21.2Z] Low birth weight of newborn, unspecified --PARENT--> [KA21.2] Low birth weight of newborn Def: A paediatric condition in which the infant is born weighing between 1500 and 2499 g.... --CHILD--> [KA21.20] Low birth weight of newborn, 1500-1999g Def: A paediatric condition in which the infant is born weighing between 1500 and 1999 g.... --- Walk 5 --- [MB48.3] Light-headedness --PARENT--> [MB48] Dizziness or giddiness Def: Terms which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Dizziness is a general feeling of being off-balance. Giddiness is the feeling that you or you... --PARENT--> [?] Symptoms or signs involving the nervous system --- Walk 6 --- [MB48.3] Light-headedness --PARENT--> [MB48] Dizziness or giddiness Def: Terms which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Dizziness is a general feeling of being off-balance. Giddiness is the feeling that you or you... --CHILD--> [MB48.0] Vertigo	[ "[1D49] Crimean-Congo haemorrhagic fever\n Def: A disease caused by an infection with Crimean-Congo haemorrhagic fever virus.\n\nThe length of the incubation period depends on the mode of acquisition of the virus. Following infection by a tick bite, ...\n --PARENT--> [?] Certain arthropod-borne viral fevers\n --CHILD--> [1D41] Colorado tick fever", "[1D49] Crimean-Congo haemorrhagic fever\n Def: A disease caused by an infection with Crimean-Congo haemorrhagic fever virus.\n\nThe length of the incubation period depends on the mode of acquisition of the virus. Following infection by a tick bite, ...\n --PARENT--> [?] Certain arthropod-borne viral fevers\n --CHILD--> [1D40] Chikungunya virus disease", "[KA21.2Z] Low birth weight of newborn, unspecified\n --PARENT--> [KA21.2] Low birth weight of newborn\n Def: A paediatric condition in which the infant is born weighing between 1500 and 2499 g....\n --CHILD--> [KA21.2Z] Low birth weight of newborn, unspecified", "[KA21.2Z] Low birth weight of newborn, unspecified\n --PARENT--> [KA21.2] Low birth weight of newborn\n Def: A paediatric condition in which the infant is born weighing between 1500 and 2499 g....\n --CHILD--> [KA21.20] Low birth weight of newborn, 1500-1999g\n Def: A paediatric condition in which the infant is born weighing between 1500 and 1999 g....", "[MB48.3] Light-headedness\n --PARENT--> [MB48] Dizziness or giddiness\n Def: Terms which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Dizziness is a general feeling of being off-balance. Giddiness is the feeling that you or you...\n --PARENT--> [?] Symptoms or signs involving the nervous system", "[MB48.3] Light-headedness\n --PARENT--> [MB48] Dizziness or giddiness\n Def: Terms which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Dizziness is a general feeling of being off-balance. Giddiness is the feeling that you or you...\n --CHILD--> [MB48.0] Vertigo" ]	1D49	Crimean-Congo haemorrhagic fever	[ { "from_icd11": "1D49", "icd10_code": "A980", "icd10_title": "Crimean-Congo hemorrhagic fever" }, { "from_icd11": "KA21.2Z", "icd10_code": "P071", "icd10_title": "Other low birth weight newborn" }, { "from_icd11": "9D45", "icd10_code": "H538", "icd10_title": "Other visual disturbances" }, { "from_icd11": "9D45", "icd10_code": "H536", "icd10_title": "Night blindness" }, { "from_icd11": "2A83.52", "icd10_code": "D477", "icd10_title": "" }, { "from_icd11": "1D60.1Z", "icd10_code": "A983", "icd10_title": "Marburg virus disease" }, { "from_icd11": "9D44", "icd10_code": "H5351", "icd10_title": "Achromatopsia" }, { "from_icd11": "9D44", "icd10_code": "H5359", "icd10_title": "Other color vision deficiencies" }, { "from_icd11": "9D44", "icd10_code": "H5350", "icd10_title": "Unspecified color vision deficiencies" }, { "from_icd11": "9D44", "icd10_code": "H5355", "icd10_title": "Tritanomaly" }, { "from_icd11": "9D44", "icd10_code": "H5353", "icd10_title": "Deuteranomaly" }, { "from_icd11": "9D44", "icd10_code": "H535", "icd10_title": "Color vision deficiencies" }, { "from_icd11": "NC72.5", "icd10_code": "S72301A", "icd10_title": "Unspecified fracture of shaft of right femur, initial encounter for closed fracture" }, { "from_icd11": "NC72.5", "icd10_code": "S72302A", "icd10_title": "Unspecified fracture of shaft of left femur, initial encounter for closed fracture" }, { "from_icd11": "NC72.5", "icd10_code": "S72342A", "icd10_title": "Displaced spiral fracture of shaft of left femur, initial encounter for closed fracture" } ]	A980	Crimean-Congo hemorrhagic fever
Only two cases of false lateralization by scalp EEG have been described in patients with temporal lobe cavernomas, specifically in the right superior temporal gyrus and the hippocampus ( Table 1 ). Here, we report a rare case with apparent false lateralization of ictal onset by scalp EEG in a patient with a left medial frontal gyrus cavernoma. We also discuss the clinical and pathophysiological mechanisms of cavernous malformation in the development of recurrent seizures and false lateralization. brainsci-10-00584-t001_Table 1 Table 1 Summary of demographic, neuroimaging, and EEG findings of false lateralization cases in the literature. Age (Years)-Sex Clinical Features and Ictal Semiology MRI (Structural Findings) Functional Neuroimaging Scalp EEG Intracraneal Ictal EEG False Lateralization Hypothesis Ref. 56, female Focal onset, awareness impairment, non-motor features. Normal No area of hypo metabolism Interictal: sharp waves from both temporal head regions. Ictal: rhythmic 5-6 ictal activity from the left temporal head region. Ictal seizure onset in the right temporal lobe. 1.5 s after seizure onset on the right: gamma activity in the left mesial temporal and the left lateral temporal electrodes. Temporal neocortex epilepsy: rapidly involve the contralateral mesolimbic structures; spread through the hippocampal commissures. Initial low voltage fast activity in the right temporal was undetectable on scalp EEG. 25, female Focal onset, awareness impairment, non-motor features and motor features (turn her head to the left, chewing, and hyperkinetic movements) Atrophic process in the left hemisphere Not reported Interictal epileptiform in both inferomesial temporal regions, left side predominance. Ictal: right temporal region onset, two seconds later it spread to the contralateral hemisphere, amplitude predominance was right Seizure onset started in the left temporal. 36 s after the seizure onset, the ictal discharge spread to the right temporal lobe Cerebral damage reduces the voltage of the ictal discharge on the side of the lesion and higher amplitude in the normal hemisphere. 21, male Unknown onset seizure with motor activity. Focal onset, and impairment awareness, motor features (automatism), and non-motor features (epigastralgic sensation) Left hemisphere atrophy Not reported Interictal. sphenoidal EEG: bilateral temporal, independent sharp waves with left sided predominance Ictal: discharge arise from the right frontotemporal regions, predominance over the right temporal region, 12 s after the seizure onset, ictal discharge spread to the contralateral hemisphere. Onset of the ictal discharge in the left temporal lobe Cerebral damage reduces the voltage of the ictal discharge on the side of the lesion and higher amplitude in the normal hemisphere. 30, male Focal onset, and impairment awareness , non motor features (fear) and motor features (automatism) Enlarged left lateral ventricle, three small areas of hypo density in the left posterior limb of the internal capsule Bitemporal independent, interictal sharp waves with right-sided predominance. Ictal EEG: seizure onset in the right temporal lobe. Seizure discharge started in the left temporal lobe. 2–3 s after seizure onset ictal discharge spread to the right temporal lobe also spread to both frontal regions. Cerebral damage reduces the voltage of the ictal discharge on the side of the lesion and higher amplitude in the normal hemisphere. 39, female 1. Focal onset, and impairment awareness , non motor features (epigastric sensation) 2. Focal onset, and impairment awareness and bilateral progression Atrophy of the left cerebral hemisphere. Interictal Ictal ECD- SPECT: left hemispheric hypo perfusion and IMZ SPECT revealed slight hypo accumulation in the left hippocampus Ictal: Right temporal side focus Interictal subdural EEG: independently in the left hippocampus region and also the right hippocampus region with spread to the lateral temporal regions. Reduced epileptiform activity in the atrophic hemisphere. Scalp EEG and MEG propagated electricals signals to the right side are easier to detect than signs to the left side. 23, male Focal onset, epigastric sensation, impaired awareness, and motor features (automatisms) Severe left hippocampal sclerosis Left temporal hypometabolism Interictal scalp EEG: mild left temporal slow, left midpost, temporal spikes. Ictal scalp: 4 right temporal, 1 left temporal Left mesial temporal “Burned-out hippocampus” syndrome with atypical spread of ictal discharges. Not enough neocortical neurons to produce a visible scalp discharge is not accomplished until propagation of the seizure to the contralateral temporal lobe. 48, male Focal onset, and motor features (automatisms) Severe left hippocampal sclerosis Not reported Interictal scalp EEG: Bitemporal spikes Ictal scalp: 5 right temporal, 2 bitemporal Left hippocampus/amygdala and lateral temporal spikes. “Burned-out hippocampus” with atypical spread of ictal discharges. Rapid bilateral spread. 38, female Bilateral tonic-clonic seizures, impaired awareness and non-motor components (panic attacks). Recalled memory, epigastric sensation. Mild right hippocampal atrophy PET: Mild right temporal hypo metabolism Interictal: mild generalized slowing, right anterior temporal spikes, rare left anterior temporal sharps Ictal scalp: theta frequency rhythmic discharge in the left temporal region. Frequent spikes in the right mesial entorhinal cortex. Right anterior hippocampus and amygdala. Propagation through the dorsal hippocampal commissure was faster than that to the overlying ipsilateral neocortex, thereby producing falsely discordant ictal scalp EEG recordings. Location and extent of the epileptogenic region: a more posterior hippocampal propagation pattern. 37, female Focal onset, impaired awareness and bilateral tonic-clonic seizures. Lightheadedness, staring, fumbling. Severe right hippocampal atrophy PET: hypo metabolism: mild right temporal Interictal infrequent left temporal sharp waves Ictal scalp: left temporal onset Initial seizures (slowing and spikes and sharp waves) bitemporal, later ones right temporal “Burned-out hippocampus” with atypical spread of ictal discharges. Interhemispheric propagation. Propagation through the dorsal hippocampal commissure was faster than that to the overlying ipsilateral neocortex, thereby producing falsely discordant ictal scalp EEG recordings 27, male Focal onset, impaired awareness and motor features (bimanual automatisms), epigastric sensation. Severe left hippocampal atrophy Not performed Interictal: left mid temporal spikes Ictal: 3 right midtemporal onset, 1 bitemporal onset Slowing and frequent spikes in the left hippocampus, some spikes in the right hippocampus. “Burned-out hippocampus” with atypical spread of ictal discharges. 12, male Auditory aura, bimanual and oral automatisms, impaired awareness and non-motor features (déjà vu) Cavernous malformation in the right superior temporal gyrus F-FDG-PET focal hypo metabolism on the right, left temporal hypo metabolism. SPECT ictal and interictal: focal hypo perfusion at the location of the cavernoma. Interictal: left temporal hypo perfusion Ictal: hyper perfusion on the left temporal lobe. Abnormal perfusion of the left temporal lobe and along the caudal margin of the right temporal cavernoma. MEG: spikes sources around the cavernoma, but also contralateral in the left miid lateral temporal region. Left frontal and posterior head quadrant spikes and a single electro clinical seizure originating in the left frontal head region. Not performed in the presurgical state Distinct site of epileptogenesis contralateral to the cavernoma (two epileptogenic foci) or rapid contralateral spread of epileptogenic activity. 34, female Focal onset, memory deficits, impaired awareness, non motor (“weird feelings”) and motor features (automatisms). Cavernous angioma in the left medial temporal lobe Not performed Interictal: epileptiform patterns (right more than left) Ictal: two seizures with a right temporal origin and two of less certain onset Right mesial temporal onset (subdural strip electrodes) Focal neurochemical abnormalities that coincide with ictal onsets. 33, not reported. Not seizure description. Left, fronto-temporal dysfunction in the NPT and Wada test. Left hippocampal sclerosis Not performed Interictal: epileptiform discharges in the left temporal region. Ictal: 2 ictal onsets in the left, 4 seizures onset in the right temporal region. Ictal onset in the left hippocampus. Seizure spreading to contralateral neocortex through functional commissural connections (i.e., dorsal hippocampal commissure) Rapid contralateral spread by activation of frontal limbic pathways. 27, not reported Not seizure description. Left, temporal dysfunction in the NPT and Wada test. Left hippocampal sclerosis Not performed Interictal: epileptiform discharges in the left side. Ictal: 2 ictal seizure onset in the right temporal region Ictal onset in the left hippocampus. Seizure spreading to contralateral neocortex through functional commissural connections (i.e., dorsal hippocampal commissure) Rapid contralateral spread by activation of frontal limbic pathways. 25, not reported Not clinical information Left hippocampal sclerosis Not performed Interictal: epileptiform discharges in the left side. Ictal: 3 ictal seizure onset in the right side Ictal onset in the left anterior inferior–mesial temporal region. Seizure spreading to contralateral neocortex through functional commissural connections (i.e., dorsal hippocampal commissure) Rapid contralateral spread by activation of frontal limbic pathways. 33, not reported Not seizure description. Right, temporal dysfunction in the NPT and Wada test. Right hippocampal sclerosis Not information Interictal: epileptiform discharges in the right side. Ictal: 4 ictal seizure onset in the left temporal region Ictal onset: right hippocampus Seizure spreading to contralateral neocortex through functional commissural connections (i.e., dorsal hippocampal commissure) Rapid contralateral spread by activation of frontal limbic pathways. 45, male Focal onset, impaired awareness, non-motor features (déjà vu and periodic nausea). Impairment of both verbal and visual memory in the NPT. Several bilateral scattered white matter hyper intensities, most prominent in the left frontal lobe. Decreased glucose uptake in the left temporal lobe as compared with the right temporal lobe in both lateral and mesial cortical regions. Onset in the right amygdala, although one subclinical seizure began in the left temporal lobe. EEG from the right amygdala showed continuous low-amplitude fast activity (>13 Hz) for extended times; at other times, this pattern was entirely absent. The fast activity was believed to be epileptic, although it was asymptomatic. Several discrete subclinical seizures with a different electrographic pattern originated in the right amygdala, later spreading to the right hippocampus. Abnormal increase in temporal lobe metabolism. 27, female Focal onset, aware, non motor features (unpleasant smell and taste, salivation, noted strange feelings in her face or body) Dilated right temporal ventricular horn with questionable decreased hippocampal volume Less FDG uptake in the left temporal lobe than in the right temporal lobe, mainly in lateral temporal cortex. Right sphenoidal spikes and intermittent arrhythmic right sphenoidal theta in wakefulness and sleep. All arose from the right amygdala. The EEG also showed frequent (several per second) sharp waves and occasional subclinical electrographic seizures in the right amygdala. Sharp waves amplify neuronal activity in temporal lobe neocortex through amygdalocortical connections, possibly increasing lateral temporal cortical metabolism. 47, male Focal onset, awareness impairment, non-motor features (déjà vu) Left hippocampal atrophy FDG PET: decreased uptake in the left temporal region Ictal EEG: Left temporal (1 min after the clinical onset of the seizure) SDE: seizure onset in the right lateral temporal region before spreading to the let lateral temporal SDE in 4 to 10 s. SEEG: Regional onset seizure arising from the left SEEG electrodes suggesting a left temporal onset Rapid contralateral spread through the hippocampal commissure or frontal limbic pathways 45, female 1. Unknown onset seizure with motor activity 2. Focal onset, awareness impairment, non motor features 3. Focal onset, awareness impairment, and progression to bilateral tonic–clonic seizures Normal FDG PET: normal. Interictal: Left temporal epileptiform discharges. Ictal recordings: no localizing and no lateralizing SEEG electrodes: seizures arising from the left temporal electrode, then spreading to the contralateral electrode first, followed 5 to 20 s later by spread to the contralateral temporal SDE; the ipsilateral SDE recordings showed no change Rapid contralateral spread through the hippocampal commissure or frontal limbic pathways Abbreviations: ECD: ethyl cysteinate dimer; EEG: electroencephalogram; FDG: [‘8F] fluorodeoxyglucose; IMZ: I-123 iomazenil; MEG: Magnetoencephalography; MRI: magnetic resonance imaging; NPT: neuropsychological test; PET: positron emission tomography; SEEG: stereotactic depth EEG; SDE: subdural electrodes; SPECT: single-photon emission computed tomography.	4.269531	0.672852	sec[0]/p[2]	en	0.999997	32846994	https://doi.org/10.3390/brainsci10090584	[ "temporal", "ictal", "onset", "seizure", "motor", "hippocampal", "spread", "lobe", "interictal", "contralateral" ]	[ { "code": "4A44.2", "title": "Giant cell arteritis" }, { "code": "8B82.Z", "title": "Disorders of trigeminal nerve, unspecified" }, { "code": "4A44.Y", "title": "Other specified vasculitis" }, { "code": "NA0Z&XA9T94", "title": "Temporal region injury" }, { "code": "NA01.Z&XA9T94", "title": "Temporal wound" }, { "code": "ND56.Y", "title": "Other specified injury of unspecified body region" }, { "code": "8A6Y", "title": "Other specified epilepsy or seizures" }, { "code": "MA81", "title": "Speech dysfluency" }, { "code": "6A01.1", "title": "Developmental speech fluency disorder" }, { "code": "4A42.0", "title": "Paediatric onset systemic sclerosis" } ]	=== ICD-11 CODES FOUND === [4A44.2] Giant cell arteritis Definition: Arteritis, often granulomatous, usually affecting the aorta and/or its major branches, with a predilection for the branches of the carotid artery. Often involves the temporal artery. Onset usually in patients older than 50 and often associated with polymyalgia rheumatica. Also known as: Giant cell arteritis \| GCA - [giant cell arteritis] \| temporal arteritis \| cranial arteritis \| Horton disease [8B82.Z] Disorders of trigeminal nerve, unspecified Also known as: Disorders of trigeminal nerve, unspecified \| Disorders of trigeminal nerve \| Disorders of 5th cranial nerve \| disorders of the fifth cranial nerve \| Gasserian ganglion lesion [4A44.Y] Other specified vasculitis Also known as: Other specified vasculitis \| Large vessel vasculitis \| Juvenile temporal arteritis \| Medium-sized vessel vasculitis \| Polyangiitis overlap syndrome [ND56.Y] Other specified injury of unspecified body region Also known as: Other specified injury of unspecified body region \| Ictal traumatic injuries \| Bone injury, not elsewhere classified \| Blast injury, unspecified site \| Injury from underwater blast, unspecified site [8A6Y] Other specified epilepsy or seizures Also known as: Other specified epilepsy or seizures \| Benign focal seizures of adolescence \| BFSA - [benign focal seizures of adolescence] \| Postictal fugue in epilepsy \| Postictal amnesia in epilepsy [MA81] Speech dysfluency Definition: Speech dysfluency is characterised by the frequent or pervasive disruption of the rhythmic flow of speech that arises subsequent to the developmental period (i.e., adult onset) and is outside the limits of normal variation and results in reduced intelligibility and significantly affects communication. It can involve repetitions of sounds, syllables or words, prolongations, word breaks, blockage of production, excessive use of interjections, and rapid short bursts of speech. Also known as: Speech dysfluency \| speech impediment NOS \| Adult onset cluttering \| Adult onset stammering \| Adult onset stuttering Excludes: Developmental language disorder \| Developmental speech or language disorders \| Developmental speech fluency disorder [6A01.1] Developmental speech fluency disorder Definition: Developmental speech fluency disorder is characterised by frequent or pervasive disruption of the normal rhythmic flow and rate of speech characterised by repetitions and prolongations in sounds, syllables, words, and phrases, as well as blocking and word avoidance or substitutions. The speech dysfluency is persistent over time. The onset of speech dysfluency occurs during the developmental period and speech fluency is markedly below what would be expected for age. Speech dysfluency results in s Also known as: Developmental speech fluency disorder \| Speech fluency disorder \| Developmental neurogenic stuttering \| childhood onset stuttering \| developmental onset stuttering Excludes: Tic disorders [4A42.0] Paediatric onset systemic sclerosis Definition: Systemic sclerosis arising before the age of 16. Involvement of internal organs is less common but arthritis and myositis are more common than in adults. Also known as: Paediatric onset systemic sclerosis \| Diffuse paediatric systemic sclerosis \| Limited paediatric systemic sclerosis === GRAPH WALKS === --- Walk 1 --- [4A44.2] Giant cell arteritis Def: Arteritis, often granulomatous, usually affecting the aorta and/or its major branches, with a predilection for the branches of the carotid artery. Often involves the temporal artery. Onset usually in ... --PARENT--> [4A44] Vasculitis Def: Vasculitides represent a heterogenous group of diseases of multifactorial aetiology characterised by inflammatory lesions of vessels. These lesions consist of fibrinoid necrosis (necrotizing arteritis... --CHILD--> [4A44.1] Aortic arch syndrome Def: Arteritis, often granulomatous, predominantly affecting the aorta and/or its major branches. Onset usually in patients younger than 50.... --- Walk 2 --- [4A44.2] Giant cell arteritis Def: Arteritis, often granulomatous, usually affecting the aorta and/or its major branches, with a predilection for the branches of the carotid artery. Often involves the temporal artery. Onset usually in ... --PARENT--> [4A44] Vasculitis Def: Vasculitides represent a heterogenous group of diseases of multifactorial aetiology characterised by inflammatory lesions of vessels. These lesions consist of fibrinoid necrosis (necrotizing arteritis... --CHILD--> [4A44.0] Rhizomelic pseudopolyarthritis --- Walk 3 --- [8B82.Z] Disorders of trigeminal nerve, unspecified --PARENT--> [8B82] Disorders of trigeminal nerve Def: The trigeminal nerve is a mixed nerve with three divisions, ophthalmic, maxillary and mandibular divisions, that provides sensory innervation to the face and mucous membrane of the oral and nasal cavi... --CHILD--> [8B82.0] Trigeminal neuralgia Def: Trigeminal neuralgia is a manifestation of orofacial neuropathic pain restricted to one or more divisions of the trigeminal nerve. The pain is recurrent, abrupt in onset and termination, triggered by ... --- Walk 4 --- [8B82.Z] Disorders of trigeminal nerve, unspecified --PARENT--> [8B82] Disorders of trigeminal nerve Def: The trigeminal nerve is a mixed nerve with three divisions, ophthalmic, maxillary and mandibular divisions, that provides sensory innervation to the face and mucous membrane of the oral and nasal cavi... --RELATED_TO--> [?] Atypical facial pain Def: This is a chronic pain of the face, which does not meet other diagnostic criteria.... --- Walk 5 --- [4A44.Y] Other specified vasculitis --PARENT--> [4A44] Vasculitis Def: Vasculitides represent a heterogenous group of diseases of multifactorial aetiology characterised by inflammatory lesions of vessels. These lesions consist of fibrinoid necrosis (necrotizing arteritis... --RELATED_TO--> [?] Thrombotic microangiopathy, not elsewhere classified Def: Thrombotic microangiopathies are microvascular occlusive disorders characterised by systemic or intrarenal aggregation of platelets, thrombocytopenia, and mechanical injury to erythrocytes. Thrombotic... --- Walk 6 --- [4A44.Y] Other specified vasculitis --PARENT--> [4A44] Vasculitis Def: Vasculitides represent a heterogenous group of diseases of multifactorial aetiology characterised by inflammatory lesions of vessels. These lesions consist of fibrinoid necrosis (necrotizing arteritis... --RELATED_TO--> [?] Behçet disease Def: Behçet disease is a disease of incompletely understood aetiopathogenesis characterised by recurrent oral and/or genital aphthous ulcers accompanied by cutaneous, ocular, articular, gastrointestinal, a...	[ "[4A44.2] Giant cell arteritis\n Def: Arteritis, often granulomatous, usually affecting the aorta and/or its major branches, with a predilection for the branches of the carotid artery. Often involves the temporal artery. Onset usually in ...\n --PARENT--> [4A44] Vasculitis\n Def: Vasculitides represent a heterogenous group of diseases of multifactorial aetiology characterised by inflammatory lesions of vessels. These lesions consist of fibrinoid necrosis (necrotizing arteritis...\n --CHILD--> [4A44.1] Aortic arch syndrome\n Def: Arteritis, often granulomatous, predominantly affecting the aorta and/or its major branches. Onset usually in patients younger than 50....", "[4A44.2] Giant cell arteritis\n Def: Arteritis, often granulomatous, usually affecting the aorta and/or its major branches, with a predilection for the branches of the carotid artery. Often involves the temporal artery. Onset usually in ...\n --PARENT--> [4A44] Vasculitis\n Def: Vasculitides represent a heterogenous group of diseases of multifactorial aetiology characterised by inflammatory lesions of vessels. These lesions consist of fibrinoid necrosis (necrotizing arteritis...\n --CHILD--> [4A44.0] Rhizomelic pseudopolyarthritis", "[8B82.Z] Disorders of trigeminal nerve, unspecified\n --PARENT--> [8B82] Disorders of trigeminal nerve\n Def: The trigeminal nerve is a mixed nerve with three divisions, ophthalmic, maxillary and mandibular divisions, that provides sensory innervation to the face and mucous membrane of the oral and nasal cavi...\n --CHILD--> [8B82.0] Trigeminal neuralgia\n Def: Trigeminal neuralgia is a manifestation of orofacial neuropathic pain restricted to one or more divisions of the trigeminal nerve. The pain is recurrent, abrupt in onset and termination, triggered by ...", "[8B82.Z] Disorders of trigeminal nerve, unspecified\n --PARENT--> [8B82] Disorders of trigeminal nerve\n Def: The trigeminal nerve is a mixed nerve with three divisions, ophthalmic, maxillary and mandibular divisions, that provides sensory innervation to the face and mucous membrane of the oral and nasal cavi...\n --RELATED_TO--> [?] Atypical facial pain\n Def: This is a chronic pain of the face, which does not meet other diagnostic criteria....", "[4A44.Y] Other specified vasculitis\n --PARENT--> [4A44] Vasculitis\n Def: Vasculitides represent a heterogenous group of diseases of multifactorial aetiology characterised by inflammatory lesions of vessels. These lesions consist of fibrinoid necrosis (necrotizing arteritis...\n --RELATED_TO--> [?] Thrombotic microangiopathy, not elsewhere classified\n Def: Thrombotic microangiopathies are microvascular occlusive disorders characterised by systemic or intrarenal aggregation of platelets, thrombocytopenia, and mechanical injury to erythrocytes. Thrombotic...", "[4A44.Y] Other specified vasculitis\n --PARENT--> [4A44] Vasculitis\n Def: Vasculitides represent a heterogenous group of diseases of multifactorial aetiology characterised by inflammatory lesions of vessels. These lesions consist of fibrinoid necrosis (necrotizing arteritis...\n --RELATED_TO--> [?] Behçet disease\n Def: Behçet disease is a disease of incompletely understood aetiopathogenesis characterised by recurrent oral and/or genital aphthous ulcers accompanied by cutaneous, ocular, articular, gastrointestinal, a..." ]	4A44.2	Giant cell arteritis	[ { "from_icd11": "4A44.2", "icd10_code": "M316", "icd10_title": "Other giant cell arteritis" }, { "from_icd11": "8B82.Z", "icd10_code": "G508", "icd10_title": "Other disorders of trigeminal nerve" }, { "from_icd11": "8B82.Z", "icd10_code": "G509", "icd10_title": "Disorder of trigeminal nerve, unspecified" }, { "from_icd11": "8B82.Z", "icd10_code": "G50", "icd10_title": "Disorders of trigeminal nerve" }, { "from_icd11": "ND56.Y", "icd10_code": "T148XXA", "icd10_title": "Other injury of unspecified body region, initial encounter" }, { "from_icd11": "MA81", "icd10_code": "R4789", "icd10_title": "Other speech disturbances" }, { "from_icd11": "MA81", "icd10_code": "R4781", "icd10_title": "Slurred speech" }, { "from_icd11": "MA81", "icd10_code": "R4782", "icd10_title": "Fluency disorder in conditions classified elsewhere" }, { "from_icd11": "MA81", "icd10_code": "R478", "icd10_title": "Other speech disturbances" }, { "from_icd11": "6A01.1", "icd10_code": "F8081", "icd10_title": "Childhood onset fluency disorder" }, { "from_icd11": "6A01.1", "icd10_code": "F8089", "icd10_title": "Other developmental disorders of speech and language" }, { "from_icd11": "6A01.1", "icd10_code": "F985", "icd10_title": "Adult onset fluency disorder" }, { "from_icd11": "6A01.1", "icd10_code": "F808", "icd10_title": "Other developmental disorders of speech and language" }, { "from_icd11": "6A01.1", "icd10_code": "F986", "icd10_title": "" }, { "from_icd11": "4A42.0", "icd10_code": "M349", "icd10_title": "Systemic sclerosis, unspecified" } ]	M316	Other giant cell arteritis
Three of the authors (RHB, YB, YO) have maintained a bipolar clinic including lithium therapy for over 30 years servicing a defined catchment area of 300,000 people in southern Israel . We reviewed our charts for evidence of patients who had developed kidney disease: ST (female, 65 years old). The patient was started on 1500 mg/day lithium at age 34 following hospitalization for acute mania. She was stable for 13 years. After the appearance of polyuria, the dose was reduced to 900 mg/day. Five years later, following a depression and reinstatement of 1500 mg/day, blood level rose to 1.8 mEq/L and creatinine levels reached 1.8 mg/dL. Nephrology consultation diagnosed mild renal failure, and the patient was switched gradually to valproate (800 mg/day); after which, no further progression of kidney damage was observed. Nine years after complete cessation of lithium, however, creatinine rose to 3.5 mg/dL and the patient began dialysis treatment 3 years ago. She is currently stable on valproate, awaiting a kidney transplant. OE (male, 38 years old). The patient was first hospitalized at age 25 with a severe psychotic mania. Symptoms proved very difficult to control without high doses of lithium plus valproate and dopamine blockers (olanzapine or clozapine). Patient relapsed with psychotic symptoms any time blood lithium levels fell below 1.2 mEq/L. Creatinine levels rose from 1.1 to 1.4 mg/dL and blood urea nitrogen (BUN) from 27 to 43 mg/dL over a period of a few months. Lithium dose was lowered to 1500 mg/day, but the kidneys continued to deteriorate. Additional decreases of lithium dosage were postponed due to the objections of the patient and family. Recently, after the introduction of asenapine 30 mg/day in addition to olanzapine 10 mg and valproate 2500 mg/day, lithium has been reduced to 600 mg/day. Creatinine levels are currently 1.5 mg/dL, BUN = 53 mg/dL, and the patient is reasonably stable. MBD (female, 77 years old). First hospitalized with severe depression at age 28, this patient began treatment with lithium (plus clomipramine) after a second hospitalization at age 50. She was stable for many years on lithium 900 mg/day, with blood levels of 0.5–0.6 mEq/L. Rheumatoid arthritis developed and was treated with azathioprine or gold; during the 6 years she received this treatment, lithium dosage was raised to 1200 mg/day and blood levels ranged from 0.6 to 1.2 mEq/L. The dosage was subsequently returned to 900 mg/day. Parkinson’s disease developed and was treated with rasagiline, carbidopa, and levodopa. When creatinine levels of 2.07–3.2 mg/dL and BUN of 66 mg/dL were observed, lithium was reduced to 150 mg/day. Creatinine and BUN levels began to improve. Shortly thereafter, at age 77, the patient left the area and was lost to follow-up. JL (female, 60 years old). First hospitalized at age 32 due to a manic psychosis, this patient had an additional hospitalization less than a year later. Lithium was started at age 34, and the patient had full remissions (with four hospitalizations) for 17 years. When hospitalized again at age 51, lithium treatment was stopped (due to “lack of efficacy”) and treatment was switched to valproic acid plus perphenazine and afterwards continued as perphenazine alone. After 5 years of fragile stability and several mood episodes which did not require hospitalization, the patient was hospitalized again at age 56 and lithium was reinstated at a low dose (600 mg/day) plus 4 mg perphenazine. One year later, creatinine rose above 1.0 mg/dL. The patient has been affectively stable for the past 4 years, and creatinine is currently 1.5 mg/dL. DL (female, 37 years old). While in her early 20s, this patient experienced major depression and attempted suicide. She was treated with valproate plus fluoxetine, which precipitated a manic episode and hospitalization. After 2 years of failed attempts at stabilization with valproate plus haloperidol or ziprasidone, including substantial weight gain, the patient was switched to lithium plus risperidone. A miscarriage and subsequent depression was treated with lithium 2100 mg/day plus perphenazine, with lithium blood levels reaching 1.5 mEq/L. The patient went through a successful pregnancy and delivery while being managed on lithium, but after 3 years, she developed nephrogenic diabetes insipidus. She was gradually switched over to lamotrigine (400 mg/day) plus perphenazine 8 mg/day and has been reasonably stable for 4 years, with creatinine levels of 1.0 mg/dL. SD (male, 47 years old). The patient began treatment with carbamazepine plus haloperidol after a severe psychotic episode at age 25. After several additional hospitalizations in quick succession, lithium was added to the treatment, at first 1800–2100 mg/day then later reduced to 900 mg/day. Initial creatinine level was measured at 1.0 mg/dL but rose to 2.5–2.7 mg/dL after being on lithium for 10 years. Nephrogenic diabetes insipidus and renal failure developed during a 3-month period in which the patient was lost to follow-up. Lithium treatment was stopped; carbamazepine was continued. Patient was again lost to follow-up for 1 year, and at the end of which, he was hospitalized and diagnosed with end-stage renal failure (creatinine = 7.2 mg/dL). Treatment was changed to chlorpromazine, and the patient began renal dialysis and subsequently underwent a kidney transplant, which failed after 1 year. He is currently stable on chlorpromazine plus diazepam and is wait-listed for a second kidney transplant. RP (male, 64 years old). Hypomanic episodes were experienced along with numerous hospitalizations for depression between the ages of 23 and 53. The patient was treated with a variety of medications and interventions not including lithium. Prior to hospitalization resulting from a suicide attempt at age 53, the patient had been treated with carbamazepine plus clonazepam. During the hospitalization, treatment was changed to lithium . The patient was stable for 8 years, but when creatinine level rose to 1.88 mg/dL and BUN to 42 mg/dL, lithium was reduced to 600 mg/day and then discontinued in favor of a combination of valproate and carbamazepine. He has been reasonably stable on this combination for approximately 3 years. Creatinine level has reduced slightly (currently 1.55 mg/dL) and BUN is currently 36 mg/dL. SP (male, 66 years old). The patient’s first affective episode, at age 18, included a switch from depression to mania and a suicide attempt. He was treated with lithium and thioridazine for 29 years, with a full remission and only one additional hospitalization, until developing nephrogenic diabetes insipidus. Lithium was stopped and treatment switched to valproic acid plus topiramate and risperidone. The patient could not be stabilized, although multiple agents were tried, and experienced six hospitalizations during the following 5 years. Lithium was reinstated (900 mg/day) when the patient was 56 years old. One year later, creatinine was 1.59 mg/dL but rose quickly to 2.3 mg/dL within a few months. Lithium dose was reduced to between 600 and 750 mg/day, with blood levels of 0.9–1.1 mEq/L, and patient was stable with only one brief hospitalization over a period of 7 years. At that time, with creatinine at 2.06 mg/dL and lithium blood levels of 0.85 mEq/L although the dose had been reduced to 300 mg/day, it was decided again to stop lithium. The patient became severely manic within a few months in spite of treatment with relatively high doses of atypical antipsychotic medication, requiring hospitalization. Lithium was reinstated at doses of 300–600 mg/day, and the patient has remained reasonably stable for 3 years. Creatinine levels have continued to increase to 2.8 mg/dL and BUN 83 mg/dL, and the patient is currently being followed by a nephrologist while continuing treatment with lithium at low doses plus olanzapine. SH (female, 66 years old). This patient, with a strong family history for bipolar disorder, experienced a psychotic postpartum depression at age 20 and began lithium prophylaxis following a successful course of electroconvulsive therapy. Lithium was continued with good remissions (though some recurrent affective episodes and hospitalizations). Hypothyroidism and parathyroid adenoma were treated by an endocrinologist without the need to stop lithium; the patient also had surgery for a cancerous growth in her breast. After 39 years of lithium treatment, the patient developed renal insufficiency with creatinine clearance of 50 ml/min, creatinine level = 1.6 mg/dL. She was successfully switched over to valproate (800 mg/day) approximately 5 years ago. She has been stable, with valproate levels in the 80s; creatinine is currently 2.0–2.2 mg/dL and BUN = 65 mg/dL. LR (male, 54 years old). First hospitalized for an acute psychotic episode at age 17, this patient experienced multiple hospitalizations over a period of 7 years until lithium was added to his treatment. He remained essentially stable for 28 years while being treated with a combination of lithium 1500 mg/day plus chlorpromazine. Complications of treatment occurred over time, including hypertension and hyperthyroidism, and at age 52, he was diagnosed with chronic renal failure (creatinine = 1.62 mg/dL, BUN = 44 mg/dL). The patient was switched to treatment with valproate 2000 mg/d plus risperidone 3 mg/day and is currently stable with creatinine level of 1.75 mg/dL. RB (male, 68 years old). Although known to have a “bad temper” and a positive family history for affective disorder, this patient was not diagnosed as having bipolar disorder until a first hospitalization for mania at age 50. He was stabilized on lithium 1500 mg/day plus low doses of various dopamine blockers. Lithium dosage was reduced to 600 mg/day when blood levels reached 1.4 mEq/L; creatinine clearance at the time was 70 mL/min, creatinine = 1.4 mg/dL, and BUN = 47 mg/dL. Stopping lithium was discussed, but due to a difficult bereavement, it was decided to continue treatment as before. The patient was stable after 1 year on lithium 300 mg/day plus risperidone 2 mg/day, with slight reduction in creatinine level (to 1.23 mg/dL) and BUN unchanged at 48 mg/dL. YA (male, 66 years old). Although pronounced episodes of depression and hypomania were evident from the age of 33, with severe effects on his occupational and personal life, this patient was first diagnosed with bipolar disorder during his first hospitalization, at age 41 (for mania). He began treatment with 1200 mg/day lithium and was stable for 9 years. Due to inconsistent adherence, valproate was added at that point and lithium reduced to 900 mg/day. Lithium was reduced to 600 mg/day when creatinine level rose to 1.2 mg/dL (BUN = 34 mg/dL) and polyuria appeared. The patient became unstable when attempts were made to further lower lithium dose, until olanzapine (5 mg/day) was added to the treatment. One year later, the patient developed diabetes mellitus. Creatinine rose slightly (to 1.3 mg/dL, BUN = 34 mg/dL), and lithium was reduced to 300 and finally to 150 mg/day (the patient is extremely reluctant to stop lithium entirely). Although affectively stable, the patient has developed early-onset dementia, apparently due to cerebral aneurysm. MO (male, 52 years old). Two years after a first hospitalization for psychotic mania at age 24, this patient with a positive family history of affective disorder began treatment with lithium. At age 43, he attempted suicide by ingesting 33 lithium tablets; creatinine level at that time was 1.4 mg/dL and BUN 34 mg/dL. Two years later, the patient again attempted suicide by ingestion of 55 lithium tablets. Lithium treatment was then terminated due to renal failure (creatinine = 1.8 mg/dL, BUN = 49 mg/dL), and the patient was switched over to clozapine. Creatinine and BUN levels continued to rise despite the cessation of lithium. In addition to chronic renal failure due to lithium poisoning, the patient also suffers from hyperthyroidism, hypercalcemia, dyslipidemia, and hypertension. GG (male, 35 years old). Although apparently ill from his teens, this patient was first hospitalized and diagnosed with bipolar illness at age 26. He was eventually stabilized on lithium 1500 mg/day (blood levels 1.1–1.2 mEq/L) plus clozapine. Creatinine began to rise to 1.5 mg/dL, and lithium dosage was reduced to 900 mg/day and then stopped gradually over a period of 6 months. The patient is currently stable on clozapine, and creatinine is currently 1.3 mg/dL and BUN 24 mg/dL. VV (female, 78 years old). This patient, with a strong family history of bipolar disorder, was first diagnosed (with mania) at age 58. For the following 17 years, she was treated with lithium (750–900 mg/day; blood lithium levels approximately 0.75 mEq/L). At age 75, she developed chronic renal failure, with creatinine = 1.4 mg/dL and BUN = 44 mg/dL. She continues to be treated with lithium at low doses (300–450 mg/day), with blood lithium levels 0.8–1.0 mg/day, and is affectively stable. Creatinine is currently 1.6 mg/dL and BUN = 62 mg/dL.	4.039063	0.952637	sec[0]/sec[2]/p[0]	en	0.999996	26043842	https://doi.org/10.1186/s40345-015-0028-y	[ "lithium", "creatinine", "plus", "hospitalization", "blood", "currently", "this", "valproate", "treated", "over" ]	[ { "code": "NE60", "title": "Harmful effects of drugs, medicaments or biological substances, not elsewhere classified" }, { "code": "PB26", "title": "Unintentional exposure to or harmful effects of antipsychotics" }, { "code": "PC96", "title": "Intentional self-harm by exposure to or harmful effects of antipsychotics" }, { "code": "PH46", "title": "Exposure to or harmful effects of undetermined intent of antipsychotics" }, { "code": "PE86", "title": "Assault by exposure to or harmful effects of antipsychotics" }, { "code": "GB42.1", "title": "Albuminuria, Grade A3" }, { "code": "GB42.0", "title": "Albuminuria, Grade A2" }, { "code": "9B71.3&XS00", "title": "Plus disease" }, { "code": "8C73.Y", "title": "Other specified mitochondrial myopathies" }, { "code": "LD21.Y", "title": "Other specified syndromes with eye anomalies as a major feature" } ]	=== ICD-11 CODES FOUND === [NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified Also known as: Harmful effects of drugs, medicaments or biological substances, not elsewhere classified \| drugs, medicaments or biological substances, toxicity not elsewhere classified \| adverse drug effects \| drug reaction NOS \| drug allergy NOS Excludes: Alcohol intoxication \| pathological drug intoxication \| hypersensitivity reaction to correctly administered drug [PB26] Unintentional exposure to or harmful effects of antipsychotics Also known as: Unintentional exposure to or harmful effects of antipsychotics \| accidental overdose of antipsychotics \| accidental poisoning by antipsychotics \| antipsychotics taken in error \| Unintentional exposure to or harmful effects of phenothiazine antipsychotics or neuroleptics Includes: accidental overdose of antipsychotics Excludes: Substances associated with injury or harm in therapeutic use [PC96] Intentional self-harm by exposure to or harmful effects of antipsychotics Also known as: Intentional self-harm by exposure to or harmful effects of antipsychotics \| intentional self-poisoning by antipsychotics \| Intentional overdose of antipsychotics \| Toxic effect of neuroleptics \| Intentional self-harm by exposure to or harmful effects of phenothiazine antipsychotics or neuroleptics [PH46] Exposure to or harmful effects of undetermined intent of antipsychotics Also known as: Exposure to or harmful effects of undetermined intent of antipsychotics \| harmful effects of neuroleptics, undetermined intent \| Harmful effects of or exposure to phenothiazine antipsychotics or neuroleptics, undetermined intent \| Harmful effects of or exposure to butyrophenone or thiothixene neuroleptics, undetermined intent \| Harmful effects of or exposure to typical, second-generation antipsychotics, undetermined intent [PE86] Assault by exposure to or harmful effects of antipsychotics Also known as: Assault by exposure to or harmful effects of antipsychotics \| Assault by exposure to or harmful effects of neuroleptics \| homicidal poisoning by exposure to or harmful effects of antipsychotics \| Assault by exposure to or harmful effects of phenothiazine antipsychotics or neuroleptics \| Assault by exposure to or harmful effects of butyrophenone or thiothixene neuroleptics [GB42.1] Albuminuria, Grade A3 Definition: Presence of excessive albumin in the urine, indicating abnormal permeability glomerular filtration. Can be quantitated by either timed collections or spot urine samples with the concentration adjusted to the urine creatinine concentration to correct for variations in overall urine concentration. When persistent and of moderate or greater severity usually indicates overt glomerular disease such as caused by diabetic glomerulosclerosis, glomerulonephritis or amyloid. Also known as: Albuminuria, Grade A3 \| albuminuria >30 mg/mmol creatinine \| macroalbuminuria \| overt albuminuria \| overt nephropathy [GB42.0] Albuminuria, Grade A2 Definition: Presence of excessive albumin in the urine, indicating abnormal permeability glomerular filtration. Can be quantitated by either timed collections or spot urine samples with the concentration adjusted to the urine creatinine concentration to correct for variations in overall urine concentration. When persistent and of moderate or greater severity usually indicates overt glomerular disease such as caused by diabetic glomerulosclerosis, glomerulonephritis or amyloid. Also known as: Albuminuria, Grade A2 \| microalbuminuria \| incipient nephropathy \| mild to moderate albuminuria \| albuminuria 3-30 mg/mmol creatinine [8C73.Y] Other specified mitochondrial myopathies Also known as: Other specified mitochondrial myopathies \| Mitochondrial myopathy with cytochrome C oxidase deficiency \| Mitochondrial myopathy with cytochrome C oxidase deficiency, severe infantile form \| Mitochondrial myopathy with coenzyme Q deficiency \| CoQ - [Mitochondrial myopathy with coenzyme Q deficiency] [LD21.Y] Other specified syndromes with eye anomalies as a major feature Also known as: Other specified syndromes with eye anomalies as a major feature \| Blepharophimosis - epicanthus inversus - ptosis \| BPES - [Blepharophimosis - epicanthus inversus - ptosis] syndrome \| Norrie disease \| Atrophia bulborum hereditaria === GRAPH WALKS === --- Walk 1 --- [NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified --EXCLUDES--> [?] Allergic or hypersensitivity conditions Def: Allergy is a hypersensitivity reaction initiated by proven immunologic mechanisms. Hypersensitivity is defined as conditions clinically resembling allergy that cause objectively reproducible symptoms... --CHILD--> [?] Allergic or hypersensitivity disorders involving the respiratory tract Def: Allergic or hypersensitivity disorders involving the respiratory tract includes several clinically different conditions that can be considered as hypersensitivity disorders of the upper and lower resp... --- Walk 2 --- [NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified --EXCLUDES--> [?] Alcohol intoxication Def: Alcohol intoxication is a clinically significant transient condition that develops during or shortly after the consumption of alcohol that is characterised by disturbances in consciousness, cognition,... --CHILD--> [?] Severe alcohol intoxication Def: Severe alcohol intoxication is a clinically significant transient condition that develops during or shortly after the administration of alcohol that is characterised by obvious disturbance in consciou... --- Walk 3 --- [PB26] Unintentional exposure to or harmful effects of antipsychotics --EXCLUDES--> [?] Substances associated with injury or harm in therapeutic use Def: Situations where a substance (drug or medicament) causes harm, in the context of intentional use for therapeutic purposes... --PARENT--> [?] Causes of healthcare related harm or injury --- Walk 4 --- [PB26] Unintentional exposure to or harmful effects of antipsychotics --EXCLUDES--> [?] Substances associated with injury or harm in therapeutic use Def: Situations where a substance (drug or medicament) causes harm, in the context of intentional use for therapeutic purposes... --EXCLUDES--> [?] Mode of injury or harm associated with exposure to a drug, medicament or biological substance --- Walk 5 --- [PC96] Intentional self-harm by exposure to or harmful effects of antipsychotics --PARENT--> [?] Intentional self-harm by exposure to or harmful effects of drugs, medicaments or biological substances --CHILD--> [PC91] Intentional self-harm by exposure to or harmful effects of sedative hypnotic drugs or other CNS depressants --- Walk 6 --- [PC96] Intentional self-harm by exposure to or harmful effects of antipsychotics --PARENT--> [?] Intentional self-harm by exposure to or harmful effects of drugs, medicaments or biological substances --CHILD--> [PC92] Intentional self-harm by exposure to or harmful effects of psychostimulants	[ "[NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified\n --EXCLUDES--> [?] Allergic or hypersensitivity conditions\n Def: Allergy is a hypersensitivity reaction initiated by proven immunologic mechanisms.\n\nHypersensitivity is defined as conditions clinically resembling allergy that cause objectively reproducible symptoms...\n --CHILD--> [?] Allergic or hypersensitivity disorders involving the respiratory tract\n Def: Allergic or hypersensitivity disorders involving the respiratory tract includes several clinically different conditions that can be considered as hypersensitivity disorders of the upper and lower resp...", "[NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified\n --EXCLUDES--> [?] Alcohol intoxication\n Def: Alcohol intoxication is a clinically significant transient condition that develops during or shortly after the consumption of alcohol that is characterised by disturbances in consciousness, cognition,...\n --CHILD--> [?] Severe alcohol intoxication\n Def: Severe alcohol intoxication is a clinically significant transient condition that develops during or shortly after the administration of alcohol that is characterised by obvious disturbance in consciou...", "[PB26] Unintentional exposure to or harmful effects of antipsychotics\n --EXCLUDES--> [?] Substances associated with injury or harm in therapeutic use\n Def: Situations where a substance (drug or medicament) causes harm, in the context of intentional use for therapeutic purposes...\n --PARENT--> [?] Causes of healthcare related harm or injury", "[PB26] Unintentional exposure to or harmful effects of antipsychotics\n --EXCLUDES--> [?] Substances associated with injury or harm in therapeutic use\n Def: Situations where a substance (drug or medicament) causes harm, in the context of intentional use for therapeutic purposes...\n --EXCLUDES--> [?] Mode of injury or harm associated with exposure to a drug, medicament or biological substance", "[PC96] Intentional self-harm by exposure to or harmful effects of antipsychotics\n --PARENT--> [?] Intentional self-harm by exposure to or harmful effects of drugs, medicaments or biological substances\n --CHILD--> [PC91] Intentional self-harm by exposure to or harmful effects of sedative hypnotic drugs or other CNS depressants", "[PC96] Intentional self-harm by exposure to or harmful effects of antipsychotics\n --PARENT--> [?] Intentional self-harm by exposure to or harmful effects of drugs, medicaments or biological substances\n --CHILD--> [PC92] Intentional self-harm by exposure to or harmful effects of psychostimulants" ]	NE60	Harmful effects of drugs, medicaments or biological substances, not elsewhere classified	[ { "from_icd11": "NE60", "icd10_code": "T50A95A", "icd10_title": "Adverse effect of other bacterial vaccines, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50Z15A", "icd10_title": "Adverse effect of immunoglobulin, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50Z95A", "icd10_title": "Adverse effect of other vaccines and biological substances, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50A95S", "icd10_title": "Adverse effect of other bacterial vaccines, sequela" }, { "from_icd11": "NE60", "icd10_code": "T50B95A", "icd10_title": "Adverse effect of other viral vaccines, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50A25A", "icd10_title": "Adverse effect of mixed bacterial vaccines without a pertussis component, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50A91A", "icd10_title": "Poisoning by other bacterial vaccines, accidental (unintentional), initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T498X5A", "icd10_title": "Adverse effect of other topical agents, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T48905A", "icd10_title": "Adverse effect of unspecified agents primarily acting on the respiratory system, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T48995A", "icd10_title": "Adverse effect of other agents primarily acting on the respiratory system, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50A15A", "icd10_title": "Adverse effect of pertussis vaccine, including combinations with a pertussis component, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50B15A", "icd10_title": "Adverse effect of smallpox vaccines, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T416X3A", "icd10_title": "" }, { "from_icd11": "NE60", "icd10_code": "T419X3A", "icd10_title": "" }, { "from_icd11": "NE60", "icd10_code": "T418X2A", "icd10_title": "" } ]	T50A95A	Adverse effect of other bacterial vaccines, initial encounter
This case highlights the emergence of two unusual filamentous IFIs in a young patient who received an allogeneic HSCT from an unrelated HLA-matched donor, first with a pulmonary mucormycosis and then with a rhinocerebral scedosporiosis. Rhizomucor sp. belongs to the order Mucorales . Recent reclassification has abolished the order Zygomycetes and placed the order Mucorales in the subphylum Mucormycotina. Therefore, we refer to infection caused by Mucorales as mucormycosis, rather than zygomycosis . The genus Scedosporium consists of two medically important species: Scedosporium apiospermum (and its teleomorph or sexual state Pseudallescheria boydii ) and Scedosporium prolificans . These mould infections are known as scedosporiosis . Invasive mucormycosis and scedosporiosis are unusual and highly lethal IFIs that can arise in the postengraftment period of HSCT. Isolated, they can achieve a mortality rate superior to 90% in this kind of patients . To our knowledge, there have been few reports of these two IFIs arising in the same patient . These moulds can be widely recovered from the environment . A common route of acquisition is the respiratory tract through inhalation of infectious spores that may establish an initial infection in the sinuses. Other less common routes of acquisition include the intestinal tract following ingestion or by inoculation through breaches in or penetrating injuries to the skin. Angioinvasion is a prominent feature of these IFIs progressing to tissue necrosis and infarction, and this presumably accounts for their ability to cause rapidly invasive infections sometimes with dissemination . From a clinical standpoint, mucormycosis describes infections characterized by one or more of a triad of rhinocerebral, pulmonary, and disseminated disease . Scedosporiosis represents a broad spectrum of clinical diseases, ranging from transient colonization of the respiratory tract to invasive localized disease (mostly involving the bones and joints but also the skin in which case it is known as mycetoma) and at times disseminated disease . The disseminated form of these IFIs is mostly seen among immunocompromised patients, especially in those with hematologic malignancies during periods of prolonged neutropenia . Innate immune defenses comprising phagocytic responses play a critical role in host defense against these filamentous fungi . So, it seems plausible that host defense defects that occur in HSCT recipients as a result of prolonged neutropenia and lymphopenia have a profound impact on the susceptibility and severity of these IFIs . Other factors could also confer high susceptibility to disseminated disease, such as steroidtherapy (maybe because they cause impaired phagocyte function), GVHD (the greater the extent of mucosal injury the greater the risk of IFIs), and serum iron availability (increased iron facilitates fungal growth), but further studies are needed . It seems that antifungal prophylaxis can also have a selection effect for these IFIs as Rhizomucor sp. are resistant to voriconazole therapy, and its usage as prophylactic therapy may cause often breakthrough mucormycosis . Scedosporium spp. have been known to emerge as pathogens in patients receiving amphotericin B, fluconazole, or itraconazole . In this reported case, the patient had multiple high-risk factors for the development of IFIs, as he received an allogeneic HSCT from an unrelated donor, had neutropenia for a long period, fever (so he received large-spectrum antibiotic therapy for several times), developed gastrointestinal GVHD, and required chronic immunosupression for GVHD control . Although prophylactic fluconazole therapy is highly effective in reducing IFIs-related morbidity and mortality in these patients, it applies only to fluconazole-susceptible Candida species infections ( Candida kruseii and some strains of Candida glabatra are not susceptible to fluconazole therapy) [ 17 – 19 ]. Because invasive candidiasis is more frequent in the pre-engraftment period, we started fluconazole at a dosage of 200–400 mg/day until day+75 . As the patient continued to require high-dose corticosteroid therapy (prednisone >1 mg/kg/day) for digestive tract GVHD control, in the postengraftment period, we changed prophylactic antifungal therapy to posaconazole, according to our service protocol, in order to prevent IA. This protocol is based in a clinical trial published in 2007 by Ullmann et al. This clinical trial enrolled 600 patients and compared fluconazole versus posaconazole prophylaxis for IFIs. It showed a clear benefit toward posaconazole prophylaxis in the prevention of IA (OR = 0.31 [0.13–0.75], P < .006) without inferior efficacy in the prevention of IFIs (OR = 0.56 [0.30–1.07], P < .07) . Nevertheless, the patient developed a breakthrough pulmonary mucormycosis while on posaconazole prophylaxis. Other similar cases have been reported . In 2010, Winston et al. published a prospective study that evaluated the efficacy, safety, breakthrough infections and antimicrobial resistance of long-term posaconazole prophylaxis in 106 consecutive adult allogeneic HSCT recipients . They reported breakthrough IFIs in 7.5% of patients while on posaconazole within 6 months after HSCT. Only 2 of 9 infecting isolates tested were resistant to posaconazole (both Candida glabrata). Mean peak and trough plasma posaconazole concentrations were relatively low in neutropenic patients with oral mucositis and other factors possibly affecting optimal absorption of posaconazole . In this case report, the isolated Rhizopus was not identified at the species level, and its sensibility to posaconazole was not tested. However, other factors may also have affected the serum levels of posaconazole. Tacrolimus could be one of such factors, because its concomitant use can reduce the optimal serum levels of posaconazole . We adjusted tacrolimus dosage according to its serum levels. on the other hand, the patient had digestive tract GVHD. This could also be responsible for reduced serum levels of posaconazole . Therefore, when using prophylactic posaconazole, we must be aware of other factors that may affect its absorption/serum levels and implement strategies to improve posaconazole exposure, including the use of higher doses, administration with an acidic beverage, or restriction of proton pump inhibitors . There are five factors that are crucial to successful treatment of these IFIs. The first one is early diagnosis: to recognize patients at increased risk and early signs of infection. This is the most important and troublesome factor, because it is difficult to make an early diagnosis of these IFIs. Initially, clinical features of pulmonary mucormycosis often resemble that of IA in severely immunocompromised patients such as occurred in this case . However, it is the consideration of mucormycosis or scedosporiosis as a diagnosis that may lead to timely confirmation by successful biopsy/culture of the causative organism . Thoracic CT scan is the most sensitive imagiologic tool to detect early pulmonary IFIs, and, therefore, it must be considered the “gold standard”. Some authors perform weekly CT for early detection of IFIs . However, due to economic reasons, this is not the usual procedure in our service. Ordinarily, these patients are monitored with thoracic X-ray performed twice a week. Thoracic CT is performed only on clinical and/or imagiologic suspicion of IFIs. This approach has several limitations, because thoracic X-ray is too insensitive for the diagnosis of IFIs. In early stages of IFIs, thoracic X-ray findings may be scarce, nonspecific, or even undetectable. Therefore, many IFIs may only be diagnosed in later stages by this technique, thus affecting the prognosis of these patients . Diagnosis can be confirmed by biopsy of affected tissues, when accessible, although cultures may prove negative. Genus/species identification is made by culturing the organism and documenting characteristic morphological features . The problem is that fungal culture identification takes long. Even the findings on pathology of Scedosporium spp. are very similar to Aspergillus spp. and other hyalohyphomycotic species, and there are no serologic or molecular specific diagnostic procedures available to make correct diagnosis faster . So, we started voriconazole empirically though galactomannan antigen was negative. Obviously, there was no response because Rhizopus sp. are resistant to this therapy and the IFIs progressed despite later adequate antifungal therapy. Research is needed in order to discover newer and faster specific diagnostic procedures. It is possible that in the near future, some serologic and molecular specific diagnostic procedures may become available (e.g., peptidorhamnomannam for Pseudallescheria boydii ) . The second consideration is to remove/reduce any reversible predisposing factor such as, for example, reducing the level of immunosuppression . The third consideration is surgical aggressive debridement as early as possible. Surgical excision of the disease has been a component of the standard of care and should be considered whenever possible as it improves survival . This is the second most important message to remember from this case report: surgery cannot be delayed and must be done as early as possible to achieve benefit as long as IFIs are suspected. Even among immunocompetent individuals, infections caused by these agents usually require extensive debridement and sometimes amputation to achieve cure . For these reasons, extensive plastic surgery may be required . The fourth consideration is antifungal therapy. Unfortunately, because the relative rarity of these infections, the choice of antifungal therapy is less well established, and it has been based on experience, supplemented by information gleaned from animal model studies and in vitro susceptibility data. Monotherapy with liposomal amphotericin B has been a classical choice for mucormycosis. Doses in the range of 10–15 mg/kg/day have been used although the optimal dose remains unclear . Posaconazole can also be an alternative to this IFIs . Once again, the optimal dosage is unknown. Dosage of 800 mg/day in divided doses has been reported . There are also case reports that describe successful outcomes with combination of liposomal amphotericin B with either caspofungin or posaconazole where single-agent therapy has failed . Caspofungin monotherapy has no in vitro activity against Mucorales. Nevertheless, Ibrahim et al. showed, in vivo , that caspofungin had significant activity against Rhizopus oryzae when it was given prophylactically but not when therapy was started after infection . This study has shown that Rhizopus oryzae , the most common pathogen causing mucormycosis, expresses the target enzyme for echinocandins (1,3 beta-glucan synthase) . Though we did not identified the isolated Rhizopus at the species level, these studies suggest that caspofungin may have a role in combination therapy against mucormycosis, and, therefore, combination antifungal therapy for mucormycosis should be considered. In the other hand, antifungal therapy with echinocandins seems to be noneffective for Scedosporium spp. infections . Newer agents, such as voriconazole, have shown variable results in the treatment of scedosporiosis with a trend toward improved survival when compared to amphotericin B in some studies . In vitro, studies have shown a synergistic action from the combination of terbinafine and voriconazole on S. prolificans . Overall the susceptibility profile for these two fungal agents is very different and antifungal therapy experience too small. Altogether, they made therapeutic choice a difficult challenge in the setting of this case report. Finally the fifth factor to be considered is adjunctive therapies. These include hyperbaric oxygen (HBO) therapy, iron chelation therapy, and immunotherapy . HBO therapy seemed to improve survival in patients with mucormycosis, provided they receive an adequate course of antifungal therapy in a series of 28 patients. Almost all patients received amphotericin B and major benefit was seen for diabetic patients and for those patients whose predisposing condition was rectified . Deferasirox iron chelation therapy has been reported to show synergy with lipid polyenes against mucormycosis . Although HBO is not worldwide available, deferasirox is a feasible therapy. Interferon- γ and granulocyte-macrophage colony-stimulating factor have shown experimentally to increase Mucorales hyphal damage by polymorphs though Rhizopus sp. were found to be less susceptible to the host response . This kind of therapies holds promise although experience with them is clearly preliminary and further experimental and clinical studies are needed.	4.445313	0.679688	sec[2]/p[0]	en	0.999997	21547214	https://doi.org/10.1155/2011/830769	[ "ifis", "this", "these", "posaconazole", "that", "patients", "mucormycosis", "antifungal", "infections", "factors" ]	[ { "code": "4A01.03", "title": "Transient hypogammaglobulinaemia of infancy" }, { "code": "9B71.1&XS5S", "title": "Hypertensive Retinopathy, Stage 2, focal arteriolar narrowing, marked generalised arteriolar narrowing, arteriovenous nicking, opacity, “copper wiring” of arteriolar wall, or a combination of these signs" }, { "code": "9B71.1&XS00", "title": "Hypertensive Retinopathy, Stage 3, Haemorrhage, blot, dot, or flame-shaped, microaneurysm, cotton-wool spot, hard exudate, or combination of these signs" }, { "code": "8A80.Z", "title": "Migraine, unspecified" }, { "code": "QA76", "title": "Medication or substance that is known to be an allergen without injury or harm" }, { "code": "PL13.6", "title": "Medication or substance that is known to be an allergen, as mode of injury or harm" }, { "code": "9C40.A0", "title": "Papilloedema" }, { "code": "PA6Z", "title": "Unintentional fall from unspecified height" }, { "code": "PL14.C", "title": "Patient received diagnostic test or treatment intended for another patient" }, { "code": "QB14", "title": "Unavailability or inaccessibility of health care facilities" } ]	=== ICD-11 CODES FOUND === [4A01.03] Transient hypogammaglobulinaemia of infancy Also known as: Transient hypogammaglobulinaemia of infancy \| immunoglobulin maturational delay \| THI - [transient hypogammaglobulinaemia of infancy] [8A80.Z] Migraine, unspecified Also known as: Migraine, unspecified \| Migraine [QA76] Medication or substance that is known to be an allergen without injury or harm Definition: Medication that has previously been identified as an allergen to the patient is administered, but does not result in injury or harm. Also known as: Medication or substance that is known to be an allergen without injury or harm Excludes: Medication or substance that is known to be an allergen, as mode of injury or harm [PL13.6] Medication or substance that is known to be an allergen, as mode of injury or harm Also known as: Medication or substance that is known to be an allergen, as mode of injury or harm \| medication error relating to known allergy to drug or substance \| adverse drug event relating to known allergy to drug or substance [9C40.A0] Papilloedema Definition: Optic disc swelling that results from increased intracranial pressure Also known as: Papilloedema \| Optic disc swelling that results from increased intracranial pressure Includes: Optic disc swelling that results from increased intracranial pressure [PA6Z] Unintentional fall from unspecified height Also known as: Unintentional fall from unspecified height \| fall NOS \| accidental fall \| fall causing injury that resulted in death \| fell NOS [PL14.C] Patient received diagnostic test or treatment intended for another patient Also known as: Patient received diagnostic test or treatment intended for another patient \| wrong patient \| incorrect patient Excludes: Procedure undertaken at wrong site or wrong side, as mode of injury or harm [QB14] Unavailability or inaccessibility of health care facilities Also known as: Unavailability or inaccessibility of health care facilities \| unavailability of medical facilities \| Unavailability of outpatient clinic \| Unavailability or inaccessibility of residential aged care service Excludes: bed unavailable === GRAPH WALKS === --- Walk 1 --- [4A01.03] Transient hypogammaglobulinaemia of infancy --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects... --CHILD--> [4A01.00] Hereditary agammaglobulinaemia with profoundly reduced or absent B cells Def: This refers to a hereditary type of primary immune deficiency disease characterised by a reduction in all types of gamma globulins, and rare X-linked genetic disorder that affects the body's ability t... --- Walk 2 --- [4A01.03] Transient hypogammaglobulinaemia of infancy --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects... --PARENT--> [4A01] Primary immunodeficiencies due to disorders of adaptive immunity --- Walk 3 --- [8A80.Z] Migraine, unspecified --PARENT--> [8A80] Migraine Def: A primary headache disorder, in most cases episodic. Disabling attacks lasting 4-72 hours are characterised by moderate or severe headache, usually accompanied by nausea, vomiting and/or photophobia a... --PARENT--> [?] Headache disorders --- Walk 4 --- [8A80.Z] Migraine, unspecified --PARENT--> [8A80] Migraine Def: A primary headache disorder, in most cases episodic. Disabling attacks lasting 4-72 hours are characterised by moderate or severe headache, usually accompanied by nausea, vomiting and/or photophobia a... --CHILD--> [8A80.0] Migraine without aura Def: Recurrent headache disorder manifesting in attacks lasting 4-72 hours. The duration of attacks may be shorter in children. Typical characteristics of the headache are unilateral location, pulsating qu... --- Walk 5 --- [QA76] Medication or substance that is known to be an allergen without injury or harm Def: Medication that has previously been identified as an allergen to the patient is administered, but does not result in injury or harm.... --PARENT--> [?] Circumstances associated with exposure to a drug, medicament or biological substance influencing the episode of care without injury or harm --CHILD--> [QA70] Overdose of substance without injury or harm Def: Overdose of a substance occurs when a patient is given more of a prescribed drug or other substance than is intended. Can be the result of inaccurate measurement of drug, including oral administration... --- Walk 6 --- [QA76] Medication or substance that is known to be an allergen without injury or harm Def: Medication that has previously been identified as an allergen to the patient is administered, but does not result in injury or harm.... --EXCLUDES--> [?] Medication or substance that is known to be an allergen, as mode of injury or harm --PARENT--> [?] Mode of injury or harm associated with exposure to a drug, medicament or biological substance	[ "[4A01.03] Transient hypogammaglobulinaemia of infancy\n --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects\n Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects...\n --CHILD--> [4A01.00] Hereditary agammaglobulinaemia with profoundly reduced or absent B cells\n Def: This refers to a hereditary type of primary immune deficiency disease characterised by a reduction in all types of gamma globulins, and rare X-linked genetic disorder that affects the body's ability t...", "[4A01.03] Transient hypogammaglobulinaemia of infancy\n --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects\n Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects...\n --PARENT--> [4A01] Primary immunodeficiencies due to disorders of adaptive immunity", "[8A80.Z] Migraine, unspecified\n --PARENT--> [8A80] Migraine\n Def: A primary headache disorder, in most cases episodic. Disabling attacks lasting 4-72 hours are characterised by moderate or severe headache, usually accompanied by nausea, vomiting and/or photophobia a...\n --PARENT--> [?] Headache disorders", "[8A80.Z] Migraine, unspecified\n --PARENT--> [8A80] Migraine\n Def: A primary headache disorder, in most cases episodic. Disabling attacks lasting 4-72 hours are characterised by moderate or severe headache, usually accompanied by nausea, vomiting and/or photophobia a...\n --CHILD--> [8A80.0] Migraine without aura\n Def: Recurrent headache disorder manifesting in attacks lasting 4-72 hours. The duration of attacks may be shorter in children. Typical characteristics of the headache are unilateral location, pulsating qu...", "[QA76] Medication or substance that is known to be an allergen without injury or harm\n Def: Medication that has previously been identified as an allergen to the patient is administered, but does not result in injury or harm....\n --PARENT--> [?] Circumstances associated with exposure to a drug, medicament or biological substance influencing the episode of care without injury or harm\n --CHILD--> [QA70] Overdose of substance without injury or harm\n Def: Overdose of a substance occurs when a patient is given more of a prescribed drug or other substance than is intended. Can be the result of inaccurate measurement of drug, including oral administration...", "[QA76] Medication or substance that is known to be an allergen without injury or harm\n Def: Medication that has previously been identified as an allergen to the patient is administered, but does not result in injury or harm....\n --EXCLUDES--> [?] Medication or substance that is known to be an allergen, as mode of injury or harm\n --PARENT--> [?] Mode of injury or harm associated with exposure to a drug, medicament or biological substance" ]	4A01.03	Transient hypogammaglobulinaemia of infancy	[ { "from_icd11": "4A01.03", "icd10_code": "D807", "icd10_title": "Transient hypogammaglobulinemia of infancy" }, { "from_icd11": "8A80.Z", "icd10_code": "G43B0", "icd10_title": "Ophthalmoplegic migraine, not intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43409", "icd10_title": "Hemiplegic migraine, not intractable, without status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43A0", "icd10_title": "Cyclical vomiting, in migraine, not intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43D0", "icd10_title": "Abdominal migraine, not intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43709", "icd10_title": "Chronic migraine without aura, not intractable, without status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43A1", "icd10_title": "Cyclical vomiting, in migraine, intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43509", "icd10_title": "Persistent migraine aura without cerebral infarction, not intractable, without status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43719", "icd10_title": "Chronic migraine without aura, intractable, without status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43501", "icd10_title": "Persistent migraine aura without cerebral infarction, not intractable, with status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43C0", "icd10_title": "Periodic headache syndromes in child or adult, not intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43401", "icd10_title": "Hemiplegic migraine, not intractable, with status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43419", "icd10_title": "Hemiplegic migraine, intractable, without status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43B1", "icd10_title": "Ophthalmoplegic migraine, intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43C1", "icd10_title": "Periodic headache syndromes in child or adult, intractable" } ]	D807	Transient hypogammaglobulinemia of infancy
The Anglo-Arab mare weighing 420 kg, submitted to food fasting for 6 h, had a basal heart rate (HR) of 38 bpm, respiratory rate (RR) of 16 mrm, rosy mucous membranes, capillary refill time (CRT) of 2 s, rectal temperature (RT) 36.6 °C and hematological parameters within the reference range (Table 4 , Basal) before starting the antibiotic treatment. After 95 mL of the ceftriaxone sodium (Day 1) solution had dripped, the mare presented paresis in the pelvic limbs, suggestive of circulatory hypotension. The antibiotic solution drip was suspended immediately, and within a few minutes, the mare was back to normal with no apparent need for pharmacological intervention. Two days after the anaphylactoid reaction (Day 3), the mare started showing signs of discomfort and slight abdominal distention. The physical examination revealed a HR of 52 bpm, RR of 34 mrm, RT 37.5 °C, CRT 3 s, pale mucosa and a severe intestinal hypomotility. No abnormalities were found upon rectal palpation, except for the presence of gas in the bowel loops and wall edema of the rectum. The colic event did not alter the hematological parameters or serum biochemistry of the patient (Tables 4 and 5 , Day 3). The support treatment consisted of administering 3 L of 10 % DMSO solution, 10 ml intravenous dexamethasone, gastric lavage and100 mL of 30 % oral silicon solution to reduce bloating and flunixin meglumine (0.5 mg/kg), intravenously. The patient showed improvement in the intestinal motility 6 h after the drug treatment had started. Three days after the tympanic colic episode (Day 6), the temperature of the dorsal hoof wall of the left forelimb (LF) increased and the mare revealed strong pulse in the palmar digital arteries . Cryotherapy was performed in the region between the hoof and carpus for 1 h, three times a day, and intravenous flunixin meglumine, anti-endotoxemic dose (0.25 mg/kg), every 12 h. Two days after initiating the cryotherapy (Day 8), no improvement was noted in the LF temperature profile . Therefore, along with cryotherapy, firocoxib was administered orally (0.1 mg/kg), every 24 h, in combination with pentoxifylline (8.4 mg/kg), every 12 h, for 10 days. At the end of the 10th day, the temperature profile of the left forelimb returned to normal values . The mare showed no signs of pain or lameness in the affected limb at any time; thus, suggesting the development of laminitis was treated within the prodromal phase. Therefore, no hoof radiographic assessment was performed. There were no alterations in the environment or feeding throughout ceftriaxone administration at the beginning of the colic period that would explain the abdominal discomfort occurrence and the resultant laminitis. Therefore, the authors suggest that the possible hypotension was associated with the liberation of inflammatory mediators which caused the subsequent laminitis. Table 6 summarizes the events that occurred with the two animals over time. Penicillins are the most important antibiotic class followed by cephalosporins, which contains a beta-lactam ring in their molecular structure. Both groups can induce hypersensitivity reactions mediated by IgE . In vitro studies demonstrated that IgE antibodies are reactive to both terminals of cephalosporin molecules. This hybridoma formation has shown that cephalosporins can generate unique structures capable of inducing specific allergic reactions, which may exhibit cross-reactivity with penicillin in 5 to 15 % of the cases . In this study, both animals had been previously treated with penicillin without any signs of an allergic reaction, which suggests an anaphylactoid reaction. To date, there are no reports regarding the manifestation of hypersensitivity to cephalosporin in horses. This was one of the reasons why a drug of this group (ceftriaxone sodium) was chosen to treat the experimental infection with Borrelia burgdorferi . In addition to the cephalosporin pharmacokinetic studies conducted in horses [ 15 – 17 ], clinical trials were also conducted in camels , dogs , calves and lactating goats without any reports regarding the occurrence of hypersensitivity reactions. The evolution of the anaphylactoid symptoms in all of the tried horses was consistent with a severe hypersensitivity reaction in the gelding (without reaching shock parameters) and moderate reaction in the mare, which showed only signs of circulatory hypotension. Typically the symptoms of mild anaphylactoid reactions and hypersensitivity in horses are limited to local and dermatological changes. During a classical anaphylaxis, it is necessary a first substance exposure to immunologic sensitization and a cascade of events associated with the IgE molecule binding to basophils and mast cells occurs, triggering the release of histamine and other vasoactive substances , such as serotonin, catecholamines, kinins, products of arachidonic acid and platelet activating factor . The anaphylactoid reaction is a non-IgE mediated hypersensitivity response, caused by immune aggregates, complement activation, coagulation activation or autoimmune mechanisms, with the same clinical appearance of a classical anaphylaxis . Both horses had never been exposed previously to sodium ceftriaxone and did not have any reaction to penicillin, resulting in an anaphylactoid reaction. Besides, it was not possible to know whether the massive death of spirochetes during antibiotic application also had correlation with clinical signs presented by both horses. Further evidences shall be collected in order to define if the anaphylactoid reaction was caused only by the sodium ceftriaxone or the interaction between the drug and the B. burgdorferi infection in horses. The pharmacological treatment with dexamethasone reversed the acute symptoms of the anaphylactoid reaction in the gelding, corroborating published studies . It has been reported that anti-inflammatory non-steroidal drugs (NSAID’s) showed greater efficacy in reversing the cardiovascular and respiratory effects of experimentally induced anaphylaxis in horses compared to antihistamines. Together with corticoids, the animals may also have benefited from epinephrine for controlling acute signs of hypotension and edema . The vascular and hemodynamic changes that occurred during reaction in the gelding resulted in a mural edema of various intestinal segments, in addition to ileus , with signs of abdominal discomfort. During celiotomy, mural edemas were observed on the colon and small intestine, as well as a large amount of liquid and gaseous content and petechiations promoted by fragility and alteration of vascular permeability. While recovering from the surgical procedure, the gelding erythrogram displayed parameters on the lower limit of normality, neutrophilia with a regenerative left shift or leukopenia (Day 3), which may have been caused by the steroid therapy or anaphylactoid reaction. Along the scenario of metabolic acidosis, there were also electrolyte abnormalities on the day following the anaphylactoid reaction, with decreased plasma concentrations of sodium, potassium and chlorine. The anaphylaxis report where a reaction was induced by intravenous administration of breast milk on a foal lists the same pattern of changes on the following day . Such changes can be directly associated to the systemic inflammatory response syndrome induced by the beta lactam compound . During an anaphylactoid reaction, large amounts of fluids are sequestered to tissue compartments richer in mast cells and basophils due to antigen-antibody bonds that promote the release of vasoactive amines and hence induce the local vasodilatation. It is known that tissue concentrations (muscle and viscera) of sodium, potassium and chloride increase during anaphylaxis, resulting in a homeostatic imbalance of these serum electrolytes . A significant increase in the concentrations of plasma glucose and lactate was also observed, which may be linked to an increased anaerobic metabolism due to difficult tissue gas exchange resulting from the edema. This fact can be explained by the concomitant increase of venous partial pressures of oxygen and carbon dioxide, shown a day after the anaphylactoid reaction in the gelding. Hematologic and metabolic changes may have predisposed the gelding to the appearance of Theileriosis on Day 18. However, the enzymatic biochemical profile of the gelding did not change significantly as a result of anaphylaxis but only after the hemoparasitosis. In the mare, it could be that the anaphylactoid mediators caused the possible hypotension and this may be responsible for starting the systemic inflammatory response that resulted in abdominal discomfort and laminitis (day 6). The inflammatory response was detected by the 10th day, through laboratory confirmation of neutrophilia and increased plasma fibrinogen. The infrared images show apparent temperature increase in the hoof of the left forelimb (day 6), which responded adequately to the non-steroidal anti-inflammatory therapy, cryotherapy and peripheral vasodilator, returning to normal on day 20 post infection. Table 4 Mare red blood cell count before and after anaphylactic reaction to sodium ceftriaxone, which occurred on day 1 Basal Day 3 Day 10 Day 28 Reference a Erythrocytes x 10 6 [cells/ml] 8.3 7.1 8.4 7.4 6.0–9.7 Hemoglobin [g/dL] 13 11.2 13 11.5 8.3–14.4 Hematocrit [%] 39 31 39 35.0 30–44 MCV [fL] 47 - 46.4 47.3 36–52.1 MCH [pg] 15.7 - 15.5 15.5 11.5–18.2 MCHC [g/dL] 33.3 - 33.3 32.9 31.2–34.9 Leucocytes [cells/uL] 8600 6600 10000 6900 6400–10600 Basophiles [cells/uL] 0 0 0 0 0 Eosinophils [cells/uL] 344 66 200 138 0–320 Segmented Neutrophils [cells/uL] 4902 4224 7300 3588 2775–7530 Rod Neutrophils [cells/uL] 258 0 800 207 94–420 Lymphocytes [cells/uL] 2924 2244 1500 2898 1088–5096 Monocytes [cells/uL] 172 66 200 69 90–318 Platelets [cells/uL] 151000 154000 191000 165000 90000–322000 a Reference ranges obtained for total blood cell count for 33 domestic horses of different breeds, serum negative for Borrelia burgdorferi , kept under the same feeding and management conditions Values in italic represent relevant modifications in the parameter Table 5 Mare serum biochemical parameters before and after anaphylactic reaction to sodium ceftriaxone, which occurred on day 1 Basal Day 3 Day 10 Day 28 Reference a Direct bilirubin [mg/dL] 0.13 0.39 1.1 0.18 0.12–0.31 Indirect bilirubin [mg/dL] 0.10 1.66 0.2 0.63 0.07–1.07 Creatine phosphokinase [U/L] 166 – 276 223 84–368 Urea [mg/dL] 13 25 18 35 14–41 Creatinine [mg/dL] 1.1 1.6 1.1 1.0 1.1–1.7 Aspartate Amino Transferase [U/L] 424 199 263 368 232–447 Gamma Glutamyl Transferase [U/L] 33 76 36 23 2.0–19.0 Total Protein [g/dL] 6.5 6.4 6.6 7.2 4.0–7.7 Albumin [g/dL] 2.4 2.44 3.4 2.3 1.7–3.2 Globulin [g/dL] 4.1 - 3.2 4.9 2.3–4.8 Fibrinogen [g/dL] 0.1 0.5 0.9 0.2 0.1–0.4 a References ranges obtained from the hematological analysis of 33 domestic horses of several breeds, serum negative for Borrelia burgdorferi , kept under the same management and feeding conditions Values in italic represent relevant modifications in the parameter Fig. 3 Infrared images to monitor the evolution of the laminitis treatment in the mare that had colic secondary to anaphylactic reactions to ceftriaxone sodium. Day 6 was the second day of temperature rise in the hoof. The crosses indicate the temperature of the hoof crown for each member. Temperature profile of the hooves was back to normal on Day 20. Spot 1: right limb, Spot 2: left limb Fig. 4 Infrared image of the four limbs of the mare 2 days after treatment started (Day 8). The crosses indicate the temperature of the hoof crown of each member. Spot 1: right forelimb, Spot 2: left forelimb, Spot 3: right hindlimb, Spot 4: left hindlimb Table 6 Timetable of the events described for the anaphylactic reaction to sodium ceftriaxone of a horse and a mare Chronology Gelding Mare Basal Total blood cell count before treatment started Total blood cell count before treatment started Day 1 Administration of ceftriaxone sodium and anaphylaxis Administration of ceftriaxone sodium and anaphylaxis Day 2 Tympanic colic and laparotomy Stable Day 3 Stable Tympanic colic resolved clinically Day 6 Stable Prodromal laminitis and treatment Day 8 Stable Change in the laminitis treatment Day 18 Theileriosis treated with imidocarb Stable Day 20 6 L of whole blood transfusion Stabilization of the clinical symptoms Day 21 Gastritis Stable Day 28 Clinical symptoms back to normal Stable	4.066406	0.963867	sec[1]/sec[1]/p[0]	en	0.999999	26265349	https://doi.org/10.1186/s12917-015-0478-6	[ "reaction", "mare", "anaphylactoid", "sodium", "that", "ceftriaxone", "cells", "which", "horses", "temperature" ]	[ { "code": "NE60", "title": "Harmful effects of drugs, medicaments or biological substances, not elsewhere classified" }, { "code": "6B43", "title": "Adjustment disorder" }, { "code": "NE80.Z", "title": "Injury or harm arising following infusion, transfusion or therapeutic injection, not elsewhere classified, unspecified" }, { "code": "4B24.Z", "title": "Graft-versus-host disease, unspecified" }, { "code": "NE80.3", "title": "Other serum reactions" }, { "code": "4A44.92", "title": "IgA vasculitis" }, { "code": "JB42.1", "title": "Amniotic fluid embolism" }, { "code": "4A84.Z", "title": "Anaphylaxis, unspecified" }, { "code": "4A44.92/8A01.1Z", "title": "Chorea due to IgA vasculitis" }, { "code": "5C72", "title": "Hypo-osmolality or hyponatraemia" } ]	=== ICD-11 CODES FOUND === [NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified Also known as: Harmful effects of drugs, medicaments or biological substances, not elsewhere classified \| drugs, medicaments or biological substances, toxicity not elsewhere classified \| adverse drug effects \| drug reaction NOS \| drug allergy NOS Excludes: Alcohol intoxication \| pathological drug intoxication \| hypersensitivity reaction to correctly administered drug [6B43] Adjustment disorder Definition: Adjustment disorder is a maladaptive reaction to an identifiable psychosocial stressor or multiple stressors (e.g. divorce, illness or disability, socio-economic problems, conflicts at home or work) that usually emerges within a month of the stressor. The disorder is characterised by preoccupation with the stressor or its consequences, including excessive worry, recurrent and distressing thoughts about the stressor, or constant rumination about its implications, as well as by failure to adapt to Also known as: Adjustment disorder \| brief situational non-psychotic disorder \| adaptation reaction NOS \| adjustment reaction \| emotional crisis Excludes: separation anxiety disorder of childhood \| Recurrent depressive disorder \| Single episode depressive disorder [NE80.Z] Injury or harm arising following infusion, transfusion or therapeutic injection, not elsewhere classified, unspecified Also known as: Injury or harm arising following infusion, transfusion or therapeutic injection, not elsewhere classified, unspecified \| Injury or harm arising following infusion, transfusion or therapeutic injection, not elsewhere classified \| transfusion reaction NOS \| Blood transfusion reaction not elsewhere classified \| blood transfusion reaction NOS [4B24.Z] Graft-versus-host disease, unspecified Also known as: Graft-versus-host disease, unspecified \| Graft-versus-host disease \| GVHD - [graft-versus-host disease] \| graft-versus-host reaction or disease \| GVH - [graft-versus-host] disease [NE80.3] Other serum reactions Also known as: Other serum reactions \| Allergic reaction to serum \| serum allergy \| Complications of vaccination, protein sickness \| Protein sickness Excludes: serum hepatitis [4A44.92] IgA vasculitis Definition: Vasculitis, with IgA1-dominant immune deposits, affecting small vessels (predominantly capillaries, venules, or arterioles). Often involves skin and gut, and frequently causes arthritis. Glomerulonephritis indistinguishable from IgA nephropathy may occur. Also known as: IgA vasculitis \| Allergic purpura \| Henoch-Schönlein purpura \| Anaphylactoid purpura \| HSP - (Henoch-Schönlein purpura) Includes: Henoch-Schönlein purpura [JB42.1] Amniotic fluid embolism Definition: Amniotic fluid embolism is a rare obstetric emergency in which it is postulated that amniotic fluid, fetal cells, hair, or other debris enter the maternal circulation, causing cardiorespiratory collapse. Also known as: Amniotic fluid embolism \| obstetric embolism of amniotic fluid \| amniotic fluid embolism in the puerperium \| amniotic fluid pulmonary embolism \| puerperal amniotic fluid embolism Includes: Anaphylactoid syndrome of pregnancy [4A84.Z] Anaphylaxis, unspecified Also known as: Anaphylaxis, unspecified \| Anaphylaxis \| anaphylactoid shock \| allergic anaphylactic shock \| anaphylactic reaction [5C72] Hypo-osmolality or hyponatraemia Definition: Serum sodium concentrations of less than 135 mEq/L; decreased serum concentration of osmotically active particles Also known as: Hypo-osmolality or hyponatraemia \| hypo-osmolality \| hyponatraemia \| hyponatremia syndrome \| hyponatremic Includes: sodium [na] deficiency Excludes: Syndrome of inappropriate secretion of antidiuretic hormone === GRAPH WALKS === --- Walk 1 --- [NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified --EXCLUDES--> [?] Allergic or hypersensitivity conditions Def: Allergy is a hypersensitivity reaction initiated by proven immunologic mechanisms. Hypersensitivity is defined as conditions clinically resembling allergy that cause objectively reproducible symptoms... --CHILD--> [?] Allergic or hypersensitivity disorders involving the respiratory tract Def: Allergic or hypersensitivity disorders involving the respiratory tract includes several clinically different conditions that can be considered as hypersensitivity disorders of the upper and lower resp... --- Walk 2 --- [NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified --EXCLUDES--> [?] Alcohol intoxication Def: Alcohol intoxication is a clinically significant transient condition that develops during or shortly after the consumption of alcohol that is characterised by disturbances in consciousness, cognition,... --CHILD--> [?] Severe alcohol intoxication Def: Severe alcohol intoxication is a clinically significant transient condition that develops during or shortly after the administration of alcohol that is characterised by obvious disturbance in consciou... --- Walk 3 --- [6B43] Adjustment disorder Def: Adjustment disorder is a maladaptive reaction to an identifiable psychosocial stressor or multiple stressors (e.g. divorce, illness or disability, socio-economic problems, conflicts at home or work) t... --EXCLUDES--> [?] Separation anxiety disorder Def: Separation anxiety disorder is characterised by marked and excessive fear or anxiety about separation from specific attachment figures. In children and adolescents, separation anxiety typically focuse... --CHILD--> [?] Separation anxiety disorder of childhood --- Walk 4 --- [6B43] Adjustment disorder Def: Adjustment disorder is a maladaptive reaction to an identifiable psychosocial stressor or multiple stressors (e.g. divorce, illness or disability, socio-economic problems, conflicts at home or work) t... --EXCLUDES--> [?] Separation anxiety disorder Def: Separation anxiety disorder is characterised by marked and excessive fear or anxiety about separation from specific attachment figures. In children and adolescents, separation anxiety typically focuse... --EXCLUDES--> [?] Selective mutism Def: Selective mutism is characterised by consistent selectivity in speaking, such that a child demonstrates adequate language competence in specific social situations, typically at home, but consistently ... --- Walk 5 --- [NE80.Z] Injury or harm arising following infusion, transfusion or therapeutic injection, not elsewhere classified, unspecified --PARENT--> [NE80] Injury or harm arising following infusion, transfusion or therapeutic injection, not elsewhere classified --EXCLUDES--> [?] Failure or rejection of transplanted organs or tissues --- Walk 6 --- [NE80.Z] Injury or harm arising following infusion, transfusion or therapeutic injection, not elsewhere classified, unspecified --PARENT--> [NE80] Injury or harm arising following infusion, transfusion or therapeutic injection, not elsewhere classified --EXCLUDES--> [?] Endophthalmitis	[ "[NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified\n --EXCLUDES--> [?] Allergic or hypersensitivity conditions\n Def: Allergy is a hypersensitivity reaction initiated by proven immunologic mechanisms.\n\nHypersensitivity is defined as conditions clinically resembling allergy that cause objectively reproducible symptoms...\n --CHILD--> [?] Allergic or hypersensitivity disorders involving the respiratory tract\n Def: Allergic or hypersensitivity disorders involving the respiratory tract includes several clinically different conditions that can be considered as hypersensitivity disorders of the upper and lower resp...", "[NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified\n --EXCLUDES--> [?] Alcohol intoxication\n Def: Alcohol intoxication is a clinically significant transient condition that develops during or shortly after the consumption of alcohol that is characterised by disturbances in consciousness, cognition,...\n --CHILD--> [?] Severe alcohol intoxication\n Def: Severe alcohol intoxication is a clinically significant transient condition that develops during or shortly after the administration of alcohol that is characterised by obvious disturbance in consciou...", "[6B43] Adjustment disorder\n Def: Adjustment disorder is a maladaptive reaction to an identifiable psychosocial stressor or multiple stressors (e.g. divorce, illness or disability, socio-economic problems, conflicts at home or work) t...\n --EXCLUDES--> [?] Separation anxiety disorder\n Def: Separation anxiety disorder is characterised by marked and excessive fear or anxiety about separation from specific attachment figures. In children and adolescents, separation anxiety typically focuse...\n --CHILD--> [?] Separation anxiety disorder of childhood", "[6B43] Adjustment disorder\n Def: Adjustment disorder is a maladaptive reaction to an identifiable psychosocial stressor or multiple stressors (e.g. divorce, illness or disability, socio-economic problems, conflicts at home or work) t...\n --EXCLUDES--> [?] Separation anxiety disorder\n Def: Separation anxiety disorder is characterised by marked and excessive fear or anxiety about separation from specific attachment figures. In children and adolescents, separation anxiety typically focuse...\n --EXCLUDES--> [?] Selective mutism\n Def: Selective mutism is characterised by consistent selectivity in speaking, such that a child demonstrates adequate language competence in specific social situations, typically at home, but consistently ...", "[NE80.Z] Injury or harm arising following infusion, transfusion or therapeutic injection, not elsewhere classified, unspecified\n --PARENT--> [NE80] Injury or harm arising following infusion, transfusion or therapeutic injection, not elsewhere classified\n --EXCLUDES--> [?] Failure or rejection of transplanted organs or tissues", "[NE80.Z] Injury or harm arising following infusion, transfusion or therapeutic injection, not elsewhere classified, unspecified\n --PARENT--> [NE80] Injury or harm arising following infusion, transfusion or therapeutic injection, not elsewhere classified\n --EXCLUDES--> [?] Endophthalmitis" ]	NE60	Harmful effects of drugs, medicaments or biological substances, not elsewhere classified	[ { "from_icd11": "NE60", "icd10_code": "T50A95A", "icd10_title": "Adverse effect of other bacterial vaccines, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50Z15A", "icd10_title": "Adverse effect of immunoglobulin, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50Z95A", "icd10_title": "Adverse effect of other vaccines and biological substances, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50A95S", "icd10_title": "Adverse effect of other bacterial vaccines, sequela" }, { "from_icd11": "NE60", "icd10_code": "T50B95A", "icd10_title": "Adverse effect of other viral vaccines, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50A25A", "icd10_title": "Adverse effect of mixed bacterial vaccines without a pertussis component, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50A91A", "icd10_title": "Poisoning by other bacterial vaccines, accidental (unintentional), initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T498X5A", "icd10_title": "Adverse effect of other topical agents, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T48905A", "icd10_title": "Adverse effect of unspecified agents primarily acting on the respiratory system, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T48995A", "icd10_title": "Adverse effect of other agents primarily acting on the respiratory system, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50A15A", "icd10_title": "Adverse effect of pertussis vaccine, including combinations with a pertussis component, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50B15A", "icd10_title": "Adverse effect of smallpox vaccines, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T416X3A", "icd10_title": "" }, { "from_icd11": "NE60", "icd10_code": "T419X3A", "icd10_title": "" }, { "from_icd11": "NE60", "icd10_code": "T418X2A", "icd10_title": "" } ]	T50A95A	Adverse effect of other bacterial vaccines, initial encounter
A 60-year-old male patient, nonsmoker, nonbruxist, and without any history of systemic disease, was referred to a single private practice (Gravedona, Como, Italy) for the evaluation and treatment of his right-maxillary central incisor. His chief complaints were of mobility and slight localized pain during oral function. The patient reported episodes of swelling in the right central incisor area. The tooth was considerably extruded . Vitality tests on tooth (cold) were positive. Clinical examination revealed poor oral hygiene, localized gingival recessions, and thick gingival tissues. Probing pocket depth (PPD) was measured using a light probing force (approximately 25 g), with a conventional periodontal probe (PCP-UNC 15, Hu-Friedy Manufacturing, Chicago, IL, USA) at 4 sites per tooth (mesially, mid-buccally, distally, and mid-lingually). PPD ranging from 3 to 6 mm were registered in all other teeth; for the right-maxillary central incisor, a localized 12 mm PPD with bleeding on probing and suppuration was detected at the buccal face, while PPD of 9, 8, and 9 mm were detected at the mesial, distal, and palatal faces, respectively. A periapical radiograph was taken, revealing a localized, severe bone resorption affecting the right-maxillary central incisor . For a better investigation of the local anatomy, CBCT datasets of the failing tooth were acquired using a modern cone beam scanner . A small, 5 × 5 cm FOV was selected, with a voxel size of 90 μ m in order to obtain the best image resolution for the selected area, at lower radiation dose. CBCT dataset was then transferred to an implant navigation software (Invivo Dental 5, Anatomage, San Jose, CA, USA) to perform a 3D reconstruction of the anterior maxilla. The CBCT with 3D reconstruction confirmed the presence of the advanced, localized bone resorption . Based on clinical and radiographic examinations, tooth extraction followed by reconstructive procedures and delayed implant placement was proposed and accepted by the patient. Information was given to the patient regarding alternative treatment options (fixed partial denture on natural teeth). The patient received thorough explanations about the planned treatment and its potential risks and complications and signed a written informed consent form. Before the start of the treatment, for aesthetic reasons, an alginate impression was taken and a plaster cast was made, to fabricate a resin-bonded fixed partial denture as interim prosthesis. In addition, a diagnostic wax-up for the missing teeth structure was done, to provide the clinician with a better understanding of the patient's prosthetic needs and to ascertain the aesthetic outcome. Two weeks before extraction, the patient underwent a periodontal treatment, involving instructions and reinforcement in his oral hygiene efforts, followed by a scaling and root planning in the entire dentition. Surgery was performed under a local anaesthesia, obtained by infiltrating articaine 4%, containing 1 : 100,000 adrenaline (Ubistesin; 3M Espe, St. Paul, MN, USA). An intrasulcular incision was done, connected by two vertical releasing incisions and a full-thickness flap was reflected. The hopeless tooth was extracted avoiding any movement that might damage the residual buccal bone plate. Once the tooth was removed, the socket was thoroughly debrided with curettes and irrigated with sterile saline. The adjacent teeth were scaled and planed. The socket walls were then carefully probed, in order to assess the presence of any fenestration or dehiscence defects. The alveolar bone review depicted a huge bone defect (>8 mm) with loss of a considerable amount of buccal bone . In particular, the residual buccal bone wall was thin (width <2 mm). A technique for ridge reconstruction was adopted. A synthetic, micromacroporous biphasic calcium-phosphate block (Biocer, Biocer Entwicklungs GmbH, Bayreuth, Germany) was placed into the socket ; then, granules of the same material were applied to completely fill the bone defect. The granules were mixed with tetracycline powder (Ambramicina; Scharper Spa, Sesto San Giovanni, Italy) to obtain a local antibiotic effect, and this mixture was moistened with physiological saline solution so that the composition could be more easily moulded to cover the defect . Finally, an absorbable collagen membrane (EZ Cure, Leone Implants, Florence, Italy) was placed over the graft, covering all the defect and adjacent bone borders . The flap was moved coronally to completely cover the membrane barrier and sutured in position by means of interruptedsutures (Supramid; Novaxa Spa, Milan, Italy) . A postoperative periapical radiograph was taken to confirm the filling of the postextraction socket . The patient was prescribed oral antibiotics, 2 g of amoxicillin/clavulanic acid each day for 6 days (Augmentin; Glaxo-Smithkline Beecham, Brentford, UK). Postoperative pain was controlled by administering 100 mg nimesulide (Aulin; Roche Pharmaceutical, Basel, Switzerland) every 12 h for 2 days, and detailed instructions about oral hygiene were given, including mouth rinses with 0.12% chlorhexidine (Chlorexidine; OralB, Boston, MA, USA) administered for 7 days. An interim prosthesis was delivered by using an adhesive system to attach to the adjacent teeth. This prosthesis was key in achieving an acceptable aesthetic outcome. The patient was seen two weeks after surgery for suture removal. He had mild swelling for 2-3 days after surgery, but no further discomfort during the healing period. Regular postoperatively examinations were performed at 3-month intervals and included oral hygiene instructions and professional plaque control. After 6 months of uneventful healing, the placement of a dental implant was planned, to restore aesthetics and function. A periapical radiograph was taken, showing an apparent good integration of the material used for regeneration . Again, local anaesthesia was obtained by infiltrating articaine 4% containing 1 : 100.000 adrenaline. Exposure of the regenerated ridge was achieved with a crestal incision and two lateral releases. Care was taken to preserve the papillae of the adjacent teeth. A mucoperiosteal flap was elevated. The patient showed great bone augmentation, confirming the possibility of placing a dental implant in the proper position . The osteotomy started with a 2 × 10 mm trephine bur, which was used to retrieve a bone core (approximately 2 × 6 mm) biopsy at the site of implant placement, via a transcrestal path, under saline solution irrigation. The bone core biopsy was retrieved with the aim of performing a histologic evaluation of the augmented bone. The biopsy was immediately stored in 10% buffered formalin and was subsequently processed (Precise 1 Automated System, Assing, Rome, Italy) to obtain thin ground sections. The specimens were dehydrated in an ascending series of alcohol rinses and embedded in glycol methacrylate resin . After polymerization, the specimens were sectioned lengthwise along the longer axis, using a high-precision diamond disk saw, to about 150 μ m and ground down to about 30 μ m. Two slides were obtained from each specimen. The slides were stained with basic fuchsin and toluidine blue and the histologic evaluation was performed. The specimens were made of preexisting, compact mature bone undergoing remodeling, marrow spaces, and newly formed trabecular bone surrounded by several residual biomaterial particles. The newly formed bone appeared well organized. Close to the porous BCP particles, new bone formation was observed, with newly formed osteoid matrix undergoing mineralization . The preparation of implant site progressed with spiral drills of increasing diameter (2.8 and 3.5 mm, to place an implant with 4.1 mm diameter) under constant saline irrigation. The socket preparation was deepened beyond the alveolar apex, engaging the native apical bone, in order to obtain an optimal implant stability. A 4.1 × 12 mm implant (Leone Implants, Florence, Italy) was installed in the prepared site, using 20 rpm at 40 Ncm torque . This implant is characterized by a cone Morse taper interference-fit (TIF) locking-taper combined with an internal hexagon. The Morse taper presents a taper angle of 1.5° . The implant was positioned at the bone crest level, 2 mm apically to the cementoenamel junction of the left maxillary central incisor. Care was taken to ensure the correct 3D position of the implant and to keep a safe distance from the reconstructed buccal bone wall. A nonsubmerged, single-stage approach was followed. Immediately after implant placement, a healing abutment was connected to the implant. The mucosal flap was adjusted to the healing abutment and then sutured in position . The patient underwent a second 5 × 5 cm FOV CBCT examination with a voxel size of 90 μ m: the 3D reconstruction confirmed the optimal implant placement in the regenerated bone . The patient was seen on a weekly basis during the first 2 weeks. At the first control visit, 7 days after the surgery, a clinically healthy marginal area was present and no postoperative pain or swelling was reported. There was no bleeding or wound infection. After 14 days, sutures were removed; the healing abutment was removed and an impression coping was connected to the implant. Impressions were taken, using a vinylpolysiloxane material (EliteHd Plus, Zhermack, Badia Polesine, Italy). One week later, a standard prefabricated prepared and finished titanium abutment was placed and activated , and the acrylic resin provisional restoration was provided and cemented with zinc-eugenol oxide cement (Temp-Bond, Kerr, Orange, CA, USA). Occlusion was checked using standard occluding papers (Bausch Articulating Papers, Bausch Inc, Nashua, NH, USA). The provisional restoration was carefully evaluated for proper occlusion; after that, it was polished with abrasive points. The acrylic provisional restoration remained in situ for 3 months: it was used to monitor the implant stability under a progressive load and to obtain a good soft-tissue healing around the implant before fabrication of the definitive restorations. At the end of this period, the patient showed remarkable healing of the soft tissues, and the gingiva showed an excellent color and texture. It also began to outline the proper and harmonious design of the facial mucosa curvatures, which were conditioned by the provisional restoration , so that the definitive, ceramo-metallic restoration could be provided and cemented with zinc-eugenol oxide cement. The prosthetic restoration showed a good aesthetic integration: the patient's smile aesthetics was improved and a satisfying harmony and symmetry with the contralateral tooth were achieved. A periapical radiograph was taken to check definitive restoration seating . Two years after implant placement, the implant was stable and in function, with no clinical issues; clinical examination showed absence of gingival recession, no probing pocket depths, and no bleeding on probing or suppuration . Periapical radiographic evaluation revealed a stable alveolar bone gain, especially in the vertical dimension . The definitive restoration was removed and a new 5 × 5 cm FOV CBCT examination with a voxel size of 90 μ m, combined with 3D reconstruction, was taken. It confirmed excellent osseointegration of the implant with unchanged peri-implant marginal bone levels, indicating that the treatment proposed was able to restore the functional and aesthetic parameters . Finally, in order to evaluate precisely the hard tissue stability along time, the data of the second (6 months after grafting) and the third (2 years) CBCT were segmented by digital imaging software (Mimics, Materialise, Leuven, Belgium). Based on the result of segmentation, according to Chappuis and colleagues a surface mesh model was generated according to conventional marching cube algorithms, followed by automated surface mesh model generation. The two-year mesh model was superimposed on the 6-month mesh model and rigidly aligned by anatomical landmarks with the help of software for the overlapping of digital images (Geomagic Studio, Morrisville, NC, USA). The distance between the 2 surface meshes was presented as color-coded graded figures to identify zones of facial bone resorption . The overlapping of digital images confirmed the hard tissue stability along time, with little or no bone resorption .	4.027344	0.973633	sec[1]/p[0]	en	0.999993	25431687	https://doi.org/10.1155/2014/183872	[ "bone", "implant", "tooth", "restoration", "italy", "using", "healing", "oral", "teeth", "cbct" ]	[ { "code": "FC0Z", "title": "Diseases of the musculoskeletal system or connective tissue, unspecified" }, { "code": "FB84.Z", "title": "Osteomyelitis or osteitis, unspecified" }, { "code": "FB80.Z", "title": "Disorder of bone density or structure, unspecified" }, { "code": "FB86.11", "title": "Hypertrophy of bone" }, { "code": "FB86.1Z", "title": "Bone hyperplasias, unspecified" }, { "code": "GC7A", "title": "Disorders of breast augmentation" }, { "code": "QB51.7", "title": "Presence of orthopaedic joint implants" }, { "code": "QB51.Y", "title": "Presence of other specified devices other than cardiac or vascular implants" }, { "code": "QB51.5", "title": "Presence of endocrine implants" }, { "code": "QB51.6", "title": "Presence of tooth-root or mandibular implants" } ]	=== ICD-11 CODES FOUND === [FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified Also known as: Diseases of the musculoskeletal system or connective tissue, unspecified \| bone disease NOS \| bone disorder NOS \| bone lesion NOS \| musculoskeletal complications NOS [FB84.Z] Osteomyelitis or osteitis, unspecified Also known as: Osteomyelitis or osteitis, unspecified \| Osteomyelitis or osteitis \| bone inflammation \| bone ulcer \| bone inflammatory disease [FB80.Z] Disorder of bone density or structure, unspecified Also known as: Disorder of bone density or structure, unspecified \| Certain specified disorders of bone density or structure [FB86.11] Hypertrophy of bone Also known as: Hypertrophy of bone \| bone thickening \| periosteum thickening \| Infantile cortical hyperostoses \| Post traumatic subperiosteal ossification [FB86.1Z] Bone hyperplasias, unspecified Also known as: Bone hyperplasias, unspecified \| Bone hyperplasias [GC7A] Disorders of breast augmentation Definition: A group of disorders that may arise in concert with or subsequent to the surgical placement of breast implants. Also known as: Disorders of breast augmentation \| Capsule contraction or scarring \| Implant rupture [QB51.7] Presence of orthopaedic joint implants Also known as: Presence of orthopaedic joint implants \| presence of joint implant \| replacement of joint by artificial or mechanical device or prosthesis \| Presence of shoulder-joint implant \| presence of shoulder joint replacment prosthesis [QB51.Y] Presence of other specified devices other than cardiac or vascular implants Also known as: Presence of other specified devices other than cardiac or vascular implants \| Presence of bone or tendon implants other than orthopaedic joint implants \| replacement of tendon by artificial or mechanical device or prosthesis \| presence of tendon implant \| Presence of skull plate [QB51.5] Presence of endocrine implants Also known as: Presence of endocrine implants \| presence of insulin pump Includes: presence of insulin pump [QB51.6] Presence of tooth-root or mandibular implants Also known as: Presence of tooth-root or mandibular implants \| presence of tooth root implant \| presence of mandibular implant === GRAPH WALKS === --- Walk 1 --- [FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified --PARENT--> [15] Diseases of the musculoskeletal system or connective tissue Def: This chapter contains diseases of musculoskeletal system and diseases of connective tissue.... --CHILD--> [?] Soft tissue disorders --- Walk 2 --- [FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified --PARENT--> [15] Diseases of the musculoskeletal system or connective tissue Def: This chapter contains diseases of musculoskeletal system and diseases of connective tissue.... --RELATED_TO--> [?] Monogenic autoinflammatory syndromes Def: Monogenic hereditary autoinflammatory diseases characterised by apparently unprovoked generalised inflammation in the absence of infection or high titre autoantibodies.... --- Walk 3 --- [FB84.Z] Osteomyelitis or osteitis, unspecified --PARENT--> [FB84] Osteomyelitis or osteitis --EXCLUDES--> [?] Infection of vertebra Def: A condition of the vertebrae, caused by an infection with a bacterial, viral, fungal, or parasitic source. This condition commonly presents with fever, chills, headache, weight loss, or may be asympto... --- Walk 4 --- [FB84.Z] Osteomyelitis or osteitis, unspecified --PARENT--> [FB84] Osteomyelitis or osteitis --CHILD--> [FB84.2] Subacute osteomyelitis --- Walk 5 --- [FB80.Z] Disorder of bone density or structure, unspecified --PARENT--> [FB80] Certain specified disorders of bone density or structure --CHILD--> [FB80.2] Osteitis condensans --- Walk 6 --- [FB80.Z] Disorder of bone density or structure, unspecified --PARENT--> [FB80] Certain specified disorders of bone density or structure --EXCLUDES--> [?] Osteopoikilosis	[ "[FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified\n --PARENT--> [15] Diseases of the musculoskeletal system or connective tissue\n Def: This chapter contains diseases of musculoskeletal system and diseases of connective tissue....\n --CHILD--> [?] Soft tissue disorders", "[FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified\n --PARENT--> [15] Diseases of the musculoskeletal system or connective tissue\n Def: This chapter contains diseases of musculoskeletal system and diseases of connective tissue....\n --RELATED_TO--> [?] Monogenic autoinflammatory syndromes\n Def: Monogenic hereditary autoinflammatory diseases characterised by apparently unprovoked generalised inflammation in the absence of infection or high titre autoantibodies....", "[FB84.Z] Osteomyelitis or osteitis, unspecified\n --PARENT--> [FB84] Osteomyelitis or osteitis\n --EXCLUDES--> [?] Infection of vertebra\n Def: A condition of the vertebrae, caused by an infection with a bacterial, viral, fungal, or parasitic source. This condition commonly presents with fever, chills, headache, weight loss, or may be asympto...", "[FB84.Z] Osteomyelitis or osteitis, unspecified\n --PARENT--> [FB84] Osteomyelitis or osteitis\n --CHILD--> [FB84.2] Subacute osteomyelitis", "[FB80.Z] Disorder of bone density or structure, unspecified\n --PARENT--> [FB80] Certain specified disorders of bone density or structure\n --CHILD--> [FB80.2] Osteitis condensans", "[FB80.Z] Disorder of bone density or structure, unspecified\n --PARENT--> [FB80] Certain specified disorders of bone density or structure\n --EXCLUDES--> [?] Osteopoikilosis" ]	FC0Z	Diseases of the musculoskeletal system or connective tissue, unspecified	[ { "from_icd11": "FC0Z", "icd10_code": "XIII", "icd10_title": "" }, { "from_icd11": "FB84.Z", "icd10_code": "M86672", "icd10_title": "Other chronic osteomyelitis, left ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M86172", "icd10_title": "Other acute osteomyelitis, left ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M86171", "icd10_title": "Other acute osteomyelitis, right ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M86671", "icd10_title": "Other chronic osteomyelitis, right ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M868X7", "icd10_title": "Other osteomyelitis, ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M868X8", "icd10_title": "Other osteomyelitis, other site" }, { "from_icd11": "FB84.Z", "icd10_code": "M868X6", "icd10_title": "Other osteomyelitis, lower leg" }, { "from_icd11": "FB84.Z", "icd10_code": "M868X9", "icd10_title": "Other osteomyelitis, unspecified sites" }, { "from_icd11": "FB84.Z", "icd10_code": "M8668", "icd10_title": "Other chronic osteomyelitis, other site" }, { "from_icd11": "FB84.Z", "icd10_code": "M86662", "icd10_title": "Other chronic osteomyelitis, left tibia and fibula" }, { "from_icd11": "FB84.Z", "icd10_code": "M86151", "icd10_title": "Other acute osteomyelitis, right femur" }, { "from_icd11": "FB84.Z", "icd10_code": "M86141", "icd10_title": "Other acute osteomyelitis, right hand" }, { "from_icd11": "FB84.Z", "icd10_code": "M86641", "icd10_title": "Other chronic osteomyelitis, right hand" }, { "from_icd11": "FB84.Z", "icd10_code": "M8669", "icd10_title": "Other chronic osteomyelitis, multiple sites" } ]	XIII
A 64-year-old Caucasian male presented in February 2022 with persistent diarrhea, bloating accompanied by abdominal pain, frequent headaches, shivering, and cold extremities lasting for 2–3 weeks each month, insomnia, and general fatigue. He had a history of Crohn’s disease (CD) with an ileocecal resection involving 42 cm of the terminal ileum and 10 cm of the cecum immediately following his initial diagnosis in early 1981, Montreal Classification A2, L3, B3 . Biopsies from the terminal ileum and ascending colon revealed transmural inflammation and epithelioid granulomas. Since surgery, CD had widely remained in remission, with occasional episodes of low-grade nonspecific ileitis and low-grade chronic colitis seen on ileocolonoscopy (Table 1 ). Inappropriate to CD in remission, the patient suffered from chronic diarrhea, up to four times a day and often imperative, which numerous medical specialists that he consulted considered to be unusual. Annual ESR, CRP, and blood count results were normal. The patient was taking cholestyramine 6 g per day, loperamide hydrochloride 2 mg per day, probiotic bacterial cultures (1.1 × 10 10 CFU per capsule) two capsules once daily (self-medication), cyanocobalamin 1000 µg IM every 6 months, and ramipril 5 mg once daily. He had no history of smoking or alcohol consumption and reported a paternal family history of asthma and neurodermatitis. There was no family history of inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS). Table 1 Timeline: patient’s symptoms, diagnoses, treatment, and significant events, based on available medical reports and patient’s self-disclosure Date Age (years) Symptoms Diagnoses Treatment Significant events, remarks 10/1957–04/1958 0–1/2 Diarrhea at age 4–12 weeks Unknown 11/1957: Breast feeding ends at age 6 weeks (diarrhea) After birth, patient is transferred to a baby nursing home for 6 months; reportedly crying most of the time, refusing food 1958–1966 1–9 frequent colds, otitis media, coughing; eczema from red currants and rhubarb Asthma, dermatitis Antibiotics 02/1966: Tonsillectomy; 04/1966: 6 weeks at a North Sea sanatorium 04/1966: Patient admitted to children’s sanatorium on the North Sea for 6 weeks (“deported child”) where he like many other children suffers psychological and physical violence 10–12/1980 23 Diarrhea 4–6/day; intermittent, then abdominal pain Weight loss 16 kg within 4 months (now 62 kg, 176 cm) Duodenal ulcer (suspected) 19 Dec 1980: Cimetidine 200 mg PO qid Pre-graduate exams (chemistry); persistent diarrhea, abdominal pain after food intake; symptoms alleviate during physical exercise. OGD, U/S; ESR, complete blood count and all other laboratory results normal 02/1981 23 Diarrhea 6–8/day; increasing pain in right lower abdomen; body temp. > 39 °C (102 °F) Crohn’s disease, ileocolitis, iliopsoas abscess Exploratory open surgery, iliopsoas abscess drained; Open abdominal surgery, ileocecal resection Sulfasalazine 2 g PO qd 26 Feb 1981: Open abdominal surgery, conglomerate of caked intestinal loops removed: 42 cm terminal ileum, 10 cm cecum; histology: transmural inflammation, epithelioid granulomas 03/1981–02/1982 23–24 Diarrhea 3–4/day Crohn’s disease, in remission; chologenic diarrhea Sulfasalazine 2 g PO qd 03/1981: Parenteral diet; weight 56 kg 04/1981: Patient resumes studies while still hospitalized 05/1981: Wt 60 kg Diet: Oatmeal, toast, rusks, banana, white rice, steamed potatoes, carrots 10/1981: Outpatient examination at Freiburg University Medical Centre. U/S, X-ray Sellink, ESR, complete blood count and all other laboratory results normal; weight 65 kg Semi-annual ESR and complete blood count results are normal 03/1982 24 Diarrhea 0–1/day Crohn’s disease, in full remission; gallstones, chologenic diarrhea Cholestyramine 2 g PO tid U/S, X-ray Sellink, ESR, complete blood count and all other laboratory results normal; weight 67 kg 09/1984 26 Diarrhea 3–4/day Crohn’s disease, mild activity; gallstones, chologenic diarrhea Cholestyramine 2 g PO tid; sulfasalazin 2 g PO qd; steroids temporarily Colonoscopy, histology: slight nonspecific inflammation in ileal mucosa U/S, X-ray Sellink, ESR, complete blood count, and all other laboratory results normal. BM 4–5/day; weight 67 kg 07/1985–10/1985 27 None Crohn’s disease, in full remission; chologenic diarrhea Cholestyramine 2 g PO tid; loperamide HCl 2 mg PO qd (self-medication); cyanocobalamin 1000 µg IM q3mos Low vitamin B12; weight 67 kg Trial and error-based vegetarian diet, for details see “Medical and lifestyle interventions” section 06/1986 28 Diarrhea 3–4/day; upper abdominal pain Crohn’s disease with low-grade chronic colitis; chologenic diarrhea; gastroduodenitis Cholestyramine 2 g PO tid; loperamide HCl 2 mg PO qd; cyanocobalamin 1000 µg IM q3mos; steroids temporarily Colonoscopy, histology: low-grade chronic colitis, low-grade chronic proctitis. OGD: moderate acute and chronic gastro-duodenitis U/S, X-ray Sellink, ESR, complete blood count and all other laboratory results normal; weight 64 kg 07/1986–08/1990 28–32 Diarrhea 1–2/day; upper abdominal pain Crohn’s disease, with low-grade chronic colitis; chologenic diarrhea Cholestyramine 2 g PO tid; loperamide HCl 2 mg PO qd; cyanocobalamin 1000 µg IM q3mos Semi-annual ESR and complete blood count results are normal, weight 64–67 kg Patient consults various gastroenterologists as to why diarrhea persists even though Crohn’s disease is in remission. General response: Reasons are unknown but your condition should actually be better 04/1989: Patient accepts position at a Federal Food Investigation Agency 01/1991 33 Diarrhea 4–6/day; upper abdominal pain Crohn’s disease with low-grade ileitis; cholecystolithiasis; chologenic diarrhea; Continued Colonoscopy, histology: low-grade nonspecific ileitis U/S, ESR, complete blood count and all lab results normal except elevated ALT, AST, and gammaGT, BM 4–6/day; weight 67 kg The more frequent diarrhea was explained by bile acid loss syndrome and a stress-related functional component 02/1992–07/1995 34–37 Diarrhea 1–3/day; upper abdominal pain Crohn’s disease in remission; cholecystolithiasis; chologenic diarrhea Continued 04/1992: Laparoscopic cholecystectomy Semi-annual ESR and complete blood count results are normal. BM 3–4/day; weight 70 kg 10/1995–06/2006 38–49 Diarrhea 1–2/day Crohn’s disease, in remission; chologenic diarrhea Continued Semi-annual ESR and complete blood count results are normal. BM 3–4/day; weight 72 kg Patient consults various gastroenterologists as to why diarrhea persists even though Crohn’s disease is in remission. General response: Reasons are unknown but your condition should actually be better 07/2006–10/2007 49–50 Diarrhea 2–4/day; more often cold symptoms Crohn’s disease with low grade ileitis; chologenic diarrhea; lactose intolerance Continued 09/2006: Prednisolone 20 mg PO qd × 4 weeks, then reduced weekly by 2.5 mg PO qd 07/2006: Patient assumes a demanding position at a European Union research institution Semi-annual ESR and complete blood count results are normal. BM 3–4/day; weight 72 kg 09/2006: Colonoscopy, histology: low-grade nonspecific ileitis 05/2007: Abdominal MRI: normal findings. Lactose intolerance test: positive result 2008–2011 49–55 Diarrhea 1–2/day Crohn’s disease in remission; chologenic diarrhea; lactose intolerance Cholestyramine 2 g PO tid; loperamide HCl 2 mg PO qd; cyanocobalamin 1000 µg IM q6mos Patient’s work is highly demanding. Patient is bullied by a superior Annual ESR and complete blood count results are normal. BM 3–4/day; weight 74, increasing to 76 kg 2012–2016 54–59 Diarrhea 1–2/day As before, new diagnosis: hypertension Continued, in addition ramipril 5 mg PO qd; 05/2012: Colonoscopy: no signs of inflammation in neoterminal ileum and colon Patient is increasingly bullied by a superior Annual ESR, CRP, and complete blood count results are normal. BM 3–4/day; weight 76, increasing to 80 kg 2017–2018 60–61 Diarrhea 2–3/day, belly pain; 6 × annually flu-like symptoms for 2–3 weeks, general fatigue, urinary urgency As before Continued Patient feels hardly sociable, often cannot keep appointments; takes light diet. Bullying by superior intensifies in 01–06/2017 07/2017: Medical leave due to deteriorating state of health BM 4–5/day; weight 82 kg 03/2019–01/2022 62–64 Diarrhea 3–4/day, bloating with belly pain; general fatigue, insomnia, flu-like symptoms 1/month for 2–3 weeks, strong unilateral hip joint pain As before Continued, in addition self-medication with probiotics 03/2019: Patients suffers an intestinal infection with vomiting diarrhea Frequent flu-like symptoms after exposure to cool air and moderate physical exercise, 1/month for 2–3 weeks: diarrhea and bloating with abdominal pain, general fatigue, insomnia; headache, brain fog, dizziness, poor memory, extreme tiredness (preceding BM); cold extremities, disturbed thermoregulation, urinary urgency, hypertension. Strong, unilateral hip joint pain since 11/2020. Probiotic bacteria trials prove ineffective Patient feels no longer sociable, makes no appointments; takes light diet 08/2019: Colonoscopy: no inflammation in neoterminal ileum and colon 04/2020: Early retirement for health reasons 09/2021 MRT and 11/2021 X-ray: Bilateral age-related low-grade hip osteoarthritis not explaining pain 11/2021: Crohn’s disease activity index (CDAI) : 183 points Patient consults various specialists in gastroenterology, internal medicine, psychosomatics and nutrition as to why his symptoms persist even though Crohn’s disease is in remission. General response: Frequent colds are attributed to a weakened immune system due to stress Annual ESR, CRP, and complete blood count results are normal. BM 4–6/day; weight 85 kg 02/2022 64 Diarrhea 3–4/day, bloating with belly pain, insomnia, general fatigue; flu-like symptoms 1/month for 2–3 weeks; strong bilateral hip joint pain As before, suspected secondary IBS Tinctura Opii 6 gtts (3 mg anhydrous morphine) PO bid instead of loperamide. Otherwise continued Patient consults a specialist in internal medicine, gastroenterology, and complementary medicine Start with multimodal complementary medicine intervention Explanation of symptoms by disturbance of the vegetative nerve system (sympathetic–parasympathetic, gut–brain axis, disturbed thermoregulation) Patient is advised of the following: 1. Tinctura Opii to reduce bowel motility 2. Light dinner should be taken early 3. Moderate physical exercise (HR < 130 bpm, pacing); relaxation techniques Patient experiences a calming positive effect by receiving an explanation for the symptoms experienced for the first time in more than 40 years 03/2022–12/2023 64–66 Diarrhea 1–2/day with bloating on 2–3 days/month; flu-like symptoms 3–4/year for 1–2 weeks; strong bilateral hip joint pain As before, suspected CFS As before, in addition lavender oil 80 mg PO bid; 01/2024: 16 mg candesartan cilexetil / 5 mg amlodipine PO qd instead of ramipril; methyl cobalamin 500 µg ODT biw instead of cyanocobalamin Patient experiences massive improvement in life quality, sociability is regained; flights to North America and Asia for the first time in 5 years Frequency of described symptoms significantly reduced; diarrhea, bloating, abdominal pain still occur after acute stress or physical exertion, and after exposure to cold air. Insomnia, headache, brain fog, dizziness, poor memory, extreme tiredness prior to BM, strong bilateral hip joint pain persists, yet frequency and intensity were noticeably reduced Trial and error-based vegetarian diet, for details see “Medical and lifestyle interventions” section ESR, CRP, complete blood count normal. BM 1–2/day; weight 80 kg 01/2024–06/2024 66 Diarrhea 1–2/day with bloating on 2–3 days/month; flu-like symptoms 3–4/year for 1–2 weeks; mild unilateral hip joint pain As before Continued, in addition L-glutamine 5 g PO qd × 1 week, 10 g PO qd × 1 month, then 10 g PO bid Further stabilization and partial disappearance of symptoms experienced since 03/2019. Diarrhea, bloating may occur after acute stress or physical exertion, now mildly and generally without abdominal pain; insomnia 2–3 days/month; no general fatigue, brain fog dizziness, poor memory or extreme tiredness. Only mild unilateral hip joint pain 06/2024: Crohn’s disease activity index (CDAI) : 87 points ESR, CRP, complete blood count normal. BM 1–2/day; weight 81 kg	4.019531	0.977539	sec[1]/sec[0]/p[0]	en	0.999998	39789666	https://doi.org/10.1186/s13256-024-05010-3	[ "diarrhea", "pain", "crohn", "weight", "blood", "count", "complete", "abdominal", "remission", "grade" ]	[ { "code": "ME05.1", "title": "Diarrhoea" }, { "code": "1A40.Z", "title": "Infectious gastroenteritis or colitis without specification of infectious agent" }, { "code": "DA90.0", "title": "Syndromic diarrhoea" }, { "code": "DD91.2", "title": "Functional diarrhoea" }, { "code": "1A2Z", "title": "Viral intestinal infections, unspecified" }, { "code": "MG3Z", "title": "Pain, unspecified" }, { "code": "8E43.Z", "title": "Pain disorders, unspecified" }, { "code": "MG31.Z", "title": "Acute pain, unspecified" }, { "code": "MG30.Z", "title": "Chronic pain, unspecified" }, { "code": "FB56.2", "title": "Myalgia" } ]	=== ICD-11 CODES FOUND === [ME05.1] Diarrhoea Definition: Diarrhoea is an acute or chronic condition in which there is an increased frequency or decreased consistency of bowel movements, usually with excessive and frequent evacuation of watery faeces. Here diarrhoea other than specifically described elsewhere, such as in motility disorders of intestine or in functional bowel diseases, is described. Also known as: Diarrhoea \| noninfectious diarrhoea \| frequent/loose bowel movements \| watery stools \| catarrhal diarrhoea Includes: frequent/loose bowel movements \| watery stools Excludes: Melaena \| Change in faeces or bowel movements \| Functional diarrhoea [1A40.Z] Infectious gastroenteritis or colitis without specification of infectious agent Also known as: Infectious gastroenteritis or colitis without specification of infectious agent \| Gastroenteritis or colitis without specification of infectious agent \| diarrhoea and gastroenteritis of presumed infectious origin \| diarrhoeal enteritis \| GE - [gastroenteritis] [DA90.0] Syndromic diarrhoea Definition: Syndromic diarrhoea (SD), also known as phenotypic diarrhoea (PD) or tricho-hepato-enteric syndrome (THE), is a congenital enteropathy presenting with early-onset of severe diarrhoea requiring parenteral nutrition (PN), associated with facial dysmorphism, woolly and poorly pigmented hair and liver disease, with extensive fibrosis or cirrhosis, in about half of the patients. Also known as: Syndromic diarrhoea \| Phenotypic diarrhoea \| THE - [tricho-hepato-enteric] syndrome Includes: Phenotypic diarrhoea [DD91.2] Functional diarrhoea Definition: Functional diarrhoea is a continuous or recurrent syndrome characterised by the passage of loose (mushy) or watery stools without abdominal pain or discomfort. Also known as: Functional diarrhoea [1A2Z] Viral intestinal infections, unspecified Also known as: Viral intestinal infections, unspecified \| viral and other specified intestinal infections \| acute infectious viral gastroenteritis \| infantile gastroenteritis virus \| infantile viral gastroenteritis [MG3Z] Pain, unspecified Also known as: Pain, unspecified \| pain observations \| pain NOS \| generalised pain \| generalised pain, NOS [8E43.Z] Pain disorders, unspecified Also known as: Pain disorders, unspecified \| Pain disorders [MG31.Z] Acute pain, unspecified Also known as: Acute pain, unspecified \| Acute pain [MG30.Z] Chronic pain, unspecified Also known as: Chronic pain, unspecified \| Chronic pain [FB56.2] Myalgia Definition: This is a disorder characterised by pain in a muscle or group of muscles. Also known as: Myalgia \| muscle ache \| muscle soreness \| muscular pain \| myalgic Excludes: Chronic primary musculoskeletal pain \| Chronic secondary musculoskeletal pain === GRAPH WALKS === --- Walk 1 --- [ME05.1] Diarrhoea Def: Diarrhoea is an acute or chronic condition in which there is an increased frequency or decreased consistency of bowel movements, usually with excessive and frequent evacuation of watery faeces. Here d... --EXCLUDES--> [?] Melaena Def: It is bloody stools that indicate bleeding from vascular system in the digestive tract. It is also described as black, tarry, and foul-smelling stools or red/maroon-coloured stools that contain degrad... --PARENT--> [?] Symptoms related to the lower gastrointestinal tract or abdomen --- Walk 2 --- [ME05.1] Diarrhoea Def: Diarrhoea is an acute or chronic condition in which there is an increased frequency or decreased consistency of bowel movements, usually with excessive and frequent evacuation of watery faeces. Here d... --EXCLUDES--> [?] Functional diarrhoea Def: Functional diarrhoea is a continuous or recurrent syndrome characterised by the passage of loose (mushy) or watery stools without abdominal pain or discomfort.... --PARENT--> [?] Irritable bowel syndrome or certain specified functional bowel disorders Def: This group incorporates functional bowel disorders which principally present symptoms attributable to the intestinal tract in the absence of specific and unique organic pathology in the small and larg... --- Walk 3 --- [1A40.Z] Infectious gastroenteritis or colitis without specification of infectious agent --PARENT--> [1A40] Gastroenteritis or colitis without specification of infectious agent --EXCLUDES--> [?] Diarrhoea Def: Diarrhoea is an acute or chronic condition in which there is an increased frequency or decreased consistency of bowel movements, usually with excessive and frequent evacuation of watery faeces. Here d... --- Walk 4 --- [1A40.Z] Infectious gastroenteritis or colitis without specification of infectious agent --PARENT--> [1A40] Gastroenteritis or colitis without specification of infectious agent --EXCLUDES--> [?] Noninfectious neonatal diarrhoea Def: Non-infectious causes of diarrhoea in neonates. Childhood diarrhoea is most often caused by infection. Much less often, however, it is due to other causes - e.g., malabsorption or dietary intolerance,... --- Walk 5 --- [DA90.0] Syndromic diarrhoea Def: Syndromic diarrhoea (SD), also known as phenotypic diarrhoea (PD) or tricho-hepato-enteric syndrome (THE), is a congenital enteropathy presenting with early-onset of severe diarrhoea requiring parente... --PARENT--> [DA90] Nonstructural developmental anomalies of small intestine Def: Any congenital defect of small intestine that results from interference with the normal growth and differentiation of the fetus. Such defects can arise at any stage of embryonic development, vary grea... --PARENT--> [?] Diseases of small intestine Def: This is a group of conditions characterised as being in or associated with the small intestine.... --- Walk 6 --- [DA90.0] Syndromic diarrhoea Def: Syndromic diarrhoea (SD), also known as phenotypic diarrhoea (PD) or tricho-hepato-enteric syndrome (THE), is a congenital enteropathy presenting with early-onset of severe diarrhoea requiring parente... --PARENT--> [DA90] Nonstructural developmental anomalies of small intestine Def: Any congenital defect of small intestine that results from interference with the normal growth and differentiation of the fetus. Such defects can arise at any stage of embryonic development, vary grea... --RELATED_TO--> [?] Maltase-glucoamylase deficiency Def: Chronic diarrhea due to glucoamylase deficiency is characterised by chronic diarrhoea in infancy or childhood in association with intestinal glucoamylase deficiency....	[ "[ME05.1] Diarrhoea\n Def: Diarrhoea is an acute or chronic condition in which there is an increased frequency or decreased consistency of bowel movements, usually with excessive and frequent evacuation of watery faeces. Here d...\n --EXCLUDES--> [?] Melaena\n Def: It is bloody stools that indicate bleeding from vascular system in the digestive tract. It is also described as black, tarry, and foul-smelling stools or red/maroon-coloured stools that contain degrad...\n --PARENT--> [?] Symptoms related to the lower gastrointestinal tract or abdomen", "[ME05.1] Diarrhoea\n Def: Diarrhoea is an acute or chronic condition in which there is an increased frequency or decreased consistency of bowel movements, usually with excessive and frequent evacuation of watery faeces. Here d...\n --EXCLUDES--> [?] Functional diarrhoea\n Def: Functional diarrhoea is a continuous or recurrent syndrome characterised by the passage of loose (mushy) or watery stools without abdominal pain or discomfort....\n --PARENT--> [?] Irritable bowel syndrome or certain specified functional bowel disorders\n Def: This group incorporates functional bowel disorders which principally present symptoms attributable to the intestinal tract in the absence of specific and unique organic pathology in the small and larg...", "[1A40.Z] Infectious gastroenteritis or colitis without specification of infectious agent\n --PARENT--> [1A40] Gastroenteritis or colitis without specification of infectious agent\n --EXCLUDES--> [?] Diarrhoea\n Def: Diarrhoea is an acute or chronic condition in which there is an increased frequency or decreased consistency of bowel movements, usually with excessive and frequent evacuation of watery faeces. Here d...", "[1A40.Z] Infectious gastroenteritis or colitis without specification of infectious agent\n --PARENT--> [1A40] Gastroenteritis or colitis without specification of infectious agent\n --EXCLUDES--> [?] Noninfectious neonatal diarrhoea\n Def: Non-infectious causes of diarrhoea in neonates. Childhood diarrhoea is most often caused by infection. Much less often, however, it is due to other causes - e.g., malabsorption or dietary intolerance,...", "[DA90.0] Syndromic diarrhoea\n Def: Syndromic diarrhoea (SD), also known as phenotypic diarrhoea (PD) or tricho-hepato-enteric syndrome (THE), is a congenital enteropathy presenting with early-onset of severe diarrhoea requiring parente...\n --PARENT--> [DA90] Nonstructural developmental anomalies of small intestine\n Def: Any congenital defect of small intestine that results from interference with the normal growth and differentiation of the fetus. Such defects can arise at any stage of embryonic development, vary grea...\n --PARENT--> [?] Diseases of small intestine\n Def: This is a group of conditions characterised as being in or associated with the small intestine....", "[DA90.0] Syndromic diarrhoea\n Def: Syndromic diarrhoea (SD), also known as phenotypic diarrhoea (PD) or tricho-hepato-enteric syndrome (THE), is a congenital enteropathy presenting with early-onset of severe diarrhoea requiring parente...\n --PARENT--> [DA90] Nonstructural developmental anomalies of small intestine\n Def: Any congenital defect of small intestine that results from interference with the normal growth and differentiation of the fetus. Such defects can arise at any stage of embryonic development, vary grea...\n --RELATED_TO--> [?] Maltase-glucoamylase deficiency\n Def: Chronic diarrhea due to glucoamylase deficiency is characterised by chronic diarrhoea in infancy or childhood in association with intestinal glucoamylase deficiency...." ]	ME05.1	Diarrhoea	[ { "from_icd11": "ME05.1", "icd10_code": "R197", "icd10_title": "Diarrhea, unspecified" }, { "from_icd11": "1A40.Z", "icd10_code": "A09", "icd10_title": "Infectious gastroenteritis and colitis, unspecified" }, { "from_icd11": "1A40.Z", "icd10_code": "A00-A09", "icd10_title": "" }, { "from_icd11": "1A40.Z", "icd10_code": "A090", "icd10_title": "" }, { "from_icd11": "DA90.0", "icd10_code": "K529", "icd10_title": "Noninfective gastroenteritis and colitis, unspecified" }, { "from_icd11": "DD91.2", "icd10_code": "K591", "icd10_title": "Functional diarrhea" }, { "from_icd11": "1A2Z", "icd10_code": "A088", "icd10_title": "Other specified intestinal infections" }, { "from_icd11": "1A2Z", "icd10_code": "A0839", "icd10_title": "Other viral enteritis" }, { "from_icd11": "1A2Z", "icd10_code": "A084", "icd10_title": "Viral intestinal infection, unspecified" }, { "from_icd11": "1A2Z", "icd10_code": "A08", "icd10_title": "Viral and other specified intestinal infections" }, { "from_icd11": "1A2Z", "icd10_code": "A083", "icd10_title": "Other viral enteritis" }, { "from_icd11": "MG3Z", "icd10_code": "R52", "icd10_title": "Pain, unspecified" }, { "from_icd11": "MG3Z", "icd10_code": "R529", "icd10_title": "" }, { "from_icd11": "MG31.Z", "icd10_code": "R520", "icd10_title": "" }, { "from_icd11": "MG30.Z", "icd10_code": "R521", "icd10_title": "" } ]	R197	Diarrhea, unspecified
To our best knowledge, this is the first case report of Hoffa fracture associated with anterolateral dislocation of the knee. Hoffa fracture is an uncommon fracture, and the combination of the dislocation of knee is an even rarer occurrence. Hoffa fracture is also an intra-articular fracture, and conservative treatment in the past often resulted in secondary displacement of fracture fragment and worse knee function. Some scholars suggested the principle of treatment of Hoffa fracture is anatomical reduction of articular surface, preservation of the blood supply of the fracture, rigid internal fixation, early aggressive rehabilitation. However, the treatment of Hoffa fracture still remains controversial and challenging due to variation of surgical approaches, fixation methods and functional exercise. Hoffa fracture is easily missed on the X-ray, particularly as it has no obvious displacement. This is also the case with intercondylar or supracondylar fractures. Therefore, in order to avoid missing the fracture and better understand the morphology of fracture, the use of computerized tomography (CT) has been recommended. In 1978, Letenneur proposed the classification of the Hoffa fracture into three types. A type I fracture line is parallel to the posterior femoral cortex and involves the intact posterior condyle. A type II fracture is still a fracture line parallel to the posterior femoral cortex, but the fracture line is posterior to type I. Type II fracture is subdivided into A, B and C according to fragment size based on percentage of condyle diameter. Type III is an oblique fracture of posterior condyle. The main significance of this classification is to predict the risk of femoral condyle avascular necrosis rather than to help us further understand the morphology of fracture. Xie et al reported the fracture line direction and the common area of comminuted fracture of 75 patients with Hoffa fracture by three-dimensional CT mapping techniques. They found that in axial view of the lateral femoral condyle, the trajectory of fracture lines was usually from anterolateral to posteromedial. In the medial condyle, the trajectory of fracture lines was commonly extending from anteromedial to posterolateral. Additional, in sagittal plane, whether in the lateral or medial condyle, the majority of fracture lines was running from anteroinferior to posterosuperior direction. Moreover, comminuted areas were discovered to be concentrated in the middle-third and weight-bearing area of the condyle. We can make a more meticulous preoperative plan by improving the understanding of the morphology of Hoffa fractures. Undoubtedly, this study has guiding significance to the choice of surgical approach and internal fixation method. When faced with a patient with dislocation of the knee joint, the major concern should be neurovascular injury and following is the sequelae of soft tissue disruption. Injury of ligamentous structures of knee does not only result in instability but also restrict the range of knee function. Schenck et al reported a case of medial Hoffa fracture with dislocation of knee joint. They provided the patient open reduction and internal fixation of fracture, and reconstructed the injured posterior cruciate ligament. However, in spite of early rehabilitation training postoperatively is performed, the patient still developed knee stiffness. Finally, he received an arthroscopic synoviectomy. Shetty et al reported an irreducible knee dislocation associated with Hoffa fracture. Preoperative MRI of the affected knee showed the patellar tendon has been avulsed from the inferior patella and incarcerated in the fracture line of the lateral femoral condyle. In addition, the anterior and posterior cruciate ligaments were torn at attachments respectively. After open reduction and internal fixation of the fracture in the first stage, the author intended to reconstruct the cruciate ligaments under arthroscopy after fracture healing. However, three months after operation, the patient started complaining that the range of motion of knee joint was obviously limited and the flexion could only be achieved to 0–80° motion. At this point, with no distinct instability of knee or ligaments laxity, X-ray of the affected knee demonstrated union of fracture. Then an arthroscopic arthrolysis was performed, but there was no significant improvement of the range of motion post-operation. Up to now, there are few literatures regarding the choice of surgical approaches and internal fixation methods for Hoffa fracture. Xie et al reported that Hoffa fracture commonly occurred in the lateral condyle. Compared with the lateral condyle, fracture lines were less concentrated in the medial condyle and comminution zones mainly distributed in the middle-third region. Consequently, the medial parapatellar approach is still the standard approach for the most medial Hoffa fracture. Viskontas et al recommend to use medial subvastus approach to treat medial Hoffa fracture, the approach was initially used for total knee arthroplasty. Compared with the traditional medial parapatellar approach, the approach can better protect the knee extensor and patellar blood supply. Moreover, the anterior and posterior regions of the medial femoral condyle can be greater exposed through two surgical window. Gao et al reported that used posteromedial approach to treat medial Hoffa fracture, they exposed the fracture line adequately through the interval space between the gracilis and the medial head of the gastrocnemius. The approach is appropriate for the Hoffa fracture in cases where the fracture line extends to the metaphysis which requires an extra medial locking plate. Recently, Orapiriyapul et al have done a lot of work regarding the option of surgical approach for Hoffa fracture. They concluded that the traditional parapatellar approach was insufficient to expose comminuted fragment for Letenneur IIb and IIc Hoffa fracture. If the fracture fragment is very small, while less than 28.7% of the diameter of the medial femoral condyle and the fracture line does not extend to metaphysis, the direct medial approach is recommended. Compared to parapatellar approach, the advantages of this approach include not damaging any knee structure and better expose the posterior aspect of medial condyle. Lian et al recommended to selecting the posterolateral approach to treat lateral Hoffa fracture, the fracture line and comminuted area can be adequately exposed to achieve rigid fixation of fracture with buttress plate and cannulated screws. In addition, all the fracture healed without complications in 12 patients. Orapiriyakul et al also preferred to use posterolateral approach for lateral Hoffa fracture if the fracture fragment is less than 19.9% of the diameter of the lateral condyle. This approach allows direct visualization of the fracture and achieves perpendicular screw fixation of the fracture line in the posterior-to-anterior direction. The option of which fixation method can provide stronger fixation for Hoffa fracture is also controversial. Only if the fixation strength achieves biomechanical stability, patients are allowed to early aggressive rehabilitation post-operation without protection, which is crucial for the knee function. Kumar and Malhotra reported three cases of Hoffa fracture were treated with anterior to posterior direction screws, and all patients obtained satisfactory results. Holmes et al. reported five patients treated with anterior to posterior direction cancellous lag screws, in one case, nonunion occurred, while in the other cases, fracture healed within three months. Jarit et al discovered that the use of two 6.5 mm partially threaded cancellous lag screws with posterior to anterior direction was more stable than the anterior to posterior screws for the first-time in vitro study. The displacement of fracture was lesser when provided the same load. Furthermore, the fixation method had a higher maximal strength to resist external force. However, P-A direction screws often required additional countersunk head, which prevents damage to the articular cartilage. Hak et al reported the biomechanical analysis of four different screw fixation methods. They found that the firmness of two 6.5 mm screws was significantly better than the use of two 3.5 mm screws and one 3.5 mm screw. There was no statistical difference in stability between the use of two 6.5 mm screws and the single 6.5 mm screw. However, if 3.5 mm screws are used, at least two screws are required to achieve the biomechanical stability of the single 6.5 mm screw. Some scholars believed that the ideal fixation method for Hoffa fracture is to use the minimum diameter and minimum number of screws to achieve sufficient rigid fixation, with minimal damage to the articular cartilage. Subsequently, Borse et al firstly used two headless compression screws in posterior to anterior direction in clinical cases. They considered that using headless compression screws in posterior to anterior direction and perpendicular to the fracture line did not only efficiently resisted shear and rotational forces but also minimized the damage to the articular surface. With the increase of the traffic accidents and aging population, high-energy comminuted Hoffa fracture or osteoporotic cases provides a challenge to orthopedists. In such situation, the use of screws alone may not provide effective fixation. In this case, providing a buttress plate seems to improve the clinical outcomes, prevent secondary displacement of fracture and even failure of internal fixation. Gao et al reviewed the previous literature sources and found that it is difficult to achieve enough stable fixation of Hoffa fracture with single plate or screws. They reported 13 cases of medial Hoffa fracture were treated with posterior medial buttress plate associated with PA direction screws. All patients achieved bone healing and restored the initial mobility through active postoperative rehabilitation training. Moreover, the Knee Society Scores (KSS) of all the patients were more than 80. Sun et al performed a biomechanical analysis of four different fixation methods by simulating a Letenneur I Hoffa fracture. They found that the control group of a 6.5 mm PA direction lag screws combined with a lateral buttress plate provided the strongest fixation and minimal displacement of fracture. In addition, the stability of the group of two 6.5 mm AP direction lag screws was worst, provided minimal fixation strength and maximal vertical displacement. Lu et al reported a retrospective study of 47 Hoffa fractures. All patients were divided into the group of screws combined with plate and single screws. All cases achieved bone healing, however, the range of movement of knee and Knee Society Scores in the group which had screws combined with plate were better than the single-screws group in the postoperative follow-up. The authors believed that the plate may provide sufficient stability to achieve early aggressive rehabilitation and result in better functional outcomes. To our knowledge, most scholars advocate early postoperative functional training. Gavaskar et al reported 18 patients of Hoffa fracture who received satisfactory knee function through early active rehabilitation. Gao et al advocated early passive training of the affected knee by CPM system after the relief of edema and pain. In general, three weeks after operation, the patients achieved a range 0–130 knee function with little or no pain. After ten weeks, the patients were able to handle partial weight-bearing with crutches. When the signs of bone healing were revealed on the X-ray, the patients were allowed to handle full weight-bearing. However, the starting point of rehabilitation varies from person to person, and individualized treatment should be performed. It is necessary to take into account the method and strength of the internal implants. Otherwise, aggressive exercises may lead to secondary displacement of the fracture and even failure of the internal fixation.	4.242188	0.79834	sec[2]/p[0]	en	0.999995	33832086	https://doi.org/10.1097/MD.0000000000025253	[ "fracture", "hoffa", "knee", "screws", "fixation", "approach", "condyle", "direction", "patients", "that" ]	[ { "code": "ND56.2", "title": "Fracture of unspecified body region" }, { "code": "ND32", "title": "Fractures involving multiple body regions" }, { "code": "NB52.Z", "title": "Fracture of lumbar spine or pelvis, unspecified" }, { "code": "FB80.B", "title": "Pathological fracture" }, { "code": "FB80.Y", "title": "Other specified disorders of bone density or structure" }, { "code": "5D0Y", "title": "Other specified metabolic disorders" }, { "code": "FA2Z", "title": "Inflammatory arthropathies, unspecified" }, { "code": "NC90.Y", "title": "Other specified superficial injury of knee or lower leg" }, { "code": "FA34.4", "title": "Ankylosis of joint" }, { "code": "FA33.4Z", "title": "Chronic instability of knee, unspecified" } ]	=== ICD-11 CODES FOUND === [ND56.2] Fracture of unspecified body region Also known as: Fracture of unspecified body region \| avulsion fracture of unspecified body site \| comminuted fracture of unspecified body site \| compression fracture of unspecified body site \| fracture dislocation of unspecified body site Excludes: multiple fractures NOS [ND32] Fractures involving multiple body regions Also known as: Fractures involving multiple body regions \| multiple skeletal fractures \| multiple fractures \| multiple compression fractures \| fracture of multiple bone sites [NB52.Z] Fracture of lumbar spine or pelvis, unspecified Also known as: Fracture of lumbar spine or pelvis, unspecified \| Fracture of lumbar spine or pelvis \| Fracture of pelvis, not elsewhere classified \| fracture pelvis NOS \| pelvic fracture [FB80.B] Pathological fracture Also known as: Pathological fracture \| pathological bone fracture \| Pathological fracture NOS \| spontaneous fracture \| spontaneous fracture with dislocation Excludes: Collapsed vertebra, not elsewhere classified [FB80.Y] Other specified disorders of bone density or structure Also known as: Other specified disorders of bone density or structure \| Bone dysplasia \| Inherited bone dysplasia \| Acquired bone dysplasia \| Drug-induced bone dysplasia [5D0Y] Other specified metabolic disorders Also known as: Other specified metabolic disorders \| Disorders of plasma-protein metabolism, not elsewhere classified \| abnormal protein transport \| dysproteinaemia \| Absence of albumin in blood [FA2Z] Inflammatory arthropathies, unspecified Also known as: Inflammatory arthropathies, unspecified \| polyarthritis NOS \| inflammatory joint disease NOS \| nonpyogenic arthritis NOS \| arthritic nodosa [NC90.Y] Other specified superficial injury of knee or lower leg Also known as: Other specified superficial injury of knee or lower leg \| Nonthermal blister of other or unspecified parts of lower leg \| Nonvenomous insect bite of other or unspecified parts of lower leg \| Superficial foreign body in other or unspecified parts of lower leg \| Splinter in other or unspecified parts of lower leg [FA34.4] Ankylosis of joint Definition: The term ankylosis denotes restricted movement in the joint, and it can be bony or fibrous. Most cases are caused by trauma, infection, radiotherapy, or severe arthritic condition. Also known as: Ankylosis of joint \| ankylosis \| ankylosis of joint, site unspecified \| frozen joint \| fusion of joint Excludes: stiffness of joint without ankylosis \| Ankylosis of spinal joint [FA33.4Z] Chronic instability of knee, unspecified Also known as: Chronic instability of knee, unspecified \| Chronic instability of knee \| instability of knee \| old disruption of ligament of knee === GRAPH WALKS === --- Walk 1 --- [ND56.2] Fracture of unspecified body region --EXCLUDES--> [?] Fractures involving multiple body regions --CHILD--> [?] Fractures involving thorax with lower back or pelvis --- Walk 2 --- [ND56.2] Fracture of unspecified body region --EXCLUDES--> [?] Fractures involving multiple body regions --CHILD--> [?] Fractures involving head with neck --- Walk 3 --- [ND32] Fractures involving multiple body regions --RELATED_TO--> [?] Fractures involving multiple body regions due to birth injury Def: A condition characterised by the presence of skeletal fractures in more than one body region due to physical pressure or injury during delivery.... --PARENT--> [?] Birth injury to skeleton Def: A condition characterised by the presence of damage to the skeleton due to physical pressure or injury during delivery.... --- Walk 4 --- [ND32] Fractures involving multiple body regions --RELATED_TO--> [?] Fractures involving multiple body regions due to birth injury Def: A condition characterised by the presence of skeletal fractures in more than one body region due to physical pressure or injury during delivery.... --PARENT--> [?] Fractures involving multiple body regions --- Walk 5 --- [NB52.Z] Fracture of lumbar spine or pelvis, unspecified --PARENT--> [NB52] Fracture of lumbar spine or pelvis Def: Broken bone in the lumbar spine or pelvis.... --CHILD--> [NB52.2] Fracture of the pelvic ring with incomplete disruption of posterior arch --- Walk 6 --- [NB52.Z] Fracture of lumbar spine or pelvis, unspecified --PARENT--> [NB52] Fracture of lumbar spine or pelvis Def: Broken bone in the lumbar spine or pelvis.... --CHILD--> [NB52.0] Fracture of lumbar vertebra	[ "[ND56.2] Fracture of unspecified body region\n --EXCLUDES--> [?] Fractures involving multiple body regions\n --CHILD--> [?] Fractures involving thorax with lower back or pelvis", "[ND56.2] Fracture of unspecified body region\n --EXCLUDES--> [?] Fractures involving multiple body regions\n --CHILD--> [?] Fractures involving head with neck", "[ND32] Fractures involving multiple body regions\n --RELATED_TO--> [?] Fractures involving multiple body regions due to birth injury\n Def: A condition characterised by the presence of skeletal fractures in more than one body region due to physical pressure or injury during delivery....\n --PARENT--> [?] Birth injury to skeleton\n Def: A condition characterised by the presence of damage to the skeleton due to physical pressure or injury during delivery....", "[ND32] Fractures involving multiple body regions\n --RELATED_TO--> [?] Fractures involving multiple body regions due to birth injury\n Def: A condition characterised by the presence of skeletal fractures in more than one body region due to physical pressure or injury during delivery....\n --PARENT--> [?] Fractures involving multiple body regions", "[NB52.Z] Fracture of lumbar spine or pelvis, unspecified\n --PARENT--> [NB52] Fracture of lumbar spine or pelvis\n Def: Broken bone in the lumbar spine or pelvis....\n --CHILD--> [NB52.2] Fracture of the pelvic ring with incomplete disruption of posterior arch", "[NB52.Z] Fracture of lumbar spine or pelvis, unspecified\n --PARENT--> [NB52] Fracture of lumbar spine or pelvis\n Def: Broken bone in the lumbar spine or pelvis....\n --CHILD--> [NB52.0] Fracture of lumbar vertebra" ]	ND56.2	Fracture of unspecified body region	[ { "from_icd11": "ND56.2", "icd10_code": "T142", "icd10_title": "" }, { "from_icd11": "ND32", "icd10_code": "T02", "icd10_title": "" }, { "from_icd11": "ND32", "icd10_code": "T020", "icd10_title": "" }, { "from_icd11": "ND32", "icd10_code": "T021", "icd10_title": "" }, { "from_icd11": "ND32", "icd10_code": "T022", "icd10_title": "" }, { "from_icd11": "ND32", "icd10_code": "T023", "icd10_title": "" }, { "from_icd11": "ND32", "icd10_code": "T024", "icd10_title": "" }, { "from_icd11": "ND32", "icd10_code": "T025", "icd10_title": "" }, { "from_icd11": "ND32", "icd10_code": "T026", "icd10_title": "" }, { "from_icd11": "ND32", "icd10_code": "T027", "icd10_title": "" }, { "from_icd11": "ND32", "icd10_code": "T028", "icd10_title": "" }, { "from_icd11": "ND32", "icd10_code": "T029", "icd10_title": "" }, { "from_icd11": "NB52.Z", "icd10_code": "S329XXD", "icd10_title": "Fracture of unspecified parts of lumbosacral spine and pelvis, subsequent encounter for fracture with routine healing" }, { "from_icd11": "NB52.Z", "icd10_code": "S32601A", "icd10_title": "Unspecified fracture of right ischium, initial encounter for closed fracture" }, { "from_icd11": "NB52.Z", "icd10_code": "S329XXG", "icd10_title": "Fracture of unspecified parts of lumbosacral spine and pelvis, subsequent encounter for fracture with delayed healing" } ]	T142
Table 1 summarizes nine cases of RBF associated with osteomyelitis or discitis, all reported from developed nations from 2008 through 2019. Ages ranged from 22-months to 80-years, with 4 females and 5 males. In only seven of the nine cases did the patient acknowledge direct exposure to rats. Four kept rats in their home for reasons including having house pets and a reptile food source. Affected joints included the cervical, thoracic, lumbar, sacral vertebrae and intervertebral discs, as well as hip, ankle, and sternoclavicular joints. Two cases required surgical debridement, while six resolved with antibiotic therapy alone (Table 1 ). A recent analysis of rat bite fever diagnosis in the United States reveals that the majority of encounters occur in persons aged 0–19 years . Our case highlights the need to consider the diagnosis in older adults as well. Table 1 Literature review summary of nine RBF cases associated with osteomyelitis or discitis, 2008 through 2019 Year Country Study Age/sex Exposure Clinical history and findings Significant biochemical findings Site of osteomyelitis/discitis Identification method of Streptobacillus moniliformis Cultures Imaging findings Surgical treatement Histological findings Diagnosis Antibiotic treatment Outcome ## France Dubois et al. 80-year/male Rooster scratch History: One week of shaking chills and back pain radiating to both legs on awakening. The pain subsided by time of presentation. On exam: Afebrile. Physical examination was without specific signs. Over following days developed disorders of consciousness and fever (Tmax 39 °C). WBC 19, neutrophil count 18, CRP 488 mg/liter, fibrinogen 8.9 g/liter, procalcitonin 13 ng/ml. Later, CRP level lowered to 240 mg/liter, then to 163 and 115 mg/liter. T5-T6 and L2-L3 16S rRNA PCR assay from psoas abscess fluid Blood specimens inoculated into paired aerobic and anaerobic bottles gave positive results after 1–5 days. Gram-staining of psoas abscess and blood smears showed pleomorphic fusiform gram-negative rods. CT thorax revealed pericardial and pleural effusions. CT abdomen showed right iliac psoas abscess communicating with a prosthesis screw. Bone scan showed increased signal at L3. MRI lumbar spine revealed psoas abscess and of spondylodiscitis at T5 and T6, and at L2 and L3. (Imaging details not provided). none n/a Spondylodiscitis and psoas abscess Began with empirical antibiotic therapy parenteral amoxicillin-clavulanic acid (1 g, Q8H) and ofloxacin (200 mg, Q12H). Switched to imipenem-cilastatin (1 g, Q12H), ciprofloxacin (400 mg, Q12H), and teicoplanin (600 mg, QD). Then an additional 9-week treatment with i.v. ofloxacin (200 mg, Q12H), i.v. clindamycin (600 mg, Q8H), and metronidazole (500 mg, Q8H). In good health at 8 month follow-up. ## United States Flannery et al. 22-month/male Two pet rats History: Two days of URI symptoms, then 5 days of fever, malaise, with a worsening and blistering rash on all extremities, including palms and soles. Irritability. On exam: Mild hypertension, tachycardia, T 38.0 °C. Scattered tender, erythematous, pustular rash on hands, feet, ankles without joint swelling or tenderness on initial exam. Fevers persisted for several days with worsening rash and pain. On day 5, refused to bear weight on feet; pain with right-hip range of motion exam. Day 1: WBC 10,200/μl, Hb 10.9 g/dl, plt 217,000/μl Day 5: WBC 18,100/μl (neutrophilic predominance), Hb 10.0 g/dl, plt 523,000/μl, CRP 5.4 mg/dl, ESR 94 mm/h. Right-hip joint 16S RNA sequencing and DNA mapping Blood, left-foot pustule fluid, synovial fluid, and femoral bone cultures grew Gram-negative rods (though bone culture may have been contaminated). Ultrasound of right hip revealed joint effusion. MRI: bone marrow edema in the right proximal femoral epiphysis with edema in the surrounding muscles and fascial planes (possibly post-op changes) Open irrigation and debridement of hip joint n/a Septic arthritis and possible osteomyelitis Started on vancomycin and ceftriaxone for empirical bacterial coverage. Switched to i.v. penicillin (250,000 units/kg of body weight/day divided every 4 h). Total of 8 weeks of antibiotics, with 4 weeks of intravenous penicillin and 4 weeks of oral amoxicillin. At one-month follow-up patient remained afebrile with normal inflammatory markers. X-rays of hips and pelvis were normal. Improved weight bearing with physical therapy. Thereafter lost to follow-up. ## United Kingdom Adizie et al. 29-year/male Owner of three rats History: Five days of malaise, feverishness, headache, sore throat, joint swellings with rash. On exam: Pustular, maculopapular and petechial rash of the extremities including palms and soles. Right knee and left ankle effusions, right second MCPJ swelling. CRP 211, ESR 36, ferritin 417, neutrophils 7.89 Left ankle 16S rRNA PCR molecular sequencing Blood cultures and joint aspirate were initially negative. Repeat joint aspirate showed S. moniliformis on 16S rRNA molecular testing. Left ankle MRI: considerable marrow edema, moderate thick walled effusion consistent with septic arthritis and associated osteomyelitis. none Rash skin biopsy: mild non-specific perivascular inflammation within the subcutis Septic arthritis and associated osteomyelitis Initially treated with a broad spectrum antibiotic; changed to i.v. benzylpenicillin; then switched to oral penicillin after 2 weeks. Good recovery ## Japan Nei et al 72-year/female Denied any direct contact with rodents. Possibility of contact with contaminated water and/or food. History: 8 days of fever and chills. On exam: T 38 C. Subsequent worsening severe lower back pain which limited ability to ambulate. WBC 13.3 (95% neutrophils), alkaline phosphatase 1035 IU/L, γ-glutamyl transferase 239 IU/L, CRP 26.92 mg/dL L3-L4 vertebrae and intervertebral disc 16S rRNA genotyping At 2 days of incubation in aerobic culture with 5% CO2 on 5% sheep blood agar, highly pleomorphic, filamentous gram-negative bacilli are visualized. Colonies described as very tiny, transparent and slightly white. MRI: Vertebral bodies L3 and L4 with low signal on T1WI, high signal on STIR. Low intervertebral disk with linear T2 high signal. Vertebral endplates at L3, L4 were destroyed with visible high-signal-intensity bone marrow edema. none n/a Vertebral spondylodiscitis Initially treated with cefazolin (2.0 g, Q8H) and NSAIDs. Switched to ampicillin (2.0 g/every 6 h). Switched again to sulbactum/ampicillin (3.0 g/Q6H) due to failed antimicrobial susceptibility tests. Gradual improvement of lower back pain; gradual recovery of exercise and walking capacity. Discharged on 71st day of hospital stay. ## Japan Sato et al. 52-year/male Rats infestation in his home; suspicion of bite during sleep. History: Four days of diffuse arthralgias beginning in knees and back. Found immobile due to severe arthralgia and was taken to hospital. On exam: Afebrile, HR 110, RR 24. Scars on his fingers and feet. Warm, swollen, and tender joints with pain with passive motion. Tenderness at L5/S1 vertebrae. Day 4 of admission: systolic fell to 70 mmHg, septic shock. WBC 10,300/mL (88% neutrophils). Creatinine kinase 789 U/L. CRP 34.6 mg/dL. L5, S1 vertebrae; L5-S1 disc MALDI-TOF MS suggested S. moniliformis DSM 12112 T (score value was 1.588 – unreliable). 16S rRNA molecular sequencing. Blood cultures positive for gram-negative bacilli at 25 h/ 35 C/ 5% CO2. T2-weighted MRI: high signal intensity in L5 and S1, destruction of L5-S1 disc space supporting diagnosis of diagnosis of vertebral osteomyelitis Surgical debridement. Cultures from site were negative. n/a Vertebral osteomyelitis Ceftriaxone, 1 g per 24 h, 6 weeks Complete resolution of arthralgia and back pain; no long-term sequelae. ## Canada Akter et al. 46-year/female Pet rat scratch History: One-week of fever and symmetric polyarthritis of the distal extremities with morning stiffness. One day nausea, vomiting, and diarrhea. On exam: Day 1 of presentation: T 38 °C, HR 130 beats/min, BP 96/64 mmHg. Effusions in wrists, ankles, and MTPJ. Day 2 of presentation: T 39 °C. Worsening synovitis, new onset lumbar spinal pain. Day 1: WBC 11.1, ESR 76 mm/hr., CRP 149 mg/L. Day 2: AST 105, ALT 114, ESR 124, CRP 170. L5-S1 intervertebral disc Cultures. (Further info not reported). Initial blood culture was negative. Repeat cultures grew S. moniliformis. Right ankle synovial fluid sample culture negative. MRI lumbosacral spine: enhancement of the vertebral end plates; T1WI showed markedly reduced signal at the L5-S1 level, while T2WI showed increased T2 signal. none n/a Discitis Initially treated with prednisone, methotrexate, sulfasalazine, and hydroxychloroquine due to erroneous diagnosis of rheumatoid arthritis. When correct diagnosis was realized these were discontinued and was started on i.v. ceftriaxone. Was discharged with 3-month course of i.v. ceftriaxone. Complete resolution of arthritis, marked improvement of back pain, normal inflammatory markers, and resolution of discitis on repeat MRI at 3 months follow-up. ## Germany Eisenberg et al. 59-year/male Snake keeper who bred rats for snake food. History: 15 days of fever and arthralgia without rash. Inability to stand and acute progressive onset of dyspnea. On exam: T 39 °C. Was initially sedated and placed on ventilator. With discontinuation of sedation, exam showed cervical pain, flaccid tetraplegia, sensitivity at the T4 level. Knees and left wrist swollen with joint effusions. WBC 15 (predominantly neutrophils); C-reactive protein 125 mg/L. C5–T1 vertebrae 16S rRNA gene sequencing from synovia Blood cultures showed negative results. Culture-negative inflammatory liquid and uric acid crystals found in joint effusions. Fat-saturated, contrast-enhanced T1-weighted MRI spine: Sagittal view of the cervical spine shows spondylodiscitis; epidural absess with C5–T1 compression. none n/a Vertebral osteomyelitis and an epidural abscess with consecutive compression of the spinal cord (C5–T1) Amoxicillin and cloxacillin Not reported. ## United Kingdom Abusalameh et al 62-year/female Denied history of rat bite; acknowledged exposure to live rats and rats droppings. History: Four-days of diarrhea and vomiting followed by acute onset of diffuse hot, swollen joints with severe lower back pain. Hx of seropositive RA (positive anti-CCP), controlled with MTX and tocilizumab. CRP 218 mg/l, creatinine 2.37 L5/S1 intervertebral disc 16S rRNA PCR Knee, ankle, wrist, and L5/S1 disc needle aspirates grew a gram-negative organism. MRI spine: edema of L5/S1 intervertebral disc. none n/a Discitis Initially on benzyl penicillin and clindamycin. Later changed to 12-week course of oral amoxicillin and clindamycin. Disc edema improvement after weeks of antibiotic treatment. ## Portugal Pena et al. 75-year/female Rat bite History: Four-day history of fever, myalgias, headache. On exam: Subfebrile, hypotensive, incised wounds on two fingers of left hand. Neck stiffness. On day 3 of admission patient developed worsening neck pain and quadriparesis. WBC 14,670/μL (86.3% neutrophils), CRP 334 mg/dL, normal LP C5, C6, and C7 vertebrae, left SC joint 16S rRNA PCR and Sanger sequencing Two blood cultures (BD BACTEC Plus Aerobic/F medium) grew gram-negative bacteria after 3 days incubation. Normal CT brain. MRI T2WI: high signal intensity in C5, C6, and C7 vertebrae with meningeal enhancement and high signal intensity the left SC joint, consistent with diagnosis of vertebral osteomyelitis and septic arthritis none n/a Vertebral osteomyelitis and septic arthritis Empirically treated on day 1 of hospitalization with i.v. ceftriaxone (2 g/day); completed 26 days of i.v. ceftriaxone followed by 8 months of oral amoxicillin-clavulanate after discharge. Complete resolution of neck pain and tetraparesis.	4.191406	0.637207	sec[2]/p[7]	en	0.999996	34039283	https://doi.org/10.1186/s12879-021-06172-x	[ "pain", "osteomyelitis", "exam", "joint", "signal", "cultures", "blood", "vertebral", "rats", "rrna" ]	[ { "code": "MG3Z", "title": "Pain, unspecified" }, { "code": "8E43.Z", "title": "Pain disorders, unspecified" }, { "code": "MG31.Z", "title": "Acute pain, unspecified" }, { "code": "MG30.Z", "title": "Chronic pain, unspecified" }, { "code": "FB56.2", "title": "Myalgia" }, { "code": "FB84.Z", "title": "Osteomyelitis or osteitis, unspecified" }, { "code": "FB84.1", "title": "Other acute osteomyelitis" }, { "code": "FB84.Y", "title": "Other specified osteomyelitis or osteitis" }, { "code": "1A72.0", "title": "Gonococcal infection of musculoskeletal system" }, { "code": "1A09.Y/FB84.Z", "title": "Salmonella osteomyelitis" } ]	=== ICD-11 CODES FOUND === [MG3Z] Pain, unspecified Also known as: Pain, unspecified \| pain observations \| pain NOS \| generalised pain \| generalised pain, NOS [8E43.Z] Pain disorders, unspecified Also known as: Pain disorders, unspecified \| Pain disorders [MG31.Z] Acute pain, unspecified Also known as: Acute pain, unspecified \| Acute pain [MG30.Z] Chronic pain, unspecified Also known as: Chronic pain, unspecified \| Chronic pain [FB56.2] Myalgia Definition: This is a disorder characterised by pain in a muscle or group of muscles. Also known as: Myalgia \| muscle ache \| muscle soreness \| muscular pain \| myalgic Excludes: Chronic primary musculoskeletal pain \| Chronic secondary musculoskeletal pain [FB84.Z] Osteomyelitis or osteitis, unspecified Also known as: Osteomyelitis or osteitis, unspecified \| Osteomyelitis or osteitis \| bone inflammation \| bone ulcer \| bone inflammatory disease [FB84.1] Other acute osteomyelitis Also known as: Other acute osteomyelitis \| Other acute osteomyelitis, multiple sites \| Other acute osteomyelitis, shoulder region \| Other acute osteomyelitis, clavicle \| Other acute osteomyelitis, scapula [FB84.Y] Other specified osteomyelitis or osteitis Also known as: Other specified osteomyelitis or osteitis \| Other chronic osteomyelitis \| Garre's disease \| chronic or old osteomyelitis with or without mention of periostitis \| chronic bone abscess [1A72.0] Gonococcal infection of musculoskeletal system Definition: This is a species of Gram-negative coffee bean-shaped diplococci bacteria responsible for the sexually transmitted infection gonorrhoea. This diagnosis is of the musculoskeletal system. Also known as: Gonococcal infection of musculoskeletal system \| Infection of the musculoskeletal system due to Neisseria gonorrhoeae \| Gonococcal infection of joint \| gonococcal infection of joint NOS \| Gonococcal arthritis Includes: Gonococcal arthritis \| Gonococcal bursitis \| Gonococcal osteomyelitis === GRAPH WALKS === --- Walk 1 --- [MG3Z] Pain, unspecified --PARENT--> [?] Pain --EXCLUDES--> [?] Mastodynia Def: The symptom of breast pain. This symptom may be classified as cyclic or non-cyclical depending on the clinical patterns.... --- Walk 2 --- [MG3Z] Pain, unspecified --PARENT--> [?] Pain --EXCLUDES--> [?] Mastodynia Def: The symptom of breast pain. This symptom may be classified as cyclic or non-cyclical depending on the clinical patterns.... --- Walk 3 --- [8E43.Z] Pain disorders, unspecified --PARENT--> [8E43] Pain disorders --EXCLUDES--> [?] Chronic neuropathic pain Def: Chronic neuropathic pain is chronic pain caused by a lesion or disease of the somatosensory nervous system. The pain may be spontaneous or evoked, as an increased response to a painful stimulus (hyper... --- Walk 4 --- [8E43.Z] Pain disorders, unspecified --PARENT--> [8E43] Pain disorders --EXCLUDES--> [?] Chronic neuropathic pain Def: Chronic neuropathic pain is chronic pain caused by a lesion or disease of the somatosensory nervous system. The pain may be spontaneous or evoked, as an increased response to a painful stimulus (hyper... --- Walk 5 --- [MG31.Z] Acute pain, unspecified --PARENT--> [MG31] Acute pain Def: Pain with a duration of less than 3 months. This code should be used only when there is no further specification of site.... --CHILD--> [MG31.1] Acute headache, not elsewhere classified --- Walk 6 --- [MG31.Z] Acute pain, unspecified --PARENT--> [MG31] Acute pain Def: Pain with a duration of less than 3 months. This code should be used only when there is no further specification of site.... --CHILD--> [MG31.2] Acute postoperative pain, not elsewhere classified Def: Pain at the intervention site or caused by an intervention....	[ "[MG3Z] Pain, unspecified\n --PARENT--> [?] Pain\n --EXCLUDES--> [?] Mastodynia\n Def: The symptom of breast pain. This symptom may be classified as cyclic or non-cyclical depending on the clinical patterns....", "[MG3Z] Pain, unspecified\n --PARENT--> [?] Pain\n --EXCLUDES--> [?] Mastodynia\n Def: The symptom of breast pain. This symptom may be classified as cyclic or non-cyclical depending on the clinical patterns....", "[8E43.Z] Pain disorders, unspecified\n --PARENT--> [8E43] Pain disorders\n --EXCLUDES--> [?] Chronic neuropathic pain\n Def: Chronic neuropathic pain is chronic pain caused by a lesion or disease of the somatosensory nervous system. The pain may be spontaneous or evoked, as an increased response to a painful stimulus (hyper...", "[8E43.Z] Pain disorders, unspecified\n --PARENT--> [8E43] Pain disorders\n --EXCLUDES--> [?] Chronic neuropathic pain\n Def: Chronic neuropathic pain is chronic pain caused by a lesion or disease of the somatosensory nervous system. The pain may be spontaneous or evoked, as an increased response to a painful stimulus (hyper...", "[MG31.Z] Acute pain, unspecified\n --PARENT--> [MG31] Acute pain\n Def: Pain with a duration of less than 3 months.\n\nThis code should be used only when there is no further specification of site....\n --CHILD--> [MG31.1] Acute headache, not elsewhere classified", "[MG31.Z] Acute pain, unspecified\n --PARENT--> [MG31] Acute pain\n Def: Pain with a duration of less than 3 months.\n\nThis code should be used only when there is no further specification of site....\n --CHILD--> [MG31.2] Acute postoperative pain, not elsewhere classified\n Def: Pain at the intervention site or caused by an intervention...." ]	MG3Z	Pain, unspecified	[ { "from_icd11": "MG3Z", "icd10_code": "R52", "icd10_title": "Pain, unspecified" }, { "from_icd11": "MG3Z", "icd10_code": "R529", "icd10_title": "" }, { "from_icd11": "MG31.Z", "icd10_code": "R520", "icd10_title": "" }, { "from_icd11": "MG30.Z", "icd10_code": "R521", "icd10_title": "" }, { "from_icd11": "MG30.Z", "icd10_code": "R522", "icd10_title": "" }, { "from_icd11": "FB56.2", "icd10_code": "M7918", "icd10_title": "Myalgia, other site" }, { "from_icd11": "FB56.2", "icd10_code": "M7910", "icd10_title": "Myalgia, unspecified site" }, { "from_icd11": "FB56.2", "icd10_code": "M7912", "icd10_title": "Myalgia of auxiliary muscles, head and neck" }, { "from_icd11": "FB56.2", "icd10_code": "M791", "icd10_title": "Myalgia" }, { "from_icd11": "FB84.Z", "icd10_code": "M86672", "icd10_title": "Other chronic osteomyelitis, left ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M86172", "icd10_title": "Other acute osteomyelitis, left ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M86171", "icd10_title": "Other acute osteomyelitis, right ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M86671", "icd10_title": "Other chronic osteomyelitis, right ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M868X7", "icd10_title": "Other osteomyelitis, ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M868X8", "icd10_title": "Other osteomyelitis, other site" } ]	R52	Pain, unspecified
Critical clinical cases and their specific challenges are summarised in Table 2 . These cases illustrate examples of the types of challenges that might be encountered during critical clinical situations in patients with MPS but should not be considered exhaustive. Challenges associated with these surgical cases and critical clinical situations, and resolutions to these challenges, are shown in Tables 3 and 4 , respectively. Table 2 Critical clinical case details Case Patient characteristics Critical clinical situation Key team members Hospital setting, preparations and management Recovery and outcome 1 – cardiac valve replacement Female patient with MPS VI, aged 34 years Aortic valve replacement Adult metabolic consultant, lysosomal storage disorder nurse, cardiologist, congenital heart disease specialist, cardiothoracic surgeon, paediatric and adult anaesthetist, ENT specialist, and respiratory consultant • Specialist cardiothoracic theatre. Clinicians had expertise in congenital heart disease and previous experience in patients with MPS • The team was prepared for risk of unsuccessful surgery, problems with intubation, bleeding, cardiac arrhythmias and post-surgical tracheostomy • After surgery, the patient was treated with warfarin and spontaneous ventilation. A nasogastric feeding tube was used because of a tracheostomy • Considered to be ‘good’ in this patient, as her tracheostomy was removed after 8 days and she was able to walk with support 14 days post-surgical • Follow-up by metabolic and cardiac specialists every 6 months 2 – spinal stenosis Female patient with MPS VI, aged 21 years Surgery to correct spinal stenosis and occipital spondyloses, involving installation of a halo device, laminectomy of the C1 vertebra, and resection of the foramen magnum Neurologist with experience of MPS, neurosurgeon, geneticist, cardiologist and anaesthetist Hospital specialising in orthopaedics • Without complications over a 2-week period in hospital with physiotherapy support • Follow-up by MDT 3 – spinal stenosis Female patient with MPS IVA, aged 21 years Surgery to correct spinal stenosis in the cervical region Metabolic specialist, orthopaedic surgeons, radiologist, neurosurgeons, anaesthetists and intensive care doctors Hospital specialising in orthopaedics • Without complications but the patient required physical rehabilitation during recovery because of muscular atrophy • Follow-up by a neurosurgery unit, with rehabilitation arranged through general practice 4 – corneal transplant Male patient with MPS VI, aged 22 years Corneal transplant – deep anterior lamellar keratoplasty Adult metabolic consultant and nurses, ophthalmologist, adult specialist in corneal transplant, paediatric anaesthetist with expertise in MPS • The team was prepared for pain, discomfort, infection and post-surgical haemorrhage • Surgery was performed under local anaesthetic • Although a local anaesthetic was planned, a full cardiac and respiratory assessment was conducted in case general anaesthesia was required • As expected, and the patient could see shortly after the procedure • Discharge within 24 h, and, along with his family, was advised on how to prevent infection and injury • Follow-up in ophthalmology and metabolic clinics every 6 months 5 - pregnancy Female patient with MPS I, aged 24 years Pregnancy, birth and infant care Obstetrician with expertise in inherited metabolic disorders, metabolic consultant, lysosomal storage disorder nurse, gynaecologist, midwife, general practitioner, cardiologist, genetic counsellor, anaesthetist and ophthalmologist • Caesarean section planned for 38 weeks • The team was prepared to support the patient in caring for the infant as skeletal deformities and respiratory problems may have a negative impact on carrying the child and breastfeeding • Baby born by uneventful spontaneous labour with epidural anaesthesia at 29 + 5 weeks • The patient developed mitral valve disease and underwent valve replacement and was treated with warfarin after surgery • She became pregnant again at this stage but, because of the teratogenic effect of warfarin, had a miscarriage 6 – thrombus development in a venous access device Male patient with MPS II (Hunter syndrome), aged 26 years Thrombus in a port-a-cath and change of venous access device needed Metabolic consultant, lysosomal storage disorder nurse, infusion nurse, intravenous team, interventional radiologist, neurosurgeon, ENT consultant and anaesthetist • Thrombus resolved using warfarin • The team was prepared for infections, further thrombi, blocked lines, and supporting the patient and family to manage the inconvenience of flushing access devices • A Hickman line was inserted as a permanent solution for venous access • He was followed up in the adult care ssetting every 6 months 7 – complex continuous symptom management Male patient with MPS II (Hunter syndrome), aged 33 years • Respiratory, cardiac, neurological, gastrointestinal, skeletal, optic and dental symptoms • Multiple surgical procedures including adenoidectomy, tonsillectomy, T-tube insertion, inguinal and umbilical hernia repair, mastoidectomy, wrist surgery, dental surgery, hip replacement, tracheostomy, appendectomy, carpal tunnel decompression, two port-a-cath insertions, and a cardiac valve replacement • Recurrent respiratory infections and otitis, hepatosplenomegaly, concentration difficulties, endocarditis, and craniocervical stenosis See Fig. 1 Managed by a metabolic adult care physician with expertise in MPS, based in a paediatric unit • Patient now requires a hip replacement, but because of previous complications with airway management during surgery, this particular issue is managed through pain relief and use of a wheelchair • The patient requires glasses and hearing aids and has been prescribed medications for cardiac dysfunction 8 – complex continuous symptom management Female patient with MPS I, aged 38 years • Motor delay, kyphosis, hip problems and pain, recurrent respiratory infections, otitis, diarrhoea, short stature, joint contractures, back pain, aortic valve insufficiency, craniocervical stenosis, severe visual loss, and loss of sensitivity in the first three fingers of both hands • Cardiac valve replacement and spinal cord decompression See Fig. 1 • Managed by a metabolic adult care physician with expertise in MPS, based in a paediatric unit • Very narrow airways, so anaesthetic equipment included paediatric intubation tubes that would not have been available in an adult hospital Symptoms managed through ERT administered in an adult dialysis ward Table 3 Challenges and resolutions associated with surgery Challenges Resolutions Cardiac valve replacement • Initial intubation resulted in high CO 2 pressure • Nasal intubation via right nostril also resulted in high CO 2 pressure • Paediatric and adult anaesthetists with experience in MPS disorders present • Intubation via left nostril successful • Patient’s short neck made central line insertion difficult • Ultrasound-guided central line insertion by paediatric anaesthetist • Pericardial adhesions from previous mitral valve replacement surgery at the age of 24 years • MPS-associated valvular pathology • Adhesions removed • Fibrous tissue, calcification and GAGs removed from mitral valve • Physically small patient • Paediatric catheters used to remove excess blood from ventricles • Smallest adult replacement valve used (size 19 mm CarboMedics Top Hat® mechanical prosthesis) • Tracheostomy required because of narrow trachea, but difficult for paediatric and adult anaesthetists to perform • ENT surgeon assisted • Pre-surgery 3D CT of chest and trachea, and fluoroscopy results were used to identify optimal site Spinal decompression • No cardiology expertise in hospital performing surgery a • Medical files provided by the treating doctor • Surgeons discussed surgery with treating doctor to understand MPS-specific requirements • Patient and family did not wish ERT to be interrupted by surgery a • ERT infusions arranged to occur during recovery at hospital performing surgery • Patient had a short stature and restricted respiratory function b • Neurosurgeon had extensive experience in paediatric patients Corneal transplant • High cardiovascular risk • Pre-surgery cardiac and respiratory function tests • Risk that patient may not tolerate procedure or epithelium may be pierced • Make preparations in case general anaesthesia is required • Risk of graft rejection • Endothelium preserved, resulting in reduced risk a Case 2. b Case 3 Table 4 Challenges and resolutions associated with critical clinical situations Challenges Resolutions Pregnancy • Breathlessness and oedema progressed as ERT stopped at 3.5 weeks of the pregnancy • Regular monthly obstetrics appointments • Regular cardiology, ophthalmology and anaesthetic appointments • Monthly fetal ultrasound scans • Spinal support required during pregnancy • Body corset worn by patient • Neonatal child had squints, jaundice and respiratory difficulties • Neonatal intensive care for 8 weeks • Supportive ventilation • Help required caring for the baby for the first year because of joint restrictions in the hands • Baby fed with expressed milk and formula • Support provided by patient’s family • Increased frequency of health visitor appointments • Appointments with occupational therapist • Chest infections more frequent and forced vital capacity reduced, as ERT cessation continued during breastfeeding • Antibiotics prescribed once bacterial infection confirmed • Contraindications confirmed with pharmacist Maintaining ERT administration after thrombus development in a venous access device • Worsening breathlessness due to obstructive sleep apnoea • Continuous positive airway pressure at night to resolve obstructive sleep apnoea prior to surgery to remove port-a-cath • Assessed by neurosurgeon, ENT consultant and anaesthetist prior to surgery • After port-a-cath removal, patient received ERT by peripheral access, leading to reduced quality of life • Port-a-caths are usually reserved for paediatric patients • Hickman line inserted • Hickman line insertion resulted in patient distress • Consider general anaesthesia for this procedure in patients with MPS • Risk of infection with Hickman line • An adult Hickman line was required for an appropriate diameter, but as the patient is short, the line is relatively long, increasing infection risk • Sterile dressings were changed frequently, and the line flushed prior to ERT • Patient and family educated on managing Hickman line and infusions • Patient travelling shortly after procedure • Sutures left in until patient was able to return Complex continuous symptom management • Wide range of symptoms experienced, and surgeries and treatments required • Adult care specialist has extensive experience of MPS and makes personal contact with the MDT to explain the requirements for each surgical procedure • Continued monitoring of symptoms that are life-threatening or may affect quality of life • Airway management during extubation a • Caused by swelling • Progressive dyspnoea developed after tracheostomy tube removal • Tracheal stenosis developed • Emergency tracheostomy • Oxygen support required on some occasions • Assess need for all future surgeries • Surgical management b • Procedures can be carried out in a paediatric hospital that has appropriately sized equipment available and expertise in MPS • Organisation of ERT infusions b • Carried out by adult care clinicians in a dialysis ward a Case 7. b Case 8	3.943359	0.730469	sec[1]/sec[1]/p[0]	en	0.999997	32410642	https://doi.org/10.1186/s13023-020-01382-z	[ "paediatric", "valve", "cardiac", "replacement", "metabolic", "line", "respiratory", "required", "challenges", "consultant" ]	[ { "code": "4B2Y", "title": "Other specified disorders involving the immune system" }, { "code": "4A42.0", "title": "Paediatric onset systemic sclerosis" }, { "code": "4A43.3", "title": "Mixed connective tissue disease" }, { "code": "4A43.22", "title": "Paediatric onset Sjögren syndrome" }, { "code": "2A80.4", "title": "Paediatric type follicular lymphoma" }, { "code": "GB61.Z", "title": "Chronic kidney disease, stage unspecified" }, { "code": "BC00", "title": "Multiple valve disease" }, { "code": "BB9Z", "title": "Pulmonary valve disease, unspecified" }, { "code": "BB6Z", "title": "Mitral valve disease, unspecified" }, { "code": "LA8Z", "title": "Structural developmental anomaly of heart or great vessels, unspecified" } ]	=== ICD-11 CODES FOUND === [4B2Y] Other specified disorders involving the immune system Also known as: Other specified disorders involving the immune system \| Certain inflammatory disorders with predominant lymph node involvement \| Histiocytic necrotising lymphadenitis of Kikuchi and Fujimoto \| Kikuchi-Fujimoto disease \| Kimura disease [4A42.0] Paediatric onset systemic sclerosis Definition: Systemic sclerosis arising before the age of 16. Involvement of internal organs is less common but arthritis and myositis are more common than in adults. Also known as: Paediatric onset systemic sclerosis \| Diffuse paediatric systemic sclerosis \| Limited paediatric systemic sclerosis [4A43.3] Mixed connective tissue disease Definition: Mixed connective tissue disease is an overlapping syndrome combining features of systemic lupus erythematosus, systemic sclerosis, and polymyositis with the presence of autoantibodies to U1-ribonucleoprotein. Raynaud’s phenomenon is seen in nearly all patients and pulmonary arterial hypertension is the most common cause of death in MCTD patients. Also known as: Mixed connective tissue disease \| Sharp syndrome \| MCTD - [mixed connective tissue disease] \| Paediatric-onset mixed connective tissue disease \| Paediatric-onset Sharp syndrome [4A43.22] Paediatric onset Sjögren syndrome Also known as: Paediatric onset Sjögren syndrome \| Paediatric onset Sjögren syndrome; primary \| Paediatric onset Sjögren syndrome, secondary \| Paediatric onset Sjögren syndrome vasculitis [2A80.4] Paediatric type follicular lymphoma Definition: A variant of follicular lymphoma often involving cervical or other peripheral lymph nodes and the Waldeyer ring. It is frequently localised, and often lacks BCL-2 protein expression and never has a BCL2 translocation. It is usually but not exclusively seen in the pediatric population. The prognosis is usually favorable. Also known as: Paediatric type follicular lymphoma \| paediatric follicular lymphoma [GB61.Z] Chronic kidney disease, stage unspecified Also known as: Chronic kidney disease, stage unspecified \| Chronic kidney disease \| chronic renal failure \| chronic kidney failure \| chronic renal disease [BC00] Multiple valve disease Also known as: Multiple valve disease \| Multiple valve disease of unspecified origin \| multiple valvular cardiac dysfunction \| multivalvular cardiac dysfunction \| Disorders of both mitral and aortic valves [BB9Z] Pulmonary valve disease, unspecified Also known as: Pulmonary valve disease, unspecified \| rheumatic heart disease of pulmonary valve, unspecified \| chronic rheumatic pulmonary valve endocarditis \| chronic rheumatic pulmonary valvular endocarditis \| rheumatic disease of pulmonary valve [BB6Z] Mitral valve disease, unspecified Also known as: Mitral valve disease, unspecified \| noninfective endocarditis of mitral valve \| rheumatic heart disease of mitral valve, unspecified \| mitral valvulopathy \| mitral valve cardiopathy [LA8Z] Structural developmental anomaly of heart or great vessels, unspecified Also known as: Structural developmental anomaly of heart or great vessels, unspecified \| Heart malformations \| Cardiac malformations \| congenital anomaly of heart \| congenital heart disease === GRAPH WALKS === --- Walk 1 --- [4B2Y] Other specified disorders involving the immune system --PARENT--> [?] Certain disorders involving the immune system Def: Disorders in which disturbed immune regulation plays an important part but which cannot be more precisely located elsewhere in the classification.... --CHILD--> [4B20] Sarcoidosis Def: Sarcoidosis is a multisystem disorder of unknown cause characterised by the formation of immune granulomas in involved organs. The lung and the lymphatic system are predominantly affected, but virtual... --- Walk 2 --- [4B2Y] Other specified disorders involving the immune system --PARENT--> [?] Certain disorders involving the immune system Def: Disorders in which disturbed immune regulation plays an important part but which cannot be more precisely located elsewhere in the classification.... --CHILD--> [4B20] Sarcoidosis Def: Sarcoidosis is a multisystem disorder of unknown cause characterised by the formation of immune granulomas in involved organs. The lung and the lymphatic system are predominantly affected, but virtual... --- Walk 3 --- [4A42.0] Paediatric onset systemic sclerosis Def: Systemic sclerosis arising before the age of 16. Involvement of internal organs is less common but arthritis and myositis are more common than in adults.... --PARENT--> [4A42] Systemic sclerosis Def: Systemic sclerosis is a systemic disorder of the connective tissue; manifested by hardening and thickening of the skin, by abnormalities involving the microvasculature and larger vessels, and by fibro... --CHILD--> [4A42.0] Paediatric onset systemic sclerosis Def: Systemic sclerosis arising before the age of 16. Involvement of internal organs is less common but arthritis and myositis are more common than in adults.... --- Walk 4 --- [4A42.0] Paediatric onset systemic sclerosis Def: Systemic sclerosis arising before the age of 16. Involvement of internal organs is less common but arthritis and myositis are more common than in adults.... --PARENT--> [4A42] Systemic sclerosis Def: Systemic sclerosis is a systemic disorder of the connective tissue; manifested by hardening and thickening of the skin, by abnormalities involving the microvasculature and larger vessels, and by fibro... --CHILD--> [4A42.1] Diffuse systemic sclerosis Def: Diffuse cutaneous systemic sclerosis (dcSSc) is a subtype of Systemic Sclerosis (SSc) characterised by truncal and acral skin fibrosis with an early and significant incidence of diffuse involvement (i... --- Walk 5 --- [4A43.3] Mixed connective tissue disease Def: Mixed connective tissue disease is an overlapping syndrome combining features of systemic lupus erythematosus, systemic sclerosis, and polymyositis with the presence of autoantibodies to U1-ribonucleo... --PARENT--> [4A43] Overlap or undifferentiated nonorgan specific systemic autoimmune disease Def: Nonorgan specific systemic autoimmune diseases which do not fulfil the diagnostic criteria for any single recognised disease entity.... --PARENT--> [?] Nonorgan specific systemic autoimmune disorders --- Walk 6 --- [4A43.3] Mixed connective tissue disease Def: Mixed connective tissue disease is an overlapping syndrome combining features of systemic lupus erythematosus, systemic sclerosis, and polymyositis with the presence of autoantibodies to U1-ribonucleo... --PARENT--> [4A43] Overlap or undifferentiated nonorgan specific systemic autoimmune disease Def: Nonorgan specific systemic autoimmune diseases which do not fulfil the diagnostic criteria for any single recognised disease entity.... --CHILD--> [4A43.0] IgG4 related disease Def: IgG4 related syndrome (IgG4-related disease: IgG4-RD) is a clinical disease characterised by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. The...	[ "[4B2Y] Other specified disorders involving the immune system\n --PARENT--> [?] Certain disorders involving the immune system\n Def: Disorders in which disturbed immune regulation plays an important part but which cannot be more precisely located elsewhere in the classification....\n --CHILD--> [4B20] Sarcoidosis\n Def: Sarcoidosis is a multisystem disorder of unknown cause characterised by the formation of immune granulomas in involved organs. The lung and the lymphatic system are predominantly affected, but virtual...", "[4B2Y] Other specified disorders involving the immune system\n --PARENT--> [?] Certain disorders involving the immune system\n Def: Disorders in which disturbed immune regulation plays an important part but which cannot be more precisely located elsewhere in the classification....\n --CHILD--> [4B20] Sarcoidosis\n Def: Sarcoidosis is a multisystem disorder of unknown cause characterised by the formation of immune granulomas in involved organs. The lung and the lymphatic system are predominantly affected, but virtual...", "[4A42.0] Paediatric onset systemic sclerosis\n Def: Systemic sclerosis arising before the age of 16. Involvement of internal organs is less common but arthritis and myositis are more common than in adults....\n --PARENT--> [4A42] Systemic sclerosis\n Def: Systemic sclerosis is a systemic disorder of the connective tissue; manifested by hardening and thickening of the skin, by abnormalities involving the microvasculature and larger vessels, and by fibro...\n --CHILD--> [4A42.0] Paediatric onset systemic sclerosis\n Def: Systemic sclerosis arising before the age of 16. Involvement of internal organs is less common but arthritis and myositis are more common than in adults....", "[4A42.0] Paediatric onset systemic sclerosis\n Def: Systemic sclerosis arising before the age of 16. Involvement of internal organs is less common but arthritis and myositis are more common than in adults....\n --PARENT--> [4A42] Systemic sclerosis\n Def: Systemic sclerosis is a systemic disorder of the connective tissue; manifested by hardening and thickening of the skin, by abnormalities involving the microvasculature and larger vessels, and by fibro...\n --CHILD--> [4A42.1] Diffuse systemic sclerosis\n Def: Diffuse cutaneous systemic sclerosis (dcSSc) is a subtype of Systemic Sclerosis (SSc) characterised by truncal and acral skin fibrosis with an early and significant incidence of diffuse involvement (i...", "[4A43.3] Mixed connective tissue disease\n Def: Mixed connective tissue disease is an overlapping syndrome combining features of systemic lupus erythematosus, systemic sclerosis, and polymyositis with the presence of autoantibodies to U1-ribonucleo...\n --PARENT--> [4A43] Overlap or undifferentiated nonorgan specific systemic autoimmune disease\n Def: Nonorgan specific systemic autoimmune diseases which do not fulfil the diagnostic criteria for any single recognised disease entity....\n --PARENT--> [?] Nonorgan specific systemic autoimmune disorders", "[4A43.3] Mixed connective tissue disease\n Def: Mixed connective tissue disease is an overlapping syndrome combining features of systemic lupus erythematosus, systemic sclerosis, and polymyositis with the presence of autoantibodies to U1-ribonucleo...\n --PARENT--> [4A43] Overlap or undifferentiated nonorgan specific systemic autoimmune disease\n Def: Nonorgan specific systemic autoimmune diseases which do not fulfil the diagnostic criteria for any single recognised disease entity....\n --CHILD--> [4A43.0] IgG4 related disease\n Def: IgG4 related syndrome (IgG4-related disease: IgG4-RD) is a clinical disease characterised by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. The..." ]	4B2Y	Other specified disorders involving the immune system	[ { "from_icd11": "4A42.0", "icd10_code": "M349", "icd10_title": "Systemic sclerosis, unspecified" }, { "from_icd11": "4A42.0", "icd10_code": "M342", "icd10_title": "Systemic sclerosis induced by drug and chemical" }, { "from_icd11": "4A42.0", "icd10_code": "M34", "icd10_title": "Systemic sclerosis [scleroderma]" }, { "from_icd11": "4A43.3", "icd10_code": "M351", "icd10_title": "Other overlap syndromes" }, { "from_icd11": "4A43.3", "icd10_code": "M35", "icd10_title": "Other systemic involvement of connective tissue" }, { "from_icd11": "4A43.22", "icd10_code": "M3500", "icd10_title": "Sicca syndrome, unspecified" }, { "from_icd11": "4A43.22", "icd10_code": "M3509", "icd10_title": "Sicca syndrome with other organ involvement" }, { "from_icd11": "4A43.22", "icd10_code": "M3502", "icd10_title": "Sicca syndrome with lung involvement" }, { "from_icd11": "4A43.22", "icd10_code": "M3501", "icd10_title": "Sicca syndrome with keratoconjunctivitis" }, { "from_icd11": "4A43.22", "icd10_code": "M350", "icd10_title": "Sicca syndrome [Sjogren]" }, { "from_icd11": "GB61.Z", "icd10_code": "N183", "icd10_title": "Chronic kidney disease, stage 3 (moderate)" }, { "from_icd11": "GB61.Z", "icd10_code": "N189", "icd10_title": "Chronic kidney disease, unspecified" }, { "from_icd11": "GB61.Z", "icd10_code": "N250", "icd10_title": "Renal osteodystrophy" }, { "from_icd11": "GB61.Z", "icd10_code": "N18", "icd10_title": "Chronic kidney disease (CKD)" }, { "from_icd11": "BC00", "icd10_code": "I081", "icd10_title": "Rheumatic disorders of both mitral and tricuspid valves" } ]	M349	Systemic sclerosis, unspecified
Our patient is a 20-year-old Filipino male diagnosed with SLE 6 months prior and was started on hydroxychloroquine. The patient presented to the emergency department after sudden onset of dyspnea, pleuritic chest pain, generalized fatigue, dry cough, fevers and chronic progressive rash. His review of systems was negative for sick contacts, recent travel, engagement in high-risk sexual activity, intravenous drug use, was a lifetime nonsmoker, and did not consume alcohol. On evaluation, vitals were notable for normal blood pressure (118/72 mmHg), tachycardia (118 beats per minute), tachypnea (respiratory rate 22 breaths per minute), and fever (100.8 °F). His cardiovascular exam was unremarkable for murmurs, elevated jugular venous pressure, splinter hemorrhages, or lower extremity edema. No cyanosis, clubbing, scleral icterus, organomegaly, or lymphadenopathy was appreciated. The skin examination showed no oral ulcers or alopecia, but demonstrated hyperpigmented to violaceous, scaly plaques with excoriated papules involving the bilateral extremities, back, and chest worsened as shown in Fig. 1 . A prior skin punch biopsy of a similar rash showed lichenoid dermatitis with features of interface changes and chronic inflammation suggestive of cutaneous SLE. This rash had improved from his index presentation following treatment with hydroxychloroquine, though not fully resolved. Laboratory data on admission revealed the following: leukopenia, anemia, and non-nephrotic range proteinuria without active urinary sediment on urine microscopy. There was evidence of acute myocardial injury with elevated cardiac biomarkers along with an elevated N-terminal pro-brain natriuretic peptide. Additionally, inflammatory biomarkers were elevated with hypocomplementemia, positive antinuclear antibody (ANA) with anti-Smith, ribonucleoprotein, chromatin, SS-A, double-stranded DNA, perinuclear anti-neutrophil cytoplasmic antibodies (pANCA), and myeloperoxidase positivity. Comprehensive laboratory evaluation for additional workup and the reference ranges is shown in Table 1 . His electrocardiogram and telemetry monitoring demonstrated normal sinus rhythm with diffuse < 1 mm ST-segment elevations in leads without any ischemic changes. Initial chest x-ray showed no acute cardiopulmonary process. Further infectious evaluation demonstrated positive blood cultures for methicillin-sensitive Staphylococcus aureus (MSSA) with a likely skin source from aggressively scratching a purulent lesion on the right anterior thigh. Initial transthoracic echocardiogram showed normal LVEF with all other normal parameters. Given concerns for sepsis secondary to presumed cellulitis, in the setting of SLE flare, he was treated with broad spectrum intravenous (IV) antibiotics and corticosteroids (methylprednisolone 1 g/kg for three days) before his transfer to our institution. Given concerns for endocarditis with persistent fevers on arrival, repeat transthoracic and transesophageal echocardiograms demonstrated mildly reduced LVEF 45% with no valvular pathology. MSSA bacteremia resolved within 72 h of intravenous antibiotics (cefazolin 2 g IV every 8 h), but the patient later developed a rapid cardiopulmonary decline on hospital day #5 with worsening dyspnea, pleuritic chest pain, and hemoptysis. A repeat chest x-ray and CT chest were obtained demonstrating dense pulmonary bilateral pleural effusions with dense consolidations, pulmonary nodules, possible pulmonary emboli within the left subsegmental pulmonary artery branches, and pericardial effusions. A repeat transthoracic echocardiogram demonstrated a severely reduced LVEF 25%, moderate global hypokinesis, and small pericardial effusion without evidence of tamponade . Other abnormal findings included elevated right atrial pressures (15 mmHg) and mild pulmonary hypertension (43 mmHg) with a normal left atrial pressure, right ventricular systolic function, left ventricular diastolic function, and valvular function. Given clearance of bacteremia with IV antibiotics, cardiogenic shock was favored over septic shock. Intravenous vasopressors (norepinephrine, 0.4mcg/kg/min IV infusion) for shock, diuretics, amiodarone drip for atrial fibrillation with a rapid ventricular response, heparin drip for submassive pulmonary emboli, high-dose corticosteroids (solumedrol 500 mg IV every 12 h) and hydroxychloroquine 400 mg daily for SLE related co-activity were initiated. A cardiac MRI (CMR) was subsequently pursued to clarify the cause of myocarditis, which demonstrated a LVEF of 25% and moderate global hypokinesis with worsening pericardial effusions . Unfortunately, the patient’s poor respiratory reserve and tachycardia limited our ability to perform late gadolinium enhancement. With his continued clinical decline potentially requiring escalating hemodynamic support, he was transferred to a medical center with advanced heart failure treatment capabilities. Fig. 1 Skin examination on hospital day #1 revealing a diffuse hyperpigmented to violaceous rash with excoriated papules with overlying hemorrhagic crust and scales (white arrows), some coalescing into small plaques distributed on trunk, bilateral thigs, knees, anterior lower legs, and feet Fig. 2 Skin examination during an outpatient clinic visit 6 months prior to his admission revealing a diffuse hyperpigmented rash with excoriated papules coalescing into plaques (black arrows) involving his bilateral upper and lower extremities and chest Table 1 Laboratory work-up performed during hospitalization Laboratory test index Results Reference ranges Total WBC count 3.7 × 10 3 mcL (L) 4.0–10.5 × 10 3 mcL Differential Neutrophils 85.5% (H) 40.0–80.0% Lymphocytes 7.9% (L) 15.0–45.0% Absolute lymphocyte count 0.6 × 10 3 mcL (L) 1.0–4.5 × 10 3 mcL Hb 10.4 g/dL (L) 13.8–17.0 g/dL MCV 80.8 fL (L) 82.0–99.0 fL Platelets 188 × 10 3 mcL 150–450 × 10 3 mcL AST 94 U/L (H) 12–39 U/L ALT 67 U/L (H) 17–63 U/L LDH 239 U/L (H) 135–225 U/L Troponin T 0.053 ng/mL (H) Peaked at 0.94 ng/mL < 0.010 ng/mL NT-proBNP 2210 pg/mL (H) < 125 pg/mL ESR 87 mm/h (H) 0–10 mm/h CRP 12.21 mg/dL (H) < 0.50 mg/dL Haptoglobin 175 mg/dL 30–200 mg/dL C3 23 mg/dL (L) 90–180 mg/dL C4 3 mg/dL (L) 10–40 mg/dL Rheumatoid factor 11 IU/mL < 13 IU/mL ANA screen, IFA, with reflex to titer and pattern Positive > 1:80; homogenous pattern < 1:40 Double-stranded DNA Ab > 300 IU/mL (H) 0–9 IU/mL Anti-Smith Ab Positive Negative Anti-RNP Ab Positive Negative Anti-ribosomal-P Ab Positive Negative Anti-chromatin Ab Positive Negative Anti-SS-A (Ro) Ab Positive Negative Anti-SS-B (La) Ab Negative Negative Jo-1 extractable nuclear Ab Negative Negative Anti-centromere Ab Negative Negative SCL-70 extractable nuclear Ab Negative Negative ANCA panel Neutrophil cytoplasmic Ab cytoplasmic Negative Negative Neutrophil cytoplasmic Ab perinuclear 1:2560 Negative Myeloperoxidase Ab 51 AU/mL 0–19.0 AU/mL Proteinase 3 Ab < 3.5 AU/mL 0–19.0 AU/mL Antiphospholipid Ab 153 mg/dL 150 – 250 mg/dL Quantitative immunoglobulin panel IgM 35 mg/dL 40–230 mg/dL IgA 231 mg/dL 70–400 mg/dL IgG 1103 mg/dL 700–1600 mg/dL IgG subclass 4 29 mg/dL 2–96 mg/dL Lupus anticoagulant 2 AU/mL 0–40 AU/mL Anti-cardiolipin Ab, IgG < 9 GPL/mL 0–14 GPL/mL Anti-cardiolipin Ab, IgM < 9 MPL/mL 0–12 MPL/mL Beta-2 glycoprotein 1 Ab, IgG < 9 GPI IgG units 0–20 GPI IgG units Beta-2 glycoprotein 1 Ab, IgM < 9 GPI IgM units 0–32 GPI IgM units Beta-2 glycoprotein 1 Ab, IgA < 9 GPI IgA units 0–25 GPI IgA units Streptolysin O Ab 22 IU/mL < 20–200 IU/mL DNase B Ab streptococcal < 78 U/mL 0–120 U/mL Angiotensin converting enzyme < 40 nmol/mL/min 0–40 nmol/mL/min Urine protein/creatinine ratio 663 mg/24 h < 0.2 mg/24 Hr Urine microscopy No active urine sediment Negative Kappa/Lambda light chain < 0.26 mg/L 0.26–1.25 mg/L Blood cultures with sensitivities HD #1 2/2 MSSA (sensitive to cefazolin, ampicillin/sulbactam, oxacillin) Positive Negative HD #2 No growth Negative HD #3 1/4 Staph epidermitidis (contaminant) Negative HD #5 No growth Negative HD #6 No growth Negative HD #7 No growth Negative Respiratory cultures HD #6 GPCs in pairs/chains, GNRs, and yeast (with squamous epithelial cells)-respiratory flora Negative Expanded respiratory viral panel Negative Negative Influenza virus A RNA Influenza virus B RNA Influenza virus A Hemagglutinin H1 RNA Influenza virus A Hemagglutinin H3 RNA Resp syncytial virus A PCR Resp syncytial virus B PCR Parainfluenza virus 1 RNA Parainfluenza virus 2 RNA Parainfluenza virus 3 RNA Parainfluenza virus 4 RNA Adenovirus DNA Human metapneumovirus RNA Rhinovirus RNA Bordetella pertussis DNA Bordetella holmseii DNA Bord Parapert/Bronchiseptica Hepatitis viral panel Hepatitis A virus Ab Reactive Reactive Hepatitis A IgM Non-reactive Non-reactive Hepatitis B virus core Ab Non-reactive Non-reactive Hepatitis B virus core Ab IgM Non-reactive Non-reactive Hepatitis B virus surface Ab Reactive Reactive Hepatitis B virus surface Ag Non-reactive Non-reactive Hepatitis C virus Ab Non-reactive Non-reactive Epstein–Barr virus capsid Ab IgG Positive (H) Negative Epstein–Barr virus capsid Ab IgM Negative Negative Cytomegalovirus Ab IgG Positive (H) Negative Cytomegalovirus Ab IgM Negative Negative Coxsackie A IgG Negative Negative Coxsackie A IgM HIV 4th gen Negative Negative HTLV-1+2 Ab Negative Negative Treponema pallidum Ab Non-reactive Non-reactive 1,3 Beta-D Glucan < 31 pg/mL < 80 pg/mL Coccidioides immitis Ab IgG Negative Negative Coccidioides immitis Ab IgM Negative Negative Cryptococcus sp. Ag Negative Negative Aspergillus galactomannan Ag 0.04 ng/mL 0.00–0.49 ng/mL Histoplasma urinary antigen Negative Negative WBC, white blood count; Hb, hemoglobin, MCV, mean corpuscular volume; AST, aspartate aminotransferase; ALT, alanine aminotransferase; LDH, lactate dehydrogenase; NT-proBNP, N-terminal (NT)-pro hormone BNP; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; C3, complement c3; C4, complement c4, ANA, antinuclear antibody; IFA, Indirect Immunofluorescence Assay; RNP, ribonucleoprotein; ANCA, antineutrophil cytoplasmic antibodies; MSSA, Methicillin-sensitive Staph aureus; GPCs, gram positive cocci; GNR, gram negative rods; HIV, human immunodeficiency virus; HTLV, human T-lymphotropic virus Fig. 3 A portable chest x-ray demonstrating bilateral interstitial infiltrates with dense consolidations in lung bases, bilateral pleural effusions, and pericardial effusion Fig. 4 An axial view on computed tomography (CT) chest imaging obtained after the patient’s rapid cardiopulmonary decline demonstrating dense pulmonary consolidations, diffuse pulmonary nodules, and moderate pericardial (black arrow) and bilateral pleural effusions white arrows) Fig. 5 An apical four-chamber view on transthoracic echocardiogram obtained on the day of the patient’s cardiopulmonary decline (HD #6) demonstrating a moderate-sized pericardial effusion (white arrows) Fig. 6 A Cardiac MRI, T-2 weighted axial image of diastolic phase with late gadolinium enhancement sequence, demonstrating left ventricular dilation and large bilateral pleural effusions and pericardial effusions (white arrows). Myocardial tissue characterization with late gadolinium hyperenhancement was unable to be performed due to patient’s inability to lie recumbent and tachypnea	3.990234	0.980469	sec[1]/p[0]	en	0.999996	34120592	https://doi.org/10.1186/s12872-021-02102-6	[ "virus", "reactive", "anti", "chest", "pulmonary", "hepatitis", "effusions", "pericardial", "rash", "respiratory" ]	[ { "code": "1D9Z", "title": "Unspecified viral infection of unspecified site" }, { "code": "1E1Z", "title": "Unspecified viral disease" }, { "code": "1E1Y", "title": "Other specified viral diseases" }, { "code": "1D85.Z", "title": "Viral carditis, unspecified" }, { "code": "KA62.Z", "title": "Viral infection in the fetus or newborn, unspecified" }, { "code": "6B44", "title": "Reactive attachment disorder" }, { "code": "3B62.Z", "title": "Qualitative platelet defects, unspecified" }, { "code": "6A70.Z", "title": "Single episode depressive disorder, unspecified" }, { "code": "2B32.1", "title": "Reactive plasmacytic hyperplasia" }, { "code": "FA11.Z", "title": "Reactive arthropathies, unspecified" } ]	=== ICD-11 CODES FOUND === [1D9Z] Unspecified viral infection of unspecified site Also known as: Unspecified viral infection of unspecified site \| viral infection NOS \| viral disorder NOS \| disease caused by virus \| unspecified viremia [1E1Z] Unspecified viral disease Also known as: Unspecified viral disease [1E1Y] Other specified viral diseases Also known as: Other specified viral diseases \| Acute infectious lymphocytosis [1D85.Z] Viral carditis, unspecified Also known as: Viral carditis, unspecified \| Viral carditis [KA62.Z] Viral infection in the fetus or newborn, unspecified Also known as: Viral infection in the fetus or newborn, unspecified \| Viral infection in the fetus or newborn \| congenital virus disorder \| congenital virus disease [6B44] Reactive attachment disorder Definition: Reactive attachment disorder is characterised by grossly abnormal attachment behaviours in early childhood, occurring in the context of a history of grossly inadequate child care (e.g., severe neglect, maltreatment, institutional deprivation). Even when an adequate primary caregiver is newly available, the child does not turn to the primary caregiver for comfort, support and nurture, rarely displays security-seeking behaviours towards any adult, and does not respond when comfort is offered. Reac Also known as: Reactive attachment disorder \| childhood reactive attachment disorder \| reactive attachment disorder of early childhood Excludes: Asperger syndrome \| disinhibited attachment disorder of childhood [3B62.Z] Qualitative platelet defects, unspecified Also known as: Qualitative platelet defects, unspecified \| Qualitative platelet defects \| Thrombocytopathy \| platelet defect \| platelet disorder [6A70.Z] Single episode depressive disorder, unspecified Also known as: Single episode depressive disorder, unspecified \| Single episode depressive disorder \| reactive depression NOS \| single episodes of depressive reaction \| single episodes of psychogenic depression [2B32.1] Reactive plasmacytic hyperplasia Also known as: Reactive plasmacytic hyperplasia [FA11.Z] Reactive arthropathies, unspecified Also known as: Reactive arthropathies, unspecified \| Reactive arthropathies \| reactive arthropathy === GRAPH WALKS === --- Walk 1 --- [1D9Z] Unspecified viral infection of unspecified site --PARENT--> [?] Viral infection of unspecified site --EXCLUDES--> [?] Herpes simplex infections Def: Any condition caused by an infection with herpes simplex virus (human herpesviruses 1 and 2). Confirmation is by identification of herpes simplex virus type 1 or 2.... --- Walk 2 --- [1D9Z] Unspecified viral infection of unspecified site --PARENT--> [?] Viral infection of unspecified site --CHILD--> [1D90] Adenovirus infection of unspecified site Def: Adenovirus infections most commonly cause illness of the respiratory system; however, depending on the infecting serotype, they may also cause various other illnesses and presentations.... --- Walk 3 --- [1E1Z] Unspecified viral disease --PARENT--> [?] Certain other viral diseases --RELATED_TO--> [?] Other viral diseases complicating pregnancy, childbirth or the puerperium --- Walk 4 --- [1E1Z] Unspecified viral disease --PARENT--> [?] Certain other viral diseases --RELATED_TO--> [?] Other viral diseases complicating pregnancy, childbirth or the puerperium --- Walk 5 --- [1E1Y] Other specified viral diseases --PARENT--> [?] Certain other viral diseases --CHILD--> [1D82] Cytomegaloviral disease Def: Any condition caused by an infection with cytomegalovirus (CMV). These conditions are commonly asymptomatic. Transmission is by direct contact with infected body fluids.... --- Walk 6 --- [1E1Y] Other specified viral diseases --PARENT--> [?] Certain other viral diseases --RELATED_TO--> [?] Congenital Varicella Zoster virus infection Def: Transplacentally acquired Varicella zoster virus infection. Both the gestational age at the time of maternal infection and the time interval between maternal infection and birth have major influences ...	[ "[1D9Z] Unspecified viral infection of unspecified site\n --PARENT--> [?] Viral infection of unspecified site\n --EXCLUDES--> [?] Herpes simplex infections\n Def: Any condition caused by an infection with herpes simplex virus (human herpesviruses 1 and 2). Confirmation is by identification of herpes simplex virus type 1 or 2....", "[1D9Z] Unspecified viral infection of unspecified site\n --PARENT--> [?] Viral infection of unspecified site\n --CHILD--> [1D90] Adenovirus infection of unspecified site\n Def: Adenovirus infections most commonly cause illness of the respiratory system; however, depending on the infecting serotype, they may also cause various other illnesses and presentations....", "[1E1Z] Unspecified viral disease\n --PARENT--> [?] Certain other viral diseases\n --RELATED_TO--> [?] Other viral diseases complicating pregnancy, childbirth or the puerperium", "[1E1Z] Unspecified viral disease\n --PARENT--> [?] Certain other viral diseases\n --RELATED_TO--> [?] Other viral diseases complicating pregnancy, childbirth or the puerperium", "[1E1Y] Other specified viral diseases\n --PARENT--> [?] Certain other viral diseases\n --CHILD--> [1D82] Cytomegaloviral disease\n Def: Any condition caused by an infection with cytomegalovirus (CMV). These conditions are commonly asymptomatic. Transmission is by direct contact with infected body fluids....", "[1E1Y] Other specified viral diseases\n --PARENT--> [?] Certain other viral diseases\n --RELATED_TO--> [?] Congenital Varicella Zoster virus infection\n Def: Transplacentally acquired Varicella zoster virus infection. Both the gestational age at the time of maternal infection and the time interval between maternal infection and birth have major influences ..." ]	1D9Z	Unspecified viral infection of unspecified site	[ { "from_icd11": "1D9Z", "icd10_code": "B348", "icd10_title": "Other viral infections of unspecified site" }, { "from_icd11": "1D9Z", "icd10_code": "B349", "icd10_title": "Viral infection, unspecified" }, { "from_icd11": "1D9Z", "icd10_code": "B344", "icd10_title": "Papovavirus infection, unspecified" }, { "from_icd11": "1D9Z", "icd10_code": "B333", "icd10_title": "Retrovirus infections, not elsewhere classified" }, { "from_icd11": "1D9Z", "icd10_code": "B34", "icd10_title": "Viral infection of unspecified site" }, { "from_icd11": "1E1Z", "icd10_code": "B338", "icd10_title": "Other specified viral diseases" }, { "from_icd11": "1E1Z", "icd10_code": "B25-B34", "icd10_title": "" }, { "from_icd11": "1E1Z", "icd10_code": "B33", "icd10_title": "Other viral diseases, not elsewhere classified" }, { "from_icd11": "1E1Z", "icd10_code": "M015", "icd10_title": "" }, { "from_icd11": "1E1Y", "icd10_code": "B9789", "icd10_title": "Other viral agents as the cause of diseases classified elsewhere" }, { "from_icd11": "1D85.Z", "icd10_code": "B3324", "icd10_title": "Viral cardiomyopathy" }, { "from_icd11": "1D85.Z", "icd10_code": "B3323", "icd10_title": "Viral pericarditis" }, { "from_icd11": "1D85.Z", "icd10_code": "B332", "icd10_title": "Viral carditis" }, { "from_icd11": "KA62.Z", "icd10_code": "P35", "icd10_title": "Congenital viral diseases" }, { "from_icd11": "KA62.Z", "icd10_code": "P358", "icd10_title": "Other congenital viral diseases" } ]	B348	Other viral infections of unspecified site
Case 1: A 59-year-old man was referred to the Liver Transplant Unit of Queen Mary Hospital, a university-affiliated hospital with 1,600 bed, for consideration of cadaveric liver transplantation due to chronic hepatitis B-related end-stage cirrhosis on 14 September 2013. Queen Mary Hospital is the only liver transplant center in Hong Kong, with approximately 80 patients undergoing liver transplantation per year. Upon admission, rectal swab with visible stool content was collected for the detection of multidrug-resistant organisms including VRE in accordance to the hospital infection control policy. Briefly, patients with history of hospitalization or receiving surgical operation outside Hong Kong within the past 12 months before admission or patients with history of admissions to other local hospitals within the past 3 months were included in the active surveillance . The patient was confirmed to be positive for vancomycin-resistant Enterococcus faecium which was resistant to ampicillin, chloramphenicol, nitrofurantoin, levofloxacin, minocycline, rifampicin, tetracycline, fosfomycin, high-level gentamicin, and high-level streptomycin. The minimal inhibitory concentration (MIC) of vancomycin was >256 μg/ml. VanA gene was detected by polymerase chain reaction (PCR). The MIC of linezolid and daptomycin was 1.5 μg/ml and 3.0 μg/ml respectively, while the MIC breakpoint of linezolid and daptomycin was ≤ 2 μg/ml and ≤ 4 μg/ml for enterococcus species respectively with reference to Clinical and Laboratory Standards Institute. Multilocus sequence typing (MLST) demonstrated that the strain was ST761 (profile 70-1-1-1-12-1-1), which is a member of the pandemic clonal complex 17 lineage. The patient was isolated in a single room with strict contact precautions since day 2 of hospitalization. Healthcare workers wore gloves and gowns during patient care practice. Alcohol-based hand rub was provided in the isolation room for hand hygiene. Dedicated medical items such as stethoscope, thermometer, and blood pressure cuff were available and solely used on this patient. Decolonization of VRE was performed between day 11 and 15 of hospitalization according to our protocol (Table 1 ). The bacterial load of VRE in rectal swabs with visible stool content was monitored daily. The VRE counts decreased from >2×10 5 colony forming units per gram (cfu/g) of stool (baseline on day 11) to 3.4×10 4 cfu/g of stool on day 12 and undetectable (<200 cfu/g) on day 13. Despite the administration of broad-spectrum antibiotics after successful decolonization, the serial rectal swabs remained negative for VRE in vancomycin and clindamycin containing enterococcal enrichment broth culture . ABO blood group matched-cadaveric liver graft became available on day 30 of hospitalization and transplantation was performed under coverage with intravenous linezolid 600 mg 30 minutes before surgical incision, and one dose postoperatively. The operation lasted for 11 hours without immediate complications. Patient was managed in the adult intensive care unit during the postoperative period and transferred to the liver transplant ward on day 32 of hospitalization (post-operative day 2). Serial rectal swabs were collected on day 1, 3, 4, 5, 7, 10, 12, 14, and 17 after liver transplantation, thereafter twice weekly until day 66, and weekly until day 107 after liver transplantation (day 137 of hospitalization) . No growth of VRE was detected in broth enrichment culture.Case 2: A 56-year-old man had living-donor liver transplantation for early stage of moderately differentiated hepatocellular carcinoma on 31 July 2012. He developed recurrent ascites as a result of portal vein and hepatic vein stenosis 6 months post-transplant requiring multiple episodes of hospitalization. On 26 February 2014, he was detected to have gastrointestinal colonization of VRE and was subjected to VRE decolonization after 13 days of hospitalization . However, patient had poor tolerance to oral ingestion of polyethylene glycol for bowel preparation due to refractory ascites. Since the procedure of decolonization was started, it was continued despite insufficient bowel preparation. Patient had transient suppression of VRE between day 14 and 19 and VRE relapsed on day 27 of hospitalization. The decolonization regimen was not successful in this case with inadequate bowel preparation.Case 3: A 44-year-old man was transferred from a regional hospital to the Liver Transplant Unit of Queen Mary Hospital for consideration of cadaveric liver transplantation due to hepatitis B-related hepatic failure on 15 March 2014. He was found to have gastrointestinal carriage of VRE upon admission screening. While waiting for a potential liver graft, VRE decolonization was initiated on day 5 of hospitalization. He remained VRE negative on serial monitoring till day 62 of hospitalization despite intermittent use of antibiotics .Case 4: A 71-year-old-lady was transferred from a regional hospital to the Cardiothoracic Surgical Unit, Queen Mary Hospital, for consideration of surgical intervention for viridans streptococci-related infective endocarditis complicated with cardiac failure. She had history of chronic rheumatic heart disease with mitral stenosis, mitral regurgitation, aortic regurgitation, and tricuspid regurgitation. She was noted to have gastrointestinal carriage of VRE upon admission screening, and was put on VRE decolonization as per protocol on day 10 of hospitalization. Serial rectal swabs culture remained VRE negative (broth enrichment culture) till day 23 of hospitalization . However, patient developed respiratory distress, metabolic acidosis, hypotension, oliguric renal impairment, and radiological appearance of dilated bowel loops suggestive of mesenteric ischemia on day 25. Urgent exploratory laparotomy revealed the presence of 300 ml foul-smelling, blood-stained peritoneal fluid with gangrenous change of bowel from duodenojejunal flexure to mid-sigmoid colon. Despite empirical use of meropenem and daptomycin, inotropic and ventilator support, patient succumbed on day 26 of hospitalization. No VRE could be detected in all her clinical specimens or serial rectal swabs after decolonization. Table 1 Protocol of vancomycin-resistant enterococci decolonization * 1. Patient was managed in isolation room A and subjected to bowel preparation according to the protocol commonly used prior to colonoscopy examination: (i) ingestion of 2 liters of polyethylene glycol (Klean prep) over 6 hours to wash out the bowel content; (ii) taking fluid diet including rice water, clear soup, and fruit juice on the first day of decolonization. 2. When the defecated bowel content became clear fluid, patient was transferred from isolation room A to B, which had been terminally disinfected with sodium hypochlorite 1,000 ppm. 3. After transferal to isolation room B, a five-day course of medication with activity against VRE was given, including oral linezolid 600 mg every 12 hourly, orally-taken intravenous preparation of daptomycin 8 mg per kg daily. 4. At the same time, the patient was cleansed with 4% chlorhexidine bath and shampoo, and oral chlorhexidine gargle for 5 days. Where possible, avoid use of other antibiotics treatment during the decolonization period. 5. At the time of bathing, the patient’s clothes, underwear, and bed linens were replaced and sent for hot laundry daily. All personal belongings were disinfected to prevent re-colonization. The isolation room was thoroughly cleaned and disinfected by sodium hypochlorite 1,000 ppm twice daily. 6. After completion of 5-day decolonization regimen, Lactobacillus rhamnosus GG 80 mg was given daily to replace the gut flora. 7. All foods and drinks throughout the decolonization procedure must be boiled. All visitors and healthcare workers must comply with hand hygiene with alcohol based hand rub. Note. VRE, vancomycin-resistant enterococci; *The decolonization protocol was designed and coordinated by the infection control team for all patients in Queen Mary Hospital. Infection control nurses closely monitored and audited the compliance of the procedures required for decolonization. Figure 1 Serial quantitative culture of gastrointestinal carriage of vancomycin - resistant Enterococcus faecium and concomitant use of antimicrobial agents in case 1. Note. Intravenous meropenem 500 mg every 8 hourly was given between day 16 and 31 for recurrent isolation of extended-spectrum β-lactamase-producing Klebsiella species in sputum; intravenous meropenem 500 mg every 8 hourly was given again between day 41 and 49 for low grade fever without microbiological documentation of infection; oral levofloxacin 750 mg daily was given between day 71 and 78 for urine isolation of extended-spectrum β-lactamase-producing Klebsiella species ; oral cotrimoxazole 480 mg twice daily was given after liver transplantation as pre-emptive prophylactic agent. The dotted horizontal line denoted the detection limit of VRE in fecal samples by broth enrichment ~ 200 cfu/g (2.3 log 10 cfu/g). Figure 2 Serial quantitative culture of gastrointestinal carriage of vancomycin - resistant Enterococcus faecium and concomitant use of antimicrobial agents in case 2. Note. Intravenous piperacillin-tazobactam 4.5 gm iv q12h, daptomycin 250 mg iv q12h, and metronidazole 500 mg iv q8h were given from day 3 for empirical treatment of spontaneous bacterial peritonitis, while intravenous piperacillin-tazobactam 4.5 gm iv q12h, and daptomycin 250 mg iv q12h were given between day 45 and 56 for clinical diagnosis of another episode of spontaneous bacterial peritonitis. The dotted horizontal line denoted the detection limit of VRE in fecal samples by broth enrichment ~ 200 cfu/g (2.3 log10 cfu/g). Figure 3 Serial quantitative culture of gastrointestinal carriage of vancomycin - resistant Enterococcus faecium and concomitant use of antimicrobial agents in case 3. Note. Intravenous cefotaxime 1 gm iv q8h was given from the referral hospital and stopped on day 1 of hospitalization. Amoxicillin-clavulanate was given on day 20 and stepped up to piperacillin-tazobactam on day 24 of hospitalization for nosocomial onset of fever of unknown source. The dotted horizontal line denoted the detection limit of VRE in fecal samples by broth enrichment ~ 200 cfu/g (2.3 log 10 cfu/g). Figure 4 Serial quantitative culture of gastrointestinal carriage of vancomycin - resistant Enterococcus faecium and concomitant use of antimicrobial agents in case 4. Note. Intravenous ampicillin 2 gm iv q8h, and gentamicin 40 mg iv q8h were given from the referral hospital for treatment of infective endocarditis due to viridans streptococci. Antibiotic was changed to benzyl penicillin 3 MU iv q4h on day 7 upon clinical consultation to microbiologist, and stopped on day 17 of hospitalization after completion of treatment. Meropenem 500 mg iv q12h and one dose of daptomycin 350 mg iv was given on day 25 for systemic sepsis complicating mesenteric ischemia and bowel gangrene. Patient succumbed on day 26 of hospitalization despite maximal supportive therapy. The dotted horizontal line denoted the detection limit of VRE in fecal samples by broth enrichment ~ 200 cfu/g (2.3 log 10 cfu/g).	4.15625	0.900391	sec[1]/sec[0]/p[0]	en	0.999998	25248287	https://doi.org/10.1186/1471-2334-14-514	[ "hospitalization", "decolonization", "liver", "resistant", "vancomycin", "serial", "bowel", "transplantation", "culture", "intravenous" ]	[ { "code": "DB9Z", "title": "Diseases of liver, unspecified" }, { "code": "DB97.Z", "title": "Inflammatory liver disease, unspecified" }, { "code": "DB99.7", "title": "Hepatic failure without mention whether acute or chronic" }, { "code": "LB20.0Y", "title": "Other specified structural developmental anomalies of liver" }, { "code": "LB20.0Z", "title": "Structural developmental anomalies of liver, unspecified" }, { "code": "MG55.0", "title": "Artemisinin resistant Plasmodium falciparum" }, { "code": "5A74.Y", "title": "Other specified adrenocortical insufficiency" }, { "code": "5A44", "title": "Insulin-resistance syndromes" }, { "code": "LD2A.4", "title": "46,XY disorder of sex development due to androgen resistance" }, { "code": "LB45.1", "title": "46,XX gonadal dysgenesis" } ]	=== ICD-11 CODES FOUND === [DB9Z] Diseases of liver, unspecified Also known as: Diseases of liver, unspecified \| liver disease \| liver condition NOS \| organ liver disease \| hepatopathy [DB97.Z] Inflammatory liver disease, unspecified Also known as: Inflammatory liver disease, unspecified \| Certain specified inflammatory liver diseases \| Nonspecific reactive hepatitis \| inflammatory liver disease \| hepatitis NOS [DB99.7] Hepatic failure without mention whether acute or chronic Also known as: Hepatic failure without mention whether acute or chronic \| liver decompensation \| liver function failure \| hepatic failure NOS \| liver failure NOS [LB20.0Y] Other specified structural developmental anomalies of liver Also known as: Other specified structural developmental anomalies of liver \| Alagille syndrome \| Alagille-Watson syndrome \| Arteriohepatic dysplasia \| Syndromic bile duct paucity [LB20.0Z] Structural developmental anomalies of liver, unspecified Also known as: Structural developmental anomalies of liver, unspecified \| Structural developmental anomalies of liver \| Malformations of liver \| congenital anomaly of liver \| congenital malformation of liver [MG55.0] Artemisinin resistant Plasmodium falciparum Also known as: Artemisinin resistant Plasmodium falciparum \| Antimicrobial resistant Plasmodium falciparum \| multidrug-resistant falciparum malaria \| artesunate monotherapy resistance \| ACT - [artemisinin-based combination therapy] resistance [5A74.Y] Other specified adrenocortical insufficiency Also known as: Other specified adrenocortical insufficiency \| Congenital adrenocortical insufficiency \| Congenital isolated ACTH deficiency \| Familial adrenal hypoplasia \| Familial hypoadrenocorticism [5A44] Insulin-resistance syndromes Also known as: Insulin-resistance syndromes \| Insulin-resistance syndrome type A \| Insulin-resistance syndrome type B \| Rabson-Mendenhall syndrome \| Laminopathy type Decaudain-Vigouroux [LD2A.4] 46,XY disorder of sex development due to androgen resistance Definition: Androgen insensitivity syndrome (AIS) is a disorder of sex development (DSD) characterised by the presence of female external genitalia, ambiguous genitalia or variable defects in virilization in a 46,XY individual with absent or partial responsiveness to age-appropriate levels of androgens. It comprises two clinical subgroups: complete AIS (CAIS) and partial AIS (PAIS). Also known as: 46,XY disorder of sex development due to androgen resistance \| Androgen resistance syndrome \| Testicular feminization syndrome \| Androgen insensitivity syndrome \| Goldberg-Maxwell syndrome [LB45.1] 46,XX gonadal dysgenesis Definition: Karyotype 46 XX; Gonads: gonadal dysgenesis (streak gonads); Phenotype female with symptoms like primary amenorrhea, hypergonadotropic hypogonadism, normal stature and no other abnormalities. Also known as: 46,XX gonadal dysgenesis \| Follicular stimulating hormone-resistant ovaries \| Resistant ovary syndrome \| 46,XX pure gonadal dysgenesis \| 46,XX complete gonadal dysgenesis === GRAPH WALKS === --- Walk 1 --- [DB9Z] Diseases of liver, unspecified --PARENT--> [?] Diseases of liver --CHILD--> [DB92] Non-alcoholic fatty liver disease Def: NAFLD is characterised by fatty liver related to insulin resistance in the absence of significant alcohol consumption. It embraces a pathological spectrum from simple steatosis to steatohepatitis. 10-... --- Walk 2 --- [DB9Z] Diseases of liver, unspecified --PARENT--> [?] Diseases of liver --CHILD--> [DB91] Acute or subacute hepatic failure Def: Acute and subacute liver failure is characterised by onset of coagulopathy and/or hepatic encephalopathy within 8 weeks of onset of symptoms in a patient without previously known liver diseases.... --- Walk 3 --- [DB97.Z] Inflammatory liver disease, unspecified --PARENT--> [DB97] Certain specified inflammatory liver diseases --EXCLUDES--> [?] Drug-induced or toxic liver disease Def: Drug-induced or toxic liver disease is hepatotoxicity as injury to the liver that is associated with impaired liver function caused by exposure to a drug or another noninfectious agent.... --- Walk 4 --- [DB97.Z] Inflammatory liver disease, unspecified --PARENT--> [DB97] Certain specified inflammatory liver diseases --EXCLUDES--> [?] Acute or subacute hepatic failure Def: Acute and subacute liver failure is characterised by onset of coagulopathy and/or hepatic encephalopathy within 8 weeks of onset of symptoms in a patient without previously known liver diseases.... --- Walk 5 --- [DB99.7] Hepatic failure without mention whether acute or chronic --PARENT--> [DB99] Certain specified diseases of liver Def: This is a group of conditions characterised as being in or associated with the liver that are not classified elsewhere.... --RELATED_TO--> [?] Cirrhotic cardiomyopathy Def: Cirrhotic cardiomyopathy is defined as chronic cardiac dysfunction in patients with cirrhosis characterised by blunted contractile responsiveness to stress/exercise and-or altered diastolic relaxation... --- Walk 6 --- [DB99.7] Hepatic failure without mention whether acute or chronic --PARENT--> [DB99] Certain specified diseases of liver Def: This is a group of conditions characterised as being in or associated with the liver that are not classified elsewhere.... --EXCLUDES--> [?] Hepatic vein thrombosis Def: Venous thrombosis within the hepatic vein....	[ "[DB9Z] Diseases of liver, unspecified\n --PARENT--> [?] Diseases of liver\n --CHILD--> [DB92] Non-alcoholic fatty liver disease\n Def: NAFLD is characterised by fatty liver related to insulin resistance in the absence of significant alcohol consumption. It embraces a pathological spectrum from simple steatosis to steatohepatitis. 10-...", "[DB9Z] Diseases of liver, unspecified\n --PARENT--> [?] Diseases of liver\n --CHILD--> [DB91] Acute or subacute hepatic failure\n Def: Acute and subacute liver failure is characterised by onset of coagulopathy and/or hepatic encephalopathy within 8 weeks of onset of symptoms in a patient without previously known liver diseases....", "[DB97.Z] Inflammatory liver disease, unspecified\n --PARENT--> [DB97] Certain specified inflammatory liver diseases\n --EXCLUDES--> [?] Drug-induced or toxic liver disease\n Def: Drug-induced or toxic liver disease is hepatotoxicity as injury to the liver that is associated with impaired liver function caused by exposure to a drug or another noninfectious agent....", "[DB97.Z] Inflammatory liver disease, unspecified\n --PARENT--> [DB97] Certain specified inflammatory liver diseases\n --EXCLUDES--> [?] Acute or subacute hepatic failure\n Def: Acute and subacute liver failure is characterised by onset of coagulopathy and/or hepatic encephalopathy within 8 weeks of onset of symptoms in a patient without previously known liver diseases....", "[DB99.7] Hepatic failure without mention whether acute or chronic\n --PARENT--> [DB99] Certain specified diseases of liver\n Def: This is a group of conditions characterised as being in or associated with the liver that are not classified elsewhere....\n --RELATED_TO--> [?] Cirrhotic cardiomyopathy\n Def: Cirrhotic cardiomyopathy is defined as chronic cardiac dysfunction in patients with cirrhosis characterised by blunted contractile responsiveness to stress/exercise and-or altered diastolic relaxation...", "[DB99.7] Hepatic failure without mention whether acute or chronic\n --PARENT--> [DB99] Certain specified diseases of liver\n Def: This is a group of conditions characterised as being in or associated with the liver that are not classified elsewhere....\n --EXCLUDES--> [?] Hepatic vein thrombosis\n Def: Venous thrombosis within the hepatic vein...." ]	DB9Z	Diseases of liver, unspecified	[ { "from_icd11": "DB9Z", "icd10_code": "K7681", "icd10_title": "Hepatopulmonary syndrome" }, { "from_icd11": "DB9Z", "icd10_code": "K7689", "icd10_title": "Other specified diseases of liver" }, { "from_icd11": "DB9Z", "icd10_code": "K769", "icd10_title": "Liver disease, unspecified" }, { "from_icd11": "DB9Z", "icd10_code": "K77", "icd10_title": "Liver disorders in diseases classified elsewhere" }, { "from_icd11": "DB9Z", "icd10_code": "K762", "icd10_title": "Central hemorrhagic necrosis of liver" }, { "from_icd11": "DB9Z", "icd10_code": "K70-K77", "icd10_title": "" }, { "from_icd11": "DB9Z", "icd10_code": "K778", "icd10_title": "" }, { "from_icd11": "DB9Z", "icd10_code": "K72", "icd10_title": "Hepatic failure, not elsewhere classified" }, { "from_icd11": "DB9Z", "icd10_code": "K76", "icd10_title": "Other diseases of liver" }, { "from_icd11": "DB9Z", "icd10_code": "K768", "icd10_title": "Other specified diseases of liver" }, { "from_icd11": "DB97.Z", "icd10_code": "K7581", "icd10_title": "Nonalcoholic steatohepatitis (NASH)" }, { "from_icd11": "DB97.Z", "icd10_code": "K7589", "icd10_title": "Other specified inflammatory liver diseases" }, { "from_icd11": "DB97.Z", "icd10_code": "K759", "icd10_title": "Inflammatory liver disease, unspecified" }, { "from_icd11": "DB97.Z", "icd10_code": "K752", "icd10_title": "Nonspecific reactive hepatitis" }, { "from_icd11": "DB97.Z", "icd10_code": "K75", "icd10_title": "Other inflammatory liver diseases" } ]	K7681	Hepatopulmonary syndrome
Surgical steps are then performed as follows: 1. All relevant skin markings are drawn, including quadriceps tendon harvest site, distal half of the previous patellar tendon harvest scar, Gerdy’s tubercle (GT), a line extending 7 cm proximally from GT for performing lateral extra-articular tenodesis (LET) with iliotibial band (ITB), and locations for anterolateral and anteromedial arthroscopic portals . Fig 5 This is a left knee. All skin markings are drawn. (ALP, anterolateral portal; AMP, anteromedial portal; GT, Gerdy’s tubercle.) 2. Arthroscopic evaluation is performed with a 30° arthroscope (Olympus Inc) using standard anterolateral and anteromedial portals. In this case, a medial meniscus peripheral bucket handle fragment was displaced in the intercondylar notch with adhesions formed anteriorly and anteromedially . These were gently resected using a 4.0-mm full-radius resector shaver (Stryker) . The periphery was gently rasped and the meniscus fragment reduced , confirming intact meniscus root and mechanical quality of the tissue for considering a later repair . At this point, the meniscus fragment was left alone to be repaired at the completion of the ACL graft passage later in order to avoid deep knee flexion after a massive meniscus repair. For surgeons who prefer repairing the meniscus before continuing to ACLR, the repair is completed at this step. Fig 6 Arthroscopic view of a left knee using a 30° arthroscope (Olympus Inc) through the anterolateral portal. A chronically displaced medial meniscus bucket handle tear in the intercondylar notch with anterior adhesions is observed. (MFC, medial femoral condyle; MM, medial meniscus.) Fig 7 Arthroscopic view of a left knee using a 30° arthroscope (Olympus Inc) through the anterolateral portal. A chronically displaced medial meniscus bucket handle tear with anteromedial adhesions is observed. Fig 8 Arthroscopic view of a left knee using a 30° arthroscope (Olympus Inc) through the anterolateral portal. Anterior and anteromedial adhesions of a chronically displaced medial meniscus bucket handle fragment were gently resected using a 4.0-mm full-radius resector shaver (Stryker). Fig 9 Arthroscopic view of a left knee using a 30° arthroscope (Olympus Inc) through the anterolateral portal. The periphery behind the meniscus fragment was gently rasped using a 4.0-mm full-radius resector shaver (Stryker) and the meniscus fragment reduced. Fig 10 Arthroscopic view of a left knee using a 30° arthroscope (Olympus Inc) through the anterolateral portal, confirming intact meniscus root and mechanical quality of the tissue for considering a later repair. 3. A cyclops lesion in front of the failed BPTB graft is observed and the insufficient BPTB graft tissue is probed . Fig 11 Arthroscopic view of a left knee using a 30° arthroscope (Olympus Inc) through the anterolateral portal. A cyclops lesion in front of the failed bone–patellar tendon–bone graft is observed. Fig 12 Arthroscopic view of a left knee using a 30° arthroscope (Olympus Inc) through the anterolateral portal. The insufficient bone–patellar tendon–bone graft tissue is probed. 4. The insufficient BPTB graft tissue is debrided using a 5.0-mm full-radius resector shaver (Stryker), and a gentle notchplasty is performed . Fig 13 Arthroscopic view of a left knee using a 30° arthroscope (Olympus Inc) through the anterolateral portal. The insufficient bone–patellar tendon–bone graft tissue is debrided using a 5.0-mm full-radius resector shaver (Stryker) and a gentle notchplasty is performed. 5. A 7 × 20-mm titanium screw (Arthrex), used as the femoral fixation screw for the BPTB graft, is identified and removed using a screwdriver, preserving the screw socket . Fig 14 Arthroscopic view of a left knee using a 30° arthroscope (Olympus Inc) through the anterolateral portal. A 7 × 20-mm titanium screw (Arthrex), which was used as the femoral fixation screw for the bone–patellar tendon–bone graft, is identified and removed using a screwdriver, revealing the screw socket. 6. With the knee at 110° of flexion, a 7-mm over-the-top femoral offset guide (Arthrex) is inserted through an anteromedial portal, and a 2.4-mm guidewire (Arthrex) through this offset guide is inserted to an anatomic femoral ACL footprint location. Using a 9.5-mm diameter low-profile reamer (Arthrex) , an 18-mm-long femoral socket for the bone plug of the quadriceps graft is created, forming a “snowman configuration” socket, preserving the already existing femoral screw socket . Fig 15 Arthroscopic view of a left knee using a 30° arthroscope (Olympus Inc) through the anterolateral portal. With the knee at 110° of flexion, a 7-mm over-the-top femoral offset guide (Arthrex) is inserted through an anteromedial portal, and a 2.4-mm guidewire (Arthrex) through this offset guide is inserted to an anatomic femoral ACL footprint location. Using a 9.5-mm diameter low-profile reamer (Arthrex), an 18-mm-length femoral socket for the bone plug of the quadriceps graft is created. Fig 16 Arthroscopic view of a left knee using a 30° arthroscope (Olympus Inc) through the anterolateral portal. A “snowman configuration” socket in relation to the already existing femoral screw socket is created. 7. After removal of the existing 9 × 20-mm titanium interference screw (Arthrex) from the tibia, which was used for the primary BPTB ACLR, a 2.4-mm drill guide is inserted into the anatomic tibial ACL attachment area and is grasped with a clamp . Fig 17 Arthroscopic view of a left knee using a 30° arthroscope (Olympus Inc) through the anterolateral portal. A tibial tunnel is created after the removal of the existing 9 × 20-mm titanium interference screw (Arthrex) from the tibia. A 2.4-mm drill guide is inserted into the anatomic tibial ACL footprint and is grasped with a clamp. 8. A 10-mm headed reamer (Arthrex) is inserted over the 2.4-mm drill guide and a 10-mm tibial tunnel is created, followed by cleaning the patellar tendon autograft remnants from the tunnel edges by using a 5.0-mm full-radius resector shaver (Stryker). 9. A shuttle suture is passed through the tibial tunnel and femoral socket , and then the medial meniscus bucket handle fragment is reduced to the anatomic location and repaired with multiple inside-out sutures as described previously . 13 Fig 18 Arthroscopic view of a left knee using a 30° arthroscope (Olympus Inc) through the anterolateral portal. A shuttle suture is passed through the tibial tunnel and femoral socket. (LFC, lateral femoral condyle.) Fig 19 Arthroscopic view of a left knee using a 30° arthroscope (Olympus Inc) through the anterolateral portal. The medial meniscus bucket handle fragment is reduced to the anatomic location and repaired with multiple inside-out sutures as described previously. 10. Thigh tourniquet cuff (Zimmer) is now inflated to a pressure of 250 mm Hg. 11. Full-thickness ipsilateral quadriceps tendon harvesting begins, measuring 9 to 10 mm wide and 80 to 90 mm long. Harvest is initiated proximally and the tendinous part of the graft is whipstitched with a No. 5 Ethibond suture (Ethicon). A 15- to 18-mm-long proximal patella bone plug, in accordance with the preoperative CT planning, by 9 to 10 mm wide is measured and harvested, ensuring to leave an 8- to 10-mm-wide bone bridge between the persistent distal patellar bone deficiency site and the current proximal patellar bone plug harvest site . The tendinous part is lifted throughout bone plug harvest to identify and protect the deep attachment area of the quadriceps tendon to the patellar bone as a safety measure to avoid inadvertent violation of the deep tendon–bone insertion during bone plug harvest. The quadriceps harvest site is irrigated, and soft tissue layers are closed. Fig 20 Ipsilateral quadriceps tendon harvest, measuring from 9 to 10 mm wide and 80 to 90 mm long. Harvest is initiated proximally and the tendinous part of the graft is whipstitched and lifted. All reference lines are identified for proper bone plug harvest according to the preoperative computed tomography measurements, including deep and superficial insertions of the quadriceps tendon to the proximal patellar pole, proximal extension of the distal patellar bone defect, and the planned distal extension of the quadriceps–patella bone plug, leaving a bone bridge between the 2 bone plug harvest sites. 12. The quadriceps tendon–bone autograft preparation is finalized on a side table. The bone plug is gently tapered with a Rongeur (Aesculap Inc) to smoothly fit the 9.5-mm femoral socket, and the tendinous part should smoothly fit the 10-mm diameter tibial tunnel. Two No. 5 Ethibond sutures (Ethicon) are passed in two 1.5-mm drill holes made in the patellar bone plug . Fig 21 Finalized quadriceps tendon–bone autograft on a side table. The bone plug is colored in blue and measured 15 to 18 mm long. The tendon is whipstitched. 13. The quadriceps tendon–bone autograft is passed into the knee through the tibia tunnel and inserted into the femoral socket while aiming the bony margin of the bone plug toward the existing interference screw socket . This bone plug manipulation is important to avoid a later inadvertent placement of the metal interference screw against a tendinous part of the graft instead of against a bony margin, which could potentially harm the graft soft tissue. Fig 22 Arthroscopic view of a left knee using a 30° arthroscope (Olympus Inc) through the anterolateral portal. The quadriceps tendon–bone autograft is passed into the knee and inserted into the femoral socket while aiming the bony margin of the bone plug toward the planned interference screw socket. 14. The graft bone plug is fixed in the femoral socket with a 7 × 20-mm titanium interference screw (Arthrex), which is inserted into the already existing screw socket . Fig 23 Arthroscopic view of a left knee using a 30° arthroscope (Olympus Inc) through the anterolateral portal. The graft bone plug is fixed in the femoral socket with a 7 × 20-mm titanium interference screw (Arthrex). 15. Proper graft location is finally confirmed and the surgery continues on the extra-articular side. Fig 24 Arthroscopic view of a left knee using a 30° arthroscope (Olympus Inc) through the anterolateral portal. Final proper graft location is confirmed. 16. After cycling the knee with full tension applied to the graft, the tendinous part of the graft is fixed in the tibial tunnel with a 10 × 25-mm titanium interference screw (Arthrex) and backed up with a 8 × 20-mm titanium tendon staple (Arthrex) while the knee is held at full extension and maximum tension is applied to the graft. 17. A lateral extra-articular tenodesis is added using the ITB. The graft is fixed just posterior to the fibular collateral ligament (FCL) femoral insertion using a 3.5-mm double-loaded titanium suture anchor corkscrew (Arthrex) . Fig 25 This is a left knee. A lateral extra-articular tenodesis is added using the iliotibial band (ITB). The graft is fixed just posterior to the fibular collateral ligament (FCL) femoral insertion using a 3.5-mm double-loaded titanium suture anchor corkscrew (Arthrex).	3.980469	0.797363	sec[0]/p[2]	en	0.999996	PMC10150001	https://doi.org/10.1016/j.eats.2022.11.032	[ "bone", "using", "knee", "graft", "portal", "femoral", "anterolateral", "arthroscopic", "tendon", "arthroscope" ]	[ { "code": "FC0Z", "title": "Diseases of the musculoskeletal system or connective tissue, unspecified" }, { "code": "FB84.Z", "title": "Osteomyelitis or osteitis, unspecified" }, { "code": "FB80.Z", "title": "Disorder of bone density or structure, unspecified" }, { "code": "FB86.11", "title": "Hypertrophy of bone" }, { "code": "FB86.1Z", "title": "Bone hyperplasias, unspecified" }, { "code": "QE11.Z", "title": "Hazardous drug use, unspecified" }, { "code": "6C4Z", "title": "Disorders due to substance use, unspecified" }, { "code": "QE11.3", "title": "Hazardous use of cocaine" }, { "code": "QE11.2", "title": "Hazardous use of sedatives, hypnotics or anxiolytics" }, { "code": "QE11.1", "title": "Hazardous use of cannabis" } ]	=== ICD-11 CODES FOUND === [FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified Also known as: Diseases of the musculoskeletal system or connective tissue, unspecified \| bone disease NOS \| bone disorder NOS \| bone lesion NOS \| musculoskeletal complications NOS [FB84.Z] Osteomyelitis or osteitis, unspecified Also known as: Osteomyelitis or osteitis, unspecified \| Osteomyelitis or osteitis \| bone inflammation \| bone ulcer \| bone inflammatory disease [FB80.Z] Disorder of bone density or structure, unspecified Also known as: Disorder of bone density or structure, unspecified \| Certain specified disorders of bone density or structure [FB86.11] Hypertrophy of bone Also known as: Hypertrophy of bone \| bone thickening \| periosteum thickening \| Infantile cortical hyperostoses \| Post traumatic subperiosteal ossification [FB86.1Z] Bone hyperplasias, unspecified Also known as: Bone hyperplasias, unspecified \| Bone hyperplasias [QE11.Z] Hazardous drug use, unspecified Also known as: Hazardous drug use, unspecified \| Hazardous drug use \| chronic drug use NOS \| chronic IV substance use \| drug use nos [6C4Z] Disorders due to substance use, unspecified Also known as: Disorders due to substance use, unspecified \| Disorders due to substance abuse \| drug use disorder \| Bad trips due to drugs [QE11.3] Hazardous use of cocaine Definition: A pattern of cocaine use that appreciably increases the risk of harmful physical or mental health consequences to the user or to others to an extent that warrants attention and advice from health professionals. The increased risk may be from the frequency of cocaine use, from the amount used on a given occasion, from risky behaviours associated with cocaine use or the context of use, from a harmful route of administration, or from a combination of these. The risk may be related to short-term eff Also known as: Hazardous use of cocaine \| cocaine use \| intravenous cocaine use \| Hazardous use of crack cocaine \| crack cocaine use Excludes: Disorders due to use of cocaine [QE11.2] Hazardous use of sedatives, hypnotics or anxiolytics Definition: A pattern of use of sedatives, hypnotics or anxiolytics that appreciably increases the risk of harmful physical or mental health consequences to the user or to others to an extent that warrants attention and advice from health professionals. The increased risk may be from the frequency of use of sedatives, hypnotics or anxiolytics, from the amount used on a given occasion, from risky behaviours associated with use of sedatives, hypnotics or anxiolytics or the context of use, from a harmful route Also known as: Hazardous use of sedatives, hypnotics or anxiolytics \| Hazardous use of anxiolytics \| Hazardous use of hypnotics \| hypnotic use \| Hazardous use of sedatives Excludes: Disorders due to use of sedatives, hypnotics or anxiolytics [QE11.1] Hazardous use of cannabis Definition: A pattern of cannabis use that appreciably increases the risk of harmful physical or mental health consequences to the user or to others to an extent that warrants attention and advice from health professionals. The increased risk may be from the frequency of cannabis use, from the amount used on a given occasion, from risky behaviours associated with cannabis use or the context of use, from a harmful route of administration, or from a combination of these. The risk may be related to short-term Also known as: Hazardous use of cannabis \| marijuana use \| cannabis use Excludes: Disorders due to use of cannabis === GRAPH WALKS === --- Walk 1 --- [FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified --PARENT--> [15] Diseases of the musculoskeletal system or connective tissue Def: This chapter contains diseases of musculoskeletal system and diseases of connective tissue.... --CHILD--> [?] Conditions associated with the spine Def: This is a group of conditions in which there is a deviation from or interruption of the normal structure or function of the spine.... --- Walk 2 --- [FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified --PARENT--> [15] Diseases of the musculoskeletal system or connective tissue Def: This chapter contains diseases of musculoskeletal system and diseases of connective tissue.... --RELATED_TO--> [?] Nonorgan specific systemic autoimmune disorders --- Walk 3 --- [FB84.Z] Osteomyelitis or osteitis, unspecified --PARENT--> [FB84] Osteomyelitis or osteitis --EXCLUDES--> [?] Inflammatory conditions of jaws --- Walk 4 --- [FB84.Z] Osteomyelitis or osteitis, unspecified --PARENT--> [FB84] Osteomyelitis or osteitis --CHILD--> [FB84.0] Acute haematogenous osteomyelitis --- Walk 5 --- [FB80.Z] Disorder of bone density or structure, unspecified --PARENT--> [FB80] Certain specified disorders of bone density or structure --EXCLUDES--> [?] Osteopetrosis Def: Osteopetrosis ('marble bone disease') is a descriptive term that refers to a group of rare, heritable disorders of the skeleton characterised by increased bone density on radiographs. Osteopetrotic co... --- Walk 6 --- [FB80.Z] Disorder of bone density or structure, unspecified --PARENT--> [FB80] Certain specified disorders of bone density or structure --RELATED_TO--> [?] Osteogenesis imperfecta Def: Osteogenesis imperfecta (OI) comprises a heterogeneous group of genetic disorders characterised by increased bone fragility, low bone mass, and susceptibility to bone fractures with variable severity....	[ "[FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified\n --PARENT--> [15] Diseases of the musculoskeletal system or connective tissue\n Def: This chapter contains diseases of musculoskeletal system and diseases of connective tissue....\n --CHILD--> [?] Conditions associated with the spine\n Def: This is a group of conditions in which there is a deviation from or interruption of the normal structure or function of the spine....", "[FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified\n --PARENT--> [15] Diseases of the musculoskeletal system or connective tissue\n Def: This chapter contains diseases of musculoskeletal system and diseases of connective tissue....\n --RELATED_TO--> [?] Nonorgan specific systemic autoimmune disorders", "[FB84.Z] Osteomyelitis or osteitis, unspecified\n --PARENT--> [FB84] Osteomyelitis or osteitis\n --EXCLUDES--> [?] Inflammatory conditions of jaws", "[FB84.Z] Osteomyelitis or osteitis, unspecified\n --PARENT--> [FB84] Osteomyelitis or osteitis\n --CHILD--> [FB84.0] Acute haematogenous osteomyelitis", "[FB80.Z] Disorder of bone density or structure, unspecified\n --PARENT--> [FB80] Certain specified disorders of bone density or structure\n --EXCLUDES--> [?] Osteopetrosis\n Def: Osteopetrosis ('marble bone disease') is a descriptive term that refers to a group of rare, heritable disorders of the skeleton characterised by increased bone density on radiographs. Osteopetrotic co...", "[FB80.Z] Disorder of bone density or structure, unspecified\n --PARENT--> [FB80] Certain specified disorders of bone density or structure\n --RELATED_TO--> [?] Osteogenesis imperfecta\n Def: Osteogenesis imperfecta (OI) comprises a heterogeneous group of genetic disorders characterised by increased bone fragility, low bone mass, and susceptibility to bone fractures with variable severity...." ]	FC0Z	Diseases of the musculoskeletal system or connective tissue, unspecified	[ { "from_icd11": "FC0Z", "icd10_code": "XIII", "icd10_title": "" }, { "from_icd11": "FB84.Z", "icd10_code": "M86672", "icd10_title": "Other chronic osteomyelitis, left ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M86172", "icd10_title": "Other acute osteomyelitis, left ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M86171", "icd10_title": "Other acute osteomyelitis, right ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M86671", "icd10_title": "Other chronic osteomyelitis, right ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M868X7", "icd10_title": "Other osteomyelitis, ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M868X8", "icd10_title": "Other osteomyelitis, other site" }, { "from_icd11": "FB84.Z", "icd10_code": "M868X6", "icd10_title": "Other osteomyelitis, lower leg" }, { "from_icd11": "FB84.Z", "icd10_code": "M868X9", "icd10_title": "Other osteomyelitis, unspecified sites" }, { "from_icd11": "FB84.Z", "icd10_code": "M8668", "icd10_title": "Other chronic osteomyelitis, other site" }, { "from_icd11": "FB84.Z", "icd10_code": "M86662", "icd10_title": "Other chronic osteomyelitis, left tibia and fibula" }, { "from_icd11": "FB84.Z", "icd10_code": "M86151", "icd10_title": "Other acute osteomyelitis, right femur" }, { "from_icd11": "FB84.Z", "icd10_code": "M86141", "icd10_title": "Other acute osteomyelitis, right hand" }, { "from_icd11": "FB84.Z", "icd10_code": "M86641", "icd10_title": "Other chronic osteomyelitis, right hand" }, { "from_icd11": "FB84.Z", "icd10_code": "M8669", "icd10_title": "Other chronic osteomyelitis, multiple sites" } ]	XIII
OFCD syndrome has been misdiagnosed as maternal exposure to rubella during pregnancy . However, in some cases, abnormal symptoms in the teeth, particularly radiculomegaly, and the absence of maternal rubella infection during pregnancy, help to differentiate the diagnosis . In addition to the four main symptoms (including ocular, facial, cardiac, and dental), OFCDs patients often have the abnormality in the ears (hearing impairment, protruding ears, hypoplastic ears) , extremities (toe syndactyly, hammer toes, radioulnar synostosis) and mental retardation . Numerous cases with several BCOR variants have been reported in the medical literature [ 8 , 9 , 13 , 14 , 17 – 27 ] (see Table 1 ). In our report, the patient's chief complaint was the appearance of a fistula developing from her left mandibular canine. She was then indicated to take a panoramic radiograph, and we found that all her canine teeth had extreme elongation with their apex opening. Clinical examination and medical history demonstrated that this patient had abnormalities in her eyes (congenital cataract, cross-eyed), her face (long and narrow faces, bifid nasal tip) , and her heart (ostium secundum atrial septal defect, pulmonary artery hypertension, and 4/4 leaky tricuspid valves). We speculated that this patient might have an OFCD syndrome. Therefore, we decided to take a screening for BCOR variants. The result showed that a heterozygous deletion variant IVS 11-2delA was detected in intron 11 of gene BCOR , a novel variant. With these above symptoms, this patient was planned to receive thorough treatment, including extracting all her root teeth, filling all decayed teeth, undergoing a root canal treatment for the left mandibular canine, and having an extraoral apicoectomy with a fistula removal on her left chin. OFCD is a rare syndrome affecting many organs. Early identification of this disease helps prevent oral complications and endocarditis progression due to caries teeth. As a result, we could combine a wide range of specialties to provide patients with comprehensive care. Table 1 Literature review of case report with BCOR variant Current study Ragge/2018/USA Kato/2018/Japan Morgan/2019/USA Zhang/2019/China Song/ 2019/Korea Tsuwaki/2005/Japan Di-Stefano/2015/Italy General information Current case Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Case 7 Case 8 Case 9 Age (year) 19 13 21 3 10 10 4 31 16 2 Gender Female Female Male Female Female Female Female Female Female Female BCOR variant IVS11-2delA c.2428C > T p.(Arg810) c.254C > T p.(Pro85Leu) c.1209_1210delCC p.(Gln404Alafs35) Exon 4 c.265G > A c.2514del(G) c.1296delT n/a n/a a de novo heterozygous del Xp11.4 Inheritance De novo De novo Maternal De novo Denovo De novo De novo Ocular Microphthalmia Left side Bilateral Bilateral (severe) Bilateral Left eye microphthalmia Bilateral Right eye Anophthalmia No Congenital cataract Bilateral Bilateral Bilateral Bilateral + + + Bilateral Glaucoma n/a Unilateral In the right eye + Strabismus + + Posterior embryotoxon n/a Other Strabismus, left side Artificial eye on the left side Hemangioma near her right eyebrow Bilateral ptosis, eyebrows curvature; mixed nystagmus; right eye exohypertropia in primary position Secondary cataract Craniofacial Long, broad face, concave facial profile in a lateral view, broad and protrusive mandible, prominent chin no Midface hypoplasia + + Nasal anomalies Broad nasal tip with separation of anterior nasal cartilage, bifid nasal tip + Broadening of the nasal tip Broad nasal tip Nasal tip was prominent and bulbous Broad nasal tip separated nasal cartilage Broad nasal tip, depressed nasal bridge Ear anomalies n/a + + Preauricular tag Protruding ears No Hearing on the right side is impaired slightly Depressed nasal bridge Cleft palate Bifid uvula – + no no High arched palate + + + Other Thick eyebrows, narrow palate, and mandible, small mouth Downslanting palpebral fissures, long face, tall forehead, thick eyebrows, Long Philtrum Elongated, biprotrusive, with a thick lower lip Flat and slightly long, dovetail-shaped uvula Broad forehead, bifid uvula Cardiac ASD Ostium secundum atrial septal defect + no + + VSD n/a no + Other Pulmonary artery hypertension, 4/4 leaky tricuspid valves Triple heart sounds Patent ductus arteriosus (PDA), persistent left superior vena cava Dental Late eruption of first teeth n/a + + n/a Impacted teeth Tooth 24 Tooth 23 was retracted and extruded Delayed loss of primary dentition n/a + + Radiculomegaly Canines, premolars, and lower anterior teeth Tautodontism Tooth 37 Teeth 13, 22, 23, 33, 34, 43, 44 Fused incisors No XQ Other Crowding with malposition of teeth 34,44, many dental caries (11,12,16,21,26,32,33,36,43,46,47) and periapical infection of tooth 33 with skin leaking Double row of teeth Recurrent dental infections Abnormal crown canines + incisors Malocclusion, anterior dental crowding, canines, central incisors, and first premolars had Open apex Long roots of her teeth with one missing tooth and first primary tooth loss at 6–7 years of age Crossbite Enamel hypoplasia, crown malformation Lateral crossbite, Oligodontia, enamel hypoplasia, Glossitis, stomatitis, heavy dental plaque, and calculus Skeletal Hands Long and slender finder Long Finger 5th Finger clinodactyly, long Finger Long Finger n/a Short No Clinodactyly of the fifth finger Feet IV-toes camptodactyly, I-hammer toes, long toes Long toes II-hammer toes n/a Hammer-type big toes; flexion deformity (2–4 toes of right foot and 2–3 toes of left foot) No I-long and wide toe, hammer-type flexion of toes 2 through 4 Syndactyly 2–3, hammer toe of the second Other n/a Scoliosis Asymmetry of hand size Forearm on the right side was slightly shorter Developmental ID No intellect defect n/a Motor delay Mental retardation + n/a n/a No No Speech delay n/a + n/a n/a No MRI findings n/a n/a n/a n/a No Lipomatous lesion n/a N n/a n/a n/a Other Moderate BA, broad lateral ventricles Other findings GU anomalies n/a Urethral hypoplasia, renal dysplasia, renal, failure, VUR Cryptorchidism, vesicoureteric reflux, primary enuresis n/a n/a n/a Other Hypotonia Primary enuresis Stage III T-cell lymphoma Bilateral papilloma of choroid plexus (PCP), supratentorial hydrocephalus Current study Mc Govern/2006/Ireland Atiq/2012/USA Danda/2014/India Martinho/2019/Portugal Türkkahraman/2006/Turkey Verm/2014/India Zhou/2018/USA Zhu/2015/China General information Current case Case 10 Case 11 Case 12 Case 13 Case 14 Case 15 Case 16 Case 17 Case 18 Age (year) 19 8 days 39 8 6 26 15 24 5 weeks 7 months Gender Female Female Female Female Female Female Female Female Female Male BCOR variant IVS11-2delA n/a c.3490C > T (p.R1164* p.R1163X p. R540Q Inheritance De novo Maternal Heterozygous Missense mutation Microphthalmia Left side + + + Anophthalmia No Congenital cataract Bilateral + + + + + + Glaucoma n/a + No + Strabismus + Posterior embryotoxon n/a Other Strabismus, left side Deep-set eyes, short palpebral fissures Craniofacial Long, broad face, concave facial profile in a lateral view, broad and protrusive mandible, prominent chin Midface hypoplasia + + Nasal anomalies Broad nasal tip with separation of anterior nasal cartilage, bifid nasal tip Broad nasal tip flat nasal bridge Ear anomalies n/a Left hearing impairment slightly low-set ears Cleft palate Bifid uvula + High arched palate + + + Other Thick eyebrows, narrow palate, and mandible, small mouth Extended long canine teeth, and nasal changes High forehead High nasal bridge Class II malocclusion on a Class III skeletal base with a prognathic mandible, increased facial proportions, and facial asymmetry long, narrow face Long and narrow face, high nasal bridge, broad nasal tip with separated cartilages, and a long philtrum eyebrows were laterally curved and thick Class II malocclusion with an extremely deep overbite Deeply set eyes and a broad nasal tip long and narrow face Class III malocclusion with a negative overjet and deep overbite Cardiac ASD Ostium secundum atrial septal defect + - + + VSD n/a + - + + + Other Pulmonary artery hypertension, 4/4 leaky tricuspid valves Pulmonary valve stenosis Mitral valve prolapse Double outlet right ventricle, pulmonary stenosis Prolapsed mitral valve Patent ductus arteriosus (PDA) Dental Late eruption of first teeth n/a + + + + Impacted teeth Tooth 24 Gummy smile, and crowded teeth Extremely long roots and open apices Delayed loss of primary dentition n/a + + Radiculomegaly Canines, premolars, and lower anterior teeth + Tautodontism Tooth 37 Fused incisors No XQ Teethskeletal class I with severe vertical growth pattern, increased gonial angle, steep mandibular plane with retroclined incisors, and competent lips Permanent teeth with extremely long roots and open apices. The roots of maxillary canines were in relation with the inferior border of the orbits and the lower canine roots almost reached the lower border of the mandible The maxillary left central incisor had dilacerated root; all four third molars were congenitally missing Other Crowding with malposition of teeth 34,44, many dental caries (11,12,16,21,26,32,33,36,43,46,47) and periapical infection of tooth 33 with skin leaking Bifid uvula Numerous missing teeth The first upper left molar, upper right canine, upper left lateral incisor, first upper left premolar, first upper right molar, first lower right molar, and first lower left molar are absent Glossitis, stomatitis, heavy dental plaque, and calculus Skeletal Hands Long and slender fingers Camptodactyly of the 4th and 5th fingers (right > left), proximally placed thumbs, restricted supination, and pronation of the left forearm, camptodactyly and syndactyly of 2nd and 3rd toes, and sandal gap Elbow radiographs at infancy showed left radioulnar synostosis Misalignment Fingers are normal Feet IV-toes camptodactyly, I-hammer toes, long toes Sandal gaps, syndactyly and camptodactyly of toes Sandal gap between the 1st and 2nd toes Valgus foot Syndactly of 2nd and 3rd toes Right clubfoot, and bilateral 2–3 toe syndactyly Other n/a Misalignment of right second toe Short stature was observed (122 cm; < 3 SD) Short stature (111 cm, < 3 SD) Developmental No ID No intellect defect + + Motor delay Mental retardation + Speech delay n/a + MRI findings n/a Lipomatous lesion n/a Other Other findings GU anomalies n/a No Other Anterior positioning of the anus Several episodes of hypoglycemia several episodes of mental confusion associated with a blood glucose level of less than 40 mg/dL reactive lymph node rare congenital disorder Tall stature Umbilical hernia at birth CHD structural brain anomalies Axenfeld–Rieger syndrome, Lenz microphthalmia syndrome, and oculo-facio-cardio-dental (OFCD) syndrome BA brain atrophy, ASD atrial septal defect, VSD ventricular septal defect, ID Intellectual delay, Cm centimeter, SD standard deviation, MRI magnetic resonance imaging, VUR vesicoureteric reflux, CHD congenital heart defects, BCOR variant The BCOR gene is responsible for coding the BCL6 corepressor protein, N/a not applicable or not available, PDA patent ductus arteriosus, N normal	4.148438	0.726563	sec[2]/p[1]	en	0.999998	PMC10765806	https://doi.org/10.1186/s13256-023-04244-x	[ "nasal", "long", "teeth", "toes", "broad", "dental", "tooth", "bcor", "hammer", "face" ]	[ { "code": "MA82.2", "title": "Nasality" }, { "code": "CA0Z", "title": "Upper respiratory tract disorders, unspecified" }, { "code": "CA0Y", "title": "Other specified upper respiratory tract disorders" }, { "code": "LA70.2", "title": "Choanal atresia" }, { "code": "NA00.3&XJ1C6", "title": "Haematoma of nose" }, { "code": "JB03.Z", "title": "Long labour, unspecified" }, { "code": "BC65.0", "title": "Long QT syndrome" }, { "code": "FB85.Y&XA4TM1", "title": "Paget disease of long bones" }, { "code": "JB03.0", "title": "Prolonged first stage of labour" }, { "code": "8C12.4", "title": "Lesion of long thoracic nerve" } ]	=== ICD-11 CODES FOUND === [MA82.2] Nasality Definition: Nasality (or resonance) refers to the quality of the voice that is determined by the balance of sound vibration in the oral, nasal, and pharyngeal cavities during speech. Abnormal resonance can occur when there is obstruction in one of the cavities, causing hyponasality, or when there is velopharyngeal dysfunction, causing hypernasality. This category should only be assigned when hyponasality or hypernasality is outside the limits of normal variation and results in reduced intelligibility and si Also known as: Nasality \| Hypernasality \| Hyponasality [CA0Z] Upper respiratory tract disorders, unspecified Also known as: Upper respiratory tract disorders, unspecified \| Disorder of the nose, unspecified \| Disease of nose, unspecified \| nasal disease \| Lesion of nose, unspecified [CA0Y] Other specified upper respiratory tract disorders Also known as: Other specified upper respiratory tract disorders \| Acute adenoiditis \| adenoid infection \| Pharyngotonsillitis \| tonsillopharyngitis [LA70.2] Choanal atresia Definition: Any condition in neonates, caused by failure of the nose to correctly develop during the antenatal period. This condition is characterised by narrowing or blockage of the nasal airway by tissue. This condition may also present with chest retraction unless child is breathing through mouth or crying, difficulty breathing, cyanosis, and inability to nurse and breathe at same time. Also known as: Choanal atresia \| choanal fusion \| atresia of nares \| congenital stenosis of nares \| congenital stenosis of choanae [JB03.Z] Long labour, unspecified Also known as: Long labour, unspecified \| Long labour \| Prolonged labour NOS [BC65.0] Long QT syndrome Definition: A congenital disorder of ventricular myocardial repolarization characterised by a prolonged QT interval on the electrocardiogram (ECG) that can lead to symptomatic ventricular arrhythmias and an increased risk of sudden cardiac death. Also known as: Long QT syndrome \| Congenital long QT syndrome \| Familial long QT syndrome \| Long QT syndrome type 1 \| Long QT syndrome type 2 [JB03.0] Prolonged first stage of labour Definition: The first stage of labour where cervical dilatation progresses less than 1 centimetre per hour for a minimum of 4 hours. Protracted descent is less than 1 centimetre per hour for nulliparas and less than 2 centimetre per hour for multiparas. Also known as: Prolonged first stage of labour \| long labour, first stage \| prolonged first stage of delivery \| long delivery, first stage \| prolonged or protracted first stage of labour [8C12.4] Lesion of long thoracic nerve Also known as: Lesion of long thoracic nerve === GRAPH WALKS === --- Walk 1 --- [MA82.2] Nasality Def: Nasality (or resonance) refers to the quality of the voice that is determined by the balance of sound vibration in the oral, nasal, and pharyngeal cavities during speech. Abnormal resonance can occur ... --PARENT--> [MA82] Voice disturbances Def: Voice disturbances include dysphonia, aphonia, hypernasality and hyponasality, and other voice disturbances.... --PARENT--> [?] Symptoms or signs involving speech, language or voice --- Walk 2 --- [MA82.2] Nasality Def: Nasality (or resonance) refers to the quality of the voice that is determined by the balance of sound vibration in the oral, nasal, and pharyngeal cavities during speech. Abnormal resonance can occur ... --PARENT--> [MA82] Voice disturbances Def: Voice disturbances include dysphonia, aphonia, hypernasality and hyponasality, and other voice disturbances.... --CHILD--> [MA82.2] Nasality Def: Nasality (or resonance) refers to the quality of the voice that is determined by the balance of sound vibration in the oral, nasal, and pharyngeal cavities during speech. Abnormal resonance can occur ... --- Walk 3 --- [CA0Z] Upper respiratory tract disorders, unspecified --PARENT--> [?] Upper respiratory tract disorders Def: This group of disorders refers to diseases of the upper airways (upper respiratory tract). The upper airways anatomically are complicated structures which extend from the airway openings at the nares ... --CHILD--> [CA02] Acute pharyngitis Def: Acute pharyngitis is defined as an infection or irritation of the pharynx and/or tonsils and is a part of the common cold symptoms. The etiology is usually infectious, with most cases being of viral o... --- Walk 4 --- [CA0Z] Upper respiratory tract disorders, unspecified --PARENT--> [?] Upper respiratory tract disorders Def: This group of disorders refers to diseases of the upper airways (upper respiratory tract). The upper airways anatomically are complicated structures which extend from the airway openings at the nares ... --EXCLUDES--> [?] Chronic obstructive pulmonary disease with acute exacerbation, unspecified Def: An acute unspecified exacerbation of COPD is an acute event characterised by a worsening of the patient’s respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medi... --- Walk 5 --- [CA0Y] Other specified upper respiratory tract disorders --PARENT--> [?] Upper respiratory tract disorders Def: This group of disorders refers to diseases of the upper airways (upper respiratory tract). The upper airways anatomically are complicated structures which extend from the airway openings at the nares ... --CHILD--> [CA00] Acute nasopharyngitis Def: A disease of the upper respiratory tract, caused by an infection with rhinovirus. This disease is characterised by pharyngitis, runny nose, stuffy nose, or cough. Transmission is by inhalation of infe... --- Walk 6 --- [CA0Y] Other specified upper respiratory tract disorders --PARENT--> [?] Upper respiratory tract disorders Def: This group of disorders refers to diseases of the upper airways (upper respiratory tract). The upper airways anatomically are complicated structures which extend from the airway openings at the nares ... --EXCLUDES--> [?] Chronic obstructive pulmonary disease with acute exacerbation, unspecified Def: An acute unspecified exacerbation of COPD is an acute event characterised by a worsening of the patient’s respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medi...	[ "[MA82.2] Nasality\n Def: Nasality (or resonance) refers to the quality of the voice that is determined by the balance of sound vibration in the oral, nasal, and pharyngeal cavities during speech. Abnormal resonance can occur ...\n --PARENT--> [MA82] Voice disturbances\n Def: Voice disturbances include dysphonia, aphonia, hypernasality and hyponasality, and other voice disturbances....\n --PARENT--> [?] Symptoms or signs involving speech, language or voice", "[MA82.2] Nasality\n Def: Nasality (or resonance) refers to the quality of the voice that is determined by the balance of sound vibration in the oral, nasal, and pharyngeal cavities during speech. Abnormal resonance can occur ...\n --PARENT--> [MA82] Voice disturbances\n Def: Voice disturbances include dysphonia, aphonia, hypernasality and hyponasality, and other voice disturbances....\n --CHILD--> [MA82.2] Nasality\n Def: Nasality (or resonance) refers to the quality of the voice that is determined by the balance of sound vibration in the oral, nasal, and pharyngeal cavities during speech. Abnormal resonance can occur ...", "[CA0Z] Upper respiratory tract disorders, unspecified\n --PARENT--> [?] Upper respiratory tract disorders\n Def: This group of disorders refers to diseases of the upper airways (upper respiratory tract). The upper airways anatomically are complicated structures which extend from the airway openings at the nares ...\n --CHILD--> [CA02] Acute pharyngitis\n Def: Acute pharyngitis is defined as an infection or irritation of the pharynx and/or tonsils and is a part of the common cold symptoms. The etiology is usually infectious, with most cases being of viral o...", "[CA0Z] Upper respiratory tract disorders, unspecified\n --PARENT--> [?] Upper respiratory tract disorders\n Def: This group of disorders refers to diseases of the upper airways (upper respiratory tract). The upper airways anatomically are complicated structures which extend from the airway openings at the nares ...\n --EXCLUDES--> [?] Chronic obstructive pulmonary disease with acute exacerbation, unspecified\n Def: An acute unspecified exacerbation of COPD is an acute event characterised by a worsening of the patient’s respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medi...", "[CA0Y] Other specified upper respiratory tract disorders\n --PARENT--> [?] Upper respiratory tract disorders\n Def: This group of disorders refers to diseases of the upper airways (upper respiratory tract). The upper airways anatomically are complicated structures which extend from the airway openings at the nares ...\n --CHILD--> [CA00] Acute nasopharyngitis\n Def: A disease of the upper respiratory tract, caused by an infection with rhinovirus. This disease is characterised by pharyngitis, runny nose, stuffy nose, or cough. Transmission is by inhalation of infe...", "[CA0Y] Other specified upper respiratory tract disorders\n --PARENT--> [?] Upper respiratory tract disorders\n Def: This group of disorders refers to diseases of the upper airways (upper respiratory tract). The upper airways anatomically are complicated structures which extend from the airway openings at the nares ...\n --EXCLUDES--> [?] Chronic obstructive pulmonary disease with acute exacerbation, unspecified\n Def: An acute unspecified exacerbation of COPD is an acute event characterised by a worsening of the patient’s respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medi..." ]	MA82.2	Nasality	[ { "from_icd11": "MA82.2", "icd10_code": "R4921", "icd10_title": "Hypernasality" }, { "from_icd11": "MA82.2", "icd10_code": "R4922", "icd10_title": "Hyponasality" }, { "from_icd11": "MA82.2", "icd10_code": "R492", "icd10_title": "Hypernasality and hyponasality" }, { "from_icd11": "CA0Z", "icd10_code": "J349", "icd10_title": "Unspecified disorder of nose and nasal sinuses" }, { "from_icd11": "CA0Z", "icd10_code": "J3489", "icd10_title": "Other specified disorders of nose and nasal sinuses" }, { "from_icd11": "CA0Z", "icd10_code": "J3481", "icd10_title": "Nasal mucositis (ulcerative)" }, { "from_icd11": "CA0Z", "icd10_code": "J398", "icd10_title": "Other specified diseases of upper respiratory tract" }, { "from_icd11": "CA0Z", "icd10_code": "J392", "icd10_title": "Other diseases of pharynx" }, { "from_icd11": "CA0Z", "icd10_code": "J399", "icd10_title": "Disease of upper respiratory tract, unspecified" }, { "from_icd11": "CA0Z", "icd10_code": "J00-J06", "icd10_title": "" }, { "from_icd11": "CA0Z", "icd10_code": "J30-J39", "icd10_title": "" }, { "from_icd11": "CA0Z", "icd10_code": "J34", "icd10_title": "Other and unspecified disorders of nose and nasal sinuses" }, { "from_icd11": "CA0Z", "icd10_code": "J348", "icd10_title": "Other specified disorders of nose and nasal sinuses" }, { "from_icd11": "CA0Z", "icd10_code": "J39", "icd10_title": "Other diseases of upper respiratory tract" }, { "from_icd11": "LA70.2", "icd10_code": "Q300", "icd10_title": "Choanal atresia" } ]	R4921	Hypernasality
Case 1 We present the case of a 67-year-old non-smoker patient at the time of diagnosis. Personal history includes dyslipidemia, elevated baseline glycemia, and prostate adenocarcinoma treated with radical prostatectomy in March 2006, with no evidence of recurrence. Our patient was enrolled in an early lung cancer diagnosis program due to first and second-degree family history. In 2010, bilateral pulmonary nodules of few millimeters were detected in a CT scan. Follow-up continued until 2018. At that point, after observing the growth of one of the nodules (15 × 13 mm), an extended atypical resection was performed using video-assisted thoracoscopy, with a diagnosis of atypical adenomatous hyperplasia. The March 2021 CT scan revealed significant growth of a peribronchovascular pulmonary nodule measuring 16 × 12 mm in the right lower lobe (doubling time of 248 days) with a solid central component and a ground glass peripheral component. PET-CT confirmed the presence of a high-uptake nodule in the right lower lobe (SUVmax of 4.9), suggesting malignant disease without evidence of distant metastasis. The patient was referred to the thoracic surgery clinic for evaluation, and surgical resection was decided in the multidisciplinary board. In April 2021, the patient underwent surgery involving right lower lobectomy, hilar lymphadenectomy, and robotic mediastinal lymphadenectomy. Pathological diagnosis indicated moderately differentiated lung adenocarcinoma with a solid pattern in 80% and micropapillary in 20% of the tumor, isolated lepidic foci without lymphatic or vascular invasion, and surgical margins free of tumor. Eleven lymph nodes were isolated, all unaffected (pT1bN0). Immunohistochemical study revealed a deletion in exon 19 of EGFR with a PDL-1 expression of 5%. Following clinical guidelines, the patient did not receive adjuvant treatment. Currently, the patient undergoes regular monitoring with CT imaging tests, and a liquid biopsy (Oncomine Pan-Cancer Cell-Free Assay) is performed every three months to determine circulating ctDNA. There has been no evidence of recurrence, with liquid biopsies conducted until October 2023 showing negative results. Additionally, imaging scans do not reveal any suspicious lesions to date. Case 2 Below, we present the case of a 77-year-old man with not known drug allergies, medical history of arterial hypertension and dyslipidemia under treatment, subclinical hypothyroidism not requiring replacement therapy, spondyloarthrosis, cholelithiasis, and hepatic steatosis. He was previously diagnosed with a depressive disorder treated with lithium until 2013 and was an ex-smoker for 58 years. There was not known family history of cancer. In late 2020, he sought medical attention due to the presence of a non-painful parotid nodule. On examination, it was identified as a mobile subcutaneous formation located in the anterior cervical region. He was seen by our otorhinolaryngology service in December 2020, where a fine needle biopsy of the parotid lesion was performed, yielding a pathological result of Warthin's tumor. To complete the study, a cervical thoracoabdominal CT scan was requested, revealing a suspicious-looking nodule in the upper segment of the right lower lobe with spiculated edges, measuring 13 × 12 mm, along with a subcentimeter satellite nodule of 7 × 6 mm, and small subpleural nodules in the middle lobe of the right lower lobe, with a maximum size of 8 × 7 mm, without significant lymph nodes. On December 21, 2020, a right parotid nodulectomy was performed with excision of the cervical lipoma, resulting in a definitive diagnosis of Warthin's tumor and subcutaneous lipoma. He was referred to the Pulmonology department, where a positron emission tomography-computed tomography (PET-CT) scan was conducted. The PET-CT showed focal uptake in the right lower lobe consistent with a pulmonary nodule, with lymph node uptake in the right pulmonary hilum, as well as in the right paratracheal, precaval, subcarinal prevascular, aortopulmonary, and right supraclavicular window (stage IIIB). Cerebral magnetic resonance imaging on December 2020 revealed no findings suggestive of malignancy. On January 4, 2021, an ultrasound bronchoscopy was performed, identifying lymph nodes in the right paratracheal region. Biopsies were carried out, resulting in a diagnosis of poorly differentiated lung adenocarcinoma with a high expression of PDL-1 (60%) and L858R mutation in exon 21 of the EGFR gene (Oncomine Pan-Cancer Cell-Free Assay). Due to the unresectable nature of the disease, chemo-radiotherapy treatment with radical intent was recommended. Considering the mutation's sensitivity response to the disease, initial completion of radical treatment with maintenance immunotherapy in case of radiological stability or improvement was not supported due to its low efficacy. The patient accepted the therapeutic recommendation, receiving first intravenous cycle of induction chemotherapy on January 18, 2021. From March 4 to April 20, 2021, concurrent chemoradiotherapy treatment was administered with a total dose of 67.32 Gy using carboplatin and weekly paclitaxel for 4 weeks. The treatment tolerance was good, with no significant toxicity. On May 27, 2021, the patient attended the first follow-up, and a liquid biopsy was performed, showing no presence of the L858R mutation (Oncomine Pan-Cancer Cell-Free Assay). Regular check-ups were recommended. On August 31, 2021, a liquid biopsy determination was performed again, revealing the presence of the mutation susceptible to follow-up in the liquid biopsy p.(L858R) in the EGFR gene . Based on these findings, a thoracic-abdominal CT was requested, detecting the appearance of a new nodule of 6.8 mm in the lower right lobe . A study with cerebral magnetic resonance ruled out metastatic involvement. It was recommended to conduct a PET-CT 4 weeks later. Fig. 2 Case 2. Thorax and abdominal CT scan . Signs of radiation pneumonitis primarily affecting the upper segment of the right inferior lobe (blue arrow). Nodule of 6.8 mm in the same lobe (red arrow). No other pathological findings. Fig. 2 PET-CT showed right pleural and retroperitoneal progression, as well as progression in the right pleura, diaphragm, and right supraclavicular lymph nodes . None of those findings were previously identified by the CT scan performed. Fig. 3 Case 2. PET/CT scan . 18 FDG uptake in the apical, posterior and lateral right pleura with ipsilateral pleural effusion. Hypermetabolic new lesion in the right cardiophrenic space, and lymph nodes with high 18-FDG uptake in the area of the gastrohepatic ligament and pre-aortic. Fig. 3 After confirming disease progression, initiating treatment with osimertinib at a daily dose of 80 mg was proposed. Initially, treatment tolerance was good. Unfortunately, the patient experienced clinical deterioration after three months of treatment, requiring hospitalization, and ultimately succumbed to disease progression. Case 3 We present the case of an 82-year-old woman at the time of diagnosis, a non-smoker with no relevant past medical history. In December 2016, she experienced pain in the right hemithorax accompanied by fever. She had no cough or expectoration. At that time, she consulted her primary care physician, who performed a chest X-ray revealing an infiltrate in the right middle lobe, leading to a provisional diagnosis of possible pneumonia. Antibiotic treatment was initiated, resulting in the resolution of fever. During a follow-up radiological examination in March 2017, no changes were observed in the image of the middle lobe. Subsequently, a chest and abdominal computed tomography (CT) scan confirmed the presence of a 3.3 cm right parahilar mass. No hilar or mediastinal adenopathies were evident. On April 25, 2017, she presented to our center, where a PET-CT scan confirmed a mass in the right middle lobe with increased uptake, reaching a maximum of 9.4. Additionally, an area of distal pneumonitis was noted. Increased uptake at the right hilar level with a maximum SUV of 3.2 raised suspicion of lymph node infiltration. An MRI ruled out the presence of brain disease. A bronchoscopy with biopsy was performed, and the diagnosis was consistent with adenocarcinoma. In May 2017, a regulated median lobectomy was carried out, accompanied by hilar and mediastinal lymphadenectomy, resulting in a diagnosis of moderately differentiated adenocarcinoma. Surgical margins were free of disease. TTF1 was negative, with no expression of p40 , ALK , or ROS-1 , and PDL-1 expression was observed in 1% of the cells. No lymph node infiltration was observed in the nodes obtained during surgery. Molecular analysis through NGS in the tumor tissue sample revealed the presence of an activating EGFR mutation, specifically L858R. With a diagnosis of moderately differentiated lung adenocarcinoma stage pT2aN0M0 (IB), she was referred to the Medical Oncology department. After assessing the advantages and disadvantages, no adjuvant treatment was given. Instead, a liquid biopsy study was conducted to determine the presence of an activating EGFR mutation (Oncomine Pan-Cancer Cell-Free Assay), with no evidence of this alteration after surgical treatment. Since then, the patient has been undergoing regular follow-ups with no recurrence of the EGFR mutation in subsequent liquid biopsy examinations. Additionally, there has been no evidence of relapse in imaging tests conducted to date. Case 4 Finally, we present the case of a 77-year-old patient at the time of diagnosis. A former smoker for 20 years, averaging one pack per week, with a medical history of unstable angina involving 2-vessel disease and incomplete revascularization in May 2021. The patient had undergone several surgeries for degenerative pathology. An incidental finding of a lung node in the right upper lobe was made in the context of a respiratory tract infection. Further investigation through a thoracic and abdominal CT scan revealed a spiculated nodule in the right upper lobe measuring 15 mm, raising suspicion of malignancy. PET-CT ruled out distant lesions but confirmed hypermetabolism of the identified nodule (SUVmax 1.6). A core needle biopsy was performed, confirming malignancy as pulmonary adenocarcinoma with a lepidic pattern. Following appropriate respiratory functional tests and cardiology assessment, on November 29, 2022, a right upper lobectomy with staging lymphadenectomy was conducted. The pathological report confirmed a pT1aN0 lung adenocarcinoma, PD-L1 <1%, and an EGFR mutation (p . L858R exon 21) was identified by Cobas® test in tissue sample. The case was presented in the multidisciplinary tumor board, and given the IA1 stage, a decision for surveillance was made. Liquid biopsy (Cobas® EGFR Test) at follow-up appointments have not detected the mutation in the blood. These findings correlated with CT studies that showed no signs of tumor recurrence.	3.917969	0.982422	sec[4]/p[0]	en	0.999998	PMC11863883	https://doi.org/10.1016/j.jlb.2024.100145	[ "lobe", "scan", "nodule", "biopsy", "mutation", "adenocarcinoma", "presence", "lymph", "egfr", "liquid" ]	[ { "code": "CB40.2", "title": "Pulmonary collapse" }, { "code": "LA75.0", "title": "Accessory lobe of lung" }, { "code": "MD41", "title": "Clinical findings on diagnostic imaging of lung" }, { "code": "LA75.1", "title": "Agenesis of lung" }, { "code": "JA8A.1", "title": "Malformation of placenta" }, { "code": "MB71.Y", "title": "Other specified clinical findings on diagnostic imaging of central nervous system" }, { "code": "NE60", "title": "Harmful effects of drugs, medicaments or biological substances, not elsewhere classified" }, { "code": "JA66.3", "title": "Abnormal ultrasonic finding on antenatal screening of mother" }, { "code": "PB28", "title": "Unintentional exposure to or harmful effects of other or unspecified drug, medicament or biological substance" }, { "code": "PC98", "title": "Intentional self-harm by exposure to other or unspecified drug, medicament or biological substance" } ]	=== ICD-11 CODES FOUND === [CB40.2] Pulmonary collapse Also known as: Pulmonary collapse \| Atelectasis \| lung collapse \| pulmonary atelectasis \| pulmonary collapse with atelectasis Includes: Atelectasis Excludes: Primary atelectasis of newborn \| tuberculous atelectasis, not confirmed \| tuberculous atelectasis, confirmed [LA75.0] Accessory lobe of lung Definition: An extra lobe of lung beyond the 3 on the right and the 2 on the left Also known as: Accessory lobe of lung \| supernumerary lung lobe \| azygos lobe of lung \| azygos lobe fissure of lung \| azygos lobe [MD41] Clinical findings on diagnostic imaging of lung Definition: Clinical findings on diagnostic imaging of lung is findings on diagnostic imaging of the lung which don't appear in normal status of the body. Diagnostic imaging refers to technologies that doctors use to look inside body for clues about a medical condition. X-rays, CT scans, nuclear medicine scans, MRI scans and ultrasound are all types of diagnostic imaging. Also known as: Clinical findings on diagnostic imaging of lung \| abnormal diagnostic imaging of lung \| Hyperinflation of lung \| Lung mass \| Pulmonary lobe mass [LA75.1] Agenesis of lung Definition: This refers to the absence or rudimentary residua of an undeveloped lung. Also known as: Agenesis of lung \| Pulmonary agenesis \| absence of lung \| aplasia of lung \| apulmonism [JA8A.1] Malformation of placenta Also known as: Malformation of placenta \| variation of placenta form \| deformity of placenta \| placental deformity \| Abnormal placenta NOS [MB71.Y] Other specified clinical findings on diagnostic imaging of central nervous system Also known as: Other specified clinical findings on diagnostic imaging of central nervous system \| Epidural haemorrhage, localised, no generalised mass effect or midline shift \| Epidural haemorrhage, confined to a small region in relation to a fracture \| Epidural haemorrhage, size less than 1 x 1 x 1 cm, not in relation to a fracture \| Epidural haemorrhage, mass effect or midline shift less than 0.5 cm [NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified Also known as: Harmful effects of drugs, medicaments or biological substances, not elsewhere classified \| drugs, medicaments or biological substances, toxicity not elsewhere classified \| adverse drug effects \| drug reaction NOS \| drug allergy NOS Excludes: Alcohol intoxication \| pathological drug intoxication \| hypersensitivity reaction to correctly administered drug [JA66.3] Abnormal ultrasonic finding on antenatal screening of mother Definition: A sign characterised by an abnormality detected by ultrasound during an antenatal screening of the mother. Also known as: Abnormal ultrasonic finding on antenatal screening of mother \| antenatal ultrasound scan abnormal [PB28] Unintentional exposure to or harmful effects of other or unspecified drug, medicament or biological substance Also known as: Unintentional exposure to or harmful effects of other or unspecified drug, medicament or biological substance \| accidental overdose of other or unspecified drug, medicament or biological substance \| accidental poisoning by other or unspecified drug, medicament or biological substance \| other or unspecified drug, medicament or biological substance taken in error \| accidental drug overdose [PC98] Intentional self-harm by exposure to other or unspecified drug, medicament or biological substance Also known as: Intentional self-harm by exposure to other or unspecified drug, medicament or biological substance \| Intentional self-poisoning by and exposure to other or unspecified drug, medicament or biological substance \| Intentional overdose of other or unspecified drug, medicament or biological substance \| self-administered overdose by drugs \| Intentional self-harm by exposure to or harmful effects of systemic antibiotics === GRAPH WALKS === --- Walk 1 --- [CB40.2] Pulmonary collapse --EXCLUDES--> [?] Primary atelectasis of newborn Def: Failure of the lungs to expand after birth, as in stillborn infants or in liveborn infants who die before respiration is established... --PARENT--> [?] Respiratory disorders specific to the perinatal or neonatal period Def: A group of conditions occurring during the period of time around childbirth, especially the five months before and one month after birth which are associated with the cardiovascular or respiratory sys... --- Walk 2 --- [CB40.2] Pulmonary collapse --EXCLUDES--> [?] Primary atelectasis of newborn Def: Failure of the lungs to expand after birth, as in stillborn infants or in liveborn infants who die before respiration is established... --PARENT--> [?] Respiratory disorders specific to the perinatal or neonatal period Def: A group of conditions occurring during the period of time around childbirth, especially the five months before and one month after birth which are associated with the cardiovascular or respiratory sys... --- Walk 3 --- [LA75.0] Accessory lobe of lung Def: An extra lobe of lung beyond the 3 on the right and the 2 on the left... --PARENT--> [LA75] Structural developmental anomalies of lungs Def: Any condition caused by failure of the lungs to correctly develop during the antenatal period.... --CHILD--> [LA75.0] Accessory lobe of lung Def: An extra lobe of lung beyond the 3 on the right and the 2 on the left... --- Walk 4 --- [LA75.0] Accessory lobe of lung Def: An extra lobe of lung beyond the 3 on the right and the 2 on the left... --PARENT--> [LA75] Structural developmental anomalies of lungs Def: Any condition caused by failure of the lungs to correctly develop during the antenatal period.... --PARENT--> [?] Structural developmental anomalies of the respiratory system --- Walk 5 --- [MD41] Clinical findings on diagnostic imaging of lung Def: Clinical findings on diagnostic imaging of lung is findings on diagnostic imaging of the lung which don't appear in normal status of the body. Diagnostic imaging refers to technologies that doctors us... --PARENT--> [?] Clinical findings in the respiratory system --CHILD--> [MD41] Clinical findings on diagnostic imaging of lung Def: Clinical findings on diagnostic imaging of lung is findings on diagnostic imaging of the lung which don't appear in normal status of the body. Diagnostic imaging refers to technologies that doctors us... --- Walk 6 --- [MD41] Clinical findings on diagnostic imaging of lung Def: Clinical findings on diagnostic imaging of lung is findings on diagnostic imaging of the lung which don't appear in normal status of the body. Diagnostic imaging refers to technologies that doctors us... --PARENT--> [?] Clinical findings in the respiratory system --PARENT--> [?] Symptoms, signs or clinical findings of the respiratory system	[ "[CB40.2] Pulmonary collapse\n --EXCLUDES--> [?] Primary atelectasis of newborn\n Def: Failure of the lungs to expand after birth, as in stillborn infants or in liveborn infants who die before respiration is established...\n --PARENT--> [?] Respiratory disorders specific to the perinatal or neonatal period\n Def: A group of conditions occurring during the period of time around childbirth, especially the five months before and one month after birth which are associated with the cardiovascular or respiratory sys...", "[CB40.2] Pulmonary collapse\n --EXCLUDES--> [?] Primary atelectasis of newborn\n Def: Failure of the lungs to expand after birth, as in stillborn infants or in liveborn infants who die before respiration is established...\n --PARENT--> [?] Respiratory disorders specific to the perinatal or neonatal period\n Def: A group of conditions occurring during the period of time around childbirth, especially the five months before and one month after birth which are associated with the cardiovascular or respiratory sys...", "[LA75.0] Accessory lobe of lung\n Def: An extra lobe of lung beyond the 3 on the right and the 2 on the left...\n --PARENT--> [LA75] Structural developmental anomalies of lungs\n Def: Any condition caused by failure of the lungs to correctly develop during the antenatal period....\n --CHILD--> [LA75.0] Accessory lobe of lung\n Def: An extra lobe of lung beyond the 3 on the right and the 2 on the left...", "[LA75.0] Accessory lobe of lung\n Def: An extra lobe of lung beyond the 3 on the right and the 2 on the left...\n --PARENT--> [LA75] Structural developmental anomalies of lungs\n Def: Any condition caused by failure of the lungs to correctly develop during the antenatal period....\n --PARENT--> [?] Structural developmental anomalies of the respiratory system", "[MD41] Clinical findings on diagnostic imaging of lung\n Def: Clinical findings on diagnostic imaging of lung is findings on diagnostic imaging of the lung which don't appear in normal status of the body. Diagnostic imaging refers to technologies that doctors us...\n --PARENT--> [?] Clinical findings in the respiratory system\n --CHILD--> [MD41] Clinical findings on diagnostic imaging of lung\n Def: Clinical findings on diagnostic imaging of lung is findings on diagnostic imaging of the lung which don't appear in normal status of the body. Diagnostic imaging refers to technologies that doctors us...", "[MD41] Clinical findings on diagnostic imaging of lung\n Def: Clinical findings on diagnostic imaging of lung is findings on diagnostic imaging of the lung which don't appear in normal status of the body. Diagnostic imaging refers to technologies that doctors us...\n --PARENT--> [?] Clinical findings in the respiratory system\n --PARENT--> [?] Symptoms, signs or clinical findings of the respiratory system" ]	CB40.2	Pulmonary collapse	[ { "from_icd11": "CB40.2", "icd10_code": "J9811", "icd10_title": "Atelectasis" }, { "from_icd11": "CB40.2", "icd10_code": "J9819", "icd10_title": "Other pulmonary collapse" }, { "from_icd11": "CB40.2", "icd10_code": "J981", "icd10_title": "Pulmonary collapse" }, { "from_icd11": "LA75.0", "icd10_code": "Q331", "icd10_title": "Accessory lobe of lung" }, { "from_icd11": "MD41", "icd10_code": "R911", "icd10_title": "Solitary pulmonary nodule" }, { "from_icd11": "MD41", "icd10_code": "R91", "icd10_title": "Abnormal findings on diagnostic imaging of lung" }, { "from_icd11": "LA75.1", "icd10_code": "Q333", "icd10_title": "Agenesis of lung" }, { "from_icd11": "JA8A.1", "icd10_code": "O43123", "icd10_title": "Velamentous insertion of umbilical cord, third trimester" }, { "from_icd11": "JA8A.1", "icd10_code": "O43193", "icd10_title": "Other malformation of placenta, third trimester" }, { "from_icd11": "JA8A.1", "icd10_code": "O43122", "icd10_title": "Velamentous insertion of umbilical cord, second trimester" }, { "from_icd11": "JA8A.1", "icd10_code": "O43113", "icd10_title": "Circumvallate placenta, third trimester" }, { "from_icd11": "JA8A.1", "icd10_code": "O43192", "icd10_title": "Other malformation of placenta, second trimester" }, { "from_icd11": "JA8A.1", "icd10_code": "O43103", "icd10_title": "Malformation of placenta, unspecified, third trimester" }, { "from_icd11": "JA8A.1", "icd10_code": "O43101", "icd10_title": "Malformation of placenta, unspecified, first trimester" }, { "from_icd11": "JA8A.1", "icd10_code": "O43102", "icd10_title": "Malformation of placenta, unspecified, second trimester" } ]	J9811	Atelectasis
The clinical and technical phases followed a previously described path and are summarized in Figure 1 . During the first meeting, a preliminary scan of the hemiarch of interest was taken with an IOS . The scan was performed in orthodontic mode, to obtain two virtual models—master model (i.e., the model with the compromised tooth to be restored with the single crown) and its antagonist. The occlusion was captured by registering the bite and the .STL files derived from this first scan were sent to CAD software (DentalCAD ® , Exocad, Darmstad, Germany) for the design and preparation of a provisional pre-milled restoration. This provisional was milled in polymethyl-methacrylate (PMMA) using a desktop milling machine (DWX-4 ® , DGShape a Roland Company, Hamamatsu, Japan) and, after being milled and characterized, it was ready for application. The damaged tooth was then prepared preliminarily and the provisional pre-milled crown in PMMA was relined on it. After relining, the provisional was finished, taking care that the relining margins were regular; the occlusion and interproximal contact points were carefully controlled, and the crown was cemented on the prosthetic abutment with temporary cement (Tempbond ® , Kerr, Orange, CA, USA). After a period of 1 to 2 weeks, the temporary pre-milled crown could be removed and replaced by a second, more precise PMMA provisional, to be adapted to the abutment without relining. For this purpose, the patient was referred to the clinic for the final preparation of the prosthetic abutment. The chosen preparation was horizontal (chamfer). The preparation of the abutment took place under 4.5× magnification (Zeiss ® , Oberchoken, Germany). At the end of this procedure, a new optical impression was recorded with the same IOS , in prosthetic mode (with higher resolution), without using any retraction method. The .STL files of the virtual models deriving from this impression (master model with prepared abutment, antagonist, and bite) were sent to CAD software (DentalCAD ® , Exocad, Darmstad, Germany) for the design and preparation of a second, more precise temporary restoration, to be cemented directly on the prosthetic abutment without any relining. Again, this restoration was milled in PMMA with a desktop milling machine (DWX-4 ® , DGShape a Roland Company, Hamamatsu, Japan), characterized, and readied for application. Once the premilled was removed, the second provisional was applied and cemented with temporary cement (Tempbond ® , Kerr, Orange, CA, USA) after careful control of the fit, the occlusion, and the contact points. This second provisional had to remain in the mouth for no more than 30 days before the final optical impression was taken, for the production of the final crown in monolithic translucent zirconia. The master model with the prepared abutment was, moreover, used for the design of a customized partial tray, for relining an analog impression. The procedure was as follows. The .STL file of the master model was imported into free CAD software (Meshmixer ® , Autodesk Research, Toronto, ON, Canada). Inside this software, a customized partial tray for impression was designed. This tray was built in order to rest on the occlusal surface of the adjacent teeth (or more teeth in the same hemiarcate) for an optimal stabilization and a simple and repeatable positioning. At this level, there was a contact between the tray and the occlusal surfaces, while the whole area around the prosthetic abutment was discharged in the CAD design, so as to have a uniform and free space of 2 mm there. This design allowed the control of the relining of the impression material, obtaining an ideal support and thrust for penetration into the gingival sulcus. The customized partial impression tray was then printed by means of a desktop 3D printer using a transparent proprietary resin certified for intraoral use. Once removed from the printing plate, the customized tray was washed in alcohol, but it was not polymerized. Hence, after 30 days of provisionalization, the patient was recalled for the final impression. The operator checked the prosthetic preparation, working again under 4.5× magnification (Zeiss ® , Oberchoken, Germany) and moved the prosthetic margins iuxta- or subgingivally, according to the specific clinical indications. The prosthetic preparation was always horizontal (chamfer) and took place with a retractor cord in place . Upon completion of the prosthetic preparation, the operator filled the customized partial 3D-printed tray with a minimum amount of polyvinyl siloxane light material. Then, immediately after removal of the retraction cord, the operator injected the polyvinyl siloxane light into the sulcus, using an injection gun, as with conventional analog impressions. He then relined the 3D-printed partial tray over the prosthetic preparation. After about 3 or 4 min, when the material was completely hardened, the tray was removed and an extraoral scan of the hollow portion of it was carried out, with the same IOS , in prosthetic mode . During this scan, it was important to be able to capture all details of the margin line, perfectly depicted by the light of the polyvinylsiloxane. The operator had to insist on capturing all the internal walls and the bottom of the impression. At the end of this procedure (which took place extraorally in 5 min and with the patient comfortably seated at the chair), the scan file of the impression was saved in .STL, and finally, a rapid intraoral scan of the arches was carried out. This scan took place without a retraction cord and therefore without paying excessive attention to the margin area . The scans of the master, antagonist, and bite models in prosthetic mode (high resolution) were then saved in .STL according to the previously described modalities. At this point, the operator had at his disposal two different optical impressions: the optical impression of the hollow portion of the relining with polyvinylsiloxane light, in a single file, extraorally captured and the patient’s models, captured intraorally. In the first impression, the details of the preparation margins were more evident because they were correctly highlighted by the impression material and able to penetrate deeply into the sulcus and read also slightly beyond. However, this impression was limited to the area of interest and therefore to the prepared abutment; it did not include other dental elements, and above all, it was reversed with respect to the second impression (i.e., it had inverted normals). In the second impression, however, the master and antagonist models were complete, with correct occlusion, but the prosthetic margins were not clearly visible. These impressions therefore had to be superimposed and fused together, in order to be able to build a unique virtual model in which the margins of the prosthetic preparations were clearly visible for the dental technician. The procedure was therefore as follows: The master and antagonist scans were imported in CAD (DentalCAD ® , Exocad, Darmstad, Germany) into a correct occlusal relationship. Before starting the editing/cropping procedures of the models and the design of the margin, the scan of polyvinylsiloxane relining was imported too, as an “additional arch scan”, and using the appropriate tool, the normals of this scan were inverted . Therefore, this additional scan was superimposed on the intraoral scans of the dentate models, through the command “register scans” . The superimposition was made by points and surfaces, generating a colorimetric map able to give an idea of the quality of the overlap between the two files. At this point, the process was completed because the additional scan (in which the prosthetic margins were clearly visible) replaced, in the area of interest, the mesh acquired in the mouth (with the margins not visible). This fusion made it possible to eliminate the part of the scan in which the margins were not visible, replacing it with the additional scan (with clearly visible margins), integrated into a single file . The technician could then proceed to the CAD modeling of the final restoration, having at his disposal a single virtual model with well visible prosthetic margins. Eventually, the intraoral scan could be imported as an additional .STL file, in order to check any possible deviation or distortion between the two models . The proof of the fit—and of the marginal closure/adaptation—of the occlusal and interproximal contacts was made first by using a replica of the final prosthetic restoration, milled in polyurethane with a desktop milling machine (DWX-4 ® , DGShape a Roland Company, Hamamatsu, Japan). In other words, from the CAD modeling file of the final restoration, a gray polyurethane crown was obtained in CAM, which was used for the control of the marginal gaps/clinical precision, the occlusion, and the contact points, before moving to the milling of the final monolithic restoration in translucent zirconia. In short, the marginal adaptation of the polyurethane replica of the final restoration was carefully checked using magnifying glasses (Zeiss 4.5x ® , Zeiss, Oberkochen, Germany) and physically probing the margin area with a periodontal probe . This procedure was performed circumferentially all around the crown, in order to intercept any possible misfit, gaps, or undercuts. The occlusion was carefully checked too, using articulating papers (Bausch Articulating Paper ® , Bausch Inc., Nashua, NH, USA). In the case of occlusal precontact, a photograph was taken and transmitted to the dental technician, as valid information for making occlusal changes on the CAD drawing of the final modeling. Finally, contact points were checked using interdental floss. If the contacts were too weak or unsatisfactory, this information was passed to the dental technician for the appropriate modifications. After checking all these elements and making the necessary corrections, the final monolithic restoration was milled in translucent zirconia, using a 5-axis milling machine (Roland DWX-50 ® , DGShape, a Roland Company, Hamamatsu, Japan). The crown was then sintered in an oven (Tabeo ® , Mihm-Vogt, Stutensee, Germany), characterized, and readied for cementation. Before cementing the final crown, the main outcomes of this study (i.e., the marginal adaptation of the final crown, the quality of occlusal contacts, and interproximal contact points) were verified again. In case of no issues, the final crown was cemented with a resinous cement (Bifix SE ® , Voco GmbH, Cuxhaven, Germany), taking care to remove all possible excesses and remnants of resin before polymerization. The cementation was obtained with the light of a dental polymerization lamp. Conversely, in case of issues or misfits evidenced during this last control, the crown was not cemented and sent back to the technician.	4.074219	0.344238	sec[1]/sec[1]/p[0]	en	0.999995	31936096	https://doi.org/10.3390/ijerph17020392	[ "this", "prosthetic", "scan", "impression", "crown", "preparation", "using", "margins", "restoration", "abutment" ]	[ { "code": "4A01.03", "title": "Transient hypogammaglobulinaemia of infancy" }, { "code": "BC01", "title": "Prosthetic valve disease" }, { "code": "BC01/BB9Z", "title": "Pulmonary prosthetic valve disease" }, { "code": "BC01/BB6Z", "title": "Mitral prosthetic valve disease" }, { "code": "BC01/BB8Z", "title": "Tricuspid prosthetic valve disease" }, { "code": "BC01/BB7Z", "title": "Aortic prosthetic valve disease" }, { "code": "MB71.Y", "title": "Other specified clinical findings on diagnostic imaging of central nervous system" }, { "code": "NE60", "title": "Harmful effects of drugs, medicaments or biological substances, not elsewhere classified" }, { "code": "JA66.3", "title": "Abnormal ultrasonic finding on antenatal screening of mother" }, { "code": "PB28", "title": "Unintentional exposure to or harmful effects of other or unspecified drug, medicament or biological substance" } ]	=== ICD-11 CODES FOUND === [4A01.03] Transient hypogammaglobulinaemia of infancy Also known as: Transient hypogammaglobulinaemia of infancy \| immunoglobulin maturational delay \| THI - [transient hypogammaglobulinaemia of infancy] [BC01] Prosthetic valve disease Also known as: Prosthetic valve disease \| homograft prosthetic valve disease \| mechanical prosthetic valve disease \| allograft prosthetic valve disease \| biological prosthetic valve disease [MB71.Y] Other specified clinical findings on diagnostic imaging of central nervous system Also known as: Other specified clinical findings on diagnostic imaging of central nervous system \| Epidural haemorrhage, localised, no generalised mass effect or midline shift \| Epidural haemorrhage, confined to a small region in relation to a fracture \| Epidural haemorrhage, size less than 1 x 1 x 1 cm, not in relation to a fracture \| Epidural haemorrhage, mass effect or midline shift less than 0.5 cm [NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified Also known as: Harmful effects of drugs, medicaments or biological substances, not elsewhere classified \| drugs, medicaments or biological substances, toxicity not elsewhere classified \| adverse drug effects \| drug reaction NOS \| drug allergy NOS Excludes: Alcohol intoxication \| pathological drug intoxication \| hypersensitivity reaction to correctly administered drug [JA66.3] Abnormal ultrasonic finding on antenatal screening of mother Definition: A sign characterised by an abnormality detected by ultrasound during an antenatal screening of the mother. Also known as: Abnormal ultrasonic finding on antenatal screening of mother \| antenatal ultrasound scan abnormal [PB28] Unintentional exposure to or harmful effects of other or unspecified drug, medicament or biological substance Also known as: Unintentional exposure to or harmful effects of other or unspecified drug, medicament or biological substance \| accidental overdose of other or unspecified drug, medicament or biological substance \| accidental poisoning by other or unspecified drug, medicament or biological substance \| other or unspecified drug, medicament or biological substance taken in error \| accidental drug overdose === GRAPH WALKS === --- Walk 1 --- [4A01.03] Transient hypogammaglobulinaemia of infancy --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects... --CHILD--> [4A01.02] Specific antibody deficiency with normal immunoglobulin concentrations or normal number of B cells --- Walk 2 --- [4A01.03] Transient hypogammaglobulinaemia of infancy --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects... --CHILD--> [4A01.00] Hereditary agammaglobulinaemia with profoundly reduced or absent B cells Def: This refers to a hereditary type of primary immune deficiency disease characterised by a reduction in all types of gamma globulins, and rare X-linked genetic disorder that affects the body's ability t... --- Walk 3 --- [BC01] Prosthetic valve disease --RELATED_TO--> [?] Infection or inflammatory reaction of heart valve prosthesis NOS --PARENT--> [?] Infection or inflammatory reaction due to other cardiac and vascular devices, implants and grafts NOS --- Walk 4 --- [BC01] Prosthetic valve disease --PARENT--> [?] Heart valve diseases --CHILD--> [?] Tricuspid valve disease	[ "[4A01.03] Transient hypogammaglobulinaemia of infancy\n --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects\n Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects...\n --CHILD--> [4A01.02] Specific antibody deficiency with normal immunoglobulin concentrations or normal number of B cells", "[4A01.03] Transient hypogammaglobulinaemia of infancy\n --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects\n Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects...\n --CHILD--> [4A01.00] Hereditary agammaglobulinaemia with profoundly reduced or absent B cells\n Def: This refers to a hereditary type of primary immune deficiency disease characterised by a reduction in all types of gamma globulins, and rare X-linked genetic disorder that affects the body's ability t...", "[BC01] Prosthetic valve disease\n --RELATED_TO--> [?] Infection or inflammatory reaction of heart valve prosthesis NOS\n --PARENT--> [?] Infection or inflammatory reaction due to other cardiac and vascular devices, implants and grafts NOS", "[BC01] Prosthetic valve disease\n --PARENT--> [?] Heart valve diseases\n --CHILD--> [?] Tricuspid valve disease" ]	4A01.03	Transient hypogammaglobulinaemia of infancy	[ { "from_icd11": "4A01.03", "icd10_code": "D807", "icd10_title": "Transient hypogammaglobulinemia of infancy" }, { "from_icd11": "BC01", "icd10_code": "T8203XA", "icd10_title": "Leakage of heart valve prosthesis, initial encounter" }, { "from_icd11": "BC01", "icd10_code": "T8209XA", "icd10_title": "Other mechanical complication of heart valve prosthesis, initial encounter" }, { "from_icd11": "BC01", "icd10_code": "T8209XD", "icd10_title": "Other mechanical complication of heart valve prosthesis, subsequent encounter" }, { "from_icd11": "BC01", "icd10_code": "T8202XA", "icd10_title": "Displacement of heart valve prosthesis, initial encounter" }, { "from_icd11": "BC01", "icd10_code": "T8201XA", "icd10_title": "Breakdown (mechanical) of heart valve prosthesis, initial encounter" }, { "from_icd11": "BC01", "icd10_code": "I340", "icd10_title": "Nonrheumatic mitral (valve) insufficiency" }, { "from_icd11": "BC01", "icd10_code": "I350", "icd10_title": "Nonrheumatic aortic (valve) stenosis" }, { "from_icd11": "BC01", "icd10_code": "I351", "icd10_title": "Nonrheumatic aortic (valve) insufficiency" }, { "from_icd11": "BC01", "icd10_code": "I361", "icd10_title": "Nonrheumatic tricuspid (valve) insufficiency" }, { "from_icd11": "BC01", "icd10_code": "I059", "icd10_title": "Rheumatic mitral valve disease, unspecified" }, { "from_icd11": "BC01", "icd10_code": "I352", "icd10_title": "Nonrheumatic aortic (valve) stenosis with insufficiency" }, { "from_icd11": "BC01", "icd10_code": "I371", "icd10_title": "Nonrheumatic pulmonary valve insufficiency" }, { "from_icd11": "BC01", "icd10_code": "I342", "icd10_title": "Nonrheumatic mitral (valve) stenosis" }, { "from_icd11": "BC01", "icd10_code": "I360", "icd10_title": "Nonrheumatic tricuspid (valve) stenosis" } ]	D807	Transient hypogammaglobulinemia of infancy
Combination of autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), and positive direct Coombs test to IgG and C3d thus the diagnosis of Evans syndrome secondary to SARS-CoV-2 infection (COVID-19) was made. Over the course of his admission, the patient received 5 units of packed red blood cells (PRBC), antiviral treatment with favipiravir (200 mg) tab 1600 mg twice daily on day 1, followed by 600 mg twice daily for a total duration of 5 days, ivermectin (Iverzine) tab 6 mg six tab as single dose day 0, day 3, day 6, and dexamethasone 8 mg IV twice a day at the first 5 days and once for 5 days, and then prednisone 1 mg/kg daily (total daily dose of 60 mg), cefatriaxone 1 g IV once a day, moxiflox 400 mg oral once daily, enoxaparin (clexan) 60 mg SC twice daily for 10 days, receive revaroxeban tab 10 mg daily and rovitan sachets twice, oral hypoglycemic (amaryl tab 3 mg twice plus metformin (cidophage) tab 750 mg once, vitamin C 500 mg oral twice a day, along with other symptomatic medicine, and was given oxygen using face mask. Follow-up CBC on 9 May 2021 shows: RBCs 2.8 × 100 3 /μl, Hgb 9.1 g/dL, MCV 91.6, HCT 25.3%, total leukocyte count (WBCs) 13.4 × 10 3 /μl, neutrophil 70.4%, lymphocyte 21.8%, and platelet count, 99 × 10 3 /μl (thrombocytopenia). The patient’s clinical condition improved, with following clinical improvements: fever subside, SO2% 98% room air, CBC parameters, and S. bilirubin direct, and indirect. On the day of discharge, 16 May 2021, his complete blood count was as follows: RBCs 3.06, Hgb 10.3 g/dL, total leukocyte count 3.8 × 10 3 , neutrophil 68%, lymphocyte 27%, and platelet count 54 × 10 3 , Reticolocyte count: 2%, total bilirubin, conjugated bilirubin, unconjugated bilirubin, CRP, D-dimer, and LDH had decreased to (2.8, 1.5, 1.3 mg/dl, 12 mg/l, 368.4 mg/l, and 618 μ/l) respectively, SO2% 98% on room air then, he got a maintenance dose of prednisolone1mg/kg/daily oral and rivaroxaban tab 10 mg daily. One week after discharge on prednisolone, his CBC: RBCs 3.5, Hgb 10.8 g/dl, HCT (hematocrit) 30.4 l/l, RDW-CV 17.1%, platelet count 70, and WBCs 5.73, mild normocytic normochromic anemia with anisopoikilocytosis, tear drop cells, pencil-shaped cells and target cells, reticulocytosis and normoblastemia, and mild thrombocytopenia. The reticolocytic count was within normal limits (2%), total, direct, indirect bilirubin, and LDH markedly decreased to 1.63, 0.5, 1.2 mg/dl, and 490 μ/l) respectively. One week after discharge, 31 May 2021, a repeat test revealed RBCs 3.8, Hgb 11.1 g/dl, HCT 33.2 L/l, RDW-CV 15.4%, platelet count 114, and WBCs 6.7. Normocytic normochromic anemia with anisocytosis, mild thrombocytopenia, and normal reticolocytic count (1.5%) and LDH 417 μ/l. A steroid taper was planned. Follow-up laboratories 4 weeks 17 June 2021, after discharge demonstrated complete hematologic response with Hgb 12.5 g/dL, RBCs 4, HCT 35.1, MCV 87.5, WBCs 4.8, neutrophils 78%, lymphocytes 20%, platelet 67,000, normocytic normochromic anemia with (erythrocytes show) anisocytosis, thrombocytopenia with some giant platelet forms and normal reticulocyte count (0.5%) and normal bilirubin (total 1.11 mg, direct 0.34 mg, indirect 0.77 mg) and LDH 340 μ/l. serum ferritin 357.1 ng/ml. The patient was continued on a prednisone taper (Tables 1 and 2 ). Table 1 Laboratory tests results Indirect Coombs Direct Coombs Lactate dehydrogenase Indirect bilirubin Direct bilirubin Total bilirubin Ferritin D-dimer C-reactive protein Lymphocytes relative % absolute Neutrophils relative % absolute Differential Total count Negative IgG +ve C3d +ve – 4.6 mg 2.4 mg 7 mg – – – 26 2.6 67 6.7 10.06 – – 947 U/L – – – 541 ng/ml 2920 84.2 24 1.99 68 5.64 8.3 – – – – – – – – – 21.8 2.9 70.4 9.5 13.4 – – 618 μ/l 1.3 1.5 2.8 mg 850 ng/ml 368.4 12 mg 27 1.03 68 2.6 3.8 – – 490 μ/l 1.2 0.5– 1.63 522.1 ng/ml – – 28 1.6 62 3.55 5.73 – – 417 μ/l – – – 612 ng/ml – – 22% 1.5 76% 5.1 6.7 – – 340 μ/l 0.77 0.34 1.11 357.1 – – 20% 0.96 78% 3.74 4.8 Indirect Coombs WBCs Platelet count Reticulocyte Peripheral blood smear RDW-CV MCHC MCH MCV HCT Hgb RBCs CBC Negative 185 3.65% – 15.7 32.2 27.5 85 19.02 6.1 2.23 3-5-21 – 117 12.5% Anisopoikilocytosis spherocytes 18.5 35.6 34.2 95.9 15.1 5.4 1.58 5–5 – 99 7.5% – 20.3 35.9 32.9 91.6 25.3 9.1 2.76 9–5 – 54 2% – 30.6 33.7 110.1 33.7 10.3 3.06 16–5 – 70 1.2 Anisopoikilocytosis, tear drop cells 17.1 35.5 30.9 86.9 30.4 10.8 3.5 22–5 – 114 1.5% Anisocytosis 15.4 33.4 29.5 88.3 33.2 11.1 3.8 31–5 – 67 0.5% Anisocytosis 13.5 35.6 31.2 87.5 35.1 12.5 4.01 17–6 All dates refer to the year of 2021 Table 2 Autoimmune hematologic complications (Evans syndrome) of SARS-CoV-2 infections Author Month Country History of the patient Clinical presentations Timing of the hematologic presentations Autoimmune disorder Treatment Outcome Li et al. Late March 2020 USA 39-year-old male First admission: fever, chills, dyspnea, hemoptysis, epistaxis, sore throat, productive cough, tachycardia, tachypnea, oral blood blister, hematemesis, melena, hematochezia and no petechiae, ecchymosis or rash Second admission (10 days later, 4 days after first discharge): intermittent fever,cough, extreme weakness, fatigue, and no bleeding About 7 days Evans syndrome First admission: proton pump inhibitor, IVIG Second admission: IVIG Recovered (in first admission that patient had ITP, resolution of bleeding and raise of Plt occurred on day 5 and the patient was discharged on day 6; Hb drop also responded to IVIG in second admission) Wahlster et al. April 2020 USA 17 -year-old male K/C of refractory chronic ITP on eltrombopag and mycophenolate mofetil Fever, fatigue, emesis, diarrhea, progressive jaundice, marked pallor, tachycardia, tachypnea, and hypoxemia 4 days Evans syndrome Steroid, packed cell transfusion Recovered (Hb became stable within 48 h of steroid administration) Vadlamudi et al. June 2020 USA 23-year-old female gravida 2, para 1, at 38 weeks of pregnancy in active labor Spontaneous rupture of membranes, contractions, blood-tinged discharge, history of ecchymosis and an episode of epistaxis 2 weeks prior, no pallor, ecchymosis or organomegaly On day 38 of postpartum: chest pain and shortness of breath Not clear Evans syndrome IV iron dextran, IVIG, rituximab, dexamethasone, packed cell and Plttransfusion, folate (1 mg daily) and B12 Recovered Demir et al April 26, 2020 Turkey A 22-year-old male patient Jaundice, weakness, shortness of breath, fever, tachycardia, tachypnea, O2 sat: 89%; and body mass index: 32.5, icteric sclerae, pale conjunctivae. Not clear Evans syndrome Patient was treated with hydroxychloroquine, moxifloxacin and favipiravir for 5 days, Subcutaneous enoxaparin 1 × 0.6 cc, continuous positive airway pressure was administered intermittently, Methylprednisolone 1 mg/kg, folic acid, vitamin B12, and a proton pump inhibitor, 2 units of erythrocyte suspension daily, intravenous immunoglobulin (IVIG) 1 g/kg/day. Recovered (on day 5 after discharge from hospital, his hemoglobin was 13 g/dL and his platelet count was 210 × 109 /L. Furthermore, his rapid antibody test (serological test) was positive for IgM and IgG against SARS-CoV 2). Zarza et al March 23, 2020 Paraguay A 30-year-old woman At the time of her first visit March 23rd 2020, she presented with upper respiratory symptoms, nasal congestion, a sore throat, a cough, and the loss of her taste and smell. Medical history for a deep venous thrombosis of the right lower limb that she experienced when she was 11 years old. On April 1st, 2020, gingivorrhagia, which was self-limited. On April 5th, incoercible epistaxis appeared, Petechiae were found on her skin all over her body. About 10 days Evans syndrome 1 g of methylprednisolone intravenously (IV) each day for three consecutive days was started, resulting in a decrease in bleeding and purpura. Empirical treatment was started with 500 mg of azithromycin PO on day 1 followed by 250 mg per day for 4 days, 400 mg of hydroxychloroquine PO every 12 h on day 1 followed by 200 mg PO every 12 h for the next 4 days, 100 mg of prednisone PO once daily, and 1 g of ceftriaxone IV every 24 h. enoxaparin at prophylactic doses of 40 mg every 24 h. She was discharged with 50 mg of prednisone daily, 200 mg of hydroxychloroquine every 12 h, and 40 mg of enoxaparin daily. A close follow-up was indicated by all of the specialists involved in her care. The progressive improvement of the patient’s health permitted her to be sent home. Barcellini et al. March 25, 2020 Italy 78-year-old male On March 25, 2020, he presented at the outpatient clinic with typical symptoms of COVID-19 pneumonia (fever, dyspnoea, desaturation to 80%). His past medical history consisted of arterial hypertension, previous myocardial infarction with ventricular fibrillation, stroke, two septic shocks, and osteonecrosis of the femoral head. Not mentioned Evans syndrome Low-flow oxygen support, steroids, hydroxychloroquine (HCQ), azithromycine, full-dose LMWH, and empirical antibiotic therapy for superimposed bacterial infection. The patient rapidly recovered from pneumonia but experienced two complications: paroxysmal atrial fibrillation treated with amiodarone, and wAIHA relapse that required IvIg and full-dose steroid (prednisone 1 mg/kg/day for 3 weeks followed by slow tapering, still ongoing). Georgy et al. July 2020 India A 33-year-old man Presented to the emergency department with a 3-week history of gum bleeding, black tarry stools, and reddish spots on the skin, no fever, cough, or dyspnea, petechial lesions over the chest, legs, and oral mucosa, Within a few hours of admission, the patient complained of sudden-onset headache and developed a generalized tonic–clonic seizure. The patient’s sensorium worsened rapidly with anisocoria, 3 weeks Evans syndrome He was shifted to the intensive care unit, he was treated with pulse dexamethasone 40 mg daily with platelet transfusions (intravenous immunoglobulin [IVIG] was not feasible),he had not received anticoagulation Despite the above measures, there was no improvement in the patient’s platelet counts nor sensorium, and he died on the third day of admission died Current study May 3, 2021 Egypt A 54-year-old male Fever, arthralgia, myalgia, fatigue, and dark color of urine, pallor, jaundice, and then patient develop dyspnea, cough, and progressive fatigue Yellow discoloration of eyes, tachycardia, tachypnea, O2 sat: 80%. Hematologic manifestations were the presenting symptoms from the start Evans syndrome Packed red blood cells, Favipiravir (200 mg) tab, Ivermectin (6 mg) tab, Dexamethasone 8 mg IV, cefatriaxone 1 g IV, moxiflox 400 mg, enoxaparin (clexan) 60 mg SC twice, oxygen using face mask, oral hypoglycemic (amaryl tab 3 mg plus metformin tab 750, Vitamin C 500 mg, along with other symptomatic medicine. Recovered	3.982422	0.971191	sec[1]/p[1]	en	0.999996	PMC9066390	https://doi.org/10.1186/s43168-022-00125-x	[ "daily", "count", "evans", "platelet", "total", "bilirubin", "twice", "fever", "oral", "ivig" ]	[ { "code": "QF21", "title": "Difficulty or need for assistance with general life tasks or life management" }, { "code": "8A83", "title": "Other primary headache disorder" }, { "code": "QB42", "title": "Dependence on renal dialysis" }, { "code": "3B63.1Z", "title": "Acquired thrombocytosis, unspecified" }, { "code": "3B64.Z", "title": "Thrombocytopenia, unspecified" }, { "code": "4B0Z", "title": "Immune system disorders involving white cell lineages, unspecified" }, { "code": "4B03.Z", "title": "Eosinophilia, unspecified" }, { "code": "4B00.1Z", "title": "Neutrophilia, unspecified" }, { "code": "3A20.5", "title": "Evans syndrome" }, { "code": "EC20.31", "title": "Focal palmoplantar keratodermas" } ]	=== ICD-11 CODES FOUND === [QF21] Difficulty or need for assistance with general life tasks or life management Also known as: Difficulty or need for assistance with general life tasks or life management \| difficulty with carrying out tasks and daily routine \| life management problem \| difficulty with life management tasks \| Difficulty with dealing with change such as relocation Includes: difficulty with carrying out tasks and daily routine [8A83] Other primary headache disorder Definition: A group of clinically heterogeneous headache disorders, believed to be primary. Although largely unrelated, they fall into four categories: headaches associated with physical exertion; headaches attributed to direct physical but innocuous stimuli; epicranial headaches; and other miscellaneous primary headache disorders. Also known as: Other primary headache disorder \| Primary cough headache \| Primary exercise headache \| Primary headache associated with sexual activity \| Preorgasmic headache [QB42] Dependence on renal dialysis Also known as: Dependence on renal dialysis \| renal dialysis status \| presence of arteriovenous shunt for dialysis \| dependence on haemodialysis \| Dependence on renal dialysis, acute haemodialysis Includes: renal dialysis status Excludes: dialysis preparation, treatment or session [3B63.1Z] Acquired thrombocytosis, unspecified Also known as: Acquired thrombocytosis, unspecified \| Acquired thrombocytosis \| Idiopathic haemorrhagic thrombocythaemia \| Essential thrombocythaemia \| primary haemorrhagic thrombocythaemia [3B64.Z] Thrombocytopenia, unspecified Also known as: Thrombocytopenia, unspecified \| Thrombocytopenia \| low platelet count \| low platelets \| decreased platelets [4B0Z] Immune system disorders involving white cell lineages, unspecified Also known as: Immune system disorders involving white cell lineages, unspecified [4B03.Z] Eosinophilia, unspecified Also known as: Eosinophilia, unspecified \| Eosinophilia \| Disorders with increased eosinophil counts \| Idiopathic hypereosinophilic syndrome [4B00.1Z] Neutrophilia, unspecified Also known as: Neutrophilia, unspecified \| Neutrophilia \| Disorders with increased neutrophil counts [3A20.5] Evans syndrome Definition: Evans syndrome is characterised by the association of autoimmune haemolytic anaemia with another haematological anomaly. The thrombocytopaenia may precede, occur concurrently with, or secondary to the autoimmune haemolytic anaemia. Also known as: Evans syndrome [EC20.31] Focal palmoplantar keratodermas Definition: Palmoplantar keratoderma in which there is focal epidermal thickening with areas of normal intervening palmar and plantar skin. Also known as: Focal palmoplantar keratodermas \| Non-syndromic nummular or linear palmoplantar keratodermas \| Striate palmoplantar keratoderma \| Keratoderma palmoplantaris striata \| Brunauer-Fuhs-Siemens keratoderma === GRAPH WALKS === --- Walk 1 --- [QF21] Difficulty or need for assistance with general life tasks or life management --PARENT--> [?] Difficulty or need for assistance with activities Def: Identifies activities for which the person needs assistance or has such difficulty with, that it affects their need for health services or their treatment.... --EXCLUDES--> [?] Dependence on enabling machines or devices --- Walk 2 --- [QF21] Difficulty or need for assistance with general life tasks or life management --PARENT--> [?] Difficulty or need for assistance with activities Def: Identifies activities for which the person needs assistance or has such difficulty with, that it affects their need for health services or their treatment.... --CHILD--> [QF21] Difficulty or need for assistance with general life tasks or life management --- Walk 3 --- [8A83] Other primary headache disorder Def: A group of clinically heterogeneous headache disorders, believed to be primary. Although largely unrelated, they fall into four categories: headaches associated with physical exertion; headaches attri... --PARENT--> [?] Headache disorders --PARENT--> [08] Diseases of the nervous system Def: This is a group of conditions characterised as being in or associated with the nervous system.... --- Walk 4 --- [8A83] Other primary headache disorder Def: A group of clinically heterogeneous headache disorders, believed to be primary. Although largely unrelated, they fall into four categories: headaches associated with physical exertion; headaches attri... --PARENT--> [?] Headache disorders --EXCLUDES--> [?] Headache, not elsewhere classified Def: Headache with characteristic features suggesting that it is a unique diagnostic entity, a finding or complaint, but not fulfilling criteria for any of the headache disorders described above.... --- Walk 5 --- [QB42] Dependence on renal dialysis --PARENT--> [?] Dependence on enabling machines or devices --CHILD--> [QB40] Dependence on aspirator --- Walk 6 --- [QB42] Dependence on renal dialysis --EXCLUDES--> [?] Care involving dialysis Def: Care involving dialysis includes the preparation and maintenance of the patient and carer(s) on dialysis whether extracorporeal or peritoneal dialysis. This includes, but is not confined to: education... --CHILD--> [?] Care involving extracorporeal dialysis	[ "[QF21] Difficulty or need for assistance with general life tasks or life management\n --PARENT--> [?] Difficulty or need for assistance with activities\n Def: Identifies activities for which the person needs assistance or has such difficulty with, that it affects their need for health services or their treatment....\n --EXCLUDES--> [?] Dependence on enabling machines or devices", "[QF21] Difficulty or need for assistance with general life tasks or life management\n --PARENT--> [?] Difficulty or need for assistance with activities\n Def: Identifies activities for which the person needs assistance or has such difficulty with, that it affects their need for health services or their treatment....\n --CHILD--> [QF21] Difficulty or need for assistance with general life tasks or life management", "[8A83] Other primary headache disorder\n Def: A group of clinically heterogeneous headache disorders, believed to be primary. Although largely unrelated, they fall into four categories: headaches associated with physical exertion; headaches attri...\n --PARENT--> [?] Headache disorders\n --PARENT--> [08] Diseases of the nervous system\n Def: This is a group of conditions characterised as being in or associated with the nervous system....", "[8A83] Other primary headache disorder\n Def: A group of clinically heterogeneous headache disorders, believed to be primary. Although largely unrelated, they fall into four categories: headaches associated with physical exertion; headaches attri...\n --PARENT--> [?] Headache disorders\n --EXCLUDES--> [?] Headache, not elsewhere classified\n Def: Headache with characteristic features suggesting that it is a unique diagnostic entity, a finding or complaint, but not fulfilling criteria for any of the headache disorders described above....", "[QB42] Dependence on renal dialysis\n --PARENT--> [?] Dependence on enabling machines or devices\n --CHILD--> [QB40] Dependence on aspirator", "[QB42] Dependence on renal dialysis\n --EXCLUDES--> [?] Care involving dialysis\n Def: Care involving dialysis includes the preparation and maintenance of the patient and carer(s) on dialysis whether extracorporeal or peritoneal dialysis. This includes, but is not confined to: education...\n --CHILD--> [?] Care involving extracorporeal dialysis" ]	QF21	Difficulty or need for assistance with general life tasks or life management	[ { "from_icd11": "QF21", "icd10_code": "Z742", "icd10_title": "Need for assistance at home and no other household member able to render care" }, { "from_icd11": "QF21", "icd10_code": "Z600", "icd10_title": "Problems of adjustment to life-cycle transitions" }, { "from_icd11": "8A83", "icd10_code": "G44209", "icd10_title": "Tension-type headache, unspecified, not intractable" }, { "from_icd11": "8A83", "icd10_code": "G44221", "icd10_title": "Chronic tension-type headache, intractable" }, { "from_icd11": "8A83", "icd10_code": "G44229", "icd10_title": "Chronic tension-type headache, not intractable" }, { "from_icd11": "8A83", "icd10_code": "G44201", "icd10_title": "Tension-type headache, unspecified, intractable" }, { "from_icd11": "8A83", "icd10_code": "G44219", "icd10_title": "Episodic tension-type headache, not intractable" }, { "from_icd11": "8A83", "icd10_code": "G442", "icd10_title": "Tension-type headache" }, { "from_icd11": "QB42", "icd10_code": "Z992", "icd10_title": "Dependence on renal dialysis" }, { "from_icd11": "3B63.1Z", "icd10_code": "D473", "icd10_title": "Essential (hemorrhagic) thrombocythemia" }, { "from_icd11": "3B64.Z", "icd10_code": "D6942", "icd10_title": "Congenital and hereditary thrombocytopenia purpura" }, { "from_icd11": "3B64.Z", "icd10_code": "D6941", "icd10_title": "Evans syndrome" }, { "from_icd11": "3B64.Z", "icd10_code": "D6949", "icd10_title": "Other primary thrombocytopenia" }, { "from_icd11": "3B64.Z", "icd10_code": "D696", "icd10_title": "Thrombocytopenia, unspecified" }, { "from_icd11": "3B64.Z", "icd10_code": "D69", "icd10_title": "Purpura and other hemorrhagic conditions" } ]	Z742	Need for assistance at home and no other household member able to render care
Patient 10 (Tables 1 and 2 ), a 76-year-old female, was referred to the department of neurology in July 2012 because of progressing cognitive decline over the last 12 months, loss of weight, nausea, gait disturbance and tremor. She was seen on May 2011 for the first time by a neurologist with a 3-month history of dull holocephalic headache who ordered a cranial magnetic resonance imaging (MRI) and diagnosed a tension-type headache and a depressive disorder. Treatment with an antidepressant (duloxetine) was started. The patient experienced no improvement and a second examination by another neurologist was undertaken 2 months later. Again no focal neurological signs could be detected. Due to the weight loss, an occult neoplasm was suspected but not detected during an extensive inpatient investigation at a medical department during February 2012; however, the MRI showed bilateral white matter lesions (WML) and an old lacunar lesion located at the left striatum, the latter was not seen in the previous MRI from May 2011. Since the patient also suffered from mild hypertension, vascular encephalopathy was thought to be the cause of the progressive cognitive decline. Extensive neurocognitive testing was carried out in a rehabilitation centre in May 2012 and disclosed a severe decline of attention, memory and executive functions corresponding to subcortical dementia . When the patient was seen for a further diagnostic work-up at the SMZ-Ost-Donauspital in July 2012, the weight was 47 kg and a weight loss of 20 kg was reported over the past year. The gait was insecure with postural instability and with a tendency to fall when turning around. Frontal signs were positive, the voice was quiet, the tonus was mildly elevated and showed a slight hesitancy (“Gegenhalten”), tendon reflexes were brisk, paresis and pyramidal signs missing. There were no signs of ataxia, but a mild bradykinesia. Action tremor was more distinct than a mild resting tremor. Again, neurocognitive testing and gait disturbances were consistent with subcortical dementia . Regarding the mild signs of parkinsonism, dementia with Lewy bodies (DLB) was also suspected but excluded by a dopamine transporter (DAT) scan. Fluorodeoxyglucose positron emission tomography (FDG-PET) demonstrated hypometabolism in the left striatum and in the left frontotemporal cortex . Cerebrospinal fluid (CSF) showed signs of a chronic lymphocytic inflammation. The CSF markers for dementia, total tau protein and phosphor-tau were within the normal range, while beta-amyloid 1-42 and the Innotest-amyloid-tau index (IATI) were found to be below the reference values (beta-amyloid 1-42: 290 pg/ml, reference value > 500 pg/ml; IATI 0.6, reference values > 1). Finally, LNB was diagnosed when further CSF examinations disclosed a highly elevated Bb-specific-AI indicating local intrathecal Bb-specific antibody synthesis (Table 2 ). The patient was treated with 2 g ceftriaxone daily for 3 weeks. Fig. 1 Patient 10, CERAD-Plus test profile a 4 months prior to antibiotic treatment and b 18 months after antibiotic treatment. BNT Boston naming test, CF copy figures, MMSE Mini Mental State Examination, TMT trail making test, VF verbal fluency, WL word list, z‑score (corrected for age, gender and educational level): negative values = worse Fig. 2 Patient 10, neurocognitive assessment. Solid lines : WMS-R subtests; round dots : CERAD-Plus subtests: BNT Boston naming test, TMT Trail making test, VF verbal fluency; dash-dot lines: IP ideomotor praxia, MT Memo test TX: antibiotic treatment; violet field: normal range (z-score −1 to +1); TMT-B z‑score for Pre-TX not shown, calculation due to delayed performance (598 s) not meaningful Table 1 Clinical- and treatment-data of 10 patients with dementia like syndromes due to Lyme neuroborreliosis. Literature search and own cases (Patient number), age at diagnosis (years), sex, (reference) History of tick bite, EM or BS Duration of symptoms prior to TX Weight-loss Nausea, malaise, vomiting Head-ache Voiding dysfunction Tremor Falls, gait disturbance Other focal neurological signs Neuroimaging STT response (1) 60, male EM? 12 m a BS? 11 m a 6 m Nm Nm Nm + Nm + No cCT: normal Nm (2) 74, female No 8 m Nm Nm Nm + Nm + No MRI: ventricular dilatation, patch-like subependymal signal abnormalities, compatible with NPH Yes/no (3) 33, male No 8 m Nm Nm Nm Nm Nm + Pyramidal signs MRI: small hyperintense lesions close to cornu anterior and capsula externa Nm (4) 76, male Nm 6 m + Nm Nm + Nm + No MRI: ventricular dilatation suggesting NPH Nm (5) 83, female Repeated tick bites 6 m 5–7 kg Nm Nm + + + Diplopia MRI: leukoaraiosis, ischemic lesion near left N lentiformis, enlarged ventricles suspicious for NPH Yes/yes (6) 69, female Remote tick bites 12 m Nm Nm Nm + Nm + Babinski, leg weakness MRI: symmetrical WML, meningeal GAD enhancement Nm (7) 75, female No 10 m Nm + + + Nm + Rigor, brady-kinesia MRI: mild periventricular white matter changes, widening of the lateral ventricles, Evans index 0.34 CSF < 10 ml (8) 80, female No 6 m Nm Nm Nm + + (+) No MRI: enlarged ventricles, periventricular lesions Yes/yes (9) 71, female Tick bite EM ? 4 m a 3 m 15 kg + + + + + No MRI: ventricles enlarged, bilateral mesiotemporal atrophy, widened insular cistern, cella media index 3.4. FDG-PET: normal No (10) 77, female No 12 m 20 kg + + Nm + + No MRI: bilateral WML, striatal lacunar lesion. FDG-PET: frontotemporal hypo-metabolism No BS Bannwarth’s syndrome, cCT cranial computed tomography, EM erythema migrans, FDG-PET fluorodeoxyglucose positron emission tomography, GAD gadolinium, MRI magnetic resonance imaging, N nucleus, Nm not mentioned, NPH normal pressure hydrocephalus, STT spinal tap-test a Prior to antibiotic treatment Table 2 Clinical- and treatment-data of 10 patients with dementia like syndromes due to Lyme neuroborreliosis. Literature search and own cases (Patient number), reference TX, follow-up Pre-/post-TX: cognitive impairment, MRI MMSE Pre-/post-TX: other neurocognitive tests Pre-/post-TX: CSF (1), Loss of memory and orientation in time, unable to cope with daily activities Nm Nm Cc: 285/µl; tp: 3600 mg/l 2 w benzylpenicillin IV Mental condition improved, memory poor, needs daily help (1 year after TX) Nm Nm Cc: 88/µl; tp: 700 mg/l AI: 20 (2), Reduced attention and memory, confused, completely dependent 20/30 Digit-symbol (WAIS): 3; CAT: phasic and tonic alertness at least 1 sd below controls Cc: 89/µl; tp: 1910 mg/l; OCB+; AI: 12.6 18 m after 2 w c Memory normal, independent; MRI: idem 29/30 Digit symbol: 11; CAT: >1 sd above controls Cc: 2/µl; tp: 290 mg/l; AI: >12.5 (3), Progressing impairment of memory and concentration Nm Nm Cc: 51/µl; tp: 260 mg/l; OCB+; AI+ 9 m after start of 2 w c Major regression of cognitive impairment Nm Nm Cc: 6/µl; AI+ (4), Amnesia for recent events, disorientation 15/30 Mattis Scale 98/144 Cc: 250/µl; tp: 3000 mg/dl (sic); AI: 19.7 4 w after start of 4? or 12? w c No cognitive impairment after reassessment; MRI: unchanged after 1 m “No impairment in neurocognitive tests” “CSF normal” (12 w after start of TX) (5), Impairment of memory and “wordfinding” 18/30 CERAD: impairment of vf and recall of world list Cc: 69/µl; tp: 3542 mg/l; lactate: 4.8 mmol/l; AI: 31.1 7 m after 2 w c followed by 3 m a No memory problems, no problems with daily activities 27/30 CERAD: vf, recall of world list improved Nd (6), Rapidly progressing dementia, short-term memory severely impaired, disoriented Nm Nm Cc: 44/µl; alb: 3570 mg/l; lactate: 6.1 mmol/l; OCB-; AI: 10.5 5 m after 3 w c No signs of cognitive impairment; MRI: improvement after 5 y Nm Nm Alb: 244 mg/l; AI: 581 (7), Not fully oriented, attention, concentration and short-term memory reduced 20/30 Nm Cc: 30/µl; tp: 1540 mg/l; lactate: 2.9 mmol/l; OCB+; AI: 18.5 a) 3 w, b) 4 m and c) 15 m after 3 w c a), b) and c): complete remission; MRI: unchanged after 15 m a) 28/30 b) 30/30 c) 30/30 Nm Cc: a) 19 b) 3/µl; tp: a) 540 b) 390 mg/l lactate: a) 1.9 b) 1.6 mmol/l OCB (a and b)+; AI: a) 21.1: b) 49.9 (8), Reduced attention and memory, amnesia for recent events, spatiotemporal disorientation 21/30 Nm Cc: 45/µl; tp: 523 mg/l; OCB+; AI: 13.6 2 m after start of 4 w c Complete recovery; MRI: unchanged 29/30 Nm Cc: 7/µl; tp: 370 mg/l; OCB+; AI: 10.9 (9), Spatiotemporal disoriented, reduced attention and memory, optic hallucinations 17/30 IDSR-5: −3.51, IDSR-7: −2.149 (z-score); CDT: 3/9 Cc: 321/µl; tp: 2351 mg/l; OCB+; AI: 7.0 (a) 11 d, (b) 12 m after start of 2 w c a) Improvement in all neuropsychological parameters; b) stable a) 27/30 b) 29/30 a) IDSR 5: +0.733, IDSR 7: −0.280 (z-score); a) CDT; 7/9 Nd (10) case report Attention-, memory-and executive deficits 22/30 CERAD, WMS-R, MT, CDT Cc: 61/µl; tp: 3690 mg/l; OCB+; AI: 7.4 6 w (CSF), 6 m after 3 w c Major improvement; MRI not improved 28/30 Improvement Cc: 17/µl; tp: 1792 mg/l; OCB+; AI: 14.1 a amoxicillin 3 × 500mg/die orally, AI Borrelia burgdorferi -specific antibody index, Alb albumin, c ceftriaxone 2 g/die intravenously, CAT computerized alertness test, Cc cell count, CDT Clock-drawing test, CERAD Consortium to Establish a Registry for Alzheimer’s Disease test, CSF cerebrospinal fluid, d days, IDSR Intercategorical Delayed Selective Reminding test, IV intravenously, m months, MMSE Mini Mental State Examination test, MRI magnetic resonance imaging, MT Memo test, Nd not done, Nm not mentioned, OCB oligoclonal banding, sd standard deviation, tp total protein, TX antibiotic treatment, vf verbal fluency, w weeks, WAIS Wechsler Adult Intelligence Scale, WMS-R Wechsler Memory Scale-Revised, y year Fig. 3 Clock-drawing test ( a ), Mini Mental State Examination test and Intercategorical Delayed Selective Reminding test ( b ) before and after antibiotic therapy. IDSR Intercategorical Delayed Selective Reminding test, MMSE Mini Mental State Examination test, TX antibiotic treatment, violet field : normal range (z-score: −1 to +1), yellow field : first 2 months after antibiotic therapy Fig. 4 Patient 10, neuroimaging. MRI (T2-weighted images) 10 days before ( a ) and 9.5 months after antibiotic therapy ( c ). FDG-PET 2 months before ( b ) and 9.5 months after onset of antibiotic therapy ( d ). Metabolism evaluated by FDG-PET is presented as comparison with age matched healthy controls. Standard deviation is displayed with a red to dark blue scale. White arrows show hypometabolism in the left frontotemporal region before therapy ( b ) which is absent after therapy ( d ). Yellow arrows show left striatal lacunar lesion ( a and b ), not reversible after therapy ( c and d ). Blue arrow show small right thalamic vascular lesion ( c ), not seen in ( a )	4.074219	0.977051	sec[2]/p[0]	en	0.999998	30046879	https://doi.org/10.1007/s00508-018-1361-9	[ "memory", "antibiotic", "impairment", "dementia", "cognitive", "attention", "cerad", "score", "idsr", "loss" ]	[ { "code": "MB21.1Z", "title": "Amnesia, unspecified" }, { "code": "MB21.0", "title": "Age-associated cognitive decline" }, { "code": "6D71", "title": "Mild neurocognitive disorder" }, { "code": "NE60", "title": "Harmful effects of drugs, medicaments or biological substances, not elsewhere classified" }, { "code": "MG50.9Z", "title": "Salmonella resistant to unspecified antibiotic" }, { "code": "MG50.AZ", "title": "Shigella resistant to unspecified antibiotic" }, { "code": "MG50.BZ", "title": "Vibrio resistant to unspecified antibiotic" }, { "code": "QC05.Y", "title": "Other specified prophylactic measures" }, { "code": "9D9Z", "title": "Vision impairment, unspecified" }, { "code": "GB6Z", "title": "Kidney failure, unspecified" } ]	=== ICD-11 CODES FOUND === [MB21.1Z] Amnesia, unspecified Also known as: Amnesia, unspecified \| Amnesia \| disturbance of memory \| lack of memory \| loss of memory [MB21.0] Age-associated cognitive decline Definition: A normative (non-pathological) deterioration of higher cortical functions such as thinking, reasoning, comprehension, calculation, learning, language, and judgment. Also known as: Age-associated cognitive decline \| Age-associated memory impairment \| Age related cognitive decline \| Ageing-related cognitive decline \| Senile degeneration of brain, not elsewhere classified [6D71] Mild neurocognitive disorder Definition: Mild neurocognitive disorder is characterized by mild impairment in one or more cognitive domains relative to that expected given the individual’s age and general premorbid level of cognitive functioning, which represents a decline from the individual’s previous level of functioning. Diagnosis is based on report from the patient, informant, or clinical observation, and is accompanied by objective evidence of impairment by quantified clinical assessment or standardized cognitive testing. Cognitiv Also known as: Mild neurocognitive disorder \| minor neurocognitive disorder \| Postconcussional syndrome \| post-concussion syndrome \| post-concussional syndrome [NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified Also known as: Harmful effects of drugs, medicaments or biological substances, not elsewhere classified \| drugs, medicaments or biological substances, toxicity not elsewhere classified \| adverse drug effects \| drug reaction NOS \| drug allergy NOS Excludes: Alcohol intoxication \| pathological drug intoxication \| hypersensitivity reaction to correctly administered drug [MG50.9Z] Salmonella resistant to unspecified antibiotic Also known as: Salmonella resistant to unspecified antibiotic \| Antibiotic resistant Salmonella [MG50.AZ] Shigella resistant to unspecified antibiotic Also known as: Shigella resistant to unspecified antibiotic \| Antibiotic resistant Shigella [MG50.BZ] Vibrio resistant to unspecified antibiotic Also known as: Vibrio resistant to unspecified antibiotic \| Antibiotic resistant Vibrio [QC05.Y] Other specified prophylactic measures Also known as: Other specified prophylactic measures \| Other prophylactic chemotherapy \| chemoprophylaxis \| prophylactic chemotherapy \| Systemic prophylactic chemotherapy [9D9Z] Vision impairment, unspecified Also known as: Vision impairment, unspecified \| sight impaired \| blindness and low vision \| impaired vision [GB6Z] Kidney failure, unspecified Also known as: Kidney failure, unspecified \| nontraumatic kidney injury \| renal failure NOS \| kidney block \| renal impairment NOS === GRAPH WALKS === --- Walk 1 --- [MB21.1Z] Amnesia, unspecified --PARENT--> [MB21.1] Amnesia Def: An inability to recall past experiences, especially where recall is to be expected.... --CHILD--> [MB21.11] Retrograde amnesia Def: An inability to recall past experiences, especially where recall is to be expected, preceding an event (psychological or physical) presumed to be responsible for the amnesia.... --- Walk 2 --- [MB21.1Z] Amnesia, unspecified --PARENT--> [MB21.1] Amnesia Def: An inability to recall past experiences, especially where recall is to be expected.... --EXCLUDES--> [?] Dissociative disorders Def: Dissociative disorders are characterised by involuntary disruption or discontinuity in the normal integration of one or more of the following: identity, sensations, perceptions, affects, thoughts, mem... --- Walk 3 --- [MB21.0] Age-associated cognitive decline Def: A normative (non-pathological) deterioration of higher cortical functions such as thinking, reasoning, comprehension, calculation, learning, language, and judgment.... --PARENT--> [MB21] Symptoms, signs or clinical findings involving cognition Def: Symptoms, signs, and clinical findings indicative of a disturbance in mental abilities and processes related to attention, memory, judgment, reasoning, problem solving, decision making, or comprehensi... --PARENT--> [?] Mental or behavioural symptoms, signs or clinical findings --- Walk 4 --- [MB21.0] Age-associated cognitive decline Def: A normative (non-pathological) deterioration of higher cortical functions such as thinking, reasoning, comprehension, calculation, learning, language, and judgment.... --PARENT--> [MB21] Symptoms, signs or clinical findings involving cognition Def: Symptoms, signs, and clinical findings indicative of a disturbance in mental abilities and processes related to attention, memory, judgment, reasoning, problem solving, decision making, or comprehensi... --CHILD--> [MB21.2] Anosognosia Def: A lack of awareness or failure to recognize one's own illness, symptoms, or functional deficits, considered to be an aspect of the illness.... --- Walk 5 --- [6D71] Mild neurocognitive disorder Def: Mild neurocognitive disorder is characterized by mild impairment in one or more cognitive domains relative to that expected given the individual’s age and general premorbid level of cognitive function... --PARENT--> [?] Neurocognitive disorders Def: Neurocognitive disorders are characterised by primary clinical deficits in cognitive functioning that are acquired rather than developmental. That is, neurocognitive disorders do not include disorders... --EXCLUDES--> [?] Neurodevelopmental disorders Def: Neurodevelopmental disorders are behavioural and cognitive disorders that arise during the developmental period that involve significant difficulties in the acquisition and execution of specific intel... --- Walk 6 --- [6D71] Mild neurocognitive disorder Def: Mild neurocognitive disorder is characterized by mild impairment in one or more cognitive domains relative to that expected given the individual’s age and general premorbid level of cognitive function... --PARENT--> [?] Neurocognitive disorders Def: Neurocognitive disorders are characterised by primary clinical deficits in cognitive functioning that are acquired rather than developmental. That is, neurocognitive disorders do not include disorders... --CHILD--> [6D70] Delirium Def: Delirium is characterized by a disturbance of attention, orientation, and awareness that develops within a short period of time, typically presenting as significant confusion or global neurocognitive ...	[ "[MB21.1Z] Amnesia, unspecified\n --PARENT--> [MB21.1] Amnesia\n Def: An inability to recall past experiences, especially where recall is to be expected....\n --CHILD--> [MB21.11] Retrograde amnesia\n Def: An inability to recall past experiences, especially where recall is to be expected, preceding an event (psychological or physical) presumed to be responsible for the amnesia....", "[MB21.1Z] Amnesia, unspecified\n --PARENT--> [MB21.1] Amnesia\n Def: An inability to recall past experiences, especially where recall is to be expected....\n --EXCLUDES--> [?] Dissociative disorders\n Def: Dissociative disorders are characterised by involuntary disruption or discontinuity in the normal integration of one or more of the following: identity, sensations, perceptions, affects, thoughts, mem...", "[MB21.0] Age-associated cognitive decline\n Def: A normative (non-pathological) deterioration of higher cortical functions such as thinking, reasoning, comprehension, calculation, learning, language, and judgment....\n --PARENT--> [MB21] Symptoms, signs or clinical findings involving cognition\n Def: Symptoms, signs, and clinical findings indicative of a disturbance in mental abilities and processes related to attention, memory, judgment, reasoning, problem solving, decision making, or comprehensi...\n --PARENT--> [?] Mental or behavioural symptoms, signs or clinical findings", "[MB21.0] Age-associated cognitive decline\n Def: A normative (non-pathological) deterioration of higher cortical functions such as thinking, reasoning, comprehension, calculation, learning, language, and judgment....\n --PARENT--> [MB21] Symptoms, signs or clinical findings involving cognition\n Def: Symptoms, signs, and clinical findings indicative of a disturbance in mental abilities and processes related to attention, memory, judgment, reasoning, problem solving, decision making, or comprehensi...\n --CHILD--> [MB21.2] Anosognosia\n Def: A lack of awareness or failure to recognize one's own illness, symptoms, or functional deficits, considered to be an aspect of the illness....", "[6D71] Mild neurocognitive disorder\n Def: Mild neurocognitive disorder is characterized by mild impairment in one or more cognitive domains relative to that expected given the individual’s age and general premorbid level of cognitive function...\n --PARENT--> [?] Neurocognitive disorders\n Def: Neurocognitive disorders are characterised by primary clinical deficits in cognitive functioning that are acquired rather than developmental. That is, neurocognitive disorders do not include disorders...\n --EXCLUDES--> [?] Neurodevelopmental disorders\n Def: Neurodevelopmental disorders are behavioural and cognitive disorders that arise during the developmental period that involve significant difficulties in the acquisition and execution of specific intel...", "[6D71] Mild neurocognitive disorder\n Def: Mild neurocognitive disorder is characterized by mild impairment in one or more cognitive domains relative to that expected given the individual’s age and general premorbid level of cognitive function...\n --PARENT--> [?] Neurocognitive disorders\n Def: Neurocognitive disorders are characterised by primary clinical deficits in cognitive functioning that are acquired rather than developmental. That is, neurocognitive disorders do not include disorders...\n --CHILD--> [6D70] Delirium\n Def: Delirium is characterized by a disturbance of attention, orientation, and awareness that develops within a short period of time, typically presenting as significant confusion or global neurocognitive ..." ]	MB21.1Z	Amnesia, unspecified	[ { "from_icd11": "MB21.1Z", "icd10_code": "R413", "icd10_title": "Other amnesia" }, { "from_icd11": "MB21.0", "icd10_code": "R4189", "icd10_title": "Other symptoms and signs involving cognitive functions and awareness" }, { "from_icd11": "MB21.0", "icd10_code": "R4181", "icd10_title": "Age-related cognitive decline" }, { "from_icd11": "MB21.0", "icd10_code": "R41840", "icd10_title": "Attention and concentration deficit" }, { "from_icd11": "MB21.0", "icd10_code": "R4183", "icd10_title": "Borderline intellectual functioning" }, { "from_icd11": "MB21.0", "icd10_code": "R41842", "icd10_title": "Visuospatial deficit" }, { "from_icd11": "MB21.0", "icd10_code": "R41841", "icd10_title": "Cognitive communication deficit" }, { "from_icd11": "MB21.0", "icd10_code": "R41844", "icd10_title": "Frontal lobe and executive function deficit" }, { "from_icd11": "MB21.0", "icd10_code": "G311", "icd10_title": "Senile degeneration of brain, not elsewhere classified" }, { "from_icd11": "MB21.0", "icd10_code": "R418", "icd10_title": "Other symptoms and signs involving cognitive functions and awareness" }, { "from_icd11": "6D71", "icd10_code": "F067", "icd10_title": "" }, { "from_icd11": "6D71", "icd10_code": "F072", "icd10_title": "" }, { "from_icd11": "NE60", "icd10_code": "T50A95A", "icd10_title": "Adverse effect of other bacterial vaccines, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50Z15A", "icd10_title": "Adverse effect of immunoglobulin, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50Z95A", "icd10_title": "Adverse effect of other vaccines and biological substances, initial encounter" } ]	R413	Other amnesia
Case report 1 A 60-year-old male patient, blind, was transferred to hospital with a diagnosis of mediastinal mass found during chest X-ray. During examination all clinical and laboratory signs of Vitamin K – dependent coagulopathy were diagnosed. Clinical interview concluded that the patient found by touch and was self-administered the tablets of Neodicumarinum (VKA from the group of coumarins). The tablets were prescribed to his wife for thrombophlebitis. He had confused these tablets with the nitrates prescribed to him. The hemorrhagic coagulopathy was stopped by the administration of Prothrombin Complex Concentrate and preparation of vitamin K. The mediastinal “mass” entirely resolved. In conclusion the hemo-mediastinum was diagnosed as tumor, mis-diagnosing the hemorrhagic syndrome signs. Case report 2 The patient K., 45, was hospitalized at the Amur Regional Clinical Hospital on 04.10.2011, due to massive sub dermal and endermic hematomas, bleeding gums and nasal bleeding. The patient reported that he had originally noticed skin hematomas and nasal and dermal bleedings in June, 2010. He was hospitalized at the therapeutic department of the city hospital where increased A-PPT up to 62.5 s was found (physiological range up to 35 s), a prolongation of the prothrombin time to 45.5 s and INR = 6. The coagulation was not studied in more details. The reason of coagulation failed to be determined: the patient categorically denied the administration of indirect anticoagulants; hepatic pathology, gall-bladder pathology and pathology of the intestinal tract were excluded. “DIC-syndrome of unknown etiology” was diagnosed. The patient received transfusions of fresh frozen plasma. It quickly led to the amelioration of the hemorrhagic syndrome and to the normalization of the coagulogram indexes. In 2 weeks the patient was dismissed from the hospital without signs of hemorrhagic syndrome. At the end of September 2011, the patient noticed again nasal bleeding. In early October the patient was admitted to the hematology department because of progressive multiple hematomas on the limbs and body. During careful questioning, the patient categorically denied the administration of any medicinal drug influencing the blood coagulation system. The patient reported diabetes mellitus type II during the last 5 years and respective treatment with Protaphane, 10 units in the morning and 10 units in the evening, with a background of suitable diet. During the examination of the liver, gall-bladder, gastro-intestinal tract and kidneys, no pathologies were found. The patient categorically denied being beaten (taking into account the location of the hematomas). The clinical blood analysis revealed anaemia (hemoglobulin – 103 g/dl) and erythrocyte sedimentation rate (ESR) of 35 mm/h. According to myelogram, hemablastosis was excluded. The coagulogram assessment revealed the following: ➢ rapid deceleration of I-II phases of the extrinsic blood coagulation ➢ deficiency of the factors of the prothrombin complex – prolongation of the echitoxic time (II factor), lebetoxic time (X factor) and prothrombin time (VII factor) ➢ decreased factor IX ➢ % V, VII, XI factors was not changed ➢ the formation of prothrombinase through the intrinsic coagulation pathway was not affected ➢ the final stage of coagulation was normal ➢ moderate hyperfibrinogenemia ➢ the activity of Antithrombin III and plasminogen was satisfactory ➢ low level of protein C (its synthesis also depends upon Vitamin K). Therefore deficiency of Vitamin K-dependent factors of coagulation and of the inhibitor of coagulation protein C was diagnosed. The patient was further interviewed with the purpose of diagnosing the possible reasons (including criminal reasons) of the severe deficiency of K-dependent factors. To the question about rat-poison use, the patient’s answer was affirmative. From March to June 2011 and from July to September 2011, the patient, a greengrocer, without any professional help and with bare hands used rat-poison in large quantities. The active agent in rat-poison was brodifacoum. The patient reported that he had worked in a closed room, the food-store, and that he consumed himself fruit and vegetables kept in this location. Therefore, brodifacoum poisoning was diagnosed. Upon treatment start with fresh frozen plasma and 1% Vikasolum solution, 1 ml 3 times a day intravenously, the hemorrhagic syndrome recessed in 3 days. During the following month the hemorrhagic syndrome was completely resolved (with the administration of Vikasolum p.o.). Coagulogram indices normalized at the beginning of the second month. Case report 3 A female patient, aged 60, was repeatedly admitted to different hematology units in Moscow, with severe hemorrhagic syndrome for several years. The huge bruises were noticed on the upper skin, except from areas difficult to approach by patient’s hands (the area of the vertebral spine). The round, smooth, painful lesions were palpated in the abdominal cavity (subserosal-haematomas of the intestine) and hematuria was present. All laboratory results of Vitamin K-dependent coagulopathy were present. The calm behavior of the patient, in spite of emergency of the situation as depicted by the medical personnel, made the doctor suspicious. The patient was hospitalized to the intensive care unit without clothes. When the patient’s clothes were examined, a unit package of neo-dicoumarin was discovered. The therapy with quarantine fresh frozen plasma and Vitamin K preparation led to clinical recovery and normalization of the laboratory results. During conversation with the patient, the attending physician let her know that the medical personnel had recognized the cause of her illness and she was recommended psychiatrist assistance. Case report 4 A female patient, aged 54 years, visited doctors for several years because of bruises and hematuria. She was treated repeatedly in the haematology units of the city hospitals in Moscow. During the latest admission, huge “bruises” were observed on the mammary gland skin and on the femora skin. During the examination of her clothes, they found a package of neo-dicoumarin. The treatment with quarantine fresh frozen plasma and Vitamin K-preparations stopped the hemorrhagic syndrome and normalized the coagulogram. The doctor explained delicately the reason of her disease. She was recommended to stop using the dangerous medicinal drugs and to visit a psychiatrist. Case report 5 The patient M, aged 53 years, was admitted to the hematology unit of Amur Regional Clinical Hospital from the district of Amur region with the provisional diagnosis “Hemophilia B”. He complained of “reasonless” bruises on his skin, recidivating nasal bleedings and urine discoloration (the color of the meat slops). He considered himself ill since June 3, 2012, when he first noticed the nasal bleeding, urine with blood mixture, in sort of meat “slops”, hematomas on his lower limbs. The symptomatic therapy was administered and the patient was transferred to the regional hospital. The blood test revealed a moderate post hemorrhagic anemia (erythrocytes 2.8 × 10 12 /l, hemoglobulin 72 g/dl). Erythrocytes abundance was observed in the urine. Coagulogram revealed hypo-coagulation (after performing clotting time according to Louis White, INR, prothrombin time, APPT). A more detailed coagulogram was not done. It was not possible to determine the etiology of such coagulation. After the transfusion with fresh frozen plasma, the nasal bleeding and nephritic bleeding stopped. The results of the coagulogram tests normalized. The physicians reached a diagnosis of DIC-syndrome of undefined etiology. The patient was discharged from the hospital on 4.07.12 with improvement of his condition; the nasal bleedings and the hemorrhagic syndrome were absent. After 10 days the clinical picture of the hemorrhagic syndrome developed again on the skin and nasal and nephritic bleedings resumed. On 23.07.12 the patient came to the Amur Advisory Clinic. The coagulogram’s analysis revealed the increase of APPT to 60 s., PTI – 40 s., INR to 5.3 and decrease of IX blood coagulation factor (Christmas factor). He was sent to the hematology unit with the provisional diagnosis “Hemophilia B”. The elderly age of the patient, absence of hereditary history, high tolerability of the physical activity, absence of the obvious bleeding from the traumas, INR increase allowed to exclude immediately the diagnosis Hemophilia B. In the hematology unit of the Amur Regional Clinical Hospital an expanded coagulogram was firstly asked. The coagulogram conclusion was the following: rapid deceleration of I-II phases of extrinsic blood coagulation; factor deficiency of prothrombin-converting complex – the prolongation of the echitox time (II factor), lebetox time (X factor) and prothrombin time (VII factor), the quantity of factor IX was decreased; the percentage composition of factors V, VIII, XI was within normal limits; the formation of prothrombinase on the intrinsic coagulation pathway was not damaged; the final stage of coagulation was in the norm; the activity of antithrombin III and plasminogen was satisfactory; a low level of protein C. It was diagnosed the deficiency of Vitamin K-dependent factors of coagulation and coagulations inhibitor protein C. A light severe anemia was observed (hemoglobulin – 102 GM/DL; erythrocytes 3.2 × 10 9 /l; leucocytes – 9.2 × 10 9 /l, thrombocytes -250 × 10 9 /l). According to the myelogram, hemablastosis was excluded. The biochemical analysis of the blood was within normal limits. There were erythrocytes throughout the urine. According to all these results vitamin K-dependent coagulopathy was diagnosed. The thorough questioning of the patient about possible reasons of coagulopathy including criminal motives did not lead to positive results, the patient categorically refused to admit VKA consumption and work with any rat-poison. At liver, gastro-intestinal tract and kidneys examination, pathology associated with the said coagulopathy was not revealed. A good clinical course was achieved with the use of PCC (Protromplex 600) and Vitamin K preparations. On the third day of the treatment, the nasal and nephritic bleedings stopped, new hematomas stopped occurring on the skin. After a month the hemorrhagic syndrome completely ended (on the background of administration of Vitamin K) and coagulogram indices normalized. The patient was discharged but physicians recorded his place of residence. As it was found out later, the coagulopathy had criminal origin. One of his relatives added rodenticide containing brodifacoum into the patient’s meal.	3.863281	0.983398	sec[2]/p[0]	en	0.999998	28416008	https://doi.org/10.1186/s40199-017-0175-z	[ "coagulation", "hemorrhagic", "vitamin", "coagulogram", "factor", "nasal", "time", "blood", "coagulopathy", "diagnosed" ]	[ { "code": "3B4Z", "title": "Coagulation defects, unspecified" }, { "code": "3B21.Z", "title": "Haemorrhagic disorder due to unspecified circulating anticoagulants or coagulation factors" }, { "code": "3B6Z", "title": "Coagulation defects, purpura or other haemorrhagic or related conditions, unspecified" }, { "code": "MA18.3", "title": "Abnormal coagulation profile" }, { "code": "NE60", "title": "Harmful effects of drugs, medicaments or biological substances, not elsewhere classified" }, { "code": "MG27", "title": "Haemorrhage, not elsewhere classified" }, { "code": "FB32.Y", "title": "Other specified disorders of muscles" }, { "code": "FA36.0", "title": "Effusion of joint containing blood" }, { "code": "JA41.Z", "title": "Antepartum haemorrhage, unspecified" }, { "code": "5B7Z", "title": "Unspecified undernutrition" } ]	=== ICD-11 CODES FOUND === [3B4Z] Coagulation defects, unspecified Also known as: Coagulation defects, unspecified \| blood clotting disturbance \| blood clotting defect \| blood clotting factor deficiency \| clotting abnormality [3B21.Z] Haemorrhagic disorder due to unspecified circulating anticoagulants or coagulation factors Also known as: Haemorrhagic disorder due to unspecified circulating anticoagulants or coagulation factors \| Haemorrhagic disorder due to circulating anticoagulants or coagulation factors inhibitors \| acquired coagulation factor inhibitor disorder \| acquired inhibitor of coagulation \| antithrombinaemia [3B6Z] Coagulation defects, purpura or other haemorrhagic or related conditions, unspecified Also known as: Coagulation defects, purpura or other haemorrhagic or related conditions, unspecified \| Haemorrhagic condition, unspecified \| unspecified hemorrhagic conditions \| haemorrhagic disease NOS \| haemorrhage diathesis [MA18.3] Abnormal coagulation profile Also known as: Abnormal coagulation profile \| raised INR - [international normalized ratio] \| subtherapeutic INR \| supratherapeutic INR [NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified Also known as: Harmful effects of drugs, medicaments or biological substances, not elsewhere classified \| drugs, medicaments or biological substances, toxicity not elsewhere classified \| adverse drug effects \| drug reaction NOS \| drug allergy NOS Excludes: Alcohol intoxication \| pathological drug intoxication \| hypersensitivity reaction to correctly administered drug [MG27] Haemorrhage, not elsewhere classified Definition: Bleeding or escape of blood from a vessel. Also known as: Haemorrhage, not elsewhere classified \| arterial haemorrhage \| bleeding \| extravasation of blood \| Haemorrhage NOS Excludes: Obstetric haemorrhage \| Haemorrhage or haematoma complicating a procedure, not elsewhere classified \| Fetal blood loss [FB32.Y] Other specified disorders of muscles Also known as: Other specified disorders of muscles \| Muscle wasting or atrophy, not elsewhere classified \| muscle wasting \| muscle wasting disorder \| Sarcopenia [FA36.0] Effusion of joint containing blood Also known as: Effusion of joint containing blood \| bleeding into joint \| hemarthrosis, site unspecified \| haemarthrosis \| joint haemorrhage Includes: haemarthrosis Excludes: Dislocation or strain or sprain of unspecified body region [JA41.Z] Antepartum haemorrhage, unspecified Also known as: Antepartum haemorrhage, unspecified \| Antepartum haemorrhage \| accidental antepartum haemorrhage \| antepartum haemorrhage NOS \| APH - [antepartum haemorrhage] [5B7Z] Unspecified undernutrition Also known as: Unspecified undernutrition \| Malnutrition NOS \| nutritional deficiency NOS \| nutritional depletion NOS \| severe malnutrition NOS === GRAPH WALKS === --- Walk 1 --- [3B4Z] Coagulation defects, unspecified --PARENT--> [?] Coagulation defects --CHILD--> [3B4Z] Coagulation defects, unspecified --- Walk 2 --- [3B4Z] Coagulation defects, unspecified --PARENT--> [?] Coagulation defects --CHILD--> [3B4Z] Coagulation defects, unspecified --- Walk 3 --- [3B21.Z] Haemorrhagic disorder due to unspecified circulating anticoagulants or coagulation factors --PARENT--> [3B21] Haemorrhagic disorder due to circulating anticoagulants or coagulation factors inhibitors Def: A disease caused by anticoagulants present in the body that prevent the blood from clotting normally. This disease is characterised by abnormalities in blood clotting. This disease may present with pr... --CHILD--> [3B21.Y] Haemorrhagic disorder due to other specified circulating anticoagulants or coagulation factors --- Walk 4 --- [3B21.Z] Haemorrhagic disorder due to unspecified circulating anticoagulants or coagulation factors --PARENT--> [3B21] Haemorrhagic disorder due to circulating anticoagulants or coagulation factors inhibitors Def: A disease caused by anticoagulants present in the body that prevent the blood from clotting normally. This disease is characterised by abnormalities in blood clotting. This disease may present with pr... --CHILD--> [3B21.1] Haemorrhage due to factor Xa inhibitor Def: A disease caused by factor Xa inhibitor that affects normal coagulation of the blood. This disease is characterised by inability of the blood to coagulate leading to bleeding. Confirmation is by ident... --- Walk 5 --- [3B6Z] Coagulation defects, purpura or other haemorrhagic or related conditions, unspecified --PARENT--> [?] Coagulation defects, purpura or other haemorrhagic or related conditions Def: A condition caused by determinants arising during the antenatal period, after birth or by genetically inherited factors, leading to coagulation defects. This condition is characterised by increased br... --CHILD--> [?] Fibrinolytic defects Def: A disease caused by determinants arising during the antenatal period, after birth or genetically inherited factors, affecting the fibrinolysis system which prevents blood clots from growing and becomi... --- Walk 6 --- [3B6Z] Coagulation defects, purpura or other haemorrhagic or related conditions, unspecified --PARENT--> [?] Coagulation defects, purpura or other haemorrhagic or related conditions Def: A condition caused by determinants arising during the antenatal period, after birth or by genetically inherited factors, leading to coagulation defects. This condition is characterised by increased br... --PARENT--> [03] Diseases of the blood or blood-forming organs Def: This chapter includes diseases of the blood as well as diseases of blood forming organs....	[ "[3B4Z] Coagulation defects, unspecified\n --PARENT--> [?] Coagulation defects\n --CHILD--> [3B4Z] Coagulation defects, unspecified", "[3B4Z] Coagulation defects, unspecified\n --PARENT--> [?] Coagulation defects\n --CHILD--> [3B4Z] Coagulation defects, unspecified", "[3B21.Z] Haemorrhagic disorder due to unspecified circulating anticoagulants or coagulation factors\n --PARENT--> [3B21] Haemorrhagic disorder due to circulating anticoagulants or coagulation factors inhibitors\n Def: A disease caused by anticoagulants present in the body that prevent the blood from clotting normally. This disease is characterised by abnormalities in blood clotting. This disease may present with pr...\n --CHILD--> [3B21.Y] Haemorrhagic disorder due to other specified circulating anticoagulants or coagulation factors", "[3B21.Z] Haemorrhagic disorder due to unspecified circulating anticoagulants or coagulation factors\n --PARENT--> [3B21] Haemorrhagic disorder due to circulating anticoagulants or coagulation factors inhibitors\n Def: A disease caused by anticoagulants present in the body that prevent the blood from clotting normally. This disease is characterised by abnormalities in blood clotting. This disease may present with pr...\n --CHILD--> [3B21.1] Haemorrhage due to factor Xa inhibitor\n Def: A disease caused by factor Xa inhibitor that affects normal coagulation of the blood. This disease is characterised by inability of the blood to coagulate leading to bleeding. Confirmation is by ident...", "[3B6Z] Coagulation defects, purpura or other haemorrhagic or related conditions, unspecified\n --PARENT--> [?] Coagulation defects, purpura or other haemorrhagic or related conditions\n Def: A condition caused by determinants arising during the antenatal period, after birth or by genetically inherited factors, leading to coagulation defects. This condition is characterised by increased br...\n --CHILD--> [?] Fibrinolytic defects\n Def: A disease caused by determinants arising during the antenatal period, after birth or genetically inherited factors, affecting the fibrinolysis system which prevents blood clots from growing and becomi...", "[3B6Z] Coagulation defects, purpura or other haemorrhagic or related conditions, unspecified\n --PARENT--> [?] Coagulation defects, purpura or other haemorrhagic or related conditions\n Def: A condition caused by determinants arising during the antenatal period, after birth or by genetically inherited factors, leading to coagulation defects. This condition is characterised by increased br...\n --PARENT--> [03] Diseases of the blood or blood-forming organs\n Def: This chapter includes diseases of the blood as well as diseases of blood forming organs...." ]	3B4Z	Coagulation defects, unspecified	[ { "from_icd11": "3B4Z", "icd10_code": "D688", "icd10_title": "Other specified coagulation defects" }, { "from_icd11": "3B4Z", "icd10_code": "D689", "icd10_title": "Coagulation defect, unspecified" }, { "from_icd11": "3B4Z", "icd10_code": "D699", "icd10_title": "Hemorrhagic condition, unspecified" }, { "from_icd11": "3B4Z", "icd10_code": "D698", "icd10_title": "Other specified hemorrhagic conditions" }, { "from_icd11": "3B4Z", "icd10_code": "D65-D69", "icd10_title": "" }, { "from_icd11": "3B4Z", "icd10_code": "D69", "icd10_title": "Purpura and other hemorrhagic conditions" }, { "from_icd11": "3B21.Z", "icd10_code": "D6832", "icd10_title": "Hemorrhagic disorder due to extrinsic circulating anticoagulants" }, { "from_icd11": "3B21.Z", "icd10_code": "D68312", "icd10_title": "Antiphospholipid antibody with hemorrhagic disorder" }, { "from_icd11": "3B21.Z", "icd10_code": "D68318", "icd10_title": "Other hemorrhagic disorder due to intrinsic circulating anticoagulants, antibodies, or inhibitors" }, { "from_icd11": "3B21.Z", "icd10_code": "D68311", "icd10_title": "Acquired hemophilia" }, { "from_icd11": "3B21.Z", "icd10_code": "D6831", "icd10_title": "Hemorrhagic disorder due to intrinsic circulating anticoagulants, antibodies, or inhibitors" }, { "from_icd11": "3B21.Z", "icd10_code": "D683", "icd10_title": "Hemorrhagic disorder due to circulating anticoagulants" }, { "from_icd11": "3B6Z", "icd10_code": "D684", "icd10_title": "Acquired coagulation factor deficiency" }, { "from_icd11": "3B6Z", "icd10_code": "D6861", "icd10_title": "Antiphospholipid syndrome" }, { "from_icd11": "3B6Z", "icd10_code": "D6869", "icd10_title": "Other thrombophilia" } ]	D688	Other specified coagulation defects
Patient 1 is a 70-year-old man with a past medical history of segmental colitis associated with diverticulosis (SCAD) who was diagnosed at the age of 73 with a right vestibular schwannoma and a large bifrontal atypical meningioma. At diagnosis, he was treated with subtotal resection and postoperative proton therapy. Two years later, he presented with recurrent bitemporal extra-cranial soft tissue meningioma treated with resection and radiation therapy. He was then started on pembrolizumab (PD-1 inhibitor) monotherapy and received two doses (Table 1 ). After receiving his second dose of pembrolizumab, he developed intermittent rectal bleeding without urgency, diarrhea, abdominal pain, cramping or bloating. He underwent a colonoscopy that showed endoscopic and histologic features of active colitis . Based on these findings, he was treated with prednisone 60 mg, azithromycin, and metronidazole for a 7-day course that led to symptomatic improvement. With tapering of the steroids, his rectal bleeding recurred which prompted a repeat flexible sigmoidoscopy that demonstrated persistent inflammation. He then received infliximab (5 mg/kg) concurrently with prednisone 50 mg which led to resolution of his symptoms after one infusion and successful rapid tapering of prednisone. Staging imaging after 2 months off pembrolizumab therapy (due to irEC) showed progression of his intracranial tumor and extracranial metastases. After an interruption of ICI for 4 months, it was decided to restart pembrolizumab with concurrent infliximab therapy. He subsequently received a total of twelve doses of pembrolizumab concurrently with infliximab (5mg/kg every 6 weeks, Table 2 ) over the course of 10.5 months. He did not experience any other irAEs or worsening rectal bleeding and a repeat flexible sigmoidoscopy showed mild active chronic colitis. Staging scans at that point showed stable intracranial and extracranial disease. Then, he developed Clostridium difficile colitis. He was treated with oral vancomycin to which he appropriately responded. However, after a few days of normal bowel movements, he started having loose bloody bowel movements and abdominal pain prompting an admission to the hospital. During that admission, he tested negative for Clostridium difficile and underwent a flexible sigmoidoscopy that showed severe colonic inflammation thought to be due to irEC. He received vancomycin, high dose intravenous steroids followed by oral steroids, and one infusion of infliximab (10 mg/kg) leading to symptom improvement. His steroids were tapered but therapy with pembrolizumab was discontinued. One month later, he developed retroperitoneal bleeding and was transitioned to hospice care. Table 1 Patient characteristics, ICI treatment history, symptomatology, and endoscopy findings Patient Age Sex Malignancy History of other ICI exposure ICI type and dose Days (doses) to onset of symptoms post ICI Diarrhea grade Other symptoms Colitis grade Endoscopic features Histopathologic features 1 75 M Meningioma None Pembrolizumab Dose: 3 mg/kg Frequency: every 3 weeks 39 days (2) 1 None 2 Colonoscopy: Sigmoid colon: localized moderate inflammation characterized by altered vascularity, congestion (edema), friability and granularity Colonoscopy: - Ileum: mucosa with hyperplastic Peyer’s patches and no diagnostic abnormality - Ascending colon: mucosa with lymphoid aggregate and no diagnostic abnormality - Sigmoid colon: moderately active colitis with neutrophilic cryptitis and crypt abscesses 2 58 F Colon - Pembrolizumab (stopped 2 years prior to current ICI): no adverse effects but disease progression Ipilimumab/Nivolumab Dose: Ipilimumab-1 mg/kg, Nivolumab- 240 mg (3 mg/kg) Frequency: combined every 6 weeks (4 doses total) followed by nivolumab alone every 2 weeks 8 days (1) 2 Abdominal pain 2 Upper endoscopy: - Gastric antrum: diffuse moderately erythematous mucosa without bleeding - Duodenum: an acquired benign-appearing, intrinsic moderate stenosis in the first portion of the duodenum Upper endoscopy: - Gastric antrum/fundus/body: active chronic gastritis - Duodenum: mucosa with ulceration, crypt dropout, marked expansion of lamina propria with prominent eosinophils and acute inflammation - Duodenal stricture: mucosa with mild expansion of the lamina propria 3 70 F Melanoma - PD-L1 inhibitor (as a part of a clinical trial): for a total of 1 year (stopped 3 years prior to current ICI). No adverse events but disease recurrence - Pembrolizumab: 200 mg 3 (mg/kg) every 3 weeks for total of 8 doses (stopped 1 year prior to current ICI): no adverse events but disease progression Ipilimumab Dose: 3 mg/kg Frequency: every 3 weeks 35 days (2) 2 Nausea, vomiting 2 Upper Endoscopy: - Stomach: normal - Duodenum: diffuse moderately scalloped mucosa Flexible Sigmoidoscopy: - Colon: examined portion was normal Upper Endoscopy: - Duodenum: diffuse active duodenitis with villous blunting, expansion of the lamina propria with mixed inflammation, and reactive epithelial changes - Stomach: antral mucosa with edema and mild patchy inflammation Flexible Sigmoidoscopy: - Colon: normal 4 73 M Melanoma Atezolizumab (in combination with cobimetinib): total of 13 cycles (stopped 2 weeks prior to current ICI) Ipilimumab/Nivolumab Dose: Ipilimumab-3 mg/kg, Nivolumab-1 mg/kg Frequency: combined every 3 weeks 11 days (1) 2 Nausea, vomiting, abdominal pain 2 Upper Endoscopy: - Stomach: non-bleeding erosive gastropathy - Duodenum: diffuse mildly congested mucosa without active bleeding Colonoscopy: - Sigmoid and descending colon: discontinuous areas of nonbleeding ulcerated mucosa with no stigmata of recent bleeding Upper Endoscopy: - Stomach: active gastritis with small stromal granuloma in antrum. Active gastritis with stromal histiocytes in the body - Duodenum: active duodenitis with villous injury Colonoscopy: - Descending colon: focal active colitis with stromal histiocytes - Colon and sigmoid ulcers: severely active colitis with ulceration 5 79 F SCC None Cemiplimab Dose: 350 mg Frequency: every 3 weeks 14 (1 dose) 1 Nausea, vomiting 2 Upper Endoscopy: - Stomach: Non-bleeding erosive gastropathy - Duodenum: normal Flexible Sigmoidoscopy: - Colon: Inflammation characterized by congestion (edema), erythema and granularity Upper Endoscopy: - Stomach: reactive gastropathy and intestinal metaplasia - Duodenum: normal Flexible Sigmoidoscopy: - Colon: mucosa with mildly increased cellularity of the lamina propria and epithelial injury. Focal acute inflammation is also noted, but there is no increase in apoptosis. Fig. 1 Infliximab and pembrolizumab for segmental colitis in meningioma. a – d (Images taken from the sigmoid colon during endoscopic evaluation. a Diagnosis of recurrent SCAD. b After completion of antibiotics and on prednisone. c Infliximab and prednisone co-treatment. d Infliximab and pembrolizumab co-treatment Table 2 IrEC management and outcomes Patient ICI type/dose Initial management Number of steroid tapering attempts Infliximab Dose-frequency Doses of infliximab to clinical remission Doses of ICI concurrently administered with infliximab Follow up endoscopy on concurrent treatment (months) Recurrence # of months of follow-up on ICI/on concurrent therapy Disease progression/Follow up 1 Pembrolizumb Dose: 3 mg/kg Frequency: every 3 weeks Prednisone 40 mg > 60 mg PO daily> taper failure +azithromycin + metronidazole 2 5 mg/kg - every 2 weeks for first 2 doses then every 6 weeks 1 12 Flexible Sigmoidoscopy (4 months): Endoscopic: erythematous mucosa in sigmoid, normal colon for 40 cm Histologic: Mild active chronic colitis Patient developed Clostridium difficile colitis then flare of irEC. Treatment: - Infliximab 10 mg/kg - Methylprednisolone 1 mg/kg BID then prednisone 75 mg PO BID followed by a taper - PO vancomycin - Immunotherapy was discontinued 14.5/10.5 - Staging scans after concurrent therapy (12 doses) showed stable disease - Developed retroperitoneal bleed and was transitioned to hospice care 2 Ipilimumab/Nivolumab Dose: Ipilimumab-1 mg/kg, Nivolumab- 240 mg (3 mg/kg) Frequency: combined every 6 weeks (4 doses total) followed by nivolumab alone every 2 weeks Prednisone 60 mg PO daily>taper 1 5 mg/kg - every 2 weeks for first 2 doses then every 4 weeks 1 3 doses of (ipilimuab+Nivolumab) and 12 doses of nivolumab alone Upper endoscopy (3 months): Endoscopic: - Gastric body: localized mild inflammation characterized by erythema and friability - Duodenum: an acquired benign-appearing, intrinsic moderate stenosis was found in the second portion of the duodenum associated with a small erosion Histologic: - Gastric body: lymphocytic involvement of gastric pits - Duodenum: no diagnostic abnormality - Duodenal stricture: ulceration and expansion of lamina propria by mononuclear cells No 12/7.5 - Staging scans after concurrent therapy (15 doses) showed stable disease and patient continues concurrent therapy - Developed mucositis/stomatitis that is being managed conservatively 3 Ipilimumab Dose: 3 mg/kg Frequency: every 3 weeks Methylprednisolone 1 mg/kg IV twice daily >taper failure 1 5 mg/kg - every 4 weeks 1 2 Not done No 6.5/3.5 - Staging scans showed stable bulk of disease after concurrent therapy (2 doses) with ongoing slight progression in one metastatic lesion in the lung - Developed skin rash (ipilimumab cutaneous toxicity) that was managed successfully with topical steroids 4 Ipilimumab/Nivolumab Dose: Ipilimumab-3 mg/kg, Nivolumab-1 mg/kg Frequency: combined every 3 weeks Prednisone 60 mg daily>taper failure 1 5 mg/kg - every 4 weeks 1 3 Upper endoscopy (1 month): Endoscopic/histologic - Stomach: normal/chronic inactive gastritis - Duodenum Normal/normal Colonoscopy (1 month): - Sigmoid/transverse colon ulcers: fragments of colonic mucosa with crypt architectural disarray and mildly increased cellularity of the lamina propria. Colonoscopy (3 months) - Colonic mucosa with scattered crypt epithelial apoptosis and minimal crypt architectural distortion No 5/3 - Staging scans showed interval progression of his disease in the chest, abdomen and pelvis. 5 Cemiplimab Dose: 350 mg Frequency: every 3 weeks Prednisone 60 mg daily>taper failure 1 5 mg/kg - once 1 2 Not done No 4/2.5 - Staging scans demonstrated interval decrease in the disease burden in the chest and lymph nodes - Patient developed radiation/checkpoint pneumonitis and was treated with high dose oral steroids	3.894531	0.97998	sec[2]/sec[0]/p[0]	en	0.999998	31439050	https://doi.org/10.1186/s40425-019-0711-0	[ "every", "doses", "colon", "mucosa", "duodenum", "active", "endoscopy", "nivolumab", "colitis", "pembrolizumab" ]	[ { "code": "NE60", "title": "Harmful effects of drugs, medicaments or biological substances, not elsewhere classified" }, { "code": "PL11.Y", "title": "Other specified mode of injury or harm associated with a surgical or other medical procedure" }, { "code": "PB28", "title": "Unintentional exposure to or harmful effects of other or unspecified drug, medicament or biological substance" }, { "code": "PH42", "title": "Exposure to or harmful effects of undetermined intent of psychostimulants" }, { "code": "PC99", "title": "Intentional self-harm by exposure to or harmful effects of multiple drugs, medicaments or biological substances" }, { "code": "1A40.0&XA03U9", "title": "Colon inflammation" }, { "code": "DB30.Y&XA03U9", "title": "Obstructed colon" }, { "code": "NB91.81", "title": "Laceration of colon" }, { "code": "DD3Z", "title": "Ischaemic vascular disorders of intestine, unspecified" }, { "code": "DB32.2Z&XA03U9", "title": "Colonic dilatation" } ]	=== ICD-11 CODES FOUND === [NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified Also known as: Harmful effects of drugs, medicaments or biological substances, not elsewhere classified \| drugs, medicaments or biological substances, toxicity not elsewhere classified \| adverse drug effects \| drug reaction NOS \| drug allergy NOS Excludes: Alcohol intoxication \| pathological drug intoxication \| hypersensitivity reaction to correctly administered drug [PL11.Y] Other specified mode of injury or harm associated with a surgical or other medical procedure Also known as: Other specified mode of injury or harm associated with a surgical or other medical procedure \| Other specified mode, as mode of injury or harm \| Overdose of radiation given during therapy \| overdose of radiation \| radiation overdose [PB28] Unintentional exposure to or harmful effects of other or unspecified drug, medicament or biological substance Also known as: Unintentional exposure to or harmful effects of other or unspecified drug, medicament or biological substance \| accidental overdose of other or unspecified drug, medicament or biological substance \| accidental poisoning by other or unspecified drug, medicament or biological substance \| other or unspecified drug, medicament or biological substance taken in error \| accidental drug overdose [PH42] Exposure to or harmful effects of undetermined intent of psychostimulants Also known as: Exposure to or harmful effects of undetermined intent of psychostimulants \| Harmful effects of or exposure to noxious substances, drugs, medicaments or biological substances, psychostimulants, central nervous system stimulants, not elsewhere classified, undetermined intent \| Harmful effects of or exposure to noxious substances, drugs, medicaments or biological substances, psychostimulants, analeptics, undetermined intent \| Harmful effects of or exposure to noxious substances, drugs, medicaments or biological substances, psychostimulants, opioid receptor antagonists, undetermined intent \| Harmful effects of or exposure to noxious substances, drugs, medicaments or biological substances, psychostimulants, caffeine, undetermined intent [PC99] Intentional self-harm by exposure to or harmful effects of multiple drugs, medicaments or biological substances Also known as: Intentional self-harm by exposure to or harmful effects of multiple drugs, medicaments or biological substances \| Intentional self-poisoning by exposure to or harmful effects of multiple drugs, medicaments or biological substances \| Intentional overdose of multiple drugs, medicaments or biological substances \| Deliberatley took an excessive amount of multiple drugs \| Polydrug overdose [NB91.81] Laceration of colon Definition: A tear or wound of large intestine. Also known as: Laceration of colon [DD3Z] Ischaemic vascular disorders of intestine, unspecified Also known as: Ischaemic vascular disorders of intestine, unspecified \| Vascular disorder of intestine, not elsewhere classified \| vascular disorder of intestine \| vascular bowel disease \| ischaemic gut NOS === GRAPH WALKS === --- Walk 1 --- [NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified --EXCLUDES--> [?] Allergic or hypersensitivity conditions Def: Allergy is a hypersensitivity reaction initiated by proven immunologic mechanisms. Hypersensitivity is defined as conditions clinically resembling allergy that cause objectively reproducible symptoms... --CHILD--> [?] Allergic or hypersensitivity disorders involving the eye Def: Allergic or hypersensitivity disorders involving the eye includes several clinically different conditions that can be considered as hypersensitivity disorders of the ocular surface. The classification... --- Walk 2 --- [NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified --EXCLUDES--> [?] Allergic or hypersensitivity conditions Def: Allergy is a hypersensitivity reaction initiated by proven immunologic mechanisms. Hypersensitivity is defined as conditions clinically resembling allergy that cause objectively reproducible symptoms... --CHILD--> [?] Allergic or hypersensitivity disorders involving skin or mucous membranes Def: Allergic or hypersensitivity disorders involving the skin and mucous includes a heterogeneous group of disorders involving skin and mucous membranes in which either allergy or hypersensitivity play a ... --- Walk 3 --- [PL11.Y] Other specified mode of injury or harm associated with a surgical or other medical procedure --PARENT--> [PL11] Mode of injury or harm associated with a surgical or other medical procedure --EXCLUDES--> [?] Mode of injury or harm associated with exposure to a drug, medicament or biological substance --- Walk 4 --- [PL11.Y] Other specified mode of injury or harm associated with a surgical or other medical procedure --PARENT--> [PL11] Mode of injury or harm associated with a surgical or other medical procedure --CHILD--> [PL11.1] Burn arising during procedure, as mode of injury or harm Def: A burn occurs when tissue is damaged by heat, electricity or fire. It can occur, for example, as the direct result of cautery equipment, warming efforts, or because of a fire.... --- Walk 5 --- [PB28] Unintentional exposure to or harmful effects of other or unspecified drug, medicament or biological substance --PARENT--> [?] Unintentional exposure to or harmful effects of drugs, medicaments or biological substances --CHILD--> [PB21] Unintentional exposure to or harmful effects of sedative hypnotic drugs or other CNS depressants --- Walk 6 --- [PB28] Unintentional exposure to or harmful effects of other or unspecified drug, medicament or biological substance --PARENT--> [?] Unintentional exposure to or harmful effects of drugs, medicaments or biological substances --CHILD--> [PB20] Unintentional exposure to or harmful effects of opioids or related analgesics	[ "[NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified\n --EXCLUDES--> [?] Allergic or hypersensitivity conditions\n Def: Allergy is a hypersensitivity reaction initiated by proven immunologic mechanisms.\n\nHypersensitivity is defined as conditions clinically resembling allergy that cause objectively reproducible symptoms...\n --CHILD--> [?] Allergic or hypersensitivity disorders involving the eye\n Def: Allergic or hypersensitivity disorders involving the eye includes several clinically different conditions that can be considered as hypersensitivity disorders of the ocular surface. The classification...", "[NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified\n --EXCLUDES--> [?] Allergic or hypersensitivity conditions\n Def: Allergy is a hypersensitivity reaction initiated by proven immunologic mechanisms.\n\nHypersensitivity is defined as conditions clinically resembling allergy that cause objectively reproducible symptoms...\n --CHILD--> [?] Allergic or hypersensitivity disorders involving skin or mucous membranes\n Def: Allergic or hypersensitivity disorders involving the skin and mucous includes a heterogeneous group of disorders involving skin and mucous membranes in which either allergy or hypersensitivity play a ...", "[PL11.Y] Other specified mode of injury or harm associated with a surgical or other medical procedure\n --PARENT--> [PL11] Mode of injury or harm associated with a surgical or other medical procedure\n --EXCLUDES--> [?] Mode of injury or harm associated with exposure to a drug, medicament or biological substance", "[PL11.Y] Other specified mode of injury or harm associated with a surgical or other medical procedure\n --PARENT--> [PL11] Mode of injury or harm associated with a surgical or other medical procedure\n --CHILD--> [PL11.1] Burn arising during procedure, as mode of injury or harm\n Def: A burn occurs when tissue is damaged by heat, electricity or fire. It can occur, for example, as the direct result of cautery equipment, warming efforts, or because of a fire....", "[PB28] Unintentional exposure to or harmful effects of other or unspecified drug, medicament or biological substance\n --PARENT--> [?] Unintentional exposure to or harmful effects of drugs, medicaments or biological substances\n --CHILD--> [PB21] Unintentional exposure to or harmful effects of sedative hypnotic drugs or other CNS depressants", "[PB28] Unintentional exposure to or harmful effects of other or unspecified drug, medicament or biological substance\n --PARENT--> [?] Unintentional exposure to or harmful effects of drugs, medicaments or biological substances\n --CHILD--> [PB20] Unintentional exposure to or harmful effects of opioids or related analgesics" ]	NE60	Harmful effects of drugs, medicaments or biological substances, not elsewhere classified	[ { "from_icd11": "NE60", "icd10_code": "T50A95A", "icd10_title": "Adverse effect of other bacterial vaccines, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50Z15A", "icd10_title": "Adverse effect of immunoglobulin, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50Z95A", "icd10_title": "Adverse effect of other vaccines and biological substances, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50A95S", "icd10_title": "Adverse effect of other bacterial vaccines, sequela" }, { "from_icd11": "NE60", "icd10_code": "T50B95A", "icd10_title": "Adverse effect of other viral vaccines, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50A25A", "icd10_title": "Adverse effect of mixed bacterial vaccines without a pertussis component, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50A91A", "icd10_title": "Poisoning by other bacterial vaccines, accidental (unintentional), initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T498X5A", "icd10_title": "Adverse effect of other topical agents, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T48905A", "icd10_title": "Adverse effect of unspecified agents primarily acting on the respiratory system, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T48995A", "icd10_title": "Adverse effect of other agents primarily acting on the respiratory system, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50A15A", "icd10_title": "Adverse effect of pertussis vaccine, including combinations with a pertussis component, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T50B15A", "icd10_title": "Adverse effect of smallpox vaccines, initial encounter" }, { "from_icd11": "NE60", "icd10_code": "T416X3A", "icd10_title": "" }, { "from_icd11": "NE60", "icd10_code": "T419X3A", "icd10_title": "" }, { "from_icd11": "NE60", "icd10_code": "T418X2A", "icd10_title": "" } ]	T50A95A	Adverse effect of other bacterial vaccines, initial encounter
• Case 1: A 49-year-old Sudanese gentleman with a history of bronchial asthma, hypertension, prediabetes, and gout tested positive for COVID-19 on November 24, 2020. He underwent polymerase chain reaction testing as mandatory screening, which was performed upon arrival in Qatar as a part of the preventive measures taken to curb the spread of coronavirus. Upon questioning, he provided a history of headache and fever over the preceding few days along with multiple episodes of vomiting and diarrhea (around 4 times a day). The patient denied any cough, shortness of breath, or sore throat. He was diagnosed with COVID-19 pneumonia and was started on the anti-retroviral favipiravir and transferred to a quarantine facility. No thyroid function tests (TFTs) were conducted during this time. He undertook a TFT in May 2019, which was normal. He subsequently made an uneventful recovery from COVID-19. Two months later, the patient undertook a general checkup to complain of a slight increase in body weight. Here, his TFT revealed a thyroid-stimulating hormone (TSH) value of 33.49 mu/L (normal range reference [NRR] 0.4–4.5 mu/L), and a free tbl4 value of 8 pmol/L (NRR 8–18 pmol/L). Repeat TFTs conducted 6 weeks later revealed a TSH value of 34.22 mu/L and the tbl4 value further dropped to 7.4 pmol/L. At this point, he was referred to our endocrine clinic. When reviewed at our clinic, he denied any history of tiredness, fatigue, sleepiness, or other symptoms of hypothyroidism other than weight gain. He had no family history of goiter or thyroid dysfunction. He was not on any medication that may have caused perturbation of the thyroid functions. On examination, his vital signs were normal. He was clinically euthyroid, with no neck swelling and an unremarkable physical examination. The test results showed TSH 49 mU/L and FT 11 pmol/L. Antithyroid peroxidase antibodies (anti-TPO Ab) were 423 IU/mL (normal < 30) and TSH receptor antibodies TRAb was negative. Neck ultrasound (US) showed heterogeneous thyroid with minimally increased vascularity and a small hyperechoic nodule measuring 5 x 4 mm. The thyroid uptake scan revealed normal morphology and function, except for a cold nodule in the postero-inferior part of the right lobe. After a discussion with the patient, it was decided to adopt the wait-and-see policy. TFT repeated after 6 weeks showed that the TSH value had risen to 61 mIU/L and FT to 4 pmol/L. He was accordingly started on levothyroxine (100 mcg, daily), and his TFT normalized after 6 weeks. • Case 2: A 50-year-old Filipino male, with a medical history of asthma and hypertension, presented with respiratory symptoms and tested positive for COVID-19 infection. His chest X-ray showed bilateral lung infiltrates. He was treated for COVID-19 pneumonia and as per the hospital protocol (azithromycin: 500 mg daily, ceftriaxone 2 mg IV once daily, hydroxychloroquine 400 mg daily, lopinavir/ritonavir 200/50 mg bid, ribavirin, and oseltamivir 150 mg bid). His hospital course was complicated by acute respiratory distress syndrome requiring intensive care unit (ICU) admission. He accordingly received tociluzimab and methylprednisolone, but did not require endotracheal intubation or mechanical ventilation. TFTs were conducted because of persistent tachycardia, which showed TSH of 0.08 mu/L, FT3 of 3.4 pmol/L (NRR 3–6), and FT4 of 23 pmol/L. When TFT was repeated after 6 weeks, it showed resolution of the thyroid dysfunction with a TSH of 0.47 mIU/L and FT4 of 18.8 pmol/L, suggesting “thyroxine thyrotoxicosis” due to COVID-19-related thyroiditis. Subsequent follow-up over 6 months revealed no further abnormality. • Case 3: A 32-year-old Sudanese female patient had hypothyroidism during her adolescence, for which she was treated with levothyroxine until the age of 16 years. She has been an euthyroid since then. She also presented with a history of thyroid nodules in 2016, which was not followed up later. In September 2020, she was diagnosed with COVID-19 following a mild respiratory illness. She made an uneventful recovery, but, after 3 months, in December 2020, she presented with the symptoms of tiredness, fatigue, bilateral hand tremors, palpitations, increased sweating, shortness of breath, and irregular periods. Her physical examination was consistent with a hyperthyroid state, with a small diffuse goiter. TFTs revealed TSH < 0.01 mIU/L, FT4: 72.3 pmol/L, and TRAb 28 U/L (normal < 0.75). A thyroid nuclear uptake scan with technetium revealed an enlarged thyroid, with an overall picture suggestive of diffuse Grave's disease (GD). She was accordingly started on carbimazole 30 mg, daily, along with propranolol (40 mg bid) and she improved. Repeated TFT after 2 months revealed TSH < 0.01 mIU/L, FT3: 7.6 pmol/L, and FT4: 24.0 pmol/L. Subsequent TFTs showed a normal level. She was followed up at the Endocrinology Clinic for her GD, and the latest TFTs conducted in January 2022 showed persistent remission with carbimazole. • Case 4: A 40-year-old Filipina lady with a history of asthma on a salbutamol inhaler was admitted to the hospital with COVID-19 pneumonia of mild to moderate severity. She was accordingly started on COVID-19 treatment as per the hospital's protocol (hydroxychloroquine, oseltamivir, and azithromycin) . She was noted to have persistent tachycardia, and hence TFT was performed, which showed hyperthyroidism with TSH < 0.01 mIU/L, FT3 30.8 pmol/L, and FT4 83.3 pmol/L. Anti-TPO Abs; 494 IU/mL. TRAb was elevated at 8.7 IU/L. She was then started on carbimazole; however, she stopped it after her discharge believing it to be a COVID-19 medication. After 8 months, she presented to the Emergency Department with severe abdominal pain and vomiting. Her examination revealed BP: 211/110 mmHg, heart rate: 136 bpm, a small goiter, but no other signs of hyperthyroidism. Computed tomography of the abdomen showed intestinal obstruction. Laboratory results revealed TSH < 0.01 mIU/L, FT3: 32.9 pmol/L, FT4 >100 pmol/L, and TRAb elevated at 7.7 u/L. Her Bursch Wartofsky's score was 35, and hence she was treated as an impending thyroid storm. Her neck US revealed enlarged thyroid lobes with increased vascularity. The intestinal obstruction was managed conservatively. She improved and was discharged home on carbimazole (20 mg twice daily) and metoprolol (75 mg twice daily). • Case 5: A 40-year-old man was referred to the Endocrine Clinic for hyperthyroidism. He reported symptoms of loss of taste and smell, muscle aches, and pains for 3 months; however, he was not tested for COVID-19. After 2 months, he developed symptoms of weight loss and anxiety and was accordingly referred to the endocrinology clinic. His TSH value was < 0.01 mIU/L and FT4 was 100 pmol/L. He was accordingly started on carbimazole 40 mg/day. After 2 months, his TFTs normalized. The presumptive diagnosis was GD precipitated by COVID-19. • Case 6: A 14-year-old Qatari girl was referred to the endocrine clinic in November 2020 for possible hyperthyroidism. All family, including the patient, suffered mild COVID-19 infection and all made uneventful recovery. She complained of weight loss (around 6–8 kg) and palpitations. Her TFTs showed TSH < 0.02 mU/L and tbl4 35 pmol/L. She was given propranolol, 10 mg thrice daily. Repeat TFTs, 5 weeks later in January 2021, showed TSH of 5.6 mIU/L and FT4, 25 pmol/L. Propranolol was then stopped. Repeat TFTs on March 15, 2021, showed TSH 7.5 mIU/L and FT4 17 pmol/L. Further, TFTs confirmed euthyroidism with the complete resolution of all abnormalities. • Case 7: A 32-year-old Filipina female with no history of any medical illness contracted COVID-19 in October 2020. She developed a mild illness. Four weeks later, she was referred by a primary physician to our Endocrine Clinic with symptoms of weight loss, palpitations, increased sweating, and shakiness. Clinically, she was in a hyperthyroid state, with TFT: TSH < 0.01 mIU/L, FT4: 46 pmol/L, TRAb: 8.7, and anti-TPO ab: 73 IU/L. US thyroid revealed bilaterally enlarged thyroid lobes with increased vascularity. She was diagnosed with GD and started on carbimazole (30 mg daily) and propranolol (40 mg twice daily). On follow-up, she remained euthyroid both clinically and biochemically. • Case 8: A 33-year-old Filipino gentleman was diagnosed with Graves’ hyperthyroidism in September 2020, following symptoms, TSH < 0.001 mIU/L, tbl4 >100 pmol/L, tbl3 39 pmol/L, TRAb 33 IU/L, and anti-TPO Abs of 119 IU (NRR, 40 IU). He was started on carbimazole and achieved remission in a few months. In January 2021, he received radioactive iodine therapy as a definitive treatment. He remained in remission after that, and, on April 19, 2021, she got infected with COVID-19, after which a mild course requiring only simple analgesics was run. On May 3, 2021, he was examined for profound tiredness and his TFTs revealed a TSH of 90 mu/L and tbl4 < 4 pmol/L. He was started on levothyroxine (100 mcg) and his follow-up after 3 months signified the requirement for replacement therapy. • Case 9: A 33-year-old Indian lady was diagnosed with uncomplicated COVID-19 in June 2021. In August, she was reviewed by her primary care physician for intense aches and pains along with joint discomfort. Investigation revealed only picture consistent with central hypothyroidism, with a low free tbl4 of 4.1 pmol/L and inappropriately low TSH at 6.5 mIU/L. Serial TFTs up to early December 2021 confirmed persistent central hypothyroidism, which necessitated thyroxine replacement therapy. Tests for pituitary function revealed normal results. The symptoms resolved following thyroxine treatment. • Case 10: A 51-year-old Filipina lady with thyrotoxicosis for 15 years was referred by her primary care physician in August 2021. She was in remission 13 years ago after taking medications for 2 years. She recently contracted COVID-19 on June 17, 2021, and, after a few weeks, she noticed weight loss and eye bulging. TFTs confirmed hyperthyroidism, with TSH 0.005 mIU/L, FT3 16.3 pmol/L, FT4 52.5 pmol/L, and TRAb 9.3 IU/L. She had TFTs in November 2020, which showed normal results with TSH 0.92 mIU/L and FT4 19 pmol/L. She was accordingly started on carbimazole, which resulted in a good response with remission in the following 2 months. Latest TFTs revealed persistent remission on maintenance carbimazole.	3.992188	0.97998	sec[1]/p[0]	en	0.999997	PMC9372494	https://doi.org/10.5339/qmj.2022.39	[ "pmol", "covid", "tfts", "thyroid", "which", "daily", "carbimazole", "clinic", "trab", "accordingly" ]	[ { "code": "RA01.0", "title": "COVID-19, virus identified" }, { "code": "RA02", "title": "Post COVID-19 condition" }, { "code": "RA01", "title": "COVID-19" }, { "code": "RA01.1", "title": "COVID-19, virus not identified" }, { "code": "QA08.5", "title": "Special screening examination for other viral diseases" }, { "code": "5A03.Z", "title": "Thyroiditis, unspecified" }, { "code": "5A0Z", "title": "Disorders of the thyroid gland or thyroid hormones system, unspecified" }, { "code": "5A03.Y", "title": "Other specified thyroiditis" }, { "code": "5A00.2Z", "title": "Acquired hypothyroidism, unspecified" }, { "code": "5A03.0", "title": "Acute thyroiditis" } ]	=== ICD-11 CODES FOUND === [RA01.0] COVID-19, virus identified Also known as: COVID-19, virus identified \| 2019-new Coronavirus acute respiratory disease (deprecated) \| 2019-nCoV acute respiratory disease [temporary name] (deprecated) \| Coronavirus disease 2019 \| SARS-CoV-2 disease Includes: Coronavirus disease 2019 \| COVID-19 NOS Excludes: Coronavirus infection, unspecified site \| Middle East respiratory syndrome \| Severe acute respiratory syndrome [RA02] Post COVID-19 condition Definition: Post COVID-19 condition occurs in individuals with a history of probable or confirmed SARS CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms, and that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, cognitive dysfunction but also others, and generally have an impact on everyday functioning. Symptoms may be new onset following initial recovery from an acute COVID-19 episode or persist fr Also known as: Post COVID-19 condition \| postCOVID condition \| post-COVID-19 condition \| long COVID [RA01] COVID-19 Definition: As definition may evolve, the URL for the Global surveillance document will be added as the short description Also known as: COVID-19 [RA01.1] COVID-19, virus not identified Also known as: COVID-19, virus not identified \| clinically diagnosed COVID-19 \| suspected COVID-19 \| probable COVID-19 \| clinical COVID-19 Excludes: COVID-19, virus identified \| Coronavirus infection, unspecified site \| Special screening examination for other viral diseases [QA08.5] Special screening examination for other viral diseases Also known as: Special screening examination for other viral diseases \| Measles screening \| Poliomyelitis screening \| Rubella screening \| Screening for Dengue fever Includes: Screening for COVID-19 Excludes: Viral intestinal infections \| Special screening examination for infections with a predominantly sexual mode of transmission \| Special screening examination for human immunodeficiency virus [5A03.Z] Thyroiditis, unspecified Also known as: Thyroiditis, unspecified \| Thyroiditis \| inflammation of thyroid \| thyroiditis NOS [5A0Z] Disorders of the thyroid gland or thyroid hormones system, unspecified Also known as: Disorders of the thyroid gland or thyroid hormones system, unspecified [5A03.Y] Other specified thyroiditis Also known as: Other specified thyroiditis \| Riedel thyroiditis \| Chronic invasive fibrous thyroiditis \| Ligneous thyroiditis \| Riedel struma [5A00.2Z] Acquired hypothyroidism, unspecified Also known as: Acquired hypothyroidism, unspecified \| Acquired hypothyroidism \| hypothyrea \| thyroid insufficiency \| hypothyroidea [5A03.0] Acute thyroiditis Definition: Acute thyroiditis is a rare form of thyroiditis directly caused by an infection, frequently bacterial. Also known as: Acute thyroiditis \| infectious thyroiditis \| Acute thyroiditis due to bacterial infection \| Acute thyroiditis due to fungal infection \| Abscess of thyroid === GRAPH WALKS === --- Walk 1 --- [RA01.0] COVID-19, virus identified --EXCLUDES--> [?] Coronavirus infection, unspecified site --EXCLUDES--> [?] Severe acute respiratory syndrome Def: A disease of the respiratory system, caused by an infection with coronavirus. This disease is characterised by fever, headache, cough, myalgia, tachycardia, or diarrhoea. This disease may also lead to... --- Walk 2 --- [RA01.0] COVID-19, virus identified --EXCLUDES--> [?] Coronavirus infection, unspecified site --EXCLUDES--> [?] Severe acute respiratory syndrome Def: A disease of the respiratory system, caused by an infection with coronavirus. This disease is characterised by fever, headache, cough, myalgia, tachycardia, or diarrhoea. This disease may also lead to... --- Walk 3 --- [RA02] Post COVID-19 condition Def: Post COVID-19 condition occurs in individuals with a history of probable or confirmed SARS CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms, and that last for at least 2 mont... --PARENT--> [?] International provisional assignment of new diseases of uncertain aetiology and emergency use --CHILD--> [RA00] Conditions of uncertain aetiology and emergency use --- Walk 4 --- [RA02] Post COVID-19 condition Def: Post COVID-19 condition occurs in individuals with a history of probable or confirmed SARS CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms, and that last for at least 2 mont... --PARENT--> [?] International provisional assignment of new diseases of uncertain aetiology and emergency use --PARENT--> [25] Codes for special purposes --- Walk 5 --- [RA01] COVID-19 Def: As definition may evolve, the URL for the Global surveillance document will be added as the short description... --CHILD--> [RA01.1] COVID-19, virus not identified --EXCLUDES--> [?] Special screening examination for other viral diseases --- Walk 6 --- [RA01] COVID-19 Def: As definition may evolve, the URL for the Global surveillance document will be added as the short description... --PARENT--> [?] International provisional assignment of new diseases of uncertain aetiology and emergency use --PARENT--> [25] Codes for special purposes	[ "[RA01.0] COVID-19, virus identified\n --EXCLUDES--> [?] Coronavirus infection, unspecified site\n --EXCLUDES--> [?] Severe acute respiratory syndrome\n Def: A disease of the respiratory system, caused by an infection with coronavirus. This disease is characterised by fever, headache, cough, myalgia, tachycardia, or diarrhoea. This disease may also lead to...", "[RA01.0] COVID-19, virus identified\n --EXCLUDES--> [?] Coronavirus infection, unspecified site\n --EXCLUDES--> [?] Severe acute respiratory syndrome\n Def: A disease of the respiratory system, caused by an infection with coronavirus. This disease is characterised by fever, headache, cough, myalgia, tachycardia, or diarrhoea. This disease may also lead to...", "[RA02] Post COVID-19 condition\n Def: Post COVID-19 condition occurs in individuals with a history of probable or confirmed SARS CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms, and that last for at least 2 mont...\n --PARENT--> [?] International provisional assignment of new diseases of uncertain aetiology and emergency use\n --CHILD--> [RA00] Conditions of uncertain aetiology and emergency use", "[RA02] Post COVID-19 condition\n Def: Post COVID-19 condition occurs in individuals with a history of probable or confirmed SARS CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms, and that last for at least 2 mont...\n --PARENT--> [?] International provisional assignment of new diseases of uncertain aetiology and emergency use\n --PARENT--> [25] Codes for special purposes", "[RA01] COVID-19\n Def: As definition may evolve, the URL for the Global surveillance document will be added as the short description...\n --CHILD--> [RA01.1] COVID-19, virus not identified\n --EXCLUDES--> [?] Special screening examination for other viral diseases", "[RA01] COVID-19\n Def: As definition may evolve, the URL for the Global surveillance document will be added as the short description...\n --PARENT--> [?] International provisional assignment of new diseases of uncertain aetiology and emergency use\n --PARENT--> [25] Codes for special purposes" ]	RA01.0	COVID-19, virus identified	[ { "from_icd11": "QA08.5", "icd10_code": "Z1159", "icd10_title": "Encounter for screening for other viral diseases" }, { "from_icd11": "QA08.5", "icd10_code": "Z1151", "icd10_title": "Encounter for screening for human papillomavirus (HPV)" }, { "from_icd11": "QA08.5", "icd10_code": "Z115", "icd10_title": "Encounter for screening for other viral diseases" }, { "from_icd11": "5A03.Z", "icd10_code": "E069", "icd10_title": "Thyroiditis, unspecified" }, { "from_icd11": "5A03.Z", "icd10_code": "E064", "icd10_title": "Drug-induced thyroiditis" }, { "from_icd11": "5A03.Z", "icd10_code": "E065", "icd10_title": "Other chronic thyroiditis" }, { "from_icd11": "5A03.Z", "icd10_code": "E06", "icd10_title": "Thyroiditis" }, { "from_icd11": "5A03.Z", "icd10_code": "E062", "icd10_title": "Chronic thyroiditis with transient thyrotoxicosis" }, { "from_icd11": "5A0Z", "icd10_code": "E0781", "icd10_title": "Sick-euthyroid syndrome" }, { "from_icd11": "5A0Z", "icd10_code": "E0789", "icd10_title": "Other specified disorders of thyroid" }, { "from_icd11": "5A0Z", "icd10_code": "E079", "icd10_title": "Disorder of thyroid, unspecified" }, { "from_icd11": "5A0Z", "icd10_code": "E034", "icd10_title": "Atrophy of thyroid (acquired)" }, { "from_icd11": "5A0Z", "icd10_code": "E00-E07", "icd10_title": "" }, { "from_icd11": "5A0Z", "icd10_code": "E07", "icd10_title": "Other disorders of thyroid" }, { "from_icd11": "5A0Z", "icd10_code": "E078", "icd10_title": "Other specified disorders of thyroid" } ]	Z1159	Encounter for screening for other viral diseases
The results of the laboratory test on admission and the function of the endocrine glands are summarized in Tables 1 and 2 . Urinary potassium excretion was inappropriately increased (Table 1 ). The serum cortisol level was increased, and diurnal rhythm was lost. The level of serum cortisol at 8 am was > 50 µg/dL after the low-dose dexamethasone suppression test(LDDST), and the patient was diagnosed with CS. ACTH dependency was confirmed based on remarkably elevated ACTH levels (Table 2 ). Pituitary MR was normal . The serum cortisol level at 8 am before and after the high-dose dexamethasone suppression test (HDDST) was 212 µg/dL and 208 µg/dL (calculated with the measured value and dilution rate), respectively (Table 2 ). Although the above results strongly suggested EAS, bilateral inferior petrosal sinus sampling (BIPSS) was routinely arranged for verification, mainly for two reasons. First, false positive and false negative results occur in both HDDST and regular imaging(pituitary MR and chest CT). For example, the HDDST results for EAS and CD sometimes overlap. Some patients with EAS have coexisting pituitary adenomas that are not the source of ACTH. Second, in very few patients, CD is caused by hyperplasia instead of adenoma, resulting in a negative finding on pituitary MR. Then, BIPSS was successfully performed (PRL left/ PRL peripheral and PRL right/ PRL peripheral were 4.3 ± 0.5 and 2.5 ± 0.3, respectively). The left, right and peripheral ACTH levels were 789.9 ± 5.2 pg/mL, 773.6 ± 18.2 pg/mL and 726.5 ± 26.7 pg/mL (three samples for each), respectively, and the left, right and peripheral ACTH/PRL levels were 12.4 ± 1.4, 21.4 ± 2.4 and 49.1 ± 2.2, respectively. The diagnosis of EAS was made based on the HDDST and BIPSS results. Chest and abdominal CT as well as neck ultrasound were further arranged. Abdominal CT showed diffuse enlargement of the bilateral adrenal glands , and there were no abnormalities in the pancreas. Chest CT indicated two nodules in the superior and middle lobes of the right lung and prominent mediastinal lymphadenopathy . Elevated tumour biomarkers, including carcinoembryonic antigen (CEA), cytokeratin 21 − 1 fragment CYFRA21-1 and neuron-specific enolase(NSE), were detected (Table 1 ). Thyroid ultrasound showed no abnormality. 68 Ga-PET/CT suggested high-density opacity in the superior lobe of the right lung with a slight abnormally increased uptake of 68 Ga-DOTA-NOC, fitting the characteristics of chronic infection . The high-density nodule in the middle lobe of the right lung was found without abnormal uptake of 68 Ga-DOTA-NOC . Multiple lymph nodes in the left supraclavicular fossa, right root of the neck, mediastinum and bilateral hili of the lung were found partially fused into a mass with abnormal uptake of 68 Ga-DOTA-NOC . Considering that the lymph nodes in the supraclavicular fossa and root of the neck might be distant metastases which is differ from the primary lesion, lymph nodes in the mediastinum and bilateral hili were preferable for biopsy. Therefore, mediastinoscopic lymph node biopsy was performed. The lymph nodes were pale and friable . The pathological diagnosis was small-cell and large-cell neuroendocrine carcinoma (LCNEC)according to the 2018 World Health Organization expert consensus proposal on the classification framework for neuroendocrine neoplasms . Mitosis was approximately 80/10 HPF , and the Ki-67 index was 80 % . ACTH staining was positive . Table 1 Laboratory findings of the patient on admission Parameter Patient’s value Reference range Blood routine WBC 11.19 3.5–9.5 × 10 9 /L Neut% 10.53 1.8–6.3 × 10 9 /L Hb 151 130–175 g/L PLT 149 125–350 × 10 9 /L Urine routine pH 7.5 5.5-8.0 Glu - - Ket - - Liver function ALT 52 9–50 U/L AST 96 15–40 U/L GGT 25 10–60 U/L ALP 77 45–125 U/L TBil 13.3 3.4–17.1 µmol/L DBil 3.9 0-3.4 µmol/L TP 50.5 65–85 g/L ALB 30.6 40–55 g/L Renal function BUN 5.91 3.9–9.5 mmol/L Cr 64 57–111 µmol/L UA 289 208–428 µmol/L eGFR 99.27 > 90 mL/min/1.73m 2 Blood gas analysis PH 7.58 7.35–7.45 PCO 2 51 35–45 mmHg PO 2 63 80–100 mmHg SB 40.8 22–27 mmol/L BE 20.5 -3-+3 mmol/L HCO 3 - 46.7 22–27 mmol/L Electrolyte Urine potassium * 155.7 25–100 mmol/24 h Synchronizing serum potassium 2.49 3.5–5.3 mmol/L Urine sodium 296.4 130.0-260.0 mmol/24 h Synchronizing serum sodium 142 137–147 mmol/L Urine calcium 9.35 25.0–38.0 mmol/24 h Synchronizing serum calcium 1.83 2.11–2.52 mmol/L Calibration of serum calcium # 2.02 2.11–2.52 mmol/L Urine phosphorus 24.68 32.3–38.4 mmol/24 h Synchronizing serum phosphorus 0.74 0.85–1.51 mmol/L FPG 7.4 3.9–6.1 mmol/L HbA1c 5.7 4–6 % OGTT Glucose-0 min 7.82 3.9–6.1 mmol/L Glucose − 30 min 8.79 Glucose − 60 min 9.41 Glucose-120 min 7.95 < 7.8 mmol/L Glucose − 180 min 6.94 Insulin-0 min 151.5 5.0–25 mIU/L Insulin-30 min 186.5 Insulin-60 min 136.2 Insulin-120 min 145.8 Insulin-180 min 174.1 Lipid CHO 3.57 3.1–5.69 mmol/L TG 1.09 0.56–1.47 mmol/L LDL 1.89 2.07–3.10 mmol/L Coagulation function PTA 84 % 84-128 % PT 14.6 11–14 s TT 17.8 14–21 s APTT 31.5 28-43.5 s INR 1.11 0.94–1.3 FIB 2.08 2–4 g/L FDP 0.98 0–5 mg/L D-D 0.77 0–1.0 mg/L Mb 741.3 0-146.9 ng/mL TnT 0.067 0-0.014 ng/mL Myocardial enzyme CK 695 50–310 U/L CKMB 73 0–24 U/L Pro-BNP 182.6 0-125 pg/mL PCT 1.45 < 0.5 ng/mL Tumour biomarkers CEA 4.930 0.00-3.40 g/mL NSE 52.36 0.00-16.30 ng/mL CYFRA21-1 8.750 0.00-3.30 ng/mL CA19-9 44.11 0–39 U/mL SCCA 0.77 < 1.5 ng/mL Free-PSA 0.474 0–4 ng/mL AFP 5.83 0–7 ng/mL CA125 21.4 0–35 U/mL CA72-4 1.6 0-9.8 U/mL WBC white blood cell count, Neut% percentage of neutrophils, Hb haemoglobin, PLT platelet, Glu glucose, Ket ketone, ALT alanine aminotransferase, AST aspartate aminotransferase, GGT glutamyltranspeptidase, TBil total bilirubin, DBil direct bilirubin, TP total protein, ALB albumin, BUN blood urea nitrogen, Cr creatinine, UA uric acid, eGFR estimated glomerular filtration ratio, FPG fasting plasma glucose, HbA1c glycosylated haemoglobin, OGTT oral glucose tolerance test, CHO cholesterol, TG triglyceride, LDL low-density lipoprotein cholesterol, PCO 2 partial pressure of carbon dioxide, PO 2 partial pressure of oxygen, SB standard bicarbonate, BE base excess, HCO3 - bicarbonate, Mb myoglobin, TnT troponin T, pro-BNP pro-brain natriuretic peptide, PCT procalcitonin, CK creatine kinase, CKMB creatine kinase isoenzyme, PTA prothrombin time activity, PT prothrombin time, TT thrombin time, APTT activated partial thrombin time, INR international normalized ratio, FIB fibrinogen, FDP fibrin degradation product, D-D D dimer, CEA carcinoembryonic antigen, NSE neuron-specific enolase, CYFRA21-1 cytokeratin 21 − 1 fragment, CA19-9 carbohydrate antigen 19 − 9, SCCA squamous cell carcinoma antigen, PSA prostate specific antigen, AFP alpha foetal protein, CA125 carbohydrate antigen 125, CA72-4 carbohydrate antigen 72 − 4. *, the criteria of inappropriate increased urinary potassium excretion are urine potassium >25mmol/24h when serum potassium <3.5mmol/L or urine potassium >20mmol/24h when serum potassium <3.0mmol/L. # , Calcium calibrated =Calcium measured +(40-serum albumin) ×0.02 Table 2 Function of the endocrine glands Parameter Patient’s value Reference range ACTH-COR ACTH-8:00 647.2 7.2–63.3 pg/mL COR-8:00 > 50 5–28 µg/dL COR-16:00 > 50 µg/dL COR-24:00 > 50 µg/dL Urine 17-KS (24 h) 221.48 20.8–76.3 µmol/24 h Urine 17-OHCS (24 h) 482.5 8.32–33.2 µmol/24 h LDDST COR-before > 50 µg/dL COR-after > 50 µg/dL HDDST a COR-before 212 µg/dL COR-after 208 µg/dL BIPSS Left PRL-1 56.27 ng/mL PRL-2 67.00 ng/mL PRL-3 69.01 ng/mL ACTH-1 787.4 pg/mL ACTH-2 795.9 pg/mL ACTH-3 786.4 pg/mL Right PRL-1 33.91 ng/mL PRL-2 40.62 ng/mL PRL-3 34.53 ng/mL ACTH-1 794.6 pg/mL ACTH-2 762.6 pg/mL ACTH-3 763.6 pg/mL Peripheral PRL-1 15.01 ng/mL PRL-2 14.4 ng/mL PRL-3 14.96 ng/mL ACTH-1 751 pg/mL ACTH-2 730.5 pg/mL ACTH-3 698 pg/mL Renin-Angiotensin-Aldosterone Renin 7.88 4–24 pg/mL Angiotensin 45.29 25–129 pg/mL Aldosterone 75.15 10–160 pg/mL ARR 9.54 0–45 Gonadal hormone E2 117.9 28–156 pmol/L Prog 5.65 0.159-0.5 nmol/L PRL 23.24 4.04–15.2 ng/mL LH 4.24 1.7–8.6 mIU/mL FSH 6.4 1.5–12.4 mIU/mL T 4.26 6.68–25.7 nmol/L DHEAS 8.48 1.4–8.01 µmol/L Thyroid function Free T3 3.23 2.91–9.08 pmol/L Free T4 15.00 9.05–25.5 pmol/L T3 < 0.05 0.78–2.20 ng/mL T4 3.21 4.2–13.5 µg/dL TSH 0.56 0.25-5 µIU/mL TPOAb < 15 < 15 U/mL Parathyroid function PTH 165.7 15–65 pg/mL 25(OH)D 3 13.3 20–40 ng/mL N-OST 9.0 14–46 ng/mL P INP 19.16 9.06–76.24 ng/mL ACTH adrenocorticotropic hormone, COR cortisol, 17-OH 17-ketosteroids, 17-hydroxycorticosteroids, LDDST low-dose dexamethasone suppression test, HDDST high-dose dexamethasone suppression test, BIPSS bilateral inferior petrosal sinus sampling, E2 oestradiol, Prog progesterone, PRL prolactin, LH luteinizing hormone, FSH follicle-stimulating hormone, T testosterone, DHEAS dehydroepiandrosterone sulfate, ARR the aldosterone and active renin ratio, TSH thyroid-stimulating hormone, T3 triiodothyronine, T4 thyroxine, TPOAb thyroid peroxidase antibody, PTH parathyroid hormone, 25(OH)D 3 25-hydroxyvitamin D3, N-OST N-osteocalcin, PINP procollagen IN-terminal peptide a calculated with the measured value and dilution rate Fig. 1 Imaging examinations. Pituitary MRI revealed no abnormalities ( a and b ). Abdominal CT showed diffuse enlargement of the bilateral adrenal glands ( c and d ). Chest CT indicated two nodules in the superior ( e ) and middle lobes of the right lung ( f ) and mediastinal lymphadenopathy ( g and h ). 68 Ga PET/CT demonstrated high-density opacity in the superior lobe of the right lung with a slight abnormally increased uptake of 68 Ga-DOTA-NOC ( i ). High-density nodules in the middle lobe of the right lung did not show abnormal uptake of 68 Ga-DOTA-NOC ( j , arrow). Multiple lymph nodes in the mediastinum and bilateral hili of the lung partially fused into a mass with abnormally increased uptake of 68 Ga-DOTA-NOC ( k and l ) Fig. 2 Mediastinoscopy revealed enlarged lymph nodes that were pale and friable ( a ). Large tumour cells with moderate to abundant cytoplasm and prominent nucleoli ( b ). Densely packed small tumour cells with scant cytoplasm, finely granular nuclear chromatin and absent nucleoli ( c ). Mitosis ( d ). Ki-67 index was 80 % ( e ). Immunohistochemical staining for ACTH ( f ). b, c and d , HE staining, 400×; e and f , 200×	4.191406	0.595703	sec[1]/p[1]	en	0.999994	33971870	https://doi.org/10.1186/s12902-021-00755-0	[ "acth", "mmol", "serum", "urine", "potassium", "lung", "glucose", "function", "antigen", "lymph" ]	[ { "code": "5A74.Y", "title": "Other specified adrenocortical insufficiency" }, { "code": "5A70.1", "title": "Ectopic ACTH syndrome" }, { "code": "5A70.Z", "title": "Cushing syndrome, unspecified" }, { "code": "5A70.Y", "title": "Other specified Cushing syndrome" }, { "code": "5A70.0", "title": "Pituitary-dependent Cushing disease" }, { "code": "GB42.1", "title": "Albuminuria, Grade A3" }, { "code": "GB42.0", "title": "Albuminuria, Grade A2" }, { "code": "MA18.0Y", "title": "Other specified elevated blood glucose level" }, { "code": "NE80.3", "title": "Other serum reactions" }, { "code": "5D0Y", "title": "Other specified metabolic disorders" } ]	=== ICD-11 CODES FOUND === [5A74.Y] Other specified adrenocortical insufficiency Also known as: Other specified adrenocortical insufficiency \| Congenital adrenocortical insufficiency \| Congenital isolated ACTH deficiency \| Familial adrenal hypoplasia \| Familial hypoadrenocorticism [5A70.1] Ectopic ACTH syndrome Also known as: Ectopic ACTH syndrome \| Cushing syndrome secondary to ectopic ACTH-secretion \| Ectopic Cushing syndrome \| hypercortisolism due to nonpituitary tumour \| ectopic ACTH - [adrenocorticotropic hormone] secretion [5A70.Z] Cushing syndrome, unspecified Also known as: Cushing syndrome, unspecified \| Cushing syndrome \| Hyperadrenocorticism \| Hypercortisolism \| Cushing syndrome NOS [5A70.Y] Other specified Cushing syndrome Also known as: Other specified Cushing syndrome \| ACTH-dependent Cushing syndrome \| ACTH-independent Cushing syndrome \| ACTH-independent Cushing syndrome due to bilateral adrenocortical hyperplasia \| ACTH-independent macronodular adrenal hyperplasia [5A70.0] Pituitary-dependent Cushing disease Definition: Pituitary-dependent Cushing disease is caused by a pituitary tumour, generally benign (adenoma) but rarely malignant (carcinoma), which secretes adrenocorticotropin (ACTH) autonomously, leading to hypercortisolism. The condition is associated with increased morbidity and mortality that can be mitigated by treatments that result in sustained endocrine remission. Transsphenoidal pituitary surgery (TSS) remains the mainstay of treatment for this disease but requires considerable neurosurgical exper Also known as: Pituitary-dependent Cushing disease \| Overproduction of pituitary ACTH \| Pituitary-dependent hyperadrenocorticism \| Corticotroph pituitary adenoma \| ACTH- [adrenocorticotropic hormone] secreting pituitary adenoma [GB42.1] Albuminuria, Grade A3 Definition: Presence of excessive albumin in the urine, indicating abnormal permeability glomerular filtration. Can be quantitated by either timed collections or spot urine samples with the concentration adjusted to the urine creatinine concentration to correct for variations in overall urine concentration. When persistent and of moderate or greater severity usually indicates overt glomerular disease such as caused by diabetic glomerulosclerosis, glomerulonephritis or amyloid. Also known as: Albuminuria, Grade A3 \| albuminuria >30 mg/mmol creatinine \| macroalbuminuria \| overt albuminuria \| overt nephropathy [GB42.0] Albuminuria, Grade A2 Definition: Presence of excessive albumin in the urine, indicating abnormal permeability glomerular filtration. Can be quantitated by either timed collections or spot urine samples with the concentration adjusted to the urine creatinine concentration to correct for variations in overall urine concentration. When persistent and of moderate or greater severity usually indicates overt glomerular disease such as caused by diabetic glomerulosclerosis, glomerulonephritis or amyloid. Also known as: Albuminuria, Grade A2 \| microalbuminuria \| incipient nephropathy \| mild to moderate albuminuria \| albuminuria 3-30 mg/mmol creatinine [MA18.0Y] Other specified elevated blood glucose level Also known as: Other specified elevated blood glucose level \| Blood glucose between 8.0 - 11.9 mmol/L pre-meal or fasting \| Blood glucose between 12.0 - 13.9 mmol/L pre-meal or fasting \| Blood glucose greater than or equal to 14.0 mmol/L pre-meal or fasting \| Blood glucose between 12.0 - 13.9 mmol/L post-meal or not otherwise specified [NE80.3] Other serum reactions Also known as: Other serum reactions \| Allergic reaction to serum \| serum allergy \| Complications of vaccination, protein sickness \| Protein sickness Excludes: serum hepatitis [5D0Y] Other specified metabolic disorders Also known as: Other specified metabolic disorders \| Disorders of plasma-protein metabolism, not elsewhere classified \| abnormal protein transport \| dysproteinaemia \| Absence of albumin in blood === GRAPH WALKS === --- Walk 1 --- [5A74.Y] Other specified adrenocortical insufficiency --PARENT--> [5A74] Adrenocortical insufficiency Def: A condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol. It may also include impaired production of aldosterone (a mineralocorticoid), which reg... --PARENT--> [?] Disorders of the adrenal glands or adrenal hormone system --- Walk 2 --- [5A74.Y] Other specified adrenocortical insufficiency --PARENT--> [5A74] Adrenocortical insufficiency Def: A condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol. It may also include impaired production of aldosterone (a mineralocorticoid), which reg... --CHILD--> [5A74.1] Adrenal crisis Def: Adrenal crisis is a life-threatening condition that indicates severe adrenal insufficiency caused by insufficient levels of cortisol.... --- Walk 3 --- [5A70.1] Ectopic ACTH syndrome --PARENT--> [5A70] Cushing syndrome Def: Cushing syndrome results from excess of corticosteroid hormones in the body due to overstimulation of the adrenal glands by excessive amounts of the hormone ACTH, secreted either by a tumuor of the pi... --CHILD--> [5A70.1] Ectopic ACTH syndrome --- Walk 4 --- [5A70.1] Ectopic ACTH syndrome --PARENT--> [5A70] Cushing syndrome Def: Cushing syndrome results from excess of corticosteroid hormones in the body due to overstimulation of the adrenal glands by excessive amounts of the hormone ACTH, secreted either by a tumuor of the pi... --CHILD--> [5A70.2] Pseudo-Cushing syndrome Def: This is a condition in which patients display the signs, symptoms, and abnormal hormone levels seen in Cushing's syndrome. However, pseudo-Cushing's syndrome is not caused by a problem with the hypoth... --- Walk 5 --- [5A70.Z] Cushing syndrome, unspecified --PARENT--> [5A70] Cushing syndrome Def: Cushing syndrome results from excess of corticosteroid hormones in the body due to overstimulation of the adrenal glands by excessive amounts of the hormone ACTH, secreted either by a tumuor of the pi... --CHILD--> [5A70.1] Ectopic ACTH syndrome --- Walk 6 --- [5A70.Z] Cushing syndrome, unspecified --PARENT--> [5A70] Cushing syndrome Def: Cushing syndrome results from excess of corticosteroid hormones in the body due to overstimulation of the adrenal glands by excessive amounts of the hormone ACTH, secreted either by a tumuor of the pi... --CHILD--> [5A70.0] Pituitary-dependent Cushing disease Def: Pituitary-dependent Cushing disease is caused by a pituitary tumour, generally benign (adenoma) but rarely malignant (carcinoma), which secretes adrenocorticotropin (ACTH) autonomously, leading to hyp...	[ "[5A74.Y] Other specified adrenocortical insufficiency\n --PARENT--> [5A74] Adrenocortical insufficiency\n Def: A condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol. It may also include impaired production of aldosterone (a mineralocorticoid), which reg...\n --PARENT--> [?] Disorders of the adrenal glands or adrenal hormone system", "[5A74.Y] Other specified adrenocortical insufficiency\n --PARENT--> [5A74] Adrenocortical insufficiency\n Def: A condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol. It may also include impaired production of aldosterone (a mineralocorticoid), which reg...\n --CHILD--> [5A74.1] Adrenal crisis\n Def: Adrenal crisis is a life-threatening condition that indicates severe adrenal insufficiency caused by insufficient levels of cortisol....", "[5A70.1] Ectopic ACTH syndrome\n --PARENT--> [5A70] Cushing syndrome\n Def: Cushing syndrome results from excess of corticosteroid hormones in the body due to overstimulation of the adrenal glands by excessive amounts of the hormone ACTH, secreted either by a tumuor of the pi...\n --CHILD--> [5A70.1] Ectopic ACTH syndrome", "[5A70.1] Ectopic ACTH syndrome\n --PARENT--> [5A70] Cushing syndrome\n Def: Cushing syndrome results from excess of corticosteroid hormones in the body due to overstimulation of the adrenal glands by excessive amounts of the hormone ACTH, secreted either by a tumuor of the pi...\n --CHILD--> [5A70.2] Pseudo-Cushing syndrome\n Def: This is a condition in which patients display the signs, symptoms, and abnormal hormone levels seen in Cushing's syndrome. However, pseudo-Cushing's syndrome is not caused by a problem with the hypoth...", "[5A70.Z] Cushing syndrome, unspecified\n --PARENT--> [5A70] Cushing syndrome\n Def: Cushing syndrome results from excess of corticosteroid hormones in the body due to overstimulation of the adrenal glands by excessive amounts of the hormone ACTH, secreted either by a tumuor of the pi...\n --CHILD--> [5A70.1] Ectopic ACTH syndrome", "[5A70.Z] Cushing syndrome, unspecified\n --PARENT--> [5A70] Cushing syndrome\n Def: Cushing syndrome results from excess of corticosteroid hormones in the body due to overstimulation of the adrenal glands by excessive amounts of the hormone ACTH, secreted either by a tumuor of the pi...\n --CHILD--> [5A70.0] Pituitary-dependent Cushing disease\n Def: Pituitary-dependent Cushing disease is caused by a pituitary tumour, generally benign (adenoma) but rarely malignant (carcinoma), which secretes adrenocorticotropin (ACTH) autonomously, leading to hyp..." ]	5A74.Y	Other specified adrenocortical insufficiency	[ { "from_icd11": "5A70.1", "icd10_code": "E243", "icd10_title": "Ectopic ACTH syndrome" }, { "from_icd11": "5A70.Z", "icd10_code": "E242", "icd10_title": "Drug-induced Cushing's syndrome" }, { "from_icd11": "5A70.Z", "icd10_code": "E249", "icd10_title": "Cushing's syndrome, unspecified" }, { "from_icd11": "5A70.Z", "icd10_code": "E248", "icd10_title": "Other Cushing's syndrome" }, { "from_icd11": "5A70.Z", "icd10_code": "E24", "icd10_title": "Cushing's syndrome" }, { "from_icd11": "5A70.0", "icd10_code": "E240", "icd10_title": "Pituitary-dependent Cushing's disease" }, { "from_icd11": "NE80.3", "icd10_code": "T880XXA", "icd10_title": "Infection following immunization, initial encounter" }, { "from_icd11": "NE80.3", "icd10_code": "T8061XA", "icd10_title": "Other serum reaction due to administration of blood and blood products, initial encounter" }, { "from_icd11": "NE80.3", "icd10_code": "T8069XA", "icd10_title": "Other serum reaction due to other serum, initial encounter" }, { "from_icd11": "NE80.3", "icd10_code": "T8062XA", "icd10_title": "Other serum reaction due to vaccination, initial encounter" }, { "from_icd11": "NE80.3", "icd10_code": "T806", "icd10_title": "Other serum reactions" }, { "from_icd11": "NE80.3", "icd10_code": "T880", "icd10_title": "Infection following immunization" } ]	E243	Ectopic ACTH syndrome
We report a case of a severe HMGCR-myopathy with diffuse muscle atrophy in a Tunisian 43-year-old man. This case represented a therapeutic challenge due to steroid dependence on one hand and resistance to immunosuppressive therapies on the other. Combined therapy with rituximab (RTX), methotrexate, and azathioprine managed to achieve partial improvement. To our knowledge, this case represents the first anti-HMGCR IMNM case to be reported in North Africa. This case underscores the underrepresentation of North African populations in current literature on idiopathic inflammatory myopathies, with limited epidemiological data from these reEnglish checkinggions contributing to diagnostic delays and underdiagnosis. The incidence of this condition in Caucasian populations ranges from 1.94 to 10.3 cases per million adults annually, depending on the immunoassays used ( 2 ).The lack of such data from African countries further exacerbates the challenge, hindering an understanding of ethnic influences on disease prevalence. Comparative analysis with similarly resource-limited settings indicates a potential gap in awareness and access to appropriate diagnostic tools. This data gap also impedes efforts to advocate for the inclusion of commercial detection immunoassays in public health budgets. Strengthening surveillance and reporting in these populations could provide more comprehensive insights into the global burden of anti-HMGCR myopathy and improve diagnostic and treatment strategies. Anti-HMGCR IMNM is considered to be among the least frequent subtypes of idiopathic inflammatory myopathies, estimated to represent around 12% after excluding inclusion body myositis (IBM) ( 3 ).The identification of anti-HMGCR antibodies dates back to 2010, when Christopher-Stine et al. reported a unique autoantibody specificity targeting 200 and 100 kDa proteins in patients exhibiting clinical and biological features of myositis ( 4 ). In fact, the HMGCR antigen is an oxidoreductase enzyme involved in the mevalonate pathway, specifically in the rate-limiting step in cholesterol synthesis. It is located at the membrane of the endoplasmic reticulum and is usually overexpressed in cancer tissues and regenerating muscle cells ( 5 ). On human epithelial type-2 (HEp-2) cells immunofluorescence, anti-HMGCR antibodies usually display a finely granular cytoplasmic appearance with perinuclear reinforcement. This aspect is observed in only 35% of patients ( 6 ). On kidney/stomach/liver substrates, these antibodies can have a scattered hepatocyte pattern with a centrolobular distribution. The staining is confined to the cytoplasm and clearly spares the nuclei. The bile ducts, endothelium, and sinusoidal cells are not stained. Stomach and kidney do not show any characteristic pattern ( 5 ). Initially, anti-HMGCR myopathy was thought to be statin-induced ( 4 ), but studies have shown this is unlikely, as only 15–44% of anti-HMGCR patients have a history of statin use ( 7 ). Statin-naive patients, often younger, are becoming more common, as with our patient. Anti-HMGCR IMNM mostly affects adults, though juvenile cases are reported, with rare overlap syndromes ( 8 ). Clinically, it primarily involves proximal muscle myalgia and weakness, sometimes affecting oropharyngeal muscles, leading to dysphagia and risk of aspiration pneumonia. Elevated CK levels, ranging from mild to severe, reflect myolysis and are useful for tracking treatment response and flares. In our patient, relapse was monitored using a combination of rising CK levels and clinical deterioration, including worsening proximal muscle weakness and functional decline ( 9 ). EMG usually reveals myogenic patterns in the proximal muscles. Imaging with muscle magnetic resonance imaging (MRI) is not always required for diagnosis but can serve multiple roles. First, it allows for the demonstration of edema reflecting muscle inflammation, usually localized to all compartments of the thighs with particular involvement of the anterior compartment. It can be more diffuse and asymmetrical. Edema also usually spares subcutaneous tissue and fascias, unlike in dermatomyositis ( 10 ). In addition to aiding in diagnosis, MRI assists surgeons in identifying accessible muscles with active lesions for biopsy when necessary. Furthermore, MRI can evaluate irreversible muscle damage, characterized by muscle atrophy with replacement by fat and connective tissue, as demonstrated in our patient’s body computed tomography ( 11 ). Similar to anti-SRP myopathy, it was initially suggested that anti-HMGCR titers correlate with muscle strength and CK level when studying all patients combined ( 12 , 13 ). Yet, when analyzing sub-groups, the correlation between antibody titers and CK levels was not found in the statin-naive and statin-exposed groups in the Allenbach study ( 12 ). The correlation was found between titers and muscle strength only in statin-naive patients. In the Mammen study ( 4 ), correlations were found between antibody titers, muscle strength, and CK titers in statin-exposed patients. Finally, Aggarwal et al. have shown that antibody titers decrease with immunosuppressive treatment and might represent a follow-up marker. Yet, they seem to remain abnormal in patients even after clinical and biological remission ( 12 ). This study, along with similar findings, suggests a possible pathogenic role of anti-HMGCR in the pathophysiology of this myopathy. Larger studies are required to better assess this potential link. In Tunisia, screening immunoassays for this antibody remain unavailable due to limited public laboratory funding. This contributes not only to the underdiagnosis of the condition but also to the inadequate monitoring of disease activity, as illustrated in our case. Muscle biopsy is not systematically conducted. It can be indicated for diagnostic purposes, especially when anti-HMGCR antibody testing is not accessible. It typically shows a dystrophic pattern with necrosis/regeneration, associated with irregular fiber size and endomysial fibrosis—hallmarks of all IMNM. Immunohistochemistry may show class I major histocompatibility complex (MHC I) upregulation and deposition of the membrane attack complex (MAC) on the sarcolemma of non-necrotic muscle fibers. Interestingly, this MAC deposition was not found in anti-Signal Recognition Particle (SRP) IMNM biopsies and, as such, may be a characteristic feature of anti-HMGCR IMNM ( 8 ). In resource-limited settings, access to diagnostic tools such as antibody testing, muscle MRI, or even muscle biopsy is often limited by cost or availability. Treatment options may also be constrained, particularly for advanced therapies like IVIg or biologics. These barriers may delay diagnosis and optimal management. Developing standardized clinical criteria and treatment algorithms tailored to such settings could help bridge these gaps. Extra-muscular involvement in anti-HMGCR myopathy, like anti-SRP myopathy, is rare, as seen in our patient with a purely muscular presentation ( 8 ). Cardiac involvement, though frequent, is usually asymptomatic and mild. Allenbach’s study found conduction abnormalities in 12.9% of patients, with only one case of heart failure, diagnosed 20 years before anti-HMGCR positivity ( 7 ). ECG abnormalities were noted in 60% of those systematically tested ( 13 ). Dysphagia occurs in 20–50% of cases ( 14 ). Ocular involvement is also rare, with only two cases reported in 2024 ( 15 ). Table 2 summarizes organ involvement in major cohorts. Patients with anti-HMGCR IMNM face a higher cancer risk than those with anti-SRP IMNM, but lower than seronegative cases ( 16 ). No guidelines exist for managing anti-HMGCR IMNM. Statin-induced cases may improve after discontinuation, but most require long-term treatment due to severity and frequent relapses. High-dose glucocorticoids, like prednisone or methylprednisolone pulses, remain the mainstay of treatment, though response varies, with some success using prednisone alone ( 12 ). Some experts recommend IVIg as first-line therapy, especially in refractory cases during prednisone taper, as seen in our patient. A report noted that IVIg monotherapy (without glucocorticoids) in three patients led to partial or full muscle strength recovery ( 4 ). Treppo’s trial in 16 patients showed that IVIg combined with glucocorticoids and/or methotrexate improved clinical and biological outcomes in over two-thirds within six months, with relapses mostly after treatment cessation ( 17 ). In our case, IVIg was used during the acute phase after treatment failure, showing an initial response, though long-term outcomes in a maintenance scheme are unknown. Azathioprine and methotrexate (3 mg/kg/day) are also recommended as first-line DMARDs, with good safety but uncertain efficacy. Recently, numerous case reports and observational studies have documented the use of rituximab in refractory cases, either as a third-line treatment or as a first-line option for severe presentations ( 18 ). However, its efficacy is still unclear, with results varying significantly across studies. Many studies have reported treatment failure, particularly for remission induction. In our case, the efficacy of rituximab cannot be definitively assessed, as it did not lead to improvement as part of the remission induction regimen. In our case, access to Rituximab and IVIg was limited by public health insurance policies, which authorize these therapies only for severe cases that have proven refractory to standard treatments such as methotrexate and azathioprine. Our case presents several limitations. First, patient adherence to treatment was not evaluated, nor were quality-of-life parameters or reported outcomes. Second, follow-up is short after the fourth rituximab infusion, not allowing full assessment of response. Finally, IVIg impact in a remission maintenance regimen was planned but not started because of limited access. This constraint underscores significant challenges in healthcare accessibility and suggests that classifying the condition as refractory may be premature. The patient demonstrated an initial positive response to IVIG, and the inability to continue this therapy due to financial limitations may have impacted the overall outcome.	4.402344	0.865723	sec[2]/p[0]	en	0.999998	40421031	https://doi.org/10.3389/fimmu.2025.1590913	[ "anti", "hmgcr", "muscle", "this", "patients", "imnm", "cases", "statin", "ivig", "myopathy" ]	[ { "code": "JA86.Y", "title": "Maternal care for other specified fetal problems" }, { "code": "MB23.1", "title": "Antisocial behaviour" }, { "code": "3B4Z", "title": "Coagulation defects, unspecified" }, { "code": "4A45.Z", "title": "Antiphospholipid syndrome, unspecified" }, { "code": "4A43.Y", "title": "Other specified overlap non-organ specific systemic autoimmune disease" }, { "code": "FB3Z", "title": "Disorders of muscles, unspecified" }, { "code": "FB32.Y", "title": "Other specified disorders of muscles" }, { "code": "8C70.Z", "title": "Muscular dystrophy, unspecified" }, { "code": "FB32.2Z", "title": "Ischaemic infarction of muscle, unspecified" }, { "code": "FB56.2", "title": "Myalgia" } ]	=== ICD-11 CODES FOUND === [JA86.Y] Maternal care for other specified fetal problems Also known as: Maternal care for other specified fetal problems \| Maternal care for other isoimmunization \| Isoimmunization NOS \| maternal antibodies NOS \| pregnancy management affected by incompatibility of blood groups NOS [MB23.1] Antisocial behaviour Definition: Behaviour in which the basic rights of others or major age-appropriate societal norms, rules, or laws, are violated. Also known as: Antisocial behaviour \| Child or adolescent antisocial behaviour [3B4Z] Coagulation defects, unspecified Also known as: Coagulation defects, unspecified \| blood clotting disturbance \| blood clotting defect \| blood clotting factor deficiency \| clotting abnormality [4A45.Z] Antiphospholipid syndrome, unspecified Also known as: Antiphospholipid syndrome, unspecified \| Antiphospholipid syndrome \| Hughes syndrome \| Anticardiolipin syndrome [4A43.Y] Other specified overlap non-organ specific systemic autoimmune disease Also known as: Other specified overlap non-organ specific systemic autoimmune disease \| Antisynthetase syndrome \| Reynolds syndrome \| Syndromic multisystem autoimmune disease due to ITCH deficiency \| Eosinophilia myalgia syndrome [FB3Z] Disorders of muscles, unspecified Also known as: Disorders of muscles, unspecified \| disorder of muscle, unspecified \| muscle disease \| muscular disease \| muscular disorder [FB32.Y] Other specified disorders of muscles Also known as: Other specified disorders of muscles \| Muscle wasting or atrophy, not elsewhere classified \| muscle wasting \| muscle wasting disorder \| Sarcopenia [8C70.Z] Muscular dystrophy, unspecified Also known as: Muscular dystrophy, unspecified \| Muscular dystrophy \| Gower's muscular dystrophy \| progressive musclular dystrophy \| pseudohypertrophic atrophy [FB32.2Z] Ischaemic infarction of muscle, unspecified Also known as: Ischaemic infarction of muscle, unspecified \| Ischaemic infarction of muscle \| muscle infarction [FB56.2] Myalgia Definition: This is a disorder characterised by pain in a muscle or group of muscles. Also known as: Myalgia \| muscle ache \| muscle soreness \| muscular pain \| myalgic Excludes: Chronic primary musculoskeletal pain \| Chronic secondary musculoskeletal pain === GRAPH WALKS === --- Walk 1 --- [JA86.Y] Maternal care for other specified fetal problems --PARENT--> [JA86] Maternal care for other fetal problems Def: A condition characterised by the provision of health interventions to the mother due to any other issue that is either suspected or known to be present in the fetus.... --EXCLUDES--> [?] Placental transfusion syndromes --- Walk 2 --- [JA86.Y] Maternal care for other specified fetal problems --PARENT--> [JA86] Maternal care for other fetal problems Def: A condition characterised by the provision of health interventions to the mother due to any other issue that is either suspected or known to be present in the fetus.... --EXCLUDES--> [?] Labour or delivery complicated by fetal distress --- Walk 3 --- [MB23.1] Antisocial behaviour Def: Behaviour in which the basic rights of others or major age-appropriate societal norms, rules, or laws, are violated.... --PARENT--> [MB23] Symptoms or signs involving appearance or behaviour --CHILD--> [MB23.2] Avoidance behaviour Def: The act of keeping away from circumstances, situations, or stimuli that cause anxiety or other negative emotions in the individual.... --- Walk 4 --- [MB23.1] Antisocial behaviour Def: Behaviour in which the basic rights of others or major age-appropriate societal norms, rules, or laws, are violated.... --PARENT--> [MB23] Symptoms or signs involving appearance or behaviour --CHILD--> [MB23.1] Antisocial behaviour Def: Behaviour in which the basic rights of others or major age-appropriate societal norms, rules, or laws, are violated.... --- Walk 5 --- [3B4Z] Coagulation defects, unspecified --PARENT--> [?] Coagulation defects --CHILD--> [?] Haemorrhagic diseases due to acquired coagulation factor defects Def: Any disease caused by determinants arising after birth. These diseases are characterised by abnormal coagulation of the blood.... --- Walk 6 --- [3B4Z] Coagulation defects, unspecified --PARENT--> [?] Coagulation defects --PARENT--> [?] Coagulation defects, purpura or other haemorrhagic or related conditions Def: A condition caused by determinants arising during the antenatal period, after birth or by genetically inherited factors, leading to coagulation defects. This condition is characterised by increased br...	[ "[JA86.Y] Maternal care for other specified fetal problems\n --PARENT--> [JA86] Maternal care for other fetal problems\n Def: A condition characterised by the provision of health interventions to the mother due to any other issue that is either suspected or known to be present in the fetus....\n --EXCLUDES--> [?] Placental transfusion syndromes", "[JA86.Y] Maternal care for other specified fetal problems\n --PARENT--> [JA86] Maternal care for other fetal problems\n Def: A condition characterised by the provision of health interventions to the mother due to any other issue that is either suspected or known to be present in the fetus....\n --EXCLUDES--> [?] Labour or delivery complicated by fetal distress", "[MB23.1] Antisocial behaviour\n Def: Behaviour in which the basic rights of others or major age-appropriate societal norms, rules, or laws, are violated....\n --PARENT--> [MB23] Symptoms or signs involving appearance or behaviour\n --CHILD--> [MB23.2] Avoidance behaviour\n Def: The act of keeping away from circumstances, situations, or stimuli that cause anxiety or other negative emotions in the individual....", "[MB23.1] Antisocial behaviour\n Def: Behaviour in which the basic rights of others or major age-appropriate societal norms, rules, or laws, are violated....\n --PARENT--> [MB23] Symptoms or signs involving appearance or behaviour\n --CHILD--> [MB23.1] Antisocial behaviour\n Def: Behaviour in which the basic rights of others or major age-appropriate societal norms, rules, or laws, are violated....", "[3B4Z] Coagulation defects, unspecified\n --PARENT--> [?] Coagulation defects\n --CHILD--> [?] Haemorrhagic diseases due to acquired coagulation factor defects\n Def: Any disease caused by determinants arising after birth. These diseases are characterised by abnormal coagulation of the blood....", "[3B4Z] Coagulation defects, unspecified\n --PARENT--> [?] Coagulation defects\n --PARENT--> [?] Coagulation defects, purpura or other haemorrhagic or related conditions\n Def: A condition caused by determinants arising during the antenatal period, after birth or by genetically inherited factors, leading to coagulation defects. This condition is characterised by increased br..." ]	JA86.Y	Maternal care for other specified fetal problems	[ { "from_icd11": "JA86.Y", "icd10_code": "O26841 ", "icd10_title": "" }, { "from_icd11": "JA86.Y", "icd10_code": "O26843 ", "icd10_title": "" }, { "from_icd11": "JA86.Y", "icd10_code": "O26849 ", "icd10_title": "" }, { "from_icd11": "JA86.Y", "icd10_code": "O3680X0 ", "icd10_title": "" }, { "from_icd11": "3B4Z", "icd10_code": "D688", "icd10_title": "Other specified coagulation defects" }, { "from_icd11": "3B4Z", "icd10_code": "D689", "icd10_title": "Coagulation defect, unspecified" }, { "from_icd11": "3B4Z", "icd10_code": "D699", "icd10_title": "Hemorrhagic condition, unspecified" }, { "from_icd11": "3B4Z", "icd10_code": "D698", "icd10_title": "Other specified hemorrhagic conditions" }, { "from_icd11": "3B4Z", "icd10_code": "D65-D69", "icd10_title": "" }, { "from_icd11": "3B4Z", "icd10_code": "D69", "icd10_title": "Purpura and other hemorrhagic conditions" }, { "from_icd11": "4A45.Z", "icd10_code": "D6861", "icd10_title": "Antiphospholipid syndrome" }, { "from_icd11": "4A45.Z", "icd10_code": "D6869", "icd10_title": "Other thrombophilia" }, { "from_icd11": "4A45.Z", "icd10_code": "D6862", "icd10_title": "Lupus anticoagulant syndrome" }, { "from_icd11": "4A45.Z", "icd10_code": "D686", "icd10_title": "Other thrombophilia" }, { "from_icd11": "FB3Z", "icd10_code": "M60831", "icd10_title": "Other myositis, right forearm" } ]	O26841
Case 1. This 3-month-old baby girl presented with frequent emesis and subsequently developed poor head control and prominent scalp veins. Head CT and MR disclosed hydrocephalus and a large inhomogeneous non-enhancing tumor in the right cerebellar hemisphere extending to the right CPA . She had a posterior fossa craniotomy and the tumor was noted in the right cerebellar hemisphere extending to the right CMF and CPA . The fourth ventricle was displaced contralaterally but not involved . The 9th, 10th and 11th nerves were engulfed by the tumor at brainstem entry zone but their anatomical continuities were preserved . The displaced seventh and eighth nerves were protected and a gross total resection of the tumor was attained on post-operative MR . Pathology report showed ATRT. Postoperatively, she showed stridor due to right vocal cord paresis and swelling. Also, she had a mild right facial weakness and left-sided esotropia, both of which resolved spontaneously. Speech evaluation indicated that she had moderate-severe oral-pharyngeal dysphagia. She was fed through NG feeding tube. She then received high-dose chemotherapy with stem-cell rescue. She was able to take oral feeding; however, 6 months postoperatively, she passed away due to septic complications of intense chemotherapy. No tumor recurrence was noted. Fig. 3 Case 1. Axial MR image ( a T1-weighted post contrast, b T2-weighted) of a 3-month-old infant showing a large poorly enhancing, inhomogeneous right cerebellar ATRT extending into the CPA Fig. 4 Surgical photograph of case 1. a Following the major bulk of tumor from the cerebellar hemisphere, the cerebellomedullary fissure is exposed and the tumor ( arrow ) is separated away from the 9th and 10th nerves and the jugular foramen is exposed ( star ). b The fourth ventricle is displaced but not involved. c Following resection of CPA/CMF ATRT, the internal auditory meatus ( arrow ) and the jugular foramen ( star ) and respective cranial nerves are shown. Note the cerebellar white matter after tumor resection ( arrow head ) Fig. 5 Case 1. Post-operative T1-weighted MRI after contrast infusion ( a axial, b coronal) showing a gross total resection of ATRT Case 2. This 12-month-old boy presented with increasing head circumference together with psychomotor developmental arrest for several months. He was also diagnosed to have “arthrogryposis” shortly after the birth which caused a delay in his developmental milestones. MRI showed a marked hydrocephalus due to very large poorly enhancing homogenous tumor extending from the left CPA to the fourth ventricle and cisterna magna . Through a posterior fossa craniotomy, the tumor was found in the subarachnoid space in the cisterna magna and upper cervical cord. After debulking the tumor and lifting it, the spinal accessory nerve was found in the CMF subarachnoid space and the jugular foramen. Also, the PICA of the left side was traced and the vertebral artery was found. The vertebral artery was surrounded by tumor but dissected free under microscope. The 9th and 10th nerves were at the CMF wrapped around by the tumor, which were also separated and their anatomical continuity was preserved. At the CPA, the tumor was extending to the tentorial surface but seventh and eighth nerve complex was preserved at resection. The tumor further extended into the lateral recess and lateral fourth ventricle space, but was removed. The tumor appeared to have an origin from the cerebellar hemisphere. A gross total resection was attained except for a small portion at the 9th and 10th nerve entry zone to the medulla . Postoperatively, he developed bilateral vocal cord palsy noted and received tracheotomy and G-tube placement. The pathology showed a tanycytic ependymoma. Postoperatively, he received no adjuvant therapy. A follow-up laryngoscopy a year later showed normal right but reduced left vocal cord mobility. However, 2 years later, the laryngoscopy examination showed normal vocal cord function on both side, and his speech and swallowing functions returned normal. He had the G-tube removed 18 months post-surgery and tracheotomy was decannulated 2 years after surgery. MR done 3 years later showed no signs of tumor recurrence Fig. 6 Case 2. Pre-operative MRI ( a T2-weighted axial view, b T2-weighted coronal view, c post-contrast T1- weighted axial view, d post-contrast T1-weighted coronal view) showing a large CPA tanycytic ependymoma and marked hydrocephalus Fig. 7 a Surgical photograph of case 2 showing a large tumor ( arrows ) extending into the cisterna magna. b Post-resection showing a enlarged lateral recess to the fourth ventricle ( star ). Ninth and 10th nerves are shown ( arrow ) and there is a small residual tumor left surrounding the rootlets of these nerves Fig. 8 Case 2. Three years post-operative MRI ( a T2-weighted axial view, b , T1-weight coronal image after contrast) showing no signs of residual or recurrent tumor Case 3. This is a 4-year-old girl who presented with intermittent headaches with fever since a year ago. Due to increasing episodes of “chemical meningitis,” she had head CT and MR, she had CT and subsequent MRI which showed a large non-enhancing mass in the midline ventral to the brain stem at the pontomedullary junction . Pre-operative neurological examination was normal, however. Pre-operative laryngoscopy showed normal vocal cord movements. She had a PF craniotomy with the bone flap primarily on the left occipital bone crossing the midline and crossing the foramen magnum . The CMF and CPA were entered by lifting the cerebellar tonsil and hemisphere of the left side . Medially to the 9th and 10th nerves and also to the 7th and 8th nerve complex was the cloudy capsule of an epidermoid . Clearly, debris from the epidermoid contents was noted floating in the CSF space. The main approach was through the space below the 10th nerve and another above the 9th nerve. The lesion was removed from the space between the basilar artery and the ventral surface of the brain stem . Postoperatively, she developed a left vocal cord palsy, needing G-tube. She started to take oral feeding by 3 months and G-tube was removed 6 months postoperatively. At the last examination 4 years following the surgery, she had normal neurological function and follow-up laryngoscopy showed normal vocal cord function. No signs of epidermoid recurrence were noted on follow-up MR Fig. 9 Case 3. Four-year-old girl with previous history of chemical meningitis. MR images ( a T2-weighted axial view, b T1-weight sagittal image after contrast infusion) showing a large mass ventral to the ponto-medullary junction. Note a severe brain stem compression by the non-enhancing tumor between the brain stem and the basilar artery Fig. 10 Surgical photographs of case 3. a Through a hockey stick incision and predominantly left posterior fossa craniotomy and dural opening, the left cerebellar hemisphere and tonsil are exposed. b By lifting the left cerebellum and tonsil, the left jugular foramen and cranial nerves are identified. c The jugular foramen ( star ) and the 9–10th nerves are identified in the CMF. The epidermoid capsule is noted ventral to the brain stem surrounded by lower cranial nerves. d Following the epidermoid resection, the vertebrobasilar artery ( arrow ) is noted Fig. 11 Case 3. Post-operative MRI ( a T2-weight axial image, b T1-weight sagittal image after contrast) showing no evidence of residual or recurrent epidermoid Case 4. This is a 5-year-old boy who presented with increasing lethargy after a minor fall a week ago. On examination, he was noted to have speech dysarthria with decreased gag reflex on the left side. He has nystagmus at lateral and upward gaze, and a mild left-sided dysmetria. Head CT and subsequent MR showed a large mass in the left CMF without hydrocephalus . Through a hockey stick incision and posterior fossa craniotomy and C1 arch resection, a large exophytic tumor was exposed in the cisterna magna and upper cervical subarachnoid space . The tumor appeared to be originating from the posterolateral medulla oblongata dorsally to the root entrance of 9th and 10th nerves. It extended medially to the lateral wall of the fourth ventricle, rostrally into the cerebellar parenchyma and laterally and anteriorly into the CPA. A gross total resection was attained sparing all visible cranial nerves of 7th to 11th. The pathology showed a juvenile pilocytic astrocytoma (JPA) and it appeared to be originating from the inferior cerebellar peduncle. Postoperatively, he had dysphagia necessitating NG feeding. He had supplemental NG feeding for 2 years which was then stopped. He had to turn his head to the left side to assist swallowing for big meals. He did not receive any adjuvant therapy for the tumor. Presently, 14 years after the resection, he attends college and his speech and swallowing were normal. The only neurological findings were a slight deviation of uvula and soft palate, minimal dysmetria of the left side, and left neurosensory hearing loss. The latest MRI showed no evidence of tumor Fig. 12 Case 4. Pre-operative T1-weight axial MRI showing a large heterogeneous tumor in the left CMF and CPA displacing the fourth ventricle Fig. 13 Surgical photograph of case 4. a Large exophytic JPA extending into the cisterna magna. b Following the resection of the exophytic tumor, the dorsal spinal cord is uncovered together with left posterior inferior cerebellar artery. c , The tumor further extends into the lateral dorsal aspect of the medulla oblongata, which was removed. Note the inspection of the lateral medulla oblongata by turning it inward following the tumor resection. Note the 9th and 10th nerves are shown entering the jugular foramen ( arrow ) and medially there is a tumor resected cavity ( star ). d The JPA appeared to originate from the inferior cerebellar peduncle and a gross total resection was attained. Note the open fourth ventricle ( arrow ) and the tumor resected cavity wall at the dorsal medulla oblongata and upper cervical cord ( star ) Fig. 14 Case 4. Post-operative T1-weighted postcontrast MRI ( a axial, b coronal). There is no evidence of disease	4.027344	0.977051	sec[2]/sec[4]/p[0]	en	0.999996	26351227	https://doi.org/10.1007/s00381-015-2747-x	[ "tumor", "nerves", "resection", "cerebellar", "large", "cord", "weighted", "axial", "fourth", "ventricle" ]	[ { "code": "2F9Z", "title": "Neoplasms of unknown behaviour of unspecified site" }, { "code": "ME61", "title": "Subcutaneous swelling, mass or lump of uncertain or unspecified nature" }, { "code": "2E6Z", "title": "Carcinoma in situ of unspecified site" }, { "code": "2F91.1", "title": "Neoplasms of unknown behaviour of trachea, bronchus or lung" }, { "code": "2F92", "title": "Neoplasms of unknown behaviour of skin" }, { "code": "8C1Z", "title": "Mononeuropathy of unspecified site" }, { "code": "ND56.4", "title": "Injury of nerve of unspecified body region" }, { "code": "8B80", "title": "Disorders of olfactory nerve" }, { "code": "8C0Z", "title": "Polyneuropathy, unspecified" }, { "code": "9C40.Z", "title": "Disorder of the optic nerve, unspecified" } ]	=== ICD-11 CODES FOUND === [2F9Z] Neoplasms of unknown behaviour of unspecified site Also known as: Neoplasms of unknown behaviour of unspecified site \| neoplasia \| neoplasm growth NOS \| tumour of unspecified site \| tumourlet of unspecified site [ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature Definition: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature Also known as: Subcutaneous swelling, mass or lump of uncertain or unspecified nature \| localised swelling, mass or lump of skin and subcutaneous tissue \| localised subcutaneous nodules \| subcutaneous nodules \| superficial subcutaneous nodules Excludes: localized adiposity \| mass and lump: breast \| enlarged lymph nodes [2E6Z] Carcinoma in situ of unspecified site Also known as: Carcinoma in situ of unspecified site \| carcinoma in situ of unspecified site \| carcinoma in situ NOS \| carcinoma in situ \| in situ neoplasm [2F91.1] Neoplasms of unknown behaviour of trachea, bronchus or lung Also known as: Neoplasms of unknown behaviour of trachea, bronchus or lung \| trachea, bronchus or lung tumour NOS \| Intravascular bronchial alveolar tumour of unspecified site \| Bronchial adenoma of unknown behaviour of unspecified site \| Intravascular bronchial alveolar tumour unknown behaviour of unspecified site [2F92] Neoplasms of unknown behaviour of skin Also known as: Neoplasms of unknown behaviour of skin \| skin tumour NOS [8C1Z] Mononeuropathy of unspecified site Also known as: Mononeuropathy of unspecified site \| inflammation of nerve NOS \| nerve condition NOS \| neuritis NOS \| nerve disease NOS [ND56.4] Injury of nerve of unspecified body region Also known as: Injury of nerve of unspecified body region \| injuries to nerves, nerve plexuses and roots \| injury to nerves, unspecified site \| nerve damage NOS \| Injury of nerve NOS Excludes: multiple injuries of nerves NOS [8B80] Disorders of olfactory nerve Also known as: Disorders of olfactory nerve \| disorders of olfactory [1st] nerve \| disorders of the first nerve \| first cranial nerve disorder \| disease of first cranial nerve Includes: Disorder of 1st cranial nerve Excludes: Idiopathic anosmia \| Idiopathic parosmia [8C0Z] Polyneuropathy, unspecified Also known as: Polyneuropathy, unspecified \| multiple neuropathy \| peripheral neuropathy NOS \| peripheral polyneuropathy \| multiple peripheral neuritis [9C40.Z] Disorder of the optic nerve, unspecified Also known as: Disorder of the optic nerve, unspecified \| Disorder of the optic nerve \| disease of optic cranial nerve \| disease of optic nerve \| disease of second cranial nerve === GRAPH WALKS === --- Walk 1 --- [2F9Z] Neoplasms of unknown behaviour of unspecified site --PARENT--> [?] Neoplasms of unknown behaviour, except of lymphoid, haematopoietic, central nervous system or related tissues --CHILD--> [2F91] Neoplasms of unknown behaviour of middle ear, respiratory or intrathoracic organs --- Walk 2 --- [2F9Z] Neoplasms of unknown behaviour of unspecified site --PARENT--> [?] Neoplasms of unknown behaviour, except of lymphoid, haematopoietic, central nervous system or related tissues --RELATED_TO--> [?] Pathological fracture in neoplastic disease of unknown behaviour --- Walk 3 --- [ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature Def: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature... --EXCLUDES--> [?] Enlarged lymph nodes Def: Enlarged lymph node is called lymphadenopathy which means the abnormal enlargement of lymph nodes.... --CHILD--> [?] Generalised lymph node enlargement --- Walk 4 --- [ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature Def: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature... --PARENT--> [?] Symptoms or signs involving the skin Def: This category allows the capture of imprecise data where a more specific diagnosis cannot be made or to supplement information about a specific diagnosis.... --CHILD--> [ME60] Skin lesion of uncertain or unspecified nature Def: To be used where there is either significant uncertainty or alternatively no information as to the nature of a circumscribed skin lesion. This is of particular importance with regard to whether or not... --- Walk 5 --- [2E6Z] Carcinoma in situ of unspecified site --PARENT--> [?] In situ neoplasms, except of lymphoid, haematopoietic, central nervous system or related tissues --CHILD--> [2E61] Carcinoma in situ of other or unspecified digestive organs --- Walk 6 --- [2E6Z] Carcinoma in situ of unspecified site --PARENT--> [?] In situ neoplasms, except of lymphoid, haematopoietic, central nervous system or related tissues --PARENT--> [02] Neoplasms Def: An abnormal or uncontrolled cellular proliferation which is not coordinated with an organism's requirements for normal tissue growth, replacement or repair....	[ "[2F9Z] Neoplasms of unknown behaviour of unspecified site\n --PARENT--> [?] Neoplasms of unknown behaviour, except of lymphoid, haematopoietic, central nervous system or related tissues\n --CHILD--> [2F91] Neoplasms of unknown behaviour of middle ear, respiratory or intrathoracic organs", "[2F9Z] Neoplasms of unknown behaviour of unspecified site\n --PARENT--> [?] Neoplasms of unknown behaviour, except of lymphoid, haematopoietic, central nervous system or related tissues\n --RELATED_TO--> [?] Pathological fracture in neoplastic disease of unknown behaviour", "[ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature\n Def: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature...\n --EXCLUDES--> [?] Enlarged lymph nodes\n Def: Enlarged lymph node is called lymphadenopathy which means the abnormal enlargement of lymph nodes....\n --CHILD--> [?] Generalised lymph node enlargement", "[ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature\n Def: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature...\n --PARENT--> [?] Symptoms or signs involving the skin\n Def: This category allows the capture of imprecise data where a more specific diagnosis cannot be made or to supplement information about a specific diagnosis....\n --CHILD--> [ME60] Skin lesion of uncertain or unspecified nature\n Def: To be used where there is either significant uncertainty or alternatively no information as to the nature of a circumscribed skin lesion. This is of particular importance with regard to whether or not...", "[2E6Z] Carcinoma in situ of unspecified site\n --PARENT--> [?] In situ neoplasms, except of lymphoid, haematopoietic, central nervous system or related tissues\n --CHILD--> [2E61] Carcinoma in situ of other or unspecified digestive organs", "[2E6Z] Carcinoma in situ of unspecified site\n --PARENT--> [?] In situ neoplasms, except of lymphoid, haematopoietic, central nervous system or related tissues\n --PARENT--> [02] Neoplasms\n Def: An abnormal or uncontrolled cellular proliferation which is not coordinated with an organism's requirements for normal tissue growth, replacement or repair...." ]	2F9Z	Neoplasms of unknown behaviour of unspecified site	[ { "from_icd11": "2F9Z", "icd10_code": "D487", "icd10_title": "Neoplasm of uncertain behavior of other specified sites" }, { "from_icd11": "2F9Z", "icd10_code": "D482", "icd10_title": "Neoplasm of uncertain behavior of peripheral nerves and autonomic nervous system" }, { "from_icd11": "2F9Z", "icd10_code": "D37-D48", "icd10_title": "" }, { "from_icd11": "2F9Z", "icd10_code": "D377", "icd10_title": "" }, { "from_icd11": "2F9Z", "icd10_code": "D48", "icd10_title": "Neoplasm of uncertain behavior of other and unspecified sites" }, { "from_icd11": "2F9Z", "icd10_code": "D489", "icd10_title": "Neoplasm of uncertain behavior, unspecified" }, { "from_icd11": "ME61", "icd10_code": "R2240", "icd10_title": "Localized swelling, mass and lump, unspecified lower limb" }, { "from_icd11": "ME61", "icd10_code": "R2232", "icd10_title": "Localized swelling, mass and lump, left upper limb" }, { "from_icd11": "ME61", "icd10_code": "R2242", "icd10_title": "Localized swelling, mass and lump, left lower limb" }, { "from_icd11": "ME61", "icd10_code": "R2231", "icd10_title": "Localized swelling, mass and lump, right upper limb" }, { "from_icd11": "ME61", "icd10_code": "R2241", "icd10_title": "Localized swelling, mass and lump, right lower limb" }, { "from_icd11": "ME61", "icd10_code": "R2233", "icd10_title": "Localized swelling, mass and lump, upper limb, bilateral" }, { "from_icd11": "ME61", "icd10_code": "R2243", "icd10_title": "Localized swelling, mass and lump, lower limb, bilateral" }, { "from_icd11": "ME61", "icd10_code": "R2230", "icd10_title": "Localized swelling, mass and lump, unspecified upper limb" }, { "from_icd11": "ME61", "icd10_code": "R220", "icd10_title": "Localized swelling, mass and lump, head" } ]	D487	Neoplasm of uncertain behavior of other specified sites
A 52-year-old previously healthy woman with no family history of endocrine disease was admitted to our hospital with suspected PA based on high blood pressure (193/105 mmHg), spontaneous hypokalemia (potassium [K], 3.4 mmol/L), and a high aldosterone-to-renin ratio (ARR 71 ng/dL per ng/mL/h [plasma renin activity (PRA) 0.2 ng/mL/h and plasma aldosterone concentration (PAC) 14.2 ng/dL]). On admission, the patient showed no clinical features of Cushing syndrome, and no catecholamine excess symptoms other than hypertension, such as headache or excessive sweating. Before the initiation of antihypertensive drugs, PA was confirmed by the positive captopril challenge test (PRA: 0.2 ng/mL/h, PAC: 9.6 ng/dL, ARR: 48 [> 20]; Table 1 ) according to the Japan Endocrine Society Clinical Practice Guidelines for PA and the Japanese Society of Hypertension Guidelines for the Management of Hypertension . Abdominal computed tomography (CT) revealed bilateral adrenal masses (right, 16 × 11 mm; left, 13 × 9 mm), with baseline CT attenuation values of 30–60 Hounsfield units (HU) on the left and 10 HU on the right , and contrast-enhanced CT showed a stronger contrast effect in the left adrenal mass than in the right adrenal mass . Although overnight 1mg dexamethasone suppression test (DST) showed mild autonomous cortisol secretion (2.25 µg/dL [< 1.8]; Table 1 ), plasma level of ACTH in the early morning before DST was not suppressed (52.1 pg/mL [> 7.07]; Table 1 ), and the diurnal variation of serum cortisol was preserved (Table 1 ). Based on the Japanese Endocrine Society criteria , adrenal subclinical Cushing's syndrome was ruled out. The 24-h urinary catecholamines were within normal limits, and the urinary fractionated metanephrines (metanephrine, 0.47 mg/day [< 0.19] and normetanephrine, 0.46 mg/day [< 0.33]) were slightly elevated but did not reach 3-fold of the upper limit of normal range (Table 2 ). Adrenal vein sampling (AVS) was performed because she requested surgical treatment at that time and the results were interpreted according to previous guidelines . The findings confirmed that the right adrenal gland was responsible for aldosterone hypersecretion (post-cosyntropin stimulation lateralization ratio 24.67 [> 4], contralateral ratio 0.575 [< 1]; Table 3 ). She refused right adrenalectomy at the last minute, and medical therapy with the mineralocorticoid receptor (MR) antagonist, eplerenone (50 mg) was initiated; however, she abruptly discontinued treatment and the follow-up visit. Five years after the first AVS, she visited a local clinic with complaints of headache and high blood pressure (208/109 mmHg) and was administered a calcium blocker (cilnidipine 10 mg). At this time, she requested surgery for PA and was readmitted to our hospital. On admission, her blood pressure was 127/96 mmHg, and she was taking oral cilnidipine 20 mg/day. No symptoms of catecholamine excess or Cushing's signs were observed. Repeated abdominal CT showed no significant change in the right adrenal mass (16 × 11 mm); however, the left adrenal mass was enlarged to 26 × 13 mm . At the surgeon's request, AVS was performed a second time to confirm PA localization. The second AVS confirmed the right unilateral hyperaldosteronism (post-cosyntropin stimulation lateralization ratio: 12.60; contralateral suppression index: 0.40) had not changed. (Table 3 ). Repeated 1mg DST showed mild autonomous cortisol secretion, but the diurnal variation of cortisol was preserved (11:00 pm cortisol: 4.46 µg/dL). The 24-h urinary excretion assay revealed that norepinephrine (142.3 μg/day), epinephrine (26.5 μg/day), and dopamine (644.0 μg/day) levels were normal; however, metanephrine (0.81 mg/day) and normetanephrine (0.60 mg/day) concentrations were higher than those measured 5 years earlier (Table 2 ). 123 I-MIBG scintigraphy showed a tracer-avid left adrenal mass but no metastatic lesions . Based on these findings, a left pheochromocytoma was diagnosed preoperatively. After the temporary discharge, we had a conference with the department of urology of our institution, and we decided to perform partial adrenalectomy for the left pheochromocytoma and medical treatment for the right unilateral PA. The patient was started on α-blocker (doxazosin, 2 mg/day), a non-steroidal MR antagonist (esaxerenone, 5 mg/day), and continued cilnidipine 20 mg/day. Two months later, she was readmitted to our hospital. After preoperative administration of saline (1 L/day) for 7 days and an α-blocker (doxazosin, 2.0 mg/day) for 2 months, laparoscopic left partial adrenalectomy was performed. No intraoperative or postoperative hemodynamic instability occurred. Histologically, the tumor cells were arranged in diffuse sheets or nests and were large with prominent nucleoli . The pheochromocytoma of the adrenal gland scaled score was 0 indicating a low grade pheochromocytoma. Immunohistochemical examination of the tumor showed that chromogranin A and synaptophysin were positive , leading to the final diagnosis of left pheochromocytoma; Succinate dehydrogenase subunit B (SDHB) was positive ; cytochrome P450 (CYP) 11B2 was negative, Ki 67 was weakly positive , and ACTH was negative . The left adrenal gland tissue adjacent to the tumor was normal . Although we could not perform genetic analysis, as consent could not be obtained from the patient, the positive immunostaining for SDHB, suggested against SDH-related paraganglioma syndromes. Doxazosin was discontinued after surgery and esaxerenone (5 mg) and cilnidipine (20 mg) were continued. One month after surgery, the patient’s blood pressure was 126/84 mmHg, and her serum K (4.27 mmol/L), PAC (47.38 ng/dL), active renin concentration (ARC) (36.57 μU/mL), and random fractionated urinary metanephrines (metanephrine 152 ng/mg Cr [29–158], normetanephrine 363 ng/mg Cr [122–500]) were normalized. One year after surgery, blood pressure and serum K levels remained well controlled. No surgical treatment for the right adrenal mass has been performed, and pheochromocytoma has not recurred. Table 1 Laboratory and endocrinological data Parameter Values Reference ranges K (mmol/L) 3.67 3.6–5.0 Creatinine (mg/dL) 0.55 0.47–0.79 PAC (ng/dL) 19.7 3.6–24 PRA (ng/mL/h) 0.3 0.2–2.3 DHEA-S (µg/dL) 97 8–188 ACTH (pg/mL) 52.1 7.2–63.3 11 pm ACTH (pg/mL) 19.26 Cortisol (µg/dL) 15.87 7.07–19.6 11 pm Cortisol (µg/dL) 3.44 < 5 Urinary Cortisol (μg/day) a 48.2 11.2–80.3 Urinary Aldosterone (μg/day) a 14.4 1.0–19.3 1 mg DST cortisol (µg/dL) 2.25 < 1.8 Captopril challenge test Pre-PAC (ng/dL) 18.3 3.6–24 PRA (ng/mL/h) 0.2 0.2–2.3 ARR 91.5 < 20 90 min-PAC (ng/dL) 9.6 PRA (ng/mL/h) 0.2 ARR 48 Abbreviations : PAC plasma aldosterone concentration, PRA plasma renin activity, DHEA-S dehydroepiandrosterone sulfate, ACTH adrenocorticotrophic hormone, DST dexamethasone suppression test, ARR plasma aldosterone/renin ratio a 24-hour urinary testing was performed in 2020 Fig. 1 A and B Computed tomography (CT) during the initial adrenal vein sampling (AVS) revealed bilateral adrenal nodules (right:16 × 11 mm, left:13 × 9 mm) with CT attenuation values of 30–60 Hounsfield units on the left and 10 Hounsfield units on the right. C and D Contrast-enhanced CT showed contrast effect in the left adrenal nodule but not in the right. E and F CT images at the second AVS (performed 5 years after the initial AVS) showed no significant changes in the right adrenal mass and enlargement of the left adrenal nodule (26 × 13 mm). G and H 123 I-MIBG scintigraphy showed marked uptake in the left adrenal nodule, but no metastatic lesions Table2 Catecholamines and their metabolites changes over 5 years First admission After 5 years Normal range Plasma Epinephrine (pg/mL) 30 60 < 100 Norepinephrine (pg/mL) 310 200 < 450 Dopamine (pg/mL) < 20 < 20 < 20 Urine Epinephrine (μg/day) 23.7 26.5 < 41 Norepinephrine (μg/day) 151.6 142.3 < 160 Dopamine (μg/day) 582.1 644.0 < 1100 Metanephrine (mg/day) 0.47 0.81 < 0.19 Normetanephrine (mg/day) 0.46 0.60 < 0.33 Table 3 Results of Adrenal vein sampling test First AVS Second AVS (5 years after first AVS) aldosterone (ng/dL) cortisol (µg/dL) A/C LR CR aldosterone (ng/dL) cortisol (µg/dL) A/C LR CR Unstimulated Right adrenal vein 328.54 62.54 5.25 63.14 938.33 76.3 12.30 24.18 Left adrenal vein 50.31 604.2 0.083 0.598 306.16 601.7 0.509 0.40 Inferior vena cava 2.33 16.78 0.139 29.63 23.4 1.265 Cosyntropin-Stimulated Right adrenal vein 1903.05 803.6 2.368 24.67 635.37 698.1 9.10 12.60 Left adrenal vein 53.05 767.8 0.096 0.575 461.9 639.6 0.722 0.40 Inferior vena cava 5.36 32.11 0.167 45.75 25.2 1.813 Localization diagnosis Right Right Abbreviations : AVS Adrenal vein sampling test, A aldosterone, C cortisol, LR lateralized ratio, CR contralateral ratio Fig. 2 Microscopic findings of pheochromocytoma. Equipment parameters: Microscope: OLYMPUS BX51TF Objective lens: UPlanSApo X40 Cameras: OLYMPUS DP73 Acquisition software: cellSens Standard Measured resolution: 72dpi. A-F , Hematoxylin–eosin (HE) staining, and immunohistochemical examination of the tumor tissue. A HE-staining revealed that the tumor was arranged in diffuse sheets or nests, and the tumor cells were large with prominent nucleoli. B-D Immunohistochemical examination revealed that the tumor was positive for CgA, synaptophysin, and SDHB. E CYP11B2 was negative, and F a few Ki-67 positive cells were detected Fig. 3 Microscopic findings of pheochromocytoma and normal adrenal gland. Equipment parameters: Microscope: OLYMPUS BX51TF Objective lens: UPlanSApo X40 Cameras: OLYMPUS DP73 Acquisition software: cellSens Standard Measured resolution: 72dpi. A Immunohistochemical examination of the tumor tissue. B-D Hematoxylin–eosin (HE) staining, and immunohistochemical examination of left adrenal gland. A There were no ACTH-positive cells in the tumor. B-D Left adrenal gland adjacent to the tumor. B HE-staining showed no specific change both in the adrenal cortex and the adrenal medulla. C CgA was positive in the adrenal medulla. D CYP11B2 was negative, and there were no CYP11B2 positive micronodules or diffuse hyperplasia in the adrenal cortex	4.234375	0.931641	sec[1]/p[0]	en	0.999997	PMC9933392	https://doi.org/10.1186/s12902-023-01297-3	[ "adrenal", "cortisol", "tumor", "aldosterone", "vein", "pheochromocytoma", "plasma", "urinary", "acth", "that" ]	[ { "code": "5A76.Y", "title": "Other specified disorders of adrenal gland" }, { "code": "5A7Z", "title": "Disorders of the adrenal glands or adrenal hormone system, unspecified" }, { "code": "5A74.Z", "title": "Adrenocortical insufficiency, unspecified" }, { "code": "5A74.Y", "title": "Other specified adrenocortical insufficiency" }, { "code": "LC8Z", "title": "Structural developmental anomalies of the adrenal glands, unspecified" }, { "code": "5A70.Y", "title": "Other specified Cushing syndrome" }, { "code": "5A70.Z", "title": "Cushing syndrome, unspecified" }, { "code": "5A74.0", "title": "Acquired adrenocortical insufficiency" }, { "code": "2F9Z", "title": "Neoplasms of unknown behaviour of unspecified site" }, { "code": "ME61", "title": "Subcutaneous swelling, mass or lump of uncertain or unspecified nature" } ]	=== ICD-11 CODES FOUND === [5A76.Y] Other specified disorders of adrenal gland Also known as: Other specified disorders of adrenal gland \| Suprarenal gland abscess \| Suprarenal abscess \| Adrenal gland inflammation \| adrenal glandular inflammation [5A7Z] Disorders of the adrenal glands or adrenal hormone system, unspecified Also known as: Disorders of the adrenal glands or adrenal hormone system, unspecified \| Adrenal gland disease, not elsewhere classified \| adrenal cortex disease \| adrenal cortical disease \| adrenal glandular disease [5A74.Z] Adrenocortical insufficiency, unspecified Also known as: Adrenocortical insufficiency, unspecified \| Adrenocortical insufficiency \| adrenal failure NOS \| Hypoadrenocorticism \| adrenocortical hypofunction [5A74.Y] Other specified adrenocortical insufficiency Also known as: Other specified adrenocortical insufficiency \| Congenital adrenocortical insufficiency \| Congenital isolated ACTH deficiency \| Familial adrenal hypoplasia \| Familial hypoadrenocorticism [LC8Z] Structural developmental anomalies of the adrenal glands, unspecified Also known as: Structural developmental anomalies of the adrenal glands, unspecified \| adrenal anomaly \| adrenal gland anomaly \| congenital anomaly of adrenal gland \| congenital malformation of adrenal gland [5A70.Y] Other specified Cushing syndrome Also known as: Other specified Cushing syndrome \| ACTH-dependent Cushing syndrome \| ACTH-independent Cushing syndrome \| ACTH-independent Cushing syndrome due to bilateral adrenocortical hyperplasia \| ACTH-independent macronodular adrenal hyperplasia [5A70.Z] Cushing syndrome, unspecified Also known as: Cushing syndrome, unspecified \| Cushing syndrome \| Hyperadrenocorticism \| Hypercortisolism \| Cushing syndrome NOS [5A74.0] Acquired adrenocortical insufficiency Definition: This is a acquired condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol; but may also include impaired production of aldosterone (a mineralocorticoid), which regulates sodium conservation, potassium secretion, and water retention. Also known as: Acquired adrenocortical insufficiency \| Addison disease \| Chronic acquired adrenal insufficiency \| Autoimmune Addison disease \| Primary Addison disease Excludes: Amyloidosis [2F9Z] Neoplasms of unknown behaviour of unspecified site Also known as: Neoplasms of unknown behaviour of unspecified site \| neoplasia \| neoplasm growth NOS \| tumour of unspecified site \| tumourlet of unspecified site [ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature Definition: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature Also known as: Subcutaneous swelling, mass or lump of uncertain or unspecified nature \| localised swelling, mass or lump of skin and subcutaneous tissue \| localised subcutaneous nodules \| subcutaneous nodules \| superficial subcutaneous nodules Excludes: localized adiposity \| mass and lump: breast \| enlarged lymph nodes === GRAPH WALKS === --- Walk 1 --- [5A76.Y] Other specified disorders of adrenal gland --PARENT--> [5A76] Certain specified disorders of adrenal gland --PARENT--> [?] Disorders of the adrenal glands or adrenal hormone system --- Walk 2 --- [5A76.Y] Other specified disorders of adrenal gland --PARENT--> [5A76] Certain specified disorders of adrenal gland --CHILD--> [5A76.0] Premature adrenarche Def: Premature development of pubic and/or axillary hair without central or peripheral precocious puberty. Children show premature clinical and/or laboratory signs of androgen action without estrogen actio... --- Walk 3 --- [5A7Z] Disorders of the adrenal glands or adrenal hormone system, unspecified --PARENT--> [?] Disorders of the adrenal glands or adrenal hormone system --CHILD--> [5A72] Hyperaldosteronism --- Walk 4 --- [5A7Z] Disorders of the adrenal glands or adrenal hormone system, unspecified --PARENT--> [?] Disorders of the adrenal glands or adrenal hormone system --CHILD--> [5A72] Hyperaldosteronism --- Walk 5 --- [5A74.Z] Adrenocortical insufficiency, unspecified --PARENT--> [5A74] Adrenocortical insufficiency Def: A condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol. It may also include impaired production of aldosterone (a mineralocorticoid), which reg... --CHILD--> [5A74.Y] Other specified adrenocortical insufficiency --- Walk 6 --- [5A74.Z] Adrenocortical insufficiency, unspecified --PARENT--> [5A74] Adrenocortical insufficiency Def: A condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol. It may also include impaired production of aldosterone (a mineralocorticoid), which reg... --RELATED_TO--> [?] X-linked adrenoleukodystrophy Def: X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disease characterised by progressive demyelinisation of the central nervous system (CNS) (brain and/or spinal cord) and peripheral adrenal insuff...	[ "[5A76.Y] Other specified disorders of adrenal gland\n --PARENT--> [5A76] Certain specified disorders of adrenal gland\n --PARENT--> [?] Disorders of the adrenal glands or adrenal hormone system", "[5A76.Y] Other specified disorders of adrenal gland\n --PARENT--> [5A76] Certain specified disorders of adrenal gland\n --CHILD--> [5A76.0] Premature adrenarche\n Def: Premature development of pubic and/or axillary hair without central or peripheral precocious puberty. Children show premature clinical and/or laboratory signs of androgen action without estrogen actio...", "[5A7Z] Disorders of the adrenal glands or adrenal hormone system, unspecified\n --PARENT--> [?] Disorders of the adrenal glands or adrenal hormone system\n --CHILD--> [5A72] Hyperaldosteronism", "[5A7Z] Disorders of the adrenal glands or adrenal hormone system, unspecified\n --PARENT--> [?] Disorders of the adrenal glands or adrenal hormone system\n --CHILD--> [5A72] Hyperaldosteronism", "[5A74.Z] Adrenocortical insufficiency, unspecified\n --PARENT--> [5A74] Adrenocortical insufficiency\n Def: A condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol. It may also include impaired production of aldosterone (a mineralocorticoid), which reg...\n --CHILD--> [5A74.Y] Other specified adrenocortical insufficiency", "[5A74.Z] Adrenocortical insufficiency, unspecified\n --PARENT--> [5A74] Adrenocortical insufficiency\n Def: A condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol. It may also include impaired production of aldosterone (a mineralocorticoid), which reg...\n --RELATED_TO--> [?] X-linked adrenoleukodystrophy\n Def: X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disease characterised by progressive demyelinisation of the central nervous system (CNS) (brain and/or spinal cord) and peripheral adrenal insuff..." ]	5A76.Y	Other specified disorders of adrenal gland	[ { "from_icd11": "5A7Z", "icd10_code": "E2740", "icd10_title": "Unspecified adrenocortical insufficiency" }, { "from_icd11": "5A7Z", "icd10_code": "E2749", "icd10_title": "Other adrenocortical insufficiency" }, { "from_icd11": "5A7Z", "icd10_code": "E279", "icd10_title": "Disorder of adrenal gland, unspecified" }, { "from_icd11": "5A7Z", "icd10_code": "E27", "icd10_title": "Other disorders of adrenal gland" }, { "from_icd11": "5A7Z", "icd10_code": "E274", "icd10_title": "Other and unspecified adrenocortical insufficiency" }, { "from_icd11": "LC8Z", "icd10_code": "Q891", "icd10_title": "Congenital malformations of adrenal gland" }, { "from_icd11": "5A70.Z", "icd10_code": "E242", "icd10_title": "Drug-induced Cushing's syndrome" }, { "from_icd11": "5A70.Z", "icd10_code": "E249", "icd10_title": "Cushing's syndrome, unspecified" }, { "from_icd11": "5A70.Z", "icd10_code": "E248", "icd10_title": "Other Cushing's syndrome" }, { "from_icd11": "5A70.Z", "icd10_code": "E24", "icd10_title": "Cushing's syndrome" }, { "from_icd11": "5A74.0", "icd10_code": "E273", "icd10_title": "Drug-induced adrenocortical insufficiency" }, { "from_icd11": "5A74.0", "icd10_code": "E271", "icd10_title": "Primary adrenocortical insufficiency" }, { "from_icd11": "5A74.0", "icd10_code": "E35", "icd10_title": "Disorders of endocrine glands in diseases classified elsewhere" }, { "from_icd11": "2F9Z", "icd10_code": "D487", "icd10_title": "Neoplasm of uncertain behavior of other specified sites" }, { "from_icd11": "2F9Z", "icd10_code": "D482", "icd10_title": "Neoplasm of uncertain behavior of peripheral nerves and autonomic nervous system" } ]	E2740	Unspecified adrenocortical insufficiency
Table 1 A discussion of each Decision Point, the impact of each on the patient’s story, and how the story could have followed a different path Decision Point What went wrong? How did this contribute to chronicity? What could have been done differently? What would have been the likely result? How might that help the patient’s story be more like that of Twin B? Strength of Recommendation I “Radiographs are ordered” without indication and the “patient is told he has two degenerative discs causing his low back pain” “Disc degeneration” is found, and this is presumed the cause of the pain, resulting in unfounded fear and catastrophizing No radiographs ordered The graphic, fear-inducing idea of having a “degenerating disc” would not have entered the patient’s mind “My back hurts a lot but that does not mean it is damaged.” A Based on consistent and good quality patient-oriented evidence II “told to stay out of work to prevent worsening of the problem and that he should avoid activities that provoke the pain” The patient is instructed to take a passive approach, and to believe that activities should be avoided A defined plan to resume activity is discussed and progressively return to all usual activities, including work Hastens recovery and early return to work “Even though my back hurts, I can engage in activity. In fact, activity will likely help.” A Based on consistent and good quality patient-oriented evidence III “.referral for physical therapy is the standard protocol prior to considering seeing a surgeon, and…the insurance carrier will not pay for the surgeon visit until after he has tried physical therapy” The patient feels that the conversation about referral for physical therapy served the purpose of following a protocol, rather than listening to him and framing the referral on his needs in overcoming the problem . And that seeing a surgeon is inevitable, and necessary; being referred for physical therapy is merely a formality After listening carefully to the patient’s concerns, a clear plan to rapidly bring about resolution of the problem, focusing on a targeted, evidence-based approach best suited to his condition Rapid resolution of the problem “They are all on the same page in helping me get better as quickly as possible.” A Based on consistent and good quality patient-oriented evidence IV The patient terminates physical therapy “because he has to pay a copayment on each visit, and it would be cheaper to just see a surgeon” The patient is disincentivized to pursue appropriate care for his condition because his insurance company policy puts a financial barrier in place that make appropriate care substantially more costly to him then inappropriate care A policy in place that, at all levels of the healthcare system, puts incentives in place that encourages high-value care and discourages low-value care No barrier is in place for the patient to pursue the most appropriate treatment “The exercise hurts a bit but I might as well stick with it – there’s no reason not to.” B Recommendation based on inconsistent or limited quality patient-oriented evidence V “He stops physical therapy” In terminating physical therapy, he loses the opportunity to gain an understanding of the discomfort he experienced when exercising . The perception of his having a “degenerating spine” is reinforced, as is the assumption that activity should be avoided in order to prevent further “damage” A policy in place that incentivizes patients to pursue active, evidence-based, patient-centered care The patient has an opportunity to be educated regarding the concept of “hurt ≠ harm”, leading him to continue an evidence-based approach “At first I was a little worried when the exercise bothered my back. But the doctor assured me that ‘hurt does not necessarily mean harm’ and, sure enough, they were right.” A Based on consistent and good quality patient-oriented evidence VI “MRI is ordered which confirms …degenerative disc disease… facet arthrosis… disc bulges” Another inappropriate imaging study reinforces in the patient’s mind that he has a degenerating spine; in fact, his perception is that the MRI showed that his spine is even more severely “damaged” than previously thought No MRI is ordered, after the practitioner listens carefully to the patient’s concerns. The practitioner provides an individualized explanation as to why MRI is unnecessary; the patient receives evidence-based information about his condition Reinforcement of the concept that he does not have a fragile spine and that there is no “damage” of concern “The doctors found the problem on examination and explained it to me. So I don’t have to take the extra time and effort to go for an MRI.” A Based on consistent and good quality patient-oriented evidence VII “The patient receives an automated message that the MRI report is available” The patient sees confusing, fear-invoking words on the MRI that is provided to him on a piece of paper, without the benefit of expert explanation, context and guidance. This further exacerbates the fear and catastrophizing already in place [If it were a situation in which an MRI had been ordered] Evidence-based explanation of the report, given verbally and/or imbedded within the report , with assurance that all the findings are age-appropriate, dynamic, and very common in patients of his age who have no back pain Enables the patient to question his own perception of having a “degenerating spine”, opening the door to reframing his situation in a more realistic, accurate and empowering manner “I have been given information about my back that makes me feel a lot better about what the pain means and what it doesn’t mean.” B Recommendation based on inconsistent or limited quality patient-oriented evidence VIII “His PCP confirms the findings of the MRI and refers him to a spine surgeon” The patient’s distress that arose from having seen the MRI report is reinforced and exacerbated by being told he has to see a surgeon In addition to the evidence-based explanation discussed above, assurance that there is no indication that an operation is necessary Further supports the patient in questioning his perception of a “degenerating spine”, opening the door to an understanding that a straightforward, non-invasive solution is likely to be successful “The doctors understand me and my back pain, and have pointed me in the right direction.” B Recommendation based on inconsistent or limited quality patient-oriented evidence IX “The first available appointment with the surgeon is scheduled in six weeks” The patient is left to stay at home and agonize over his predicament, reinforcing both his perceptions of pain and disability, rather than engaging in active steps toward improvement The patient is immediately directed toward an active, productive approach, with return to activity and work (even if limited) Avoids the detrimental impact of passivity “I have been given a bunch of simple things to do for myself. So I don’t have to wait for someone else to do things for me.” C Recommendation based on consensus, usual practice, expert opinion X “The surgeon reviews the MRI with him, confirming the multi-level degenerative changes and explaining that he may need fusion surgery, but that the standard protocol is to try injections first” Two invasive approaches are discussed without sound evidence supporting their role for his condition Educating the patient regarding the benign nature of the MRI findings, assuring him that no invasive interventions are needed and indicating that active strategies, founded in self-care, is the best option Reframes the patient’s impression of a “degenerating spine” that needs passive, invasive treatments “At first my back hurt so much, I wondered if I would end up needing an operation. I am so relieved that they helped me understand what was going on and get me on the right path.” A Based on consistent and good quality patient-oriented evidence XI “A series of three injections is recommended, each occurring one month apart” A non-evidence-supported approach is recommended (a “series of three”) that further prolongs the patient’s period of disability and passivity, further leading him on the downward spiral toward chronic pain Educating the patient regarding the benign nature of the MRI findings, assuring him that no invasive interventions are needed and indicating that active strategies, founded in self-care, is the best option Reframes his unrealistic perception of his condition and redirects him toward an active approach to the problem “I was surprised that back pain like this could be get better so quickly and simply.” A Based on consistent and good quality patient-oriented evidence XII “It is explained to the patient that he has two choices: have surgery to attempt to correct the problem or ‘learn to live with it’” Reinforces his despondency and his inaccurate (though understandable) notion that he has no control over the condition, and that the only hope for him is a passive, invasive, non-evidence-based approach Educating the patient regarding the benign and dynamic nature of the MRI findings, assuring him that no invasive interventions are needed and pointing out that active strategies, founded in self-care, are the best option Reframes his inaccurate perception of his condition and redirects him toward an active approach to the problem By this point, the patient still has a “back pain story”, but only as a memory, and as a useful tool. He can use his back pain story as a reminder, if he has a recurrence of back pain (which many people do), of the helpful approach that was taken, the speed with which he recovered, and the benefit of activity in the recovery. In addition, he can tell his story to others who find themselves in a similar back pain situation as encouragement, and as useful information regarding what worked so well for him. A Based on consistent and good quality patient-oriented evidence	3.847656	0.49707	sec[2]/sec[0]/p[2]	en	0.999998	37553703	https://doi.org/10.1186/s12998-023-00499-9	[ "that", "evidence", "based", "back", "pain", "quality", "oriented", "approach", "consistent", "good" ]	[ { "code": "8A80.Z", "title": "Migraine, unspecified" }, { "code": "QA76", "title": "Medication or substance that is known to be an allergen without injury or harm" }, { "code": "PL13.6", "title": "Medication or substance that is known to be an allergen, as mode of injury or harm" }, { "code": "9C40.A0", "title": "Papilloedema" }, { "code": "PA6Z", "title": "Unintentional fall from unspecified height" }, { "code": "QA04.Y", "title": "Other specified examination or observation for reasons other than suspected diseases or conditions or administrative purposes" }, { "code": "JB07.Z", "title": "Labour or delivery complicated by fetal distress, unspecified" }, { "code": "MA14.0", "title": "Laboratory evidence of human immunodeficiency virus" }, { "code": "2C64", "title": "Solid papillary carcinoma of breast with evidence of invasion" }, { "code": "JB07.2", "title": "Labour or delivery complicated by biochemical evidence of fetal stress" } ]	=== ICD-11 CODES FOUND === [8A80.Z] Migraine, unspecified Also known as: Migraine, unspecified \| Migraine [QA76] Medication or substance that is known to be an allergen without injury or harm Definition: Medication that has previously been identified as an allergen to the patient is administered, but does not result in injury or harm. Also known as: Medication or substance that is known to be an allergen without injury or harm Excludes: Medication or substance that is known to be an allergen, as mode of injury or harm [PL13.6] Medication or substance that is known to be an allergen, as mode of injury or harm Also known as: Medication or substance that is known to be an allergen, as mode of injury or harm \| medication error relating to known allergy to drug or substance \| adverse drug event relating to known allergy to drug or substance [9C40.A0] Papilloedema Definition: Optic disc swelling that results from increased intracranial pressure Also known as: Papilloedema \| Optic disc swelling that results from increased intracranial pressure Includes: Optic disc swelling that results from increased intracranial pressure [PA6Z] Unintentional fall from unspecified height Also known as: Unintentional fall from unspecified height \| fall NOS \| accidental fall \| fall causing injury that resulted in death \| fell NOS [QA04.Y] Other specified examination or observation for reasons other than suspected diseases or conditions or administrative purposes Also known as: Other specified examination or observation for reasons other than suspected diseases or conditions or administrative purposes \| Examination and observation following other inflicted injury \| Examination of victim or culprit following other inflicted injury \| Observation for concussion \| Request for expert evidence [JB07.Z] Labour or delivery complicated by fetal distress, unspecified Also known as: Labour or delivery complicated by fetal distress, unspecified \| Labour or delivery complicated by fetal distress \| Labour and delivery complicated by fetal stress \| fetal distress affecting labour and delivery \| Electrocardiographic evidence of fetal distress [MA14.0] Laboratory evidence of human immunodeficiency virus Also known as: Laboratory evidence of human immunodeficiency virus \| human immunodeficiency virus test positive \| positive test for HIV \| laboratory evidence of HIV \| Nonconclusive HIV-test finding in infants Excludes: Human immunodeficiency disease complicating pregnancy, childbirth or the puerperium \| Human immunodeficiency virus disease \| Asymptomatic human immunodeficiency virus infection [2C64] Solid papillary carcinoma of breast with evidence of invasion Also known as: Solid papillary carcinoma of breast with evidence of invasion [JB07.2] Labour or delivery complicated by biochemical evidence of fetal stress Definition: A condition characterised by complications during labour and delivery that is caused by biochemical evidence of fetal distress. Confirmation is by a fetal blood sample from a scalp prick through the open cervix during labour. Also known as: Labour or delivery complicated by biochemical evidence of fetal stress \| Labour or delivery complicated by abnormal fetal acid-base balance \| Labour or delivery complicated by abnormal fetal acidaemia === GRAPH WALKS === --- Walk 1 --- [8A80.Z] Migraine, unspecified --PARENT--> [8A80] Migraine Def: A primary headache disorder, in most cases episodic. Disabling attacks lasting 4-72 hours are characterised by moderate or severe headache, usually accompanied by nausea, vomiting and/or photophobia a... --CHILD--> [8A80.0] Migraine without aura Def: Recurrent headache disorder manifesting in attacks lasting 4-72 hours. The duration of attacks may be shorter in children. Typical characteristics of the headache are unilateral location, pulsating qu... --- Walk 2 --- [8A80.Z] Migraine, unspecified --PARENT--> [8A80] Migraine Def: A primary headache disorder, in most cases episodic. Disabling attacks lasting 4-72 hours are characterised by moderate or severe headache, usually accompanied by nausea, vomiting and/or photophobia a... --EXCLUDES--> [?] Headache, not elsewhere classified Def: Headache with characteristic features suggesting that it is a unique diagnostic entity, a finding or complaint, but not fulfilling criteria for any of the headache disorders described above.... --- Walk 3 --- [QA76] Medication or substance that is known to be an allergen without injury or harm Def: Medication that has previously been identified as an allergen to the patient is administered, but does not result in injury or harm.... --PARENT--> [?] Circumstances associated with exposure to a drug, medicament or biological substance influencing the episode of care without injury or harm --CHILD--> [QA72] Incorrect substance without injury or harm Def: Incorrect substance administration occurs when a substance is given which was not the intended or prescribed drug and does not result in injury or harm.... --- Walk 4 --- [QA76] Medication or substance that is known to be an allergen without injury or harm Def: Medication that has previously been identified as an allergen to the patient is administered, but does not result in injury or harm.... --PARENT--> [?] Circumstances associated with exposure to a drug, medicament or biological substance influencing the episode of care without injury or harm --PARENT--> [?] Health care related circumstances influencing the episode of care without injury or harm --- Walk 5 --- [PL13.6] Medication or substance that is known to be an allergen, as mode of injury or harm --PARENT--> [PL13] Mode of injury or harm associated with exposure to a drug, medicament or biological substance --CHILD--> [PL13.1] Underdosing, as mode of injury or harm --- Walk 6 --- [PL13.6] Medication or substance that is known to be an allergen, as mode of injury or harm --PARENT--> [PL13] Mode of injury or harm associated with exposure to a drug, medicament or biological substance --CHILD--> [PL13.1] Underdosing, as mode of injury or harm	[ "[8A80.Z] Migraine, unspecified\n --PARENT--> [8A80] Migraine\n Def: A primary headache disorder, in most cases episodic. Disabling attacks lasting 4-72 hours are characterised by moderate or severe headache, usually accompanied by nausea, vomiting and/or photophobia a...\n --CHILD--> [8A80.0] Migraine without aura\n Def: Recurrent headache disorder manifesting in attacks lasting 4-72 hours. The duration of attacks may be shorter in children. Typical characteristics of the headache are unilateral location, pulsating qu...", "[8A80.Z] Migraine, unspecified\n --PARENT--> [8A80] Migraine\n Def: A primary headache disorder, in most cases episodic. Disabling attacks lasting 4-72 hours are characterised by moderate or severe headache, usually accompanied by nausea, vomiting and/or photophobia a...\n --EXCLUDES--> [?] Headache, not elsewhere classified\n Def: Headache with characteristic features suggesting that it is a unique diagnostic entity, a finding or complaint, but not fulfilling criteria for any of the headache disorders described above....", "[QA76] Medication or substance that is known to be an allergen without injury or harm\n Def: Medication that has previously been identified as an allergen to the patient is administered, but does not result in injury or harm....\n --PARENT--> [?] Circumstances associated with exposure to a drug, medicament or biological substance influencing the episode of care without injury or harm\n --CHILD--> [QA72] Incorrect substance without injury or harm\n Def: Incorrect substance administration occurs when a substance is given which was not the intended or prescribed drug and does not result in injury or harm....", "[QA76] Medication or substance that is known to be an allergen without injury or harm\n Def: Medication that has previously been identified as an allergen to the patient is administered, but does not result in injury or harm....\n --PARENT--> [?] Circumstances associated with exposure to a drug, medicament or biological substance influencing the episode of care without injury or harm\n --PARENT--> [?] Health care related circumstances influencing the episode of care without injury or harm", "[PL13.6] Medication or substance that is known to be an allergen, as mode of injury or harm\n --PARENT--> [PL13] Mode of injury or harm associated with exposure to a drug, medicament or biological substance\n --CHILD--> [PL13.1] Underdosing, as mode of injury or harm", "[PL13.6] Medication or substance that is known to be an allergen, as mode of injury or harm\n --PARENT--> [PL13] Mode of injury or harm associated with exposure to a drug, medicament or biological substance\n --CHILD--> [PL13.1] Underdosing, as mode of injury or harm" ]	8A80.Z	Migraine, unspecified	[ { "from_icd11": "8A80.Z", "icd10_code": "G43B0", "icd10_title": "Ophthalmoplegic migraine, not intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43409", "icd10_title": "Hemiplegic migraine, not intractable, without status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43A0", "icd10_title": "Cyclical vomiting, in migraine, not intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43D0", "icd10_title": "Abdominal migraine, not intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43709", "icd10_title": "Chronic migraine without aura, not intractable, without status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43A1", "icd10_title": "Cyclical vomiting, in migraine, intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43509", "icd10_title": "Persistent migraine aura without cerebral infarction, not intractable, without status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43719", "icd10_title": "Chronic migraine without aura, intractable, without status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43501", "icd10_title": "Persistent migraine aura without cerebral infarction, not intractable, with status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43C0", "icd10_title": "Periodic headache syndromes in child or adult, not intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43401", "icd10_title": "Hemiplegic migraine, not intractable, with status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43419", "icd10_title": "Hemiplegic migraine, intractable, without status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43B1", "icd10_title": "Ophthalmoplegic migraine, intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43C1", "icd10_title": "Periodic headache syndromes in child or adult, intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43D1", "icd10_title": "Abdominal migraine, intractable" } ]	G43B0	Ophthalmoplegic migraine, not intractable
A 15-year-old male presented to our pulmonary service with a 6-week history of bloody noses, hemoptysis, cough, fatigue, weight loss, fevers, and dark urine. He denied cardiac symptoms and was without palpitations, chest pain, or chest tightness. He had hypertension with blood pressures in the range of 120–166 / 44–92 mmHg, hemoglobinuria (large) with red blood cells (RBC) > 100 per high-powered field (hpf), proteinuria (100 mg per deciliter (mg/dL)) with urine protein to creatinine ratio of 2.07, erythrocyte sedimentation rate (ESR) 59 mm per hour (mm/hr), C-reactive protein (CRP) 12.9 mg/dL, and hemoglobin 7.3 g per deciliter (GM/dL) (Table 2 ). He was intermittently febrile with a maximum body temperature of 38.8 degrees Celsius. His serum creatinine peaked at 0.98 mg/dL during his hospital stay. His chest CT showed widespread bilateral ill-defined ground-glass opacities along the bronchovascular bundles . Rheumatology, Nephrology, and Infectious Disease services were consulted. Serum ANCA showed a cytoplasmic (C-ANCA) pattern with a titer of 1:640 and Proteinase-3 (PR3) value of 812 AU/mL. Additional rheumatologic laboratory tests returned normal/negative. A thorough evaluation for infection on admission was unremarkable (Table 2 ). On hospital day 3, he underwent renal biopsy due to persistent hypertension and elevated urine protein/creatinine ratio. The renal biopsy specimen showed focal necrotizing and crescentic glomerulonephritis . Immune complex deposits were not seen in glomeruli by immunofluorescent and electron microscopy (i.e., pauci-immune), compatible with AAV. During his renal biopsy, he incidentally was found to have Mobitz II heart block on telemetry, which ultimately lead to his cardiac evaluation and cardiology consultation. Of note, he had an EKG on admission that was normal. His echocardiogram obtained on hospital day 3 showed thickened aortic valve leaflets with perforation within the right coronary leaflet, one to two small areas with vegetation on the aortic valve with mild aortic regurgitation and thickening of the anterior leaflet of the mitral valve with Ejection Fraction 60% . He remained asymptomatic without palpitations, chest pain, or chest tightness. On hospital day 3, after completion of his echocardiogram, he experienced an acute ischemic event that resulted in left facial droop and left-sided hemineglect with abnormal sensations on his left side. Magnetic Resonance Angiogram (MRA) confirmed moderate-sized acute infarct involving the right insula, adjacent frontoparietal operculum and right parietal lobe with scattered foci of punctate infarcts bilaterally, suggesting thromboembolic phenomenon. Due to concern for bacterial endocarditis with newfound valvular lesions, blood cultures were drawn. Greater than 24 hours after collection, one bottle out of four grew coagulase-negative Staphylococcus, a common contaminant (Table 2 ). He received therapeutic plasma exchange for five days and was treated with Rituximab 1000 mg (mg) at week 0 and week 2 per ANCA-Vasculitis protocol, and methylprednisolone pulse (30 mg per kilogram (mg/kg) × 3 days, maximum 1000 mg) followed by high-dose oral glucocorticoids 2 mg/kg/day . He was initiated on lisinopril 10 mg daily for hypertension, improvement in heart muscle function, and prevention of cardiac remodeling. Due to inability to exclude bacterial endocarditis based on one positive blood culture and findings on echocardiogram of valvular vegetations, he was also treated for 4 weeks with Ceftriaxone. Six months post-induction with Rituximab he was asymptomatic and displayed normalization of inflammatory markers and ANCA serology, resolution of proteinuria and hematuria, resolution of his aortic valve vegetation with stable mild-moderate aortic valve regurgitation with perforation, and no neurological or cognitive deficits. Table 2 Lab Results for Case 1 and Case 2 during hospitalization(s) Laboratory Investigations: General Laboratory Reference Ranges Case 1 Laboratory Results Case 2 Laboratory Results Erythrocyte Sedimentation Rate (ESR) 0–15 mm/hr 59 mm/hr at presentation; 2 mm/hr 6 months post-treatment 14 mm/hr at presentation; 2 mm/hr 6 months post-treatment C-reactive Protein (CRP) < 0.5 mg/dL 12.9 mg/dL at presentation; < 0.5 mg/dL 6 months post-treatment 25 mg/dL at presentation; < 0.5 mg/dL 6 months post-treatment Hemoglobin 13.0–16.0 g/dL 7.3 GM/dL 8.3 GM/dL Creatinine 0.71–1.16 g/dL 0.98 at presentation 1.21 at presentation Urinalysis RBC: 0–2/hpf Protein: Negative RBC > 100/hpf Protein 100 mg/dL RBC 6–10/hpf at admission; > 100/hpf day 9 hosopitalization Protein/Creatinine ratio 0- < 0.2 2.07 3.72 Laboratory Investigations: Rheumatologic Anti-Nuclear Antibody (ANA) < 1:80 1:80 < 1:80 Double-Stranded DNA 0–9 IU/mL 0 IU/mL 0 IU/mL Complements (C3, C4) C3: 82–193 mg/dL C4: 15–57 mg/dL C3: 154 mg/dL C4: 32 mg/dL C3: 169 mg/dL C4:26 mg/dL Anti-Smith 0.0–0.9 < 0.2 < 0.2 anti-RNP 0.0–0.9 < 0.2 < 0.2 SSA 0.0–0.9 < 0.2 < 0.2 SSB 0.0–0.9 < 0.2 < 0.2 Cardiolipin IgG < 20 GPL U/mL 0 GPL U/mL 0 GPL U/mL Cardiolipin IgM < 20 MPL U/mL 0 MPL U/mL 0 MPL U/mL Beta-2-Glycoprotein IgG < 20 SGU Not detected Not detected Beta-2-Glycoprotein IgM < 20 SMU Not detected Not detected DRVVT 33–43 seconds 35 seconds 38 seconds STACLOT No lupus anti-coagulant detected No lupus anti-coagulant detected No lupus anti-coagulant detected Anti-glomerular basement membrane antibody IgG (EU) 0–19 AU/mL 0 AU/mL 0 AU/mL ANCA profile (during hospitalization) < 1:20 AU/mL, PR3 0 C-ANCA pattern 1:640, PR3 812 AU/mL c-ANCA pattern 1:5120, PR3 1242 AU/mL ANCA profile (6 months post-treatment) < 1:20 AU/mL, PR3 0 < 1:20 AU/mL, PR3 0 < 1:20 AU/mL, PR3 0 Laboratory Investigations: Infectious Hepatitis A Antibodies, total Hepatitis A Antibody, IgM Negative Negative Negative Hepatitis B Virus Core Antibodies (total) Hepatitis B Virus Core Antibody, IgM Hepatitis B Virus Surface Antibody Hepatitis B Virus Surface Antigen Negative Negative Negative Hepatitis C Virus Genotype Hepatitis C Virus Antibody Hepatitis C Virus by Quantitative NAAT Negative Negative Negative Bartonella henselae Antibody, IgG and IgM Negative Negative Negative Bartonella quintana Antibody, IgG and IgM Negative Negative Negative Herpes Simplex Virus (HSV) DFA with Reflex to HSV Culture Negative Negative Negative Blood cultures Negative 1 of 4 bottles positive for Coagulase-Negative Staphylococcus > 24 hours after collection Negative PCR Respiratory Viral Panel a Negative Negative Negative AFB Stain and culture: Bronchoalveolar lavage (BAL) No organisms on gram stain; negative cultures Negative Negative Fungal stain and culture: BAL No organisms on gram stain; negative cultures Negative Negative Bacterial stain and culture: BAL No organisms on gram stain; negative cultures Negative Negative Universal PCR: BAL Negative Negative Negative Aspergillus antigen Index: BAL < 0.5 < 0.5 0.55 Anti-Streptolysin O 0–240 IU/mL 125 IU/mL 200 IU/mL DNAse B 0–250 U/mL < 250 U/mL < 250 U/mL Tuberculosis Negative Negative Negative Histoplasmosis antigen (urine) < 0.5 ng/mL < 0.5 ng/mL < 0.5 ng/mL Histoplasmosis antigen (serum) 0.19–60.0 ng/mL Not detected Not detected Human Immunodeficiency Virus (HIV) Negative Negative Negative a Respiratory Viral Panel: PCR swab for Parainfluenza, Respiratory Syncytial virus (RSV), Bordetella parapertussis , Bordetella pertussis , Chlamydia pneumoniae , Mycoplasma pneumoniae , COVID-19, Human Metapneumovirus, Human Rhinovirus/Enterovirus, Adenovirus, Coronavirus 229E, Coronavirus HKU1, Coronavirus NL63, Coronavirus OC43, Influenza A and Influenza B Fig. 1 CT scan findings for patient 1 ( A-C ) and patient 2 ( D - F ). A , B , C : CT chest of Patient 1. Final read: Ill-defined, confluent groundglass attenuation is present bilaterally in the lungs, roughly following the bronchovascular bundles. No dense consolidation is seen. No pleural effusions are identified. D , E , F : CT Chest of Patient 2. Final read: Subtle diffuse symmetric ground glass opacities throughout both lungs. Findings may represent pulmonary hemosiderosis related to sequela of prior diffuse bilateral pulmonary hemorrhage. Two well defined solid appearing soft tissue density nodules within the right middle lobe with surrounding tiny parenchymal cysts are present. Another similar appearing well defined nodule centered in the upper aspect of the major fissure of the left lung where it contacts the mediastinum is present. These nodular opacities are without cavitation or calcification and were not clearly seen on prior portable chest radiographs. Evaluation is limited due to the lack of IV contrast and their etiology is unclear. The tiny parenchymal cysts adjacent to the nodules in the right middle lobe could represent sequela of a necrotizing lung process. These nodules could represent organized parenchymal or pleural hematomas. The appearance is not highly suggestive of infection due to lack of surrounding inflammation. Neoplasm seems unlikely given the history Fig. 2 Renal histology photomicrographs for patient 1 ( A ) and patient 2 ( B ). Light microscopy: Paraffin tissue sections from formalin-fixed kidney biopsy specimens were stained with Jones’ silver. Panel A from patient 1 shows a representative glomerulus with segmental fibrinoid necrosis and early cellular crescent formation (extracapillary hypercellularity is most pronounced at urinary pole near proximal tubule/PT). Panel B from patient 2 shows segmental fibrinoid necrosis in a single glomerulus, which was not accompanied by a crescent. In both panels the arrows point to ruptured glomerular capillary loop basement membranes. Fibrin tactoids are marked with asterisks. Original magnification 40x Fig. 3 Echocardiogram abnormalities for patient 1 ( A , B ) and patient 2 ( C , D ). A , B Demonstration of Aortic Valve Vegetation for Patient 1. C , D Demonstration of Mitral Valve Vegetation for Patient 2	3.982422	0.978516	sec[1]/sec[0]/p[0]	en	0.999997	PMC9616620	https://doi.org/10.1186/s12969-022-00750-2	[ "virus", "hepatitis", "chest", "anca", "anti", "antibody", "protein", "laboratory", "valve", "aortic" ]	[ { "code": "1D9Z", "title": "Unspecified viral infection of unspecified site" }, { "code": "1E1Z", "title": "Unspecified viral disease" }, { "code": "1E1Y", "title": "Other specified viral diseases" }, { "code": "1D85.Z", "title": "Viral carditis, unspecified" }, { "code": "KA62.Z", "title": "Viral infection in the fetus or newborn, unspecified" }, { "code": "DB97.Z", "title": "Inflammatory liver disease, unspecified" }, { "code": "1E50.Z", "title": "Acute viral hepatitis, unspecified" }, { "code": "DB97.2", "title": "Chronic hepatitis, not elsewhere classified" }, { "code": "1E5Z", "title": "Viral hepatitis, unspecified" }, { "code": "1E51.0Z", "title": "Chronic hepatitis B, unspecified" } ]	=== ICD-11 CODES FOUND === [1D9Z] Unspecified viral infection of unspecified site Also known as: Unspecified viral infection of unspecified site \| viral infection NOS \| viral disorder NOS \| disease caused by virus \| unspecified viremia [1E1Z] Unspecified viral disease Also known as: Unspecified viral disease [1E1Y] Other specified viral diseases Also known as: Other specified viral diseases \| Acute infectious lymphocytosis [1D85.Z] Viral carditis, unspecified Also known as: Viral carditis, unspecified \| Viral carditis [KA62.Z] Viral infection in the fetus or newborn, unspecified Also known as: Viral infection in the fetus or newborn, unspecified \| Viral infection in the fetus or newborn \| congenital virus disorder \| congenital virus disease [DB97.Z] Inflammatory liver disease, unspecified Also known as: Inflammatory liver disease, unspecified \| Certain specified inflammatory liver diseases \| Nonspecific reactive hepatitis \| inflammatory liver disease \| hepatitis NOS [1E50.Z] Acute viral hepatitis, unspecified Also known as: Acute viral hepatitis, unspecified \| Acute viral hepatitis \| acute anicteric hepatitis \| Acute hepatitis NOS \| acute viral hepatitis non-A non-B NEC [DB97.2] Chronic hepatitis, not elsewhere classified Also known as: Chronic hepatitis, not elsewhere classified \| Chronic hepatitis, unspecified \| Chronic active hepatitis NEC \| Other specified chronic hepatitis \| Chronic persistent hepatitis NEC Includes: Chronic hepatitis, unspecified \| Other specified chronic hepatitis Excludes: hepatitis (chronic): granulomatous NEC \| Drug-induced or toxic liver disease \| hepatitis (chronic): viral [1E5Z] Viral hepatitis, unspecified Also known as: Viral hepatitis, unspecified \| anicteric hepatitis [1E51.0Z] Chronic hepatitis B, unspecified Also known as: Chronic hepatitis B, unspecified \| Chronic hepatitis B \| Chronic hepatitis B without delta agent \| chronic HBV - [hepatitis B virus] infection \| hepatitis B NOS === GRAPH WALKS === --- Walk 1 --- [1D9Z] Unspecified viral infection of unspecified site --PARENT--> [?] Viral infection of unspecified site --EXCLUDES--> [?] Herpes simplex infections Def: Any condition caused by an infection with herpes simplex virus (human herpesviruses 1 and 2). Confirmation is by identification of herpes simplex virus type 1 or 2.... --- Walk 2 --- [1D9Z] Unspecified viral infection of unspecified site --PARENT--> [?] Viral infection of unspecified site --EXCLUDES--> [?] Cytomegaloviral disease Def: Any condition caused by an infection with cytomegalovirus (CMV). These conditions are commonly asymptomatic. Transmission is by direct contact with infected body fluids.... --- Walk 3 --- [1E1Z] Unspecified viral disease --PARENT--> [?] Certain other viral diseases --RELATED_TO--> [?] Congenital Varicella Zoster virus infection Def: Transplacentally acquired Varicella zoster virus infection. Both the gestational age at the time of maternal infection and the time interval between maternal infection and birth have major influences ... --- Walk 4 --- [1E1Z] Unspecified viral disease --PARENT--> [?] Certain other viral diseases --RELATED_TO--> [?] Viral duodenitis Def: Duodenitis caused by infection with virus. This includes infection with cytomegalovirus, herpes virus, HIV and other viral infections in the duodenum.... --- Walk 5 --- [1E1Y] Other specified viral diseases --PARENT--> [?] Certain other viral diseases --RELATED_TO--> [?] Other viral diseases complicating pregnancy, childbirth or the puerperium --- Walk 6 --- [1E1Y] Other specified viral diseases --PARENT--> [?] Certain other viral diseases --RELATED_TO--> [?] Viral duodenitis Def: Duodenitis caused by infection with virus. This includes infection with cytomegalovirus, herpes virus, HIV and other viral infections in the duodenum....	[ "[1D9Z] Unspecified viral infection of unspecified site\n --PARENT--> [?] Viral infection of unspecified site\n --EXCLUDES--> [?] Herpes simplex infections\n Def: Any condition caused by an infection with herpes simplex virus (human herpesviruses 1 and 2). Confirmation is by identification of herpes simplex virus type 1 or 2....", "[1D9Z] Unspecified viral infection of unspecified site\n --PARENT--> [?] Viral infection of unspecified site\n --EXCLUDES--> [?] Cytomegaloviral disease\n Def: Any condition caused by an infection with cytomegalovirus (CMV). These conditions are commonly asymptomatic. Transmission is by direct contact with infected body fluids....", "[1E1Z] Unspecified viral disease\n --PARENT--> [?] Certain other viral diseases\n --RELATED_TO--> [?] Congenital Varicella Zoster virus infection\n Def: Transplacentally acquired Varicella zoster virus infection. Both the gestational age at the time of maternal infection and the time interval between maternal infection and birth have major influences ...", "[1E1Z] Unspecified viral disease\n --PARENT--> [?] Certain other viral diseases\n --RELATED_TO--> [?] Viral duodenitis\n Def: Duodenitis caused by infection with virus. This includes infection with cytomegalovirus, herpes virus, HIV and other viral infections in the duodenum....", "[1E1Y] Other specified viral diseases\n --PARENT--> [?] Certain other viral diseases\n --RELATED_TO--> [?] Other viral diseases complicating pregnancy, childbirth or the puerperium", "[1E1Y] Other specified viral diseases\n --PARENT--> [?] Certain other viral diseases\n --RELATED_TO--> [?] Viral duodenitis\n Def: Duodenitis caused by infection with virus. This includes infection with cytomegalovirus, herpes virus, HIV and other viral infections in the duodenum...." ]	1D9Z	Unspecified viral infection of unspecified site	[ { "from_icd11": "1D9Z", "icd10_code": "B348", "icd10_title": "Other viral infections of unspecified site" }, { "from_icd11": "1D9Z", "icd10_code": "B349", "icd10_title": "Viral infection, unspecified" }, { "from_icd11": "1D9Z", "icd10_code": "B344", "icd10_title": "Papovavirus infection, unspecified" }, { "from_icd11": "1D9Z", "icd10_code": "B333", "icd10_title": "Retrovirus infections, not elsewhere classified" }, { "from_icd11": "1D9Z", "icd10_code": "B34", "icd10_title": "Viral infection of unspecified site" }, { "from_icd11": "1E1Z", "icd10_code": "B338", "icd10_title": "Other specified viral diseases" }, { "from_icd11": "1E1Z", "icd10_code": "B25-B34", "icd10_title": "" }, { "from_icd11": "1E1Z", "icd10_code": "B33", "icd10_title": "Other viral diseases, not elsewhere classified" }, { "from_icd11": "1E1Z", "icd10_code": "M015", "icd10_title": "" }, { "from_icd11": "1E1Y", "icd10_code": "B9789", "icd10_title": "Other viral agents as the cause of diseases classified elsewhere" }, { "from_icd11": "1D85.Z", "icd10_code": "B3324", "icd10_title": "Viral cardiomyopathy" }, { "from_icd11": "1D85.Z", "icd10_code": "B3323", "icd10_title": "Viral pericarditis" }, { "from_icd11": "1D85.Z", "icd10_code": "B332", "icd10_title": "Viral carditis" }, { "from_icd11": "KA62.Z", "icd10_code": "P35", "icd10_title": "Congenital viral diseases" }, { "from_icd11": "KA62.Z", "icd10_code": "P358", "icd10_title": "Other congenital viral diseases" } ]	B348	Other viral infections of unspecified site
The patient was a 19-years-old man who, despite very good clinical conditions, presented with abnormal peripheral blood counts before receiving a scheduled surgical procedure. Physical examination revealed only a moderate splenomegaly. He was hyperleucocytotic, with a peripheral WBC count of 40.7×10 9 /L, a normal hemoglobin value and a moderate thrombocytopenia. A bone marrow aspirate showed 88% lymphoblasts, expressing the CD19, CD10, CD22, CD34, CD58, and CD45 antigens. Chromosome banding analysis of bone marrow revealed a normal karyotype; however, polymerase chain reaction revealed the BCR-ABL1 e1a2 fusion transcript. BCR-ABL1 transcript level assessed by real-time quantitative RT-PCR (RQ-PCR) was 111.09%. No involvement of central nervous system was detected, since all lumbar punctures performed showed the absence of leukemic cells in cerebrospinal fluid. Thus, a diagnosis of BCR-ABL1 (p190)-positive B-ALL was made. After informed consent was obtained, treatment was initiated according to the GIMEMA LAL1509 clinical trial that included a steroid-based pre-phase, followed by dasatinib induction therapy at 140 mg/daily for 84 days. After 52 days of dasatinib therapy, the patient obtained a complete hematological response with a mild decrease of the BCR-ABL1 transcript levels (1.22%). At day 85 the patient unfortunately progressed. Conventional Sanger Sequencing analysis showed evidence of a C to T nucleotide substitution at position 1091 of the ABL1 sequence in a proportion of BCR-ABL1 transcripts, resulting in the dasatinib-resistant T315I mutation. According to protocol schedule, the patient was treated with one course of standard chemotherapy, consisting of clofarabine 80 mg/daily, for 5 days and cyclophosphamide 800 mg/daily, for 5 days. The patient achieved complete hematological remission, but persistence of the BCR-ABL1 fusion transcript at the molecular level was observed (1.69%). A severe cardiac toxicity contraindicated the administration of an additional course of consolidation chemotherapy. Therefore, because of the minimal residual disease persistence, the patient was enrolled in the MT103–203 clinical study of blinatumomab, an anti-CD19 T cell engager antibody, as continuous intravenous infusion for 28-days cycles. After one course of treatment with 15 mcg/sqm/daily, which was well tolerated, a brilliant response was observed: the BCR-ABL1 transcript level significantly decreased down to 0.008% and the T315I mutation disappeared at conventional sequencing analysis. In consideration of the persistently suboptimal heart function, which would have seriously compromised the outcome of a transplantation procedure, a second course of therapy with blinatumomab was then started two weeks after the end of the first one, as required by protocol schedule. Unfortunately, the patient suddenly and unexpectedly relapsed after 10 days, with a remarkable hyperleucocytosis and a high percentage of lymphoblasts, with the same immunophenotypic signature detected at diagnosis. Conventional Sanger Sequencing showed that the T315I mutation had reappeared in a proportion of BCR-ABL1 transcripts. Salvage therapy with ponatinib at the dosage of 45 mg/daily was immediately started, but despite a very good tolerance to the compound, only a hematological improvement was observed, without significant changes in BCR-ABL1 transcript levels. At this timepoint, conventional Sanger Sequencing analysis displayed an unusual pattern of nucleotide substitutions: a C to T substitution at position 1091 and a T to C substitution at the adjacent 1092 position, suggesting the presence of two clones that could not be further characterized. Deep Sequencing was then performed as detailed in Soverini et al. ; a median of 4166 high quality reads were obtained across the different runs. The analysis demonstrated that two distinct T315I-positive subclones were coexisisting: one subclone, with a relative abundance of 58%, had the usual ‘act’ to ‘att’ codon shift resulting from the c.1091c>t nucleotide change, whereas the other one, with a relative abundance of 47.14%, had both a c.1091c>t and a c.1092 t>c nucleotide change, thus leading to an ‘act’ to ‘atc’ codon shift still translating into a threonine to isoleucine amino acid change at position 315 . Since TKI resistant BCR-ABL1 mutations existing prior to exposure may exist, we looked for the T315I mutation at diagnosis prior to dasatinib start, but Deep Sequencing didn’t find evidence. Deep Sequencing was then used to retrospectively investigate all the previous samples and revealed that the two distinct T315I-positive subclones were detectable since day 52 of dasatinib therapy, where both were identified at very low level: T315I act>att 0.56% and T315I act>atc 1.44%. At day 85, when the patient had relapsed on dasatinib, the proportions of the two clones had increased to 82,17% and 15.49% respectively. After chemotherapy, the T315I act>att subclone accounted for 100% of BCR-ABL1 transcripts, and then became undetectable, too, after the first course of blinatumomab. However, both subclones had quickly become detectable again by Deep Sequencing (act>att 79.91%; act>atc 7.06%) when the patient had relapsed during the second cycle. In the presence of a matched-related stem cell donor, and in the absence of further available therapeutic tools, the patient underwent allogeneic transplantation, with a conditioning regimen consisting of fludarabine, busulfan and thiotepa, in addition to ATG as graft-versus-host disease prophylaxis. A total of 16.12×10 8 /kg nucleated cells were infused, including 7.4×10 6 /kg CD34+ cells. No signs or symptoms of graft-versus-host disease occurred, and a full recovery on peripheral blood was observed after 16 days from transplantation. After one month from this procedure, the bone marrow evaluation showed a complete morphological remission. FISH analysis revealed an almost complete full donor chimerism; BCR-ABL1 transcript level was 0.48%. Although the mutation analysis performed by conventional sequencing did not show evidence of mutations, the greater sensitivity of Deep Sequencing allowed to identify, again, both the T315I-positive subclones at very low levels (act>att 1.27%; act>atc 0.77%). After 3 months from allogeneic stem cell transplantation, despite good clinical conditions and in the absence of symptoms of leukemia progression, the patient developed hyperleukocytosis, with mild anemia and thrombocytopenia. Bone marrow analysis showed a full hematological relapse, confirmed by a marked increase in BCR-ABL1 fusion transcripts (65.3%). The Deep Sequencing analysis performed at this time point showed the quick regrowth of both T315I-mutated subclones (act>att 44%; act>atc 9.16%). Unexpectedly, the first clone was found to harbor additional point mutations: the F359V (16.34%) and H396R (9.47%). The rapid worsening of peripheral hematological values required an immediate therapeutic intervention. Therefore, after a brief and ineffective course of steroids and 6-mercaptopurine and hydroxyurea as cytoreductive agents, the patient received salvage chemotherapy according to HAM schedule with high dose of cytarabine and mitoxantrone. Treatment was well tolerated, but subsequent iatrogenic bone marrow aplasia was complicated by a severe pulmonary infection, with microbiological and radiological images diagnostic for an invasive fungal infection. Therefore, the patient received dual antimycotic therapy with voriconazole and liposomal amphotericin b, achieving a significant improvement of imaging reports after 3 weeks of treatment. Bone marrow examination, which was performed one month after the end of chemotherapy, showed the persistence of a relevant amount of CD19+ lymphoid blast cells and BCR-ABL1 transcript level had further increased (87.8%). Deep Sequencing analysis showed again all the sub-clones previously identified T315I act>att (17.93%), T315I act>atc (67%), F359V (3.17%), H396R (0.73%). At this time point we observed the emergence of the Y253H point mutation, with an abundance of 5.05%. Two T315I-inclusive compound mutations were observed: T315I act>att + F359V (0.67%) and the T315I act>atc + Y253H (3.98%) . In the following days, due to the onset of specific symptoms, related with leukemic progression, mainly represented by fever and lumbar pain, the patient received further cytoreductive chemotherapy, obtaining a partial response. Unfortunately, the patient developed a severe fungal pulmonary infection, and he died two months after, in progression disease. An overview of the BCR-ABL1 transcript levels, for each time point, assessed by real-time quantitative RT-PCR is reported in Fig. 3 . Results of BCR-ABL1 KD mutation analysis performed by conventional Sanger sequencing and Deep Sequencing are reported in Additional file 1 Table S1. Fig. 1 Example of clonal analysis for sample ALL-8. a ) Conventional Sanger Sequencing results showing the double nucleotide substitution at codon 315; b ) screenshot showing a portion of the global alignment of sequence reads obtained with AVA software, where codon 315 maps. Deep Sequencing allowed to resolve two distinct populations of mutants at this codon, one harboring the T315I (att) and one harboring the T315I (atc). Sequence were compared to the wild-type sequence ( green at the top) using BLAST, GenBank Accession Number X16416 Fig. 2 Overview of BCR-ABL1 KD mutations dynamics and their relative frequency at different time-points during treatment. Graphical illustration of the kinetics of mutated population abundances for each time points in relation to therapeutic intervention Fig. 3 Overview of BCR-ABL1 transcript levels at different time-points during treatment. Graphical illustration of the BCR-ABL1 transcript levels for each time-points in relation to therapeutic intervention assessed by real-time quantitative RT-PCR	4.324219	0.869141	sec[1]/p[0]	en	0.999996	28779753	https://doi.org/10.1186/s12885-017-3511-2	[ "sequencing", "transcript", "time", "conventional", "mutation", "bone", "marrow", "dasatinib", "course", "chemotherapy" ]	[ { "code": "LB73.10", "title": "Poland syndrome" }, { "code": "LD44.N0", "title": "CATCH 22 phenotype" }, { "code": "LB31.3", "title": "Exstrophy of urinary bladder" }, { "code": "LD2F.1Y", "title": "Other specified syndromes with multiple structural anomalies, not of environmental origin" }, { "code": "LA56", "title": "Pierre Robin syndrome" }, { "code": "5A61.41", "title": "Congenital central hypothyroidism" }, { "code": "4A00.2", "title": "Genetic susceptibility to particular pathogens" }, { "code": "PL13.52", "title": "Incorrect timing of drug or medicament, as mode of injury" }, { "code": "QF2A", "title": "Difficulty or need for assistance with community participation" }, { "code": "MF50.1", "title": "Pollakiuria" } ]	=== ICD-11 CODES FOUND === [LB73.10] Poland syndrome Definition: Poland syndrome is characterised by a unilateral absence or hypoplasia of the pectoralis major muscle (most frequently involving the sternocostal portion), and a variable degree of ipsilateral hand anomalies, including symbrachydactyly. Also known as: Poland syndrome \| Poland sequence \| Poland anomaly [LD44.N0] CATCH 22 phenotype Definition: Monosomy 22q11 (DiGeorge Velocardiofacial syndrome, DGS/VCF) syndrome is a chromosomal anomaly characterised by the association of several variable malformations: hypoplastic thymus and parathyroid glands, congenital conotruncal heart defects, a subtle but characteristic facial dysmorphism, cleft palate or velar insufficiency, and learning difficulties. Also known as: CATCH 22 phenotype \| Conotruncal anomalies face syndrome \| Velocardiofacial syndrome \| Shprintzen syndrome \| Sedlackova syndrome Includes: Pharyngeal pouch syndrome \| DiGeorge syndrome \| Velocardiofacial syndrome [LB31.3] Exstrophy of urinary bladder Definition: Bladder exstrophy (or classic bladder exstrophy) is a congenital genitourinary malformation belonging to the spectrum of the exstrophy-epispadias complex and is characterised by an evaginated bladder plate, epispadias and an anterior defect of the pelvis, pelvic floor and abdominal wall. Also known as: Exstrophy of urinary bladder \| Ectopia vesicae \| Extroversion of bladder \| bladder ectopia \| congenital ectopic bladder Includes: Ectopia vesicae \| Extroversion of bladder [LD2F.1Y] Other specified syndromes with multiple structural anomalies, not of environmental origin Also known as: Other specified syndromes with multiple structural anomalies, not of environmental origin \| 46,XX disorder of sex development - anorectal anomalies \| 46,XX DSD - anorectal anomalies \| Aarskog-Scott syndrome \| Aarskog syndrome [LA56] Pierre Robin syndrome Definition: Pierre-Robin syndrome (or Pierre-Robin sequence) is characterised by triad of orofacial morphological anomalies consisting of retrognathism, glossoptosis and a posterior median velopalatal cleft. This condition is referred to as a sequence because the posterior cleft palate is a secondary defect associated with abnormal mandibular development: mandibular hypoplasia occurring early in gestation causes the tongue to be maintained high-up in the oral cavity, preventing fusion of the palatal shelves Also known as: Pierre Robin syndrome \| Pierre Robin sequence [5A61.41] Congenital central hypothyroidism Also known as: Congenital central hypothyroidism \| Congenital central hypothyroidism due to isolated TSH deficiency \| isolated TSH deficiency \| congenital hypothyroidism due to thyroid-stimulating hormone beta chain deficiency \| Congenital central hypothyroidism due to thyrotropin-releasing hormone deficiency [4A00.2] Genetic susceptibility to particular pathogens Also known as: Genetic susceptibility to particular pathogens \| Idiopathic CD4 lymphocytopenia \| Immunodeficiency due to interleukin-1 receptor-associated kinase-4 deficiency \| IRAK4 - [interleukin-1 receptor-associated kinase-4 deficiency] \| Lung fibrosis - immunodeficiency - gonadal dysgenesis [PL13.52] Incorrect timing of drug or medicament, as mode of injury Also known as: Incorrect timing of drug or medicament, as mode of injury \| wrong timing of drug \| timing error in giving drug \| timing mistake in administration of drug \| administration error involving timing of drug Excludes: Problem with delayed treatment \| Overdose of substance, as mode of injury or harm [QF2A] Difficulty or need for assistance with community participation Also known as: Difficulty or need for assistance with community participation \| difficulty with community participation \| need for assistance with community participation \| need for assistance with community, social and civic life \| difficulty with community, social and civic life Includes: Lack of relaxation or leisure [MF50.1] Pollakiuria Also known as: Pollakiuria \| pollakisuria \| Daytime frequency of micturition === GRAPH WALKS === --- Walk 1 --- [LB73.10] Poland syndrome Def: Poland syndrome is characterised by a unilateral absence or hypoplasia of the pectoralis major muscle (most frequently involving the sternocostal portion), and a variable degree of ipsilateral hand an... --PARENT--> [LB73.1] Structural developmental anomalies of chest wall Def: Any condition caused by failure of the chest wall to correctly develop during the antenatal period.... --CHILD--> [LB73.11] Bifid rib --- Walk 2 --- [LB73.10] Poland syndrome Def: Poland syndrome is characterised by a unilateral absence or hypoplasia of the pectoralis major muscle (most frequently involving the sternocostal portion), and a variable degree of ipsilateral hand an... --PARENT--> [LB73.1] Structural developmental anomalies of chest wall Def: Any condition caused by failure of the chest wall to correctly develop during the antenatal period.... --CHILD--> [LB73.12] Accessory rib Def: A condition caused by failure of the ribs to correctly develop during the antenatal period. This condition is characterised by a supernumerary rib arising from a cervical or lumbar vertebra. This cond... --- Walk 3 --- [LD44.N0] CATCH 22 phenotype Def: Monosomy 22q11 (DiGeorge Velocardiofacial syndrome, DGS/VCF) syndrome is a chromosomal anomaly characterised by the association of several variable malformations: hypoplastic thymus and parathyroid gl... --PARENT--> [LD44.N] Deletions of chromosome 22 --CHILD--> [LD44.NZ] Deletions of chromosome 22, unspecified --- Walk 4 --- [LD44.N0] CATCH 22 phenotype Def: Monosomy 22q11 (DiGeorge Velocardiofacial syndrome, DGS/VCF) syndrome is a chromosomal anomaly characterised by the association of several variable malformations: hypoplastic thymus and parathyroid gl... --PARENT--> [LD44.N] Deletions of chromosome 22 --CHILD--> [LD44.NY] Other specified deletions of chromosome 22 --- Walk 5 --- [LB31.3] Exstrophy of urinary bladder Def: Bladder exstrophy (or classic bladder exstrophy) is a congenital genitourinary malformation belonging to the spectrum of the exstrophy-epispadias complex and is characterised by an evaginated bladder ... --PARENT--> [LB31] Structural developmental anomalies of urinary tract Def: Any condition caused by failure of the urinary tract to correctly develop during the antenatal period.... --RELATED_TO--> [?] Persistent urogenital sinus Def: A urogenital sinus anomaly is a rare birth defect in women where the urethra and vagina both open into a common channel. The urogenital sinus is a part of the human body only present in the developmen... --- Walk 6 --- [LB31.3] Exstrophy of urinary bladder Def: Bladder exstrophy (or classic bladder exstrophy) is a congenital genitourinary malformation belonging to the spectrum of the exstrophy-epispadias complex and is characterised by an evaginated bladder ... --PARENT--> [LB31] Structural developmental anomalies of urinary tract Def: Any condition caused by failure of the urinary tract to correctly develop during the antenatal period.... --RELATED_TO--> [?] Persistent urogenital sinus Def: A urogenital sinus anomaly is a rare birth defect in women where the urethra and vagina both open into a common channel. The urogenital sinus is a part of the human body only present in the developmen...	[ "[LB73.10] Poland syndrome\n Def: Poland syndrome is characterised by a unilateral absence or hypoplasia of the pectoralis major muscle (most frequently involving the sternocostal portion), and a variable degree of ipsilateral hand an...\n --PARENT--> [LB73.1] Structural developmental anomalies of chest wall\n Def: Any condition caused by failure of the chest wall to correctly develop during the antenatal period....\n --CHILD--> [LB73.11] Bifid rib", "[LB73.10] Poland syndrome\n Def: Poland syndrome is characterised by a unilateral absence or hypoplasia of the pectoralis major muscle (most frequently involving the sternocostal portion), and a variable degree of ipsilateral hand an...\n --PARENT--> [LB73.1] Structural developmental anomalies of chest wall\n Def: Any condition caused by failure of the chest wall to correctly develop during the antenatal period....\n --CHILD--> [LB73.12] Accessory rib\n Def: A condition caused by failure of the ribs to correctly develop during the antenatal period. This condition is characterised by a supernumerary rib arising from a cervical or lumbar vertebra. This cond...", "[LD44.N0] CATCH 22 phenotype\n Def: Monosomy 22q11 (DiGeorge Velocardiofacial syndrome, DGS/VCF) syndrome is a chromosomal anomaly characterised by the association of several variable malformations: hypoplastic thymus and parathyroid gl...\n --PARENT--> [LD44.N] Deletions of chromosome 22\n --CHILD--> [LD44.NZ] Deletions of chromosome 22, unspecified", "[LD44.N0] CATCH 22 phenotype\n Def: Monosomy 22q11 (DiGeorge Velocardiofacial syndrome, DGS/VCF) syndrome is a chromosomal anomaly characterised by the association of several variable malformations: hypoplastic thymus and parathyroid gl...\n --PARENT--> [LD44.N] Deletions of chromosome 22\n --CHILD--> [LD44.NY] Other specified deletions of chromosome 22", "[LB31.3] Exstrophy of urinary bladder\n Def: Bladder exstrophy (or classic bladder exstrophy) is a congenital genitourinary malformation belonging to the spectrum of the exstrophy-epispadias complex and is characterised by an evaginated bladder ...\n --PARENT--> [LB31] Structural developmental anomalies of urinary tract\n Def: Any condition caused by failure of the urinary tract to correctly develop during the antenatal period....\n --RELATED_TO--> [?] Persistent urogenital sinus\n Def: A urogenital sinus anomaly is a rare birth defect in women where the urethra and vagina both open into a common channel. The urogenital sinus is a part of the human body only present in the developmen...", "[LB31.3] Exstrophy of urinary bladder\n Def: Bladder exstrophy (or classic bladder exstrophy) is a congenital genitourinary malformation belonging to the spectrum of the exstrophy-epispadias complex and is characterised by an evaginated bladder ...\n --PARENT--> [LB31] Structural developmental anomalies of urinary tract\n Def: Any condition caused by failure of the urinary tract to correctly develop during the antenatal period....\n --RELATED_TO--> [?] Persistent urogenital sinus\n Def: A urogenital sinus anomaly is a rare birth defect in women where the urethra and vagina both open into a common channel. The urogenital sinus is a part of the human body only present in the developmen..." ]	LB73.10	Poland syndrome	[ { "from_icd11": "LD44.N0", "icd10_code": "D821", "icd10_title": "Di George's syndrome" }, { "from_icd11": "LB31.3", "icd10_code": "Q6412", "icd10_title": "Cloacal exstrophy of urinary bladder" }, { "from_icd11": "LB31.3", "icd10_code": "Q6419", "icd10_title": "Other exstrophy of urinary bladder" }, { "from_icd11": "LB31.3", "icd10_code": "Q6410", "icd10_title": "Exstrophy of urinary bladder, unspecified" }, { "from_icd11": "LB31.3", "icd10_code": "Q64", "icd10_title": "Other congenital malformations of urinary system" }, { "from_icd11": "LB31.3", "icd10_code": "Q641", "icd10_title": "Exstrophy of urinary bladder" }, { "from_icd11": "LA56", "icd10_code": "Q870", "icd10_title": "Congenital malformation syndromes predominantly affecting facial appearance" }, { "from_icd11": "4A00.2", "icd10_code": "D848", "icd10_title": "Other specified immunodeficiencies" }, { "from_icd11": "QF2A", "icd10_code": "Z7389", "icd10_title": "Other problems related to life management difficulty" }, { "from_icd11": "QF2A", "icd10_code": "Z7382", "icd10_title": "Dual sensory impairment" }, { "from_icd11": "QF2A", "icd10_code": "Z73", "icd10_title": "Problems related to life management difficulty" }, { "from_icd11": "QF2A", "icd10_code": "Z732", "icd10_title": "Lack of relaxation and leisure" }, { "from_icd11": "QF2A", "icd10_code": "Z738", "icd10_title": "Other problems related to life management difficulty" }, { "from_icd11": "QF2A", "icd10_code": "Z739", "icd10_title": "Problem related to life management difficulty, unspecified" }, { "from_icd11": "MF50.1", "icd10_code": "R351", "icd10_title": "Nocturia" } ]	D821	Di George's syndrome
A 38-year-old man with schizophrenia presented after his second suicide attempt through an overdose with 48 tablets of burotizolam, 42 tablets of haloxazolam and 14 tablets of levomepromazine. The patient's childhood and adolescent development was normal. He was a good student and an active soccer player in high school. His social skills were standard, and he had no family history of mental illness. When he was 23 years old and a fourth year university student, he became convinced that he was being observed and he withdrew from social activities. His parents brought him to a psychiatric hospital, and he was diagnosed with schizophrenia according to DSM-IV-TR ( 24 ). The prescribed medication worked well and he was able to graduate from university at 27 years old. After graduating, he worked part time in a convenience store or at a nursery for several years. He then started to work at a distribution business under a handicapped employment program. His father committed suicide 3 years before he first presented at our hospital and a friend also died from a sickness. Because his auditory hallucinations repeatedly told him that he was responsible for their deaths, he could not stop blaming himself for their passing, in spite of his mother and brother telling him that he was not responsible. He was pessimistic about his future partly because he was able to earn only a meager income. In order to increase his income, he started a second part-time job at a supermarket in addition to his distribution job. He slept less and felt the accumulation of fatigue. He started to stockpile sleeping medications and he eventually took 76 tablets of brotizolam and 30 tablets of eszopiclone. The next morning his mother found him unconscious and called an ambulance. His mother brought his empty medicine containers to the hospital. At his first presentation, his physical examinations and vital signs were normal. He appeared to be very sleepy, but he managed to speak. The emergency department doctor ordered a blood test, a chest x-ray, an electrocardiogram test, a urine toxicology test, and a computed tomography brain scan. All results were within normal range, except a positive result for benzodiazepine in his urine and a slightly elevated white blood cell count (10.92 × 10 3 /μL). The emergency doctor enlisted a psychiatric doctor to evaluate his mental state. The patient claimed that his auditory hallucinations sounded like someone was booing in addition to radio sounds from a distance. He also claimed he was being tracked by the police. He admitted suicidal ideation and reported that he was sad because he could not die. Because his depressive symptoms occurred 4 weeks prior to his first admission, the authors carefully excluded the possibility of schizoaffective disorder and depressive disorders or bipolar disorder. However, the patient did not show manic symptom or markedly diminished interest, and his depressive thoughts seemed to ease shortly after his admission. Obviously, his mood episodes have been present for a minority of the total duration of the active and residual phases of illness; however, his memory changing delusion and auditory hallucination remains continuously. Furthermore, he showed negative symptom that he had withdrew from social activity except working. The authors diagnosed schizophrenia according to DSM 5 ( 25 ). His decreased ability to discriminate between his thought and true memories as mentioned previously suggests the presence of disturbance of the self which also supports this diagnosis ( 26 ). The authors prescribed risperidone 6 mg, brotizolam 0.25 mg, and eszopiclone 2 mg. Soon after the treatment started, he became calm and claimed his suicidal ideation disappeared. However, during the patient's second hospitalization, 6 months later, he admitted that he had lied. He wanted to go home quickly so he pretended to be healthy. He subsequently obtained a distribution job contract for the coming season by himself and he was supposed to be followed by a nearby clinic as a condition of his hospital discharge. He started his distribution job but he could not work regularly. Again, he wanted to earn more money so he started attending lectures to get a healthcare worker license. Consequently, his sleep time was reduced and he started to feel life was troublesome once again. He subsequently overdosed as mentioned previously. The next morning, his mother brought him to the emergency department again. She had no idea when he attempted to commit suicide but she last saw him the previous night at 10 p.m. His mother brought his empty medicine containers. His vital signs were normal, and he managed to speak. The emergency doctor conducted a blood test, a chest x-ray and a computed tomography brain scan. All the results were normal, except an elevated white blood cell count (12.16 × 10 3 /μL), creatine kinase (429 U/L), and chloride (109 mmol/L). His mother brought with her more than 100 risperidone tablets. It became obvious that he had not taken his pills regularly. The authors thought his adherence worsened during his psychotic period and started a long acting injectable antipsychotic (LAI). Because the patient worked regularly, the authors choose an injection given once in a 4-week period. Furthermore, because several studies showed it made significant improvements in the quality of life ( 22 ), the authors chose aripiprazole LAI at 400 mg. The authors also prescribed 20 mg of suvorexant per day and gradually discontinued brotizolam 0.25 mg and flunitrazepam 2 mg because the authors were concerned about a possible third suicide attempt while using benzodiazepine. Because both of the patient's admissions were associated with poor sleep, the authors examined the patient by polysomnography (PSG) and a multiple sleep latency test (MSLT) to exclude comorbid diseases such as sleep apnea syndrome or restless legs syndrome. As shown in Figure 1 , he woke frequently during his sleep and he lived with excessive daytime sleepiness . His Apnea-Hypopnea Index (AHI) was slightly elevated (5.1 times/hour), and respiratory events were not associated with significant desaturations (the minimum SpO2 was 95%). His BMI was 19.8. Malocclusion or tonsil swelling was not observed. Figure 2 shows the patient's sleep log. The patient did not show sleep phase advance or delay. The patient's Pittsburgh Sleep Quality Index (PSQI) score was 13, while over 5 points on the PSQI represents insomnia ( 27 ). Two months after his second admission, he was discharged while being prescribed suvorexant 20 mg, and chlorpromazine 25 mg per day in addition to aripiprazole LAI 400 mg per month. His Brief Psychiatric Rating Scale (BPRS) ( 28 ) dropped form 48 at admission to 42 at discharge. Six months after his second admission, the authors and the patient started CBT-i according to the CBT-i therapeutic manual ( 29 ). The authors also referred to the four causes cited by Chiu et al. ( 30 ): (a) beliefs that sleep problems cannot be changed; (b) trauma and adversity; (c) lifestyle choices and lack of motivation; (d) medication side effects and the 12 problems cited by Waite et al. ( 31 ): (a) Poor sleep environment; (b) Lack of daytime activity; (c) Lack of evening activity; (d) Disrupted circadian rhythm; (e) Sleep as an escape from distressing experiences; (f) Fear of bed; (g) Nightmares; (h) Night-time awakenings; (i) Sleep disrupted by voices/paranoia; (j) Worry; (k) Neuroleptic medication side effects; and (l) Reducing hypnotics. Our CBT-i consisted of eight sessions with each session ranging from 30 to 45 min. The first two sessions were educational sessions that attempted to find disturbances such as a misunderstanding of sleep hygiene or an inadequate sleep environment. In the other six sessions the authors and the patient tried to find other targets to tackle. For instance, the patient tried eating a carbohydrate (banana) before sleep, stopped checking his watch, warmed his body before going to bed, turned off small lights in his room, changed his routine of taking a bath before eating dinner to prevent him from taking a nap after dinner, bought a blackout curtain and an air conditioner. He also tried to wake up early in order to exercise in the morning instead of doing in the middle of the night because he believed he can fall asleep soon after the exercise. The whole course of sleep and psychological tendencies are shown in Figure 3 . The patient's BPRS dropped to 24 and his PSQI dropped to 8. His sleep time increased steadily however, at his sixth session, he claimed that he could not sleep at night and he felt a strong sense of sleepiness during the day. His mental health care team consisted of two physician groups; with one group treating his psychiatric symptoms and the other group (the authors) treating his sleep abnormality. The first physician group increased the patient's chlorpromazine from 25 to 37.5 mg. The authors, as the second physician group treating the patient's sleep abnormality, discussed reducing the patient's chlorpromazine with the first physician group because the authors believed that his sleep troubles were not caused by a difficulty in falling asleep but by the dosage of chlorpromazine being too high for the patient's current ability to fall asleep which was gradually being strengthened by CBT-i. At the seventh session, the authors encountered another misunderstanding of the patient in which the authors believed the patient's headaches were being caused by a lack of sleep, while the patient used chlorpromazine as a painkiller. The authors prescribed acetaminophen 400 mg as a painkiller, and stopped the administration of chlorpromazine. At the eighth session, the patient claimed that he had almost no trouble sleeping except when he forgets to take suvorexant.	3.814453	0.983887	sec[1]/p[0]	en	0.999997	29946274	https://doi.org/10.3389/fpsyt.2018.00260	[ "sleep", "authors", "that", "because", "tablets", "mother", "chlorpromazine", "brought", "prescribed", "time" ]	[ { "code": "7B2Z", "title": "Sleep-wake disorders, unspecified" }, { "code": "MG41", "title": "Sleep disturbance, not elsewhere classified" }, { "code": "7A20.Z", "title": "Narcolepsy, unspecified" }, { "code": "7B00.1", "title": "Sleepwalking disorder" }, { "code": "7A26", "title": "Insufficient sleep syndrome" }, { "code": "QA04.6", "title": "General mental examination, requested by authority" }, { "code": "8A80.Z", "title": "Migraine, unspecified" }, { "code": "QA76", "title": "Medication or substance that is known to be an allergen without injury or harm" }, { "code": "PL13.6", "title": "Medication or substance that is known to be an allergen, as mode of injury or harm" }, { "code": "9C40.A0", "title": "Papilloedema" } ]	=== ICD-11 CODES FOUND === [7B2Z] Sleep-wake disorders, unspecified Also known as: Sleep-wake disorders, unspecified \| sleep disorders [MG41] Sleep disturbance, not elsewhere classified Also known as: Sleep disturbance, not elsewhere classified \| sleep disturbance, unspecified Excludes: Sleep-wake disorders [7A20.Z] Narcolepsy, unspecified Also known as: Narcolepsy, unspecified \| Narcolepsy \| narcolepsy nos \| narcoleptic syndrome \| paroxysmal sleep [7B00.1] Sleepwalking disorder Definition: Sleepwalking disorder is characterised by ambulation and other complex behaviours during a partial arousal from deep sleep. Also known as: Sleepwalking disorder \| sleep walking \| sleepwalking \| somnambulism \| sleep walking disorder [7A26] Insufficient sleep syndrome Definition: Insufficient sleep syndrome occurs when an individual persistently fails to obtain the amount of sleep required relative to their own physiological sleep requirements to maintain normal levels of alertness and wakefulness and is thus chronically sleep deprived. The curtailed sleep pattern is present most days for at least several months. The person’s ability to initiate and maintain sleep is unimpaired. Sleep time is often markedly extended on weekend nights or during holidays compared to weekd Also known as: Insufficient sleep syndrome \| Behaviourally induced hypersomnia \| nonorganic origin somnolence \| primary hypersomnia \| hypersomnia of nonorganic origin Includes: Behaviourally induced hypersomnia Excludes: Narcolepsy [QA04.6] General mental examination, requested by authority Also known as: General mental examination, requested by authority \| evaluation of mental health requested by authority \| psychiatric examination requested by authority \| general psychiatric examination, requested by authority [8A80.Z] Migraine, unspecified Also known as: Migraine, unspecified \| Migraine [QA76] Medication or substance that is known to be an allergen without injury or harm Definition: Medication that has previously been identified as an allergen to the patient is administered, but does not result in injury or harm. Also known as: Medication or substance that is known to be an allergen without injury or harm Excludes: Medication or substance that is known to be an allergen, as mode of injury or harm [PL13.6] Medication or substance that is known to be an allergen, as mode of injury or harm Also known as: Medication or substance that is known to be an allergen, as mode of injury or harm \| medication error relating to known allergy to drug or substance \| adverse drug event relating to known allergy to drug or substance [9C40.A0] Papilloedema Definition: Optic disc swelling that results from increased intracranial pressure Also known as: Papilloedema \| Optic disc swelling that results from increased intracranial pressure Includes: Optic disc swelling that results from increased intracranial pressure === GRAPH WALKS === --- Walk 1 --- [7B2Z] Sleep-wake disorders, unspecified --PARENT--> [07] Sleep-wake disorders Def: Sleep-wake disorders are characterised by difficulty initiating or maintaining sleep (insomnia disorders), excessive sleepiness (hypersomnolence disorders), respiratory disturbance during sleep (sleep... --CHILD--> [?] Sleep-related breathing disorders Def: Sleep related breathing disorders are characterised by abnormalities of respiration during sleep. In some of these disorders, respiration is also abnormal during wakefulness. The disorders are grouped... --- Walk 2 --- [7B2Z] Sleep-wake disorders, unspecified --PARENT--> [07] Sleep-wake disorders Def: Sleep-wake disorders are characterised by difficulty initiating or maintaining sleep (insomnia disorders), excessive sleepiness (hypersomnolence disorders), respiratory disturbance during sleep (sleep... --CHILD--> [?] Sleep-related breathing disorders Def: Sleep related breathing disorders are characterised by abnormalities of respiration during sleep. In some of these disorders, respiration is also abnormal during wakefulness. The disorders are grouped... --- Walk 3 --- [MG41] Sleep disturbance, not elsewhere classified --EXCLUDES--> [?] Sleep-wake disorders Def: Sleep-wake disorders are characterised by difficulty initiating or maintaining sleep (insomnia disorders), excessive sleepiness (hypersomnolence disorders), respiratory disturbance during sleep (sleep... --CHILD--> [?] Hypersomnolence disorders Def: Hypersomnolence disorders are characterised by a complaint of daytime sleepiness that is not due to another sleep-wake disorder (e.g. disturbed nocturnal sleep, misaligned circadian rhythm, or breathi... --- Walk 4 --- [MG41] Sleep disturbance, not elsewhere classified --EXCLUDES--> [?] Sleep-wake disorders Def: Sleep-wake disorders are characterised by difficulty initiating or maintaining sleep (insomnia disorders), excessive sleepiness (hypersomnolence disorders), respiratory disturbance during sleep (sleep... --CHILD--> [?] Hypersomnolence disorders Def: Hypersomnolence disorders are characterised by a complaint of daytime sleepiness that is not due to another sleep-wake disorder (e.g. disturbed nocturnal sleep, misaligned circadian rhythm, or breathi... --- Walk 5 --- [7A20.Z] Narcolepsy, unspecified --PARENT--> [7A20] Narcolepsy Def: Narcolepsy is a disorder characterised by daily periods of irrepressible need to sleep or daytime lapses into sleep occurring for at least several months, accompanied by abnormal manifestations of REM... --CHILD--> [7A20.Z] Narcolepsy, unspecified --- Walk 6 --- [7A20.Z] Narcolepsy, unspecified --PARENT--> [7A20] Narcolepsy Def: Narcolepsy is a disorder characterised by daily periods of irrepressible need to sleep or daytime lapses into sleep occurring for at least several months, accompanied by abnormal manifestations of REM... --CHILD--> [7A20.0] Narcolepsy, Type 1 Def: Type 1 narcolepsy is a disorder of excessive sleepiness due to a deficiency of hypothalamic hypocretin (orexin) signaling. In addition to daily periods of irrepressible need to sleep or daytime lapses...	[ "[7B2Z] Sleep-wake disorders, unspecified\n --PARENT--> [07] Sleep-wake disorders\n Def: Sleep-wake disorders are characterised by difficulty initiating or maintaining sleep (insomnia disorders), excessive sleepiness (hypersomnolence disorders), respiratory disturbance during sleep (sleep...\n --CHILD--> [?] Sleep-related breathing disorders\n Def: Sleep related breathing disorders are characterised by abnormalities of respiration during sleep. In some of these disorders, respiration is also abnormal during wakefulness. The disorders are grouped...", "[7B2Z] Sleep-wake disorders, unspecified\n --PARENT--> [07] Sleep-wake disorders\n Def: Sleep-wake disorders are characterised by difficulty initiating or maintaining sleep (insomnia disorders), excessive sleepiness (hypersomnolence disorders), respiratory disturbance during sleep (sleep...\n --CHILD--> [?] Sleep-related breathing disorders\n Def: Sleep related breathing disorders are characterised by abnormalities of respiration during sleep. In some of these disorders, respiration is also abnormal during wakefulness. The disorders are grouped...", "[MG41] Sleep disturbance, not elsewhere classified\n --EXCLUDES--> [?] Sleep-wake disorders\n Def: Sleep-wake disorders are characterised by difficulty initiating or maintaining sleep (insomnia disorders), excessive sleepiness (hypersomnolence disorders), respiratory disturbance during sleep (sleep...\n --CHILD--> [?] Hypersomnolence disorders\n Def: Hypersomnolence disorders are characterised by a complaint of daytime sleepiness that is not due to another sleep-wake disorder (e.g. disturbed nocturnal sleep, misaligned circadian rhythm, or breathi...", "[MG41] Sleep disturbance, not elsewhere classified\n --EXCLUDES--> [?] Sleep-wake disorders\n Def: Sleep-wake disorders are characterised by difficulty initiating or maintaining sleep (insomnia disorders), excessive sleepiness (hypersomnolence disorders), respiratory disturbance during sleep (sleep...\n --CHILD--> [?] Hypersomnolence disorders\n Def: Hypersomnolence disorders are characterised by a complaint of daytime sleepiness that is not due to another sleep-wake disorder (e.g. disturbed nocturnal sleep, misaligned circadian rhythm, or breathi...", "[7A20.Z] Narcolepsy, unspecified\n --PARENT--> [7A20] Narcolepsy\n Def: Narcolepsy is a disorder characterised by daily periods of irrepressible need to sleep or daytime lapses into sleep occurring for at least several months, accompanied by abnormal manifestations of REM...\n --CHILD--> [7A20.Z] Narcolepsy, unspecified", "[7A20.Z] Narcolepsy, unspecified\n --PARENT--> [7A20] Narcolepsy\n Def: Narcolepsy is a disorder characterised by daily periods of irrepressible need to sleep or daytime lapses into sleep occurring for at least several months, accompanied by abnormal manifestations of REM...\n --CHILD--> [7A20.0] Narcolepsy, Type 1\n Def: Type 1 narcolepsy is a disorder of excessive sleepiness due to a deficiency of hypothalamic hypocretin (orexin) signaling. In addition to daily periods of irrepressible need to sleep or daytime lapses..." ]	7B2Z	Sleep-wake disorders, unspecified	[ { "from_icd11": "7B2Z", "icd10_code": "G4753", "icd10_title": "Recurrent isolated sleep paralysis" }, { "from_icd11": "7B2Z", "icd10_code": "G4762", "icd10_title": "Sleep related leg cramps" }, { "from_icd11": "7B2Z", "icd10_code": "G4761", "icd10_title": "Periodic limb movement disorder" }, { "from_icd11": "7B2Z", "icd10_code": "G4752", "icd10_title": "REM sleep behavior disorder" }, { "from_icd11": "7B2Z", "icd10_code": "G4750", "icd10_title": "Parasomnia, unspecified" }, { "from_icd11": "7B2Z", "icd10_code": "G4763", "icd10_title": "Sleep related bruxism" }, { "from_icd11": "7B2Z", "icd10_code": "G4754", "icd10_title": "Parasomnia in conditions classified elsewhere" }, { "from_icd11": "7B2Z", "icd10_code": "G4769", "icd10_title": "Other sleep related movement disorders" }, { "from_icd11": "7B2Z", "icd10_code": "F519", "icd10_title": "Sleep disorder not due to a substance or known physiological condition, unspecified" }, { "from_icd11": "7B2Z", "icd10_code": "G478", "icd10_title": "Other sleep disorders" }, { "from_icd11": "7B2Z", "icd10_code": "G479", "icd10_title": "Sleep disorder, unspecified" }, { "from_icd11": "7B2Z", "icd10_code": "F518", "icd10_title": "Other sleep disorders not due to a substance or known physiological condition" }, { "from_icd11": "7B2Z", "icd10_code": "F51", "icd10_title": "Sleep disorders not due to a substance or known physiological condition" }, { "from_icd11": "7B2Z", "icd10_code": "F512", "icd10_title": "" }, { "from_icd11": "7B2Z", "icd10_code": "G47", "icd10_title": "Sleep disorders" } ]	G4753	Recurrent isolated sleep paralysis
Figure 1 A 9-year-old boy presented with a 3-month history of left knee pain and effusion. Two months before presentation, his family consulted with a local physician. An X-ray revealed a radiolucent lesion with a sclerotic rim on the medial aspect of the distal femoral diaphysis ( A ; red arrow). However, no periosteal reaction or intraosseous mass was observed ( A , B ). The final diagnosis was benign bone tumor and growing pains, and acetaminophen was prescribed. The knee pain improved but then worsened, followed by knee effusion for 2 weeks. Considering the potential progression of the bone tumor, he was referred to our hospital for further examinations. A physical examination revealed no fever and the presence of knee joint pain and swelling, with a good range of motion. The results of laboratory tests showed a white blood cell (WBC) count of 6770/µL and C-reactive protein (CRP) of 0.24 mg/dL (normal: 0–0.14), suggesting mild inflammation. A rheumatoid factor and antinuclear antibodies analysis showed negative results. The patient played tennis but had no history of trauma. Figure 2 Computed tomography (CT) showed a tumor-like lesion on the medial aspect of the distal femoral diaphysis, suggesting a non-ossifying fibroma (NOF) ( A ), along with joint effusion ( B , C ). No soft tissue tumor was found. The initial diagnosis was NOF and arthritis or growing pains, and acetaminophen was administered for 30 d. The knee pain and effusion persisted despite continued management, and magnetic resonance imaging (MRI) was performed. Growing pains are common in children; nonetheless, the differential diagnosis of mechanical, infectious, inflammatory, and neoplastic conditions is challenging . Considering the patient’s age, primary malignant bone tumors, such as osteosarcoma and Ewing’s sarcoma, and other malignancies, including leukemia and neuroblastoma, were suspected, underscoring the need for a definitive diagnosis . The presence of knee pain, joint effusion, and mildly elevated CRP levels raised the possibility of a serious underlying condition. After excluding NOF as the cause of these symptoms, we suspected juvenile idiopathic arthritis (JIA) and initiated acetaminophen treatment and follow-up. JIA is a chronic inflammatory disorder that typically affects children < 16 years and is characterized by arthritic symptoms lasting for at least 6 weeks . The clinical manifestations of JIA are broad, with monoarticular, polyarticular, or systemic onset. Diagnosis is challenging and is made by exclusion because of the lack of a definitive diagnostic test . Although monoarticular JIA was suspected, the diagnosis of other conditions, including septic arthritis, reactive arthritis, malignant tumors, hemophilia, and trauma, needed to be excluded . The mean WBC count and CRP level in patients with JIA are 8810/µL and 4.3 mg/dL, respectively. Although these values were higher than in our patient, the wide range of CRP values in JIA does not exclude diagnosis in patients with lower values . Furthermore, although pain and swelling are typical symptoms of tenosynovial giant cell tumor (TSGCT), the absence of tumor lesions on the imaging and the patient’s age excluded TSGCT diagnosis. MRI should have been performed because of persistent knee swelling and pain. A study involving nine children with knee TSGCT reported a mean diagnostic delay of 18 months (range: 3–48 months), and 44% of cases were misdiagnosed as JIA . The diagnosis of septic arthritis must be ruled out in cases of joint effusion. However, the absence of fever and inflammatory markers precluded the need to perform joint aspiration. Joint fluid culture and analysis can help confirm the diagnosis. Figure 3 MRI showing a hypointense mass on T1-weighted images ( A ; red arrow), T2-weighted images ( B ), and short-TI inversion recovery images ( C ; red arrow), with hypointensity on T2*-weighted images ( D ), indicating blooming. The tumor was located behind the posterior cruciate ligament, and joint effusion was present. Although rare in children, TSGCT was suspected because of its intra-articular location and the presence of hemosiderin deposition. Other possible conditions were synovial hemangioma, hemophilic arthropathy, expanding hematoma, and chronic synovitis. CT scans revealed a mass with a density that was similar to that of muscle . MRI is useful for detecting intra-articular masses. Characteristic findings of TSGCT include isointensity or hypointensity on T1- and T2-weighted images with variable degrees of contrast enhancement . Similar MRI findings have been observed in children with TSGCT . Blooming, a common feature of TSGCT, is common in diffuse TSGCT (DTSGCT) and rare in localized TSGCT (LTSGCT) . CT imaging may have limitations in detecting TSGCT without bone invasion, as demonstrated by the initial imaging in this case. Hemosiderosis synovitis (HS) is an important differential diagnosis for TSGCT. A few studies identified characteristics distinguishing HS from TSGCT, including lateral meniscus and cartilage injury, synovial thickening, and contrast enhancement. Nonetheless, the number of reported cases in children is small . In some cases, MRI failed to detect TSGCT in the preoperative diagnosis of meniscal tears , and TSGCT is difficult to differentiate from septic arthritis , indicating the potential limitations of MRI. Figure 4 Arthroscopic resection of the tumor was performed to establish a definitive diagnosis. The macroscopic examination revealed a brown mass ( A ). Microscopy showed histiocyte-like mononuclear cells, fibroblast-like cells, and osteoclast-type multinucleated giant cells with focal areas of foam cells ( B , C ). Prussian blue staining showed hemosiderin-laden macrophages (basophilic cells) ( D ), and immunohistochemistry (IHC) revealed the presence of histiocyte-like mononuclear cells that were positive for clusterin ( E ) and CSF-1 ( F ) and negative results for desmin ( G ). Additionally, the osteoclast-like multinucleated giant cells were positive for CD68 (PGM-1) and negative for CD163. Therefore, the final diagnosis was TSGCT, which includes tumors arising from synovial joints, bursae, and tendon sheaths with synovial differentiation and pigmented villonodular synovitis. LTSGCT is more common than DTSGCT. The hands, particularly the fingers, are the most common site of LTSGCT, accounting for approximately 85% of cases . Although TSGCT affects predominantly women , Du et al. reported that the incidence of pediatric LTSGCT was higher in boys, with an equal distribution between hands and feet. LTSGCT usually occurs in a single joint; however, a few cases of bilateral involvement have been reported . LTSGCT affects the following knee structures in decreasing order: lateral recessus, suprapatellar recessus, Hoffa fat pad, posterior compartment, femoral notch, and lateral and medial compartments . The typical age of onset is 30–50 years, and pediatric cases are rare . Differential diagnoses for TSGCT include HS and giant cell tumor of soft tissue (GCTST) . GCTST shares histological similarities with giant cell tumors of bone, comprising mononuclear cells and osteoclast-like multinucleated giant cells, sometimes with metaplastic bone formation . Additionally, the key features that differentiate TSGCT from GCTST include the heterogeneous distribution of multinucleated giant cells, the small number of giant cell nuclei, the presence of large histiocyte-like mononuclear cells, stromal collagenization, and a heterogeneous population of foamy macrophages and inflammatory cells . However, HS is difficult to differentiate from TSGCT. Unlike TSGCT, HS lacks clusters of oval histiocyte-like mononuclear cells and has fewer osteoclastic multinucleated giant and foam cells . Clusterin, CSF-1, and desmin are common IHC markers of TSGCT . Clusterin was shown to be highly expressed in large mononuclear cells in both DTSGCT and LTSGCT . Moreover, 77%, 75%, and 80% of cases of TSGCT, DTSGCT, and LTSGCT, respectively, were positive for CSF-1 . Nevertheless, the utility of these markers in differentiating GCTST and HS from TSGCT is unknown. Desmin, with a positivity rate of 45–80% in TSGCT, is used to identify dendritic processes; however, it lacks specificity because of its expression in various tumors . The primary treatment for TSGCT is arthroscopic or open resection. The rate of recurrence is significantly lower in LTSGCT than in DTSGCT. However, the recurrence rates are similar between open and arthroscopic resection in LTSGCT; thus, the latter is the preferred approach . Conversely, the recurrence rates between open and arthroscopic resection in DTSGCT are unknown . Regarding other treatment modalities, radiation therapy is recommended for TSGCT because of its benign nature and potential long-term adverse effects . The CSF-1R inhibitor vimseltinib treats TSGCT by targeting CSF-1. In this respect, biologics can become the gold standard for treating primary or recurrent TSGCT in children, potentially replacing surgery. A phase 3 trial involving patients aged ≥18 years demonstrated that vimseltinib was more effective for tumor suppression, clinical function, and symptom improvement than placebo . Nonetheless, the effectiveness of vimseltinib in children is unknown. In conclusion, this report describes a rare case of pediatric LTSGCT of the knee with a delayed diagnosis. Arthritis, particularly JIA, is an important differential for pediatric knee pain. Similarly, other conditions, including malignant bone tumors and trauma, must be eliminated. In cases of persistent knee pain and swelling, MRI is essential for detecting tumors and evaluating the degree of arthritis. However, even with MRI, a definitive diagnosis involves a histopathological examination.	4.085938	0.975586	sec[0]/p[0]	en	0.999997	PMC11816834	https://doi.org/10.3390/diagnostics15030281	[ "tsgct", "cells", "knee", "ltsgct", "tumor", "pain", "giant", "cases", "joint", "like" ]	[ { "code": "MF9Y", "title": "Other specified clinical findings on examination of urine, without diagnosis" }, { "code": "5C56.20", "title": "Mucolipidosis" }, { "code": "3A51.1", "title": "Sickle cell disease without crisis" }, { "code": "9A96.3", "title": "Primary anterior uveitis" }, { "code": "3A61.Z", "title": "Acquired pure red cell aplasia, unspecified" }, { "code": "FA2Z", "title": "Inflammatory arthropathies, unspecified" }, { "code": "NC90.Y", "title": "Other specified superficial injury of knee or lower leg" }, { "code": "FA34.4", "title": "Ankylosis of joint" }, { "code": "FA33.4Z", "title": "Chronic instability of knee, unspecified" }, { "code": "NC90.0", "title": "Abrasion of knee" } ]	=== ICD-11 CODES FOUND === [MF9Y] Other specified clinical findings on examination of urine, without diagnosis Also known as: Other specified clinical findings on examination of urine, without diagnosis \| Methaemoglobinuria \| Other and unspecified abnormal findings in urine \| Calciuria \| Cells and casts in urine [5C56.20] Mucolipidosis Also known as: Mucolipidosis \| Mucolipidosis type 3 \| Pseudo-Hurler polydystrophy \| Pseudo-Hurler disease \| Mucolipidosis type 2 Excludes: Sialidosis (mucolipidosis type 1) [3A51.1] Sickle cell disease without crisis Definition: A disorder caused by a HbS mutation in the haemoglobin gene. This disorder is characterised by abnormal rigid sickle-shaped red blood cells decreasing its ability to carry oxygen. This disorder may present with fatigue, shortness of breath, dizziness, headaches, pallor of skin or mucous membranes, and jaundice. This disorder is confirmed by identification of HbS mutation by genetic testing. Also known as: Sickle cell disease without crisis \| Hb-SS disease without crisis \| HbSS without crisis \| Sickle-cell anaemia without crisis \| SCD - [sickle cell disease] [9A96.3] Primary anterior uveitis Definition: This refers to primary inflammation of the uvea. The uvea consists of the middle, pigmented, vascular structures of the eye and includes the iris, ciliary body, and choroid. Also known as: Primary anterior uveitis \| anterior chamber cell [3A61.Z] Acquired pure red cell aplasia, unspecified Also known as: Acquired pure red cell aplasia, unspecified \| Acquired pure red cell aplasia \| acquired red cell aplasia \| red cell aplasia NOS \| pure red cell aplastic anaemia [FA2Z] Inflammatory arthropathies, unspecified Also known as: Inflammatory arthropathies, unspecified \| polyarthritis NOS \| inflammatory joint disease NOS \| nonpyogenic arthritis NOS \| arthritic nodosa [NC90.Y] Other specified superficial injury of knee or lower leg Also known as: Other specified superficial injury of knee or lower leg \| Nonthermal blister of other or unspecified parts of lower leg \| Nonvenomous insect bite of other or unspecified parts of lower leg \| Superficial foreign body in other or unspecified parts of lower leg \| Splinter in other or unspecified parts of lower leg [FA34.4] Ankylosis of joint Definition: The term ankylosis denotes restricted movement in the joint, and it can be bony or fibrous. Most cases are caused by trauma, infection, radiotherapy, or severe arthritic condition. Also known as: Ankylosis of joint \| ankylosis \| ankylosis of joint, site unspecified \| frozen joint \| fusion of joint Excludes: stiffness of joint without ankylosis \| Ankylosis of spinal joint [FA33.4Z] Chronic instability of knee, unspecified Also known as: Chronic instability of knee, unspecified \| Chronic instability of knee \| instability of knee \| old disruption of ligament of knee [NC90.0] Abrasion of knee Also known as: Abrasion of knee === GRAPH WALKS === --- Walk 1 --- [MF9Y] Other specified clinical findings on examination of urine, without diagnosis --PARENT--> [?] Clinical findings on examination of urine, without diagnosis --EXCLUDES--> [?] Inborn errors of carbohydrate metabolism --- Walk 2 --- [MF9Y] Other specified clinical findings on examination of urine, without diagnosis --PARENT--> [?] Clinical findings on examination of urine, without diagnosis --CHILD--> [MF91] Bilirubinuria Def: Bilirubinuria means the presence of any bile pigment in the urine.... --- Walk 3 --- [5C56.20] Mucolipidosis --RELATED_TO--> [?] Mucolipidosis type 4 Def: Mucolipidosis type IV (ML IV) is a lysosomal storage disease characterised clinically by psychomotor retardation and visual abnormalities including corneal clouding, retinal degeneration, or strabismu... --PARENT--> [?] Mucolipidosis --- Walk 4 --- [5C56.20] Mucolipidosis --RELATED_TO--> [?] Wolman disease Def: Wolman disease represents the most severe manifestation of lysosomal acid lipase deficiency and can present in the fetus (hepatomegaly, ascites, calcified adrenal glands), or more typically in the fir... --PARENT--> [?] Lysosomal acid lipase deficiency Def: Lysosomal Acid Lipase (LAL) Deficiency happens when the body does not produce enough active lysosomal acid lipase (LAL or LIPA) enzyme. This enzyme plays an important role in breaking down fatty mater... --- Walk 5 --- [3A51.1] Sickle cell disease without crisis Def: A disorder caused by a HbS mutation in the haemoglobin gene. This disorder is characterised by abnormal rigid sickle-shaped red blood cells decreasing its ability to carry oxygen. This disorder may pr... --PARENT--> [3A51] Sickle cell disorders or other haemoglobinopathies Def: Any disorder caused by a HbS mutation in the haemoglobin gene. This disorder is characterised by abnormal rigid sickle-shaped red blood cells decreasing its ability to carry oxygen. This disorder may ... --PARENT--> [?] Anaemias or other erythrocyte disorders --- Walk 6 --- [3A51.1] Sickle cell disease without crisis Def: A disorder caused by a HbS mutation in the haemoglobin gene. This disorder is characterised by abnormal rigid sickle-shaped red blood cells decreasing its ability to carry oxygen. This disorder may pr... --PARENT--> [3A51] Sickle cell disorders or other haemoglobinopathies Def: Any disorder caused by a HbS mutation in the haemoglobin gene. This disorder is characterised by abnormal rigid sickle-shaped red blood cells decreasing its ability to carry oxygen. This disorder may ... --RELATED_TO--> [?] Other sickle-cell disorders with retinopathy Def: This is an autosomal recessive genetic blood disorder with overdominance, characterised by red blood cells that assume an abnormal, rigid, sickle shape. This diagnosis is due to persistent or acute da...	[ "[MF9Y] Other specified clinical findings on examination of urine, without diagnosis\n --PARENT--> [?] Clinical findings on examination of urine, without diagnosis\n --EXCLUDES--> [?] Inborn errors of carbohydrate metabolism", "[MF9Y] Other specified clinical findings on examination of urine, without diagnosis\n --PARENT--> [?] Clinical findings on examination of urine, without diagnosis\n --CHILD--> [MF91] Bilirubinuria\n Def: Bilirubinuria means the presence of any bile pigment in the urine....", "[5C56.20] Mucolipidosis\n --RELATED_TO--> [?] Mucolipidosis type 4\n Def: Mucolipidosis type IV (ML IV) is a lysosomal storage disease characterised clinically by psychomotor retardation and visual abnormalities including corneal clouding, retinal degeneration, or strabismu...\n --PARENT--> [?] Mucolipidosis", "[5C56.20] Mucolipidosis\n --RELATED_TO--> [?] Wolman disease\n Def: Wolman disease represents the most severe manifestation of lysosomal acid lipase deficiency and can present in the fetus (hepatomegaly, ascites, calcified adrenal glands), or more typically in the fir...\n --PARENT--> [?] Lysosomal acid lipase deficiency\n Def: Lysosomal Acid Lipase (LAL) Deficiency happens when the body does not produce enough active lysosomal acid lipase (LAL or LIPA) enzyme. This enzyme plays an important role in breaking down fatty mater...", "[3A51.1] Sickle cell disease without crisis\n Def: A disorder caused by a HbS mutation in the haemoglobin gene. This disorder is characterised by abnormal rigid sickle-shaped red blood cells decreasing its ability to carry oxygen. This disorder may pr...\n --PARENT--> [3A51] Sickle cell disorders or other haemoglobinopathies\n Def: Any disorder caused by a HbS mutation in the haemoglobin gene. This disorder is characterised by abnormal rigid sickle-shaped red blood cells decreasing its ability to carry oxygen. This disorder may ...\n --PARENT--> [?] Anaemias or other erythrocyte disorders", "[3A51.1] Sickle cell disease without crisis\n Def: A disorder caused by a HbS mutation in the haemoglobin gene. This disorder is characterised by abnormal rigid sickle-shaped red blood cells decreasing its ability to carry oxygen. This disorder may pr...\n --PARENT--> [3A51] Sickle cell disorders or other haemoglobinopathies\n Def: Any disorder caused by a HbS mutation in the haemoglobin gene. This disorder is characterised by abnormal rigid sickle-shaped red blood cells decreasing its ability to carry oxygen. This disorder may ...\n --RELATED_TO--> [?] Other sickle-cell disorders with retinopathy\n Def: This is an autosomal recessive genetic blood disorder with overdominance, characterised by red blood cells that assume an abnormal, rigid, sickle shape. This diagnosis is due to persistent or acute da..." ]	MF9Y	Other specified clinical findings on examination of urine, without diagnosis	[ { "from_icd11": "3A51.1", "icd10_code": "D571", "icd10_title": "Sickle-cell disease without crisis" }, { "from_icd11": "3A61.Z", "icd10_code": "D609", "icd10_title": "Acquired pure red cell aplasia, unspecified" }, { "from_icd11": "3A61.Z", "icd10_code": "D608", "icd10_title": "Other acquired pure red cell aplasias" }, { "from_icd11": "3A61.Z", "icd10_code": "D60", "icd10_title": "Acquired pure red cell aplasia [erythroblastopenia]" }, { "from_icd11": "FA2Z", "icd10_code": "M1389", "icd10_title": "Other specified arthritis, multiple sites" }, { "from_icd11": "FA2Z", "icd10_code": "M1380", "icd10_title": "Other specified arthritis, unspecified site" }, { "from_icd11": "FA2Z", "icd10_code": "M13862", "icd10_title": "Other specified arthritis, left knee" }, { "from_icd11": "FA2Z", "icd10_code": "M13872", "icd10_title": "Other specified arthritis, left ankle and foot" }, { "from_icd11": "FA2Z", "icd10_code": "M13871", "icd10_title": "Other specified arthritis, right ankle and foot" }, { "from_icd11": "FA2Z", "icd10_code": "M13861", "icd10_title": "Other specified arthritis, right knee" }, { "from_icd11": "FA2Z", "icd10_code": "M13879", "icd10_title": "Other specified arthritis, unspecified ankle and foot" }, { "from_icd11": "FA2Z", "icd10_code": "M13842", "icd10_title": "Other specified arthritis, left hand" }, { "from_icd11": "FA2Z", "icd10_code": "M13841", "icd10_title": "Other specified arthritis, right hand" }, { "from_icd11": "FA2Z", "icd10_code": "M13811", "icd10_title": "Other specified arthritis, right shoulder" }, { "from_icd11": "FA2Z", "icd10_code": "M13162", "icd10_title": "Monoarthritis, not elsewhere classified, left knee" } ]	D571	Sickle-cell disease without crisis
A 40-year old female was transferred to our Department of Medicine for the assessment and treatment of pleuropericarditis following lower respiratory tract infection. Her body mass index was 25.7 kg/m 2 and her personal history was positive for current smoking (~ 10 cigarettes/day, 40 pack years) and arterial hypertension (occasional use of amlodipine 5 mg). The present history of the patient begins 5 weeks ago with a hospitalization in a Respiratory Department for CAP (fever, dyspnea, chest X-ray positive for consolidation on the left upper lobe; Additional File 1 ). The patient received ceftriaxone and moxifloxacin for 10 days without any medical report on causative pathogen. Four weeks after her discharge the patient presented with fever, shortness of breath especially in exertion and pleuritic chest pain and was admitted to a Respiratory Department where bilateral pleural (mainly left) and mild pericardial effusion were found. Pericardial friction rub was not identified. Her blood tests revealed increased neutrophils and indices of inflammation (Table 1 , Additional File 1 ). Piperacillin/tazobactam and linezolid were initially administered. Thoracocentesis on the left side revealed neutrophilic exudate with pH 7.40. Despite antibiotic treatment, patient was not improved. Moreover C-reactive protein (CRP), pleural and pericardial effusions remained unchanged. Procalcitonin, high-sensitive troponin and brain natriuretic peptide levels were within normal limits during hospitalization. Blood and sputum cultures were negative. Extensive rheumatological workup was negative. In electrocardiography sinus tachycardia (112 bpm), frequent premature ventricular contractions, periods of ventricular trigeminy and inverted T-wave in V1–V6 were observed. Echocardiography was positive for mild mitral and triscupid valve regurgitation and mild pericardial effusion, without any sign of hemodynamic decompensation. Computed tomography (CT) imaging (including CT pulmonary angiogram) did not reveal pulmonary embolism or pathological findings from lung parenchyma and was positive only for the presence of pleural and pericardial effusions (Additional File 1 ). Pulmonologists administered ibuprofen 600 mg three times daily with the indication of idiopathic pleuropericarditis. The patient presented allergic reaction to ibuprofen and was transferred to our Department of Medicine on day (D) 12. Upon her admission, the patient presented with diffuse maculo-papular rash that was attributed to the allergic reaction to ibuprofen. Ibuprofen was withdrawn and IV methylprednisolone 40 mg once daily was initiated. Antibiotic treatment was suspended due to the lack of evidence of bacterial infection. Due to sinus tachycardia and premature ventricular complexes metoprolol 25 mg twice daily was administered. Patient’s file was reviewed and pericarditis investigation and differential diagnosis was conducted according to current guidelines . The patient fulfilled two out of four major criteria (pericardial chest pain and new pericardial effusion), along with one of the additional supporting findings (elevated CRP, white blood cells and erythrocyte sedimentation rate), rendering the diagnosis of pericarditis evidence-based . Colchicine 0.5 mg once daily (patient’s weight 66 kg) was initiated, for the treatment of pericarditis under investigation. The patient presented clinical improvement and CRP dropped to nearly normal (Additional File 1 ). Methylprednisolone was stopped after 3 days, as it was administered to treat the allergic reaction to ibuprophen. Low grade fever and pleuritic chest pain recurred rapidly, along with rising CRP levels. A new chest X-ray revealed bilateral pleural effusion but this time mainly on the right side. A repeat thoracocentesis revealed neutrophilic exudate with pH 7.40 and in a new chest CT the only new finding was the reduction of the left pleural effusion in combination with the increase of the right sided pleural effusion. Empirical initiation of meropenem was decided (Additional File 1 ). Clinical and laboratory findings did not improve with the addition of antibiotics; thus, antibiotics were suspended due to lack of evidence in favor of a bacterial cause for the new fever and IV methylprednisolone 40 mg once daily was again initiated. Table 1 Characteristics of cases with Chlamydia pneumoniae-associated pericarditis after systematic literature search Case 1 2 3 4 5 6 Study Kyriakoulis et al ( present study ) Oztek Celebi et al. Suesaowalak et al. Rýzlová et al. Tenenbaum et al. Zver et al. Year 2020 2020 2008 2008 2005 1997 Country Greece Turkey Thailand Czech Republic Germany Slovenia Age (years) 40 13 11 52 13 27 Sex Female Male Male Male Female Male Main diagnosis Pleuropericarditis Pericarditis Myopericarditis Pericarditis Pericarditis Pericarditis Signs/Symptoms Fever Shortness of breath after excessive physical activity Chest pain Chest pain Rhinitis for 3 weeks Cough for 3 weeks No fever Fever Rash Headache Myalgia Neck pain Intermittent vomiting Fever Shortness of breath after excessive physical activity Dry cough Chest pain Fever Tachypnoea Shortness of breath exacerbated by exertion Throat pain Nausea Fever Dry cough Pericardial friction rub Chest pain Cardiac tamponade Pre-existing medical conditions Arterial hypertension No No Respiratory tract infection 2 weeks ago (clarithromycin) Skeletal dysplasia of unknown cause, scoliosis, generalized gingivitis, mild aortic valve regurgitation Acute myeloblastic leukemia, pancytopenia Pleural effusion Bilateral Bilateral Small bilateral Left No NR Pericardial effusion Yes (mild) Yes (large) Yes (small) Yes (large) Yes Yes Pericardiocentesis No Yes, 1000 ml hemorrhagic No No Yes, 500 ml hemorrhagic Yes, 320 ml sanguinous exudate ECG Sinus tachycardia (112 bpm), PVCs, ventricular trigeminy, inverted T-wave in V1-V6 NR Sinus tachycardia (129 bpm), low QRS voltage, inverted T-wave in III, aVF, and V1–V4 Sinus tachycardia (106 bpm), 1 mm elevations ST in II, III, aVF, V2–V6 NR NR WBC 13.25 × 10 9 /l (neutrophils 89%) 12.9 × 10 9 /l (neutrophils 80%) 11.6 × 10 9 /l (neutrophils 70%) Normal 12.6 × 10 9 /l NR Troponin < 1.9 pg/ml (r < 15.6) 0 ng/ml (r < 0.06) 0.9 ng/ml (r < 0.04) Negative NR NR BNP 95 pg/ml (r < 100) NR 2.493 pg/ml (r < 100) NR NR NR CRP 8 mg/dl (r < 0.70) 719 nmol/L (r < 48) 16.18 mg/dl (r < 0.75) 302 mg/l (r NR) 20 mg/l (r NR) NR ESR 120 mm/h (r < 10) 13 mm/h (r < 10) 92 mm/h (r < 10) NR NR NR ANA Negative Negative NR 1: 160 NR NR RF < 10.2 (r < 15) NR NR NR NR NR Chest X-ray Small amount of bilateral pleural effusion mainly left, cardiomegaly Bilateral pleural effusions, lung infiltrations, cardiomegaly Pulmonary venous congestion, small amount of bilateral pleural effusion, cardiomegaly Left side infiltrate 3 × 2 cm Central bilateral infiltration and an enlarged cardiac silhouette Bronchopneumonia of right middle lobe Echocardiography Mild pleural effusion, normal systolic function, mild mitral and triscupid valve regurgitation Large pericardial effusion Mildly depressed left ventricular systolic function, EF 51%, small pericardial effusion Pericardial effusion up to 18 mm, no signs of tamponade Pericardial effusion Pericardial effusion up to 27 mm, fibrous strands attached to pericardium Chest CT Pericardial and bilateral pleural effusion, negative for pulmonary embolism (CTPA) Consolidations in the superior and inferior lobes of the left lung and the inferior lobe of the right lung NR Pericardial and left-sided pleural effusion, left side infiltrate 3 × 2 cm NR NR Diagnosis IgM 20 U/ml (r < 15), IgG 14 (r < 12)–10 days later IgM 11 U/ml (r < 15), IgG 17 (r < 12)–10 days later IgM 11 U/ml (r < 15), IgG 22 (r < 12) IgM 5.63 (r < 0.9), IgG 1.63 (r < 0.9)–2 weeks later IgM 3.49 (r < 0.9), IgG 2.31 (r < 0.9) IgM ≥ 1:160 (r < 1:10), IgG ≥ 1:1024 (r < 1:64), IgA ≥ 1:256 (r < 1:16) Positive IgG and IgA Positive IgG and IgA, Taq-Man PCR with the pericardial fluid Cultures and direct immunofluorescence of the pericardial fluid using specific monoclonal amtibodies revealed elementary bodies, IgG 1:64, ΙgM negative Treatment Moxifloxacin and ceftriaxone 5 weeks ago for previous CAP, Methylprednisolone, Colchicine Ceftriaxone 100 mg/kg once daily for 14 days, Clarithromycin 15 mg/kg was added on the third day of ceftriaxone therapy for 10 days Azithromycin 10 mg/kg once daily for 7 days Clarithromycin 500 mg 1 × 2 for 6 weeks, Prednisone 60 mg with careful slow tapering Azithromycin, Cefuroxime, Ibuprofen Erythromycin 0.5 g 1 × 4 Follow-Up Discharged after 18 days, follow-up visits every 3–4 weeks, in excellent clinical condition Discharged after 14 days, follow-up after 2 weeks with new C. pneumoniae IgM and IgG evaluation Discharged after 9 days (well controlled with anticongestive medication in subsequent visit) Relapse 4 weeks after stopping treatment; retreated with antibiotic therapy (clarithromycin + metronidazole); now 9 months without symptoms Discharged after 14 days Discharged after 14 days; died several months later (first relapse of acute leukemia, intracerebral hemorrhage) ANA antinuclear antibodies, BNP brain natriuretic peptide, bpm beats per minute, CAP community acquired pneumonia, CRP C-reactive protein, CT computed tomography, CTPA computed tomography pulmonary angiography, ECG electrocardiography, ESR erythrocyte sedimentation rate, NR not reported, RF rheumatoid factor, PVCs premature ventricular contractions, r reference, WBC white blood cells	3.925781	0.977539	sec[1]/p[0]	en	0.999998	34809625	https://doi.org/10.1186/s12890-021-01743-9	[ "pericardial", "effusion", "pleural", "chest", "fever", "pain", "pericarditis", "daily", "additional", "file" ]	[ { "code": "BB2Z", "title": "Pericarditis, unspecified" }, { "code": "LA8D", "title": "Congenital pericardial anomaly" }, { "code": "BB2Y", "title": "Other specified pericarditis" }, { "code": "BB22", "title": "Constrictive pericarditis" }, { "code": "GA10.E&XA2XU0", "title": "Endometriosis of pericardium" }, { "code": "FA36.Z", "title": "Effusion of joint, unspecified" }, { "code": "1D01.Z", "title": "Infectious meningitis, unspecified" }, { "code": "FA36.Y", "title": "Other specified effusion of joint" }, { "code": "8D60.1", "title": "Cerebral oedema" }, { "code": "ME04.0", "title": "Fluid in peritoneal cavity" } ]	=== ICD-11 CODES FOUND === [BB2Z] Pericarditis, unspecified Also known as: Pericarditis, unspecified \| pericarditis NOS \| pericardial inflammation \| pericardium inflammation [LA8D] Congenital pericardial anomaly Definition: A congenital cardiovascular malformation in which there is a structural and/or functional abnormality of the pericardium. Also known as: Congenital pericardial anomaly \| malformations of pericardium \| structural developmental anomalies of the pericardium \| congenital anomaly of pericardium \| structural developmental anomaly of the pericardium [BB2Y] Other specified pericarditis Also known as: Other specified pericarditis \| Certain diseases of pericardium \| Chronic adhesive pericarditis \| adherent pericarditis \| adherent pericardium [BB22] Constrictive pericarditis Definition: Chronic fibrous pericarditis due to the presence of dense fibrous tissue between the parietal and visceral layers of pericardium and neighbouring structures. Also known as: Constrictive pericarditis \| pericarditis calculosa \| Hutinel-Pick syndrome \| chronic tamponade \| chronic pericardial constriction Includes: concretio cordis [FA36.Z] Effusion of joint, unspecified Also known as: Effusion of joint, unspecified \| Effusion of joint \| effusion into joint \| effusion of joint, site unspecified \| hydrarthrosis [1D01.Z] Infectious meningitis, unspecified Also known as: Infectious meningitis, unspecified \| Infectious meningitis, not elsewhere classified \| acute meningomyelitis \| septic meningitis NOS \| infectious meningitis NEC [FA36.Y] Other specified effusion of joint Also known as: Other specified effusion of joint \| Non aspirated effusion of joint \| Effusion of joint without blood \| Effusion of joint, multiple sites \| Effusion of joint, shoulder region [8D60.1] Cerebral oedema Definition: Is an excess accumulation of fluid in the intracellular and/or extracellular spaces of the brain. Also known as: Cerebral oedema \| brain effusion \| brain oedema \| cerebral effusion \| intracranial effusion Excludes: Traumatic cerebral oedema \| Cerebral oedema due to birth injury [ME04.0] Fluid in peritoneal cavity Also known as: Fluid in peritoneal cavity \| chronic peritoneal effusion \| hydroperitoneum \| hydroperitonia \| peritoneal cavity fluid Excludes: Malignant ascites === GRAPH WALKS === --- Walk 1 --- [BB2Z] Pericarditis, unspecified --PARENT--> [?] Pericarditis --RELATED_TO--> [?] Acute rheumatic pericarditis Def: A disease of the pericardium, caused by acute rheumatic fever. This disease is characterised by fever, dry cough, rapid heart rate, fatigue, or low blood pressure. Confirmation is by echocardiography,... --- Walk 2 --- [BB2Z] Pericarditis, unspecified --PARENT--> [?] Pericarditis --RELATED_TO--> [?] Pneumopericardium originating in the perinatal period Def: Presence of air in the pericardial cavity usually from tracking of free air from ruptured alveolar ducts along the perivascular sheaths of pulmonary blood vessels, or rupture of subpleural bleb... --- Walk 3 --- [LA8D] Congenital pericardial anomaly Def: A congenital cardiovascular malformation in which there is a structural and/or functional abnormality of the pericardium.... --PARENT--> [?] Structural developmental anomaly of heart or great vessels Def: A congenital malformation of the heart and/or great vessels or an acquired abnormality unique to the congenitally malformed heart.... --RELATED_TO--> [?] Congenital great vessel related acquired abnormality Def: Any postnatal pathological change in form or function of the heart and/or great vessels consequent to the presence of congenital cardiovascular disease.... --- Walk 4 --- [LA8D] Congenital pericardial anomaly Def: A congenital cardiovascular malformation in which there is a structural and/or functional abnormality of the pericardium.... --PARENT--> [?] Structural developmental anomaly of heart or great vessels Def: A congenital malformation of the heart and/or great vessels or an acquired abnormality unique to the congenitally malformed heart.... --PARENT--> [?] Structural developmental anomalies of the circulatory system --- Walk 5 --- [BB2Y] Other specified pericarditis --PARENT--> [?] Pericarditis --RELATED_TO--> [?] Pneumopericardium originating in the perinatal period Def: Presence of air in the pericardial cavity usually from tracking of free air from ruptured alveolar ducts along the perivascular sheaths of pulmonary blood vessels, or rupture of subpleural bleb... --- Walk 6 --- [BB2Y] Other specified pericarditis --PARENT--> [?] Pericarditis --PARENT--> [11] Diseases of the circulatory system Def: This refers to diseases of the organ system that passes nutrients (such as amino acids, electrolytes and lymph), gases, hormones, blood cells, etc. to and from cells in the body to help fight diseases...	[ "[BB2Z] Pericarditis, unspecified\n --PARENT--> [?] Pericarditis\n --RELATED_TO--> [?] Acute rheumatic pericarditis\n Def: A disease of the pericardium, caused by acute rheumatic fever. This disease is characterised by fever, dry cough, rapid heart rate, fatigue, or low blood pressure. Confirmation is by echocardiography,...", "[BB2Z] Pericarditis, unspecified\n --PARENT--> [?] Pericarditis\n --RELATED_TO--> [?] Pneumopericardium originating in the perinatal period\n Def: Presence of air in the pericardial cavity usually from tracking of free air from ruptured alveolar ducts along the perivascular sheaths of pulmonary blood vessels, or rupture of subpleural bleb...", "[LA8D] Congenital pericardial anomaly\n Def: A congenital cardiovascular malformation in which there is a structural and/or functional abnormality of the pericardium....\n --PARENT--> [?] Structural developmental anomaly of heart or great vessels\n Def: A congenital malformation of the heart and/or great vessels or an acquired abnormality unique to the congenitally malformed heart....\n --RELATED_TO--> [?] Congenital great vessel related acquired abnormality\n Def: Any postnatal pathological change in form or function of the heart and/or great vessels consequent to the presence of congenital cardiovascular disease....", "[LA8D] Congenital pericardial anomaly\n Def: A congenital cardiovascular malformation in which there is a structural and/or functional abnormality of the pericardium....\n --PARENT--> [?] Structural developmental anomaly of heart or great vessels\n Def: A congenital malformation of the heart and/or great vessels or an acquired abnormality unique to the congenitally malformed heart....\n --PARENT--> [?] Structural developmental anomalies of the circulatory system", "[BB2Y] Other specified pericarditis\n --PARENT--> [?] Pericarditis\n --RELATED_TO--> [?] Pneumopericardium originating in the perinatal period\n Def: Presence of air in the pericardial cavity usually from tracking of free air from ruptured alveolar ducts along the perivascular sheaths of pulmonary blood vessels, or rupture of subpleural bleb...", "[BB2Y] Other specified pericarditis\n --PARENT--> [?] Pericarditis\n --PARENT--> [11] Diseases of the circulatory system\n Def: This refers to diseases of the organ system that passes nutrients (such as amino acids, electrolytes and lymph), gases, hormones, blood cells, etc. to and from cells in the body to help fight diseases..." ]	BB2Z	Pericarditis, unspecified	[ { "from_icd11": "BB2Z", "icd10_code": "I314", "icd10_title": "Cardiac tamponade" }, { "from_icd11": "BB2Z", "icd10_code": "I319", "icd10_title": "Disease of pericardium, unspecified" }, { "from_icd11": "BB2Z", "icd10_code": "I310", "icd10_title": "Chronic adhesive pericarditis" }, { "from_icd11": "BB2Z", "icd10_code": "I318", "icd10_title": "Other specified diseases of pericardium" }, { "from_icd11": "BB2Z", "icd10_code": "I31", "icd10_title": "Other diseases of pericardium" }, { "from_icd11": "LA8D", "icd10_code": "Q248", "icd10_title": "Other specified congenital malformations of heart" }, { "from_icd11": "BB22", "icd10_code": "I311", "icd10_title": "Chronic constrictive pericarditis" }, { "from_icd11": "FA36.Z", "icd10_code": "M25471", "icd10_title": "Effusion, right ankle" }, { "from_icd11": "FA36.Z", "icd10_code": "M25461", "icd10_title": "Effusion, right knee" }, { "from_icd11": "FA36.Z", "icd10_code": "M25462", "icd10_title": "Effusion, left knee" }, { "from_icd11": "FA36.Z", "icd10_code": "M25431", "icd10_title": "Effusion, right wrist" }, { "from_icd11": "FA36.Z", "icd10_code": "M25472", "icd10_title": "Effusion, left ankle" }, { "from_icd11": "FA36.Z", "icd10_code": "M25451", "icd10_title": "Effusion, right hip" }, { "from_icd11": "FA36.Z", "icd10_code": "M2548", "icd10_title": "Effusion, other site" }, { "from_icd11": "FA36.Z", "icd10_code": "M25411", "icd10_title": "Effusion, right shoulder" } ]	I314	Cardiac tamponade
Figure 1 Low-power view of pancreatic neuroendocrine tumor by immunostaining. Neuroendocrine tumor (G1), lymph node metastasis: around common hepatic artery (3+/5), around pancreas head (1+/3). Immunohistochemistry: (lymph nodes E): CgA (+), Syn (+), NSE (+), CD56 (+), CKpan (+), Ki-67 approximately 2%; (lymph nodes Q): CKpan (+), CD 56 (+), CgA (+), NSE (+), Syn (+), Ki-67 < 1%, Glucagon (+), insulin (−), somatostatin (−). CgA: Chromogranin A; Syn: Synaptophysin; NSE: Neuron-specific enolase. Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant genetic disease with a prevalence of about 2~3/100,000 , which is typically characterized by a higher occurrence of pituitary neoplasia, primary hyperparathyroidism and gastroenteropancreatic neuroendocrine tumors . Currently, the pathogenesis of MEN1 is considered to be mutations in the MEN1 gene . Here, we report a MEN1 patient, who suffered recurrent primary hyperparathyroidism (PHPT) after the initial surgery, and had his recurrent PHPT treated with ultrasound-guided radiofrequency ablation (RFA). The patient was a 52-year-old Han Chinese male, whose grandmother was intermarried to her cousin. His brother and cousin died of thymic carcinoid with bone metastasis and neuroendocrine neoplasms with liver metastasis, respectively. Seven years ago, due to recurrent upper abdominal pain, peptic ulcer and urinary calculi, the patient was found in the following physical condition: a level of gastrin 768.73 pg/mL (reference ranges, 13–115 pg/mL), albumin-corrected serum calcium 2.85 mmol/L (reference ranges, 2.11–2.52 mmol/L) and intact parathyroid hormone (iPTH) 163 pg/mL (reference ranges, 11.0–67.0 pg/mL); both parathyroid ultrasonography and emission computed tomography (ECT) indicated a lesion of right inferior parathyroid. The patient was diagnosed with PHPT and underwent endoscopic-assisted right inferior parathyroidectomy in August 2014. The patient had not been diagnosed with MEN1 at the time of the single gland resection of parathyroid gland, and only single gland lesion as the initial treatment of PHPT. The pathological sections showed right inferior parathyroid adenoma. Although the serum calcium returned to normal after surgery, the peptic ulcer was still not cured, and the gastrin level was significantly higher than the normal value. The subsequent genetic testing pointed to mutations of the MEN1 gene, CDS5 sub-region, c.866C>A nucleotide variation and p.Ala289Glu amino acid variation ( Table 1 ). The patient underwent laparoscopic pancreaticoduodenectomy with total meso-pancreas excision in December 2014. The pathologic results showed neuroendocrine neoplasm in histological type (G1) . The patient had been diagnosed with gastrinoma according to clinical manifestation and immunohistochemistry results. diagnostics-12-02553-t001_Table 1 Table 1 MEN1 genetic detecting analysis. Gene MEN1 NM_130803 Inheritance mode Autosomal dominant (AD) Gene subregion CDS5 Nucleotide alteration c.866C>A Amino acid alteration p.Ala289Glu Functional change Missense Homozygous/heterozygous Heterozygous Figure 2 The image of the parathyroid glands in 99mTc MIBI scintigraphy; MIBI accumulation was observed at 120 min as well as at 30 min in neck lesion which was thought to be parathyroid lesion (arrows in both panels). Gastrin levels returned to normal after surgery, and the patient took Esomeprazole 20 mg/d for 7 years, with regular follow-up. The latest reexamination showed a gradual increase in his serum calcium. The latest albumin-corrected serum calcium was 2.63 mmol/L (reference ranges, 2.11–2.52 mmol/L), serum phosphorus level was 0.72 mmol/L (reference ranges, 0.85–1.51 mmol/L) and PTH level was 141 pg/mL (reference ranges, 11.0–67.0 pg/mL). Parathyroid gland ECT indicated a slight increase of delayed uptake tracer in the right middle and upper pole of the thyroid, left middle and upper pole of the thyroid, and left lower pole of the thyroid, suggesting possible parathyroid origin . Dual-energy X-ray examination suggested osteoporosis (T value of left femoral neck −2.8). Figure 3 Changes of two left parathyroid glands before and after RFA by neck ultrasonography. US examination revealed 6 mm × 3 mm × 7 mm ( A ) and 9 mm × 6 mm × 3 mm ( C ) parathyroid nodules posterior to the left lobe of the thyroid gland pre-RFA. Two months after RFA, nonenhancement area (arrows) covered PHPT nodules on contrast-enhanced ultrasound (CEUS) ( B , D ), and the volume of the nodules decreased to about 0.01 mL (3.6 mm × 2.5 mm × 2.8 mm, superior left) ( B ) and 0.02 mL (4.6 mm × 2.8 mm × 2.7 mm, inferior left) ( D ). Ultimately, the patient was diagnosed with MEN1, based on their medical history and examination data as follows: (1) gastrinoma; (2) multiple parathyroid adenoma; (3) c.866C>A nucleotide variation in MEN1 gene. As the patient had multiple parathyroid lesions, surgery was one of main choices, including subtotal parathyroidectomy or total parathyroidectomy and parathyroid forearm transplantation. The patient was fully informed before treatment that the preferred treatment option was surgical resection. However, the patient had strong resistance to surgery since he had undergone multiple surgeries. A prospective study showed that complete ablation was achieved in 38 of the 39 nodules in the 39 enrolled participants in RFA in patients with PHPT. Recurrent laryngeal nerve paralysis occurred in 5.1% of the patients, who recovered spontaneously within three months . These data indicate that RFA might be an alternative therapy for patients who cannot tolerate undergoing surgery. Due to postoperative recurrence, the patient underwent RFA of two left parathyroids under the ultrasound guidance and saw remarkably reduced dimensions of parathyroids . The patient had no hoarseness, no local pressure and no neck pain after RFA. In the latest follow-up, the patient’s serum calcium had declined to within the normal range (2.45 mmol/L at Day 60 follow-up after RFA), and the parathyroid hormone (PTH) concentration declined from 141.0 pg/mL to 81.8 pg/mL ( Table 2 ). More prolonged follow-up is necessary. In this report, we showed a case of MEN 1 with a germline frameshift mutation (c.866C>A in MEN1 gene) accompanied by multiple parathyroid adenomas and gastrinoma. A diagnosis of MEN1 was established in an individual by one of three criteria . Firstly, on the basis of the occurrence of two or more primary MEN1-associated endocrine tumors, such as parathyroid adenoma, enteropancreatic tumor and pituitary adenoma. Secondly, the occurrence of the MEN1-associated tumors in a first-degree relative of a patient with a clinical diagnosis of MEN1. Thirdly, the identification of a germline MEN1 mutation in an individual, who might be asymptomatic and has not yet developed serum biochemical or radiological abnormalities indicative of tumor development. The patient met the two diagnostic criteria and was diagnosed with MEN1. Systemic screening of endocrine organ functions and imaging was performed, and no other lesions except parathyroid adenoma and gastrinoma were found. After the biochemical diagnosis of PHPT in MEN1 patients, surgical indications are similar to those of sporadic PHPT, including evidence of symptomatic or significant hypercalcemia, renal calculi and bone diseases such as decreased bone mineral density or fracture . The surgical methods of MEN1 with PHPT remain controversial. Several studies showed that nearly 42% patients with less than three parathyroidectomies still suffer from PHPT after the surgical treatment, while only 12% of patients with more than three parathyroidectomies have persistent PHPT. Nevertheless, they have a higher risk of permanent hypothyroidism . Furthermore, patients with the MEN1 gene mutation are prone to relapse of PHPT. After the parathyroidectomy, scar tissue around the parathyroid gland makes the second surgery more difficult for patients with recurrence, and the complication rate during reoperation is higher than during the primary surgery . The patient’s history of parathyroid surgery seven years ago introduced even more difficulties to our treatment in this instance. In the management of PHPT, thermal ablation has been recommended as an alternative in the last ten years . Thermal ablation resulted in less estimated blood loss, shorter treatment time, no scars on the neck and required only local anesthesia compared to surgery . It was found that the cure rate of thermal ablation could reach nearly 95%, which is comparable to surgery in PHPT patients . Compared with the incidence of permanent recurrent laryngeal nerve injury in parathyroidectomy, the rate of permanent nerve palsy hoarseness was lower in thermal ablation (0.8% vs. 3.9%) . The patient chose ultrasound-guided RFA to reduce the trauma and risk of reoperation, since many clinical studies showed the efficacy and safety of thermal ablation for PHPT, coupled with our successful experience in treating PHPT with RFA. The serum calcium was reduced to the normal range merely two days after RFA with satisfactory efficacy and safety. Individualized therapy significantly benefits the prognosis of MEN1 patients. diagnostics-12-02553-t002_Table 2 Table 2 The patient’s serum calcium and PTH changes before and after RFA. Administration Time (Day) Serum Calcium (mmol/L) PTH (pg/mL) Before RFA 2.63 141.0 Day 0 after RFA 2.71 32.8 Day 1 after RFA 2.52 60.8 Day 2 after RFA 2.4 81.6 Day 60 after RFA 2.45 81.8	4.144531	0.949219	sec[0]/p[0]	en	0.999996	PMC9600646	https://doi.org/10.3390/diagnostics12102553	[ "parathyroid", "phpt", "serum", "patients", "calcium", "mmol", "gene", "ablation", "reference", "ranges" ]	[ { "code": "5A5Z", "title": "Disorders of the parathyroids or parathyroid hormone system, unspecified" }, { "code": "5A51.0", "title": "Primary hyperparathyroidism" }, { "code": "5A50.Z", "title": "Hypoparathyroidism, unspecified" }, { "code": "5D42", "title": "Postprocedural hypoparathyroidism" }, { "code": "NA21.0&XA1342", "title": "Laceration of parathyroid gland" }, { "code": "NE80.3", "title": "Other serum reactions" }, { "code": "5D0Y", "title": "Other specified metabolic disorders" }, { "code": "5B91.0", "title": "Hypercalcaemia" }, { "code": "4A84.Y", "title": "Other specified anaphylaxis" }, { "code": "5C50.F2", "title": "Homocarnosinosis" } ]	=== ICD-11 CODES FOUND === [5A5Z] Disorders of the parathyroids or parathyroid hormone system, unspecified Also known as: Disorders of the parathyroids or parathyroid hormone system, unspecified \| parathyroidal disturbance \| disorder of parathyroid gland \| parathyroid gland disease \| parathyroid disease [5A51.0] Primary hyperparathyroidism Definition: Primary hyperparathyroidism is a condition with enhanced PTH secretion and high circulatory PTH level caused by abnormal parathyroid pathology such as adenoma, hyperplasia and cancer. Primary hyperparathyroidism usually causes hypercalcaemia by enhanced PTH actions. Also known as: Primary hyperparathyroidism \| parathyroid enlargement \| Familial primary hyperparathyroidism \| Hereditary primary hyperparathyroidism \| Familial isolated hyperparathyroidism [5A50.Z] Hypoparathyroidism, unspecified Also known as: Hypoparathyroidism, unspecified \| Hypoparathyroidism \| deficiency of parathyroid hormone \| parathyroid gland insufficiency \| parathyroid insufficiency [5D42] Postprocedural hypoparathyroidism Definition: This refers to a postprocedural decreased function of the parathyroid glands with underproduction of parathyroid hormone. This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany (involuntary muscle contraction), and several other symptoms. Also known as: Postprocedural hypoparathyroidism \| absence of parathyroid gland \| postoperative tetany \| Parathyroprival tetany Includes: Parathyroprival tetany [NE80.3] Other serum reactions Also known as: Other serum reactions \| Allergic reaction to serum \| serum allergy \| Complications of vaccination, protein sickness \| Protein sickness Excludes: serum hepatitis [5D0Y] Other specified metabolic disorders Also known as: Other specified metabolic disorders \| Disorders of plasma-protein metabolism, not elsewhere classified \| abnormal protein transport \| dysproteinaemia \| Absence of albumin in blood [5B91.0] Hypercalcaemia Definition: Hypercalcaemia is a condition caused by increased calcium levels. The higher the calcium levels and the faster its level rises, the more severe will be the symptoms. When present, symptoms are caused by dehydration secondary to urinary losses of calcium, water and other electrolytes, and to an increase in membrane potential caused by the elevation in extracellular fluid ionized calcium concentration. Patients with moderate to severe hypercalcaemia often complain of nausea and vomiting, symptoms Also known as: Hypercalcaemia \| Calcium excess \| elevated serum calcium \| hypercalcaemic crisis \| hypercalcaemic syndrome [4A84.Y] Other specified anaphylaxis Also known as: Other specified anaphylaxis \| Latex-induced anaphylaxis \| Anaphylaxis due to latex \| Latex anaphylaxis \| Anaphylactic shock due to serum [5C50.F2] Homocarnosinosis Definition: Homocarnosinosis is a metabolic defect characterised by progressive spastic diplegia, intellectual deficit and retinitis pigmentosa. This extremely rare disorder has been reported in only one family, namely a woman and three of her children. The latter showed but their mother was symptom free. It is therefore uncertain whether there is a relationship between the biochemical defect and the clinical symptoms. Inheritance in the reported family seems to be autosomal dominant. Also known as: Homocarnosinosis \| Homocarnosinase deficiency \| Serum carnosinase deficiency === GRAPH WALKS === --- Walk 1 --- [5A5Z] Disorders of the parathyroids or parathyroid hormone system, unspecified --PARENT--> [?] Disorders of the parathyroids or parathyroid hormone system Def: Disorders of the parathyroids and parathyroid hormone system generally refer to conditions with inappropriate secretion and/or actions of parathyroid hormone that cause dysregulation of calcium metabo... --CHILD--> [5A5Y] Other specified disorders of the parathyroids or parathyroid hormone system --- Walk 2 --- [5A5Z] Disorders of the parathyroids or parathyroid hormone system, unspecified --PARENT--> [?] Disorders of the parathyroids or parathyroid hormone system Def: Disorders of the parathyroids and parathyroid hormone system generally refer to conditions with inappropriate secretion and/or actions of parathyroid hormone that cause dysregulation of calcium metabo... --EXCLUDES--> [?] Hypocalcaemic vitamin D dependent rickets Def: Hypocalcaemic vitamin D-dependent rickets (VDDR-I) is an early-onset hereditary vitamin D metabolism disorder characterised by severe hypocalcaemia leading to osteomalacia and rachitic bone deformatio... --- Walk 3 --- [5A51.0] Primary hyperparathyroidism Def: Primary hyperparathyroidism is a condition with enhanced PTH secretion and high circulatory PTH level caused by abnormal parathyroid pathology such as adenoma, hyperplasia and cancer. Primary hyperpar... --PARENT--> [5A51] Hyperparathyroidism Def: Hyperparathyroidism refers to overproduction of parathormone and is most frequently due to a tumour in one of the parathyroid glands. It may also occur in response to low calcium levels, as encountere... --EXCLUDES--> [?] Adult osteomalacia Def: A disease characterised by defects in bone mineralization and bone softening secondary to vitamin D deficiency.... --- Walk 4 --- [5A51.0] Primary hyperparathyroidism Def: Primary hyperparathyroidism is a condition with enhanced PTH secretion and high circulatory PTH level caused by abnormal parathyroid pathology such as adenoma, hyperplasia and cancer. Primary hyperpar... --PARENT--> [5A51] Hyperparathyroidism Def: Hyperparathyroidism refers to overproduction of parathormone and is most frequently due to a tumour in one of the parathyroid glands. It may also occur in response to low calcium levels, as encountere... --EXCLUDES--> [?] Vitamin D deficiency rickets Def: Rickets is a disease of growing bone that is due to unmineralized matrix at the growth plates and occurs in children only before fusion of the epiphyses. There are many causes of rickets, including vi... --- Walk 5 --- [5A50.Z] Hypoparathyroidism, unspecified --PARENT--> [5A50] Hypoparathyroidism Def: Hypoparathyroidism is a condition with insufficient biological actions of parathyroid hormone due to impaired secretion of parathyroid hormone or refractoriness of target tissues to parathyroid hormon... --CHILD--> [5A50.1] Pseudohypoparathyroidism Def: Pseudohypoparathyroidism is a condition with refractoriness to parathyroid hormone of its target tissues especially kidney that causes hypocalcaemia and hyperphosphataemia even in the presence of high... --- Walk 6 --- [5A50.Z] Hypoparathyroidism, unspecified --PARENT--> [5A50] Hypoparathyroidism Def: Hypoparathyroidism is a condition with insufficient biological actions of parathyroid hormone due to impaired secretion of parathyroid hormone or refractoriness of target tissues to parathyroid hormon... --CHILD--> [5A50.0] Hypoparathyroidism due to impaired parathyroid hormone secretion Def: Hypoparathyroidism due to impaired PTH secretion is a condition with low circulating PTH level and hypocalcaemia caused by being unable to secrete PTH from parathyroids in response to hypocalcaemia wi...	[ "[5A5Z] Disorders of the parathyroids or parathyroid hormone system, unspecified\n --PARENT--> [?] Disorders of the parathyroids or parathyroid hormone system\n Def: Disorders of the parathyroids and parathyroid hormone system generally refer to conditions with inappropriate secretion and/or actions of parathyroid hormone that cause dysregulation of calcium metabo...\n --CHILD--> [5A5Y] Other specified disorders of the parathyroids or parathyroid hormone system", "[5A5Z] Disorders of the parathyroids or parathyroid hormone system, unspecified\n --PARENT--> [?] Disorders of the parathyroids or parathyroid hormone system\n Def: Disorders of the parathyroids and parathyroid hormone system generally refer to conditions with inappropriate secretion and/or actions of parathyroid hormone that cause dysregulation of calcium metabo...\n --EXCLUDES--> [?] Hypocalcaemic vitamin D dependent rickets\n Def: Hypocalcaemic vitamin D-dependent rickets (VDDR-I) is an early-onset hereditary vitamin D metabolism disorder characterised by severe hypocalcaemia leading to osteomalacia and rachitic bone deformatio...", "[5A51.0] Primary hyperparathyroidism\n Def: Primary hyperparathyroidism is a condition with enhanced PTH secretion and high circulatory PTH level caused by abnormal parathyroid pathology such as adenoma, hyperplasia and cancer. Primary hyperpar...\n --PARENT--> [5A51] Hyperparathyroidism\n Def: Hyperparathyroidism refers to overproduction of parathormone and is most frequently due to a tumour in one of the parathyroid glands. It may also occur in response to low calcium levels, as encountere...\n --EXCLUDES--> [?] Adult osteomalacia\n Def: A disease characterised by defects in bone mineralization and bone softening secondary to vitamin D deficiency....", "[5A51.0] Primary hyperparathyroidism\n Def: Primary hyperparathyroidism is a condition with enhanced PTH secretion and high circulatory PTH level caused by abnormal parathyroid pathology such as adenoma, hyperplasia and cancer. Primary hyperpar...\n --PARENT--> [5A51] Hyperparathyroidism\n Def: Hyperparathyroidism refers to overproduction of parathormone and is most frequently due to a tumour in one of the parathyroid glands. It may also occur in response to low calcium levels, as encountere...\n --EXCLUDES--> [?] Vitamin D deficiency rickets\n Def: Rickets is a disease of growing bone that is due to unmineralized matrix at the growth plates and occurs in children only before fusion of the epiphyses. There are many causes of rickets, including vi...", "[5A50.Z] Hypoparathyroidism, unspecified\n --PARENT--> [5A50] Hypoparathyroidism\n Def: Hypoparathyroidism is a condition with insufficient biological actions of parathyroid hormone due to impaired secretion of parathyroid hormone or refractoriness of target tissues to parathyroid hormon...\n --CHILD--> [5A50.1] Pseudohypoparathyroidism\n Def: Pseudohypoparathyroidism is a condition with refractoriness to parathyroid hormone of its target tissues especially kidney that causes hypocalcaemia and hyperphosphataemia even in the presence of high...", "[5A50.Z] Hypoparathyroidism, unspecified\n --PARENT--> [5A50] Hypoparathyroidism\n Def: Hypoparathyroidism is a condition with insufficient biological actions of parathyroid hormone due to impaired secretion of parathyroid hormone or refractoriness of target tissues to parathyroid hormon...\n --CHILD--> [5A50.0] Hypoparathyroidism due to impaired parathyroid hormone secretion\n Def: Hypoparathyroidism due to impaired PTH secretion is a condition with low circulating PTH level and hypocalcaemia caused by being unable to secrete PTH from parathyroids in response to hypocalcaemia wi..." ]	5A5Z	Disorders of the parathyroids or parathyroid hormone system, unspecified	[ { "from_icd11": "5A5Z", "icd10_code": "E213", "icd10_title": "Hyperparathyroidism, unspecified" }, { "from_icd11": "5A5Z", "icd10_code": "E212", "icd10_title": "Other hyperparathyroidism" }, { "from_icd11": "5A5Z", "icd10_code": "E214", "icd10_title": "Other specified disorders of parathyroid gland" }, { "from_icd11": "5A5Z", "icd10_code": "E215", "icd10_title": "Disorder of parathyroid gland, unspecified" }, { "from_icd11": "5A5Z", "icd10_code": "E21", "icd10_title": "Hyperparathyroidism and other disorders of parathyroid gland" }, { "from_icd11": "5A51.0", "icd10_code": "E210", "icd10_title": "Primary hyperparathyroidism" }, { "from_icd11": "5A50.Z", "icd10_code": "E209", "icd10_title": "Hypoparathyroidism, unspecified" }, { "from_icd11": "5A50.Z", "icd10_code": "E208", "icd10_title": "Other hypoparathyroidism" }, { "from_icd11": "5A50.Z", "icd10_code": "E20", "icd10_title": "Hypoparathyroidism" }, { "from_icd11": "5D42", "icd10_code": "E892", "icd10_title": "Postprocedural hypoparathyroidism" }, { "from_icd11": "NE80.3", "icd10_code": "T880XXA", "icd10_title": "Infection following immunization, initial encounter" }, { "from_icd11": "NE80.3", "icd10_code": "T8061XA", "icd10_title": "Other serum reaction due to administration of blood and blood products, initial encounter" }, { "from_icd11": "NE80.3", "icd10_code": "T8069XA", "icd10_title": "Other serum reaction due to other serum, initial encounter" }, { "from_icd11": "NE80.3", "icd10_code": "T8062XA", "icd10_title": "Other serum reaction due to vaccination, initial encounter" }, { "from_icd11": "NE80.3", "icd10_code": "T806", "icd10_title": "Other serum reactions" } ]	E213	Hyperparathyroidism, unspecified
A 39 year-old woman of Turkish-Iraqi descent presented in September 2007 to the emergency department with low grade fever, signs of weakness and difficulty walking due to diffuse bone pain mostly in the knees and both pectoral and pelvic girdles. Shortly before her admission the patient began experiencing alternating hot flashes and cold bouts disproportionate to the weather or clothing and suffered from frequent night sweats. Approximately six months prior to this incident, fatigue and leg pain slowly developed. The pain originally began as a tingling sensation, accompanied by paresthesia. It had escalated over several months and progressed to fully fledged bone pain. At the time of presentation, the pain was described as initiating at rest and constant, occasionally accompanied by episodes of fever. The patient was admitted for several consecutive hospitalizations. Upon inspection of her face, both exophthalmos and yellowish peri-orbital xanthelasmae-like lesions were apparent. The remainder of her physical examination was unremarkable, without deformation or bony swelling and without neurological deficits. It is noteworthy that the patient was polydypsic and polyuric for approximately five years prior to the onset of bone pain, consuming and excreting up to 12 liters of water per day. Despite this, a diagnosis of central diabetes insipidus was established and treatment with intranasal desmopressin initiated only upon hospitalization, presumably due to the patient’s adjustment to the gradual changes in water metabolism over the years. Apart from her known iron deficiency anemia, laboratory studies revealed increased levels of C-reactive protein (CRP: 70 mg/L) and elevated erythrocyte sedimentation rate (ESR: 72 mm/hour). A broad panel of immunologic studies, including rheumatoid factor (RF) and anti-nuclear antibodies was unremarkable. Negative blood and urine cultures ruled out an infectious etiology. Protein electrophoresis (PEP) yielded no monoclonal spike and the oncological markers were found to be within normal limits. Further investigations included radiography, which revealed bilateral sclerotic changes in the femoral and tibial bones and electromyography, which demonstrated normal muscle and nerve functionality. A subsequent 99m Tc bone scintigraphy demonstrated increased tracer uptake in the superior aspect of both orbits, the central sphenoidal region, left humeral head, right femoral greater trochanter and lateral superior aspect of the left iliac crest as well as diffuse, symmetric, bilateral increased tracer uptake in the femurs and tibiae enveloping both knees . A CT of the femurs and tibiae exhibited an irregular osseous texture demonstrating bones riddled with mixed patchy lesions of sclerotic and lytic nature. This was suggestive of either a metabolic, malignant or granulomatous process. An additional CT of the thorax, abdomen and pelvis revealed congestion of both renal sinuses with slightly distended ureters . CT and later MRI of the brain revealed bilateral retro-orbital nodular lesions , diffuse thickening and tortuosity of the optic nerves, enlargement of both lacrimal glands and soft tissue fullness of the sphenoid sinus . An MRI dedicated to the pituitary revealed no deviation from the normal anatomy. Over the two week period between two consecutive hospitalizations papilledema developed, accompanied by headaches, blurred vision and nausea. A lumbar puncture revealed an increased opening pressure of 44 cmH 2 O. Treatment with acetazolamide (250 mg X3 daily) was initiated, the increased intracranial pressure normalized and related symptoms abated. Biopsies were obtained from the tibial bone marrow and from a lacrimal gland. A microscopic examination of the tibial biopsy revealed bony trabeculae separated by a xanthomatous, diffuse spindle cell macrophage population with few interspersed giant cells . The spindle cells stained relatively uniformly for the presence of CD163, and in a more patchy fashion but quite strongly for factor XIIIa , surface staining for CD14 and granular intense staining for CD68 . CD1a and S-100 staining were globally negative except for one focus of S-100(+) cells, suggesting infiltration of the marrow with Langerhans cells. Overall, these findings were most consistent with a diagnosis of ECD with a component of Langerhans cell histiocytosis. Over the five years pursuant to her diagnosis on May 2007, the patient was treated with several treatment protocols. At first, steroids (prednisone, 60 mg/day) provided a temporary relief - a marked decrease in bone pain, decrease in CRP levels and normalization of fever. Two months later vinblastine (6 mg/m 2 /week) was introduced as a steroid sparing agent. This protocol failed to evoke a favorable long lasting response and was substituted for treatment with interferon-α. Since then, interferon-α has served as the primary therapeutic agent administered at dosages as low as 3 × 10 6 IU X 3 times weekly and as high as 6 × 10 6 IU X 5 times weekly. Initially, interferon-α was administered as a single agent. Later on, it was complemented by vinblastine (8 mg/1 to 4 months) and by pamidronic acid (60 mg/1 to 3 months) in order to better control the lytic lesions. It is noteworthy that this patient continued to deteriorate neurologically even at the highest doses of interferon-α administered (6 × 10 6 IU X 5 times weekly). However, the addition of vinblastine to this regimen succeeded in stabilizing the patient clinically and allowed for a gradual decrease in the dosage of interferon-α to a maintenance dose of 6 × 10 6 IU X 2 times weekly over a two year period. Three years after the diagnosis of ECD, a four-month trial of anakinra (100 mg/day) was attempted, mainly due to multifocal disease progression. However, this agent yielded unsatisfactory results. This attempt was followed by a five-month trial of cladribine (0.14 mg/kg/day for five consecutive days, every four weeks), a drug which yielded no apparent benefit to the patient and was very poorly tolerated. By this time, the patient’s neurological symptoms, vis-à-vis her lingual and motor capabilities, had deteriorated greatly once again. She was markedly dysarthric and confined to a wheelchair. Consequently, a biopsy obtained from the peri-renal mass was attempted and found to contain ECD histiocytes which harbor the V600E BRAF mutation. After receiving proper counseling and signing an informed consent, treatment with vemurafenib (1,920 mg/day later tapered to 960 mg/day) was initiated with no less than a spectacular improvement. After two weeks of treatment the patient began to exhibit clinical improvement. Ultimately, following treatment with this agent, the patient regained her ability to walk distances of up to 500 meters and recovered her ability to speak fluently. Figure 1 99m Tc bone scintigraphs of patients #1 (A), #2 (B), #3 (C) and #5 (D) taken prior to diagnosis. Note the characteristic bilateral symmetric pattern of increased tracer uptake, particularly involving the femoral and tibial long bones and the periarticular regions of the knees. Despite an obvious variability in the degree of tracer uptake among patients in these series, the intensity of tracer uptake did not necessarily correlate with the degree of bone pain at the time of presentation. Figure 2 Coronal reformatted contrast enhanced computed tomography images of patient #1, obtained at the time of the diagnosis (A) and 4.5 years after the diagnosis (B). The latter reveals severe hydronephrosis and marked cortical thinning of the left kidney and a peri-renal mass compressing the right kidney. Also, note the fine bilateral peri-renal infiltrate forming a ‘hairy kidney’ appearance. Figure 3 Various intracranial MRI findings of patients #1, #2 and #4. Coronal T1 weighted, gadolinium enhanced MR images of the retro-bulbar regions of patient #1 one year following diagnosis (A) and 4.5 years after diagnosis (B) . The former (A) demonstrates bilateral nodular masses located at the superior lateral aspect of the retro-orbit. These masses involve both the lacrimal glands and superior rectus muscles and undergo heterogeneous enhancement following gadolinium administration. The latter (B) demonstrates a marked reduction in the size of these lesions, presumably due to treatment with interferon-α. (C) Coronal T1 weighted, gadolinium enhanced MR image of patient #1 showing mucosal thickening in the sphenoidal sinus as well as soft tissue fullness which undergoes enhancement following gadolinium administration. This finding is also apparent in patient #4 (F) , who also exhibits an extra axial enhancing lesion situated in the vicinity of the planum sphenoidale (E) . In SWI sequence, both patients #4 (D) and #2 (G) exhibit multiple punctate hypointensities in the basal ganglia. These patterns are not typical for senile calcifications. Patient #2 also exhibits infiltrative enhancing tissue which narrows the transverse left sinus, adjacent to the falx and tentorium (I) . The same tissue is seen displacing the superior sagittal sinus (H) . MR, magnetic resonance; SWI, susceptibility weighted imaging. Figure 4 Histological sample from the tibia of patient #1. (A) H&E. Bony trabeculae separated by fibrosis and sheets of foamy macrophages. (B) Histiocytes demonstrating intense granular staining for CD68. (C) Histiocytes demonstrating patchy staining for factor XIIIa. (D) S-100 protein staining of the biopsy specimen.	4.070313	0.976074	sec[1]/sec[0]/p[0]	en	0.999995	25434739	https://doi.org/10.1186/s12916-014-0221-3	[ "this", "bone", "pain", "both", "which", "staining", "interferon", "over", "lesions", "tracer" ]	[ { "code": "4A01.03", "title": "Transient hypogammaglobulinaemia of infancy" }, { "code": "FC0Z", "title": "Diseases of the musculoskeletal system or connective tissue, unspecified" }, { "code": "FB84.Z", "title": "Osteomyelitis or osteitis, unspecified" }, { "code": "FB80.Z", "title": "Disorder of bone density or structure, unspecified" }, { "code": "FB86.11", "title": "Hypertrophy of bone" }, { "code": "FB86.1Z", "title": "Bone hyperplasias, unspecified" }, { "code": "MG3Z", "title": "Pain, unspecified" }, { "code": "8E43.Z", "title": "Pain disorders, unspecified" }, { "code": "MG31.Z", "title": "Acute pain, unspecified" }, { "code": "MG30.Z", "title": "Chronic pain, unspecified" } ]	=== ICD-11 CODES FOUND === [4A01.03] Transient hypogammaglobulinaemia of infancy Also known as: Transient hypogammaglobulinaemia of infancy \| immunoglobulin maturational delay \| THI - [transient hypogammaglobulinaemia of infancy] [FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified Also known as: Diseases of the musculoskeletal system or connective tissue, unspecified \| bone disease NOS \| bone disorder NOS \| bone lesion NOS \| musculoskeletal complications NOS [FB84.Z] Osteomyelitis or osteitis, unspecified Also known as: Osteomyelitis or osteitis, unspecified \| Osteomyelitis or osteitis \| bone inflammation \| bone ulcer \| bone inflammatory disease [FB80.Z] Disorder of bone density or structure, unspecified Also known as: Disorder of bone density or structure, unspecified \| Certain specified disorders of bone density or structure [FB86.11] Hypertrophy of bone Also known as: Hypertrophy of bone \| bone thickening \| periosteum thickening \| Infantile cortical hyperostoses \| Post traumatic subperiosteal ossification [FB86.1Z] Bone hyperplasias, unspecified Also known as: Bone hyperplasias, unspecified \| Bone hyperplasias [MG3Z] Pain, unspecified Also known as: Pain, unspecified \| pain observations \| pain NOS \| generalised pain \| generalised pain, NOS [8E43.Z] Pain disorders, unspecified Also known as: Pain disorders, unspecified \| Pain disorders [MG31.Z] Acute pain, unspecified Also known as: Acute pain, unspecified \| Acute pain [MG30.Z] Chronic pain, unspecified Also known as: Chronic pain, unspecified \| Chronic pain === GRAPH WALKS === --- Walk 1 --- [4A01.03] Transient hypogammaglobulinaemia of infancy --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects... --CHILD--> [4A01.01] Immunodeficiencies with severe reduction in at least two serum immunoglobulin isotypes with normal or low numbers of B cells Def: This refers to a nonfamilial type of primary immune deficiency disease characterised by a reduction in at least two serum immunoglobulin isotypes. Circulating B cells may be normal or low.... --- Walk 2 --- [4A01.03] Transient hypogammaglobulinaemia of infancy --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects... --PARENT--> [4A01] Primary immunodeficiencies due to disorders of adaptive immunity --- Walk 3 --- [FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified --PARENT--> [15] Diseases of the musculoskeletal system or connective tissue Def: This chapter contains diseases of musculoskeletal system and diseases of connective tissue.... --EXCLUDES--> [?] Injury, poisoning or certain other consequences of external causes Def: !markdown In the ICD, injury means physical or physiological bodily harm resulting from interaction of the body with energy (mechanical, thermal, electrical, chemical or radiant, or due to extreme pre... --- Walk 4 --- [FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified --PARENT--> [15] Diseases of the musculoskeletal system or connective tissue Def: This chapter contains diseases of musculoskeletal system and diseases of connective tissue.... --RELATED_TO--> [?] Symptoms, signs or clinical findings of the musculoskeletal system --- Walk 5 --- [FB84.Z] Osteomyelitis or osteitis, unspecified --PARENT--> [FB84] Osteomyelitis or osteitis --CHILD--> [FB84.1] Other acute osteomyelitis --- Walk 6 --- [FB84.Z] Osteomyelitis or osteitis, unspecified --PARENT--> [FB84] Osteomyelitis or osteitis --CHILD--> [FB84.0] Acute haematogenous osteomyelitis	[ "[4A01.03] Transient hypogammaglobulinaemia of infancy\n --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects\n Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects...\n --CHILD--> [4A01.01] Immunodeficiencies with severe reduction in at least two serum immunoglobulin isotypes with normal or low numbers of B cells\n Def: This refers to a nonfamilial type of primary immune deficiency disease characterised by a reduction in at least two serum immunoglobulin isotypes. Circulating B cells may be normal or low....", "[4A01.03] Transient hypogammaglobulinaemia of infancy\n --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects\n Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects...\n --PARENT--> [4A01] Primary immunodeficiencies due to disorders of adaptive immunity", "[FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified\n --PARENT--> [15] Diseases of the musculoskeletal system or connective tissue\n Def: This chapter contains diseases of musculoskeletal system and diseases of connective tissue....\n --EXCLUDES--> [?] Injury, poisoning or certain other consequences of external causes\n Def: !markdown\nIn the ICD, injury means physical or physiological bodily harm resulting from interaction of the body with energy (mechanical, thermal, electrical, chemical or radiant, or due to extreme pre...", "[FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified\n --PARENT--> [15] Diseases of the musculoskeletal system or connective tissue\n Def: This chapter contains diseases of musculoskeletal system and diseases of connective tissue....\n --RELATED_TO--> [?] Symptoms, signs or clinical findings of the musculoskeletal system", "[FB84.Z] Osteomyelitis or osteitis, unspecified\n --PARENT--> [FB84] Osteomyelitis or osteitis\n --CHILD--> [FB84.1] Other acute osteomyelitis", "[FB84.Z] Osteomyelitis or osteitis, unspecified\n --PARENT--> [FB84] Osteomyelitis or osteitis\n --CHILD--> [FB84.0] Acute haematogenous osteomyelitis" ]	4A01.03	Transient hypogammaglobulinaemia of infancy	[ { "from_icd11": "4A01.03", "icd10_code": "D807", "icd10_title": "Transient hypogammaglobulinemia of infancy" }, { "from_icd11": "FC0Z", "icd10_code": "XIII", "icd10_title": "" }, { "from_icd11": "FB84.Z", "icd10_code": "M86672", "icd10_title": "Other chronic osteomyelitis, left ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M86172", "icd10_title": "Other acute osteomyelitis, left ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M86171", "icd10_title": "Other acute osteomyelitis, right ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M86671", "icd10_title": "Other chronic osteomyelitis, right ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M868X7", "icd10_title": "Other osteomyelitis, ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M868X8", "icd10_title": "Other osteomyelitis, other site" }, { "from_icd11": "FB84.Z", "icd10_code": "M868X6", "icd10_title": "Other osteomyelitis, lower leg" }, { "from_icd11": "FB84.Z", "icd10_code": "M868X9", "icd10_title": "Other osteomyelitis, unspecified sites" }, { "from_icd11": "FB84.Z", "icd10_code": "M8668", "icd10_title": "Other chronic osteomyelitis, other site" }, { "from_icd11": "FB84.Z", "icd10_code": "M86662", "icd10_title": "Other chronic osteomyelitis, left tibia and fibula" }, { "from_icd11": "FB84.Z", "icd10_code": "M86151", "icd10_title": "Other acute osteomyelitis, right femur" }, { "from_icd11": "FB84.Z", "icd10_code": "M86141", "icd10_title": "Other acute osteomyelitis, right hand" }, { "from_icd11": "FB84.Z", "icd10_code": "M86641", "icd10_title": "Other chronic osteomyelitis, right hand" } ]	D807	Transient hypogammaglobulinemia of infancy
On Day 16, the patient developed auditory hallucinations, paranoia and referential beliefs. However, her insight was intact, and she had minimal thought form disorganization. Her symptoms were thought to be secondary to varenicline, and she met criteria for a substance/medication-induced psychotic disorder as per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria. On Day 17, the patient reported hearing auditory hallucinations of a derogatory nature described as “voices of people [she] knows” (Table 1 ). In addition, the patient’s affect appeared to be more distressed and irritable on Day 18, compared to MSE results recorded from Day 5 to Day 15 (Table 2 ). During this time, the patient also expressed interest of returning to the province that she grew up in despite her family’s disagreement. Urgent reassessment occurred given the need to balance treatment of her nicotine use disorder with the risk of ongoing psychotic symptoms. After consultation between the addiction medicine and psychiatry teams, varenicline was discontinued on Day 18 and the patient was monitored for resolution of these symptoms (Table 3 ). In her destabilized condition, she was thought to be at high risk in community given her history of high risk sex work and sex trafficking. The original plan for discharge was therefore halted due to the vulnerability of this patient. Table 1 Reports of AH during patient’s (pt) main admission Date Noted Auditory Hallucinations Day 5 Patient (pt) feels safe in hospital and denies any auditory/visual hallucinations Day 14 Denies hearing any AH and states “I only hear them when I’m manic” Day 15 Had reportedly voiced AH to nursing staff, and she states during notes “I sometimes hear a mumble” but it did not appear to be overtly hallucinations Day 17 AH present. Pt states voices occur with her mania. Reports voices tell her what to wear when she is deciding on an outfit to put on. Reports to hear voices while walking in the hallway. States she turns her head to look, no one is there. Reports she hears voices coming from people sitting beside her. When she looks, their mouths are not moving, and she continues to hear the voices. Pt states listening to loud music helps her cope with AH.—pt states voices are “louder”. “States she had auditory hallucinations earlier in the day of a derogatory nature-states they are voices of people she knows. Denies they are command. Reports previous medications helpful reducing them. Settled on unit. Loxapine 10 mg, Ativan 2 mg, and Seroquel 50 mg po prn with evening medications Day 18 AH present. Pt reports AH are “quieter” than yesterday. Pt denies AH to be derogatory. AH are not command in nature. As per nursing notes, patient endorsed having an upset stomach and AH that tell her how to dress. Coping mechanism being listening to music. AH endorsed as command. Pt absconded while on a group walk. Returned on her own on the same day. Day 19 Asked about AH today—“nothing yet today” Reports that AH “are not present this morning”- she states that she thinks they were because “of that new medication for stopping smoking that they gave me”; reports that the AH have decreased since stopping the same. No other voiced or observed perceptual disturbances present. No formal cognitive testing completed; however, the patient was attentive throughout the interview and there were no observed memory impairments present. Insight is increasingly becoming fuller as she becomes more self-aware and experiencing less manic symptoms -recognizes that her previous drug use has [led] to these current problems and that she is better without them Day 20 Pt reports AH occurring in the middle of the day. Pt unsure of [the] same being voices or overhearing nursing staff speak. Student Nurse—Brief AH reported; however [the] same was not bothersome. From MSE—Perceptual Abnormality—Denies Varenicline dosage was initiated on Day 14 and discontinued on Day 18 following concerns of persistent AH reported by the patient Table 2 Baseline mental status examination results prior to varenicline administration MSE Factor Day 5 Day 6 Day 7 Day 8 Day 11 Day 12 Appearance and Behavior Fair grooming and hygiene. No psychomotor disturbances were noted Good rapport but somewhat superficial Somewhat over familiar—making some facial gestures and leaning in during conversation. Fair grooming and hygiene. No psychomotor disturbances. Fair eye contact Less overfamiliar today. Fair grooming and hygiene. No psychomotor disturbances. Fair eye contact Good eye contact. did not appear over familiar or disinhibited today. reasonable grooming. no psychomotor agitation Good eye contact. did not appear over familiar or disinhibited today. reasonable grooming. no psychomotor agitation Speech Her speech was fast and often difficult to interrupt Soft but rapid. Not pressured. Interruptible Speech—Soft but rapid. Not pressured. Interruptible Soft but rapid. Not pressured. Interruptible Rapid speech verging pressured at times Speech less rapid, pressured today Affect/Mood Affect was labile, dysphoric. Mood was described as low Mood "pretty good" and affect mildly labile. More tearful today Affect/Mood—Mood "pretty good" and affect mildly labile. Some tearfulness Mood "pretty good" and affect mildly labile. More irritable today Mood 'down' affect—calm, no lability. no irritability Mood 'better' affect—calm, mild irritability when writer was having difficulty following her mildly disorganized account of the recent months Thought Form Fairly organized Initially organized though became quite tangential when discussing male acquaintance Fairly organized Difficult to follow events of the last few years—convoluted at times, Convoluted at times Thought Content There were delusions of paranoia and referential delusions as well. Thought process was circumstantial and at times tangential. She denied any perceptual disturbances and she did not appear to be responding to any internal stimuli No suicidal ideation (SI) or homicidal ideation (HI); no overt paranoia voiced today. (May hear [mumbling] at times but this does not sound like AH) No SI or HI; remains paranoid about men in community (may be based in reality) Denies perceptual abnormality No SI or HI; remains paranoid about men in community (may be based in reality) Denies perceptual abnormality No SI or HI; remains paranoid about "pimp ring' in community (? reality based). not attending to internal stimuli during interview No SI or HI; remains paranoid about "pimp ring' in community (? appears reality based) Insight Fair Intact, superficial Intact, superficial Intact, superficial Intact, superficial Intact, superficial Judgment Fair Likely poor Likely poor Likely poor Slowly improving Slowly improving Psychiatrist l Psychiatrist 1 Psychiatrist 2 Psychiatrist 2 Psychiatrist 2 Psychiatrist 3 Psychiatrist 3 Table 3 Mental status examination results during and after termination of varenicline use MSE Factor Day 15 Day 18 Day 19 Day 20 Day 25 Day 26 Appearance and Behavior Good rapport but somewhat superficial Good eye contact, did not appear overfamiliar or disinhibited today. Reasonable grooming. no psychomotor agitation Good eye contact. Settled. Did not appear overfamiliar or disinhibited today. reasonable grooming. No psychomotor agitation Caucasian female, blond hair and hospital gown. Looks her stated age. Wearing baggy t-shirt. Good rapport but somewhat superficial Caucasian female, blond hair in her own clothes. Wearing an oversized sweatshirt and leggings, and hair tied back in a ponytail. appears her stated age. good eye contact. Settled. No longer appears overfamiliar or disinhibited. reasonable grooming. No psychomotor agitation Caucasian female, blond hair in her own clothes. Dress, vest, well dressed and groomed, hair tied back in a ponytail. Appears her stated age. Good eye contact. Settled. No longer appears overfamiliar or disinhibited. reasonable grooming. No psychomotor agitation Speech Soft but rapid. Not pressured. [Interruptible] Soft and less rapid. Not pressured. [Interruptible] Affect/Mood Mood “pretty good” and affect mildly labile. More tearful today Mood ‘6–7/10’ affect—distressed Mood ‘irritable’ affect—less distressed compared to yesterday Mood pretty good and affect much more steady today Mood ‘stable’ affect – settled, [euthymic] Mood ‘stable’ affect – anxious, mildly distressed Thought Form Fairly organized Linear Linear Fairly organized Linear Linear Thought Content No SI or HI; no overt paranoia voiced today. (May hear [mumbling] at times but this does not sound like AH) No SI or HI; AH – benign command AH, derogatory AH, referential delusions No SI or HI; denies psychotic symptoms today (AH, TB, referential delusions) No SI or HI; vague residual paranoia No SI or HI; denies psychotic symptoms today (AH including mumbling, thought blocking, referential delusions). some somatic preoccupation, able to reality test No SI or HI; AH, mumbling, thought blocking. No somatic concerns today Insight Intact, superficial Able to reality test, with prompting Able to reality test Intact, superficial Improved compared to last week, able to reality test Improved compared to last week, able to reality test Judgement Likely poor Limited – recent running away from group walk Limited re: recent brief leave from group walk Likely poor Improving Improving Psychiatrist l Psychiatrist 2 Psychiatrist 3 Psychiatrist 3 Psychiatrist 2 Psychiatrist 3 Psychiatrist 3	3.873047	0.956543	sec[1]/sec[3]/p[2]	en	0.999997	36597062	https://doi.org/10.1186/s12888-022-04348-6	[ "today", "affect", "mood", "good", "psychiatrist", "thought", "voices", "that", "denies", "states" ]	[ { "code": "MB24.6Z", "title": "Disturbance of affect, unspecified" }, { "code": "MB28.A", "title": "Negative affectivity" }, { "code": "MB24.64", "title": "Inappropriate affect" }, { "code": "MB24.61", "title": "Blunted affect" }, { "code": "6E62", "title": "Secondary mood syndrome" }, { "code": "6A8Z", "title": "Mood disorders, unspecified" }, { "code": "6A8Y", "title": "Other specified mood disorders" }, { "code": "MB24.8", "title": "Elevated mood" }, { "code": "6D10.Z", "title": "Personality disorder, severity unspecified" }, { "code": "6E62.1", "title": "Secondary mood syndrome, with manic symptoms" } ]	=== ICD-11 CODES FOUND === [MB24.6Z] Disturbance of affect, unspecified Also known as: Disturbance of affect, unspecified \| Disturbance of affect [MB28.A] Negative affectivity Definition: A tendency to experience a broad range of distressing emotions, e.g. anxiety, anger irritability, depression, and other negative emotional states, often in response to even relatively minor actual or perceived stressors. Also known as: Negative affectivity \| negative emotionality \| proneness to negative emotional states \| neuroticism Includes: negative emotionality \| proneness to negative emotional states [MB24.64] Inappropriate affect Definition: Affective expression that is discordant with the content of the person's speech or ideation, or incompatible with the demands of a particular situation. Also known as: Inappropriate affect [MB24.61] Blunted affect Definition: A severe reduction in the expressive range and intensity of affect, but less than is observed in Flat affect. Also known as: Blunted affect [6E62] Secondary mood syndrome Definition: A syndrome characterised by the presence of prominent mood symptoms (i.e., depression, elevated mood, irritability) judged to be a direct pathophysiological consequence of a health condition not classified under mental and behavioural disorders, based on evidence from the history, physical examination, or laboratory findings. The symptoms are not accounted for by delirium or by another mental and behavioural disorder, and are not a psychologically mediated response to a severe medical condition Also known as: Secondary mood syndrome \| medical condition causing mood disorder \| organic affective disorder \| organic bipolar disorder \| Mood syndrome due to health condition not classified under mental and behavioural disorders Excludes: Adjustment disorder \| Delirium [6A8Z] Mood disorders, unspecified Also known as: Mood disorders, unspecified \| mood disorders, nonorganic or unspecified [6A8Y] Other specified mood disorders Also known as: Other specified mood disorders [MB24.8] Elevated mood Definition: A positive mood state typically characterised by increased energy and self-esteem which may be out of proportion to the individual's life circumstances. Also known as: Elevated mood [6D10.Z] Personality disorder, severity unspecified Also known as: Personality disorder, severity unspecified \| Personality disorder \| Specific personality disorders \| Enduring personality change after psychiatric illness (deprecated) \| Anankastic personality disorder [6E62.1] Secondary mood syndrome, with manic symptoms Definition: A syndrome characterised by the presence of prominent manic symptoms such as elevated, euphoric, irritable, or expansive mood states, rapid changes among different mood states (i.e., mood lability), or increased energy or activity that is judged to be a direct pathophysiological consequence of a health condition not classified under mental and behavioural disorders based on evidence from the history, physical examination, or laboratory findings. Also known as: Secondary mood syndrome, with manic symptoms \| Organic manic disorder \| Manic symptoms \| organic mood disorder of manic type \| organic mood disorder Includes: mood syndrome due to disorders or diseases not classified under Mental and behavioural disorders, with manic symptoms Excludes: Adjustment disorder \| Delirium === GRAPH WALKS === --- Walk 1 --- [MB24.6Z] Disturbance of affect, unspecified --PARENT--> [MB24.6] Disturbance of affect Def: A disturbance in the expression or outward manifestation of mood.... --CHILD--> [MB24.60] Constricted affect Def: A marked reduction in the expressive range and intensity of affect, but less than is observed in Blunted affect.... --- Walk 2 --- [MB24.6Z] Disturbance of affect, unspecified --PARENT--> [MB24.6] Disturbance of affect Def: A disturbance in the expression or outward manifestation of mood.... --CHILD--> [MB24.61] Blunted affect Def: A severe reduction in the expressive range and intensity of affect, but less than is observed in Flat affect.... --- Walk 3 --- [MB28.A] Negative affectivity Def: A tendency to experience a broad range of distressing emotions, e.g. anxiety, anger irritability, depression, and other negative emotional states, often in response to even relatively minor actual or ... --PARENT--> [MB28] Symptoms or signs related to personality features Def: Symptoms and signs involving the characteristics or qualities possessed by a person that uniquely influence his or her cognition, motivations, and behaviours in various situations.... --CHILD--> [MB28.2] Eccentricity Def: A tendency toward appearance or behaviour that is odd, unusual, peculiar, or unconventional, and is inconsistent with cultural or subcultural norms.... --- Walk 4 --- [MB28.A] Negative affectivity Def: A tendency to experience a broad range of distressing emotions, e.g. anxiety, anger irritability, depression, and other negative emotional states, often in response to even relatively minor actual or ... --PARENT--> [MB28] Symptoms or signs related to personality features Def: Symptoms and signs involving the characteristics or qualities possessed by a person that uniquely influence his or her cognition, motivations, and behaviours in various situations.... --PARENT--> [?] Mental or behavioural symptoms, signs or clinical findings --- Walk 5 --- [MB24.64] Inappropriate affect Def: Affective expression that is discordant with the content of the person's speech or ideation, or incompatible with the demands of a particular situation.... --PARENT--> [MB24.6] Disturbance of affect Def: A disturbance in the expression or outward manifestation of mood.... --PARENT--> [MB24] Symptoms or signs involving mood or affect Def: Symptoms and signs involving the regulation and expression of emotions or feeling states.... --- Walk 6 --- [MB24.64] Inappropriate affect Def: Affective expression that is discordant with the content of the person's speech or ideation, or incompatible with the demands of a particular situation.... --PARENT--> [MB24.6] Disturbance of affect Def: A disturbance in the expression or outward manifestation of mood.... --CHILD--> [MB24.60] Constricted affect Def: A marked reduction in the expressive range and intensity of affect, but less than is observed in Blunted affect....	[ "[MB24.6Z] Disturbance of affect, unspecified\n --PARENT--> [MB24.6] Disturbance of affect\n Def: A disturbance in the expression or outward manifestation of mood....\n --CHILD--> [MB24.60] Constricted affect\n Def: A marked reduction in the expressive range and intensity of affect, but less than is observed in Blunted affect....", "[MB24.6Z] Disturbance of affect, unspecified\n --PARENT--> [MB24.6] Disturbance of affect\n Def: A disturbance in the expression or outward manifestation of mood....\n --CHILD--> [MB24.61] Blunted affect\n Def: A severe reduction in the expressive range and intensity of affect, but less than is observed in Flat affect....", "[MB28.A] Negative affectivity\n Def: A tendency to experience a broad range of distressing emotions, e.g. anxiety, anger irritability, depression, and other negative emotional states, often in response to even relatively minor actual or ...\n --PARENT--> [MB28] Symptoms or signs related to personality features\n Def: Symptoms and signs involving the characteristics or qualities possessed by a person that uniquely influence his or her cognition, motivations, and behaviours in various situations....\n --CHILD--> [MB28.2] Eccentricity\n Def: A tendency toward appearance or behaviour that is odd, unusual, peculiar, or unconventional, and is inconsistent with cultural or subcultural norms....", "[MB28.A] Negative affectivity\n Def: A tendency to experience a broad range of distressing emotions, e.g. anxiety, anger irritability, depression, and other negative emotional states, often in response to even relatively minor actual or ...\n --PARENT--> [MB28] Symptoms or signs related to personality features\n Def: Symptoms and signs involving the characteristics or qualities possessed by a person that uniquely influence his or her cognition, motivations, and behaviours in various situations....\n --PARENT--> [?] Mental or behavioural symptoms, signs or clinical findings", "[MB24.64] Inappropriate affect\n Def: Affective expression that is discordant with the content of the person's speech or ideation, or incompatible with the demands of a particular situation....\n --PARENT--> [MB24.6] Disturbance of affect\n Def: A disturbance in the expression or outward manifestation of mood....\n --PARENT--> [MB24] Symptoms or signs involving mood or affect\n Def: Symptoms and signs involving the regulation and expression of emotions or feeling states....", "[MB24.64] Inappropriate affect\n Def: Affective expression that is discordant with the content of the person's speech or ideation, or incompatible with the demands of a particular situation....\n --PARENT--> [MB24.6] Disturbance of affect\n Def: A disturbance in the expression or outward manifestation of mood....\n --CHILD--> [MB24.60] Constricted affect\n Def: A marked reduction in the expressive range and intensity of affect, but less than is observed in Blunted affect...." ]	MB24.6Z	Disturbance of affect, unspecified	[ { "from_icd11": "6E62", "icd10_code": "F0631", "icd10_title": "Mood disorder due to known physiological condition with depressive features" }, { "from_icd11": "6E62", "icd10_code": "F0630", "icd10_title": "Mood disorder due to known physiological condition, unspecified" }, { "from_icd11": "6E62", "icd10_code": "F0633", "icd10_title": "Mood disorder due to known physiological condition with manic features" }, { "from_icd11": "6E62", "icd10_code": "F0632", "icd10_title": "Mood disorder due to known physiological condition with major depressive-like episode" }, { "from_icd11": "6E62", "icd10_code": "F063", "icd10_title": "Mood disorder due to known physiological condition" }, { "from_icd11": "6A8Z", "icd10_code": "F3010", "icd10_title": "Manic episode without psychotic symptoms, unspecified" }, { "from_icd11": "6A8Z", "icd10_code": "F3481", "icd10_title": "Disruptive mood dysregulation disorder" }, { "from_icd11": "6A8Z", "icd10_code": "F3013", "icd10_title": "Manic episode, severe, without psychotic symptoms" }, { "from_icd11": "6A8Z", "icd10_code": "F3011", "icd10_title": "Manic episode without psychotic symptoms, mild" }, { "from_icd11": "6A8Z", "icd10_code": "F39", "icd10_title": "Unspecified mood [affective] disorder" }, { "from_icd11": "6A8Z", "icd10_code": "F309", "icd10_title": "Manic episode, unspecified" }, { "from_icd11": "6A8Z", "icd10_code": "F302", "icd10_title": "Manic episode, severe with psychotic symptoms" }, { "from_icd11": "6A8Z", "icd10_code": "F308", "icd10_title": "Other manic episodes" }, { "from_icd11": "6A8Z", "icd10_code": "F349", "icd10_title": "Persistent mood [affective] disorder, unspecified" }, { "from_icd11": "6A8Z", "icd10_code": "F348", "icd10_title": "Other persistent mood [affective] disorders" } ]	F0631	Mood disorder due to known physiological condition with depressive features
The 62-year-old female patient was referred to and admitted at the clinic of the Max-Planck-Institute of Psychiatry in Munich, Germany, for diagnostic clarification and treatment of recurring paroxysmal psychovegetative episodes. The patient, a retired school teacher from an urban upper-middle-class socioeconomic background, reported a history of insomnia, fatigue, and depressed mood, which preceded the onset of PD symptoms and worsened after being diagnosed with PD. She was premorbidly well-adjusted before the onset of motor symptoms and had no prior neurologic or psychiatric history. No developmental difficulties were reported. The patient's medical history includes the diagnosis of idiopathic Parkinson's syndrome, a moderate obstructive sleep apnea syndrome treated with a continuous positive airway pressure (CPAP) device, and chronic hypothyroidism following Hashimoto's disease approximately three decades ago and treated with thyroid hormone replacement since. About 6 months before clinical admission in our psychiatric ward, the patient noticed a reduced resilience to physical activity. In the last 4 months, she experienced shortness of breath after walking short distances and her general condition was affected by a feeling of physical weakness, shivering, headaches, and the sensation of facial heat. Unpredictable episodes of anxiety and vegetative symptoms occurred even out of quiescent states. Three months prior to this admission, she was assessed at an emergency department for thoracic pain and dyspnoea. Electrocardiogram (ECG), echocardiography, and blood work did not reveal any abnormalities. She was discharged with the suspected diagnosis of arterial hypertension and was started on ranolazine. Despite this intervention, her symptoms reoccurred and additionally worsened in the weeks prior to this admission. Her general practitioner (GP) recommended a beta blocker to be taken as needed. As ranolazine had no effect on her symptoms, the patient took ranolazine occasionally and discontinued the beta blocker treatment. There was no history of fever, altered sensorium, or neurological deficits except fluctuating motor symptoms associated with her diagnosis of PD. The patient described weight gain of approximately 4 kg during the last year. The patient's prevailing difficulties over the 4 months prior to admission were described as recurring paroxysmal episodes of jitteriness, perioral and acral formications, palpitations, thoracic tightness, elevated blood pressure, and a darkish red discoloration of scalp and neck. These episodes emerged unexpectedly and were not associated with physical or emotional stress or other triggering factors. The patient reported that she had contacted an emergency physician on several occasions and had been admitted to hospitals twice approximately 3-4 months before her neurologist referred her to the clinic at the Max-Planck-Institute of Psychiatry in Munich, Germany, with a working diagnosis of panic disorder. Medication at admission consisted of moclobemide (450 mg/day), agomelatine (50 mg/day), pramipexole (0.525 mg/day), rasagiline (1 mg/day), L-DOPA+benserazide retard (200+50 mg/day), ranolazine (375 mg/day), and L-thyroxine (100 μ g/day). The dose of moclobemide had been increased from 150 mg/day to the current dose about 1 year prior to admission. At the time of the initial mental status examination, the patient was fully alert, attentive, and oriented. She maintained eye contact and provided an informative report. No apparent abnormalities in thought form and content were observed. Cognitive and amnestic functions were intact. Her effect initially appeared euthymic with a normal range though intermittently depressed during the conversation. Her impetus towards social activities and daily activities was decreased. Her psychomotor domain was calm; her voice was quiet and showed tendencies towards decreased prosody. Both her mimic and overall expressive gestures were scarce. Severe insomnia with sleep-onset and disturbed sleep, and daytime fatigue were reported. Appetite was reported as increased over the past months. The patient did not endorse symptoms indicating specific phobia, social anxiety, or generalized anxiety. She reported paroxysmal episodes of psychovegetative strain. The patient was not suicidal; there were no safety concerns with respect to herself or others. General and neurological examination of the 62-year-old female patient (height: 165 cm, weight: 65 kg; BMI: 23.9 kg/m 2 ) revealed a moderate rigor of the right upper extremity, adiadochokinesia, normal gait pattern, onychomycosis of toe nails, bilateral hallux valgus, and hyperkyphosis of the thoracic spine. No other physical or neurological abnormalities were detected. There was no postural imbalance or tremor. Vital signs at admission included blood pressure of 140/80 mmHg, heartrate of 84/min, and temperature of 36.4°C. Differential diagnoses considered at admission for reported paroxysmal episodes of psychovegetative symptoms included panic attacks/panic disorder, somatoform autonomic disorder, arterial hypertension with hypertensive exacerbations, iatrogenic hyperthyroidism, asthmatic disorder, and drug-induced serotonin toxicity. Clinical laboratory analyses did not reveal abnormal findings in CBC (complete blood count), hepatic and renal function, glucose and lipid profile, and electrolytes. Free T3 (triiodothyronine), free T4 (thyroxine), and TSH (thyroid stimulating hormone) were within normal limits. The plasma concentration of moclobemide was above the reference range of 300-1000 ng/ml. Plasma concentrations of agomelatine were not detectable (<1 ng/ml). We suspected potential pharmacological interactions to be a contributing factor to the symptoms reported by the patient at admission, and moclobemide, rasagiline, and ranolazine were discontinued. On the following day, the patient already experienced a decrease of psychovegetative symptoms. The blood work showed normal thyroid parameters, and no remarkable structural abnormalities of the thyroid gland were detected by sonography. Thus, we could rule out the possibility of iatrogenic hyperthyroidism. Moreover, repeated ECG examinations did not show signs of cardiac abnormalities explaining the patient's vegetative symptoms (ECG showed normal sinus rhythm, heart rate 81/min, QTc 429 ms, and vertical position). The changes of anti-parkinson medications during the stay were performed under repeated supervision of the consultant neurologists. As the discontinuation of ranolazine, which was prescribed as an antianginal medication, did not result in changes of blood pressure, we could also rule out arterial hypertension as a causative factor. The electroencephalogram (EEG) showed a regular, well-modulated, indistinct alpha-EEG with occipital accentuation and a frequency of 10-11 Hz and amplitudes reaching up to 100 μ V, a well-pronounced visual blockade and intermitted alpha-disintegration. A second EEG did not show any relevant changes. The magnetic resonance imaging (MRI) of the brain showed a slight expansion of the external frontal cerebrospinal fluid space and around the upper cerebellar vermis space. Disseminated, age-inappropriate, supratentorial small hyperintensities of the medullary layer were found. MRI-scan of the cervical and thoracic spine did not show any pathological findings. Due to the atypical localization of some lesions (i.e., near the corpus callosum and the right temporo-polar region), additional brain MRI-scan with contrast (gadolinium) was performed but results did not indicate an inflammatory process. In addition, lumbar puncture was discussed with the patient, who decided not to undergo this procedure after risks and benefits were explained. As the patient reported insomnia for nearly one decade and as agomelatine 50 mg daily was not effective, this medication was discontinued. After moclobemide, rasagiline, and ranolazine were discontinued based on the hypothesis of serotonergic overstimulation, no further episodic psychovegetative or panic-related symptoms occurred during hospitalization. The patient's blood pressure, which initially showed hypertensive episodes, went back to normal, and no antihypertensive medication was required. For persistent insomnia treatment trials with mirtazapine and trazodone were conducted, mirtazapine was not tolerated and trazodone was inefficient. Finally, sleep-associated symptoms slightly decreased with trimipramine 10 mg at bedtime. We established an antidepressive treatment with escitalopram, which was titrated to a dose of 10 mg. As per suggestions of consulting neurologists, pramipexole was reduced and discontinued. Because this was followed by an increase in PD-associated motor symptoms, we initiated treatment with rotigotine transdermal application of 8 mg/day. Levodopa/benserazide retard was switched to nonretard formulation of 125 mg three times a day. With this medication regimen, a stable and sufficient mobility could be achieved. Medication at discharge included escitalopram 10 mg/day, levodopa/benserazide 125 mg three times per day, rotigotine transdermal 8 mg/day, trimipramine 10 mg/day, and levothyroxine 100 μ g/day. The patient rated her mood as 9-10/10 on a scale from 0 to 10 with 10 being euthymic mood. The symptoms leading to admission subsided following discontinuation of MAO inhibitors moclobemide and rasagiline and did not reoccur during hospitalization.	3.919922	0.979004	sec[1]/p[0]	en	0.999997	33728085	https://doi.org/10.1155/2021/8868023	[ "episodes", "this", "blood", "ranolazine", "medication", "moclobemide", "psychovegetative", "pressure", "abnormalities", "discontinued" ]	[ { "code": "8A68.Y", "title": "Other specified type of seizure" }, { "code": "MD11.1", "title": "Asphyxia" }, { "code": "AB31.Z", "title": "Episodic vestibular syndrome, unspecified" }, { "code": "AB31.Y", "title": "Other specified episodic vestibular syndrome" }, { "code": "6C45.0", "title": "Episode of harmful use of cocaine" }, { "code": "4A01.03", "title": "Transient hypogammaglobulinaemia of infancy" }, { "code": "3C0Z", "title": "Diseases of the blood or blood-forming organs, unspecified" }, { "code": "MF50.4Z", "title": "Haematuria, unspecified" }, { "code": "MA12.1", "title": "Finding of cocaine in blood" }, { "code": "MA12.4", "title": "Finding of steroid agent in blood" } ]	=== ICD-11 CODES FOUND === [8A68.Y] Other specified type of seizure Also known as: Other specified type of seizure \| Absence episode \| Absence seizure episode \| Pseudotetanus \| Clonic seizure disorder [MD11.1] Asphyxia Definition: Asphyxia is a life-threatening condition in which oxygen is prevented from reaching the tissues by obstruction of or damage to any part of the respiratory system. More generally the term indicates all the conditions generating impaired or impeded breathing. Also known as: Asphyxia \| pathological asphyxia \| decreased oxygen supply \| oxygen deficiency \| positional asphyxia Excludes: asphyxia due to foreign body in respiratory tract \| asphyxia due to carbon monoxide \| asphyxia due to traumatic [AB31.Z] Episodic vestibular syndrome, unspecified Also known as: Episodic vestibular syndrome, unspecified \| Episodic vestibular syndrome [AB31.Y] Other specified episodic vestibular syndrome Also known as: Other specified episodic vestibular syndrome \| Secondary episodic vestibular syndrome \| Episodic vestibular syndrome in diseases classified elsewhere \| Episodic vestibular syndrome due to cerebrovascular disease \| Episodic vestibular syndrome due to diseases of the circulatory system [6C45.0] Episode of harmful use of cocaine Definition: An episode of use of cocaine that has caused damage to a person’s physical or mental health or has resulted in behaviour leading to harm to the health of others. Harm to health of the individual occurs due to one or more of the following: (1) behaviour related to intoxication; (2) direct or secondary toxic effects on body organs and systems; or (3) a harmful route of administration. Harm to health of others includes any form of physical harm, including trauma, or mental disorder that is directly Also known as: Episode of harmful use of cocaine Excludes: Cocaine dependence \| Harmful pattern of use of cocaine [4A01.03] Transient hypogammaglobulinaemia of infancy Also known as: Transient hypogammaglobulinaemia of infancy \| immunoglobulin maturational delay \| THI - [transient hypogammaglobulinaemia of infancy] [3C0Z] Diseases of the blood or blood-forming organs, unspecified Also known as: Diseases of the blood or blood-forming organs, unspecified \| Blood, lymph or spleen disease \| blood condition NOS \| blood disorder NOS \| bone marrow disease NOS [MF50.4Z] Haematuria, unspecified Also known as: Haematuria, unspecified \| Haematuria \| blood in urine \| urinary blood \| haematuria NOS [MA12.1] Finding of cocaine in blood Also known as: Finding of cocaine in blood \| cocaine in blood [MA12.4] Finding of steroid agent in blood Also known as: Finding of steroid agent in blood \| steroid in blood === GRAPH WALKS === --- Walk 1 --- [8A68.Y] Other specified type of seizure --PARENT--> [8A68] Types of seizures --CHILD--> [8A68.0] Focal unaware seizure Def: Previously termed “complex partial seizures”, define seizures originating within networks limited to one hemisphere and accompanied by loss of awareness (i.e., knowledge of self or environment).... --- Walk 2 --- [8A68.Y] Other specified type of seizure --PARENT--> [8A68] Types of seizures --PARENT--> [?] Epilepsy or seizures Def: At least 2 unprovoked (or reflex) seizures occurring more than 24 hours apart.... --- Walk 3 --- [MD11.1] Asphyxia Def: Asphyxia is a life-threatening condition in which oxygen is prevented from reaching the tissues by obstruction of or damage to any part of the respiratory system. More generally the term indicates all... --RELATED_TO--> [?] Intrauterine hypoxia Def: Intrauterine hypoxia occurs when the fetus is deprived of an adequate supply of oxygen. This may occur with prolapse or occlusion of the umbilical cord, placental infarction and maternal smoking. This... --EXCLUDES--> [?] Metabolic acidaemia in newborn Def: Metabolic acidaemia represents an increase in hydrogen ion concentration, usually due to the production of lactic acid following hypoxia or ischemia induced anaerobic metabolism. Acidaemia can also re... --- Walk 4 --- [MD11.1] Asphyxia Def: Asphyxia is a life-threatening condition in which oxygen is prevented from reaching the tissues by obstruction of or damage to any part of the respiratory system. More generally the term indicates all... --RELATED_TO--> [?] Birth asphyxia --CHILD--> [?] Mild and moderate birth asphyxia Def: Normal respiration not established within one minute, but heart rate 100 or above, some muscle tone present, some response to stimulation.... --- Walk 5 --- [AB31.Z] Episodic vestibular syndrome, unspecified --PARENT--> [AB31] Episodic vestibular syndrome Def: A clinical syndrome of transient vertigo, dizziness, or unsteadiness lasting seconds to hours, occasionally days, and generally including features suggestive of temporary, short-lived vestibular syste... --CHILD--> [AB31.2] Benign positional paroxysmal vertigo Def: Benign paroxysmal positional vertigo is defined as an abnormal sensation of motion that is elicited by certain critical provocative physical positions of the patient (e.g. becoming dorsal recumbent). ... --- Walk 6 --- [AB31.Z] Episodic vestibular syndrome, unspecified --PARENT--> [AB31] Episodic vestibular syndrome Def: A clinical syndrome of transient vertigo, dizziness, or unsteadiness lasting seconds to hours, occasionally days, and generally including features suggestive of temporary, short-lived vestibular syste... --CHILD--> [AB31.2] Benign positional paroxysmal vertigo Def: Benign paroxysmal positional vertigo is defined as an abnormal sensation of motion that is elicited by certain critical provocative physical positions of the patient (e.g. becoming dorsal recumbent). ...	[ "[8A68.Y] Other specified type of seizure\n --PARENT--> [8A68] Types of seizures\n --CHILD--> [8A68.0] Focal unaware seizure\n Def: Previously termed “complex partial seizures”, define seizures originating within networks limited to one hemisphere and accompanied by loss of awareness (i.e., knowledge of self or environment)....", "[8A68.Y] Other specified type of seizure\n --PARENT--> [8A68] Types of seizures\n --PARENT--> [?] Epilepsy or seizures\n Def: At least 2 unprovoked (or reflex) seizures occurring more than 24 hours apart....", "[MD11.1] Asphyxia\n Def: Asphyxia is a life-threatening condition in which oxygen is prevented from reaching the tissues by obstruction of or damage to any part of the respiratory system. More generally the term indicates all...\n --RELATED_TO--> [?] Intrauterine hypoxia\n Def: Intrauterine hypoxia occurs when the fetus is deprived of an adequate supply of oxygen. This may occur with prolapse or occlusion of the umbilical cord, placental infarction and maternal smoking. This...\n --EXCLUDES--> [?] Metabolic acidaemia in newborn\n Def: Metabolic acidaemia represents an increase in hydrogen ion concentration, usually due to the production of lactic acid following hypoxia or ischemia induced anaerobic metabolism. Acidaemia can also re...", "[MD11.1] Asphyxia\n Def: Asphyxia is a life-threatening condition in which oxygen is prevented from reaching the tissues by obstruction of or damage to any part of the respiratory system. More generally the term indicates all...\n --RELATED_TO--> [?] Birth asphyxia\n --CHILD--> [?] Mild and moderate birth asphyxia\n Def: Normal respiration not established within one minute, but heart rate 100 or above, some muscle tone present, some response to stimulation....", "[AB31.Z] Episodic vestibular syndrome, unspecified\n --PARENT--> [AB31] Episodic vestibular syndrome\n Def: A clinical syndrome of transient vertigo, dizziness, or unsteadiness lasting seconds to hours, occasionally days, and generally including features suggestive of temporary, short-lived vestibular syste...\n --CHILD--> [AB31.2] Benign positional paroxysmal vertigo\n Def: Benign paroxysmal positional vertigo is defined as an abnormal sensation of motion that is elicited by certain critical provocative physical positions of the patient (e.g. becoming dorsal recumbent). ...", "[AB31.Z] Episodic vestibular syndrome, unspecified\n --PARENT--> [AB31] Episodic vestibular syndrome\n Def: A clinical syndrome of transient vertigo, dizziness, or unsteadiness lasting seconds to hours, occasionally days, and generally including features suggestive of temporary, short-lived vestibular syste...\n --CHILD--> [AB31.2] Benign positional paroxysmal vertigo\n Def: Benign paroxysmal positional vertigo is defined as an abnormal sensation of motion that is elicited by certain critical provocative physical positions of the patient (e.g. becoming dorsal recumbent). ..." ]	8A68.Y	Other specified type of seizure	[ { "from_icd11": "MD11.1", "icd10_code": "R0901", "icd10_title": "Asphyxia" }, { "from_icd11": "MD11.1", "icd10_code": "R0902", "icd10_title": "Hypoxemia" }, { "from_icd11": "MD11.1", "icd10_code": "R090", "icd10_title": "Asphyxia and hypoxemia" }, { "from_icd11": "4A01.03", "icd10_code": "D807", "icd10_title": "Transient hypogammaglobulinemia of infancy" }, { "from_icd11": "3C0Z", "icd10_code": "D75A", "icd10_title": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency without anemia" }, { "from_icd11": "3C0Z", "icd10_code": "D7581", "icd10_title": "Myelofibrosis" }, { "from_icd11": "3C0Z", "icd10_code": "D7582", "icd10_title": "Heparin induced thrombocytopenia (HIT)" }, { "from_icd11": "3C0Z", "icd10_code": "D7589", "icd10_title": "Other specified diseases of blood and blood-forming organs" }, { "from_icd11": "3C0Z", "icd10_code": "D759", "icd10_title": "Disease of blood and blood-forming organs, unspecified" }, { "from_icd11": "3C0Z", "icd10_code": "D763", "icd10_title": "Other histiocytosis syndromes" }, { "from_icd11": "3C0Z", "icd10_code": "Q899", "icd10_title": "Congenital malformation, unspecified" }, { "from_icd11": "3C0Z", "icd10_code": "III", "icd10_title": "" }, { "from_icd11": "3C0Z", "icd10_code": "D70-D77", "icd10_title": "" }, { "from_icd11": "3C0Z", "icd10_code": "D75", "icd10_title": "Other and unspecified diseases of blood and blood-forming organs" }, { "from_icd11": "3C0Z", "icd10_code": "D77", "icd10_title": "Other disorders of blood and blood-forming organs in diseases classified elsewhere" } ]	R0901	Asphyxia
A 57-year-old nulliparous Japanese woman visited our clinic for the first time, presenting with dull left lower abdominal pain lasting for a few weeks. Transvaginal ultrasound (TVS) showed a left unilocular ovarian cystic mass, measuring 60 mm, containing a solid component on the cul-de-sac of Douglas . The patient was referred to the Department of Gynecology, Nara Medical University Hospital in September 2020 for the diagnosis of ovarian tumor. The patient was a housewife with normal social, emotional, and cognitive development and had normal environmental and employment history. There was no past medical, surgical, and medication history. She had never smoked or consumed alcohol. Neurological examinations were unremarkable. Evaluation of the patient’s family history revealed that her father died of lung cancer, all three of her paternal uncles succumbed to colon cancer, two paternal aunts died of gastric cancer and colon cancer, respectively, and one maternal uncle was treated for leukemia. In addition, her paternal grandfather died of gastric cancer. All three of her brothers are fine. Vital signs on admission showed a body temperature of 36.3 °C, blood pressure of 132/74 mm Hg, and respiratory rate of 20/minute. She was obese (weight 79 kg, height 158 cm, body mass index 31.6 kg/m 2 ). A pelvic mass was palpated on the left side of the uterus during physical examination. Pelvic magnetic resonance imaging (MRI) showed a 57 × 41 × 39 mm cystic mass with solid component originating in the left adnexa. The cystic part is of liquid signal, the solid component had high signal intensity on T2-weighted imaging (T2WI), and had low signal intensity on T1-weighted imaging (T1WI), with hyperintensity on diffusion-weighted images (DWI) . In addition, 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan revealed increased FDG uptake in solid components of the tumor [maximum standardized uptake value (SUVmax): 19.9] . No distant metastases were detected with staging CT and FDG-PET/CT. The patient had elevated serum levels of cancer antigen (CA) 125 (89 U/mL), but CA19-9 and carcinoembryonic antigen (CEA) were within the normal range. Imaging studies suspected ovarian malignancy, and she received primary debulking surgery. Following surgery, the pathological evaluation revealed the International Federation of Gynecology and Obstetrics stage IIIB high-grade serous ovarian cancer (pT3bN1M0). The patient underwent complete cytoreductive surgery. On postoperative day 27, the patient received the first cycle of combination chemotherapy comprising paclitaxel (175 mg/m 2 ; 3-hour infusion) and carboplatin (at a dose corresponding to an area under the curve of 5 mg/mL/minute). The patient subsequently received five cycles of standard carboplatin–paclitaxel chemotherapy combined with bevacizumab (15 mg/kg every 3 weeks). Genetic analysis of peripheral blood DNA revealed that BRCA1 and BRCA2 gene mutations were absent, but tissue samples from a pretreatment tumor biopsy were positive for the homologous recombination deficiency (HRD) test (Myriad Genetics, Inc.). The patient received oral niraparib maintenance therapy at a bolus of 200 mg daily after first-line chemotherapy. Figure 4 and Table 1 show the laboratory data. Her RBC count, hemoglobin, white blood cell count, and platelet count were 297 × 10 4 /μL, 10.5 g/dL, 35 × 10 2 /μL, and 21.1 × 10 4 /μL, respectively, when she started niraparib therapy. Immediately after the start of niraparib treatment (that is, 6 months after surgery), sodium ferrous citrate (SFC) was orally administered to treat anemia. Forty days after the start of niraparib therapy, peripheral blood cell counts, hematocrit levels, platelet counts, white blood cell count, and neutrophil count decreased to 231 × 10 4 /μL, 7.8 g/dL, 9.6 × 10 4 /μL, 18 × 10 2 /μL, and 323/μL, respectively (Table 1 ). Niraparib therapy was discontinued, but hemoglobin levels were further reduced to 7.0 g/dL. The patient had transient neutropenia and thrombocytopenia. Blood examination showed macrocytic anemia [mean corpuscular volume, 99.1 fL (82–98 fL); mean corpuscular hemoglobin, 33.8 pg (26–32 pg/mL); and mean corpuscular hemoglobin concentration, 35.1 g/dL (31–34 g/dL)]. Furthermore, blood tests showed high serum ferritin levels 350 ng/mL (10–148 ng/mL) and reticulocyte 3.5% (0.5–2.0%), low serum total iron-binding capacity 260 μg/dL (263–457 μg/dL), and serum levels of iron 141 μg/dL (32–170 μg/dL), bilirubin 0.6 mg/dL (0.4–1.5 mg/dL), lactate dehydrogenase 190 U/L (120–225 U/L), folic acid 8.0 ng/mL (2.1–10.1 ng/mL), vitamin B12 401 pg/mL (180–914 pg/mL), and transferrin 211 mg/dL (190–320 mg/dL) were in the normal range. Chest radiography, electrocardiogram, abdominal ultrasound, and thorax, abdominal, and pelvic computerized tomography were normal. Therefore, the patient was diagnosed with niraparib-related anemia. Niraparib therapy was discontinued for 2 weeks, and two units of packed RBC were transfused. Thereafter, the patient resumed oral niraparib therapy at a bolus of 100 mg daily and then increased to 200 mg 2 weeks later, but immediately exhibited grade 3 anemia. The patients required two units of packed RBC transfusions twice to maintain serum hemoglobin levels above 10 g/dL. RBC transfusions, dose interruption, and dose reduction were used to manage grade 3 anemia. SFC was discontinued and changed to oral FCH after blood transfusion. She began taking oral FCH at a dose of 500 mg daily 10 months after her surgery. Niraparib therapy was maintained at a daily dose of 100 mg until the following month. After continuous administration of FCH, the peripheral blood cell counts recovered gradually with stable Hb counts fluctuating between 10.7 and 12.5 g/dL. One year after surgery, niraparib therapy is still maintained at a daily dose of 200 mg. Oral administration of FCH was discontinued because the hemoglobin level exceeded 12 g/dL. Then, the serum hemoglobin levels decreased again. However, our patient no longer required blood transfusions and Hb levels stabilized at around 10–11 g/dL. She resumed oral FCH therapy after 8 weeks of pause, showing efficacy again. The follow-up is ongoing, and she has never been transfused. Table 1 presents laboratory findings in this patient before and after treatment with FCH. She has survived disease-free for 25 months after initial surgery. There is no sign of radiological recurrence with a normal serum CA125 level until now. She reached a total dose of approximately 90,000 mg and 135,000 mg of niraparib and FCH, respectively. We obtained the patient’s informed consent to publish this case report. Fig. 1 TVS of a cystic mass with solid component in the pelvis. Cystic and solid components measuring 60 × 35 mm in diameter localized at the left adnexa, suggestive of a lesion of the left ovary. *, a cystic mass with a maximum diameter of 4.8 cm. Arrow, a solid mass with a maximum diameter of 3.1 cm. TVS transvaginal ultrasound Fig. 2 MRI of a mass in the pelvis. A 57 × 41 × 39 mm cystic mass with solid component originating in the left adnexa. A and C T2-weighted MRI; B T1-weighted MRI; D diffusion-weighted images. A and B MRI in sagittal planes. C and D MRI in axial planes. MRI magnetic resonance imaging Fig. 3 PET/CT scan of a mass in the pelvis. A PET/CT fusion image; and B coronal image. PET/CT positron emission tomography/computed tomography Fig. 4 Effect of oral iron treatment on hemoglobin levels. Niraparib-related anemia was managed by dose interruption, dose reduction, or discontinuation. The patient was treated with oral SFC and blood transfusions for anemia. Thereafter, she began taking oral FCH depending on hemoglobin level. Hb, hemoglobin (g/dL); black arrow, surgery; red arrow, packed red blood cell transfusion; black square, chemotherapy consisting of paclitaxel (175 mg/m 2 ; 3-hour infusion) and carboplatin [at a dose corresponding to an area under the curve (AUC) of 5 mg/mL/minute] combined with bevacizumab (15 mg/kg every 3 weeks); blue square, oral niraparib maintenance therapy at a bolus of 200 mg daily (wide blue square) and 100 mg daily (narrow blue square); SFC oral sodium ferrous citrate, SCH oral ferric citrate hydrate Table 1 Laboratory findings before and after treatment with ferric citrate hydrate (FCH) Before oral administration of FCH After oral administration of FCH Normal reference range Peripheral blood cell counts, × 10 4 /μL 231 324 386–492 Hemoglobin 7.8 11.6 11.6–14.8 Hematocrit levels, g/dL 22.8 32.4 35.1–44.4 Platelet counts, × 10 4 /μL 9.6 19.7 15.8–34.8 White blood cell count, × 10 2 /μL 18 32 33–86 Neutrophil count, /μL 323 2394 CA125, U/mL 22 7 < 35 Serum ferritin level, ng/mL 350 361 10–148 Reticulocyte, % 3.5 3.1 0.5–2.0 Total iron-binding capacity, μg/dL 260 263–457 Iron, μg/dL 141 32–170 Bilirubin, mg/dL 0.6 0.5 0.4–1.5 Folic acid, ng/mL 8.0 2.1–10.1 Vitamin B12, pg/mL 401 180–914 Transferrin, mg/dL 211 190–320 Aspartate aminotransferase (AST), U/L 19 32 13–30 Alanine aminotransferase (ALT), U/L 20 46 7–23 Lactate dehydrogenase (LDH), U/L 190 185 120–225 Alkaline phosphatase (ALP), U/L 111 147 38–113 Blood urea nitrogen (BUN), mg/dL 15 12 8–20 Creatinine 0.81 0.77 0.46–0.79 Urine pH 6.5 6.5 Urine protein, mg/dL 300 30 Urine glucose, mg/dL – – Urine ketone bodies – – Urinary occult blood – – Urine urobilinogen, EU/dL 0.1 0.1 Urine bilirubin – –	3.990234	0.979492	sec[1]/p[0]	en	0.999997	36424618	https://doi.org/10.1186/s13256-022-03666-3	[ "blood", "oral", "niraparib", "hemoglobin", "solid", "serum", "cystic", "cancer", "daily", "count" ]	[ { "code": "3C0Z", "title": "Diseases of the blood or blood-forming organs, unspecified" }, { "code": "MF50.4Z", "title": "Haematuria, unspecified" }, { "code": "MA12.1", "title": "Finding of cocaine in blood" }, { "code": "MA12.4", "title": "Finding of steroid agent in blood" }, { "code": "MA12.2", "title": "Finding of hallucinogen in blood" }, { "code": "MD11.8Z", "title": "Mouth breathing, unspecified" }, { "code": "DA01.00", "title": "Oral leukoplakia" }, { "code": "DA01.10", "title": "Oral aphthae or aphtha-like ulceration" }, { "code": "MD80.1", "title": "Symptom or complaint of the mouth, tongue or lip" }, { "code": "DA01.1Y", "title": "Other specified noninfectious erosive or ulcerative disorders of oral mucosa" } ]	=== ICD-11 CODES FOUND === [3C0Z] Diseases of the blood or blood-forming organs, unspecified Also known as: Diseases of the blood or blood-forming organs, unspecified \| Blood, lymph or spleen disease \| blood condition NOS \| blood disorder NOS \| bone marrow disease NOS [MF50.4Z] Haematuria, unspecified Also known as: Haematuria, unspecified \| Haematuria \| blood in urine \| urinary blood \| haematuria NOS [MA12.1] Finding of cocaine in blood Also known as: Finding of cocaine in blood \| cocaine in blood [MA12.4] Finding of steroid agent in blood Also known as: Finding of steroid agent in blood \| steroid in blood [MA12.2] Finding of hallucinogen in blood Also known as: Finding of hallucinogen in blood \| hallucinogen in blood [MD11.8Z] Mouth breathing, unspecified Also known as: Mouth breathing, unspecified \| Mouth breathing \| breathing orally \| mouth respiration [DA01.00] Oral leukoplakia Definition: Leukoplakia is a condition where areas of keratosis appear as adherent white patches on the mucous membranes of the oral cavity. Leukoplakia may affect other gastrointestinal tract mucosal sites, or mucosal surfaces of the urinary tract and genitals. Also known as: Oral leukoplakia \| Leukoplakia of gingiva \| leukoplakia of oral epithelium \| leucoplakia of oral mucosa \| leukokeratosis of oral mucosa Includes: Leukoplakia of gingiva Excludes: Hairy leukoplakia [DA01.10] Oral aphthae or aphtha-like ulceration Definition: This is a frequent small, shallow, painful ulceration in the oral mucosa. Recurrent oral ulceration that clinically resembles recurrent aphthous stomatitis but presents atypically, including commencement after adolescence, with fever, with a strong family history, or failing to resolve with age. Also known as: Oral aphthae or aphtha-like ulceration \| Recurrent aphthous stomatitis \| Recurrent oral aphthae \| Major recurrent aphthous stomatitis \| major aphthous stomatitis [MD80.1] Symptom or complaint of the mouth, tongue or lip Also known as: Symptom or complaint of the mouth, tongue or lip \| Mouth swelling \| mouth oedema \| swollen mouth \| Lip swelling [DA01.1Y] Other specified noninfectious erosive or ulcerative disorders of oral mucosa Also known as: Other specified noninfectious erosive or ulcerative disorders of oral mucosa \| Oral ulceration due to immunobullous disease \| Oral mucosal involvement by immunobullous disorder classified elsewhere \| Oral ulceration due to physical injury \| Mechanical oral ulceration === GRAPH WALKS === --- Walk 1 --- [3C0Z] Diseases of the blood or blood-forming organs, unspecified --PARENT--> [03] Diseases of the blood or blood-forming organs Def: This chapter includes diseases of the blood as well as diseases of blood forming organs.... --EXCLUDES--> [?] Certain conditions originating in the perinatal period Def: This chapter includes conditions that have their origin in the perinatal period even though death or morbidity occurs later.... --- Walk 2 --- [3C0Z] Diseases of the blood or blood-forming organs, unspecified --PARENT--> [03] Diseases of the blood or blood-forming organs Def: This chapter includes diseases of the blood as well as diseases of blood forming organs.... --RELATED_TO--> [?] Symptoms, signs or clinical findings of blood, blood-forming organs, or the immune system --- Walk 3 --- [MF50.4Z] Haematuria, unspecified --PARENT--> [MF50.4] Haematuria Def: Hematuria means presence of blood or red blood cells (RBCs) in the urine. There are two types of hematuria: gross hematuria (when one can see the blood in the urine) and microscopic hematuria (when th... --CHILD--> [MF50.4Z] Haematuria, unspecified --- Walk 4 --- [MF50.4Z] Haematuria, unspecified --PARENT--> [MF50.4] Haematuria Def: Hematuria means presence of blood or red blood cells (RBCs) in the urine. There are two types of hematuria: gross hematuria (when one can see the blood in the urine) and microscopic hematuria (when th... --CHILD--> [MF50.40] Macroscopic haematuria --- Walk 5 --- [MA12.1] Finding of cocaine in blood --PARENT--> [MA12] Clinical findings of drugs, medicaments and biological substances in blood, blood-forming organs, or the immune system --PARENT--> [?] Clinical findings in blood, blood-forming organs, or the immune system --- Walk 6 --- [MA12.1] Finding of cocaine in blood --PARENT--> [MA12] Clinical findings of drugs, medicaments and biological substances in blood, blood-forming organs, or the immune system --PARENT--> [?] Clinical findings in blood, blood-forming organs, or the immune system	[ "[3C0Z] Diseases of the blood or blood-forming organs, unspecified\n --PARENT--> [03] Diseases of the blood or blood-forming organs\n Def: This chapter includes diseases of the blood as well as diseases of blood forming organs....\n --EXCLUDES--> [?] Certain conditions originating in the perinatal period\n Def: This chapter includes conditions that have their origin in the perinatal period even though death or morbidity occurs later....", "[3C0Z] Diseases of the blood or blood-forming organs, unspecified\n --PARENT--> [03] Diseases of the blood or blood-forming organs\n Def: This chapter includes diseases of the blood as well as diseases of blood forming organs....\n --RELATED_TO--> [?] Symptoms, signs or clinical findings of blood, blood-forming organs, or the immune system", "[MF50.4Z] Haematuria, unspecified\n --PARENT--> [MF50.4] Haematuria\n Def: Hematuria means presence of blood or red blood cells (RBCs) in the urine. There are two types of hematuria: gross hematuria (when one can see the blood in the urine) and microscopic hematuria (when th...\n --CHILD--> [MF50.4Z] Haematuria, unspecified", "[MF50.4Z] Haematuria, unspecified\n --PARENT--> [MF50.4] Haematuria\n Def: Hematuria means presence of blood or red blood cells (RBCs) in the urine. There are two types of hematuria: gross hematuria (when one can see the blood in the urine) and microscopic hematuria (when th...\n --CHILD--> [MF50.40] Macroscopic haematuria", "[MA12.1] Finding of cocaine in blood\n --PARENT--> [MA12] Clinical findings of drugs, medicaments and biological substances in blood, blood-forming organs, or the immune system\n --PARENT--> [?] Clinical findings in blood, blood-forming organs, or the immune system", "[MA12.1] Finding of cocaine in blood\n --PARENT--> [MA12] Clinical findings of drugs, medicaments and biological substances in blood, blood-forming organs, or the immune system\n --PARENT--> [?] Clinical findings in blood, blood-forming organs, or the immune system" ]	3C0Z	Diseases of the blood or blood-forming organs, unspecified	[ { "from_icd11": "3C0Z", "icd10_code": "D75A", "icd10_title": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency without anemia" }, { "from_icd11": "3C0Z", "icd10_code": "D7581", "icd10_title": "Myelofibrosis" }, { "from_icd11": "3C0Z", "icd10_code": "D7582", "icd10_title": "Heparin induced thrombocytopenia (HIT)" }, { "from_icd11": "3C0Z", "icd10_code": "D7589", "icd10_title": "Other specified diseases of blood and blood-forming organs" }, { "from_icd11": "3C0Z", "icd10_code": "D759", "icd10_title": "Disease of blood and blood-forming organs, unspecified" }, { "from_icd11": "3C0Z", "icd10_code": "D763", "icd10_title": "Other histiocytosis syndromes" }, { "from_icd11": "3C0Z", "icd10_code": "Q899", "icd10_title": "Congenital malformation, unspecified" }, { "from_icd11": "3C0Z", "icd10_code": "III", "icd10_title": "" }, { "from_icd11": "3C0Z", "icd10_code": "D70-D77", "icd10_title": "" }, { "from_icd11": "3C0Z", "icd10_code": "D75", "icd10_title": "Other and unspecified diseases of blood and blood-forming organs" }, { "from_icd11": "3C0Z", "icd10_code": "D77", "icd10_title": "Other disorders of blood and blood-forming organs in diseases classified elsewhere" }, { "from_icd11": "3C0Z", "icd10_code": "D758", "icd10_title": "Other specified diseases of blood and blood-forming organs" }, { "from_icd11": "3C0Z", "icd10_code": "D76", "icd10_title": "Other specified diseases with participation of lymphoreticular and reticulohistiocytic tissue" }, { "from_icd11": "MF50.4Z", "icd10_code": "R310", "icd10_title": "Gross hematuria" }, { "from_icd11": "MF50.4Z", "icd10_code": "R312", "icd10_title": "Other microscopic hematuria" } ]	D75A	Glucose-6-phosphate dehydrogenase (G6PD) deficiency without anemia
Of the total cohort, eleven (55%) patients were under anticoagulant medication (Table 2 ). One patient was under anticoagulant medication and had undergone a lumbar puncture before MR imaging for diagnosis was conducted. However, the patient was already admitted to the hospital with symptoms attributed to the spinal bleeding. Conclusively, the lumbar puncture was part of the diagnostic assessments and was not seen as cause of the hemorrhage. We present four representative cases with spinal hematoma Table 2 Etiology of spinal hematomas Etiology N (%) Anticoagulant medication 11 (55) Type of anticoagulant Coumarin 3 (27) NOAC 3 (27) Aspirin 2 (18) Clopidogrel 1 (9) Coumarin + Aspirin 1 (9) NOAC + Aspirin 1 (9) Vascular anomality 5 (25) Type of vascular anomality AVM 3 (27) Cavernoma 1 (9) Hemangioblastoma 1 (9) Idiopathic 4 (20) Fig. 3 Case 1: 39-year-old man with spontaneous spinal subdural hematoma. A 39-year-old male patient presented to the emergency department ten days after a COVID infection, reporting symptoms such as fever, fatigue, and back pain persisting for one week. The patient had experienced intermittent episodes of back pain, self-treated with aspirin as needed before seeking medical attention. Subsequently, the patient developed a severe headache and meningism. There was no history of trauma, coagulation disorder, or other pre-existing diseases. Coagulation and infection parameters in the laboratory results were observed to be within typical ranges. Neurological examination revealed, except for meningism, no further neurological deficits. Gadolinium-enhanced MRI and MR angiography (MRA) identified the presence of subdural hematoma along the cervical and thoracic spine, initially without a clearly identified structural source of bleeding ( A ). Additional spinal DSA was conducted, revealing a small suspicious lesion situated within the left lateral spinal canal at the T3/4 level ( B + D ). Surgical intervention, specifically a hemilaminectomy at T3 and T4 on the left side, was conducted. No definite vascular malformation was found except for pathologically coagulated veins. Postoperatively, the patient presented with hemihypesthesia below T6 on the left side, proximal paresis of the left leg (MRC 3/5), and bladder/bowel dysfunction. A subsequent gadolinium-enhanced MRI revealed residual pathological hypervascularization at T3/4 on the left ( C ). A re-operation with an extended approach was performed as follows: The midline skin incision was reopened, and the left L3 hemilaminectomy was extended cranially. The dura was reopened, and a likely thrombosed hemangioblastoma with associated vessels was exposed and excised. Motor-evoked potentials remained stable throughout the procedure. Following the second surgery, the patient manifested without further neurological deficits as previously described. Postoperative digital subtraction angiography revealed no residual vascular irregularities and histopathologic examination identified the lesion as vascular malformation. He was transferred to a rehabilitation center on postoperative day (POD) 2 Fig. 4 Case 2: 61-year-old woman with spontaneous spinal epi- and subdural hematoma. A 61-year-old female patient was referred from a community hospital with symptoms of generalized pain, primarily localized in the upper abdomen, and paraparesis (MRC 3/5) without sensory deficits. Laboratory findings indicated the absence of anomalies in coagulation parameters, with a slight increase observed in infection markers. Furthermore, cardiac parameters were elevated, including cardiac troponin, creatine kinase, and its cardiac isoform (CK-MB). Despite the elevation, myocardial infarction was excluded, and the increased levels were attributed to mild cardiac decompensation. Gadolinium-enhanced spinal MRI disclosed a hemorrhage classified as epidural extending from T6 to L2 without a clearly identified structural source ( A + B ). Emergency evacuation of the epidural hematoma was performed through left-sided interlaminar fenestrations at T4, 6, 8, and 10, along with hemilaminectomy at L2. Postoperatively, there was no improvement in neurological function, but pain intensity decreased. Subsequent MRA revealed discrete contrast enhancement at the T9/10 level on the left lateral intraspinal region ( C + D ). Additional DSA confirmed a suspicious structure on the left side at the T9/10 level ( E + F ). The patient underwent a second surgery: The midline skin incision was reopened. Hemilaminectomy of T9 and T10 on the left-hand side was performed with undercutting to the opposite side. A recurrent hematoma was completely removed from the epidural space. The dura was opened and an additional intradural hematoma was evacuated. A vascular anomaly arising from the segmental artery was identified, resulting in elongation of the perimedullary vessel. The vessel was carefully coagulated, transected, and sent for histopathological examination. Motor-evoked potentials were not obtainable from the beginning of the surgery. Following the second surgery, paralysis of the left leg was observed, while the paresis of the right leg resolved. Gadolinium-enhanced MRA and DSA conducted after surgery verified the complete elimination of the AVM. Histopathologic examination confirmed the presence of an AVM. At discharge to a rehabilitation facility, there was a modest improvement in the motor impairment of the left leg, characterized by subtle movements of the foot but no motor function in the proximal leg Fig. 5 Case 3: 59-year-old woman with spontaneous spinal subarachnoid hemorrhage. A 59-year-old female patient with sudden-onset severe headache and intense neck pain, indicative of suspected subarachnoid hemorrhage (SAH), was referred to our department. Neurological examination showed, except for meningism, no further neurological deficits. Cranial Computed Tomography (CT) with angiography and cranial gadolinium-enhanced MRI were conducted to exclude SAH. Subsequent spinal MRA revealed spinal subarachnoid hemorrhage along T3-8 with contiguous myelomalacia and minor hemorrhages distributed at levels S3-5, initially without a clearly identified source of bleeding ( A ). The patient was not under anticoagulant medication and had no history of coagulation disorder or trauma. Laboratory findings revealed no abnormalities nor indications of infection. Spinal DSA revealed the presence of a small, arterialized vessel entering the intraspinal region on the right side at the level of T8 ( B ). First, laminoplasty on T3-6 (where the punctum maximum of the hematoma was) and evacuation of the hemorrhage were performed. However, no obvious vascular malformation was identified. Immediately postoperatively, the patient exhibited only mild right-sided proximal leg weakness (MRC 4/5). However, overnight, this deteriorated to paralysis. Postoperative MRA ruled out re-bleeding, but additional DSA revealed a suspicious vascular lesion at the T3 level. Another spinal MRA disclosed the presence of a nodular lesion, consistent with DSA findings, within the dorsal median extramedullary space at the T3 level ( C ). Subsequently, the patient underwent reoperation, extending the approach: The previous skin incision was reopened. Laminoplasty was extended cranially by one level (T2). The dura was opened, and small pathological vessels along the right T2 and T3 nerve roots were identified, resected, and submitted for histological examination. Motor-evoked potentials remained stable on the left side but were absent on the right. The histopathological assessment of intraoperatively obtained samples corroborated the diagnosis of an AVM. Following the second surgery, although the right leg paralysis persisted, there was noticeable motor deterioration in the left leg (MRC 2/5). Additional symptoms encompassed sensory deficits below T5 and bladder dysfunction. Gadolinium-enhanced MRI effectively ruled out rebleeding but revealed an extended thoracic myelomalacia ( D ). Subsequent DSA did not find any other vascular abnormalities. The motor function of the left leg gradually improved, reaching a proximal MRC of 4/5 and a distal MRC of 5/5 over time. Hypesthesia below the T5 level and bladder dysfunction endured, along with persistent paralysis in the right leg. The patient was referred to a rehabilitation facility Fig. 6 Case 4: 66-year-old man with spontaneous epidural hematoma. A 66-year-old male presented to the outpatient clinic for clinical and imaging follow-up. One month earlier, he had consulted the emergency department, experiencing pain between the shoulder blades. MRI revealed a spontaneous epidural hematoma from C2 to T3 ( A + C ), which was treated conservatively. At follow-up, the patient reported a complete resolution of his pain. A subsequent MRI showed a contrast-enhancing lesion at the T9 level on the right side ( B + D ). Upon discussion of the case in our neuro-oncology tumor conference, a resection of the lesion was recommended due to suspicion of a tumor. A preoperative DSA was not performed. The patient had no neurological deficits, and laboratory results were normal. Elective microsurgical excision of the extradural lesion was performed without any postoperative complications. The patient exhibited no sensorimotor symptoms. Histopathological examination confirmed the lesion as a hemangioma. The patient was discharged on the second postoperative day	4.074219	0.833008	sec[2]/sec[1]/p[0]	en	0.999998	39196426	https://doi.org/10.1007/s00701-024-06240-6	[ "spinal", "hematoma", "vascular", "lesion", "side", "pain", "neurological", "motor", "hemorrhage", "deficits" ]	[ { "code": "FB1Z", "title": "Conditions associated with the spine, unspecified" }, { "code": "FA7Z", "title": "Structural disorders of spine, unspecified" }, { "code": "FA9Z", "title": "Inflammation of spine, unspecified" }, { "code": "LB73.2Z", "title": "Structural developmental anomalies of spine, unspecified" }, { "code": "FA82", "title": "Spinal stenosis" }, { "code": "ND30", "title": "Superficial injuries involving multiple body regions" }, { "code": "ND56.0", "title": "Superficial injury of unspecified body region" }, { "code": "GA34.Y", "title": "Other specified female pelvic pain associated with genital organs or menstrual cycle" }, { "code": "NB32.3Y", "title": "Other injury of lung" }, { "code": "ND56.5", "title": "Injury of blood vessel of unspecified body region" } ]	=== ICD-11 CODES FOUND === [FB1Z] Conditions associated with the spine, unspecified Also known as: Conditions associated with the spine, unspecified \| dorsopathies \| disorder of spine \| spinal disorder [FA7Z] Structural disorders of spine, unspecified Also known as: Structural disorders of spine, unspecified \| spinal disease [FA9Z] Inflammation of spine, unspecified Also known as: Inflammation of spine, unspecified \| spinal inflammation \| discitis, unspecified [LB73.2Z] Structural developmental anomalies of spine, unspecified Also known as: Structural developmental anomalies of spine, unspecified \| Structural developmental anomalies of spine \| Malformations of spine \| maldevelopment of spine [FA82] Spinal stenosis Definition: This is a condition characterised by narrowing of the spinal canal. Also known as: Spinal stenosis \| spinal canal stenosis \| Spinal stenosis with no determinant \| primary spinal stenosis \| Spinal stenosis with determinant [ND30] Superficial injuries involving multiple body regions Also known as: Superficial injuries involving multiple body regions \| Superficial injuries involving head with neck \| multiple superficial injuries of head with neck \| Superficial injuries of sites classifiable as injuries to the head and injuries to the neck \| Superficial injuries involving thorax with abdomen, lower back or pelvis [ND56.0] Superficial injury of unspecified body region Also known as: Superficial injury of unspecified body region \| superficial injury of limb NOS \| Superficial injury NOS \| scratch NOS \| Cutaneous wounds, injuries or scars Excludes: multiple superficial injuries NOS [GA34.Y] Other specified female pelvic pain associated with genital organs or menstrual cycle Also known as: Other specified female pelvic pain associated with genital organs or menstrual cycle \| Pelvic congestion syndrome \| Pelvic varicosities \| Female frozen pelvis \| Female intrapelvic haemorrhage [NB32.3Y] Other injury of lung Also known as: Other injury of lung \| Haematoma of lung \| Traumatic hydropneumothorax \| Acute traumatic lung congestion \| Rupture of lung [ND56.5] Injury of blood vessel of unspecified body region Also known as: Injury of blood vessel of unspecified body region \| Injury of blood vessel(s) NOS \| blood vessel wound \| blood vessel trauma \| Avulsion of blood vessel Excludes: multiple injuries of blood vessels NOS === GRAPH WALKS === --- Walk 1 --- [FB1Z] Conditions associated with the spine, unspecified --PARENT--> [?] Conditions associated with the spine Def: This is a group of conditions in which there is a deviation from or interruption of the normal structure or function of the spine.... --CHILD--> [?] Inflammation of spine --- Walk 2 --- [FB1Z] Conditions associated with the spine, unspecified --PARENT--> [?] Conditions associated with the spine Def: This is a group of conditions in which there is a deviation from or interruption of the normal structure or function of the spine.... --CHILD--> [?] Structural disorders of spine --- Walk 3 --- [FA7Z] Structural disorders of spine, unspecified --PARENT--> [?] Structural disorders of spine --PARENT--> [?] Conditions associated with the spine Def: This is a group of conditions in which there is a deviation from or interruption of the normal structure or function of the spine.... --- Walk 4 --- [FA7Z] Structural disorders of spine, unspecified --PARENT--> [?] Structural disorders of spine --CHILD--> [FA72] Disorders of vertebra Def: Changes in the structure of the spine causing damage to vertebrae and surrounding tissue secondary to infection, injury, tumours, infections, bone changes that come with age etc. Spinal diseases often... --- Walk 5 --- [FA9Z] Inflammation of spine, unspecified --PARENT--> [?] Inflammation of spine --CHILD--> [FA91] Infection of intervertebral disc Def: A condition of the intervertebral discs, caused by an infection with a bacterial, viral, fungal, or parasitic source. This condition commonly presents with fever, chills, headache, stiffness of the ne... --- Walk 6 --- [FA9Z] Inflammation of spine, unspecified --PARENT--> [?] Inflammation of spine --CHILD--> [FA91] Infection of intervertebral disc Def: A condition of the intervertebral discs, caused by an infection with a bacterial, viral, fungal, or parasitic source. This condition commonly presents with fever, chills, headache, stiffness of the ne...	[ "[FB1Z] Conditions associated with the spine, unspecified\n --PARENT--> [?] Conditions associated with the spine\n Def: This is a group of conditions in which there is a deviation from or interruption of the normal structure or function of the spine....\n --CHILD--> [?] Inflammation of spine", "[FB1Z] Conditions associated with the spine, unspecified\n --PARENT--> [?] Conditions associated with the spine\n Def: This is a group of conditions in which there is a deviation from or interruption of the normal structure or function of the spine....\n --CHILD--> [?] Structural disorders of spine", "[FA7Z] Structural disorders of spine, unspecified\n --PARENT--> [?] Structural disorders of spine\n --PARENT--> [?] Conditions associated with the spine\n Def: This is a group of conditions in which there is a deviation from or interruption of the normal structure or function of the spine....", "[FA7Z] Structural disorders of spine, unspecified\n --PARENT--> [?] Structural disorders of spine\n --CHILD--> [FA72] Disorders of vertebra\n Def: Changes in the structure of the spine causing damage to vertebrae and surrounding tissue secondary to infection, injury, tumours, infections, bone changes that come with age etc. Spinal diseases often...", "[FA9Z] Inflammation of spine, unspecified\n --PARENT--> [?] Inflammation of spine\n --CHILD--> [FA91] Infection of intervertebral disc\n Def: A condition of the intervertebral discs, caused by an infection with a bacterial, viral, fungal, or parasitic source. This condition commonly presents with fever, chills, headache, stiffness of the ne...", "[FA9Z] Inflammation of spine, unspecified\n --PARENT--> [?] Inflammation of spine\n --CHILD--> [FA91] Infection of intervertebral disc\n Def: A condition of the intervertebral discs, caused by an infection with a bacterial, viral, fungal, or parasitic source. This condition commonly presents with fever, chills, headache, stiffness of the ne..." ]	FB1Z	Conditions associated with the spine, unspecified	[ { "from_icd11": "FB1Z", "icd10_code": "M435X2", "icd10_title": "Other recurrent vertebral dislocation, cervical region" }, { "from_icd11": "FB1Z", "icd10_code": "M438X4", "icd10_title": "Other specified deforming dorsopathies, thoracic region" }, { "from_icd11": "FB1Z", "icd10_code": "M4324", "icd10_title": "Fusion of spine, thoracic region" }, { "from_icd11": "FB1Z", "icd10_code": "M4325", "icd10_title": "Fusion of spine, thoracolumbar region" }, { "from_icd11": "FB1Z", "icd10_code": "M438X6", "icd10_title": "Other specified deforming dorsopathies, lumbar region" }, { "from_icd11": "FB1Z", "icd10_code": "M4320", "icd10_title": "Fusion of spine, site unspecified" }, { "from_icd11": "FB1Z", "icd10_code": "M438X7", "icd10_title": "Other specified deforming dorsopathies, lumbosacral region" }, { "from_icd11": "FB1Z", "icd10_code": "M438X5", "icd10_title": "Other specified deforming dorsopathies, thoracolumbar region" }, { "from_icd11": "FB1Z", "icd10_code": "M4326", "icd10_title": "Fusion of spine, lumbar region" }, { "from_icd11": "FB1Z", "icd10_code": "M438X2", "icd10_title": "Other specified deforming dorsopathies, cervical region" }, { "from_icd11": "FB1Z", "icd10_code": "M4327", "icd10_title": "Fusion of spine, lumbosacral region" }, { "from_icd11": "FB1Z", "icd10_code": "M4322", "icd10_title": "Fusion of spine, cervical region" }, { "from_icd11": "FB1Z", "icd10_code": "M4321", "icd10_title": "Fusion of spine, occipito-atlanto-axial region" }, { "from_icd11": "FB1Z", "icd10_code": "M438X9", "icd10_title": "Other specified deforming dorsopathies, site unspecified" }, { "from_icd11": "FB1Z", "icd10_code": "M4328", "icd10_title": "Fusion of spine, sacral and sacrococcygeal region" } ]	M435X2	Other recurrent vertebral dislocation, cervical region
The patient was a 40-year-old woman. She has no family history of endocrine disease, including hyperparathyroidism, pituitary adenoma and pancreatic gastrointestinal endocrine tumors. She was married at age 31, started fertility treatment at age 35 and became pregnant at age 39 by in vitro fertilization. During the 3 rd month of pregnancy, she had difficulty consuming meals due to hyperemesis gravidarum; she was treated in the emergency room of her nearby hospital after she was found unconscious at home. Upon arrival at the hospital, her plasma glucose level was 36 mg/dL. Because her symptoms disappeared soon after an intravenous glucose infusion, she was discharged from the emergency room without further investigation of the cause of the hypoglycemic episode. Afterward, she had no hypoglycemic coma, abnormalities of plasma glucose or significant body weight gain in regular checkups during the pregnancy. No abnormalities were noted in the 75-g oral glucose tolerance test performed at week 33 of pregnancy (Plasma glucose levels: 0 min, 60 mg/dL, 60 min, 100 mg/dL and 120 min, 138 mg/dL). Because the baby was in breech position near the due date, she underwent caesarean section at week 38 of pregnancy and gave birth to a healthy child with body weight of 2,595 g. She had no complications associated with the caesarean section; she began eating meals 2 days after the operation. However, she was found unconscious in her home early in the morning 3 days after the operation. Her point-of-care blood glucose level was 16 mg/dL; her symptoms disappeared soon after an intravenous glucose infusion. She was then referred to an endocrinologist in the same hospital, who undertook further investigation of the hypoglycemic episode. isCGM revealed frequent nocturnal hypoglycemic episodes. She was negative for insulin autoantibodies and her cortisol level in the early morning was 38.2 μg/dL (normal range, 4.5–21.1 μg/dL), which excluded the possibilities of insulin autoimmune syndrome and adrenal insufficiency as the cause. She was then hospitalized and subjected to a 72-h fasting test. The test was stopped 7 h after beginning because of her low plasma glucose level (30 mg/dL). Despite the low plasma glucose, her insulin (7.30 μU/mL: normal range, < 18.7 μU/mL) and C-peptide (1.97 ng/mL: normal range, 0.61–2.09 ng/mL) levels were inappropriately high, and the blood glucose level was increased to 109 mg /dL at 20 min after an intravenous glucagon infusion, all of which findings are consistent with insulinoma. However, CE-CT and EUS failed to detect responsible lesions in the pancreas. Consequently, she started receiving diazoxide 50 mg t.i.d. orally, which reduced the frequency of the hypoglycemic episodes, but she had difficulty with the drug due to the development of lower leg edema. She was therefore referred to our institution for further evaluation and treatment. Upon admission, her BMI was 25.4 kg/m 2 (height 153.2 cm; body weight 59.5 kg). She had no family history of diabetes or other endocrine disorders. Her serum insulin level (6.34 μU/mL) was relatively high compared to her plasma glucose level (67 mg/dL) (Table 1 ). No tumor was found in the pancreas by CE-CT, gadolinium enhanced magnetic-resonance imaging (Gd-MRI) or somatostatin receptor scintigraphy . Thereafter, (SACST) in conjunction with computer tomography angiography, which visualizes the arteries feeding the pancreas, was performed to localize the responsible lesion after 3-day discontinuation of diazoxide. A significant increase in insulin level was observed, especially in the gastroduodenal and proximal splenic arteries, indicating localization of an insulin-secreting tumor in the pancreatic body and tail . EUS was then performed on the pancreatic body and tail, revealing a 7-mm low-echoic mass in the pancreatic body . Histological analysis of a specimen aspirated from the mass found it to be an insulin-secreting neuroendocrine tumor . An open spleen-preserving distal pancreatectomy was then performed under intraoperative ultrasound guidance. The operating time was 4 h and 15 min, and the blood loss was 155 ml. Intraoperative insulin measurements showed a rapid decline in serum insulin levels after the resection, indicating successful removal of the tumor . The insulin-secreting tumor was 10-mm in diameter and consisted microscopically of atypical cells positive for chromogranin A, synaptophysin and insulin but negative for glucagon and somatostatin. Both the mitotic and Ki-67 indices were low, and the tumor was classified as NET, G1, according to the WHO 2019 criteria . There were periods of fasting and administration of antibiotics due to abdominal pain and effusion in the pancreatic stump, and she was discharged on the 22 nd post operative day. After the operation, the patient showed no further symptoms of hypoglycemia. Table 1 Biochemistry and complete blood count upon hospitalization in our institution Biochemistry Blood count coagulation T-Bil 0.5 mg/dL HbA1c 4.7% WBC 3190 /μL TP 6.0 g/dL GLU 67 mg/dL RBC 388 × 10 4 /μL ALB 3.6 g/dL TG 67 mg/dL Hb 11.0 g/dL CK 52 U/L HDL-C 72 mg/dL Hct 33.2% AST 14 U/L LDL-C 98 mg/dL PLT 14.9 × 10 4 /μL ALT 9 U/L Endocrine APTT 30.3秒 γ-GTP 8 U/L TSH 2.46 mIU/mL PT > 120% Cre 0.57 mg/dL FT3 2.77 pg/mL PT-INR 0.88 UA 4.9 mg/dL FT4 1.03 ng/dL Urinalysis BUN 16.1 mg/dL ACTH 12.0 pg/mL Specific gravity 1.022 Na 141 mEq/L Cortisol 5.2 μg/dL pH 7.0 K 3.7 mEq/L Insulin 6.34μIU/mL Protein ( ±) Cl 109 mEq/L Autoantibodies Glucose (-) Ca 8.1 mEq/L Anti-insulin Ab < 0.4 U/mL Ketone body (-) IP 2.8 mg/dL Blood (-) ALP Alkaline phosphatase, AST Aspartate aminotransferase, ALT Alanine aminotransferase, Hb Hemoglobin, Ht Hematocrit, γGTP γ-glutamyltransferase, LDH Lactate dehydrogenase, RBC Red blood cells, TP Toral protein, WBC White blood cells, ALB Albumin, T-Bil Total bilirubin, HDL-C HDL-cholesterol, LDL-C LDL-cholesterol, TSH thyroid-stimulating hormone, FT3 free triiodothyronine, FT4 Free thyroxine, ACTH Adenocorticotropic hormone, Anti-insulin Ab Anti-insulin antibody Fig. 1 Imaging analyses of the pancreas of the case. A Contrast-enhanced computer tomography. B Gadolinium-enhanced magnetic resonance imaging. C Somatostatin receptor scintigraphy Fig. 2 Selective arterial calcium stimulation test in the case. A Selective arterial calcium stimulation test (SACST) was performed after confirming vascular supply of the pancreas by computer tomography angiography. Insulin levels are plotted before and after injection of calcium gluconate into indicated arteries. As she experienced hypoglycemia (plasma glucose level 30 mg/dL or less) during SACST, 50% glucose solution was given intravenously before injection of calcium gluconate into the arteries denoted by asterisks (i.e., the superior mesenteric artery and the distal splenic artery). B Fold changes in insulin levels before and 60 s after injection of calcium gluconate (Insulin 60 s/Insulin 0 s) are shown for each indicated artery. Note that fold changes for the superior mesenteric artery and the distal splenic artery are relatively low, presumably because insulin levels before the injection of calcium gluconate were relatively high and the patient had experienced hypoglycemia and received intravenous injection of 50% glucose solution. C Computer tomography angiography visualization of the vascular supply of the pancreas. Note that injection of contrast medium into the hepatic artery proper and the superior mesenteric artery did not result in significant contrast effects in the pancreas. D Schematics of the vascular supply in the pancreas. Note that the gastroduodenal artery feeds a relatively large area of the pancreas (head and body) Fig. 3 Endoscopic ultrasound and histological analyses of specimen aspirated from the pancreatic tumor. A Endoscopic ultrasound image of a 7 mm-hypoechoic tumor of the pancreatic body. B Histological findings of specimen aspirated from the pancreatic tumor. Sections of the aspirated specimen were stained by hematoxylin and eosin as well as by chromogranin A, synaptophysin, insulin and Ki67 (Magnification × 400). Tumor cells were positive for chromogranin A and synaptophysin, which is typical of neuroendocrine tumors. The proliferation index, assessed by Ki67 immunostaining, was < 2.0%. Tumor cells were positive for insulin but not for glucagon, gastrin, or somatostatin (data not shown) Fig. 4 Change of insulin levels before and after resection of the pancreatic tumor. Insulin levels are plotted before and after resection of the pancreatic tumor. Intraoperative ultrasound examination was performed to confirm the localization of a 7 mm-sized hard and palpable tumor in the tail of the pancreas near the body of the pancreas. After removal of the tumor, insulin levels were drastically declined Fig. 5 Histological analyses of the resected pancreatic tumor. A Macroscopic image of the resected tumor (Arrow, 10 × 8 mm, well-defined yellowish mass). B Histological findings of the resected pancreatic tumor. Sections of the tumor were stained by hematoxylin and eosin (H&E) as well as chromogranin A, synaptophysin, insulin and Ki67 (Magnification × 400). Tumor cells were positive for chromogranin A, synaptophysin and insulin, and the proliferation index, assessed by Ki67 immunostaining, was < 2.0% . Tumor cells were negative for glucagon, gastrin, and somatostatin (data not shown)	3.998047	0.978027	sec[1]/p[0]	en	0.999996	37563593	https://doi.org/10.1186/s12902-023-01415-1	[ "insulin", "tumor", "glucose", "pancreatic", "pancreas", "body", "blood", "artery", "plasma", "cells" ]	[ { "code": "5A44", "title": "Insulin-resistance syndromes" }, { "code": "5A4Y", "title": "Other specified disorders of glucose regulation or pancreatic internal secretion" }, { "code": "QB51.5", "title": "Presence of endocrine implants" }, { "code": "EF02.0", "title": "Fat hypertrophy" }, { "code": "PK9C.2", "title": "Other or unspecified medical devices associated with injury or harm, prosthetic or other implants, materials or accessory devices" }, { "code": "2F9Z", "title": "Neoplasms of unknown behaviour of unspecified site" }, { "code": "ME61", "title": "Subcutaneous swelling, mass or lump of uncertain or unspecified nature" }, { "code": "2E6Z", "title": "Carcinoma in situ of unspecified site" }, { "code": "2F91.1", "title": "Neoplasms of unknown behaviour of trachea, bronchus or lung" }, { "code": "2F92", "title": "Neoplasms of unknown behaviour of skin" } ]	=== ICD-11 CODES FOUND === [5A44] Insulin-resistance syndromes Also known as: Insulin-resistance syndromes \| Insulin-resistance syndrome type A \| Insulin-resistance syndrome type B \| Rabson-Mendenhall syndrome \| Laminopathy type Decaudain-Vigouroux [5A4Y] Other specified disorders of glucose regulation or pancreatic internal secretion Also known as: Other specified disorders of glucose regulation or pancreatic internal secretion \| Other hypoglycaemia \| Hyperinsulinaemia \| hyperinsulinism \| functional hyperinsulinaemia [QB51.5] Presence of endocrine implants Also known as: Presence of endocrine implants \| presence of insulin pump Includes: presence of insulin pump [EF02.0] Fat hypertrophy Definition: Focal hypertrophy of subcutaneous adipose tissue. It is a common sequela of long-term insulin injection into the skin. Also known as: Fat hypertrophy \| Insulin-induced localised fat hypertrophy \| Insulin-induced lipohypertrophy [PK9C.2] Other or unspecified medical devices associated with injury or harm, prosthetic or other implants, materials or accessory devices Also known as: Other or unspecified medical devices associated with injury or harm, prosthetic or other implants, materials or accessory devices \| Surgical operation with implant of other or unspecified artificial internal device associated with abnormal reaction of the patient, or of later complication, without mention of misadventure at the time of the procedure \| Mechanical complication of other specified internal prosthetic devices, implants and grafts \| Mechanical complication of insulin pump Excludes: Circumstances associated with a surgical or other medical device influencing the episode of care without injury or harm [2F9Z] Neoplasms of unknown behaviour of unspecified site Also known as: Neoplasms of unknown behaviour of unspecified site \| neoplasia \| neoplasm growth NOS \| tumour of unspecified site \| tumourlet of unspecified site [ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature Definition: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature Also known as: Subcutaneous swelling, mass or lump of uncertain or unspecified nature \| localised swelling, mass or lump of skin and subcutaneous tissue \| localised subcutaneous nodules \| subcutaneous nodules \| superficial subcutaneous nodules Excludes: localized adiposity \| mass and lump: breast \| enlarged lymph nodes [2E6Z] Carcinoma in situ of unspecified site Also known as: Carcinoma in situ of unspecified site \| carcinoma in situ of unspecified site \| carcinoma in situ NOS \| carcinoma in situ \| in situ neoplasm [2F91.1] Neoplasms of unknown behaviour of trachea, bronchus or lung Also known as: Neoplasms of unknown behaviour of trachea, bronchus or lung \| trachea, bronchus or lung tumour NOS \| Intravascular bronchial alveolar tumour of unspecified site \| Bronchial adenoma of unknown behaviour of unspecified site \| Intravascular bronchial alveolar tumour unknown behaviour of unspecified site [2F92] Neoplasms of unknown behaviour of skin Also known as: Neoplasms of unknown behaviour of skin \| skin tumour NOS === GRAPH WALKS === --- Walk 1 --- [5A44] Insulin-resistance syndromes --PARENT--> [?] Other disorders of glucose regulation or pancreatic internal secretion --EXCLUDES--> [?] Benign neoplasm of endocrine pancreas --- Walk 2 --- [5A44] Insulin-resistance syndromes --PARENT--> [?] Other disorders of glucose regulation or pancreatic internal secretion --EXCLUDES--> [?] Malignant neoplasm of pancreas Def: A primary malignant tumour of the pancreas. Most are adenocarcinomas.... --- Walk 3 --- [5A4Y] Other specified disorders of glucose regulation or pancreatic internal secretion --PARENT--> [?] Other disorders of glucose regulation or pancreatic internal secretion --CHILD--> [5A42] Increased secretion of glucagon --- Walk 4 --- [5A4Y] Other specified disorders of glucose regulation or pancreatic internal secretion --PARENT--> [?] Other disorders of glucose regulation or pancreatic internal secretion --CHILD--> [5A41] Hypoglycaemia without associated diabetes --- Walk 5 --- [QB51.5] Presence of endocrine implants --PARENT--> [QB51] Presence of devices other than cardiac or vascular implants --PARENT--> [?] Presence of device, implants or grafts --- Walk 6 --- [QB51.5] Presence of endocrine implants --PARENT--> [QB51] Presence of devices other than cardiac or vascular implants --CHILD--> [QB51.0] Presence of a neurostimulator	[ "[5A44] Insulin-resistance syndromes\n --PARENT--> [?] Other disorders of glucose regulation or pancreatic internal secretion\n --EXCLUDES--> [?] Benign neoplasm of endocrine pancreas", "[5A44] Insulin-resistance syndromes\n --PARENT--> [?] Other disorders of glucose regulation or pancreatic internal secretion\n --EXCLUDES--> [?] Malignant neoplasm of pancreas\n Def: A primary malignant tumour of the pancreas. Most are adenocarcinomas....", "[5A4Y] Other specified disorders of glucose regulation or pancreatic internal secretion\n --PARENT--> [?] Other disorders of glucose regulation or pancreatic internal secretion\n --CHILD--> [5A42] Increased secretion of glucagon", "[5A4Y] Other specified disorders of glucose regulation or pancreatic internal secretion\n --PARENT--> [?] Other disorders of glucose regulation or pancreatic internal secretion\n --CHILD--> [5A41] Hypoglycaemia without associated diabetes", "[QB51.5] Presence of endocrine implants\n --PARENT--> [QB51] Presence of devices other than cardiac or vascular implants\n --PARENT--> [?] Presence of device, implants or grafts", "[QB51.5] Presence of endocrine implants\n --PARENT--> [QB51] Presence of devices other than cardiac or vascular implants\n --CHILD--> [QB51.0] Presence of a neurostimulator" ]	5A44	Insulin-resistance syndromes	[ { "from_icd11": "5A44", "icd10_code": "E10-E14", "icd10_title": "" }, { "from_icd11": "QB51.5", "icd10_code": "Z9641", "icd10_title": "Presence of insulin pump (external) (internal)" }, { "from_icd11": "QB51.5", "icd10_code": "Z964", "icd10_title": "Presence of endocrine implants" }, { "from_icd11": "EF02.0", "icd10_code": "L988", "icd10_title": "Other specified disorders of the skin and subcutaneous tissue" }, { "from_icd11": "EF02.0", "icd10_code": "E881", "icd10_title": "Lipodystrophy, not elsewhere classified" }, { "from_icd11": "PK9C.2", "icd10_code": "T85694A", "icd10_title": "Other mechanical complication of insulin pump, initial encounter" }, { "from_icd11": "PK9C.2", "icd10_code": "T85614A", "icd10_title": "Breakdown (mechanical) of insulin pump, initial encounter" }, { "from_icd11": "PK9C.2", "icd10_code": "T85624A", "icd10_title": "Displacement of insulin pump, initial encounter" }, { "from_icd11": "PK9C.2", "icd10_code": "T85618A", "icd10_title": "Breakdown (mechanical) of other specified internal prosthetic devices, implants and grafts, initial encounter" }, { "from_icd11": "PK9C.2", "icd10_code": "T85628A", "icd10_title": "Displacement of other specified internal prosthetic devices, implants and grafts, initial encounter" }, { "from_icd11": "PK9C.2", "icd10_code": "T85621A", "icd10_title": "Displacement of intraperitoneal dialysis catheter, initial encounter" }, { "from_icd11": "PK9C.2", "icd10_code": "T85611A", "icd10_title": "Breakdown (mechanical) of intraperitoneal dialysis catheter, initial encounter" }, { "from_icd11": "PK9C.2", "icd10_code": "T85698A", "icd10_title": "Other mechanical complication of other specified internal prosthetic devices, implants and grafts, initial encounter" }, { "from_icd11": "PK9C.2", "icd10_code": "T85638A", "icd10_title": "Leakage of other specified internal prosthetic devices, implants and grafts, initial encounter" }, { "from_icd11": "PK9C.2", "icd10_code": "T85610A", "icd10_title": "Breakdown (mechanical) of cranial or spinal infusion catheter, initial encounter" } ]	E10-E14
A 35-year-old man with hypertension experienced weight gain and lower limb weakness for several months. He first visited a neighboring hospital for a thorough examination, where he presented with a Cushingoid appearance that included a moon-face, proximal limb muscles weakness, central obesity, and thinning of the skin. He had no family history associated with multiple endocrine neoplasia type 1. Enhanced computed tomography (CT) revealed a pancreatic tail tumor (55 mm in diameter) and bilateral adrenal enlargement . Elevated plasma ACTH at 791 pg/mL (normal range: 7.2–63.3 pg/mL) and serum cortisol at 121 µg/dL (normal range: 3.7–19.4 µg/dL) were also noted. The patient’s cortisol level was not suppressed by the dexamethasone suppression test, and his ACTH level was not suppressed by either the dexamethasone suppression test or the octreotide test. Biopsy under endoscopic ultrasonography revealed the tumor to be an ACTH-producing pNEN. The patient was then referred to our hospital for further treatment. The patient had pneumocystis pneumonia and was treated with sulfamethoxazole and an adjunctive glucocorticoid (60 mg of prednisone per day), which were gradually tapered and discontinued. Concurrently, his hypercortisolism was controlled with metyrapone and trilostane. In addition to the pancreatic tail tumor, ethoxybenzyl magnetic resonance imaging (MRI) and somatostatin receptor scintigraphy detected two new lesions in the pancreatic head . However, 2-[18F] fluoro-2-deoxy- d -glucose (FDG) positron emission tomography (PET)–CT revealed FDG deposition in the pancreatic tail tumor alone . Contrast-enhanced endoscopic ultrasonography revealed a lesion (55 mm in diameter) in the pancreatic tail and another lesion (5 mm in diameter) without enhancement in the pancreatic head . Taking the possibility of intrapancreatic metastasis or multicentric tumorigenesis into consideration, a total pancreatectomy was planned, pending confirmation of the pancreatic head lesion by an intraoperative ultrasound (IOUS) examination. The IOUS examination confirmed the lesion in the pancreatic head, and a total pancreatectomy combined with splenectomy was performed. The operation time was 592 min and the intraoperative blood loss was 1,327 mL. Central obesity and fragile adipose tissue made surgery difficult. The plasma ACTH and serum cortisol levels normalized the day after the operation (8.5 pg/mL and 6.7 µg/dL, respectively). Cefotiam hydrochloride was administered for 2 days as a prophylactic antibiotic. A high dose of hydrocortisone (225 mg/day) was administered during the perioperative period to prevent an adrenal crisis; it was gradually tapered to physiologic replacement doses. For blood glucose control after the total pancreatectomy, the patient was administered a continuous venous infusion of insulin during fasting and multiple daily insulin injections after the start of meals. Consequently, the blood glucose level was maintained at approximately 200 mg/dL. Because the C-reactive protein level was elevated (21.25 mg/L) on postoperative day (POD) 2, tazobactam and piperacillin hydrate was administered as empirical therapy. However, central venous catheter-associated bacteremia occurred on POD 11; therefore, the patient was secondarily administered with meropenem hydrate and vancomycin hydrochloride . The central venous catheter inserted in the operating room had been removed after the first blood culture was collected. S. hominis was identified in both catheter and blood cultures, and susceptibility testing revealed that the organism was sensitive to the already administered antibiotics (Table 1 ). However, despite the administration of several antibiotics that the bacterium is susceptible to (such as daptomycin, levofloxacin hydrate, or linezolid), S. hominis was repeatedly positive in the blood cultures for more than a month. Intravenous immunoglobulin was also administrated as adjunctive therapy for bacteremia during PODs 30–32 and 42–44. Specialized examinations, including enhanced CT, ultrasound cardiography, and FDG-PET–CT, were performed to investigate the source of the infection. Various bacterial cultures were performed using the bile, urine, and drainage fluid. However, except for the blood, no other apparent source was detected. Eventually, after more than 3 weeks of the combined administration of three antibiotics (meropenem hydrate, vancomycin hydrochloride, and clindamycin phosphate), the S. hominis -associated bacteremia improved. The patient was discharged 79 days after the surgery. Pathological examination revealed that the pancreatic tail tumor was NEN G2, T3N1aM0 Stage IIB with ACTH (+), somatostatin receptor (SSTR2) (+), and a Ki-67 of 15%. The pancreatic head lesion was identified as SSTR-positive hyperplasia of the islet of Langerhans cells . The patient did not receive any postoperative adjuvant therapy. Eight months after the surgery, scheduled enhanced CT revealed a recurrence in the para-aortic lymph nodes; furthermore, the plasma ACTH level, which had decreased to within its normal range after the pancreatectomy, was elevated to 153 pg/mL. The lymph node recurrence was resected, because these lesions were resectable. Pathological examination indicated that the para-aortic lymph node tumors were NEN G3 with ACTH (−), SSTR2 (+), and a Ki-67 of 20%. Soon after the second operation, multiple recurrences in the lymph nodes around the common hepatic artery, liver, and peritoneum occurred. After the para-aortic lymph node resection, the plasma ACTH level had dropped to 35.8 pg/mL; however, it increased again to 121 pg/mL at the time the multiple recurrences were detected. Currently, i.e., 14 months after his initial surgery, the patient is alive and is preparing to undergo chemotherapy with streptozocin and fluorouracil for the NEN G3. Fig. 1 Enhanced CT imaging. a Plain CT reveals the tumor located in the pancreatic tail (55 mm in diameter; white arrow). b Enhanced CT reveals the tumor with enhancement (white arrow) and bilateral adrenal enlargement (white arrowhead). c Enhanced CT reveals the tumor persisting with weak enhancement (dotted white arrow). CT computed tomography Fig. 2 MRI diffusion-weighted imaging. a The tumor located in the pancreatic tail is seen (white arrow). b The tumor located in the pancreatic head is seen (white arrowhead). c The tumor located in the uncinate process of the pancreas is seen (dotted white arrow). MRI magnetic resonance imaging Fig. 3 SRS. a SRS reveals a high accumulation of radioactive tracer in the pancreatic tail (white arrow). b SRS reveals a high accumulation of radioactive tracer in the pancreatic head (white arrowhead). c SRS reveals a high accumulation of radioactive tracer in the uncinate process of the pancreas (dotted white arrow). SRS somatostatin receptor scintigraphy Fig. 4 FDG PET–CT imaging. FDG PET–CT reveals FDG deposition in the pancreatic tail: the maximum standardized uptake value is 16 (white arrow). FDG PET–CT: 2-[18F] fluoro-2-deoxy- d -glucose positron emission tomography computed tomography Fig. 5 Endoscopic ultrasonography. a A hypoechoic lesion, 55 mm in diameter, is detected in the pancreatic tail (white arrow). b A hypoechoic lesion, 5 mm in diameter, is detected in the pancreatic head (white arrowhead). c A hypoechoic lesion is not enhanced with Sonazoid (white arrowhead) Fig. 6 The postoperative course and antibiotic treatments. The black arrow indicates S. hominis -positive blood culture, while the white arrow indicates S. hominis -negative blood culture. The white arrowhead indicates the timing of intravenous immunoglobulin administration. CTM cefotiam hydrochloride, TAZ/PIPC tazobactam, piperacillin hydrate, VCM vancomycin hydrochloride, MEPM meropenem hydrate, DAP daptomycin, LVFX levofloxacin hydrate, LZD linezolid, CLDM clindamycin phosphate, CRP C-reactive protein Table 1 Results of the susceptibility testing of Staphylococcus hominis Antibiotics POD 11 POD 14 POD 19 POD 27 POD 35 POD 44 MIC Interpretation MIC Interpretation MIC Interpretation MIC Interpretation MIC Interpretation MIC Interpretation Cefazolin sodium < 2 S < 2 S < 2 S < 2 S < 2 S < 2 S Ampicillin/sulbactam < 8 S < 8 S < 8 S < 8 S < 8 S < 8 S Amoxicillin/clavulanate < 2 S < 2 S < 2 S < 2 S < 2 S < 2 S Levofloxacin hydrate < 0.5 S < 0.5 S < 0.5 S < 0.5 S < 0.5 S < 0.5 S Meropenem hydrate < 1 S < 1 S < 1 S < 1 S < 1 S < 1 S Daptomycin < 0.25 S < 0.25 S < 0.25 S < 0.25 S < 0.25 S < 0.25 S Linezolid < 1 S < 1 S < 1 S < 1 S < 1 S < 1 S Vancomycin hydrochloride < 0.5 S < 0.5 S < 0.5 S < 0.5 S 1 S < 0.5 S Clindamycin phosphate < 0.25 S < 0.25 S < 0.25 S < 0.25 S < 0.25 S < 0.25 S POD postoperative day, MIC minimum inhibitory concentration, S susceptible, I intermediate Fig. 7 Histopathological examination. a The tumor located in the pancreatic tail is 6 cm in diameter. b The tumor located in the pancreatic tail contains rosette-like components when viewed microscopically. c Immunohistochemical examination shows ACTH positivity. d SSTR2 expression in the tumor is weakly positive. e Multiple lesions of islet of Langerhans cell hyperplasia are seen in the head of the pancreas. The maximal size of the islets is 2 mm. f Immunoreactivity for ACTH is negative. g The tumor cells are positive for SSTR2. HE hematoxylin and eosin stain, ACTH adrenocorticotropic hormone, SSTR somatostatin receptor	4.046875	0.975098	sec[1]/p[0]	en	0.999998	PMC9240135	https://doi.org/10.1186/s40792-022-01485-8	[ "pancreatic", "white", "tumor", "tail", "acth", "arrow", "head", "blood", "hydrate", "enhanced" ]	[ { "code": "DC3Z", "title": "Diseases of pancreas, unspecified" }, { "code": "DC3Y", "title": "Other specified diseases of pancreas" }, { "code": "LB21.3", "title": "Agenesis-aplasia of pancreas" }, { "code": "LB21.Z", "title": "Structural developmental anomalies of pancreas, unspecified" }, { "code": "DC35.0", "title": "Atrophy of pancreas" }, { "code": "EF5Y", "title": "Other specified dermatoses attributable to hyperviscosity or microvascular occlusion" }, { "code": "JB41.1", "title": "Deep phlebothrombosis in the puerperium" }, { "code": "EB60.Y", "title": "Lichen sclerosus of other specified sites" }, { "code": "MC80.00", "title": "White coat hypertension" }, { "code": "1F2D.2", "title": "White piedra" } ]	=== ICD-11 CODES FOUND === [DC3Z] Diseases of pancreas, unspecified Also known as: Diseases of pancreas, unspecified [DC3Y] Other specified diseases of pancreas Also known as: Other specified diseases of pancreas \| Calculus of pancreas \| pancreas calculi \| pancreas duct calculus \| pancreas duct lithiasis [LB21.3] Agenesis-aplasia of pancreas Definition: This refers to the failure of an organ to develop during embryonic growth and development due to the absence of primordial tissue of the pancreas. Also known as: Agenesis-aplasia of pancreas \| Congenital absence of pancreas \| Congenital pancreas absence \| Congenital pancreatic absence \| Absent pancreas [LB21.Z] Structural developmental anomalies of pancreas, unspecified Also known as: Structural developmental anomalies of pancreas, unspecified \| Structural developmental anomalies of pancreas \| malformations of pancreas \| anomalies of pancreas \| congenital abnormality of pancreas [DC35.0] Atrophy of pancreas Also known as: Atrophy of pancreas \| pancreatic atrophy \| pancreas ductal atrophy [EF5Y] Other specified dermatoses attributable to hyperviscosity or microvascular occlusion Also known as: Other specified dermatoses attributable to hyperviscosity or microvascular occlusion \| Cutaneous microvascular occlusion by platelet plugs \| Cutaneous microvascular disturbances due to myeloproliferative disorder-associated platelet plugs \| Cutaneous microvascular disturbances due to paroxysmal nocturnal haemoglobinuria-associated platelet plugs \| Cutaneous microvascular occlusion by emboli [JB41.1] Deep phlebothrombosis in the puerperium Also known as: Deep phlebothrombosis in the puerperium \| postnatal deep vein thrombosis \| postpartum deep phlebothrombosis \| postpartum deep-vein thrombosis \| DVT - [deep venous thrombosis] postnatal [EB60.Y] Lichen sclerosus of other specified sites Also known as: Lichen sclerosus of other specified sites \| Extragenital lichen sclerosus \| Guttate lichen sclerosus \| White spot disease \| Guttate scleroderma [MC80.00] White coat hypertension Definition: Persistently elevated office blood pressure readings with persistently normal out-of-the-office readings. Also known as: White coat hypertension \| white coat syndrome [1F2D.2] White piedra Definition: A disease of the hair shaft, caused by an infection with the fungi Trichosporon beigelii. This disease is characterised by irregular, soft, white, or light brown nodules which adhere to the hair follicle. Transmission is by direct contact with contaminated soil or water, or by airborne transmission. Confirmation is by identification of Trichosporon beigelii in a hair follicle sample. Also known as: White piedra \| Trichosporosis nodosa Includes: Trichosporosis nodosa === GRAPH WALKS === --- Walk 1 --- [DC3Z] Diseases of pancreas, unspecified --PARENT--> [?] Diseases of pancreas Def: This is a group of conditions characterised as being in or associated with the pancreas.... --CHILD--> [DC31] Acute pancreatitis Def: Inflammation of the pancreas with sudden onset. Pathological changes range from oedema to necrosis. While mild cases often recover without complications, severe cases have high mortality due to system... --- Walk 2 --- [DC3Z] Diseases of pancreas, unspecified --PARENT--> [?] Diseases of pancreas Def: This is a group of conditions characterised as being in or associated with the pancreas.... --CHILD--> [DC32] Chronic pancreatitis --- Walk 3 --- [DC3Y] Other specified diseases of pancreas --PARENT--> [?] Diseases of pancreas Def: This is a group of conditions characterised as being in or associated with the pancreas.... --RELATED_TO--> [?] Structural developmental anomalies of pancreas --- Walk 4 --- [DC3Y] Other specified diseases of pancreas --PARENT--> [?] Diseases of pancreas Def: This is a group of conditions characterised as being in or associated with the pancreas.... --RELATED_TO--> [?] Structural developmental anomalies of pancreas --- Walk 5 --- [LB21.3] Agenesis-aplasia of pancreas Def: This refers to the failure of an organ to develop during embryonic growth and development due to the absence of primordial tissue of the pancreas.... --PARENT--> [LB21] Structural developmental anomalies of pancreas --CHILD--> [LB21.0] Annular pancreas Def: Annular pancreas is a distinct form of duodenal atresia in which the head of the pancreas forms a ring around the second portion of the duodenum. During the neonatal period, the clinical picture is do... --- Walk 6 --- [LB21.3] Agenesis-aplasia of pancreas Def: This refers to the failure of an organ to develop during embryonic growth and development due to the absence of primordial tissue of the pancreas.... --PARENT--> [LB21] Structural developmental anomalies of pancreas --CHILD--> [LB21.1] Pancreas divisum Def: This is a congenital anomaly in the anatomy of the ducts of the pancreas in which a single pancreatic duct is not formed, but rather remains as two distinct dorsal and ventral ducts....	[ "[DC3Z] Diseases of pancreas, unspecified\n --PARENT--> [?] Diseases of pancreas\n Def: This is a group of conditions characterised as being in or associated with the pancreas....\n --CHILD--> [DC31] Acute pancreatitis\n Def: Inflammation of the pancreas with sudden onset. Pathological changes range from oedema to necrosis. While mild cases often recover without complications, severe cases have high mortality due to system...", "[DC3Z] Diseases of pancreas, unspecified\n --PARENT--> [?] Diseases of pancreas\n Def: This is a group of conditions characterised as being in or associated with the pancreas....\n --CHILD--> [DC32] Chronic pancreatitis", "[DC3Y] Other specified diseases of pancreas\n --PARENT--> [?] Diseases of pancreas\n Def: This is a group of conditions characterised as being in or associated with the pancreas....\n --RELATED_TO--> [?] Structural developmental anomalies of pancreas", "[DC3Y] Other specified diseases of pancreas\n --PARENT--> [?] Diseases of pancreas\n Def: This is a group of conditions characterised as being in or associated with the pancreas....\n --RELATED_TO--> [?] Structural developmental anomalies of pancreas", "[LB21.3] Agenesis-aplasia of pancreas\n Def: This refers to the failure of an organ to develop during embryonic growth and development due to the absence of primordial tissue of the pancreas....\n --PARENT--> [LB21] Structural developmental anomalies of pancreas\n --CHILD--> [LB21.0] Annular pancreas\n Def: Annular pancreas is a distinct form of duodenal atresia in which the head of the pancreas forms a ring around the second portion of the duodenum. During the neonatal period, the clinical picture is do...", "[LB21.3] Agenesis-aplasia of pancreas\n Def: This refers to the failure of an organ to develop during embryonic growth and development due to the absence of primordial tissue of the pancreas....\n --PARENT--> [LB21] Structural developmental anomalies of pancreas\n --CHILD--> [LB21.1] Pancreas divisum\n Def: This is a congenital anomaly in the anatomy of the ducts of the pancreas in which a single pancreatic duct is not formed, but rather remains as two distinct dorsal and ventral ducts...." ]	DC3Z	Diseases of pancreas, unspecified	[ { "from_icd11": "DC3Z", "icd10_code": "K8681", "icd10_title": "Exocrine pancreatic insufficiency" }, { "from_icd11": "DC3Z", "icd10_code": "K8689", "icd10_title": "Other specified diseases of pancreas" }, { "from_icd11": "DC3Z", "icd10_code": "K869", "icd10_title": "Disease of pancreas, unspecified" }, { "from_icd11": "DC3Z", "icd10_code": "K868", "icd10_title": "Other specified diseases of pancreas" }, { "from_icd11": "DC3Z", "icd10_code": "K87", "icd10_title": "Disorders of gallbladder, biliary tract and pancreas in diseases classified elsewhere" }, { "from_icd11": "DC3Z", "icd10_code": "K80-K87", "icd10_title": "" }, { "from_icd11": "DC3Z", "icd10_code": "K86", "icd10_title": "Other diseases of pancreas" }, { "from_icd11": "DC3Z", "icd10_code": "K871", "icd10_title": "" }, { "from_icd11": "LB21.Z", "icd10_code": "Q450", "icd10_title": "Agenesis, aplasia and hypoplasia of pancreas" }, { "from_icd11": "LB21.Z", "icd10_code": "Q38-Q45", "icd10_title": "" }, { "from_icd11": "LB21.Z", "icd10_code": "Q45", "icd10_title": "Other congenital malformations of digestive system" }, { "from_icd11": "LB21.Z", "icd10_code": "Q452", "icd10_title": "Congenital pancreatic cyst" }, { "from_icd11": "JB41.1", "icd10_code": "O871", "icd10_title": "Deep phlebothrombosis in the puerperium" }, { "from_icd11": "1F2D.2", "icd10_code": "B362", "icd10_title": "White piedra" } ]	K8681	Exocrine pancreatic insufficiency
A 30-year-old woman of Polish descent presented to the Head and Neck Cancer Clinic of the National Research Institute of Oncology in Warsaw with a three-month history of a mass on the right side of her neck. She also complained of dizziness, hearing problems, difficulty swallowing, and abdominal pain, which had been worsening in frequency and severity. She had normal bowel movements and denied smoking or drinking alcohol. Her medical history was unremarkable, except for the loss of her parents in a car accident when she was 5 years old. There was no family history of genetic, metabolic, or neoplastic disorders. Concerned about the neck tumor and abdominal pain, she mentioned plans to conceive and attributed the symptoms to a possible infectious condition due to her job as a teacher. The basic laboratory tests, including WBC (white blood cells), RBC (red blood cells), HGB (hemoglobin), protein, and calcium levels, were within normal limits. Her vital signs were also normal. The physical examination revealed a right-sided neck mass of 6 centimeters in diameter. The mass was pulsatile, but the overlying skin was normal in color, texture, and temperature. Abdominal examination did not reveal any abnormality, as the abdomen was soft on palpation with a good peristaltic wave. The patient was then scheduled for a neck ultrasound and a CT scan of her body, including the head, neck, thorax, abdominal cavity, and pelvis. The ultrasound exam revealed a rounded mass with mixed echogenicity and well-defined margins, localized in the carotid bifurcation on the right side. The color Doppler function displayed hypervascularity of the tumor, so the biopsy was postponed. On the CT scans at the level of the bifurcation of the right common carotid artery and behind it, a fairly well-defined tumor was noticed, with strong, homogeneous contrast enhancement, measuring 34 × 31 mm in the transverse plane and approximately 60 mm in the cc dimension . The tumor modeled the vascular structures but did not infiltrate them. No other abnormalities were detected on imaging studies, and the basic blood work-up proved to be normal. Subsequently, the patient underwent neck surgery, during which the tumor was removed with prior vascular embolization, with an uncomplicated post-surgical recovery. The histopathology results confirmed the diagnosis of a paraganglioma tumor with rounded cells with eosinophilic cytoplasm, and regular centralized nuclei. The proliferative index, evaluated by the Ki67 expression, was 1–3%. Expression of chromogranin, synaptophysin, and S100 protein were detected, but no somatic mutations in the tumor tissue were found. Due to the patient’s young age and the unknown family history of hereditary disorders, genetic testing was performed to rule out the hereditary origin of the tumor. Targeted next-generation sequencing was conducted following this protocol. DNA extraction was performed on 200 µl of whole blood (anti-coagulated with EDTA) and the genomic DNA isolation was carried out using the QIA symphony instrument from QIAGEN GmbH. The gene panel included, among others, RET, MEN1, SDHA, SDHAF2, SDHC, SDHD genes and was then employed to identify pathogenic changes in all coding exons and 30 bp of flanking non-coding sequences, using Roche’s SeqCap EZ HyperCap kit. Subsequently, sequencing was performed using an Illumina MiniSeq device. The results underwent analysis through the bioinformatics tools of the JSI SeqPilot platform, ensuring a minimum average coverage of gene coding sequences not less than 100 reads. The analysis included the identification of single nucleotide changes and multi-nucleotide deletions/insertions in gene coding sequences. The notation of changes/mutations followed the Human Genome Variation Society (HGVS) nomenclature. The presence of the identified pathogenic variants was confirmed by Sanger direct sequencing on the 3500 Genetic Analyzer Applied Biosystems/HITACHI. The NGS screening revealed a pathogenic SDHD variant - c.64 C > T (p.Arg22Ter) and a pathogenic RET variant: c.2410G > A (p.Val804Met). The RET gene heterozygous change c.2410G > A (p. Val804Met) is documented in the ClinVar and HGMD databases. Additionally, a SDHD gene heterozygous change c.64 C > T (p.Arg22Ter) is also documented in the ClinVar and HGMD databases. The SeqPilot program view of NGS sequencing and the chromatogram from Sanger direct sequencing of the detected variants, is presented in Fig. 2 a and b. Based on the test results, the tumor appeared to have a genetic origin, necessitating a multidisciplinary approach. Therefore, the patient was referred for a genetic consult. Next-generation sequencing confirmed only two variants in SDHD and RET genes, respectively, with no abnormalities in MAX, VHL , or other SDH genes. Further diagnostic workup was ordered by a genetics specialist to confirm the diagnosis of FPGL1 syndrome and MEN2A as well. Regarding the RET variant, the patient subsequently underwent an ultrasonographic evaluation of the thyroid gland, which did not detect any thyroid or parathyroid abnormalities at that time. Nevertheless, the endocrinology consultation recommended thyroidectomy due to the significant risk of medullary thyroid carcinoma. Complete blood tests were ordered, including assessments of calcium levels, calcitonin, parathormone, thyroid stimulating hormone (TSH), carcinoembryonic antigen (CEA), complete blood count, vitamin D levels, estradiol, adrenocorticotropin, dehydroepiandrosterone sulfate, chromogranin A, testosterone, insulin, glucose, androstenedione, and cortisol. Only the calcitonin level showed a slight elevation, reaching about 15.8 pg/ml (Table 1 ). Daily urine collection, including urine catecholamines, was also conducted, revealing normal results (Table 1 ). Although imaging studies did not reveal any abnormalities besides the neck paraganglioma, the patient’s history of periodic abdominal pain prompted the necessity of imaging with [131I]/[123I] metaiodobenzylguanidine (MIBG), which ultimately yielded results within normal limits. With pheochromocytoma ruled out, the patient underwent a thyroidectomy procedure, which was successful and the recovery was uneventful. Due to the increased risk of gastrointestinal stromal tumor (GIST) associated with the inherited SDHD variant, the patient also underwent a gastroscopic exam in conjunction with an ultrasonographic exam four weeks after the thyroidectomy. The endoscopy revealed no findings suggestive of GIST. Nevertheless, the genetic variants of RET and SDHD genes place the patient at a lifetime risk of various cancers. Therefore, detailed follow-up tests are of utmost importance. An annual blood biochemical work-up, including plasma metanephrines, calcitonin, parathormone, and calcium levels, was ordered. Moreover, a 24-hour urine collection was also recommended to search for elevated fractionated metanephrines and catecholamines. Imaging studies, such as a total body CT scan with computed tomography angiography (CTA) examination, were performed once every two years. The patient has remained under close supervision of the National Institute of Oncology and has not developed any signs of hyperparathyroidism, pheochromocytoma, GIST, or other malignancies. Follow-up visits were scheduled every 3 and 6 months during the first and second year after diagnosis, respectively. Furthermore, genetic tests were offered for the patient’s first-line relatives. Although the patient seemed stressed about the inherited genetic conditions, she remained grateful as the diagnosis was made early, and the patient proceeded with the appropriate treatment plan. Table 1 Results from laboratory tests of both presented patients Patient 1 Patient 2 Normal Value Gender Female Female - Calcitonin 15.8 0.82 < 6.40 [pg/mL] Parathormone 24.12 33.86 15–65 [pg/mL] Adrenocorticotropin 8.1 9.3 7.2–63.6 [pg/mL] TSH 1.390 1.060 0.300–4.200 [ulU/mL] FT3 2.58 3.34 2.00-4.40 [pg/mL] FT4 1.36 1.22 0.93–1.70 [ng/dL] Estradiol 10.4 9.3 7.2–63.6 [pg/mL] Dehydroepiandrosterone sulfate 177.70 169.60 60.90–337.00 [ug/dL] Chromogranin A 48.3 57.09 < 101.9 [ng/mL] Testosterone 10.5 13.4 8.4–48.1 [ng/dL] Insulin 7.2 8.50 2.60–24.90 [ulU/mL] Androstendione 0.878 0.999 0.490–1.310 [ng/mL] Cortisol 2.01 2.04 Morning: 4.82–19.5 2.47–11.9 [ug/dL] CEA 0.7 2.16 < 5.0 [ng/mL] Calcium 2.52 2.33 2.20–2.65 [ mmol/L] Phosphorus 1.09 1.21 0.81–1.45[ mmol/L] Vitamin D 13.55 62.89 30–50 [ng/mL] Glucose 81 98 70–99 [mg/dL] Plasma Dopamine 2.3 3.1 0–30 [pg/mL] Plasma Epinephrine 12.4 15.3 0–140 [pg/mL] Plasma Norepinephrine 145.8 136.2 70–1700 [pg/mL] Plasma Metanephrine 334 421.2 < 1180 [pmol/L] Plasma Normetanephrine 233.1 178 < 510 [pmol/L] Plasma 3-methoxytyramine 56.3 67.2 < 180 [pmol/L] Urine Dopamine 490 511 420–2612 [nmol/24 hours] Urine Metanephrine 245.5 221 140–785 [mcg/24 hours] Urine Epinephrine 5.4 6.1 0.5–20 [mcg/24 hours] Fig. 1 CT scan of a tumor in patient 1. a and b Horizontal CT scans of a well-defined tumor with robust, homogeneous contrast enhancement, measuring 34 × 31 mm in the transverse plane and approximately 60 mm in the craniocaudal dimension on the right side of the neck Fig. 2 Results of next generation sequencing in two patients. SeqPilot program view of NGS sequencing and chromatogram from Sanger direct sequencing of the ( a ) RET and ( b ) SDHD gene	4.039063	0.977051	sec[0]/sec[0]/p[0]	en	0.999997	PMC11129478	https://doi.org/10.1186/s12957-024-03418-1	[ "tumor", "neck", "sequencing", "genetic", "blood", "sdhd", "plasma", "gene", "urine", "abdominal" ]	[ { "code": "2F9Z", "title": "Neoplasms of unknown behaviour of unspecified site" }, { "code": "ME61", "title": "Subcutaneous swelling, mass or lump of uncertain or unspecified nature" }, { "code": "2E6Z", "title": "Carcinoma in situ of unspecified site" }, { "code": "2F91.1", "title": "Neoplasms of unknown behaviour of trachea, bronchus or lung" }, { "code": "2F92", "title": "Neoplasms of unknown behaviour of skin" }, { "code": "ME86.C", "title": "Symptom or complaint of the neck" }, { "code": "LA6Z", "title": "Structural developmental anomalies of the neck, unspecified" }, { "code": "ME84.0", "title": "Cervical spine pain" }, { "code": "FA71", "title": "Torticollis" }, { "code": "NA23.4Y", "title": "Other specified strain or sprain of cervical spine" } ]	=== ICD-11 CODES FOUND === [2F9Z] Neoplasms of unknown behaviour of unspecified site Also known as: Neoplasms of unknown behaviour of unspecified site \| neoplasia \| neoplasm growth NOS \| tumour of unspecified site \| tumourlet of unspecified site [ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature Definition: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature Also known as: Subcutaneous swelling, mass or lump of uncertain or unspecified nature \| localised swelling, mass or lump of skin and subcutaneous tissue \| localised subcutaneous nodules \| subcutaneous nodules \| superficial subcutaneous nodules Excludes: localized adiposity \| mass and lump: breast \| enlarged lymph nodes [2E6Z] Carcinoma in situ of unspecified site Also known as: Carcinoma in situ of unspecified site \| carcinoma in situ of unspecified site \| carcinoma in situ NOS \| carcinoma in situ \| in situ neoplasm [2F91.1] Neoplasms of unknown behaviour of trachea, bronchus or lung Also known as: Neoplasms of unknown behaviour of trachea, bronchus or lung \| trachea, bronchus or lung tumour NOS \| Intravascular bronchial alveolar tumour of unspecified site \| Bronchial adenoma of unknown behaviour of unspecified site \| Intravascular bronchial alveolar tumour unknown behaviour of unspecified site [2F92] Neoplasms of unknown behaviour of skin Also known as: Neoplasms of unknown behaviour of skin \| skin tumour NOS [ME86.C] Symptom or complaint of the neck Also known as: Symptom or complaint of the neck \| Neck syndrome Excludes: Chronic primary musculoskeletal pain \| Chronic secondary musculoskeletal pain [LA6Z] Structural developmental anomalies of the neck, unspecified Also known as: Structural developmental anomalies of the neck, unspecified \| Malformations of the neck [ME84.0] Cervical spine pain Definition: This is a condition which is usually characterised by pain or discomfort in the neck region and can be caused by numerous spinal problems. It may be a feature of virtually every disorder and disease that occurs above the shoulder blades. Also known as: Cervical spine pain \| cervical pain \| neck ache \| nonspecific pain in the neck region \| cervicalgia Includes: cervicalgia Excludes: cervical disc degeneration \| Chronic primary cervical pain \| Chronic secondary musculoskeletal pain [FA71] Torticollis Also known as: Torticollis \| contracture of neck \| wry neck \| wry neck/torticollis \| Intermittent torticollis Excludes: Cervical dystonia \| Congenital torticollis \| current injury - see injury of spine by body region [NA23.4Y] Other specified strain or sprain of cervical spine Also known as: Other specified strain or sprain of cervical spine \| Strain of cervical spine \| cervical strain \| Strain of cervical anterior longitudinal ligament \| Sprain of cervical spine === GRAPH WALKS === --- Walk 1 --- [2F9Z] Neoplasms of unknown behaviour of unspecified site --PARENT--> [?] Neoplasms of unknown behaviour, except of lymphoid, haematopoietic, central nervous system or related tissues --RELATED_TO--> [?] Pathological fracture in neoplastic disease of unknown behaviour --- Walk 2 --- [2F9Z] Neoplasms of unknown behaviour of unspecified site --PARENT--> [?] Neoplasms of unknown behaviour, except of lymphoid, haematopoietic, central nervous system or related tissues --CHILD--> [2F90] Neoplasms of unknown behaviour of oral cavity or digestive organs --- Walk 3 --- [ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature Def: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature... --EXCLUDES--> [?] Enlarged lymph nodes Def: Enlarged lymph node is called lymphadenopathy which means the abnormal enlargement of lymph nodes.... --CHILD--> [?] Generalised lymph node enlargement --- Walk 4 --- [ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature Def: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature... --EXCLUDES--> [?] Localised adiposity Def: A condition characterised by accumulation of adipose tissue in specific regions of the body.... --CHILD--> [?] Fat pad Def: A condition characterised by a mass of closely packed adipose cells surrounded by fibrous tissue septa. When localised in the heel this condition may present with dull pain when pressure is applied.... --- Walk 5 --- [2E6Z] Carcinoma in situ of unspecified site --PARENT--> [?] In situ neoplasms, except of lymphoid, haematopoietic, central nervous system or related tissues --CHILD--> [2E60] Carcinoma in situ of oral cavity, oesophagus or stomach --- Walk 6 --- [2E6Z] Carcinoma in situ of unspecified site --PARENT--> [?] In situ neoplasms, except of lymphoid, haematopoietic, central nervous system or related tissues --CHILD--> [2E62] Carcinoma in situ of middle ear or respiratory system	[ "[2F9Z] Neoplasms of unknown behaviour of unspecified site\n --PARENT--> [?] Neoplasms of unknown behaviour, except of lymphoid, haematopoietic, central nervous system or related tissues\n --RELATED_TO--> [?] Pathological fracture in neoplastic disease of unknown behaviour", "[2F9Z] Neoplasms of unknown behaviour of unspecified site\n --PARENT--> [?] Neoplasms of unknown behaviour, except of lymphoid, haematopoietic, central nervous system or related tissues\n --CHILD--> [2F90] Neoplasms of unknown behaviour of oral cavity or digestive organs", "[ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature\n Def: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature...\n --EXCLUDES--> [?] Enlarged lymph nodes\n Def: Enlarged lymph node is called lymphadenopathy which means the abnormal enlargement of lymph nodes....\n --CHILD--> [?] Generalised lymph node enlargement", "[ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature\n Def: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature...\n --EXCLUDES--> [?] Localised adiposity\n Def: A condition characterised by accumulation of adipose tissue in specific regions of the body....\n --CHILD--> [?] Fat pad\n Def: A condition characterised by a mass of closely packed adipose cells surrounded by fibrous tissue septa. When localised in the heel this condition may present with dull pain when pressure is applied....", "[2E6Z] Carcinoma in situ of unspecified site\n --PARENT--> [?] In situ neoplasms, except of lymphoid, haematopoietic, central nervous system or related tissues\n --CHILD--> [2E60] Carcinoma in situ of oral cavity, oesophagus or stomach", "[2E6Z] Carcinoma in situ of unspecified site\n --PARENT--> [?] In situ neoplasms, except of lymphoid, haematopoietic, central nervous system or related tissues\n --CHILD--> [2E62] Carcinoma in situ of middle ear or respiratory system" ]	2F9Z	Neoplasms of unknown behaviour of unspecified site	[ { "from_icd11": "2F9Z", "icd10_code": "D487", "icd10_title": "Neoplasm of uncertain behavior of other specified sites" }, { "from_icd11": "2F9Z", "icd10_code": "D482", "icd10_title": "Neoplasm of uncertain behavior of peripheral nerves and autonomic nervous system" }, { "from_icd11": "2F9Z", "icd10_code": "D37-D48", "icd10_title": "" }, { "from_icd11": "2F9Z", "icd10_code": "D377", "icd10_title": "" }, { "from_icd11": "2F9Z", "icd10_code": "D48", "icd10_title": "Neoplasm of uncertain behavior of other and unspecified sites" }, { "from_icd11": "2F9Z", "icd10_code": "D489", "icd10_title": "Neoplasm of uncertain behavior, unspecified" }, { "from_icd11": "ME61", "icd10_code": "R2240", "icd10_title": "Localized swelling, mass and lump, unspecified lower limb" }, { "from_icd11": "ME61", "icd10_code": "R2232", "icd10_title": "Localized swelling, mass and lump, left upper limb" }, { "from_icd11": "ME61", "icd10_code": "R2242", "icd10_title": "Localized swelling, mass and lump, left lower limb" }, { "from_icd11": "ME61", "icd10_code": "R2231", "icd10_title": "Localized swelling, mass and lump, right upper limb" }, { "from_icd11": "ME61", "icd10_code": "R2241", "icd10_title": "Localized swelling, mass and lump, right lower limb" }, { "from_icd11": "ME61", "icd10_code": "R2233", "icd10_title": "Localized swelling, mass and lump, upper limb, bilateral" }, { "from_icd11": "ME61", "icd10_code": "R2243", "icd10_title": "Localized swelling, mass and lump, lower limb, bilateral" }, { "from_icd11": "ME61", "icd10_code": "R2230", "icd10_title": "Localized swelling, mass and lump, unspecified upper limb" }, { "from_icd11": "ME61", "icd10_code": "R220", "icd10_title": "Localized swelling, mass and lump, head" } ]	D487	Neoplasm of uncertain behavior of other specified sites
A 59-year-old female with a medical history of rheumatic valvular heart disease with atrial fibrillation (Af), hypertension, type II diabetes, and hyperlipemia presented to the cardiac surgery ward with chest tightness and palpitation for the past two months. She admitted a family history of the sudden death of her mother, but she had no history of syncope or TdP. She denied food and medication allergies. The patient was taking digoxin, furosemide, spironolactone, sacubitril valsartan sodium tablets, metformin, dapagliflozin, and atorvastatin at the time of presentation to the hospital. Physical examination showed a blood pressure of 115/89 mmHg, an irregular heart rate of 98/min with a pulse rate of 76/min, a respiratory rate of 16/min, oxygen saturation levels of 100 % at room air, a body temperature of 36.2 °C, and weight 61 kg. A systolic blowing murmur can be heard in the apical region. She had no rales on pulmonary auscultation. There was no pitting edema in the lower extremities. On admission, the N-terminal B-type brain natriuretic peptide precursor (NT-proBNP) was 2709 pg/ml (reference range 0–300 pg/ml). Autoantibody ANA and related antibodies were negative. Serum immunoglobulins were in the normal range. Interleukin-6 (IL-6) was 5.4 pg/ml (reference range 0–7pg/ml). The initial electrocardiography (ECG) showed Af with a normal QTc of 435 ms, as shown in Fig. 1 . Transthoracic echocardiogram showed left heart enlargement, left atrium anteroposterior diameter of 54mm, left ventricular end-diastolic diameter (LVEDD) of 62mm, moderate-to-severe mitral regurgitation, mild-to-moderate tricuspid regurgitation and left ventricular ejection fraction (LVEF) of 57 %. After optimization of cardiac function and fluid status, the patient underwent mitral valve replacement, tricuspid valvuloplasty, COX-maze IV procedure, epicardial temporary pacing electrode implantation on day 8 of admission, and the postoperative ECG showed a normal QTc of 448 ms. On day 9, a bedside echocardiogram showed that LVEDD was 56mm and a reduced LVEF of 35 % with the normal function of the prosthetic mitral valve. Laboratory tests suggested significantly elevated IL-6 of 91.3 pg/ml. Limitation of fluid, furosemide, dopamine, and dapagliflozin were prescribed to improve the cardiac output. From day 12 to day 13, levosimendan was prescribed for continuous intravenous infusion at the speed of 0.14μg/kg per minute for 24 hours, and synchronous cardiac telemetry showed that the patient was in sinus rhythm with occasional premature ventricular beats and heart rate ranging from 79/min to 95/min during the infusion. On day 13, the patient developed a sudden loss of consciousness with hemodynamic instability that lasted for 50 seconds. ECG monitoring showed an R-on-T event-initiated episode of TdP deteriorated into ventricular fibrillation and then converted to Af with a QTc of 454 ms under a heart rate of 140/min rapidly with chest compressions . Lab work showed normal serum electrolytes (Na, K, Ca, Cl), arterial blood gas analysis, and a mild elevated troponin T and troponin I, 0.417 ng/ml and 0.587 ng/ml, respectively due to cardiac surgery. Craniocerebral computed tomography showed no abnormality compared with the previous image. The bedside echocardiogram showed no significant change from the previous. Five hours after the first TdP, cardiac arrest due to ventricular tachycardia and ventricular fibrillation appeared, and the patient was resuscitated with electric defibrillation, epinephrine, dopamine, lidocaine, chest compression, and urgent trachea intubation. She was transferred to the surgical intensive care unit. Upon arrival, the patient was in subcoma. Vital signs showed a blood pressure of 58/25 mmHg with continuous intravenous pumping of epinephrine (0.05 μg/kg per minute), dopamine (5 μg/kg per minute), and norepinephrine (0.04 μg/kg per minute), an irregular heart rate of 198 beats per minute with continuous infusion of lidocaine, oxygen saturation levels varying between 98 and 100 % with mechanical ventilation, and a temperature of 36.2 °C. Asynchronous electrical cardioversion, with the energy of 50J and 70J, respectively, was conducted because of tachycardia and severe hypotension, then atrioventricular node rhythm was restored and a prolonged QTc of 532 ms was shown on ECG. Repeated echocardiogram revealed reduced LVEF of 30 % with the normal function of the mechanical mitral valve, a newly emerged weakened motion of the left ventricle apex and middle segment, and normal movement of the basal segment which indicated the possibility of Takotsubo cardiomyopathy without left ventricular outflow tract obstruction so epinephrin was stopped. Urgent coronary angiography proved normal blood flow of coronaries without stenosis, and a temporary cardiac pacemaker via the right femoral vein was implanted at the same time to ensure the patient's safety in case the epicardial temporary pacing lost efficacy. On day 14, the patient's condition was still unstable with intravenous pumping of dopamine, norepinephrine, and lidocaine; T-wave alternation can be observed followed by VT recurred including episodes of torsades de pointes and epicardial temporary pacing was used with the rate of 90/min to suppress the ventricular arrhythmias effectively besides intravenous infusion of magnesium sulfate to maintain the serum magnesium in high normal levels (0.66–1.07mmol/L). Any medication that may cause a prolonged QT interval was prohibited. From day 15 to day 17, the patient had no further ventricular arrhythmia events with cardiac pacing. On day 17, lidocaine and norepinephrine were taken off, and atenolol was added at the dose of 6.25mg twice a day, which was withdrawn on day 18 because of severe bradycardia. On day 19, digoxin was prescribed at the dose of 0.125mg once a day, dopamine was reduced from 5ug/(kg. min) to 3ug/(kg. min) because of symptom relief and blood pressure in the normal range, and discontinued on day 20. On day 29, the follow-up echocardiography suggested that LVEDD reduced to 48mm and LVEF elevated to 45 %. Given the concern for genetic susceptibility to drug-induced long QT syndrome (LQTS), the patient's peripheral blood genomic DNA was sequenced, and positive pathogenic variant KCNQ1 (c.642C > T) was found, which had definitive evidence as a genetic cause of typical long QT syndrome type 1 (LQT1). From day 35, bradycardia occurred while the patient was taking digoxin, which was stopped immediately. On day 41, a prolonged QTc interval of 516 ms under a heart rate of 56 bpm was observed on ECG, and concern for ongoing TdP and cardiac arrest risk, a dual chamber implantable cardioverter defibrillator (Medtronic DDBC3D4) was placed on day 43. The patient was discharged from the hospital on day 46 with the prescription of potassium magnesium aspartate tablets, warfarin, dapagliflozin, furosemide, and spironolactone ( Table 1 ). Fig. 1 ECG on admission showing atrial fibrillation with a normal QTc interval of 435 ms under a heart rate of 93 bpm. Fig. 1 Fig. 2 ECG monitoring showed an R-on-T event (arrow) that initiated the episode of TdP which deteriorated into ventricular fibrillation (a) and then converted to Af with a mild prolonged QTc of 454 ms under a heart rate of 140 beats per minute with compressions (b). Fig. 2 Fig. 3 ECG showed T-wave alternation on 12 leads following the pattern of ABAB (arrow) on day 14. Fig. 3 Fig. 4 ECG monitoring showed episodes of TdP on day 14. Fig. 4 Table 1 Time line. Table 1 Date Clinical events QTc (ms) IL-6 (0–7pg/ml) NT-proBNP (0–300 pg/ml) Medications 1 admission (Af) 435 5.4 2709 DIG, furosemide, spironolactone, sacubitril/valsartan, dapagliflozin 8 surgery 448 – – furosemide, KCl 9 paroxysmal Af 452 91.3 2621 warfarin, furosemide, KCl 10 sinus 441 149.9 4525 DA, warfarin, furosemide, KCl, dapagliflozin 12 10:01 sinus – – – start of levosimendan infusion, DA, furosemide, KCl, warfarin 13 10:05 PVC – – – end of levosimendan infusion, DA, furosemide, KCl 11:07 first TdP 454 – – DA, KCl 18:21 VT, VF – – – DA, lidocaine, KCl 18:29 CPR – – – E, DA, lidocaine 18:50 AV node rhythm 532 – – E, DA, NE, lidocaine, MgSO 4 20:02 Takotsubo cardiomyopathy 495 – – E, DA, NE, lidocaine, MgSO 4 14 T-wave alternation,TdP 453 41.9 6918 DA, NE, lidocaine, MgSO 4, warfarin 15 VPR – 59.6 8979 DA, NE, lidocaine, warfarin 16 VPR – 38.6 1754 DA, NE, lidocaine, warfarin 17 VPR – 27.0 1438 Atenolol, DA, warfarin 18 VPR – 9.0 623 DA, furosemide, KCl,warfarin 19 Af – 5.2 495 DIG, DA,warfarin 25 Af 437 – – DIG,warfarin 35 Af – – – warfarin 41 VPR 516 – – warfarin 43 ICD (atrial pacing) 473 – – warfarin 46 Discharge (atrial pacing) – – – potassium magnesium aspartate, dapagliflozin, furosemide,spironolacton, warfarin Af: atrial fibrillation; QTc: QT intervals corrected for cardiac frequency using Fridericia's formula; IL-6: Interleukin-6; NT-proBNP: N-terminal B-type brain natriuretic peptide precursor; Af: atrial fibrillation; DIG: digoxin; KCl: potassium chloride; PVC: premature ventricular contraction; DA: dopamin; TdP: Torsades de points; VT: ventricular tachycardia; VF: ventricular fibrillation; CPR: cardiopulmonary resuscitation; E: epinephrin; NE: norepinephrin; AV node: atrioventricular node; MgSO 4 : magnesium sulfate; VPR: ventricular pacing rhythym; ICD: implantable cardioverter defibrillator.	4.019531	0.975098	sec[0]/sec[0]/p[0]	en	0.999995	38644859	https://doi.org/10.1016/j.heliyon.2024.e29300	[ "warfarin", "ventricular", "furosemide", "lidocaine", "cardiac", "heart", "fibrillation", "pacing", "atrial", "dapagliflozin" ]	[ { "code": "LD2F.02", "title": "Embryofetopathy due to oral anticoagulant therapy" }, { "code": "NE61", "title": "Harmful effects of or exposure to noxious substances, chiefly nonmedicinal as to source, not elsewhere classified" }, { "code": "EH76.3/PL00&XM86W0", "title": "Warfarin necrosis" }, { "code": "LA89.Z", "title": "Functionally univentricular heart, unspecified" }, { "code": "BC45", "title": "Cardiomegaly" }, { "code": "BA41.Z", "title": "Acute myocardial infarction, unspecified" }, { "code": "BC46&XA7XU8", "title": "Ventricular thrombosis" }, { "code": "BD1Z&XT5R", "title": "Acute heart failure" }, { "code": "NE60", "title": "Harmful effects of drugs, medicaments or biological substances, not elsewhere classified" }, { "code": "BE2Y", "title": "Other specified diseases of the circulatory system" } ]	=== ICD-11 CODES FOUND === [LD2F.02] Embryofetopathy due to oral anticoagulant therapy Definition: A condition caused by exposure of the embryo or fetus to anticoagulants during the antenatal period. This disease may present with optic nerve anomaly, optic atrophy, anomaly of the papilla, blindness, or choanal atresia. Also known as: Embryofetopathy due to oral anticoagulant therapy \| Fetal warfarin syndrome \| Coumarin embryopathy \| Vitamin K antagonists embryofetopathy \| Dysmorphism due to warfarin [NE61] Harmful effects of or exposure to noxious substances, chiefly nonmedicinal as to source, not elsewhere classified Also known as: Harmful effects of or exposure to noxious substances, chiefly nonmedicinal as to source, not elsewhere classified \| Harmful effects of or exposure to noxious substances chiefly nonmedicinal as to source, alcohols \| alcohol poisoning \| alcohol toxicity \| Harmful effects of or exposure to noxious substances chiefly nonmedicinal as to source, Ethanol Excludes: corrosions \| Bacterial foodborne intoxications [LA89.Z] Functionally univentricular heart, unspecified Also known as: Functionally univentricular heart, unspecified \| Functionally univentricular heart \| Univentricular cardiopathy \| Single ventricle \| univentricular heart [BC45] Cardiomegaly Also known as: Cardiomegaly \| enlargement of heart \| hypertrophic heart \| heart hypertrophy \| Cardiac hypertrophy Includes: Left ventricular hyperplasia [BA41.Z] Acute myocardial infarction, unspecified Also known as: Acute myocardial infarction, unspecified \| Acute myocardial infarction \| cardiac attack \| heart attack \| acute cardiac infarction [NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified Also known as: Harmful effects of drugs, medicaments or biological substances, not elsewhere classified \| drugs, medicaments or biological substances, toxicity not elsewhere classified \| adverse drug effects \| drug reaction NOS \| drug allergy NOS Excludes: Alcohol intoxication \| pathological drug intoxication \| hypersensitivity reaction to correctly administered drug [BE2Y] Other specified diseases of the circulatory system Also known as: Other specified diseases of the circulatory system \| Certain specified forms of heart disease \| Cardiac disorder, unspecified \| disorder of heart NOS \| organic disease or disorder of heart === GRAPH WALKS === --- Walk 1 --- [LD2F.02] Embryofetopathy due to oral anticoagulant therapy Def: A condition caused by exposure of the embryo or fetus to anticoagulants during the antenatal period. This disease may present with optic nerve anomaly, optic atrophy, anomaly of the papilla, blindness... --PARENT--> [LD2F.0] Toxic or drug-related embryofetopathies --RELATED_TO--> [?] Uterovaginal malformation due to diethylstilbestrol syndrome Def: Fetal diethylstilbestrol syndrome is characterised by a group of symptoms likely to occur in children and grandchildren of a woman who was treated while pregnant with diethylstilbestrol (DES). The dru... --- Walk 2 --- [LD2F.02] Embryofetopathy due to oral anticoagulant therapy Def: A condition caused by exposure of the embryo or fetus to anticoagulants during the antenatal period. This disease may present with optic nerve anomaly, optic atrophy, anomaly of the papilla, blindness... --PARENT--> [LD2F.0] Toxic or drug-related embryofetopathies --CHILD--> [LD2F.00] Fetal alcohol syndrome Def: Fetal alcohol syndrome is a malformation syndrome caused by maternal consumption of alcohol during pregnancy. It is characterised by prenatal and/or postnatal growth deficiency (weight and/or height <... --- Walk 3 --- [NE61] Harmful effects of or exposure to noxious substances, chiefly nonmedicinal as to source, not elsewhere classified --EXCLUDES--> [?] Burns Def: A burn is an injury to the tissues caused by a pathological flux of energy which causes cellular destruction and irreversible denaturation of proteins and is primarily caused by thermal or other acute... --EXCLUDES--> [?] Sunburn Def: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight.... --- Walk 4 --- [NE61] Harmful effects of or exposure to noxious substances, chiefly nonmedicinal as to source, not elsewhere classified --EXCLUDES--> [?] Burns Def: A burn is an injury to the tissues caused by a pathological flux of energy which causes cellular destruction and irreversible denaturation of proteins and is primarily caused by thermal or other acute... --EXCLUDES--> [?] Sunburn Def: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight.... --- Walk 5 --- [LA89.Z] Functionally univentricular heart, unspecified --PARENT--> [LA89] Functionally univentricular heart Def: The term “functionally univentricular heart” describes a spectrum of congenital cardiovascular malformations in which the ventricular mass may not readily lend itself to partitioning that commits one ... --CHILD--> [LA89.2] Mitral atresia Def: A congenital cardiovascular malformation with absence of the mitral valvar annulus (connection/junction) or an imperforate mitral valve.... --- Walk 6 --- [LA89.Z] Functionally univentricular heart, unspecified --PARENT--> [LA89] Functionally univentricular heart Def: The term “functionally univentricular heart” describes a spectrum of congenital cardiovascular malformations in which the ventricular mass may not readily lend itself to partitioning that commits one ... --CHILD--> [LA89.1] Tricuspid atresia Def: A congenital cardiovascular malformation with absence of the tricuspid valvar annulus (connection/junction) or an imperforate tricuspid valve....	[ "[LD2F.02] Embryofetopathy due to oral anticoagulant therapy\n Def: A condition caused by exposure of the embryo or fetus to anticoagulants during the antenatal period. This disease may present with optic nerve anomaly, optic atrophy, anomaly of the papilla, blindness...\n --PARENT--> [LD2F.0] Toxic or drug-related embryofetopathies\n --RELATED_TO--> [?] Uterovaginal malformation due to diethylstilbestrol syndrome\n Def: Fetal diethylstilbestrol syndrome is characterised by a group of symptoms likely to occur in children and grandchildren of a woman who was treated while pregnant with diethylstilbestrol (DES). The dru...", "[LD2F.02] Embryofetopathy due to oral anticoagulant therapy\n Def: A condition caused by exposure of the embryo or fetus to anticoagulants during the antenatal period. This disease may present with optic nerve anomaly, optic atrophy, anomaly of the papilla, blindness...\n --PARENT--> [LD2F.0] Toxic or drug-related embryofetopathies\n --CHILD--> [LD2F.00] Fetal alcohol syndrome\n Def: Fetal alcohol syndrome is a malformation syndrome caused by maternal consumption of alcohol during pregnancy. It is characterised by prenatal and/or postnatal growth deficiency (weight and/or height <...", "[NE61] Harmful effects of or exposure to noxious substances, chiefly nonmedicinal as to source, not elsewhere classified\n --EXCLUDES--> [?] Burns\n Def: A burn is an injury to the tissues caused by a pathological flux of energy which causes cellular destruction and irreversible denaturation of proteins and is primarily caused by thermal or other acute...\n --EXCLUDES--> [?] Sunburn\n Def: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight....", "[NE61] Harmful effects of or exposure to noxious substances, chiefly nonmedicinal as to source, not elsewhere classified\n --EXCLUDES--> [?] Burns\n Def: A burn is an injury to the tissues caused by a pathological flux of energy which causes cellular destruction and irreversible denaturation of proteins and is primarily caused by thermal or other acute...\n --EXCLUDES--> [?] Sunburn\n Def: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight....", "[LA89.Z] Functionally univentricular heart, unspecified\n --PARENT--> [LA89] Functionally univentricular heart\n Def: The term “functionally univentricular heart” describes a spectrum of congenital cardiovascular malformations in which the ventricular mass may not readily lend itself to partitioning that commits one ...\n --CHILD--> [LA89.2] Mitral atresia\n Def: A congenital cardiovascular malformation with absence of the mitral valvar annulus (connection/junction) or an imperforate mitral valve....", "[LA89.Z] Functionally univentricular heart, unspecified\n --PARENT--> [LA89] Functionally univentricular heart\n Def: The term “functionally univentricular heart” describes a spectrum of congenital cardiovascular malformations in which the ventricular mass may not readily lend itself to partitioning that commits one ...\n --CHILD--> [LA89.1] Tricuspid atresia\n Def: A congenital cardiovascular malformation with absence of the tricuspid valvar annulus (connection/junction) or an imperforate tricuspid valve...." ]	LD2F.02	Embryofetopathy due to oral anticoagulant therapy	[ { "from_icd11": "LD2F.02", "icd10_code": "Q862", "icd10_title": "Dysmorphism due to warfarin" }, { "from_icd11": "NE61", "icd10_code": "T5802XA", "icd10_title": "Toxic effect of carbon monoxide from motor vehicle exhaust, intentional self-harm, initial encounter" }, { "from_icd11": "NE61", "icd10_code": "T550X2A", "icd10_title": "Toxic effect of soaps, intentional self-harm, initial encounter" }, { "from_icd11": "NE61", "icd10_code": "T61781A", "icd10_title": "Other shellfish poisoning, accidental (unintentional), initial encounter" }, { "from_icd11": "NE61", "icd10_code": "T551X2A", "icd10_title": "Toxic effect of detergents, intentional self-harm, initial encounter" }, { "from_icd11": "NE61", "icd10_code": "T5891XA", "icd10_title": "Toxic effect of carbon monoxide from unspecified source, accidental (unintentional), initial encounter" }, { "from_icd11": "NE61", "icd10_code": "T63711A", "icd10_title": "Toxic effect of contact with venomous marine plant, accidental (unintentional), initial encounter" }, { "from_icd11": "NE61", "icd10_code": "T63712A", "icd10_title": "Toxic effect of contact with venomous marine plant, intentional self-harm, initial encounter" }, { "from_icd11": "NE61", "icd10_code": "T63713A", "icd10_title": "Toxic effect of contact with venomous marine plant, assault, initial encounter" }, { "from_icd11": "NE61", "icd10_code": "T63714A", "icd10_title": "Toxic effect of contact with venomous marine plant, undetermined, initial encounter" }, { "from_icd11": "NE61", "icd10_code": "T63791A", "icd10_title": "Toxic effect of contact with other venomous plant, accidental (unintentional), initial encounter" }, { "from_icd11": "NE61", "icd10_code": "T63792A", "icd10_title": "Toxic effect of contact with other venomous plant, intentional self-harm, initial encounter" }, { "from_icd11": "NE61", "icd10_code": "T63793A", "icd10_title": "Toxic effect of contact with other venomous plant, assault, initial encounter" }, { "from_icd11": "NE61", "icd10_code": "T63794A", "icd10_title": "Toxic effect of contact with other venomous plant, undetermined, initial encounter" }, { "from_icd11": "NE61", "icd10_code": "T61771A", "icd10_title": "Other fish poisoning, accidental (unintentional), initial encounter" } ]	Q862	Dysmorphism due to warfarin
The clinical course was characterized by the need of non-invasive ventilatory support during the first week of life. Due to lack of sucking/swallowing coordination, nasogastric tube feeding was initially required. Laboratory analyses including complete blood count, serum electrolytes, liver, kidney, and thyroid function tests showed normal results. Ophthalmologic examination revealed a bilateral decreased accommodation reflex, secondary to ophthalmoplegia. Except for mild enlargement of the left ventricle, major structural brain anomalies were ruled out on head US. Moreover, abdominal US documented no abnormalities, and the echocardiographic evaluation, revealed an isolated patent foramen ovale . Conversely, skeletal X-Ray confirmed the clinically observed abnormalities of the extremities, consisting of ulnar deviation of the hands, talipes equinus-varus-adductus-supinatus , in addition to proximal set and short first and fifth fingers and toes. No bone anomalies were identified in the proximal segments of the extremities, chest, spine and hips. Then, having considered the family history along with the clinical, laboratory and image findings, a targeted next generation sequencing analysis (NGS) of the genes associated to AMC and of those involved in distal arthrogryposis and digital synostosis (Table 1 ) was performed. The gain-of-function heterozygous pathogenic variant c.8181_8183delAGA of the PIEZO2 gene was identified in the proband, and the same mutation was also found in his mother. Genetic investigations of the other family members were not carried out due to restrictions related to the COVID-19 pandemic emergency occurring at the time of the hospital stay of our patient. Table 1 Genes included and quality of target NGS analysis Name HGNC Full name OMIM Coding sequence length (bases number) >5x Coverage% > 10x >20x Depth of medium coverage (x) maximum Arthrogryposis multiplex congenita ADCY6 Adenylate cyclase 6 600,294 3507 100.00 100.00 100.00 380.13 832 ASCC1 Activating signal cointegrator 1 complex subunit 1 614,215 1203 100.00 100.00 99.17 172.73 423 CNTN1 Contactin 1 600,016 3024 100.00 100.00 100.00 196.61 458 CNTNAP1 Contactin associated protein 1 602,346 4155 100.00 100.00 100.00 358.82 923 DOK7 Docking protein 7 610,285 1515 100.00 99.74 97.43 331.79 736 ERGIC1 Endoplasmic reticulum-golgi intermediate compartment 1 617,946 873 100.00 100.00 100.00 444.82 747 FKBP10 FKBP prolyl isomerase 10 607,063 1749 100.00 100.00 100.00 359.79 769 GLE1 GLE1 RNA export mediator 603,371 2097 100.00 100.00 100.00 194.62 387 KIF14 Kinesin family member 14 611,279 4947 100.00 100.00 100.00 167.48 323 LGI14 Leucine rich repeat LGI family member 4 608,303 1614 100.00 100.00 100.00 222.95 429 MUSK Muscle associated receptor tyrosine kinase 601,296 2610 100.00 100.00 100.00 222.38 508 MYBPC1 Myosin binding protein C, slow type 160,794 3522 100.00 100.00 100.00 183.71 581 MYOD1 Myogenic differentiation 1 159,970 963 100.00 100.00 100.00 623.24 1438 NUP88 Nucleoporin 88 602,552 2226 100.00 100.00 100.00 206.06 482 PIEZO2 Piezo type mechanosensitive ion channel component 2 613,629 8259 100.00 100.00 99.94 191.65 677 RAPSN Receptor associated protein of the synapse 601,592 1239 100.00 100.00 100.00 419.22 935 SCARF2 Scavenger receptor class F member 2 613,619 2598 100.00 100.00 100.00 209.97 618 SYNE1 Spectrin repeat containing nuclear envelope protein 1 608,441 26,394 100.00 100.00 100.00 193.42 680 TRIP4 Thyroid hormone receptor interactor 4 604,501 1746 100.00 100.00 100.00 140.63 238 UBA1 Ubiquitin like modifier activating enzyme 1 314,370 3177 100.00 100.00 100.00 215.59 532 VIPAS39 VPS33B late endosome and lysosome associated 608,552 1854 100.00 100.00 100.00 218.34 597 ZC4H2 Zinc finger C4H2-type containing 300,897 675 100.00 100.00 100.00 103.71 158 Distal arthrogryposis CHST14 Carbohydrate sulfotransferase 14 608,429 1131 100.00 100.00 100.00 260.38 467 DSE Dermatan sulfate epimerase 605,942 2877 100.00 100.00 100.00 206.13 547 ECEL1 Endothelin converting enzyme like 1 605,896 2328 100.00 100.00 98.80 248.47 929 FBN2 Fibrillin 2 612,570 8739 100.00 100.00 100.00 225.84 600 MYBPC1 Myosin binding protein C, slow type 160,794 3522 100.00 100.00 100.00 183.71 581 MYH3 Myosin heavy chain 3 160,720 5823 100.00 100.00 100.00 211.55 551 MYH8 Myosin heavy chain 8 160,741 5814 100.00 100.00 99.47 191.77 746 NALCN Sodium leak channel, non-selective 611,549 5217 100.00 100.00 100.00 177.57 395 PIEZO2 Piezo type mechanosensitive ion channel component 2 613,629 8259 100.00 100.00 99.94 191.65 677 SLC35A3 Solute carrier family 35 member A3 605,632 1104 100.00 100.00 100.00 156.35 264 TNNI2 Troponin I2, fast skeletal type 191,043 549 100.00 100.00 100.00 355.52 890 TNNT1 Troponin T1, slow skeletal type 191,041 837 100.00 100.00 100.00 196.36 370 Other genes ACTA1 Actin alpha 1, skeletal muscle 102,610 1134 100.00 100.00 100.00 250.29 714 AGRN Agrin 103,320 6138 100.00 100.00 99.54 351.00 897 BIN1 Bridging integrator 1 601,248 1782 100.00 100.00 100.00 283.67 580 CASK Calcium/calmodulin dependent serine protein kinase 300,172 2766 100.00 100.00 100.00 110.05 307 CFL2 Cofilin 2 601,443 501 100.00 100.00 100.00 142.68 262 CHAT Choline O-acetyltransferase 118,490 2247 100.00 100.00 98.00 234.82 481 CHRNA1 Cholinergic receptor nicotinic alpha 1 subunit 100,690 1374 100.00 100.00 100.00 219.81 422 CHRNB1 Cholinergic receptor nicotinic beta 1 subunit 100,710 1506 100.00 100.00 100.00 257.88 591 CHRND Cholinergic receptor nicotinic delta subunit 100,720 1554 100.00 100.00 100.00 326.22 666 CHRNE Cholinergic receptor nicotinic epsilon subunit 100,725 1482 100.00 100.00 100.00 311.97 705 CHRNG Cholinergic receptor nicotinic gamma subunit 100,730 1554 100.00 100.00 100.00 309.39 644 COL6A2 Collagen type VI alpha 2 chain 120,240 3060 100.00 100.00 100.00 380.62 701 COLQ Collagen like tail subunit of asymmetric acetylcholinesterase 603,033 1368 100.00 100.00 100.00 193.63 454 DHCR24 24-dehydrocholesterol reductase 606,418 1551 100.00 100.00 100.00 305.51 710 DPAGT1 Dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 191,350 1227 100.00 100.00 100.00 209.58 349 EGR2 Early growth response 2 129,010 1431 100.00 100.00 100.00 313.71 523 ERCC5 ERCC excision repair 5, endonuclease 133,530 3561 100.00 100.00 100.00 171.74 386 ERCC6 ERCC excision repair 6, chromatin remodeling factor 609,413 4482 100.00 100.00 100.00 229.78 501 EXOSC3 Exosome component 3 606,489 828 100.00 100.00 99.88 292.51 690 FHL1 Four and a half LIM domains 1 300,163 972 100.00 100.00 98.66 96.30 207 FKTN Fukutin 607,440 1386 100.00 100.00 100.00 198.58 376 GBA Glucosylceramidase beta 606,463 1611 100.00 100.00 100.00 602.97 1174 GBE1 1,4-alpha-glucan branching enzyme 1 607,839 2109 100.00 100.00 100.00 204.50 501 GFPT1 Glutamine-fructose-6-phosphate transaminase 1 138,292 2100 100.00 100.00 100.00 162.87 429 GLDN Gliomedin 608,603 1656 100.00 100.00 100.00 157.95 407 KAT6B Lysine acetyltransferase 6B 605,880 6222 100.00 100.00 100.00 276.88 1144 KLHL40 Kelch like family member 40 615,340 1866 100.00 100.00 100.00 307.58 611 MPZ Myelin protein zero 159,440 747 100.00 100.00 100.00 293.78 823 MTM1 Myotubularin 1 300,415 1812 100.00 100.00 100.00 111.02 238 MYH2 Myosin heavy chain 2 160,740 5826 100.00 100.00 100.00 200.07 480 NEB Nebulin 161,650 19,974 100.00 100.00 100.00 193.18 564 PLOD2 Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 601,865 2277 100.00 100.00 100.00 166.51 435 PMM2 Phosphomannomutase 2 601,785 741 100.00 100.00 100.00 202.86 369 RARS2 Arginyl-tRNA synthetase 2, mitochondrial 611,524 1737 100.00 100.00 100.00 164.02 377 SCO2 SCO cytochrome c oxidase assembly protein 2 604,272 801 100.00 100.00 100.00 325.72 627 TGFB3 Transforming growth factor beta 3 190,230 1239 100.00 100.00 100.00 280.94 449 TK2 Thymidine kinase 2 188,250 798 100.00 100.00 99.25 212.26 474 TNNT3 Troponin T3, fast skeletal type 600,692 771 100.00 100.00 100.00 286.03 564 TPM3 Tropomyosin 3 191,030 858 100.00 100.00 100.00 181.98 368 TRPV4 Transient receptor potential cation channel subfamily V member 4 605,427 2616 100.00 100.00 100.00 308.90 554 TSEN2 tRNA splicing endonuclease subunit 2 608,753 1398 100.00 100.00 100.00 223.97 579 TSEN54 tRNA splicing endonuclease subunit 54 608,755 1581 100.00 99.11 97.28 273.41 462 VRK1 VRK serine/threonine kinase 1 602,168 1191 100.00 100.00 100.00 177.52 298 ZBTB42 Zinc finger and BTB domain containing 42 613,915 1269 100.00 100.00 100.00 372.32 655 Digital synostosis BHLHA9 Basic helix-loop-helix family member a9 615,416 708 100.00 89.27 81.50 135.39 384 BMPR1B Bone morphogenetic protein receptor type 1B 603,248 1599 100.00 100.00 100.00 210.72 332 CHSY1 Chondroitin sulfate synthase 1 608,183 2409 100.00 99.63 98.13 215.28 398 FGF9 Fibroblast growth factor 9 600,921 627 100.00 100.00 100.00 187.26 287 GDF5 Growth differentiation factor 5 601,146 1506 100.00 100.00 100.00 364.68 699 GDF6 Growth differentiation factor 6 601,147 1368 100.00 100.00 100.00 262.93 704 IHH Indian hedgehog signaling molecule 600,726 1236 100.00 100.00 100.00 303.92 420 NOG Noggin 602,991 699 100.00 100.00 100.00 416.59 809 PCNT Pericentrin 605,925 10,011 100.00 100.00 99.91 207.88 569 PTDSS1 Phosphatidylserine synthase 1 612,792 1422 100.00 100.00 100.00 197.51 399vements restriction	4.28125	0.546875	sec[1]/p[1]	en	0.999995	PMC9336156	https://doi.org/10.1186/s13052-022-01329-z	[ "receptor", "protein", "type", "subunit", "family", "member", "skeletal", "associated", "myosin", "cholinergic" ]	[ { "code": "5A61.0", "title": "Hypopituitarism" }, { "code": "4A01.0Y", "title": "Other specified immunodeficiencies with predominantly antibody defects" }, { "code": "LD2A.4", "title": "46,XY disorder of sex development due to androgen resistance" }, { "code": "LD24.04", "title": "Chondrodysplasia punctata" }, { "code": "4A00.Y", "title": "Other specified primary immunodeficiencies due to disorders of innate immunity" }, { "code": "5B71", "title": "Protein deficiency" }, { "code": "5B7Z", "title": "Unspecified undernutrition" }, { "code": "DA96.02", "title": "Malabsorption or intolerance of specific nutrients" }, { "code": "MF96.Z", "title": "Proteinuria, unspecified" }, { "code": "3B61.1", "title": "Acquired thrombophilia" } ]	=== ICD-11 CODES FOUND === [5A61.0] Hypopituitarism Definition: A disorder manifesting a deficiency or decrease of one or more pituitary hormones, which is caused by a variety of diseases such as tumour, trauma/surgery, irradiation, inflammation and haemorrhage/infarction. Also known as: Hypopituitarism \| subpituitarism \| hypophyseal dystrophy \| hypohypophysism \| anterior pituitary insufficiency (in part) Includes: pituitary cachexia \| pituitary short stature [4A01.0Y] Other specified immunodeficiencies with predominantly antibody defects Also known as: Other specified immunodeficiencies with predominantly antibody defects \| Common variable immunodeficiency \| B-cell activating factor receptor deficiency \| BAFF - [ B-cell activating factor] receptor deficiency \| Cluster of differentiation 19 deficiency [LD2A.4] 46,XY disorder of sex development due to androgen resistance Definition: Androgen insensitivity syndrome (AIS) is a disorder of sex development (DSD) characterised by the presence of female external genitalia, ambiguous genitalia or variable defects in virilization in a 46,XY individual with absent or partial responsiveness to age-appropriate levels of androgens. It comprises two clinical subgroups: complete AIS (CAIS) and partial AIS (PAIS). Also known as: 46,XY disorder of sex development due to androgen resistance \| Androgen resistance syndrome \| Testicular feminization syndrome \| Androgen insensitivity syndrome \| Goldberg-Maxwell syndrome [LD24.04] Chondrodysplasia punctata Also known as: Chondrodysplasia punctata \| chondrodysplasia punctata (stippled epiphyses) group \| chondrodysplasia punctata congenita \| dysplasia punctata epiphysis \| dysplasia punctata [4A00.Y] Other specified primary immunodeficiencies due to disorders of innate immunity Also known as: Other specified primary immunodeficiencies due to disorders of innate immunity \| Autoinflammatory syndromes with immunodeficiency \| Autoinflammatory disease due to interleukin-1 receptor antagonist deficiency \| Sterile multifocal osteomyelitis with periostitis and pustulosis \| Deficiency of interleukin 1 receptor antagonist [5B71] Protein deficiency Also known as: Protein deficiency \| protein deprivation [5B7Z] Unspecified undernutrition Also known as: Unspecified undernutrition \| Malnutrition NOS \| nutritional deficiency NOS \| nutritional depletion NOS \| severe malnutrition NOS [DA96.02] Malabsorption or intolerance of specific nutrients Definition: Food intolerance is a term used for difficulty in digesting a food due to various physiological responses associated with a particular food, or compound found. Food intolerance should not be mistaken for food allergy, which is primarily involving the immune reaction against the food. Also known as: Malabsorption or intolerance of specific nutrients \| Carbohydrate intolerance other than lactose \| disorder of carbohydrate absorption \| Malabsorption due to intolerance to carbohydrate \| carbohydrate intolerance [MF96.Z] Proteinuria, unspecified Also known as: Proteinuria, unspecified \| Proteinuria \| Albuminuria NOS \| Proteinuria NOS [3B61.1] Acquired thrombophilia Definition: A disease caused by determinants arising after birth. This disease is characterised by abnormality of blood coagulation that increases the risk of thrombosis, clots in blood vessels. This disease may present with deep vein thrombosis or pulmonary embolism. Confirmation is identification of abnormal blood coagulation in a blood sample. Also known as: Acquired thrombophilia \| Gaisbock syndrome \| polycythaemia due to stress \| stress erythrocytosis \| stress polycythaemia === GRAPH WALKS === --- Walk 1 --- [5A61.0] Hypopituitarism Def: A disorder manifesting a deficiency or decrease of one or more pituitary hormones, which is caused by a variety of diseases such as tumour, trauma/surgery, irradiation, inflammation and haemorrhage/in... --RELATED_TO--> [?] Argonz-del Castillo Syndrome --PARENT--> [?] Functional hyperprolactinoma Def: Increased blood level of prolactin caused by non-tumourous mechanisms such as disruption of pituitary stalk, severe hypothyroidism, or administration of dopamine receptor antagonists.... --- Walk 2 --- [5A61.0] Hypopituitarism Def: A disorder manifesting a deficiency or decrease of one or more pituitary hormones, which is caused by a variety of diseases such as tumour, trauma/surgery, irradiation, inflammation and haemorrhage/in... --RELATED_TO--> [?] Prader-Willi syndrome Def: Prader-Willi syndrome is a rare genetic disorder characterised by hypothalamic-pituitary abnormalities with severe hypotonia during the neonatal period and first two years of life and the onset of hyp... --PARENT--> [?] Syndromes with obesity as a major feature --- Walk 3 --- [4A01.0Y] Other specified immunodeficiencies with predominantly antibody defects --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects... --CHILD--> [4A01.01] Immunodeficiencies with severe reduction in at least two serum immunoglobulin isotypes with normal or low numbers of B cells Def: This refers to a nonfamilial type of primary immune deficiency disease characterised by a reduction in at least two serum immunoglobulin isotypes. Circulating B cells may be normal or low.... --- Walk 4 --- [4A01.0Y] Other specified immunodeficiencies with predominantly antibody defects --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects... --CHILD--> [4A01.01] Immunodeficiencies with severe reduction in at least two serum immunoglobulin isotypes with normal or low numbers of B cells Def: This refers to a nonfamilial type of primary immune deficiency disease characterised by a reduction in at least two serum immunoglobulin isotypes. Circulating B cells may be normal or low.... --- Walk 5 --- [LD2A.4] 46,XY disorder of sex development due to androgen resistance Def: Androgen insensitivity syndrome (AIS) is a disorder of sex development (DSD) characterised by the presence of female external genitalia, ambiguous genitalia or variable defects in virilization in a 46... --PARENT--> [LD2A] Malformative disorders of sex development Def: Any condition caused by failure of the genitals to correctly develop during the antenatal period.... --EXCLUDES--> [?] Adrenogenital disorders Def: Disorders of the reproductive system resulting from pathologic androgen production secondary to abnormalities in cortisol and/or aldosterone production... --- Walk 6 --- [LD2A.4] 46,XY disorder of sex development due to androgen resistance Def: Androgen insensitivity syndrome (AIS) is a disorder of sex development (DSD) characterised by the presence of female external genitalia, ambiguous genitalia or variable defects in virilization in a 46... --PARENT--> [LD2A] Malformative disorders of sex development Def: Any condition caused by failure of the genitals to correctly develop during the antenatal period.... --RELATED_TO--> [?] Congenital adrenal hyperplasia Def: Congenital adrenal hyperplasia (CAH) refers to a group of conditions associated with either complete (classical form) or partial (non-classical) anomalies in the biosynthesis of adrenal hormones. The ...	[ "[5A61.0] Hypopituitarism\n Def: A disorder manifesting a deficiency or decrease of one or more pituitary hormones, which is caused by a variety of diseases such as tumour, trauma/surgery, irradiation, inflammation and haemorrhage/in...\n --RELATED_TO--> [?] Argonz-del Castillo Syndrome\n --PARENT--> [?] Functional hyperprolactinoma\n Def: Increased blood level of prolactin caused by non-tumourous mechanisms such as disruption of pituitary stalk, severe hypothyroidism, or administration of dopamine receptor antagonists....", "[5A61.0] Hypopituitarism\n Def: A disorder manifesting a deficiency or decrease of one or more pituitary hormones, which is caused by a variety of diseases such as tumour, trauma/surgery, irradiation, inflammation and haemorrhage/in...\n --RELATED_TO--> [?] Prader-Willi syndrome\n Def: Prader-Willi syndrome is a rare genetic disorder characterised by hypothalamic-pituitary abnormalities with severe hypotonia during the neonatal period and first two years of life and the onset of hyp...\n --PARENT--> [?] Syndromes with obesity as a major feature", "[4A01.0Y] Other specified immunodeficiencies with predominantly antibody defects\n --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects\n Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects...\n --CHILD--> [4A01.01] Immunodeficiencies with severe reduction in at least two serum immunoglobulin isotypes with normal or low numbers of B cells\n Def: This refers to a nonfamilial type of primary immune deficiency disease characterised by a reduction in at least two serum immunoglobulin isotypes. Circulating B cells may be normal or low....", "[4A01.0Y] Other specified immunodeficiencies with predominantly antibody defects\n --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects\n Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects...\n --CHILD--> [4A01.01] Immunodeficiencies with severe reduction in at least two serum immunoglobulin isotypes with normal or low numbers of B cells\n Def: This refers to a nonfamilial type of primary immune deficiency disease characterised by a reduction in at least two serum immunoglobulin isotypes. Circulating B cells may be normal or low....", "[LD2A.4] 46,XY disorder of sex development due to androgen resistance\n Def: Androgen insensitivity syndrome (AIS) is a disorder of sex development (DSD) characterised by the presence of female external genitalia, ambiguous genitalia or variable defects in virilization in a 46...\n --PARENT--> [LD2A] Malformative disorders of sex development\n Def: Any condition caused by failure of the genitals to correctly develop during the antenatal period....\n --EXCLUDES--> [?] Adrenogenital disorders\n Def: Disorders of the reproductive system resulting from pathologic androgen production secondary to abnormalities in cortisol and/or aldosterone production...", "[LD2A.4] 46,XY disorder of sex development due to androgen resistance\n Def: Androgen insensitivity syndrome (AIS) is a disorder of sex development (DSD) characterised by the presence of female external genitalia, ambiguous genitalia or variable defects in virilization in a 46...\n --PARENT--> [LD2A] Malformative disorders of sex development\n Def: Any condition caused by failure of the genitals to correctly develop during the antenatal period....\n --RELATED_TO--> [?] Congenital adrenal hyperplasia\n Def: Congenital adrenal hyperplasia (CAH) refers to a group of conditions associated with either complete (classical form) or partial (non-classical) anomalies in the biosynthesis of adrenal hormones. The ..." ]	5A61.0	Hypopituitarism	[ { "from_icd11": "5A61.0", "icd10_code": "E230", "icd10_title": "Hypopituitarism" }, { "from_icd11": "5A61.0", "icd10_code": "Q044", "icd10_title": "Septo-optic dysplasia of brain" }, { "from_icd11": "5A61.0", "icd10_code": "E231", "icd10_title": "Drug-induced hypopituitarism" }, { "from_icd11": "LD2A.4", "icd10_code": "E3450", "icd10_title": "Androgen insensitivity syndrome, unspecified" }, { "from_icd11": "LD2A.4", "icd10_code": "E3451", "icd10_title": "Complete androgen insensitivity syndrome" }, { "from_icd11": "LD2A.4", "icd10_code": "E345", "icd10_title": "Androgen insensitivity syndrome" }, { "from_icd11": "LD24.04", "icd10_code": "Q773", "icd10_title": "Chondrodysplasia punctata" }, { "from_icd11": "5B71", "icd10_code": "E46", "icd10_title": "Unspecified protein-calorie malnutrition" }, { "from_icd11": "5B71", "icd10_code": "E440", "icd10_title": "Moderate protein-calorie malnutrition" }, { "from_icd11": "5B71", "icd10_code": "E441", "icd10_title": "Mild protein-calorie malnutrition" }, { "from_icd11": "5B71", "icd10_code": "E640", "icd10_title": "Sequelae of protein-calorie malnutrition" }, { "from_icd11": "5B71", "icd10_code": "E44", "icd10_title": "Protein-calorie malnutrition of moderate and mild degree" }, { "from_icd11": "5B71", "icd10_code": "E45", "icd10_title": "Retarded development following protein-calorie malnutrition" }, { "from_icd11": "5B7Z", "icd10_code": "E43", "icd10_title": "Unspecified severe protein-calorie malnutrition" }, { "from_icd11": "5B7Z", "icd10_code": "E538", "icd10_title": "Deficiency of other specified B group vitamins" } ]	E230	Hypopituitarism
A 79-year-old man with a sustained virological response due to liver cirrhosis secondary to hepatitis C virus infection was diagnosed with a liver tumor on regular abdominal ultrasonography. The tumor, suspected to be HCC, was found in liver segment 5 on enhanced computed tomography (CT), and the patient was referred to our department for detailed examination and treatment. The patient was diagnosed with congenital FV deficiency approximately 20 years ago, and was hospitalized twice for epistaxis. As indicated in Table 1 , blood tests showed markedly decreased FV activity of < 2.6%, PT activity of 11%, and prolonged APTT by 100.3 s, which are indicative of coagulopathy. Other coagulation factor activities, were within the normal range. The patient’s FV activity had been tested several times over the past 20 years and consistently resulted in markedly decreased FV activity. No FV inhibitors were detected using the Bethesda assay at our hospital . Cross-mixing tests revealed a pattern of coagulation factor deficiency. Although he had not undergone genetic testing, based on the blood test results and the reproducibility and ubiquity of these blood tests, he was diagnosed with congenital FV deficiency. The liver function reserve was Child–Pugh grade B (7 points). Liver damage was grade A, and the hepatic reserve was judged to be good . As no esophageal varices, gastric varices, or splenomegaly were observed, severe portal hypertension was ruled out. We consulted a cardiologist regarding the patient's cardiac function. The patient’s exercise tolerance was good, and no abnormalities were observed in active cardiac conditions and the revised cardiac risk index . Based on the above findings, the patient's cardiac function was considered acceptable for surgery, although caution was advised against excessive fluid infusion. Pulmonary function was good. Computed tomography (CT) showed a 24 mm-sized nodule in liver segment 5, which was deeply stained in the arterial phase and washed out in the delayed phase . Magnetic resonance imaging also showed a contrast effect in the segment 5 tumor in the early phase and wash-out in the delayed phase. A well-differentiated HCC was suspected. Based on the radiological findings, the patient was diagnosed with HCC (T2N0M0 stage II, according to the 8th edition of the Union for International Cancer Control staging system). Based on the Barcelona Clinic Liver Cancer (BCLC) staging algorithm, this case was regarded as early stage (A). It was confirmed that surgery was recommended as the tumor was an isolated nodule, and portal pressure and bilirubin were normal. We also considered radiofrequency ablation (RFA); however, since the tumor was in contact with the Glissonean pedicle 5 + 6 and RFA may cause bile duct injury due to a rapid increase in intratumoral pressure during cauterization, surgery was judged to be superior from the viewpoint of safety and curability. However, invasive treatment involved a high risk due to the coexistence of congenital FV deficiency. After discussing the safety of the operation with a hematologist, we decided that surgery was possible by transfusing fresh frozen plasma (FFP) during the perioperative period, maintaining FV activity at ≥ 15% and closely monitoring PT and APTT. Two days before the operation, 480 mL (approximately 7.4 mL/kg) of FFP was transfused, coagulation FV activity was ≥ 15% was confirmed, and PT and APTT were reduced. As our hospital can only measure FV activity once per week, we estimated the necessary FFP based on the above results and created an FFP transfusion plan. The FV activity immediately before the operation was 14.5%, and the operation was performed with a transfusion of 480 mL of FFP. The changes in perioperative coagulation data are presented in Table 2 . The surgical procedure and results of this case were as follows: the patient was placed in the left lateral decubitus position, and six ports, including a Pringle method taping port, were used. The pneumoperitoneum pressure was maintained at 10 mmHg. An ultrasonic scalpel and Cavitron Ultrasonic Surgical Aspirator (CUSA; AMCO Inc., Tokyo, Japan) were used for the incision of the liver parenchyma. The tip of the CUSA was connected to a VIO 300 D generator (ERBE Elektromedizin GmbH, Tubingen, Germany), and hemostasis was performed in soft coagulation mode using bipolar forceps held in the operator's left hand. Intermittent pedicle clamps (15-minocclusion, 5-min reperfusion, Pringle method) were used during parenchymal cutting. Hemodynamic control aimed at maintaining low central venous pressure (< 5 mmHg) under anesthesia and weight loss perfusion minimizes blood loss Airway pressure was maintained at 14–16 cmH 2 O, reducing central venous pressure and volumetric perfusion. We adjusted the volume of transfusion during liver parenchymal cutting to approximately 5 mL/kg/h and aimed to achieve a urine volume of 0.5 mL/kg/h. Preoperative three-dimensional simulation was conducted using a SYNAPSE VINCENT volume analyzer (Fujiflim Co., Tokyo, Japan) . To resect the Glissonean pedicle 5 + 6, we first secured it by clamping . Segments 5 and 6 of the liver were identified by negative staining using indocyanine green fluorescent imaging navigation, and hepatectomy was performed Bleeding was minimized during the transection of the liver parenchyma and no bleeding tendency was observed . After hepatectomy, no bleeding was observed on the cut surface of the liver . Tachosil ® was applied around the hepatic vein and Gleason stump, and Bolheal ® was dripped onto the cut surface of the liver. Surgical procedures included laparoscopic hepatic segment 5 + 6 subsegmental resection and cholecystectomy. The operative time was 445 min, and the amount of intraoperative bleeding was 171 mL. The cumulative time of the Pringle method was 208 min and 51 s. Immediately after the operation, FV activity was 17.7%, and no bleeding from the wound or drain was observed. FFP (240 mL) was transfused on postoperative days 1 and 2. FV activity decreased to < 2.6% on the fifth postoperative day; therefore, another 240 mL of FFP was transfused and the drain was removed. The postoperative course was uneventful, and the patient was discharged 8 days after the operation . Postoperative pathological examination revealed that the tumor was macroscopically demarcated and accompanied by a capsule, which was diagnosed as a stage IB (pT1bN0M0) HCC . One month after the surgery, no complications were observed. Table1 Preoperative blood test results Inspection items Results Reference range WBC (10 3 /μl) 6.9 4.0–9.6 Hb (g/dl) 14.9 13.2–17.3 Platelet count (10 3 /μl) 179 160–350 T-bil (mg/dL) 0.4 0.3–1.2 D-Bil (mg/dL) 0.04 0.0–0.2 AST (U/L) 30 13–33 ALT (U/L) 34 8–42 Alb (g/dl) 4.4 3.9–5.0 BNP (pg/mL) 5.6 0–18.4 ICG-R15 (%) 10.9 PT activity (%) 11 0.85–1.23 PT-INR 4.28 APTT (second) 100.3 27.0–39.0 Factor I (%) 82.9 70–120 Factor V (%) 2.6 70–120 Factor VII (%) 98.3 70–120 Factor VIII (%) 183.7 70–120 Factor IX (%) 108.3 70–120 Factor X (%) 85 70–120 Factor XI (%) 101.2 70–120 Factor XII (%) 86.3 70–120 Von Willebrand factor (%) 183 70–120 Factor V inhibitor (–) Factor VIII-like antigen (%) 269 70–120 PT prothrombin time, APTT activated partial thromboplastin time Fig. 1 Dynamic abdominal CT imaging findings. a Arterial phase, b portal vein phase, c delayed phase. A nodule measuring 24 mm was found in hepatic segment 5, which was deeply stained in the arterial phase and washed out during the delayed phase Table 2 Perioperative blood coagulation data transition POD-2 (Before FFP) POD -2 (After FFP) POD-1 POD 0 (Preoperative) POD0 (Postoperative) POD 1 POD 2 POD 3 POD 5 POD 7 PT activity (%) 11 55 43 44 49 39 34 36 22 24 PT-INR 4.02 1.31 1.48 1.46 1.39 1.57 1.64 2.31 2.31 2.08 APTT (s) 95.5 36.9 37.8 38 35.9 40.2 46.4 45.2 60.8 56.4 Factor V activity (%) < 2.6 19.4 12.7 14.5 17.7 11.8 7.4 – < 2.6 – POD postoperative day, FFP fresh frozen plasma, FV factor V, PT prothrombin time, APTT activated partial thromboplastin time Fig. 2 Intraoperative findings. a Three-dimensional image of hepatectomy simulation. The tumor was found in the hepatic segment 5 of the cranial side of the right hepatic vein (arrowhead). We performed a simulation in which P5 + 6 (arrow) was scheduled to be resected. b Captured image after clamping the Glissonean pedicle 5 + 6 (arrow). c Cut surface of the liver during transection of the liver parenchyma. d Cut surface of the liver after hepatectomy. The Glissonean pedicle 5 + 6 (arrow) is collectively resected using the Signia™ stapling system (Covidien Japan, Tokyo) Fig. 3 Perioperative treatment course and changes in coagulation data. FV activity increased with FFP transfusion and remained at approximately 15%. The patient consumed food on the first night after the operation, the drain was removed on the fifth day postoperatively, and the patient was discharged on the eighth day postoperatively. FV factor V, PT prothrombin time, APTT activated partial thromboplastin time, FFP fresh frozen plasma, POD postoperative day Fig. 4 Macroscopic findings. a Resection specimen of the hepatic segment 5 + 6 subsegmental. b Cross section of the tumor. The tumor was 2.6 × 2.1 × 1.8 cm in size with a capsule and a well-defined white nodule	4.078125	0.974121	sec[1]/p[0]	en	0.999998	36271957	https://doi.org/10.1186/s40792-022-01559-7	[ "liver", "factor", "activity", "tumor", "phase", "aptt", "time", "segment", "coagulation", "hepatic" ]	[ { "code": "DB9Z", "title": "Diseases of liver, unspecified" }, { "code": "DB97.Z", "title": "Inflammatory liver disease, unspecified" }, { "code": "DB99.7", "title": "Hepatic failure without mention whether acute or chronic" }, { "code": "LB20.0Y", "title": "Other specified structural developmental anomalies of liver" }, { "code": "LB20.0Z", "title": "Structural developmental anomalies of liver, unspecified" }, { "code": "3B14.0", "title": "Hereditary deficiency of factor I" }, { "code": "3B14.Z", "title": "Other inherited coagulation factor deficiency with bleeding tendency, unspecified" }, { "code": "3B14.1", "title": "Hereditary factor X deficiency" }, { "code": "3B11.Z", "title": "Hereditary factor IX deficiency, unspecified" }, { "code": "PB6Z", "title": "Unspecified unintentional cause of morbidity or mortality" } ]	=== ICD-11 CODES FOUND === [DB9Z] Diseases of liver, unspecified Also known as: Diseases of liver, unspecified \| liver disease \| liver condition NOS \| organ liver disease \| hepatopathy [DB97.Z] Inflammatory liver disease, unspecified Also known as: Inflammatory liver disease, unspecified \| Certain specified inflammatory liver diseases \| Nonspecific reactive hepatitis \| inflammatory liver disease \| hepatitis NOS [DB99.7] Hepatic failure without mention whether acute or chronic Also known as: Hepatic failure without mention whether acute or chronic \| liver decompensation \| liver function failure \| hepatic failure NOS \| liver failure NOS [LB20.0Y] Other specified structural developmental anomalies of liver Also known as: Other specified structural developmental anomalies of liver \| Alagille syndrome \| Alagille-Watson syndrome \| Arteriohepatic dysplasia \| Syndromic bile duct paucity [LB20.0Z] Structural developmental anomalies of liver, unspecified Also known as: Structural developmental anomalies of liver, unspecified \| Structural developmental anomalies of liver \| Malformations of liver \| congenital anomaly of liver \| congenital malformation of liver [3B14.0] Hereditary deficiency of factor I Definition: Congenital deficiencies of fibrinogen are coagulation disorders characterised by bleeding symptoms ranging from mild to severe resulting from reduced quantity and/or quality of circulating fibrinogen. Afibrinogenaemia (complete absence of fibrinogen) and hypofibrinogenaemia (reduced plasma fibrinogen concentration) correspond to quantitative anomalies of fibrinogen while dysfibrinogenaemia corresponds to a functional anomaly of fibrinogen. Hypo- and dysfibrinogenaemia may be frequently combined Also known as: Hereditary deficiency of factor I \| Deficiency of factor 1 \| Hereditary fibrinogen deficiency \| Deficiency of fibrinogen \| congenital fibrinogenopenia [3B14.Z] Other inherited coagulation factor deficiency with bleeding tendency, unspecified Also known as: Other inherited coagulation factor deficiency with bleeding tendency, unspecified \| Other inherited coagulation factor deficiency with bleeding tendency \| Hereditary factor V deficiency \| Proaccelerin deficiency \| Owren disease [3B14.1] Hereditary factor X deficiency Definition: Congenital factor X deficiency is an inherited bleeding disorder with a decreased antigen and/or activity of factor X (FX) and characterised by mild to severe bleeding symptoms. Also known as: Hereditary factor X deficiency \| Congenital Stuart factor deficiency \| Stuart-Prower factor deficiency \| Deficiency of factor X \| congenital factor x deficiency [3B11.Z] Hereditary factor IX deficiency, unspecified Also known as: Hereditary factor IX deficiency, unspecified \| Hereditary factor IX deficiency \| factor 9 deficiency \| factor IX deficiency \| hereditary factor IX deficiency disease [PB6Z] Unspecified unintentional cause of morbidity or mortality Also known as: Unspecified unintentional cause of morbidity or mortality \| Exposure to unspecified factor \| Exposure to unspecified factor causing fracture \| Exposure to unspecified factor causing other and unspecified injury \| accidental cause NOS === GRAPH WALKS === --- Walk 1 --- [DB9Z] Diseases of liver, unspecified --PARENT--> [?] Diseases of liver --EXCLUDES--> [?] Unspecified jaundice Def: A clinical manifestation of hyperbilirubinemia of unspecified origin, characterised by the yellowish staining of the skin; mucus membranes and sclera.... --- Walk 2 --- [DB9Z] Diseases of liver, unspecified --PARENT--> [?] Diseases of liver --RELATED_TO--> [?] Viral hepatitis Def: A group of liver diseases caused by infection with one or more of the five hepatitis viruses, hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus and hepatitis E viruses. The in... --- Walk 3 --- [DB97.Z] Inflammatory liver disease, unspecified --PARENT--> [DB97] Certain specified inflammatory liver diseases --RELATED_TO--> [?] Hepatic sarcoidosis Def: This is a syndrome involving abnormal collections of chronic inflammatory cells (granulomas) that can form as nodules in multiple organs, of the liver.... --- Walk 4 --- [DB97.Z] Inflammatory liver disease, unspecified --PARENT--> [DB97] Certain specified inflammatory liver diseases --EXCLUDES--> [?] Acute or subacute hepatic failure Def: Acute and subacute liver failure is characterised by onset of coagulopathy and/or hepatic encephalopathy within 8 weeks of onset of symptoms in a patient without previously known liver diseases.... --- Walk 5 --- [DB99.7] Hepatic failure without mention whether acute or chronic --PARENT--> [DB99] Certain specified diseases of liver Def: This is a group of conditions characterised as being in or associated with the liver that are not classified elsewhere.... --CHILD--> [DB99.2] Hepatorenal syndrome --- Walk 6 --- [DB99.7] Hepatic failure without mention whether acute or chronic --PARENT--> [DB99] Certain specified diseases of liver Def: This is a group of conditions characterised as being in or associated with the liver that are not classified elsewhere.... --RELATED_TO--> [?] Cirrhotic cardiomyopathy Def: Cirrhotic cardiomyopathy is defined as chronic cardiac dysfunction in patients with cirrhosis characterised by blunted contractile responsiveness to stress/exercise and-or altered diastolic relaxation...	[ "[DB9Z] Diseases of liver, unspecified\n --PARENT--> [?] Diseases of liver\n --EXCLUDES--> [?] Unspecified jaundice\n Def: A clinical manifestation of hyperbilirubinemia of unspecified origin, characterised by the yellowish staining of the skin; mucus membranes and sclera....", "[DB9Z] Diseases of liver, unspecified\n --PARENT--> [?] Diseases of liver\n --RELATED_TO--> [?] Viral hepatitis\n Def: A group of liver diseases caused by infection with one or more of the five hepatitis viruses, hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus and hepatitis E viruses. The in...", "[DB97.Z] Inflammatory liver disease, unspecified\n --PARENT--> [DB97] Certain specified inflammatory liver diseases\n --RELATED_TO--> [?] Hepatic sarcoidosis\n Def: This is a syndrome involving abnormal collections of chronic inflammatory cells (granulomas) that can form as nodules in multiple organs, of the liver....", "[DB97.Z] Inflammatory liver disease, unspecified\n --PARENT--> [DB97] Certain specified inflammatory liver diseases\n --EXCLUDES--> [?] Acute or subacute hepatic failure\n Def: Acute and subacute liver failure is characterised by onset of coagulopathy and/or hepatic encephalopathy within 8 weeks of onset of symptoms in a patient without previously known liver diseases....", "[DB99.7] Hepatic failure without mention whether acute or chronic\n --PARENT--> [DB99] Certain specified diseases of liver\n Def: This is a group of conditions characterised as being in or associated with the liver that are not classified elsewhere....\n --CHILD--> [DB99.2] Hepatorenal syndrome", "[DB99.7] Hepatic failure without mention whether acute or chronic\n --PARENT--> [DB99] Certain specified diseases of liver\n Def: This is a group of conditions characterised as being in or associated with the liver that are not classified elsewhere....\n --RELATED_TO--> [?] Cirrhotic cardiomyopathy\n Def: Cirrhotic cardiomyopathy is defined as chronic cardiac dysfunction in patients with cirrhosis characterised by blunted contractile responsiveness to stress/exercise and-or altered diastolic relaxation..." ]	DB9Z	Diseases of liver, unspecified	[ { "from_icd11": "DB9Z", "icd10_code": "K7681", "icd10_title": "Hepatopulmonary syndrome" }, { "from_icd11": "DB9Z", "icd10_code": "K7689", "icd10_title": "Other specified diseases of liver" }, { "from_icd11": "DB9Z", "icd10_code": "K769", "icd10_title": "Liver disease, unspecified" }, { "from_icd11": "DB9Z", "icd10_code": "K77", "icd10_title": "Liver disorders in diseases classified elsewhere" }, { "from_icd11": "DB9Z", "icd10_code": "K762", "icd10_title": "Central hemorrhagic necrosis of liver" }, { "from_icd11": "DB9Z", "icd10_code": "K70-K77", "icd10_title": "" }, { "from_icd11": "DB9Z", "icd10_code": "K778", "icd10_title": "" }, { "from_icd11": "DB9Z", "icd10_code": "K72", "icd10_title": "Hepatic failure, not elsewhere classified" }, { "from_icd11": "DB9Z", "icd10_code": "K76", "icd10_title": "Other diseases of liver" }, { "from_icd11": "DB9Z", "icd10_code": "K768", "icd10_title": "Other specified diseases of liver" }, { "from_icd11": "DB97.Z", "icd10_code": "K7581", "icd10_title": "Nonalcoholic steatohepatitis (NASH)" }, { "from_icd11": "DB97.Z", "icd10_code": "K7589", "icd10_title": "Other specified inflammatory liver diseases" }, { "from_icd11": "DB97.Z", "icd10_code": "K759", "icd10_title": "Inflammatory liver disease, unspecified" }, { "from_icd11": "DB97.Z", "icd10_code": "K752", "icd10_title": "Nonspecific reactive hepatitis" }, { "from_icd11": "DB97.Z", "icd10_code": "K75", "icd10_title": "Other inflammatory liver diseases" } ]	K7681	Hepatopulmonary syndrome
A 65-year old male patient was referred to our hospital with several space-occupying lesions in inferior lobe of right lung and enlarged lymph nodes in mediastinum and bilateral hilum detected occasionally by chest computed tomography (CT) scanning during the annual health examination in April 2015 . Sequential brain magnetic resonance imaging (MRI) showed a space-occupying lesion in left parietal lobe . One of the lesions in right lung obtained by percutaneous lung biopsy (PNLB) was proved to be adenocarcinoma . Subsequent drive gene analysis with the method of amplification refractory mutation system (ARMS) using a collected tissue sample suggested a deletion of EGFR exon 19 without T790 M mutation. Hence, a clinical diagnosis was made as adenocarcinoma in inferior lobe of right lung, in association with multiple lesions among bilateral lungs, enlargement of lymph nodes in mediastinum and bilateral hilum, and solitary lesion in left parietal lobe of brain suggesting metastasis . The patient was treated with two cycles of chemotherapy (pemetrexed plus cisplatin) as first-line therapy until June 2015, due to the delayed report of drive gene analysis. After the finish of chemotherapy, repeating chest CT scan revealed an increased lump in inferior lobe of right lung, as well as lymph nodes in mediastinum and bilateral hilum . Brain MRI in the same week showed a stable node . We therefore, evaluated the efficacy of the first-line chemotherapy as progressive disease (PD) according to response evaluation criteria in solid tumors (RECIST version 1.1). Icotinib was then administrated as the second-line treatment in June 2015. Subsequent CT scans, as expected, revealed a partial response (PR) for lesions in lung and a complete response (CR) in brain in the following 8months . In February 2016, regular chest CT scanning showed a secondary enlargement of neoplasm in primary location of right lung . Next-generation sequencing (NGS) technique using the patient’s plasma sample suggested an acquired T790 M mutation by frequency of 4% accompanied with the deletion of EGFR exon 19 by 7% . The third-generation TKI of AZD9291, therefore, was prescribed as the third-line therapy in March 2016. After a ten-months duration of response , significant PD of lump in inferior lobe of right lung with atelectasis was detected again by chest CT scanning in January 2017 , while without any lesions in brain . Hence, two cycles of cytotoxic drug with docetaxel were administrated as the fourth-line management then. However, the re-enlargement of primary neoplasm in lung and multiply emerging lesions in brain signified a PD again in March 2017 , with symptoms of cough and hemoptysis aggravated seriously. Repeating NGS with plasma was developed on March 10th 2017. It was detected that the deletion of EGFR exon 19 (p745–750 del) with frequency by 78.3% and T790 M mutation by 0.2%, with concurring Leu792H mutation by 0.2%, rather than C797S mutation . In addition to those, other drive genes in the NGS panel including anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 (ROS1), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), RET proto-oncogene (RET), V-raf murine sarcoma viral oncogene homologB1 (BRAF), receptor tyrosine-protein kinase erbB-2 (ERBB2), RAC-alpha serine/threonine-protein kinase (AKT1), discoidin domain receptor tyrosine kinase 2 (DDR2), fibroblast growth factor receptor 1 (FGFR1), MNNG HOS transforming gene (MET), phosphatase and tensin homolog (PTEN), phosphatidylinosito-4,5-bisphosphate 3-kinase (PIK3CA), and mitogen-activated protein kinase 1 (MAP2K1) were detected as wild type. In view of the primary resistance to chemotherapy, lack of potentially effective selection, and high frequency of EGFR exon 19 mutation, repeating icotinib was attempted as salvage treatment. After 2 months treatment, multiply lesions in brain were dramatically disappeared according to brain MRI , as well as symptoms of cough and hemoptysis relieved apparently. The repeating icotinib was administrated till November 30th 2017 , on which a sudden syncope happened. An emergency brain MRI suggested recurrence of tumors, with an enlarged lesion in left parietal lobe surrounded by encephaledema severely. Coinstantaneous chest CT scanning suggested a PD of the target lesion in right lung . After symptomatic treatment of dehydration with mannitol, whole brain radiotherapy (WBRT) was developed as palliative management. PNLB was operated again on December 18th 2017, result of which reconfirm adenocarcinoma in lung , accompanied with the deletion of EGFR exon 19 (p.745–750 del) with frequency by 87.5% and T790 M mutation by 9.4%, without Leu792H mutation any more obtained from plasma or tissue . Sixth-line treatment of repeating AZD9291 was restarted on January 6th 2018 due to the increased frequency of T790 M mutation. One month later on February 5th 2018, repeating pictures of chest CT showed a response of lump in right lung, with partial remission of lesions in brain as MRI presented . The variation of tumor markers including carcino-embryonic antigen (CEA, normal range, 0–0.5 ng/mL) and carbohydrate antigen 72–4 (CA72–4, normal range, 0–6.9 U/mL) are showed in Fig. 6 for each visit from the initial treatment to the present. In addition, variations of tumor size during the whole treatment according to RECIST version 1.1 were listed in Table 1 . The patient feels good without any symptoms and still receives AZD9291 treatment now. The overall survival has been 36 months and still in the extension. Fig. 1 Chest CT scan and brain MRI from April 2015 to February 2016. a Chest CT scan and brain MRI at the time of diagnosis in April 2015. b Chest CT scan and brain MRI after 2 cycles of pemetrexed plus cisplatin treatment in June 2015. c Chest CT scan and brain MRI after 1 month treatment of icotinib in July 2015. d Chest CT scan and brain MRI after 3 months treatment of icotinib in September 2015. e Chest CT scan and brain MRI after 6 months treatment of icotinib in December 2015. f Chest CT scan and brain MRI after 8 months treatment of icotinib in February 2016 Fig. 2 Histological findings of tumor tissue. a Histological finding with hematoxylin and eosin–stained biopsy specimen from PNLB on April 15th 2015. b Histological finding with hematoxylin and eosin–stained biopsy specimen from PNLB on December 7th 2015 Fig. 3 Drive gene detecting during the treatment. a NGS analysis of EGFR exon 19 deletion mutation in February 2016. b Acquiring T790 M mutation with plasma after resistant to icotinib in February 2016. c NGS analysis of EGFR exon 19 deletion mutation in March 2017. d NGS analysis of EGFR T790 M mutation, as well as Leu792H mutation with plasma after resistant to AZD9291 in March 2017. e NGS analysis of EGFR exon 19 deletion mutation in December 2017. f NGS analysis of EGFR T790 M mutation, without Leu792H mutation any more with plasma after resistant to repeating icotinib in December 2017 Fig. 4 Chest CT scan and brain MRI from April 2016 to March 2017. a Chest CT scan after 1 month treatment of AZD9291 in April 2016. b Chest CT scan after 3 months treatment of AZD9291 in June 2016. c Chest CT scan after 6 months treatment of AZD9291 in September 2016. d Chest CT scan and brain MRI after 10 months treatment of AZD9291 in January 2017. e Chest CT scan and brain MRI after 2 cycles of docetaxel treatment in March 2017 Fig. 5 Chest CT scan and brain MRI from May 2017 to February 2018. a Chest CT scan and brain MRI after 2 months treatment of repeating icotinib in May 2017. b Chest CT scan after 3 months treatment of repeating icotinib in June 2017. c Chest CT scan and brain MRI after 6 months treatment of repeating icotinib in September 2017. d Chest CT scan and brain MRI after 8 months treatment of repeating icotinib in November 2017. e Chest CT scan and brain MRI after 1 month treatment of repeating AZD9291 in February 2018 Fig. 6 The variation CEA and CA72–4 for each visit from the initial treatment to the present Table 1 Variations of tumor size during treatment according to RECIST version 1.1 Date Exposure Duration Target lesions in lung (LD×SD, millimeter) Target lesions in brain (LD×SD, millimeter) 2015.04 Baseline N/A 35 × 24 6.5 × 4.2 2015.06 AP 2 cycles 48 × 42 5.1 × 4.0 2015.07 Icotinib 1 month 22 × 17 2.3 × 2.1 2015.09 Icotinib 3 months 21 × 18 2.0 × 1.8 2015.12 Icotinib 6 months 23 × 21 0 2016.02 Icotinib 8 months 29 × 26 0 2016.04 AZD9291 1 month 17 × 15 N/A 2016.06 AZD9291 3 months 18 × 17 N/A 2016.09 AZD9291 6 months 20 × 16 N/A 2017.01 AZD9291 10 months 61 × 48 0 2017.03 Docetaxel 2 cycles 88 × 39 Multiple lesions 2017.05 Icotinib 2 months 90 × 49 0 2017.06 Icotinib 3 months 64 × 28 N/A 2017.09 Icotinib 6 months 71 × 38 7.1 × 4.2, 3.4 × 2.2 2017.11 Icotinib 8 months 78 × 53 9.5 × 7.1, 6.0 × 5.3 2017.12 WBRT 15F N/A N/A 2018.02 AZD9291 1 month 58 × 43 3.0 × 2.1, 0 Abbreviations: LD Longest Diameter, SD Shortest Diameter, N/A Not/Applicable, AP Pemetrexed + Cisplatin, WBRT Whole Brain Radiation Therapy	4.027344	0.973145	sec[1]/p[0]	en	0.999997	30736738	https://doi.org/10.1186/s12885-019-5352-7	[ "brain", "chest", "icotinib", "scan", "mutation", "lung", "repeating", "lesions", "egfr", "exon" ]	[ { "code": "8E7Y", "title": "Other specified diseases of the nervous system" }, { "code": "LA05.Z", "title": "Cerebral structural developmental anomalies, unspecified" }, { "code": "1D00.Z", "title": "Infectious encephalitis, unspecified" }, { "code": "LA00.0Z", "title": "Anencephaly, unspecified" }, { "code": "NA07.3Y", "title": "Other specified diffuse brain injury" }, { "code": "CB7Z", "title": "Diseases of the respiratory system, unspecified" }, { "code": "CB27", "title": "Pleural effusion" }, { "code": "CA44", "title": "Pyothorax" }, { "code": "MD30.Z", "title": "Chest pain, unspecified" }, { "code": "NA80.Y&XJ1C6", "title": "Thoracic haematoma" } ]	=== ICD-11 CODES FOUND === [8E7Y] Other specified diseases of the nervous system Also known as: Other specified diseases of the nervous system \| Circumscribed brain atrophy \| circumscribed cerebral atrophy \| atrophic lobar sclerosis \| atrophic lobar brain sclerosis [LA05.Z] Cerebral structural developmental anomalies, unspecified Also known as: Cerebral structural developmental anomalies, unspecified \| Cerebral structural developmental anomalies \| Malformations of brain \| brain abnormality NOS \| brain deformity NOS [1D00.Z] Infectious encephalitis, unspecified Also known as: Infectious encephalitis, unspecified \| Infectious encephalitis, not elsewhere classified \| encephalitis NOS \| acute encephalitis NOS \| acute brain inflammation [LA00.0Z] Anencephaly, unspecified Also known as: Anencephaly, unspecified \| Anencephaly \| anencephalic monster \| anencephalus \| brain absence [NA07.3Y] Other specified diffuse brain injury Also known as: Other specified diffuse brain injury \| Brain contusion \| Cerebral contusion NOS \| Diffuse cortex contusion \| diffuse cortical contusion [CB7Z] Diseases of the respiratory system, unspecified Also known as: Diseases of the respiratory system, unspecified \| disorder of respiratory system \| respiratory disease NOS \| respiratory tract disease \| respiratory disorder NOS [CB27] Pleural effusion Definition: Presence of fluid in the pleural cavity resulting from excessive transudation or exudation from the pleural surfaces. Also known as: Pleural effusion \| PE - [pleural effusion] \| Pleurisy with effusion \| pleurisy with effusion NOS \| pleural effusion with transudate Includes: Pleurisy with effusion Excludes: Tuberculosis of the respiratory system \| Chylous effusion \| Pleurisy [CA44] Pyothorax Definition: Suppurative inflammation of the pleural space, typically due to acute bacterial infection. It can occur as a complication of pneumonia, thoracotomy, abscesses (lung, hepatic, or subdiaphragmatic), or penetrating trauma with a secondary infection. Also known as: Pyothorax \| empyema \| pyopneumothorax \| Pyothorax with fistula \| empyema with fistula Includes: empyema \| pyopneumothorax Excludes: due to tuberculosis [MD30.Z] Chest pain, unspecified Also known as: Chest pain, unspecified \| Pain in throat or chest \| chest pain NOS \| pain in chest \| chest pressure === GRAPH WALKS === --- Walk 1 --- [8E7Y] Other specified diseases of the nervous system --PARENT--> [08] Diseases of the nervous system Def: This is a group of conditions characterised as being in or associated with the nervous system.... --EXCLUDES--> [?] Endocrine, nutritional or metabolic diseases Def: This chapter includes endocrine diseases, nutritional diseases as well as metabolic diseases.... --- Walk 2 --- [8E7Y] Other specified diseases of the nervous system --PARENT--> [08] Diseases of the nervous system Def: This is a group of conditions characterised as being in or associated with the nervous system.... --EXCLUDES--> [?] Pregnancy, childbirth or the puerperium Def: A group of conditions characterised as occurring during the period of time from conception to delivery (pregnancy), during labour and delivery (childbirth) or during the approximately six weeks after ... --- Walk 3 --- [LA05.Z] Cerebral structural developmental anomalies, unspecified --PARENT--> [LA05] Cerebral structural developmental anomalies Def: Any condition caused by failure of the brain to correctly develop during the antenatal period.... --CHILD--> [LA05.0] Microcephaly Def: A condition caused by failure of the head to correctly develop during the antenatal period. This condition is characterised by a head size that is significantly smaller than normal for their age and s... --- Walk 4 --- [LA05.Z] Cerebral structural developmental anomalies, unspecified --PARENT--> [LA05] Cerebral structural developmental anomalies Def: Any condition caused by failure of the brain to correctly develop during the antenatal period.... --CHILD--> [LA05.2] Holoprosencephaly Def: Holoprosencephaly is a brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and the 28th day of gestation and affecting both the forebrain and the fa... --- Walk 5 --- [1D00.Z] Infectious encephalitis, unspecified --PARENT--> [1D00] Infectious encephalitis, not elsewhere classified Def: A disease of the brain, caused by an infection.... --CHILD--> [1D00.2] Parasitic or protozoal encephalitis Def: A disease of the brain, caused by an infection with a parasitic or protozoal source.... --- Walk 6 --- [1D00.Z] Infectious encephalitis, unspecified --PARENT--> [1D00] Infectious encephalitis, not elsewhere classified Def: A disease of the brain, caused by an infection.... --CHILD--> [1D00.0] Bacterial encephalitis	[ "[8E7Y] Other specified diseases of the nervous system\n --PARENT--> [08] Diseases of the nervous system\n Def: This is a group of conditions characterised as being in or associated with the nervous system....\n --EXCLUDES--> [?] Endocrine, nutritional or metabolic diseases\n Def: This chapter includes endocrine diseases, nutritional diseases as well as metabolic diseases....", "[8E7Y] Other specified diseases of the nervous system\n --PARENT--> [08] Diseases of the nervous system\n Def: This is a group of conditions characterised as being in or associated with the nervous system....\n --EXCLUDES--> [?] Pregnancy, childbirth or the puerperium\n Def: A group of conditions characterised as occurring during the period of time from conception to delivery (pregnancy), during labour and delivery (childbirth) or during the approximately six weeks after ...", "[LA05.Z] Cerebral structural developmental anomalies, unspecified\n --PARENT--> [LA05] Cerebral structural developmental anomalies\n Def: Any condition caused by failure of the brain to correctly develop during the antenatal period....\n --CHILD--> [LA05.0] Microcephaly\n Def: A condition caused by failure of the head to correctly develop during the antenatal period. This condition is characterised by a head size that is significantly smaller than normal for their age and s...", "[LA05.Z] Cerebral structural developmental anomalies, unspecified\n --PARENT--> [LA05] Cerebral structural developmental anomalies\n Def: Any condition caused by failure of the brain to correctly develop during the antenatal period....\n --CHILD--> [LA05.2] Holoprosencephaly\n Def: Holoprosencephaly is a brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and the 28th day of gestation and affecting both the forebrain and the fa...", "[1D00.Z] Infectious encephalitis, unspecified\n --PARENT--> [1D00] Infectious encephalitis, not elsewhere classified\n Def: A disease of the brain, caused by an infection....\n --CHILD--> [1D00.2] Parasitic or protozoal encephalitis\n Def: A disease of the brain, caused by an infection with a parasitic or protozoal source....", "[1D00.Z] Infectious encephalitis, unspecified\n --PARENT--> [1D00] Infectious encephalitis, not elsewhere classified\n Def: A disease of the brain, caused by an infection....\n --CHILD--> [1D00.0] Bacterial encephalitis" ]	8E7Y	Other specified diseases of the nervous system	[ { "from_icd11": "LA05.Z", "icd10_code": "Q048", "icd10_title": "Other specified congenital malformations of brain" }, { "from_icd11": "LA05.Z", "icd10_code": "Q043", "icd10_title": "Other reduction deformities of brain" }, { "from_icd11": "LA05.Z", "icd10_code": "Q049", "icd10_title": "Congenital malformation of brain, unspecified" }, { "from_icd11": "LA05.Z", "icd10_code": "Q04", "icd10_title": "Other congenital malformations of brain" }, { "from_icd11": "1D00.Z", "icd10_code": "G0490", "icd10_title": "Encephalitis and encephalomyelitis, unspecified" }, { "from_icd11": "1D00.Z", "icd10_code": "G0491", "icd10_title": "Myelitis, unspecified" }, { "from_icd11": "1D00.Z", "icd10_code": "G0430", "icd10_title": "Acute necrotizing hemorrhagic encephalopathy, unspecified" }, { "from_icd11": "1D00.Z", "icd10_code": "G0431", "icd10_title": "Postinfectious acute necrotizing hemorrhagic encephalopathy" }, { "from_icd11": "1D00.Z", "icd10_code": "G0439", "icd10_title": "Other acute necrotizing hemorrhagic encephalopathy" }, { "from_icd11": "1D00.Z", "icd10_code": "G0481", "icd10_title": "Other encephalitis and encephalomyelitis" }, { "from_icd11": "1D00.Z", "icd10_code": "G0489", "icd10_title": "Other myelitis" }, { "from_icd11": "1D00.Z", "icd10_code": "G04", "icd10_title": "Encephalitis, myelitis and encephalomyelitis" }, { "from_icd11": "1D00.Z", "icd10_code": "G048", "icd10_title": "Other encephalitis, myelitis and encephalomyelitis" }, { "from_icd11": "LA00.0Z", "icd10_code": "Q000", "icd10_title": "Anencephaly" }, { "from_icd11": "CB7Z", "icd10_code": "J989", "icd10_title": "Respiratory disorder, unspecified" } ]	Q048	Other specified congenital malformations of brain
One-sided retro-orbital pain associated with ipsilateral lacrimation, conjunctival injection, chemosis, proptosis, and diplopia could be attributed to a primary form of trigeminal autonomic cephalalgias (TACs) such as cluster headache, especially at its first presentations . The duration of the pain, the worsening of symptoms, and the physical evolution of ocular alterations led us to further investigations to exclude secondary and potentially dangerous diseases such as tumors, inflammation, infections, or vascular abnormalities (i.e., arterovenous malformations, cerebral venous thrombosis, or intracranial dural fistulas, as in this case) . Intracranial dural fistulas are acquired, abnormal connections between dural arteries from the internal and external carotid or vertebral arteries and the dural sinuses or their closest venous collectors; they can also receive contributions from pial branches. The clinical features are extremely variable depending on the location and the subtype of the fistula and on the angioarchitecture of the disease itself. A CS-DAVF is a well-known subtype of dural fistulas in which dural feeders from the internal and external carotid arteries connect with the CS. They account for 10–15% of all cerebral vascular malformations . They develop spontaneously and differentiate from other vascular diseases affecting this region, such as the so-called direct carotico-cavernous fistulas that are high-flow, single-hole communications between the carotid syphon and the CS that can be caused by the rupture of a carotid syphon aneurysm or a direct trauma (i.e., skull base fractures). The Barrow classification categorizes these vascular conditions into four subtypes according to their anatomical features provided by angiographical studies : Type A fistulas are direct shunts between the internal carotid artery and the CS, usually post-traumatic or due to the rupture of a carotid syphon aneurysm, “indirect” fistulas are dural arteriovenous fistulas of the CS fed by dural branches of the internal carotid artery (Type B), of the external carotid artery (Type C) or both (Type D). Our case featured the pattern of a Type D fistula. The CS is an epidural plexus located between the periosteum and the dura mater on both sides of the sella. It is a crucial venous hub as it drains the face-orbit region as well as the brain, and it can function as a rerouting pathway in case of obstruction or diseases affecting the normal venous outlets; anteriorly, it receives the superior and inferior (or common venous confluent) ophthalmic veins . In CS-DAVF, several abnormal small arterial feeders converge to the CS plexus so that the normal flow within the plexus is increased and a venous hypertension is created. This determines flow reversal in one or many of the veins that anastomose with the CS itself. The superior ophthalmic vein is the most common drainage in CS-DAVFs; in this condition, it often becomes enlarged and engorged and determines, mainly by mass effect on extrinsic ocular muscles and the optic nerve, the clinical features of this disease. Patients affected by a CS-DAVF can present with eye pain, proptosis, diplopia, conjunctival injection, chemosis, and loss of vision . The CS communicates with many other venous collectors; on the lateral side, it receives the cortical veins (i.e., the sylvian veins) through the sphenoparietal sinus . In cases of CS-DAVF with drainage into cortical veins, the most feared clinical issue can be cerebral hemorrhage. Indications for CS-DAVF treatment are severe or progressive symptoms and/or cortical venous reflux (for the hemorrhagic risk). Endovascular treatment is the first-line option through transvenous coil obliteration of the diseased portion of the sinus or, more precisely, of the fistulous point. In a review from a Japanese group , this treatment showed great rates of success with complete disappearance of the fistula in 72.5% of the series (median), immediately after the procedure. This rate increases up to 100% (in the series reporting long-term follow-ups). The reason is that even in those cases with a partial shunt occlusion immediately after the procedure the disappearance of the fistula progresses for the thrombogenic effect of the coils and not only for the direct packing of the sinus . The embolization of the several narrow and tortuous arterial branches that feed the fistula is usually not only time consuming and very often technically demanding but can also be a treatment failure because it is easy to miss the arterio-venous shunt because the small diameter of the arterial feeders does not allow for the deep penetration of our embolic materials. Several venous routes are available for endovascular access to the CS but not all are straightforward, and in this case, the venous outlets of the fistula were not large enough and easily accessible. A surgical exposure of the SOV or the CS is possible but the risk-to-benefit ratio was deemed unfavorable. The association of TAO and CS-DAVF has seldom been reported. Lore et al. presented the case of a woman affected by Graves’ disease, with previous hyperthyroid state, treated for 10 years with methimazole then with 131 I. She was admitted for a bilateral progressive ophthalmopathy, in a state of subclinical hyperthyroidism, initially treated with steroids. She presented only asymmetric improvement of the ocular symptoms, and this feature led clinicians to perform further investigations that demonstrated the presence of a CS-DAVF. She was successfully treated with transvenous embolization with immediate clinical improvement. Celik and colleagues reported one more case: a woman with known Graves’ disease with progressive ophthalmopathy. She was initially treated with glucocorticoids but partially responded with residual right exophthalmos. A subsequent angiography showed the presence of a right CS-DAVF with bilateral superior ophthalmic vein drainage, more pronounced on the right side. An endovascular embolization of the right CS was performed, leaving untouched the small left-sided venous drainage, with regression of the symptoms and radiological improvement. In the two reported cases, the patients have been initially treated with glucocorticoids, and only after partial failure of the pharmacological approach and asymmetric persistence of ocular signs and symptoms was a dural fistula suspected. TAO generally is associated with autoimmune hyperthyroidism, but in 5–10% of the cases, it can occur with hypothyroidism or normal thyroid function . In these cases, the diagnosis of TAO is based on the presence of one or more autoimmune thyroid-associated autoantibodies. Antibodies anti-thyroid peroxidase (TPO-Ab) are generally associated with main chronic autoimmune thyroid disorders (Hashimoto’s thyroiditis, Graves’ disease), while autoantibodies against the TSH receptor (TRAb) are specific and pathogenic for Graves’ disease or mixed thyroid autoimmune thyroid disorders (Hashitoxicosis). In the presence of ocular symptoms and the clear absence of thyroid disfunction or antibodies, such as in our case, a different etiology must be taken into account, and further imaging workout has to be planned (brain CT or MR) to exclude other causes of ophthalmopathy (CS-DAVFs, meningiomas, lymphomas, cellulitis, pseudotumor cerebri, metastatic tumors, and sarcoidosis). The possible causes for negative TRAbs are technical issues, such as the use of an assay lacking adequate sensitivity to detect low level of antibodies, especially in patients with mild disease, or the presence of intrathyroidal, noncirculating antibodies. Furthermore, other factors are involved in the pathogenesis of TAO, such as the insulin-like growth factor receptor (IGF1R), which can be expressed on the surface of orbital fibroblast cells and can be one of the target autoantigens in TAO . Patients with clinical features that fit with the diagnosis of TAO should receive a thorough evaluation with imaging studies even if the laboratory tests are negative: the full expression of the thyroid disease can develop years after the orbital signs. The relative asymmetrical involvement of the extrinsic ocular muscles in our case and the presence of a CS-DAVF led us to think that the ocular disease can be primarily a consequence of the vascular pathology, whereas its complete disappearance with the reduction of the edema to the muscles after medical therapy is in favor of a secondary nature of the fistula. A direct effect of the extrinsic ocular muscle disease on the orbital veins in TAO was postulated long ago and has extensively been demonstrated. Enlargement and stasis and even thrombosis of the superior ophthalmic vein can develop mainly from apical crowding or enlargement of the superior rectus muscle or even muscle inflammation, which involves the vascular network leading finally to a periphlebitis. Venous congestion or venous thrombosis is one of the primary causes inducing dural fistulas development.	4.484375	0.623535	sec[2]/p[0]	en	0.999996	PMC8773681	https://doi.org/10.3390/brainsci12010045	[ "venous", "dural", "this", "davf", "that", "ocular", "fistulas", "carotid", "fistula", "thyroid" ]	[ { "code": "BD74.Z", "title": "Chronic peripheral venous insufficiency of lower extremities, unspecified" }, { "code": "BD75.Y", "title": "Venous varicosities of other specified sites" }, { "code": "BD75.Z", "title": "Venous varicosities of unspecified site" }, { "code": "JA61.Z", "title": "Venous complications in pregnancy, unspecified" }, { "code": "BD74.0", "title": "Uncomplicated lower limb venous hypertension" }, { "code": "LA90.2Y", "title": "Other specified peripheral venous malformations" }, { "code": "NA07.5", "title": "Traumatic epidural haemorrhage" }, { "code": "1D03.2", "title": "Intraspinal extradural abscess" }, { "code": "NA07.6Z", "title": "Traumatic subdural haemorrhage, unspecified whether acute or chronic" }, { "code": "NA07.61", "title": "Chronic traumatic subdural haemorrhage" } ]	=== ICD-11 CODES FOUND === [BD74.Z] Chronic peripheral venous insufficiency of lower extremities, unspecified Also known as: Chronic peripheral venous insufficiency of lower extremities, unspecified \| Chronic peripheral venous insufficiency of lower extremities \| Chronic venous insufficiency \| postthrombotic syndrome \| postphlebitic syndrome [BD75.Y] Venous varicosities of other specified sites Also known as: Venous varicosities of other specified sites \| Caput medusae \| Jugular venous aneurysm \| jugular vein aneurysm \| Orbital varices [BD75.Z] Venous varicosities of unspecified site Also known as: Venous varicosities of unspecified site \| Venous varicosities of sites other than lower extremity \| Venous varix [JA61.Z] Venous complications in pregnancy, unspecified Also known as: Venous complications in pregnancy, unspecified \| Venous complications in pregnancy \| Gestational phlebopathy, NOS [BD74.0] Uncomplicated lower limb venous hypertension Definition: The presence of lower limb venous incompetence or hypertension as may be manifest by the presence of haemosiderin pigmentation of the skin, telangiectasia or finely dilated superficial veins. Also known as: Uncomplicated lower limb venous hypertension \| Lower limb haemosiderosis due to venous insufficiency \| Lower limb haemosiderosis secondary to venous insufficiency \| Lower limb superficial venous ectasia \| Venous flare [LA90.2Y] Other specified peripheral venous malformations Also known as: Other specified peripheral venous malformations \| Dural sinus malformation \| Cranial dural arteriovenous malformations \| Cranial dural arteriovenous fistula [NA07.5] Traumatic epidural haemorrhage Also known as: Traumatic epidural haemorrhage \| extradural haemorrhage \| traumatic epidural haematoma \| traumatic extradural haemorrhage \| extradural brain haematoma [1D03.2] Intraspinal extradural abscess Also known as: Intraspinal extradural abscess \| extradural abscess of spinal cord \| extradural embolic abscess of spinal cord \| extradural embolic abscess of spinal cord, any part \| extradural abscess NOS [NA07.6Z] Traumatic subdural haemorrhage, unspecified whether acute or chronic Also known as: Traumatic subdural haemorrhage, unspecified whether acute or chronic \| Traumatic subdural haemorrhage \| subdural haemorrhage following injury \| traumatic subdural haematoma \| acute subdural haematoma NOS [NA07.61] Chronic traumatic subdural haemorrhage Also known as: Chronic traumatic subdural haemorrhage \| chronic subdural haematoma Includes: chronic subdural haematoma === GRAPH WALKS === --- Walk 1 --- [BD74.Z] Chronic peripheral venous insufficiency of lower extremities, unspecified --PARENT--> [BD74] Chronic peripheral venous insufficiency of lower extremities Def: The presence of increased pressure in the peripheral venous system, particularly of the lower extremities. Peripheral venous hypertension may be due to incompetence of venous valves following deep vei... --CHILD--> [BD74.1] Lower limb varicose veins Def: The commonest manifestation of chronic peripheral venous insufficiency, varicose veins present as dilatation and tortuosity of the superficial veins of the lower extremities. Incompetence of the super... --- Walk 2 --- [BD74.Z] Chronic peripheral venous insufficiency of lower extremities, unspecified --PARENT--> [BD74] Chronic peripheral venous insufficiency of lower extremities Def: The presence of increased pressure in the peripheral venous system, particularly of the lower extremities. Peripheral venous hypertension may be due to incompetence of venous valves following deep vei... --CHILD--> [BD74.2] Lipodermatosclerosis Def: Lipodermatosclerosis is a form of panniculitis of the lower legs that develops in the context of venous insufficiency, giving rise to features that include oedema, erythema, hyperpigmentation and indu... --- Walk 3 --- [BD75.Y] Venous varicosities of other specified sites --PARENT--> [BD75] Venous varicosities of sites other than lower extremity --CHILD--> [BD75.2] Vulval varices Def: Congested and dilated vulval veins, occurring particularly in association with pregnancy.... --- Walk 4 --- [BD75.Y] Venous varicosities of other specified sites --PARENT--> [BD75] Venous varicosities of sites other than lower extremity --CHILD--> [BD75.1] Scrotal varices --- Walk 5 --- [BD75.Z] Venous varicosities of unspecified site --PARENT--> [BD75] Venous varicosities of sites other than lower extremity --PARENT--> [?] Diseases of veins --- Walk 6 --- [BD75.Z] Venous varicosities of unspecified site --PARENT--> [BD75] Venous varicosities of sites other than lower extremity --RELATED_TO--> [?] Gastric varices Def: Abnormally dilated veins developed as portosystemic shunts in the lining of stomach (fundus and/or cardia) in patients with portal hypertension. Once gastric varices develop, they continue to grow, an...	[ "[BD74.Z] Chronic peripheral venous insufficiency of lower extremities, unspecified\n --PARENT--> [BD74] Chronic peripheral venous insufficiency of lower extremities\n Def: The presence of increased pressure in the peripheral venous system, particularly of the lower extremities. Peripheral venous hypertension may be due to incompetence of venous valves following deep vei...\n --CHILD--> [BD74.1] Lower limb varicose veins\n Def: The commonest manifestation of chronic peripheral venous insufficiency, varicose veins present as dilatation and tortuosity of the superficial veins of the lower extremities. Incompetence of the super...", "[BD74.Z] Chronic peripheral venous insufficiency of lower extremities, unspecified\n --PARENT--> [BD74] Chronic peripheral venous insufficiency of lower extremities\n Def: The presence of increased pressure in the peripheral venous system, particularly of the lower extremities. Peripheral venous hypertension may be due to incompetence of venous valves following deep vei...\n --CHILD--> [BD74.2] Lipodermatosclerosis\n Def: Lipodermatosclerosis is a form of panniculitis of the lower legs that develops in the context of venous insufficiency, giving rise to features that include oedema, erythema, hyperpigmentation and indu...", "[BD75.Y] Venous varicosities of other specified sites\n --PARENT--> [BD75] Venous varicosities of sites other than lower extremity\n --CHILD--> [BD75.2] Vulval varices\n Def: Congested and dilated vulval veins, occurring particularly in association with pregnancy....", "[BD75.Y] Venous varicosities of other specified sites\n --PARENT--> [BD75] Venous varicosities of sites other than lower extremity\n --CHILD--> [BD75.1] Scrotal varices", "[BD75.Z] Venous varicosities of unspecified site\n --PARENT--> [BD75] Venous varicosities of sites other than lower extremity\n --PARENT--> [?] Diseases of veins", "[BD75.Z] Venous varicosities of unspecified site\n --PARENT--> [BD75] Venous varicosities of sites other than lower extremity\n --RELATED_TO--> [?] Gastric varices\n Def: Abnormally dilated veins developed as portosystemic shunts in the lining of stomach (fundus and/or cardia) in patients with portal hypertension. Once gastric varices develop, they continue to grow, an..." ]	BD74.Z	Chronic peripheral venous insufficiency of lower extremities, unspecified	[ { "from_icd11": "BD74.Z", "icd10_code": "I87313", "icd10_title": "Chronic venous hypertension (idiopathic) with ulcer of bilateral lower extremity" }, { "from_icd11": "BD74.Z", "icd10_code": "I87393", "icd10_title": "Chronic venous hypertension (idiopathic) with other complications of bilateral lower extremity" }, { "from_icd11": "BD74.Z", "icd10_code": "I87309", "icd10_title": "Chronic venous hypertension (idiopathic) without complications of unspecified lower extremity" }, { "from_icd11": "BD74.Z", "icd10_code": "I87302", "icd10_title": "Chronic venous hypertension (idiopathic) without complications of left lower extremity" }, { "from_icd11": "BD74.Z", "icd10_code": "I87339", "icd10_title": "Chronic venous hypertension (idiopathic) with ulcer and inflammation of unspecified lower extremity" }, { "from_icd11": "BD74.Z", "icd10_code": "I87319", "icd10_title": "Chronic venous hypertension (idiopathic) with ulcer of unspecified lower extremity" }, { "from_icd11": "BD74.Z", "icd10_code": "I87399", "icd10_title": "Chronic venous hypertension (idiopathic) with other complications of unspecified lower extremity" }, { "from_icd11": "BD74.Z", "icd10_code": "I87031", "icd10_title": "Postthrombotic syndrome with ulcer and inflammation of right lower extremity" }, { "from_icd11": "BD74.Z", "icd10_code": "I83208", "icd10_title": "Varicose veins of unspecified lower extremity with both ulcer of other part of lower extremity and inflammation" }, { "from_icd11": "BD74.Z", "icd10_code": "I87002", "icd10_title": "Postthrombotic syndrome without complications of left lower extremity" }, { "from_icd11": "BD74.Z", "icd10_code": "I83228", "icd10_title": "Varicose veins of left lower extremity with both ulcer of other part of lower extremity and inflammation" }, { "from_icd11": "BD74.Z", "icd10_code": "I87012", "icd10_title": "Postthrombotic syndrome with ulcer of left lower extremity" }, { "from_icd11": "BD74.Z", "icd10_code": "I87092", "icd10_title": "Postthrombotic syndrome with other complications of left lower extremity" }, { "from_icd11": "BD74.Z", "icd10_code": "I83223", "icd10_title": "Varicose veins of left lower extremity with both ulcer of ankle and inflammation" }, { "from_icd11": "BD74.Z", "icd10_code": "I83218", "icd10_title": "Varicose veins of right lower extremity with both ulcer of other part of lower extremity and inflammation" } ]	I87313	Chronic venous hypertension (idiopathic) with ulcer of bilateral lower extremity
In 2022, the patient was admitted to our hospital with cardiac symptoms. Tachycardia-bradycardia syndrome was detected on dynamic ECG. The ECG revealed junctional escape-sinus capture bigeminy. Although the slowest heart rate was not captured on this ECG, 24 h bedside monitoring revealed a tachycardia-bradycardia syndrome, with a heart rate of 140 beats/minute during atrial flutter and a heart rate of only 40 beats/minute during bradycardia. Based on the patient's clinical symptoms and electrocardiographic abnormalities, the diagnosis of sick sinus node syndrome (SSS) was considered. The echocardiogram revealed a space-occupying lesion with moderate echogenicity located in the right atrium, measuring approximately 55 × 30 mm in size, bi-atrial enlargement, tricuspid regurgitation (mild-moderate), and a small amount of fluid in the pericardial cavity, while left ventricular ejection fraction (67%), and segmental motion of the ventricular wall were both normal. Cardiac CT (CCT) revealed multiple nodules and masses in the right atrial wall, peri-coronary artery, and left side of the inferior vena cava . CRP (27.3 mg/L, normal; < 10 mg/L), ESR (40 mm/h; normal: < 20 mm/h),Serum B-type natriuretic peptide (133 pg/ml; normal < 100 pg/ml), fibrinogen (6.25 g/L; normal 2–4 g/L), immunoglobulin G (IgG)-LAMBDA light chain (2.73 g/L; normal 0.9–2.1 g/L), KAPPA light chain (5.20 g/L; normal 1.7–3.7 g/L), and IgG4 (2.545 g/L; normal 0.03–2 g/L) levels were elevated. No clinical evidence of other autoimmune diseases was found. Moreover, examinations of potentially pathogenic agents, including antibodies to syphilis spirochetes, human immunodeficiency virus, hepatitis A, B, and C viruses, and mycobacterium tuberculosis, were all negative. The results of autoimmune antibody testing demonstrated negative for the following antibodies: anti-Scl-70 antibody, anti-mitochondrial antibody, anti-PCNA antibody, anti-nucleolar antibody, anti-Jo-1 antibody, anti-histone antibody, anti-U1-nRNP antibody, anti-centromere antibody, anti-SS-A antibody, anti-SS-B antibody, and anti-Sm antibody. The levels of anti-smooth muscle antibody (9.90 U, normal: 0–22 U), anti-nuclear antibody (11.1 U/ml, normal: 0–55 U/ml), anti-double stranded DNA antibody (23.95 IU/ml, normal: ≤ 200 IU/ml), anti-glomerular basement membrane antibody (2.4 Units, normal: 0–20 Units), and anti-intrinsic factor antibody (4.4 Units, normal: 0–22 Units) were all within the normal range. Due to the friable texture of the inflammatory mass, we were concerned that the mass could easily fragment after EMB and lead to severe complications such as embolism. Furthermore, the size of the right atrial mass made it difficult to pass through the tricuspid valve, increasing the risk of injury and embolism. Therefore, we opted for cardiac tumor resection instead of EMB. Other than aGCM, our suspected diagnoses of this patient before surgery included atrial myxoma, atrial malignant tumor (primary or metastatic), and IgG4 related disease (Table 1 ). Four days after admission, cardiac tumor resection was conducted . However, during the surgery, we found that the lesion was scattered and multifocal, making it impossible to remove completely. Therefore, only a biopsy was performed to remove the atrial mass and part of the pericardium by wrapping the lesion tissue on the surface of the right atrium. The histopathological examination of resected tissue (size: 0.8 × 0.8 × 0.4 cm 3 ) revealed large areas of myocyte replacement by hyperplastic fibrous tissues and inflammatory cell infiltrate composed of T-lymphocytes, plasma cells, eosinophils, and scattered multinucleated giant cells, which was consistent with the pathological features of GCM. Immunohistochemical results documented the lymphocytic infiltrate with CD3+ and CD5+ T lymphocytes, fewer CD20+ B lymphocytes, scattered CD68+ histiocytes and giant cells, without IgG4+ plasma cells. No bacteria, such as acid-resistant bacilli, fungi, or other parasites were found, and no foreign body was detected. After the surgery, the patient developed atrial flutter (140–180 beats/minute), accompanied by bradycardia (38 beats/minute). In addition, the patient had a symptom of chest tightness. Due to the complexity of the condition, temporary transvenous pacing (VVI mode) was performed to maintain the heart rate. Considering that the patient may benefit from anti-inflammatory treatment, he received continuous intravenous infusion of methylprednisolone for five days (80 mg daily), followed by a combination of methylprednisolone (40 mg daily) and cyclosporine (50 mg twice daily). However, after ten days of pharmacological intervention, there was no improvement in the arrhythmia, and thus a dual-chamber permanent pacemaker (DDD mode) was implanted. After permanent pacemaker implantation, the patient was treated with immunosuppressive therapy including methylprednisolone (24 mg once daily) and cyclosporine (50 mg twice daily). At outpatient follow-up one month after starting the immunosuppressive therapy, the patient reported significant symptom relief. Subsequently, the dosages of methylprednisolone and cyclosporine were gradually reduced. The total duration of immunosuppressive therapy after permanent pacemaker implantation was six months. At present, the patient continues to do well. Fig. 1 The ECGs of our case on the day of admission and on the morning of the day of cardiac tumor resection both demonstrated junctional escape-sinus capture bigeminy ( A and B ). After one week of pharmacological intervention following the temporary transvenous pacemaker implantation, the patient's ECG ( C ) showed the absence of P waves in all leads and the appearance of rapid and regular sawtooth-shaped F waves (250–350 bpm), predominantly with a 2:1 atrioventricular conduction ratio and occasional irregular f waves (350–450 bpm). The patient's ECG ( D ) after the implantation of a permanent pacemaker showed pacemaker-induced rhythm Fig. 2 The echocardiogram revealed the presence of a moderately echogenic mass (white crosses) within the right atrium. The mass measures approximately 53 × 30 mm in size with an irregular morphology and relatively well-defined margins, displaying relatively uniform internal echo. RV Right ventricle, LA Left atrium, RA Right atrium, LV Left ventricle Fig. 3 Both the axial and coronal CT images demonstrated anomalous soft tissue masses (pentagon) present in the right atrium, diffusely infiltrating and penetrating the atrial wall, resulting in the disappearance of the normal structure of the right atrium. Visible pericardial effusion (white arrow) was observed surrounding the heart. Abnormal nodules (pentagon) were observed around the left anterior descending coronary artery on the coronal image. LA Left atrium, RA Right atrium, LV Left ventricle Table 1 Suspected preoperative diagnosis of this patient and the basis for the final exclusion of these diagnoses Suspected diagnoses Exclusion reasons Atrial myxoma Atrial myxomas are mostly located in the left atrium, and most have a pedicle attached to the atrial septum or left atrial wall. They have good activity and move with the heart cycle . But the patient's echocardiography showed that the mass was located in the right atrium, with a fixed position. Combined with the ultrasound findings and the location of the mass, it was not like a typical atrial myxoma Primary cardiac angiosarcoma Primary cardiac angiosarcoma is a rare malignant tumor that originates in the heart, with the majority of cases arising from the right atrium . Typically presenting as a large mass, it has a tendency to invade adjacent tissues and can easily metastasize to the lungs, liver, and brain in the early stage . Given that the mass in this patient was localized to the right atrium and there was no indication of distant metastasis, insufficient diagnostic evidence existed to support a diagnosis of angiosarcoma Atrial metastatic tumors Based on our clinical experience, the majority of tumors that metastasize to the heart are located in the right atrium, with poor activity and irregular morphology. In this patient, normal levels of tumor markers were observed in blood tests, and no signs of tumors were found in abdominal ultrasonography or head CT scans, indicating no evidence of malignant tumor metastasis IgG4-related disease The patient's CCT showed multiple nodules surrounding each coronary artery and on the left side of the inferior vena cava. Additionally, the serum IgG4 level was mildly elevated. Therefore, we considered IgG4 related disease before surgery and ultimately ruled out this disease through pathological examination Fig. 4 The surgeon opened the mediastinum and observed a nodular lesion on the outer wall of the right atrium (black arrow) Fig. 5 Histology of our case showed lymphocytic cells (thick arrow), eosinophils (thin arrow), multinucleated giant cells (black triangle) infiltration, and myocardial fibrosis ( A and B )	4.171875	0.936035	sec[1]/p[1]	en	0.999997	PMC10347761	https://doi.org/10.1186/s13019-023-02316-z	[ "antibody", "anti", "atrial", "atrium", "heart", "cardiac", "that", "tumor", "this", "cells" ]	[ { "code": "JA86.Y", "title": "Maternal care for other specified fetal problems" }, { "code": "MA14.14", "title": "Anti-nuclear antibody positive" }, { "code": "MA14.13", "title": "Anti-nuclear antibody negative" }, { "code": "JA86.0", "title": "Maternal care for red cell antibodies" }, { "code": "MA14.1C", "title": "Raised antibody titre" }, { "code": "MB23.1", "title": "Antisocial behaviour" }, { "code": "3B4Z", "title": "Coagulation defects, unspecified" }, { "code": "4A45.Z", "title": "Antiphospholipid syndrome, unspecified" }, { "code": "4A43.Y", "title": "Other specified overlap non-organ specific systemic autoimmune disease" }, { "code": "BC46&XA91S4", "title": "Atrial thrombosis" } ]	=== ICD-11 CODES FOUND === [JA86.Y] Maternal care for other specified fetal problems Also known as: Maternal care for other specified fetal problems \| Maternal care for other isoimmunization \| Isoimmunization NOS \| maternal antibodies NOS \| pregnancy management affected by incompatibility of blood groups NOS [MA14.14] Anti-nuclear antibody positive Also known as: Anti-nuclear antibody positive \| ANA - [anti-nuclear antibody] positive [MA14.13] Anti-nuclear antibody negative Also known as: Anti-nuclear antibody negative \| ANA - [anti-nuclear antibody] negative [JA86.0] Maternal care for red cell antibodies Definition: Maternal care for rhesus or other isoimmunization Also known as: Maternal care for red cell antibodies \| Maternal care for rhesus isoimmunization \| Rh factor immunization affecting management of pregnancy \| Rh incompatibility \| Rh incompatibility with hydrops fetalis [MA14.1C] Raised antibody titre Also known as: Raised antibody titre \| antibody titre above reference range \| high antibody titre \| increased antibody titre Excludes: isoimmunization, in pregnancy affecting fetus or newborn [MB23.1] Antisocial behaviour Definition: Behaviour in which the basic rights of others or major age-appropriate societal norms, rules, or laws, are violated. Also known as: Antisocial behaviour \| Child or adolescent antisocial behaviour [3B4Z] Coagulation defects, unspecified Also known as: Coagulation defects, unspecified \| blood clotting disturbance \| blood clotting defect \| blood clotting factor deficiency \| clotting abnormality [4A45.Z] Antiphospholipid syndrome, unspecified Also known as: Antiphospholipid syndrome, unspecified \| Antiphospholipid syndrome \| Hughes syndrome \| Anticardiolipin syndrome [4A43.Y] Other specified overlap non-organ specific systemic autoimmune disease Also known as: Other specified overlap non-organ specific systemic autoimmune disease \| Antisynthetase syndrome \| Reynolds syndrome \| Syndromic multisystem autoimmune disease due to ITCH deficiency \| Eosinophilia myalgia syndrome === GRAPH WALKS === --- Walk 1 --- [JA86.Y] Maternal care for other specified fetal problems --PARENT--> [JA86] Maternal care for other fetal problems Def: A condition characterised by the provision of health interventions to the mother due to any other issue that is either suspected or known to be present in the fetus.... --EXCLUDES--> [?] Labour or delivery complicated by fetal distress --- Walk 2 --- [JA86.Y] Maternal care for other specified fetal problems --PARENT--> [JA86] Maternal care for other fetal problems Def: A condition characterised by the provision of health interventions to the mother due to any other issue that is either suspected or known to be present in the fetus.... --EXCLUDES--> [?] Labour or delivery complicated by fetal distress --- Walk 3 --- [MA14.14] Anti-nuclear antibody positive --PARENT--> [MA14.1] Certain specified immunological findings --CHILD--> [MA14.11] Anticitrullinated protein antibody negative --- Walk 4 --- [MA14.14] Anti-nuclear antibody positive --PARENT--> [MA14.1] Certain specified immunological findings --CHILD--> [MA14.12] Anticitrullinated protein antibody positive --- Walk 5 --- [MA14.13] Anti-nuclear antibody negative --PARENT--> [MA14.1] Certain specified immunological findings --CHILD--> [MA14.10] Abnormal reaction to tuberculin test --- Walk 6 --- [MA14.13] Anti-nuclear antibody negative --PARENT--> [MA14.1] Certain specified immunological findings --CHILD--> [MA14.10] Abnormal reaction to tuberculin test	[ "[JA86.Y] Maternal care for other specified fetal problems\n --PARENT--> [JA86] Maternal care for other fetal problems\n Def: A condition characterised by the provision of health interventions to the mother due to any other issue that is either suspected or known to be present in the fetus....\n --EXCLUDES--> [?] Labour or delivery complicated by fetal distress", "[JA86.Y] Maternal care for other specified fetal problems\n --PARENT--> [JA86] Maternal care for other fetal problems\n Def: A condition characterised by the provision of health interventions to the mother due to any other issue that is either suspected or known to be present in the fetus....\n --EXCLUDES--> [?] Labour or delivery complicated by fetal distress", "[MA14.14] Anti-nuclear antibody positive\n --PARENT--> [MA14.1] Certain specified immunological findings\n --CHILD--> [MA14.11] Anticitrullinated protein antibody negative", "[MA14.14] Anti-nuclear antibody positive\n --PARENT--> [MA14.1] Certain specified immunological findings\n --CHILD--> [MA14.12] Anticitrullinated protein antibody positive", "[MA14.13] Anti-nuclear antibody negative\n --PARENT--> [MA14.1] Certain specified immunological findings\n --CHILD--> [MA14.10] Abnormal reaction to tuberculin test", "[MA14.13] Anti-nuclear antibody negative\n --PARENT--> [MA14.1] Certain specified immunological findings\n --CHILD--> [MA14.10] Abnormal reaction to tuberculin test" ]	JA86.Y	Maternal care for other specified fetal problems	[ { "from_icd11": "JA86.Y", "icd10_code": "O26841 ", "icd10_title": "" }, { "from_icd11": "JA86.Y", "icd10_code": "O26843 ", "icd10_title": "" }, { "from_icd11": "JA86.Y", "icd10_code": "O26849 ", "icd10_title": "" }, { "from_icd11": "JA86.Y", "icd10_code": "O3680X0 ", "icd10_title": "" }, { "from_icd11": "JA86.0", "icd10_code": "O360930", "icd10_title": "Maternal care for other rhesus isoimmunization, third trimester, not applicable or unspecified" }, { "from_icd11": "JA86.0", "icd10_code": "O360920", "icd10_title": "Maternal care for other rhesus isoimmunization, second trimester, not applicable or unspecified" }, { "from_icd11": "JA86.0", "icd10_code": "O360130", "icd10_title": "Maternal care for anti-D [Rh] antibodies, third trimester, not applicable or unspecified" }, { "from_icd11": "JA86.0", "icd10_code": "O360932", "icd10_title": "Maternal care for other rhesus isoimmunization, third trimester, fetus 2" }, { "from_icd11": "JA86.0", "icd10_code": "O360922", "icd10_title": "Maternal care for other rhesus isoimmunization, second trimester, fetus 2" }, { "from_icd11": "JA86.0", "icd10_code": "O360990", "icd10_title": "Maternal care for other rhesus isoimmunization, unspecified trimester, not applicable or unspecified" }, { "from_icd11": "JA86.0", "icd10_code": "O360110", "icd10_title": "Maternal care for anti-D [Rh] antibodies, first trimester, not applicable or unspecified" }, { "from_icd11": "JA86.0", "icd10_code": "O360120", "icd10_title": "Maternal care for anti-D [Rh] antibodies, second trimester, not applicable or unspecified" }, { "from_icd11": "JA86.0", "icd10_code": "O360910", "icd10_title": "Maternal care for other rhesus isoimmunization, first trimester, not applicable or unspecified" }, { "from_icd11": "JA86.0", "icd10_code": "O360", "icd10_title": "Maternal care for rhesus isoimmunization" }, { "from_icd11": "MA14.1C", "icd10_code": "R760", "icd10_title": "Raised antibody titer" } ]	O26841
The AD diagnosis was performed on two 4 years old mixed breed dogs, weighing around 20 kg, one male (Dog 1) and one female (Dog 2). The owner reported that both dogs were led hunting in the early hours of the morning in a large area adjacent to the Nebrodi Natural Park. The area is known for its high density of feral pigs and wild boars. No other dogs were involved in the hunting day. During the hunt, both dogs contracted repeated direct and indirect contact with wild boars only in the approach phase, a typical phase in which once the wild boar has been traced, the dog chases and leads the prey towards the place where the hunter places himslef in order to facilitate the kill. At the end of the hunt, culminating in the killing of a wild boar, on the same day, both dogs were given offal and viscera from the same hunted animal. Both individuals showed no significant symptoms in the following hours of the same day, appetite was preserved, and general behaviour was normal, apart from a small lacerated bruised wound near the lip margin showed by Dog 1. Clinical symptoms were evident 24 h and 72 h after the hunt for Dog 1 and Dog 2, respectively. Both dogs presented the same clinical picture and thus will be described together. Incoercible itching in the labial region and the neck, non-responsive to corticosteroid treatment, dominated the clinical picture reported by the referring veterinarian. Self-traumatic lesions due to the extreme itching were evident. Inspection of the buccal and ocular mucous membranes revealed massive congestion. The body temperature progressively increased until reaching values of 42° C in the sub-terminal stages. Both dogs showed sialorrhea and an increase in respiratory and heart rate. Neurological alterations were also observed with progressive depression, prostration and unresponsiveness to external stimuli. At intermittent intervals, the dogs manifested tonic–clonic contractions involving the main muscle groups. Both dogs died 48 h after the onset of clinical symptoms. The carcasses were referred to the Istituto Zooprofilattico Sperimentale della Sicilia (IZSS) – Area Barcellona Pozzo di Gotto (Messina), to perform post-mortem diagnostic investigations. Both carcasses were subjected to necropsy according to the internal procedures of the IZSS. The inspection was performed on skin and skin appendages, body cavities, splanchnic organs, central and peripheral nervous system. Both carcasses had a good nutrition state at the macroscopic examination with a Body Condition Score of 3 (scale of 1–5). Inspection of the skin and skin appendages did not reveal any significant alterations except for the presence of alopecic, hyperemic and erosive lesions present at the periocular and labial regions found in Dog 1 and 2, respectively . In Dog 2, the lesions affecting the labial region were traumatic and lacerated-contused, extending to the skin overlying the masseters and appearing as a large hyperemic alopecic area . The explorable mucous membranes (oculo-conjunctival and buccal) were hyperemic and congested. Inspection of the thoracic and abdominal cavities and the viscera revealed no significant alterations, except for muscle fragments and wild boar offal in the stomach . Inspection of the brain, spinal cord and peripheral nerves showed alterations in the meningeal vessels of the telencephalon and especially the brainstem with the evident presence of hyperemia and congestion . During the necropsy, samples of the brain, liver, kidney, spleen and cerebrospinal fluid were collected from both dogs and frozen at -80° C until virologic investigations. At the virology laboratories of the IZSS—Palermo area, the samples collected were processed and subjected to Real-time PCR for SuHV-1, as described by Yoon et. al 2005 . The Real-Time PCR positive samples were then submitted to isolation on rabbit kidney cell lines (RK13) and porcine kidney cell lines (PK15) according to the standard operating procedures of the IZSS. All the samples were also subjected to Real-Time PCR for Rabies virus to exclude the disease as a differential diagnosis, thus resulting negative. Real-time PCR for SuHV-1 resulted positive in brain samples from both dogs (sample 344,427–1 from Dog 1 and sample 344,427–2 from Dog 2). Viral isolation on PK15 and RK13 cell lines was achieved only for sample n. 344,427–1, and immunofluorescence and Real-Time PCR were used as additional confirmatory tests for the presence of the virus. Molecular typing and sequencing of the Real-Time PCR products were performed at the National Reference Center for Aujeszky's Disease, Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emila Romagna (IZSLER). Partial sequencing of the UL44 and US8 genes of two positive samples was performed, as previously described . The sequences were edited using the SeqMan program (DNASTAR, Madison®, USA) and were compared to reference sequences and wild-type SuHV-1 strains available in GenBank for phylogenetic analysis. Phylogenetic trees were constructed using the maximum likelihood (ML) method within the IQ-tree software with bootstrap analyses involving 1000 replicates. The sequence alignments were performed using the ClustalW method (DNASTAR, Madison, USA) and were manually optimized. The best-fit model of the nucleotide substitution was determined using the jModelTest v.0.1.1 . All the models were compared using the Akaike’s information criterion (AIC) and the Bayesian information criterion (BIC). The preferred model was the HKY85 + I + G model. The topologies were verified with the neighbour-joining method and the Kimura two-parameter model using MEGA 7 . Blast analysis of the gC sequences showed the highest identity rates (100%) with two Italian sequences, wild boar/Italy/309516/2/2011 and dog/Italy/325409/2010 . The first came from a wild boar in the Alps (Northern Italy) and the second from a hunting dog in the province of Bologna, both from locations far from the geographic origin of the canine sequences analyzed in this study. The phylogenetic tree of the UL44 genes, which is one of the most variable genes, showed three clades: A, B, and Asian . The Italian strains all belong to the A clade except for three strains isolated in the 1990s that belong to the Asian clade . The sequences studied here were placed in the Italian Clade 1 and wild boars and hunting dogs from Italy and France . The Italian gC sequences obtained from pigs and farm dogs formed the Italian clade 2 . Italian strains belonging to Italian clades 1 and 2 showed different amino acid changes in the gC protein, which are highlighted in supplementary figure n. 1 . The sequences of the UL44 gene obtained in the present study from Dog 1 and Dog 2 were submitted in GenBank . The US8 gene encoding the gE protein was found to be a very conserved gene and, therefore, much less informative than the UL44 gene. Thus, the low number of information sites has led to a phylogenetic tree with not very high bootstrap values. Blast analysis of the two gE sequences showed 100% identity with most of the Italian wild boar, dog and pig samples whose gC sequences belonged to both Italian clades 1 and 2 . Phylogenetic analysis of the US8 gene revealed the presence of 4 clades, named A, B, C and Asia, as reported in the study of Fonseca et al. . The sequences of the two dogs were placed in the C clade together with all the Italian sequences that formed the Italian clades 1 and 2 in the UL44 phylogenetic tree. Interestingly, this clade was reported by Fonseca et al. as a new clade that included only the strain IB341/86 isolated in Brazil in 1986. The sequences of the US8 gene obtained in the present study from Dog 1 and Dog 2 were submitted in GenBank . The sequencing of the complete genome of some samples characterized by gC sequences belonging to both Italian clades 1 and 2 should be performed to investigate better the different positions of the gC and gE sequences in their phylogenetic trees. Fig. 1 Dog 1: Injuries of traumatic origin due to intense itching in the peri-ocular region Fig. 2 Dog 2: Injuries of traumatic origin due to intense itching in the peri-ocular region, cheek and labial region Fig. 3 Dog 2: Examination of the splanchnic cavities and inspection of stomach contents. Highlighting of the presence of wild boar meat and offal Fig. 4 Dog 2: Evidence of hyperemia affecting the meninges and meningeal vessels Fig. 5 Phylogenetic tree based on partial sequencing of the UL44 gene. The tree was obtained using the maximum likelihood method and the HKY85 + I + G model with 1000 bootstrap replicates. The bootstrap percentage values are indicated at nodes. The Italian sequences are underlined Fig. 6 Phylogenetic tree based on partial sequencing of the US8 gene. The tree was obtained using the maximum likelihood method and the HKY85 + I + G model with 1000 bootstrap replicates. The bootstrap percentage values are indicated at nodes. The Italian sequences are underlined	4.148438	0.854492	sec[1]/p[0]	en	0.999998	34996475	https://doi.org/10.1186/s12917-022-03138-2	[ "sequences", "dogs", "both", "italian", "wild", "phylogenetic", "samples", "using", "tree", "gene" ]	[ { "code": "LB73.10", "title": "Poland syndrome" }, { "code": "LD44.N0", "title": "CATCH 22 phenotype" }, { "code": "LB31.3", "title": "Exstrophy of urinary bladder" }, { "code": "LD2F.1Y", "title": "Other specified syndromes with multiple structural anomalies, not of environmental origin" }, { "code": "LA56", "title": "Pierre Robin syndrome" }, { "code": "1F72", "title": "Dipylidiasis" }, { "code": "1F73.Z", "title": "Echinococcosis, unspecified" }, { "code": "1F7Y", "title": "Other specified diseases due to cestodes" }, { "code": "LB99.6", "title": "Acheiria" }, { "code": "MB51.Z", "title": "Diplegia of upper extremities, unspecified" } ]	=== ICD-11 CODES FOUND === [LB73.10] Poland syndrome Definition: Poland syndrome is characterised by a unilateral absence or hypoplasia of the pectoralis major muscle (most frequently involving the sternocostal portion), and a variable degree of ipsilateral hand anomalies, including symbrachydactyly. Also known as: Poland syndrome \| Poland sequence \| Poland anomaly [LD44.N0] CATCH 22 phenotype Definition: Monosomy 22q11 (DiGeorge Velocardiofacial syndrome, DGS/VCF) syndrome is a chromosomal anomaly characterised by the association of several variable malformations: hypoplastic thymus and parathyroid glands, congenital conotruncal heart defects, a subtle but characteristic facial dysmorphism, cleft palate or velar insufficiency, and learning difficulties. Also known as: CATCH 22 phenotype \| Conotruncal anomalies face syndrome \| Velocardiofacial syndrome \| Shprintzen syndrome \| Sedlackova syndrome Includes: Pharyngeal pouch syndrome \| DiGeorge syndrome \| Velocardiofacial syndrome [LB31.3] Exstrophy of urinary bladder Definition: Bladder exstrophy (or classic bladder exstrophy) is a congenital genitourinary malformation belonging to the spectrum of the exstrophy-epispadias complex and is characterised by an evaginated bladder plate, epispadias and an anterior defect of the pelvis, pelvic floor and abdominal wall. Also known as: Exstrophy of urinary bladder \| Ectopia vesicae \| Extroversion of bladder \| bladder ectopia \| congenital ectopic bladder Includes: Ectopia vesicae \| Extroversion of bladder [LD2F.1Y] Other specified syndromes with multiple structural anomalies, not of environmental origin Also known as: Other specified syndromes with multiple structural anomalies, not of environmental origin \| 46,XX disorder of sex development - anorectal anomalies \| 46,XX DSD - anorectal anomalies \| Aarskog-Scott syndrome \| Aarskog syndrome [LA56] Pierre Robin syndrome Definition: Pierre-Robin syndrome (or Pierre-Robin sequence) is characterised by triad of orofacial morphological anomalies consisting of retrognathism, glossoptosis and a posterior median velopalatal cleft. This condition is referred to as a sequence because the posterior cleft palate is a secondary defect associated with abnormal mandibular development: mandibular hypoplasia occurring early in gestation causes the tongue to be maintained high-up in the oral cavity, preventing fusion of the palatal shelves Also known as: Pierre Robin syndrome \| Pierre Robin sequence [1F72] Dipylidiasis Definition: A condition caused by an infection with the parasitic worm Dipylidium caninum. This condition is commonly present with abdominal pain, diarrhoea, anal pruritus, or may be asymptomatic. Transmission is by ingestion of an infected flea. Confirmation is by identification of Dipylidium caninum eggs in a faecal sample. Also known as: Dipylidiasis \| dipylidiosis \| dipylidium infection \| dog fleaworm \| infection by dipylidium caninum [1F73.Z] Echinococcosis, unspecified Also known as: Echinococcosis, unspecified \| Echinococcosis \| unilocular echinococcosis \| Echinococcus disease \| echinococcus granulosus infection [1F7Y] Other specified diseases due to cestodes Also known as: Other specified diseases due to cestodes \| Other cestode infestations \| Other specified cestode infections \| Coenurosis \| coenuriasis [LB99.6] Acheiria Definition: A condition caused by failure of one or both hands to develop during the antenatal period. Also known as: Acheiria \| Congenital absence of hand \| agenesis of hand \| congenital absence of hand and finger \| congenital absence of hand and wrist [MB51.Z] Diplegia of upper extremities, unspecified Also known as: Diplegia of upper extremities, unspecified \| Diplegia of upper extremities \| paralysis of both upper limbs \| both upper extremity paralysis \| diplegia of upper limbs === GRAPH WALKS === --- Walk 1 --- [LB73.10] Poland syndrome Def: Poland syndrome is characterised by a unilateral absence or hypoplasia of the pectoralis major muscle (most frequently involving the sternocostal portion), and a variable degree of ipsilateral hand an... --PARENT--> [LB73.1] Structural developmental anomalies of chest wall Def: Any condition caused by failure of the chest wall to correctly develop during the antenatal period.... --CHILD--> [LB73.10] Poland syndrome Def: Poland syndrome is characterised by a unilateral absence or hypoplasia of the pectoralis major muscle (most frequently involving the sternocostal portion), and a variable degree of ipsilateral hand an... --- Walk 2 --- [LB73.10] Poland syndrome Def: Poland syndrome is characterised by a unilateral absence or hypoplasia of the pectoralis major muscle (most frequently involving the sternocostal portion), and a variable degree of ipsilateral hand an... --PARENT--> [LB73.1] Structural developmental anomalies of chest wall Def: Any condition caused by failure of the chest wall to correctly develop during the antenatal period.... --CHILD--> [LB73.10] Poland syndrome Def: Poland syndrome is characterised by a unilateral absence or hypoplasia of the pectoralis major muscle (most frequently involving the sternocostal portion), and a variable degree of ipsilateral hand an... --- Walk 3 --- [LD44.N0] CATCH 22 phenotype Def: Monosomy 22q11 (DiGeorge Velocardiofacial syndrome, DGS/VCF) syndrome is a chromosomal anomaly characterised by the association of several variable malformations: hypoplastic thymus and parathyroid gl... --PARENT--> [LD44.N] Deletions of chromosome 22 --CHILD--> [LD44.NY] Other specified deletions of chromosome 22 --- Walk 4 --- [LD44.N0] CATCH 22 phenotype Def: Monosomy 22q11 (DiGeorge Velocardiofacial syndrome, DGS/VCF) syndrome is a chromosomal anomaly characterised by the association of several variable malformations: hypoplastic thymus and parathyroid gl... --PARENT--> [LD44.N] Deletions of chromosome 22 --CHILD--> [LD44.NZ] Deletions of chromosome 22, unspecified --- Walk 5 --- [LB31.3] Exstrophy of urinary bladder Def: Bladder exstrophy (or classic bladder exstrophy) is a congenital genitourinary malformation belonging to the spectrum of the exstrophy-epispadias complex and is characterised by an evaginated bladder ... --PARENT--> [LB31] Structural developmental anomalies of urinary tract Def: Any condition caused by failure of the urinary tract to correctly develop during the antenatal period.... --CHILD--> [LB31.2] Fetal lower urinary tract obstruction Def: A disease caused by partial or complete obstruction of the urethra, during the antenatal period. This disease can present with enlarged bladder, oligohydramnios, or pulmonary hypoplasia. Confirmation ... --- Walk 6 --- [LB31.3] Exstrophy of urinary bladder Def: Bladder exstrophy (or classic bladder exstrophy) is a congenital genitourinary malformation belonging to the spectrum of the exstrophy-epispadias complex and is characterised by an evaginated bladder ... --PARENT--> [LB31] Structural developmental anomalies of urinary tract Def: Any condition caused by failure of the urinary tract to correctly develop during the antenatal period.... --CHILD--> [LB31.0] Congenital hydronephrosis Def: Congenital hydronephrosis is a renal urinary disease characterised by distension and dilation of the renal pelvis and calyces secondary to various congenital obstructive malformations of the kidneys a...	[ "[LB73.10] Poland syndrome\n Def: Poland syndrome is characterised by a unilateral absence or hypoplasia of the pectoralis major muscle (most frequently involving the sternocostal portion), and a variable degree of ipsilateral hand an...\n --PARENT--> [LB73.1] Structural developmental anomalies of chest wall\n Def: Any condition caused by failure of the chest wall to correctly develop during the antenatal period....\n --CHILD--> [LB73.10] Poland syndrome\n Def: Poland syndrome is characterised by a unilateral absence or hypoplasia of the pectoralis major muscle (most frequently involving the sternocostal portion), and a variable degree of ipsilateral hand an...", "[LB73.10] Poland syndrome\n Def: Poland syndrome is characterised by a unilateral absence or hypoplasia of the pectoralis major muscle (most frequently involving the sternocostal portion), and a variable degree of ipsilateral hand an...\n --PARENT--> [LB73.1] Structural developmental anomalies of chest wall\n Def: Any condition caused by failure of the chest wall to correctly develop during the antenatal period....\n --CHILD--> [LB73.10] Poland syndrome\n Def: Poland syndrome is characterised by a unilateral absence or hypoplasia of the pectoralis major muscle (most frequently involving the sternocostal portion), and a variable degree of ipsilateral hand an...", "[LD44.N0] CATCH 22 phenotype\n Def: Monosomy 22q11 (DiGeorge Velocardiofacial syndrome, DGS/VCF) syndrome is a chromosomal anomaly characterised by the association of several variable malformations: hypoplastic thymus and parathyroid gl...\n --PARENT--> [LD44.N] Deletions of chromosome 22\n --CHILD--> [LD44.NY] Other specified deletions of chromosome 22", "[LD44.N0] CATCH 22 phenotype\n Def: Monosomy 22q11 (DiGeorge Velocardiofacial syndrome, DGS/VCF) syndrome is a chromosomal anomaly characterised by the association of several variable malformations: hypoplastic thymus and parathyroid gl...\n --PARENT--> [LD44.N] Deletions of chromosome 22\n --CHILD--> [LD44.NZ] Deletions of chromosome 22, unspecified", "[LB31.3] Exstrophy of urinary bladder\n Def: Bladder exstrophy (or classic bladder exstrophy) is a congenital genitourinary malformation belonging to the spectrum of the exstrophy-epispadias complex and is characterised by an evaginated bladder ...\n --PARENT--> [LB31] Structural developmental anomalies of urinary tract\n Def: Any condition caused by failure of the urinary tract to correctly develop during the antenatal period....\n --CHILD--> [LB31.2] Fetal lower urinary tract obstruction\n Def: A disease caused by partial or complete obstruction of the urethra, during the antenatal period. This disease can present with enlarged bladder, oligohydramnios, or pulmonary hypoplasia. Confirmation ...", "[LB31.3] Exstrophy of urinary bladder\n Def: Bladder exstrophy (or classic bladder exstrophy) is a congenital genitourinary malformation belonging to the spectrum of the exstrophy-epispadias complex and is characterised by an evaginated bladder ...\n --PARENT--> [LB31] Structural developmental anomalies of urinary tract\n Def: Any condition caused by failure of the urinary tract to correctly develop during the antenatal period....\n --CHILD--> [LB31.0] Congenital hydronephrosis\n Def: Congenital hydronephrosis is a renal urinary disease characterised by distension and dilation of the renal pelvis and calyces secondary to various congenital obstructive malformations of the kidneys a..." ]	LB73.10	Poland syndrome	[ { "from_icd11": "LD44.N0", "icd10_code": "D821", "icd10_title": "Di George's syndrome" }, { "from_icd11": "LB31.3", "icd10_code": "Q6412", "icd10_title": "Cloacal exstrophy of urinary bladder" }, { "from_icd11": "LB31.3", "icd10_code": "Q6419", "icd10_title": "Other exstrophy of urinary bladder" }, { "from_icd11": "LB31.3", "icd10_code": "Q6410", "icd10_title": "Exstrophy of urinary bladder, unspecified" }, { "from_icd11": "LB31.3", "icd10_code": "Q64", "icd10_title": "Other congenital malformations of urinary system" }, { "from_icd11": "LB31.3", "icd10_code": "Q641", "icd10_title": "Exstrophy of urinary bladder" }, { "from_icd11": "LA56", "icd10_code": "Q870", "icd10_title": "Congenital malformation syndromes predominantly affecting facial appearance" }, { "from_icd11": "1F72", "icd10_code": "B711", "icd10_title": "Dipylidiasis" }, { "from_icd11": "1F73.Z", "icd10_code": "B6790", "icd10_title": "Echinococcosis, unspecified" }, { "from_icd11": "1F73.Z", "icd10_code": "B6799", "icd10_title": "Other echinococcosis" }, { "from_icd11": "1F73.Z", "icd10_code": "B67", "icd10_title": "Echinococcosis" }, { "from_icd11": "1F73.Z", "icd10_code": "B673", "icd10_title": "Echinococcus granulosus infection, other and multiple sites" }, { "from_icd11": "1F73.Z", "icd10_code": "B674", "icd10_title": "Echinococcus granulosus infection, unspecified" }, { "from_icd11": "1F73.Z", "icd10_code": "B676", "icd10_title": "Echinococcus multilocularis infection, other and multiple sites" }, { "from_icd11": "1F73.Z", "icd10_code": "B677", "icd10_title": "Echinococcus multilocularis infection, unspecified" } ]	D821	Di George's syndrome
Polymyositis is a rare but serious cause of respiratory failure and cardiac arrest. Its diagnosis can be particularly challenging due to the overlap of symptoms with other autoimmune and neuromuscular diseases . This case highlights the importance of a comprehensive diagnostic approach and a multidisciplinary management strategy to optimize patient outcomes. Early initiation of immunosuppressive therapy and supportive care were critical in improving this patient's condition, as demonstrated in several case reports and studies . This patient presented a significant diagnostic challenge because of the muscle weakness and respiratory involvement, which are characteristics of polymyositis but can also overlap with other conditions like inclusion body myositis, dermatomyositis, and even neuromuscular diseases such as Sjögren's syndrome . The initial differential diagnosis was complicated by these overlapping features. For example, dermatomyositis typically presents with cutaneous symptoms, but in some cases, especially those with minimal skin involvement, the disease may resemble polymyositis, as seen in a study by Syue et al. , who reported a similar diagnostic dilemma. This underscores the importance of thorough clinical evaluation and autoimmune workup, including serological tests for ANA and anti-SSA/Ro antibodies, as performed in this case. MRI played a pivotal role in this patient's diagnosis. In this case, MRI findings correlated well with the clinical presentation and laboratory results, reinforcing the diagnosis of polymyositis. MRI of the thighs revealed extensive subcutaneous and muscle edema, which is a hallmark of polymyositis . Unlike other imaging modalities, MRI provides superior soft-tissue resolution, enabling the early detection of muscle inflammation and edema even before clinical symptoms fully develop. Similar findings were reported in a study by Dauriat et al. , where MRI was instrumental in diagnosing diaphragmatic weakness in a patient with polymyositis. Moreover, muscle biopsy played a crucial role in confirming the diagnosis of polymyositis in this patient. Muscle biopsy confirmed the diagnosis by revealing characteristic histopathological features such as endomysial inflammation, muscle fiber necrosis, and muscle fiber regeneration, which are consistent with polymyositis. This is in line with findings from Kalluri and Oddis , who emphasized the importance of muscle biopsy in cases where clinical presentation overlaps with other inflammatory myopathies. Utilizing the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups, which include a combination of clinical, laboratory, and histopathological features, we were able to systematically assess and diagnose this patient accurately. The biopsy findings, along with elevated muscle enzymes and positive autoimmune markers (ANA, anti-SSA/Ro antibody), met the classification criteria for polymyositis, thereby solidifying the diagnosis . This comprehensive approach highlights the importance of muscle biopsy in the diagnostic algorithm of idiopathic inflammatory myopathies, ensuring the precise identification and appropriate management of the disease. Respiratory failure due to respiratory muscle weakness is a major complication of polymyositis. Similar to findings reported by Selva-O'Callaghan et al. , this patient initially required mechanical ventilation due to diaphragmatic paralysis. Mechanical ventilation is often required in patients with significant respiratory muscle involvement, as it provides support until muscle strength improves. Our patient was successfully weaned from mechanical ventilation, transitioning from bilevel positive airway pressure (BiPAP) to continuous positive airway pressure (CPAP) and eventually to room air, demonstrating significant recovery in respiratory function. Dauriat et al. noted that diaphragmatic weakness can be a key feature of respiratory involvement in polymyositis and early detection is crucial for managing respiratory failure. The gradual weaning process in our case, aided by physiotherapy and muscle strength improvement, aligns with recommendations from Kalluri and Oddis , who reported similar successful extubations after prolonged ventilator support in polymyositis patients. Cardiac arrest in polymyositis is a rare but serious complication, often linked to diaphragmatic weakness and its impact on autonomic nervous system regulation . The cardiac arrest in this patient can be attributed to the unique interplay of diaphragmatic paralysis and its impact on cardiac conduction and rhythm. The presence of these disturbances predominantly in the supine position suggests a mechanical influence on the cardiac plexuses. The bilateral diaphragmatic paralysis likely caused the compression of the vegetative cardiac plexuses (a network of autonomic nerves at the base of the heart, comprising sympathetic and parasympathetic fibers that regulate heart rate, rhythm, and conduction) and upward traction of the celiac plexus due to the elevated diaphragm, leading to parasympathetic stimulation. This mechanism is consistent with studies by Dregoesc et al. and Srivatsav et al. , who reported similar occurrences of cardiac arrhythmias and cardiac arrest in polymyositis patients with diaphragmatic involvement. Additionally, severe hypoxemia exacerbated by diaphragmatic weakness may have further precipitated cardiac arrest, a scenario observed by Ramana Raju et al. in a case of seronegative polymyositis. In the present case, the patient may have been able to maintain acceptable breathing while upright due to the effect of gravity assisting diaphragmatic function. However, when lying flat, the loss of gravitational assistance likely exacerbated respiratory compromise, leading to significant hypoxemia and subsequent cardiac arrest. Cardiac involvement in polymyositis is an area that is still under-explored, but several studies have highlighted its significance. Ramana Raju et al. and recent reviews on cardiac manifestations of inflammatory myopathies suggest that patients with polymyositis may present with a range of cardiac arrhythmias and even heart failure . This supports the need for careful cardiac monitoring in polymyositis patients, particularly those with significant diaphragmatic dysfunction. The management of polymyositis can be complicated by concurrent infections, as was evident in this case. While high-dose corticosteroids and immunosuppressive agents like methotrexate and IVIG are essential to manage the underlying autoimmune process, these treatments can predispose patients to infections . In this case, methotrexate therapy was delayed due to nosocomial infections, highlighting the challenge of balancing immunosuppression with the need for infection control. This is consistent with the findings of Syue et al. , who highlighted the need for careful monitoring and adjustment of immunosuppressive therapy in polymyositis patients with infections. The use of IVIG and rituximab, in this case, helped manage disease activity while minimizing the risk of infection, which aligns with recent studies advocating for the early use of biological agents in polymyositis patients with severe disease . The multidisciplinary approach was fundamental in the effective management and diagnosis of this complex case of polymyositis. Collaboration between various specialties, including neurology and rheumatology, enabled a comprehensive and cohesive treatment strategy. The neurology team was pivotal in assessing and managing the neuromuscular complications, conducting NCS and EMG, which provided critical insights into the extent of muscle involvement. Concurrently, the rheumatology team played a crucial role in the autoimmune workup, interpreting serological tests and guiding immunosuppressive therapy. Regular multidisciplinary meetings facilitated coordinated care, allowing for timely adjustments in the treatment plan, such as the transition from initial steroid therapy to more aggressive immunosuppressive treatments like IVIG and rituximab. This integrated approach not only optimized patient outcomes but also ensured that all potential complications, such as respiratory failure and cardiac involvement, were promptly addressed. The early involvement of physiotherapists further contributed to the patient's recovery, highlighting the value of holistic and collaborative medical practice in managing rare and severe autoimmune conditions, as also emphasized in other case reports . Future studies should investigate the pathophysiological basis of cardiac involvement in polymyositis, specifically examining the contributions of autonomic dysregulation, diaphragmatic compromise, and direct myocardial inflammation, to inform targeted monitoring strategies and optimize therapeutic interventions.	4.375	0.813965	sec[2]/p[0]	en	0.999998	40416264	https://doi.org/10.7759/cureus.82887	[ "polymyositis", "this", "cardiac", "muscle", "diaphragmatic", "respiratory", "involvement", "patients", "arrest", "autoimmune" ]	[ { "code": "4A41.1Z", "title": "Polymyositis, unspecified" }, { "code": "4A41.1Y", "title": "Other specified polymyositis" }, { "code": "4A41.10", "title": "Juvenile polymyositis" }, { "code": "FB31.1", "title": "Fibrodysplasia ossificans progressiva" }, { "code": "CB05.1", "title": "Interstitial lung diseases associated with connective tissue diseases" }, { "code": "4A01.03", "title": "Transient hypogammaglobulinaemia of infancy" }, { "code": "BE2Y", "title": "Other specified diseases of the circulatory system" }, { "code": "BC4Z", "title": "Diseases of the myocardium or cardiac chambers, unspecified" }, { "code": "BD1Z", "title": "Heart failure, unspecified" }, { "code": "LA8Z", "title": "Structural developmental anomaly of heart or great vessels, unspecified" } ]	=== ICD-11 CODES FOUND === [4A41.1Z] Polymyositis, unspecified Also known as: Polymyositis, unspecified \| Polymyositis \| PM - [polymyositis] [4A41.1Y] Other specified polymyositis Also known as: Other specified polymyositis \| Anti-synthetase syndrome with polymyositis \| Necrotising polymyositis \| Polymyositis with overlap to nonorgan specific systemic autoimmune disorders [4A41.10] Juvenile polymyositis Definition: Juvenile polymyositis is a rare childhood idiopathic inflammatory myopathy. It is frequently misdiagnosed, as it lacks a unique clinical phenotype. Traditionally, it presents with weakness of the proximal muscles that evolves over weeks to months. The primary histologic features are fibre size variability, scattered necrotic and regenerating fibres, and perivascular and endomysial cellular infiltrates. Also known as: Juvenile polymyositis \| Juvenile polymyositis, necrotising \| Juvenile polymyositis, paraneoplastic \| Juvenile polymyositis with anti-synthetase auto-antibody \| Juvenile polymyositis with interstitial lung disease Excludes: Systemic sclerosis \| Overlap or undifferentiated nonorgan specific systemic autoimmune disease \| Antiphospholipid syndrome [FB31.1] Fibrodysplasia ossificans progressiva Definition: This is an extremely rare disease of the connective tissue where a mutation of the body's repair mechanism causes fibrous tissue (including muscle, tendon, and ligament) to be ossified when damaged. Also known as: Fibrodysplasia ossificans progressiva \| Myositis ossificans progressiva \| Man of stone \| diffuse progressive ossifying polymyositis \| fibrodysplasia ossificans congenita [CB05.1] Interstitial lung diseases associated with connective tissue diseases Definition: Interstitial lung diseases associated with connective tissue diseases refers to a group of lung diseases affecting the interstitium (the tissue and space around the air sacs of the lungs) associated with connective tissue diseases. Also known as: Interstitial lung diseases associated with connective tissue diseases \| Respiratory disorders in idiopathic inflammatory myopathies \| Respiratory disorders in juvenile dermatomyositis \| Respiratory disorders in juvenile idiopathic arthritis \| Respiratory disorders in mixed connective tissue disease [4A01.03] Transient hypogammaglobulinaemia of infancy Also known as: Transient hypogammaglobulinaemia of infancy \| immunoglobulin maturational delay \| THI - [transient hypogammaglobulinaemia of infancy] [BE2Y] Other specified diseases of the circulatory system Also known as: Other specified diseases of the circulatory system \| Certain specified forms of heart disease \| Cardiac disorder, unspecified \| disorder of heart NOS \| organic disease or disorder of heart [BC4Z] Diseases of the myocardium or cardiac chambers, unspecified Also known as: Diseases of the myocardium or cardiac chambers, unspecified \| Heart disease NOS \| cardiac disease NOS [BD1Z] Heart failure, unspecified Also known as: Heart failure, unspecified \| myocardial failure \| cardiac decompensation \| cardiac failure \| cardiac failure NOS [LA8Z] Structural developmental anomaly of heart or great vessels, unspecified Also known as: Structural developmental anomaly of heart or great vessels, unspecified \| Heart malformations \| Cardiac malformations \| congenital anomaly of heart \| congenital heart disease === GRAPH WALKS === --- Walk 1 --- [4A41.1Z] Polymyositis, unspecified --PARENT--> [4A41.1] Polymyositis Def: Polymyositis is an inflammatory muscle disease of unknown aetiology occurring predominantly in adults and characterised clinically by proximal muscle weakness (shoulders, arms, thighs), often with ass... --CHILD--> [4A41.11] Paraneoplastic polymyositis Def: Paraneoplastic is a rare cancer associated entity. It presents sub-, or acutely with proximal weakness, often including the neck flexors, dysphagia, rarely the respiratory muscles and the heart are in... --- Walk 2 --- [4A41.1Z] Polymyositis, unspecified --PARENT--> [4A41.1] Polymyositis Def: Polymyositis is an inflammatory muscle disease of unknown aetiology occurring predominantly in adults and characterised clinically by proximal muscle weakness (shoulders, arms, thighs), often with ass... --CHILD--> [4A41.10] Juvenile polymyositis Def: Juvenile polymyositis is a rare childhood idiopathic inflammatory myopathy. It is frequently misdiagnosed, as it lacks a unique clinical phenotype. Traditionally, it presents with weakness of the prox... --- Walk 3 --- [4A41.1Y] Other specified polymyositis --PARENT--> [4A41.1] Polymyositis Def: Polymyositis is an inflammatory muscle disease of unknown aetiology occurring predominantly in adults and characterised clinically by proximal muscle weakness (shoulders, arms, thighs), often with ass... --CHILD--> [4A41.11] Paraneoplastic polymyositis Def: Paraneoplastic is a rare cancer associated entity. It presents sub-, or acutely with proximal weakness, often including the neck flexors, dysphagia, rarely the respiratory muscles and the heart are in... --- Walk 4 --- [4A41.1Y] Other specified polymyositis --PARENT--> [4A41.1] Polymyositis Def: Polymyositis is an inflammatory muscle disease of unknown aetiology occurring predominantly in adults and characterised clinically by proximal muscle weakness (shoulders, arms, thighs), often with ass... --CHILD--> [4A41.10] Juvenile polymyositis Def: Juvenile polymyositis is a rare childhood idiopathic inflammatory myopathy. It is frequently misdiagnosed, as it lacks a unique clinical phenotype. Traditionally, it presents with weakness of the prox... --- Walk 5 --- [4A41.10] Juvenile polymyositis Def: Juvenile polymyositis is a rare childhood idiopathic inflammatory myopathy. It is frequently misdiagnosed, as it lacks a unique clinical phenotype. Traditionally, it presents with weakness of the prox... --PARENT--> [4A41.1] Polymyositis Def: Polymyositis is an inflammatory muscle disease of unknown aetiology occurring predominantly in adults and characterised clinically by proximal muscle weakness (shoulders, arms, thighs), often with ass... --CHILD--> [4A41.11] Paraneoplastic polymyositis Def: Paraneoplastic is a rare cancer associated entity. It presents sub-, or acutely with proximal weakness, often including the neck flexors, dysphagia, rarely the respiratory muscles and the heart are in... --- Walk 6 --- [4A41.10] Juvenile polymyositis Def: Juvenile polymyositis is a rare childhood idiopathic inflammatory myopathy. It is frequently misdiagnosed, as it lacks a unique clinical phenotype. Traditionally, it presents with weakness of the prox... --EXCLUDES--> [?] Systemic sclerosis Def: Systemic sclerosis is a systemic disorder of the connective tissue; manifested by hardening and thickening of the skin, by abnormalities involving the microvasculature and larger vessels, and by fibro... --EXCLUDES--> [?] Plaque morphoea Def: The commonest form of morphoea which presents as indurated waxy plaques, often with a violaceous border and commonly affecting the trunk, especially in the submammary folds and around the waist. The c...	[ "[4A41.1Z] Polymyositis, unspecified\n --PARENT--> [4A41.1] Polymyositis\n Def: Polymyositis is an inflammatory muscle disease of unknown aetiology occurring predominantly in adults and characterised clinically by proximal muscle weakness (shoulders, arms, thighs), often with ass...\n --CHILD--> [4A41.11] Paraneoplastic polymyositis\n Def: Paraneoplastic is a rare cancer associated entity. It presents sub-, or acutely with proximal weakness, often including the neck flexors, dysphagia, rarely the respiratory muscles and the heart are in...", "[4A41.1Z] Polymyositis, unspecified\n --PARENT--> [4A41.1] Polymyositis\n Def: Polymyositis is an inflammatory muscle disease of unknown aetiology occurring predominantly in adults and characterised clinically by proximal muscle weakness (shoulders, arms, thighs), often with ass...\n --CHILD--> [4A41.10] Juvenile polymyositis\n Def: Juvenile polymyositis is a rare childhood idiopathic inflammatory myopathy. It is frequently misdiagnosed, as it lacks a unique clinical phenotype. Traditionally, it presents with weakness of the prox...", "[4A41.1Y] Other specified polymyositis\n --PARENT--> [4A41.1] Polymyositis\n Def: Polymyositis is an inflammatory muscle disease of unknown aetiology occurring predominantly in adults and characterised clinically by proximal muscle weakness (shoulders, arms, thighs), often with ass...\n --CHILD--> [4A41.11] Paraneoplastic polymyositis\n Def: Paraneoplastic is a rare cancer associated entity. It presents sub-, or acutely with proximal weakness, often including the neck flexors, dysphagia, rarely the respiratory muscles and the heart are in...", "[4A41.1Y] Other specified polymyositis\n --PARENT--> [4A41.1] Polymyositis\n Def: Polymyositis is an inflammatory muscle disease of unknown aetiology occurring predominantly in adults and characterised clinically by proximal muscle weakness (shoulders, arms, thighs), often with ass...\n --CHILD--> [4A41.10] Juvenile polymyositis\n Def: Juvenile polymyositis is a rare childhood idiopathic inflammatory myopathy. It is frequently misdiagnosed, as it lacks a unique clinical phenotype. Traditionally, it presents with weakness of the prox...", "[4A41.10] Juvenile polymyositis\n Def: Juvenile polymyositis is a rare childhood idiopathic inflammatory myopathy. It is frequently misdiagnosed, as it lacks a unique clinical phenotype. Traditionally, it presents with weakness of the prox...\n --PARENT--> [4A41.1] Polymyositis\n Def: Polymyositis is an inflammatory muscle disease of unknown aetiology occurring predominantly in adults and characterised clinically by proximal muscle weakness (shoulders, arms, thighs), often with ass...\n --CHILD--> [4A41.11] Paraneoplastic polymyositis\n Def: Paraneoplastic is a rare cancer associated entity. It presents sub-, or acutely with proximal weakness, often including the neck flexors, dysphagia, rarely the respiratory muscles and the heart are in...", "[4A41.10] Juvenile polymyositis\n Def: Juvenile polymyositis is a rare childhood idiopathic inflammatory myopathy. It is frequently misdiagnosed, as it lacks a unique clinical phenotype. Traditionally, it presents with weakness of the prox...\n --EXCLUDES--> [?] Systemic sclerosis\n Def: Systemic sclerosis is a systemic disorder of the connective tissue; manifested by hardening and thickening of the skin, by abnormalities involving the microvasculature and larger vessels, and by fibro...\n --EXCLUDES--> [?] Plaque morphoea\n Def: The commonest form of morphoea which presents as indurated waxy plaques, often with a violaceous border and commonly affecting the trunk, especially in the submammary folds and around the waist. The c..." ]	4A41.1Z	Polymyositis, unspecified	[ { "from_icd11": "4A41.1Z", "icd10_code": "M3321", "icd10_title": "Polymyositis with respiratory involvement" }, { "from_icd11": "4A41.1Z", "icd10_code": "M3320", "icd10_title": "Polymyositis, organ involvement unspecified" }, { "from_icd11": "4A41.1Z", "icd10_code": "M3322", "icd10_title": "Polymyositis with myopathy" }, { "from_icd11": "4A41.1Z", "icd10_code": "M3329", "icd10_title": "Polymyositis with other organ involvement" }, { "from_icd11": "4A41.1Z", "icd10_code": "M332", "icd10_title": "Polymyositis" }, { "from_icd11": "FB31.1", "icd10_code": "M611", "icd10_title": "Myositis ossificans progressiva" }, { "from_icd11": "CB05.1", "icd10_code": "J991", "icd10_title": "" }, { "from_icd11": "4A01.03", "icd10_code": "D807", "icd10_title": "Transient hypogammaglobulinemia of infancy" }, { "from_icd11": "BC4Z", "icd10_code": "I5181", "icd10_title": "Takotsubo syndrome" }, { "from_icd11": "BC4Z", "icd10_code": "I5189", "icd10_title": "Other ill-defined heart diseases" }, { "from_icd11": "BC4Z", "icd10_code": "I519", "icd10_title": "Heart disease, unspecified" }, { "from_icd11": "BC4Z", "icd10_code": "I510", "icd10_title": "Cardiac septal defect, acquired" }, { "from_icd11": "BC4Z", "icd10_code": "I515", "icd10_title": "Myocardial degeneration" }, { "from_icd11": "BC4Z", "icd10_code": "I51", "icd10_title": "Complications and ill-defined descriptions of heart disease" }, { "from_icd11": "BC4Z", "icd10_code": "I516", "icd10_title": "" } ]	M3321	Polymyositis with respiratory involvement
A male purebred Arabian horse weighing 410 kg, submitted to 6 h of food fasting had a heart rate (HR) of 40 bpm, respiratory rate (RR) of 22 mrm, rosy mucous membranes, capillary refill time (CRT) of 2 s, rectal temperature (RT) of 37.1 °C and hematological parameters within the reference range for the species (Table 1 , Basal) before the administration of the antibiotic. About 17 min into the administration of ceftriaxone sodium (Day 1), after 205 mL of the solution had dripped, the horse showed tachycardia (heart rate = 96 bpm), dyspnea and urticaria on the neck left side (the same side where the drug was being injected). The drug dripping was discontinued immediately, but the animal still presented severe dyspnea. The gelding respiratory function normalized a minute after 0.05 mg/kg dexamethasone was injected. A noticeable swelling of eyelids was observed an hour after the allergic event. At this time the patient had a HR of 48 bpm, RR of 20 mrm, pale mucosa, RT of 37.7 °C and a slight reduction of intestinal motility. The horse behavior remained apathetic for the rest of the day, with no significant changes upon physical examination and was fed only hay. On day 2 in the morning, the gelding was fed 1.0 kg of commercial feed, but due to abdominal discomfort it positioned itself on lateral recumbency. Upon examination, the horse had severe bilateral abdominal distention, a HR of 37 bpm, RR 20 mrm, RT 37.2 °C, pale mucosa, intestinal hypomotility and yellowish and turbid peritoneal fluid. In the laboratory, the peritoneal fluid was characterized by total protein of 96 g/dL; pH 7.6; density 1.010 g/dL and 1250 cells/ml (71 % segmented neutrophils, 22 % lymphocytes and 7 % macrophages). Hematological and blood gas evaluation of venous blood showed anemia and hemoconcentration (Table 1 , Day 2), metabolic and respiratory acidosis, hyponatremia, hypokalemia, hypochloremia, hyperglycemia, and a blood lactate concentration (Table 2 , Day 2). The abdominal ultrasonography showed severe gaseous distension, ileus , along with wall thickening of small intestine . The ultrasonography results were consistent with volvulus of the small intestine; therefore, the gelding was referred to the surgical center for exploratory celitomy. Before the surgery, an intravenous antibiotic therapy with 20.000U/kg potassium penicillin 3 was initiated. During surgery, were observed gas distention throughout the small bowel, wall edema of the small and large colon, cecum, jejunum and ileus . There were also retroflexion of the pelvic flexure and displacement of cecum. The small intestine milking was followed by gas aspiration of the cecum, colon repositioning and washing of the abdominal cavity with neomycin diluted in 10 % Sodium lactate Ringer's solution. After surgery, the horse recovered uneventful from anesthesia and defecated upon rising. The antibiotic therapy was continued post operatively with penicillin potassium (20,000U/kg), every 8 h, for three consecutive days. The patient was also treated with a single dose of both furosemide (0.5 mg/kg) and dexamethasone (0.05 mg/kg) to reduce the intestinal edema; 30 mL of Potassium Chloride (150 mg/mL) diluted in 1 L of Sodium Lactate Ringer's solution to correct the hypokalemia; 3 l of solution of 10 % DMSO solution (100 mL/L in Ringer's lactate solution), once daily for 2 days; and, flunixin meglumine (0.25 mg/kg) once daily for 3 days. The abdominal incision was cleaned using aqueous chlorhexidine solution while repellent was applied around the surgical wound twice a day, for 10 days. This patient progressed steadily until the eighteenth day after anaphylaxis, when it showed apathy, loss of appetite, fever of 40.1 °C, pale mucosa, 3 s CRT, HR 72 bpm, RR 44 mrm and severe back pain. A blood sample was collected using EDTA tube and sent to the Parasitology Laboratory for Polymerase Chain Reaction (Nested-PCR) to detect the presence of Babesia caballi and Theileria equi , as well as Real-Time PCR for Anaplasma phagocytophilum . The test revealed Theileria equi infection. Therefore, intramuscular treatment with imidocarb 4 (4.0 mg/kg) was instituted, divided into two daily doses for 2 days, along with Dipyrone (25 mg/kg), every 12 h for 2 days. Subsequent to treating piroplasmosis, the gelding also revealed high serum concentrations of indirect bilirubin, creatine kinase, gamma glutamyl transferase, globulin and fibrinogen (Table 3 , Day 20). On the twentieth day after anaphylactoid reaction, the gelding showed marked hypochromic normocytic anemia and neutrophilia (Table 1 , day 20) and the patient was transfused with 6 L of whole blood. The following day, the blood parameters improved (Tables 1 and 3 , Day 21). However, the horse showed signs of abdominal discomfort though sternal recumbence and anorexia with normal intestinal motility, fecal output and consistency, mild tachycardia and depression, suggestive of gastritis. A twenty-day course of omeprazole 5 was instituted and a satisfactory improvement of its clinical and hematological status occurred 28 days after the anaphylaxis (Tables 1 , 2 and 3 , Day 28). Table 1 Gelding red blood cell count before and after anaphylactic reaction to sodium ceftriaxone, which occurred on day 1 Basal Day 2 Day 3 Day 6 Day 10 Day 20 Day 21 Day 28 Reference a Erythrocytes x 10 6 [cells/ml] 8.40 6.72 6.10 6.32 6.30 3.10 6.20 6.50 6.0–9.7 Hemoglobin [g/dL] 12.5 10.6 9.8 9.8 9.2 4.2 8.6 10.0 8.3–14.4 Hematocrit [%] 38.0 29.5 26.7 27.4 28.0 13.0 27.0 30.0 30–44 MCV [fL] 45.2 - - - 44.4 41.9 43.5 46.2 36–52.1 MCH [pg] 14.9 - - - 14.6 13.5 13.9 15.4 11.5–18.2 MCHC [g/dL] 32.9 - - - 32.9 32.3 31.9 33.4 31.2–34.9 Leucocytes [cells/uL] 10100 9800 12900 5700 11200 10800 14800 9500 6400–10600 Basophiles [cells/uL] 0 0 0 0 0 0 0 0 0 Eosinophils [cells/uL] 808 0 0 100 112 216 148 285 0–320 Segmented Neutrophils [cells/uL] 6060 7800 9100 6600 8736 6804 11692 5700 2775–7530 Rod Neutrophils [cells/uL] 202 0 100 0 448 216 1480 285 94–420 Lymphocytes [cells/uL] 2727 2100 800 2900 1680 3348 1184 3135 1088–5096 Monocytes [cells/uL] 303 100 0 400 224 216 296 190 90–318 Platelets [cells/uL] 194000 246000 242000 279000 323000 90000 96000 368000 90000–322000 MCV mean corpuscular volume; MCH mean corpuscular hemoglobin; MCHC mean corpuscular hemoglobin concentration a Reference ranges obtained for total blood cell count for 33 domestic horses of different breeds, serum negative for Borrelia burgdorferi , kept under the same feeding and management conditions Table 2 Gelding blood gas analysis after anaphylactic reaction to sodium ceftriaxone, which occurred on day 1 Day 2 Day 3 Day 28 Reference a pH 7.271 7.467 7.374 7.384–7.408 pCO 2 [mmHg] 69.6 42.3 45.1 35–45 pO 2 [mmHg] 55.4 38.5 35 35–45 HCO 3 − [mmol/L] 17.7 27.8 26.4 21–53 Na + [mmol/L] 116.4 130.1 138 135–148 K + [mmol/L] 2.96 2.51 4.0 3.5–4.5 Cl − [mmol/L] 88.5 100.5 102.2 98–107 Glucose [mmol/L] 7.3 8.1 4.0 4.1–5.9 Lactate [mmol/L] 5.6 1.1 1.2 1.0–1.7 pCO 2 partial pressure of carbon dioxide; pO 2 partial pressure of oxygen; HCO 3 − bicarbonate ion; Na + sodium ion; K + potassium ion; Cl − chloride ion a Reference ranges obtained with the iStat EG7+ device Values in italic represent relevant modifications in the parameter Fig. 1 Abdominal ultrasound of the gelding with tympanic colic as a result of anaphylactic reaction to sodium ceftriaxone. Image obtained by ventral-abdominal positioning of the probe, caudal to xiphoid. Note the thickening of intestinal wall, distention, atony and ileus in segments of the small intestine. Diagnostic Imaging Sector - FCAV - UNESP - Jaboticabal Fig. 2 Exposure of the gelding cecum and jejunum during exploratory celiotomy. Full line arrow: cecum. Dashed line arrow: jejunal serosa showing edema due to anaphylaxis caused by sodium ceftriaxone, in lighter color compared to other intestinal loops Table 3 Gelding serum biochemical parameters before and after anaphylactic reaction to sodium ceftriaxone, which occurred on day 1 Basal Day 6 Day 10 Day 20 Day 21 Day 28 Reference a Direct bilirubin [mg/dL] 0.28 - 1.10 0.29 0.35 0.27 0.12–0.31 Indirect bilirubin [mg/dL] 0.06 - 0.40 2.25 4.12 0.51 0.07–1.07 Creatine phosphokinase [U/L] 146 - 80 448 1162 120 84–368 Urea [mg/dL] 15 21 26 26 20 41 14–41 Creatinine [mg/dL] 1.3 1.6 0.9 0.9 0.7 1.3 1.1–1.7 Aspartate Amino Transferase [U/L] 302 220 173 296 426 271 232–447 Gamma Glutamyl Transferase [U/L] 18 68 21 16 18 17 2.0–19.0 Total Protein [g/dL] 6.4 6.4 5.4 6.9 7.6 6.7 4.0–7.7 Albumin [g/dL] 2.4 - 2.9 2.1 2.3 1.7 1.7–3.2 Globulin [g/dL] 4.0 - 2.5 4.8 5.3 5.0 2.3–4.8 Fibrinogen [g/dL] 0.1 0.4 0.5 1.2 0.9 0.2 0.1–0.4 a References ranges obtained from the hematological analysis of 33 domestic horses of several breeds, serum negative for Borrelia burgdorferi , kept under the same management and feeding conditions Values in italic represent relevant modifications in the parameter	4.167969	0.941895	sec[1]/sec[0]/p[0]	en	0.999998	26265349	https://doi.org/10.1186/s12917-015-0478-6	[ "gelding", "cells", "sodium", "blood", "abdominal", "solution", "horse", "reference", "ceftriaxone", "intestinal" ]	[ { "code": "MF9Y", "title": "Other specified clinical findings on examination of urine, without diagnosis" }, { "code": "5C56.20", "title": "Mucolipidosis" }, { "code": "3A51.1", "title": "Sickle cell disease without crisis" }, { "code": "9A96.3", "title": "Primary anterior uveitis" }, { "code": "3A61.Z", "title": "Acquired pure red cell aplasia, unspecified" }, { "code": "5C72", "title": "Hypo-osmolality or hyponatraemia" }, { "code": "5C71", "title": "Hyperosmolality or hypernatraemia" }, { "code": "5C64.6", "title": "Disorders of sodium metabolism" }, { "code": "5B5K.5", "title": "Sodium chloride deficiency" }, { "code": "5B91.2", "title": "Sodium chloride excess" } ]	=== ICD-11 CODES FOUND === [MF9Y] Other specified clinical findings on examination of urine, without diagnosis Also known as: Other specified clinical findings on examination of urine, without diagnosis \| Methaemoglobinuria \| Other and unspecified abnormal findings in urine \| Calciuria \| Cells and casts in urine [5C56.20] Mucolipidosis Also known as: Mucolipidosis \| Mucolipidosis type 3 \| Pseudo-Hurler polydystrophy \| Pseudo-Hurler disease \| Mucolipidosis type 2 Excludes: Sialidosis (mucolipidosis type 1) [3A51.1] Sickle cell disease without crisis Definition: A disorder caused by a HbS mutation in the haemoglobin gene. This disorder is characterised by abnormal rigid sickle-shaped red blood cells decreasing its ability to carry oxygen. This disorder may present with fatigue, shortness of breath, dizziness, headaches, pallor of skin or mucous membranes, and jaundice. This disorder is confirmed by identification of HbS mutation by genetic testing. Also known as: Sickle cell disease without crisis \| Hb-SS disease without crisis \| HbSS without crisis \| Sickle-cell anaemia without crisis \| SCD - [sickle cell disease] [9A96.3] Primary anterior uveitis Definition: This refers to primary inflammation of the uvea. The uvea consists of the middle, pigmented, vascular structures of the eye and includes the iris, ciliary body, and choroid. Also known as: Primary anterior uveitis \| anterior chamber cell [3A61.Z] Acquired pure red cell aplasia, unspecified Also known as: Acquired pure red cell aplasia, unspecified \| Acquired pure red cell aplasia \| acquired red cell aplasia \| red cell aplasia NOS \| pure red cell aplastic anaemia [5C72] Hypo-osmolality or hyponatraemia Definition: Serum sodium concentrations of less than 135 mEq/L; decreased serum concentration of osmotically active particles Also known as: Hypo-osmolality or hyponatraemia \| hypo-osmolality \| hyponatraemia \| hyponatremia syndrome \| hyponatremic Includes: sodium [na] deficiency Excludes: Syndrome of inappropriate secretion of antidiuretic hormone [5C71] Hyperosmolality or hypernatraemia Definition: Serum sodium concentrations in excess of 145 mmol/L; increased serum concentration of osmotically active particles Also known as: Hyperosmolality or hypernatraemia \| Hyperosmolality \| hyperosmolality syndrome \| nonketotic hyperosmolar syndrome \| hyperosmolar syndrome [5C64.6] Disorders of sodium metabolism Also known as: Disorders of sodium metabolism [5B5K.5] Sodium chloride deficiency Definition: Sodium and chloride are usually found together in most foods as sodium chloride, also termed salt. For that reason, the effects of sodium and chloride deficiency are considered together. Deficiency can be caused by poor intake or increased losses (e.g., diuretics increase the urinary excretion of water, sodium, and chloride; in cystic fibrosis the sodium and chloride content of sweat is very high; gastrointestinal losses are associated with diarrhoeal diseases, emesis, ostomy output and other ca Also known as: Sodium chloride deficiency [5B91.2] Sodium chloride excess Definition: The main adverse effect of increased sodium chloride in the diet is increased blood pressure, which is a major risk factor for cardiovascular-renal diseases. However, evidence from a variety of studies, including observational studies and clinical trials, has demonstrated heterogeneity in the blood pressure responses to sodium intake. Those individuals with the greatest reductions in blood pressure in response to decreased sodium intake are termed “salt sensitive”. Also known as: Sodium chloride excess === GRAPH WALKS === --- Walk 1 --- [MF9Y] Other specified clinical findings on examination of urine, without diagnosis --PARENT--> [?] Clinical findings on examination of urine, without diagnosis --CHILD--> [MF91] Bilirubinuria Def: Bilirubinuria means the presence of any bile pigment in the urine.... --- Walk 2 --- [MF9Y] Other specified clinical findings on examination of urine, without diagnosis --PARENT--> [?] Clinical findings on examination of urine, without diagnosis --EXCLUDES--> [?] Clinical findings on antenatal screening of mother Def: Any sign characterised by an abnormality detected during an antenatal screening of the mother.... --- Walk 3 --- [5C56.20] Mucolipidosis --EXCLUDES--> [?] Sialidosis --PARENT--> [?] Oligosaccharidosis --- Walk 4 --- [5C56.20] Mucolipidosis --EXCLUDES--> [?] Sialidosis --CHILD--> [?] Sialidosis type 2 Def: Sialidosis is a lysosomal storage disease belonging to the group of oligosaccharidoses or glycoproteinoses. Two types of sialidosis have been defined, type 2 (also referred to as the infantile, dysmor... --- Walk 5 --- [3A51.1] Sickle cell disease without crisis Def: A disorder caused by a HbS mutation in the haemoglobin gene. This disorder is characterised by abnormal rigid sickle-shaped red blood cells decreasing its ability to carry oxygen. This disorder may pr... --PARENT--> [3A51] Sickle cell disorders or other haemoglobinopathies Def: Any disorder caused by a HbS mutation in the haemoglobin gene. This disorder is characterised by abnormal rigid sickle-shaped red blood cells decreasing its ability to carry oxygen. This disorder may ... --CHILD--> [3A51.1] Sickle cell disease without crisis Def: A disorder caused by a HbS mutation in the haemoglobin gene. This disorder is characterised by abnormal rigid sickle-shaped red blood cells decreasing its ability to carry oxygen. This disorder may pr... --- Walk 6 --- [3A51.1] Sickle cell disease without crisis Def: A disorder caused by a HbS mutation in the haemoglobin gene. This disorder is characterised by abnormal rigid sickle-shaped red blood cells decreasing its ability to carry oxygen. This disorder may pr... --PARENT--> [3A51] Sickle cell disorders or other haemoglobinopathies Def: Any disorder caused by a HbS mutation in the haemoglobin gene. This disorder is characterised by abnormal rigid sickle-shaped red blood cells decreasing its ability to carry oxygen. This disorder may ... --CHILD--> [3A51.2] Sickle cell disease with crisis Def: Sickle cell crisis occurs when the sickle cells block blood flow, thus decreasing oxygen delivery to the tissues. This results in intense to severe pain in the extremities, lower back, abdomen, and ch...	[ "[MF9Y] Other specified clinical findings on examination of urine, without diagnosis\n --PARENT--> [?] Clinical findings on examination of urine, without diagnosis\n --CHILD--> [MF91] Bilirubinuria\n Def: Bilirubinuria means the presence of any bile pigment in the urine....", "[MF9Y] Other specified clinical findings on examination of urine, without diagnosis\n --PARENT--> [?] Clinical findings on examination of urine, without diagnosis\n --EXCLUDES--> [?] Clinical findings on antenatal screening of mother\n Def: Any sign characterised by an abnormality detected during an antenatal screening of the mother....", "[5C56.20] Mucolipidosis\n --EXCLUDES--> [?] Sialidosis\n --PARENT--> [?] Oligosaccharidosis", "[5C56.20] Mucolipidosis\n --EXCLUDES--> [?] Sialidosis\n --CHILD--> [?] Sialidosis type 2\n Def: Sialidosis is a lysosomal storage disease belonging to the group of oligosaccharidoses or glycoproteinoses. Two types of sialidosis have been defined, type 2 (also referred to as the infantile, dysmor...", "[3A51.1] Sickle cell disease without crisis\n Def: A disorder caused by a HbS mutation in the haemoglobin gene. This disorder is characterised by abnormal rigid sickle-shaped red blood cells decreasing its ability to carry oxygen. This disorder may pr...\n --PARENT--> [3A51] Sickle cell disorders or other haemoglobinopathies\n Def: Any disorder caused by a HbS mutation in the haemoglobin gene. This disorder is characterised by abnormal rigid sickle-shaped red blood cells decreasing its ability to carry oxygen. This disorder may ...\n --CHILD--> [3A51.1] Sickle cell disease without crisis\n Def: A disorder caused by a HbS mutation in the haemoglobin gene. This disorder is characterised by abnormal rigid sickle-shaped red blood cells decreasing its ability to carry oxygen. This disorder may pr...", "[3A51.1] Sickle cell disease without crisis\n Def: A disorder caused by a HbS mutation in the haemoglobin gene. This disorder is characterised by abnormal rigid sickle-shaped red blood cells decreasing its ability to carry oxygen. This disorder may pr...\n --PARENT--> [3A51] Sickle cell disorders or other haemoglobinopathies\n Def: Any disorder caused by a HbS mutation in the haemoglobin gene. This disorder is characterised by abnormal rigid sickle-shaped red blood cells decreasing its ability to carry oxygen. This disorder may ...\n --CHILD--> [3A51.2] Sickle cell disease with crisis\n Def: Sickle cell crisis occurs when the sickle cells block blood flow, thus decreasing oxygen delivery to the tissues. This results in intense to severe pain in the extremities, lower back, abdomen, and ch..." ]	MF9Y	Other specified clinical findings on examination of urine, without diagnosis	[ { "from_icd11": "3A51.1", "icd10_code": "D571", "icd10_title": "Sickle-cell disease without crisis" }, { "from_icd11": "3A61.Z", "icd10_code": "D609", "icd10_title": "Acquired pure red cell aplasia, unspecified" }, { "from_icd11": "3A61.Z", "icd10_code": "D608", "icd10_title": "Other acquired pure red cell aplasias" }, { "from_icd11": "3A61.Z", "icd10_code": "D60", "icd10_title": "Acquired pure red cell aplasia [erythroblastopenia]" }, { "from_icd11": "5C72", "icd10_code": "E871", "icd10_title": "Hypo-osmolality and hyponatremia" }, { "from_icd11": "5C71", "icd10_code": "E870", "icd10_title": "Hyperosmolality and hypernatremia" }, { "from_icd11": "5B5K.5", "icd10_code": "E618", "icd10_title": "Deficiency of other specified nutrient elements" }, { "from_icd11": "5B91.2", "icd10_code": "E678", "icd10_title": "Other specified hyperalimentation" } ]	D571	Sickle-cell disease without crisis
Chronic inflammatory demyelinating polyneuropathy (CIPD) has been described in two patients in association with Bartonella infection . Considered an autoimmune condition, CIPD is predominantly diagnosed in older male individuals and classically presents with an insidious onset, followed by progressive signs of relapsing and recurring symmetric peripheral muscle weakness, sensory alterations and paresthesia . Loss of reflexes, neuropathic pain, autonomic dysfunction and cranial nerve abnormalities can coexist because of segmental demyelination related to inflammatory cell infiltration within the nervous system . Infection or immunization has also been associated with the development of CIPD, and this population tends to be of younger age . There is a case report of a 3-year-old male subject who developed symmetric distal muscular weakness and numbness with loss of deep tendon reflexes 6 weeks after being treated for lymphadenitis secondary to B. henselae infection (Table 2 ) . Diagnosis of CIPD was based on clinical signs in combination with cerebrospinal fluid (CSF) findings of elevated monocytes, protein, oligoclonal banding and evidence of intrathecal IgG synthesis. Interestingly, serum IgG titers remained high following treatment with clarithromycin, which could indicate persistent infection. Functional recovery occurred over a period of 4 months with a tapering corticosteroid dose . The second case involved a family that suffered from woodlouse hunter spider bites in their home following a flood and subsequent infestation of woodlice . Spiders had been visualized on both sons and in their bedding. Suspected spider bites on the youngest son were documented by the child’s pediatrician when he was 5 months of age, and signs of muscle weakness and pain developed in toddlerhood. After an initial diagnosis of Guillain-Barré syndrome (GBS), this patient was subsequently diagnosed with CIPD following episodic relapsing weakness and evidence of demyelination on EMG (Table 2 ). This patient displayed rising titers during serial testing to several Bartonella species, which diminished after antibiotic therapy (refer to Table 2 ). His older brother also experienced symptoms following spider bites, including disruptive sleep, and both boys developed anxiety, irritability and panic attacks that could not be attributed to another somatic disease. The older son developed cervical lymphadenopathy about a year after experiencing the spider bites, and his mother, although she could not confirm being bitten by a spider, experienced headaches, eye pain, weakness and loss of sensation in her extremities along with joint pain, fatigue and neurocognitive signs of memory loss, insomnia and disorientation in the months pursuant to the presence of spiders in the dwelling. Interestingly, all three family members tested positive by immunofluorescent antibody (IFA serology) to B. henselae San Antonio 2 (SA2) and B. vinsonii subsp . berkhoffii type II, although at a lower titer than the youngest son. There was no history of cat interaction, although the family dog had a history of fleas. The dog’s blood was screened during the same time interval as the mother and found to be serologically negative to all tested Bartonella species . Thirteen spiders and four woodlice were collected from the home for Bartonella screening. Compellingly, B. henselae SA2 DNA was genetically sequenced from two spiders and one woodlouse and B. vinsonii subsp. berkhoffii sequenced from a third spider . Although vector competency was not confirmed for these species, the findings bear consideration due to the temporal association of spider bites and the development of bartonellosis . Table 2 Peripheral nerve paresis associated with Bartonella species infection Peripheral neuropathies: peripheral nerve paresis Diagnosis Patient age/sex Initial symptoms/clinical findings Elapsed time to neurological symptoms Key diagnostic results Bartonella serology/PCR Treatment/ duration Outcome Refs. Chronic inflammatory demyelinating polyneuropathy (CIPD) 3/M Lymphadenitis 6 weeks Symmetric distal muscle weakness, sensory ataxia, ↓ to absent deep tendon reflexes Infectious and autoimmune panels NSF 1 CSF mild ↑ protein, oligoclonal bands and slight intrathecal IgG synthesis. Decreased motor neuron conduction Bh IgG > 1:850 IgM > 1:250 Serum PCR neg CSF serology and PCR neg Clarithromycin + prednisone taper over 4 months Recovery of motor and sensory function, reflexes, repeat titers IgM < 1:250, no change to IgG. Nerve conduction normalized at 1 year 2/M Previous history of woodlouse hunter spider bites, intermittent rashes and sinusitis 2 years Ataxia, leg pain, dizziness, visual floaters and constipation CSF: ↑ protein. MRI: enhancement of ventral nerve roots/pia from 11th thoracic vertebrae to sacrum Not initially obtained IVIG × 4 d. for suspected GBS Rapid improvement then relapsing muscle weakness 2 months later Weakness and pain in legs, tingling around mouth EMG: chronic sensory motor demyelinating polyneuropathy Bh IgM/IgG not detected at 1:16 IVIG + prednisone + gabapentin × 4 w Azithromycin × 10 d Antibiotic helpful, relapsing muscle weakness 1 year later Weakness in legs None noted Titer 1: + Bh, Bk , Titer 2: + Bvb I-III, BhSA2 / H1 and Bk Titer 3: all decreasing IVIG Azithromycin × 30 d Improvement on antibiotics and IVIG Taper of IVIG Clarithromycin + rifampin × 6 months Full recovery with minimal stiffness in legs after 2 months Cranial nerve paralysis 29/F Fever, night sweats, headache, left parotid enlargement and facial weakness 5 weeks OS ptosis, mydriasis and enlarged occipital LN MRI: regional lymphadenopathy Histopathology: granulomatous inflammation Bartonella sp. positive serology (not specified) None Complete recovery over 4 months 28/M Headache, fever, fatigue and myalgia × 3d, followed by right preauricular LN swelling 1 week later 16 days Blurred vision, right eyelid weakness CBC, EBV, CMV NSF No initial Bartonella diagnostics Prednisone Improvement with relapse upon treatment cessation 1 week later Recurrent ocular, facial nerve symptoms, fever, chills and myalgia. New ↑ cervical LNs CBC mild ↑WBC, viral and STI screening NSF 3 CT: cortical necrosis right preauricular LN and parotid sialadentis Bh IgG > 1:640 IgM neg Bq neg Azithromycin × 5d Resolution 2 weeks after treatment 7/M Transient fever, cat scratch left cheek 1 month Left facial palsy with recurrent fever and cervical lymphadenopathy WBC and CRP normal No initial Bartonella diagnostics IV Acyclovir + prednisolone Fever initially responded then relapsed Repeat WBC ↑, CRP normal CSF normal Flomoxef + azithromycin No clinical improvement, WBC returns to normal Ultrasound/MRI cervical/parotid swelling + facial nerve compression Bh IgG > 1:1024 IgM neg Minocycline + ceftriaxone Improvement Amoxicillin + pred Resolution over 6 months 5/F 19-day history of fever, headache, fatigue, weight loss. Strep. pharyngitis 21 days Left sided facial palsy ↑CRP, ESR. Blood culture and cranium CT NSF. Infectious disease testing NSF 4 .Ultrasound: hypoechoic splenic and hepatic foci. Brain MRI NSF Suspected disseminated CSD, no specific Bartonella diagnostics Azithromycin + Rifampin × 14d Resolution of all clinical signs Subscripted numbers indicate additional laboratory findings associated with individual patients 1 Negative for adenovirus, respiratory syncytial virus, coronavirus, influenza, parainfluenza, Sendai virus, mumps, measles, herpes simplex, varicella zoster, Mycoplasma pneumoniae , Chlamydia psittici, Coxiella burnetti, Mycobacterium tuberculosis , atypical Mycobacterium . Enolase, myelin basic protein autoantibodies, glucose and lactate normal. ANA, ANCA and complement 3, 4 normal 2 Blood draws for titers were obtained every other day for 3 samples. Titer 1: Bh SA2 and Bh H1 1:256, Bk 1:128. Titer 2: Bvb I 1:64, Bvb II 1:1024, Bvb III 1:128, Bh SA2 1:512, Bh H1 1:512, Bk 1:2048. Titer 3: Bvb I 1:32, Bvb II 1: 512, Bvb III 1: 128, Bh SA2 1:256, Bh H1 1:256, Bk 1:512. All negative by 2 months follow-up 3 Gonorrhea, chlamydia PCR, HIV antigen/antibody, plasma reagin, hepatitis B and C, Epstein-Barr virus IgM, cytomegalovirus IgG, LDH all negative/normal 4 Rickettsia, Lyme ( Borrelia ), West Nile virus, varicella, mumps, Epstein-Barr virus, cytomegalovirus and herpes simplex virus 1 and 2 NSF no significant findings, CSF cerebrospinal fluid, Bh Bartonella henselae, PCR polymerase chain reaction, LN lymph node OS-left eye, MRI magnetic resonance imaging, CBC complete blood count, EBV Epstein-Barr virus, CMV cytomegalovirus, WBC white blood cells, STI sexually transmitted infections, CT computerized tomography, Bq Bartonella quintana, CRP C reactive protein, IV intravenous, ESR erythrocyte sedimentation rate, CSD cat scratch disease. ANA antinuclear antibody, ANCA anti-neutrophil cytoplasmic antibody, LDH lactate dehydrogenase	4.308594	0.742676	sec[0]/sec[1]/sec[1]/p[0]	en	0.999996	PMC11452993	https://doi.org/10.1186/s13071-024-06491-3	[ "bartonella", "weakness", "nerve", "spider", "titer", "fever", "virus", "cipd", "pain", "bites" ]	[ { "code": "1C11.00", "title": "Oroya fever" }, { "code": "1C11.1", "title": "Trench fever" }, { "code": "1C11.01", "title": "Verruga peruana" }, { "code": "MG22", "title": "Fatigue" }, { "code": "FB32.Y", "title": "Other specified disorders of muscles" }, { "code": "MB5Z", "title": "Paralytic symptoms, unspecified" }, { "code": "FA31.5", "title": "Acquired pes planus" }, { "code": "MF50.2Y", "title": "Other specified urinary incontinence" }, { "code": "8C1Z", "title": "Mononeuropathy of unspecified site" }, { "code": "ND56.4", "title": "Injury of nerve of unspecified body region" } ]	=== ICD-11 CODES FOUND === [1C11.00] Oroya fever Definition: A disease commonly caused by an infection with the gram-negative bacteria Bartonella bacilliformis. This disease is characterised by severe haemolytic anaemia and transient immunosuppression. This disease may present with fever, malaise, or jaundice. Transmission is through the bite of infected sandflies from the genus Lutzomyia. Confirmation is by identification of Bartonella bacilliformis in a blood sample. Also known as: Oroya fever \| Systemic bartonellosis due to Bartonella bacilliformis \| Systemic Carrión disease \| systemic bartonellosis \| Bartonella fever [1C11.1] Trench fever Definition: A disease caused by an infection with the gram-negative bacteria Bartonella quintana. This disease is characterised by fever, headache, rash, bone pain, or may be asymptomatic. Transmission is through the bite of infected body lice. Confirmation is by identification of Bartonella quintana in a blood sample. Bartonella quintana was formerly known as Rickettsia quintana. Also known as: Trench fever \| Quintan fever \| febris quintata \| five day fever \| fever due to Rickettsia quintana Includes: Quintan fever [1C11.01] Verruga peruana Definition: A disease caused by an infection with the gram-negative bacteria Bartonella bacilliformis. This disease is characterised by multiple nodular and red-to-purple vascular skin lesions, subsequent to Oroya fever. Transmission is through the bite of infected sandflies from the genus Lutzomyia. Also known as: Verruga peruana \| Cutaneous and mucocutaneous bartonellosis due to Bartonella bacilliformis \| Cutaneous Carrión disease \| cutaneous and mucocutaneous bartonellosis \| cutaneous bartonellosis [MG22] Fatigue Definition: A feeling of exhaustion, lethargy, or decreased energy, usually experienced as a weakening or depletion of one's physical or mental resource and characterised by a decreased capacity for work and reduced efficiency in responding to stimuli. Fatigue is normal following a period of exertion, mental or physical, but sometimes may occur in the absence of such exertion as a symptom of health conditions. Also known as: Fatigue \| decreased energy \| worn out \| Lethargy \| lethargic Includes: General physical deterioration \| Lethargy Excludes: Combat fatigue \| Exhaustion due to exposure \| heat exhaustion [FB32.Y] Other specified disorders of muscles Also known as: Other specified disorders of muscles \| Muscle wasting or atrophy, not elsewhere classified \| muscle wasting \| muscle wasting disorder \| Sarcopenia [MB5Z] Paralytic symptoms, unspecified Also known as: Paralytic symptoms, unspecified \| paralysis syndrome \| incomplete paralysis \| complete paralysis \| paresis [FA31.5] Acquired pes planus Also known as: Acquired pes planus \| acquired flat foot \| acquired talipes planus \| fallen arch \| flat foot Excludes: Congenital pes planus [MF50.2Y] Other specified urinary incontinence Also known as: Other specified urinary incontinence \| Overflow Incontinence \| Extraurethral urinary incontinence \| Dribbling of urine \| Urethra sphincter incontinence [8C1Z] Mononeuropathy of unspecified site Also known as: Mononeuropathy of unspecified site \| inflammation of nerve NOS \| nerve condition NOS \| neuritis NOS \| nerve disease NOS [ND56.4] Injury of nerve of unspecified body region Also known as: Injury of nerve of unspecified body region \| injuries to nerves, nerve plexuses and roots \| injury to nerves, unspecified site \| nerve damage NOS \| Injury of nerve NOS Excludes: multiple injuries of nerves NOS === GRAPH WALKS === --- Walk 1 --- [1C11.00] Oroya fever Def: A disease commonly caused by an infection with the gram-negative bacteria Bartonella bacilliformis. This disease is characterised by severe haemolytic anaemia and transient immunosuppression. This dis... --PARENT--> [1C11.0] Carrion disease Def: Infection by Bartonella bacilliformis which can present as a systemic illness, Oroya fever, or as a benign skin eruption, verruga peruana.... --CHILD--> [1C11.01] Verruga peruana Def: A disease caused by an infection with the gram-negative bacteria Bartonella bacilliformis. This disease is characterised by multiple nodular and red-to-purple vascular skin lesions, subsequent to Oroy... --- Walk 2 --- [1C11.00] Oroya fever Def: A disease commonly caused by an infection with the gram-negative bacteria Bartonella bacilliformis. This disease is characterised by severe haemolytic anaemia and transient immunosuppression. This dis... --PARENT--> [1C11.0] Carrion disease Def: Infection by Bartonella bacilliformis which can present as a systemic illness, Oroya fever, or as a benign skin eruption, verruga peruana.... --CHILD--> [1C11.01] Verruga peruana Def: A disease caused by an infection with the gram-negative bacteria Bartonella bacilliformis. This disease is characterised by multiple nodular and red-to-purple vascular skin lesions, subsequent to Oroy... --- Walk 3 --- [1C11.1] Trench fever Def: A disease caused by an infection with the gram-negative bacteria Bartonella quintana. This disease is characterised by fever, headache, rash, bone pain, or may be asymptomatic. Transmission is through... --PARENT--> [1C11] Bartonellosis Def: Any infection caused by the gram-negative bacteria Bartonella.... --PARENT--> [?] Other bacterial diseases --- Walk 4 --- [1C11.1] Trench fever Def: A disease caused by an infection with the gram-negative bacteria Bartonella quintana. This disease is characterised by fever, headache, rash, bone pain, or may be asymptomatic. Transmission is through... --PARENT--> [1C11] Bartonellosis Def: Any infection caused by the gram-negative bacteria Bartonella.... --CHILD--> [1C11.1] Trench fever Def: A disease caused by an infection with the gram-negative bacteria Bartonella quintana. This disease is characterised by fever, headache, rash, bone pain, or may be asymptomatic. Transmission is through... --- Walk 5 --- [1C11.01] Verruga peruana Def: A disease caused by an infection with the gram-negative bacteria Bartonella bacilliformis. This disease is characterised by multiple nodular and red-to-purple vascular skin lesions, subsequent to Oroy... --PARENT--> [1C11.0] Carrion disease Def: Infection by Bartonella bacilliformis which can present as a systemic illness, Oroya fever, or as a benign skin eruption, verruga peruana.... --PARENT--> [1C11] Bartonellosis Def: Any infection caused by the gram-negative bacteria Bartonella.... --- Walk 6 --- [1C11.01] Verruga peruana Def: A disease caused by an infection with the gram-negative bacteria Bartonella bacilliformis. This disease is characterised by multiple nodular and red-to-purple vascular skin lesions, subsequent to Oroy... --PARENT--> [1C11.0] Carrion disease Def: Infection by Bartonella bacilliformis which can present as a systemic illness, Oroya fever, or as a benign skin eruption, verruga peruana.... --PARENT--> [1C11] Bartonellosis Def: Any infection caused by the gram-negative bacteria Bartonella....	[ "[1C11.00] Oroya fever\n Def: A disease commonly caused by an infection with the gram-negative bacteria Bartonella bacilliformis. This disease is characterised by severe haemolytic anaemia and transient immunosuppression. This dis...\n --PARENT--> [1C11.0] Carrion disease\n Def: Infection by Bartonella bacilliformis which can present as a systemic illness, Oroya fever, or as a benign skin eruption, verruga peruana....\n --CHILD--> [1C11.01] Verruga peruana\n Def: A disease caused by an infection with the gram-negative bacteria Bartonella bacilliformis. This disease is characterised by multiple nodular and red-to-purple vascular skin lesions, subsequent to Oroy...", "[1C11.00] Oroya fever\n Def: A disease commonly caused by an infection with the gram-negative bacteria Bartonella bacilliformis. This disease is characterised by severe haemolytic anaemia and transient immunosuppression. This dis...\n --PARENT--> [1C11.0] Carrion disease\n Def: Infection by Bartonella bacilliformis which can present as a systemic illness, Oroya fever, or as a benign skin eruption, verruga peruana....\n --CHILD--> [1C11.01] Verruga peruana\n Def: A disease caused by an infection with the gram-negative bacteria Bartonella bacilliformis. This disease is characterised by multiple nodular and red-to-purple vascular skin lesions, subsequent to Oroy...", "[1C11.1] Trench fever\n Def: A disease caused by an infection with the gram-negative bacteria Bartonella quintana. This disease is characterised by fever, headache, rash, bone pain, or may be asymptomatic. Transmission is through...\n --PARENT--> [1C11] Bartonellosis\n Def: Any infection caused by the gram-negative bacteria Bartonella....\n --PARENT--> [?] Other bacterial diseases", "[1C11.1] Trench fever\n Def: A disease caused by an infection with the gram-negative bacteria Bartonella quintana. This disease is characterised by fever, headache, rash, bone pain, or may be asymptomatic. Transmission is through...\n --PARENT--> [1C11] Bartonellosis\n Def: Any infection caused by the gram-negative bacteria Bartonella....\n --CHILD--> [1C11.1] Trench fever\n Def: A disease caused by an infection with the gram-negative bacteria Bartonella quintana. This disease is characterised by fever, headache, rash, bone pain, or may be asymptomatic. Transmission is through...", "[1C11.01] Verruga peruana\n Def: A disease caused by an infection with the gram-negative bacteria Bartonella bacilliformis. This disease is characterised by multiple nodular and red-to-purple vascular skin lesions, subsequent to Oroy...\n --PARENT--> [1C11.0] Carrion disease\n Def: Infection by Bartonella bacilliformis which can present as a systemic illness, Oroya fever, or as a benign skin eruption, verruga peruana....\n --PARENT--> [1C11] Bartonellosis\n Def: Any infection caused by the gram-negative bacteria Bartonella....", "[1C11.01] Verruga peruana\n Def: A disease caused by an infection with the gram-negative bacteria Bartonella bacilliformis. This disease is characterised by multiple nodular and red-to-purple vascular skin lesions, subsequent to Oroy...\n --PARENT--> [1C11.0] Carrion disease\n Def: Infection by Bartonella bacilliformis which can present as a systemic illness, Oroya fever, or as a benign skin eruption, verruga peruana....\n --PARENT--> [1C11] Bartonellosis\n Def: Any infection caused by the gram-negative bacteria Bartonella...." ]	1C11.00	Oroya fever	[ { "from_icd11": "1C11.00", "icd10_code": "A440", "icd10_title": "Systemic bartonellosis" }, { "from_icd11": "1C11.1", "icd10_code": "A790", "icd10_title": "Trench fever" }, { "from_icd11": "1C11.01", "icd10_code": "A441", "icd10_title": "Cutaneous and mucocutaneous bartonellosis" }, { "from_icd11": "MG22", "icd10_code": "R5382", "icd10_title": "Chronic fatigue, unspecified" }, { "from_icd11": "MG22", "icd10_code": "R530", "icd10_title": "Neoplastic (malignant) related fatigue" }, { "from_icd11": "MG22", "icd10_code": "R532", "icd10_title": "Functional quadriplegia" }, { "from_icd11": "MG22", "icd10_code": "R531", "icd10_title": "Weakness" }, { "from_icd11": "MG22", "icd10_code": "R5383", "icd10_title": "Other fatigue" }, { "from_icd11": "MG22", "icd10_code": "R53", "icd10_title": "Malaise and fatigue" }, { "from_icd11": "FB32.Y", "icd10_code": "M6281", "icd10_title": "Muscle weakness (generalized)" }, { "from_icd11": "MB5Z", "icd10_code": "G8384", "icd10_title": "Todd's paralysis (postepileptic)" }, { "from_icd11": "MB5Z", "icd10_code": "G8331", "icd10_title": "Monoplegia, unspecified affecting right dominant side" }, { "from_icd11": "MB5Z", "icd10_code": "G8389", "icd10_title": "Other specified paralytic syndromes" }, { "from_icd11": "MB5Z", "icd10_code": "G8383", "icd10_title": "Posterior cord syndrome" }, { "from_icd11": "MB5Z", "icd10_code": "G8381", "icd10_title": "Brown-Sequard syndrome" } ]	A440	Systemic bartonellosis
Initial blood analysis revealed profoundly reduced phosphate levels around 0.58 mmol/l (normal range 1.0-1.95 mmol/l) , a reduced calcifediol level of 10 ng/ml (> 30 ng/ml) and highly increased FGF23 levels of >70.000 RU/ml (normal range 25-110 RU/ml). Osteocalcin and calcium were in the age-appropriate normal range . Parathyroid hormone, as an important calcium and vitamin D regulator, was increased 12 pmol/l (normal range 1.6-6.9 pmol/l) . As a marker for osteomalacia, bone specific alkaline phosphatase was tested and found to be significantly increased to 754 μg/l (normal range 37-97 μg/l) . Renal function parameters: creatinine, urea and glomerular filtration rate, were unrestricted, and urine analysis showed increased phosphate excretion, indicating a decrease in tubular phosphate reabsorption. To assess the walking ability, we performed a six-minutes-walk test, revealing dramatically impaired skills with a walking distance of 15 meters. Radiographic examination revealed a gracile, undermineralized bone structure with loss of definition of the provisional calcification zone at the epiphyseal-/metaphyseal interface and disorganization of the growth plate . Height parameters were persistently below the third percentile (height 77.5 cm, SDS -4.9), while bone age was determined to correspond to 1 year (at the age of 3 years). Abdominal ultrasound confirmed a right-sided multicystic dysplastic kidney, without other intra-abdominal malformations. After a legionella pneumonia our patient developed a persistent chronic oxygen demand. A CT scan of the lungs confirmed the severe thoracic deformity and additionally revealed a diffuse consolidation of the lung parenchyma, accompanied by ground glass opacifications in both lower lobes. A bronchoalveolar lavage did not show any signs of inflammation, pathogens, or alveolar hemorrhage. The combination of clinical and diagnostic findings, except lung involvement, was suggestive for an underlying epidermal nevus syndrome. A biopsy of the epidermal nevus was performed for histological and genetic examination. To investigate the oxygen demand and to exclude a parenchymal lung disease, as well as to determine the histology of the hemangioma, we also performed biopsies of the lung, and skin lesion at the right mandible within the same procedure. Histology of the skin biopsy of the epidermal nevus confirmed the clinical diagnosis of a nevus sebaceous. Ultra-deep next generation sequencing, yielding an average coverage of 5000x of the target regions, was performed on a DNA sample extracted from the biopsy material using a TruSeq™ Custom Amplicon Kit (Illumina) and sequenced on a MiSeq system (Illumina). This revealed a known pathogenic variant in NRAS (neuroblastoma RAS viral oncogene homolog), c.182A>G; p.Gln61Arg , thereby confirming a mosaic RASopathy. Histology of the lung biopsy showed an alveolar hypoplasia and neuroendocrine cell hyperplasia without further signs of diffuse parenchymal lung disease. Genetic testing of the lung tissue biopsy did not show the mosaic NRAS variant, that was detected in the nevus biopsy. To exclude neurological abnormalities, we performed a cranial MRI, revealing a single small arachnoid cyst as an incidental finding without further necessity for intervention. We immediately initiated a conventional therapy with oral phosphate und calcitriol supplementation to establish mineral homeostasis. The therapy with phosphate initially caused diarrhea, while the calcitriol supplementation was well tolerated. As a side effect of the calcitriol supplementation our patient developed nephrocalcinosis type 2a, that was detected on routine ultrasound examination. Our patient continued to suffer from severe bone pain and impaired mobility, with an ongoing need of the wheelchair. With the conventional supplementation therapy, we were unable to achieve serum phosphate levels above 0.6 mmol/l. After two years without satisfying therapeutic success under conventional management, and 1 month after its approval, we initiated an off-label treatment with burosumab in May 2018. Two weeks prior to the initiation of burosumab therapy, we stopped the supplementation therapy, and started with bi-weekly subcutaneous burosumab injections with a dose of 0.4 mg/kg. Clinical trials in XLH patients recommended to increase the dose to 1.2 mg/kg if the serum phosphate levels do not increase by > 0,16 mmol/l from baseline, or if 2 consecutive parameters were below the normal range ( 6 ). After 4 weeks of therapy, we observed an increase of the phosphate levels from initially 0.58 to 0.68 mmol/l which was still below the normal range of 1.05-1.8 mmol/l. We, therefore, increased the dose to 0.8 mg/kg. Serum phosphate levels then normalized and have, subsequently, remained within the age-appropriate range . Importantly, after an initial training session by the nursing staff, parents were able to administer the injections at home, avoiding unnecessary hospital visits. Over the complete therapy course of 42 months, only 1 dose change was necessary to adjust for increasing body weight, while the dose per body weight was effectively decreased to 0.7 mg/kg in July 2020. During 42 months of treatment, the patient was closely monitored for overall clinical condition, laboratory values for mineral homeostasis, as well as radiographic imaging, and occurrence of any adverse effects. During the first six months, follow-up was performed every 4-6 weeks. As the clinical status and the laboratory parameters remained stable, we extended the follow-up intervals to 6 months. After the therapy start with burosumab serum phosphate levels increased to an age-appropriate range after only 4 weeks and remained constantly in the age-adjusted normal range between 1.0-1.8 mmol/l . Furthermore, we achieved a satisfying serum concentration of calcitriol (62 pg/ml [22-75 pg/ml]) without an increase in ionized calcium levels [1.21 mmol/l (1.12-1.37 mmol/l)] . PTH and urine calcium excretion levels remained normal. We also detected a significant decrease of alkaline phosphatase levels (from 754 μg/l to 75 μg/l [normal range 37-97 μg/l]) after only a few weeks of therapy . The urine calcium and phosphate excretion were normal, with a normalized tubular phosphate reabsorption rate. The nephrocalcinosis and the initially observed right multicystic dysplastic kidney were unchanged on ultrasound exams. To evaluate the rickets improvement, a seven-point scale (radiographic global impression of change score (RGI-C)) was used to monitor bone structure and skeletal maturity (−3 = severe worsening, 0 = no change; +3= near/complete healing) ( 7 ). Hallmarks were the level of osteopenia, metaphyseal fraying, and irregularity of the provisional zone of calcification. According to the RGI-C score, our patient showed a substantial improvement in rickets severity (+2). A radiograph of the left hand in February 2018 demonstrated rickets with a determined bone age of 1-3 years . Conversely, the current radiograph, after 42 months of burosumab treatment, presented a nearly age-appropriate bone age of 7 years and 5 months (patient´s age: 8 years) . In addition, the bone growth velocity increased from 5 cm per year to 7.5 cm per year. The increasing size of the thorax led to improved respiratory mechanics and termination of oxygen administration. A leading symptom before initiation of the burosumab therapy was an almost daily occurrence of bone pain that required frequent NSAID intake. This had also significantly improved with the characteristic bone pain now only occurring in the night before the next burosumab application. Originally, skeletal abnormalities and bone pain had an immense impact on the patient’s mobility. After 8 weeks of burosumab therapy, we noticed an improvement in her walking pattern, with an increase of wheelchair-free time of 1-2 hours per day. In the following year, wheelchair-free time further increased and since the patient started primary school at the age of 7 years, she only needed to use the wheelchair during some group activities in physical education class. She was able to walk for 4 to 5 consecutive hours during a weekday and 2 to 3 hours on weekends. Furthermore, she was capable to walk distances from 1 to 2 kilometers without interruption. For stairs or to cover distances beyond 2 kilometers, the patient still uses crutches. In summary, after initiation of burosumab treatment, constant improvements of the walking pattern and walking distances were observed by both the parents and physicians. To date, no adverse events occurred, especially no local reactions at the injection site (hypersensitivity, pruritus, swelling or rash) were noted. Compliance to the therapeutic regimen was high, mainly due to significant decrease in bone pain immediately after the injections.	4.335938	0.755371	sec[3]/p[0]	en	0.999997	PMC9120998	https://doi.org/10.3389/fendo.2022.866831	[ "phosphate", "bone", "range", "mmol", "burosumab", "lung", "without", "biopsy", "calcium", "walking" ]	[ { "code": "5C64.3", "title": "Disorders of phosphorus metabolism or phosphatases" }, { "code": "GB61.Z", "title": "Chronic kidney disease, stage unspecified" }, { "code": "GB90.48", "title": "Disorders of calcium or phosphate excretion" }, { "code": "5C53.30", "title": "Mitochondrial substrate carrier disorders" }, { "code": "5C53.Y", "title": "Other specified inborn errors of energy metabolism" }, { "code": "FC0Z", "title": "Diseases of the musculoskeletal system or connective tissue, unspecified" }, { "code": "FB84.Z", "title": "Osteomyelitis or osteitis, unspecified" }, { "code": "FB80.Z", "title": "Disorder of bone density or structure, unspecified" }, { "code": "FB86.11", "title": "Hypertrophy of bone" }, { "code": "FB86.1Z", "title": "Bone hyperplasias, unspecified" } ]	=== ICD-11 CODES FOUND === [5C64.3] Disorders of phosphorus metabolism or phosphatases Definition: Any condition caused by errors in phosphorus metabolism, or in phosphatase activity. Also known as: Disorders of phosphorus metabolism or phosphatases \| disorders of phosphorus metabolism \| Hypophosphatasia \| Rathbun syndrome \| Congenital hypophosphatasia Includes: Hypophosphatasia Excludes: Adult osteomalacia \| Osteoporosis [GB61.Z] Chronic kidney disease, stage unspecified Also known as: Chronic kidney disease, stage unspecified \| Chronic kidney disease \| chronic renal failure \| chronic kidney failure \| chronic renal disease [GB90.48] Disorders of calcium or phosphate excretion Definition: Conditions in which renal excretion of calcium and / or phosphate is deranged. Also known as: Disorders of calcium or phosphate excretion \| Phosphate losing hypophosphataemia \| hereditary hypophosphatemia \| Phosphate losing hypophosphataemia associated with familial or genetic disorders elsewhere classified \| Familial hypophosphataemia [5C53.30] Mitochondrial substrate carrier disorders Also known as: Mitochondrial substrate carrier disorders \| Cardiomyopathy - hypotonia - lactic acidosis \| Mitochondrial phosphate carrier deficiency \| Mitochondrial aspartate glutamate carrier 1 deficiency \| Mitochondrial glutamate carrier 1 deficiency [5C53.Y] Other specified inborn errors of energy metabolism Also known as: Other specified inborn errors of energy metabolism \| Unspecified mitochondrial disorders \| mitochondrial disease NOS \| Leigh syndrome with no known genetic or respiratory chain deficiency \| Cataract - cardiomyopathy [FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified Also known as: Diseases of the musculoskeletal system or connective tissue, unspecified \| bone disease NOS \| bone disorder NOS \| bone lesion NOS \| musculoskeletal complications NOS [FB84.Z] Osteomyelitis or osteitis, unspecified Also known as: Osteomyelitis or osteitis, unspecified \| Osteomyelitis or osteitis \| bone inflammation \| bone ulcer \| bone inflammatory disease [FB80.Z] Disorder of bone density or structure, unspecified Also known as: Disorder of bone density or structure, unspecified \| Certain specified disorders of bone density or structure [FB86.11] Hypertrophy of bone Also known as: Hypertrophy of bone \| bone thickening \| periosteum thickening \| Infantile cortical hyperostoses \| Post traumatic subperiosteal ossification [FB86.1Z] Bone hyperplasias, unspecified Also known as: Bone hyperplasias, unspecified \| Bone hyperplasias === GRAPH WALKS === --- Walk 1 --- [5C64.3] Disorders of phosphorus metabolism or phosphatases Def: Any condition caused by errors in phosphorus metabolism, or in phosphatase activity.... --EXCLUDES--> [?] Osteoporosis --CHILD--> [?] Postmenopausal osteoporosis Def: Susceptibility to bone fracture secondary to a systemic decrease in bone mass and micro-architectural deterioration of bone tissue related to hormonal changes associated with menopause... --- Walk 2 --- [5C64.3] Disorders of phosphorus metabolism or phosphatases Def: Any condition caused by errors in phosphorus metabolism, or in phosphatase activity.... --RELATED_TO--> [?] Phosphate losing hypophosphataemia --PARENT--> [?] Disorders of calcium or phosphate excretion Def: Conditions in which renal excretion of calcium and / or phosphate is deranged.... --- Walk 3 --- [GB61.Z] Chronic kidney disease, stage unspecified --PARENT--> [GB61] Chronic kidney disease Def: Glomerular Filtration Rate (GFR) < 60 ml/min/1.73m² or presence of kidney damage that is present for more than 3 months. Evidence of kidney damage can include structural abnormalities (imaging or hist... --CHILD--> [GB61.0] Chronic kidney disease, stage 1 Def: Kidney damage with normal or increased GFR (>90 ml/min/1.73m²)... --- Walk 4 --- [GB61.Z] Chronic kidney disease, stage unspecified --PARENT--> [GB61] Chronic kidney disease Def: Glomerular Filtration Rate (GFR) < 60 ml/min/1.73m² or presence of kidney damage that is present for more than 3 months. Evidence of kidney damage can include structural abnormalities (imaging or hist... --EXCLUDES--> [?] Hypertensive renal disease Def: Hypertensive renal disease is a medical condition referring to damage to the kidney due to chronic high blood pressure.... --- Walk 5 --- [GB90.48] Disorders of calcium or phosphate excretion Def: Conditions in which renal excretion of calcium and / or phosphate is deranged.... --RELATED_TO--> [?] Pseudohypoparathyroidism Def: Pseudohypoparathyroidism is a condition with refractoriness to parathyroid hormone of its target tissues especially kidney that causes hypocalcaemia and hyperphosphataemia even in the presence of high... --CHILD--> [?] Cataract in pseudohypoparathyroidism Def: This is a clouding of the lens inside the eye which leads to a decrease in vision, in an inherited disorder, named for its similarity to pseudohypoparathyroidism in presentation. The term pseudopseudo... --- Walk 6 --- [GB90.48] Disorders of calcium or phosphate excretion Def: Conditions in which renal excretion of calcium and / or phosphate is deranged.... --RELATED_TO--> [?] Hypophosphataemic rickets Def: Hypophosphatemic rickets is a group of genetic diseases characterised by hypophosphatemia, rickets, and normal serum levels of calcium.... --CHILD--> [?] Autosomal recessive hypophosphataemic rickets Def: Autosomal recessive hypophosphatemic rickets (ARHR) is a hereditary renal phosphate-wasting disorder characterised by hypophosphatemia, rickets and/or osteomalacia and slow growth....	[ "[5C64.3] Disorders of phosphorus metabolism or phosphatases\n Def: Any condition caused by errors in phosphorus metabolism, or in phosphatase activity....\n --EXCLUDES--> [?] Osteoporosis\n --CHILD--> [?] Postmenopausal osteoporosis\n Def: Susceptibility to bone fracture secondary to a systemic decrease in bone mass and micro-architectural deterioration of bone tissue related to hormonal changes associated with menopause...", "[5C64.3] Disorders of phosphorus metabolism or phosphatases\n Def: Any condition caused by errors in phosphorus metabolism, or in phosphatase activity....\n --RELATED_TO--> [?] Phosphate losing hypophosphataemia\n --PARENT--> [?] Disorders of calcium or phosphate excretion\n Def: Conditions in which renal excretion of calcium and / or phosphate is deranged....", "[GB61.Z] Chronic kidney disease, stage unspecified\n --PARENT--> [GB61] Chronic kidney disease\n Def: Glomerular Filtration Rate (GFR) < 60 ml/min/1.73m² or presence of kidney damage that is present for more than 3 months. Evidence of kidney damage can include structural abnormalities (imaging or hist...\n --CHILD--> [GB61.0] Chronic kidney disease, stage 1\n Def: Kidney damage with normal or increased GFR (>90 ml/min/1.73m²)...", "[GB61.Z] Chronic kidney disease, stage unspecified\n --PARENT--> [GB61] Chronic kidney disease\n Def: Glomerular Filtration Rate (GFR) < 60 ml/min/1.73m² or presence of kidney damage that is present for more than 3 months. Evidence of kidney damage can include structural abnormalities (imaging or hist...\n --EXCLUDES--> [?] Hypertensive renal disease\n Def: Hypertensive renal disease is a medical condition referring to damage to the kidney due to chronic high blood pressure....", "[GB90.48] Disorders of calcium or phosphate excretion\n Def: Conditions in which renal excretion of calcium and / or phosphate is deranged....\n --RELATED_TO--> [?] Pseudohypoparathyroidism\n Def: Pseudohypoparathyroidism is a condition with refractoriness to parathyroid hormone of its target tissues especially kidney that causes hypocalcaemia and hyperphosphataemia even in the presence of high...\n --CHILD--> [?] Cataract in pseudohypoparathyroidism\n Def: This is a clouding of the lens inside the eye which leads to a decrease in vision, in an inherited disorder, named for its similarity to pseudohypoparathyroidism in presentation. The term pseudopseudo...", "[GB90.48] Disorders of calcium or phosphate excretion\n Def: Conditions in which renal excretion of calcium and / or phosphate is deranged....\n --RELATED_TO--> [?] Hypophosphataemic rickets\n Def: Hypophosphatemic rickets is a group of genetic diseases characterised by hypophosphatemia, rickets, and normal serum levels of calcium....\n --CHILD--> [?] Autosomal recessive hypophosphataemic rickets\n Def: Autosomal recessive hypophosphatemic rickets (ARHR) is a hereditary renal phosphate-wasting disorder characterised by hypophosphatemia, rickets and/or osteomalacia and slow growth...." ]	5C64.3	Disorders of phosphorus metabolism or phosphatases	[ { "from_icd11": "5C64.3", "icd10_code": "E8339", "icd10_title": "Other disorders of phosphorus metabolism" }, { "from_icd11": "5C64.3", "icd10_code": "E8332", "icd10_title": "Hereditary vitamin D-dependent rickets (type 1) (type 2)" }, { "from_icd11": "5C64.3", "icd10_code": "E8331", "icd10_title": "Familial hypophosphatemia" }, { "from_icd11": "5C64.3", "icd10_code": "E8330", "icd10_title": "Disorder of phosphorus metabolism, unspecified" }, { "from_icd11": "5C64.3", "icd10_code": "E833", "icd10_title": "Disorders of phosphorus metabolism and phosphatases" }, { "from_icd11": "GB61.Z", "icd10_code": "N183", "icd10_title": "Chronic kidney disease, stage 3 (moderate)" }, { "from_icd11": "GB61.Z", "icd10_code": "N189", "icd10_title": "Chronic kidney disease, unspecified" }, { "from_icd11": "GB61.Z", "icd10_code": "N250", "icd10_title": "Renal osteodystrophy" }, { "from_icd11": "GB61.Z", "icd10_code": "N18", "icd10_title": "Chronic kidney disease (CKD)" }, { "from_icd11": "FC0Z", "icd10_code": "XIII", "icd10_title": "" }, { "from_icd11": "FB84.Z", "icd10_code": "M86672", "icd10_title": "Other chronic osteomyelitis, left ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M86172", "icd10_title": "Other acute osteomyelitis, left ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M86171", "icd10_title": "Other acute osteomyelitis, right ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M86671", "icd10_title": "Other chronic osteomyelitis, right ankle and foot" }, { "from_icd11": "FB84.Z", "icd10_code": "M868X7", "icd10_title": "Other osteomyelitis, ankle and foot" } ]	E8339	Other disorders of phosphorus metabolism
Patient 1 The patient was a 58-year-old, right-handed man who was admitted to our hospital. At 57 years of age, he developed dysarthria and weakness of the fingers on the right hand. A few months prior to admission, he started to experience leg muscle cramps and occasionally noticed diplopia during lateral gaze. The severity of diplopia and dysarthria fluctuated within a day and on a daily basis. He had a history of cervical spondylosis with no surgical treatment. His family history was unremarkable. On neurological examination, the abducent ocular movement was incomplete bilaterally. Moreover, he had dysarthria and mild tongue atrophy with fasciculation. His hand muscles showed atrophy with weakness on the right side, with Medical Research Council (MRC) grade 4/5. Although there was no apparent atrophy of other muscles, fasciculations were observed bilaterally in the upper and lower limbs and trunk muscles. The grip strength on the right side was weaker than that on the left (34 and 35 kg, respectively). He could not maintain a raised head for 90 s in a supine position because of the progressive fatigability of neck muscles. Sensory examination revealed nothing of note. Deep tendon reflexes were normal, whereas the Wartenberg reflex was present bilaterally. The edrophonium test revealed moderate improvements of his dysarthria and ocular movement impairment, whereas the hand muscle weakness on the right side showed no improvement. A routine nerve conduction study (NCS) revealed nothing of note except for prolonged distal latency in the right median nerve, and repetitive nerve stimulation testing (RNST) of the ulnar, facial, and accessory nerves also yielded results within normal limits. On electromyography (EMG), fibrillation potentials and polyphasic motor unit potentials were detected in the right first dorsal interossei (FDI) and right biceps brachii muscles, and fasciculation potentials (FPs) were observed in the right trapezius, FDI, biceps brachii, vastus lateral, and tibialis anterior (TA) muscles. Stimulated-single fiber electromyography (s-SFEMG) showed increased jitter in the right extensor digitrum communis (EDC) muscle. On motor-evoked potential (MEP) testing recorded at the abductor hallucis (AH) muscle, the motor action potential was typically evoked on the left but not on the right side. Serological examination revealed that anti-AChR and anti-MuSK antibodies were negative. Head magnetic resonance imaging (MRI) showed a laminar high-intensity lesion along the left motor cortex on susceptibility-weighted imaging, which indicated iron deposition. Cervical MRI revealed cervical spondylosis at the C4/5/6/7/Th1 level, as well as mild compression of the spinal cord at the C4/5 level with no myelomalacia. Abundant fasciculations in EMG and MEP and MRI findings suggesting upper motor neuron dysfunction indicated a diagnosis of ALS, whereas his ocular movement dysfunction, fatigability of neck muscles, and results of the edrophonium test were consistent with a diagnosis of MG. A few weeks following admission, anti-LRP4 antibody was positive (antibody index (A.I.): 1.08) using the luciferase immunoprecipitation systems (LIPS) . In this report, the antibody levels are expressed as A.I., calculated as follows: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ \mathrm{A}.\mathrm{I}. = \left[\mathrm{measurement}\ \mathrm{value}\ \mathrm{of}\ \mathrm{the}\ \mathrm{sample}\ \mathrm{serum}\ \left(\mathrm{relative}\ \mathrm{luminescence}\ \mathrm{units}\right)\right]/\left[\mathrm{cut}-\mathrm{off}\ \mathrm{value}\ \left(\mathrm{relative}\ \mathrm{luminescence}\ \mathrm{units}\right)\right]. $$\end{document} A . I . = measurement value of the sample serum relative luminescence units / cut − off value relative luminescence units . The normal value established for healthy individuals is <1.0 . Therefore, we started immunotherapy while considering his condition to be immune-mediated. Initially, steroid pulse therapy was conducted. The dysarthria and neck muscle fatigability partially improved, and the frequency of fasciculations decreased throughout his body. The quantitative myasthenia gravis (QMG) score improved from 11 points before to 6 points after treatment . Four weeks after the treatment, his symptoms progressed again. Subsequently, treatments with oral corticosteroids, intravenous immunoglobulin, and plasmapheresis therapy were performed. The ocular movements, diplopia, and dysarthria improved mildly and transiently by each treatment, and the titer of anti-LRP4 antibody normalized after these treatments (A.I.: 0.67). However, all immunotherapies had limited effects, and weakness and fatigability progressed gradually. Six months after admission, muscle atrophy and weakness of the left hand and both legs developed, and his grip strength decreased (right: 21 kg, left: 11 kg). In addition, a bilateral Babinski sign appeared 12 months after admission. A follow-up EMG study showed the spread of active denervations of the limbs. At that time, he fulfilled the diagnostic category of probable ALS using the Awaji criteria . The clinical course is shown in Fig. 1a . Fig. 1 The clinical course of anti-low-density lipoprotein receptor-related protein 4 antibody-seropositive amyotrophic lateral sclerosis patients with myasthenic symptoms. a patient 1, b patient 2 Patient 2 A 74-year-old Japanese right-handed man was admitted to hospital with weakness of the right hand and both legs and a dropped head. Ten months before admission, he was aware of clumsiness and suffered painful cramps of his right hand. His dropped head aggravated in the evening. He had no previous history of diplopia or dysphagia. His previous medical and family histories were unremarkable. On neurological examination, he presented with diplopia with a horizontal gaze to the right side for over 15 s. He had no dysarthria, and no tongue abnormality. His grip strength on the right side was lower than that on the left (28 and 32 kg, respectively). He had mild weakness of MRC grade 4/5 and atrophy of the right upper limb, neck, paraspinal, and abdominal muscles. Fasciculations were extensively observed in the limbs and truncal muscles. The deep tendon reflexes were increased in the upper and lower limbs. Sensory examination was normal. The edrophonium test demonstrated the improvement of diplopia, but muscle weakness remained unchanged. NCS and RNST revealed decreased compound muscle action potential amplitudes in the right abductor pollicis brevis (APB) and FDI muscles with normal conduction velocities and a 10.6% decrement in the right ADM muscle on 3-Hz stimulation, respectively. Increased jitter was also seen in s-SFEMG recorded at the right EDC muscle. In EMG performed on the right side, FPs were detected in the trapezius, paraspinal, and upper and lower limbs muscles, and fibrillation potentials or positive sharp waves were identified in the FDI, paraspinal, and tibialis anterior muscles. Reduced recruitment with high-amplitude motor unit potentials was also observed in the trapezius, FDI, and vastus lateralis muscles. On MEP testing of the AH muscles, the central motor conduction time was prolonged on the right side. In the serological test, anti-AChR and anti-MuSK antibodies were negative. Brain MRI was normal, and whole-spine MRI showed mild lumbar spondylosis. The patient was diagnosed with probable ALS using the Awaji criteria, whereas the fluctuation of his dropped head symptom and diplopia after loading were not consistent with the diagnosis of ALS, but suggested a diagnosis of MG. A few weeks after admission, anti-LRP4 antibody in serum was positive (A.I.: 1.50) based on LIPS. As in patient 1, steroid pulse therapy was conducted. A few days after the therapy, the frequency of clinical fasciculations and FPs on EMG decreased. However, fatigability of the upper limb and neck muscles worsened, and decrement at the right trapezius muscle was newly detected in the follow-up RNST. The QMG score worsened from 9 to 12 points. This clinical course was thought to represent an initial escalation of MG at that time. Subsequently, we conducted plasmapheresis therapy. Fatigability improved, and the decrease in the RNST was reduced after this therapy, but auto-LRP4 antibody remained positive (A.I.: 1.15). Six months after admission, dyspnea due to respiratory muscle weakness developed, and he died 7 months after admission. Clinical examination just prior to his death revealed mild muscle weakness of MRC grade 4/5 of the neck and limbs, without tongue muscle atrophy or dysphagia. His clinical course is shown in Fig. 1b .	4.152344	0.972656	sec[1]/p[0]	en	0.999998	27863479	https://doi.org/10.1186/s12883-016-0758-1	[ "mathrm", "muscles", "muscle", "weakness", "side", "anti", "dysarthria", "diplopia", "motor", "antibody" ]	[ { "code": "FB3Z", "title": "Disorders of muscles, unspecified" }, { "code": "FB32.Y", "title": "Other specified disorders of muscles" }, { "code": "8C70.Z", "title": "Muscular dystrophy, unspecified" }, { "code": "FB32.2Z", "title": "Ischaemic infarction of muscle, unspecified" }, { "code": "FB56.2", "title": "Myalgia" }, { "code": "MG22", "title": "Fatigue" }, { "code": "MB5Z", "title": "Paralytic symptoms, unspecified" }, { "code": "FA31.5", "title": "Acquired pes planus" }, { "code": "MF50.2Y", "title": "Other specified urinary incontinence" }, { "code": "NE60", "title": "Harmful effects of drugs, medicaments or biological substances, not elsewhere classified" } ]	=== ICD-11 CODES FOUND === [FB3Z] Disorders of muscles, unspecified Also known as: Disorders of muscles, unspecified \| disorder of muscle, unspecified \| muscle disease \| muscular disease \| muscular disorder [FB32.Y] Other specified disorders of muscles Also known as: Other specified disorders of muscles \| Muscle wasting or atrophy, not elsewhere classified \| muscle wasting \| muscle wasting disorder \| Sarcopenia [8C70.Z] Muscular dystrophy, unspecified Also known as: Muscular dystrophy, unspecified \| Muscular dystrophy \| Gower's muscular dystrophy \| progressive musclular dystrophy \| pseudohypertrophic atrophy [FB32.2Z] Ischaemic infarction of muscle, unspecified Also known as: Ischaemic infarction of muscle, unspecified \| Ischaemic infarction of muscle \| muscle infarction [FB56.2] Myalgia Definition: This is a disorder characterised by pain in a muscle or group of muscles. Also known as: Myalgia \| muscle ache \| muscle soreness \| muscular pain \| myalgic Excludes: Chronic primary musculoskeletal pain \| Chronic secondary musculoskeletal pain [MG22] Fatigue Definition: A feeling of exhaustion, lethargy, or decreased energy, usually experienced as a weakening or depletion of one's physical or mental resource and characterised by a decreased capacity for work and reduced efficiency in responding to stimuli. Fatigue is normal following a period of exertion, mental or physical, but sometimes may occur in the absence of such exertion as a symptom of health conditions. Also known as: Fatigue \| decreased energy \| worn out \| Lethargy \| lethargic Includes: General physical deterioration \| Lethargy Excludes: Combat fatigue \| Exhaustion due to exposure \| heat exhaustion [MB5Z] Paralytic symptoms, unspecified Also known as: Paralytic symptoms, unspecified \| paralysis syndrome \| incomplete paralysis \| complete paralysis \| paresis [FA31.5] Acquired pes planus Also known as: Acquired pes planus \| acquired flat foot \| acquired talipes planus \| fallen arch \| flat foot Excludes: Congenital pes planus [MF50.2Y] Other specified urinary incontinence Also known as: Other specified urinary incontinence \| Overflow Incontinence \| Extraurethral urinary incontinence \| Dribbling of urine \| Urethra sphincter incontinence [NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified Also known as: Harmful effects of drugs, medicaments or biological substances, not elsewhere classified \| drugs, medicaments or biological substances, toxicity not elsewhere classified \| adverse drug effects \| drug reaction NOS \| drug allergy NOS Excludes: Alcohol intoxication \| pathological drug intoxication \| hypersensitivity reaction to correctly administered drug === GRAPH WALKS === --- Walk 1 --- [FB3Z] Disorders of muscles, unspecified --PARENT--> [?] Disorders of muscles --CHILD--> [FB30] Infectious myositis Def: Infective myositis is an acute, subacute, or chronic infection of skeletal muscle and may be caused by a wide range of infecting organisms. Immunosuppression, particularly as the result of HIV infecti... --- Walk 2 --- [FB3Z] Disorders of muscles, unspecified --PARENT--> [?] Disorders of muscles --RELATED_TO--> [?] Foreign body granuloma of soft tissue, not elsewhere classified --- Walk 3 --- [FB32.Y] Other specified disorders of muscles --PARENT--> [FB32] Certain specified disorders of muscle Def: This is an impairment of health or a condition of abnormal functioning of the muscle that does not fit in another category.... --EXCLUDES--> [?] Alcoholic myopathy Def: Myopathy secondary to alcohol use and includes acute and chronic alcoholic myopathy. Several forms have been described: acute necrotizing myopathy, acute hypokalaemic myopathy, chronic alcoholic myopa... --- Walk 4 --- [FB32.Y] Other specified disorders of muscles --PARENT--> [FB32] Certain specified disorders of muscle Def: This is an impairment of health or a condition of abnormal functioning of the muscle that does not fit in another category.... --CHILD--> [FB32.1] Spontaneous rupture of muscle Def: This is a spontaneous tearing or separation of muscle fibres from other muscle fibres and/or tendons in the absence of trauma.... --- Walk 5 --- [8C70.Z] Muscular dystrophy, unspecified --PARENT--> [8C70] Muscular dystrophy Def: Progressive, hereditary skeletal muscle diseases characterised by muscle weakness, wasting, defects in muscle proteins, necrosis of muscle tissue and replacement of muscle tissue with connective and f... --RELATED_TO--> [?] Barth syndrome Def: Barth syndrome is an inborn error of phospholipid metabolism characterised by dilated cardiomyopathy (DCM), skeletal myopathy, neutropaenia, growth delay and organic aciduria.... --- Walk 6 --- [8C70.Z] Muscular dystrophy, unspecified --PARENT--> [8C70] Muscular dystrophy Def: Progressive, hereditary skeletal muscle diseases characterised by muscle weakness, wasting, defects in muscle proteins, necrosis of muscle tissue and replacement of muscle tissue with connective and f... --RELATED_TO--> [?] Epidermolysis bullosa simplex with muscular dystrophy Def: Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD) is an autosomal recessive basal subtype of EBS due to mutations the PLEC gene encoding plectin. It is characterised by generalised bliste...	[ "[FB3Z] Disorders of muscles, unspecified\n --PARENT--> [?] Disorders of muscles\n --CHILD--> [FB30] Infectious myositis\n Def: Infective myositis is an acute, subacute, or chronic infection of skeletal muscle and may be caused by a wide range of infecting organisms. Immunosuppression, particularly as the result of HIV infecti...", "[FB3Z] Disorders of muscles, unspecified\n --PARENT--> [?] Disorders of muscles\n --RELATED_TO--> [?] Foreign body granuloma of soft tissue, not elsewhere classified", "[FB32.Y] Other specified disorders of muscles\n --PARENT--> [FB32] Certain specified disorders of muscle\n Def: This is an impairment of health or a condition of abnormal functioning of the muscle that does not fit in another category....\n --EXCLUDES--> [?] Alcoholic myopathy\n Def: Myopathy secondary to alcohol use and includes acute and chronic alcoholic myopathy. Several forms have been described: acute necrotizing myopathy, acute hypokalaemic myopathy, chronic alcoholic myopa...", "[FB32.Y] Other specified disorders of muscles\n --PARENT--> [FB32] Certain specified disorders of muscle\n Def: This is an impairment of health or a condition of abnormal functioning of the muscle that does not fit in another category....\n --CHILD--> [FB32.1] Spontaneous rupture of muscle\n Def: This is a spontaneous tearing or separation of muscle fibres from other muscle fibres and/or tendons in the absence of trauma....", "[8C70.Z] Muscular dystrophy, unspecified\n --PARENT--> [8C70] Muscular dystrophy\n Def: Progressive, hereditary skeletal muscle diseases characterised by muscle weakness, wasting, defects in muscle proteins, necrosis of muscle tissue and replacement of muscle tissue with connective and f...\n --RELATED_TO--> [?] Barth syndrome\n Def: Barth syndrome is an inborn error of phospholipid metabolism characterised by dilated cardiomyopathy (DCM), skeletal myopathy, neutropaenia, growth delay and organic aciduria....", "[8C70.Z] Muscular dystrophy, unspecified\n --PARENT--> [8C70] Muscular dystrophy\n Def: Progressive, hereditary skeletal muscle diseases characterised by muscle weakness, wasting, defects in muscle proteins, necrosis of muscle tissue and replacement of muscle tissue with connective and f...\n --RELATED_TO--> [?] Epidermolysis bullosa simplex with muscular dystrophy\n Def: Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD) is an autosomal recessive basal subtype of EBS due to mutations the PLEC gene encoding plectin. It is characterised by generalised bliste..." ]	FB3Z	Disorders of muscles, unspecified	[ { "from_icd11": "FB3Z", "icd10_code": "M60831", "icd10_title": "Other myositis, right forearm" }, { "from_icd11": "FB3Z", "icd10_code": "M60869", "icd10_title": "Other myositis, unspecified lower leg" }, { "from_icd11": "FB3Z", "icd10_code": "M60811", "icd10_title": "Other myositis, right shoulder" }, { "from_icd11": "FB3Z", "icd10_code": "M6080", "icd10_title": "Other myositis, unspecified site" }, { "from_icd11": "FB3Z", "icd10_code": "M60851", "icd10_title": "Other myositis, right thigh" }, { "from_icd11": "FB3Z", "icd10_code": "M6010", "icd10_title": "Interstitial myositis of unspecified site" }, { "from_icd11": "FB3Z", "icd10_code": "M6018", "icd10_title": "Interstitial myositis, other site" }, { "from_icd11": "FB3Z", "icd10_code": "M6088", "icd10_title": "Other myositis, other site" }, { "from_icd11": "FB3Z", "icd10_code": "M60862", "icd10_title": "Other myositis, left lower leg" }, { "from_icd11": "FB3Z", "icd10_code": "M60861", "icd10_title": "Other myositis, right lower leg" }, { "from_icd11": "FB3Z", "icd10_code": "M6089", "icd10_title": "Other myositis, multiple sites" }, { "from_icd11": "FB3Z", "icd10_code": "M60852", "icd10_title": "Other myositis, left thigh" }, { "from_icd11": "FB3Z", "icd10_code": "M60821", "icd10_title": "Other myositis, right upper arm" }, { "from_icd11": "FB3Z", "icd10_code": "M60871", "icd10_title": "Other myositis, right ankle and foot" }, { "from_icd11": "FB3Z", "icd10_code": "M60812", "icd10_title": "Other myositis, left shoulder" } ]	M60831	Other myositis, right forearm
As an example of the development of focal brain damage after aSAH, Fig. 1 shows an ICH and damage from ECI on postoperative MRI on Day 2 and the development of a large delayed ischemic infarct between the early MRI scan on Day 2 and two CT scans on Days 7 and 9 in a typical female patient in her forties. In order to ease understanding of the electrographic basis of the delayed infarct development in this patient, which is explained in Figs. 2 and 3 , we would like to provide some general background information on SDs in the following. Fig. 1 Development of a large delayed ischemic infarct between an MRI scan on Day 2 and two CT scans on Days 7 and 9 in a 46-year-old woman with aneurysmal subarachnoid hemorrhage (aSAH) due to rupture of an anterior communicating artery aneurysm. Representative CT and MRI slices in axial orientation. All images were aligned to the first postoperative T1 spin echo scan with a slice thickness of 5 mm. The initial CT scan on admission demonstrated subarachnoid blood in the basal cisterns and more superior in the callosal cistern and the interhemispheric fissure. Blood from the callosal cistern extended into the right frontal lobe and formed a small intracerebral hemorrhage (ICH) of 1 ml at a distance of 24 mm from subdural electrode 1. A small ICH with a volume of 4 ml was also found in the left medial frontal lobe originating from subarachnoid blood in the left cingulate sulcus. The postoperative MRI scan 52 h (Day 2) after onset of the initial hemorrhage showed symmetric, hyperintense bands in the cortex of the left and right superomedial margin on fluid attenuation inversion recovery (FLAIR) images with restricted diffusion on the apparent diffusion coefficient (ADC) map (see arrowheads). Furthermore, four hyperintense spots were found on diffusion-weighted imaging (DWI) in the right frontal and occipital cortex, the left frontal cortex, and the cerebellum (not shown). These findings are consistent with early brain infarction. Quantification yielded an infarct volume of 3 ml in the right hemisphere (shortest distance between infarct border and subdural electrode 5, 29 mm), 2 ml in the left hemisphere, and 1 ml in the cerebellum. Also note perihematomal edema surrounding ICH in both the right and left frontal lobe (hyperintense on FLAIR images, hypointense on the ADC map). On Day 7, CT revealed loss of gray-white matter differentiation in the right insular and frontal cortex. On Day 9, hypodensity and swelling became more marked with a midline shift of 6 mm and compression of the lateral ventricles. These findings are consistent with delayed cerebral infarction involving the vascular territories of the right middle cerebral artery (MCA) and anterior cerebral artery (ACA). Volume analysis revealed a tissue loss of 107 ml due to delayed cerebral ischemia (DCI) ipsilateral to the subdural electrodes. The lowest row presents the CT scan (bone window) on Day 9. The subdural electrode strip is visible over the medial and lateral surface of the right frontal lobe (electrodes are marked with red arrows). Additionally, the quantified lesions from the scans above are projected onto the CT images. The red-labeled area indicates ICH, the blue area early infarction in the MRI on Day 2, and the green area delayed infarction in the CT on Day 9. Note the proximity between the delayed ischemic infarct and electrode 6, which was at 6 mm from the infarct Fig. 2 A cluster of spreading depolarizations (SD) precedes the development of the large delayed ischemic infarct that is shown in Fig. 1 between the MRI scan on Day 2 and the CT scan on Day 7. The patient already had 6 single SDs before the SD cluster shown started on Day 6. Five of those also occurred on Day 6. Traces 1–5 give the raw direct current (DC)/alternating current (AC) electrocorticography (ECoG) recordings (bandpass: 0-45 Hz), demonstrating the propagation of the negative DC shifts along the cortex from electrode 6 to electrode 2, which identify the SDs. The ECoG traces are oriented according to the convention of electroencephalography (EEG) with negativity up and positivity down. The distance between two neighboring electrodes is always 1 cm. As shown in Fig. 1 , electrode 6 was located at 6 mm from the infarct which was first seen as a loss of gray-white matter differentiation on the CT scan of Day 7 5 h after onset of the SD cluster. Note that the negative DC shifts that were closer to the developing infarct were longer than those that were further away from the developing infarct. At electrode 6, the DC signal no longer returned to the baseline, i.e., a shallow negative ultraslow potential (NUP) emerged there. In contrast, NUPs measured in the core of newly developing infarcts have a much greater amplitude . The depressive effect of the SDs on the spontaneous activity is assessed here using the power (traces 7–12) and the integral of the power (traces 13–18) in the AC frequency band between 0.5 and 45 Hz (red asterisks and short red arrows mark the onset of spreading depression). It is relevant to first identify the artifacts and not to include them in the assessment of the durations of the depression periods. Importantly, the spontaneous activity remained persistently depressed at electrode 6 (red arrow), resulting in a very long peak total SD-induced depression duration of a recording day (PTDDD). PTDDD of the delayed neuromonitoring period (PTDDD delayed ) is the strongest currently known real-time predictor of delayed cerebral ischemia (DCI) . If the recording strip had been placed further forward and only electrodes 3–5 had been available to determine the duration of the longest depression period, the evaluation would have been more difficult, as the power of spontaneous activity at these electrodes showed some recovery relatively quickly. However, the integral of power demonstrates that the recovery of spontaneous activity in these electrodes was indeed minimal (red dotted arrows). The intracranial pressure (ICP) was measured via an external ventricular drain (trace 19) and the arterial pressure via a catheter in the radial artery (trace 20) Fig. 3 a A direct current (DC)/alternating current (AC)-electrocorticography (ECoG) amplifier is superior to a near-DC/AC-ECoG amplifier for recording spreading depolarizations (SD) and the development of cerebral infarction. Traces 1–6 show the same raw DC/AC-ECoG recordings (band-pass, 0–45 Hz) as traces 1–6 in Fig. 2 . However, traces 7–12 give the near-DC/AC-ECoG recordings (band-pass, 0.01–45 Hz) to illustrate that the longer negative DC shifts at electrodes 4–6 near the developing infarct become invisible in the near-DC/AC-ECoG recordings. In other words, the occurrence of SDs can be paradoxically underestimated in regions where SD is most important, if only near-DC/AC-ECoG recordings are available. The ECoG traces are oriented with negativity upward and positivity downward according to the electroencephalography (EEG) convention. b Row 1 from top to bottom shows the progression of focal brain damage from the MRI on Day 2 to the CT on Day 7, when the delayed infarct first became visible in the form of a loss of differentiation between gray and white matter in the right insular and frontal cortex . Row 2 shows the time course of the transcranial Doppler-sonography (TCD)-measured mean blood flow velocity in the ipsilateral middle cerebral artery (MCA). Rows 3 and 4 show the time course of the SD variables: For each day, SDs were counted and depression durations were scored to determine the total duration of SD-induced activity depression per recording day (TDDD) (row 3) and the total number of SDs per recording day (row 4). The peak TDDD (PTDDD) and peak SDs/day were defined for each patient as the maximal values among all recording days (indicated as a dark gray and dark blue bar, respectively). The delayed SDs started on Day 6 and reached its maximum on Day 7, i.e., they started many hours before the early signs of delayed infarction were seen on CT . The highest TCD-measured mean blood flow velocity in the ipsilateral MCA was 220 cm/s measured on Day 9 and the ipsilateral qualitative digital subtraction angiography (DSA) score was 2.57 on Day 9 suggesting that the patient had severe angiographic vasospasm on the affected side. However, on Day 6, when the electrographic processes leading to infarction began, the TCD-measured mean blood flow velocity was only 139 cm/s. On Day 7, when the delayed infarction was already visible on CT by the loss of differentiation between gray and white matter, it was only 158 cm/s. This temporal lag of the TCD-measured peak mean blood flow velocities after infarct development was typical for DISCHARGE-1 , if the delayed infarcts were accompanied by proximal vasospasm at all	4.183594	0.481689	sec[2]/p[2]	en	0.999997	38396252	https://doi.org/10.1007/s12975-024-01237-w	[ "infarct", "scan", "electrode", "ecog", "frontal", "infarction", "traces", "development", "blood", "cerebral" ]	[ { "code": "FB32.2Z", "title": "Ischaemic infarction of muscle, unspecified" }, { "code": "DD30.Z", "title": "Acute vascular disorders of intestine, unspecified" }, { "code": "8B26.Y", "title": "Other specified vascular syndromes of brain in cerebrovascular diseases" }, { "code": "GB90.3", "title": "Ischaemia or infarction of kidney" }, { "code": "DB98.0", "title": "Infarction of liver" }, { "code": "MB71.Y", "title": "Other specified clinical findings on diagnostic imaging of central nervous system" }, { "code": "NE60", "title": "Harmful effects of drugs, medicaments or biological substances, not elsewhere classified" }, { "code": "JA66.3", "title": "Abnormal ultrasonic finding on antenatal screening of mother" }, { "code": "PB28", "title": "Unintentional exposure to or harmful effects of other or unspecified drug, medicament or biological substance" }, { "code": "PC98", "title": "Intentional self-harm by exposure to other or unspecified drug, medicament or biological substance" } ]	=== ICD-11 CODES FOUND === [FB32.2Z] Ischaemic infarction of muscle, unspecified Also known as: Ischaemic infarction of muscle, unspecified \| Ischaemic infarction of muscle \| muscle infarction [DD30.Z] Acute vascular disorders of intestine, unspecified Also known as: Acute vascular disorders of intestine, unspecified \| Acute vascular disorders of intestine \| acute intestinal ischemia NOS \| acute intestinal ischemic syndrome \| acute ischaemic bowel disease [8B26.Y] Other specified vascular syndromes of brain in cerebrovascular diseases Also known as: Other specified vascular syndromes of brain in cerebrovascular diseases \| Subcortical ischaemic stroke \| subcortical infarction \| Cortical ischaemic stroke \| cortical infarction [GB90.3] Ischaemia or infarction of kidney Also known as: Ischaemia or infarction of kidney \| Complete arterial ischaemia or infarction of kidney \| Complete arterial ischaemia or infarction of kidney due to renal artery obstruction \| obstructed renal artery \| renal artery clot Excludes: Atherosclerosis of renal artery \| Goldblatt kidney \| Congenital renal artery stenosis [DB98.0] Infarction of liver Definition: Infarction of the liver is hepatic damage caused by limited blood supply to the liver due to obstruction or reduced blood flow of hepatic artery, portal vein or both. Also known as: Infarction of liver \| hepatic infarct \| hepatic infarction \| liver infarct \| liver infarction [MB71.Y] Other specified clinical findings on diagnostic imaging of central nervous system Also known as: Other specified clinical findings on diagnostic imaging of central nervous system \| Epidural haemorrhage, localised, no generalised mass effect or midline shift \| Epidural haemorrhage, confined to a small region in relation to a fracture \| Epidural haemorrhage, size less than 1 x 1 x 1 cm, not in relation to a fracture \| Epidural haemorrhage, mass effect or midline shift less than 0.5 cm [NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified Also known as: Harmful effects of drugs, medicaments or biological substances, not elsewhere classified \| drugs, medicaments or biological substances, toxicity not elsewhere classified \| adverse drug effects \| drug reaction NOS \| drug allergy NOS Excludes: Alcohol intoxication \| pathological drug intoxication \| hypersensitivity reaction to correctly administered drug [JA66.3] Abnormal ultrasonic finding on antenatal screening of mother Definition: A sign characterised by an abnormality detected by ultrasound during an antenatal screening of the mother. Also known as: Abnormal ultrasonic finding on antenatal screening of mother \| antenatal ultrasound scan abnormal [PB28] Unintentional exposure to or harmful effects of other or unspecified drug, medicament or biological substance Also known as: Unintentional exposure to or harmful effects of other or unspecified drug, medicament or biological substance \| accidental overdose of other or unspecified drug, medicament or biological substance \| accidental poisoning by other or unspecified drug, medicament or biological substance \| other or unspecified drug, medicament or biological substance taken in error \| accidental drug overdose [PC98] Intentional self-harm by exposure to other or unspecified drug, medicament or biological substance Also known as: Intentional self-harm by exposure to other or unspecified drug, medicament or biological substance \| Intentional self-poisoning by and exposure to other or unspecified drug, medicament or biological substance \| Intentional overdose of other or unspecified drug, medicament or biological substance \| self-administered overdose by drugs \| Intentional self-harm by exposure to or harmful effects of systemic antibiotics === GRAPH WALKS === --- Walk 1 --- [FB32.2Z] Ischaemic infarction of muscle, unspecified --PARENT--> [FB32.2] Ischaemic infarction of muscle --CHILD--> [FB32.2Y] Other specified ischaemic infarction of muscle --- Walk 2 --- [FB32.2Z] Ischaemic infarction of muscle, unspecified --PARENT--> [FB32.2] Ischaemic infarction of muscle --EXCLUDES--> [?] Traumatic ischaemia of muscle, not elsewhere classified --- Walk 3 --- [DD30.Z] Acute vascular disorders of intestine, unspecified --PARENT--> [DD30] Acute vascular disorders of intestine Def: Intestinal ischaemia has an associated vascular block, usually due to atheroma, thrombus, or embolus but occasionally the result of an arteritis, vasculitis, or other condition.... --PARENT--> [?] Ischaemic vascular disorders of intestine Def: Intestinal ischemia characterised by blood supply to the gastrointestinal tract that is inadequate to meet its metabolic demand... --- Walk 4 --- [DD30.Z] Acute vascular disorders of intestine, unspecified --PARENT--> [DD30] Acute vascular disorders of intestine Def: Intestinal ischaemia has an associated vascular block, usually due to atheroma, thrombus, or embolus but occasionally the result of an arteritis, vasculitis, or other condition.... --RELATED_TO--> [?] Non-occlusive mesenteric ischaemia Def: Non-occlusive mesenteric ischaemia causes 20% to 30% of acute mesenteric ischaemia episodes. Mesenteric ischaemia without anatomic arterial or venous obstruction is due to mesenteric vasospasm, which ... --- Walk 5 --- [8B26.Y] Other specified vascular syndromes of brain in cerebrovascular diseases --PARENT--> [8B26] Vascular syndromes of brain in cerebrovascular diseases --CHILD--> [8B26.0] Brainstem stroke syndrome --- Walk 6 --- [8B26.Y] Other specified vascular syndromes of brain in cerebrovascular diseases --PARENT--> [8B26] Vascular syndromes of brain in cerebrovascular diseases --CHILD--> [8B26.0] Brainstem stroke syndrome	[ "[FB32.2Z] Ischaemic infarction of muscle, unspecified\n --PARENT--> [FB32.2] Ischaemic infarction of muscle\n --CHILD--> [FB32.2Y] Other specified ischaemic infarction of muscle", "[FB32.2Z] Ischaemic infarction of muscle, unspecified\n --PARENT--> [FB32.2] Ischaemic infarction of muscle\n --EXCLUDES--> [?] Traumatic ischaemia of muscle, not elsewhere classified", "[DD30.Z] Acute vascular disorders of intestine, unspecified\n --PARENT--> [DD30] Acute vascular disorders of intestine\n Def: Intestinal ischaemia has an associated vascular block, usually due to atheroma, thrombus, or embolus but occasionally the result of an arteritis, vasculitis, or other condition....\n --PARENT--> [?] Ischaemic vascular disorders of intestine\n Def: Intestinal ischemia characterised by blood supply to the gastrointestinal tract that is inadequate to meet its metabolic demand...", "[DD30.Z] Acute vascular disorders of intestine, unspecified\n --PARENT--> [DD30] Acute vascular disorders of intestine\n Def: Intestinal ischaemia has an associated vascular block, usually due to atheroma, thrombus, or embolus but occasionally the result of an arteritis, vasculitis, or other condition....\n --RELATED_TO--> [?] Non-occlusive mesenteric ischaemia\n Def: Non-occlusive mesenteric ischaemia causes 20% to 30% of acute mesenteric ischaemia episodes. Mesenteric ischaemia without anatomic arterial or venous obstruction is due to mesenteric vasospasm, which ...", "[8B26.Y] Other specified vascular syndromes of brain in cerebrovascular diseases\n --PARENT--> [8B26] Vascular syndromes of brain in cerebrovascular diseases\n --CHILD--> [8B26.0] Brainstem stroke syndrome", "[8B26.Y] Other specified vascular syndromes of brain in cerebrovascular diseases\n --PARENT--> [8B26] Vascular syndromes of brain in cerebrovascular diseases\n --CHILD--> [8B26.0] Brainstem stroke syndrome" ]	FB32.2Z	Ischaemic infarction of muscle, unspecified	[ { "from_icd11": "FB32.2Z", "icd10_code": "M62261", "icd10_title": "Nontraumatic ischemic infarction of muscle, right lower leg" }, { "from_icd11": "FB32.2Z", "icd10_code": "M62252", "icd10_title": "Nontraumatic ischemic infarction of muscle, left thigh" }, { "from_icd11": "FB32.2Z", "icd10_code": "M62251", "icd10_title": "Nontraumatic ischemic infarction of muscle, right thigh" }, { "from_icd11": "FB32.2Z", "icd10_code": "M62242", "icd10_title": "Nontraumatic ischemic infarction of muscle, left hand" }, { "from_icd11": "FB32.2Z", "icd10_code": "M6220", "icd10_title": "Nontraumatic ischemic infarction of muscle, unspecified site" }, { "from_icd11": "FB32.2Z", "icd10_code": "M622", "icd10_title": "Nontraumatic ischemic infarction of muscle" }, { "from_icd11": "DD30.Z", "icd10_code": "K55019", "icd10_title": "Acute (reversible) ischemia of small intestine, extent unspecified" }, { "from_icd11": "DD30.Z", "icd10_code": "K55029", "icd10_title": "Acute infarction of small intestine, extent unspecified" }, { "from_icd11": "DD30.Z", "icd10_code": "K55069", "icd10_title": "Acute infarction of intestine, part and extent unspecified" }, { "from_icd11": "DD30.Z", "icd10_code": "K55021", "icd10_title": "Focal (segmental) acute infarction of small intestine" }, { "from_icd11": "DD30.Z", "icd10_code": "K55039", "icd10_title": "Acute (reversible) ischemia of large intestine, extent unspecified" }, { "from_icd11": "DD30.Z", "icd10_code": "K55059", "icd10_title": "Acute (reversible) ischemia of intestine, part and extent unspecified" }, { "from_icd11": "DD30.Z", "icd10_code": "K55042", "icd10_title": "Diffuse acute infarction of large intestine" }, { "from_icd11": "DD30.Z", "icd10_code": "K55041", "icd10_title": "Focal (segmental) acute infarction of large intestine" }, { "from_icd11": "DD30.Z", "icd10_code": "K55011", "icd10_title": "Focal (segmental) acute (reversible) ischemia of small intestine" } ]	M62261	Nontraumatic ischemic infarction of muscle, right lower leg
The patient, a 28-year-old man, was admitted to the Endocrinology Department of Peking University International Hospital on November 15, 2022, due to “six years of excessive drinking and urination, 6 months of paroxysmal nausea and vomiting”. The patient had symptoms of thirst, polydipsia, and polyuria without inducement 6 years ago and was not diagnosed or treated. The fasting plasma glucose was 8.5 mmol/L (normal reference range is 3.9–6.1 mmol/L) in the posterior examination. Then, he was diagnosed with T1DM after examinations in an external hospital. The patient was given short-acting insulin for three meals and long-acting insulin before bed for anti-hyperglycaemic treatment. He was hospitalized many times for diabetic ketoacidosis (DKA) because of irregular insulin injections. When discharged from the hospital, the patient was given a preprandial subcutaneous injection of insulin lispro and a presleep subcutaneous injection of insulin glargine. The daily insulin consumption was approximately 47–64 units adjusted according to the blood glucose level. Six months prior, he had intermittent nausea and vomiting with no obvious inducement without abdominal pain and diarrhoea. He was diagnosed with diabetic ketosis (DK) by random intravenous plasma glucose with 21.4 mmol/L, arterial blood gas with pH 7.37, and urine ketone body with 3+. The symptoms were alleviated, and ketone bodies were negative after rehydration and insulin supplementation in the emergency department and then our endocrine department. After discharge, he still had intermittent nausea, vomiting, abdominal distension, and abdominal pain, especially after meals. He was given itopride hydrochloride tablets to promote gastrointestinal motility, pancreatin enteric-coated capsules to supplement digestive enzymes, and pinaverium bromide tablets to relieve symptomatic pain. Additionally, psychologists evaluated the patient’s anxiety state and gave duloxetine and oxazepam to relieve anxiety. Unfortunately, the above treatment was not effective. Therefore, the patient himself stopped insulin injections and occasionally measured random peripheral blood glucose > 20 mmol/L. He was then admitted to our department for further diagnosis and treatment. During the course of DM, the patient had no blurred vision, numbness of limbs, cold feeling, acupuncture feeling, sleeve-like feeling, or intermittent claudication. He lost approximately 5 kg of weight in 9 months. For his past history, the patient was diagnosed with a renal cyst, kidney stone, and prostate cyst 3.5 years ago, 8 months ago, and 6 months ago, respectively. He denied a history of pancreatitis or pancreatic surgery. He was born at full term with a birth weight of 2.5 kg without hypoglycaemia. His growth and development are comparable to those of his peers. His mother and other family members did not have a history of DM. Physical examination results were as follows: temperature, 36.2°C; pulse, 72 times/min; respiration, 20 times/min; blood pressure, 140/87 mmHg; height, 175 cm; weight, 50 kg; BMI, 16.33 kg/m 2 ; waistline, 65 cm; hip, 77 cm; and waist-to-hip ratio, 0.84. He did not have a Cushing appearance. He had clear breath sounds in both lungs, no obvious dry and wet rales, regular heart rhythm, no murmur, and additional heart sounds in the auscultation area of each valve. He had boat-shaped abdomen, soft whole abdomen, mild tenderness in the upper abdomen, no rebound pain and muscle tension, normal bowel sounds, no oedema in both lower limbs, normal pulsation of bilateral dorsalis pedis arteries, normal sense of pain, temperature, and vibration, and a negative 10 g elastic wire test on both sides. Laboratory examination revealed that the venous fasting plasma glucose was 26.3 mmol/L, urine glucose 3+, and urine ketone body +. The arterial blood gas analysis was as follows: pH 7.46 (7.35–7.45), PaO 2 81 mmHg (80–100 mmHg), PaCO 2 48 mmHg (35–45 mmHg), HCO3 − 35.0 mmol/L (22–27 mmol/L), BE-b 10.5 mmol/L (−3.0 to 3.0 mmol/L), venous serum potassium ion 3.5 mmol/L (3.5–5.5 mmol/L), sodium ion 134 mmol/L (137–147 mmol/L), chloride ion 93 mmol/L (99–110 mmol/L), glycosylated haemoglobin 11.2% (4.0%–6.0%), and fasting serum C-peptide level fluctuated between 0.34–1.15 ng/ml (1.1–4.4 ng/ml) and 0.39–2.02 ng/ml 2 hours after breakfast . The patient was negative for glutamic acid decarboxylase antibody (GADA), islet cell antibody (ICA), and insulin autoantibody (IAA). The serum magnesium level fluctuated between 0.39 and 0.71 mmol/L (0.75–1.02 mmol/L). His liver function, glomerular filtration rate, serum lipids, uric acid, calcium, phosphorus, parathyroid hormone, and thyroid function were all within the normal range. The complications of diabetes were examined. No diabetic retinopathy was found in fundus photography, but cataracts were found in the right eye. The successive urinary microalbumin/creatinine ratio (UACR) was measured three times, and the values were 22.32 mg/g, 16.7 mg/g, and 15.85 mg/g (0–30 mg/g). Colour Doppler ultrasound of the carotid artery and lower limb artery showed no atherosclerotic plaque formation. Measurements of pulse wave velocity (PWV), ankle–brachial index (ABI), and quantitative sensory disturbance were normal. Digestive system diseases were evaluated. The enhanced CT scan of the abdomen showed agenesis of the dorsal pancreas (ADP) (considering pancreatic developmental variation), complex cysts of both kidneys, and small stones in the right kidney . An abdominal dynamic contrast-enhanced magnetic resonance scan did not show pancreatic duct dilation. Gastric emptying imaging showed that the gastric half-emptying time of semisolid food was approximately 80.53 min (37.25 ± 15.7 min). The tumor markers of the digestive tract, serum amylase, and lipase were normal. Gastroscopy showed chronic non-atrophic gastritis with bile reflux and a positive urease Helicobacter pylori (HP) test. Enteroscopy showed that the intestinal preparation was poor and that the mucosa below the sigmoid colon was normal. No abnormality was found in the upright abdominal plain film radiography and the ultrasound of the superior and inferior mesenteric arteries. The characteristics of this case are summarized as follows: 1) young onset of illness with a primary diagnosis of T1DM and therapy with long-term insulin replacement; 2) no family history of DM; 3) islet β cell dysfunction, but no absolute deficiency was observed; 4) negative for diabetes-related antibodies; and 5) abnormal development of multiple organs. Therefore, the diagnosis of T1DM was challenged. Specific types of DM could not be excluded. After informed consent of the patient was obtained, a peripheral blood sample was taken to Beijing Hope Group Biotechnology Co., Ltd., for examination. First, DNA interruption was performed, and a library was prepared. Then, DNA sample capture and PCR amplification were performed. Finally, the captured DNA samples were submitted for high-throughput sequencing. After the sequencing data were evaluated by Illumina Sequence Control Software (SCS) and qualified, data reading and bioinformatics analysis were performed. The results showed that the patient was suspected to have a heterozygous deletion mutation at [GRCh37 (hg19)] chr17:34842526-36347106 (1.5 Mb) that included 24 genes in total: AATF , ACACA , C17orf78 , DDX52 , DHRS11 , DUSP14 , GGNBP2 , HMGB1P24 , HNF1B , LHX1 , LHX1-DT , MIR2909 , MIR378J , MRM1 , MYO19 , PIGW , RNA5SP439 , RNU6-489P , SYNRG , TADA2A , TBC1D3K , TBC1D3L , YWHAEP7 , and ZNHIT3 . This region contained the complete 17q12 recurrent region (including HNF1B gene), which is not enough to cause a disease with the confirmed single dose. According to the results of gene detection, the diagnosis was revised to 17q12 deletion syndrome. Considering the findings of poor long-term blood glucose control, significantly delayed gastric emptying time, and the digestive tract history, the patient was considered to have DGP. The treatment plan was as follows: 1) diet guidance of low-fat diabetes soft food or semiliquid food and multiple meals with small amounts for each, 2) insulin subcutaneous injection for glucose-lowering treatment, 3) mosapride citrate tablets for promoting total gastrointestinal motility, and 4) pancreatin enteric capsules for supplementing pancreatin. Treatment results and follow-up indicated that the patient’s blood glucose fluctuation was reduced, with his fasting blood glucose fluctuating between 4 and 8 mmol/L and his 2-hour postprandial glucose fluctuating between 6 and 11 mmol/L. No symptomatic hypoglycaemia events occurred. His abdominal symptoms were significantly alleviated. Afterward, he did not seek medical attention due to unbearable abdominal pain ( Table 1 ).	3.820313	0.982422	sec[1]/p[0]	en	0.999994	PMC10682700	https://doi.org/10.3389/fendo.2023.1205431	[ "mmol", "glucose", "insulin", "blood", "abdominal", "that", "pain", "mmhg", "serum", "department" ]	[ { "code": "GB42.1", "title": "Albuminuria, Grade A3" }, { "code": "GB42.0", "title": "Albuminuria, Grade A2" }, { "code": "MA18.0Y", "title": "Other specified elevated blood glucose level" }, { "code": "5A40.Z", "title": "Intermediate hyperglycaemia, unspecified" }, { "code": "5C61.Y", "title": "Other specified disorders of carbohydrate absorption or transport" }, { "code": "5A40.1", "title": "Impaired glucose tolerance" }, { "code": "5A40.0", "title": "Impaired fasting glucose" }, { "code": "5C61.5", "title": "Disorders of facilitated glucose transport" }, { "code": "5A44", "title": "Insulin-resistance syndromes" }, { "code": "5A4Y", "title": "Other specified disorders of glucose regulation or pancreatic internal secretion" } ]	=== ICD-11 CODES FOUND === [GB42.1] Albuminuria, Grade A3 Definition: Presence of excessive albumin in the urine, indicating abnormal permeability glomerular filtration. Can be quantitated by either timed collections or spot urine samples with the concentration adjusted to the urine creatinine concentration to correct for variations in overall urine concentration. When persistent and of moderate or greater severity usually indicates overt glomerular disease such as caused by diabetic glomerulosclerosis, glomerulonephritis or amyloid. Also known as: Albuminuria, Grade A3 \| albuminuria >30 mg/mmol creatinine \| macroalbuminuria \| overt albuminuria \| overt nephropathy [GB42.0] Albuminuria, Grade A2 Definition: Presence of excessive albumin in the urine, indicating abnormal permeability glomerular filtration. Can be quantitated by either timed collections or spot urine samples with the concentration adjusted to the urine creatinine concentration to correct for variations in overall urine concentration. When persistent and of moderate or greater severity usually indicates overt glomerular disease such as caused by diabetic glomerulosclerosis, glomerulonephritis or amyloid. Also known as: Albuminuria, Grade A2 \| microalbuminuria \| incipient nephropathy \| mild to moderate albuminuria \| albuminuria 3-30 mg/mmol creatinine [MA18.0Y] Other specified elevated blood glucose level Also known as: Other specified elevated blood glucose level \| Blood glucose between 8.0 - 11.9 mmol/L pre-meal or fasting \| Blood glucose between 12.0 - 13.9 mmol/L pre-meal or fasting \| Blood glucose greater than or equal to 14.0 mmol/L pre-meal or fasting \| Blood glucose between 12.0 - 13.9 mmol/L post-meal or not otherwise specified [5A40.Z] Intermediate hyperglycaemia, unspecified Also known as: Intermediate hyperglycaemia, unspecified \| Intermediate hyperglycaemia \| Impaired glucose regulation \| prediabetes \| latent diabetes [5C61.Y] Other specified disorders of carbohydrate absorption or transport Also known as: Other specified disorders of carbohydrate absorption or transport \| Other disorders of intestinal carbohydrate absorption \| Glucose malabsorption \| Isomaltose malabsorption \| Sucrose malabsorption [5A40.1] Impaired glucose tolerance Definition: Impaired glucose tolerance (IGT) is a metabolic disorder, which is characterised by 2-h postload glucose 140–199 mg/dl (7.8–11.1 mmol/l). Also known as: Impaired glucose tolerance \| IGT - [impaired glucose tolerance] \| Impaired glucose tolerance with unspecified complication \| Impaired glucose tolerance without complication \| abnormal glucose tolerance [5A40.0] Impaired fasting glucose Definition: Impaired fasting tolerance is a metabolic disorder with Fasting Plasma Glucose (FPG) 110–125 mg/dl (6.1–6.9 mmol/l). Also known as: Impaired fasting glucose \| IFG - [impaired fasting glucose] \| impaired fasting glycaemia \| elevated fasting glucose \| high fasting blood sugar [5C61.5] Disorders of facilitated glucose transport Also known as: Disorders of facilitated glucose transport \| Encephalopathy due to GLUT1 deficiency \| Glucose transporter defect, blood-brain barrier \| Facilitated glucose transporter protein type 1 deficiency \| Familial renal glucosuria [5A44] Insulin-resistance syndromes Also known as: Insulin-resistance syndromes \| Insulin-resistance syndrome type A \| Insulin-resistance syndrome type B \| Rabson-Mendenhall syndrome \| Laminopathy type Decaudain-Vigouroux [5A4Y] Other specified disorders of glucose regulation or pancreatic internal secretion Also known as: Other specified disorders of glucose regulation or pancreatic internal secretion \| Other hypoglycaemia \| Hyperinsulinaemia \| hyperinsulinism \| functional hyperinsulinaemia === GRAPH WALKS === --- Walk 1 --- [GB42.1] Albuminuria, Grade A3 Def: Presence of excessive albumin in the urine, indicating abnormal permeability glomerular filtration. Can be quantitated by either timed collections or spot urine samples with the concentration adjusted... --PARENT--> [GB42] Persistent proteinuria or albuminuria Def: Persistent albuminuria >3mg/mmol creatinine or >30mg/day is regarded as abnormal, indicative and often the first manifestation of chronic kidney disease (CKD). In surveillance for CKD in “at risk” pat... --EXCLUDES--> [?] Gestational proteinuria without hypertension --- Walk 2 --- [GB42.1] Albuminuria, Grade A3 Def: Presence of excessive albumin in the urine, indicating abnormal permeability glomerular filtration. Can be quantitated by either timed collections or spot urine samples with the concentration adjusted... --PARENT--> [GB42] Persistent proteinuria or albuminuria Def: Persistent albuminuria >3mg/mmol creatinine or >30mg/day is regarded as abnormal, indicative and often the first manifestation of chronic kidney disease (CKD). In surveillance for CKD in “at risk” pat... --EXCLUDES--> [?] Gestational proteinuria without hypertension --- Walk 3 --- [GB42.0] Albuminuria, Grade A2 Def: Presence of excessive albumin in the urine, indicating abnormal permeability glomerular filtration. Can be quantitated by either timed collections or spot urine samples with the concentration adjusted... --PARENT--> [GB42] Persistent proteinuria or albuminuria Def: Persistent albuminuria >3mg/mmol creatinine or >30mg/day is regarded as abnormal, indicative and often the first manifestation of chronic kidney disease (CKD). In surveillance for CKD in “at risk” pat... --CHILD--> [GB42.Y] Other specified persistent proteinuria or albuminuria --- Walk 4 --- [GB42.0] Albuminuria, Grade A2 Def: Presence of excessive albumin in the urine, indicating abnormal permeability glomerular filtration. Can be quantitated by either timed collections or spot urine samples with the concentration adjusted... --PARENT--> [GB42] Persistent proteinuria or albuminuria Def: Persistent albuminuria >3mg/mmol creatinine or >30mg/day is regarded as abnormal, indicative and often the first manifestation of chronic kidney disease (CKD). In surveillance for CKD in “at risk” pat... --EXCLUDES--> [?] Proteinuria Def: Excessive serum proteins in the urine, such as in renal disease when albumin is the main protein, but also may be due to other proteins such as immunoglobulin light chains in plasma cell dyscrasia suc... --- Walk 5 --- [MA18.0Y] Other specified elevated blood glucose level --PARENT--> [MA18.0] Elevated blood glucose level --EXCLUDES--> [?] Syndrome of infant of mother with gestational diabetes Def: Describes the range of effects on the infant born to a woman with gestational diabetes (onset or first recognition of carbohydrate intolerance of variable severity in pregnancy). Common neonatal effec... --- Walk 6 --- [MA18.0Y] Other specified elevated blood glucose level --PARENT--> [MA18.0] Elevated blood glucose level --EXCLUDES--> [?] Postprocedural hypoinsulinaemia Def: This is a low level of insulin that can result after medical procedures, including radiation, and it carries a risk of developing diabetes mellitus....	[ "[GB42.1] Albuminuria, Grade A3\n Def: Presence of excessive albumin in the urine, indicating abnormal permeability glomerular filtration. Can be quantitated by either timed collections or spot urine samples with the concentration adjusted...\n --PARENT--> [GB42] Persistent proteinuria or albuminuria\n Def: Persistent albuminuria >3mg/mmol creatinine or >30mg/day is regarded as abnormal, indicative and often the first manifestation of chronic kidney disease (CKD). In surveillance for CKD in “at risk” pat...\n --EXCLUDES--> [?] Gestational proteinuria without hypertension", "[GB42.1] Albuminuria, Grade A3\n Def: Presence of excessive albumin in the urine, indicating abnormal permeability glomerular filtration. Can be quantitated by either timed collections or spot urine samples with the concentration adjusted...\n --PARENT--> [GB42] Persistent proteinuria or albuminuria\n Def: Persistent albuminuria >3mg/mmol creatinine or >30mg/day is regarded as abnormal, indicative and often the first manifestation of chronic kidney disease (CKD). In surveillance for CKD in “at risk” pat...\n --EXCLUDES--> [?] Gestational proteinuria without hypertension", "[GB42.0] Albuminuria, Grade A2\n Def: Presence of excessive albumin in the urine, indicating abnormal permeability glomerular filtration. Can be quantitated by either timed collections or spot urine samples with the concentration adjusted...\n --PARENT--> [GB42] Persistent proteinuria or albuminuria\n Def: Persistent albuminuria >3mg/mmol creatinine or >30mg/day is regarded as abnormal, indicative and often the first manifestation of chronic kidney disease (CKD). In surveillance for CKD in “at risk” pat...\n --CHILD--> [GB42.Y] Other specified persistent proteinuria or albuminuria", "[GB42.0] Albuminuria, Grade A2\n Def: Presence of excessive albumin in the urine, indicating abnormal permeability glomerular filtration. Can be quantitated by either timed collections or spot urine samples with the concentration adjusted...\n --PARENT--> [GB42] Persistent proteinuria or albuminuria\n Def: Persistent albuminuria >3mg/mmol creatinine or >30mg/day is regarded as abnormal, indicative and often the first manifestation of chronic kidney disease (CKD). In surveillance for CKD in “at risk” pat...\n --EXCLUDES--> [?] Proteinuria\n Def: Excessive serum proteins in the urine, such as in renal disease when albumin is the main protein, but also may be due to other proteins such as immunoglobulin light chains in plasma cell dyscrasia suc...", "[MA18.0Y] Other specified elevated blood glucose level\n --PARENT--> [MA18.0] Elevated blood glucose level\n --EXCLUDES--> [?] Syndrome of infant of mother with gestational diabetes\n Def: Describes the range of effects on the infant born to a woman with gestational diabetes (onset or first recognition of carbohydrate intolerance of variable severity in pregnancy). Common neonatal effec...", "[MA18.0Y] Other specified elevated blood glucose level\n --PARENT--> [MA18.0] Elevated blood glucose level\n --EXCLUDES--> [?] Postprocedural hypoinsulinaemia\n Def: This is a low level of insulin that can result after medical procedures, including radiation, and it carries a risk of developing diabetes mellitus...." ]	GB42.1	Albuminuria, Grade A3	[ { "from_icd11": "5A40.Z", "icd10_code": "R7309", "icd10_title": "Other abnormal glucose" }, { "from_icd11": "5A40.0", "icd10_code": "R7301", "icd10_title": "Impaired fasting glucose" }, { "from_icd11": "5C61.5", "icd10_code": "E748", "icd10_title": "Other specified disorders of carbohydrate metabolism" }, { "from_icd11": "5A44", "icd10_code": "E10-E14", "icd10_title": "" } ]	R7309	Other abnormal glucose
MTC, 42, married to a man aged 47, with two prior attempts at IVF in another fertility center, described it as "a very difficult experience." She had her first cycle in 2013, with three transfers. The first ended in a miscarriage (Down syndrome) and the second and third did not result in pregnancy. Her husband was a quiet man. He only said that he wanted his name to be correctly spelled. They came to the center in August of 2015 for a new cycle and to undergo PGS. During consultation with the nurse she reported a history of vaginismus, which she had omitted to the physician, and asked for sedation during the transfer procedure. She said she could "tolerate" the transvaginal probe, but that the speculum would be impossible to bear since it would remind her of a course of dilation therapy she had had in the past. She asked the nurse to inform the physicians of her condition because she was too embarrassed to do it herself. While sedated for the oocyte pick-up, she strongly tried to adduce her legs when the speculum touched her vagina. She was due for a transfer under sedation, but the couple had no embryos to transfer (two aneuploid blastocysts) and decided to consider implanting donor oocytes. TBB, 38, married to a man aged 39, came to our center asking for IVF because she "did not tolerate vaginal penetration". She was seen by a sexologist/psychologist, and she could bear nothing beyond her husband touching her perineum. It was decided she would undergo pelvic ultrasound examination and her transfers would take place under sedation. In the beginning of the oocyte pick-up procedure, while sedated with Propofol ® , she broke the disposable speculum with a vaginal spasm. The pelvic contractions ceased only after her psychoanalyst, who was in the room, whispered in her ear: "you are here by choice, and nobody will invade you against your will." Cycle 1 resulted in biochemical pregnancy. During cycle 2, in May of 2016 (frozen eggs from cycle 1 plus the product of cycle 2), she underwent PGS. Prior to aspiration, by request of her gynecologist, a Pap smear was collected, since she had never allowed the placement of a speculum. In the first sedated frozen embryo transfer (FET) with one blastocyst, she got pregnant but had a miscarriage in the first trimester. She had another transfer under sedation in December of 2016 and had a positive pregnancy test. When she returned for ultrasound examination (7 weeks and 1 day), she allowed the use of a transvaginal probe for the first time. To our surprise, the examination was uneventful. Her husband was present, and the two were very happy. LV, 37, married to a man aged 38, came to the clinic in November of 2014, saying she had had "an IVF cycle in September that did not work" in another ART center. A high dose stimulation protocol was attempted in the first cycle (Gonal F ® - rFSH- 300/450IU + Luveris ® rLH- 75 IU, Cetrotide ® for 5 days, Ovidrel ® ). Only two oocytes were retrieved. In her words, transvaginal ultrasound examinations and the embryo transfer procedure felt "horrible." The cycle resulted only in one cleavage state embryo. She "hated" everything. The couple was offered a procedure with donor oocytes. Further examination in our center revealed an antral follicle count (AFC) of 17 and an AMH of 2.22 ng/mL. During the anamnesis the couple reported "difficulty" with vaginal penetration. She added: "I'm OK with the video examination, but I have to relax and breathe as I've learned to do. And the doctor must take it easy. But the thing is nobody would listen to me in the other center." For reasons linked to religion, the couple preferred not to have their embryos frozen. A new cycle was scheduled in our center using an antagonist (Cetrotide ® ) protocol with Letrozol ® (5mg per day) plus Pergoveris ® (1 vial per day). They decided that no more than four oocytes would be injected with spermatozoa. From eight oocytes, four metaphase II specimens were frozen and four proceeded to ICSI. The strategy resulted in three cleavage state embryos, two transferred in day 3 after ICSI and one vitrified the same day. She got pregnant and had a term elective cesarean section. In May of 2016 they came in for a frozen embryo transfer (FET) with the previously vitrified embryo plus the resulting embryos from the thawed oocytes. However, the cycle did not result in pregnancy. In July of 2016, a new IVF cycle resulted in the retrieval of 11 oocytes. Again, four M2 oocytes were injected and four were vitrified. She underwent a fresh transfer with two embryos in D3 that resulted in an ongoing gestation (3rd trimester). At every ultrasound check she would be given some time "to concentrate," mostly without the husband present, so that she could endure examination with a vaginal probe. In a noteworthy episode, on her last embryo transfer she asked her husband to remain silent. When he tried to comment on the images of her uterus, she said: "I do not want to see you, I do not want to hear you, I want to relax." As she said it, she had a vaginal spasm. TPC, 41, married to a man aged 37, although off contraceptives for seven years, had been unable to get pregnant. They underwent IUI in 2014 and an IVF cycle in March of 2015 in another ART center, neither of which resulting in pregnancy. The patient came to the clinic in April of 2015. Since they lived abroad, her husband would arrive at a later date. During their infertility investigation, she presented a sperm test with asthenozoospermia, which she considered the cause of their infertility problems. Her AMH level was 0,44 ng/mL. They had two IVF cycles in our center, one in December of 2015 and another in March of 2016. Unfortunately they resulted in three aneuploid blastocysts, and no transfer was performed. Before aspiration on cycle 3, she told the psychoanalyst that she had a really difficult time during penetration. According to her, they could have intercourse but it was always painful. There was an untold past of sexual abuse, depression treatment, and symptoms of suffocation. Her husband had erectile problems. PGB, 34, had been married to a man aged 34 for five years in September of 2016, but had never allowed penetration because of great pain. However, the couple stressed the fact that they loved each other. She said she was unable to undergo gynecological examination. She had previously tried dilation therapy, but could not tolerate it. The prospect of having an anatomical obstruction scared her. During her first visit, it was pointed to her that she had a functioning vagina, since she reported having regular cycles and no dysmenorrhea. A few visits later, the physician gently asked her for permission to perform a gynecological assessment. She allowed the introduction of Hegar dilators until number 8. She was progressively informed that there were no issues with the inside of her vagina. However, she had a very fibrotic hymen. The couple was offered a simple surgical procedure to facilitate penetration. The procedure resulted in a very adequate and anatomically shaped vaginal introitus. Nevertheless, she was unable to have adequate intercourse, because she still feared feeling pain again. The couple did not accept the idea of starting psychotherapy. IVF was then proposed. MDLN, 37, had been married to a man "in his sixties" for five and a half years and sought help because of vaginismus. They had never had successful intercourse, and he had no children. They came from a very religious background, and the two had been priests. She said she was not sure if she would be able to tolerate transvaginal examination, but she was willing to give it a try. In fact, during IVF treatment she had four TVUS, all performed by two female physicians previously informed of the situation and told to proceed very carefully. During oocyte pick-up her hymen was found to be ruptured. The day after she complained of abdominal pain and headache. However, clinical, abdominal and transvaginal ultrasound examination indicated everything was normal. She had a transfer under sedation of two D3 embryos, but was unable to achieve pregnancy. JSGH, 36, married to a man aged 38, sought help in November of 2011 (when she was 30) because of dyspareunia. An obstetrician-gynecologist associated to our clinic reported she was unable to bear gynecological examination. She was diagnosed with vaginismus and after some time and relaxation therapy, she allowed the introduction of a small speculum, the collection of a sample for a Pap smear, and even TVUS, although only with specific physicians. She managed to have intercourse, but was unable to get pregnant. In November of 2016, the couple had an unsuccessful IUI. Now, they are preparing for IVF.	3.810547	0.977051	sec[2]/sec[0]/p[0]	en	0.999997	29257632	https://doi.org/10.5935/1518-0557.20180013	[ "cycle", "they", "transfer", "that", "center", "couple", "oocytes", "married", "husband", "resulted" ]	[ { "code": "6A80.5", "title": "Rapid cycling" }, { "code": "PA03", "title": "Unintentional land transport traffic event injuring a motor cyclist" }, { "code": "5C50.AZ", "title": "Disorders of urea cycle metabolism, unspecified" }, { "code": "PA23", "title": "Unintentional land transport event unknown whether traffic or nontraffic injuring a motor cyclist" }, { "code": "PA02", "title": "Unintentional land transport traffic event injuring a pedal cyclist" }, { "code": "QB1Y", "title": "Other specified factors related to medical facilities or other health care" }, { "code": "PL14.2", "title": "Problem associated with physical transfer of patient" }, { "code": "QA30.12", "title": "Contact with health services for embryo transfer" }, { "code": "QA82", "title": "Problem associated with physical transfer of patient without injury or harm" }, { "code": "5C80.3", "title": "Hyperalphalipoproteinaemia" } ]	=== ICD-11 CODES FOUND === [6A80.5] Rapid cycling Definition: In the context of bipolar type I or bipolar type II disorder, there has been a high frequency of mood episodes (at least four) over the past 12 months. There may be a switch from one polarity of mood to the other, or the mood episodes may be demarcated by a period of remission. In individuals with a high frequency of mood episodes, some may have a shorter duration than those usually observed in bipolar type I or bipolar type II disorder. In particular, depressive periods may only last several da Also known as: Rapid cycling [PA03] Unintentional land transport traffic event injuring a motor cyclist Also known as: Unintentional land transport traffic event injuring a motor cyclist \| motorcycle rider injured in transport accident \| unintentional land transport accident motorbike \| motorbike accident \| motorbike traffic accident Excludes: Unintentional land transport traffic event injuring an occupant of a low powered passenger vehicle [5C50.AZ] Disorders of urea cycle metabolism, unspecified Also known as: Disorders of urea cycle metabolism, unspecified \| Disorders of urea cycle metabolism \| disorder of urea cycle \| disorders of metabolism of ornithine, citrulline, argininosuccinic acid, arginine and ammonia \| ammonia metabolic disorder [PA23] Unintentional land transport event unknown whether traffic or nontraffic injuring a motor cyclist Also known as: Unintentional land transport event unknown whether traffic or nontraffic injuring a motor cyclist \| unintentional off-road crash injuring a motor cyclist, unknown whether on road \| motor bike crash NOS \| motor cycle crash NOS \| Motorcycle rider injured in collision with railway train or railway vehicle [PA02] Unintentional land transport traffic event injuring a pedal cyclist Also known as: Unintentional land transport traffic event injuring a pedal cyclist \| Pedal cyclist injured in collision with pedestrian or animal \| Pedal cyclist injured in collision with pedestrian or animal, person injured while boarding or alighting \| Pedal cyclist injured in collision with pedestrian or animal, driver injured in traffic accident \| Pedal cyclist injured in collision with pedestrian or animal, passenger injured in traffic accident [QB1Y] Other specified factors related to medical facilities or other health care Also known as: Other specified factors related to medical facilities or other health care \| Transfer for suspected condition [PL14.2] Problem associated with physical transfer of patient Also known as: Problem associated with physical transfer of patient [QA30.12] Contact with health services for embryo transfer Definition: The procedure in which one or more embryos are placed in the uterus or Fallopian tube. Also known as: Contact with health services for embryo transfer \| ET - [embryo transfer] [QA82] Problem associated with physical transfer of patient without injury or harm Definition: Fall, bump, slip, entanglement, drop of patient during movement with healthcare personnel, without documented injury or harm Also known as: Problem associated with physical transfer of patient without injury or harm \| Patient slip during movement with healthcare personnel, without documented injury or harm \| Patient entanglement during movement with healthcare personnel, without documented injury or harm \| Drop of patient during movement or transfer with healthcare personnel, without documented injury or harm \| Patient bumped during movement or transfer with healthcare personnel without documented injury or harm Excludes: Problem associated with physical transfer of patient [5C80.3] Hyperalphalipoproteinaemia Definition: A condition in which high-density lipoprotein is elevated in the blood. Also known as: Hyperalphalipoproteinaemia \| Hyperalphalipoproteinaemia due to cholesteryl ester transfer protein deficiency \| Cholesterol-ester transfer protein deficiency \| Familial hyperalphalipoproteinaemia \| CEPT - [cholesterol-ester transfer protein deficiency] deficiency === GRAPH WALKS === --- Walk 1 --- [6A80.5] Rapid cycling Def: In the context of bipolar type I or bipolar type II disorder, there has been a high frequency of mood episodes (at least four) over the past 12 months. There may be a switch from one polarity of mood ... --PARENT--> [6A80] Symptomatic and course presentations for mood episodes in mood disorders Def: These categories may be applied to describe the presentation and characteristics of mood episodes in the context of single episode depressive disorder, recurrent depressive disorder, bipolar type I di... --RELATED_TO--> [?] Mental or behavioural disorders associated with pregnancy, childbirth or the puerperium, with psychotic symptoms Def: A syndrome associated with pregnancy or the puerperium (commencing within about 6 weeks after delivery) that involves significant mental and behavioural features, including delusions, hallucinations, ... --- Walk 2 --- [6A80.5] Rapid cycling Def: In the context of bipolar type I or bipolar type II disorder, there has been a high frequency of mood episodes (at least four) over the past 12 months. There may be a switch from one polarity of mood ... --PARENT--> [6A80] Symptomatic and course presentations for mood episodes in mood disorders Def: These categories may be applied to describe the presentation and characteristics of mood episodes in the context of single episode depressive disorder, recurrent depressive disorder, bipolar type I di... --RELATED_TO--> [?] Mental or behavioural disorders associated with pregnancy, childbirth or the puerperium, without psychotic symptoms Def: A syndrome associated with pregnancy or the puerperium (commencing within about 6 weeks after delivery) that involves significant mental and behavioural features, most commonly depressive symptoms. Th... --- Walk 3 --- [PA03] Unintentional land transport traffic event injuring a motor cyclist --PARENT--> [?] Unintentional land transport road traffic injury event --CHILD--> [PA01] Unintentional land transport traffic event injuring the user of a pedestrian conveyance --- Walk 4 --- [PA03] Unintentional land transport traffic event injuring a motor cyclist --PARENT--> [?] Unintentional land transport road traffic injury event --CHILD--> [PA01] Unintentional land transport traffic event injuring the user of a pedestrian conveyance --- Walk 5 --- [5C50.AZ] Disorders of urea cycle metabolism, unspecified --PARENT--> [5C50.A] Disorders of urea cycle metabolism --PARENT--> [5C50] Inborn errors of amino acid or other organic acid metabolism --- Walk 6 --- [5C50.AZ] Disorders of urea cycle metabolism, unspecified --PARENT--> [5C50.A] Disorders of urea cycle metabolism --CHILD--> [5C50.A2] Argininaemia Def: Arginase deficiency is a rare autosomal recessive amino acid metabolism disorder characterised clinically by variable degrees of hyperammonemia, developing from about 3 years of age, and leading to pr...	[ "[6A80.5] Rapid cycling\n Def: In the context of bipolar type I or bipolar type II disorder, there has been a high frequency of mood episodes (at least four) over the past 12 months. There may be a switch from one polarity of mood ...\n --PARENT--> [6A80] Symptomatic and course presentations for mood episodes in mood disorders\n Def: These categories may be applied to describe the presentation and characteristics of mood episodes in the context of single episode depressive disorder, recurrent depressive disorder, bipolar type I di...\n --RELATED_TO--> [?] Mental or behavioural disorders associated with pregnancy, childbirth or the puerperium, with psychotic symptoms\n Def: A syndrome associated with pregnancy or the puerperium (commencing within about 6 weeks after delivery) that involves significant mental and behavioural features, including delusions, hallucinations, ...", "[6A80.5] Rapid cycling\n Def: In the context of bipolar type I or bipolar type II disorder, there has been a high frequency of mood episodes (at least four) over the past 12 months. There may be a switch from one polarity of mood ...\n --PARENT--> [6A80] Symptomatic and course presentations for mood episodes in mood disorders\n Def: These categories may be applied to describe the presentation and characteristics of mood episodes in the context of single episode depressive disorder, recurrent depressive disorder, bipolar type I di...\n --RELATED_TO--> [?] Mental or behavioural disorders associated with pregnancy, childbirth or the puerperium, without psychotic symptoms\n Def: A syndrome associated with pregnancy or the puerperium (commencing within about 6 weeks after delivery) that involves significant mental and behavioural features, most commonly depressive symptoms. Th...", "[PA03] Unintentional land transport traffic event injuring a motor cyclist\n --PARENT--> [?] Unintentional land transport road traffic injury event\n --CHILD--> [PA01] Unintentional land transport traffic event injuring the user of a pedestrian conveyance", "[PA03] Unintentional land transport traffic event injuring a motor cyclist\n --PARENT--> [?] Unintentional land transport road traffic injury event\n --CHILD--> [PA01] Unintentional land transport traffic event injuring the user of a pedestrian conveyance", "[5C50.AZ] Disorders of urea cycle metabolism, unspecified\n --PARENT--> [5C50.A] Disorders of urea cycle metabolism\n --PARENT--> [5C50] Inborn errors of amino acid or other organic acid metabolism", "[5C50.AZ] Disorders of urea cycle metabolism, unspecified\n --PARENT--> [5C50.A] Disorders of urea cycle metabolism\n --CHILD--> [5C50.A2] Argininaemia\n Def: Arginase deficiency is a rare autosomal recessive amino acid metabolism disorder characterised clinically by variable degrees of hyperammonemia, developing from about 3 years of age, and leading to pr..." ]	6A80.5	Rapid cycling	[ { "from_icd11": "PA03", "icd10_code": "V299XXD", "icd10_title": "Motorcycle rider (driver) (passenger) injured in unspecified traffic accident, subsequent encounter" }, { "from_icd11": "PA03", "icd10_code": "V234XXA", "icd10_title": "Motorcycle driver injured in collision with car, pick-up truck or van in traffic accident, initial encounter" }, { "from_icd11": "PA03", "icd10_code": "V299XXA", "icd10_title": "Motorcycle rider (driver) (passenger) injured in unspecified traffic accident, initial encounter" }, { "from_icd11": "PA03", "icd10_code": "V2940XA", "icd10_title": "Motorcycle driver injured in collision with unspecified motor vehicles in traffic accident, initial encounter" }, { "from_icd11": "PA03", "icd10_code": "V239XXD", "icd10_title": "Unspecified motorcycle rider injured in collision with car, pick-up truck or van in traffic accident, subsequent encounter" }, { "from_icd11": "PA03", "icd10_code": "V299XXS", "icd10_title": "Motorcycle rider (driver) (passenger) injured in unspecified traffic accident, sequela" }, { "from_icd11": "PA03", "icd10_code": "V2988XA", "icd10_title": "Motorcycle rider (driver) (passenger) injured in other specified transport accidents, initial encounter" }, { "from_icd11": "PA03", "icd10_code": "V2950XA", "icd10_title": "Motorcycle passenger injured in collision with unspecified motor vehicles in traffic accident, initial encounter" }, { "from_icd11": "PA03", "icd10_code": "V2960XA", "icd10_title": "Unspecified motorcycle rider injured in collision with unspecified motor vehicles in traffic accident, initial encounter" }, { "from_icd11": "PA03", "icd10_code": "V2949XS", "icd10_title": "Motorcycle driver injured in collision with other motor vehicles in traffic accident, sequela" }, { "from_icd11": "PA03", "icd10_code": "V234XXS", "icd10_title": "Motorcycle driver injured in collision with car, pick-up truck or van in traffic accident, sequela" }, { "from_icd11": "PA03", "icd10_code": "V235XXA", "icd10_title": "Motorcycle passenger injured in collision with car, pick-up truck or van in traffic accident, initial encounter" }, { "from_icd11": "PA03", "icd10_code": "V234XXD", "icd10_title": "Motorcycle driver injured in collision with car, pick-up truck or van in traffic accident, subsequent encounter" }, { "from_icd11": "PA03", "icd10_code": "V2949XA", "icd10_title": "Motorcycle driver injured in collision with other motor vehicles in traffic accident, initial encounter" }, { "from_icd11": "PA03", "icd10_code": "V2949XD", "icd10_title": "Motorcycle driver injured in collision with other motor vehicles in traffic accident, subsequent encounter" } ]	V299XXD	Motorcycle rider (driver) (passenger) injured in unspecified traffic accident, subsequent encounter
Video Legends: Video segment 1: Video segment 1 demonstrates examples of dystonia mimics and psychogenic dystonia. Patient 1 was referred for evaluation of head tilt, concerning for “cervical dystonia”. However, on examination the left head tilt was relatively fixed even when she turned her head in different directions. Palpation revealed a harder-than-normal consistency of her left sternocleidomastoid muscle due to fibrosis. She was referrred for surgical evaluation after our diagnosis of congenital muscular torticollis. Patient 2 had a history of previous trauma to the left foot several months prior. Examination demonstrated relatively fixed inversion of the left foot when sitting and walking, and no improvement when walking backwards. She was diagnosed with complex regional pain syndrome. Patient 3 presented with difficulty moving the left leg. Examination revealed a slight increase in tone of the left leg to passive range of motion, as well as a slightly brisker quadriceps reflex on the left. His left leg was slightly more clumsy than the right with active range of motion and when walking. The diagnosis of stiff limb syndrome, a variant of stiff person syndrome, was confirmed by marked elevation (>250 U/ml) of anti-glutamic acid decarboxylase (anti-GAD) antibody. The next videos demonstrate a variety of psychogenic dystonias including psychogenic jaw dystonia presenting with left jaw deviation ( Patient 4 ), psychogenic laryngeal dystonia with choking-like symptom ( Patient 5 ), psychogenic upper and lower limb dystonia ( Patient 6 ), psychogenic left foot dystonia ( Patient 7 ), and psychogenic right hand dystonia ( Patient 8 ). Video segment 2: Video segment 2 demonstrates select examples of “don’t-miss” diagnoses. Patient 1 is a teenage girl with Wilson’s disease. She had prominent lower facial dystonia, a risus sardonicus, and a jerky 6-Hz tremor of the left fingers. Patient 2 also has a diagnosis of Wilson’s disease. She presented with cervical dystonia, left shift, slight head tilting to the right (with her chin pointing to the left) and prominent right shoulder elevation. Lateral rotation of her neck to the right was more difficult than to the left. A low amplitude dystonic jerky head tremor was intermittently seen. Her parkinsonian features including facial masking and bradykinesia on finger tapping were mild. A classic Kayser-Fleischer ring was demonstrated as a relatively thick brown rim along the entire circumference of the limbus. Both Patients 1 and 2 experienced marked benefit from oral copper chelating therapy. Patient 3 is a 10-year-old girl with a genetically confirmed mutation in the ATP1A3 gene. She presented with an intermediate phenotype between alternating hemiplegia of childhood and rapid-onset dystonia parkinsonism . The home video demonstrated an episode of upward oculogyria with slight head tilting to the left, during which her consciousness remained intact. Oculogyric episodes disappeared when she was treated with levodopa 300 mg/day, but moderate residual dystonic posturing of the left hand was still present. Video segment 3: Video segment 3 demonstrates example of patients with primary dystonia. The first three patients have childhood-onset genetically confirmed DYT1 dystonia with predominant foot or leg involvement. Patient 1 was unable to stand or walk independently due to bilateral foot dystonia. With 15 mg/day of trihexyphenidyl and 30 mg/day of baclofen, she was able to stand and take a few steps with minimal support. Patient 2 demonstrated flexion dystonia of her left more than right foot that was moderately improved with trihexyphenidyl 45 mg/day and baclofen 30 mg/day. Patient 3 demonstrated prominent inversion of the left foot, with much milder right foot dystonia. His dystonia was more prominent with activation such as during the swing phase of walking. With trihexyphenidyl 10 mg/day, the left foot dystonia improved only slighlty, and the residual right foot dystonia was minimal. Patient 4 is a girl who presented with dystonia, negative for DYT1 and DYT6 mutations. Her dystonia involved the trunk and, to a lesser degree, all extremities. Prominent truncal twisting was demonstrated even when she was sitting in the chair. This improved with trihexyphenidyl 30 mg/day, but she still had residual truncal dystonia seen as pelvic tilting when walking. She ultimately underwent bilateral GPi DBS surgery with marked improvement in her dystonia. Video segment 4: Video segment 4 demonstrates dopa-responsive dystonia (DRD; Patients 1–2 ), one of the most crucial “don’t-miss” diagnoses in dystonia, and paroxysmal kinesigenic dyskinesia ( Patients 3–5 ). These two disorders are treated with, in respective order, low dose levodopa and low dose carbamazepine with dramatic benefits. Patient 1 had residual minimal dystonia of her feet after she was given a low dose levodopa. Patient 2 , her mother, unfortunately underwent the orthopedic surgical corrections of her deformities in childhood due to a missed diagnosis. Recognition of DRD and a levodopa trial would have prevented her from these unnecessary invasive procedure. Patient 3 had an episode of paroxysmal dystonia involving mainly his trunk (extension and flexion) lasting a few seconds while standing. The second home video displayed another episode of dystonia involving both hands and arms while he was sitting. He returned to his normal state after each episode. Patient 4 presented with episodes of truncal dystonia. The one captured in this home video demonstrated truncal twisting while standing. He held the chair during the episode which lasted several seconds before returning to his normal baseline. Home videos of Patient 5 demonstrate episodes of dystonia primarily involving both legs and feet. Each episode lasted a few seconds. The first one occurred while he was sitting in the bed. During the second episode, he deliberately made a step with his right foot due to paroxysmal dystonia. Video segment 5: Video segment 5 demonstrates a variety of focal dystonias. The first two patients have velopharyngeal dystonia, a form of focal task-specific dystonia involving pharyngeal muscles and soft palate (velopharynx) which leads to inabilty to close the air passage connecting the mouth and nasal cavity, producing a nasal quality of speech. Patient 1 is a 41-year-old woman who presented with breathy and hypernasal voice. Stroboscopic examination of her larynx did not reveal evidence of spasmodic dysphonia. She was started on trihexyphenidyl which was titrated up to 12 mg/day, and on follow-up visit two months later her speech improved by approximately 75%. Patient 2 is a 61-year-old man who presented with two years of nasal speech. Marked improvement with trihexyphenidyl 12 mg/day was seen. Patients 3 and 4 demonstrate a variety of idiopathic lower cranial dystonias (iLCrD). Further details about this particular topic can be found in Ref . Patient 3 demonstrates pure left jaw deviation aggravated by speaking, improved with trihexyphenidyl 2 mg/day. Patient 4 is a woman with severe jaw opening dystonia triggered by speaking. Light touching of her chin served as a geste antagoniste that improved her dystonia. She tried multiple medications including trihexyphenidyl, baclofen, clonazepam and leveteiracetam without success due to side effects before achieving an adequate response with diazepam 15 mg/day. Video segment 6: Video segment 6 demonstrates a woman with left hemidystonia. She placed her left hand underneatth her left leg in order to compensate. When walking, dystonia of the left arm, seen as flexion of the left elbow, extension of the left wrist and flexion of her fingers was demonstrated. The left arm braced her trunk while walking with marked reduction in arm swing. On follow up visit several years later, on lorazepam 2 mg/day, she had moderate dystonic posturing of the left hand at rest and when holding her arms in outstretched position. Mild dystonic posturing of the left foot was also demonstrated when sitting. Dystonic posturing of the left arm was less prominent compared to the previous examination. Video segment 7: Video segment 7 demonstrates a variety of tardive dystonias. Both patients had a history of dopamine receptor blocking agent use in the past. Patient 1 had phasic cervical dystonia, characterized by intermittent jerky anterior neck shifting in commbination with neck flexion. Dystonia of the forehead muscles included frontalis and procerus involvement. The dystonia was alleviated by lightly touching her face with her hand. Patient 2 demonstrated intermittent truncal flexion when sitting and walking. He underwent bilateral pallidal DBS surgery with resolution of his truncal dystonia.	4.058594	0.951172	sec[2]/p[1]	en	0.999998	28031858	https://doi.org/10.1186/s40734-016-0047-6	[ "dystonia", "video", "segment", "foot", "demonstrates", "walking", "patients", "trihexyphenidyl", "psychogenic", "episode" ]	[ { "code": "MB47.4", "title": "Dystonia" }, { "code": "8A02.0Z", "title": "Primary dystonia, unspecified" }, { "code": "8A02.1Y", "title": "Other specified secondary dystonia" }, { "code": "8A02.0Y", "title": "Other specified primary dystonia" }, { "code": "8A02.11", "title": "Dystonia-plus" }, { "code": "6C51.Z", "title": "Gaming disorder, unspecified" }, { "code": "ME93.0", "title": "Segmental and somatic dysfunction" }, { "code": "8A06.1", "title": "Segmental myoclonus" }, { "code": "EC23.0", "title": "Non-syndromic genetically-determined hypermelanosis or lentiginosis" }, { "code": "GB40/MF8Y&XT8W", "title": "Chronic nephritic syndrome : focal and segmental glomerular lesions" } ]	=== ICD-11 CODES FOUND === [MB47.4] Dystonia Definition: Sustained muscle contraction, involuntary movements that can lead to fixed abnormal postures Also known as: Dystonia \| dystonia disorder \| Dyskinesia NOS \| dyskinetic [8A02.0Z] Primary dystonia, unspecified Also known as: Primary dystonia, unspecified \| Primary dystonia \| neuroleptic dyskinesia [8A02.1Y] Other specified secondary dystonia Also known as: Other specified secondary dystonia \| Dystonia due to perinatal cerebral injury \| Dystonia due to cerebral anoxia \| Dystonia due to encephalitis \| postencephalitic dystonia [8A02.0Y] Other specified primary dystonia Also known as: Other specified primary dystonia \| Primary Dystonia DYT1 Type \| Primary dystonia, DYT2 type \| Primary dystonia, DYT4 type \| Primary dystonia, DYT6 type [8A02.11] Dystonia-plus Definition: This is a group of heterogenous syndromes present with dystonia – a disorder of involuntary muscle contractions – along with other clinical features, but not in tandem with a neurodegenerative disease. Examples include myoclonus dystonia and dopa responsive dystonia. Also known as: Dystonia-plus \| Myoclonus-dystonia \| Dopa-responsive dystonia \| Segawa syndrome \| DYT5 [6C51.Z] Gaming disorder, unspecified Also known as: Gaming disorder, unspecified \| Gaming disorder \| Digital gaming disorder \| Video gaming disorder [ME93.0] Segmental and somatic dysfunction Also known as: Segmental and somatic dysfunction \| segmental dysfunction \| somatic dysfunction \| Segmental and somatic dysfunction, head region \| Segmental and somatic dysfunction, occipitocervical region [8A06.1] Segmental myoclonus Definition: Rhythmic or semi-rhythmic involuntary contractions of muscle groups supplied by one or more contiguous segments of the brainstem and/or spinal cord. Also known as: Segmental myoclonus \| Spinal segmental myoclonus \| Propriospinal myoclonus [EC23.0] Non-syndromic genetically-determined hypermelanosis or lentiginosis Also known as: Non-syndromic genetically-determined hypermelanosis or lentiginosis \| Familial progressive hyperpigmentation \| Familial generalised lentiginosis \| Inherited patterned lentiginosis \| Centrofacial lentiginosis === GRAPH WALKS === --- Walk 1 --- [MB47.4] Dystonia Def: Sustained muscle contraction, involuntary movements that can lead to fixed abnormal postures... --PARENT--> [MB47] Abnormality of tonus or reflex --CHILD--> [MB47.0] Abnormal reflex --- Walk 2 --- [MB47.4] Dystonia Def: Sustained muscle contraction, involuntary movements that can lead to fixed abnormal postures... --PARENT--> [MB47] Abnormality of tonus or reflex --CHILD--> [MB47.1] Abnormal posture --- Walk 3 --- [8A02.0Z] Primary dystonia, unspecified --PARENT--> [8A02.0] Primary dystonia Def: Primary dystonias (primary torsion dystonias) are disorders where dystonia is the sole neurological manifestation. These disorders are slowly progressive and may be familial/genetic or sporadic in ori... --PARENT--> [8A02] Dystonic disorders --- Walk 4 --- [8A02.0Z] Primary dystonia, unspecified --PARENT--> [8A02.0] Primary dystonia Def: Primary dystonias (primary torsion dystonias) are disorders where dystonia is the sole neurological manifestation. These disorders are slowly progressive and may be familial/genetic or sporadic in ori... --CHILD--> [8A02.00] Benign essential blepharospasm Def: This is a neurological condition characterised by forcible closure of the eyelids due to involuntary and sustained contraction of the muscles around the eyes.... --- Walk 5 --- [8A02.1Y] Other specified secondary dystonia --PARENT--> [8A02.1] Secondary dystonia Def: This is dystonia – a disorder of involuntary muscle contractions – of an acquired nature. Causes include substance toxicity, injury, hypoxia and tumours.... --CHILD--> [8A02.12] Dystonia associated with heredodegenerative disorders Def: Dystonia occurring as a part of a more complex heredodegenerative disorder. It is not a pure dystonia and other neurological findings such as ataxia, pyramidal signs and cognitive issues may be seen.... --- Walk 6 --- [8A02.1Y] Other specified secondary dystonia --PARENT--> [8A02.1] Secondary dystonia Def: This is dystonia – a disorder of involuntary muscle contractions – of an acquired nature. Causes include substance toxicity, injury, hypoxia and tumours.... --CHILD--> [8A02.10] Drug-induced dystonia Def: This is dystonia due to medications either as an idiosyncratic side effect or due to overdose of medications....	[ "[MB47.4] Dystonia\n Def: Sustained muscle contraction, involuntary movements that can lead to fixed abnormal postures...\n --PARENT--> [MB47] Abnormality of tonus or reflex\n --CHILD--> [MB47.0] Abnormal reflex", "[MB47.4] Dystonia\n Def: Sustained muscle contraction, involuntary movements that can lead to fixed abnormal postures...\n --PARENT--> [MB47] Abnormality of tonus or reflex\n --CHILD--> [MB47.1] Abnormal posture", "[8A02.0Z] Primary dystonia, unspecified\n --PARENT--> [8A02.0] Primary dystonia\n Def: Primary dystonias (primary torsion dystonias) are disorders where dystonia is the sole neurological manifestation. These disorders are slowly progressive and may be familial/genetic or sporadic in ori...\n --PARENT--> [8A02] Dystonic disorders", "[8A02.0Z] Primary dystonia, unspecified\n --PARENT--> [8A02.0] Primary dystonia\n Def: Primary dystonias (primary torsion dystonias) are disorders where dystonia is the sole neurological manifestation. These disorders are slowly progressive and may be familial/genetic or sporadic in ori...\n --CHILD--> [8A02.00] Benign essential blepharospasm\n Def: This is a neurological condition characterised by forcible closure of the eyelids due to involuntary and sustained contraction of the muscles around the eyes....", "[8A02.1Y] Other specified secondary dystonia\n --PARENT--> [8A02.1] Secondary dystonia\n Def: This is dystonia – a disorder of involuntary muscle contractions – of an acquired nature. Causes include substance toxicity, injury, hypoxia and tumours....\n --CHILD--> [8A02.12] Dystonia associated with heredodegenerative disorders\n Def: Dystonia occurring as a part of a more complex heredodegenerative disorder. It is not a pure dystonia and other neurological findings such as ataxia, pyramidal signs and cognitive issues may be seen....", "[8A02.1Y] Other specified secondary dystonia\n --PARENT--> [8A02.1] Secondary dystonia\n Def: This is dystonia – a disorder of involuntary muscle contractions – of an acquired nature. Causes include substance toxicity, injury, hypoxia and tumours....\n --CHILD--> [8A02.10] Drug-induced dystonia\n Def: This is dystonia due to medications either as an idiosyncratic side effect or due to overdose of medications...." ]	MB47.4	Dystonia	[ { "from_icd11": "8A02.0Z", "icd10_code": "G249", "icd10_title": "Dystonia, unspecified" }, { "from_icd11": "8A02.0Z", "icd10_code": "G241", "icd10_title": "Genetic torsion dystonia" }, { "from_icd11": "8A02.0Z", "icd10_code": "G243", "icd10_title": "Spasmodic torticollis" }, { "from_icd11": "8A02.0Z", "icd10_code": "G242", "icd10_title": "Idiopathic nonfamilial dystonia" }, { "from_icd11": "6C51.Z", "icd10_code": "F6381", "icd10_title": "Intermittent explosive disorder" }, { "from_icd11": "6C51.Z", "icd10_code": "F6389", "icd10_title": "Other impulse disorders" }, { "from_icd11": "6C51.Z", "icd10_code": "F638", "icd10_title": "Other impulse disorders" }, { "from_icd11": "ME93.0", "icd10_code": "M9905", "icd10_title": "Segmental and somatic dysfunction of pelvic region" }, { "from_icd11": "ME93.0", "icd10_code": "M990", "icd10_title": "Segmental and somatic dysfunction" }, { "from_icd11": "EC23.0", "icd10_code": "L814", "icd10_title": "Other melanin hyperpigmentation" }, { "from_icd11": "EC23.0", "icd10_code": "L80-L99", "icd10_title": "" }, { "from_icd11": "EC23.0", "icd10_code": "L81", "icd10_title": "Other disorders of pigmentation" }, { "from_icd11": "EC23.0", "icd10_code": "L813", "icd10_title": "Cafe au lait spots" } ]	G249	Dystonia, unspecified
A female patient was diagnosed with idiopathic IP in 2010 when she was 62 years old and had been followed up without therapy at our hospital. The serum KL-6 levels had been increasing gradually after Apr 2014. Specifically, values of 2400, 2774, 3075 and 3821 U/ml (normal range, < 500 U/ml) were recorded in Apr, Jul, Sep and Dec 2014, respectively . However, there were no findings to indicate worsening of IP. In Sep 2014, a screening for breast cancer was performed, but nothing particular was detected. In Dec 2014, a contrast-enhanced computed tomography (CT) showed a tumorous lesion on the body of the gallbladder . In addition, 18 F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT showed an abnormally high uptake on the tumorous lesion, with a maximum standardized uptake value (SUV max ) of 8.1 . The PET/CT also showed an abnormally high uptake on a regional lymph node with an SUV max of 2.9 , while the corresponding lymph-node swelling was not detected in the CT image . Thus, the patient was diagnosed with gallbladder cancer with a suspected lymph-node metastasis. Chest X-rays on admission showed ground-glass opacities in the bilateral lower lung fields and a chest CT taken preoperatively showed ground-glass opacities and reticular shadows in the bilateral lung fields . These findings did not change during the follow-up period of IP after Apr 2014. Routine blood analysis on admission showed that complete blood counts, liver function, renal function, and electrolytes were within normal limits except for slightly elevated levels of c-reactive protein (CRP) (0.55 mg/dl; normal range, ≤ 0.5 mg/dl), alkaline phosphatase (ALP) (325 IU/L; normal range, 100–320 IU/L), and amylase (182 IU/L; normal range, 40–130 IU/L) (Table 1 ). The serum levels of carcinoembryonic antigen (CEA) and cancer antigen (CA)19-9 were elevated in Jan 2015 (5.0 ng/dl; normal range, < 5.0 ng/dl, 86.6 U/ml; normal range, < 37.0 U/ml, respectively), although their serum levels had been within normal limits in Sep 2014 (Table 1 ). Arterial blood gas analysis on admission showed slight hypoxia under ambient air (67.6 Torr; normal range, 74–108 Torr) and a slightly elevated level of bicarbonate ions (29.7 mmol/l; normal range, 21–29 mmol/l), and a pulmonary function test revealed normal vital capacity (Table 1 ). In Jan 2015, we performed a radical extended cholecystectomy, which consists of a cholecystectomy, wedge resection of the gallbladder bed, bile duct resection, en bloc regional lymph-node dissection, and choledochojejunostomy. She did well in the postoperative period. Formalin‑fixed paraffin‑embedded 4 μm sections of the resected specimen were used for hematoxylin and eosin staining and immunostaining. The resected specimen showed the size of the tumor was 34 × 27 mm. Pathological examination revealed that the tumor was a well-to-moderately differentiated adenocarcinoma with components of papillary adenocarcinoma and poorly differentiated adenocarcinoma . Two metastatic lymph nodes were identified in 12p and 13a stations according to numbers of lymph-node stations described in the Japanese classification of biliary tract cancers third English edition . One of them corresponded to the abnormally high uptake shown by PET/CT preoperatively. According to the staging system described in the UICC eigth edition , the pathological stage of the tumor was pT2N1M1 (posterior superior pancreaticoduodenal lymph node) stage IV. Twenty-eight days after the operation, serum KL-6 levels showed a steep decline to 590 U/ml . As gallbladder cancer was suspected to have caused the elevation of serum KL-6 levels, we performed further investigation by immunostaining for KL-6 (mouse anti-human KL-6 monoclonal antibody was kindly provided by Sekisui Medical, Tokyo, Japan) and MUC1 (mouse anti-human DF3 monoclonal antibody, Fujirebio Diagnostics, Tokyo, Japan). Immunohistochemical study showed that ~ 80% of the cancer cells of the primary lesion were positive for KL-6 and MUC1, with both antigens showing the same distribution pattern . In addition, it showed that the cancer cells of the lymph-node metastases were also positive for KL-6 and MUC1 . On the other hand, it showed that only the apical side of the noncancerous epithelia in the gallbladder was positive for KL-6 and MUC1 . Although the patient was given adjuvant chemotherapy, the levels of serum KL-6 gradually increased. A lymph-node metastasis was found in Sep 2015. At that time, the serum KL-6 level was 3511 U/ml. Liver metastasis was found in Nov 2015, lung metastasis in Aug 2016, and the patient subsequently died in Oct 2016. Because there had been no reports about KL-6 expression on the cancerous and noncancerous epithelia of gallbladders, we examined KL-6 and MUC1 expression in these areas using a further six resected specimens of gallbladder cancers from 2016 through 2019 in our hospital. The immunohistochemical localization of KL-6 and MUC1 was classified into apical and cytoplasmic types: apical type (A), KL-6, and MUC1 being restricted to the apical borders of the epithelia; cytoplasmic type (C), they being observed not only on the apical surfaces but also on the basolateral surfaces and in the cytoplasm of the epithelia . KL-6 was expressed as the cytoplasmic type on more than 80% of the cancerous epithelia in all seven cases, and MUC1 was expressed as the cytoplasmic type on more than 80% of the cancerous epithelia in six out of the seven cases (Table 2 ). On the other hand, KL-6 was expressed as the apical type on the noncancerous epithelia in five out of six cases and MUC1 was expressed as the apical type on the noncancerous epithelia in three out of six cases (Table 2 ). Fig. 1 Time course of serum KL-6 levels Fig. 2 Imaging findings. a and c enhanced abdominal computed tomography (CT) showed a tumorous lesion on the body of the gallbladder (arrow). b 18 F-fluorodeoxyglucose-positron emission tomography (PET)/CT showed an abnormally high uptake on the tumorous lesion (arrow). d The PET/CT also showed an abnormally high uptake on a regional lymph node (arrowhead), but a corresponding lymph-node swelling was not detected in the CT image ( c ) Fig. 3 Preoperative pulmonary findings. a chest radiograph on admission showed ground-glass opacities in the bilateral lower lung fields. b chest CT showed ground-glass opacities and reticular shadows in the bilateral lung fields Table 1 Laboratory findings WBC 5000 /μL RBC 420 × 10 4 /μl Hb 13.0 g/dl Ht 39.1% PLT 27.4 × 10 4 /μl CRP 0.55 mg/dl AST 20 IU/L ALT 9 IU/L ALP 325 IU/L γ GTP 13 IU/L TP 7.4 g/dl ALB 3.8 g/dl T Bil 0.31 mg/dl D Bil 0.08 mg/dl CRE 0.50 mg/dl BUN 12.9 mg/dl AMY 182 IU/L Na 142 mEq/L K 4.3 mEq/L Cl 104 mEq/L CEA 5.0 ng/ml CA19-9 86.6 U/ml KL-6 3821 U/ml Blood gas analysis (supine, room air) pH 7.428 PaCO 2 45.4 Torr PaO 2 67.6 Torr HCO 3 29.4 mmol/l SaO 2 95.1% Pulmonary function test VC 2.09 L %VC 92.9% FEV 1 1.75 L FEV 1% 83.7% Fig. 4 Microscopic findings. a and b the tumor represented well-to-moderately differentiated adenocarcinoma (hematoxylin and eosin staining at a × 10 and b × 200 magnification). c and d the tumor cells were ~ 80% cytoplasmic positive for KL-6 (immunostaining at c × 10 and d × 200 magnification). e and f the tumor cells were ~ 80% cytoplasmic positive for MUC1 (immunostaining at e × 10 and f × 200 magnification) Fig. 5 Microscopic findings. a The tumor cells in the metastatic lymph node were positive for KL-6 (immunostaining at × 200 magnification). b The tumor cells in the metastatic lymph node were positive for MUC1 (immunostaining at × 200 magnification). c The apical side of the noncancerous epithelia in the gallbladder was positive for KL-6 (immunostaining at × 200 magnification). d The apical side of the noncancerous epithelia in the gallbladder was positive for MUC1 (immunostaining at × 200 magnification) Table 2 KL-6 and MUC1 expression Case pT KL-6 in the cancerous epithelia KL-6 in the noncancerous epithelia MUC1 in the cancerous epithelia MUC1 in the noncancerous epithelia 1 2 Positive (C) Positive (A) Positive (C) Positive (A) 2 2 Positive (C) Positive (A) Positive (C) Negative b 3 2 Positive (C) NA Positive (C) NA 4 3 Positive (C) Positive (A) Positive (C) Negative 5 2 Positive (C) Positive (A), focally Positive a (C) Positive (C) Positive (A) 6 2 Positive (C) Positive (A) Negative Negative b 7(the current case) 2 Positive (C) Positive (A) Positive (C) Positive (A) NA not available. The normal epithelia scarcely remained, C cytoplasmic pattern, A apical pattern, Negative less than 10% positive of staining, a around 10% positive of staining, b a few positive cells identified but less than 10% positive of staining	4.140625	0.918945	sec[1]/p[0]	en	0.999995	33782643	https://doi.org/10.1007/s13691-020-00460-0	[ "epithelia", "lymph", "node", "apical", "gallbladder", "serum", "range", "immunostaining", "tumor", "noncancerous" ]	[ { "code": "BD9Z", "title": "Disorders of lymphatic vessels or lymph nodes, unspecified" }, { "code": "BD90.Z", "title": "Lymphadenitis, unspecified" }, { "code": "BD90.Y", "title": "Other specified lymphadenitis" }, { "code": "BD9Y", "title": "Other specified disorders of lymphatic vessels or lymph nodes" }, { "code": "MA01.Z", "title": "Enlarged lymph nodes, unspecified" }, { "code": "FA20.0", "title": "Seropositive rheumatoid arthritis" }, { "code": "MF30", "title": "Breast lump or mass female" }, { "code": "BB40", "title": "Acute or subacute infectious endocarditis" }, { "code": "FA0Z", "title": "Osteoarthritis, unspecified" }, { "code": "FA85.10", "title": "Localised central endplate defect" } ]	=== ICD-11 CODES FOUND === [BD9Z] Disorders of lymphatic vessels or lymph nodes, unspecified Also known as: Disorders of lymphatic vessels or lymph nodes, unspecified \| Lymphatic system disorders \| lymph disease NOS \| lymph gland disease \| Lymphatic system disease NOS [BD90.Z] Lymphadenitis, unspecified Also known as: Lymphadenitis, unspecified \| Lymphadenitis \| adenitis NOS \| inflammation of gland \| lymphatic gland inflammation [BD90.Y] Other specified lymphadenitis Also known as: Other specified lymphadenitis \| Dermatopathic lymphadenopathy \| lipomelanotic reticulosis \| Infective inguinal bubo \| bubo [BD9Y] Other specified disorders of lymphatic vessels or lymph nodes Also known as: Other specified disorders of lymphatic vessels or lymph nodes \| Chylous cyst \| Mesentery chylous cyst \| Peritoneum chylous cyst \| Lymphocele [MA01.Z] Enlarged lymph nodes, unspecified Also known as: Enlarged lymph nodes, unspecified \| Enlarged lymph nodes \| swollen glands \| Lymphadenopathy \| adenopathy [FA20.0] Seropositive rheumatoid arthritis Also known as: Seropositive rheumatoid arthritis \| high positive rheumatoid factor \| low positive rheumatoid factor \| high positive anticitrullinated protein antibody \| low positive anticitrullinated protein antibody [MF30] Breast lump or mass female Also known as: Breast lump or mass female \| breast irregular nodularity \| breast node \| lump in breast \| lump or mass in breast NOS [BB40] Acute or subacute infectious endocarditis Also known as: Acute or subacute infectious endocarditis \| subacute infective endocarditis NOS \| infective endocarditis NOS \| acute infective endocarditis NOS \| infectious endocarditis Excludes: Infectious myocarditis [FA0Z] Osteoarthritis, unspecified Also known as: Osteoarthritis, unspecified \| osteoarthritis NOS \| arthrosis NOS \| OA - [osteoarthritis] \| Osteoarthritis with determinants [FA85.10] Localised central endplate defect Also known as: Localised central endplate defect \| Schmorl nodes \| schmorl's nodes \| schmorl's nodules === GRAPH WALKS === --- Walk 1 --- [BD9Z] Disorders of lymphatic vessels or lymph nodes, unspecified --PARENT--> [?] Disorders of lymphatic vessels or lymph nodes Def: Disorders due to developmental and acquired disturbances of lymph circulation and drainage and to infective disorders of lymph vessels and nodes.... --RELATED_TO--> [?] Lymphatic malformations Def: Lymphatic malformations (LM), formerly referred to by the term lymphangioma, are malformations of the lymphatic system which result in obstructed lymphatic drainage. There are two types of LM: macrocy... --- Walk 2 --- [BD9Z] Disorders of lymphatic vessels or lymph nodes, unspecified --PARENT--> [?] Disorders of lymphatic vessels or lymph nodes Def: Disorders due to developmental and acquired disturbances of lymph circulation and drainage and to infective disorders of lymph vessels and nodes.... --CHILD--> [BD91] Lymphangitis Def: Lymphangitis is an inflammation of lymphatic vessels. It is most often caused by infection from bacteria, virus or fungus or infiltration by cancer cells.... --- Walk 3 --- [BD90.Z] Lymphadenitis, unspecified --PARENT--> [BD90] Lymphadenitis --PARENT--> [?] Disorders of lymphatic vessels or lymph nodes Def: Disorders due to developmental and acquired disturbances of lymph circulation and drainage and to infective disorders of lymph vessels and nodes.... --- Walk 4 --- [BD90.Z] Lymphadenitis, unspecified --PARENT--> [BD90] Lymphadenitis --EXCLUDES--> [?] Human immunodeficiency virus disease Def: A case of HIV infection is defined as an individual with HIV infection irrespective of clinical stage including severe or stage 4 clinical disease (also known as AIDS) confirmed by laboratory criteria... --- Walk 5 --- [BD90.Y] Other specified lymphadenitis --PARENT--> [BD90] Lymphadenitis --CHILD--> [BD90.0] Acute lymphadenitis --- Walk 6 --- [BD90.Y] Other specified lymphadenitis --PARENT--> [BD90] Lymphadenitis --EXCLUDES--> [?] Enlarged lymph nodes Def: Enlarged lymph node is called lymphadenopathy which means the abnormal enlargement of lymph nodes....	[ "[BD9Z] Disorders of lymphatic vessels or lymph nodes, unspecified\n --PARENT--> [?] Disorders of lymphatic vessels or lymph nodes\n Def: Disorders due to developmental and acquired disturbances of lymph circulation and drainage and to infective disorders of lymph vessels and nodes....\n --RELATED_TO--> [?] Lymphatic malformations\n Def: Lymphatic malformations (LM), formerly referred to by the term lymphangioma, are malformations of the lymphatic system which result in obstructed lymphatic drainage. There are two types of LM: macrocy...", "[BD9Z] Disorders of lymphatic vessels or lymph nodes, unspecified\n --PARENT--> [?] Disorders of lymphatic vessels or lymph nodes\n Def: Disorders due to developmental and acquired disturbances of lymph circulation and drainage and to infective disorders of lymph vessels and nodes....\n --CHILD--> [BD91] Lymphangitis\n Def: Lymphangitis is an inflammation of lymphatic vessels. It is most often caused by infection from bacteria, virus or fungus or infiltration by cancer cells....", "[BD90.Z] Lymphadenitis, unspecified\n --PARENT--> [BD90] Lymphadenitis\n --PARENT--> [?] Disorders of lymphatic vessels or lymph nodes\n Def: Disorders due to developmental and acquired disturbances of lymph circulation and drainage and to infective disorders of lymph vessels and nodes....", "[BD90.Z] Lymphadenitis, unspecified\n --PARENT--> [BD90] Lymphadenitis\n --EXCLUDES--> [?] Human immunodeficiency virus disease\n Def: A case of HIV infection is defined as an individual with HIV infection irrespective of clinical stage including severe or stage 4 clinical disease (also known as AIDS) confirmed by laboratory criteria...", "[BD90.Y] Other specified lymphadenitis\n --PARENT--> [BD90] Lymphadenitis\n --CHILD--> [BD90.0] Acute lymphadenitis", "[BD90.Y] Other specified lymphadenitis\n --PARENT--> [BD90] Lymphadenitis\n --EXCLUDES--> [?] Enlarged lymph nodes\n Def: Enlarged lymph node is called lymphadenopathy which means the abnormal enlargement of lymph nodes...." ]	BD9Z	Disorders of lymphatic vessels or lymph nodes, unspecified	[ { "from_icd11": "BD9Z", "icd10_code": "I898", "icd10_title": "Other specified noninfective disorders of lymphatic vessels and lymph nodes" }, { "from_icd11": "BD9Z", "icd10_code": "I899", "icd10_title": "Noninfective disorder of lymphatic vessels and lymph nodes, unspecified" }, { "from_icd11": "BD9Z", "icd10_code": "I89", "icd10_title": "Other noninfective disorders of lymphatic vessels and lymph nodes" }, { "from_icd11": "BD90.Z", "icd10_code": "I889", "icd10_title": "Nonspecific lymphadenitis, unspecified" }, { "from_icd11": "BD90.Z", "icd10_code": "I88", "icd10_title": "Nonspecific lymphadenitis" }, { "from_icd11": "BD90.Z", "icd10_code": "I888", "icd10_title": "Other nonspecific lymphadenitis" }, { "from_icd11": "BD90.Z", "icd10_code": "L00-L08", "icd10_title": "" }, { "from_icd11": "MA01.Z", "icd10_code": "R599", "icd10_title": "Enlarged lymph nodes, unspecified" }, { "from_icd11": "MA01.Z", "icd10_code": "R59", "icd10_title": "Enlarged lymph nodes" }, { "from_icd11": "FA20.0", "icd10_code": "M0569", "icd10_title": "Rheumatoid arthritis of multiple sites with involvement of other organs and systems" }, { "from_icd11": "FA20.0", "icd10_code": "M0579", "icd10_title": "Rheumatoid arthritis with rheumatoid factor of multiple sites without organ or systems involvement" }, { "from_icd11": "FA20.0", "icd10_code": "M05612", "icd10_title": "Rheumatoid arthritis of left shoulder with involvement of other organs and systems" }, { "from_icd11": "FA20.0", "icd10_code": "M0570", "icd10_title": "Rheumatoid arthritis with rheumatoid factor of unspecified site without organ or systems involvement" }, { "from_icd11": "FA20.0", "icd10_code": "M0560", "icd10_title": "Rheumatoid arthritis of unspecified site with involvement of other organs and systems" }, { "from_icd11": "FA20.0", "icd10_code": "M0500", "icd10_title": "Felty's syndrome, unspecified site" } ]	I898	Other specified noninfective disorders of lymphatic vessels and lymph nodes
On November 25, 2020, a 30-year-old woman with a 13-year history of systemic lupus erythematosus (SLE) exhibited painful leg swelling and was diagnosed with deep venous thrombosis (DVT). She was treated with enoxaparin, followed by an oral anticoagulant (warfarin). Her SLE initially presented as proteinuria, nephritis, and autoimmune hemolytic anemia was well-controlled and stable. She was treated during the last year with mycophenolate mofetil 250mg twice daily, prednisone 20mg/d, and hydroxychloroquine 200 mg/d. Several days following the development of DVT, the patient manifested symptoms of respiratory infection (subfebrile temperature up to 37.3°C, weakness, anosmia). She was tested (PCR of the nasopharyngeal swab) and found to be positive for SARS-CoV-2 on December 8. Due to the mild course of the disease, normal chest radiography, and good oxygen saturation of 99%, she was prescribed therapy and kept in home isolation. Nevertheless, the recovery from COVID-19 was not satisfactory as the patient complained of shortness of breath, persistent dull chest pain, extreme exhaustion, and tachycardia up to 130 bpm for weeks after the onset of the infection. She visited her immunologist on January 21, 2021. The laboratory analyses showed elevated inflammatory markers (CRP 27.5 mg/l [<5 mg/l]), d-dimer 3990 [<500], LDH 589 IU/l, WBC 8.3 × 10 9 /l, Lymphocyte 0.4 × 10 9 /l, and INR 1.93. Immunological analyses (Anti-nuclear antibodies -ANA, anti-Cardiolipin antibodies – aCLA IgM and IgG, anti-beta2 glycoprotein1 – anti-β 2 GPI IgM and IgG, lupus anticoagulant – LAC) were negative, total serum IgM and IgG were in the normal range, while total IgA was 0.62 g/l [0.8–2.4]. Computed tomographic pulmonary angiography (CTPA) demonstrated massive pulmonary embolism with the clot at the main branching of the pulmonary artery. She was hospitalized and treated until discharge home on February 8. Due to an allergy to warfarin, she has been prescribed rivaroxaban as further therapy. Two weeks following hospital discharge, the patient’s symptoms aggravated as she manifested morning fever up to 39°C, intense fatigue, dry cough, and chest pain. The persistence of these symptoms was the basis for admission to the pulmonology unit on March 12. On admission, she was slightly dyspneic with an oxygen saturation of 95% on room air. She had marked lymphopenia (0.3 × 10 9 /l), elevated CRP (91.9 mg/l), normal procalcitonin (0.05 ng/ml), and anemia (hemoglobin 91 g/L) with high ferritin value (856 μg/l). Initial chest CT scan demonstrated a multilocular irregular cystic formation (45 × 35 × 45 mm) in the right middle lobe adjacent to the visceral pleura, surrounded by a “tree in buds” appearance. It also showed ground-glass opacities (GGO) in both inferior lobes and the right middle lobe with the posterolateral and subpleural distribution. We performed ultrasound-guided lung biopsy to obtain samples to refer to microbiology and cytology analyses. They showed dense infiltration with lymphocytes, erythrocytes, and neutrophils, without malignant cells, while the microbiological culture showed no growth of microorganisms. Fiberoptic bronchoscopy revealed normal findings, and the specimen demonstrated rare neutrophils and Pseudomonas spp. (over 1 million CFU/mL) sensitive to amikacin. Hemoculture was negative, and the infection with Mycobacterium tuberculosis was excluded with smear acid-fast staining, PCR, MGIT culture test, Quantiferon TB Gold blood test, and negative Lowenstein culture growth. Galactomannan antigen (serum and bronchoalveolar) were negative, while serum mannan antigen was positive. The patient was initially treated with broad-spectrum antibiotics (Meropenem and Vancomycin), with the subsequent addition of amikacin and caspofungin. During hospitalization, the patient developed a cephalic vein thrombosis while on anticoagulant therapy, and she was thoroughly investigated for thrombophilia. Her antithrombin III, protein C, and protein S were in the normal range, and Anti-Cardiolipin antibodies (IgG, IgM, IgA) were negative. At the same time, the genetic screening for mutations revealed no variants typical for inherited thrombophilia. The patient gradually recovered and was discharged home on April 15. On April 30, she had an episode of seizures with loss of consciousness. She was urgently admitted to the isolation unit of the neurology department of a regional hospital since she tested positive for SARS-CoV-2 again. Brain computed tomography (CT) revealed a solitary lesion with perifocal edema in the right parietal lobe. Antiedematous and anticonvulsant therapy diminished the neurological symptoms, and the patient was planned for referral to a tertiary center for further diagnostics and treatment. It was postponed as she tested positive again, and ordered home isolation. On June 15, the patient underwent brain magnetic resonance imaging (MRI). It showed a 4.6 × 4.3 × 3.9 cm multilocular lesion in the right frontoparietal region with a mass effect on the adjacent lateral ventricle . She tested positive for SARS-CoV-2 the same day and was denied admission to the neurosurgical clinic that offered no isolation ward. Instead, the patient was sent to a COVID hospital. At the time of admission, her symptoms were dry cough, stuffy nose, and mild left-sided weakness. Neurological examination showed subtle left side hemiparesis, right arm pronator drift, positive Mingazzini, and negative Romberg test. Laboratory workup revealed pancytopenia and normal tumor markers. Four days later, the neurological symptoms progressed with the development of holocranial headache, nausea, vomiting, and worsening of hemiparesis. An urgent CT of the brain was done, demonstrating enlargement of the perilesional edema with the shift of midline structures and completely effaced right lateral ventricle. A small lesion with perifocal edema was observed in the left occipital lobe. Right-sided compression of the mesencephalon suggested an imminent transtentorial uncal herniation. The patient was sent for emergency surgery on June 21 as she rapidly deteriorated with the development of a coma and right pupilar dilatation. The thick-walled multilocular abscess was found at surgery, and total excision was performed. Pus aspirated from one of the abscess collections was sent for gram staining and culture. The remaining was sent to histopathology. After the operation, the patient was transferred to the intensive care unit and started treatment with broad-spectrum antibiotics. Her postoperative laboratory was remarkable for severe thrombocytopenia, anemia, hypogammaglobulinemia, and low CD4 lymphocyte count (24/μL). Human immunodeficiency virus infection (HIV) was excluded by repeated testing. She was administered intravenous immunoglobulins (0.4 g/kg daily for 5 days). Hematoxylin-eosin staining revealed necrotizing granulomas, while the histochemical Grocott Methamine Silver staining highlighted the filamentous branching rods . Smears from cultures demonstrated gram-positive, partially acid-fast filaments, and the growth of Nocardia species. She was started on meropenem (3 × 2g) and trimethoprim/sulfamethoxazole via intravenous route while waiting for species determination and susceptibility testing. To transfer the patient to a non-COVID tertiary neurosurgical hospital, we tested her for SARS-CoV2 again, and the PCR result was positive. Final identification of Nocardia cyriacigeorgica was performed with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The susceptibility testing showed that the agent was susceptible to trimethoprim/sulfamethoxazole (TMP/SMX), ceftriaxone, cefotaxime, imipenem, and linezolid. The test demonstrated resistance to ampicillin, amoxicillin/clavulanate, and fluoroquinolones. TPM/SMX was continued as monotherapy after 3 weeks. Neurological deficits before surgery gradually resolved, and the CT of the brain showed significant improvement. Over the next 5 weeks, the patient was tested for SARS-CoV2 seven times, and the result was always positive . The serum sample was tested for antibodies against the spike protein of the virus, and no antibodies were detected. The patient was discharged home on July 30 on an oral TPM/SMX (160/800 mg) for at least 12 months. We decided to prescribe a prolonged course of TPM/SMX because her control CD4 was still low (79/μL), and she needed to continue corticosteroid therapy (prednisone 10mg/d) for SLE. On a follow-up as an outpatient after 1 month, 3 months, and 6 months the patient was in an excellent clinical state, fully active, with no symptoms and neurological deficits.	4.027344	0.978516	sec[1]/p[0]	en	0.999994	PMC9434960	https://doi.org/10.3389/fmed.2022.973817	[ "tested", "while", "sars", "home", "anti", "antibodies", "neurological", "treated", "infection", "chest" ]	[ { "code": "QA40", "title": "Pregnancy examination or test" }, { "code": "QA00.6Z", "title": "Examination of eyes or vision, unspecified" }, { "code": "QA00.7", "title": "Examination of ears and hearing" }, { "code": "QA00.A", "title": "Skin or other sensitisation tests" }, { "code": "QA3Y", "title": "Contact with health services for other specified procreative management" }, { "code": "PA60", "title": "Unintentional fall on the same level or from less than 1 metre" }, { "code": "PA4Z", "title": "Unintentional water transport injury event with damage to water vessel unspecified" }, { "code": "PA50.Z&XE1JR&XE9Y1", "title": "Person injured while boarding or alighting from aircraft" }, { "code": "PA08&XE9EE&XE6LC", "title": "Person injured while boarding or alighting from streetcar" }, { "code": "PA0C&XE9EE&XE9Y1", "title": "Person injured while boarding or alighting from special construction vehicle" } ]	=== ICD-11 CODES FOUND === [QA40] Pregnancy examination or test Also known as: Pregnancy examination or test \| pregnancy examination \| pregnancy test \| Pregnancy examination or test, pregnancy not confirmed \| pregnancy not yet confirmed [QA00.6Z] Examination of eyes or vision, unspecified Also known as: Examination of eyes or vision, unspecified \| Examination of eyes or vision \| general eye examination \| routine eye examination \| vision examination [QA00.7] Examination of ears and hearing Also known as: Examination of ears and hearing \| examination of ear \| hearing examination \| hearing test [QA00.A] Skin or other sensitisation tests Also known as: Skin or other sensitisation tests \| diagnostic skin or sensitisation tests \| general skin examination \| Skin tests for bacterial disease \| Skin tests for hypersensitivity [QA3Y] Contact with health services for other specified procreative management Also known as: Contact with health services for other specified procreative management \| Procreative investigation or testing \| procreative test \| Fallopian tube insufflation \| Sperm count for procreative test [PA60] Unintentional fall on the same level or from less than 1 metre Also known as: Unintentional fall on the same level or from less than 1 metre \| ground level fall \| fell while ambulating \| fall from standing height \| fall from standing position Excludes: Fall in health care \| Fall while in hospital \| Fall from hospital bed [PA4Z] Unintentional water transport injury event with damage to water vessel unspecified Also known as: Unintentional water transport injury event with damage to water vessel unspecified \| Water transport accidents \| Boat transport accident NOS \| ship transport accident NOS \| Watercraft transport accident NOS === GRAPH WALKS === --- Walk 1 --- [QA40] Pregnancy examination or test --PARENT--> [?] Contact with health services for reasons associated with reproduction --RELATED_TO--> [?] Contact with health services for concerns about body image related to pregnancy --- Walk 2 --- [QA40] Pregnancy examination or test --PARENT--> [?] Contact with health services for reasons associated with reproduction --RELATED_TO--> [?] Contact with health services for concerns about body image related to pregnancy --- Walk 3 --- [QA00.6Z] Examination of eyes or vision, unspecified --PARENT--> [QA00.6] Examination of eyes or vision --CHILD--> [QA00.6Y] Other specified examination of eyes or vision --- Walk 4 --- [QA00.6Z] Examination of eyes or vision, unspecified --PARENT--> [QA00.6] Examination of eyes or vision --EXCLUDES--> [?] Examination for driving license --- Walk 5 --- [QA00.7] Examination of ears and hearing --PARENT--> [QA00] General examination or investigation of persons without complaint or reported diagnosis --CHILD--> [QA00.0] General adult medical examination Def: Encounter for periodic examination (annual) (physical) and any associated laboratory and radiologic examinations on adult.... --- Walk 6 --- [QA00.7] Examination of ears and hearing --PARENT--> [QA00] General examination or investigation of persons without complaint or reported diagnosis --EXCLUDES--> [?] Special screening examination for infectious diseases Def: A reason for encounter to screen for an infection with a bacterial, viral, fungal, or parasitic source....	[ "[QA40] Pregnancy examination or test\n --PARENT--> [?] Contact with health services for reasons associated with reproduction\n --RELATED_TO--> [?] Contact with health services for concerns about body image related to pregnancy", "[QA40] Pregnancy examination or test\n --PARENT--> [?] Contact with health services for reasons associated with reproduction\n --RELATED_TO--> [?] Contact with health services for concerns about body image related to pregnancy", "[QA00.6Z] Examination of eyes or vision, unspecified\n --PARENT--> [QA00.6] Examination of eyes or vision\n --CHILD--> [QA00.6Y] Other specified examination of eyes or vision", "[QA00.6Z] Examination of eyes or vision, unspecified\n --PARENT--> [QA00.6] Examination of eyes or vision\n --EXCLUDES--> [?] Examination for driving license", "[QA00.7] Examination of ears and hearing\n --PARENT--> [QA00] General examination or investigation of persons without complaint or reported diagnosis\n --CHILD--> [QA00.0] General adult medical examination\n Def: Encounter for periodic examination (annual) (physical) and any associated laboratory and radiologic examinations on adult....", "[QA00.7] Examination of ears and hearing\n --PARENT--> [QA00] General examination or investigation of persons without complaint or reported diagnosis\n --EXCLUDES--> [?] Special screening examination for infectious diseases\n Def: A reason for encounter to screen for an infection with a bacterial, viral, fungal, or parasitic source...." ]	QA40	Pregnancy examination or test	[ { "from_icd11": "QA40", "icd10_code": "Z3201", "icd10_title": "Encounter for pregnancy test, result positive" }, { "from_icd11": "QA40", "icd10_code": "Z3200", "icd10_title": "Encounter for pregnancy test, result unknown" }, { "from_icd11": "QA40", "icd10_code": "Z3202", "icd10_title": "Encounter for pregnancy test, result negative" }, { "from_icd11": "QA40", "icd10_code": "Z32", "icd10_title": "Encounter for pregnancy test and childbirth and childcare instruction" }, { "from_icd11": "QA40", "icd10_code": "Z320", "icd10_title": "Encounter for pregnancy test" }, { "from_icd11": "QA40", "icd10_code": "Z321", "icd10_title": "" }, { "from_icd11": "QA00.6Z", "icd10_code": "Z010", "icd10_title": "Encounter for examination of eyes and vision" }, { "from_icd11": "QA00.7", "icd10_code": "Z011", "icd10_title": "Encounter for examination of ears and hearing" }, { "from_icd11": "QA00.A", "icd10_code": "Z015", "icd10_title": "" }, { "from_icd11": "PA60", "icd10_code": "W03XXXA", "icd10_title": "Other fall on same level due to collision with another person, initial encounter" }, { "from_icd11": "PA60", "icd10_code": "W04XXXA", "icd10_title": "Fall while being carried or supported by other persons, initial encounter" }, { "from_icd11": "PA60", "icd10_code": "W010XXA", "icd10_title": "Fall on same level from slipping, tripping and stumbling without subsequent striking against object, initial encounter" }, { "from_icd11": "PA60", "icd10_code": "W1839XA", "icd10_title": "Other fall on same level, initial encounter" }, { "from_icd11": "PA60", "icd10_code": "W01198A", "icd10_title": "Fall on same level from slipping, tripping and stumbling with subsequent striking against other object, initial encounter" }, { "from_icd11": "PA60", "icd10_code": "W1830XA", "icd10_title": "Fall on same level, unspecified, initial encounter" } ]	Z3201	Encounter for pregnancy test, result positive
We present the case of a patient misdiagnosed as having poorly controlled type 1 diabetes for more than 30 years but finally identified as having FPLD3 with typical body clinical features and unusually low serum leptin concentration. Conventional and intensified antidiabetic treatment failed to normalize glycemic control but the introduction of metreleptin resulted in a drastic improvement of glycemic control and plasma triglycerides. Research data regarding the use of glucagon-like-peptide-1(GLP-1) agonists in patients with lipodystrophy are scarce and their effect has been described only in case reports ( 21 , 22 ). Contrary to our case, in these previous reports authors pointed out that these regimens resulted in improvement of glycemic control and in reduction of insulin requirements, suggesting the positive effect of GLP-1 analogues in the management of diabetes in lipodystrophy syndromes ( 21 , 22 ). It is noteworthy to mention that there is a concern regarding the use of GLP-1 analogues in patients with lipodystrophy and high TG levels. In previous cases, the triglycerides levels were lower (TG: 200–350 mg/dl) compared to our patient. However, the authors did not mention any adverse event ( 21 , 22 ). Studies with more patients are required to evaluate the safety of these drugs in patients with lipodystrophy and severe hypertriglyceridemia. The risk of pancreatitis should be taken into account with the initiation of GLP-1 analogues in these patients. Metreleptin is an analogue of human leptin which imitates the physiological effects of endogenous leptin by binding to and activating the leptin receptor. Metreleptin treatment seems to ameliorate metabolic abnormalities including hypertriglyceridemia, hyperglycemia and insulin resistance. However, the mechanisms by which metreleptin improves these metabolic derangements are not fully elucidated. Leptin has a key role in the regulation of energy reserves and appetite by signaling the hypothalamus. In this regard, the reduction of hunger and calorie intake has been suggested as a mechanism responsible for the beneficial effect of leptin replacement ( 23 – 25 ). Püschel et al. showed that metreleptin treatment in four cases of FPLD3 improves satiety, reduces hunger and meal frequency ( 25 ). However, Oral et al. observed an additional favorable effect of leptin replacement on insulin sensitivity and on triglycerides metabolism that was independent of food intake ( 26 ). Additionally, Peterson et al. demonstrated that leptin treatment resulted in remarkable amelioration of insulin-dependent glucose metabolism which could be attributed to the improvement in insulin sensitivity in liver and muscle. These alterations are associated with a reduced hepatic and muscle triglyceride content ( 27 ). In accordance with these results, recently Brown et al. pointed out that metreleptin reduced peripheral and hepatic insulin resistance, decreased fasting glucose and triglycerides, and decreased liver fat content in patients with lipodystrophy whose food intake was held constant by a controlled diet ( 28 ). The preponderance of studies evaluating the efficacy of leptin treatment in patients with familial partial lipodystrophy included patients with lamin A/C ( LMNA ) pathogenic variants. However, the data regarding the effects of metreleptin in patients with FPLD3 are limited. So far, a few cases have been reported concerning the response of patients with PPARG pathogenic variant to metreleptin treatment, with controversial outcomes ( 16 – 18 ). Guettier et al. were the first who reported the efficacy of recombinant human leptin therapy in a case of a 36-year-old female patient with a heterozygous PPARG mutation. The patient presented a substantial amelioration in glycemic parameters along with a significant reduction in triglycerides after eighteen months of leptin treatment ( 18 ). Chong et al. conducted a prospective study to evaluate the effects of leptin replacement in 48 patients with different forms of lipodystrophy including two patients with mutation in PPARG genes. The results demonstrated that leptin replacement leads to significant and sustained amelioration of serum triglycerides and HbA1C ( 17 ). Recently, Sekizkardes et al. assessed the efficacy of metreleptin treatment in 22 patients with LMNA and in seven patients with PPARG pathogenic variants and highlighted that a 12-month metreleptin treatment led to significant reduction in HbA1C and insulin requirements. However, the efficacy of metreleptin treatment in terms of triglycerides levels was significant only in patients with LMNA pathogenic variants. The authors pointed out that the improvement in HbA1C and triglycerides levels following metreleptin treatment was more significant in patients with triglycerides >500 mg/dL or HbA1c >8% at baseline ( 16 ). According to the aforementioned research data, metreleptin treatment seems to improve glycemic control in patients with FPLD3. However, the data regarding the efficacy of metreleptin in hypertriglyceridemia in these groups of patients are inconsistent. Diker-Kohen et al., in a prospective open-label study, evaluated the efficacy of metreleptin in PLD compared to generalized lipodystrophy (GLD) and demonstrated that metreleptin treatment reduced HbA1C and triglycerides levels in GLD in a wider range of severity of baseline metabolic abnormalities compared to patients with PLD. Regarding PLD, patients with severe metabolic derangements and low endogenous leptin levels are more likely to respond to metreleptin treatment ( 29 ). In addition, the authors reported a significant reduction in antidiabetic and lipid-lowering medication and in total daily insulin in GLD patients after twelve months of metreleptin treatment. Interestingly, a decreased percentage of insulin use was also observed in GLD. However, only a trend for lower daily insulin requirements was observed in patients with PLD ( 29 ). In accordance with these results, Oral et al. demonstrated that improvements in metabolic parameters including HbA1C, fasting plasma glucose and triglycerides levels appeared to be less significant in PLD compared to GLD. In both PLD and GLD, higher levels of HbA1C and fasting TGs in baseline are associated with a greater response to metreleptin treatment ( 15 , 30 ). Multi-society practice guidelines suggest metreleptin as a possible therapeutic option in patients with partial lipodystrophy who present with low levels of leptin (leptin <4 ng/ml) and severe metabolic abnormalities (HbA1c >8% and/or triglycerides >500 mg/dl) ( 31 ). Therefore, the degree of leptin deficiency and the severity of metabolic derangement may predict the efficacy of metreleptin in PLD, including FPLD3.The phenotypic heterogenity of lipodystrophy syndromes usually challenges the diagnosis between the different forms of lipodystrophy. Subcutaneous fat loss in FPLD is usually observed in extremities and gluteal area while the truncal fat is preserved ( 12 ). However, patients with partial lipodystrophy, like in our case, may possibly present with a more extensive fat loss which makes difficult the distinction between partial and generalized lipodystrophy ( 15 ). Furthermore, contrary to our case, PLD patients usually display slightly decreased leptin levels depending on the extent of fat loss, while in generalized lipodystrophy the widespread lack of adipose tissue results in low leptin levels ( 29 ). Thus, our case should raise awareness that patients with PLD may present with very low leptin levels and extensive fat loss. Due to the rarity of lipodystrophysyndromes, many general practitioners and medical specialists are not familiar with their diagnosis and their management and lipodystrophy disorders may frequently be unrecognized or misdiagnosed. Therefore, the delayed diagnosis in patients with lipodystrophies leads to the deterioration of quality of life and the increase of mortality and morbidity rates. Specifically, in patients with diabetes, the type of diabetes should be reassessed in cases of poor glycemic control despite the high doses of insulin, in conjunction with decreased body mass index and signs of insulin resistance. Furthermore, the suspicion is enhanced by the coexistence of negative antibody testing and residual insulin secretion in glucagon stimulation test. The case should: 1) raise awareness to clinicians of the diagnosis of lipodystrophy in patients with severe metabolic disorders despite intensified metabolic treatment, 2) affirm that patients with FPLD3 may benefit from metreleptin treatment, and 3) once again challenge the entity of difficult-to-manage diabetes patients.	4.410156	0.77002	sec[2]/p[0]	en	0.999998	34168618	https://doi.org/10.3389/fendo.2021.684182	[ "patients", "metreleptin", "leptin", "lipodystrophy", "that", "insulin", "triglycerides", "these", "metabolic", "however" ]	[ { "code": "PL14.C", "title": "Patient received diagnostic test or treatment intended for another patient" }, { "code": "QB14", "title": "Unavailability or inaccessibility of health care facilities" }, { "code": "PL14.2", "title": "Problem associated with physical transfer of patient" }, { "code": "QB12.0", "title": "Organ transplant candidate" }, { "code": "QA15.1", "title": "Counselling related to sexual behaviour and orientation or sexual relationships of the person" }, { "code": "5B81.Y", "title": "Other specified obesity" }, { "code": "DA96.0Y", "title": "Other specified intestinal malabsorption" }, { "code": "LD27.6Z", "title": "Genetic lipodystrophy, unspecified" }, { "code": "LD27.60", "title": "Congenital generalised lipodystrophy" }, { "code": "5A44", "title": "Insulin-resistance syndromes" } ]	=== ICD-11 CODES FOUND === [PL14.C] Patient received diagnostic test or treatment intended for another patient Also known as: Patient received diagnostic test or treatment intended for another patient \| wrong patient \| incorrect patient Excludes: Procedure undertaken at wrong site or wrong side, as mode of injury or harm [QB14] Unavailability or inaccessibility of health care facilities Also known as: Unavailability or inaccessibility of health care facilities \| unavailability of medical facilities \| Unavailability of outpatient clinic \| Unavailability or inaccessibility of residential aged care service Excludes: bed unavailable [PL14.2] Problem associated with physical transfer of patient Also known as: Problem associated with physical transfer of patient [QB12.0] Organ transplant candidate Also known as: Organ transplant candidate \| patient waiting for organ availability \| health services provided because of need for organ transplant \| organ transplant candidate awaiting organ availability \| person on organ transplant waiting list [QA15.1] Counselling related to sexual behaviour and orientation or sexual relationships of the person Also known as: Counselling related to sexual behaviour and orientation or sexual relationships of the person \| advice on sexual behaviour or orientation \| counselling on sexual behaviour or orientation \| promiscuity counselling \| patient concerned regarding sexual orientation [5B81.Y] Other specified obesity Also known as: Other specified obesity \| Leptin-related genetic obesity \| Obesity due to congenital leptin deficiency \| Obesity due to congenital leptin resistance \| Obesity due to prohormone convertase-1 deficiency [DA96.0Y] Other specified intestinal malabsorption Also known as: Other specified intestinal malabsorption \| Certain intestinal malabsorption \| Autoimmune enteropathy \| Structural enterocyte defects due to other diseases \| Collagenous sprue [LD27.6Z] Genetic lipodystrophy, unspecified Also known as: Genetic lipodystrophy, unspecified \| Genetic lipodystrophy \| Hereditary lipodystrophy \| Lipodystrophy due to peptidic growth factors deficiency \| Hoepffner-Dreyer-Reimers syndrome [LD27.60] Congenital generalised lipodystrophy Also known as: Congenital generalised lipodystrophy \| generalised congenital lipodystrophy \| GCL - [generalised congenital lipodystrophy] \| Generalised congenital lipodystrophy with myopathy \| congenital lipomyodystrophy [5A44] Insulin-resistance syndromes Also known as: Insulin-resistance syndromes \| Insulin-resistance syndrome type A \| Insulin-resistance syndrome type B \| Rabson-Mendenhall syndrome \| Laminopathy type Decaudain-Vigouroux === GRAPH WALKS === --- Walk 1 --- [PL14.C] Patient received diagnostic test or treatment intended for another patient --EXCLUDES--> [?] Procedure undertaken at wrong site or wrong side, as mode of injury or harm --CHILD--> [?] Performance of inappropriate operation --- Walk 2 --- [PL14.C] Patient received diagnostic test or treatment intended for another patient --PARENT--> [PL14] Mode of injury or harm associated with other health care related causes --CHILD--> [PL14.1] Non provision of necessary procedure --- Walk 3 --- [QB14] Unavailability or inaccessibility of health care facilities --PARENT--> [?] Factors related to medical facilities or other health care --CHILD--> [QB12] Waiting period for investigation or treatment other than awaiting admission to adequate facility elsewhere --- Walk 4 --- [QB14] Unavailability or inaccessibility of health care facilities --EXCLUDES--> [?] Person awaiting admission to adequate facility elsewhere --CHILD--> [?] Person awaiting admission to mental health facility or unit --- Walk 5 --- [PL14.2] Problem associated with physical transfer of patient --PARENT--> [PL14] Mode of injury or harm associated with other health care related causes --EXCLUDES--> [?] Mode of injury or harm associated with a surgical or other medical device, implant or graft --- Walk 6 --- [PL14.2] Problem associated with physical transfer of patient --PARENT--> [PL14] Mode of injury or harm associated with other health care related causes --EXCLUDES--> [?] Mode of injury or harm associated with exposure to a drug, medicament or biological substance	[ "[PL14.C] Patient received diagnostic test or treatment intended for another patient\n --EXCLUDES--> [?] Procedure undertaken at wrong site or wrong side, as mode of injury or harm\n --CHILD--> [?] Performance of inappropriate operation", "[PL14.C] Patient received diagnostic test or treatment intended for another patient\n --PARENT--> [PL14] Mode of injury or harm associated with other health care related causes\n --CHILD--> [PL14.1] Non provision of necessary procedure", "[QB14] Unavailability or inaccessibility of health care facilities\n --PARENT--> [?] Factors related to medical facilities or other health care\n --CHILD--> [QB12] Waiting period for investigation or treatment other than awaiting admission to adequate facility elsewhere", "[QB14] Unavailability or inaccessibility of health care facilities\n --EXCLUDES--> [?] Person awaiting admission to adequate facility elsewhere\n --CHILD--> [?] Person awaiting admission to mental health facility or unit", "[PL14.2] Problem associated with physical transfer of patient\n --PARENT--> [PL14] Mode of injury or harm associated with other health care related causes\n --EXCLUDES--> [?] Mode of injury or harm associated with a surgical or other medical device, implant or graft", "[PL14.2] Problem associated with physical transfer of patient\n --PARENT--> [PL14] Mode of injury or harm associated with other health care related causes\n --EXCLUDES--> [?] Mode of injury or harm associated with exposure to a drug, medicament or biological substance" ]	PL14.C	Patient received diagnostic test or treatment intended for another patient	[ { "from_icd11": "QB14", "icd10_code": "Z753", "icd10_title": "Unavailability and inaccessibility of health-care facilities" }, { "from_icd11": "QA15.1", "icd10_code": "F66", "icd10_title": "Other sexual disorders" }, { "from_icd11": "QA15.1", "icd10_code": "F660", "icd10_title": "" }, { "from_icd11": "QA15.1", "icd10_code": "F661", "icd10_title": "" }, { "from_icd11": "QA15.1", "icd10_code": "F662", "icd10_title": "" }, { "from_icd11": "QA15.1", "icd10_code": "F668", "icd10_title": "" }, { "from_icd11": "QA15.1", "icd10_code": "F669", "icd10_title": "" }, { "from_icd11": "QA15.1", "icd10_code": "Z701", "icd10_title": "Counseling related to patient's sexual behavior and orientation" }, { "from_icd11": "LD27.6Z", "icd10_code": "E881", "icd10_title": "Lipodystrophy, not elsewhere classified" }, { "from_icd11": "5A44", "icd10_code": "E10-E14", "icd10_title": "" } ]	Z753	Unavailability and inaccessibility of health-care facilities
In 2014, he underwent right hemicolectomy surgery for right colon adenocarcinoma, which was then followed by adjuvant chemotherapy with oxaliplatin and capecitabine for two months. During oncological follow-up, the patient underwent a CT scan of the abdomen, which showed discrete signs of interstitial disease, so a subsequent high-resolution computed tomography (HRCT) scan of the chest was performed showing discrete signs of interstitiopathy with reticular appearance due to thickening of inter- and intralobular septa to which bronchiectasis with slightly thickened bronchial walls and lobular air trapping. HRCT results, shown in Figure 2 , corresponded to radiological features of probable usual interstitial pneumonia (UIP), the hallmark of IPF, as described in detail in the 2018 guidelines for diagnosis of IPF and in the 2022 update on IPF diagnosis . The patient had already ultimate chemotherapy cycle since three years, so as some cases of pulmonary fibrosis, also with UIP pattern, associated with Oxaliplatin intake are well described in literature , we decided to monitor the radiological picture over time. Despite discontinuation of the drug, which had led to the hypothesis of secondary pulmonary fibrosis, there was radiological progression and functional worsening, consequently drug strategies for treatment of IPF were evaluated. Despite the clinical recommendations, the patient did not agree to start the therapy with antifribotic drugs and underwent pneumological follow-up. In 2019 the patient was admitted to the Pulmonology Unit in Trieste with dyspnea on exertion, cough and a moderate-grade restrictive ventilatory deficit with severe reduction of alveolus capillary diffusion of carbon monoxide (DLCO) on previous respiratory function tests. During 2019, the patient underwent respiratory function tests that revealed moderate-grade restrictive ventilatory deficit (TLC 57%, RV 45%, FEV1/FVC 86–113%, FVC 59%, FEV1 67%, FEF 25–75% 130%) with moderate reduction in alveolar capillary diffusion of carbon monoxide (DLCO 44%). The patient performed the 6-min walk test (6MWT), which showed significant exertional desaturation (initial SpO2 94% and final 84%). He performed a bronchoscopy with bronco-alveolar-lavage (BAL) that showed the presence of lymphocytic alveolar inflammation for which Prednisone was administered at a dosage of 25 mg in combination with lansoprazole 30 mg for secondary prevention of gastric or duodenal ulcers associated with long-term non-steroidal anti-inflammatory drug (NSAID) therapy. During pulmonology follow-up, blood tests and urine analysis were performed revealing worsening of creatinine values (2 mg/dL) and proteinuria that reached the value of 3 g/24 h. Due to the nephrotic proteinuria and chronic renal failure, a renal biopsy was therefore performed, showing nephropathy with multifactorial genesis, diabetic and hypertensive, associated with focal centers of subacute tubulo-interstitial nephritis. In 2021, the patient was admitted to the pulmonology department for acute and chronic respiratory failure in exacerbation of congestive heart failure, for which oxygen therapy (2 L/min) was prescribed. At the same time, routine blood tests showed a further worsening of renal function with a creatinine of 2.36 mg/dL and an eGFR of 18 mL/min 1.73 m 2 bringing chronic renal failure to stage 3B. In 2022, the patient had a paucisymptomatic SARS-CoV-2 infection that last for one week. The follow-up chest CT scan showed thickening of the intralobular septa and shaded areas of ground-glass-opacity, traction bronchiectasis some cystic formations in a picture referable to fibrosing pathology. Due to the radiological and clinical patterns, the case was presented in the context of multidisciplinary discussion after which it was decided to perform a fiberoptic bronchoscopy with bronchoalveolar lavage, lung biopsy and TransBronchial Needle Aspiration (TBNA) in lymphonode 11 L. Histological investigation confirmed the diagnostic suspicion of IPF, showing dense fibrosis with architectural distortion. Microscopic and culture examination was negative for mycobacteria, viruses and Aspergillus galactomannan. Due to the examinations performed and the clinical-laboratory state, at the end of June 2022 therapy with nintedanib at the dosage of 150 mg 1 cp twice a day was recommended and well tolerated by the patient. The rationale for the choice of antifibrotic drug, as usual, was shared with the patient by evaluating both his clinical situation and his preferences. The patient’s personal preferences regarding treatment, including fears regarding side effects and the desire to avoid certain types of side effects, are always taken into account. In particular, in our case study the patient preferred nintedanib both for the therapeutic regimen and the profile of possible adverse reactions of pirfenidone. In fact, nintedanib is administered at a fixed dosage of 150 mg twice a day, while pirfenidone requires an incremental dosage (up to 801 mg per day), which was complicated for the studied patient. Furthermore, pirfenidone is more frequently associated with skin rash and our patient was very afraid of this adverse event because he lives near the sea and has gardening as a hobby. After the introduction of nintedanib the prednisone has been tapering to 6.25 mg. The 6MWT improved with less final desaturation for the same distance walked (initial SpO2 96% and final 92%). Routine blood tests highlight worsening of renal function (chronic renal failure stage 4) with creatinine values of 3.21 mg/dL referred to the diuretic effect and thus to pre-renal condition. An abdominal ultrasound was performed showing chronic nephropathy without hydrourethronephrosis with multiple cystic formations. In 2023 the patient reported clinical stability with onset of productive cough, especially in the morning, with greenish color sputum sample and reduced sputum expectoration due to reduced exercise tolerance and dyspnea. Chest CT scan showed at basal level the appearance of some thickening patches, partly with consolidative appearance partly with ground glass appearance; persistence of irregular thickening of inter- and intralobular septa and traction bronchiectasis. The respiratory function tests revealed worsening of ventilation with severe grade restrictive ventilatory deficit associated with a severe reduction in alveolar capillary diffusion of carbon monoxide. At discharge the patient clinically improved, with no longer dyspnea or coughing. The patient has been taking nintedanib therapy for eight months. Due to the possibility of the chronic renal failure at stage 4/5 in association with nintedanib, it was decided to stop therapy with nintedanib for two months and continue therapy with Prednisone increasing the dose to 12.5 mg/die. After one month, the patient referred worsening of the clinical status with cough, dyspnea on mild exertion. The respiratory function tests were stable but the 6MWT was worsening with a significant oxygen desaturation of 86% without oxygen supplementation; arterial blood gases analysis highlights increased hypoxemia compared with discharged (pH 7.39, PaO 2 73 mmHg, PaCO 2 38 mmHg, HCO 3 − 23, SpO 2 95.7%). The patient, due to the significant oxygen desaturation, decided to independently take therapy with nintedanib 150 mg twice daily after two months of stopping, a dose that was well tolerated and helped the patients to get a remission of dyspnea and coughing. The patient reinitiated therapy for fifteen months until now. Creatinine values were stable (3.42 mg/dL). After two months, the patient presented acute on chronic respiratory failure with worsening of renal failure for which the patient underwent Central Venous Catheter (CVC) insertion for initiation of hemodialysis treatment. The patient underwent fiberoptic bronchoscopy with bronchoalveolar lavage, with showed FilmArray Pneumonia Panel positive for Legionella Pneumophila for which he started targeted antibiotic therapy. Maintenance of hemodialysis treatment three times a week was planned. Respiratory symptoms improved so the patient was discharged. At the last pneumology follow-up, the patient reported stability of exertional dyspnea, modest cough with yellowish-white sputum, no fever, no wheezing, no paroxysmal nocturnal dyspnea and an improvement in renal function. Respiratory function tests were slightly improving. He is currently taking regular therapy with nintedanib 150 mg 1 cp twice a day, which it is well tolerated, oxygen therapy 1 L/min at rest and 2–3 L/min under exertion. He is also performing regularly respiratory physiotherapy with benefit.	4.109375	0.966309	sec[1]/p[1]	en	0.999997	PMC11434627	https://doi.org/10.3390/ph17091147	[ "which", "renal", "respiratory", "nintedanib", "function", "failure", "dyspnea", "associated", "that", "oxygen" ]	[ { "code": "BD50.41", "title": "Abdominal aortic aneurysm with rupture" }, { "code": "EK91", "title": "Dermatoses which may presage cutaneous lymphoma" }, { "code": "MH12.1", "title": "Death occurring less than 24 hours from onset of symptoms, not otherwise explained" }, { "code": "8A44.3", "title": "Certain specified leukodystrophies" }, { "code": "GC2Z&XA6KU8", "title": "Disease of kidney, not elsewhere classified" }, { "code": "GB6Z", "title": "Kidney failure, unspecified" }, { "code": "LB30.1", "title": "Renal dysplasia" }, { "code": "NB92.0Y", "title": "Other specified injury of kidney" }, { "code": "LB30.7", "title": "Ectopic or pelvic kidney" }, { "code": "CB7Z", "title": "Diseases of the respiratory system, unspecified" } ]	=== ICD-11 CODES FOUND === [BD50.41] Abdominal aortic aneurysm with rupture Also known as: Abdominal aortic aneurysm with rupture \| abdominal aorta aneurysm rupture \| abdominal aorta aneurysm ruptured \| abdominal aortic aneurysm which has ruptured \| ruptured AAA [EK91] Dermatoses which may presage cutaneous lymphoma Definition: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature. Also known as: Dermatoses which may presage cutaneous lymphoma [MH12.1] Death occurring less than 24 hours from onset of symptoms, not otherwise explained Also known as: Death occurring less than 24 hours from onset of symptoms, not otherwise explained \| died without sign of disease \| Death known not to be violent or instantaneous for which no cause can be discovered \| death known not to be violent or instantaneous, cause unknown \| Death without sign of disease Includes: Death known not to be violent or instantaneous for which no cause can be discovered \| Death without sign of disease [8A44.3] Certain specified leukodystrophies Also known as: Certain specified leukodystrophies \| CACH syndrome \| Vanishing white matter disease \| Childhood ataxia with central nervous system hypomyelination \| Congenital or early infantile CACH syndrome [GB6Z] Kidney failure, unspecified Also known as: Kidney failure, unspecified \| nontraumatic kidney injury \| renal failure NOS \| kidney block \| renal impairment NOS [LB30.1] Renal dysplasia Definition: A condition characterised by abnormal development of one or both kidneys. Also known as: Renal dysplasia \| congenital renal dysplasia \| dysplasia of kidney \| dysplastic kidney \| Primary renal dysplasia Excludes: Autosomal dominant polycystic kidney disease [NB92.0Y] Other specified injury of kidney Also known as: Other specified injury of kidney \| Injury of kidney without open wound into cavity \| Injury of kidney with open wound into cavity \| Haematoma of kidney \| traumatic perirenal haematoma [LB30.7] Ectopic or pelvic kidney Definition: A birth defect characterised by an abnormally positioned kidney; may be asymptomatic or result in urine blockage, infection or kidney stones Also known as: Ectopic or pelvic kidney \| Congenital displaced kidney \| congenital misplaced kidney \| congenital malposition of kidney \| congenital prolapsed kidney Includes: Congenital displaced kidney \| Malrotation of kidney [CB7Z] Diseases of the respiratory system, unspecified Also known as: Diseases of the respiratory system, unspecified \| disorder of respiratory system \| respiratory disease NOS \| respiratory tract disease \| respiratory disorder NOS === GRAPH WALKS === --- Walk 1 --- [BD50.41] Abdominal aortic aneurysm with rupture --PARENT--> [BD50.4] Abdominal aortic aneurysm --PARENT--> [BD50] Aortic aneurysm or dissection Def: Aortic aneurysm is a term for any swelling (dilation or aneurysm) of the aorta to greater than 1.5 times normal, usually representing an underlying weakness in the wall of the aorta at that location. ... --- Walk 2 --- [BD50.41] Abdominal aortic aneurysm with rupture --PARENT--> [BD50.4] Abdominal aortic aneurysm --CHILD--> [BD50.40] Abdominal aortic aneurysm with perforation --- Walk 3 --- [EK91] Dermatoses which may presage cutaneous lymphoma Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature.... --CHILD--> [EK91.2] Primary cutaneous plasmacytosis Def: A skin disorder resulting from focal or multifocal dense infiltration of the skin by plasma cell aggregates. It may be associated with high levels of serum IgG4. It typically presents as widespread re... --PARENT--> [EK91] Dermatoses which may presage cutaneous lymphoma Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature.... --- Walk 4 --- [EK91] Dermatoses which may presage cutaneous lymphoma Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature.... --CHILD--> [EK91.0] Large plaque parapsoriasis Def: Large plaque parapsoriasis is a chronic skin disorder characterised by the indolent development over years or decades of scaly patches or slightly elevated plaques which may be clinically indistinguis... --PARENT--> [EK91] Dermatoses which may presage cutaneous lymphoma Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature.... --- Walk 5 --- [MH12.1] Death occurring less than 24 hours from onset of symptoms, not otherwise explained --PARENT--> [MH12] Other sudden death, cause unknown --PARENT--> [?] Ill-defined and unknown causes of mortality --- Walk 6 --- [MH12.1] Death occurring less than 24 hours from onset of symptoms, not otherwise explained --PARENT--> [MH12] Other sudden death, cause unknown --CHILD--> [MH12.0] Instantaneous death	[ "[BD50.41] Abdominal aortic aneurysm with rupture\n --PARENT--> [BD50.4] Abdominal aortic aneurysm\n --PARENT--> [BD50] Aortic aneurysm or dissection\n Def: Aortic aneurysm is a term for any swelling (dilation or aneurysm) of the aorta to greater than 1.5 times normal, usually representing an underlying weakness in the wall of the aorta at that location. ...", "[BD50.41] Abdominal aortic aneurysm with rupture\n --PARENT--> [BD50.4] Abdominal aortic aneurysm\n --CHILD--> [BD50.40] Abdominal aortic aneurysm with perforation", "[EK91] Dermatoses which may presage cutaneous lymphoma\n Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature....\n --CHILD--> [EK91.2] Primary cutaneous plasmacytosis\n Def: A skin disorder resulting from focal or multifocal dense infiltration of the skin by plasma cell aggregates. It may be associated with high levels of serum IgG4. It typically presents as widespread re...\n --PARENT--> [EK91] Dermatoses which may presage cutaneous lymphoma\n Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature....", "[EK91] Dermatoses which may presage cutaneous lymphoma\n Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature....\n --CHILD--> [EK91.0] Large plaque parapsoriasis\n Def: Large plaque parapsoriasis is a chronic skin disorder characterised by the indolent development over years or decades of scaly patches or slightly elevated plaques which may be clinically indistinguis...\n --PARENT--> [EK91] Dermatoses which may presage cutaneous lymphoma\n Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature....", "[MH12.1] Death occurring less than 24 hours from onset of symptoms, not otherwise explained\n --PARENT--> [MH12] Other sudden death, cause unknown\n --PARENT--> [?] Ill-defined and unknown causes of mortality", "[MH12.1] Death occurring less than 24 hours from onset of symptoms, not otherwise explained\n --PARENT--> [MH12] Other sudden death, cause unknown\n --CHILD--> [MH12.0] Instantaneous death" ]	BD50.41	Abdominal aortic aneurysm with rupture	[ { "from_icd11": "BD50.41", "icd10_code": "I713", "icd10_title": "Abdominal aortic aneurysm, ruptured" }, { "from_icd11": "EK91", "icd10_code": "L989", "icd10_title": "Disorder of the skin and subcutaneous tissue, unspecified" }, { "from_icd11": "MH12.1", "icd10_code": "R961", "icd10_title": "" }, { "from_icd11": "GB6Z", "icd10_code": "N19", "icd10_title": "Unspecified kidney failure" }, { "from_icd11": "GB6Z", "icd10_code": "N17-N19", "icd10_title": "" }, { "from_icd11": "GB6Z", "icd10_code": "N17", "icd10_title": "Acute kidney failure" }, { "from_icd11": "LB30.1", "icd10_code": "Q614", "icd10_title": "Renal dysplasia" }, { "from_icd11": "LB30.7", "icd10_code": "Q632", "icd10_title": "Ectopic kidney" }, { "from_icd11": "LB30.7", "icd10_code": "Q63", "icd10_title": "Other congenital malformations of kidney" }, { "from_icd11": "CB7Z", "icd10_code": "J989", "icd10_title": "Respiratory disorder, unspecified" }, { "from_icd11": "CB7Z", "icd10_code": "X", "icd10_title": "" }, { "from_icd11": "CB7Z", "icd10_code": "J09-J18", "icd10_title": "" } ]	I713	Abdominal aortic aneurysm, ruptured
According to our opinion, the perioperative management of this clinical case is interesting for the possible consideration of the severe complications which could occur during and after major surgery in patients with Beckwith–Wiedemann syndrome. The multidisciplinary approach is mandatory for the management of this complex surgery. In the preoperative phase, a complete assessment of the patient’s clinical and morphological conditions is essential to collect a complete medical history. Also, the psychological aspects of a demolitive, painful facial surgery limiting feeding and specking are important. The work carried out by the psychologist present during the interviews with family members is to reassure the parents and, indirectly, the child. On the day of surgery, a quick re-evaluation avoids encountering adverse conditions during the anesthesia induction phase (e.g., onset of infections, colds, increased secretions, etc.). There is little literature on the subject of Premedication with off-label Clonidine in pediatric patients; in our service, this drug is used routinely both in premedication and in the context of intensive care. In recent years, its use has increased, which allows anxiolysis and prevents drooling, essential in the context of a patient with these problems, and helps the analgesic action of intra- and post-operative opioids . In the case of a patient in which a reduced oxygen reserve is observed, as in this case, it is possible to take advantage of the pharmacodynamics of Clonidine, which allows one to avoid the depression of the respiratory drive, as opposed to other sedative drugs such as Midazolam. The use of a nasal vasoconstrictor avoids the onset of a dangerous event, such as bleeding during the passage of the tube in the nose, causing a reduction in vision and the tarnishing of the optics of the video laryngoscope used in this case, in a patient who already has a considerable bulk in the mouth . Pre-oxygenation with nasal cannulae with 100% O 2 minimizes the risk of desaturation during the intubation procedure. The fibrobronchoscopy, in case of an inability to perform a valid laryngoscopy or a difficulty in ventilation and/or intubation, was present and available in the operating room, as was a cricotomy kit . The use of these devices, which necessarily involves adequate training, is an essential skill in all areas of difficult airway management. The administration of high concentrations of Sevoflurane or muscle relaxants to patients in the supine position could cause the tongue to fall into the retro-lingual space, with severe airway obstruction during induction of anesthesia. For these reasons, ventilation was performed using a face mask using Sevoflurane, gradually increasing its concentration until an adequate depth of anesthesia was obtained. Curaries are not considered routine drugs in the intubation of pediatric patients; in this context, the use of a local anesthetic sprayed directly on the vocal cords through a special cannula was preferred . Lingual Nerve Block is an effective and easy-to-implement analgesic technique , and has potentially reduced intra- and post-operative opioid dosages according to a policy of opioid spearing and preemptive analgesia . Complete intraoperative monitoring seemed necessary to minimize the risks, in particular the constant evaluation of the temperature, a particularly important parameter in a pediatric patient, given the ease of heat loss , and a control of blood loss, given the very perfused surgical area. Regarding the surgical technique, there are various options that can be used in this context. The goal above all is to achieve an almost normal level of lingual anatomy both in terms of size and shape, such that the organ remains behind the incisors with sufficient mobility to moisturize the lips . In our case, the technique chosen was a partial glossectomy according to Egyedi and Obwegeser, which consists of a symmetrical resection (see case report), and is particularly suitable for bilateral macroglossia. According to the experience of the operators, this method guarantees a better functionality of the tongue in the long term, both for language and for food; it also reduces the risk of intraoperative bleeding as well as avoiding the collapse of the tissues of the soft palate and tongue, reducing the risk of post-operative airway obstruction . Balaji et al. claim that “the main stay of surgical treatment of macroglossia is to provide a tongue that can function in the most efficient aspect in terms of form and function”, and they proposed a classification of efficient management of macroglossia; for situations where the length and width abnormalities occur, Egyedi–Obwegeser offers a solution . Recently, in 2023, The American Association of Oral and Maxillofacial Surgeons presented an algorithm for the management of idiopathic macroglossia. The Egyedi and Obwegeser technique is described as a technique used in many patients, because it allows both narrowing and shortening of the tongue and preserves the lingual nerve and hypoglossal nerves, whereas the loss of the tip has not been reported to result in a marked sensory deficiency . Consequently, in more recent studies, we described the Egyedi and Obwegeser technique as safer for tongue reduction in our little patient. Macroglossia is definitely a growth stimulus for the jaw; in fact, macroglossia could be a factor of structural and functional changes in the growth of the facial mass and, in particular, of the mandible, to compensate for the largeness of the tongue. However, whether this is the only trigger for prognathism, or if the genetic component contributes an additional role, is not known . It can be considered that an early intervention to reduce the tongue is recommended to reduce the risk of structural alteration of the stomatognathic system and to develop both the mandibular prognathism and the anterior open bite, in addition to any social and psychological problems for the child. The optimal age for surgery is unclear; in general, it is recommended to perform the reduction of the tongue after one year of age to reduce the risk of perioperative complications, if there is no condition that involves problems for the child’s survival . No noticeable changes and/or complications were observed in the post-operative phase. Transportation to the ICU was mandatory due to the risk of tongue edema and bleeding. According to our experience, the peak of lingual edema is observed within the first 48 h. Daily surgical re-evaluation is essential to avoid these complications. After extubation, the positioning of high flow nasal cannula (HFNC) in this patient reduces the risk of respiratory crises, as described in the literature . An HFNC application decreases nasopharyngeal dead space and increases the alveolar fraction of oxygen, reduces work of breathing and respiratory muscle fatigue, improves management of respiratory secretions, and reduces upper airway obstruction episodes through the humidified oxygen and the positive end expiratory pressure applied to the airway . An alpha 2 agonist, such as Dexmetomidine, and an opioid, in this case Remifentanil, have receptor synergism, as reducing the dosages will achieve similar or higher efficacy than drugs administered individually, and will have fewer side effects . Furthermore, by exploiting the pharmacodynamics of Dexmetomidine, we obtain a valid sedation while maintaining spontaneous breathing. As regards Remifentanil being an insensitive context drug with a very rapid off-set, we have the possibility of modulating analgesia and reducing or increasing the dosage in a continuous infusion without the problem of accumulation or excessive respiratory depression . Paracetamol was imbricated following extubation, in the control of post-operative analgesia, by administering 350 mg intravenously up to three times a day, observing a valid result. Rapid enteral refeeding, early mobilization, and discharge in the shortest possible time in accordance with the indications of the ERAS protocol indicate a reduction in long-term complications and the onset of infections in the patient in intensive care or in any case following surgery . Rehabilitation followed by consultation with a speech therapist is essential for the child to resume normal daily life for sociability, language, and cognitive development in an age of growth in which these aspects are very important. Finally, a conservative functional orthodontic treatment could be useful to prevent dental and skeletal malformations and lead to a regular craniofacial physiognomy over the years .	4.1875	0.836914	sec[2]/p[0]	en	0.999994	PMC10529883	https://doi.org/10.3390/children10091467	[ "this", "tongue", "which", "risk", "technique", "that", "macroglossia", "according", "complications", "patients" ]	[ { "code": "4A01.03", "title": "Transient hypogammaglobulinaemia of infancy" }, { "code": "DA03.Z", "title": "Diseases of tongue, unspecified" }, { "code": "DA03.0", "title": "Glossitis" }, { "code": "NA0Z&XA1T19", "title": "Injury of tongue" }, { "code": "LA31.Z", "title": "Structural developmental anomalies of mouth or tongue, unspecified" }, { "code": "NA01.Z&XA1T19", "title": "Laceration of tongue" }, { "code": "BD50.41", "title": "Abdominal aortic aneurysm with rupture" }, { "code": "EK91", "title": "Dermatoses which may presage cutaneous lymphoma" }, { "code": "MH12.1", "title": "Death occurring less than 24 hours from onset of symptoms, not otherwise explained" }, { "code": "8A44.3", "title": "Certain specified leukodystrophies" } ]	=== ICD-11 CODES FOUND === [4A01.03] Transient hypogammaglobulinaemia of infancy Also known as: Transient hypogammaglobulinaemia of infancy \| immunoglobulin maturational delay \| THI - [transient hypogammaglobulinaemia of infancy] [DA03.Z] Diseases of tongue, unspecified Also known as: Diseases of tongue, unspecified \| Diseases of tongue \| disorder of tongue \| Glossopathy \| unspecified condition of the tongue [DA03.0] Glossitis Definition: Inflammation of the tongue Also known as: Glossitis \| inflammation of tongue \| tongue inflammation \| glazed tongue \| Papillitis of tongue Excludes: atrophic glossitis [LA31.Z] Structural developmental anomalies of mouth or tongue, unspecified Also known as: Structural developmental anomalies of mouth or tongue, unspecified \| Structural developmental anomalies of mouth or tongue \| malformations of mouth or tongue \| structural developmental anomalies of mouth NOS \| malformations of mouth NOS [BD50.41] Abdominal aortic aneurysm with rupture Also known as: Abdominal aortic aneurysm with rupture \| abdominal aorta aneurysm rupture \| abdominal aorta aneurysm ruptured \| abdominal aortic aneurysm which has ruptured \| ruptured AAA [EK91] Dermatoses which may presage cutaneous lymphoma Definition: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature. Also known as: Dermatoses which may presage cutaneous lymphoma [MH12.1] Death occurring less than 24 hours from onset of symptoms, not otherwise explained Also known as: Death occurring less than 24 hours from onset of symptoms, not otherwise explained \| died without sign of disease \| Death known not to be violent or instantaneous for which no cause can be discovered \| death known not to be violent or instantaneous, cause unknown \| Death without sign of disease Includes: Death known not to be violent or instantaneous for which no cause can be discovered \| Death without sign of disease [8A44.3] Certain specified leukodystrophies Also known as: Certain specified leukodystrophies \| CACH syndrome \| Vanishing white matter disease \| Childhood ataxia with central nervous system hypomyelination \| Congenital or early infantile CACH syndrome === GRAPH WALKS === --- Walk 1 --- [4A01.03] Transient hypogammaglobulinaemia of infancy --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects... --CHILD--> [4A01.02] Specific antibody deficiency with normal immunoglobulin concentrations or normal number of B cells --- Walk 2 --- [4A01.03] Transient hypogammaglobulinaemia of infancy --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects... --CHILD--> [4A01.02] Specific antibody deficiency with normal immunoglobulin concentrations or normal number of B cells --- Walk 3 --- [DA03.Z] Diseases of tongue, unspecified --PARENT--> [DA03] Diseases of tongue Def: Any pathological process affecting the structural tissues of the tongue with or without interference of its normal functions.... --RELATED_TO--> [?] Sublingual varices Def: Varicose veins on the underside of the tongue... --- Walk 4 --- [DA03.Z] Diseases of tongue, unspecified --PARENT--> [DA03] Diseases of tongue Def: Any pathological process affecting the structural tissues of the tongue with or without interference of its normal functions.... --CHILD--> [DA03.0] Glossitis Def: Inflammation of the tongue... --- Walk 5 --- [DA03.0] Glossitis Def: Inflammation of the tongue... --PARENT--> [DA03] Diseases of tongue Def: Any pathological process affecting the structural tissues of the tongue with or without interference of its normal functions.... --PARENT--> [?] Diseases or disorders of orofacial complex Def: Morbid process, derangement or abnormality localised in the mouth or related tissues of the face... --- Walk 6 --- [DA03.0] Glossitis Def: Inflammation of the tongue... --PARENT--> [DA03] Diseases of tongue Def: Any pathological process affecting the structural tissues of the tongue with or without interference of its normal functions.... --EXCLUDES--> [?] Oral leukoplakia Def: Leukoplakia is a condition where areas of keratosis appear as adherent white patches on the mucous membranes of the oral cavity. Leukoplakia may affect other gastrointestinal tract mucosal sites, or m...	[ "[4A01.03] Transient hypogammaglobulinaemia of infancy\n --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects\n Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects...\n --CHILD--> [4A01.02] Specific antibody deficiency with normal immunoglobulin concentrations or normal number of B cells", "[4A01.03] Transient hypogammaglobulinaemia of infancy\n --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects\n Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects...\n --CHILD--> [4A01.02] Specific antibody deficiency with normal immunoglobulin concentrations or normal number of B cells", "[DA03.Z] Diseases of tongue, unspecified\n --PARENT--> [DA03] Diseases of tongue\n Def: Any pathological process affecting the structural tissues of the tongue with or without interference of its normal functions....\n --RELATED_TO--> [?] Sublingual varices\n Def: Varicose veins on the underside of the tongue...", "[DA03.Z] Diseases of tongue, unspecified\n --PARENT--> [DA03] Diseases of tongue\n Def: Any pathological process affecting the structural tissues of the tongue with or without interference of its normal functions....\n --CHILD--> [DA03.0] Glossitis\n Def: Inflammation of the tongue...", "[DA03.0] Glossitis\n Def: Inflammation of the tongue...\n --PARENT--> [DA03] Diseases of tongue\n Def: Any pathological process affecting the structural tissues of the tongue with or without interference of its normal functions....\n --PARENT--> [?] Diseases or disorders of orofacial complex\n Def: Morbid process, derangement or abnormality localised in the mouth or related tissues of the face...", "[DA03.0] Glossitis\n Def: Inflammation of the tongue...\n --PARENT--> [DA03] Diseases of tongue\n Def: Any pathological process affecting the structural tissues of the tongue with or without interference of its normal functions....\n --EXCLUDES--> [?] Oral leukoplakia\n Def: Leukoplakia is a condition where areas of keratosis appear as adherent white patches on the mucous membranes of the oral cavity. Leukoplakia may affect other gastrointestinal tract mucosal sites, or m..." ]	4A01.03	Transient hypogammaglobulinaemia of infancy	[ { "from_icd11": "4A01.03", "icd10_code": "D807", "icd10_title": "Transient hypogammaglobulinemia of infancy" }, { "from_icd11": "DA03.0", "icd10_code": "K140", "icd10_title": "Glossitis" }, { "from_icd11": "BD50.41", "icd10_code": "I713", "icd10_title": "Abdominal aortic aneurysm, ruptured" }, { "from_icd11": "EK91", "icd10_code": "L989", "icd10_title": "Disorder of the skin and subcutaneous tissue, unspecified" }, { "from_icd11": "MH12.1", "icd10_code": "R961", "icd10_title": "" } ]	D807	Transient hypogammaglobulinemia of infancy
A 28-year-old gravida 1, para 0 woman of Caucasian ethnicity without relevant past medical history was admitted to the emergency ward at 26 weeks and 1 day of gestation because of progressive dyspnea due to SARS-CoV-2 pneumonia with the Alpha variant (B.1.1.7). Despite conventional therapy with supplemental oxygen, dexamethasone, and prophylactic treatment with ceftriaxone, increasing respiratory failure and impending need of endotracheal intubation forced the decision to primary cesarean section at 27 weeks and 2 days of gestation. The child’s apgar scores were 3, 5, and 6 at 1, 5, and 10 minutes, respectively. Due to prematurity, associated respiratory insufficiency, recurrent bradycardia, and infant respiratory distress syndrome, the boy of Caucasian ethnicity needed mechanical ventilation. First clinical examination after admission to the neonatal intensive care unit did not reveal any congenital malformations, except a secundum type atrial septal defect. Body temperature was initially elevated (38.0 °C), but inflammatory parameters remained normal [C-reactive protein (CRP) levels < 0.4 mg/dl]. The growth indices were below average with a birth weight of 980 g (10th–50th percentile), a head circumference of 25 cm (10th–50th percentile), and a length of 36 cm (10th–50th percentile). His clinical status stabilized in the further course and the boy was extubated on the 4th day of life. SARS-CoV-2 RNA was not detected in sequential respiratory and stool samples [polymerase chain reaction (PCR) targets: E-gene and ORF-region, limit of detection (LoD): about 50 genome equivalents/ml, Roche diagnostics, Switzerland]. Furthermore, SARS-CoV-2 immunoglobulin (Ig)M was not detected in a serum sample collected on the 3rd day of life, while SARS-CoV-2 antinucleocapside IgG was positive by chemiluminescent microparticle immunoassay [(CMIA), AdviseDx SARS-CoV-2 IgM und IgG test, Abbott Laboratories, USA]. An umbilical blood sample revealed a weak positive result for the E-gene target (cycle threshold value 36.83) and a negative result for the ORF-region target, which, considering the unremarkable follow-up samples, was not interpreted as evidence of a congenital SARS-CoV-2 infection. Surprisingly, postpartum maternal infection screening revealed a so far unknown T. gondii infection of the mother. Although the woman had no pet or similar exposure at home, serology clearly indicated a primary maternal infection during pregnancy, with proof of Toxoplasma -specific IgM antibodies and increasing titers of specific IgA and IgG antibodies . Due to a low IgG avidity (index 0.036) a maternal infection in the preceding 3–4 months could not be excluded. A PCR from maternal ethylenediamine tetraacetic acid (EDTA) blood was negative (target gene: 529 bp tandem repeat element, limit of detection: 4 T. gondii DNA copies per PCR reaction, Sacace Biotechnologies, Italy). Immediately after detection of the maternal T. gondii infection, serum of the premature child was analyzed. A low IgG titer was detected by indirect immunofluorescence testing (IFT), while IgM (IFT) and IgA [Enzyme-linked immunosorbent assay (ELISA), Immunosorbent agglutination assay (ISAGA)] tested negative . The competition test in a serum sample 1 week later was weakly positive, whereas selective screening for IgG, IgM [all enzyme-linked fluorescent immunoassay (ELFA)] and IgA antibodies (ELISA) against T. gondii remained surprisingly negative (Table 1 ). In addition, the IgG immunoblot profile (LDBIO Diagnostics, France) of mother and child was identical, suggesting a weak transfer of maternal IgG antibodies to the premature child . Accordingly, a T. gondii -specific PCR from neonatal EDTA blood was negative. A follow-up serum sample 4 weeks after birth showed no significant serological changes (Table 1 ). Cerebral ultrasound, and ophthalmological and neurological examinations of the premature child were without any pathological findings. In addition, SARS-CoV-2 IgG had fallen below the cut-off value in a serum sample collected 5 weeks later, supporting the hypothesis of maternal IgG transfer. Six weeks after birth, the child was discharged from the intensive care unit. Unfortunately, the mother died 7 weeks after birth, despite maximum intensive care, including extracorporeal membrane oxygenation over a period of 6 weeks. Surprisingly, 11 weeks after birth, significant serological changes in the child’s serum were detected indicating congenital toxoplasmosis. At this timepoint, all Toxoplasma -specific antibody classes were detected to be clearly positive (Table 1 ). In addition, a significant increase of T. gondii -specific IgG antibody titers using the IFT was shown . Accordingly, the IgG immunoblot profile of mother and child now indicated independent IgG synthesis by the child . Immunoblots for IgA and IgM antibodies against T. gondii were negative, but IgA was confirmed to be positive by ISAGA. The child had not received any blood products so far. Moreover, a neonatal cerebrospinal fluid (CSF) sample revealed a positive T. gondii -PCR result (target gene: 529 bp tandem repeat element, limit of detection: 1–10 parasites per PCR reaction) and serum/liquor comparison blots for IgG indicated intrathecal IgG synthesis. CSF white blood cell count was 5/µl, glucose was 45 mg/dl, and protein was 1315 mg/l. Despite these pathologic CSF results, neither cerebral ultrasound nor magnetic resonance tomography (MRT) imaging indicated any cerebral abnormalities, and, moreover, neither ophthalmological nor clinical neurological manifestations were detected. Though the premature child appeared clinically asymptomatic, a T. gondii -specific treatment with pyrimethamine (1 mg/kg per day), sulfadiazine (50 mg/kg twice daily), and folinic acid (10 mg/week) was initiated to prevent or to minimize long-term sequelae of the Toxoplasma infection. The boy developed well and was discharged from hospital 4 months after birth. However, because of recurrent episodes of neutropenia, pyrimethamine had to be paused after 5 weeks. Dose increase of folinic acid only led to temporary improvement of neutropenia. Thus, sulfadiazine was additionally paused 11 weeks after start of therapy. No other antiparasitic therapy was initialized as the boy was still clinically asymptomatic and the serum control 29 weeks after birth was stable, with slightly descending IgG titers and absence of IgA . Ophthalmological, neurological, and pedaudiological examinations did not detect any abnormalities. Despite continuous folinic acid substitution, further episodes of neutropenia occurred. Thirteen weeks after stopping sulfadiazine treatment, a significant increase in IgG titers by IFT , and occurrence of IgA by ISAGA, were observed suggesting a possible rebound phenomenon . As neither cerebral MRT imaging nor standard control examinations revealed any pathological findings, it was decided to continue the concept of frequent serological, ophthalmological, neurological, and pedaudiological controls (every 3–6 months) without further antiparasitic therapy. Fig. 1 Time course of T. gondii antibody titers in mother’s and child’s sera. IgG and IgM were measured by indirect immunofluorescence testing (IFT; Euroimmun, Germany; titers < 16 are evaluated as negative). IgA was tested by immunosorbent agglutination assay [Ravo Diagnostika, Germany, titers < 16 (newborns) or < 64 (all other patients) are evaluated as negative] Table 1 T. gondii antibody screening results in the mother’s and child’s sera in time course Serum Time after birth (weeks) IgG IgM IgA ELFA a (U/ml) ELFA a (index) ELISA b (ratio) Mother 1 Positive (23) Positive (4.49) Positive (2.78) 6 Positive (260) Positive (4.32) Positive (> 5) Child 1 – c – c Negative (0.03) 2 Negative d (< 4.0) Negative d (< 0.55) Negative d (< 0.8) 4 Negative d (< 4.0) Negative d (< 0.55) Negative d (< 0.8) 11 Positive d (46) Positive d (2.32) Positive d (6.97) 29 Positive (95) Negative (< 0.55) Negative (0.14) 41 Positive (> 300) Negative (< 0.55) Negative (0.22) a Enzyme-linked fluorescent immunoassay , bioMérieux, France b Enzyme-linked immunosorbent assay, Euroimmun, Germany c This antibody class was only measured by indirect immunofluorescence testing because of a shortage of material d Results of the German consulting laboratory for Toxoplasma (Göttingen, Germany): ELFA, bioMérieux, France; ELISA, Biorad, USA Fig. 2 Comparative immunoblot analysis of mother (lane M) and child (lanes C1 and C2). The sera were taken 1 week (M, C1) and 11 weeks (C2) after birth. The arrows indicate the child’s neosynthesized antibodies	4.160156	0.960938	sec[1]/p[0]	en	0.999998	37013596	https://doi.org/10.1186/s13256-023-03855-8	[ "gondii", "birth", "serum", "mother", "sars", "infection", "maternal", "titers", "sample", "specific" ]	[ { "code": "1F57.Y/GB5Z", "title": "Renal tubulo-interstitial disorders due to toxoplasmoa gondii" }, { "code": "1F57.2", "title": "Pulmonary toxoplasmosis due to Toxoplasma gondii" }, { "code": "1F57.3", "title": "Eye disease due to Toxoplasma gondii" }, { "code": "1F57.Z", "title": "Toxoplasmosis, unspecified" }, { "code": "1F57.1", "title": "Meningoencephalitis due to Toxoplasma gondii" }, { "code": "QA46.Z", "title": "Outcome of delivery, unspecified" }, { "code": "LD9Z", "title": "Developmental anomalies, unspecified" }, { "code": "LD2Z", "title": "Multiple developmental anomalies or syndromes, unspecified" }, { "code": "KA4Z", "title": "Birth injury, unspecified" }, { "code": "QA46.0", "title": "Single live birth" } ]	=== ICD-11 CODES FOUND === [1F57.2] Pulmonary toxoplasmosis due to Toxoplasma gondii Definition: In immunodeficient patients, toxoplasmosis most often occurs in persons with defects in T cell–mediated immunity such as those receiving corticosteroids, anti–tumour necrosis factor (TNF) therapies, or cytotoxic drugs and those with hematologic malignancies, organ transplants, or acquired immunodeficiency syndrome (AIDS). Pulmonary toxoplasmosis in the immunodeficient patient may appear in the form of interstitial pneumonitis, necrotizing pneumonitis, consolidation, pleural effusion, or empyema Also known as: Pulmonary toxoplasmosis due to Toxoplasma gondii \| pneumonia with toxoplasmosis \| pneumonitis due to acquired toxoplasmosis \| pneumonitis due to toxoplasmosis \| toxoplasma pneumonia Includes: Pulmonary toxoplasmosis [1F57.3] Eye disease due to Toxoplasma gondii Definition: Chorioretinitis or ocular toxoplasmosis is a relatively common manifestation of T. gondii infection. Ocular toxoplasmosis occurs when cysts deposited in or near the retina become active, producing tachyzoites. Focal necrotizing retinitis is the characteristic lesion, but retinal scars from prior reactivation are typically present. Also known as: Eye disease due to Toxoplasma gondii \| Toxoplasma oculopathy \| Toxoplasma posterior uveitis \| Toxoplasma chorioretinitis \| chorioretinitis due to toxoplasmosis Includes: Toxoplasma oculopathy [1F57.Z] Toxoplasmosis, unspecified Also known as: Toxoplasmosis, unspecified \| Toxoplasmosis \| acquired toxoplasmosis \| toxoplasmosis disease or disorder \| infection by toxoplasma gondii [1F57.1] Meningoencephalitis due to Toxoplasma gondii Definition: A disease of the meninges and brain, caused by an infection with the protozoan parasite Toxoplasma gondii. This disease is characterised by seizures, neck pain, neurological deficits, or alterations in behaviour, cognition, or consciousness. Transmission is by haematogenous spread to the meninges and brain after direct ingestion of contaminated food, or indirect transmission by consumption of food or water contaminated with infected cat faeces. Confirmation is by detection of antibodies against Also known as: Meningoencephalitis due to Toxoplasma gondii \| acquired toxoplasmal meningoencephalitis \| meningoencephalitis due to acquired toxoplasmosis \| meningoencephalitis due to toxoplasmosis \| Toxoplasma meningoencephalitis Includes: Toxoplasma meningoencephalitis [QA46.Z] Outcome of delivery, unspecified Also known as: Outcome of delivery, unspecified \| Outcome of delivery \| Multiple birth, unspecified \| Single birth, unspecified [LD9Z] Developmental anomalies, unspecified Also known as: Developmental anomalies, unspecified \| congenital malformations, deformations and chromosomal abnormalities \| congenital malformation NOS \| developmental abnormality NOS \| fetal abnormality NOS [LD2Z] Multiple developmental anomalies or syndromes, unspecified Also known as: Multiple developmental anomalies or syndromes, unspecified \| multiple congenital birth defects NOS \| multiple congenital birth deformities NOS \| multiple fetal abnormalities NOS \| severe birth deformities NOS [KA4Z] Birth injury, unspecified Also known as: Birth injury, unspecified \| childbirth trauma \| birth injury nos \| birth trauma of fetus \| childbirth injury [QA46.0] Single live birth Definition: Live birth is the complete expulsion or extraction from a woman of a fetus, irrespective of the duration of the pregnancy, which, after such separation, shows signs of life. Also known as: Single live birth \| single liveborn \| outcome of delivery of single liveborn === GRAPH WALKS === --- Walk 1 --- [1F57.2] Pulmonary toxoplasmosis due to Toxoplasma gondii Def: In immunodeficient patients, toxoplasmosis most often occurs in persons with defects in T cell–mediated immunity such as those receiving corticosteroids, anti–tumour necrosis factor (TNF) therapies, o... --PARENT--> [1F57] Toxoplasmosis Def: A disease caused by an infection with the protozoan parasite Toxoplasma gondii. This disease is characterised by fever, lymphadenitis, sore throat, or rash. Transmission is by direct ingestion of cont... --CHILD--> [1F57.0] Hepatitis due to Toxoplasma gondii Def: A disease of the liver, caused by an infection with the protozoan parasite Toxoplasma gondii. This disease is characterised by jaundice. Transmission is by haematogenous spread to the liver after dire... --- Walk 2 --- [1F57.2] Pulmonary toxoplasmosis due to Toxoplasma gondii Def: In immunodeficient patients, toxoplasmosis most often occurs in persons with defects in T cell–mediated immunity such as those receiving corticosteroids, anti–tumour necrosis factor (TNF) therapies, o... --PARENT--> [1F57] Toxoplasmosis Def: A disease caused by an infection with the protozoan parasite Toxoplasma gondii. This disease is characterised by fever, lymphadenitis, sore throat, or rash. Transmission is by direct ingestion of cont... --RELATED_TO--> [?] Congenital toxoplasmosis Def: A disease caused by an infection with the protozoan parasite Toxoplasma gondii in utero. This disease is characterised by chorioretinitis, hydrocephalus, intracranial calcifications, anaemia, or neuro... --- Walk 3 --- [1F57.3] Eye disease due to Toxoplasma gondii Def: Chorioretinitis or ocular toxoplasmosis is a relatively common manifestation of T. gondii infection. Ocular toxoplasmosis occurs when cysts deposited in or near the retina become active, producing tac... --PARENT--> [1F57] Toxoplasmosis Def: A disease caused by an infection with the protozoan parasite Toxoplasma gondii. This disease is characterised by fever, lymphadenitis, sore throat, or rash. Transmission is by direct ingestion of cont... --RELATED_TO--> [?] Congenital toxoplasmosis Def: A disease caused by an infection with the protozoan parasite Toxoplasma gondii in utero. This disease is characterised by chorioretinitis, hydrocephalus, intracranial calcifications, anaemia, or neuro... --- Walk 4 --- [1F57.3] Eye disease due to Toxoplasma gondii Def: Chorioretinitis or ocular toxoplasmosis is a relatively common manifestation of T. gondii infection. Ocular toxoplasmosis occurs when cysts deposited in or near the retina become active, producing tac... --PARENT--> [1F57] Toxoplasmosis Def: A disease caused by an infection with the protozoan parasite Toxoplasma gondii. This disease is characterised by fever, lymphadenitis, sore throat, or rash. Transmission is by direct ingestion of cont... --PARENT--> [?] Nonintestinal protozoal diseases Def: Infections with unicellular organisms of the subkingdom Protozoa.... --- Walk 5 --- [1F57.Z] Toxoplasmosis, unspecified --PARENT--> [1F57] Toxoplasmosis Def: A disease caused by an infection with the protozoan parasite Toxoplasma gondii. This disease is characterised by fever, lymphadenitis, sore throat, or rash. Transmission is by direct ingestion of cont... --CHILD--> [1F57.0] Hepatitis due to Toxoplasma gondii Def: A disease of the liver, caused by an infection with the protozoan parasite Toxoplasma gondii. This disease is characterised by jaundice. Transmission is by haematogenous spread to the liver after dire... --- Walk 6 --- [1F57.Z] Toxoplasmosis, unspecified --PARENT--> [1F57] Toxoplasmosis Def: A disease caused by an infection with the protozoan parasite Toxoplasma gondii. This disease is characterised by fever, lymphadenitis, sore throat, or rash. Transmission is by direct ingestion of cont... --CHILD--> [1F57.1] Meningoencephalitis due to Toxoplasma gondii Def: A disease of the meninges and brain, caused by an infection with the protozoan parasite Toxoplasma gondii. This disease is characterised by seizures, neck pain, neurological deficits, or alterations i...	[ "[1F57.2] Pulmonary toxoplasmosis due to Toxoplasma gondii\n Def: In immunodeficient patients, toxoplasmosis most often occurs in persons with defects in T cell–mediated immunity such as those receiving corticosteroids, anti–tumour necrosis factor (TNF) therapies, o...\n --PARENT--> [1F57] Toxoplasmosis\n Def: A disease caused by an infection with the protozoan parasite Toxoplasma gondii. This disease is characterised by fever, lymphadenitis, sore throat, or rash. Transmission is by direct ingestion of cont...\n --CHILD--> [1F57.0] Hepatitis due to Toxoplasma gondii\n Def: A disease of the liver, caused by an infection with the protozoan parasite Toxoplasma gondii. This disease is characterised by jaundice. Transmission is by haematogenous spread to the liver after dire...", "[1F57.2] Pulmonary toxoplasmosis due to Toxoplasma gondii\n Def: In immunodeficient patients, toxoplasmosis most often occurs in persons with defects in T cell–mediated immunity such as those receiving corticosteroids, anti–tumour necrosis factor (TNF) therapies, o...\n --PARENT--> [1F57] Toxoplasmosis\n Def: A disease caused by an infection with the protozoan parasite Toxoplasma gondii. This disease is characterised by fever, lymphadenitis, sore throat, or rash. Transmission is by direct ingestion of cont...\n --RELATED_TO--> [?] Congenital toxoplasmosis\n Def: A disease caused by an infection with the protozoan parasite Toxoplasma gondii in utero. This disease is characterised by chorioretinitis, hydrocephalus, intracranial calcifications, anaemia, or neuro...", "[1F57.3] Eye disease due to Toxoplasma gondii\n Def: Chorioretinitis or ocular toxoplasmosis is a relatively common manifestation of T. gondii infection. Ocular toxoplasmosis occurs when cysts deposited in or near the retina become active, producing tac...\n --PARENT--> [1F57] Toxoplasmosis\n Def: A disease caused by an infection with the protozoan parasite Toxoplasma gondii. This disease is characterised by fever, lymphadenitis, sore throat, or rash. Transmission is by direct ingestion of cont...\n --RELATED_TO--> [?] Congenital toxoplasmosis\n Def: A disease caused by an infection with the protozoan parasite Toxoplasma gondii in utero. This disease is characterised by chorioretinitis, hydrocephalus, intracranial calcifications, anaemia, or neuro...", "[1F57.3] Eye disease due to Toxoplasma gondii\n Def: Chorioretinitis or ocular toxoplasmosis is a relatively common manifestation of T. gondii infection. Ocular toxoplasmosis occurs when cysts deposited in or near the retina become active, producing tac...\n --PARENT--> [1F57] Toxoplasmosis\n Def: A disease caused by an infection with the protozoan parasite Toxoplasma gondii. This disease is characterised by fever, lymphadenitis, sore throat, or rash. Transmission is by direct ingestion of cont...\n --PARENT--> [?] Nonintestinal protozoal diseases\n Def: Infections with unicellular organisms of the subkingdom Protozoa....", "[1F57.Z] Toxoplasmosis, unspecified\n --PARENT--> [1F57] Toxoplasmosis\n Def: A disease caused by an infection with the protozoan parasite Toxoplasma gondii. This disease is characterised by fever, lymphadenitis, sore throat, or rash. Transmission is by direct ingestion of cont...\n --CHILD--> [1F57.0] Hepatitis due to Toxoplasma gondii\n Def: A disease of the liver, caused by an infection with the protozoan parasite Toxoplasma gondii. This disease is characterised by jaundice. Transmission is by haematogenous spread to the liver after dire...", "[1F57.Z] Toxoplasmosis, unspecified\n --PARENT--> [1F57] Toxoplasmosis\n Def: A disease caused by an infection with the protozoan parasite Toxoplasma gondii. This disease is characterised by fever, lymphadenitis, sore throat, or rash. Transmission is by direct ingestion of cont...\n --CHILD--> [1F57.1] Meningoencephalitis due to Toxoplasma gondii\n Def: A disease of the meninges and brain, caused by an infection with the protozoan parasite Toxoplasma gondii. This disease is characterised by seizures, neck pain, neurological deficits, or alterations i..." ]	1F57.Y/GB5Z	Renal tubulo-interstitial disorders due to toxoplasmoa gondii	[ { "from_icd11": "1F57.2", "icd10_code": "B583", "icd10_title": "Pulmonary toxoplasmosis" }, { "from_icd11": "1F57.3", "icd10_code": "B5800", "icd10_title": "Toxoplasma oculopathy, unspecified" }, { "from_icd11": "1F57.3", "icd10_code": "B580", "icd10_title": "Toxoplasma oculopathy" }, { "from_icd11": "1F57.Z", "icd10_code": "B5889", "icd10_title": "Toxoplasmosis with other organ involvement" }, { "from_icd11": "1F57.Z", "icd10_code": "B589", "icd10_title": "Toxoplasmosis, unspecified" }, { "from_icd11": "1F57.Z", "icd10_code": "B58", "icd10_title": "Toxoplasmosis" }, { "from_icd11": "1F57.Z", "icd10_code": "B588", "icd10_title": "Toxoplasmosis with other organ involvement" }, { "from_icd11": "1F57.1", "icd10_code": "B582", "icd10_title": "Toxoplasma meningoencephalitis" }, { "from_icd11": "QA46.Z", "icd10_code": "Z379", "icd10_title": "Outcome of delivery, unspecified" }, { "from_icd11": "QA46.Z", "icd10_code": "Z37", "icd10_title": "Outcome of delivery" }, { "from_icd11": "LD9Z", "icd10_code": "Q898", "icd10_title": "Other specified congenital malformations" }, { "from_icd11": "LD9Z", "icd10_code": "Q899", "icd10_title": "Congenital malformation, unspecified" }, { "from_icd11": "LD9Z", "icd10_code": "Q89", "icd10_title": "Other congenital malformations, not elsewhere classified" }, { "from_icd11": "LD9Z", "icd10_code": "XVII", "icd10_title": "" }, { "from_icd11": "LD9Z", "icd10_code": "Q10-Q18", "icd10_title": "" } ]	B583	Pulmonary toxoplasmosis
Case history: We have shown above a background of this case. During the course of LGESS progression, the patient had one gravida and one caesarian section. At the time of diagnosis, she had no relevant past history or family history. When she was 45 years old, a remnant tumor between her right diaphragm and liver relapsed. TC (Table 1 a: paclitaxel (140 mg/m 2 ) and carboplatin (area under the curve (AUC): 4), 7 cycles), and ifosfamide and doxorubicin combination chemotherapy (Table 1 b: ifosfamide (2 g) for 4 days + doxorubicin (30 mg) for 2 days, 3 cycles), in addition to hormonal therapy, did not decrease the tumor size . At age 46, the tumor was treated with proton therapy 70.2 GyE/26 Fr, for 40 days . The tumors in the irradiation field almost disappeared and liquefied . The remnant tumors in the thoracic and abdominal cavity, which were out of the irradiation field, were resected (Table 1 d). Originally, the tumor was pathologically diagnosed as “neuroendocrine carcinoma (NEC).” Thrombosis in the inferior vena cava led to the discontinuation of MPA (Table 1 e). Thereafter, 4 cycles of cisplatin and irinotecan combination chemotherapy were administrated for NEC (Table 1 f: cisplatin 70 mg + irinotecan 70 mg, 4 cycles, every 4 weeks). Seven months after the previous surgery, two enlarged liver metastases were detected, and another surgery was performed. After the resection of the two liver metastases and a small number of disseminated tumors, no disseminated tumors remained in the abdominal cavity. The pathological diagnosis of the resected tumor was also NEC. Although the chemotherapy was not effective for the larger liver metastases, it effectively eliminated smaller disseminated tumors. Therefore, 2 cycles of cisplatin and irinotecan combination chemotherapy were administered at 1 month and at 4 months after the operation to prevent the recurrence of dissemination (Table 1 h: cisplatin 70 mg + irinotecan 70 mg, 2 cycles, every 3 months). However, chemotherapy was discontinued because of diarrhea, lack of appetite, and general fatigue. Following this, TC (Table 1 i: paclitaxel (140 mg/m 2 ) and carboplatin (AUC: 4), 1 cycle, Table 1 l: paclitaxel (140 mg/m 2 ) and carboplatin (AUC: 4), 3 cycles), eribulin (Table 1 k: eribulin 1.4 mg/m 2 , 3 cycles.), and paclitaxel single agent (Table 1 m: paclitaxel (140 mg/m 2 ) 2 cycles) were administered. However, these chemotherapies did not show any efficacy. Surgery for liver metastases and dissemination in the spleen (Table 1 j) were successful in controlling the disease. At age 48, common biliary duct obstruction by enlarged liver metastatic tumor induced jaundice and liver dysfunction (Table 1 n). Common bile duct stents were inserted using endoscopic retrograde biliary drainage. After recovery from the condition, pazopanib (800 mg/day) was started with leuprorelin, and anastrozole (Table 1 o). Computed tomography (CT) images are shown in Fig. 2 . Before administration, multiple lung metastases, a large hepatic hilar metastatic tumor, large volume of ascites, and pelvic cavity disseminations were detected. After 12 weeks of administration, the medicine was effective. The sizes of tumors invading the right lung were reduced. The left lung metastases and pelvic disseminations reduced, and the liver metastasis partially resolved too. However, after 24 weeks of administration, the lung metastases markedly increased along with the ascites. After 3 months of the best supportive care, she had a fever and developed a hard-raised palpable lesion under the skin on the right lower back of the chest. Blood culture revealed bacteremia due to Enterobacter cloacae . CT images at 4 weeks before her death are shown in Fig. 3 . The tumor between the right diaphragm and the liver invaded into the right lung via the right thoracic cavity and into the subcutaneous tissues via the intercostal muscles. Cystic lesions were observed in the liver, which were shown in the axial slice. Finally, she died at age 49 due to sepsis after long-term treatment of advanced refractory LGESS (Table 1 p). Autopsy was then performed. The infection progressed to the liver metastatic tumor via the stented biliary ducts. Table 1 The course of treatment for this Low-grade Endometrial Stromal Sarcoma case Age The patient’s condition Treatment The outcome a : 45 y 1 m The tumor between liver and right diaphragm increased TC a , 7 cycles SD b : 45 y 9 m The tumor between liver and right diaphragm increased Ifosfamide + Doxorubicin b , 3 cycles PD c : 45 y 11 m The tumor between liver and right diaphragm increased Proton therapy, 70.2 GyE/26 Fr. For 40 days PR d : 46 y 3 m The tumors outside of the irradiation field remained Surgery for the left pleural and abdominal tumors Neuroendocrine carcinoma e : 46 y 5 m Thrombosis in inferior vena cava distal part An inferior vena cava filter. Discontinued MPA c . Disappeared 11 months later. f : 46 y 5 m Small disseminations remained at the end of the surgery d Cisplatin + Irinotecan, 4 cycles, every 4 weeks PD g : 46 y 8 m Liver metastasis increased Surgery for liver metastasis. No remnant in surgical field h : 46 y 11 m Effective for small dissemination tumors d Cisplatin + Irinotecan, 2 cycles, every 3 months Discontinued by dehydration i : 47 y 4 m Multiple lung metastases recurred TC a , one cycle. Discontinued by pneumothorax j : 47 y 11 m Abdominal and spleen dissemination increased Splenectomy and dissemination resection No remnant in surgical field k : 48 y 1 m Vaginal bleeding by recurrence in vaginal stump Eribulin 1.4 mg/m 2 , 3 cycles. PD l : 48 y 4 m The tumors increased. TC a , 3 cycles Hypersensitivity for carboplatin m : 48 y 7 m Discontinuation of carboplatin Paclitaxel (140 mg/m 2 ) 2 cycles PD n : 48 y 8 m Jaundice and liver dysfunction The common bile duct stents . Recovered liver dysfunction o : 48 y 9 m Liver metastasis increased Pazopanib hydrochloride 800 mg/day started SD to PD p : 49 y 7 m Bacterial infection from liver tumor via bile duct Antibiotics and palliative care Died with sepsis Alphabet letters before age indicate sentences concerning events in the main text. a TC: paclitaxel (140 mg/m 2 ) and carboplatin (area under the curve (AUC): 4) combination chemotherapy. b Ifosfamide + Doxorubicin: Ifosfamide (2 g) for 4 days + Doxorubicin (30 mg) for 2 days. c MPA: Medroxyprogesterone 600 mg/day. Hormonal therapy by MPA, leuprorelin 3.75 mg every 28 days, and anastrozole 1 mg/day was continued until thrombosis ( e ) except for the periods of proton therapy and surgery. After this time, hormonal therapy by leuprorelin, and anastrozole was continued until patient died. d Cisplatin + Irinotecan: Cisplatin 70 mg + Irinotecan 70 mg. PR partial response, SD stable disease, PD progress disease Fig. 1 Diagnostic image after recurrence around the right diaphragm, liver, and thoracic cavity. a Enhanced computed tomography (CT) image before proton therapy, and after chemotherapy. Red arrows indicate the tumor between the right diaphragm and liver. b Positron emission tomography-CT image during the same time as in “a”. c Planning of proton therapy. d Enhanced CT after 4 months of proton therapy. The tumors in the irradiation field disappeared and were liquefied. Red arrows indicate the liquefied tumors. e Enhanced CT image when liver metastases increased. Red arrows indicate the liver metastases Fig. 2 Computed tomography (CT) images showing the effect of pazopanib (800 mg/day). The upper, middle, and lower lines indicate chest CT, liver CT, and pelvic CT, respectively. The left, central, and right rows indicate before administration of pazopanib, 12 weeks later, and 24 weeks later, respectively. Red arrows and green arrows indicate tumors, and common bile duct stents, respectively. Chest CT images show that lung metastases reduced after 12 weeks of treatment and recurred after 24 weeks, in comparison with the first scan. Liver CT images show that liver metastatic tumors reduced and liquefied, while continuing the administration of pazopanib. Pelvic CT images show that the right pelvic dissemination tumor reduced, and there was a decrease in ascites after 12 weeks of treatment and an increase in ascites 24 weeks later Fig. 3 Diagnostic computed tomography (CT) image before the patient’s death. Axial slice and frontal slice CT scans at 4 weeks before the patient’s death. The tumor invaded into the subcutaneous tissue via the intercostal muscle. Furthermore, the tumor invaded into the pleural cavity from the liver surface via the right diaphragm	4.023438	0.972656	sec[1]/p[0]	en	0.999998	32711524	https://doi.org/10.1186/s12905-020-01019-0	[ "liver", "tumor", "cycles", "tumors", "metastases", "diaphragm", "cisplatin", "irinotecan", "paclitaxel", "chemotherapy" ]	[ { "code": "DB9Z", "title": "Diseases of liver, unspecified" }, { "code": "DB97.Z", "title": "Inflammatory liver disease, unspecified" }, { "code": "DB99.7", "title": "Hepatic failure without mention whether acute or chronic" }, { "code": "LB20.0Y", "title": "Other specified structural developmental anomalies of liver" }, { "code": "LB20.0Z", "title": "Structural developmental anomalies of liver, unspecified" }, { "code": "2F9Z", "title": "Neoplasms of unknown behaviour of unspecified site" }, { "code": "ME61", "title": "Subcutaneous swelling, mass or lump of uncertain or unspecified nature" }, { "code": "2E6Z", "title": "Carcinoma in situ of unspecified site" }, { "code": "2F91.1", "title": "Neoplasms of unknown behaviour of trachea, bronchus or lung" }, { "code": "2F92", "title": "Neoplasms of unknown behaviour of skin" } ]	=== ICD-11 CODES FOUND === [DB9Z] Diseases of liver, unspecified Also known as: Diseases of liver, unspecified \| liver disease \| liver condition NOS \| organ liver disease \| hepatopathy [DB97.Z] Inflammatory liver disease, unspecified Also known as: Inflammatory liver disease, unspecified \| Certain specified inflammatory liver diseases \| Nonspecific reactive hepatitis \| inflammatory liver disease \| hepatitis NOS [DB99.7] Hepatic failure without mention whether acute or chronic Also known as: Hepatic failure without mention whether acute or chronic \| liver decompensation \| liver function failure \| hepatic failure NOS \| liver failure NOS [LB20.0Y] Other specified structural developmental anomalies of liver Also known as: Other specified structural developmental anomalies of liver \| Alagille syndrome \| Alagille-Watson syndrome \| Arteriohepatic dysplasia \| Syndromic bile duct paucity [LB20.0Z] Structural developmental anomalies of liver, unspecified Also known as: Structural developmental anomalies of liver, unspecified \| Structural developmental anomalies of liver \| Malformations of liver \| congenital anomaly of liver \| congenital malformation of liver [2F9Z] Neoplasms of unknown behaviour of unspecified site Also known as: Neoplasms of unknown behaviour of unspecified site \| neoplasia \| neoplasm growth NOS \| tumour of unspecified site \| tumourlet of unspecified site [ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature Definition: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature Also known as: Subcutaneous swelling, mass or lump of uncertain or unspecified nature \| localised swelling, mass or lump of skin and subcutaneous tissue \| localised subcutaneous nodules \| subcutaneous nodules \| superficial subcutaneous nodules Excludes: localized adiposity \| mass and lump: breast \| enlarged lymph nodes [2E6Z] Carcinoma in situ of unspecified site Also known as: Carcinoma in situ of unspecified site \| carcinoma in situ of unspecified site \| carcinoma in situ NOS \| carcinoma in situ \| in situ neoplasm [2F91.1] Neoplasms of unknown behaviour of trachea, bronchus or lung Also known as: Neoplasms of unknown behaviour of trachea, bronchus or lung \| trachea, bronchus or lung tumour NOS \| Intravascular bronchial alveolar tumour of unspecified site \| Bronchial adenoma of unknown behaviour of unspecified site \| Intravascular bronchial alveolar tumour unknown behaviour of unspecified site [2F92] Neoplasms of unknown behaviour of skin Also known as: Neoplasms of unknown behaviour of skin \| skin tumour NOS === GRAPH WALKS === --- Walk 1 --- [DB9Z] Diseases of liver, unspecified --PARENT--> [?] Diseases of liver --RELATED_TO--> [?] Structural developmental anomalies of liver --- Walk 2 --- [DB9Z] Diseases of liver, unspecified --PARENT--> [?] Diseases of liver --RELATED_TO--> [?] Metabolic or transporter liver disease --- Walk 3 --- [DB97.Z] Inflammatory liver disease, unspecified --PARENT--> [DB97] Certain specified inflammatory liver diseases --CHILD--> [DB97.2] Chronic hepatitis, not elsewhere classified --- Walk 4 --- [DB97.Z] Inflammatory liver disease, unspecified --PARENT--> [DB97] Certain specified inflammatory liver diseases --EXCLUDES--> [?] Drug-induced or toxic liver disease Def: Drug-induced or toxic liver disease is hepatotoxicity as injury to the liver that is associated with impaired liver function caused by exposure to a drug or another noninfectious agent.... --- Walk 5 --- [DB99.7] Hepatic failure without mention whether acute or chronic --PARENT--> [DB99] Certain specified diseases of liver Def: This is a group of conditions characterised as being in or associated with the liver that are not classified elsewhere.... --CHILD--> [DB99.1] Hepatic cyst Def: This is a closed sac, having a distinct membrane and division compared to the nearby tissue. It may contain air, fluids, or semi-solid material of the liver.... --- Walk 6 --- [DB99.7] Hepatic failure without mention whether acute or chronic --PARENT--> [DB99] Certain specified diseases of liver Def: This is a group of conditions characterised as being in or associated with the liver that are not classified elsewhere.... --CHILD--> [DB99.0] Chronic liver disease	[ "[DB9Z] Diseases of liver, unspecified\n --PARENT--> [?] Diseases of liver\n --RELATED_TO--> [?] Structural developmental anomalies of liver", "[DB9Z] Diseases of liver, unspecified\n --PARENT--> [?] Diseases of liver\n --RELATED_TO--> [?] Metabolic or transporter liver disease", "[DB97.Z] Inflammatory liver disease, unspecified\n --PARENT--> [DB97] Certain specified inflammatory liver diseases\n --CHILD--> [DB97.2] Chronic hepatitis, not elsewhere classified", "[DB97.Z] Inflammatory liver disease, unspecified\n --PARENT--> [DB97] Certain specified inflammatory liver diseases\n --EXCLUDES--> [?] Drug-induced or toxic liver disease\n Def: Drug-induced or toxic liver disease is hepatotoxicity as injury to the liver that is associated with impaired liver function caused by exposure to a drug or another noninfectious agent....", "[DB99.7] Hepatic failure without mention whether acute or chronic\n --PARENT--> [DB99] Certain specified diseases of liver\n Def: This is a group of conditions characterised as being in or associated with the liver that are not classified elsewhere....\n --CHILD--> [DB99.1] Hepatic cyst\n Def: This is a closed sac, having a distinct membrane and division compared to the nearby tissue. It may contain air, fluids, or semi-solid material of the liver....", "[DB99.7] Hepatic failure without mention whether acute or chronic\n --PARENT--> [DB99] Certain specified diseases of liver\n Def: This is a group of conditions characterised as being in or associated with the liver that are not classified elsewhere....\n --CHILD--> [DB99.0] Chronic liver disease" ]	DB9Z	Diseases of liver, unspecified	[ { "from_icd11": "DB9Z", "icd10_code": "K7681", "icd10_title": "Hepatopulmonary syndrome" }, { "from_icd11": "DB9Z", "icd10_code": "K7689", "icd10_title": "Other specified diseases of liver" }, { "from_icd11": "DB9Z", "icd10_code": "K769", "icd10_title": "Liver disease, unspecified" }, { "from_icd11": "DB9Z", "icd10_code": "K77", "icd10_title": "Liver disorders in diseases classified elsewhere" }, { "from_icd11": "DB9Z", "icd10_code": "K762", "icd10_title": "Central hemorrhagic necrosis of liver" }, { "from_icd11": "DB9Z", "icd10_code": "K70-K77", "icd10_title": "" }, { "from_icd11": "DB9Z", "icd10_code": "K778", "icd10_title": "" }, { "from_icd11": "DB9Z", "icd10_code": "K72", "icd10_title": "Hepatic failure, not elsewhere classified" }, { "from_icd11": "DB9Z", "icd10_code": "K76", "icd10_title": "Other diseases of liver" }, { "from_icd11": "DB9Z", "icd10_code": "K768", "icd10_title": "Other specified diseases of liver" }, { "from_icd11": "DB97.Z", "icd10_code": "K7581", "icd10_title": "Nonalcoholic steatohepatitis (NASH)" }, { "from_icd11": "DB97.Z", "icd10_code": "K7589", "icd10_title": "Other specified inflammatory liver diseases" }, { "from_icd11": "DB97.Z", "icd10_code": "K759", "icd10_title": "Inflammatory liver disease, unspecified" }, { "from_icd11": "DB97.Z", "icd10_code": "K752", "icd10_title": "Nonspecific reactive hepatitis" }, { "from_icd11": "DB97.Z", "icd10_code": "K75", "icd10_title": "Other inflammatory liver diseases" } ]	K7681	Hepatopulmonary syndrome
Herein, we describe an unusual mesenchymal tumor occurring intracranially in a 43-year-old male, characterized by aggressive course, peculiar morphological features and showing a genetic rearrangement, involving chromosome chr12 (q13.12) and chr10 (q23.31) with loss of PTEN expression. Because of the radiological and histological features, the initial interpretation was of anaplastic meningioma . In our case, tumor cells showed patchy positivity for EMA, similarly to meningiomas, and negativity for progesterone receptor. However, tumor cells also showed diffuse positivity for CD34 and MUC4, patchy positivity for SMA, and focal positivity for CD99 and desmin, suggesting a wide spectrum of differential diagnoses. Mesenchymal non-meningothelial tumors are rare and include many entities, classified on the basis of their differentiation. Solitary fibrous tumors (SFTs) are usually dural based neoplasms, characterized by NAB2 and STAT6 fusion . SFT has a wide histological spectrum. Immunohistochemically, CD34 is typically positive, although its expression is reduced in higher grades . Other markers, such as EMA, progesterone receptor, desmin and SMA may be focally expressed. As a consequence of NAB2::STAT6 fusion, SFT usually shows diffuse and intense STAT6 nuclear expression . The case described in our study is a dural neoplasm, showing a wide morphological spectrum and CD34 immunohistochemical positivity. Conversely, STAT6 negativity and the absence of NAB2::STAT6 fusion, as confirmed by RNA sequencing, excluded the diagnosis of SFT. On the basis of the clinico-pathological features, we also excluded other mesenchymal non-meningothelial tumors and focused our attention on the subgroup of tumors with uncertain differentiation. Ewing sarcoma was also excluded, considering the different clinical, histological and molecular aspects. In the 5th edition of the WHO Classification of CNS Tumors, among the subgroup of tumors of uncertain differentiation, there are other three newly recognized entities: primary intracranial sarcoma, DICER1-mutant; CIC-rearranged sarcoma; intracranial mesenchymal tumor, FET::CREB fusion-positive. Primary intracranial sarcoma, DICER1-mutant, has been firstly described by Koelsche et al. . All these tumors were characterized by rhabdomyoblastic differentiation and DICER1 inactivating mutations. Afterward, other studies better characterized this entity, describing various histological and immunohistochemical aspects . CIC-rearranged sarcoma more commonly occurs outside the CNS, but some cases have been observed also in the brain . Some of these tumors were previously included in the wide category of CNS-PNETs, which has been now eliminated . Similarly to Ewing sarcoma, it is composed of CD99-positive undifferentiated cells, but with a more patchy pattern of expression. Molecularly, they are characterized by the presence of a fusion of CIC with various partners . Intracranial mesenchymal tumor, FET::CREB fusion-positive has been introduced in the 2021 WHO Classification of CNS tumors as a provisional entity . This tumor has been firstly described by Kao et al. , who identified a group of intracranial myxoid mesenchymal tumors, histologically resembling myxoid variant of angiomatoid fibrous histiocytoma (AFH) and characterized by fusions of EWSR1 with CREB family transcription factors ( CREB1, CREM or ATF1 ). Soon after, other studies identified similar cases, reporting variable morphological features and novel fusions involving FUS , another FET family gene, instead of EWSR1 . Histologically, they demonstrate a wide morphological spectrum. The immunohistochemical profile is also variable, but they most commonly show positivity for EMA, CD99 and desmin. Because of the broad histological and immunohistochemical spectrum, the demonstration of FET::CREB family fusions is an essential criterion for the diagnosis. After central pathology review, a possible diagnosis of FET::CREB fusion-positive intracranial mesenchymal tumor was considered. FISH assay revealed no EWSR1 rearrangements and RNA sequencing excluded other FET::CREB family fusions. Furthermore, DNA methylation profile found no matches with other known entities. The closer match in CNS tumors classifier v12.5, with 0.69 calibrated score, was malignant peripheral nerve sheath tumor (MPNST), but negativity for S100 and SOX10, along with preserved H3K27me3 nuclear expression, suggested this diagnosis as improbable . However, when analyzed by the sarcoma classifier, the tumor clustered within the methylation class “Sarcoma, MPNST-like”, with a calibrated score of 0.89. Such class has a provisional name and is based on tumors with morphological features of malignant peripheral nerve sheath tumor, but with retained expression of H3K27me3 . This subgroup has been described by Röhrich et al. In their study, they identified 6 cases (5 sporadic, 1 NF1-associated), all with spinal or paravertebral localization and with a median age of 50 years (age range 10–77). All of them were characterized by retained H3K27 trimethylation marker, distinguishing them from MPNSTs. Copy number alterations were numerous with frequent losses on chromosome arms 3q (> 80%), 5q (> 80%), 9p (100%) and 17q (> 70%). Copy number analysis showed a high frequency of CDKN2A/B homozygous deletion on chromosome arm 9p (> 40%). Further molecular features of this class included mutations in NF1. Some of copy number alterations seemed to be shared with MPNSTs, but others were more frequently encountered in this class, such as 3q loss, 5p gain and CDKN2A homozygous deletion. In our case, CNV analysis showed several structural alterations. In particular, CDKN2A deletion, as observed in MPNST-like tumors, and loss of PTEN as a possible consequence of the genetic imbalance due to the above-mentioned rearrangement. Searching in literature and in the ChimerDB 4.0, a comprehensive and updated database of fusion genes (available online at http://www.kobic.re.kr/chimerdb/ ) , we found no data regarding this specific rearrangement. Instead, the two genes, COX14 and PTEN , are independently involved, with other genes as fusion partners, in rare cases of gliomas and mesenchymal tumors. The COX14 gene is located on the long arm of chromosome 12 and encodes for a core protein component of the enzyme MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex), which is required for the proper assembly of complex IV of the mitochondrial respiratory chain . COX14 variants have been associated with complex IV deficiency, characterized by different phenotypes, such as myopathy, cardiomyopathy, liver dysfunction and mental retardation . Even though high levels of mRNA have been reported in different types of malignant neoplasms, particularly in prostatic adenocarcinoma , the role of COX14 in cancer pathogenesis is still unclear. The PTEN gene is located on the long arm of chromosome 10 and encodes for PTEN protein (phosphatase and tensin homolog), an enzyme with phosphatase activity and crucial role as tumor suppressor. In fact, its loss of function is frequently observed in both heritable and sporadic neoplasms . In our case, PTEN rearrangement showed disruption of C2 domain, suggesting PTEN loss of function, as demonstrated by its loss of expression in immunohistochemistry, and a pathogenic role in the tumor development. In a study by Williams et al. , PTEN gene has been found altered in some cases of high-grade meningiomas. In this study, PTEN alterations were mainly represented by mutation or focal gene deletions, with only one case showing a PTEN-TMEM38A rearrangement. Additionally, PTEN mutations were found to be more frequently associated with a WHO grade 3 than grade 2 or 1. PTEN is rarely mutated in MPNST , but in two studies MPNST showed reduced PTEN expression compared to neurofibroma . Interestingly, the lack of both NF1 and PTEN led to accelerated neurofibroma development and favored progression from low-grade to high-grade PNSTs in a transgenic murine model . However, PTEN has been found downregulated, with variable frequency, also in other sarcoma subtypes. These findings highlight its important role as tumor suppressor, but its prognostic and predictive role are still controversial. Only a small percentage of PTEN-deficient tumors have inactivating mutations, while PTEN function can also be lost through non-genomic mechanisms, including protein-protein interactions, epigenetic and transcriptional silencing and post-translational modifications .	4.492188	0.625	sec[3]/p[0]	en	0.999997	37312212	https://doi.org/10.1186/s40478-023-01596-9	[ "pten", "tumors", "tumor", "fusion", "sarcoma", "mesenchymal", "characterized", "expression", "this", "features" ]	[ { "code": "LD2D.Y", "title": "Other specified phakomatoses or hamartoneoplastic syndromes" }, { "code": "2F9Z", "title": "Neoplasms of unknown behaviour of unspecified site" }, { "code": "ME61", "title": "Subcutaneous swelling, mass or lump of uncertain or unspecified nature" }, { "code": "2E6Z", "title": "Carcinoma in situ of unspecified site" }, { "code": "2F91.1", "title": "Neoplasms of unknown behaviour of trachea, bronchus or lung" }, { "code": "2F92", "title": "Neoplasms of unknown behaviour of skin" }, { "code": "FA34.4", "title": "Ankylosis of joint" }, { "code": "LB17.2", "title": "Persistent cloaca" }, { "code": "FB00", "title": "Ankylosis of spinal joint" }, { "code": "LD2G", "title": "Conjoined twins" } ]	=== ICD-11 CODES FOUND === [LD2D.Y] Other specified phakomatoses or hamartoneoplastic syndromes Also known as: Other specified phakomatoses or hamartoneoplastic syndromes \| Congenital hypothalamic hamartoma syndrome \| Segmental outgrowth - lipomatosis - arteriovenous malformation - epidermal naevus \| Hereditary neurocutaneous angioma \| Bannayan-Riley-Ruvalcaba syndrome [2F9Z] Neoplasms of unknown behaviour of unspecified site Also known as: Neoplasms of unknown behaviour of unspecified site \| neoplasia \| neoplasm growth NOS \| tumour of unspecified site \| tumourlet of unspecified site [ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature Definition: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature Also known as: Subcutaneous swelling, mass or lump of uncertain or unspecified nature \| localised swelling, mass or lump of skin and subcutaneous tissue \| localised subcutaneous nodules \| subcutaneous nodules \| superficial subcutaneous nodules Excludes: localized adiposity \| mass and lump: breast \| enlarged lymph nodes [2E6Z] Carcinoma in situ of unspecified site Also known as: Carcinoma in situ of unspecified site \| carcinoma in situ of unspecified site \| carcinoma in situ NOS \| carcinoma in situ \| in situ neoplasm [2F91.1] Neoplasms of unknown behaviour of trachea, bronchus or lung Also known as: Neoplasms of unknown behaviour of trachea, bronchus or lung \| trachea, bronchus or lung tumour NOS \| Intravascular bronchial alveolar tumour of unspecified site \| Bronchial adenoma of unknown behaviour of unspecified site \| Intravascular bronchial alveolar tumour unknown behaviour of unspecified site [2F92] Neoplasms of unknown behaviour of skin Also known as: Neoplasms of unknown behaviour of skin \| skin tumour NOS [FA34.4] Ankylosis of joint Definition: The term ankylosis denotes restricted movement in the joint, and it can be bony or fibrous. Most cases are caused by trauma, infection, radiotherapy, or severe arthritic condition. Also known as: Ankylosis of joint \| ankylosis \| ankylosis of joint, site unspecified \| frozen joint \| fusion of joint Excludes: stiffness of joint without ankylosis \| Ankylosis of spinal joint [LB17.2] Persistent cloaca Definition: A congenital anomaly in which the intestinal, urinary, and reproductive ducts open into a common cavity, a result of the failure of the urorectal septum to form during prenatal development. They occur exclusively in girls and comprise the most complex defect in the spectrum of anorectal malformations. Also known as: Persistent cloaca \| anal and urogenital canal fusion \| anal fusion \| Cloaca NOS [FB00] Ankylosis of spinal joint Also known as: Ankylosis of spinal joint \| ankylosis of spine nos \| fusion of vertebra NOS \| fusion of spine NOS \| Ankylosis of cervical spinal joint [LD2G] Conjoined twins Definition: A condition characterised as twins that are physically united at some part or parts of their bodies at the time of birth. Also known as: Conjoined twins \| siamese twin \| twin fusion \| Thoracopagus \| thorax-joined twins === GRAPH WALKS === --- Walk 1 --- [LD2D.Y] Other specified phakomatoses or hamartoneoplastic syndromes --PARENT--> [LD2D] Phakomatoses or hamartoneoplastic syndromes --EXCLUDES--> [?] Hereditary haemorrhagic telangiectasia Def: Rendu-Osler-Weber disease, also called hereditary haemorrhagic telangiectasia (HHT), is a genetic disorder of angiogenesis leading to arteriovenous dilatations: cutaneo-mucosal haemorrhagic telangiect... --- Walk 2 --- [LD2D.Y] Other specified phakomatoses or hamartoneoplastic syndromes --PARENT--> [LD2D] Phakomatoses or hamartoneoplastic syndromes --RELATED_TO--> [?] NAME syndrome --- Walk 3 --- [2F9Z] Neoplasms of unknown behaviour of unspecified site --PARENT--> [?] Neoplasms of unknown behaviour, except of lymphoid, haematopoietic, central nervous system or related tissues --CHILD--> [2F92] Neoplasms of unknown behaviour of skin --- Walk 4 --- [2F9Z] Neoplasms of unknown behaviour of unspecified site --PARENT--> [?] Neoplasms of unknown behaviour, except of lymphoid, haematopoietic, central nervous system or related tissues --CHILD--> [2F91] Neoplasms of unknown behaviour of middle ear, respiratory or intrathoracic organs --- Walk 5 --- [ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature Def: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature... --EXCLUDES--> [?] Breast lump or mass female --PARENT--> [?] Symptoms, signs or clinical findings involving the female genital system --- Walk 6 --- [ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature Def: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature... --EXCLUDES--> [?] Localised adiposity Def: A condition characterised by accumulation of adipose tissue in specific regions of the body.... --CHILD--> [?] Fatty apron	[ "[LD2D.Y] Other specified phakomatoses or hamartoneoplastic syndromes\n --PARENT--> [LD2D] Phakomatoses or hamartoneoplastic syndromes\n --EXCLUDES--> [?] Hereditary haemorrhagic telangiectasia\n Def: Rendu-Osler-Weber disease, also called hereditary haemorrhagic telangiectasia (HHT), is a genetic disorder of angiogenesis leading to arteriovenous dilatations: cutaneo-mucosal haemorrhagic telangiect...", "[LD2D.Y] Other specified phakomatoses or hamartoneoplastic syndromes\n --PARENT--> [LD2D] Phakomatoses or hamartoneoplastic syndromes\n --RELATED_TO--> [?] NAME syndrome", "[2F9Z] Neoplasms of unknown behaviour of unspecified site\n --PARENT--> [?] Neoplasms of unknown behaviour, except of lymphoid, haematopoietic, central nervous system or related tissues\n --CHILD--> [2F92] Neoplasms of unknown behaviour of skin", "[2F9Z] Neoplasms of unknown behaviour of unspecified site\n --PARENT--> [?] Neoplasms of unknown behaviour, except of lymphoid, haematopoietic, central nervous system or related tissues\n --CHILD--> [2F91] Neoplasms of unknown behaviour of middle ear, respiratory or intrathoracic organs", "[ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature\n Def: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature...\n --EXCLUDES--> [?] Breast lump or mass female\n --PARENT--> [?] Symptoms, signs or clinical findings involving the female genital system", "[ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature\n Def: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature...\n --EXCLUDES--> [?] Localised adiposity\n Def: A condition characterised by accumulation of adipose tissue in specific regions of the body....\n --CHILD--> [?] Fatty apron" ]	LD2D.Y	Other specified phakomatoses or hamartoneoplastic syndromes	[ { "from_icd11": "2F9Z", "icd10_code": "D487", "icd10_title": "Neoplasm of uncertain behavior of other specified sites" }, { "from_icd11": "2F9Z", "icd10_code": "D482", "icd10_title": "Neoplasm of uncertain behavior of peripheral nerves and autonomic nervous system" }, { "from_icd11": "2F9Z", "icd10_code": "D37-D48", "icd10_title": "" }, { "from_icd11": "2F9Z", "icd10_code": "D377", "icd10_title": "" }, { "from_icd11": "2F9Z", "icd10_code": "D48", "icd10_title": "Neoplasm of uncertain behavior of other and unspecified sites" }, { "from_icd11": "2F9Z", "icd10_code": "D489", "icd10_title": "Neoplasm of uncertain behavior, unspecified" }, { "from_icd11": "ME61", "icd10_code": "R2240", "icd10_title": "Localized swelling, mass and lump, unspecified lower limb" }, { "from_icd11": "ME61", "icd10_code": "R2232", "icd10_title": "Localized swelling, mass and lump, left upper limb" }, { "from_icd11": "ME61", "icd10_code": "R2242", "icd10_title": "Localized swelling, mass and lump, left lower limb" }, { "from_icd11": "ME61", "icd10_code": "R2231", "icd10_title": "Localized swelling, mass and lump, right upper limb" }, { "from_icd11": "ME61", "icd10_code": "R2241", "icd10_title": "Localized swelling, mass and lump, right lower limb" }, { "from_icd11": "ME61", "icd10_code": "R2233", "icd10_title": "Localized swelling, mass and lump, upper limb, bilateral" }, { "from_icd11": "ME61", "icd10_code": "R2243", "icd10_title": "Localized swelling, mass and lump, lower limb, bilateral" }, { "from_icd11": "ME61", "icd10_code": "R2230", "icd10_title": "Localized swelling, mass and lump, unspecified upper limb" }, { "from_icd11": "ME61", "icd10_code": "R220", "icd10_title": "Localized swelling, mass and lump, head" } ]	D487	Neoplasm of uncertain behavior of other specified sites
The patient was born at 39 weeks of gestation and delivered by Cesarean section due to polyhydramnios. She was 3295 g at birth. Although short stature and abnormal facial features such as depressed nose, deeply grooved philtrum, and macroglossia were recognized at birth, the signs were not associated with any particular diagnosis. At 1 year of age, she was diagnosed with pulmonary valve stenosis. At 5 years of age, a balloon valvuloplasty for severe PS was performed; however, it was not sufficient to reduce the pressure gradient of PS (from 80 mmHg to 50 mmHg). At 6 years of age, surgical valvuloplasty to enlarge the annulus and reconstruct the right ventricular outflow tract was performed, which resulted in the disappearance of the PS pressure gradient. She was followed-up at our hospital yearly. Although echocardiogram showed mild PR, her clinical condition was good without specific medical treatment. When she was a high school student, she discontinued regular medical follow-up, and started studying abroad at 18 years of age. She occasionally experienced transient leg edema during this time. At 21 years of age, she developed dyspnea, edema, and abdominal bloating. She returned to Japan; thereafter, she required an emergency hospitalization. She was diagnosed with acute decompensated heart failure, which was mainly right-sided heart failure due to severe PR and TR. It was thought that PR had been subclinically exacerbated after the surgical valvuloplasty, resulting in right-ventricular volume overload. She was also diagnosed with protein-losing enteropathy associated with abnormalities in lymphatic drainage. Echocardiography showed no evidence of HCM, MS, or PS recurrence. Cardiac catheterization revealed a normal cardiac index of 3.9 L/min/m 2 , and a normal estimated mitral valve area of 4.13 cm 2 /m 2 . On the basis of the history of PS and characteristic physical features including short stature, webbed neck, and hypertelorism, she was clinically diagnosed with NS for the first time. A chromosomal study showed 46XX with no abnormality of chromosome 12. The patient refused genetic testing. She was successfully treated with a loop diuretic, beta-blocker, angiotensin-converting enzyme inhibitor, and aldosterone inhibitor. After discharge, she resumed regular follow-up at the local hospital. Although the symptoms of heart failure, such as dyspnea and edema, persisted with a New York Heart Association class of II these symptoms could be controlled with oral medical treatment. There were no records regarding the follow-up echocardiographic findings at the local hospital. At 25 years of age, she was admitted to the local hospital again for massive ascites and marked edema and was referred to our hospital. Her height was 107 cm and her weight was 33 kg. She had a body temperature of 36.8 °C, blood pressure of 90/50 mmHg, regular pulse rate of 125 beats/min, respiratory rate of 18 breaths/min, and oxygen saturation of 95% without oxygen administration. On physical examination, she exhibited jugular venous distention at her neck, and systolic and diastolic regurgitant murmur at the left sternal border. Her breath sounds were decreased, and she had abdominal distention with no tenderness and significant leg edema. Laboratory data upon hospitalization are shown in Table 1 . Chest radiography showed heart enlargement with cardiothoracic ratio of 63%, pulmonary edema, and bilateral pleural effusion . Electrocardiogram showed sinus tachycardia with right axis deviation. Echocardiogram showed enlargement of the right-side heart with displacement of the ventricular septal wall, as well as severe PR, TR, and severe MS with a mean pressure gradient of 10 mmHg and mild thickening of the mitral valve leaflets . Since diastolic function based on the early diastolic mitral septal annular velocity was normal, it was unlikely that the patient had restrictive cardiomyopathy or constrictive pericarditis. Cardiac catheterization revealed a mean pulmonary artery pressure of 49 mmHg, a mean pulmonary artery wedge pressure of 33 mmHg, a left ventricular end-diastolic pressure of 24 mmHg, a low cardiac index of 1.9 L/min/m 2 , and confirmed severe MS with an estimated mitral valve area of 0.81 cm 2 /m 2 . Coronary arteries were intact. There was no evidence of rheumatic change or infectious endocarditis; the etiology of the late-onset MS was uncertain. Computed tomography of the chest and abdomen showed massive ascites as well as plural effusion and atelectasis in the right lung. On the basis of these findings, she was diagnosed with heart failure of both sides, which was mainly caused by severe PR and TR after surgical valvuloplasty for PS as well as the late-onset severe MS with uncertain etiology. Moreover, her abdominal ultrasonogram findings, including irregular external contour, enlarged left liver lobe, and splenomegaly, indicated that she had developed cirrhosis. This was thought to be associated with long-standing right-side heart failure, because of the negative viral or other hepatitis screening. Results of the analysis of ascites and plural effusion were consistent with a pure transudate. Thus, excessive fluid of the chest and abdomen was considered to have been caused by the chronic right-side heart failure in addition to the severe hypoalbuminemia associated with advanced cirrhosis and protein-losing enteropathy. In addition to the abdominal and chest drainage, fluid management using furosemide, tolvaptan, and carperitide was successfully performed. We discussed a treatment strategy with surgeons, including mitral valve replacement, tricuspid valvuloplasty, and right ventricular outflow tract reconstruction; however, considering the patient’s low left ventricular function, cirrhosis, very low albumin level, and atelectasis caused by the long-standing pleural effusion, surgical options were considered to be extremely high risk. In addition, transcatheter cardiac intervention could not be performed in Japan at that time. Therefore, we continued the optimal medication treatment as well as the occasional abdominal cavity drainage for recurrent ascites. Unfortunately, after repeated hospitalizations for ascites and edema, she died of decompensated heart failure 2 years later. Table 1 Laboratory data Parameter Recorded value Standard value White blood cell count 10.5 × 10^3 /L 3.40–7.30 × 10^3 /L Red blood cell count 3.98 × 10^6 /L 3.62–4.99 × 10^6 /L Hemoglobin 11.7 g/dL 11.7–15.1 g/dL Hematocrit 36.5% 34.1–45.3% Platelet 407 × 10^3 /L 160–327 × 10^3 /L C-reactive protein 0.60 mg/dL ≦0.20 mg/dL Total protein 3.5 g/dL 6.4–8.4 g/dL Albumin 1.8 g/dL 3.9–5.2 g/dL Total bilirubin 0.23 mg/dL 0.2–1.0 mg/dL Aspartate aminotransferase 19 U/L 12–35 U/L Alanine aminotransferase 13 U/L 6–33 U/L Lactate dehydrogenase 226 U/L 114–243 U/L Alkaline phosphatase 274 U/L 120–362 U/L γ-glutamyltranspeptidase 57 U/L 3–54 IU/L Creatinine 0.20 mg/dL 0.30–1.10 mg/dL Sodium 137 mEq/L 138–150 mEq/L Potassium 4.4 mEq/L 3.6–5.0 mEq/L Glucose 99 mg/dl 98–109 mg/dl B-type natriuretic peptide 39.1 pg/mL < 18.4 pg/mL Total cholesterol 156 mg/dL 125–220 mg/dL Glucose 102 mg/dL 65–110 mg/dL Thyroid stimulating hormone 3.647 μIU/mL 0.350–4.940μIU/mL Free-T3 1.97 pg/mL 1.71–3.71 pg/mL Free-T4 0.87 ng/dL 0.70–1.48 ng/dL Type IV collagen 7S 9.2 ng/mL < 6.0 ng/mL Hyaluronic acid 97 ng/mL < 50 ng/mL Prothrombin time 12.4 s 10.2–14.0 s Fig. 1 Chest radiogram showing heart enlargement with cardiothoracic ratio of 63%, pulmonary edema, and bilateral pleural effusion Fig. 2 Echocardiogram in the parasternal long axis view showing the enlargement of the right-side heart and the thickening of the mitral valve leaflets. RV, right ventricle; LV, left ventricle; LA, left atrium Fig. 3 Echocardiogram in the short-axis view showing displacement of the ventricular septal wall due to the enlarged right-side heart. RV, right ventricle; LV, left ventricle Fig. 4 Echocardiogram in the short-axis view of aortic valve level showing severe pulmonary regurgitation. a : B-mode image; b : Color Doppler image. RV, right ventricle; RVOT, right ventricle outflow tract Fig. 5 Echocardiogram in the apical view showing severe tricuspid regurgitation a : B-mode image, b : Color Doppler image. RV, right ventricle; RA, right atrium Fig. 6 Echocardiogram in the apical view showing severe mitral stenosis with a mean pressure gradient of 10 mmHg with mild thickening of the mitral valve leaflets. a : B-mode image, b : Continuous-wave Doppler method. RV, right ventricle; LV, left ventricle	3.921875	0.981445	sec[1]/p[0]	en	0.999997	30012103	https://doi.org/10.1186/s12872-018-0878-1	[ "heart", "ventricle", "valve", "pressure", "mmhg", "edema", "mitral", "ventricular", "echocardiogram", "failure" ]	[ { "code": "BE2Y", "title": "Other specified diseases of the circulatory system" }, { "code": "BC4Z", "title": "Diseases of the myocardium or cardiac chambers, unspecified" }, { "code": "BD1Z", "title": "Heart failure, unspecified" }, { "code": "LA8Z", "title": "Structural developmental anomaly of heart or great vessels, unspecified" }, { "code": "BA41.Z", "title": "Acute myocardial infarction, unspecified" }, { "code": "LA89.Z", "title": "Functionally univentricular heart, unspecified" }, { "code": "BC45", "title": "Cardiomegaly" }, { "code": "BC46&XA7XU8", "title": "Ventricular thrombosis" }, { "code": "BD1Z&XT5R", "title": "Acute heart failure" }, { "code": "GB61.Z", "title": "Chronic kidney disease, stage unspecified" } ]	=== ICD-11 CODES FOUND === [BE2Y] Other specified diseases of the circulatory system Also known as: Other specified diseases of the circulatory system \| Certain specified forms of heart disease \| Cardiac disorder, unspecified \| disorder of heart NOS \| organic disease or disorder of heart [BC4Z] Diseases of the myocardium or cardiac chambers, unspecified Also known as: Diseases of the myocardium or cardiac chambers, unspecified \| Heart disease NOS \| cardiac disease NOS [BD1Z] Heart failure, unspecified Also known as: Heart failure, unspecified \| myocardial failure \| cardiac decompensation \| cardiac failure \| cardiac failure NOS [LA8Z] Structural developmental anomaly of heart or great vessels, unspecified Also known as: Structural developmental anomaly of heart or great vessels, unspecified \| Heart malformations \| Cardiac malformations \| congenital anomaly of heart \| congenital heart disease [BA41.Z] Acute myocardial infarction, unspecified Also known as: Acute myocardial infarction, unspecified \| Acute myocardial infarction \| cardiac attack \| heart attack \| acute cardiac infarction [LA89.Z] Functionally univentricular heart, unspecified Also known as: Functionally univentricular heart, unspecified \| Functionally univentricular heart \| Univentricular cardiopathy \| Single ventricle \| univentricular heart [BC45] Cardiomegaly Also known as: Cardiomegaly \| enlargement of heart \| hypertrophic heart \| heart hypertrophy \| Cardiac hypertrophy Includes: Left ventricular hyperplasia [GB61.Z] Chronic kidney disease, stage unspecified Also known as: Chronic kidney disease, stage unspecified \| Chronic kidney disease \| chronic renal failure \| chronic kidney failure \| chronic renal disease === GRAPH WALKS === --- Walk 1 --- [BE2Y] Other specified diseases of the circulatory system --PARENT--> [11] Diseases of the circulatory system Def: This refers to diseases of the organ system that passes nutrients (such as amino acids, electrolytes and lymph), gases, hormones, blood cells, etc. to and from cells in the body to help fight diseases... --EXCLUDES--> [?] Certain infectious or parasitic diseases Def: This chapter includes certain conditions caused by pathogenic organisms or microorganisms, such as bacteria, viruses, parasites or fungi.... --- Walk 2 --- [BE2Y] Other specified diseases of the circulatory system --PARENT--> [11] Diseases of the circulatory system Def: This refers to diseases of the organ system that passes nutrients (such as amino acids, electrolytes and lymph), gases, hormones, blood cells, etc. to and from cells in the body to help fight diseases... --RELATED_TO--> [?] Functional vascular disorders of the skin Def: Skin disorders due to disturbances in vascular tone and skin blood flow.... --- Walk 3 --- [BC4Z] Diseases of the myocardium or cardiac chambers, unspecified --PARENT--> [?] Diseases of the myocardium or cardiac chambers Def: This refers to diseases of a type of involuntary striated muscle found in the walls and histological foundation of the heart, with specific reference to the atrial and ventricular chambers, as well as... --CHILD--> [BC42] Myocarditis Def: Myocarditis (inflammatory cardiomyopathy) is inflammation of the heart muscle generally in the presence of a dilated cardiomyopathy that results from exposure to either discrete infectious external an... --- Walk 4 --- [BC4Z] Diseases of the myocardium or cardiac chambers, unspecified --PARENT--> [?] Diseases of the myocardium or cardiac chambers Def: This refers to diseases of a type of involuntary striated muscle found in the walls and histological foundation of the heart, with specific reference to the atrial and ventricular chambers, as well as... --PARENT--> [11] Diseases of the circulatory system Def: This refers to diseases of the organ system that passes nutrients (such as amino acids, electrolytes and lymph), gases, hormones, blood cells, etc. to and from cells in the body to help fight diseases... --- Walk 5 --- [BD1Z] Heart failure, unspecified --PARENT--> [?] Heart failure --PARENT--> [11] Diseases of the circulatory system Def: This refers to diseases of the organ system that passes nutrients (such as amino acids, electrolytes and lymph), gases, hormones, blood cells, etc. to and from cells in the body to help fight diseases... --- Walk 6 --- [BD1Z] Heart failure, unspecified --PARENT--> [?] Heart failure --EXCLUDES--> [?] Complications following abortion, ectopic or molar pregnancy Def: Any complication affecting pregnant females, caused by or subsequent to abortion, ectopic, and molar pregnancy....	[ "[BE2Y] Other specified diseases of the circulatory system\n --PARENT--> [11] Diseases of the circulatory system\n Def: This refers to diseases of the organ system that passes nutrients (such as amino acids, electrolytes and lymph), gases, hormones, blood cells, etc. to and from cells in the body to help fight diseases...\n --EXCLUDES--> [?] Certain infectious or parasitic diseases\n Def: This chapter includes certain conditions caused by pathogenic organisms or microorganisms, such as bacteria, viruses, parasites or fungi....", "[BE2Y] Other specified diseases of the circulatory system\n --PARENT--> [11] Diseases of the circulatory system\n Def: This refers to diseases of the organ system that passes nutrients (such as amino acids, electrolytes and lymph), gases, hormones, blood cells, etc. to and from cells in the body to help fight diseases...\n --RELATED_TO--> [?] Functional vascular disorders of the skin\n Def: Skin disorders due to disturbances in vascular tone and skin blood flow....", "[BC4Z] Diseases of the myocardium or cardiac chambers, unspecified\n --PARENT--> [?] Diseases of the myocardium or cardiac chambers\n Def: This refers to diseases of a type of involuntary striated muscle found in the walls and histological foundation of the heart, with specific reference to the atrial and ventricular chambers, as well as...\n --CHILD--> [BC42] Myocarditis\n Def: Myocarditis (inflammatory cardiomyopathy) is inflammation of the heart muscle generally in the presence of a dilated cardiomyopathy that results from exposure to either discrete infectious external an...", "[BC4Z] Diseases of the myocardium or cardiac chambers, unspecified\n --PARENT--> [?] Diseases of the myocardium or cardiac chambers\n Def: This refers to diseases of a type of involuntary striated muscle found in the walls and histological foundation of the heart, with specific reference to the atrial and ventricular chambers, as well as...\n --PARENT--> [11] Diseases of the circulatory system\n Def: This refers to diseases of the organ system that passes nutrients (such as amino acids, electrolytes and lymph), gases, hormones, blood cells, etc. to and from cells in the body to help fight diseases...", "[BD1Z] Heart failure, unspecified\n --PARENT--> [?] Heart failure\n --PARENT--> [11] Diseases of the circulatory system\n Def: This refers to diseases of the organ system that passes nutrients (such as amino acids, electrolytes and lymph), gases, hormones, blood cells, etc. to and from cells in the body to help fight diseases...", "[BD1Z] Heart failure, unspecified\n --PARENT--> [?] Heart failure\n --EXCLUDES--> [?] Complications following abortion, ectopic or molar pregnancy\n Def: Any complication affecting pregnant females, caused by or subsequent to abortion, ectopic, and molar pregnancy...." ]	BE2Y	Other specified diseases of the circulatory system	[ { "from_icd11": "BC4Z", "icd10_code": "I5181", "icd10_title": "Takotsubo syndrome" }, { "from_icd11": "BC4Z", "icd10_code": "I5189", "icd10_title": "Other ill-defined heart diseases" }, { "from_icd11": "BC4Z", "icd10_code": "I519", "icd10_title": "Heart disease, unspecified" }, { "from_icd11": "BC4Z", "icd10_code": "I510", "icd10_title": "Cardiac septal defect, acquired" }, { "from_icd11": "BC4Z", "icd10_code": "I515", "icd10_title": "Myocardial degeneration" }, { "from_icd11": "BC4Z", "icd10_code": "I51", "icd10_title": "Complications and ill-defined descriptions of heart disease" }, { "from_icd11": "BC4Z", "icd10_code": "I516", "icd10_title": "" }, { "from_icd11": "BC4Z", "icd10_code": "I518", "icd10_title": "Other ill-defined heart diseases" }, { "from_icd11": "BD1Z", "icd10_code": "I5023", "icd10_title": "Acute on chronic systolic (congestive) heart failure" }, { "from_icd11": "BD1Z", "icd10_code": "I5030", "icd10_title": "Unspecified diastolic (congestive) heart failure" }, { "from_icd11": "BD1Z", "icd10_code": "I5031", "icd10_title": "Acute diastolic (congestive) heart failure" }, { "from_icd11": "BD1Z", "icd10_code": "I5022", "icd10_title": "Chronic systolic (congestive) heart failure" }, { "from_icd11": "BD1Z", "icd10_code": "I5084", "icd10_title": "End stage heart failure" }, { "from_icd11": "BD1Z", "icd10_code": "I5020", "icd10_title": "Unspecified systolic (congestive) heart failure" }, { "from_icd11": "BD1Z", "icd10_code": "I5021", "icd10_title": "Acute systolic (congestive) heart failure" } ]	I5181	Takotsubo syndrome
Throughout the patient's hospitalization in our department, the majority of laboratory tests and cerebrospinal fluid analysis yielded normal results. However, the patient did indeed exhibit motor paralysis in the left upper limb, as evidenced by a score of 3 out of 5 on the manual muscle test (MMT). The plain cerebral MRI scan showed the presence of patchy mixed signal shadows in the right fronto-parietal lobe, particularly in the precentral gyrus area. These shadows were characterized by slightly prolonged T1 and T2 signals, mixed with patchy areas of short T2 signals. Additionally, a significant area of edema was observed surrounding these lesions. In the right parietal and occipital lobes, some lesions exhibited low signal intensity while others displayed high signal intensity, indicative of potential softening lesions . Enhanced brain MRI imaging revealed a heterogeneous nodular mixed signal shadow in the right precentral gyrus, surrounded by a large area of edema, suggesting a potential presence of space-occupying lesion in this area. Some lesions in the right parieto-occipital lobe showed low signal intensity, while other lesions showed high signal intensity, indicating the possibility of softening lesions forming in the right parieto-occipital lobe . The video electroencephalogram (VEEG) results showed the occasional presense of atypical sharp wave components with medium amplitude (46–78 µV) around 5.4 Hz in the right frontal area during light sleep, but no abnormalities were detected in the rest . Thorough questioning of the patient's history revealed that he had the habit of consuming raw food during his time working in the coastal area of Guangdong Province. Additionally, the patient had suffered trauma to his right occipital region over a decade ago. Following a comprehensive multimodal assessment and multidisciplinary discussion, the patient's diagnosis was considered as “1.space-occupying lesions in the right frontal lobes and parietal lobes; 2.space-occupying lesions in the right occipital lobe; 3.secondary epilepsy: Jacksonian epilepsy without disturbance of consciousness”. The medical team considered that the space-occupying lesion present on the patient's right frontal and parietal lobe was highly suspected to be caused by parasitic infection. Furthermore, the space-occupying lesion in the right occipital lobe was identified as the underlying cause of the patient's visual field defect, which may stem from a previous brain trauma during his adolescence. Our team provided a detailed explanation of the patient’s condition, feasible treatment options and related risks to the patient and his family. The primary concern for the patient is to solve the problem of the recurrence of epilepsy. The critical approach to addressing this issue involved accurate localization and maximal resection of epileptic lesions within the functional brain areas, while minimizing unnecessary damage to surrounding brain tissue. Meanwhile, two surgical methods: traditional craniotomy to remove lesions or stereotactic intracranial lesion biopsy technology were provided to patient and his families. We also recommended the patient for further parasite-specific testing identify etiology, but this proposal was rejected. Finally, the patient and his families chose stereotaxic intracranial lesion biopsy technology including framed and frameless stereotactic techniques . Frameless stereotactic technology consists of two main types: neurosurgical navigation systems and neurosurgical robots [ 10 – 13 ]. Our epilepsy team utilized neurosurgery robot-assisted frameless stereotaxic technology along with intraoperative SEEG monitoring technology. The neurosurgical robot used in the operation utilizes the Huake Precision® SR1-3D independently developed by Huake Precision (Beijing) Medical Technology Co., Ltd, using 3D structured light technology and HoloShot intelligent sensing technology to provide neurosurgeons with precise, convenient and effective surgical assistance during the operation. The surgical plan and surgical procedures are generally summarized as follows. In the preoperative preparation stage, three steps were involved: (1) replicated the patient’s preoperative head CT, MRI and other imaging examination information to formulate a surgical plan; (2) inserted 5 metal markers at different positions on the patient's skull, performed a thin-slice CT positioning scan with a slice thickness of 1–2 mm, and copied the acquired image information to the neurosurgery robot computer workstation in the operating room; (3) the epilepsy surgery team utilized the “surgical treatment planning” software on the neurosurgical robot’s computer to integrate the surgical plan and thin-slice CT images information through multi-modal image fusion for accurate positioning. During the operation, the specific surgical steps were as follows. (1) The patient was brought into the operating room and placed supine on the operating bed, where he underwent general anesthesia. The epilepsy surgeon used a head frame to fix the patient's head on the operating bed, and then connected and fixed the position between the patient's operating bed and the neurosurgery robot. Subsequently, the team used the robotic arm working platform of the neurosurgical robot to register and matched the markers, outlining the lesion and creating a three-dimensional visualization of the target path. This process involved obtaining the three-dimensional coordinates of the target (X, Y, Z), calculating the optimal cranial entry point and biopsy trajectory, as well as determining the precise location of the target coordinates. (2) Following the determination of the optimal cranial entry point coordinates, the surgeon designed a linear incision centered on the right fronto-parietal lobe lesion measuring about 5 cm in length. After routine disinfection and draping procedures, the galea aponeurosis of the scalp was incised in layers. Bipolar electrocoagulation was employed to stop bleeding, and a spreader was used to expand the skin and muscle flaps for the skull exposure. A hole was then drilled into the skull to form a circular bone flap, which was subsequently removed to form a 4*3 cm bone window. After the bone flap being extracted, the cross-shaped incision was made in the dura mater. (3) The surgeon determined the lesion and the cortex at the surgical site according to the robot's positioning system. Initially, deep electrodes were utilized for intraoperative SEEG monitoring, revealing the presence of a small amount of sharp waves deep within the brain tissue of the surgical area. Following the monitoring, brain cotton pads were used to protect brain tissue beyond the precentral sulcus. (4) Bipolar electrocoagulation and a nerve dissector were utilized to create a cortical fistula for exploration of the lesion center. About 0.5 cm below the cortex, the brain tissue exhibited white and relatively firm texture. The nerve dissector was employed to identify the clear boundary between the surrounding and normal white matter. Carefully dissection along this boundary allowed for the separation of a small round nodule from the lesion. The capsule of this nodule was visible, after it being sent for pathological examination, the surgen continued the exploration. Surprisingly, three live milky-white parasites were extracted from the lesion and its surroundings, the longest of which was 12 cm in length (see Video 1 s in the online-only Supplementary material for a living intracranial parasite.). Exploring to a depth of approximately 3 cm below the cortex and microscopic examination, the lesion had been completely excised, and the parasites along with the affected tissue were sent for pathological analysis to identify the nature. Subsequent electrophysiological monitoring showed a return to basically normal brain activity in the surgical area. A large amount of normal saline and an appropriate amount of hemostatic gauze were used to flush and packed. (5) Cranial closure operation was complete. Fig. 1 Preoperative MRI images in axial ( a ) T1-weighted, sagittal ( b ) T2/FLAIR-weighted, and sagittal ( c ) T2-weighted scans. Preoperative contrast-enhanced T1-weighted MRI images in the axial ( d ), sagittal ( e ), and coronal ( f ) planes are presented. Neurosurgery robot-assisted frameless stereotactic technology was applied to implement the surgical strategy for lesion biopsy and resection in functional areas ( g ) Fig. 2 The video electroencephalogram (VEEG) recordings of the patient	4.066406	0.96875	sec[0]/sec[0]/p[1]	en	0.999998	PMC11960289	https://doi.org/10.1186/s42494-024-00161-8	[ "lesion", "lesions", "brain", "technology", "area", "robot", "lobe", "signal", "occipital", "this" ]	[ { "code": "FA5Z", "title": "Arthropathies, unspecified" }, { "code": "FC0Z", "title": "Diseases of the musculoskeletal system or connective tissue, unspecified" }, { "code": "ME60.Z", "title": "Skin lesion of unspecified nature" }, { "code": "MD41", "title": "Clinical findings on diagnostic imaging of lung" }, { "code": "GC2Z&XA6KU8", "title": "Disease of kidney, not elsewhere classified" }, { "code": "8E7Y", "title": "Other specified diseases of the nervous system" }, { "code": "LA05.Z", "title": "Cerebral structural developmental anomalies, unspecified" }, { "code": "1D00.Z", "title": "Infectious encephalitis, unspecified" }, { "code": "LA00.0Z", "title": "Anencephaly, unspecified" }, { "code": "NA07.3Y", "title": "Other specified diffuse brain injury" } ]	=== ICD-11 CODES FOUND === [FA5Z] Arthropathies, unspecified Also known as: Arthropathies, unspecified \| Disorders affecting predominantly peripheral joints \| Disorders affecting predominantly peripheral limb joints \| arthropathy NOS \| arthropathic [FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified Also known as: Diseases of the musculoskeletal system or connective tissue, unspecified \| bone disease NOS \| bone disorder NOS \| bone lesion NOS \| musculoskeletal complications NOS [ME60.Z] Skin lesion of unspecified nature Also known as: Skin lesion of unspecified nature \| Skin lesion of uncertain or unspecified nature \| Skin lesion without established diagnosis \| Pigmented skin lesion of unspecified nature \| Ulcer of skin of unspecified nature [MD41] Clinical findings on diagnostic imaging of lung Definition: Clinical findings on diagnostic imaging of lung is findings on diagnostic imaging of the lung which don't appear in normal status of the body. Diagnostic imaging refers to technologies that doctors use to look inside body for clues about a medical condition. X-rays, CT scans, nuclear medicine scans, MRI scans and ultrasound are all types of diagnostic imaging. Also known as: Clinical findings on diagnostic imaging of lung \| abnormal diagnostic imaging of lung \| Hyperinflation of lung \| Lung mass \| Pulmonary lobe mass [8E7Y] Other specified diseases of the nervous system Also known as: Other specified diseases of the nervous system \| Circumscribed brain atrophy \| circumscribed cerebral atrophy \| atrophic lobar sclerosis \| atrophic lobar brain sclerosis [LA05.Z] Cerebral structural developmental anomalies, unspecified Also known as: Cerebral structural developmental anomalies, unspecified \| Cerebral structural developmental anomalies \| Malformations of brain \| brain abnormality NOS \| brain deformity NOS [1D00.Z] Infectious encephalitis, unspecified Also known as: Infectious encephalitis, unspecified \| Infectious encephalitis, not elsewhere classified \| encephalitis NOS \| acute encephalitis NOS \| acute brain inflammation [LA00.0Z] Anencephaly, unspecified Also known as: Anencephaly, unspecified \| Anencephaly \| anencephalic monster \| anencephalus \| brain absence [NA07.3Y] Other specified diffuse brain injury Also known as: Other specified diffuse brain injury \| Brain contusion \| Cerebral contusion NOS \| Diffuse cortex contusion \| diffuse cortical contusion === GRAPH WALKS === --- Walk 1 --- [FA5Z] Arthropathies, unspecified --PARENT--> [?] Arthropathies --CHILD--> [?] Osteoarthritis Def: Osteoarthritis (OA) can be defined as a group of distinct, but overlapping diseases, which may have different etiologies, but similar biological, morphological, and clinical outcomes affecting the art... --- Walk 2 --- [FA5Z] Arthropathies, unspecified --PARENT--> [?] Arthropathies --PARENT--> [15] Diseases of the musculoskeletal system or connective tissue Def: This chapter contains diseases of musculoskeletal system and diseases of connective tissue.... --- Walk 3 --- [FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified --PARENT--> [15] Diseases of the musculoskeletal system or connective tissue Def: This chapter contains diseases of musculoskeletal system and diseases of connective tissue.... --EXCLUDES--> [?] Injury, poisoning or certain other consequences of external causes Def: !markdown In the ICD, injury means physical or physiological bodily harm resulting from interaction of the body with energy (mechanical, thermal, electrical, chemical or radiant, or due to extreme pre... --- Walk 4 --- [FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified --PARENT--> [15] Diseases of the musculoskeletal system or connective tissue Def: This chapter contains diseases of musculoskeletal system and diseases of connective tissue.... --CHILD--> [?] Conditions associated with the spine Def: This is a group of conditions in which there is a deviation from or interruption of the normal structure or function of the spine.... --- Walk 5 --- [ME60.Z] Skin lesion of unspecified nature --PARENT--> [ME60] Skin lesion of uncertain or unspecified nature Def: To be used where there is either significant uncertainty or alternatively no information as to the nature of a circumscribed skin lesion. This is of particular importance with regard to whether or not... --CHILD--> [ME60.2] Ulcer of skin of uncertain nature Def: This denotes the presence of a skin ulcer but uncertainty as to its nature. No inference as to whether the ulcer might be of serious significance (e.g. suspected skin cancer) is made.... --- Walk 6 --- [ME60.Z] Skin lesion of unspecified nature --PARENT--> [ME60] Skin lesion of uncertain or unspecified nature Def: To be used where there is either significant uncertainty or alternatively no information as to the nature of a circumscribed skin lesion. This is of particular importance with regard to whether or not... --CHILD--> [ME60.2] Ulcer of skin of uncertain nature Def: This denotes the presence of a skin ulcer but uncertainty as to its nature. No inference as to whether the ulcer might be of serious significance (e.g. suspected skin cancer) is made....	[ "[FA5Z] Arthropathies, unspecified\n --PARENT--> [?] Arthropathies\n --CHILD--> [?] Osteoarthritis\n Def: Osteoarthritis (OA) can be defined as a group of distinct, but overlapping diseases, which may have different etiologies, but similar biological, morphological, and clinical outcomes affecting the art...", "[FA5Z] Arthropathies, unspecified\n --PARENT--> [?] Arthropathies\n --PARENT--> [15] Diseases of the musculoskeletal system or connective tissue\n Def: This chapter contains diseases of musculoskeletal system and diseases of connective tissue....", "[FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified\n --PARENT--> [15] Diseases of the musculoskeletal system or connective tissue\n Def: This chapter contains diseases of musculoskeletal system and diseases of connective tissue....\n --EXCLUDES--> [?] Injury, poisoning or certain other consequences of external causes\n Def: !markdown\nIn the ICD, injury means physical or physiological bodily harm resulting from interaction of the body with energy (mechanical, thermal, electrical, chemical or radiant, or due to extreme pre...", "[FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified\n --PARENT--> [15] Diseases of the musculoskeletal system or connective tissue\n Def: This chapter contains diseases of musculoskeletal system and diseases of connective tissue....\n --CHILD--> [?] Conditions associated with the spine\n Def: This is a group of conditions in which there is a deviation from or interruption of the normal structure or function of the spine....", "[ME60.Z] Skin lesion of unspecified nature\n --PARENT--> [ME60] Skin lesion of uncertain or unspecified nature\n Def: To be used where there is either significant uncertainty or alternatively no information as to the nature of a circumscribed skin lesion. This is of particular importance with regard to whether or not...\n --CHILD--> [ME60.2] Ulcer of skin of uncertain nature\n Def: This denotes the presence of a skin ulcer but uncertainty as to its nature. No inference as to whether the ulcer might be of serious significance (e.g. suspected skin cancer) is made....", "[ME60.Z] Skin lesion of unspecified nature\n --PARENT--> [ME60] Skin lesion of uncertain or unspecified nature\n Def: To be used where there is either significant uncertainty or alternatively no information as to the nature of a circumscribed skin lesion. This is of particular importance with regard to whether or not...\n --CHILD--> [ME60.2] Ulcer of skin of uncertain nature\n Def: This denotes the presence of a skin ulcer but uncertainty as to its nature. No inference as to whether the ulcer might be of serious significance (e.g. suspected skin cancer) is made...." ]	FA5Z	Arthropathies, unspecified	[ { "from_icd11": "FA5Z", "icd10_code": "M00-M25", "icd10_title": "" }, { "from_icd11": "FC0Z", "icd10_code": "XIII", "icd10_title": "" }, { "from_icd11": "ME60.Z", "icd10_code": "L989", "icd10_title": "Disorder of the skin and subcutaneous tissue, unspecified" }, { "from_icd11": "MD41", "icd10_code": "R911", "icd10_title": "Solitary pulmonary nodule" }, { "from_icd11": "MD41", "icd10_code": "R91", "icd10_title": "Abnormal findings on diagnostic imaging of lung" }, { "from_icd11": "LA05.Z", "icd10_code": "Q048", "icd10_title": "Other specified congenital malformations of brain" }, { "from_icd11": "LA05.Z", "icd10_code": "Q043", "icd10_title": "Other reduction deformities of brain" }, { "from_icd11": "LA05.Z", "icd10_code": "Q049", "icd10_title": "Congenital malformation of brain, unspecified" }, { "from_icd11": "LA05.Z", "icd10_code": "Q04", "icd10_title": "Other congenital malformations of brain" }, { "from_icd11": "1D00.Z", "icd10_code": "G0490", "icd10_title": "Encephalitis and encephalomyelitis, unspecified" }, { "from_icd11": "1D00.Z", "icd10_code": "G0491", "icd10_title": "Myelitis, unspecified" }, { "from_icd11": "1D00.Z", "icd10_code": "G0430", "icd10_title": "Acute necrotizing hemorrhagic encephalopathy, unspecified" }, { "from_icd11": "1D00.Z", "icd10_code": "G0431", "icd10_title": "Postinfectious acute necrotizing hemorrhagic encephalopathy" }, { "from_icd11": "1D00.Z", "icd10_code": "G0439", "icd10_title": "Other acute necrotizing hemorrhagic encephalopathy" }, { "from_icd11": "1D00.Z", "icd10_code": "G0481", "icd10_title": "Other encephalitis and encephalomyelitis" } ]	M00-M25
A 70-year-old female presented to our hospital with complains of appetite loss and epigastric discomfort. Physical examination revealed unremarkable findings. Laboratory examination of blood showed: carbohydrate antigen 19-9 (CA19-9) level, 1369.1U/mL (> 37 U/mL); DUPAN-2, 330 U/ml (> 150 U/mL); and Span-1 210 U/ml (> 30 U/mL). Liver function tests were within normal range. On computed tomography (CT), an enhancing tumor measuring 15 mm was observed, which extended to the right secondary biliary confluence . The tumor was also associated with wall thickening of the right posterior glissonean pedicle, in conjunction of the perihilar tumor and a cystic dilatation of the segment 6 bile duct (B6), measuring 7 mm in diameter . No findings suggestive of lymphadenopathy or distant metastasis were noted. Magnetic resonance cholangiopancreatography (MRCP) revealed stenosis at the bifurcation of the posterior glissonean pedicle and diffuse dilatation of the B6. On aT1-weighted contrast-enhanced image, a 15 mm enhancing mass was observed on the dorsal side of the right hepatic hilum, extending to the posterior glissonean pedicle . The tumor was associated with irregular wall thickening at bifurcation of the posterior glissonean pedicle . Fluoro-deoxy-glucose–positron emission tomography (FDG–PET)–CT scan revealed an abnormal accumulation of FDG in the mass with a maximal standardized uptake value (SUV) of 4.6. Endoscopic retrograde cholangiopancreatography (ERCP) demonstrated a stricture at the bifurcation of the segment 6 (B6) and 7 (B7) bile ducts . Any intraductal neoplastic lesions were not identified. Mapping biopsies of the bile duct were not performed. Nonetheless, the diagnosis of adenocarcinoma was confirmed through bile duct cytology . Based on these findings, the patient was diagnosed with a MF + PI type ICC involving the right posterior glissonean pedicle. The imaging studies, including cholangiography or MRCP, revealed no evidence of infiltrative changes such as sclerosis and narrowing in the root of right hepatic duct. Therefore, an R0 resection was anticipated without requiring additional resection of the extrahepatic bile duct. The patient underwent a right hepatectomy and lymph node dissection along with hepatoduodenal ligament, postpancreatic head and common hepatic artery. Macroscopically, a 15 × 12 mm whitish, poorly circumscribed solid tumor was observed adjacent to the dorsal side of the posterior glissonean pedicle . Continuous with the perihilar tumor, the bile ducts at the intrahepatic secondary biliary confluence showed wall thickening with a whitish appearance. No gross intraductal tumor was observed in the dilated bile ducts. Histopathologically, the tumor was diagnosed as moderately differentiated adenocarcinomas with an irregular tubular pattern, exhibiting perineural and lymphovascular invasion . Diffuse micropapillary or sessile proliferations of columnar epithelial cells were observed in the posterior bile ducts. These lesions exhibited marked nuclear atypia, loss of nuclear polarity, and presence of mitoses, leading to a diagnosis of high-grade BilIN . Immunohistochemical results of the perihilar tumor showed MUC1 (2 +), MUC2 (-) and MUC5AC (3 +), and the BilIN lesions exhibited MUC1 (-). MUC2 (-), and MUC5AC (3 +) . The length of intraepithelial extension was approximately 120 mm. The high-grade BilIN lesions demonstrated continuous extension, and a transition between the BilIN lesions and the perihilar tumor was observed. Furthermore, two foci of invasive atypical epithelial cells were noted in peripheral hepatic parenchyma. The maximum size of each observed cell clusters was approximately two millimeters in diameter . Small clusters of atypical epithelial cells were observed in one regional lymph node. No neoplastic lesions were identified at the bile duct margin, and a 10 mm resection margin was achieved. This suggests that the BilIN lesions originated from a large duct, extended in the bile duct and involved the posterior glissonean pedicle, leading to diagnosis as a MF + PI type ICC. A schematic representation of the distribution of the high-grade BilIN, two foci of minimally invasions in the peripheral hepatic parenchyma, and a perihilar mass lesion is depicted in Fig. 8 . The pathological diagnosis was ICC pT4N1M0 Stage IVA according to the TNM classification system. Adjuvant chemotherapy was administered using gemcitabine and S-1 for 12 months. As of the 5 years following resection, no recurrence has been observed. Fig. 1 Preoperative contrast-enhanced CT findings. A In the axial view of the arterial phase, a 15 mm irregular circumferential ring-enhancing mass lesion was observed on the dorsal side of the right hepatic hilum (arrowheads). B In the coronal view of the venous phase, a cystic dilatation of the bile duct measuring 7 mm in diameter was observed in segment 6 bile ducts (B6) (arrows) Fig. 2 MRI findings. A In the axial section of contrast-enhanced T1-weighted images in the early phase, an irregular circumferential ring-enhancing mass was observed at the right hepatic hilum (arrowheads). B In the axial section at a level of the posterior glissonean confluence, marked wall thickening with enhancement was noted at the bifurcation of the posterior glissonean pedicle (arrowheads) Fig. 3 Endoscopic retrograde cholangiography (ERC) image. A Cholangiography showed a severe stenosis at the bifurcation of the segment 6 (B6) and 7 (B7) bile duct (arrow). B After cannulating the catheter, cystic dilatation of the segment 6 bile ducts (B6) was observed (arrowheads) Fig. 4 Bile cytology. The cytology examination revealed clusters of epithelial cells with features, such as anisokaryosis and hyperchromatic nuclei with irregular shape. This finding definitively confirmed the presence of adenocarcinoma cells Fig. 5 Macroscopic image of the cut surface of the resected specimen. A whitish solid tumor measuring 15 × 12 mm was observed adjacent to the dorsal side of the right hepatic hilum, involving the posterior glissonean pedicle (white circle). The posterior glissonean pedicle showed wall thickening (arrow), and this was associated with diffuse dilatation of the segment 6 bile ducts (dotted red circle). No gross intraductal tumor was noted in the dilated bile ducts. The white bar indicates the transection line of the right hepatic duct. The margin of the bile duct was approximately 1 cm from the mass Fig. 6 Macroscopic and histopathologic image of the specimen. 6A-1 Sagittal slice of the specimen at the level of the right hepatic hilum. A whitish solid and poor circumscribed tumor involved the right hepatic hilum (arrow) and extended along the posterior glissonean pedicle (arrowheads). The white line indicates the surgical cut margin of the bile duct. 6A-2 Tumor involved the posterior glissonean pedicle and surrounding hepatic parenchyma (arrowheads). H.E. staining. Scale bar = 500 µm. 6A-3 Tumor was composed of moderately differentiated tubular adenocarcinoma with a desmoplastic reaction. Perineural and lymphovascular invasion were observed. H.E. staining. Magnification of × 400. 6B-1 Sagittal slice at the middle of the segment 6. Grossly, the segment 6 bile ducts were cystically dilated, and no gross intraductal tumor was identified. 6B-2 Micropapillary or sessile proliferations of columnar epithelial cells were diffusely observed. The length of intraepithelial extension was approximately 120 mm. H.E. staining. Scale bar = 5 µm. 6B-3 Neoplastic lesions exhibited marked nuclear atypia, loss of nuclear polarity, and presence of mitoses, leading to a diagnosis of high-grade BilIN. H.E. staining. Magnification of × 400. 6C-1 At the peripheral slice of the segment 6. Similarly, diffuse bile duct dilatation was observed at the peripheral side of segment 6. 6C-2 Minimally invasive foci of atypical epithelial cells were observed in the peripheral hepatic parenchyma of segment 6 (arrowheads). The maximum size of invasion was approximately 2.1 mm in diameter. H.E. staining. Scale bar = 5 µm. 6C-3 Moderately differentiated tubular adenocarcinomas with desmoplastic reactions were observed. H.E. staining. Magnification of × 400. Fig. 7 Immunohistochemical image of the specimen. The perihilar tumor exhibited strong positivity for MUC1 and MUC5AC. The BilIN lesions showed negativity for MUC1 and positivity for MUC5AC Fig. 8 Schematic presentation of the distribution of the high-grade BilIN lesions, two foci of minimally invasions, and the perihilar intrahepatic cholangiocarcinoma	4.058594	0.974609	sec[1]/p[0]	en	0.999996	37721561	https://doi.org/10.1186/s40792-023-01748-y	[ "bile", "tumor", "duct", "glissonean", "hepatic", "pedicle", "segment", "lesions", "ducts", "bilin" ]	[ { "code": "DC10.2", "title": "Fistula of gallbladder or bile duct" }, { "code": "DC10.02", "title": "Obstruction of bile duct" }, { "code": "DC13", "title": "Cholangitis" }, { "code": "LB20.2Y", "title": "Other specified structural developmental anomalies of bile ducts" }, { "code": "ME24.35&XA6R80", "title": "Perforation of bile duct" }, { "code": "2F9Z", "title": "Neoplasms of unknown behaviour of unspecified site" }, { "code": "ME61", "title": "Subcutaneous swelling, mass or lump of uncertain or unspecified nature" }, { "code": "2E6Z", "title": "Carcinoma in situ of unspecified site" }, { "code": "2F91.1", "title": "Neoplasms of unknown behaviour of trachea, bronchus or lung" }, { "code": "2F92", "title": "Neoplasms of unknown behaviour of skin" } ]	=== ICD-11 CODES FOUND === [DC10.2] Fistula of gallbladder or bile duct Definition: This is an abnormal connection or passageway between gallbladder or bile duct and other organs. Also known as: Fistula of gallbladder or bile duct \| fistula of gallbladder \| gallbladder fistula \| Cholecystocolic fistula \| Cholecystoduodenal fistula [DC10.02] Obstruction of bile duct Also known as: Obstruction of bile duct \| extrahepatic biliary obstruction \| extrahepatic bile duct obstruction \| bile duct obstruction \| bile stasis Excludes: with cholelithiasis [DC13] Cholangitis Also known as: Cholangitis \| acute cholangiolitis \| ascending cholangitis \| cholangiolitis \| cholangitis NOS Excludes: chronic nonsuppurative destructive cholangitis \| cholangitis with cholelithiasis \| Primary sclerosing cholangitis [LB20.2Y] Other specified structural developmental anomalies of bile ducts Also known as: Other specified structural developmental anomalies of bile ducts \| Anomalous arrangement of pancreatobiliary ducts \| Aberrant hepatic duct \| Accessory hepatic duct \| accessory liver duct [2F9Z] Neoplasms of unknown behaviour of unspecified site Also known as: Neoplasms of unknown behaviour of unspecified site \| neoplasia \| neoplasm growth NOS \| tumour of unspecified site \| tumourlet of unspecified site [ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature Definition: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature Also known as: Subcutaneous swelling, mass or lump of uncertain or unspecified nature \| localised swelling, mass or lump of skin and subcutaneous tissue \| localised subcutaneous nodules \| subcutaneous nodules \| superficial subcutaneous nodules Excludes: localized adiposity \| mass and lump: breast \| enlarged lymph nodes [2E6Z] Carcinoma in situ of unspecified site Also known as: Carcinoma in situ of unspecified site \| carcinoma in situ of unspecified site \| carcinoma in situ NOS \| carcinoma in situ \| in situ neoplasm [2F91.1] Neoplasms of unknown behaviour of trachea, bronchus or lung Also known as: Neoplasms of unknown behaviour of trachea, bronchus or lung \| trachea, bronchus or lung tumour NOS \| Intravascular bronchial alveolar tumour of unspecified site \| Bronchial adenoma of unknown behaviour of unspecified site \| Intravascular bronchial alveolar tumour unknown behaviour of unspecified site [2F92] Neoplasms of unknown behaviour of skin Also known as: Neoplasms of unknown behaviour of skin \| skin tumour NOS === GRAPH WALKS === --- Walk 1 --- [DC10.2] Fistula of gallbladder or bile duct Def: This is an abnormal connection or passageway between gallbladder or bile duct and other organs.... --PARENT--> [DC10] Acquired anatomical alterations of gallbladder or bile ducts Def: This considers the structure in the alterations of the gall bladder and the long tube-like structures that carry bile.... --CHILD--> [DC10.1] Hydrops of gallbladder Def: Abnormal accumulation of serous fluid in the gallbladder... --- Walk 2 --- [DC10.2] Fistula of gallbladder or bile duct Def: This is an abnormal connection or passageway between gallbladder or bile duct and other organs.... --PARENT--> [DC10] Acquired anatomical alterations of gallbladder or bile ducts Def: This considers the structure in the alterations of the gall bladder and the long tube-like structures that carry bile.... --RELATED_TO--> [?] Perforation of gallbladder or bile ducts Def: This is perforation in the small organ that aids mainly in fat digestion and concentrates bile produced by the liver and in any of a number of long tube-like structures that carry bile.... --- Walk 3 --- [DC10.02] Obstruction of bile duct --EXCLUDES--> [?] Cholelithiasis Def: Cholelithiasis is calculus of gallbladder, cystic duct or bile duct. Most stones in the gallbladder are asymptomatic, but the most common initial symptom is biliary colic before the development of com... --CHILD--> [?] Calculus of gallbladder or cystic duct with other cholecystitis Def: Stones in gallbladder or cystic duct present with inflammation of the gall bladder wall and cystic duct.... --- Walk 4 --- [DC10.02] Obstruction of bile duct --EXCLUDES--> [?] Cholelithiasis Def: Cholelithiasis is calculus of gallbladder, cystic duct or bile duct. Most stones in the gallbladder are asymptomatic, but the most common initial symptom is biliary colic before the development of com... --CHILD--> [?] Mirizzi syndrome Def: This is a rare complication in which a gallstone becomes impacted in the cystic duct or neck of the gallbladder causing compression of the common bile duct (CBD) or common hepatic duct, resulting in o... --- Walk 5 --- [DC13] Cholangitis --EXCLUDES--> [?] Primary biliary cholangitis Def: Primary biliary cholangitis is characterised by progressive destruction and disappearance of the intralobular bile duct epithelial cells leading to cholestasis (high alkaline phosphatase and GGT {gamm... --EXCLUDES--> [?] Primary sclerosing cholangitis Def: Primary sclerosing cholangitis is a chronic disease which shows focal or multifocal strictures of intra- and/or extra-hepatic bile ducts without any apparent causes, leading to cholestasis and ultimat... --- Walk 6 --- [DC13] Cholangitis --EXCLUDES--> [?] Primary sclerosing cholangitis Def: Primary sclerosing cholangitis is a chronic disease which shows focal or multifocal strictures of intra- and/or extra-hepatic bile ducts without any apparent causes, leading to cholestasis and ultimat... --CHILD--> [?] Primary sclerosing cholangitis with cirrhosis Def: Primary sclerosing cholangitis with cirrhosis is primary sclerosing cholangitis complicated with liver cirrhosis....	[ "[DC10.2] Fistula of gallbladder or bile duct\n Def: This is an abnormal connection or passageway between gallbladder or bile duct and other organs....\n --PARENT--> [DC10] Acquired anatomical alterations of gallbladder or bile ducts\n Def: This considers the structure in the alterations of the gall bladder and the long tube-like structures that carry bile....\n --CHILD--> [DC10.1] Hydrops of gallbladder\n Def: Abnormal accumulation of serous fluid in the gallbladder...", "[DC10.2] Fistula of gallbladder or bile duct\n Def: This is an abnormal connection or passageway between gallbladder or bile duct and other organs....\n --PARENT--> [DC10] Acquired anatomical alterations of gallbladder or bile ducts\n Def: This considers the structure in the alterations of the gall bladder and the long tube-like structures that carry bile....\n --RELATED_TO--> [?] Perforation of gallbladder or bile ducts\n Def: This is perforation in the small organ that aids mainly in fat digestion and concentrates bile produced by the liver and in any of a number of long tube-like structures that carry bile....", "[DC10.02] Obstruction of bile duct\n --EXCLUDES--> [?] Cholelithiasis\n Def: Cholelithiasis is calculus of gallbladder, cystic duct or bile duct. Most stones in the gallbladder are asymptomatic, but the most common initial symptom is biliary colic before the development of com...\n --CHILD--> [?] Calculus of gallbladder or cystic duct with other cholecystitis\n Def: Stones in gallbladder or cystic duct present with inflammation of the gall bladder wall and cystic duct....", "[DC10.02] Obstruction of bile duct\n --EXCLUDES--> [?] Cholelithiasis\n Def: Cholelithiasis is calculus of gallbladder, cystic duct or bile duct. Most stones in the gallbladder are asymptomatic, but the most common initial symptom is biliary colic before the development of com...\n --CHILD--> [?] Mirizzi syndrome\n Def: This is a rare complication in which a gallstone becomes impacted in the cystic duct or neck of the gallbladder causing compression of the common bile duct (CBD) or common hepatic duct, resulting in o...", "[DC13] Cholangitis\n --EXCLUDES--> [?] Primary biliary cholangitis\n Def: Primary biliary cholangitis is characterised by progressive destruction and disappearance of the intralobular bile duct epithelial cells leading to cholestasis (high alkaline phosphatase and GGT {gamm...\n --EXCLUDES--> [?] Primary sclerosing cholangitis\n Def: Primary sclerosing cholangitis is a chronic disease which shows focal or multifocal strictures of intra- and/or extra-hepatic bile ducts without any apparent causes, leading to cholestasis and ultimat...", "[DC13] Cholangitis\n --EXCLUDES--> [?] Primary sclerosing cholangitis\n Def: Primary sclerosing cholangitis is a chronic disease which shows focal or multifocal strictures of intra- and/or extra-hepatic bile ducts without any apparent causes, leading to cholestasis and ultimat...\n --CHILD--> [?] Primary sclerosing cholangitis with cirrhosis\n Def: Primary sclerosing cholangitis with cirrhosis is primary sclerosing cholangitis complicated with liver cirrhosis...." ]	DC10.2	Fistula of gallbladder or bile duct	[ { "from_icd11": "DC10.2", "icd10_code": "K833", "icd10_title": "Fistula of bile duct" }, { "from_icd11": "DC10.2", "icd10_code": "K823", "icd10_title": "Fistula of gallbladder" }, { "from_icd11": "DC10.02", "icd10_code": "K831", "icd10_title": "Obstruction of bile duct" }, { "from_icd11": "DC13", "icd10_code": "K8309", "icd10_title": "Other cholangitis" }, { "from_icd11": "DC13", "icd10_code": "K8301", "icd10_title": "Primary sclerosing cholangitis" }, { "from_icd11": "DC13", "icd10_code": "K830", "icd10_title": "Cholangitis" }, { "from_icd11": "2F9Z", "icd10_code": "D487", "icd10_title": "Neoplasm of uncertain behavior of other specified sites" }, { "from_icd11": "2F9Z", "icd10_code": "D482", "icd10_title": "Neoplasm of uncertain behavior of peripheral nerves and autonomic nervous system" }, { "from_icd11": "2F9Z", "icd10_code": "D37-D48", "icd10_title": "" }, { "from_icd11": "2F9Z", "icd10_code": "D377", "icd10_title": "" }, { "from_icd11": "2F9Z", "icd10_code": "D48", "icd10_title": "Neoplasm of uncertain behavior of other and unspecified sites" }, { "from_icd11": "2F9Z", "icd10_code": "D489", "icd10_title": "Neoplasm of uncertain behavior, unspecified" }, { "from_icd11": "ME61", "icd10_code": "R2240", "icd10_title": "Localized swelling, mass and lump, unspecified lower limb" }, { "from_icd11": "ME61", "icd10_code": "R2232", "icd10_title": "Localized swelling, mass and lump, left upper limb" }, { "from_icd11": "ME61", "icd10_code": "R2242", "icd10_title": "Localized swelling, mass and lump, left lower limb" } ]	K833	Fistula of bile duct
The case of these family members demonstrates how DD-I can go undiagnosed for a long time and even be ignored if its unequivocal radiographic signs are not recognized. The importance of the early diagnosis of rare odontological diseases is evident because it is the key to preventing and controlling the negative effects of these diseases, which affect the oral health and quality of life of affected individuals . In the literature, there are other reports of late family diagnoses with important manifestations of DD-I in pediatric patients that have captured the parents’ attention because their children have become symptomatic (hypermobility on permanent elements, abscesses, and dental pain), from which the diagnosis was then made for one of the parents who had been treated for premature loss of permanent teeth with prosthetics and for whom the diagnostic suspicion of rare odontological diseases had not even been raised . The etiology of DD-I remains unclear . The hypotheses proposed over the years differ, but according to the etiology currently considered most likely, the abnormal root morphology is caused by abnormal differentiation and/or function of the odontoblasts that form dentin. The odontoblasts are derived from the epithelial cells of the Hertwig sheath and start their differentiation after having detached and migrated into the dental papilla . Dental management of patients with DD-I poses several problems . When pulp necrosis and periapical abscess occur, extraction is suggested as a treatment . For this reason, patients with DD-I in permanent dentition need to be monitored regularly for any abscess/apical lesion . The therapeutic approach to DD-I is as conservative as possible to preserve an already very vulnerable dentition . Endodontic treatment of teeth affected by DD-I is not appropriate due to the complexity of root canals or to the completely altered internal structure of the pulp . Peri-apical surgery and retrograde filling are recommended in teeth with long roots . Orthodontic treatment is suggested but with caution. In fact, further root resorption, loosening of teeth, and premature exfoliation may occur due to the resistance of the short roots to the orthodontic forces . In patient A, we cannot exclude that the orthodontic treatment could have contributed to accelerating the root resorption of the teeth of the upper arch. A correct diagnosis before orthodontic treatment would perhaps have allowed for preserving the lost teeth and the root structures of the other elements for a longer time. External root resorption (EER) often occurs in subjects treated with rapid maxillary expansion. The first molars and the upper incisors are the teeth most affected by the resorption process, with a significant reduction in radicular volume and length . The choice to use a bone-borne expansion and not traditional tooth-borne expansion, as in this patient, does not significantly reduce this risk . According to recent data on cone beam computed tomography (CBCT), the volume of the pulp chamber of posterior teeth, especially at the level of the horns, is also affected by a volumetric reduction with any type of rapid expander . These data must be taken into account if this pathology is recognized before starting orthodontic therapy, even when an expansion of the upper arch is necessary. Early tooth exfoliation promotes maxillomandibular bone atrophy, so treatment with a combination of onlay bone graft and sinus lift may be required to achieve implant rehabilitation . The main goal in the dental management of this disorder remains to preserve the natural teeth for as long as possible to preserve the bone. For this reason, in children, in particular, strict oral hygiene measures and dietary instructions must be established and maintained, as in other syndromic situations affecting teeth . It should be noted that the loss of permanent upper lateral incisors (in an advanced state of compromise already at the time of our first observation) in the older brother occurred during the first wave of the COVID-19 pandemic. The delayed prosthetic rehabilitation had an important psychological impact on the child, although, in that period, many remote-control strategies were implemented not to make pediatric patients feel neglected . The dentist has a fundamental role in the early diagnosis of this disorder and in guiding patients in the choice of measures to prolong the retention of the affected teeth . These cases demonstrate the importance of pediatric dental and orthodontic examination, as some rare genetic conditions such as DD-I may remain unknown and undiagnosed or misdiagnosed until problems such as dental abscesses or the tooth mobility of the permanent teeth arise in the absence of trauma or other factors. The diagnostic suspicion that is confirmed only by genetic research can be raised by the knowledge of this and of similar rare oral conditions and their clinical manifestation and radiographic aspects of the deciduous and permanent teeth . In this regard, the cases presented offer a genetic connotation different from the most widespread ones. DD-I is frequently described as a condition that follows an autosomal dominant pattern of inheritance caused by mutations in the DSSP genes . The mutated genes SSUH2-SSU-2 homolog and vPS4B-vascular protein sorting 4 homolog B are responsible for DD-I, too . The mutation of the SPARC-related modular calcium binding 2 gene, called SMOC2 (located on 6q27chromosome), is associated with an atypical dentin dysplasia due to SMOC2 deficiency. This subtype of DD-I, which follows an autosomal recessive inheritance, is characterized by extreme microdontia, oligodontia, abnormal tooth shape, short roots, enamel hypoplasia, and anterior open bite . Our patients were found to carry a SMOC2 mutation with a phenotype suggestive of an autosomal dominant inheritance showing the wide yet unknown genetic heterogeneity of this disease . Orthodontic treatment in persons affected by this kind of condition based on the genetic heritage (root length reduced, decreased crown/root ratio, and premature loss) can be highly counterproductive, as can endodontic treatment . For this reason, it is extremely important for the oral health of the growing affected individual to make a diagnosis early and to involve other family members who can be equally affected by this condition and have been ignored by dentists by attributing the premature loss of dental elements to other causes, as in the case of the father presented here. Although no similar cases are described in the literature, other cases of arrested root formation underline the importance of always considering an alarming signal of the lack or malformations of dental elements in the family members of a patient who has abnormal and insufficient root development . In fact, the authors in one of these studies state, “Arrested root development is difficult to predict, but a potential warning sign is a family history of malformed or missing teeth. Proper, adequate, and accurate records continue to remain critical for both medical and legal purposes in the treatment of patients with potential problems in root agenesis” . We agree with this statement, which is also applicable to our case, in that the diagnosis of the children’s father could have led to a further early diagnosis for the children, given the 50% probability that the children of an affected individual will present the same pathology. This may have allowed for better management of the father’s oral health, which indirectly would have been preventive for the children’s health, even by visiting a non-pediatric dentist or orthodontist. As rightly observed by other authors, when a dentist, general practitioner, or specialist is faced with a rare condition and ignores it due to his ignorance or negligence in performing a thorough diagnostic workup, the lack of diagnosis cannot be attributed to others and the clinician must be considered responsible not only ethically but also legally . Diagnostic errors are a known problem in health care practice, but even if data on diagnostic errors in the dental field are lacking , it is extremely important to report dental diagnostic errors and misdiagnosed dental conditions, such as the case of the father reported here, for whom the lack of diagnosis was not the only failure, as the dentistry profession, the members of which sometimes present themselves as too self-confident and superficial in taking care of patients, was also affected.	4.441406	0.544434	sec[2]/p[0]	en	0.999996	PMC10456812	https://doi.org/10.3390/medicina59081477	[ "this", "teeth", "root", "dental", "affected", "that", "patients", "orthodontic", "which", "children" ]	[ { "code": "4A01.03", "title": "Transient hypogammaglobulinaemia of infancy" }, { "code": "DA07.6Y", "title": "Other specified disturbances in tooth eruption" }, { "code": "LA30.0", "title": "Anodontia" }, { "code": "QA00.8", "title": "Dental examination" }, { "code": "LA30.3", "title": "Hyperdontia" }, { "code": "DA0A.Y", "title": "Other specified disorders of teeth and supporting structures" }, { "code": "DA07.4", "title": "Root anomaly" }, { "code": "DA0A.3", "title": "Retained dental root" }, { "code": "MD80.Y", "title": "Other specified symptoms or signs of the orofacial complex" }, { "code": "NA0D.06", "title": "Root fracture" } ]	=== ICD-11 CODES FOUND === [4A01.03] Transient hypogammaglobulinaemia of infancy Also known as: Transient hypogammaglobulinaemia of infancy \| immunoglobulin maturational delay \| THI - [transient hypogammaglobulinaemia of infancy] [DA07.6Y] Other specified disturbances in tooth eruption Also known as: Other specified disturbances in tooth eruption \| Neonatal teeth \| Natal teeth \| Advanced tooth eruption \| precocious dentition Includes: Neonatal teeth \| Advanced tooth eruption [LA30.0] Anodontia Definition: Anodontia is a genetic disorder commonly defined as the absence of all teeth, affecting both temporary and permanent dentitions, and is extremely rarely encountered in a pure form without any associated abnormalities. Rare but more common than complete anodontia is hypodontia. Also known as: Anodontia \| agomphiasis \| agomphosis \| anodontism \| complete absence of teeth [QA00.8] Dental examination Also known as: Dental examination \| examination of teeth [LA30.3] Hyperdontia Definition: Hyperdontia is the condition of having supernumerary teeth, or teeth which appear in addition to the regular number of teeth. Also known as: Hyperdontia \| Supplementary teeth \| Supernumerary teeth \| supernumerary tooth \| supplemental teeth Includes: Supplementary teeth \| Supernumerary teeth \| distomolar [DA0A.Y] Other specified disorders of teeth and supporting structures Also known as: Other specified disorders of teeth and supporting structures \| Alveolar process haemorrhage \| alveolar haemorrhage \| Barodontalgia \| aerodontalgia [DA07.4] Root anomaly Definition: Common presence of fused roots showed by X-ray film that short or long root, supernumerary root, or fused roots. These root anomalies are commonly seen in permanent molars, especially in third molars which are the most anomaly in one fused root, 2 or 3 fused roots, even 4 fused roots, round apical root or dilacerations. Also known as: Root anomaly \| Supernumerary roots [DA0A.3] Retained dental root Definition: Complete or fragment of root structure that remains in the jaw usually as result of fracture during the corresponding tooth extraction procedure. Also known as: Retained dental root \| dental root \| dental root retention [MD80.Y] Other specified symptoms or signs of the orofacial complex Also known as: Other specified symptoms or signs of the orofacial complex \| Bleeding gums \| gum haemorrhage \| gingival haemorrhage \| gingiva haemorrhage [NA0D.06] Root fracture Definition: A fracture involving dentin, cementum and the pulp. Also known as: Root fracture \| Fracture of tooth root === GRAPH WALKS === --- Walk 1 --- [4A01.03] Transient hypogammaglobulinaemia of infancy --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects... --PARENT--> [4A01] Primary immunodeficiencies due to disorders of adaptive immunity --- Walk 2 --- [4A01.03] Transient hypogammaglobulinaemia of infancy --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects... --CHILD--> [4A01.01] Immunodeficiencies with severe reduction in at least two serum immunoglobulin isotypes with normal or low numbers of B cells Def: This refers to a nonfamilial type of primary immune deficiency disease characterised by a reduction in at least two serum immunoglobulin isotypes. Circulating B cells may be normal or low.... --- Walk 3 --- [DA07.6Y] Other specified disturbances in tooth eruption --PARENT--> [DA07.6] Disturbances in tooth eruption --CHILD--> [DA07.60] Teething syndrome Def: Gum and jaw discomfort when an infant’s teeth emerges. Teething typically starts between 4 and 7 months of age and lasts until about the age of 3 years. Most common symptoms include irritability, cryi... --- Walk 4 --- [DA07.6Y] Other specified disturbances in tooth eruption --PARENT--> [DA07.6] Disturbances in tooth eruption --CHILD--> [DA07.61] Ankylosis of teeth Def: Tooth ankylosis is the solid fixation of a tooth, resulting from fusion of the cementum and alveolar bone, with obliteration of the periodontal ligament. It is uncommon in deciduous dentition, and ver... --- Walk 5 --- [LA30.0] Anodontia Def: Anodontia is a genetic disorder commonly defined as the absence of all teeth, affecting both temporary and permanent dentitions, and is extremely rarely encountered in a pure form without any associat... --PARENT--> [LA30] Structural developmental anomalies of teeth and periodontal tissues --CHILD--> [LA30.1] Hypodontia Def: Hypodontia presents as a lack of one or a few (less than 6) permanent teeth, without any systemic disorders.... --- Walk 6 --- [LA30.0] Anodontia Def: Anodontia is a genetic disorder commonly defined as the absence of all teeth, affecting both temporary and permanent dentitions, and is extremely rarely encountered in a pure form without any associat... --PARENT--> [LA30] Structural developmental anomalies of teeth and periodontal tissues --RELATED_TO--> [?] Disturbances in tooth eruption	[ "[4A01.03] Transient hypogammaglobulinaemia of infancy\n --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects\n Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects...\n --PARENT--> [4A01] Primary immunodeficiencies due to disorders of adaptive immunity", "[4A01.03] Transient hypogammaglobulinaemia of infancy\n --PARENT--> [4A01.0] Immunodeficiencies with predominantly antibody defects\n Def: A disorder characterised by an inability to mount a normal immune response due to antibody (i.e. immunoglobulin) defects...\n --CHILD--> [4A01.01] Immunodeficiencies with severe reduction in at least two serum immunoglobulin isotypes with normal or low numbers of B cells\n Def: This refers to a nonfamilial type of primary immune deficiency disease characterised by a reduction in at least two serum immunoglobulin isotypes. Circulating B cells may be normal or low....", "[DA07.6Y] Other specified disturbances in tooth eruption\n --PARENT--> [DA07.6] Disturbances in tooth eruption\n --CHILD--> [DA07.60] Teething syndrome\n Def: Gum and jaw discomfort when an infant’s teeth emerges. Teething typically starts between 4 and 7 months of age and lasts until about the age of 3 years. Most common symptoms include irritability, cryi...", "[DA07.6Y] Other specified disturbances in tooth eruption\n --PARENT--> [DA07.6] Disturbances in tooth eruption\n --CHILD--> [DA07.61] Ankylosis of teeth\n Def: Tooth ankylosis is the solid fixation of a tooth, resulting from fusion of the cementum and alveolar bone, with obliteration of the periodontal ligament. It is uncommon in deciduous dentition, and ver...", "[LA30.0] Anodontia\n Def: Anodontia is a genetic disorder commonly defined as the absence of all teeth, affecting both temporary and permanent dentitions, and is extremely rarely encountered in a pure form without any associat...\n --PARENT--> [LA30] Structural developmental anomalies of teeth and periodontal tissues\n --CHILD--> [LA30.1] Hypodontia\n Def: Hypodontia presents as a lack of one or a few (less than 6) permanent teeth, without any systemic disorders....", "[LA30.0] Anodontia\n Def: Anodontia is a genetic disorder commonly defined as the absence of all teeth, affecting both temporary and permanent dentitions, and is extremely rarely encountered in a pure form without any associat...\n --PARENT--> [LA30] Structural developmental anomalies of teeth and periodontal tissues\n --RELATED_TO--> [?] Disturbances in tooth eruption" ]	4A01.03	Transient hypogammaglobulinaemia of infancy	[ { "from_icd11": "4A01.03", "icd10_code": "D807", "icd10_title": "Transient hypogammaglobulinemia of infancy" }, { "from_icd11": "LA30.0", "icd10_code": "K000", "icd10_title": "Anodontia" }, { "from_icd11": "QA00.8", "icd10_code": "Z012", "icd10_title": "Encounter for dental examination and cleaning" }, { "from_icd11": "LA30.3", "icd10_code": "K001", "icd10_title": "Supernumerary teeth" }, { "from_icd11": "DA0A.3", "icd10_code": "K083", "icd10_title": "Retained dental root" } ]	D807	Transient hypogammaglobulinemia of infancy
We report a now 5-year-old girl with recurring hyperinflammatory episodes. The patient descends from a family of Turkish origin and was born in Austria. Both parents and siblings (1 sister and 2 brothers) have been clinically unremarkable, and the family history was negative for inborn errors of immunity or SAIDs. The patient initially presented at 9 months of age with a hyperinflammatory episode including fever, arthritis, aphthous stomatitis, and maculopapular rash , 13 , 14 but no trigger could be identified. Apart from this episode, the prior medical history was unremarkable. At the age of 2 years, the patient presented with a second episode of high fever (up to 40°C) and hepatomegaly, without splenomegaly or lymphadenopathy. Blood inflammatory parameters such as calprotectin (>25,000 μg/L [normal range <3,000 μg/L]), C-reactive protein (4.54 mg/dL [normal rage <0.5 mg/dL]), ferritin (1,442 μg/L [normal range 7-60 μg/L]), and erythrocyte sedimentation rate (130 mm/h [normal range <20 mm/h]) were elevated. Additionally, the patient showed severe hematological involvement with severe normochromic, microcytic anemia with hemoglobin (Hb) levels of 7.2 g/dL (normal range 9.5-14 g/dL). Hb electrophoresis showed a normal distribution of Hb fractions. Consistently, iron levels were normal. The patient also developed thrombocytopenia (25 × 10 3 /μL [normal range 150-450 × 10 3 /μL]) and granulocytopenia (0.3 × 10 3 /μL [normal range 2.5-7 × 10 3 /μL]). Due to the pancytopenia, a hematologic disease was considered. Bone marrow aspiration showed normal thrombo- and granulopoiesis with a strongly reduced erythropoiesis. Due to the differential diagnosis of inborn errors of immunity and SAIDs, a complete immunological workup was done. These results revealed normal kidney and liver function tests, normal immunophenotyping, and normal values for immunoglobulins (IgA, IgM, IgG, IgE) and IgG subclasses. An analysis of the complement system was unremarkable. Infectious diseases were excluded. Electrocardiography, echocardiography, electroencephalography, and the chest x-ray results were normal, and the abdominal sonography presented only the hepatomegaly. Supportive treatment with intravenous erythrocyte supplementation once and daily subcutaneous G-CSF (granulocyte colony-stimulating factor, 120 µg) injections were initiated for a total of 3 months, resulting in normalized neutrophil counts. Due to the suspected autoinflammatory disease, organic acid analysis of urine was performed during an episode of fever that revealed a significant elevated mevalonate to creatinine ratio of 11.8 μmol/mmol (normal range < 0.3), which is suggestive of MKD. Thus, genetic testing was performed. Initially, a targeted next-generation-sequencing–based protocol ruled out the presence of potentially pathogenic variants in the following genes: MEFV, NLRP3, NOD2, MVK, NLRP12, TNFRSF1A, CARD14, IL10RA, PLCG2, SLC29A3, CECR1, IL10RB, PSMB8, TMEM173, IL1RN, IL36RN, PSTPIP1, TNFRSF11A, IL10, LPIN2, SH3BP2, TNFAIP3, NLRC4, HAX 1 , ELANE, G6PC3, and GFI1 . Next, whole-exome sequencing was performed and identified a rare homozygous variant in PMVK . The evaluation of all rare homozygous variants based on literature and criteria such as gene function, expression patterns, mouse model data, and deleteriousness-prediction scores including CADD (Combined Annotation Dependent Depletion) score, revealed PMVK p.Val131Ala as the most likely cause of disease. The variant segregated under the assumption of autosomal recessive inheritance and none of the healthy family members were homozygous for the variant . Homozygosity mapping based on whole-exome sequencing data indicated the existence of several homozygous regions, which points toward a distant degree of consanguinity between the parents of the index patient. Thus, additional homozygous variants with high prediction scores were observed, yet no pathogenic variants in MVK or other SAID genes could be identified. Further stringent filtering, segregation analysis, and literature research ruled out other heterozygous and homozygous variants. The identified PMVK variant was not found in the gnomAD (Genome Aggregation Database) (v3.1.2), or the GME (Greater Middle East Variome) database and bioinformatic prediction scores predicted a high likelihood of functional relevance (CADD v1.6 of 23.5) , suggesting that it may be disruptive to PMVK function. Structural analysis of the variant showed that the valine at p.131 is located in the β4 strand adjacent to the Lid domain. Through the buried position of its side chain, it has spatial proximity to the helix α 1 linked to the p-loop, an element crucially involved in phosphate binding . 15 Fig 1 A, Aphthous stomatitis and maculopapular cervical rash in one febrile episode. B, Family pedigree and chromatograms of each family member with the p.Val131Ala variant highlighted. C, CADD score (y-axis) versus minor allele frequency ( MAF ) (x-axis) plot generated with PopViz ( https://hgidsoft.rockefeller.edu/PopViz/ ) with the patient’s mutation highlighted in red . CADD score v1.6 and gnomAD v2.1.1. Mutation significance cutoff set with 95% CI . D, PMVK genomic DNA ( gDNA ) and 2-dimensional protein structure with the location of the mutation highlighted. For the gDNA, the flat dark gray boxes flanking the figure represent untranslated regions ( UTRs ), the thick light gray boxes represent the exons, and the black lines represent the introns. For the protein, the different colors represent the different regions: core region in blue , acceptor substrate binding region in green, and Lid region in orange . E, Illustration of the 3-dimensional PMVK protein structure with the wild-type p.Val131 residue highlighted in red ( spheres ). The 3 protein domains are shown in blue (core region), green (acceptor substrate binding region), and orange (Lid region). The p-loop, a core element with a crucial role in phosphate binding, is shown in gray . Table I Clinical table Clinical characteristics PMVK deficiency MKD Van der Hilst 2008 13 Ter Haar 2016 14 Patients, n 1 103 114 Age at onset (mo), median 9 6 6 Fever Yes 100% 100% Disease pattern Reoccurrence of attacks (wk) 2-12 NS 4 Duration of attacks (d) 3-7 NS 4 Recurrent Yes 87% NS Continuous with exacerbations No 8% NS Continuous No 5% NS Mucocutaneous involvement Aphthous ulcers Yes 48.5% 60% Urticarial rash Yes 68.9% (NS) 15% Exudative pharyngitis Yes NS 28% Maculopapular rash No 68.9% (NS) 39% Musculoskeletal involvement Arthralgia Yes 83.5% 71% Myalgia No NS 57% Monoarthritis Yes 55.3% (NS) NS Oligoarthritis No 55.3% (NS) NS Polyarthritis No 55.3% (NS) 57% Eye involvement Periorbital edema No NS NS Uveitis No NS 2% Conjunctivitis No NS 10% Gastrointestinal involvement Abdominal pain No 85.4% 88% Diarrhea No 71.6% 84% Colitis No NS NS Hepatomegaly Yes 21% NS Vomiting No 70.9% 69% Reticuloendothelial involvement Lymphadenopathy No 87.4% 90% Splenomegaly No 32.4% NS Cardiovascular involvement Chest pain No NS NS Cutaneous vasculitis No NS NS Pulmonary involvement Respiratory infections Yes NS NS Neurological involvement Headache No 62.7% 38% Hematological involvement Anemia Yes NS NS Granulocytopenia Yes NS NS Thrombocytopenia Yes NS NS Acute phase parameters Leukocytes (10 3 /μL), median 8.3 15 NS CRP (mg/dL), median (range) 5.8 (1.6-19) 16.3 (3.6-40.4) NS ESR (mm/h), median 152 76 NS CRP , C-reactive protein; ESR , erythrocyte sedimentation rate; NS , not specified in the original paper. Table II Genetic characterization of the PMVK variant Gene description HGNC_ID HGNC:9141 CCDS SIZE (INCLUDING UTRS) 1002 EXONS, N 5 LOEUF SCORE (GNOMAD V2.1.1) 1.395 UNIQUE PROTEIN-CODING VARIANTS (GNOMAD V2.1.1), N 97 missense, 8 pLoF Variant description Genome Reference Consortium Human Build B38 CHROMOSOME Chr1 POSITION 154926404 NT_REF A NT_ALT G CDNA_CHANGE NM_006556.4: c.392T>C AA_CHANGE p.Val131Ala Gnomad_Af (Gnomad V3.1.2) NA I n silico pathogenicity assessment PolyPhen2_HVAR_score (PolyPhen-2 v2.2.2) 0,992 PolyPhen_prediction Probably damaging SIFT_score (SIFT ENSEMBL 66) 0 SIFT_prediction Deleterious CADD_v1.6 23.5 REVEL 0.389 MutationTaster2 0.999983 PROVEAN_score (version 1.1 ENSEMBL 66) −3.86 AA, Aminoacid; AF , allel frequency; ALT , alternative allele; CCDS , Consensus coding sequence; HGNC_ID , HUGO Gene Nomenclature Committee identifier; HVAR , HumVar training set; LOEUF , Loss-of-function observed/expected upper bound fraction; NA , not available; pLoF , putative loss of function; REF , reference allele.	4.128906	0.972656	sec[1]/p[0]	en	0.999995	37364720	https://doi.org/10.1016/j.jaci.2023.06.013	[ "involvement", "range", "variant", "pmvk", "protein", "variants", "homozygous", "region", "family", "episode" ]	[ { "code": "DA0B.5", "title": "Developmental or acquired deformities or conditions of gingiva" }, { "code": "4B2Y", "title": "Other specified disorders involving the immune system" }, { "code": "4A42.Z", "title": "Systemic sclerosis, unspecified" }, { "code": "KC20.Z", "title": "Conditions involving the umbilical cord, unspecified" }, { "code": "ED3Y", "title": "Cutaneous involvement in other specified neurological condition" }, { "code": "QA00.6Y", "title": "Other specified examination of eyes or vision" }, { "code": "4B00.0Z", "title": "Neutropaenia, unspecified" }, { "code": "3B63.1Z", "title": "Acquired thrombocytosis, unspecified" }, { "code": "MA14.1C", "title": "Raised antibody titre" }, { "code": "BD11.1", "title": "Left ventricular failure with mid range ejection fraction" } ]	=== ICD-11 CODES FOUND === [DA0B.5] Developmental or acquired deformities or conditions of gingiva Definition: This is a major developmental difference in the shape of a body part or organ compared to the average shape of that part. Also known as: Developmental or acquired deformities or conditions of gingiva \| Gingival cleft \| Furcation involvement \| Inadequately attached gingiva \| Minimally attached gingiva [4B2Y] Other specified disorders involving the immune system Also known as: Other specified disorders involving the immune system \| Certain inflammatory disorders with predominant lymph node involvement \| Histiocytic necrotising lymphadenitis of Kikuchi and Fujimoto \| Kikuchi-Fujimoto disease \| Kimura disease [4A42.Z] Systemic sclerosis, unspecified Also known as: Systemic sclerosis, unspecified \| Systemic sclerosis \| Systemic scleroderma \| progressive scleroderma \| Acroscleriasis [KC20.Z] Conditions involving the umbilical cord, unspecified Also known as: Conditions involving the umbilical cord, unspecified \| Conditions involving the umbilical cord [ED3Y] Cutaneous involvement in other specified neurological condition Also known as: Cutaneous involvement in other specified neurological condition \| Spinal cord defect affecting the skin \| Miscellaneous neurological conditions affecting the skin [QA00.6Y] Other specified examination of eyes or vision Also known as: Other specified examination of eyes or vision \| No Impairment of Contrast vision \| Normal colour vision \| No Impairment of Dark adaptation \| No diplopia [4B00.0Z] Neutropaenia, unspecified Also known as: Neutropaenia, unspecified \| Neutropenia \| Disorders with decreased neutrophil counts \| neutropaenic disorder \| neutrophil count below reference range [3B63.1Z] Acquired thrombocytosis, unspecified Also known as: Acquired thrombocytosis, unspecified \| Acquired thrombocytosis \| Idiopathic haemorrhagic thrombocythaemia \| Essential thrombocythaemia \| primary haemorrhagic thrombocythaemia [MA14.1C] Raised antibody titre Also known as: Raised antibody titre \| antibody titre above reference range \| high antibody titre \| increased antibody titre Excludes: isoimmunization, in pregnancy affecting fetus or newborn [BD11.1] Left ventricular failure with mid range ejection fraction Also known as: Left ventricular failure with mid range ejection fraction \| HFmEF - [heart failure with mid range ejection fraction] \| Left ventricular failure with mid range ejection fraction due to cardiomyopathy \| Left ventricular failure with mid range ejection fraction due to coronary artery disease \| Left ventricular failure with mid range ejection fraction due to myocarditis === GRAPH WALKS === --- Walk 1 --- [DA0B.5] Developmental or acquired deformities or conditions of gingiva Def: This is a major developmental difference in the shape of a body part or organ compared to the average shape of that part.... --PARENT--> [DA0B] Gingival diseases Def: Gingivitis is inflammation of the tissues of the gingiva (gum) without loss of connective tissue.... --PARENT--> [?] Diseases or disorders of orofacial complex Def: Morbid process, derangement or abnormality localised in the mouth or related tissues of the face... --- Walk 2 --- [DA0B.5] Developmental or acquired deformities or conditions of gingiva Def: This is a major developmental difference in the shape of a body part or organ compared to the average shape of that part.... --PARENT--> [DA0B] Gingival diseases Def: Gingivitis is inflammation of the tissues of the gingiva (gum) without loss of connective tissue.... --RELATED_TO--> [?] Periodontal pocket Def: A periodontal pocket is an unusually deep gap in the gingival sulcus.... --- Walk 3 --- [4B2Y] Other specified disorders involving the immune system --PARENT--> [?] Certain disorders involving the immune system Def: Disorders in which disturbed immune regulation plays an important part but which cannot be more precisely located elsewhere in the classification.... --RELATED_TO--> [?] Hereditary angioedema Def: Hereditary angioedema is caused in the majority of cases by genetically determined low absolute (type I) or functional (type II) levels of C1 inhibitor, a plasma proteinase inhibitor involved in regul... --- Walk 4 --- [4B2Y] Other specified disorders involving the immune system --PARENT--> [?] Certain disorders involving the immune system Def: Disorders in which disturbed immune regulation plays an important part but which cannot be more precisely located elsewhere in the classification.... --CHILD--> [4B22] Cryoglobulinaemia --- Walk 5 --- [4A42.Z] Systemic sclerosis, unspecified --PARENT--> [4A42] Systemic sclerosis Def: Systemic sclerosis is a systemic disorder of the connective tissue; manifested by hardening and thickening of the skin, by abnormalities involving the microvasculature and larger vessels, and by fibro... --CHILD--> [4A42.0] Paediatric onset systemic sclerosis Def: Systemic sclerosis arising before the age of 16. Involvement of internal organs is less common but arthritis and myositis are more common than in adults.... --- Walk 6 --- [4A42.Z] Systemic sclerosis, unspecified --PARENT--> [4A42] Systemic sclerosis Def: Systemic sclerosis is a systemic disorder of the connective tissue; manifested by hardening and thickening of the skin, by abnormalities involving the microvasculature and larger vessels, and by fibro... --CHILD--> [4A42.1] Diffuse systemic sclerosis Def: Diffuse cutaneous systemic sclerosis (dcSSc) is a subtype of Systemic Sclerosis (SSc) characterised by truncal and acral skin fibrosis with an early and significant incidence of diffuse involvement (i...	[ "[DA0B.5] Developmental or acquired deformities or conditions of gingiva\n Def: This is a major developmental difference in the shape of a body part or organ compared to the average shape of that part....\n --PARENT--> [DA0B] Gingival diseases\n Def: Gingivitis is inflammation of the tissues of the gingiva (gum) without loss of connective tissue....\n --PARENT--> [?] Diseases or disorders of orofacial complex\n Def: Morbid process, derangement or abnormality localised in the mouth or related tissues of the face...", "[DA0B.5] Developmental or acquired deformities or conditions of gingiva\n Def: This is a major developmental difference in the shape of a body part or organ compared to the average shape of that part....\n --PARENT--> [DA0B] Gingival diseases\n Def: Gingivitis is inflammation of the tissues of the gingiva (gum) without loss of connective tissue....\n --RELATED_TO--> [?] Periodontal pocket\n Def: A periodontal pocket is an unusually deep gap in the gingival sulcus....", "[4B2Y] Other specified disorders involving the immune system\n --PARENT--> [?] Certain disorders involving the immune system\n Def: Disorders in which disturbed immune regulation plays an important part but which cannot be more precisely located elsewhere in the classification....\n --RELATED_TO--> [?] Hereditary angioedema\n Def: Hereditary angioedema is caused in the majority of cases by genetically determined low absolute (type I) or functional (type II) levels of C1 inhibitor, a plasma proteinase inhibitor involved in regul...", "[4B2Y] Other specified disorders involving the immune system\n --PARENT--> [?] Certain disorders involving the immune system\n Def: Disorders in which disturbed immune regulation plays an important part but which cannot be more precisely located elsewhere in the classification....\n --CHILD--> [4B22] Cryoglobulinaemia", "[4A42.Z] Systemic sclerosis, unspecified\n --PARENT--> [4A42] Systemic sclerosis\n Def: Systemic sclerosis is a systemic disorder of the connective tissue; manifested by hardening and thickening of the skin, by abnormalities involving the microvasculature and larger vessels, and by fibro...\n --CHILD--> [4A42.0] Paediatric onset systemic sclerosis\n Def: Systemic sclerosis arising before the age of 16. Involvement of internal organs is less common but arthritis and myositis are more common than in adults....", "[4A42.Z] Systemic sclerosis, unspecified\n --PARENT--> [4A42] Systemic sclerosis\n Def: Systemic sclerosis is a systemic disorder of the connective tissue; manifested by hardening and thickening of the skin, by abnormalities involving the microvasculature and larger vessels, and by fibro...\n --CHILD--> [4A42.1] Diffuse systemic sclerosis\n Def: Diffuse cutaneous systemic sclerosis (dcSSc) is a subtype of Systemic Sclerosis (SSc) characterised by truncal and acral skin fibrosis with an early and significant incidence of diffuse involvement (i..." ]	DA0B.5	Developmental or acquired deformities or conditions of gingiva	[ { "from_icd11": "4A42.Z", "icd10_code": "M3481", "icd10_title": "Systemic sclerosis with lung involvement" }, { "from_icd11": "4A42.Z", "icd10_code": "M3489", "icd10_title": "Other systemic sclerosis" }, { "from_icd11": "4A42.Z", "icd10_code": "M3483", "icd10_title": "Systemic sclerosis with polyneuropathy" }, { "from_icd11": "4A42.Z", "icd10_code": "M349", "icd10_title": "Systemic sclerosis, unspecified" }, { "from_icd11": "4A42.Z", "icd10_code": "M342", "icd10_title": "Systemic sclerosis induced by drug and chemical" }, { "from_icd11": "4A42.Z", "icd10_code": "M34", "icd10_title": "Systemic sclerosis [scleroderma]" }, { "from_icd11": "4A42.Z", "icd10_code": "M348", "icd10_title": "Other forms of systemic sclerosis" }, { "from_icd11": "3B63.1Z", "icd10_code": "D473", "icd10_title": "Essential (hemorrhagic) thrombocythemia" }, { "from_icd11": "MA14.1C", "icd10_code": "R760", "icd10_title": "Raised antibody titer" } ]	M3481	Systemic sclerosis with lung involvement
A previously healthy 33-year-old female patient was submitted to a local emergency department with a flu-like infection and febrile temperatures up to 39 °C. The medical history solely contained a pre-existing bronchial asthma. The nasal swab tested negative for SARS-CoV-2 and positive for type-A influenza. Further 2 swabs of bronchoalveolar lavage were negative for SARS-CoV-2. Treatment with oseltamivir was initiated 1 h after receiving the laboratory report for type-A influenza. Just a few hours later, her respiratory insufficiency worsened, and the patient was admitted to the intensive care unit. After further respiratory deterioration under non-invasive ventilation, endotracheal intubation was performed. Despite escalated invasive ventilation, refractory hypercapnia (paCO 2 : 22 kPa) with severe respiratory acidosis (pH: 6.9) occurred within a few hours. A CT scan of the lungs showed swollen bronchioles, however, acute respiratory distress syndrome (ARDS) like infiltrates were absent. Reversible causes like tension pneumothorax, cardiac tamponade or pulmonary embolism were ruled out. Because of a transitory anisocoria the radiological diagnostics were supplemented with a native CT-scan of the brain, showing a mild cerebral oedema. In correspondence with a highly reduced pulmonary compliance, persisting hypercapnia and a Horovitz-Index < 100, out-of-centre veno-venous-ECMO (vv-ECMO)-implantation was performed due to a presumed refractory status asthmaticus. Immediately after ECMO-implantation, multiple episodes of tachycardia due to atrial fibrillation (Afib) had to be terminated by electrical cardioversion and amiodarone. However, the Afib episodes contributed to progressive haemodynamic instability. The transoesophageal echocardiography (TOE) initially showed hyperdynamic ventricular contractility with preserved left ventricular ejection fraction (LVEF), compatible with a sepsis-like constellation. Though hypercapnia was rapidly declining during ECMO-therapy, anisocoria and hypotension continued. This prompted a further whole-body CT-scan, which ruled out aggravation of cerebral oedema or any abdominal or thoracic bleeding after ECMO-cannulation as possible causes. The patient was transferred to our university hospital with a high norepinephrine rate (1.6 mcg/kg/min) for further complex intensive care treatment. We initiated an empiric treatment with meropenem and clarithromycin in accordance with a presumed septic shock following concomitant community-acquired pneumonia. Aiming at diagnosing the origin of persisting anisocoria, a third CT-scan of the brain with contrast medium was carried out, which now revealed an extended dissection of the right vertebral artery. Somatosensory evoked potentials (SEP) were conducted, showing an extremely reduced cortical action potential (N20) in agreement with a distinct brainstem damage. Due to rising doses of norepinephrine , we carried out transthoracic echocardiography (TTE), which revealed severe global hypokinesia and LVEF 19%, consistent with severe cardiogenic shock. There was no hint for regional hypokinesia patterns consistent with takotsubo syndrome (TTS). After angiographic exclusion of relevant coronary artery stenoses, we decided to support left ventricular function and LV unloading by gearing up MCS , and implanted an Impella CP in the heart catheterization laboratory. The patient required epinephrine in addition to rising doses of norepinephrine , which prompted us to subsequently expand to veno-venous-arterial ECMO (vva-ECMO) in terms of a vva-ECMELLA . The TTE performed immediately after completion of ECMELLA revealed a severely depressed LVEF of approximately 15%, confirmed the right position of Impella CP in the LV and identified circular pericardial effusion without evidence for compression of the right ventricle or right atrium . Under ECMELLA, the haemodynamic situation of the patient improved on the ICU, accompanied by substantially decreasing catecholamines infusion rates. The complex clinical course of the patient is illustrated in Fig. 2 . Coagulation was severely compromised related to high-dose heparin administration for the pertinent anticoagulation of the ECMELLA and the incidental hypothermia, contributing to spontaneous bleeding from mucous membranes and all punctured lines, demanding a massive transfusion. Unfortunately, bleeding from the punctured sites of the bilateral femoral arteries aggravated, so that the patient was subjected to vascular surgical treatment, which substantially improved the bleeding situation. From out-of-hospital ECMO-implantation and up until surgical bleeding control, the patient received 19 units of packed red blood cells, 17 units of fresh frozen plasma, 3 units of high concentrated platelets and multiple coagulation factors . The applied catecholamines could be reduced substantially in the subsequent days under ECMELLA. Coincidentally, a severe orbital compartment syndrome due to an initially anticoagulation-related retrobulbar hematoma resulted in a central retinal artery occlusion. Despite lateral canthotomy and orbital decompression, a right-sided amaurosis unfortunately remained in the course. Further on, MCS led to a step-by-step cardiac recompensation with increasing LVEF (to approximately 40%) in TTE 2 days after the initiation of ECMELLA . Aiming first to reduce the left ventricular afterload, the arterial cannula of the vva-ECMO was explanted after weaning of the ECMO on day 4, followed by removal of the Impella CP one day later after uncomplicated weaning from “auto-mode” with 3.5 l/min to P2. To facilitate respiratory weaning, dilatative tracheotomy was performed and subsequently vv-ECMO weaning was carried out without any complications on day 9. After total removal of MCS, echocardiography showed a completely restored LV function . No neurological impairments were present after reduction of sedation. Along this line, under supportive intensive care treatment the patient was decannulated 12 days after tracheotomy and was transferred to the peripheral cardiology ward. Her NT-proBNP, which had peaked at 4791 pg/ml 3 days after referral to our hospital, had decreased to 601 pg/ml 5 days before being discharged to rehabilitation (25 days after the initial admission to hospital) in a neurologically unaffected condition. The 33-year-old female patient was very grateful for having survived the severe, life-threatening cardiogenic shock and being able to meet her children (1 and 3 years old) and her husband again. Fig. 1 Aspects of ECMELLA treatment. a Fluoroscopy of the Impella CP implanted in the left ventricle (red arrow), and the venous cannula of the ECMO implanted in the inferior vena cava and in the right atrium (yellow asterisk). b TTE showing the severely hypokinetic left ventricle with the implanted Impella CP (red arrow) immediately after completion of the ECMELLA concept. Please note the non-compressing circular pericardial effusion (PE; yellow arrows). c TTE showing the risen LVEF (ca. 40%) 2 days after the initiation of ECMELLA. Please note the Impella CP in the LV (red arrow). d 2D echocardiography showing recovery of LVEF (68%) and LV dimensions after severe cardiogenic shock treated with ECMELLA. No residual PE is discernible Fig. 2 Time course of cardiogenic shock, ECMELLA and ICU treatment. Chronological events and applied procedures in context of the underlying hemodynamics, point-of-care and laboratory parameters. The time period from referral to external hospital up to 144 h after admission to university hospital is shown. Note the remarkable respiratory acidosis with excessive elevated paCO 2 before vv-ECMO implantation, the significant reduction of catecholamines under ECMELLA therapy and the impressive derangement in haemostatic parameters related to bleeding complications demanding massive transfusion. Due to a better overview, 1 cCT and 1 WB-CT, immediately performed after vv-ECMO implantation, are not shown in the figure. ext. hosp., univ. hosp. Admission to external/university hospital, ICU intensive care unit, intub. intubation, coronary angr. coronary angiography, vv(a)-ECMO veno-venous (arterial) extracorporeal membrane oxygenation, cCT cranial CT-scan, WB-CT whole body CT-scan, OR operation room, MAP mean arterial pressure, MCS mechanical circulatory support, pTT partial thromboplastin time, INR international normalized ratio, Fib fibrinogen, ATIII antihrombin III, CRP C-reactive protein, PCT procalcitonin, NSE neuron specific enolase	3.947266	0.975586	sec[1]/p[0]	en	0.999996	34743690	https://doi.org/10.1186/s12872-021-02346-2	[ "ecmo", "ecmella", "respiratory", "scan", "lvef", "which", "bleeding", "impella", "implantation", "shock" ]	[ { "code": "PK81.1", "title": "Extracorporeal life support procedure associated with injury or harm in therapeutic use" }, { "code": "QC48.Y", "title": "Other specified personal history of medical treatment" }, { "code": "CB7Z", "title": "Diseases of the respiratory system, unspecified" }, { "code": "CB41", "title": "Respiratory failure" }, { "code": "CB41.2Z", "title": "Respiratory failure, unspecified" }, { "code": "CB40.Y", "title": "Other specified diseases of the respiratory system" }, { "code": "MD11.Y", "title": "Other specified abnormalities of breathing" }, { "code": "MB71.Y", "title": "Other specified clinical findings on diagnostic imaging of central nervous system" }, { "code": "NE60", "title": "Harmful effects of drugs, medicaments or biological substances, not elsewhere classified" }, { "code": "JA66.3", "title": "Abnormal ultrasonic finding on antenatal screening of mother" } ]	=== ICD-11 CODES FOUND === [PK81.1] Extracorporeal life support procedure associated with injury or harm in therapeutic use Also known as: Extracorporeal life support procedure associated with injury or harm in therapeutic use \| ECMO - [extracorporeal membrane oxygenation] \| complication during or following extracorporeal life support procedure Excludes: Circumstances associated with a surgical or other medical procedure influencing the episode of care, without injury or harm [QC48.Y] Other specified personal history of medical treatment Also known as: Other specified personal history of medical treatment \| Personal history of contraception \| history of contraception \| Personal history of long-term use of medicaments other than anticoagulants \| personal history of long term current use of medicaments [CB7Z] Diseases of the respiratory system, unspecified Also known as: Diseases of the respiratory system, unspecified \| disorder of respiratory system \| respiratory disease NOS \| respiratory tract disease \| respiratory disorder NOS [CB41] Respiratory failure Definition: Respiratory failure is a life-threatening impairment of oxygenation or carbon dioxide (CO2) elimination. Respiratory failure may occur because of impaired gas exchange, decreased ventilation, or both. The level of oxygen in the blood becomes dangerously low or the level of carbon dioxide becomes dangerously high. Also known as: Respiratory failure \| lung failure NOS \| pulmonary failure Excludes: Acute respiratory distress syndrome \| Respiratory arrest \| Respiratory distress of newborn [CB41.2Z] Respiratory failure, unspecified Also known as: Respiratory failure, unspecified \| Respiratory failure, unspecified as acute or chronic \| respiration failure \| respiratory failure NOS \| respiration failed [CB40.Y] Other specified diseases of the respiratory system Also known as: Other specified diseases of the respiratory system \| Secondary respiratory disorders \| Respiratory disorders in diseases classified elsewhere \| Diseases of bronchus, not elsewhere classified \| Acquired bronchial diverticulum [MD11.Y] Other specified abnormalities of breathing Also known as: Other specified abnormalities of breathing \| Bradypnoea \| Choking sensation \| Hypoventilation \| hypoventilation syndrome NOS [MB71.Y] Other specified clinical findings on diagnostic imaging of central nervous system Also known as: Other specified clinical findings on diagnostic imaging of central nervous system \| Epidural haemorrhage, localised, no generalised mass effect or midline shift \| Epidural haemorrhage, confined to a small region in relation to a fracture \| Epidural haemorrhage, size less than 1 x 1 x 1 cm, not in relation to a fracture \| Epidural haemorrhage, mass effect or midline shift less than 0.5 cm [NE60] Harmful effects of drugs, medicaments or biological substances, not elsewhere classified Also known as: Harmful effects of drugs, medicaments or biological substances, not elsewhere classified \| drugs, medicaments or biological substances, toxicity not elsewhere classified \| adverse drug effects \| drug reaction NOS \| drug allergy NOS Excludes: Alcohol intoxication \| pathological drug intoxication \| hypersensitivity reaction to correctly administered drug [JA66.3] Abnormal ultrasonic finding on antenatal screening of mother Definition: A sign characterised by an abnormality detected by ultrasound during an antenatal screening of the mother. Also known as: Abnormal ultrasonic finding on antenatal screening of mother \| antenatal ultrasound scan abnormal === GRAPH WALKS === --- Walk 1 --- [PK81.1] Extracorporeal life support procedure associated with injury or harm in therapeutic use --EXCLUDES--> [?] Circumstances associated with a surgical or other medical procedure influencing the episode of care, without injury or harm --CHILD--> [?] Embolisation without injury or harm Def: An embolisation without documented injury or harm occurs when a solid object within the venous or arterial circulation propagates to a distal location and becomes lodged there.... --- Walk 2 --- [PK81.1] Extracorporeal life support procedure associated with injury or harm in therapeutic use --EXCLUDES--> [?] Circumstances associated with a surgical or other medical procedure influencing the episode of care, without injury or harm --CHILD--> [?] Foreign body accidentally left in body without injury or harm Def: A foreign body is any solid material not normally found in the human body. It is accidentally left in the body if there was no specific intention to keep it in the body.... --- Walk 3 --- [QC48.Y] Other specified personal history of medical treatment --PARENT--> [QC48] Personal history of medical treatment --CHILD--> [QC48.Y] Other specified personal history of medical treatment --- Walk 4 --- [QC48.Y] Other specified personal history of medical treatment --PARENT--> [QC48] Personal history of medical treatment --PARENT--> [?] Personal history of health problems --- Walk 5 --- [CB7Z] Diseases of the respiratory system, unspecified --PARENT--> [12] Diseases of the respiratory system --RELATED_TO--> [?] Pulmonary heart disease or diseases of pulmonary circulation --- Walk 6 --- [CB7Z] Diseases of the respiratory system, unspecified --PARENT--> [12] Diseases of the respiratory system --RELATED_TO--> [?] Sleep-related breathing disorders Def: Sleep related breathing disorders are characterised by abnormalities of respiration during sleep. In some of these disorders, respiration is also abnormal during wakefulness. The disorders are grouped...	[ "[PK81.1] Extracorporeal life support procedure associated with injury or harm in therapeutic use\n --EXCLUDES--> [?] Circumstances associated with a surgical or other medical procedure influencing the episode of care, without injury or harm\n --CHILD--> [?] Embolisation without injury or harm\n Def: An embolisation without documented injury or harm occurs when a solid object within the venous or arterial circulation propagates to a distal location and becomes lodged there....", "[PK81.1] Extracorporeal life support procedure associated with injury or harm in therapeutic use\n --EXCLUDES--> [?] Circumstances associated with a surgical or other medical procedure influencing the episode of care, without injury or harm\n --CHILD--> [?] Foreign body accidentally left in body without injury or harm\n Def: A foreign body is any solid material not normally found in the human body. It is accidentally left in the body if there was no specific intention to keep it in the body....", "[QC48.Y] Other specified personal history of medical treatment\n --PARENT--> [QC48] Personal history of medical treatment\n --CHILD--> [QC48.Y] Other specified personal history of medical treatment", "[QC48.Y] Other specified personal history of medical treatment\n --PARENT--> [QC48] Personal history of medical treatment\n --PARENT--> [?] Personal history of health problems", "[CB7Z] Diseases of the respiratory system, unspecified\n --PARENT--> [12] Diseases of the respiratory system\n --RELATED_TO--> [?] Pulmonary heart disease or diseases of pulmonary circulation", "[CB7Z] Diseases of the respiratory system, unspecified\n --PARENT--> [12] Diseases of the respiratory system\n --RELATED_TO--> [?] Sleep-related breathing disorders\n Def: Sleep related breathing disorders are characterised by abnormalities of respiration during sleep. In some of these disorders, respiration is also abnormal during wakefulness. The disorders are grouped..." ]	PK81.1	Extracorporeal life support procedure associated with injury or harm in therapeutic use	[ { "from_icd11": "QC48.Y", "icd10_code": "Z794", "icd10_title": "Long term (current) use of insulin" }, { "from_icd11": "QC48.Y", "icd10_code": "Z7902", "icd10_title": "Long term (current) use of antithrombotics/antiplatelets" }, { "from_icd11": "QC48.Y", "icd10_code": "Z7982", "icd10_title": "Long term (current) use of aspirin" }, { "from_icd11": "QC48.Y", "icd10_code": "Z7984", "icd10_title": "Long term (current) use of oral hypoglycemic drugs" }, { "from_icd11": "QC48.Y", "icd10_code": "Z79899", "icd10_title": "Other long term (current) drug therapy" }, { "from_icd11": "CB7Z", "icd10_code": "J989", "icd10_title": "Respiratory disorder, unspecified" }, { "from_icd11": "CB7Z", "icd10_code": "X", "icd10_title": "" }, { "from_icd11": "CB7Z", "icd10_code": "J09-J18", "icd10_title": "" }, { "from_icd11": "CB41", "icd10_code": "J9622", "icd10_title": "Acute and chronic respiratory failure with hypercapnia" }, { "from_icd11": "CB41", "icd10_code": "J9620", "icd10_title": "Acute and chronic respiratory failure, unspecified whether with hypoxia or hypercapnia" }, { "from_icd11": "CB41", "icd10_code": "J96", "icd10_title": "Respiratory failure, not elsewhere classified" }, { "from_icd11": "CB41.2Z", "icd10_code": "J9691", "icd10_title": "Respiratory failure, unspecified with hypoxia" }, { "from_icd11": "CB41.2Z", "icd10_code": "J9690", "icd10_title": "Respiratory failure, unspecified, unspecified whether with hypoxia or hypercapnia" }, { "from_icd11": "CB41.2Z", "icd10_code": "J9692", "icd10_title": "Respiratory failure, unspecified with hypercapnia" }, { "from_icd11": "CB41.2Z", "icd10_code": "J9621", "icd10_title": "Acute and chronic respiratory failure with hypoxia" } ]	Z794	Long term (current) use of insulin
Based on the initial presentation of macroscopic hematuria, proteinuria, and renal failure following an episode of pharyngitis with a typical time lag of 2 weeks, the differential diagnosis consists primarily of acute post-infectious glomerulonephritis (PIGN), the first presentation of either immune complex, or complement-mediated membranoproliferative nephritis (MPGN), or IgA nephropathy (IgAN) triggered by an infection. Less likely, but not excluded, are ANCA vasculitis, lupus nephritis, anti-glomerular basement (GBM) glomerulonephritis, and toxicity-/medication-induced glomerulonephritis. The young age and lack of sinusitis or pulmonary symptoms make ANCA vasculitis less likely and there were neither physical nor anamnestic signs of systemic lupus erythematosus (SLE). Macroscopic hematuria and nephrotic proteinuria are less consistent with a toxic cause of acute kidney injury. Given the clinical course, the patient had suspected rapidly progressive glomerulonephritis (RPGN). Additional laboratory investigations should be aimed at possible causes of RPGN . The few available studies on pediatric RPGN report that it is caused in over 80% by a form of immune-complex-mediated glomerulonephritis, with MPGN, Henoch–Schönlein purpura (HSP)/IgA nephropathy and PIGN as the most frequent underlying causes [ 2 – 5 ]. Lupus nephritis, C3 glomerulonephritis (C3GN), and ANCA vasculitis are more infrequent causes of pediatric RPGN [ 2 – 5 ]. In our patient, additional serum measurements included anti-streptolysin titer (AST) and anti-DNAse B titer, mycoplasma, hepatitis B and C serology, ANA, anti-PR3 ANCA, anti-MPO ANCA, anti-GBM measurements, and a full complement cascade for assessment of both the classical and alternative pathways (C3, C4, C3d, AP50, CH50, C3 nephritic factor, C5b-9). On the day after admission, the patient developed oliguria and a steep rise in creatinine level, indicating a rapid progression of renal failure. Although there was a high degree of suspicion regarding PIGN, serum complement C3 and C4 levels and AST and anti-DNAse B titer were not yet available. Generally, a renal biopsy is not mandatory when PIGN is suspected. However, certain features atypical of PIGN should prompt a biopsy. These include RPGN, extra-renal manifestations, a patient’s age <2 years, persistent gross hematuria, hypertension or nephritic syndrome, and hypocomplementemia lasting >6 weeks . In view of the rapid course of the acute kidney injury in our patient, a renal biopsy was planned for the next available appointment, which was the next day. There is little evidence regarding the treatment of RPGN in children and existing guidelines are based on studies in adults, in whom the underlying cause of the glomerulonephritis is usually different. For instance, adults have a higher likelihood of ANCA vasculitis . Nevertheless, there is a general consensus that methylprednisolone pulse therapy with or without cyclophosphamide, is the first therapeutic regimen in RPGN [ 2 – 5 , 7 ]. In our patient, we refrained from immunosuppressive treatment before a biopsy had been obtained. At the time, there was a high degree of suspicion regarding either PIGN or MPGN (immune complex- or complement-mediated). Methylprednisolone pulse therapy was not started, as there is a lack of evidence for a beneficial effect of immunosuppressive therapy in PIGN . Also, we feared that high doses of steroids might influence the renal biopsy. “Blind” administration of eculizumab was also considered but rejected for lack of a diagnosis and in view of its high costs. Supportive treatment consisting of fluid restriction, diuretics, and antibiotics was continued, awaiting the serum complement results. In our patient, the renal biopsy and serum complement results imposed a diagnostic dilemma, which is described below. On the third day of admission, a Monday, serum complement measurements were found to be normal (C3: 1.15 g/l, reference value 0.9–1.8 g/l; C4: 0.43 g/l; reference value 0.1–0.49 g/l). AST and anti-DNAse B titer were not yet available. Creatinine levels continued to rise to 640 μmol/l (7.2 mg/dl) and oliguria persisted. Because of the clinical picture of RPGN, together with the absence of hypocomplementemia characteristic of PIGN, this initial diagnosis was considered less likely, as was a complement-mediated MPGN. A renal biopsy was performed on the same day, combined with the placement of a central venous line for hemodialysis. Methylprednisolone pulse therapy (three daily pulses of 500 mg/m 2 body surface area) was started immediately after the renal biopsy. Histopathological evaluation of the renal biopsy showed crescentic glomerulonephritis in all 25 glomeruli (100% crescents), together with some endocapillary hypercellularity due to granulocyte infiltration. All crescents were cellular, with no signs of chronicity . There was also mild interstitial edema and tubules were dilated and filled with erythrocytes and granulocytes . Immunofluorescence was negative for IgG , IgM, IgA, kappa, lambda, and C1q, but revealed coarse granular C3c deposits along the capillary walls (2+), the so-called “starry-sky” pattern . C4d staining was negative and C5b9 staining was similar to C3c. Electron microscopy showed several (subepithelial) humps and tiny subendothelial electron dense deposits. Intramembranous garland-like electron dense deposits compatible with dense deposit disease (DDD) were not observed. These findings could be associated with both C3GN and severe PIGN. Fig. 1 Light microscopy, immunofluorescence, and electron microscopy findings in the renal biopsy. a Light microscopy shows three crescentic glomeruli (100% crescents in the whole biopsy), together with some interstitial edema and dilated tubules (silver staining, ×10). No signs of chronicity. b Higher magnification of a crescentic glomerulus with some endocapillary hypercellularity due to granulocyte infiltration (silver staining, ×20). c Light microcopy shows dilated tubules filled with erythrocytes and granulocytes (silver staining, ×20). d Negative immunofluorescent staining of a glomerulus for IgG (×20). e C3c immunofluorescent staining showing coarse granular deposits along the capillary walls (2+), the so-called “starry-sky” pattern (×20). f Electron microscopy showing large sub-epithelial electron-dense deposits (“humps”) marked with asterisks associated with effacement of the podocytes Intermittent hemodialysis was started on the fourth day after admission. AST and anti-DNAse B titer were still not available, nor were the bacterial and viral serology investigations. As renal biopsy findings were consistent with both PIGN and C3GN, a diagnosis of C3GN due to an intrinsic complement defect, triggered by an infection, could not be ruled out, despite the normal complement C3 level. In view of the severity of the clinical course, the biopsy findings with 100% crescents and recent publications reporting promising results of the complement inhibitor eculizumab for C3GN [ 9 – 11 ], a single dose of eculizumab (375 mg/m 2 body surface area) was administered intravenously awaiting further results. Complement cascade diagnostic investigations had been undertaken before eculizumab administration to prevent difficulties in interpretation of the results. Over the following days, intermittent hemodialysis was continued. The AST returned highly positive (1,600 U/ml), as did the anti-DNAse B titer (>1,600 U/ml), indicative of a recent streptococcal infection. Mycoplasma and hepatitis B/C serology were negative. Complement cascade analysis showed mild complement alternative pathway route activation (114%; reference value: 40–110%), with elevated alternative complement byproduct C3d (4.8%; reference value: 0.5–3.1%) and normal C5b-9 (<1,2 AE/ml; reference value:<4 AE/ml). C3 nephritic factor was negative, as were ANA, ANCA, and anti-GBM antibodies. From the sixth day after admission onward, renal function improved rapidly and hemodialysis treatment was discontinued. The patient was discharged 11 days after admission, with a serum creatinine level of 106 μmol/l (1.2 mg/dl) and without medication. At last follow-up, 2 months after presentation, renal function had completely recovered (creatinine 42 μmol/l (0.5 mg/dl), eGFR according to Schwartz was 116 ml/min/1.73 m 2 ), and proteinuria levels had declined significantly (protein to creatinine ratio: 55.2 mg/mmol Cr). This clinical course of rapid improvement favors the diagnosis of PIGN with RPGN presentation.	4.324219	0.882813	sec[0]/p[0]	en	0.999997	28280937	https://doi.org/10.1007/s00467-017-3626-3	[ "complement", "renal", "biopsy", "pign", "anti", "rpgn", "glomerulonephritis", "anca", "staining", "serum" ]	[ { "code": "4A00.1Z", "title": "Defects in the complement system, unspecified" }, { "code": "4A00.1Y", "title": "Other specified defects in the complement system" }, { "code": "4A00.11", "title": "Immunodeficiency with a late component of complement deficiency" }, { "code": "4A00.10", "title": "Immunodeficiency with an early component of complement deficiency" }, { "code": "4A00.13", "title": "Immunodeficiency with factor D anomaly" }, { "code": "GC2Z&XA6KU8", "title": "Disease of kidney, not elsewhere classified" }, { "code": "GB6Z", "title": "Kidney failure, unspecified" }, { "code": "LB30.1", "title": "Renal dysplasia" }, { "code": "NB92.0Y", "title": "Other specified injury of kidney" }, { "code": "LB30.7", "title": "Ectopic or pelvic kidney" } ]	=== ICD-11 CODES FOUND === [4A00.1Z] Defects in the complement system, unspecified Also known as: Defects in the complement system, unspecified \| Defects in the complement system \| Immunodeficiency with a complement cascade protein anomaly \| complement deficiency disease \| complement system defect [4A00.1Y] Other specified defects in the complement system Also known as: Other specified defects in the complement system \| Complement component C3 deficiency \| Recurrent Neisseria infections due to factor D deficiency \| Complement component C4b-binding protein deficiency \| Immunodeficiency with CD46 deficiency [4A00.11] Immunodeficiency with a late component of complement deficiency Also known as: Immunodeficiency with a late component of complement deficiency \| Deficiency of complement terminal pathway \| Complement component C5 deficiency \| Complement component C6 deficiency \| Complement component C7 deficiency [4A00.10] Immunodeficiency with an early component of complement deficiency Also known as: Immunodeficiency with an early component of complement deficiency \| Deficiency of complement initial pathway \| Complement component C1q deficiency \| Complement component C1r/C1s deficiency \| Complement component C2 deficiency [4A00.13] Immunodeficiency with factor D anomaly Definition: Factor D deficiency is an autosomal recessive immunologic disorder characterised by increased susceptibility to bacterial infections, particularly Neisseria infections, due to a defect in the alternative complement pathway. Also known as: Immunodeficiency with factor D anomaly \| CFDD - [Complement factor D deficiency] [GB6Z] Kidney failure, unspecified Also known as: Kidney failure, unspecified \| nontraumatic kidney injury \| renal failure NOS \| kidney block \| renal impairment NOS [LB30.1] Renal dysplasia Definition: A condition characterised by abnormal development of one or both kidneys. Also known as: Renal dysplasia \| congenital renal dysplasia \| dysplasia of kidney \| dysplastic kidney \| Primary renal dysplasia Excludes: Autosomal dominant polycystic kidney disease [NB92.0Y] Other specified injury of kidney Also known as: Other specified injury of kidney \| Injury of kidney without open wound into cavity \| Injury of kidney with open wound into cavity \| Haematoma of kidney \| traumatic perirenal haematoma [LB30.7] Ectopic or pelvic kidney Definition: A birth defect characterised by an abnormally positioned kidney; may be asymptomatic or result in urine blockage, infection or kidney stones Also known as: Ectopic or pelvic kidney \| Congenital displaced kidney \| congenital misplaced kidney \| congenital malposition of kidney \| congenital prolapsed kidney Includes: Congenital displaced kidney \| Malrotation of kidney === GRAPH WALKS === --- Walk 1 --- [4A00.1Z] Defects in the complement system, unspecified --PARENT--> [4A00.1] Defects in the complement system --CHILD--> [4A00.12] Immunodeficiency with factor B deficiency --- Walk 2 --- [4A00.1Z] Defects in the complement system, unspecified --PARENT--> [4A00.1] Defects in the complement system --CHILD--> [4A00.10] Immunodeficiency with an early component of complement deficiency --- Walk 3 --- [4A00.1Y] Other specified defects in the complement system --PARENT--> [4A00.1] Defects in the complement system --PARENT--> [4A00] Primary immunodeficiencies due to disorders of innate immunity --- Walk 4 --- [4A00.1Y] Other specified defects in the complement system --PARENT--> [4A00.1] Defects in the complement system --CHILD--> [4A00.10] Immunodeficiency with an early component of complement deficiency --- Walk 5 --- [4A00.11] Immunodeficiency with a late component of complement deficiency --PARENT--> [4A00.1] Defects in the complement system --CHILD--> [4A00.10] Immunodeficiency with an early component of complement deficiency --- Walk 6 --- [4A00.11] Immunodeficiency with a late component of complement deficiency --PARENT--> [4A00.1] Defects in the complement system --EXCLUDES--> [?] Paroxysmal nocturnal haemoglobinuria Def: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder characterised by corpuscular haemolytic anaemia, bone marrow failure and frequent thrombotic events....	[ "[4A00.1Z] Defects in the complement system, unspecified\n --PARENT--> [4A00.1] Defects in the complement system\n --CHILD--> [4A00.12] Immunodeficiency with factor B deficiency", "[4A00.1Z] Defects in the complement system, unspecified\n --PARENT--> [4A00.1] Defects in the complement system\n --CHILD--> [4A00.10] Immunodeficiency with an early component of complement deficiency", "[4A00.1Y] Other specified defects in the complement system\n --PARENT--> [4A00.1] Defects in the complement system\n --PARENT--> [4A00] Primary immunodeficiencies due to disorders of innate immunity", "[4A00.1Y] Other specified defects in the complement system\n --PARENT--> [4A00.1] Defects in the complement system\n --CHILD--> [4A00.10] Immunodeficiency with an early component of complement deficiency", "[4A00.11] Immunodeficiency with a late component of complement deficiency\n --PARENT--> [4A00.1] Defects in the complement system\n --CHILD--> [4A00.10] Immunodeficiency with an early component of complement deficiency", "[4A00.11] Immunodeficiency with a late component of complement deficiency\n --PARENT--> [4A00.1] Defects in the complement system\n --EXCLUDES--> [?] Paroxysmal nocturnal haemoglobinuria\n Def: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder characterised by corpuscular haemolytic anaemia, bone marrow failure and frequent thrombotic events...." ]	4A00.1Z	Defects in the complement system, unspecified	[ { "from_icd11": "4A00.1Z", "icd10_code": "D841", "icd10_title": "Defects in the complement system" }, { "from_icd11": "GB6Z", "icd10_code": "N19", "icd10_title": "Unspecified kidney failure" }, { "from_icd11": "GB6Z", "icd10_code": "N17-N19", "icd10_title": "" }, { "from_icd11": "GB6Z", "icd10_code": "N17", "icd10_title": "Acute kidney failure" }, { "from_icd11": "LB30.1", "icd10_code": "Q614", "icd10_title": "Renal dysplasia" }, { "from_icd11": "LB30.7", "icd10_code": "Q632", "icd10_title": "Ectopic kidney" }, { "from_icd11": "LB30.7", "icd10_code": "Q63", "icd10_title": "Other congenital malformations of kidney" } ]	D841	Defects in the complement system
A 78-year-old asymptomatic man with no significant past medical history, who had smoked 20 cigarettes a day for 50 years underwent preoperative computed tomographic imaging (CT) for chronic perforated otitis media; the imaging examination incidentally revealed an irregular tumor measured about 50 mm in diameter in the lower pole of the left kidney and also a large left lung tumor with multiple lymph node metastases, involving the nodes in the left pulmonary hilum, mediastinum, and bronchial bifurcation . The Karnofsky performance status was rated as 0. First of all, video-assisted thoracic surgery to obtain histological confirmation of lung metastasis from the RCC revealed invasion of the chest wall by the left lung tumor. On the other hand, histological examination of the left lung tumor showed features consistent with SCC, and IHC revealed a positive result for tumor PD-L1 expression (clone 22C3, tumor proportion score (TPS): 1–49%) . Positron emission tomography revealed supraclavicular lymph node metastases. The R.E.N.A.L. nephrometry score was 6 (maximal diameter: 2; exophytic properties: 1; nearness of the tumor to the collecting system: 1; location relative to the polar line was entirely below the lower polar line: 2) . Three weeks after the lung surgery, the renal tumor was treated by intraperitoneal RAPN performed by an expert surgeon, and the postoperative course was uneventful. Histological examination of the left renal tumor revealed clear cell carcinoma (WHO/ISUP nuclear grade 3) invading the perirenal fat tissue, but neither invading the renal pelvis nor the surgical margin . No venous or lymphatic invasion was seen either. While additional treatment of the left lung carcinoma was necessary, the patient refused any treatment due to the intense burden posed by the repeated examinations and surgeries. Four months after the RAPN, the patient neither had hematuria nor positive urinary cytology, but CT revealed left hydronephrosis caused by a markedly enhancing upper ureteral tumor. Multiple right lung metastases appeared and the left lung tumor also increased in size . Considering the volumes of the tumors, treatment of the lung SCC seemed to take priority over that of the metastases from the RCC, which was categorized into the intermediate category according to the IMDC classification (the detection of neutrophilia and metastases within 1 year of the nephrectomy) . Treatment with a combination of atezolizumab , nanoparticle albumin-bound paclitaxel (100 mg/m 2 ), and carboplatin (area under the blood concentration–time curve 6) was administered by intravenous infusion of the drugs every 3 to 4 weeks for up to 4 cycles. The primary lung SCC with the lymph node metastases showed marked regression, while the patient developed persistent appetite loss. Moreover, 4 cycles of atezolizumab alone were administered for maintenance by intravenous infusion every 4–6 weeks. By 6 months later, the left lung SCC with lymph node metastases had almost disappeared, whereas the left upper ureteral metastasis and right lung metastases from the RCC showed rapid progression . The patient showed a good performance status and the tumor volumes of all the metastatic tumors in the multiple organs seemed low, and therefore, open intraperitoneal nephroureterectomy was selected, even though treatment with other ICIs, tyrosine kinase inhibitors (TKIs), or a combination of the two was considered. Intraoperative exploration showed that the left upper ureteral tumor was tightly adherent to the mesenterium of the descending colon, and the left renal hilum was completely covered with hard bulky inflammatory tissues. Histological examination of the tumor in the ureteral wall compressing the lumen, which measured approximately 20 mm in diameter, revealed features consistent with clear cell carcinoma (WHO/ISUP grade 2) . Then, four right lung metastases measuring less than 20 mm in diameter were treated by partial lobectomy via a small thoracic incision. Histological examination of these tumors also revealed findings consistent with clear cell carcinoma . Two months after nephroureterectomy, a left lung metastasis in the lower lobe that appeared measuring about 10 mm in diameter seemed to be a metastasis from the RCC rather than a primary SCC, based on the previous clinical course. Considering the lack of efficacy of atezolizumab reported previously, it was thought that the lung metastasis would respond to TKI or TKI therapy combined with ICI therapy rather than to sequential ICI therapy . However, after repeated attempts were made to obtain informed consent, the patient expressed a strong desire to continue to work rather than to live longer and rejected the therapies, including TKI therapy, considering the risk of adverse events, such as diarrhea and hand-foot syndrome that occur often and deteriorate the quality of life . Therefore, ICIs that exert their efficacy via a mechanism of action different from that of avelumab are desirable. The patient was treated with the combination of nivolumab (240 mg) and ipilimumab (1 mg/kg) administered concomitantly by intravenous infusion every 3 weeks . A month later, the patient complained of back pain. Vertebral magnetic resonance imaging (MRI) performed 2 months later revealed a compression fracture without bone metastasis. After 2 cycles of this regimen, the patient needed hospitalization for general fatigue and appetite loss. The results of thyroid and adrenal hormone tests were almost within normal range, while the hypercalcemia associated with elevated levels of parathyroid hormone-related protein improved with subcutaneous injection of denosumab. While the lung SCC showed sustained response, CT revealed new metastatic lesions in the right lung and progression of the left lung metastasis, accompanied by liver metastasis, peritoneal carcinomatosis, and left retroperitoneal recurrence. Vertebral MRI showed multiple bone metastases. Radiotherapy was administered for the thoracic and lumbar vertebrae to relieve the severe back pain. One week after the hospitalization, the patient was diagnosed as having respiratory insufficiency caused by cancerous lymphangiomatosis with congestive heart failure. Six months after nephroureterectomy, the patient died of RCC. Subsequent studies revealed negative results of IHC (TPS < 1%) for PD-L1 in the primary RCC and ureteral and lung metastases from the RCC , these in RCC could have not routinely been performed in Japanese clinical diagnosis. Fig. 1 Contrast-enhanced computed tomographic image at the first visit. A The tumor in the lower pole of the left kidney, measuring about 50 mm in diameter, appears to protrude slightly into the peri-renal fat tissue. B The tumor was located in the lower portion of the left lung. The left hilar nodes ( C ) and nodes at the bronchial bifurcation ( D ) were enlarged (white arrow) Fig. 2 A The left lung squamous cell carcinoma (SCC) specimen obtained after resection by video-assisted thoracic surgery. Histological findings of the specimens obtained after robotic-assisted partial nephrectomy. B Clear cell carcinoma in the resected left primary renal tumor. Most cancer cells were classified into WHO/ISUP nuclear grade 2, but C there were also some partially grade 3 cancer cells. Hematoxylin–eosin stain (HE), reduced from 100 × Fig. 3 Contrast-enhanced computed tomographic images obtained before and non-enhanced computed tomographic images obtained after the combined multidrug therapy including atezolizumab. A Well-enhanced mass in the left upper ureter (white arrow), B right lung metastasis from the renal cell carcinoma (RCC), and C primary SCC in the left lung before the therapy. D The ureteral (white arrow) and E right lung metastasis from the RCC grew after the therapy, while F the primary SCC in the left lung almost disappeared Fig. 4 Histological findings after the combined multidrug therapy including atezolizumab. A Viable clear cell carcinoma (WHO/ISUP nuclear grade 2) in the left ureteral wall. HE, reduced from 100 × . B The right lung metastasis resected by partial lobectomy via a small thoracic incision also revealed vivid features of clear cell carcinoma. HE, reduced from 100x Fig. 5 Programmed death-ligand 1 (PD-L1 clone 22C3) immunohistochemistry in A lung SCC, B the renal tumor, C ureteral metastasis, and D lung metastasis from the RCC. The tumor proportion score (TPS) in B , C , and D was < 1%, whereas that in A was 1–49%. PD-L1, reduced from 100 ×	4.164063	0.95166	sec[1]/p[0]	en	0.999995	PMC9900908	https://doi.org/10.1186/s12957-023-02920-2	[ "lung", "tumor", "metastasis", "metastases", "carcinoma", "renal", "cell", "ureteral", "that", "histological" ]	[ { "code": "CB40.Y", "title": "Other specified diseases of the respiratory system" }, { "code": "LA75.1", "title": "Agenesis of lung" }, { "code": "CA40.Z", "title": "Pneumonia, organism unspecified" }, { "code": "CB41", "title": "Respiratory failure" }, { "code": "NB32.3Y", "title": "Other injury of lung" }, { "code": "2F9Z", "title": "Neoplasms of unknown behaviour of unspecified site" }, { "code": "ME61", "title": "Subcutaneous swelling, mass or lump of uncertain or unspecified nature" }, { "code": "2E6Z", "title": "Carcinoma in situ of unspecified site" }, { "code": "2F91.1", "title": "Neoplasms of unknown behaviour of trachea, bronchus or lung" }, { "code": "2F92", "title": "Neoplasms of unknown behaviour of skin" } ]	=== ICD-11 CODES FOUND === [CB40.Y] Other specified diseases of the respiratory system Also known as: Other specified diseases of the respiratory system \| Secondary respiratory disorders \| Respiratory disorders in diseases classified elsewhere \| Diseases of bronchus, not elsewhere classified \| Acquired bronchial diverticulum [LA75.1] Agenesis of lung Definition: This refers to the absence or rudimentary residua of an undeveloped lung. Also known as: Agenesis of lung \| Pulmonary agenesis \| absence of lung \| aplasia of lung \| apulmonism [CA40.Z] Pneumonia, organism unspecified Also known as: Pneumonia, organism unspecified \| Pneumonia \| infectious pneumonia \| PN - [pneumonia] \| lobar pneumonia NOS [CB41] Respiratory failure Definition: Respiratory failure is a life-threatening impairment of oxygenation or carbon dioxide (CO2) elimination. Respiratory failure may occur because of impaired gas exchange, decreased ventilation, or both. The level of oxygen in the blood becomes dangerously low or the level of carbon dioxide becomes dangerously high. Also known as: Respiratory failure \| lung failure NOS \| pulmonary failure Excludes: Acute respiratory distress syndrome \| Respiratory arrest \| Respiratory distress of newborn [NB32.3Y] Other injury of lung Also known as: Other injury of lung \| Haematoma of lung \| Traumatic hydropneumothorax \| Acute traumatic lung congestion \| Rupture of lung [2F9Z] Neoplasms of unknown behaviour of unspecified site Also known as: Neoplasms of unknown behaviour of unspecified site \| neoplasia \| neoplasm growth NOS \| tumour of unspecified site \| tumourlet of unspecified site [ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature Definition: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature Also known as: Subcutaneous swelling, mass or lump of uncertain or unspecified nature \| localised swelling, mass or lump of skin and subcutaneous tissue \| localised subcutaneous nodules \| subcutaneous nodules \| superficial subcutaneous nodules Excludes: localized adiposity \| mass and lump: breast \| enlarged lymph nodes [2E6Z] Carcinoma in situ of unspecified site Also known as: Carcinoma in situ of unspecified site \| carcinoma in situ of unspecified site \| carcinoma in situ NOS \| carcinoma in situ \| in situ neoplasm [2F91.1] Neoplasms of unknown behaviour of trachea, bronchus or lung Also known as: Neoplasms of unknown behaviour of trachea, bronchus or lung \| trachea, bronchus or lung tumour NOS \| Intravascular bronchial alveolar tumour of unspecified site \| Bronchial adenoma of unknown behaviour of unspecified site \| Intravascular bronchial alveolar tumour unknown behaviour of unspecified site [2F92] Neoplasms of unknown behaviour of skin Also known as: Neoplasms of unknown behaviour of skin \| skin tumour NOS === GRAPH WALKS === --- Walk 1 --- [CB40.Y] Other specified diseases of the respiratory system --PARENT--> [CB40] Certain diseases of the respiratory system --CHILD--> [CB40.0] Ciliary dyskinesia Def: Defective function of the cilia lining the respiratory tract (lower and upper, sinuses, Eustachian tube, middle ear) resulting in altered mucociliary transport and manifesting as recurrent upper and l... --- Walk 2 --- [CB40.Y] Other specified diseases of the respiratory system --PARENT--> [CB40] Certain diseases of the respiratory system --RELATED_TO--> [?] Pulmonary sporotrichosis Def: Pulmonary forms of infection, although uncommon, can occur when Sporothrix schenckii conidia are inhaled. Symptoms of pulmonary sporotrichosis mimic those of tuberculosis including constitutional com... --- Walk 3 --- [LA75.1] Agenesis of lung Def: This refers to the absence or rudimentary residua of an undeveloped lung.... --PARENT--> [LA75] Structural developmental anomalies of lungs Def: Any condition caused by failure of the lungs to correctly develop during the antenatal period.... --CHILD--> [LA75.2] Congenital hypoplasia of lung --- Walk 4 --- [LA75.1] Agenesis of lung Def: This refers to the absence or rudimentary residua of an undeveloped lung.... --PARENT--> [LA75] Structural developmental anomalies of lungs Def: Any condition caused by failure of the lungs to correctly develop during the antenatal period.... --CHILD--> [LA75.1] Agenesis of lung Def: This refers to the absence or rudimentary residua of an undeveloped lung.... --- Walk 5 --- [CA40.Z] Pneumonia, organism unspecified --PARENT--> [CA40] Pneumonia Def: A disease of the lungs, frequently but not always caused by an infection with bacteria, virus, fungus, or parasite. This disease is characterised by fever, chills, cough with sputum production, chest ... --CHILD--> [CA40.0] Bacterial pneumonia Def: A disease of the pulmonary system, caused by an infection with a bacterial source. This disease is characterised by fever, lethargy, headache, myalgia, vomiting, or coughing. Transmission is by inhala... --- Walk 6 --- [CA40.Z] Pneumonia, organism unspecified --PARENT--> [CA40] Pneumonia Def: A disease of the lungs, frequently but not always caused by an infection with bacteria, virus, fungus, or parasite. This disease is characterised by fever, chills, cough with sputum production, chest ... --RELATED_TO--> [?] Severe acute respiratory syndrome Def: A disease of the respiratory system, caused by an infection with coronavirus. This disease is characterised by fever, headache, cough, myalgia, tachycardia, or diarrhoea. This disease may also lead to...	[ "[CB40.Y] Other specified diseases of the respiratory system\n --PARENT--> [CB40] Certain diseases of the respiratory system\n --CHILD--> [CB40.0] Ciliary dyskinesia\n Def: Defective function of the cilia lining the respiratory tract (lower and upper, sinuses, Eustachian tube, middle ear) resulting in altered mucociliary transport and manifesting as recurrent upper and l...", "[CB40.Y] Other specified diseases of the respiratory system\n --PARENT--> [CB40] Certain diseases of the respiratory system\n --RELATED_TO--> [?] Pulmonary sporotrichosis\n Def: Pulmonary forms of infection, although uncommon, can occur when Sporothrix schenckii conidia are inhaled. \nSymptoms of pulmonary sporotrichosis mimic those of tuberculosis including constitutional com...", "[LA75.1] Agenesis of lung\n Def: This refers to the absence or rudimentary residua of an undeveloped lung....\n --PARENT--> [LA75] Structural developmental anomalies of lungs\n Def: Any condition caused by failure of the lungs to correctly develop during the antenatal period....\n --CHILD--> [LA75.2] Congenital hypoplasia of lung", "[LA75.1] Agenesis of lung\n Def: This refers to the absence or rudimentary residua of an undeveloped lung....\n --PARENT--> [LA75] Structural developmental anomalies of lungs\n Def: Any condition caused by failure of the lungs to correctly develop during the antenatal period....\n --CHILD--> [LA75.1] Agenesis of lung\n Def: This refers to the absence or rudimentary residua of an undeveloped lung....", "[CA40.Z] Pneumonia, organism unspecified\n --PARENT--> [CA40] Pneumonia\n Def: A disease of the lungs, frequently but not always caused by an infection with bacteria, virus, fungus, or parasite. This disease is characterised by fever, chills, cough with sputum production, chest ...\n --CHILD--> [CA40.0] Bacterial pneumonia\n Def: A disease of the pulmonary system, caused by an infection with a bacterial source. This disease is characterised by fever, lethargy, headache, myalgia, vomiting, or coughing. Transmission is by inhala...", "[CA40.Z] Pneumonia, organism unspecified\n --PARENT--> [CA40] Pneumonia\n Def: A disease of the lungs, frequently but not always caused by an infection with bacteria, virus, fungus, or parasite. This disease is characterised by fever, chills, cough with sputum production, chest ...\n --RELATED_TO--> [?] Severe acute respiratory syndrome\n Def: A disease of the respiratory system, caused by an infection with coronavirus. This disease is characterised by fever, headache, cough, myalgia, tachycardia, or diarrhoea. This disease may also lead to..." ]	CB40.Y	Other specified diseases of the respiratory system	[ { "from_icd11": "LA75.1", "icd10_code": "Q333", "icd10_title": "Agenesis of lung" }, { "from_icd11": "CA40.Z", "icd10_code": "J189", "icd10_title": "Pneumonia, unspecified organism" }, { "from_icd11": "CA40.Z", "icd10_code": "J181", "icd10_title": "Lobar pneumonia, unspecified organism" }, { "from_icd11": "CA40.Z", "icd10_code": "J188", "icd10_title": "Other pneumonia, unspecified organism" }, { "from_icd11": "CA40.Z", "icd10_code": "J168", "icd10_title": "Pneumonia due to other specified infectious organisms" }, { "from_icd11": "CA40.Z", "icd10_code": "J180", "icd10_title": "Bronchopneumonia, unspecified organism" }, { "from_icd11": "CA40.Z", "icd10_code": "J17", "icd10_title": "Pneumonia in diseases classified elsewhere" }, { "from_icd11": "CA40.Z", "icd10_code": "J182", "icd10_title": "Hypostatic pneumonia, unspecified organism" }, { "from_icd11": "CA40.Z", "icd10_code": "J16", "icd10_title": "Pneumonia due to other infectious organisms, not elsewhere classified" }, { "from_icd11": "CA40.Z", "icd10_code": "J171", "icd10_title": "" }, { "from_icd11": "CA40.Z", "icd10_code": "J173", "icd10_title": "" }, { "from_icd11": "CA40.Z", "icd10_code": "J178", "icd10_title": "" }, { "from_icd11": "CA40.Z", "icd10_code": "J18", "icd10_title": "Pneumonia, unspecified organism" }, { "from_icd11": "CB41", "icd10_code": "J9622", "icd10_title": "Acute and chronic respiratory failure with hypercapnia" }, { "from_icd11": "CB41", "icd10_code": "J9620", "icd10_title": "Acute and chronic respiratory failure, unspecified whether with hypoxia or hypercapnia" } ]	Q333	Agenesis of lung
Here we report on a 27-year-old woman with the first neurological symptoms suggesting MS in 1999 at the age of 12. Her medical and psychosocial history was negative, but her family history was positive. Patient’s father is also treated for MS. The patient’s clinical timeline follows : Fig. 1 a FLAIR, Fluid-Attenuated Inversion Recovery, sagittal : Periventricular high–signal intensity lesions exhibiting distribution of ovoid demyelinated periventricular lesions radially oriented to ventricles, which is typical for multiple sclerosis. b FLAIR, Fluid-Attenuated Inversion Recovery, transverse : Atypical tumefactive periventricular demyelinated lesion connected to the frontal pole of the lateral ventricle. c T2w, T2-weighted MRI, transeverse : Atypical hyperintensive tumefactive periventricular demyelinated lesion connected to the frontal pole of the lateral ventricle Fig. 2 a Dual Fast SE, Dual Fast Spin-Echo, transverse : Enlargement of the atypical hyperintensive tumefactive demyelinated lesion in the right frontal lobe. b FLAIR, Fluid -Attenuated Inversion Recovery, transverse : Enlargement of the atypical tumefactive demyelinated lesion in the right frontal lobe Fig. 3 a FLAIR, Fluid-Attenuated Inversion Recovery, transverse : Progression of the non-homogeneously hyper-intensive demyelinated lesion of the right frontal lobe, involving U-fibers. The lesion is well-defined to cortex, confluent with white mater, and irregular in shape. b T1w, T1-weighted MRI, transverse : Hypointense irregular lesion at the rim of the right corner of the lateral ventricle in the right frontal lobe and several slightly hypointensive areas subcortically with no post-Gad enhancement. c T2w, T2-weighted MRI, transverse : Irregular signal intensity within the lesion in the right frontal lobe. d DWI, Diffusion Weighted Imaging : High signal intensity in the right frontal cortico-subcortical region and slightly increased signal in periventricular regions of both hemispheres Fig. 4 a FLAIR, Fluid-Attenuated Inversion Recovery, sagittal : Large non-homogenous hyperintense lesion of the right frontal lobe involving demyelination and oedema with mild mass-effect. It is relatively sharply defined to grey matter and confluent with white matter. Glial tumour is undetectable. b FLAIR, Fluid -Attenuated Inversion Recovery, transverse : Diffuse hyperintense lesion of the right frontal lobe - demyelination. It has mild mass-effect. It is well-defined to cortex and to white matter and irregular in shape. c 3D DIR, 3D Double Inversion Recovery, sagittal : Multifocal cortical involvement in the right frontal cortex adjacent to demyelinated lesions, diffuse confluent hyperintensive lesion in cortico-subcortical fronto-polar region Fig. 5 1 HMRS, 1 H–magnetic resonance spectroscopy : 1H–MRS of the right and left frontal lobes - Creatine to Cholin maps, the decreased ratio may indicate tumorous tissue (red-contoured squares) Fig. 6 Histopathology findings. (HE, LFB-PAS, Bielschowsky, CD3, SV40, Olig2, GFAP, Vimentin, Nogo-A, Ki67, IDH1, p53): a The hematoxylin-eosin (HE) staining revealed grey and white matter with a markedly increased cellularity. Cells appeared pleomorphic and demonstrated a diffuse invasion into the CNS tissue. The tumour cells were embedded into a glial matrix. The nuclei showed a pronounced variation with respect to size and shape and depicted an increased nucleolar prominence. Mitosis was detectable. Signs of necrosis or microvascular proliferation were absent. b The immunohistochemical staining for Glial Fibrillary Acidic Protein (GFAP). Vimentin marked the majority of the tumour cells. c Some of the tumour cells were positive for Olig2. The tumour cells were not positive for NogoA. The proliferation ranged between 2 and 3% as determined by Ki67 immunohistochemistry. d The tumour cells were positive for isocitrate dehydrogenase1 (IDH1) and p53. e, f T-lymphocytes were not increased in the CD3 immunohistochemistry No SV40 positive cells were detected Fig. 7 11 -MET PET, 11 Methyl-Methionine Positron Emission Tomography : Increased uptake of 11 C–methionine in anaplastic astrocytoma in the right frontal cortico-subcortical region, showing high proliferation index of the tumour. Lower uptake was also detected in left frontal and occcipital cortical areas 1999 A 12-year-old girl with negative medical history presents with vestibular syndrome lasting three weeks 1999–2006 After having experienced several relapses with various symptoms (paresthesias of her left and right upper limbs, paresthesias of her distal limbs, weakness of upper limbs), she fulfilled McDonald criteria for definite relapsing-remitting MS due to demyelinating lesions in MRI , positive oligoclonal bands type 2 in cerebrospinal fluid (CSF) and positive visual evoked potentials (VEP). 2006 October Several rounds of intravenous boluses of methylprednisolon were effective and the patient improved. When she started treatment by interferon beta Ia (Rebif® Merck-Serono), her Expanded Disability Status Scale (EDSS) was 2.0. 2008–2009 The treatment was interrupted due to her pregnancy in February 2008. In January 2009 she gave birth. During the early postpartum period the patient’s neurological status was unstable. 2009 January to April The patient suffered three relapses (sensitive symptoms, left-sided hemiparesis, paraparesis of distal limbs) and her EDSS increased to 4.0 although she obtained several rounds of intravenous methylprednisolon. 2009 May She resumed interferon beta Ia (Rebif® Merck-Serono) and reached remission. 2011 March to May Her disease progressed again, her EDSS increased to 4.5 and follow-up MRI reflected clinical activity . Central quadruparesis was more pronounced in her left limbs and spinal ataxia varied over time between a need of assistance when walking longer distances and mild deficit. She responded well to intravenous methylprednisolon rounds. 2012 August To stop the disease progression, she was indicated to natalizumab (Tysabri® Biogen Idec), receiving 12 infusions . 2013 September The follow-up brain 3.0 Tesla MRI showed enlargement of the lesion in the right frontal lobe, evaluated by radiologists as PML . We also noticed seroconversion of JCV antibodies, but JCV index was low (0.38) and CSF PCR of DNA revealed no copies of JCV (Focus diagnostics, CYPRESS, California, USA). 2013 December Not meeting Slovak indication criteria, the patient ceased taking natalizumab. The patient started treatment with fingolimod (Gilenya® Novartis Pharmaceuticals UK). At that time she was quadruparetic, more prominent on the left side. She needed assistance due to wide-based gait and she had intermittent headaches (mild to moderate congestive-dull or pulsating headache located in bi-temporal areas, partially alleviated by analgesics) EDSS was 5.0. 2014 February A follow-up 3.0 Tesla MRI of the brain showed enlargement of the prior frontal lobe lesion , misinterpreted as PML again. A new CSF examination showed normal proteinorhachia (0.22g/l) and cellularity (1lymphocyte), not increased lactate (1.91 mmol/l), positive oligoclonal bands type 2 (14 bands), and increased IgG index 1.44. The PCR test of DNA JCV was negative again (0 copies UNILABS, Denmark). We decided to continue with fingolimod. 2014 December Over the following several months she developed new clinical symptoms: headache, sporadic epileptic seizures, disorientation. Immunomodulatory treatment was stopped. Repeated MRI was comparable with the MRI from February 2014, the atypical lesion in the right frontal lobe was in mild progression. 2015 May 1 H-magnetic resonance spectroscopy ( 1 H-MRS) detected decreased creatin to cholin ratio in several small areas of the frontal lobe, possibly suggesting tumorous mass Brain biopsy of the tumefactive lesion from the right frontal lobe. Histopathological findings revealed presence of anaplastic astrocytoma 2015 June The patient needed anti-oedematous (dexamethason or methylprednisolon, boluses of manitol) and anti-epileptic therapy (valproic acid and levetiracetam) due to repeated secondary generalized epileptic seizures and intracranial hypertension syndrome. 2015 August Before starting oncological treatment, 11methyl-methionine positron emission tomography ( 11 C MET PET) showed cortical localization of the brain tumor . Patient’s condition remained unstable due to frequent epileptic seizures. Three weeks later she suddenly died during status epilepticus .	4.144531	0.964844	sec[1]/p[0]	en	0.999997	28629398	https://doi.org/10.1186/s12885-017-3415-1	[ "frontal", "lesion", "lobe", "fluid", "inversion", "recovery", "demyelinated", "transverse", "tumour", "cells" ]	[ { "code": "9C82.4", "title": "Oculomotor apraxia" }, { "code": "CA0A.Y&XA91G8", "title": "Frontal sinus fistula" }, { "code": "CA0J.Y&XA91G8", "title": "Polyp of frontal sinus" }, { "code": "NA02.14", "title": "Fracture of frontal sinus of skull" }, { "code": "CA0C&XA91G8", "title": "Cyst of frontal sinus" }, { "code": "FA5Z", "title": "Arthropathies, unspecified" }, { "code": "FC0Z", "title": "Diseases of the musculoskeletal system or connective tissue, unspecified" }, { "code": "ME60.Z", "title": "Skin lesion of unspecified nature" }, { "code": "MD41", "title": "Clinical findings on diagnostic imaging of lung" }, { "code": "GC2Z&XA6KU8", "title": "Disease of kidney, not elsewhere classified" } ]	=== ICD-11 CODES FOUND === [9C82.4] Oculomotor apraxia Also known as: Oculomotor apraxia \| Congenital ocular motor apraxia \| Cogan’s congenital ocular motor apraxia \| Saccadic palsy \| Head thrust movement [NA02.14] Fracture of frontal sinus of skull Also known as: Fracture of frontal sinus of skull \| fracture of frontal sinus \| frontal sinus bone fracture [FA5Z] Arthropathies, unspecified Also known as: Arthropathies, unspecified \| Disorders affecting predominantly peripheral joints \| Disorders affecting predominantly peripheral limb joints \| arthropathy NOS \| arthropathic [FC0Z] Diseases of the musculoskeletal system or connective tissue, unspecified Also known as: Diseases of the musculoskeletal system or connective tissue, unspecified \| bone disease NOS \| bone disorder NOS \| bone lesion NOS \| musculoskeletal complications NOS [ME60.Z] Skin lesion of unspecified nature Also known as: Skin lesion of unspecified nature \| Skin lesion of uncertain or unspecified nature \| Skin lesion without established diagnosis \| Pigmented skin lesion of unspecified nature \| Ulcer of skin of unspecified nature [MD41] Clinical findings on diagnostic imaging of lung Definition: Clinical findings on diagnostic imaging of lung is findings on diagnostic imaging of the lung which don't appear in normal status of the body. Diagnostic imaging refers to technologies that doctors use to look inside body for clues about a medical condition. X-rays, CT scans, nuclear medicine scans, MRI scans and ultrasound are all types of diagnostic imaging. Also known as: Clinical findings on diagnostic imaging of lung \| abnormal diagnostic imaging of lung \| Hyperinflation of lung \| Lung mass \| Pulmonary lobe mass === GRAPH WALKS === --- Walk 1 --- [9C82.4] Oculomotor apraxia --PARENT--> [9C82] Disorders of extraocular muscles --CHILD--> [9C82.1] Muscular dystrophy affecting extraocular muscle Def: Non-specific term that is used to describe a range of primary myopathies that affect the extraocular muscles.... --- Walk 2 --- [9C82.4] Oculomotor apraxia --PARENT--> [9C82] Disorders of extraocular muscles --CHILD--> [9C82.0] Progressive external ophthalmoplegia Def: Chronic ophthalmoplegia is characterised by progressive weakness of ocular muscles and levator muscle of the upper eyelid. The condition is mainly manifested in adults. It may be totally and permanent... --- Walk 3 --- [NA02.14] Fracture of frontal sinus of skull --PARENT--> [NA02.1] Fracture of base of skull Def: Fractures which extend through the base of the skull, usually involving the petrous bone.... --CHILD--> [NA02.11] Fracture of middle fossa of base of skull --- Walk 4 --- [NA02.14] Fracture of frontal sinus of skull --PARENT--> [NA02.1] Fracture of base of skull Def: Fractures which extend through the base of the skull, usually involving the petrous bone.... --CHILD--> [NA02.11] Fracture of middle fossa of base of skull	[ "[9C82.4] Oculomotor apraxia\n --PARENT--> [9C82] Disorders of extraocular muscles\n --CHILD--> [9C82.1] Muscular dystrophy affecting extraocular muscle\n Def: Non-specific term that is used to describe a range of primary myopathies that affect the extraocular muscles....", "[9C82.4] Oculomotor apraxia\n --PARENT--> [9C82] Disorders of extraocular muscles\n --CHILD--> [9C82.0] Progressive external ophthalmoplegia\n Def: Chronic ophthalmoplegia is characterised by progressive weakness of ocular muscles and levator muscle of the upper eyelid. The condition is mainly manifested in adults. It may be totally and permanent...", "[NA02.14] Fracture of frontal sinus of skull\n --PARENT--> [NA02.1] Fracture of base of skull\n Def: Fractures which extend through the base of the skull, usually involving the petrous bone....\n --CHILD--> [NA02.11] Fracture of middle fossa of base of skull", "[NA02.14] Fracture of frontal sinus of skull\n --PARENT--> [NA02.1] Fracture of base of skull\n Def: Fractures which extend through the base of the skull, usually involving the petrous bone....\n --CHILD--> [NA02.11] Fracture of middle fossa of base of skull" ]	9C82.4	Oculomotor apraxia	[ { "from_icd11": "9C82.4", "icd10_code": "H518", "icd10_title": "Other specified disorders of binocular movement" }, { "from_icd11": "FA5Z", "icd10_code": "M00-M25", "icd10_title": "" }, { "from_icd11": "FC0Z", "icd10_code": "XIII", "icd10_title": "" }, { "from_icd11": "ME60.Z", "icd10_code": "L989", "icd10_title": "Disorder of the skin and subcutaneous tissue, unspecified" }, { "from_icd11": "MD41", "icd10_code": "R911", "icd10_title": "Solitary pulmonary nodule" }, { "from_icd11": "MD41", "icd10_code": "R91", "icd10_title": "Abnormal findings on diagnostic imaging of lung" } ]	H518	Other specified disorders of binocular movement
A woman in her 50 s developed a skin rash and dry cough in November 2020. In April 2021, the patient was diagnosed with anti-MDA5 antibody-positive dermatomyositis at the Department of Dermatology at our hospital. The physical and skin findings at the time of diagnosis are shown in Fig. 1 A, B, and C. Histopathology of the skin biopsy was consistent with dermatomyositis. The serum anti-MDA5 antibody level was 2,105 U/mL, and ferritin markedly elevated at 1,527 ng/mL. Additionally, infiltrative and interstitial shadows were observed at the pleural margins of both lungs on CT . The polymerase chain reaction test result for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in saliva was negative. Although respiratory failure was not observed, RP-ILD was suspected, and the patient was immediately admitted to the hospital, where high-dose prednisolone therapy (1 mg/kg), tacrolimus administration (4 mg/day), and cyclophosphamide pulse therapy (500 mg/m 2 ) were initiated. After treatment with high-dose intravenous immunoglobulin (IVIG: 1 g/day for 5 days), the dermatomyositis and interstitial shadows improved. The patient was discharged from the hospital 2 months after admission because her condition improved. The prednisolone dose was reduced to 25 mg/day, and cyclophosphamide pulse therapy was terminated after three sessions owing to pronounced leukopenia and thrombocytopenia following cyclophosphamide administration. Figure 2 shows the changes in the CT images. However, 8 months after admission, the GGO worsened with Krebs von den Lungen (KL-6) elevation, and respiratory failure developed. Although the anti-MDA5 antibody levels tended to decrease and there was no worsening of myositis, we judged that this was another exacerbation of interstitial pneumonia complicated by anti-MDA5 antibody-positive dermatomyositis. Hence, we treated the patient with an increased dose of prednisolone (30 mg/day) and tacrolimus (6.5 mg/day). Furthermore, we repeated cyclophosphamide pulse therapy as an outpatient for three courses. Despite these treatments, the GGO worsened, and respiratory failure developed, further warranting home oxygen therapy. Fourteen months after the onset of dermatomyositis, the patient was hospitalized for further examination. Upon admission, chest radiography revealed frosted shadows in both lungs . CT showed a new diffuse crazy-paving appearance . Blood test results on admission showed elevated levels of KL-6, surfactant protein-D, and cytokeratin 19 fragment, while the ferritin level was low, and anti-MDA-5 antibodies tended to decrease (Table 1 ). Bronchoalveolar lavage was performed on the fourth day after admission, and 88 ml of 150 mL bronchalveolar lavage fluid (BALF), which was milky white, was collected . Further analysis of the cellular composition revealed macrophage predominance, with numerous foamy macrophages and a large amount of acidophilic unstructured material in the background (Table 2 ). Based on these examination results, a diagnosis of PAP was made. Subsequently, we measured GMAb, which was high at 34.3 U/mL, and finally diagnosed the patient with APAP. Thereafter, the prednisolone dose was reduced to 10 mg/day every two weeks to reduce the risk of post-procedural infection, and whole-lung lavage was performed 16 months after the onset of dermatomyositis. The clinical course of the patient is shown in Fig. 4 A. After whole lung lavage, the GGO area on the CT scan decreased compared with that prior to whole lung lavage, shortness of breath improved, and the amount of oxygen needed for inhalation was markedly reduced . We later measured the GMAb in two serum samples stored in our hospital collected at the onset and 11 months after the onset of dermatomyositis and found the levels were both high at 37.5 U/mL and 93.3 U/mL, respectively . Fig. 1 Characteristic findings of anti-MDA5 antibody-positive dermatomyositis. A Reverse Gottron’s sign and B exudative erythema, representing characteristic findings of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis. C Dermatopathological findings showed liquid degeneration of the epidermal basement membrane, dermal mucin deposition, and perivascular inflammatory cell infiltration of the dermis. D Computed tomography (CT) findings on first admission. Infiltrative and interstitial shadows are observed just below the pleura Fig. 2 Course of findings of interstitial pneumonia on chest computed tomography (CT). A At the diagnosis of dermatomyositis, B 2 months after initiation of treatment, C 8 months after initiation of treatment, and D 14 months after initiation of treatment (before bronchoscopy). On initial admission ( A ), interstitial shadows were observed just below the pleura in both lungs. At discharge 2 months later, the interstitial shadows temporarily improved ( B ). However, 8 months later ( C ), new ground-glass shadows appeared in both lungs. Fourteen months later ( D ), the ground-glass shadows were further aggravated, as indicated by the arrow Fig. 3 Chest x-ray on admission for bronchoscopy and bronchoalveolar lavage fluid (BALF). A Chest radiograph before bronchoscopy showing ground-glass shadows in both lungs. B The collected alveolar lavage fluid was thick and milky white in color Table 1 Blood tests on admission for bronchoscopy Hematology Biochemistry White blood cells 8,300 /μL Total protein 6.7 g/dL Neutrophils 91.4 % Serum albumin 4 g/dL Eosinophils 0.1 % Total bilirubin 0.6 mg/dL Basophils 0.2 % Aspartate transaminase 20 U/L Monocytes 1.1 % Alanine transaminase 18 U/L Lymphocytes 7.2 % Lactate dehydrogenase 325 U/L Neutrophils 7,586 /μL Alkaline phosphatase 44 U/L Eosinophils 8.3 /μL Creatine kinase 40 U/L Basophils 16.6 /μL Blood urea nitrogen 15 mg/dL Monocytes 91.3 /μL Creatinine 0.71 mg/dL Lymphocytes 597.6 /μL C-reactive protein 0.07 mg/dL Hemoglobin 16.8 g/dL Serum sodium 145 mEq/L Platelets 237,000 /μL Serum potassium 4.6 mEq/L Coagulation Serum chloride 107 mEq/L Prothrombin time 112 % Glucose 174 mg/dL Activated partial thromboplastin time 25.8 second Ferritin 20.3 ng/mL D-dimer 0.5 µg/mL Serology Sialylated carbohydrate antigen KL-6 4,689 ng/mL Surfactant protein D 211 ng/mL Perinuclear anti-neutrophil cytoplasmic antibody < 1.0 U/mL Classic anti-neutrophil cytoplasmic autoantibody < 1.0 U/mL Cytokeratin 19 fragment 12.7 ng/mL Cytomegalovirus antigenaemia test (-) Anti-Trichosporon asahii antibody (-) anti-nuclear antibody < 40 β-Dglcan < 2.6 pg/mL Blood tests on admission revealed marked elevation in KL-6 and SP-D levels, whereas ferritin and CRP levels were low Table 2 Properties of bronchoalveolar lavage fluid and results of each test Bronchoalveolar lavage fluid Recovery rate 58.7 (88/150 mL) % Total cells 45,000 /mL Macrophages 76 % Lymphocytes 12 % Neutrophils 12 % Eosinophils 0 % Basophils 0 % CD4/CD8 0.9 General bacterial culture Negative Antimicrobial culture Negative Candida quantification < 4 × 10 1 copy/mL Aspergillus quantification < 4 × 10 1 copy/mL Pneumocystis determination < 4 × 10 1 copy/mL Cytodiagnosis no malignancy In the bronchoalveolar lavage fluid (BALF), antigen quantification testing of this alveolar lavage fluid for infectious agents showed that Pneumocystis , Aspergillus , and Candida were extremely few. Cellular fractionation showed an increased macrophage ratio, with no infectious or malignant findings Fig. 4 Clinical course and images after whole lung lavage. A Changes in therapeutic agents and laboratory values. Anti-MDA-5 antibody levels decreased after treatment with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis complicated by interstitial pneumonia, but KL-6 tended to increase after 8 months. After diagnosis of APAP, prednisolone (PSL) was tapered off and whole-lung lavage was performed, after which KL-6 decreased. The anti-GM-CSF antibody titer was high from the first admission, suggesting that it remained high until the onset of APAP. B Chest radiograph and computed tomography (CT) after whole lung lavage. Significant improvement in ground-glass shadows in both lungs was found after whole lung lavage. PSL, prednisolone; TAC, tacrolimus; IVCY, intravenous cyclophosphamide; IVIg, intravenous immunoglobulin; MDA-5, melanoma differentiation-associated gene 5; GM-CSF, granulocyte–macrophage colony-stimulating factor; KL-6, Krebs von den Lungen 6; APAP, autoimmune pulmonary alveolar proteinosis	4.027344	0.976563	sec[0]/sec[0]/p[0]	en	0.999997	38589870	https://doi.org/10.1186/s12890-024-02989-9	[ "lavage", "anti", "antibody", "dermatomyositis", "shadows", "interstitial", "both", "fluid", "whole", "lung" ]	[ { "code": "JA86.Y", "title": "Maternal care for other specified fetal problems" }, { "code": "MB23.1", "title": "Antisocial behaviour" }, { "code": "3B4Z", "title": "Coagulation defects, unspecified" }, { "code": "4A45.Z", "title": "Antiphospholipid syndrome, unspecified" }, { "code": "4A43.Y", "title": "Other specified overlap non-organ specific systemic autoimmune disease" }, { "code": "MA14.14", "title": "Anti-nuclear antibody positive" }, { "code": "MA14.13", "title": "Anti-nuclear antibody negative" }, { "code": "JA86.0", "title": "Maternal care for red cell antibodies" }, { "code": "MA14.1C", "title": "Raised antibody titre" }, { "code": "4A41.0Z", "title": "Dermatomyositis, unspecified" } ]	=== ICD-11 CODES FOUND === [JA86.Y] Maternal care for other specified fetal problems Also known as: Maternal care for other specified fetal problems \| Maternal care for other isoimmunization \| Isoimmunization NOS \| maternal antibodies NOS \| pregnancy management affected by incompatibility of blood groups NOS [MB23.1] Antisocial behaviour Definition: Behaviour in which the basic rights of others or major age-appropriate societal norms, rules, or laws, are violated. Also known as: Antisocial behaviour \| Child or adolescent antisocial behaviour [3B4Z] Coagulation defects, unspecified Also known as: Coagulation defects, unspecified \| blood clotting disturbance \| blood clotting defect \| blood clotting factor deficiency \| clotting abnormality [4A45.Z] Antiphospholipid syndrome, unspecified Also known as: Antiphospholipid syndrome, unspecified \| Antiphospholipid syndrome \| Hughes syndrome \| Anticardiolipin syndrome [4A43.Y] Other specified overlap non-organ specific systemic autoimmune disease Also known as: Other specified overlap non-organ specific systemic autoimmune disease \| Antisynthetase syndrome \| Reynolds syndrome \| Syndromic multisystem autoimmune disease due to ITCH deficiency \| Eosinophilia myalgia syndrome [MA14.14] Anti-nuclear antibody positive Also known as: Anti-nuclear antibody positive \| ANA - [anti-nuclear antibody] positive [MA14.13] Anti-nuclear antibody negative Also known as: Anti-nuclear antibody negative \| ANA - [anti-nuclear antibody] negative [JA86.0] Maternal care for red cell antibodies Definition: Maternal care for rhesus or other isoimmunization Also known as: Maternal care for red cell antibodies \| Maternal care for rhesus isoimmunization \| Rh factor immunization affecting management of pregnancy \| Rh incompatibility \| Rh incompatibility with hydrops fetalis [MA14.1C] Raised antibody titre Also known as: Raised antibody titre \| antibody titre above reference range \| high antibody titre \| increased antibody titre Excludes: isoimmunization, in pregnancy affecting fetus or newborn [4A41.0Z] Dermatomyositis, unspecified Also known as: Dermatomyositis, unspecified \| Dermatomyositis \| Petges-Clejat syndrome === GRAPH WALKS === --- Walk 1 --- [JA86.Y] Maternal care for other specified fetal problems --PARENT--> [JA86] Maternal care for other fetal problems Def: A condition characterised by the provision of health interventions to the mother due to any other issue that is either suspected or known to be present in the fetus.... --CHILD--> [JA86.2] Maternal care for signs of fetal hypoxia --- Walk 2 --- [JA86.Y] Maternal care for other specified fetal problems --PARENT--> [JA86] Maternal care for other fetal problems Def: A condition characterised by the provision of health interventions to the mother due to any other issue that is either suspected or known to be present in the fetus.... --EXCLUDES--> [?] Placental transfusion syndromes --- Walk 3 --- [MB23.1] Antisocial behaviour Def: Behaviour in which the basic rights of others or major age-appropriate societal norms, rules, or laws, are violated.... --PARENT--> [MB23] Symptoms or signs involving appearance or behaviour --CHILD--> [MB23.0] Aggressive behaviour Def: Actions intended to threaten or hurt another person or to damage property that may be physical, verbal, or symbolic (e.g., acting against the other person's interests). Aggressive behaviour may be app... --- Walk 4 --- [MB23.1] Antisocial behaviour Def: Behaviour in which the basic rights of others or major age-appropriate societal norms, rules, or laws, are violated.... --PARENT--> [MB23] Symptoms or signs involving appearance or behaviour --CHILD--> [MB23.0] Aggressive behaviour Def: Actions intended to threaten or hurt another person or to damage property that may be physical, verbal, or symbolic (e.g., acting against the other person's interests). Aggressive behaviour may be app... --- Walk 5 --- [3B4Z] Coagulation defects, unspecified --PARENT--> [?] Coagulation defects --CHILD--> [3B4Z] Coagulation defects, unspecified --- Walk 6 --- [3B4Z] Coagulation defects, unspecified --PARENT--> [?] Coagulation defects --CHILD--> [3B4Z] Coagulation defects, unspecified	[ "[JA86.Y] Maternal care for other specified fetal problems\n --PARENT--> [JA86] Maternal care for other fetal problems\n Def: A condition characterised by the provision of health interventions to the mother due to any other issue that is either suspected or known to be present in the fetus....\n --CHILD--> [JA86.2] Maternal care for signs of fetal hypoxia", "[JA86.Y] Maternal care for other specified fetal problems\n --PARENT--> [JA86] Maternal care for other fetal problems\n Def: A condition characterised by the provision of health interventions to the mother due to any other issue that is either suspected or known to be present in the fetus....\n --EXCLUDES--> [?] Placental transfusion syndromes", "[MB23.1] Antisocial behaviour\n Def: Behaviour in which the basic rights of others or major age-appropriate societal norms, rules, or laws, are violated....\n --PARENT--> [MB23] Symptoms or signs involving appearance or behaviour\n --CHILD--> [MB23.0] Aggressive behaviour\n Def: Actions intended to threaten or hurt another person or to damage property that may be physical, verbal, or symbolic (e.g., acting against the other person's interests). Aggressive behaviour may be app...", "[MB23.1] Antisocial behaviour\n Def: Behaviour in which the basic rights of others or major age-appropriate societal norms, rules, or laws, are violated....\n --PARENT--> [MB23] Symptoms or signs involving appearance or behaviour\n --CHILD--> [MB23.0] Aggressive behaviour\n Def: Actions intended to threaten or hurt another person or to damage property that may be physical, verbal, or symbolic (e.g., acting against the other person's interests). Aggressive behaviour may be app...", "[3B4Z] Coagulation defects, unspecified\n --PARENT--> [?] Coagulation defects\n --CHILD--> [3B4Z] Coagulation defects, unspecified", "[3B4Z] Coagulation defects, unspecified\n --PARENT--> [?] Coagulation defects\n --CHILD--> [3B4Z] Coagulation defects, unspecified" ]	JA86.Y	Maternal care for other specified fetal problems	[ { "from_icd11": "JA86.Y", "icd10_code": "O26841 ", "icd10_title": "" }, { "from_icd11": "JA86.Y", "icd10_code": "O26843 ", "icd10_title": "" }, { "from_icd11": "JA86.Y", "icd10_code": "O26849 ", "icd10_title": "" }, { "from_icd11": "JA86.Y", "icd10_code": "O3680X0 ", "icd10_title": "" }, { "from_icd11": "3B4Z", "icd10_code": "D688", "icd10_title": "Other specified coagulation defects" }, { "from_icd11": "3B4Z", "icd10_code": "D689", "icd10_title": "Coagulation defect, unspecified" }, { "from_icd11": "3B4Z", "icd10_code": "D699", "icd10_title": "Hemorrhagic condition, unspecified" }, { "from_icd11": "3B4Z", "icd10_code": "D698", "icd10_title": "Other specified hemorrhagic conditions" }, { "from_icd11": "3B4Z", "icd10_code": "D65-D69", "icd10_title": "" }, { "from_icd11": "3B4Z", "icd10_code": "D69", "icd10_title": "Purpura and other hemorrhagic conditions" }, { "from_icd11": "4A45.Z", "icd10_code": "D6861", "icd10_title": "Antiphospholipid syndrome" }, { "from_icd11": "4A45.Z", "icd10_code": "D6869", "icd10_title": "Other thrombophilia" }, { "from_icd11": "4A45.Z", "icd10_code": "D6862", "icd10_title": "Lupus anticoagulant syndrome" }, { "from_icd11": "4A45.Z", "icd10_code": "D686", "icd10_title": "Other thrombophilia" }, { "from_icd11": "JA86.0", "icd10_code": "O360930", "icd10_title": "Maternal care for other rhesus isoimmunization, third trimester, not applicable or unspecified" } ]	O26841
A 21-year-old male presented at our institute with complaints of holocranial headache, vomiting, and blurring of vision of an 8-month duration. Neuroimaging evaluation performed elsewhere at 2 months following the onset of symptoms showed communicating hydrocephalus and features of raised intracranial tension (bilateral peri-optic CSF space prominence). Diffuse thin leptomeningeal enhancement was seen enveloping the entire neuraxis. Few small cysts were noted along the dorsal spinal cord . With an empirical diagnosis of tubercular meningitis with hydrocephalus (TBM with HCP), anti-tubercular therapy was initiated empirically and ventriculo-peritoneal shunt was placed. The patient received an oral fixed dose combination of isoniazid (75 mg), rifampicin (150 mg), pyrazinamide (400 mg), and ethambutol (275 mg) and was administered as 3 tablets per day for 2 months. This was followed by an oral fixed dose combination of isoniazid (75 mg), rifampicin (150 mg), and ethambutol (275 mg), given as 3 tablets per day for 4 months. The patient tolerated the anti-tubercular medication without any adverse effects. However, the patient clinically deteriorated over the next 6 months despite antitubercular therapy and ventriculoperitoneal shunt placement. A review of the imaging acquired elsewhere at the first time point (2 months) was done at our institute. Nodularity of enhancement was observed at a few foci. The basal cisterns and bilateral Meckel’s caves appeared prominent with inhomogeneous CSF signal on T2W images. In spite of complete suppression of the signal on FLAIR in the abovementioned areas, an intense post-contrast enhancement was observed in the corresponding regions . An MRI performed at the current presentation showed an interval increase in the thickness and extent of the leptomeningeal enhancement. Multiple discrete, well-defined sub-pial cysts were present along the bilateral cerebral hemispheres, corpus callosum, cerebellum, brainstem, and along the spinal cord . On follow-up MRI, an extension of the lesion was evident with more florid involvement of the basal cisterns and ballooning of the Meckel’s caves was noted bilaterally. The lesion was distorting the optic chiasm and appeared to extend along the left optic nerve sheath. However, there was an absence of lesional FLAIR inversion in the current scan, and more avid enhancement was evident. Asymmetric enhancement (left > right) was also noted along the bilateral optic nerves , Meckel’s cave, and internal acoustic canal. Within the sulcal spaces, the admix of CSF loculations and tumoral cyst were evident, weighing in the non-enhancement, FLAIR inversion possibly corresponded to loculated CSF . Susceptibility and diffusion characteristics were unremarkable. Considering the distinct imaging findings, a diagnosis of DLGNT was suggested. The CSF analysis, with 30 ml of sample volume obtained with standard lumbar puncture technique, showed 24 cells/mm 3 (lymphocytes) with no atypical cells. Previous CSF analysis report was not available with the patient for comparison. Nucleic acid amplification test was negative for Mycobacterium tuberculosis . The CSF protein level was 3174 mg/dl (normal range 15–45 mg/dl), CSF glucose level was 104 mg/dl (normal range 40–0 mg/dl), and CSF lactate level was 38 mg/dl (normal range 10–22 mg/dl). CSF culture failed to grow any organism at 48 h. India Ink staining for Cryptococcus neoformans , fungal stains, and fungal cultures were negative. Fig. 1 Magnetic resonance imaging of the brain and dorsal spine at 2 months following the onset of symptoms. A T2W coronal image of the brain at the level of the foramen of Monro shows dilated bilateral lateral ventricles. The black arrows point to the dilated frontal and temporal horn of the right lateral ventricle. B T1W post-contrast image of the brain at the level of the mid-brain shows diffuse and thin leptomeningeal enhancement. The black arrow is pointing towards the leptomeningeal enhancement along the quadrigeminal cistern. C T2W coronal image of the brain at the level of the orbits (zoomed to demonstrate optic nerves) shows distended per-optic CSF spaces. The white arrows point towards the distended peri-optic CSF spaces. D Sagittal T2W MRI of the dorsal spine shows few cysts along the dorsal spinal cord. The white arrows point towards the intramedullary cysts within the dorsal cord. E Post-contrast T1W sagittal image of the spine. There is diffuse leptomeningeal enhancement noted along the cord surface and the nerve roots of cauda equina. The white arrows point towards the leptomeningeal enhancement along the dorsal cord and also the cauda equina Fig. 2 Magnetic resonance imaging of the brain at 2 months following the onset of symptoms. A Axial T1W post-gadolinium image of the brain at the level of the mid-brain shows nodularity of leptomeningeal enhancement. The black arrows point towards the nodular leptomeningeal enhancement along the Sylvian fissures. B T2W axial image of the brain at the level of the mid-brain shows expansion of the quadrigeminal cistern with inhomogeneous signal of the CSF. The black arrows are seen to point towards the inhomogeneous CSF signal in the quadrigeminal cistern. C Axial FLAIR image of the brain at the level of mid-brain shows complete signal suppression as compared with T2W image in B . The black arrows depict the suppression of CSF signal on FLAIR. D Post-contrast T1W axial images of the brain show enhancement along the CSF spaces corresponding to the T2 and FLAIR images. The black arrows point towards the enhancement along the CSF spaces Fig. 3 Follow-up magnetic resonance imaging of the brain at our institute 8 months after the onset of the symptoms. A Post-contrast T1W axial image of the brain at the basal ganglia level shows enhancement along the CSF spaces. The white arrow points towards the enhancement along the CSF spaces in the velum interpositum cistern. B T2W sagittal image of the brain in the mid-sagittal plane shows multiple small cysts of varying sizes along the cerebellar folia and the pial surfaces of the corpus callosum. The white arrows point towards the small cysts along the cerebellar folia and the corpus callosum Fig. 4 Follow-up magnetic resonance imaging of the brain at our institute 8 months after the onset of the symptoms. A T2W axial image of the brain at the level of the Meckel’s caves shows ballooning of the Meckel’s cave bilaterally. The white arrows point towards the ballooning of bilateral Mecksl’s caves. B T2W coronal image of the brain at the level of the optic chiasm shows expanded chiasmatic cistern with displaced optic chiasm. The white arrow points towards the displaced optic chiasm. C T2W axial image of the brain at the level of the velum interpositum. There is expansion of the velum interpositum with hyperintense signal as demonstrated with black arrow. D Axial FLAIR image of the brain at the level of velum interpositum shows no signal suppression in the velum intrepositum on FLAIR, as pointed out with black arrow, in comparison with T2W image shown in C . E Post-contrast T1W coronal image of the brain at the level of the orbits depicts enhancement along bilateral optic nerves as pointed out with white arrows. F Post-contrast T1W coronal image at the level of the Meckel’s cave shows avid enhancement is noted along bilateral Meckel’s caves and internal acoustic canals as shown with the help of white arrows. G Post-contrast T1W axial image at the level of the internal acoustic canals showing avid contrast enhancement along the bilateral Meckel’s caves and the internal acoustic canals as demonastrated with white arrows Fig. 5 Follow-up magnetic resonance imaging of the brain at our institute 8 months after the onset of the symptoms. A T2W axial image of the brain at the level of the basal ganglia shows T2 hyperintense cystic structures in the right temporal operculum and the anterior interhemispheric fissure as pointed out with the help of black arrows. B Axial FLAIR image of the brain at the level of the basal ganglia shows the signal suppression in the cystic lesions on FLAIR as compared with T2W image shown in A . This finding is pointed out with the black arrows. C Post-contrast T1W axial image of the brain at the level of basal ganglia shows no evidence of enhancement of the cystic structures, pointed out with white arrows. These cystic structures may represent encysted or loculated CSF	4.082031	0.974609	sec[1]/p[0]	en	0.999998	PMC8193168	https://doi.org/10.1186/s43055-021-00522-0	[ "brain", "enhancement", "along", "arrows", "axial", "optic", "towards", "white", "point", "flair" ]	[ { "code": "8E7Y", "title": "Other specified diseases of the nervous system" }, { "code": "LA05.Z", "title": "Cerebral structural developmental anomalies, unspecified" }, { "code": "1D00.Z", "title": "Infectious encephalitis, unspecified" }, { "code": "LA00.0Z", "title": "Anencephaly, unspecified" }, { "code": "NA07.3Y", "title": "Other specified diffuse brain injury" }, { "code": "8A04.0", "title": "Enhanced physiological tremor" }, { "code": "8E4A.0", "title": "Paraneoplastic or autoimmune disorders of the central nervous system, brain or spinal cord" }, { "code": "NA22.1Z", "title": "Fracture of second cervical vertebra, unspecified" }, { "code": "9A20.0Z", "title": "Axial displacement of eyeball, unspecified" }, { "code": "9A20.0Y", "title": "Other specified axial displacement of eyeball" } ]	=== ICD-11 CODES FOUND === [8E7Y] Other specified diseases of the nervous system Also known as: Other specified diseases of the nervous system \| Circumscribed brain atrophy \| circumscribed cerebral atrophy \| atrophic lobar sclerosis \| atrophic lobar brain sclerosis [LA05.Z] Cerebral structural developmental anomalies, unspecified Also known as: Cerebral structural developmental anomalies, unspecified \| Cerebral structural developmental anomalies \| Malformations of brain \| brain abnormality NOS \| brain deformity NOS [1D00.Z] Infectious encephalitis, unspecified Also known as: Infectious encephalitis, unspecified \| Infectious encephalitis, not elsewhere classified \| encephalitis NOS \| acute encephalitis NOS \| acute brain inflammation [LA00.0Z] Anencephaly, unspecified Also known as: Anencephaly, unspecified \| Anencephaly \| anencephalic monster \| anencephalus \| brain absence [NA07.3Y] Other specified diffuse brain injury Also known as: Other specified diffuse brain injury \| Brain contusion \| Cerebral contusion NOS \| Diffuse cortex contusion \| diffuse cortical contusion [8A04.0] Enhanced physiological tremor Definition: This is a high frequency, low amplitude tremor present with posture or action. It represents an exacerbation of a physiologic tremor which may have been worsened by drugs, stress, anxiety, etc. Also known as: Enhanced physiological tremor [8E4A.0] Paraneoplastic or autoimmune disorders of the central nervous system, brain or spinal cord Definition: Paraneoplastic and autoimmune disorders of the central nervous system, brain and spinal cord nervous system result from a targeted immune attack on neurons or glial cells in the central (e.g. encephalopathy, ataxia, myelopathy, myelitis) nervous system. In the paraneoplastic context, this attack is a consequence of a potentially effective tumour immune response initiated by onco-neural antigens derived from a systemic cancer. In the non-paraneoplastic context termed ‘autoimmune’ the etiology rem Also known as: Paraneoplastic or autoimmune disorders of the central nervous system, brain or spinal cord \| Paraneoplastic encephalitis \| Paraneoplastic encephalitis, neural autoantibody positive \| Paraneoplastic encephalitis, neural autoantibody negative \| Autoimmune encephalitis [NA22.1Z] Fracture of second cervical vertebra, unspecified Also known as: Fracture of second cervical vertebra, unspecified \| Fracture of second cervical vertebra \| fracture of axis of spine \| C2 fracture \| axial fracture dislocation [9A20.0Z] Axial displacement of eyeball, unspecified Also known as: Axial displacement of eyeball, unspecified \| Axial displacement of eyeball [9A20.0Y] Other specified axial displacement of eyeball Also known as: Other specified axial displacement of eyeball === GRAPH WALKS === --- Walk 1 --- [8E7Y] Other specified diseases of the nervous system --PARENT--> [08] Diseases of the nervous system Def: This is a group of conditions characterised as being in or associated with the nervous system.... --PARENT--> [?] ICD-11 for Mortality and Morbidity Statistics --- Walk 2 --- [8E7Y] Other specified diseases of the nervous system --PARENT--> [08] Diseases of the nervous system Def: This is a group of conditions characterised as being in or associated with the nervous system.... --EXCLUDES--> [?] Endocrine, nutritional or metabolic diseases Def: This chapter includes endocrine diseases, nutritional diseases as well as metabolic diseases.... --- Walk 3 --- [LA05.Z] Cerebral structural developmental anomalies, unspecified --PARENT--> [LA05] Cerebral structural developmental anomalies Def: Any condition caused by failure of the brain to correctly develop during the antenatal period.... --CHILD--> [LA05.2] Holoprosencephaly Def: Holoprosencephaly is a brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and the 28th day of gestation and affecting both the forebrain and the fa... --- Walk 4 --- [LA05.Z] Cerebral structural developmental anomalies, unspecified --PARENT--> [LA05] Cerebral structural developmental anomalies Def: Any condition caused by failure of the brain to correctly develop during the antenatal period.... --CHILD--> [LA05.1] Megalencephaly Def: A condition caused by failure of the brain to correctly develop during the antenatal period. This condition is characterised by increased size or weight of an otherwise correctly formed brain. This co... --- Walk 5 --- [1D00.Z] Infectious encephalitis, unspecified --PARENT--> [1D00] Infectious encephalitis, not elsewhere classified Def: A disease of the brain, caused by an infection.... --CHILD--> [1D00.1] Fungal encephalitis --- Walk 6 --- [1D00.Z] Infectious encephalitis, unspecified --PARENT--> [1D00] Infectious encephalitis, not elsewhere classified Def: A disease of the brain, caused by an infection.... --CHILD--> [1D00.0] Bacterial encephalitis	[ "[8E7Y] Other specified diseases of the nervous system\n --PARENT--> [08] Diseases of the nervous system\n Def: This is a group of conditions characterised as being in or associated with the nervous system....\n --PARENT--> [?] ICD-11 for Mortality and Morbidity Statistics", "[8E7Y] Other specified diseases of the nervous system\n --PARENT--> [08] Diseases of the nervous system\n Def: This is a group of conditions characterised as being in or associated with the nervous system....\n --EXCLUDES--> [?] Endocrine, nutritional or metabolic diseases\n Def: This chapter includes endocrine diseases, nutritional diseases as well as metabolic diseases....", "[LA05.Z] Cerebral structural developmental anomalies, unspecified\n --PARENT--> [LA05] Cerebral structural developmental anomalies\n Def: Any condition caused by failure of the brain to correctly develop during the antenatal period....\n --CHILD--> [LA05.2] Holoprosencephaly\n Def: Holoprosencephaly is a brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and the 28th day of gestation and affecting both the forebrain and the fa...", "[LA05.Z] Cerebral structural developmental anomalies, unspecified\n --PARENT--> [LA05] Cerebral structural developmental anomalies\n Def: Any condition caused by failure of the brain to correctly develop during the antenatal period....\n --CHILD--> [LA05.1] Megalencephaly\n Def: A condition caused by failure of the brain to correctly develop during the antenatal period. This condition is characterised by increased size or weight of an otherwise correctly formed brain. This co...", "[1D00.Z] Infectious encephalitis, unspecified\n --PARENT--> [1D00] Infectious encephalitis, not elsewhere classified\n Def: A disease of the brain, caused by an infection....\n --CHILD--> [1D00.1] Fungal encephalitis", "[1D00.Z] Infectious encephalitis, unspecified\n --PARENT--> [1D00] Infectious encephalitis, not elsewhere classified\n Def: A disease of the brain, caused by an infection....\n --CHILD--> [1D00.0] Bacterial encephalitis" ]	8E7Y	Other specified diseases of the nervous system	[ { "from_icd11": "LA05.Z", "icd10_code": "Q048", "icd10_title": "Other specified congenital malformations of brain" }, { "from_icd11": "LA05.Z", "icd10_code": "Q043", "icd10_title": "Other reduction deformities of brain" }, { "from_icd11": "LA05.Z", "icd10_code": "Q049", "icd10_title": "Congenital malformation of brain, unspecified" }, { "from_icd11": "LA05.Z", "icd10_code": "Q04", "icd10_title": "Other congenital malformations of brain" }, { "from_icd11": "1D00.Z", "icd10_code": "G0490", "icd10_title": "Encephalitis and encephalomyelitis, unspecified" }, { "from_icd11": "1D00.Z", "icd10_code": "G0491", "icd10_title": "Myelitis, unspecified" }, { "from_icd11": "1D00.Z", "icd10_code": "G0430", "icd10_title": "Acute necrotizing hemorrhagic encephalopathy, unspecified" }, { "from_icd11": "1D00.Z", "icd10_code": "G0431", "icd10_title": "Postinfectious acute necrotizing hemorrhagic encephalopathy" }, { "from_icd11": "1D00.Z", "icd10_code": "G0439", "icd10_title": "Other acute necrotizing hemorrhagic encephalopathy" }, { "from_icd11": "1D00.Z", "icd10_code": "G0481", "icd10_title": "Other encephalitis and encephalomyelitis" }, { "from_icd11": "1D00.Z", "icd10_code": "G0489", "icd10_title": "Other myelitis" }, { "from_icd11": "1D00.Z", "icd10_code": "G04", "icd10_title": "Encephalitis, myelitis and encephalomyelitis" }, { "from_icd11": "1D00.Z", "icd10_code": "G048", "icd10_title": "Other encephalitis, myelitis and encephalomyelitis" }, { "from_icd11": "LA00.0Z", "icd10_code": "Q000", "icd10_title": "Anencephaly" }, { "from_icd11": "8A04.0", "icd10_code": "G252", "icd10_title": "Other specified forms of tremor" } ]	Q048	Other specified congenital malformations of brain
It is worthy to mention that ocular nerve palsies are rare in childhood . Specifically, the third cranial nerve is the less affected in children . RPON is one of the rarest causes of third cranial nerve palsy . Herein, we report a case of third cranial nerve paresis in a 17-month-old male child, presenting a neuroradiological pattern highly suggestive of schwannoma, aneurism or RPON. Even if the MRI at the first attack was highly suggestive of RPON, the diagnosis according to the ICHD was not possible. Thus, as shown in Tables 1 and 2 , we systematically reviewed the pediatric cases of RPON/OM occurred within 2 years of age comparing them with our case. Table 1 Reports from 1996 to 2007 Main features Østergaard Østergaard Ramelli Lance Weiss Carlow Carlow Age at onset 18 mo 7 mo 20 mo 9 mo 24 mo 18 mo 18 mo Current age 8 yr 19 yr 8 yr 16 yr 7 yr - - Sex F F F F M F F CN involved (side) III (L) III(L) III (R) III (L) III (L) - - Headache (side) Yes (starting with the 2nd episode; bilateral or left sided) Yes (starting with her 5th episode; left-sided and eye pain) Yes (starting with the 2nd episode at the age of 6 yr and 8 mo after a fall backwards – no apparent headache at 1st episode) Yes (behind the left eye, described as sharp and fluctuating in intensity) Yes (L; supraorbital) Yes Yes Associated symptoms No Yes No Yes No - - Photophobia - - - Yes - - - Phonophobia - - - Yes - - - Nausea - - - Yes - - - Vomiting - Yes - Yes (sometimes) - - - Irritability - Yes - - - - - Other findings Signs of varicella infection at 2nd episode Dizziness at 4th episode Drowsiness - Attacks of screaming - - - Ocular symptoms/signs Yes Yes Yes Yes Yes - - Diplopia NS NS Yes NS Yes - - Ophthalmoplegia Yes (not always present) Yes Yes Yes Yes - - Palpebral ptosis Yes Yes Yes Yes Yes - - Pupillary dilation Yes (poorly reactive pupil to light) Yes Yes (poorly reactive to light) Yes (reactive to light with progression to unresponsive pupil) Yes (sluggish response to light) No Yes MRI findings in the acute phase MRI perfomerd 12 days later 2nd episode onset (ptosis partially resolved) Not performed Yes – At second episode (not performed at the 1st episode) Yes Yes – performed after 2 weeks of onset (several foci of white matter hyperintensity measuring 3 mm or less identified in the dorsal periventricular region) Yes Yes Nerve thickening Yes (from the brainstem through the prepontin cistern to the carvernous sinus) - Yes No No Yes Yes Post-contrast enhancement Yes - Yes Yes—at the point of exit of the nerve from the midbrain, continuing along the line of the nerve No Yes Yes Altered CSF if lumbar puncture performed No (2nd episode) No No NS - - - Headache duration 3–4 days NS NS NS NS - - Ophthalmoplegia duration NS NS NS NS NS - - Interval between headache onset and ophthalmoplegia 3–4 days 1 day 4 days (second episode) NS – 3–4 days between headache and palpebral ptosis NS - - Time to resolution of Symptoms/Signs 6–8 weeks 6 mo (1st episode) Within 2 weeks (first episode) From few days (2–11) to 2 months NS - - Therapy in the acute phase Prednisone (2 mg/kg/day) for about 10 days with apparent response NS NS NS - - - Follow-up Yes ( refered migraine attacks without ophthalmoplegia) Yes (permanent partial III CN palsy) - Yes (with apparent decreased number of episodes) NS - - Prophylactic therapy - Propranolol Metoclopramide Diazepam Acetaminophen - Cafergot; Aspirin; Amitriptyline; Pizotifen; Flunarizine ( 10 mg/day with apparent response) NS - - Control MRI Performed after 3 months of the 3rd episode onset (persistent enlargement of III CN but to a lesser degree) MRIs at 14, 15, 16-years-of-age showing persistent enlargement (from the brainstem through the prepontin cistern to the carvernous sinus) NS A repeat MRI scan showed enhancement of the oculomotor nerve still present but less intense; unenhanced MRIs of the brain at the ages of 12 and 14 years were normal - - - Number of acute episodes NS ( about four episodes) NS NS NS – About 38 episodes - - - Interval between episodes Range 15 mo -3 yr 6–9 mo NS NS - - - Comorbidity Migraine - Migraine without aura - Migraine - - Family history of migraine No No Yes (on the maternal side) Yes (on the maternal side) No Yes No Table 2 Reports from 2007 to 2015 Main features McMillan Bharucha Vecino López Vieira Riadh Ghosh Age at onset 12 mo 18 mo Before 6 mo 9 mo 9 mo 18 mo Current age 6 yr 16 yr 3 yr and 11 mo 7 yr 3 yr NS Sex M F F M F M CN involved (side) III (L) III (R) III(R) III(R) III(L) III(R) Headache (side) Yes (starting with his 4th episode) Yes (R) - Yes(R, frontotemporal and orbital pain) Yes(L) Yes(starting with 2nd episode) Associated symptoms No No - Yes Yes No Photophobia - - - Yes - - Phonophobia - - - Yes - - Nausea - - - Yes Yes - Vomiting - - - Yes(occasional-ly during the first days of a episode) Yes - Irritability - - - - - - Other findings - - - - Yes (abdominal pain) - Ocular symptoms/signs Yes Yes Yes Yes Yes Yes Diplopia - Yes NS NS - Yes (starting with 2nd episode) Ophthalmoplegia Yes Yes Yes Yes Yes No Palpebral ptosis Yes Yes Yes Yes Yes Yes Pupillary dilation No—During his fourth episode, at 29-months-of-age, the authors describe a left sluggish pupil response Yes (not reactive to light) Yes (sluggish pupil response) Yes Yes (mildly dilated, reactive to light) No MRI findings in the acute phase Yes Yes (during last episode on the day of onset of symptoms; all previous MRI exams had yielded normal findings Yes Yes (infundibular dilatation of a perforating branch of the posterior cerebral artery emerging just above the superior cerebellar artery, adjacent to the affected nerve) No Yes Nerve thickening Yes – at the forth episode (29 mo of age; cisternal part of nerve root) Yes (at nerve root origin) Yes (cisternal part) No - Yes [cisternal part – performed at 18 mo(first episode)] Post-contrast enhancement Yes – during first episode (12 mo of age; at the site of exit of nerve root) and forth episode (29 mo of age; cisternal part of nerve root) Yes (at nerve root origin) No No - No Altered CSF if lumbar puncture performed No No (during last episode) NS NS NS No Headache duration 2–3 days (4th episode) NS - 3–7 days NS 6–7 days (before development of ptosis Ophthalmoplegia duration From 2–3 days (1st episode) to 2–3 weeks (4th episode) NS 3 mo 2–5 days (initially) 1–4 weeks NS - Interval between headache onset and ophthalmoplegia 2–3 days (4th episode) Within 6 h of onset NS At onset of pain NS - Time to resolution of Symptoms/Signs From 2–3 days (1st episode) to 2–3 weeks (4th episode)- The authors describe periodic recurrence with each episode taking longer to recupera-te Within 1 week of symptom onset (last episode) 3 mo ( the authors report the use of botulinum toxin for squint) 1–4 weeks NS 3 weeks (1st episode) Therapy in the acute phase Prednisone(2 mg/kg for 10 days) with tapering over the following week and apparent response Methylprednisolone iv 25 mg/Kg for 5 days (at last episode, started immediately on the first day of onset) Oral corticosteroids Oral prednisone (1 mg/kg/day) with apparent response This treatment was used twice and the pain subsided much earlier (within 24–48 h) 3 pulses of methyl-prednisolone followed by an oral steroid therapy (1 mg/kg/day) for 1 week with gradual tapering over 6 weeks Methylprednisolone iv 30 mg/Kg for 3 days (1st episode); Immunoglobulin iv 2 g/kg for 2 days (2nd episode) Follow-up At the age of 6 years, periodic recurrence of complete left III CN paresis, with each episode taking longer to recuperate – episodes of migraine without aura—permanent neurological damage with relative mydriasis (reactive to light) Yes Yes ( not fully recovering from ophthalmople-gia) No episodes Normal neurologic examination Prophylactic therapy Pizotifen (beneficial for migraine,not for ophthalmople-gia) - Flunarizine (decreased number of episodes) - - Control MRI MRI at 15 mo of age with normal findings Yes (at 3 and 7 months after the onset of symptoms with demonstrated reversal of abnormalities) MRI after four mo of onset (reduced III CN enlargement) NS - - Number of acute episodes NS ( the authors describes surely foru episodes at 12, 17, 23 and 29-months-of-age) 8 NS NS 4 (9 mo, 1y, 2y, 3y) 3 ( 18mo, 3y, 5y) Interval between episodes NS - NS From weeks to months Range 3–12 mo Range 16–24 mo Comorbidity No No - No - - Family history of migraine No - - Yes (on the maternal side) Yes Yes (on the maternal side)	4.195313	0.675293	sec[0]/p[1]	en	0.999996	PMC9164546	https://doi.org/10.1186/s13052-022-01274-x	[ "episode", "nerve", "onset", "episodes", "side", "headache", "migraine", "ophthalmoplegia", "light", "response" ]	[ { "code": "8A68.Y", "title": "Other specified type of seizure" }, { "code": "MD11.1", "title": "Asphyxia" }, { "code": "AB31.Z", "title": "Episodic vestibular syndrome, unspecified" }, { "code": "AB31.Y", "title": "Other specified episodic vestibular syndrome" }, { "code": "6C45.0", "title": "Episode of harmful use of cocaine" }, { "code": "8C1Z", "title": "Mononeuropathy of unspecified site" }, { "code": "ND56.4", "title": "Injury of nerve of unspecified body region" }, { "code": "8B80", "title": "Disorders of olfactory nerve" }, { "code": "8C0Z", "title": "Polyneuropathy, unspecified" }, { "code": "9C40.Z", "title": "Disorder of the optic nerve, unspecified" } ]	=== ICD-11 CODES FOUND === [8A68.Y] Other specified type of seizure Also known as: Other specified type of seizure \| Absence episode \| Absence seizure episode \| Pseudotetanus \| Clonic seizure disorder [MD11.1] Asphyxia Definition: Asphyxia is a life-threatening condition in which oxygen is prevented from reaching the tissues by obstruction of or damage to any part of the respiratory system. More generally the term indicates all the conditions generating impaired or impeded breathing. Also known as: Asphyxia \| pathological asphyxia \| decreased oxygen supply \| oxygen deficiency \| positional asphyxia Excludes: asphyxia due to foreign body in respiratory tract \| asphyxia due to carbon monoxide \| asphyxia due to traumatic [AB31.Z] Episodic vestibular syndrome, unspecified Also known as: Episodic vestibular syndrome, unspecified \| Episodic vestibular syndrome [AB31.Y] Other specified episodic vestibular syndrome Also known as: Other specified episodic vestibular syndrome \| Secondary episodic vestibular syndrome \| Episodic vestibular syndrome in diseases classified elsewhere \| Episodic vestibular syndrome due to cerebrovascular disease \| Episodic vestibular syndrome due to diseases of the circulatory system [6C45.0] Episode of harmful use of cocaine Definition: An episode of use of cocaine that has caused damage to a person’s physical or mental health or has resulted in behaviour leading to harm to the health of others. Harm to health of the individual occurs due to one or more of the following: (1) behaviour related to intoxication; (2) direct or secondary toxic effects on body organs and systems; or (3) a harmful route of administration. Harm to health of others includes any form of physical harm, including trauma, or mental disorder that is directly Also known as: Episode of harmful use of cocaine Excludes: Cocaine dependence \| Harmful pattern of use of cocaine [8C1Z] Mononeuropathy of unspecified site Also known as: Mononeuropathy of unspecified site \| inflammation of nerve NOS \| nerve condition NOS \| neuritis NOS \| nerve disease NOS [ND56.4] Injury of nerve of unspecified body region Also known as: Injury of nerve of unspecified body region \| injuries to nerves, nerve plexuses and roots \| injury to nerves, unspecified site \| nerve damage NOS \| Injury of nerve NOS Excludes: multiple injuries of nerves NOS [8B80] Disorders of olfactory nerve Also known as: Disorders of olfactory nerve \| disorders of olfactory [1st] nerve \| disorders of the first nerve \| first cranial nerve disorder \| disease of first cranial nerve Includes: Disorder of 1st cranial nerve Excludes: Idiopathic anosmia \| Idiopathic parosmia [8C0Z] Polyneuropathy, unspecified Also known as: Polyneuropathy, unspecified \| multiple neuropathy \| peripheral neuropathy NOS \| peripheral polyneuropathy \| multiple peripheral neuritis [9C40.Z] Disorder of the optic nerve, unspecified Also known as: Disorder of the optic nerve, unspecified \| Disorder of the optic nerve \| disease of optic cranial nerve \| disease of optic nerve \| disease of second cranial nerve === GRAPH WALKS === --- Walk 1 --- [8A68.Y] Other specified type of seizure --PARENT--> [8A68] Types of seizures --EXCLUDES--> [?] Dissociative neurological symptom disorder, with non-epileptic seizures Def: Dissociative neurological symptom disorder, with non-epileptic seizures is characterised by a symptomatic presentation of seizures or convulsions that are not consistent with a recognised disease of t... --- Walk 2 --- [8A68.Y] Other specified type of seizure --PARENT--> [8A68] Types of seizures --EXCLUDES--> [?] Neonatal seizures Def: A paediatric condition characterised by rapid and repeated muscle contraction and relaxation, resulting in an uncontrolled shaking of the body of a newborn.... --- Walk 3 --- [MD11.1] Asphyxia Def: Asphyxia is a life-threatening condition in which oxygen is prevented from reaching the tissues by obstruction of or damage to any part of the respiratory system. More generally the term indicates all... --RELATED_TO--> [?] Birth asphyxia --EXCLUDES--> [?] Intrauterine hypoxia Def: Intrauterine hypoxia occurs when the fetus is deprived of an adequate supply of oxygen. This may occur with prolapse or occlusion of the umbilical cord, placental infarction and maternal smoking. This... --- Walk 4 --- [MD11.1] Asphyxia Def: Asphyxia is a life-threatening condition in which oxygen is prevented from reaching the tissues by obstruction of or damage to any part of the respiratory system. More generally the term indicates all... --EXCLUDES--> [?] Foreign body in respiratory tract --CHILD--> [?] Foreign body in pharynx Def: Objects that inadvertently enter the pharynx from the environment.... --- Walk 5 --- [AB31.Z] Episodic vestibular syndrome, unspecified --PARENT--> [AB31] Episodic vestibular syndrome Def: A clinical syndrome of transient vertigo, dizziness, or unsteadiness lasting seconds to hours, occasionally days, and generally including features suggestive of temporary, short-lived vestibular syste... --CHILD--> [AB31.0] Meniere disease Def: Meniere Disease (MD) is a chronic progressive inner ear disease, with endolymphatic hydrops. It is characterised by recurrent attacks of debilitating spontaneous vertigo lasting from 20 minutes to up ... --- Walk 6 --- [AB31.Z] Episodic vestibular syndrome, unspecified --PARENT--> [AB31] Episodic vestibular syndrome Def: A clinical syndrome of transient vertigo, dizziness, or unsteadiness lasting seconds to hours, occasionally days, and generally including features suggestive of temporary, short-lived vestibular syste... --CHILD--> [AB31.2] Benign positional paroxysmal vertigo Def: Benign paroxysmal positional vertigo is defined as an abnormal sensation of motion that is elicited by certain critical provocative physical positions of the patient (e.g. becoming dorsal recumbent). ...	[ "[8A68.Y] Other specified type of seizure\n --PARENT--> [8A68] Types of seizures\n --EXCLUDES--> [?] Dissociative neurological symptom disorder, with non-epileptic seizures\n Def: Dissociative neurological symptom disorder, with non-epileptic seizures is characterised by a symptomatic presentation of seizures or convulsions that are not consistent with a recognised disease of t...", "[8A68.Y] Other specified type of seizure\n --PARENT--> [8A68] Types of seizures\n --EXCLUDES--> [?] Neonatal seizures\n Def: A paediatric condition characterised by rapid and repeated muscle contraction and relaxation, resulting in an uncontrolled shaking of the body of a newborn....", "[MD11.1] Asphyxia\n Def: Asphyxia is a life-threatening condition in which oxygen is prevented from reaching the tissues by obstruction of or damage to any part of the respiratory system. More generally the term indicates all...\n --RELATED_TO--> [?] Birth asphyxia\n --EXCLUDES--> [?] Intrauterine hypoxia\n Def: Intrauterine hypoxia occurs when the fetus is deprived of an adequate supply of oxygen. This may occur with prolapse or occlusion of the umbilical cord, placental infarction and maternal smoking. This...", "[MD11.1] Asphyxia\n Def: Asphyxia is a life-threatening condition in which oxygen is prevented from reaching the tissues by obstruction of or damage to any part of the respiratory system. More generally the term indicates all...\n --EXCLUDES--> [?] Foreign body in respiratory tract\n --CHILD--> [?] Foreign body in pharynx\n Def: Objects that inadvertently enter the pharynx from the environment....", "[AB31.Z] Episodic vestibular syndrome, unspecified\n --PARENT--> [AB31] Episodic vestibular syndrome\n Def: A clinical syndrome of transient vertigo, dizziness, or unsteadiness lasting seconds to hours, occasionally days, and generally including features suggestive of temporary, short-lived vestibular syste...\n --CHILD--> [AB31.0] Meniere disease\n Def: Meniere Disease (MD) is a chronic progressive inner ear disease, with endolymphatic hydrops. It is characterised by recurrent attacks of debilitating spontaneous vertigo lasting from 20 minutes to up ...", "[AB31.Z] Episodic vestibular syndrome, unspecified\n --PARENT--> [AB31] Episodic vestibular syndrome\n Def: A clinical syndrome of transient vertigo, dizziness, or unsteadiness lasting seconds to hours, occasionally days, and generally including features suggestive of temporary, short-lived vestibular syste...\n --CHILD--> [AB31.2] Benign positional paroxysmal vertigo\n Def: Benign paroxysmal positional vertigo is defined as an abnormal sensation of motion that is elicited by certain critical provocative physical positions of the patient (e.g. becoming dorsal recumbent). ..." ]	8A68.Y	Other specified type of seizure	[ { "from_icd11": "MD11.1", "icd10_code": "R0901", "icd10_title": "Asphyxia" }, { "from_icd11": "MD11.1", "icd10_code": "R0902", "icd10_title": "Hypoxemia" }, { "from_icd11": "MD11.1", "icd10_code": "R090", "icd10_title": "Asphyxia and hypoxemia" }, { "from_icd11": "8C1Z", "icd10_code": "G59", "icd10_title": "Mononeuropathy in diseases classified elsewhere" }, { "from_icd11": "8C1Z", "icd10_code": "G598", "icd10_title": "" }, { "from_icd11": "ND56.4", "icd10_code": "T144", "icd10_title": "" }, { "from_icd11": "8B80", "icd10_code": "G520", "icd10_title": "Disorders of olfactory nerve" }, { "from_icd11": "8C0Z", "icd10_code": "G629", "icd10_title": "Polyneuropathy, unspecified" }, { "from_icd11": "8C0Z", "icd10_code": "G53", "icd10_title": "Cranial nerve disorders in diseases classified elsewhere" }, { "from_icd11": "8C0Z", "icd10_code": "G538", "icd10_title": "" }, { "from_icd11": "9C40.Z", "icd10_code": "H47012", "icd10_title": "Ischemic optic neuropathy, left eye" }, { "from_icd11": "9C40.Z", "icd10_code": "H47099", "icd10_title": "Other disorders of optic nerve, not elsewhere classified, unspecified eye" }, { "from_icd11": "9C40.Z", "icd10_code": "H47091", "icd10_title": "Other disorders of optic nerve, not elsewhere classified, right eye" }, { "from_icd11": "9C40.Z", "icd10_code": "H47093", "icd10_title": "Other disorders of optic nerve, not elsewhere classified, bilateral" }, { "from_icd11": "9C40.Z", "icd10_code": "H47019", "icd10_title": "Ischemic optic neuropathy, unspecified eye" } ]	R0901	Asphyxia
This patient’s history is based on an original case observed and managed by the authors at our clinic. A 34-year-old female presented with a complex constellation of symptoms that ultimately led to the diagnosis and management of WPW syndrome. Her case underscores the critical importance of meticulous assessment and tailored management in patients with this condition. The patient initially presented with a history of recurrent palpitations and episodes of lightheadedness over the past 18 months. She described the palpitations as sudden onset, lasting for several minutes, and often associated with dizziness and shortness of breath. Her episodes were infrequent but had become progressively more intense and distressing, prompting her to seek medical attention. Upon further inquiry, it was revealed that the patient had no significant past medical history. She was otherwise healthy and did not have any notable family history of cardiovascular disease. She was a nonsmoker with no history of excessive alcohol consumption or drug use. Her physical examination was largely unremarkable, except for a regular pulse and blood pressure within normal limits. However, an ECG conducted during an episode of palpitations showed characteristic findings of WPW syndrome, including a short PR interval and a delta wave, indicative of preexcitation. Given the clinical presentation and ECG findings, a referral to a cardiologist was made for further evaluation. The cardiologist, noting the presence of symptoms consistent with WPW syndrome, recommended an ambulatory Holter monitor to assess the frequency and duration of arrhythmias. The Holter monitor captured several episodes of SVT, reinforcing the suspicion of WPW syndrome and demonstrating the need for intervention. The patient was subsequently referred for an EPS. The EPS revealed the presence of a concealed accessory pathway, which was responsible for the recurrent episodes of SVT. The study also highlighted that the accessory pathway was located on the left side of the heart, a finding that guided the subsequent management plan. The patient was advised to undergo catheter ablation, which is considered the treatment of choice for symptomatic WPW syndrome, particularly in the presence of a significant accessory pathway. The catheter ablation procedure used radiofrequency energy to destroy the aberrant conduction pathway. The procedure was successful, with no immediate complications, and post-procedure ECG showed no evidence of the accessory pathway or abnormal conduction. The patient was monitored in the recovery unit and discharged with instructions to follow up in the clinic for ongoing assessment. Following the ablation, the patient reported significantly reducing the frequency and severity of her arrhythmia episodes. Her follow-up visits included regular clinical evaluations and repeated ECGs to ensure that the arrhythmias had not recurred. During these visits, the patient was encouraged to use a wearable ECG monitor to track her heart rhythms and provide real-time data to her healthcare provider. This technology proved invaluable, allowing continuous monitoring and immediate feedback, helping reassure the patient and the medical team. Over the subsequent months, the patient remained asymptomatic, and follow-up ECGs consistently showed normal sinus rhythm with no evidence of preexcitation. The wearable device confirmed the absence of arrhythmias and reassured the patient. Regular follow-up and monitoring were emphasized, including maintaining a healthy lifestyle and adhering to prescribed medications as necessary. The case of this patient highlights the intricate nature of diagnosing and managing WPW syndrome. It illustrates the effectiveness of catheter ablation as a treatment for symptomatic WPW syndrome and the role of advanced diagnostic tools, such as EPS and wearable technology, in guiding and monitoring treatment. The patient’s successful outcome underscores the importance of individualized care and ongoing follow-up in managing complex arrhythmias. Upon entering the examination room, the patient appeared alert and well-nourished, with no signs of acute distress. She was dressed appropriately for the weather and was calm and cooperative. The examination began with a thorough assessment of her general appearance and vital signs, which provided essential baseline information. The patient’s vital signs were recorded: her blood pressure was 118/76 mmHg, her heart rate was 78 beats per minute, her respiratory rate was 16 breaths per minute, and her temperature was 98.6°F (37°C). These values were within normal limits, and there were no indications of fever, hypotension, or tachycardia at rest. Her body mass index was 22.5 kg/m 2 , indicating a normal weight for her height and age. Inspection of the patient’s skin revealed no rashes, lesions, or cyanosis. The skin was warm and dry, with no signs of pallor or jaundice. Her extremities were well-perfused, with normal capillary refill time and no evidence of edema. The patient’s jugular venous pressure (JVP) was assessed at a 45° angle. The JVP was within normal limits, with no signs of elevated venous pressure that could suggest right heart failure or fluid overload. A thorough cardiovascular examination was performed, beginning with palpation of the precordium. The chest was inspected for any visible pulsations, and palpation revealed a normal point of maximal impulse located in the fifth intercostal space at the midclavicular line. No abnormal thrills or heaves were detected. The heart sounds were auscultated using a stethoscope placed at the four traditional areas: the aortic, pulmonic, tricuspid, and mitral regions. The heart sounds were regular and normal in frequency and intensity. No additional heart sounds, such as S3 or S4, were heard, and no abnormal murmurs or extra sounds were detected. The auscultation of the heart revealed a normal S1 and S2, with no evidence of split sounds or abnormal murmurs. Palpation of the peripheral pulses was performed to assess for any abnormalities in the arterial system. The radial pulses were found to be equal and symmetric bilaterally, with a normal rate and rhythm. The femoral pulses were palpable and symmetric, as were the popliteal, dorsalis pedis, and posterior tibial pulses. The quality of the pulses was strong and regular, with no signs of diminished or absent pulses that could suggest peripheral arterial disease or other vascular issues. A thorough respiratory examination was conducted next. The patient’s chest was inspected for signs of respiratory distress or abnormal respiratory patterns. The patient did not use accessory muscles or signs of labored breathing. Palpation of the chest wall revealed no tenderness or abnormal vibrations. Percussion of the lung fields was performed to assess for any abnormalities in lung density or the presence of fluid or consolidation. Normal resonance was noted over all lung fields, with no dullness or hyperresonance that could indicate pathological changes. Auscultation of the lung fields revealed clear breath sounds bilaterally, with no added sounds such as wheezes, crackles, or rhonchi. The breath sounds were equal and symmetrical, indicating normal airflow through the lungs. The patient demonstrated a normal respiratory pattern with no signs of wheezing or crackles that could suggest underlying respiratory pathology. The abdominal examination was conducted to assess for any signs of abdominal or systemic disease. The abdomen was inspected for visible abnormalities, such as distension or asymmetry. Palpation of the abdomen revealed no tenderness, masses, or organomegaly. The liver and spleen were not palpable below the costal margins, and there were no signs of ascites. Percussion of the abdomen produced normal tympanic sounds, and bowel sounds were auscultated as normal, indicating healthy gastrointestinal function. Finally, a brief neurological examination was performed to ensure no signs of neurological deficits could explain the patient’s episodes of dizziness. The patient was alert and oriented to person, place, and time. Cranial nerves II through XII were intact, with normal visual acuity, pupillary reactions, and extraocular movements. Motor and sensory examinations revealed normal strength and sensation in all extremities, with no signs of weakness, numbness, or abnormal reflexes.	3.958984	0.977539	sec[4]/p[0]	en	0.999997	PMC12055097	https://doi.org/10.1097/MS9.0000000000003068	[ "sounds", "that", "heart", "episodes", "respiratory", "pulses", "regular", "accessory", "pathway", "palpation" ]	[ { "code": "6A01.0", "title": "Developmental speech sound disorder" }, { "code": "ME03.Z", "title": "Abnormal bowel sounds, unspecified" }, { "code": "MD11.Z", "title": "Abnormalities of breathing, unspecified" }, { "code": "ME03.1", "title": "Absent bowel sounds" }, { "code": "MD3Y", "title": "Other specified symptoms or signs involving the respiratory system" }, { "code": "8A80.Z", "title": "Migraine, unspecified" }, { "code": "QA76", "title": "Medication or substance that is known to be an allergen without injury or harm" }, { "code": "PL13.6", "title": "Medication or substance that is known to be an allergen, as mode of injury or harm" }, { "code": "9C40.A0", "title": "Papilloedema" }, { "code": "PA6Z", "title": "Unintentional fall from unspecified height" } ]	=== ICD-11 CODES FOUND === [6A01.0] Developmental speech sound disorder Definition: Developmental speech sound disorder is characterised by difficulties in the acquisition, production and perception of speech that result in errors of pronunciation, either in number or types of speech errors made or the overall quality of speech production, that are outside the limits of normal variation expected for age and level of intellectual functioning and result in reduced intelligibility and significantly affect communication. The errors in pronunciation arise during the early developmen Also known as: Developmental speech sound disorder \| specific speech articulation disorder \| articulation disorder \| developmental phonological disorder \| developmental speech articulation disorder Includes: Functional speech articulation disorder Excludes: Deafness not otherwise specified \| Diseases of the nervous system \| Dysarthria [ME03.Z] Abnormal bowel sounds, unspecified Also known as: Abnormal bowel sounds, unspecified \| Abnormal bowel sounds \| abnormal bowel sounds NOS [MD11.Z] Abnormalities of breathing, unspecified Also known as: Abnormalities of breathing, unspecified \| Abnormalities of breathing \| abnormal respiration \| abnormal breath sounds \| abnormal respiratory rate [ME03.1] Absent bowel sounds Also known as: Absent bowel sounds \| absence of bowel sounds [MD3Y] Other specified symptoms or signs involving the respiratory system Also known as: Other specified symptoms or signs involving the respiratory system \| Chest, tympany \| percussion of chest abnormal \| friction sounds in chest \| Other symptom or complaint of breathing [8A80.Z] Migraine, unspecified Also known as: Migraine, unspecified \| Migraine [QA76] Medication or substance that is known to be an allergen without injury or harm Definition: Medication that has previously been identified as an allergen to the patient is administered, but does not result in injury or harm. Also known as: Medication or substance that is known to be an allergen without injury or harm Excludes: Medication or substance that is known to be an allergen, as mode of injury or harm [PL13.6] Medication or substance that is known to be an allergen, as mode of injury or harm Also known as: Medication or substance that is known to be an allergen, as mode of injury or harm \| medication error relating to known allergy to drug or substance \| adverse drug event relating to known allergy to drug or substance [9C40.A0] Papilloedema Definition: Optic disc swelling that results from increased intracranial pressure Also known as: Papilloedema \| Optic disc swelling that results from increased intracranial pressure Includes: Optic disc swelling that results from increased intracranial pressure [PA6Z] Unintentional fall from unspecified height Also known as: Unintentional fall from unspecified height \| fall NOS \| accidental fall \| fall causing injury that resulted in death \| fell NOS === GRAPH WALKS === --- Walk 1 --- [6A01.0] Developmental speech sound disorder Def: Developmental speech sound disorder is characterised by difficulties in the acquisition, production and perception of speech that result in errors of pronunciation, either in number or types of speech... --EXCLUDES--> [?] Diseases of the nervous system Def: This is a group of conditions characterised as being in or associated with the nervous system.... --EXCLUDES--> [?] Pregnancy, childbirth or the puerperium Def: A group of conditions characterised as occurring during the period of time from conception to delivery (pregnancy), during labour and delivery (childbirth) or during the approximately six weeks after ... --- Walk 2 --- [6A01.0] Developmental speech sound disorder Def: Developmental speech sound disorder is characterised by difficulties in the acquisition, production and perception of speech that result in errors of pronunciation, either in number or types of speech... --EXCLUDES--> [?] Diseases of the nervous system Def: This is a group of conditions characterised as being in or associated with the nervous system.... --EXCLUDES--> [?] Pregnancy, childbirth or the puerperium Def: A group of conditions characterised as occurring during the period of time from conception to delivery (pregnancy), during labour and delivery (childbirth) or during the approximately six weeks after ... --- Walk 3 --- [ME03.Z] Abnormal bowel sounds, unspecified --PARENT--> [ME03] Abnormal bowel sounds Def: Bowel sounds are caused by the products of digestion as they move through the lower gastrointestinal tract, usually heard on auscultation. Abnormal bowel sounds are reduced or increased bowel sounds w... --CHILD--> [ME03.0] Hyperactive bowel sounds --- Walk 4 --- [ME03.Z] Abnormal bowel sounds, unspecified --PARENT--> [ME03] Abnormal bowel sounds Def: Bowel sounds are caused by the products of digestion as they move through the lower gastrointestinal tract, usually heard on auscultation. Abnormal bowel sounds are reduced or increased bowel sounds w... --CHILD--> [ME03.Z] Abnormal bowel sounds, unspecified --- Walk 5 --- [MD11.Z] Abnormalities of breathing, unspecified --PARENT--> [MD11] Abnormalities of breathing Def: Abnormalities of breathing includes dyspnoea, stridor, wheezing, periodic breathing, hyperventilation, mouth breathing, hiccough, sneezing, and other abnormalities of breathing.... --CHILD--> [MD11.2] Ataxic breathing Def: An irregular breathing pattern that usually progresses to complete apnoea.... --- Walk 6 --- [MD11.Z] Abnormalities of breathing, unspecified --PARENT--> [MD11] Abnormalities of breathing Def: Abnormalities of breathing includes dyspnoea, stridor, wheezing, periodic breathing, hyperventilation, mouth breathing, hiccough, sneezing, and other abnormalities of breathing.... --CHILD--> [MD11.1] Asphyxia Def: Asphyxia is a life-threatening condition in which oxygen is prevented from reaching the tissues by obstruction of or damage to any part of the respiratory system. More generally the term indicates all...	[ "[6A01.0] Developmental speech sound disorder\n Def: Developmental speech sound disorder is characterised by difficulties in the acquisition, production and perception of speech that result in errors of pronunciation, either in number or types of speech...\n --EXCLUDES--> [?] Diseases of the nervous system\n Def: This is a group of conditions characterised as being in or associated with the nervous system....\n --EXCLUDES--> [?] Pregnancy, childbirth or the puerperium\n Def: A group of conditions characterised as occurring during the period of time from conception to delivery (pregnancy), during labour and delivery (childbirth) or during the approximately six weeks after ...", "[6A01.0] Developmental speech sound disorder\n Def: Developmental speech sound disorder is characterised by difficulties in the acquisition, production and perception of speech that result in errors of pronunciation, either in number or types of speech...\n --EXCLUDES--> [?] Diseases of the nervous system\n Def: This is a group of conditions characterised as being in or associated with the nervous system....\n --EXCLUDES--> [?] Pregnancy, childbirth or the puerperium\n Def: A group of conditions characterised as occurring during the period of time from conception to delivery (pregnancy), during labour and delivery (childbirth) or during the approximately six weeks after ...", "[ME03.Z] Abnormal bowel sounds, unspecified\n --PARENT--> [ME03] Abnormal bowel sounds\n Def: Bowel sounds are caused by the products of digestion as they move through the lower gastrointestinal tract, usually heard on auscultation. Abnormal bowel sounds are reduced or increased bowel sounds w...\n --CHILD--> [ME03.0] Hyperactive bowel sounds", "[ME03.Z] Abnormal bowel sounds, unspecified\n --PARENT--> [ME03] Abnormal bowel sounds\n Def: Bowel sounds are caused by the products of digestion as they move through the lower gastrointestinal tract, usually heard on auscultation. Abnormal bowel sounds are reduced or increased bowel sounds w...\n --CHILD--> [ME03.Z] Abnormal bowel sounds, unspecified", "[MD11.Z] Abnormalities of breathing, unspecified\n --PARENT--> [MD11] Abnormalities of breathing\n Def: Abnormalities of breathing includes dyspnoea, stridor, wheezing, periodic breathing, hyperventilation, mouth breathing, hiccough, sneezing, and other abnormalities of breathing....\n --CHILD--> [MD11.2] Ataxic breathing\n Def: An irregular breathing pattern that usually progresses to complete apnoea....", "[MD11.Z] Abnormalities of breathing, unspecified\n --PARENT--> [MD11] Abnormalities of breathing\n Def: Abnormalities of breathing includes dyspnoea, stridor, wheezing, periodic breathing, hyperventilation, mouth breathing, hiccough, sneezing, and other abnormalities of breathing....\n --CHILD--> [MD11.1] Asphyxia\n Def: Asphyxia is a life-threatening condition in which oxygen is prevented from reaching the tissues by obstruction of or damage to any part of the respiratory system. More generally the term indicates all..." ]	6A01.0	Developmental speech sound disorder	[ { "from_icd11": "6A01.0", "icd10_code": "F800", "icd10_title": "Phonological disorder" }, { "from_icd11": "ME03.Z", "icd10_code": "R191", "icd10_title": "Abnormal bowel sounds" }, { "from_icd11": "MD11.Z", "icd10_code": "R069", "icd10_title": "Unspecified abnormalities of breathing" }, { "from_icd11": "MD11.Z", "icd10_code": "R0681", "icd10_title": "Apnea, not elsewhere classified" }, { "from_icd11": "MD11.Z", "icd10_code": "R0683", "icd10_title": "Snoring" }, { "from_icd11": "MD11.Z", "icd10_code": "R0682", "icd10_title": "Tachypnea, not elsewhere classified" }, { "from_icd11": "MD11.Z", "icd10_code": "R0689", "icd10_title": "Other abnormalities of breathing" }, { "from_icd11": "MD11.Z", "icd10_code": "R06", "icd10_title": "Abnormalities of breathing" }, { "from_icd11": "MD11.Z", "icd10_code": "R068", "icd10_title": "Other abnormalities of breathing" }, { "from_icd11": "8A80.Z", "icd10_code": "G43B0", "icd10_title": "Ophthalmoplegic migraine, not intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43409", "icd10_title": "Hemiplegic migraine, not intractable, without status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43A0", "icd10_title": "Cyclical vomiting, in migraine, not intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43D0", "icd10_title": "Abdominal migraine, not intractable" }, { "from_icd11": "8A80.Z", "icd10_code": "G43709", "icd10_title": "Chronic migraine without aura, not intractable, without status migrainosus" }, { "from_icd11": "8A80.Z", "icd10_code": "G43A1", "icd10_title": "Cyclical vomiting, in migraine, intractable" } ]	F800	Phonological disorder
In this article, a case involving a 27-year-old woman with gravida 2, para 1, and gestational weeks of 26 was reported. This patient suffered from a fever shortly after she became soaked in the rain 6 days previously, with the highest temperature of 40°C. Then, she had cough 3 days previously, with white phlegm and occasional bloody sputum, combined with chest tightness and asthma. These symptoms were not improved after the administration of mezlocillin sodium and sulbactam sodium as anti-infectives in the outpatient department. Subsequently, she visited the emergency department of the First Affiliated Hospital of Anhui Medical University (Anhui, China) on October 22, 2020, where she was admitted to the hospital with “fever and pregnancy status (26 weeks pregnant).” This patient developed intermittent diarrhea in the previous 3 days, with the clinical manifestations of yellow watery stool and dark urine. The patient was previously in good condition and had no other diseases. Through auscultation, breathing sounds in both lungs were thick, with obvious moist rales. On the admission day, the temperature of the patient was 38.5°C, with a heart rate of 150 beats/min, a blood pressure of 105/69 mmHg, and a respiratory rate of 35 breaths/min. The findings of laboratory examinations were as follows: hemoglobin, 88 g/L; C-reactive protein (CRP), 145.46 mg/L; white blood cell count (WBC), 14.73 × 10 9 /L; platelet count, 189 × 10 9 /L; procalcitonin (PCT), 19.36 ng/mL; D-dimer, 12.85 μg/mL; glutamic-oxaloacetic transaminase, 125 U/L; and creatinine, 39.3 μmol/L. Chest X-ray revealed bilateral lung inflammation, lung abscess in the superior lobe of the left lung, and right pleural effusion. The preliminary differential diagnosis included severe pneumonia, acute respiratory distress syndrome, septic shock, and pregnancy. Although meropenem and oseltamivir were administered to resist infection, the patient's dyspnea symptoms persisted, and her high-flow oxygenation index was < 100 mmHg. After endotracheal intubation, the patient was transferred to the intensive care unit (ICU). On October 23, 2020, the patient was examined through fiberoptic bronchoscopy, sputum and alveolar lavage fluid in the left and right bronchi were aspirated, and meropenem, vancomycin, azithromycin, and oseltamivir were administered with mechanical-assisted ventilation. On October 25, 2020, the patient received metagenomic next-generation sequencing (mNGS) of alveolar lavage fluid and blood, with both results indicating C. psittaci . Therefore, the diagnosis of C. psittaci pneumonia was confirmed, and the antibiotic regimen was adjusted to include doxycycline, cefoperazone sodium and sulbactam sodium, and moxifloxacin. Symptomatic treatment, including mechanical ventilation, anti-shock, protection of important organs, nutritional support, sedation, and analgesia, was actively administered. On October 29, 2020, bronchoscopy was performed again, with the results of metagenomic next-generation sequencing (mNGS) of alveolar lavage fluid and blood continuing to show C. psittaci . However, the level of C. psittaci in the alveolar lavage fluid decreased compared to the earlier analysis, although the level of C. psittaci in the blood increased. On October 31, 2020, the oxygenation index of the patient reached 280 mmHg, which was significantly improved, the temperature of the patient was 40°C, with a heart rate of 105 beats/min and a blood pressure of 120/60 mmHg. The findings of laboratory examinations were as follows: hemoglobin, 93 g/L; CRP, 80.19 mg/L;WBC, 14.36 × 10 9 /L; platelet count, 140 × 10 9 /L; PCT, 4.87 ng/mL; D-dimer, 8.35 μg/mL; glutamic-oxaloacetic transaminase, 54 U/L; and creatinine, 26.7 μmol/L. Chest X-ray revealed improved bilateral lung inflammation and lung lesions compared with the condition at admission. However, the peak temperature of this patient was higher than before. As for those patients suffering from long-term high fever, if the temperature is not effectively controlled after extensive coverage with broad-spectrum and powerful antibiotics, non-infectious fever should be taken into account at the same time. In other cases, non-infectious fever is common in the rheumatic blood system and tumor diseases. Bone marrow puncture and smear examination were performed on November 2, 2020, and the tumor index of the patient was elevated, which was considered to be related to pregnancy and hypoproteinemia. Sputum and blood cultures showed Acinetobacter baumannii , and sputum and urine cultures showed Candida albicans and Candida tropicalis . Therefore, the antibiotic regimen was adjusted to include polymyxin + cefoperazone sodium and sulbactam sodium + doxycycline + teicoplanin + voriconazole on November 9, 2020. On November 15, 2020, ultrasound indicated that the umbilical cord was wound around the neck of the fetus for 2 weeks, the volume of amniotic fluid was decreased, and fetal kidney parenchyma echo was enhanced. After communicating with the family members of the patient and obstetrics physicians, rivanol was injected into the amniotic cavity to induce labor. On November 19, 2020, the patient became conscious, and her breathing and circulation were stable; however, she developed a cough reaction, and tried to break away from the ventilator and remove tracheal intubation. Pulmonary imaging revealed mitigated fever (temperature > 38.5°C), reduced red blood cell (RBC) count (1.99 × 10 12 /L) and platelet count (111 × 10 9 /L), hypertriglyceridemia (triglycerides, 6.21 mmol/L), and hyperferritinemia (ferritin, 2,284 μg/L). Phagocytic cells were apparent on bone marrow smear and HPS could not be excluded. Besides, natural killer (NK) cell activity and soluble CD25 levels were examined, and the CD107a excitation test was improved. These results indicated that the level of sCD25 increased, and NK cell activity decreased. Therefore, the diagnosis of HPS caused by infection was confirmed. The HLH-2004 regimen, recommended by the International Histocyte Association, was applied in the treatment of HPS. Etoposide combined with hormone therapy can significantly mitigate—if not eliminate—symptoms, and immunosuppressants, such as cyclosporine A (CSA) and anti-thymocyte globulin (ATG), could be added according to the condition ( 4 ). On November 20, 2020, VP-16 (150 mg) and dexamethasone (10 mg) were administered to eliminate symptoms. On November 22, 2020, the temperature of the patient returned to 36.8°C.On November 27, 2020, the temperature of the patient was basically maintained within the normal range. The finding of laboratory examinations were as follows: hemoglobin, 92 g/L; CRP, 7.48 mg/L;WBC, 11.43 × 10 9 /L; platelet count, 103 × 10 9 /L; PCT, 0.11 ng/mL; D-dimer, 0.93 μg/mL; glutamic-oxaloacetic transaminase, 62 U/L; creatinine, 13.3 μmol/L; RBC count, 2.83 × 10 12 /L; hypertriglyceridemia (triglycerides, 5.68 mmol/L); and hyperferritinemia (ferritin, 2,212 μg/L). The indices of ferritin and triglycerides for the patient did not decrease significantly compared with the previous time, and HPS had not been completely controlled. On November 27, 2020, etoposide (100 mg) was administered on the basis of dexamethasone to control the primary disease. The findings of laboratory examinations on December 3, 2020, were as follows: WBC, 6.55 × 10 9 /L; platelet count, 155 × 10 9 /L; triglycerides, 2.34 mmol/L; ferritin, 1,807 μg/L; and glutamic-oxaloacetic transaminase, 14 U/L. Etoposide (100 mg) was administered for the third time on December 6, 2020. On December 10, 2020, NK cell activity and sCD25 levels were re-examined, with the results showing that NK cell activity did not decrease and the level of sCD25 returned to the normal range. Therefore, it was not necessary to continue the treatment with etoposide, and dexamethasone was gradually decreased. On December 23, 2020, the fever, cough, and expectoration were obviously mitigated and breath sounds in both lungs became clear. Chest CT revealed that the lung lesions were absorbed, and the level of sCD25 and NK cell activity suggested that the condition of the patient was basically stable; therefore, the patient was discharged from the hospital. The telephone follow-up 1 week later revealed that the patient had no complaints of discomfort, fever, cough, or expectoration, and she was advised to conduct outpatient reviews regularly .	3.941406	0.980957	sec[1]/p[0]	en	0.999997	34869453	https://doi.org/10.3389/fmed.2021.755669	[ "blood", "fever", "temperature", "count", "november", "cell", "sodium", "lung", "that", "october" ]	[ { "code": "3C0Z", "title": "Diseases of the blood or blood-forming organs, unspecified" }, { "code": "MF50.4Z", "title": "Haematuria, unspecified" }, { "code": "MA12.1", "title": "Finding of cocaine in blood" }, { "code": "MA12.4", "title": "Finding of steroid agent in blood" }, { "code": "MA12.2", "title": "Finding of hallucinogen in blood" }, { "code": "MG26", "title": "Fever of other or unknown origin" }, { "code": "1D81.Z", "title": "Infectious mononucleosis, unspecified" }, { "code": "1B99", "title": "Pasteurellosis" }, { "code": "4A60.0", "title": "Familial Mediterranean fever" }, { "code": "JB40.0", "title": "Puerperal sepsis" } ]	=== ICD-11 CODES FOUND === [3C0Z] Diseases of the blood or blood-forming organs, unspecified Also known as: Diseases of the blood or blood-forming organs, unspecified \| Blood, lymph or spleen disease \| blood condition NOS \| blood disorder NOS \| bone marrow disease NOS [MF50.4Z] Haematuria, unspecified Also known as: Haematuria, unspecified \| Haematuria \| blood in urine \| urinary blood \| haematuria NOS [MA12.1] Finding of cocaine in blood Also known as: Finding of cocaine in blood \| cocaine in blood [MA12.4] Finding of steroid agent in blood Also known as: Finding of steroid agent in blood \| steroid in blood [MA12.2] Finding of hallucinogen in blood Also known as: Finding of hallucinogen in blood \| hallucinogen in blood [MG26] Fever of other or unknown origin Definition: An abnormal elevation of body temperature of unknown origin, often as a result of a pathologic process. Also known as: Fever of other or unknown origin \| febrile \| febris \| fever \| feverish Excludes: fever of unknown origin in newborn \| Malignant hyperthermia due to anaesthesia [1D81.Z] Infectious mononucleosis, unspecified Also known as: Infectious mononucleosis, unspecified \| Infectious mononucleosis \| Glandular fever \| Gammaherpesviral mononucleosis \| kissing disease [1B99] Pasteurellosis Definition: A disease caused by an infection with the gram-negative bacteria Pasteurella. This disease is characterised by local cellulitis and may lead to other clinical signs depending on the route of infection. Transmission is commonly by direct contact through the bite, scratch, or lick from an infected animal, inhalation of infected respiratory secretions, or ingestion of contaminated meat. Confirmation is by identification of Pasteurella from the affected individual. Also known as: Pasteurellosis \| pasteurella infection \| shipping fever \| transport fever [4A60.0] Familial Mediterranean fever Definition: FMF is an autoinflammatory disease associated with mutations in pyrin resulting in enhanced IL1 beta production. This results in clinical attacks of inflammation in the form of fever and serositis in the form of peritoneal, pleural or synovial inflammation along with increased acute phase reactants. Also known as: Familial Mediterranean fever \| Periodic disease \| FMF - [familial mediterranean fever] \| periodic fever \| periodic polyserositis [JB40.0] Puerperal sepsis Also known as: Puerperal sepsis \| puerperal fever \| postpartum sepsis \| generalised puerperal infection \| major puerperal infection Excludes: Obstetric pyaemic or septic embolism \| sepsis during labour === GRAPH WALKS === --- Walk 1 --- [3C0Z] Diseases of the blood or blood-forming organs, unspecified --PARENT--> [03] Diseases of the blood or blood-forming organs Def: This chapter includes diseases of the blood as well as diseases of blood forming organs.... --CHILD--> [?] Coagulation defects, purpura or other haemorrhagic or related conditions Def: A condition caused by determinants arising during the antenatal period, after birth or by genetically inherited factors, leading to coagulation defects. This condition is characterised by increased br... --- Walk 2 --- [3C0Z] Diseases of the blood or blood-forming organs, unspecified --PARENT--> [03] Diseases of the blood or blood-forming organs Def: This chapter includes diseases of the blood as well as diseases of blood forming organs.... --RELATED_TO--> [?] Neoplasms of haematopoietic or lymphoid tissues Def: A neoplasm arising from hematopoietic or lymphoid cells found in the bone marrow, peripheral blood, lymph nodes and spleen (organs of the hematopoietic or lymphoid system). Hematopoietic or lymphoid c... --- Walk 3 --- [MF50.4Z] Haematuria, unspecified --PARENT--> [MF50.4] Haematuria Def: Hematuria means presence of blood or red blood cells (RBCs) in the urine. There are two types of hematuria: gross hematuria (when one can see the blood in the urine) and microscopic hematuria (when th... --CHILD--> [MF50.41] Microscopic haematuria --- Walk 4 --- [MF50.4Z] Haematuria, unspecified --PARENT--> [MF50.4] Haematuria Def: Hematuria means presence of blood or red blood cells (RBCs) in the urine. There are two types of hematuria: gross hematuria (when one can see the blood in the urine) and microscopic hematuria (when th... --CHILD--> [MF50.4Z] Haematuria, unspecified --- Walk 5 --- [MA12.1] Finding of cocaine in blood --PARENT--> [MA12] Clinical findings of drugs, medicaments and biological substances in blood, blood-forming organs, or the immune system --CHILD--> [MA12.2] Finding of hallucinogen in blood --- Walk 6 --- [MA12.1] Finding of cocaine in blood --PARENT--> [MA12] Clinical findings of drugs, medicaments and biological substances in blood, blood-forming organs, or the immune system --CHILD--> [MA12.0] Finding of opiate drug in blood	[ "[3C0Z] Diseases of the blood or blood-forming organs, unspecified\n --PARENT--> [03] Diseases of the blood or blood-forming organs\n Def: This chapter includes diseases of the blood as well as diseases of blood forming organs....\n --CHILD--> [?] Coagulation defects, purpura or other haemorrhagic or related conditions\n Def: A condition caused by determinants arising during the antenatal period, after birth or by genetically inherited factors, leading to coagulation defects. This condition is characterised by increased br...", "[3C0Z] Diseases of the blood or blood-forming organs, unspecified\n --PARENT--> [03] Diseases of the blood or blood-forming organs\n Def: This chapter includes diseases of the blood as well as diseases of blood forming organs....\n --RELATED_TO--> [?] Neoplasms of haematopoietic or lymphoid tissues\n Def: A neoplasm arising from hematopoietic or lymphoid cells found in the bone marrow, peripheral blood, lymph nodes and spleen (organs of the hematopoietic or lymphoid system). Hematopoietic or lymphoid c...", "[MF50.4Z] Haematuria, unspecified\n --PARENT--> [MF50.4] Haematuria\n Def: Hematuria means presence of blood or red blood cells (RBCs) in the urine. There are two types of hematuria: gross hematuria (when one can see the blood in the urine) and microscopic hematuria (when th...\n --CHILD--> [MF50.41] Microscopic haematuria", "[MF50.4Z] Haematuria, unspecified\n --PARENT--> [MF50.4] Haematuria\n Def: Hematuria means presence of blood or red blood cells (RBCs) in the urine. There are two types of hematuria: gross hematuria (when one can see the blood in the urine) and microscopic hematuria (when th...\n --CHILD--> [MF50.4Z] Haematuria, unspecified", "[MA12.1] Finding of cocaine in blood\n --PARENT--> [MA12] Clinical findings of drugs, medicaments and biological substances in blood, blood-forming organs, or the immune system\n --CHILD--> [MA12.2] Finding of hallucinogen in blood", "[MA12.1] Finding of cocaine in blood\n --PARENT--> [MA12] Clinical findings of drugs, medicaments and biological substances in blood, blood-forming organs, or the immune system\n --CHILD--> [MA12.0] Finding of opiate drug in blood" ]	3C0Z	Diseases of the blood or blood-forming organs, unspecified	[ { "from_icd11": "3C0Z", "icd10_code": "D75A", "icd10_title": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency without anemia" }, { "from_icd11": "3C0Z", "icd10_code": "D7581", "icd10_title": "Myelofibrosis" }, { "from_icd11": "3C0Z", "icd10_code": "D7582", "icd10_title": "Heparin induced thrombocytopenia (HIT)" }, { "from_icd11": "3C0Z", "icd10_code": "D7589", "icd10_title": "Other specified diseases of blood and blood-forming organs" }, { "from_icd11": "3C0Z", "icd10_code": "D759", "icd10_title": "Disease of blood and blood-forming organs, unspecified" }, { "from_icd11": "3C0Z", "icd10_code": "D763", "icd10_title": "Other histiocytosis syndromes" }, { "from_icd11": "3C0Z", "icd10_code": "Q899", "icd10_title": "Congenital malformation, unspecified" }, { "from_icd11": "3C0Z", "icd10_code": "III", "icd10_title": "" }, { "from_icd11": "3C0Z", "icd10_code": "D70-D77", "icd10_title": "" }, { "from_icd11": "3C0Z", "icd10_code": "D75", "icd10_title": "Other and unspecified diseases of blood and blood-forming organs" }, { "from_icd11": "3C0Z", "icd10_code": "D77", "icd10_title": "Other disorders of blood and blood-forming organs in diseases classified elsewhere" }, { "from_icd11": "3C0Z", "icd10_code": "D758", "icd10_title": "Other specified diseases of blood and blood-forming organs" }, { "from_icd11": "3C0Z", "icd10_code": "D76", "icd10_title": "Other specified diseases with participation of lymphoreticular and reticulohistiocytic tissue" }, { "from_icd11": "MF50.4Z", "icd10_code": "R310", "icd10_title": "Gross hematuria" }, { "from_icd11": "MF50.4Z", "icd10_code": "R312", "icd10_title": "Other microscopic hematuria" } ]	D75A	Glucose-6-phosphate dehydrogenase (G6PD) deficiency without anemia
Examination revealed a young man in painful distress with pyrexia (temperature 38.3 °C), palor, slight jaundice, no significant peripheral lymphadenopathy, and no pedal edema. Respiratory rate was 24 breaths/minute. Pulse was 120 beats/minute, regular, but of small volume. Blood pressure was \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\frac{120}{70}$$\end{document} 120 70 mmHg, while the apex beat was palpable at the fifth left intercostal space, mid-axillary line. The first (S 1 ) and second (S 2 ) heart sounds were heard. There was no abdominal tenderness, but the liver was palpably enlarged, 4 cm below the right costal margin and had a span of 18 cm. The spleen was not palpable, and the kidneys not ballotable. He had no neurological abnormality. Baseline full blood count (FBC) showed severe anemia (hemoglobin concentration 4.6 g/dl), leukocytosis (WBC 44.3 × 10 9 /L) and platelet count of 335.0 × 10 9 /L. Blood film microscopy for malaria showed trophozoites of Plasmodium falciparum . Hb electrophoresis on agarose gel with densitometric quantification (Hellabio, Thessaloniki, Greece) done at presentation revealed HbS 93.6%, HbF 2.9%, HbA 2 3.5%. Steady-state hematocrit was unknown. An initial diagnosis of VOC with severe anemia was made. He was treated with artesunate-based antimalarial and transfused with packed cells. However, a review of the peripheral blood film showed sickled and target cells in addition to leukocytosis that consisted of heterogeneous lymphoblasts (81%), myelocytes (2%), neutrophils (10%), and lymphocytes (7%) . Urine analysis was normal. Abdominal ultrasound scan showed hepatomegaly and autosplenectomy. Electrocardiogram (ECG) showed left ventricular hypertrophy (LVH), while echocardiogram (ECHO) showed LVH with normal systolic and diastolic function. Serology tests for human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus were negative. Bone marrow aspiration (BMA) revealed a hypercellular marrow with numerous heterogeneous lymphoblasts constituting about 60% of marrow nucleated cells. Flow cytometry of the peripheral blood revealed blasts that were CD20+, CD3−, CD13−, and CD33−. Multiplex reverse transcriptase polymerase chain reaction (RT-PCR) was done for BCR-ABL1 analysis (Seeplex Leukemia BCR-ABL kit, Seegene, Seoul, Korea) and showed the presence of e1a3 transcript . A diagnosis of B-lineage BCR-ABL1 positive ALL in a known patient with SCA was made. Lymphoblasts were not visualized on cytospin analysis of CSF, thus excluding CNS involvement. However, he was classified as being at high risk for meningeal relapse on the basis of high WBC count (WBC >30.0 × 10 9 /L), mature B-cell phenotype and Ph expression.He was commenced on the modified MCP 841 regimen (Table 1 ) . This protocol included four induction cycles (1A, 2A, 2B, 1B); one cycle of consolidation and six cycles of maintenance therapy. Induction 1A involved the administration of prednisolone, vincristine, l -asparaginase, and daunorubicin. He was also given three-drug intrathecal therapy (IT) [methotrexate, hydrocortisone, and cytarabine, that is, triple IT] by aseptic technique for CNS prophylaxis as per protocol for patients at high risk for CNS relapse during induction and consolidation. Cytospin analysis of the CSF was performed routinely prior to each IT, and no lymphoblasts were seen. In addition, Imatinib mesylate (Novartis Pharmaceuticals, Basel, Switzerland) 600 mg was given simultaneously, courtesy of The Max Foundation (Max Access Solutions © , The Max Foundation, Seattle, Washington, USA). Packed red cell and platelet transfusions were given as necessary. Induction 1A was complicated by neutropenic fever, sepsis and pityriasis versicolor for which he received granulocyte colony stimulating factor (G-CSF), antibiotics (ciprofloxacin, metronidazole), acyclovir, topical clotrimazole and fluconazole. Co-trimoxazole was also given as prophylaxis against Pneumocystis jirovecii . Samples were taken from the two siblings and the parents for human leukocyte antigen (HLA) typing in preparation for allogeneic hemopoietic stem cell transplantation (Allo-HSCT). He achieved remission after induction 1A as confirmed by BMA on day 30. The BCR-ABL1 analysis and flow cytometry could not be repeated due to financial constraints. Induction 2A and 2B was complicated by the development of multiple subcutaneous abscesses. Microbiological culture yielded methicillin-resistant Staphylococcal aureus . He was treated with meropenem and linezolid. He continued chemotherapy until the consolidation phase when, exactly six months from diagnosis, he developed high-grade fever, headache and vomiting. On admission at the emergency department, he was restless with altered consciousness, fever (temperature 39.4 °C), and palor. The Glasgow Coma Scale (GCS) score was 9 out of 15 based on eye opening to pain, utterance of incomprehensible sounds, and localization of pain. The pupils were both 3 mm in diameter with normal light reactivity. He had neck stiffness and generalized hypertonia, with positive Kernig and Brudzinski signs. Pulse rate was 122 beats per minute; blood pressure was \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\frac{144}{70}$$\end{document} 144 70 mmHg. A diagnosis of meningoencephalitis with raised intracranial pressure (ICP) was made. The clinical suspicion of raised ICP was based on headache, vomiting, and increased blood pressure that prevented the collection of CSF for cytology and culture. He was placed on intravenous ceftriaxone 2 g 12-hourly and intravenous dexamethasone 8 mg 8-hourly, but died within a few hours in the intensive care unit (ICU) while arrangements were being made for cranial computed tomography (CT) scan. The relatives declined autopsy. Fig. 1 Peripheral blood film of the patient. Different views of the peripheral blood film of the patient showing numerous heterogeneous lymphoblasts, sickle cells (solid arrows), and target cells (dashed arrows) Fig. 2 Polymerase chain reaction analysis of BCR-ABL1 transcripts. Lane L: DNA ladder, Lane 1: e1a3 (index patient), Lane 2: e13a2 + e14a2, Lane 3: e14a2, Lane 4: e14a2 (low value), NC: negative control, Lane 5: e14a2, Lane 6: e14a2, PC: positive control Table 1 Modified MCP 841 Protocol Phase and duration Medication Dosage Route and schedule Induction 1A 29 days 1. Pre-induction prednisolone 60 mg/m 2 PO day 1–7 2. Prednisolone 40 g/m 2 PO day 8–28 3. Vincristine 1.4 mg/m 2 IV day 8, 15, 22, 29 4. Daunorubicin 20 mg/m 2 IV day 8, 15, 29 5. l -Asparaginase 6000 U/m 2 SC day 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 6. CNS prophylaxis: *Triple prophylaxis Methotrexate 12 mg; IT day 8, 15, 22, 29 Cytarabine 30 mg; IT day 8, 15, 22, 29 Hydrocortisone 20 mg; IT day 8, 15, 22, 29 Induction 2A 28 days Cyclophosphamide 750 mg/m 2 ; IV day 1, 15 6-Mercaptopurine 60 mg/m 2 ; PO day 1–28 Cytarabine 75 mg/m 2 ; IV day 1–4, 8–11, 15–18, 22–25 CNS prophylaxis as Induction 1A IT day 8, 15, 22, 29 Induction 2B 56 days Cyclophosphamide 6-Mercaptopurine 750 mg/m 2 ; IV day 1, 15 60 mg/m 2 ; PO day 1–56 Methotrexate Low risk : 20 mg/m 2 ; IV day 1, 11, 21, 31, 41 High risk : Start at 100 mg/m 2 and increase by 50 mg/m2 up to 5 doses CNS prophylaxis as in Induction 1A IT day 8, 15, 22, 29 Induction 1B 28 days Repeat Induction 1A As in Induction 1A Consolidation 28 days Cytarabine Vincristine Cyclophosphamide Daunorubicin 6-Mercaptopurine 100 mg/m 2 ; SC 12-hourly day 1–3, 15–17 1.4 mg/m 2 ; IV day 1, 15 750 mg/m 2 ; IV day 1 20 mg/m 2 ; IV day 15 75 mg/m 2 ; PO day 1–7, 15–21 CNS prophylaxis:- Drugs as in Induction 1A IT day 1 Maintenance 8 cycles for B-ALL (12 weeks per cycle) 96 weeks Prednisolone Vincristine Daunorubicin l -Asparaginase 6-Mercaptopurine Methotrexate 40 g/m 2 ; PO day 1–7 1.4 mg/m 2 ; IV day 1 20 mg/m 2 ; IV day 1 6000 U/m 2 ; SC day 1, 3, 5, 7 75 mg/m 2 ; PO daily × 12 doses 15 mg/m 2 ; PO weekly CNS prophylaxis:- Methotrexate 12 mg; IT day 1 of each cycle	4.011719	0.978027	sec[1]/p[1]	en	0.999997	34625105	https://doi.org/10.1186/s13256-021-03060-5	[ "induction", "usepackage", "blood", "prophylaxis", "lane", "cells", "lymphoblasts", "methotrexate", "pressure", "document" ]	[ { "code": "JB01.Z", "title": "Failed induction of labour, unspecified" }, { "code": "JB01.0", "title": "Failed medical induction of labour" }, { "code": "JB01.1", "title": "Failed instrumental induction of labour" }, { "code": "QA30.22", "title": "Contact with health services for ovulation induction" }, { "code": "JA00.39", "title": "Other or unspecified failed attempted abortion, without complication" }, { "code": "3C0Z", "title": "Diseases of the blood or blood-forming organs, unspecified" }, { "code": "MF50.4Z", "title": "Haematuria, unspecified" }, { "code": "MA12.1", "title": "Finding of cocaine in blood" }, { "code": "MA12.4", "title": "Finding of steroid agent in blood" }, { "code": "MA12.2", "title": "Finding of hallucinogen in blood" } ]	=== ICD-11 CODES FOUND === [JB01.Z] Failed induction of labour, unspecified Also known as: Failed induction of labour, unspecified \| Failed induction of labour \| failed induction \| unsuccessful attempt to induce labour \| unsuccessfully induced labour [JB01.0] Failed medical induction of labour Definition: A condition characterised by a failed attempt to stimulate contractions pharmacologically before the spontaneous onset of labour. This condition may occur with or without ruptured membranes. Also known as: Failed medical induction of labour \| failed medical induction \| Failed induction of labour by oxytocin \| failure induction by oxytocic drugs \| Failed induction of labour by prostaglandins [JB01.1] Failed instrumental induction of labour Definition: A condition characterised by a failed attempt to instrumentally stimulate contractions before the spontaneous onset of labour. This condition may occur with or without ruptured membranes. Also known as: Failed instrumental induction of labour \| failed mechanical induction of labour \| failure instrumental induction of labour \| failed surgical induction of labour [QA30.22] Contact with health services for ovulation induction Definition: Ovulation Induction (OI): Pharmacological treatment for women with anovulation or oligo-ovulation to result in normal ovulatory cycles. Also known as: Contact with health services for ovulation induction \| OI - [ovulation induction] [JA00.39] Other or unspecified failed attempted abortion, without complication Also known as: Other or unspecified failed attempted abortion, without complication \| attempted abortion \| Failed attempted abortion NOS \| failed attempted termination of pregnancy \| failed induced abortion [3C0Z] Diseases of the blood or blood-forming organs, unspecified Also known as: Diseases of the blood or blood-forming organs, unspecified \| Blood, lymph or spleen disease \| blood condition NOS \| blood disorder NOS \| bone marrow disease NOS [MF50.4Z] Haematuria, unspecified Also known as: Haematuria, unspecified \| Haematuria \| blood in urine \| urinary blood \| haematuria NOS [MA12.1] Finding of cocaine in blood Also known as: Finding of cocaine in blood \| cocaine in blood [MA12.4] Finding of steroid agent in blood Also known as: Finding of steroid agent in blood \| steroid in blood [MA12.2] Finding of hallucinogen in blood Also known as: Finding of hallucinogen in blood \| hallucinogen in blood === GRAPH WALKS === --- Walk 1 --- [JB01.Z] Failed induction of labour, unspecified --PARENT--> [JB01] Failed induction of labour Def: A condition characterised by a failed attempt to stimulate contractions before the spontaneous onset of labour. This condition may occur with or without ruptured membranes.... --CHILD--> [JB01.0] Failed medical induction of labour Def: A condition characterised by a failed attempt to stimulate contractions pharmacologically before the spontaneous onset of labour. This condition may occur with or without ruptured membranes.... --- Walk 2 --- [JB01.Z] Failed induction of labour, unspecified --PARENT--> [JB01] Failed induction of labour Def: A condition characterised by a failed attempt to stimulate contractions before the spontaneous onset of labour. This condition may occur with or without ruptured membranes.... --CHILD--> [JB01.1] Failed instrumental induction of labour Def: A condition characterised by a failed attempt to instrumentally stimulate contractions before the spontaneous onset of labour. This condition may occur with or without ruptured membranes.... --- Walk 3 --- [JB01.0] Failed medical induction of labour Def: A condition characterised by a failed attempt to stimulate contractions pharmacologically before the spontaneous onset of labour. This condition may occur with or without ruptured membranes.... --PARENT--> [JB01] Failed induction of labour Def: A condition characterised by a failed attempt to stimulate contractions before the spontaneous onset of labour. This condition may occur with or without ruptured membranes.... --PARENT--> [?] Complications of labour or delivery Def: Any complication characterised by the adverse evolution of a condition that arises during any one of the three stages of labour and delivery.... --- Walk 4 --- [JB01.0] Failed medical induction of labour Def: A condition characterised by a failed attempt to stimulate contractions pharmacologically before the spontaneous onset of labour. This condition may occur with or without ruptured membranes.... --PARENT--> [JB01] Failed induction of labour Def: A condition characterised by a failed attempt to stimulate contractions before the spontaneous onset of labour. This condition may occur with or without ruptured membranes.... --CHILD--> [JB01.0] Failed medical induction of labour Def: A condition characterised by a failed attempt to stimulate contractions pharmacologically before the spontaneous onset of labour. This condition may occur with or without ruptured membranes.... --- Walk 5 --- [JB01.1] Failed instrumental induction of labour Def: A condition characterised by a failed attempt to instrumentally stimulate contractions before the spontaneous onset of labour. This condition may occur with or without ruptured membranes.... --PARENT--> [JB01] Failed induction of labour Def: A condition characterised by a failed attempt to stimulate contractions before the spontaneous onset of labour. This condition may occur with or without ruptured membranes.... --CHILD--> [JB01.0] Failed medical induction of labour Def: A condition characterised by a failed attempt to stimulate contractions pharmacologically before the spontaneous onset of labour. This condition may occur with or without ruptured membranes.... --- Walk 6 --- [JB01.1] Failed instrumental induction of labour Def: A condition characterised by a failed attempt to instrumentally stimulate contractions before the spontaneous onset of labour. This condition may occur with or without ruptured membranes.... --PARENT--> [JB01] Failed induction of labour Def: A condition characterised by a failed attempt to stimulate contractions before the spontaneous onset of labour. This condition may occur with or without ruptured membranes.... --CHILD--> [JB01.0] Failed medical induction of labour Def: A condition characterised by a failed attempt to stimulate contractions pharmacologically before the spontaneous onset of labour. This condition may occur with or without ruptured membranes....	[ "[JB01.Z] Failed induction of labour, unspecified\n --PARENT--> [JB01] Failed induction of labour\n Def: A condition characterised by a failed attempt to stimulate contractions before the spontaneous onset of labour. This condition may occur with or without ruptured membranes....\n --CHILD--> [JB01.0] Failed medical induction of labour\n Def: A condition characterised by a failed attempt to stimulate contractions pharmacologically before the spontaneous onset of labour. This condition may occur with or without ruptured membranes....", "[JB01.Z] Failed induction of labour, unspecified\n --PARENT--> [JB01] Failed induction of labour\n Def: A condition characterised by a failed attempt to stimulate contractions before the spontaneous onset of labour. This condition may occur with or without ruptured membranes....\n --CHILD--> [JB01.1] Failed instrumental induction of labour\n Def: A condition characterised by a failed attempt to instrumentally stimulate contractions before the spontaneous onset of labour. This condition may occur with or without ruptured membranes....", "[JB01.0] Failed medical induction of labour\n Def: A condition characterised by a failed attempt to stimulate contractions pharmacologically before the spontaneous onset of labour. This condition may occur with or without ruptured membranes....\n --PARENT--> [JB01] Failed induction of labour\n Def: A condition characterised by a failed attempt to stimulate contractions before the spontaneous onset of labour. This condition may occur with or without ruptured membranes....\n --PARENT--> [?] Complications of labour or delivery\n Def: Any complication characterised by the adverse evolution of a condition that arises during any one of the three stages of labour and delivery....", "[JB01.0] Failed medical induction of labour\n Def: A condition characterised by a failed attempt to stimulate contractions pharmacologically before the spontaneous onset of labour. This condition may occur with or without ruptured membranes....\n --PARENT--> [JB01] Failed induction of labour\n Def: A condition characterised by a failed attempt to stimulate contractions before the spontaneous onset of labour. This condition may occur with or without ruptured membranes....\n --CHILD--> [JB01.0] Failed medical induction of labour\n Def: A condition characterised by a failed attempt to stimulate contractions pharmacologically before the spontaneous onset of labour. This condition may occur with or without ruptured membranes....", "[JB01.1] Failed instrumental induction of labour\n Def: A condition characterised by a failed attempt to instrumentally stimulate contractions before the spontaneous onset of labour. This condition may occur with or without ruptured membranes....\n --PARENT--> [JB01] Failed induction of labour\n Def: A condition characterised by a failed attempt to stimulate contractions before the spontaneous onset of labour. This condition may occur with or without ruptured membranes....\n --CHILD--> [JB01.0] Failed medical induction of labour\n Def: A condition characterised by a failed attempt to stimulate contractions pharmacologically before the spontaneous onset of labour. This condition may occur with or without ruptured membranes....", "[JB01.1] Failed instrumental induction of labour\n Def: A condition characterised by a failed attempt to instrumentally stimulate contractions before the spontaneous onset of labour. This condition may occur with or without ruptured membranes....\n --PARENT--> [JB01] Failed induction of labour\n Def: A condition characterised by a failed attempt to stimulate contractions before the spontaneous onset of labour. This condition may occur with or without ruptured membranes....\n --CHILD--> [JB01.0] Failed medical induction of labour\n Def: A condition characterised by a failed attempt to stimulate contractions pharmacologically before the spontaneous onset of labour. This condition may occur with or without ruptured membranes...." ]	JB01.Z	Failed induction of labour, unspecified	[ { "from_icd11": "JB01.Z", "icd10_code": "O618", "icd10_title": "Other failed induction of labor" }, { "from_icd11": "JB01.Z", "icd10_code": "O619", "icd10_title": "Failed induction of labor, unspecified" }, { "from_icd11": "JB01.Z", "icd10_code": "O61", "icd10_title": "Failed induction of labor" }, { "from_icd11": "JB01.0", "icd10_code": "O610", "icd10_title": "Failed medical induction of labor" }, { "from_icd11": "JB01.1", "icd10_code": "O611", "icd10_title": "Failed instrumental induction of labor" }, { "from_icd11": "3C0Z", "icd10_code": "D75A", "icd10_title": "Glucose-6-phosphate dehydrogenase (G6PD) deficiency without anemia" }, { "from_icd11": "3C0Z", "icd10_code": "D7581", "icd10_title": "Myelofibrosis" }, { "from_icd11": "3C0Z", "icd10_code": "D7582", "icd10_title": "Heparin induced thrombocytopenia (HIT)" }, { "from_icd11": "3C0Z", "icd10_code": "D7589", "icd10_title": "Other specified diseases of blood and blood-forming organs" }, { "from_icd11": "3C0Z", "icd10_code": "D759", "icd10_title": "Disease of blood and blood-forming organs, unspecified" }, { "from_icd11": "3C0Z", "icd10_code": "D763", "icd10_title": "Other histiocytosis syndromes" }, { "from_icd11": "3C0Z", "icd10_code": "Q899", "icd10_title": "Congenital malformation, unspecified" }, { "from_icd11": "3C0Z", "icd10_code": "III", "icd10_title": "" }, { "from_icd11": "3C0Z", "icd10_code": "D70-D77", "icd10_title": "" }, { "from_icd11": "3C0Z", "icd10_code": "D75", "icd10_title": "Other and unspecified diseases of blood and blood-forming organs" } ]	O618	Other failed induction of labor
Table 2 Clinical cases from three major modules (Partial) Module 1 Home Health Care and Nursing for Children Children’s Growth and Healthcare Xiaoming, male, 1 month old, was taken to the community hospital for a physical examination by his parents. The nurse conducted measurements of physical growth and development, which showed a weighed of 8.5 kg, length of 60 cm, head circumference of 40 cm, and chest circumference of 39 cm. While changing the diaper, the nurse noticed pus-like yellow fluid oozing from the umbilical area. Xiaoming’ s parents lacked knowledge on how to safely bathe their baby, change diapers, and perform newborn massage. The nurse is also prepared to administer vaccines to Xiaoming Questions for Theoretical Class: (1)What laws does the physical growth and development of children follow? (2)What are the commonly used indicators for physical growth and development? what are their normal values, and what do these values signify? (3)What does the pus-like yellow fluid oozing from Xiaoming’ s umbilical area indicate? How should it be handled? (4)What vaccines should be administered to Xiaoming at his current age? What are the common adverse reactions to these vaccines? Questions for Laboratory Class: (1)Are Xiaoming’ s physical examination results indicators normal? (2)Please perform the correct measurement of physical growth and development for Xiaoming (3)Please address the pus-like yellow fluid oozing from Xiaoming’ s umbilical area (4)Please demonstrate to Xiaoming’ s parents the procedures for bathing the baby, changing diapers, and performing newborn massage (5)Please administer the necessary vaccines to Xiaoming Module 2 Nursing Care for Common Pediatric Diseases Nursing Care for Children with Malnutrition Lily, female, 2 years old Chief Complaint: refusal to eat accompanied by weight loss for 1 year History of Present Illness: One year prior to admission, the child experienced recurrent diarrhea, poor appetite, with daily milk intake less than 200 ml and gradually lagging growth and development. The patient also exhibited delayed motor function, lethargy, and restless sleep Physical Examination: Temperature (T) 36 °C, Heart Rate (HR) 95 beats per minute, Respiratory Rate (R) 35 breaths per minute, Weight 8 kg, Height 84 cm. The patient appeared lethargic with pale complexion, dry skin, dull and yellow hair, and significant weight loss. The head circumference was normal. The pharynx was normal (-), and the lung sounds were clear bilaterally. The heart rate was 95 beats per minute, with a regular rhythm and no pathological murmurs. The abdomen was soft, with the liver palpable 2 cm below the costal margin and 1 cm below the xiphoid process, with a moderate consistency. The spleen was not palpable. Subcutaneous fat was almost completely absent, and there was no edema. The muscle tone of the limbs was low, with normal physiological reflexes and no elicited pathological reflexes Laboratory Tests: Complete blood count (CBC) showed hemoglobin (Hb) at 92 g/L, other parameters were within normal range. Urinalysis, stool examination, and liver function tests were normal. Serum iron and zinc levels were below reference values. Chest X-ray did not reveal any abnormalities Diagnosis: Marasmus (wasting type of malnutrition) Questions for Theoretical Class: (1)What is malnutrition, and how many clinical types can it be classified into? (2)To what extent does this Lily suffer from malnutrition, and what evidence supports your judgment? (3)What are the causes of malnutrition among children in China, and what is the primary cause for this Lily’ s malnutrition? (4)What are the clinical manifestations of this Lily’ s malnutrition, and in what order does fat reduction occur? Which complication is most lethal? (5)What abnormal values do you see in the Lily’ s auxiliary tests, and what do they indicate? (6)What are the current nursing issues for Lily? How should targeted dietary care measures be developed for the existing nutritional problems? Questions for Laboratory Class: (1)Assuming the parents bring the child to the pediatric health clinic for a physical examination, please conduct a scenario role-play in groups to demonstrate the process and content of the physical examination (2)Lily’ s parents have questions about the introduction of complementary foods. Please explain in simple terms and understandable language the types of complementary foods suitable for this age group, as well as methods for preparing and combining these foods (3)Currently, the child is unable to eat orally, and the doctor has prescribed nasogastric feeding with milk. Please demonstrate the correct method of preparing the milk to the parents and perform the operation of inserting a nasogastric tube (4)Now that the child’ s condition has improved and they can eat by mouth, please instruct the parents on the correct bottle feeding method and emphasize the precautions Module 3 Nursing for Pediatric Critical Illnesses Nursing Care for Children with Convulsions Hanhan, male,1 year and 3 months old Chief Complaint: Cough with phlegm for 2 days, fever for 1 day, and one episode of seizure (as reported by parents) History of Present Illness: The child was brought to the hospital by his parents due to the aforementioned symptoms. While waiting for approximately 20 min in the outpatient area, the child suddenly became unconscious, stared upwards with both eyes, had cyanotic lips, clenched teeth, and convulsions in all four limbs. He was immediately transferred to the emergency room for resuscitation. One day prior to admission, the child developed a fever without any obvious cause. Six hours before admission, when his temperature peaked at around 38.8 °C, he experienced one episode of seizure characterized by upward rolling eyes, clenched teeth, and loss of consciousness, but no incontinence of urine or stool. This episode resolved spontaneously after about one minute. After resolution, he regained consciousness but appeared slightly weak, without sore throat, cough, headache, or vomiting. At the age of 6 months, the child had a similar episode associated with fever. There is no family history of seizures or epilepsy Physical Examination: Temperature (T) 39 °C, Heart Rate (HR) 142 beats per minute, Respiratory Rate (R) 40 breaths per minute. Examination revealed hyperemia of the pharynx, bilateral tonsils were mildly enlarged and congested (Grade I), without purulent discharge. Meningeal irritation signs were negative. Cardiovascular and pulmonary examinations were normal. Abdomen was soft and flat Laboratory Tests: White Blood Cell (WBC) count 15.66 × 10^9/L, Neutrophils (N) 76.3% Preliminary Diagnosis: 1. Febrile Seizure (Simple Type); 2. Acute Tonsillitis Questions for Theoretical Class: (1)What is a convulsion, and how does it differ from epilepsy? (2)What are the causes of Hanhan's convulsion, and why are children more prone to convulsion during children? (3)Which symptoms of a convulsion can help you quickly diagnose the condition, and what are the typical clinical manifestations? (4)Considering the current condition, which auxiliary examination do you think is most important to perform? (5)How would you provide first aid if you find Hanhan experiencing another seizure? (6)What are the main nursing issues currently facing Hanhan, and what corresponding nursing measures should be taken? (7)Discharge Health Education Poster for Hanhan and Family Questions for Laboratory Class: (1)Hanhan is currently having a seizure. Please conduct a scenario-based simulation in groups and implement the correct emergency measures for him (2)The child’ s seizure has stopped, and the nurse needs to understand the current body temperature situation. Please measure his vital signs (3)Doctor’ s order: 0.9% Saline 100 ml + Cefotaxime 0.35 g, intravenous infusion, once a day (Cefotaxime specification: 0.75 g/vial). Please prepare the medication solution and perform the scalp vein infusion according to the doctor’ s order (4)Hanhan currently has a body temperature of 38.5 °C. Please implement nursing measures of high fever for him (5)To enhance the awareness of convulsion prevention for Hanhan and his parents at home, please create an educational video on convulsion in children as a group project	3.693359	0.947754	sec[1]/sec[1]/sec[2]/sec[0]/p[1]	en	0.999998	PMC12004747	https://doi.org/10.1186/s12909-025-07073-2	[ "what", "please", "xiaoming", "physical", "parents", "nursing", "children", "hanhan", "questions", "malnutrition" ]	[ { "code": "MG44.1Z", "title": "Lack of expected normal physiological development, unspecified" }, { "code": "PJ20", "title": "Physical maltreatment" }, { "code": "MB23.0", "title": "Aggressive behaviour" }, { "code": "QD70.Z", "title": "Problems associated with the natural environment or human-made changes to the environment, unspecified" }, { "code": "QE82.0", "title": "Personal history of physical abuse" }, { "code": "QE50.4", "title": "Relationship with parents, in-laws or other family members" }, { "code": "QE52.1", "title": "Loss of love relationship in childhood" }, { "code": "QE9Y", "title": "Other specified problems associated with upbringing" }, { "code": "QE52.0", "title": "Caregiver-child relationship problem" }, { "code": "QE95", "title": "Inappropriate parental pressure or other abnormal qualities of upbringing" } ]	=== ICD-11 CODES FOUND === [MG44.1Z] Lack of expected normal physiological development, unspecified Also known as: Lack of expected normal physiological development, unspecified \| Lack of expected normal physiological development \| delayed physiological development \| unspecified delay in development \| development arrest [PJ20] Physical maltreatment Definition: Non-accidental acts of physical force that result, or have reasonable potential to result, in physical harm or that evoke significant fear. The category is applied to the victim of the maltreatment, not the perpetrator. Also known as: Physical maltreatment \| physical abuse \| Shaken infant syndrome \| shaken baby syndrome \| Battered baby syndrome [MB23.0] Aggressive behaviour Definition: Actions intended to threaten or hurt another person or to damage property that may be physical, verbal, or symbolic (e.g., acting against the other person's interests). Aggressive behaviour may be appropriate and self-protective, or inappropriate, hostile, and destructive. Also known as: Aggressive behaviour \| Violent behaviour \| physical violence [QD70.Z] Problems associated with the natural environment or human-made changes to the environment, unspecified Also known as: Problems associated with the natural environment or human-made changes to the environment, unspecified \| Problems associated with the natural environment or human-made changes to the environment \| physical environment problem \| exposure to pollution NOS \| unsatisfactory physical environment [QE82.0] Personal history of physical abuse Definition: Personal history of non-accidental acts of physical force that result, or have reasonable potential to result, in physical harm or that evoke significant fear. This category is applied to the victim of the maltreatment, not the perpetrator. Also known as: Personal history of physical abuse \| Personal history of physical maltreatment \| Physical abuse of child Excludes: History of spouse or partner violence, physical [QE50.4] Relationship with parents, in-laws or other family members Also known as: Relationship with parents, in-laws or other family members \| Problems in relationship with parents \| problem with parent \| Problem with aged parent \| Problem with sibling Excludes: Caregiver-child relationship problem \| Problems associated with upbringing \| Problem associated with interactions with spouse or partner [QE52.1] Loss of love relationship in childhood Definition: Loss of an emotionally close relationship, such as of a parent, a sibling, a very special friend or a loved pet, by death or permanent departure or rejection. Also known as: Loss of love relationship in childhood \| negative life event in childhood of loss of love relationship \| life event in childhood of loss of love relationship \| Loss of parent in childhood [QE9Y] Other specified problems associated with upbringing Also known as: Other specified problems associated with upbringing \| Lack of learning or play experience \| Problem with a parenting situation \| problem with atypical parenting situation [QE52.0] Caregiver-child relationship problem Definition: Substantial and sustained dissatisfaction within a caregiver-child relationship, including a parental relationship, associated with significant disturbance in functioning. Also known as: Caregiver-child relationship problem \| parent-child relationship problem \| Caregiver-child relationship problem with current caregiver \| Caregiver-child relationship problem with former caregiver [QE95] Inappropriate parental pressure or other abnormal qualities of upbringing Definition: Parents forcing the child to be different from the local norm, either sex-inappropriate (e.g. dressing a boy in girl's clothes), age-inappropriate (e.g. forcing a child to take on responsibilities above her or his own age) or otherwise inappropriate (e.g. pressing the child to engage in unwanted or too difficult activities). Also known as: Inappropriate parental pressure or other abnormal qualities of upbringing \| problem of inappropriate parental pressure === GRAPH WALKS === --- Walk 1 --- [MG44.1Z] Lack of expected normal physiological development, unspecified --PARENT--> [MG44.1] Lack of expected normal physiological development Def: Lack of expected normal physiological development includes delayed milestone of development and other lack of expected normal physiological development including gross and fine motor development, lang... --EXCLUDES--> [?] Disorders of intellectual development Def: Disorders of intellectual development are a group of etiologically diverse conditions originating during the developmental period characterised by significantly below average intellectual functioning ... --- Walk 2 --- [MG44.1Z] Lack of expected normal physiological development, unspecified --PARENT--> [MG44.1] Lack of expected normal physiological development Def: Lack of expected normal physiological development includes delayed milestone of development and other lack of expected normal physiological development including gross and fine motor development, lang... --EXCLUDES--> [?] Disorders of intellectual development Def: Disorders of intellectual development are a group of etiologically diverse conditions originating during the developmental period characterised by significantly below average intellectual functioning ... --- Walk 3 --- [PJ20] Physical maltreatment Def: Non-accidental acts of physical force that result, or have reasonable potential to result, in physical harm or that evoke significant fear. The category is applied to the victim of the maltreatment, n... --PARENT--> [?] Maltreatment Def: Non-accidental acts of physical force, forced or coerced sexual acts, verbal or symbolic acts, or significant caregiving omissions that result in harm or have a reasonable potential for harm. These ca... --CHILD--> [PJ21] Sexual maltreatment Def: In adults, forced or coerced sexual acts or sexual acts with someone who is unable to consent; in children, sexual acts involving a child that are intended to provide sexual gratification to an adult.... --- Walk 4 --- [PJ20] Physical maltreatment Def: Non-accidental acts of physical force that result, or have reasonable potential to result, in physical harm or that evoke significant fear. The category is applied to the victim of the maltreatment, n... --PARENT--> [?] Maltreatment Def: Non-accidental acts of physical force, forced or coerced sexual acts, verbal or symbolic acts, or significant caregiving omissions that result in harm or have a reasonable potential for harm. These ca... --CHILD--> [PJ22] Psychological maltreatment Def: Non-accidental verbal or symbolic acts that result in significant psychological harm. The category is applied to the victim of the maltreatment, not the perpetrator.... --- Walk 5 --- [MB23.0] Aggressive behaviour Def: Actions intended to threaten or hurt another person or to damage property that may be physical, verbal, or symbolic (e.g., acting against the other person's interests). Aggressive behaviour may be app... --PARENT--> [MB23] Symptoms or signs involving appearance or behaviour --CHILD--> [MB23.2] Avoidance behaviour Def: The act of keeping away from circumstances, situations, or stimuli that cause anxiety or other negative emotions in the individual.... --- Walk 6 --- [MB23.0] Aggressive behaviour Def: Actions intended to threaten or hurt another person or to damage property that may be physical, verbal, or symbolic (e.g., acting against the other person's interests). Aggressive behaviour may be app... --PARENT--> [MB23] Symptoms or signs involving appearance or behaviour --RELATED_TO--> [?] Speech dysfluency Def: Speech dysfluency is characterised by the frequent or pervasive disruption of the rhythmic flow of speech that arises subsequent to the developmental period (i.e., adult onset) and is outside the limi...	[ "[MG44.1Z] Lack of expected normal physiological development, unspecified\n --PARENT--> [MG44.1] Lack of expected normal physiological development\n Def: Lack of expected normal physiological development includes delayed milestone of development and other lack of expected normal physiological development including gross and fine motor development, lang...\n --EXCLUDES--> [?] Disorders of intellectual development\n Def: Disorders of intellectual development are a group of etiologically diverse conditions originating during the developmental period characterised by significantly below average intellectual functioning ...", "[MG44.1Z] Lack of expected normal physiological development, unspecified\n --PARENT--> [MG44.1] Lack of expected normal physiological development\n Def: Lack of expected normal physiological development includes delayed milestone of development and other lack of expected normal physiological development including gross and fine motor development, lang...\n --EXCLUDES--> [?] Disorders of intellectual development\n Def: Disorders of intellectual development are a group of etiologically diverse conditions originating during the developmental period characterised by significantly below average intellectual functioning ...", "[PJ20] Physical maltreatment\n Def: Non-accidental acts of physical force that result, or have reasonable potential to result, in physical harm or that evoke significant fear. The category is applied to the victim of the maltreatment, n...\n --PARENT--> [?] Maltreatment\n Def: Non-accidental acts of physical force, forced or coerced sexual acts, verbal or symbolic acts, or significant caregiving omissions that result in harm or have a reasonable potential for harm. These ca...\n --CHILD--> [PJ21] Sexual maltreatment\n Def: In adults, forced or coerced sexual acts or sexual acts with someone who is unable to consent; in children, sexual acts involving a child that are intended to provide sexual gratification to an adult....", "[PJ20] Physical maltreatment\n Def: Non-accidental acts of physical force that result, or have reasonable potential to result, in physical harm or that evoke significant fear. The category is applied to the victim of the maltreatment, n...\n --PARENT--> [?] Maltreatment\n Def: Non-accidental acts of physical force, forced or coerced sexual acts, verbal or symbolic acts, or significant caregiving omissions that result in harm or have a reasonable potential for harm. These ca...\n --CHILD--> [PJ22] Psychological maltreatment\n Def: Non-accidental verbal or symbolic acts that result in significant psychological harm. The category is applied to the victim of the maltreatment, not the perpetrator....", "[MB23.0] Aggressive behaviour\n Def: Actions intended to threaten or hurt another person or to damage property that may be physical, verbal, or symbolic (e.g., acting against the other person's interests). Aggressive behaviour may be app...\n --PARENT--> [MB23] Symptoms or signs involving appearance or behaviour\n --CHILD--> [MB23.2] Avoidance behaviour\n Def: The act of keeping away from circumstances, situations, or stimuli that cause anxiety or other negative emotions in the individual....", "[MB23.0] Aggressive behaviour\n Def: Actions intended to threaten or hurt another person or to damage property that may be physical, verbal, or symbolic (e.g., acting against the other person's interests). Aggressive behaviour may be app...\n --PARENT--> [MB23] Symptoms or signs involving appearance or behaviour\n --RELATED_TO--> [?] Speech dysfluency\n Def: Speech dysfluency is characterised by the frequent or pervasive disruption of the rhythmic flow of speech that arises subsequent to the developmental period (i.e., adult onset) and is outside the limi..." ]	MG44.1Z	Lack of expected normal physiological development, unspecified	[ { "from_icd11": "MG44.1Z", "icd10_code": "R6250", "icd10_title": "Unspecified lack of expected normal physiological development in childhood" }, { "from_icd11": "MG44.1Z", "icd10_code": "R6259", "icd10_title": "Other lack of expected normal physiological development in childhood" }, { "from_icd11": "MG44.1Z", "icd10_code": "R6251", "icd10_title": "Failure to thrive (child)" }, { "from_icd11": "MG44.1Z", "icd10_code": "R6252", "icd10_title": "Short stature (child)" }, { "from_icd11": "MG44.1Z", "icd10_code": "R62", "icd10_title": "Lack of expected normal physiological development in childhood and adults" }, { "from_icd11": "MG44.1Z", "icd10_code": "R628", "icd10_title": "" }, { "from_icd11": "MG44.1Z", "icd10_code": "R629", "icd10_title": "" }, { "from_icd11": "PJ20", "icd10_code": "T7411XA", "icd10_title": "Adult physical abuse, confirmed, initial encounter" }, { "from_icd11": "PJ20", "icd10_code": "T7411XS", "icd10_title": "Adult physical abuse, confirmed, sequela" }, { "from_icd11": "PJ20", "icd10_code": "T741", "icd10_title": "Physical abuse, confirmed" }, { "from_icd11": "PJ20", "icd10_code": "Y06", "icd10_title": "" }, { "from_icd11": "MB23.0", "icd10_code": "R456", "icd10_title": "Violent behavior" }, { "from_icd11": "QD70.Z", "icd10_code": "Z58", "icd10_title": "" }, { "from_icd11": "QD70.Z", "icd10_code": "Z585", "icd10_title": "" }, { "from_icd11": "QD70.Z", "icd10_code": "Z588", "icd10_title": "" } ]	R6250	Unspecified lack of expected normal physiological development in childhood
The current case presented with a complete dentition and an abnormally large central incisor. This may be due to the fusion between a permanent central incisor and a supernumerary mesiodens. The term “double‐tooth” therefore seems more applicable in such a case. The main problems encountered in the management of double teeth are the lack of sufficient information reporting the best line of treatment and the relative absence of long‐term follow‐up of these interventions. 3 Consensus indicates that a multidisciplinary approach is the best choice for dealing with these cases. Therefore, a combined endodontic, periodontal, and orthodontic intervention was applied. The management strategy determined was dependent on clinical and radiographic findings and anticipated topography following hemisectioning of the twinned tooth. The current case reports a five‐year follow‐up period. The main observations were that this protocol resulted in improved function, maintenance of alveolar bone height as well as patient and parent satisfaction with the treatment. Orthodontic results were stable and resulted in a normal occlusion and a drastic improvement in esthetics. There was no root resorption and barely any mobility after the end of therapy. Endodontic therapy using a mineral trioxide aggregate (MTA) monoblock was selected since MTA represents a highly biocompatible material that has excellent sealing properties, in addition to exceptional antibacterial and bioinductive abilities. 12 MTA monoblock filling has been suggested for filling of immature necrotic teeth with open apices and has been shown not only to strengthen the roots but that upon its removal for post space preparation, its sealing properties appear not to be affected. 12 , 13 , 14 MTA is also most commonly used as a retrograde filling material to seal apical ramifications during endodontic root resection due to its previously mentioned properties. 12 In the current case report, since endodontic therapy was commenced prior to surgical intervention, it was crucial to select a filling material that would not only maintain long‐term sealing but would also have bioactive properties once it was exposed to the periodontal and bone tissues upon hemisectioning of the fused tooth. 12 This in addition to the presence of the bone graft material and enamel matrix derivative which would—together with the MTA—potentially provide an excellent substrate for new hard tissue formation and periodontal re‐attachment. The periodontal strategy applied was to try and obliterate the resultant socket from extraction of the mesiodens in order to promote tissue regeneration and preserve bone around the remaining central incisor. Splinting was also applied to prevent tooth movement and stabilize the ensuing clot. The lag period between surgery and commencement of active orthodontic therapy in the current work was to allow these tissues to regenerate uninterrupted. The use of enamel matrix derivative (EMD) in conjunction with the bone alloplast plays a crucial role in orchestrating tissue healing and bone formation. Studies indicate that EMD significantly decreases interleukin‐1 beta (IL‐1β) and RANKL expression, thereby promoting bone remodeling. EMD increases bacterial and tissue debris clearance, as well as fibroplasia and angiogenesis by inducing endothelial cell proliferation, migration, and capillary‐like sprout formation. 15 Another important aspect of EMD is its reported biomimetic effect and its capacity to play a role in dentin, acellular cementum, and alveolar bone formation during embryonic tooth development. 16 Therefore, the use of EMD was an attempt to prompt the regeneration of not only new bone, but also of a more favorable periodontal attachment to the hemisectioned tooth. With the same methodology, a reported study showed a higher incidence of healed periodontal ligament tissues (PDL) around re‐implanted teeth in beagle dogs. 17 Other histologic studies demonstrated that EMD results in limited epithelial down growth. Moreover, human biopsies have reported the possibility of complete periodontal regeneration or new connective tissue attachment after EMD application to roots in intra bony periodontal defects. 18 Unlike regular periodontal surgery, periodontal measurements at the mesiolabial aspect of tooth #21 at the site of the extracted mesiodens were constantly changing. Three months after surgery, there was a 3 mm CAL which increased to 7 mm at one year. After starting the orthodontic movement, further CAL reached 9mm then stabilized at 7 mm after 4 years. An explanation is the possibility that moving the tooth led to bone and tissue remodeling and hence the increased measurements during active orthodontic movement. Moreover, clinical and radiographic examination revealed the presence of a deep groove running from the cervical aspect of the tooth including a great aspect of the root, probably due to cutting through the root of the mesiodens at a slightly more distal plane. This groove might have predisposed to plaque retention and some attachment loss. Although the deep periodontal pocket that developed may be considered a clinical shortcoming of this case, a decision to delay the second intervention was made to avoid disturbing bone remodeling during the phase of active orthodontic intervention. Additionally, a mid‐line diastema remained again possibly due to the retained root apex which may have prevented closure of this space during orthodontic activation. These sub‐optimal outcomes lead to the decision to perform a second surgery to improve the final outcome which may include orthodontic management again in the future. Other cases studies such as that by Kim et al 19 while show a better final outcome did not represent the same challenges as found in the current case including the presence of pulpal communication which entailed root canal therapy of the tooth prior to resection and profound treatment planning using multiple CBCT scans. While this case is similar to ours, it appears very difficult to have ideal results due to the many variables involved. A compromise is usually reached, and satisfactory, stable clinical, and esthetic results are considered sufficient by the clinician particularly if the patient is satisfied with the final result. Indeed, the remaining sites at both central incisors were normal and in line with a clinically healthy periodontal attachment. Continuous follow‐up and periodontal maintenance were carried out during the follow‐up period and a second surgical intervention was performed using PRF. The choice to use PRF was done to avoid excessive costs by the re‐use of EMD for the second surgery in addition to the ability of PRF to serve as a membrane to augment the mucoperisoteal flap thereby possibly contributing as well to the overall enhanced results. This is in virtue of its well‐documented benefits in regenerative dentistry applications and oral surgery indications. 20 Indeed, this lead to further probing depth and attachment loss reduction. Regarding the orthodontic results, they showed improvement and normalization of facial and dental arch relationships due to the use of retraction mechanics in the upper arch with gentle force control, which was chosen to suite the surgical‐endodontic treatment that was performed in the area of the upper central incisors, as well as facilitating proper follow‐up of changes in the periodontally and endodontically treated tooth. During the initial evaluation of the patient, the decision to extract the fused central and supernumerary tooth could have resulted in correction of the overjet and have stable occlusion results, yet it would have jeopardized the chance to have a normally shaped dentition and smile similar to that in the presence of the natural centrals, laterals, and canines. The risk of undergoing retraction of the surgically managed segment was finally evaluated after one‐year follow‐up, since the patient and his family did not accept removal of the fused teeth and could sustain such a prolonged procedure with necessary follow‐up. In conclusion, the collaboration between the different specialties facilitated treatment and tailored the needed protocol for the correction of such a clinically challenging situation.	4.207031	0.947266	sec[2]/p[0]	en	0.999997	33598244	https://doi.org/10.1002/ccr3.3629	[ "periodontal", "tooth", "that", "bone", "this", "orthodontic", "root", "which", "tissue", "attachment" ]	[ { "code": "DA0C.Y", "title": "Other specified periodontal disease" }, { "code": "DA0C.Z", "title": "Periodontal disease, unspecified" }, { "code": "DA0C.0", "title": "Acute periodontitis" }, { "code": "DA0C.1", "title": "Aggressive periodontitis" }, { "code": "DA09.71", "title": "Chronic apical periodontitis" }, { "code": "DA07.6Y", "title": "Other specified disturbances in tooth eruption" }, { "code": "LA30.0", "title": "Anodontia" }, { "code": "QA00.8", "title": "Dental examination" }, { "code": "LA30.3", "title": "Hyperdontia" }, { "code": "DA0A.Y", "title": "Other specified disorders of teeth and supporting structures" } ]	=== ICD-11 CODES FOUND === [DA0C.Y] Other specified periodontal disease Also known as: Other specified periodontal disease \| Chronic periodontitis \| Adult periodontitis \| adult-onset periodontitis \| chronic pericementitis [DA0C.Z] Periodontal disease, unspecified Also known as: Periodontal disease, unspecified \| Periodontal disease [DA0C.0] Acute periodontitis Definition: This is an acute disease affecting the tooth-supporting structures, i.e. gingiva, alveolar bone and periodontal membrane. Also known as: Acute periodontitis \| acute pericementitis \| aggressive and acute periodontitis \| peridental infection \| periodontal infection Excludes: Periapical abscess without sinus \| Acute apical periodontitis of pulpal origin \| Periapical abscess with sinus [DA0C.1] Aggressive periodontitis Definition: A type of periodontal disease and includes localised aggressive periodontitis (LAP), and Generalised aggressive periodontitis (GAP). Also known as: Aggressive periodontitis \| Juvenile periodontitis \| prepubertal periodontitis \| Generalised aggressive periodontitis \| Localised aggresssive periodontitis Includes: Juvenile periodontitis [DA09.71] Chronic apical periodontitis Definition: A periapical inflammation characterised by dental granuloma formation. Also known as: Chronic apical periodontitis \| Apical periodontitis NOS \| apex periodontitis \| periapical infection NOS \| Apical or periapical granuloma [DA07.6Y] Other specified disturbances in tooth eruption Also known as: Other specified disturbances in tooth eruption \| Neonatal teeth \| Natal teeth \| Advanced tooth eruption \| precocious dentition Includes: Neonatal teeth \| Advanced tooth eruption [LA30.0] Anodontia Definition: Anodontia is a genetic disorder commonly defined as the absence of all teeth, affecting both temporary and permanent dentitions, and is extremely rarely encountered in a pure form without any associated abnormalities. Rare but more common than complete anodontia is hypodontia. Also known as: Anodontia \| agomphiasis \| agomphosis \| anodontism \| complete absence of teeth [QA00.8] Dental examination Also known as: Dental examination \| examination of teeth [LA30.3] Hyperdontia Definition: Hyperdontia is the condition of having supernumerary teeth, or teeth which appear in addition to the regular number of teeth. Also known as: Hyperdontia \| Supplementary teeth \| Supernumerary teeth \| supernumerary tooth \| supplemental teeth Includes: Supplementary teeth \| Supernumerary teeth \| distomolar [DA0A.Y] Other specified disorders of teeth and supporting structures Also known as: Other specified disorders of teeth and supporting structures \| Alveolar process haemorrhage \| alveolar haemorrhage \| Barodontalgia \| aerodontalgia === GRAPH WALKS === --- Walk 1 --- [DA0C.Y] Other specified periodontal disease --PARENT--> [DA0C] Periodontal disease Def: Periodontal disease can refer to any pathological process involving the gum (GINGIVA), the alveolar bone (alveolar process), the dental cementum, and / or the periodontal ligament... --CHILD--> [DA0C.2] Periodontosis Def: Periodontosis defined as a disease of the periodontium occurring in an otherwise healthy adolescent and characterised by a rapid loss of the alveolar bone around more than one tooth of the permanent d... --- Walk 2 --- [DA0C.Y] Other specified periodontal disease --PARENT--> [DA0C] Periodontal disease Def: Periodontal disease can refer to any pathological process involving the gum (GINGIVA), the alveolar bone (alveolar process), the dental cementum, and / or the periodontal ligament... --PARENT--> [?] Diseases or disorders of orofacial complex Def: Morbid process, derangement or abnormality localised in the mouth or related tissues of the face... --- Walk 3 --- [DA0C.Z] Periodontal disease, unspecified --PARENT--> [DA0C] Periodontal disease Def: Periodontal disease can refer to any pathological process involving the gum (GINGIVA), the alveolar bone (alveolar process), the dental cementum, and / or the periodontal ligament... --CHILD--> [DA0C.1] Aggressive periodontitis Def: A type of periodontal disease and includes localised aggressive periodontitis (LAP), and Generalised aggressive periodontitis (GAP).... --- Walk 4 --- [DA0C.Z] Periodontal disease, unspecified --PARENT--> [DA0C] Periodontal disease Def: Periodontal disease can refer to any pathological process involving the gum (GINGIVA), the alveolar bone (alveolar process), the dental cementum, and / or the periodontal ligament... --CHILD--> [DA0C.2] Periodontosis Def: Periodontosis defined as a disease of the periodontium occurring in an otherwise healthy adolescent and characterised by a rapid loss of the alveolar bone around more than one tooth of the permanent d... --- Walk 5 --- [DA0C.0] Acute periodontitis Def: This is an acute disease affecting the tooth-supporting structures, i.e. gingiva, alveolar bone and periodontal membrane.... --EXCLUDES--> [?] Periapical abscess without sinus --PARENT--> [?] Periapical abscess --- Walk 6 --- [DA0C.0] Acute periodontitis Def: This is an acute disease affecting the tooth-supporting structures, i.e. gingiva, alveolar bone and periodontal membrane.... --EXCLUDES--> [?] Periapical abscess without sinus --CHILD--> [?] Alveolar abscess	[ "[DA0C.Y] Other specified periodontal disease\n --PARENT--> [DA0C] Periodontal disease\n Def: Periodontal disease can refer to any pathological process involving the gum (GINGIVA), the alveolar bone (alveolar process), the dental cementum, and / or the periodontal ligament...\n --CHILD--> [DA0C.2] Periodontosis\n Def: Periodontosis defined as a disease of the periodontium occurring in an otherwise healthy adolescent and characterised by a rapid loss of the alveolar bone around more than one tooth of the permanent d...", "[DA0C.Y] Other specified periodontal disease\n --PARENT--> [DA0C] Periodontal disease\n Def: Periodontal disease can refer to any pathological process involving the gum (GINGIVA), the alveolar bone (alveolar process), the dental cementum, and / or the periodontal ligament...\n --PARENT--> [?] Diseases or disorders of orofacial complex\n Def: Morbid process, derangement or abnormality localised in the mouth or related tissues of the face...", "[DA0C.Z] Periodontal disease, unspecified\n --PARENT--> [DA0C] Periodontal disease\n Def: Periodontal disease can refer to any pathological process involving the gum (GINGIVA), the alveolar bone (alveolar process), the dental cementum, and / or the periodontal ligament...\n --CHILD--> [DA0C.1] Aggressive periodontitis\n Def: A type of periodontal disease and includes localised aggressive periodontitis (LAP), and Generalised aggressive periodontitis (GAP)....", "[DA0C.Z] Periodontal disease, unspecified\n --PARENT--> [DA0C] Periodontal disease\n Def: Periodontal disease can refer to any pathological process involving the gum (GINGIVA), the alveolar bone (alveolar process), the dental cementum, and / or the periodontal ligament...\n --CHILD--> [DA0C.2] Periodontosis\n Def: Periodontosis defined as a disease of the periodontium occurring in an otherwise healthy adolescent and characterised by a rapid loss of the alveolar bone around more than one tooth of the permanent d...", "[DA0C.0] Acute periodontitis\n Def: This is an acute disease affecting the tooth-supporting structures, i.e. gingiva, alveolar bone and periodontal membrane....\n --EXCLUDES--> [?] Periapical abscess without sinus\n --PARENT--> [?] Periapical abscess", "[DA0C.0] Acute periodontitis\n Def: This is an acute disease affecting the tooth-supporting structures, i.e. gingiva, alveolar bone and periodontal membrane....\n --EXCLUDES--> [?] Periapical abscess without sinus\n --CHILD--> [?] Alveolar abscess" ]	DA0C.Y	Other specified periodontal disease	[ { "from_icd11": "DA0C.Z", "icd10_code": "K0530", "icd10_title": "Chronic periodontitis, unspecified" }, { "from_icd11": "DA0C.Z", "icd10_code": "K05319", "icd10_title": "Chronic periodontitis, localized, unspecified severity" }, { "from_icd11": "DA0C.Z", "icd10_code": "K05329", "icd10_title": "Chronic periodontitis, generalized, unspecified severity" }, { "from_icd11": "DA0C.Z", "icd10_code": "K0532", "icd10_title": "Chronic periodontitis, generalized" }, { "from_icd11": "DA0C.Z", "icd10_code": "K056", "icd10_title": "Periodontal disease, unspecified" }, { "from_icd11": "DA0C.Z", "icd10_code": "K055", "icd10_title": "Other periodontal diseases" }, { "from_icd11": "DA0C.Z", "icd10_code": "K05", "icd10_title": "Gingivitis and periodontal diseases" }, { "from_icd11": "DA0C.Z", "icd10_code": "K053", "icd10_title": "Chronic periodontitis" }, { "from_icd11": "DA0C.0", "icd10_code": "K05219", "icd10_title": "Aggressive periodontitis, localized, unspecified severity" }, { "from_icd11": "DA0C.0", "icd10_code": "K0520", "icd10_title": "Aggressive periodontitis, unspecified" }, { "from_icd11": "DA0C.0", "icd10_code": "K0521", "icd10_title": "Aggressive periodontitis, localized" }, { "from_icd11": "DA0C.0", "icd10_code": "K052", "icd10_title": "Aggressive periodontitis" }, { "from_icd11": "DA09.71", "icd10_code": "K045", "icd10_title": "Chronic apical periodontitis" }, { "from_icd11": "LA30.0", "icd10_code": "K000", "icd10_title": "Anodontia" }, { "from_icd11": "QA00.8", "icd10_code": "Z012", "icd10_title": "Encounter for dental examination and cleaning" } ]	K0530	Chronic periodontitis, unspecified
The 66-year-old Moroccan male patient had a cumulative smoking index of 30 pack-years. The patient stopped smoking 5 years earlier, had no alcoholism, and had no personal or family history or professional or environmental exposure for bilateral jugular thrombosis. He was put on antivitamin K for 1 month and still developed thoracic pains with productive coughing bringing up hemoptoic sputum, lumbago, dysphonia, epistaxis, and deafness of the left ear of acute installation. At admission, the patient was respiratorily and hemodynamically stable. The general examination on admission revealed a conscious patient with good orientation in time and space, with a heart rate of 63 beats per minute, blood pressure of 120/60 mm Hg, respiratory rate of 16 breaths per minute, and temperature of 37 °C. On neurological examination, mobility, sensitivity, and osteotendinous reflexes were preserved. Examination of the cranial nerves was without anomalies. The rest of the physical examination was unremarkable except for red eyes and some leg purpuric lesions (Table 1 ). There were no peripheral signs of heart failure and no signs of peritoneal irritation on percussion, and chest X-ray showed several excavated opacities . The thoracoabdominopelvic computed tomography scan revealed multiple thromboses, particularly in the jugular veins , extended to the brachiocephalic trunk and the superior vena cava, and in the left common femoral vein, a left intraventricular thrombus. The sinus scan revealed chronic maxillary sinusitis with episcleritis perforation of its medial wall , excavated bilateral nodular pulmonary lesions associated with a periaortic adenopathy flow, and a fly sheathing the aorta suggestive of retroperitoneal fibrosis .The routine blood and urine analysis detected anemia. Renal and hepatic function were normal, and hepatitis B and C and human immunodeficiency virus (HIV) serologies were negative. There was an increase of the acute phase reactant C-reactive protein (CRP) 188 mg/L (normal value ≤ 6 mg/L), an increase of 24-hour proteinuria to 1.4 g/L (normal value 0.3 g/L), microscopic hematuria detected on cytobacteriological examination of urine, urinary sediment positive for blood and albumin, acid–alcohol resistant bacillus in sputum negative with GeneXpert analysis, antiphospholipid antibodies negative, and anticytoplasmic antibodies of neutrophilic polynuclear antibodies ANCA-PR3 positive to 63 UI/mL. Ear, nose, and throat examination showed a highly inflamed nasal mucosa, suggesting bacterial infection. The patient received antibiotic treatment, the examination also showed subglottic stenosis causing dysphonia. Ophthalmologic examination was indicative of bilateral episcleritis. Transthoracic ultrasound showed ischemic cardiomyopathy, which was complicated by a left intraventricular thrombus and a circumferential effusion with fibrin deposits. Other complementary tests, such as PET scan or biopsy (pulmonary, nasal, renal, retroperitoneal fibrosis), did not lead to suspicion of neoplastic pathology or therapeutic urgency. Based on these results, we diagnosed GPA with cardiovascular, pulmonary, renal, and nasal involvement associated with retroperitoneal fibrosis (Tables 2 , 3 ). In addition to the anticoagulant [warfarin 2 mg with international normalized ratio (INR) of 2], the patient was treated with immunosuppressive therapy [bolus of methylprednisolone 15 mg/kg/day 3 days in a row, bolus of cyclophosphamide Endoxan 500 mg/m 2 with Uromitexan (mesna) 500 mg/ m 2 ), and oral corticosteroids (1 m/kg)], (Tables 4 , 5 ), with clinical improvement including the disappearance of dyspnea and hemoptysis, radiological improvement including regression of excavated nodules , decrease in the size of the periaortic infiltrate , and a slight improvement in renal function (24-hour proteinuria of control at 0.7 mg/L) and ANCA levels (ANCA of control at 53 UI/mL) (Table 4 ). The follow-up was complicated by several relapses, hospitalization, and an increase of corticosteroid therapy Table 1 The chronology of clinical signs Time Clinical presentation T0 Bilateral jugular thrombosis T1 1 month Chest pain with productive cough bringing up hemoptoid sputum T2 1 month and 1 week Lumbago, dysphonia, epistaxis, deafness of the left ear T3 1 month and 10 days Red eyes and some purpuric lesions on the legs Fig. 1 The frontal chest X-ray shows several excavated opacities Fig. 2 Partial thrombosis of the jugular vein Fig. 3 Sinus CT scan, axial section, frontal section: filling of the right maxillary sinus (sinusitis) with an erosion of the bone wall Fig. 4 Thoracic CT scan, parenchymal window, axial sections: multiple excavated intraparenchymal lung nodules, irregularly contoured, thick-walled Fig. 5 Abdominal CT scan, axial section:; tissue density infiltrate (or sleeve), homogeneous, perivascular, sheathing the abdominal aorta ( a , arrowheads), extending to the iliac arteries ( b , red arrow) and iliac ureters ( c , blue arrows) in favor of retroperitoneal fibrosis (RFP) Table 2 The diagnostic criteria in our patient Diagnostic criteria Arguments Clinical Lung: chest pain with hemoptoic sputum, bilateral nodular excavated lung lesions Kidney: microscopic hematuria, positive urine sediment, 24-hour proteinuria ENT: dysphonia, epistaxis, left ear deafness, subglottic stenosis on nasofibroscopy, perforation of the medial sinus wall Ophthalmic: red eyes, bilateral episcleritis Cardiovascular involvement: multiple thrombosis, circumferential pericardial effusion Lumbar: lumbago, retroperitoneal fibrosis Biology Anticytoplasmic neutrophil antibodies ANCA-PR3 positive at 63 IU/mL Histology Biopsies not done because of the therapeutic emergency and the impossibility of stopping the anticoagulant treatment ENT : Eyes, Nose, Throat; ANCA-PR3 : anti-neutrophil cytoplasmic antibodies proteinase 3 Table 3 Diagnostic criteria Diagnostic criteria granulomatosis with polyangiitis: should show two or more criteria Nasal or oral inflammation Abnormal thoracic X-ray Active urinary sediment Granulomatous inflammation in the biopsy Table 4 Clinical course and follow-up visits Time Treatment administered Clinical, biological, and radiological evolution T0 A bolus of methylprednisolone 3 days in a row Disappearance of purpuric lesions T1 day 4 A first bolus of Endoxan + 60 mg prednisone Disappearance of chest pain Cessation of hemoptysis and epistaxis T2 2 weeks Second bolus of Endoxan + 60 mg prednisone Regression of pulmonary nodules and periaortic infiltration T3 2 weeks 3rd bolus of Endoxan + 60 mg prednisone Decrease in cANCA Decrease in 24-hour proteinuria T4 3 weeks Fourth bolus of Endoxan + 60 mg prednisone Regression of jugular thrombosis T5 3 weeks Fifth bolus of Endoxan + 40 mg prednisone Clinical, biological, radiological stability T6 3 weeks Sixth bolus of Endoxan + 40 mg prednisone Clinical, biological, radiological stability T7 1 week from the end of sixth bolus Azathioprine 50 mg + 30 mg prednisone Relapse leading to increase in corticotherapy Table 5 Bolus of Endoxan and monitoring Hour 0 Hour 1 Hour 2 Hour 3 Hour 4 Hour 5 500 saline serum (SS 0.9%) Endoxan 1 g/500 cc of glycolic serum (GS 5%) 1/3 solution mesna (600 mg/ 100 cc GS 5%) 500 cc of SS 0.9% Furosemide 40 mg intravenous 1/3 solution mesna (600 mg/100 cc GS 5%) Drinking water 1/3 solution mesna (600 mg/100 cc GS 5%) Drinking water Monitoring Hour 0 Hour 1 Hour 2 Hour 3 Hour 5 Hour 6 Hour 7 Blood pressure 120/60 mmHg 120/60 mmHg 130/70 mmHg 130/70 mmHg 120/60 mmHg 120/60 mmHg 120/60 mmHg Respiratory frequency 16 breaths per minute 16 breaths per minute 17 breaths per minute 16 breaths per minute 16 breaths per minute 16 breaths per minute 16 breaths per minute Pulse 63 beats per minute 70 beats per minute 73 beats per minute 75 beats per minute 70 beats per minute 65 beats per minute 65 beats per minute Temperature 37 °C 37 °C 37 °C 37 °C 37 °C 37 °C 37 °C Fig. 6 Thoracic CT scan (performed after the second bolus of cyclophosphamide) showed radiological improvement of excavated nodules with the disappearance of condensation Fig. 7 Spontaneous contrast abdominal CT scan (performed after the second bolus of cyclophosphamide) shows clear regression of periaortic tissue infiltrate	4.023438	0.979492	sec[1]/p[0]	en	0.999998	PMC8790920	https://doi.org/10.1186/s13256-021-03235-0	[ "hour", "minute", "bolus", "endoxan", "beats", "breaths", "scan", "excavated", "prednisone", "mmhg" ]	[ { "code": "LB13.Y", "title": "Other specified structural developmental anomalies of stomach" }, { "code": "DA40.4", "title": "Hourglass stricture and stenosis of stomach" }, { "code": "JB02.4", "title": "Hypertonic, incoordinate, or prolonged uterine contractions" }, { "code": "GC01.Y", "title": "Other specified disorders of bladder" }, { "code": "8B10.Y", "title": "Other specified transient ischaemic attack" }, { "code": "ED5Y", "title": "Other specified disorders of epidermal keratinisation" }, { "code": "KD30.0", "title": "Birth depression with 5 minute Apgar score 0-3" }, { "code": "KD30.1", "title": "Birth depression with 5 minute Apgar score 4-6" }, { "code": "KB21.0", "title": "Severe birth asphyxia" }, { "code": "KB21.1", "title": "Mild and moderate birth asphyxia" } ]	=== ICD-11 CODES FOUND === [LB13.Y] Other specified structural developmental anomalies of stomach Also known as: Other specified structural developmental anomalies of stomach \| Congenital megalogastria \| congenital gastromegaly \| congenital enlarged stomach \| Congenital displacement of the stomach [DA40.4] Hourglass stricture and stenosis of stomach Definition: This is a structural change of stomach in which one more or less completely divided into two parts, resembling an hourglass in shape, due to often scarring which complicates chronic gastric ulcer. Also known as: Hourglass stricture and stenosis of stomach \| hourglass contraction of stomach \| hourglass stenosis of stomach \| hourglass stricture of stomach \| Bilocular stomach [JB02.4] Hypertonic, incoordinate, or prolonged uterine contractions Definition: A condition affecting pregnant females that is idiopathic. This condition is characterised by uterine dysfunction leading to hypertonic, uncoordinated, and prolonged rhythmic activity of the myometrium during labour. Also known as: Hypertonic, incoordinate, or prolonged uterine contractions \| Uterine dystocia NOS \| Hypertonic uterus dysfunction complicating delivery \| hypertonic uterine activity \| hypertonic uterine contraction Excludes: dystocia (fetal)(maternal) NOS [GC01.Y] Other specified disorders of bladder Also known as: Other specified disorders of bladder \| Non-neurogenic neurogenic bladder \| Occult neuropathic bladder \| Hinman syndrome \| Hinman-Allen syndrome [8B10.Y] Other specified transient ischaemic attack Also known as: Other specified transient ischaemic attack \| Vertebrobasilar artery syndrome \| vertebrobasilar arterial insufficiency \| vertebrobasilar insufficiency \| vertebro-basilar artery syndrome, course of resolution unspecified [ED5Y] Other specified disorders of epidermal keratinisation Also known as: Other specified disorders of epidermal keratinisation \| Follicular digitate keratoses \| Lichen spinulosus \| Keratosis spinulosa \| Keratosis circumscripta [KD30.0] Birth depression with 5 minute Apgar score 0-3 Definition: A condition characterised by cardiorespiratory and neurological depression, defined as an Apgar score between 0 to 3 at 5 minutes following birth. Also known as: Birth depression with 5 minute Apgar score 0-3 [KD30.1] Birth depression with 5 minute Apgar score 4-6 Definition: A condition characterised by cardiorespiratory and neurological depression, defined as an Apgar score between 4 and 6 at 5 minutes following birth. Also known as: Birth depression with 5 minute Apgar score 4-6 [KB21.0] Severe birth asphyxia Definition: Pulse less than 100 per minute at birth and falling or steady, respiration absent or gasping, colour poor, tone absent. Also known as: Severe birth asphyxia \| severe perinatal hypoxia \| asphyxia pallida of newborn \| Asphyxia with 5-minute Apgar score 0-3 \| newborn severe asphyxia [KB21.1] Mild and moderate birth asphyxia Definition: Normal respiration not established within one minute, but heart rate 100 or above, some muscle tone present, some response to stimulation. Also known as: Mild and moderate birth asphyxia \| asphyxia livida of newborn \| Asphyxia with 5-minute Apgar score 4-7 \| Blue asphyxia === GRAPH WALKS === --- Walk 1 --- [LB13.Y] Other specified structural developmental anomalies of stomach --PARENT--> [LB13] Structural developmental anomalies of stomach Def: Any congenital defect of stomach that results from interference with the normal growth and differentiation of the fetus. Such defects can arise at any stage of embryonic development, vary greatly in t... --RELATED_TO--> [?] Gastric volvulus Def: Gastric volvulus is an uncommon clinical entity defined as an abnormal rotation (twisting) of all or part of the stomach by more than 180 degrees, creating a closed-loop obstruction of the flow of mat... --- Walk 2 --- [LB13.Y] Other specified structural developmental anomalies of stomach --PARENT--> [LB13] Structural developmental anomalies of stomach Def: Any congenital defect of stomach that results from interference with the normal growth and differentiation of the fetus. Such defects can arise at any stage of embryonic development, vary greatly in t... --RELATED_TO--> [?] Gastric volvulus Def: Gastric volvulus is an uncommon clinical entity defined as an abnormal rotation (twisting) of all or part of the stomach by more than 180 degrees, creating a closed-loop obstruction of the flow of mat... --- Walk 3 --- [DA40.4] Hourglass stricture and stenosis of stomach Def: This is a structural change of stomach in which one more or less completely divided into two parts, resembling an hourglass in shape, due to often scarring which complicates chronic gastric ulcer.... --PARENT--> [DA40] Acquired anatomical alterations of the stomach Def: This group incorporates gastric disorders principally due to acquired morphological changes of the stomach.... --EXCLUDES--> [?] Diaphragmatic hernia Def: A hernia occurs through the foramen in the diaphragm.... --- Walk 4 --- [DA40.4] Hourglass stricture and stenosis of stomach Def: This is a structural change of stomach in which one more or less completely divided into two parts, resembling an hourglass in shape, due to often scarring which complicates chronic gastric ulcer.... --PARENT--> [DA40] Acquired anatomical alterations of the stomach Def: This group incorporates gastric disorders principally due to acquired morphological changes of the stomach.... --CHILD--> [DA40.1] Gastric fistula, acquired Def: Acquired gastric fistula is an opening through the gastric wall and into the peritoneal cavity, into another organ and vessels that normally do not connect, or through the abdominal wall.... --- Walk 5 --- [JB02.4] Hypertonic, incoordinate, or prolonged uterine contractions Def: A condition affecting pregnant females that is idiopathic. This condition is characterised by uterine dysfunction leading to hypertonic, uncoordinated, and prolonged rhythmic activity of the myometriu... --PARENT--> [JB02] Abnormalities of forces of labour Def: Any condition affecting pregnant females, characterised by an anomaly or dysfunction to the tissues or processes associated with the natural progression of labour. These conditions may lead to further... --CHILD--> [JB02.0] Primary uterine inertia Def: A condition affecting pregnant females characterised by insufficiently strong or inappropriately coordinated rhythmic activity of the myometrium during labour to efface and dilate the cervix.... --- Walk 6 --- [JB02.4] Hypertonic, incoordinate, or prolonged uterine contractions Def: A condition affecting pregnant females that is idiopathic. This condition is characterised by uterine dysfunction leading to hypertonic, uncoordinated, and prolonged rhythmic activity of the myometriu... --EXCLUDES--> [?] Obstructed labour due to other causes Def: Any other condition characterised by the inability of the presenting part of the fetus to progress into the birth canal for any reason.... --CHILD--> [?] Obstructed labour due to locked twins	[ "[LB13.Y] Other specified structural developmental anomalies of stomach\n --PARENT--> [LB13] Structural developmental anomalies of stomach\n Def: Any congenital defect of stomach that results from interference with the normal growth and differentiation of the fetus. Such defects can arise at any stage of embryonic development, vary greatly in t...\n --RELATED_TO--> [?] Gastric volvulus\n Def: Gastric volvulus is an uncommon clinical entity defined as an abnormal rotation (twisting) of all or part of the stomach by more than 180 degrees, creating a closed-loop obstruction of the flow of mat...", "[LB13.Y] Other specified structural developmental anomalies of stomach\n --PARENT--> [LB13] Structural developmental anomalies of stomach\n Def: Any congenital defect of stomach that results from interference with the normal growth and differentiation of the fetus. Such defects can arise at any stage of embryonic development, vary greatly in t...\n --RELATED_TO--> [?] Gastric volvulus\n Def: Gastric volvulus is an uncommon clinical entity defined as an abnormal rotation (twisting) of all or part of the stomach by more than 180 degrees, creating a closed-loop obstruction of the flow of mat...", "[DA40.4] Hourglass stricture and stenosis of stomach\n Def: This is a structural change of stomach in which one more or less completely divided into two parts, resembling an hourglass in shape, due to often scarring which complicates chronic gastric ulcer....\n --PARENT--> [DA40] Acquired anatomical alterations of the stomach\n Def: This group incorporates gastric disorders principally due to acquired morphological changes of the stomach....\n --EXCLUDES--> [?] Diaphragmatic hernia\n Def: A hernia occurs through the foramen in the diaphragm....", "[DA40.4] Hourglass stricture and stenosis of stomach\n Def: This is a structural change of stomach in which one more or less completely divided into two parts, resembling an hourglass in shape, due to often scarring which complicates chronic gastric ulcer....\n --PARENT--> [DA40] Acquired anatomical alterations of the stomach\n Def: This group incorporates gastric disorders principally due to acquired morphological changes of the stomach....\n --CHILD--> [DA40.1] Gastric fistula, acquired\n Def: Acquired gastric fistula is an opening through the gastric wall and into the peritoneal cavity, into another organ and vessels that normally do not connect, or through the abdominal wall....", "[JB02.4] Hypertonic, incoordinate, or prolonged uterine contractions\n Def: A condition affecting pregnant females that is idiopathic. This condition is characterised by uterine dysfunction leading to hypertonic, uncoordinated, and prolonged rhythmic activity of the myometriu...\n --PARENT--> [JB02] Abnormalities of forces of labour\n Def: Any condition affecting pregnant females, characterised by an anomaly or dysfunction to the tissues or processes associated with the natural progression of labour. These conditions may lead to further...\n --CHILD--> [JB02.0] Primary uterine inertia\n Def: A condition affecting pregnant females characterised by insufficiently strong or inappropriately coordinated rhythmic activity of the myometrium during labour to efface and dilate the cervix....", "[JB02.4] Hypertonic, incoordinate, or prolonged uterine contractions\n Def: A condition affecting pregnant females that is idiopathic. This condition is characterised by uterine dysfunction leading to hypertonic, uncoordinated, and prolonged rhythmic activity of the myometriu...\n --EXCLUDES--> [?] Obstructed labour due to other causes\n Def: Any other condition characterised by the inability of the presenting part of the fetus to progress into the birth canal for any reason....\n --CHILD--> [?] Obstructed labour due to locked twins" ]	LB13.Y	Other specified structural developmental anomalies of stomach	[ { "from_icd11": "DA40.4", "icd10_code": "K312", "icd10_title": "Hourglass stricture and stenosis of stomach" }, { "from_icd11": "JB02.4", "icd10_code": "O624", "icd10_title": "Hypertonic, incoordinate, and prolonged uterine contractions" }, { "from_icd11": "KD30.0", "icd10_code": "P210", "icd10_title": "" }, { "from_icd11": "KD30.1", "icd10_code": "P211", "icd10_title": "" } ]	K312	Hourglass stricture and stenosis of stomach
We presented the case of a 46 years-old woman affected by intracranial hemangiopericytoma surgically removed and treated with adjuvant radiotherapy at our institution. Such a primary, multimodal therapeutic approach provided local control of disease and a disease-free interval of 7 years. Upfront radical surgery is the treatment of choice for newly diagnosed HPCs . Because of their tendency to recur, resection must be radical whenever possible. Actually, there are no validated criteria for surgical resection . The extent of resection is reported in many studies as an important factor influencing local control; more controversial is the impact surgery may have on overall survival. Two published series by Soyuer and Kim showed better local control in patients treated with gross-total removal than patients who underwent partial excision, but they were not able to find a statistically significant effect on overall survival . On the other hand, Guthrie et al. reported a similar time to first recurrence in both patients treated with radical or partial removal of the lesion, but they found a statistically significant impact of surgery on overall survival (109 vs. 65 months) . In another retrospective study in 2011, Schiariti et al. found that gross-total resection followed by adjuvant external-beam radiotherapy (EBRT) provided patients with the highest probability of an increased recurrence-free interval and overall survival . Additionally, Ghia et al., in one of the largest single series of patients with intracranial HPC reported in the literature (number of patients = 88), showed a strong correlation between the extent of resection and both cause-specific survival and overall survival on multivariate analysis . Since the invasive nature of HPC and the involvement of dural sinuses may often preclude a radical excision, the use of postoperative radiotherapy (RT) seems to be attractive. Ciliberti and colleagues investigated the role of radiation in the management of such an unusual mesenchymal tumor . Currently, a multimodal management—surgery followed by adjuvant RT—is recommended to treat localized disease . However, the results reported in the literature are controversial. Adjuvant RT, either EBRT or Gamma Knife stereotactic radiosurgery (SRS) and/or proton beam therapy, has proven to increase the recurrence-free interval but does not have a clear impact on overall survival (OS) . As stated before, one of the largest retrospective series supporting the efficacy of improving local control of radiation therapy was published by Guthrie and Dufour. Among the 44 HPC cases reported by the former, those receiving adjuvant RT had a significantly increased disease-free survival time (mean of 74 vs. 29 months, p < 0.05), as well as a longer OS (92 vs. 62 months) . Moreover, the authors defined a dose-response relationship without local recurrences among patients receiving ≥50 Gy. Dufour et al. recorded 17 patients with HPC who were followed for 34 years. The local recurrence rate was 12.5% in patients treated with postoperative RT, compared to 88% after surgery alone . In 2001, Alen et al. reported eight intracranial HPC patients treated with EBRT at some time during the course of their disease; among these, five patients were treated after surgery and received doses ranging from 60 to 64 Gy. Four of them survived 6, 15, 16, and 85 months without evidence of recurrence, respectively, and the remaining one, who had only subtotal resection, died 76 months after surgery . A recent series of 48 patients by Haas and colleagues showed 90% of local control after surgery and adjuvant RT, compared to 60% after surgical excision alone ( p : 0.052), but local control probability was significantly associated with adjuvant RT (HR 0.25; p ≤ 0.001), while there was no impact of multimodal treatment on OS . In 2004, Soyuer et al. reported the M. D. Anderson Cancer Center experience over a 20-year period; surgery was the primary treatment for all 29 patients. Adjuvant RT was performed in 10 cases, with delivered doses of 3340–6120 cGy . Postoperative irradiation did not have a significant effect on local control after radical exeresis in this case ( p = 0.18), but it could be attributable to the limited number of patients . In this study, as stated by the authors, it is noteworthy that none of the 3 patients undergoing adjuvant RT after gross-total removal of the lesion locally relapsed, whereas 5 of 11 patients treated with radical surgery and radiation therapy experienced local recurrence. Additionally, Kim et al. did not find adjuvant RT to have a statistically significant effect on local control of disease. However, the 5-year recurrence-free survival (RFS) rates associated with complete excision followed by postoperative RT were higher than radical surgery alone (100% and 70%, respectively) . Rutkowski et al. published another series of 40 consecutive patients with intracranial HPC . Radiotherapy was performed in 9 of 16 patients who underwent radical surgery and in 14 of 19 patients with subtotal removal of the lesion. The authors did not demonstrate a statistically significant benefit in terms of time to recurrence with the prescription of adjuvant RT. Despite this, they showed a trend towards statistical significance, with an improvement of median time to recurrence from 3.9 years in patients not treated with RT to 6.6 years in the group who underwent RT ( p = 0.082). A retrospective study of 15 patients by Kumar et al. showed that postoperative RT (median dose 50 Gy) led to a median time to local recurrence of 68 months vs. 37 months in patients who did not receive it, but also that adjuvant treatment did not confer any significant protection against the development of distant metastases . Jeon and colleagues also reported a decrease in local tumor recurrence with the addition of RT after surgery but no differences in OS or distant metastases-free survival (DMFS) . A retrospective comparison between 29 patients treated with adjuvant EBRT (intensity-modulated radiotherapy (IMRT) or SRS) and 37 patients undergoing upfront surgery alone showed no impact of postoperative radiation on local tumor control nor survival, but similar local control rates after IMRT and SRS, therefore, they both remain viable therapeutic options . In the retrospective analysis of Ghia et al., there was a strong correlation between the use of upfront postoperative irradiation and improved survival outcome. The authors recommend an RT dose ≥ 60 Gy to optimize local control of disease . None of these studies were able to definitely demonstrate the advantage of adjuvant RT, especially in the group of completely resected patients. The main limit of these studies is obviously represented by the small number of involved patients, which means a small statistical power. Nevertheless, almost all authors’ conclusions favor the use of adjuvant RT, at least in patients treated with no radical surgery. A Korean multicenter study by Lee et al. recently confirmed the role of postoperative radiation in improving disease control of intracranial HPC. Among 133 included patients, they found 10-year progression-free survival (PFS) and OS rates of 45% and 71%, respectively. Moreover, there were significantly higher local control rates and PFS than surgery alone, irrespective of the surgical extent and WHO grading ( p < 0.001 in both cases), as long as to enclose the tumor bed with a large, 1.0–2.0 cm margin of the target volume . It is also known that hemangiopericytoma tends to relapse also after a gross-total removal of the lesion. For this reason, in our opinion, limited field radiotherapy should also be prescribed to this group of patients. Another controversial issue is represented by the optimal radiation total dose to achieve good control of the disease. It has been shown that receiving more than 45 Gy is necessary to have fewer local disease recurrences. Guthrie et al. reported that seven of eight patients receiving less than 45 Gy irradiation experienced local disease relapse, while only two of nine patients treated with more than 45 Gy on the tumor bed locally relapsed. None of the three patients who received more than 50 Gy experienced disease recurrence .	4.40625	0.71582	sec[2]/p[3]	en	0.999997	PMC9497113	https://doi.org/10.3390/brainsci12091209	[ "patients", "local", "adjuvant", "control", "survival", "recurrence", "treated", "radical", "postoperative", "free" ]	[ { "code": "PL14.C", "title": "Patient received diagnostic test or treatment intended for another patient" }, { "code": "QB14", "title": "Unavailability or inaccessibility of health care facilities" }, { "code": "PL14.2", "title": "Problem associated with physical transfer of patient" }, { "code": "QB12.0", "title": "Organ transplant candidate" }, { "code": "QA15.1", "title": "Counselling related to sexual behaviour and orientation or sexual relationships of the person" }, { "code": "ME61", "title": "Subcutaneous swelling, mass or lump of uncertain or unspecified nature" }, { "code": "EC30", "title": "Epidermolysis bullosa simplex" }, { "code": "5B80.1", "title": "Localised adiposity" }, { "code": "8B61.4", "title": "Localised spinal muscular atrophy" }, { "code": "EB61.0", "title": "Plaque morphoea" } ]	=== ICD-11 CODES FOUND === [PL14.C] Patient received diagnostic test or treatment intended for another patient Also known as: Patient received diagnostic test or treatment intended for another patient \| wrong patient \| incorrect patient Excludes: Procedure undertaken at wrong site or wrong side, as mode of injury or harm [QB14] Unavailability or inaccessibility of health care facilities Also known as: Unavailability or inaccessibility of health care facilities \| unavailability of medical facilities \| Unavailability of outpatient clinic \| Unavailability or inaccessibility of residential aged care service Excludes: bed unavailable [PL14.2] Problem associated with physical transfer of patient Also known as: Problem associated with physical transfer of patient [QB12.0] Organ transplant candidate Also known as: Organ transplant candidate \| patient waiting for organ availability \| health services provided because of need for organ transplant \| organ transplant candidate awaiting organ availability \| person on organ transplant waiting list [QA15.1] Counselling related to sexual behaviour and orientation or sexual relationships of the person Also known as: Counselling related to sexual behaviour and orientation or sexual relationships of the person \| advice on sexual behaviour or orientation \| counselling on sexual behaviour or orientation \| promiscuity counselling \| patient concerned regarding sexual orientation [ME61] Subcutaneous swelling, mass or lump of uncertain or unspecified nature Definition: One or more localised subcutaneous soft tissue masses of undetermined or unspecified nature Also known as: Subcutaneous swelling, mass or lump of uncertain or unspecified nature \| localised swelling, mass or lump of skin and subcutaneous tissue \| localised subcutaneous nodules \| subcutaneous nodules \| superficial subcutaneous nodules Excludes: localized adiposity \| mass and lump: breast \| enlarged lymph nodes [EC30] Epidermolysis bullosa simplex Definition: Epidermolysis bullosa simplex is the name given to a heterogeneous group of genetically-determined defects in epidermal cell-cell adhesion. These give rise to blistering in response to frictional and shearing stresses. Also known as: Epidermolysis bullosa simplex \| Epidermolytic epidermolysis bullosa \| Suprabasal epidermolysis bullosa simplex \| Suprabasal EBS \| Acantholytic epidermolysis bullosa [5B80.1] Localised adiposity Definition: A condition characterised by accumulation of adipose tissue in specific regions of the body. Also known as: Localised adiposity \| Fat pad \| Fatty apron [8B61.4] Localised spinal muscular atrophy Definition: This category comprises a group of disorders with a varied pattern of weakness and autosomal dominant or X-linked recessive inheritance with specific genetic profiles. Also known as: Localised spinal muscular atrophy \| localised SMA - [spinal muscular atrophy] \| Distal form of spinal muscular atrophy \| Distal hereditary motor neuropathy \| Distal HMN - [hereditary motor neuropathy] [EB61.0] Plaque morphoea Definition: The commonest form of morphoea which presents as indurated waxy plaques, often with a violaceous border and commonly affecting the trunk, especially in the submammary folds and around the waist. The cause is unknown. It is commoner in women than men. Also known as: Plaque morphoea \| Circumscribed scleroderma \| plaque morphea \| localised scleroderma Includes: Circumscribed scleroderma === GRAPH WALKS === --- Walk 1 --- [PL14.C] Patient received diagnostic test or treatment intended for another patient --EXCLUDES--> [?] Procedure undertaken at wrong site or wrong side, as mode of injury or harm --EXCLUDES--> [?] Patient received diagnostic test or treatment intended for another patient --- Walk 2 --- [PL14.C] Patient received diagnostic test or treatment intended for another patient --EXCLUDES--> [?] Procedure undertaken at wrong site or wrong side, as mode of injury or harm --CHILD--> [?] Performance of inappropriate operation --- Walk 3 --- [QB14] Unavailability or inaccessibility of health care facilities --PARENT--> [?] Factors related to medical facilities or other health care --CHILD--> [QB10] Medical services not available in home --- Walk 4 --- [QB14] Unavailability or inaccessibility of health care facilities --EXCLUDES--> [?] Person awaiting admission to adequate facility elsewhere --PARENT--> [?] Factors related to medical facilities or other health care --- Walk 5 --- [PL14.2] Problem associated with physical transfer of patient --PARENT--> [PL14] Mode of injury or harm associated with other health care related causes --CHILD--> [PL14.2] Problem associated with physical transfer of patient --- Walk 6 --- [PL14.2] Problem associated with physical transfer of patient --PARENT--> [PL14] Mode of injury or harm associated with other health care related causes --EXCLUDES--> [?] Mode of injury or harm associated with a surgical or other medical device, implant or graft	[ "[PL14.C] Patient received diagnostic test or treatment intended for another patient\n --EXCLUDES--> [?] Procedure undertaken at wrong site or wrong side, as mode of injury or harm\n --EXCLUDES--> [?] Patient received diagnostic test or treatment intended for another patient", "[PL14.C] Patient received diagnostic test or treatment intended for another patient\n --EXCLUDES--> [?] Procedure undertaken at wrong site or wrong side, as mode of injury or harm\n --CHILD--> [?] Performance of inappropriate operation", "[QB14] Unavailability or inaccessibility of health care facilities\n --PARENT--> [?] Factors related to medical facilities or other health care\n --CHILD--> [QB10] Medical services not available in home", "[QB14] Unavailability or inaccessibility of health care facilities\n --EXCLUDES--> [?] Person awaiting admission to adequate facility elsewhere\n --PARENT--> [?] Factors related to medical facilities or other health care", "[PL14.2] Problem associated with physical transfer of patient\n --PARENT--> [PL14] Mode of injury or harm associated with other health care related causes\n --CHILD--> [PL14.2] Problem associated with physical transfer of patient", "[PL14.2] Problem associated with physical transfer of patient\n --PARENT--> [PL14] Mode of injury or harm associated with other health care related causes\n --EXCLUDES--> [?] Mode of injury or harm associated with a surgical or other medical device, implant or graft" ]	PL14.C	Patient received diagnostic test or treatment intended for another patient	[ { "from_icd11": "QB14", "icd10_code": "Z753", "icd10_title": "Unavailability and inaccessibility of health-care facilities" }, { "from_icd11": "QA15.1", "icd10_code": "F66", "icd10_title": "Other sexual disorders" }, { "from_icd11": "QA15.1", "icd10_code": "F660", "icd10_title": "" }, { "from_icd11": "QA15.1", "icd10_code": "F661", "icd10_title": "" }, { "from_icd11": "QA15.1", "icd10_code": "F662", "icd10_title": "" }, { "from_icd11": "QA15.1", "icd10_code": "F668", "icd10_title": "" }, { "from_icd11": "QA15.1", "icd10_code": "F669", "icd10_title": "" }, { "from_icd11": "QA15.1", "icd10_code": "Z701", "icd10_title": "Counseling related to patient's sexual behavior and orientation" }, { "from_icd11": "ME61", "icd10_code": "R2240", "icd10_title": "Localized swelling, mass and lump, unspecified lower limb" }, { "from_icd11": "ME61", "icd10_code": "R2232", "icd10_title": "Localized swelling, mass and lump, left upper limb" }, { "from_icd11": "ME61", "icd10_code": "R2242", "icd10_title": "Localized swelling, mass and lump, left lower limb" }, { "from_icd11": "ME61", "icd10_code": "R2231", "icd10_title": "Localized swelling, mass and lump, right upper limb" }, { "from_icd11": "ME61", "icd10_code": "R2241", "icd10_title": "Localized swelling, mass and lump, right lower limb" }, { "from_icd11": "ME61", "icd10_code": "R2233", "icd10_title": "Localized swelling, mass and lump, upper limb, bilateral" }, { "from_icd11": "ME61", "icd10_code": "R2243", "icd10_title": "Localized swelling, mass and lump, lower limb, bilateral" } ]	Z753	Unavailability and inaccessibility of health-care facilities
A 40-year-old male patient presented to our emergency department with right upper abdominal pain with intermittent fever for 5 days and was considered to have gallstones with cholecystitis after an abdominal ultrasound examination. After the patient was admitted to the Department of Hepatobiliary Surgery, the patient’s epigastric pain improved after 11 days of symptomatic treatment, but creatinine gradually increased, and fever still appeared intermittently. Therefore, the patient was referred to our department for further treatment of abnormal renal function and fever. The patient had no history of underlying disease, hypertension, diabetes, hematological system, family history of hereditary diseases, and trauma. One month before admission, he underwent a holmium laser lithotripsy and right double J-tube placement in a local hospital for right upper ureteral calculi and hydronephrosis . The operation went successfully. The patient was followed up at the local hospital 1 month after surgery. ESWL was performed on the right upper ureter because the ultrasound indicated a few residual stones in the upper right ureter. Other laboratory tests: WBC 8.50 × 10 9 /L, N 0.75, HB 115 g/L, PLT 273 × 10 9 /L, Cre 86 μmol/L, urine WBC 4/μL, urine RBC 3/μL, PT 15.60 s, APTT 35.50 s, Fib 4.26 g/L. Three days after the operation, the urine and blood routine were not significantly abnormal, so it was decided to remove the right double J-tube, and the patient did not feel discomfort during and after the operation. The patient began to appear with these symptoms after the double J-tube removal. Therefore, the patient was immediately referred to our hospital. Physical examination showed pressure pain in the right upper abdomen, Murphy’s sign (+), no pressure pain, rebound pain, and muscle tension in the rest of the abdomen, no percussion pain in both kidney areas, and no significant abnormalities in other systemic examinations. Laboratory tests at admission showed: WBC 16.08 × 10 9 /L, N 0.82, HB 120 g/L, PLT 391 × 10 9 /L, Cre 131 μmol/L, Urine WBC 11/μL, Urine RBC 357/μL, ESR 120 mm/h, RF 143 IU/mL, ANA 1:40; Other laboratory results, including blood potassium, blood glucose, coagulation, liver function, and CRP levels were within normal limits. After transfer to our department, a computed tomography (CT) of the abdomen showed no significant abnormalities in both kidneys and bilateral ureters . Other laboratory tests: WBC 8.83 × 10 9 /L, N 0.77, HB 97 g/L, PLT 373 × 10 9 /L, Cre 336 μmol/L, creatinine clearance 50.97 mL/min/1.73 m 2 , urine WBC 19/μL, urine RBC 14168/μL, PT 13.90 s, APTT 29.90 s, Fib 3.95 g/L. Four days later, the patient presented with significant gross hematuria with difficulty in urination, and a repeat abdominal CT showed multiple hemorrhages and hypodense lesions in the right kidney , and the bladder was filled with a blood clot. The bladder clot removal and bilateral ureteral double-J tube placement were performed immediately. Intraoperatively, the right ureter was filled with a strip of the blood clot, and persistent hematuria emanated from the ureteral opening. With the patient’s and family’s consent, selective right renal artery embolization was performed immediately (Seldinger method, puncture of right femoral artery), and intraoperative angiography revealed multiple hemorrhages and pseudoaneurysm formation in the lower pole of the right kidney , and the lower pole of the right renal artery was embolized using 2 platinum spring coils and 350 μm gelatin sponge particles. After embolization, the hematuria was relieved. Unfortunately, the patient reappeared with hematuria 3 days later. The relevant indexes were immediately reviewed: WBC 16.87 × 10 9 /L, N 0.86, HB 70 g/L, PLT 168 × 10 9 /L, urine WBC 0/μL, urine RBC 16,356/μL, PT 14.80 s, APTT 29.70 s, Fib 4.05 g/L. Abdominal CT showed hemorrhage and pneumatization in the right kidney and blood in the bladder, and it was considered that there was still active bleeding in the right kidney . Since the patient and family strongly desired to preserve the kidney and refused to perform a right nephrectomy, selective right renal artery embolization was performed again (Seldinger method, puncture of right femoral artery). Intraoperative contrast reveals multiple hemorrhagic spots in the upper pole of the right kidney , and the same was embolized using 2 platinum spring coils and 350 μm gelatin sponge particles in the upper pole artery of the right kidney. After two embolizations, the right kidney function was severely impaired, with less than 10% of normal kidney tissue preserved. Two hours after surgery, the patient developed sudden orthopnea, dyspnea, and coughing of pink foamy sputum, which was considered acute heart failure due to volume overload. No significant symptom improvement was seen after diuresis, volume vasodilation, and hemodialysis. At the same time, the patient presented with anuria and relevant laboratory tests: Cre 793 μmol/L, creatinine clearance 5.77 mL/min/1.73 m 2 , HB 82 g/L, NT-ProBNP 35,000 pg./mL. Therefore, he was transferred to the intensive care unit (ICU) during the night of the same day. After transfer, the patient was immediately treated with analgesia, sedation, absolute bed rest, and continuous hemodialysis for the ruptured right kidney bleeding. No recurrence of hematuria was seen during this period. Five days later, fungal spores and hyphae were found in the patient’s sputum, and fungal pneumonia was diagnosed. Related laboratory tests: WBC 13.23 × 10 9 /L, N 0.88, HB 59 g/L, PLT 203 × 10 9 /L, CRP 175.317 mg/L, PT 11.80 s, APTT 27.90 s, Fib 3.50 g/L, chest CT showed blurred lung texture in both lungs, and multiple patchy and striated high-density images were seen in both lung fields. On the sixth day in the ICU, the patient had a sudden onset of persistent lumbago on the left side. A repeat abdominal CT showed bleeding in both kidneys, with additional bleeding in the left kidney . Other relevant laboratory tests: WBC 13.99 × 10 9 /L, N 0.90, HB 60 g/L, PLT 195 × 10 9 /L, urine WBC 3/μL, urine RBC 21,772/μL, Cre 373 μmol/L, creatinine clearance 14.36 mL/min/1.73 m 2 , Anti-neutrophil cytoplasmic antibody (ANCA) (−), PT 11.70 s, APTT 26.60 s, Fib 3.56 g/L; The patient’s bleeding in the left kidney was indicated for re-interventional embolization to stop the bleeding, but irreversible renal failure might occur after left kidney embolization, so the patient’s family refused interventional embolization. After up to 20 days of conservative treatment, the patient’s hemoglobin fluctuated at 52–72 g/L under constant red blood cell transfusion. Under continuous bedside ultrasound monitoring, the left perirenal hematoma gradually increased from 82 × 22 mm to 107 × 45 mm. The patient’s hemoglobin continued not to rise, and the left renal hematoma gradually increased. We considered that there was still active bleeding in the body. With the consent of the patient’s family, a left renal arteriogram was attempted on the patient (Seldinge method, puncture of the left femoral artery), a suspicious bleeding point in the left inferior pole artery was found intraoperatively , therefore, 350 μm gelatin sponge particles were used to embolize this vessel. After up to 48 days of treatment, the patient’s condition gradually stabilized, with hemoglobin fluctuating at 60–76 g/L, creatinine fluctuating at 218–486 μmol/L, and the rest of the indicators in the normal range. Unfortunately, after three embolizations, the patient’s total renal function was severely impaired and irreversible, and he was dependent on hemodialysis to sustain his life. The patient was followed up 3 months after discharge and is currently on regular dialysis, able to take care of himself in daily life, with a daily urine output of about 600–1000 mL and creatinine fluctuating at 350–500 μmol/L. Ultrasound showed severe atrophy of the right kidney, mild atrophy of the left kidney, and no hydronephrosis in both kidneys. The diagnosis was chronic renal insufficiency. The patient is now undergoing regular monthly follow-ups and is considering a kidney transplant. The timeline from the first surgery to discharge is presented in Figure 4 .	3.871094	0.97998	sec[1]/p[0]	en	0.999999	PMC10587595	https://doi.org/10.3389/fmed.2023.1173386	[ "kidney", "urine", "renal", "artery", "bleeding", "laboratory", "blood", "pain", "creatinine", "both" ]	[ { "code": "GC2Z&XA6KU8", "title": "Disease of kidney, not elsewhere classified" }, { "code": "GB6Z", "title": "Kidney failure, unspecified" }, { "code": "LB30.1", "title": "Renal dysplasia" }, { "code": "NB92.0Y", "title": "Other specified injury of kidney" }, { "code": "LB30.7", "title": "Ectopic or pelvic kidney" }, { "code": "MF9Y", "title": "Other specified clinical findings on examination of urine, without diagnosis" }, { "code": "MF50.6Z", "title": "Difficulties with micturition, unspecified" }, { "code": "MF50.0", "title": "Frequent micturition" }, { "code": "MF50.3", "title": "Retention of urine" }, { "code": "MF50.4Z", "title": "Haematuria, unspecified" } ]	=== ICD-11 CODES FOUND === [GB6Z] Kidney failure, unspecified Also known as: Kidney failure, unspecified \| nontraumatic kidney injury \| renal failure NOS \| kidney block \| renal impairment NOS [LB30.1] Renal dysplasia Definition: A condition characterised by abnormal development of one or both kidneys. Also known as: Renal dysplasia \| congenital renal dysplasia \| dysplasia of kidney \| dysplastic kidney \| Primary renal dysplasia Excludes: Autosomal dominant polycystic kidney disease [NB92.0Y] Other specified injury of kidney Also known as: Other specified injury of kidney \| Injury of kidney without open wound into cavity \| Injury of kidney with open wound into cavity \| Haematoma of kidney \| traumatic perirenal haematoma [LB30.7] Ectopic or pelvic kidney Definition: A birth defect characterised by an abnormally positioned kidney; may be asymptomatic or result in urine blockage, infection or kidney stones Also known as: Ectopic or pelvic kidney \| Congenital displaced kidney \| congenital misplaced kidney \| congenital malposition of kidney \| congenital prolapsed kidney Includes: Congenital displaced kidney \| Malrotation of kidney [MF9Y] Other specified clinical findings on examination of urine, without diagnosis Also known as: Other specified clinical findings on examination of urine, without diagnosis \| Methaemoglobinuria \| Other and unspecified abnormal findings in urine \| Calciuria \| Cells and casts in urine [MF50.6Z] Difficulties with micturition, unspecified Also known as: Difficulties with micturition, unspecified \| Other difficulties with micturition \| difficulty passing urine NOS \| difficulty urinating NOS \| other difficulties with urination [MF50.0] Frequent micturition Definition: Needing to urinate more often than normal. Also known as: Frequent micturition \| Urinary frequency \| Frequency of micturition NOS \| Frequent urination \| Micturition frequency Excludes: Pollakiuria [MF50.3] Retention of urine Definition: Incomplete emptying of the bladder Also known as: Retention of urine \| bladder retention of urine \| not passing urine \| unable to empty bladder \| unable to pass urine [MF50.4Z] Haematuria, unspecified Also known as: Haematuria, unspecified \| Haematuria \| blood in urine \| urinary blood \| haematuria NOS === GRAPH WALKS === --- Walk 1 --- [GB6Z] Kidney failure, unspecified --PARENT--> [?] Kidney failure Def: Inability of the kidneys to adequately filter the blood of waste products, with a lower than normal glomerular filtration rate (GFR). Can be abrupt and potentially reversible (acute kidney injury) or ... --EXCLUDES--> [?] Hypertensive renal disease Def: Hypertensive renal disease is a medical condition referring to damage to the kidney due to chronic high blood pressure.... --- Walk 2 --- [GB6Z] Kidney failure, unspecified --PARENT--> [?] Kidney failure Def: Inability of the kidneys to adequately filter the blood of waste products, with a lower than normal glomerular filtration rate (GFR). Can be abrupt and potentially reversible (acute kidney injury) or ... --CHILD--> [GB61] Chronic kidney disease Def: Glomerular Filtration Rate (GFR) < 60 ml/min/1.73m² or presence of kidney damage that is present for more than 3 months. Evidence of kidney damage can include structural abnormalities (imaging or hist... --- Walk 3 --- [LB30.1] Renal dysplasia Def: A condition characterised by abnormal development of one or both kidneys.... --EXCLUDES--> [?] Autosomal dominant polycystic kidney disease Def: Multiple cysts in both kidneys increasing in number and size from adolescence, associated with development of hypertension and chronic renal failure. Autosomal dominant familial pattern is usual and d... --CHILD--> [?] Autosomal dominant polycystic kidney disease type 1 without tuberous sclerosis Def: Autosomal dominant polycystic kidney disease due to mutations on Polycystin1 gene on chromosome 16 (PKD1 gene)... --- Walk 4 --- [LB30.1] Renal dysplasia Def: A condition characterised by abnormal development of one or both kidneys.... --EXCLUDES--> [?] Autosomal dominant polycystic kidney disease Def: Multiple cysts in both kidneys increasing in number and size from adolescence, associated with development of hypertension and chronic renal failure. Autosomal dominant familial pattern is usual and d... --PARENT--> [?] Hereditary cystic or dysplastic kidney disease, dominant inheritance Def: Cystic or dysplastic renal diseases that are inherited in an autosomal dominant fashion. Usually monogenetic, and can be associated with abnormalities in other organs.... --- Walk 5 --- [NB92.0Y] Other specified injury of kidney --PARENT--> [NB92.0] Injury of kidney --CHILD--> [NB92.02] Laceration of kidney, minor --- Walk 6 --- [NB92.0Y] Other specified injury of kidney --PARENT--> [NB92.0] Injury of kidney --CHILD--> [NB92.01] Contusion of kidney, major	[ "[GB6Z] Kidney failure, unspecified\n --PARENT--> [?] Kidney failure\n Def: Inability of the kidneys to adequately filter the blood of waste products, with a lower than normal glomerular filtration rate (GFR). Can be abrupt and potentially reversible (acute kidney injury) or ...\n --EXCLUDES--> [?] Hypertensive renal disease\n Def: Hypertensive renal disease is a medical condition referring to damage to the kidney due to chronic high blood pressure....", "[GB6Z] Kidney failure, unspecified\n --PARENT--> [?] Kidney failure\n Def: Inability of the kidneys to adequately filter the blood of waste products, with a lower than normal glomerular filtration rate (GFR). Can be abrupt and potentially reversible (acute kidney injury) or ...\n --CHILD--> [GB61] Chronic kidney disease\n Def: Glomerular Filtration Rate (GFR) < 60 ml/min/1.73m² or presence of kidney damage that is present for more than 3 months. Evidence of kidney damage can include structural abnormalities (imaging or hist...", "[LB30.1] Renal dysplasia\n Def: A condition characterised by abnormal development of one or both kidneys....\n --EXCLUDES--> [?] Autosomal dominant polycystic kidney disease\n Def: Multiple cysts in both kidneys increasing in number and size from adolescence, associated with development of hypertension and chronic renal failure. Autosomal dominant familial pattern is usual and d...\n --CHILD--> [?] Autosomal dominant polycystic kidney disease type 1 without tuberous sclerosis\n Def: Autosomal dominant polycystic kidney disease due to mutations on Polycystin1 gene on chromosome 16 (PKD1 gene)...", "[LB30.1] Renal dysplasia\n Def: A condition characterised by abnormal development of one or both kidneys....\n --EXCLUDES--> [?] Autosomal dominant polycystic kidney disease\n Def: Multiple cysts in both kidneys increasing in number and size from adolescence, associated with development of hypertension and chronic renal failure. Autosomal dominant familial pattern is usual and d...\n --PARENT--> [?] Hereditary cystic or dysplastic kidney disease, dominant inheritance\n Def: Cystic or dysplastic renal diseases that are inherited in an autosomal dominant fashion. Usually monogenetic, and can be associated with abnormalities in other organs....", "[NB92.0Y] Other specified injury of kidney\n --PARENT--> [NB92.0] Injury of kidney\n --CHILD--> [NB92.02] Laceration of kidney, minor", "[NB92.0Y] Other specified injury of kidney\n --PARENT--> [NB92.0] Injury of kidney\n --CHILD--> [NB92.01] Contusion of kidney, major" ]	GC2Z&XA6KU8	Disease of kidney, not elsewhere classified	[ { "from_icd11": "GB6Z", "icd10_code": "N19", "icd10_title": "Unspecified kidney failure" }, { "from_icd11": "GB6Z", "icd10_code": "N17-N19", "icd10_title": "" }, { "from_icd11": "GB6Z", "icd10_code": "N17", "icd10_title": "Acute kidney failure" }, { "from_icd11": "LB30.1", "icd10_code": "Q614", "icd10_title": "Renal dysplasia" }, { "from_icd11": "LB30.7", "icd10_code": "Q632", "icd10_title": "Ectopic kidney" }, { "from_icd11": "LB30.7", "icd10_code": "Q63", "icd10_title": "Other congenital malformations of kidney" }, { "from_icd11": "MF50.6Z", "icd10_code": "R3915", "icd10_title": "Urgency of urination" }, { "from_icd11": "MF50.6Z", "icd10_code": "R3911", "icd10_title": "Hesitancy of micturition" }, { "from_icd11": "MF50.6Z", "icd10_code": "R3914", "icd10_title": "Feeling of incomplete bladder emptying" }, { "from_icd11": "MF50.6Z", "icd10_code": "R3912", "icd10_title": "Poor urinary stream" }, { "from_icd11": "MF50.6Z", "icd10_code": "R39198", "icd10_title": "Other difficulties with micturition" }, { "from_icd11": "MF50.6Z", "icd10_code": "R3916", "icd10_title": "Straining to void" }, { "from_icd11": "MF50.6Z", "icd10_code": "R3919", "icd10_title": "Other difficulties with micturition" }, { "from_icd11": "MF50.6Z", "icd10_code": "R3913", "icd10_title": "Splitting of urinary stream" }, { "from_icd11": "MF50.6Z", "icd10_code": "R391", "icd10_title": "Other difficulties with micturition" } ]	N19	Unspecified kidney failure
A 47-year-old man from Syria was admitted to a regional Swedish hospital due to a three-month history of recurrent episodes of frontal headache and fever. Otherwise, he showed no further infection-related symptoms. The past medical history revealed longstanding problems (approximately for the last 20 years) with difficult to treat arterial hypertension, where numerous medications had been tested without success or withdrawn due to side effects. No previous work-up concerning eventual secondary hypertension had been undertaken. Additionally, the patient experienced recurrent episodes of chest discomfort in relation with food intake during the last nine months, which was empirically treated with proton-pump inhibitors without success. Upon admission, the patient had a blood pressure of 160/100 mmHg, an initial heart rate of 99 beats per minute, a saturation of 96%, and an elevated body temperature of 40° Celsius. Otherwise, the initial physical exam was unremarkable. The electrocardiogram showed regular sinus rhythm without ST-T segment alterations or Q-waves and the initial blood analysis was normal (including the liver and thyroid function) apart from an elevated C-reactive protein (Table 1 ). Subsequently, blood and urine cultures were taken, which were all negative. A serum and urine electrophoresis showed normal findings as well as a lumbar puncture. Echocardiography showed no signs of infective endocarditis. Additionally, both thoracic and abdominal computed tomography were performed in search of the origin of the patient’s recurrent fever, which revealed a right-sided adrenal mass with central necrosis as well as a renal cyst . Consecutive endocrinological investigations according to current guidelines substantiated the suspicion of an underlying pheochromocytoma (Table 1 ). 4 The initial symptoms upon presentation as well as the increase in C-reactive protein were interpreted as secondary to a suspected viral infection. In the following, the patient was referred to the regional University hospital for further diagnostic work-up and treatment. Subsequently, the patient underwent a Gallium-68 ( 68 Ga) DOTATOC PET/CT, which revealed high uptake in the right-sided adrenal mass consistent with a pheochromocytoma . Additionally, low cardiac uptake was incidentally discovered in the basal inferolateral segment of the left ventricle . This uptake of low intensity was interpreted as a suspected area with myocardial inflammation due to recent myocardial infarction or myocarditis. A primary or secondary (metastatic) cardiac NET was considered as less likely. In the light of these findings, a new thorough medical history revealed that the patient’s recurrent episodes of chest discomfort had even a relation to physical activity and not only food intake. This made the diagnosis of an underlying coronary artery disease even more likely together with the presence of coronary calcification on the previously performed thoracic computed tomography. Furthermore, the patient had several cardiovascular risk factors such as longstanding arterial hypertension, smoking (approximately 10 cigarettes per day for at least 20 years) and a positive family history for cardiovascular disease. To further determine the underlying etiology of the incidental cardiac finding, a complementary cardiovascular magnetic resonance (CMR) study was performed, which revealed in the same region subendocardial delayed enhancement consistent with an ischemic etiology as well as regional hypokinesia . T2-weighted images showed no signs of edema. Furthermore, CMR revealed mild concentric left ventricular hypertrophy and a reduced left ventricular ejection fraction of 41%. Taken together, the presence of myocardial inflammation on 68 Ga-DOTATOC PET/CT and subendocardial delayed enhancement as well as regional wall motion abnormality on CMR suggested that the patient had most likely suffered of a recent “silent” myocardial infarction (no recent clinical symptoms of persistent or worsening chest pain). Therefore, the patient underwent an invasive coronary angiography that unveiled the presence of a multi-vessel coronary artery disease including an occluded left circumflex artery, which supplies the inferolateral segments of the left ventricle with blood . Subsequently, a percutaneous transluminal coronary angioplasty with stent implantation was performed that could, among others, successfully reopen the left circumflex artery . Afterwards, medical treatment was optimized according to current guidelines and the patient was relieved of his previous recurrent episodes of chest discomfort. Furthermore, the patient underwent an uncomplicated right-sided laparoscopic adrenalectomy prior to the earlier mentioned invasive coronary angiography, which resulted in the resolution of his previous symptoms as well as normalization of the plasma free normetanephrine concentration (Table 1 ). This strategy was favored as the patient was clinically stable, the perioperative risk considered as acceptable and to avoid the dilemma arising from dual antiplatelet therapy preceding non-cardiac surgery. Routine histopathologic analysis of the removed adrenal mass revealed a classic appearance of a pheochromocytoma . Figure 1 Normal resting electrocardiogram without signs of ischemia or prior myocardial infarction Table 1 Laboratory results Initial work-up Post-surgical follow-up Reference values Hematology and blood chemistry WBC, 10 9 /L 8,7 – 3.5–8.8 RBC, 10 12 /L 4,7 – 4.2–5.7 Hb, g/L 131 – 134–170 Platelets, 10 9 /L 297 – 145–348 Creatinine, µmol/L 63 – 60–105 Sodium, mmol/L 133 – 137–145 Potassium, mmol/L 3.7 – 3.5–4.4 C-reactive protein, mg/L 79 – < 5 Endocrinological investigations Plasma Metanephrine, nmol/L 0,7 0.2 < 0.5 Normetanephrine, nmol/L 57 0.6 < 1.1 Chromogranin A, µg/L 940 – < 102 Aldosterone/renin ratio, pmol/mIE 0.7 – 4–65 Cortisol after DST, nmol/L 370 – 133–537 Urine Urinary adrenalin, nmol/24 hours 23 – 9–101 Urinary noradrenalin, nmol/24 hours 799 – 62–560 Urinary metanephrine/creatinine ratio, mmol/mol creatinine 0.1 – – Urinary normetanephrine/creatinine ratio, mmol/mol creatinine 6.7 – – 5-HIAA, µmol/24 hours 21 – 0–50 WBC , white blood cell count; RBC , red blood cell count; Hb , hemoglobin; DST , dexamethasone suppression test; 5-HIAA , 5-hydroxyindoleacetic acid Figure 2 Abdominal computed tomography ( A ) revealed a large (approximately 7 × 6 × 6 cm) right-sided adrenal mass with central necrosis (as indicated by a black star), which showed clearly pathologic uptake on 68 Ga-DOTATOC PET/CT (as indicated by a white star in the maximum intensity projection image ( B ) and a black star in the PET/CT fusion image ( C )). Additionally, the maximum intensity projection image ( B ) displayed a low cardiac uptake (as indicated by a black arrow). Furthermore, a renal cyst was found in the right kidney (as indicated by a white arrow ( A and C )). Maximum standardized uptake values: liver 7.5, spleen 35.3, adrenal mass 135.9, and heart 5.0 Figure 3 CMR revealed the presence of inferolateral subendocardial delayed enhancement in the basal part of the left ventricle (LV) in the short-axis projection ( A ). In the same region, 68 Ga-DOTA-TOC PET/CT showed pathologic myocardial uptake ( B ). Image fusion of the 68 Ga-DOTA-TOC PET and CMR confirmed the colocalization of both findings ( C ). White arrows indicate pathologic findings Figure 4 Invasive coronary angiography ( A ) unveiled an occluded left circumflex artery (as indicated by a white arrow) with collateral flow in two obtuse marginal branches (as indicated by a black arrow). Furthermore, a borderline significant stenosis was found in the left anterior descending artery as well as a high degree stenosis in the right coronary artery (not shown). Subsequently, percutaneous transluminal coronary angioplasty with stent implantation could, among others, successfully reopen the left circumflex artery (as indicated by a white arrow, B ) Figure 5 Classic histopathologic appearance of a pheochromocytoma with large polygonal cells arranged in small nests (so-called Zellballen), which are separated by capillaries filled with erythrocytes (hematoxylin and eosin staining)	4.019531	0.978027	sec[1]/p[0]	en	0.999998	33502695	https://doi.org/10.1007/s12350-021-02526-9	[ "which", "coronary", "artery", "blood", "well", "uptake", "myocardial", "white", "recurrent", "adrenal" ]	[ { "code": "BD50.41", "title": "Abdominal aortic aneurysm with rupture" }, { "code": "EK91", "title": "Dermatoses which may presage cutaneous lymphoma" }, { "code": "MH12.1", "title": "Death occurring less than 24 hours from onset of symptoms, not otherwise explained" }, { "code": "8A44.3", "title": "Certain specified leukodystrophies" }, { "code": "BA8Z", "title": "Diseases of coronary artery, unspecified" }, { "code": "BA4Z", "title": "Acute ischaemic heart disease, unspecified" }, { "code": "BA41.Z", "title": "Acute myocardial infarction, unspecified" }, { "code": "BA5Z", "title": "Chronic ischaemic heart disease, unspecified" }, { "code": "LA8C.2", "title": "Congenital coronary arterial fistula" }, { "code": "BD5Z", "title": "Diseases of arteries or arterioles, unspecified" } ]	=== ICD-11 CODES FOUND === [BD50.41] Abdominal aortic aneurysm with rupture Also known as: Abdominal aortic aneurysm with rupture \| abdominal aorta aneurysm rupture \| abdominal aorta aneurysm ruptured \| abdominal aortic aneurysm which has ruptured \| ruptured AAA [EK91] Dermatoses which may presage cutaneous lymphoma Definition: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature. Also known as: Dermatoses which may presage cutaneous lymphoma [MH12.1] Death occurring less than 24 hours from onset of symptoms, not otherwise explained Also known as: Death occurring less than 24 hours from onset of symptoms, not otherwise explained \| died without sign of disease \| Death known not to be violent or instantaneous for which no cause can be discovered \| death known not to be violent or instantaneous, cause unknown \| Death without sign of disease Includes: Death known not to be violent or instantaneous for which no cause can be discovered \| Death without sign of disease [8A44.3] Certain specified leukodystrophies Also known as: Certain specified leukodystrophies \| CACH syndrome \| Vanishing white matter disease \| Childhood ataxia with central nervous system hypomyelination \| Congenital or early infantile CACH syndrome [BA8Z] Diseases of coronary artery, unspecified Also known as: Diseases of coronary artery, unspecified \| coronary artery insufficiency \| coronary artery heart disease \| CAD - [coronary artery disease] \| coronary artery disorder [BA4Z] Acute ischaemic heart disease, unspecified Also known as: Acute ischaemic heart disease, unspecified \| acute coronary syndrome \| ACS - [acute coronary syndrome] \| Silent myocardial ischaemia \| asymptomatic ischemia [BA41.Z] Acute myocardial infarction, unspecified Also known as: Acute myocardial infarction, unspecified \| Acute myocardial infarction \| cardiac attack \| heart attack \| acute cardiac infarction [BA5Z] Chronic ischaemic heart disease, unspecified Also known as: Chronic ischaemic heart disease, unspecified \| Ischaemic heart disease (chronic) NOS \| coronary ischaemia \| coronary damage NOS \| atheroma of heart [LA8C.2] Congenital coronary arterial fistula Definition: A congenital cardiovascular malformation in which a coronary artery communicates, through an anomalous channel, with a cardiac chamber or with any segment of the systemic or pulmonary circulation. Additional information: this communication may be simple and direct or may be tortuous and dilated. In order of frequency the involved coronary artery is the right, the left and, rarely, both coronary arteries. Occasionally multiple fistulas are present. Also known as: Congenital coronary arterial fistula \| coronary fistula \| congenital arteriovenous coronary fistula \| congenital coronary fistula to pulmonary artery \| Congenital coronary arterial fistula to right ventricle Includes: congenital coronary fistula to pulmonary artery Excludes: anomalous origin of coronary artery from pulmonary arterial tree [BD5Z] Diseases of arteries or arterioles, unspecified Also known as: Diseases of arteries or arterioles, unspecified \| artery disease NOS \| arterial disease NOS \| arteriolar disease NOS \| disorder of artery NOS === GRAPH WALKS === --- Walk 1 --- [BD50.41] Abdominal aortic aneurysm with rupture --PARENT--> [BD50.4] Abdominal aortic aneurysm --CHILD--> [BD50.41] Abdominal aortic aneurysm with rupture --- Walk 2 --- [BD50.41] Abdominal aortic aneurysm with rupture --PARENT--> [BD50.4] Abdominal aortic aneurysm --CHILD--> [BD50.40] Abdominal aortic aneurysm with perforation --- Walk 3 --- [EK91] Dermatoses which may presage cutaneous lymphoma Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature.... --CHILD--> [EK91.0] Large plaque parapsoriasis Def: Large plaque parapsoriasis is a chronic skin disorder characterised by the indolent development over years or decades of scaly patches or slightly elevated plaques which may be clinically indistinguis... --PARENT--> [EK91] Dermatoses which may presage cutaneous lymphoma Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature.... --- Walk 4 --- [EK91] Dermatoses which may presage cutaneous lymphoma Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature.... --CHILD--> [EK91.1] Poikiloderma vasculare atrophicans Def: Poikiloderma vasculare atrophicans is a cutaneous reaction pattern characterised by mottled hyper- and hypomelanosis, telangiectasia and progressive dermal and epidermal atrophy. It may manifest as a ... --PARENT--> [EK91] Dermatoses which may presage cutaneous lymphoma Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature.... --- Walk 5 --- [MH12.1] Death occurring less than 24 hours from onset of symptoms, not otherwise explained --PARENT--> [MH12] Other sudden death, cause unknown --CHILD--> [MH12.1] Death occurring less than 24 hours from onset of symptoms, not otherwise explained --- Walk 6 --- [MH12.1] Death occurring less than 24 hours from onset of symptoms, not otherwise explained --PARENT--> [MH12] Other sudden death, cause unknown --EXCLUDES--> [?] Sudden infant death syndrome Def: Sudden infant death syndrome is the abrupt and unexplained death of an apparently healthy infant under one year of age, remaining unexplained after a thorough case investigation, including performance...	[ "[BD50.41] Abdominal aortic aneurysm with rupture\n --PARENT--> [BD50.4] Abdominal aortic aneurysm\n --CHILD--> [BD50.41] Abdominal aortic aneurysm with rupture", "[BD50.41] Abdominal aortic aneurysm with rupture\n --PARENT--> [BD50.4] Abdominal aortic aneurysm\n --CHILD--> [BD50.40] Abdominal aortic aneurysm with perforation", "[EK91] Dermatoses which may presage cutaneous lymphoma\n Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature....\n --CHILD--> [EK91.0] Large plaque parapsoriasis\n Def: Large plaque parapsoriasis is a chronic skin disorder characterised by the indolent development over years or decades of scaly patches or slightly elevated plaques which may be clinically indistinguis...\n --PARENT--> [EK91] Dermatoses which may presage cutaneous lymphoma\n Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature....", "[EK91] Dermatoses which may presage cutaneous lymphoma\n Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature....\n --CHILD--> [EK91.1] Poikiloderma vasculare atrophicans\n Def: Poikiloderma vasculare atrophicans is a cutaneous reaction pattern characterised by mottled hyper- and hypomelanosis, telangiectasia and progressive dermal and epidermal atrophy. It may manifest as a ...\n --PARENT--> [EK91] Dermatoses which may presage cutaneous lymphoma\n Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature....", "[MH12.1] Death occurring less than 24 hours from onset of symptoms, not otherwise explained\n --PARENT--> [MH12] Other sudden death, cause unknown\n --CHILD--> [MH12.1] Death occurring less than 24 hours from onset of symptoms, not otherwise explained", "[MH12.1] Death occurring less than 24 hours from onset of symptoms, not otherwise explained\n --PARENT--> [MH12] Other sudden death, cause unknown\n --EXCLUDES--> [?] Sudden infant death syndrome\n Def: Sudden infant death syndrome is the abrupt and unexplained death of an apparently healthy infant under one year of age, remaining unexplained after a thorough case investigation, including performance..." ]	BD50.41	Abdominal aortic aneurysm with rupture	[ { "from_icd11": "BD50.41", "icd10_code": "I713", "icd10_title": "Abdominal aortic aneurysm, ruptured" }, { "from_icd11": "EK91", "icd10_code": "L989", "icd10_title": "Disorder of the skin and subcutaneous tissue, unspecified" }, { "from_icd11": "MH12.1", "icd10_code": "R961", "icd10_title": "" }, { "from_icd11": "BA4Z", "icd10_code": "I248", "icd10_title": "Other forms of acute ischemic heart disease" }, { "from_icd11": "BA4Z", "icd10_code": "I256", "icd10_title": "Silent myocardial ischemia" }, { "from_icd11": "BA4Z", "icd10_code": "I249", "icd10_title": "Acute ischemic heart disease, unspecified" }, { "from_icd11": "BA4Z", "icd10_code": "I24", "icd10_title": "Other acute ischemic heart diseases" }, { "from_icd11": "BA41.Z", "icd10_code": "I21A1", "icd10_title": "Myocardial infarction type 2" }, { "from_icd11": "BA41.Z", "icd10_code": "I21A9", "icd10_title": "Other myocardial infarction type" }, { "from_icd11": "BA41.Z", "icd10_code": "I2109", "icd10_title": "ST elevation (STEMI) myocardial infarction involving other coronary artery of anterior wall" }, { "from_icd11": "BA41.Z", "icd10_code": "I2119", "icd10_title": "ST elevation (STEMI) myocardial infarction involving other coronary artery of inferior wall" }, { "from_icd11": "BA41.Z", "icd10_code": "I2111", "icd10_title": "ST elevation (STEMI) myocardial infarction involving right coronary artery" }, { "from_icd11": "BA41.Z", "icd10_code": "I2102", "icd10_title": "ST elevation (STEMI) myocardial infarction involving left anterior descending coronary artery" }, { "from_icd11": "BA41.Z", "icd10_code": "I2129", "icd10_title": "ST elevation (STEMI) myocardial infarction involving other sites" }, { "from_icd11": "BA41.Z", "icd10_code": "I2121", "icd10_title": "ST elevation (STEMI) myocardial infarction involving left circumflex coronary artery" } ]	I713	Abdominal aortic aneurysm, ruptured
Twelve hours following the cesarean section, the woman started to experience pain in her lower right leg, and by 28 hours, she had developed clinical symptoms of an ACS. She was treated with antibiotics for possible cellulitis. Her symptoms did not improve, and a Doppler ultrasound examination was performed to exclude deep venous thrombosis (DVT) but showed no remarkable findings. ACS was definitively diagnosed on postpartum day 10 and confirmed by magnetic resonance imaging. The ACS was managed nonsurgically, and the woman remained in the hospital with her baby for 15 days following the birth. A detailed timeline of events and clinical management following the cesarean section is provided in Table 1 . Table 1 Timeline of events following birth Time Clinical details 1.5 hours Returned to the postnatal ward following an emergency cesarean section; full sensation and movement were noted in both legs. 12 hours Onset of pain and swelling in right lower leg. 14 hours The postpartum woman complained of pain in her right shin. An obstetrics and gynecology assessment revealed extreme pain on mobilization and weight bearing in the lower right leg, with worsening pain upon movement over the tibialis anterior with plantar flexion. A physical examination revealed a decreased range of motion in the right foot and decreased extension of the right great toe. Minimal pitting edema was noted on the right foot, and capillary refill was normal in both feet. A small and very painful soft lump was palpable over the anterior midshin area of the right leg. Range of motion in both knees and ankles was normal, as were the lower limb reflexes and pedal pulses. No calf tenderness or skin changes were noted, and skin temperature was normal. Sensation was normal, and the postpartum woman was afebrile. The impression at the time was deemed to be muscle-related pain, and therefore she was commenced on analgesia and encouraged to mobilize and to elevate the leg on a pillow. A deep venous thrombosis was not considered at this stage, because there was no calf tenderness. A heat pack was applied to the lower right leg and antiembolism stockings were applied to both legs. 23 hours Swelling in the right leg and foot had worsened, and the postpartum woman experienced a burning sensation along the muscle. By this stage, she was no longer able to bear weight. 28 hours The antiembolism stockings were removed due to increased pain, and this resulted in sudden and extreme pain and further swelling in the right lower leg and foot. Assessment revealed that the right leg and foot were very swollen and the foot was curving inward and was painful to touch. The postpartum woman was unable to move her toes or lift her foot due to pain, and a review was conducted by the obstetrics and gynecology registrar. By this stage, the woman was in extreme pain and reported constant throbbing in the leg. Examination revealed a decreased range of motion in the right foot; the right foot was markedly more swollen than the left; and the anterior right leg and anterior foot were very tender to touch. Pedal pulses were palpable, and perfusion to the toes was noted. The nodule over the anterior midshin remained palpable, and the skin now appeared red. There was no reported calf pain, and she remained afebrile. Cellulitis was diagnosed, and a blood sample collected at this time revealed deranged liver function test results. The woman was then commenced on intravenous antibiotics and enoxaparin sodium (Clexane; Sanofi-Aventis, Macquarie Park, Australia), an anticoagulant, prophylactically because she was now immobile. Subcutaneous morphine was administered with no effect, and the antiembolism stocking was unable to be reapplied to the right leg due to extreme pain. Six hours following this acute stage, the postpartum woman reported feeling more comfortable, and her right leg was less swollen and less tender; however, the limb remained red. An anesthetic review at this time excluded an epidural-related cause for the ongoing right great toe weakness. Day 2 There was still visible swelling and worsening of pain after mobilizing; therefore, the patient remained on bedrest. Clexane was changed to a therapeutic dose, and analgesia was continued (Endone [oxycodone hydrochloride], Alphapharm Pty Ltd, Millers Park, Australia; Panadol [acetaminophen], GlaxoSmithKline Australia, Ermington, Australia; and Voltaren [diclofenac], GlaxoSmithKline Australia). Venous Doppler ultrasound was performed to exclude deep venous thrombosis, and the findings were unremarkable. The leg was more inflamed and reddened following the Doppler ultrasound, and the postpartum woman was now completely unable to bear weight on the right leg. Day 3 Some improvement in pain and redness was noted, but weakness of the right great toe remained. The postpartum woman was still unable to hyperflex the right great toe, and the results of her liver function tests were more deranged. Clexane was reverted to a prophylactic dose, and antibiotics were changed again; the woman remained afebrile. A second anesthetic examination confirmed ongoing weakness of the great toe, and sensation was intact. The differential diagnosis at this stage included possible neurological problems, cellulitis, or gout. Day 4 Skin redness had started to improve, but mobility was limited due to pain. Neurological symptoms remained unchanged, and some reduction in plantar adduction was noted. Upon examination by a neurologist, the leg was tender and swollen below the knee. There was severe pain upon examination, and the neurologist was unable to check right inversion due to the pain. Sensation was found to be decreased to the peroneal region. The differential diagnoses queried by the neurologist included right peroneal nerve palsy, pressure effect, compartment syndrome, and cellulitis. The postpartum woman was referred to the infectious diseases team for management of cellulitis and for a vascular opinion regarding possible compartment syndrome. Antibiotics were changed again, and a surgical review deemed that symptoms were not diagnostic of compartment syndrome. Day 4 (95 hours) By this stage, the postpartum woman reported numbness between the right great toe and the second toe, a new symptom. Day 5 An examination revealed increased redness and loss of sensation over the first web space of the right foot. The postpartum woman continued to complain of increased pain. The diagnosis at the time was worsening cellulitis and worsening of neurological symptoms secondary to the worsening cellulitis. Antibiotics were changed again, and the woman was continued on Clexane. Day 7 Symptoms of cellulitis remained unchanged. Antibiotics were changed again in consultation with the infectious diseases team. Day 8 Neurological symptoms remained unresolved, so a neurologist was consulted again. Day 10 Magnetic resonance imaging was performed, and the findings were consistent with acute compartment syndrome. Day 11 Orthopedic consultation was obtained. There were clinical features of a compartment syndrome affecting the anterior compartment of the right lower leg. An examination showed foot drop and paresthesia along the deep and superficial peroneal nerves. Pain had moderated by that time, but there was still evident swelling of the anterior compartment with associated tenderness and some dusky erythema. There was no active contraction of the great toe extensor, and there was reduced extensor function of the lesser toes and the tibialis anterior. The anterior compartment pressure was measured as 19 mmHg, and pressure in the peroneal compartment was 23 mmHg. Following consultation with other orthopedic and vascular surgeons at a tertiary referral hospital, the compartment syndrome was managed nonsurgically, given that 11 days had elapsed since the onset of symptoms and a fasciotomy at this stage would not prevent any further damage. Days 11–15 The woman was commenced on physiotherapy and fitted with a foot drop splint and a rollator frame to assist with mobilization. Intravenous antibiotics were continued until discharge from the postnatal ward. Day 15 The woman was discharged to home on a course of oral antibiotics.	3.869141	0.976563	sec[2]/p[2]	en	0.999998	32883339	https://doi.org/10.1186/s13256-020-02459-w	[ "pain", "foot", "postpartum", "remained", "this", "compartment", "hours", "antibiotics", "cellulitis", "great" ]	[ { "code": "MG3Z", "title": "Pain, unspecified" }, { "code": "8E43.Z", "title": "Pain disorders, unspecified" }, { "code": "MG31.Z", "title": "Acute pain, unspecified" }, { "code": "MG30.Z", "title": "Chronic pain, unspecified" }, { "code": "FB56.2", "title": "Myalgia" }, { "code": "ND19.Z", "title": "Traumatic amputation of ankle or foot, unspecified" }, { "code": "QF00", "title": "Acquired absence of limb" }, { "code": "ND14.A", "title": "Strain or sprain of other or unspecified parts of foot" }, { "code": "ND11.Y", "title": "Other specified superficial injury of ankle or foot" }, { "code": "LB9A.6", "title": "Split foot" } ]	=== ICD-11 CODES FOUND === [MG3Z] Pain, unspecified Also known as: Pain, unspecified \| pain observations \| pain NOS \| generalised pain \| generalised pain, NOS [8E43.Z] Pain disorders, unspecified Also known as: Pain disorders, unspecified \| Pain disorders [MG31.Z] Acute pain, unspecified Also known as: Acute pain, unspecified \| Acute pain [MG30.Z] Chronic pain, unspecified Also known as: Chronic pain, unspecified \| Chronic pain [FB56.2] Myalgia Definition: This is a disorder characterised by pain in a muscle or group of muscles. Also known as: Myalgia \| muscle ache \| muscle soreness \| muscular pain \| myalgic Excludes: Chronic primary musculoskeletal pain \| Chronic secondary musculoskeletal pain [ND19.Z] Traumatic amputation of ankle or foot, unspecified Also known as: Traumatic amputation of ankle or foot, unspecified \| Traumatic amputation of ankle or foot \| traumatic amputation of foot \| avulsion of foot \| severed foot [QF00] Acquired absence of limb Also known as: Acquired absence of limb \| post traumatic loss of limb \| postoperative loss of limb \| bilateral amputee \| amputee Includes: postoperative loss of limb \| post traumatic loss of limb Excludes: Other acquired deformities of limbs \| Congenital absence of thigh or lower leg with foot present \| Congenital absence of both lower leg and foot [ND14.A] Strain or sprain of other or unspecified parts of foot Also known as: Strain or sprain of other or unspecified parts of foot \| Sprain of foot \| Strain of foot \| Midtarsal sprain \| Midtarsal strain [ND11.Y] Other specified superficial injury of ankle or foot Also known as: Other specified superficial injury of ankle or foot \| Contusion of toe with damage to nail \| Haematoma of foot \| feet haematoma \| Nonthermal blister of toe [LB9A.6] Split foot Definition: A condition caused by malformation of the foot during the antenatal period. This condition is characterised by a deep median cleft of the foot due to the absence of the central rays. Also known as: Split foot \| lobster claw foot \| split foot, unspecified side \| cleft of foot \| Split foot, unilateral === GRAPH WALKS === --- Walk 1 --- [MG3Z] Pain, unspecified --PARENT--> [?] Pain --CHILD--> [MG30] Chronic pain Def: Pain is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage. Chronic pain is pain that persists or recurs for longer t... --- Walk 2 --- [MG3Z] Pain, unspecified --PARENT--> [?] Pain --EXCLUDES--> [?] Headache disorders --- Walk 3 --- [8E43.Z] Pain disorders, unspecified --PARENT--> [8E43] Pain disorders --CHILD--> [8E43.Y] Other specified pain disorders --- Walk 4 --- [8E43.Z] Pain disorders, unspecified --PARENT--> [8E43] Pain disorders --CHILD--> [8E43.Z] Pain disorders, unspecified --- Walk 5 --- [MG31.Z] Acute pain, unspecified --PARENT--> [MG31] Acute pain Def: Pain with a duration of less than 3 months. This code should be used only when there is no further specification of site.... --CHILD--> [MG31.0] Acute pain in the face, not elsewhere classified --- Walk 6 --- [MG31.Z] Acute pain, unspecified --PARENT--> [MG31] Acute pain Def: Pain with a duration of less than 3 months. This code should be used only when there is no further specification of site.... --CHILD--> [MG31.0] Acute pain in the face, not elsewhere classified	[ "[MG3Z] Pain, unspecified\n --PARENT--> [?] Pain\n --CHILD--> [MG30] Chronic pain\n Def: Pain is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage. Chronic pain is pain that persists or recurs for longer t...", "[MG3Z] Pain, unspecified\n --PARENT--> [?] Pain\n --EXCLUDES--> [?] Headache disorders", "[8E43.Z] Pain disorders, unspecified\n --PARENT--> [8E43] Pain disorders\n --CHILD--> [8E43.Y] Other specified pain disorders", "[8E43.Z] Pain disorders, unspecified\n --PARENT--> [8E43] Pain disorders\n --CHILD--> [8E43.Z] Pain disorders, unspecified", "[MG31.Z] Acute pain, unspecified\n --PARENT--> [MG31] Acute pain\n Def: Pain with a duration of less than 3 months.\n\nThis code should be used only when there is no further specification of site....\n --CHILD--> [MG31.0] Acute pain in the face, not elsewhere classified", "[MG31.Z] Acute pain, unspecified\n --PARENT--> [MG31] Acute pain\n Def: Pain with a duration of less than 3 months.\n\nThis code should be used only when there is no further specification of site....\n --CHILD--> [MG31.0] Acute pain in the face, not elsewhere classified" ]	MG3Z	Pain, unspecified	[ { "from_icd11": "MG3Z", "icd10_code": "R52", "icd10_title": "Pain, unspecified" }, { "from_icd11": "MG3Z", "icd10_code": "R529", "icd10_title": "" }, { "from_icd11": "MG31.Z", "icd10_code": "R520", "icd10_title": "" }, { "from_icd11": "MG30.Z", "icd10_code": "R521", "icd10_title": "" }, { "from_icd11": "MG30.Z", "icd10_code": "R522", "icd10_title": "" }, { "from_icd11": "FB56.2", "icd10_code": "M7918", "icd10_title": "Myalgia, other site" }, { "from_icd11": "FB56.2", "icd10_code": "M7910", "icd10_title": "Myalgia, unspecified site" }, { "from_icd11": "FB56.2", "icd10_code": "M7912", "icd10_title": "Myalgia of auxiliary muscles, head and neck" }, { "from_icd11": "FB56.2", "icd10_code": "M791", "icd10_title": "Myalgia" }, { "from_icd11": "ND19.Z", "icd10_code": "S98919A", "icd10_title": "Complete traumatic amputation of unspecified foot, level unspecified, initial encounter" }, { "from_icd11": "ND19.Z", "icd10_code": "S98929A", "icd10_title": "Partial traumatic amputation of unspecified foot, level unspecified, initial encounter" }, { "from_icd11": "ND19.Z", "icd10_code": "S98", "icd10_title": "Traumatic amputation of ankle and foot" }, { "from_icd11": "ND19.Z", "icd10_code": "S984", "icd10_title": "" }, { "from_icd11": "QF00", "icd10_code": "Z89412", "icd10_title": "Acquired absence of left great toe" }, { "from_icd11": "QF00", "icd10_code": "Z89611", "icd10_title": "Acquired absence of right leg above knee" } ]	R52	Pain, unspecified
During the second week of June 2022 at 12:00 AM, a 40-year-old man was admitted to the Infectious Disease Emergency Room (IDER) at Cotugno Hospital in Naples. He reported clinical features for the past three days and fever for one day (with the highest peak at 38.2 °C) with the onset of asynchronous and mild vesicular rash mainly on the trunk , and also genital and perineal pain. On the day of IDER admission, he only suffered intense headaches and myalgia without further fever episodes but was responsive to paracetamol. Upon clinical examination, we found several pustules, about 2–4 mm each, on an erythematous base with central umbilication interesting the face, neck, abdomen and hands. A few 2–3 mm round painful erosions were noted in the perineal area while an intact pustule was observed in the lower abdominal region . We did not observe cervical lymphadenopathy, pneumonia signs or the involvement of abdominal organs. According to the vesicle onset, the patient reported the first one localized on the scalp about 5 days before and being in the crustification phase at the moment of clinical examination. He did not report any significant risk factor; he had not traveled abroad to countries at risk or had any contact with possible cases or subjects being confirmed as monkeypox-infected. On the contrary, he reported a relative absence of social contact in the previous 14 days from the onset of fever. He only reported local travel to work in the surrounding area of Naples. Despite the patient not presenting any risk, in consideration of the current monkeypox outbreak , we decided to manage him according to our internal protocol for differential diagnosis for Monkeypox or Varicella Zoster Virus (VZV) and therefore he underwent our protocol for Emerging Infectious Disease . The laboratory tests did not show any increase in inflammation markers such as PCR, IL-6, PCT and WBC, we only found a mild increase in the interleukin 2 receptor IL2R. No other significant blood parameters alterations were found; neither positive IgM or IgG for Chickenpox (Varicella zoster Virus—VZV) ( Table 1 ). A molecular test for Monkeypox was found to be positive on vesicles and on a nasal swab specimen. The test was based on viral DNA extraction with a Qiamp Viral RNA mini kit (Qiagen, Italy Branch, Milan, Italy) and two real-time PCRs were used to assess the presence of MPXV DNA. A Real-Star Orthopoxvirus PCR Kit (Altona Diagnostics GmbH, Hamburg, Germany) was used as the screening PCR. This method recognizes a region common to all Orthopoxviruses without distinction of species. The second PCR (G2R_G assay) is based on previous evidence . Notably, a further real-time PCR assay was carried out according to the protocol of Li and colleagues that allows for the detection of generic MPXV DNA and further differentiation between West African and Congo Basin strains . The reactions were carried out in a 25 µL final volume, containing KAPA PROBE FORCE qPCR Master Mix Universal 1× (Kapa Biosystems Pty, Cape Town, South Africa), 0.4 µM for each primer set and 0.2 µM for probes (FAM-labeled). An internal control (0.4 µM final concentration) was added to exclude any possible inhibition using Beta Actin Mix (VIC-labeled). The thermal profile included enzyme inactivation/template denaturation at 98 °C for 3 min, followed by 45 cycles of denaturation and annealing/extension at 95 °C for 5 s and 60 °C for 20 s, respectively, for MPXV and the Congo Basin strain, while the annealing/extension phase was 62 °C for 20 s for the West African strain. The amplifications were performed on a QuantStudio 5 real-time PCR system (Applied Biosystems, Foster City, CA, USA) thermal cycler. Positive results were obtained for MPXV and for West African lineage, showing threshold cycle (Ct) values of 23 for both the real-time PCR assays . The sample was then submitted to an end-point PCR modifying a protocol already described , thus using the MPXV-ext_FOR forward primer of the protocol of Dumont and colleagues, while we designed the reverse primer (MPXV_REV_2: 5′-ATCCATGTATTGCGCCAAATA-3′) giving rise to a 571 bp amplicon. The reaction was carried out in a 25 µL volume, including Kapa2G Robust HotStart Ready Mix 1× (Kapa Biosystems), along with 0.2 µM final concentration for each primer and 5 µL template. The amplification was performed on Mastercycler Nexus X2 thermal cycler (Eppendorf) applying the following thermal cycle, 95 °C for 3 min for activation and 40 cycles at 94 °C for 30 s for denaturation, 57 °C for 30 s for annealing and 72 °C for 30 s for extension, followed by the last extension cycle at 72 °C for 10 min. Next, 1 µL of the amplification product was used for the capillary electrophoresis with D1000 screen tape and reagents, followed by Sanger sequencing, carried out with a Big Dye Terminator Cycle Sequencing Kit v.1.1 (Applied Biosystems, Warrington, UK). Finally, the reaction was applied to a 3500 Genetic Analyzer capillary electrophoresis system (Applied Biosystems). The forward and reverse sequences were assembled using the Geneious R9 software package (Biomatter, Auckland, New Zealand) and compared to analogous sequences in the BLAST genetic database ( http://www.ncbi.nlm.nih.gov/Blast.cgi accessed on 21 July 2022 A phylogenetic analysis was carried out using Mega X software . The evolutionary history was inferred by using the Maximum-Likelihood method and the Jukes–Cantor model (5). The bootstrap consensus tree inferred from 1000 replicates is taken to represent the evolutionary history of the taxa analyzed . Branches corresponding to partitions reproduced in less than 50% bootstrap replicates are collapsed. The percentage of replicate trees in which the associated taxa clustered together in the bootstrap test are shown next to the branches . Initial tree(s) for the heuristic search were obtained by applying the neighbor-joining method to a matrix of pairwise distances estimated using the Maximum Composite Likelihood (MCL) approach. A discrete Gamma distribution was used to model evolutionary rate differences among sites (4 categories ). The rate variation model allowed for some sites to be evolutionarily invariable ([+I], 15.11% sites). This analysis involved 18 nucleotide sequences. Codon positions included were first, second, third and non-coding. The sequence was compared to other orthopoxviruses, along with Central African and West African reference genomes. Results confirmed that our sample belonged to the West African clade . The reactions were carried out in a 25 µL final volume, containing KAPA PROBE FORCE qPCR Master Mix Universal 1X (Kapa Biosystems Pty, Cape Town, South Africa), 0.4 µM for each primer set and 0.2 µM for probes (FAM-labeled) (2) . According to the results, based on the Italian Ministry of Health law and based on clinical presentation, the patient opted for home isolation with a clinical follow-up by the Local Health Unit after a fluid in vein therapy with paracetamol for the headache. Following the first Monkeypox case in the Campania Region, the next day we had a new admission in our IDER of a 75-year-old man with a recent onset of vesicles starting from the scalp and spreading to the trunk, arms, palm of the hands and legs . He did not report fever nor had other clinical symptoms on the previous day of the vesicles occurrence. As with the first case, he had not returned from foreign travel, nor had he had contact with people suffering from signs or symptoms of infection. At clinical examination, he did not show any increase in lymph nodes. A chest clinical examination showed the presence of crackles in the pulmonary area with an absence of abdominal organ involvement upon further clinical examination. According to the age and clinical features, a lung CT scan was performed but it did not show any significant signs of pneumonia. Following our internal protocol, like with the first patient, all laboratory tests were performed showing the absence of any significant inflammatory marker and being negative for Monkeypox but positive for (VZV) IgM ( Table 1 ). After receiving a prescription for acyclovir the patient preferred home isolation with a local health unit follow-up.	4.175781	0.886719	sec[0]/p[0]	en	0.999997	PMC9414193	https://doi.org/10.3390/pathogens11080869	[ "monkeypox", "protocol", "carried", "african", "biosystems", "using", "according", "real", "mpxv", "west" ]	[ { "code": "1E71", "title": "Mpox" }, { "code": "PL14.6", "title": "Problem associated with isolation protocol" }, { "code": "QA86", "title": "Problem with isolation protocol without injury or harm" }, { "code": "QC1Z", "title": "Intervention not carried out, unspecified reason" }, { "code": "QC1Y", "title": "Intervention not carried out for other reasons" }, { "code": "PA60", "title": "Unintentional fall on the same level or from less than 1 metre" }, { "code": "QC04.Z", "title": "Immunization not carried out for unspecified reason" }, { "code": "QF21", "title": "Difficulty or need for assistance with general life tasks or life management" }, { "code": "1F51.Z", "title": "African trypanosomiasis, unspecified" }, { "code": "1F51.Y", "title": "Other specified african trypanosomiasis" } ]	=== ICD-11 CODES FOUND === [1E71] Mpox Definition: A disease caused by an infection with monkeypox virus. In the first phase, this disease is characterised by lymphadenopathy, fever, headache, or malaise; in the second phase, this disease is characterised by a rash that starts as maculopapules and progresses to vesicles, then pustules, followed by crusts (may occur on the face, palms of the hands, soles of the feet, body, and mucous membranes). Transmission is by direct contact with infected animals (including body fluids or lesions), direct con Also known as: Mpox \| MPX (deprecated) \| monkeypox \| monkeypox disease Includes: monkeypox [PL14.6] Problem associated with isolation protocol Definition: Isolation of patient for infection cause injury to occur Also known as: Problem associated with isolation protocol \| isolation technique broken or not followed \| patient mistakenly or inappropriately put on isolation [QA86] Problem with isolation protocol without injury or harm Definition: Patient not monitored as frequently as required or ordered; or patient mistakenly or inappropriately put on isolation; or isolation technique broken and contamination possible by patient, health provider, or visitor. No injury or harm resulted. Also known as: Problem with isolation protocol without injury or harm \| isolation technique broken and contamination possible without documented injury or harm \| patient mistakenly or inappropriately put on isolation without documented injury or harm \| Patient not monitored as frequently as required or ordered without documented injury or harm Excludes: Problem associated with isolation protocol [QC1Z] Intervention not carried out, unspecified reason Also known as: Intervention not carried out, unspecified reason \| procedure not carried out \| procedure not done \| cancelled procedure NOS [QC1Y] Intervention not carried out for other reasons Also known as: Intervention not carried out for other reasons [PA60] Unintentional fall on the same level or from less than 1 metre Also known as: Unintentional fall on the same level or from less than 1 metre \| ground level fall \| fell while ambulating \| fall from standing height \| fall from standing position Excludes: Fall in health care \| Fall while in hospital \| Fall from hospital bed [QC04.Z] Immunization not carried out for unspecified reason Also known as: Immunization not carried out for unspecified reason \| Immunization not carried out \| vaccination not done \| Immunization not carried out because of contraindication, not otherwise specified [QF21] Difficulty or need for assistance with general life tasks or life management Also known as: Difficulty or need for assistance with general life tasks or life management \| difficulty with carrying out tasks and daily routine \| life management problem \| difficulty with life management tasks \| Difficulty with dealing with change such as relocation Includes: difficulty with carrying out tasks and daily routine [1F51.Z] African trypanosomiasis, unspecified Also known as: African trypanosomiasis, unspecified \| African trypanosomiasis \| Meningitis in African trypanosomiasis \| Meningitis due to African trypanosomiasis \| Encephalitis in African trypanosomiasis [1F51.Y] Other specified african trypanosomiasis Also known as: Other specified african trypanosomiasis === GRAPH WALKS === --- Walk 1 --- [1E71] Mpox Def: A disease caused by an infection with monkeypox virus. In the first phase, this disease is characterised by lymphadenopathy, fever, headache, or malaise; in the second phase, this disease is character... --PARENT--> [?] Infections due to poxvirus --CHILD--> [1E70] Smallpox Def: A disease caused by an infection with variola virus. This disease is characterised by a maculopapular rash that progresses to vesicles (commonly on the face, arms, and legs), and fever. Transmission i... --- Walk 2 --- [1E71] Mpox Def: A disease caused by an infection with monkeypox virus. In the first phase, this disease is characterised by lymphadenopathy, fever, headache, or malaise; in the second phase, this disease is character... --PARENT--> [?] Infections due to poxvirus --CHILD--> [1E71] Mpox Def: A disease caused by an infection with monkeypox virus. In the first phase, this disease is characterised by lymphadenopathy, fever, headache, or malaise; in the second phase, this disease is character... --- Walk 3 --- [PL14.6] Problem associated with isolation protocol Def: Isolation of patient for infection cause injury to occur... --PARENT--> [PL14] Mode of injury or harm associated with other health care related causes --EXCLUDES--> [?] Mode of injury or harm associated with a surgical or other medical procedure --- Walk 4 --- [PL14.6] Problem associated with isolation protocol Def: Isolation of patient for infection cause injury to occur... --PARENT--> [PL14] Mode of injury or harm associated with other health care related causes --CHILD--> [PL14.2] Problem associated with physical transfer of patient --- Walk 5 --- [QA86] Problem with isolation protocol without injury or harm Def: Patient not monitored as frequently as required or ordered; or patient mistakenly or inappropriately put on isolation; or isolation technique broken and contamination possible by patient, health provi... --EXCLUDES--> [?] Problem associated with isolation protocol Def: Isolation of patient for infection cause injury to occur... --PARENT--> [?] Mode of injury or harm associated with other health care related causes --- Walk 6 --- [QA86] Problem with isolation protocol without injury or harm Def: Patient not monitored as frequently as required or ordered; or patient mistakenly or inappropriately put on isolation; or isolation technique broken and contamination possible by patient, health provi... --PARENT--> [?] Circumstances associated with other aspects of care influencing the episode of care without injury or harm --PARENT--> [?] Health care related circumstances influencing the episode of care without injury or harm	[ "[1E71] Mpox\n Def: A disease caused by an infection with monkeypox virus. In the first phase, this disease is characterised by lymphadenopathy, fever, headache, or malaise; in the second phase, this disease is character...\n --PARENT--> [?] Infections due to poxvirus\n --CHILD--> [1E70] Smallpox\n Def: A disease caused by an infection with variola virus. This disease is characterised by a maculopapular rash that progresses to vesicles (commonly on the face, arms, and legs), and fever. Transmission i...", "[1E71] Mpox\n Def: A disease caused by an infection with monkeypox virus. In the first phase, this disease is characterised by lymphadenopathy, fever, headache, or malaise; in the second phase, this disease is character...\n --PARENT--> [?] Infections due to poxvirus\n --CHILD--> [1E71] Mpox\n Def: A disease caused by an infection with monkeypox virus. In the first phase, this disease is characterised by lymphadenopathy, fever, headache, or malaise; in the second phase, this disease is character...", "[PL14.6] Problem associated with isolation protocol\n Def: Isolation of patient for infection cause injury to occur...\n --PARENT--> [PL14] Mode of injury or harm associated with other health care related causes\n --EXCLUDES--> [?] Mode of injury or harm associated with a surgical or other medical procedure", "[PL14.6] Problem associated with isolation protocol\n Def: Isolation of patient for infection cause injury to occur...\n --PARENT--> [PL14] Mode of injury or harm associated with other health care related causes\n --CHILD--> [PL14.2] Problem associated with physical transfer of patient", "[QA86] Problem with isolation protocol without injury or harm\n Def: Patient not monitored as frequently as required or ordered; or patient mistakenly or inappropriately put on isolation; or isolation technique broken and contamination possible by patient, health provi...\n --EXCLUDES--> [?] Problem associated with isolation protocol\n Def: Isolation of patient for infection cause injury to occur...\n --PARENT--> [?] Mode of injury or harm associated with other health care related causes", "[QA86] Problem with isolation protocol without injury or harm\n Def: Patient not monitored as frequently as required or ordered; or patient mistakenly or inappropriately put on isolation; or isolation technique broken and contamination possible by patient, health provi...\n --PARENT--> [?] Circumstances associated with other aspects of care influencing the episode of care without injury or harm\n --PARENT--> [?] Health care related circumstances influencing the episode of care without injury or harm" ]	1E71	Mpox	[ { "from_icd11": "1E71", "icd10_code": "B04", "icd10_title": "Monkeypox" }, { "from_icd11": "QA86", "icd10_code": "XXI", "icd10_title": "" }, { "from_icd11": "QC1Z", "icd10_code": "Z5331", "icd10_title": "Laparoscopic surgical procedure converted to open procedure" }, { "from_icd11": "QC1Z", "icd10_code": "Z5332", "icd10_title": "Thoracoscopic surgical procedure converted to open procedure" }, { "from_icd11": "QC1Z", "icd10_code": "Z5339", "icd10_title": "Other specified procedure converted to open procedure" }, { "from_icd11": "QC1Z", "icd10_code": "Z5333", "icd10_title": "Arthroscopic surgical procedure converted to open procedure" }, { "from_icd11": "QC1Z", "icd10_code": "Z538", "icd10_title": "Procedure and treatment not carried out for other reasons" }, { "from_icd11": "QC1Z", "icd10_code": "Z539", "icd10_title": "Procedure and treatment not carried out, unspecified reason" }, { "from_icd11": "QC1Z", "icd10_code": "Z53", "icd10_title": "Persons encountering health services for specific procedures and treatment, not carried out" }, { "from_icd11": "PA60", "icd10_code": "W03XXXA", "icd10_title": "Other fall on same level due to collision with another person, initial encounter" }, { "from_icd11": "PA60", "icd10_code": "W04XXXA", "icd10_title": "Fall while being carried or supported by other persons, initial encounter" }, { "from_icd11": "PA60", "icd10_code": "W010XXA", "icd10_title": "Fall on same level from slipping, tripping and stumbling without subsequent striking against object, initial encounter" }, { "from_icd11": "PA60", "icd10_code": "W1839XA", "icd10_title": "Other fall on same level, initial encounter" }, { "from_icd11": "PA60", "icd10_code": "W01198A", "icd10_title": "Fall on same level from slipping, tripping and stumbling with subsequent striking against other object, initial encounter" }, { "from_icd11": "PA60", "icd10_code": "W1830XA", "icd10_title": "Fall on same level, unspecified, initial encounter" } ]	B04	Monkeypox
A 14 old-month girl was admitted at the PICU after a severe TBI secondary to a car accident. At admission the neurologic examination showed a glasgow coma scale (GCS) of 4. Brain MRI showed diffuse brain edema, hemorrhagic petechiae in the grey matter, multiple frontal and temporal cortico-subcortical hemorrhagic contusions, signs of diffuse axonal injury at brainstem, and thinning of cerebral circumvolutions (data not shown). After 7 days the sedation was stopped and the child evidenced a failure of respiratory trigger, so the patient underwent tracheostomy and gastrostomy. After about 3 months from TBI the patient showed inability to speech, reflex movements without response to command and minimally conscious state in the presence of post-traumatic UWS. Communication was possible only through eye movements. Somatosensory evoked potentials (SSEP) showed a marked distress functional tract of the upper and lower limbs. The child also presented a spastic-dystonic tetraparesis and developed an epileptic encephalopathy requiring appropriate therapy. At this time, the neurological examination showed an alert and conscious child with severe communicative and neuropsychological impairment. The child also lost bladder and bowel functions; an oral-motor dyspraxia was also detected with the presence of loss of skin sensitiveness, while a progressive increase of muscle tone, especially in the upper and lower limbs, was noticed. Due to persistence of increased muscle tone and spasticity, a targeted management of spasticity with botulinum toxin injection was performed without any improvement. Ten months after TBI, at the age of 2 years, due to the persistent of post-traumatic UWS and after proper and standardized medical, neuro-intensive and rehabilitative care, treatment with intranasal hr-NGF administration was started. After NGF treatment, significant improvements were observed in some cognitive processes, mainly in attention and verbal comprehension. At the end of intranasal NGF administration, the patient showed an improvement in the capacity to knit eyebrows, curl nose, crying with tears, major symmetry in the smile and more meaning to eyelids closure in communicating. The child was also able to eat from the mouth; in fact, some improvements were also observed in oral motility and head rotation. Due to these neurological and clinical modifications, an alternative and increasing communication program, involving all the family members, was started with great success. Oral motor dyspraxia progressively improved too, with enhanced oral motility control including mouth opening, tongue motility, mastication and swallowing. The ability to feed also improved and the child became able to eat little amounts of food. In association with the improvement in oral motor dyspraxia, other acquired skills, included phonation with more explicit emission of sounds, were observed. Moreover, during the cycles of NGF therapy, a progressive but constant enhancement of head movements (mainly in head lateral rotation and minimally in up and down movements) was reported. The child responded more effectively to visual stimuli, fixating and tracking the targets. She managed to keep her eyes open and to recognize familiar voices, turning her head towards the source of the sound. The left deviation of her eyes was no longer present and her eyes were well-positioned on the midline; horizontal nystagmus ameliorated and was present only after position changes. The corneal, vestibulo-ocular, and inducible cough reflexes, which had previously been absent, were also restored. Another important amelioration was represented by the improvement in bowel function, losing the need for stimulation to evacuate. We observed also an increased tolerance to passive mobilization, with a significant reduction of muscular hypertone and trophism, spasticity and dystonic seizures. According to these clinical and neurological modifications, also GMFM total score increased from 3.4 to 6.6% after the treatment, while a significant improvement in spasticity (assessed by modified Ashworth Scale) of 4 points was reported, with progressive reduction of muscle hypertonus . Moreover, the DRS collected an initial score suggestive of an extreme vegetative state (25–29 points). At the end of the treatment, there was an improvement of 4 points in her DRS, with a consequent change of category from Extreme Vegetative State to Severe Disability (17–21 points). PET and SPECT, before the treatment, pointed out a marked and global reduction in tracer uptake at the cortical, subcortical, thalami, and cerebellar levels . At the end of hr-NGF administration, PET and SPET showed a remarkable increase in radiotracer uptake in the right frontal, temporal, parietal and occipital cortex, right and left thalamus and cerebellum . Figures 5 and 6 highlighted the modifications of neuroimaging before and after the treatment. EEG recording performed before NGF treatment showed severe low-voltage background activity. Sporadic theta-delta activity in the right fronto-temporal regions could be appreciated. Sleep was scarcely distinguished from wakefulness and the activity was markedly and diffusely depressed. The EEG examination carried out at the end of NGF treatment showed an improvement in the electrical cerebral activity: a quantifiable 4–5 Hz background theta-delta activity is evident bilaterally on the anterior regions (right > left), intermixed with abundant diffuse rapid rhythms. Topographical analysis of the PSD distribution of the EEG signal showed a mean cumulative increase of slow and organized rhythms at the expense of fast and disorganized ones. These changes had a different distribution, as highlighted in Fig. 7 a–e . No adverse effects were described during the study period. Fig. 5 PET before and after the treatment with hr-NGF. a, b: Brain 18F-FDG PET axial slices performed before ( a ) and after b hr-NGF treatment. A severe reduction in 18F-FDG uptake was observed in all cortical and subcortical regions of the left hemisphere, whereas a mild reduction was detected in the whole cerebellum and all cortical and subcortical regions of the right hemisphere ( a ). After hr-NGF administration, an increase in radiotracer uptake was found in the right frontal cortex (+ 11%), right temporal cortex (+ 15%), right parietal cortex (+ 14%), right occipital cortex (+ 22%), right and left thalamus (+ 10% and + 7%, respectively) and cerebellum (+ 33%) ( b ) Fig. 6 SPECT before and after the treatment with hr-NGF. a, b: Perfusion SPECT images before ( a ) and after ( b ) hr-NGF administration. 99m Tc-HMPAO SPECT images (transaxial slices) before hr-NGF treatment showed a severe reduction in radiotracer uptake (hypoperfusion) in all cortical regions of the left hemisphere. A moderate-to-severe reduction in 99m Tc-HMPAO uptake was observed in the left subcortical areas, right cortical regions as well as right subcortical areas, whereas a mild reduction was detected in the cerebellum ( a ). After hr-NGF treatment, an increase in radiotracer uptake was found in the right frontal cortex (+ 16%), right temporal cortex (+ 20%), right parietal cortex (+ 14%), right occipital cortex (+ 26%) right and left thalamus (7.5% and 9%, respectively) and cerebellum (+ 34%) ( b ) Fig. 7 Power Spectral Density. a–e. Comparison of topographic distribution of EEG Power Spectral Density before vs after intranasal NGF administration showed a mean cumulative increase of slow and organized rhythms at the expense of fast and disorganized ones. Blue coloring corresponds to a better expression of waves in post treatment EEG, despite to a red shades that indicate a wider expression in pretreatment pathways. In particular: diffuse increase of theta activity, mainly evident on the midline regions (a) ; diffuse increase of alfa activity, particularly evident on the parieto-occipital regions (b) ; improvements in delta waves mainly in Broadman areas and limbic region with cingulum zone (c); diffuse decrease of beta activity, which does not occur on the left on the parieto-occipital regions (d) ; diffuse decrease of gamma activity, particularly evident in parietal-midline areas (e)	4.089844	0.973633	sec[2]/sec[2]/p[0]	en	0.999997	37789391	https://doi.org/10.1186/s13062-023-00418-1	[ "cortex", "activity", "regions", "increase", "reduction", "improvement", "uptake", "subcortical", "administration", "temporal" ]	[ { "code": "LA05.51", "title": "Cortical dysplasia" }, { "code": "8E7Y", "title": "Other specified diseases of the nervous system" }, { "code": "NA07.3Y&XA1M33", "title": "Laceration of cerebrum" }, { "code": "8B26.Y", "title": "Other specified vascular syndromes of brain in cerebrovascular diseases" }, { "code": "9C43", "title": "Disorder of visual cortex" }, { "code": "QF2Z", "title": "Difficulty or need for assistance with unspecified activity" }, { "code": "6A05.Z", "title": "Attention deficit hyperactivity disorder, presentation unspecified" }, { "code": "QF23", "title": "Difficulty or need for assistance with mobility" }, { "code": "QF28", "title": "Difficulty or need for assistance with work activities" }, { "code": "CA40.Z", "title": "Pneumonia, organism unspecified" } ]	=== ICD-11 CODES FOUND === [LA05.51] Cortical dysplasia Definition: A condition caused by failure of the cortex to correctly develop during the antenatal period, or by trauma. This condition is characterised by epileptic seizures. This condition may also present with learning impairments. Also known as: Cortical dysplasia \| Focal cortical dysplasia \| Focal cortical dysplasia type I \| Focal cortical dysplasia type Ia \| Focal cortical dysplasia type Ib [8E7Y] Other specified diseases of the nervous system Also known as: Other specified diseases of the nervous system \| Circumscribed brain atrophy \| circumscribed cerebral atrophy \| atrophic lobar sclerosis \| atrophic lobar brain sclerosis [8B26.Y] Other specified vascular syndromes of brain in cerebrovascular diseases Also known as: Other specified vascular syndromes of brain in cerebrovascular diseases \| Subcortical ischaemic stroke \| subcortical infarction \| Cortical ischaemic stroke \| cortical infarction [9C43] Disorder of visual cortex Also known as: Disorder of visual cortex \| visual cortex dysfunction \| visual cortical disorder \| disease of visual cortex [QF2Z] Difficulty or need for assistance with unspecified activity Also known as: Difficulty or need for assistance with unspecified activity \| need for assistance with activities \| dependence on care provider \| difficulty with activities [6A05.Z] Attention deficit hyperactivity disorder, presentation unspecified Also known as: Attention deficit hyperactivity disorder, presentation unspecified \| Attention deficit hyperactivity disorder \| disturbance of activity and attention \| disorder of activity and attention \| ADHD - [attention deficit hyperactivity disorder] [QF23] Difficulty or need for assistance with mobility Also known as: Difficulty or need for assistance with mobility \| difficulty with mobility \| need for assistance due to reduced mobility \| need for assistance with mobility \| problem with impaired mobility Excludes: Abnormalities of gait or mobility [QF28] Difficulty or need for assistance with work activities Also known as: Difficulty or need for assistance with work activities \| need for assistance with work activities \| difficulty with work activities [CA40.Z] Pneumonia, organism unspecified Also known as: Pneumonia, organism unspecified \| Pneumonia \| infectious pneumonia \| PN - [pneumonia] \| lobar pneumonia NOS === GRAPH WALKS === --- Walk 1 --- [LA05.51] Cortical dysplasia Def: A condition caused by failure of the cortex to correctly develop during the antenatal period, or by trauma. This condition is characterised by epileptic seizures. This condition may also present with ... --PARENT--> [LA05.5] Abnormal neuronal migration Def: Any condition caused by abnormal migration of neuronal cells during the antenatal period. These conditions may present with poor muscle tone and motor function, seizures, developmental delays, mental ... --CHILD--> [LA05.5Y] Other specified abnormal neuronal migration --- Walk 2 --- [LA05.51] Cortical dysplasia Def: A condition caused by failure of the cortex to correctly develop during the antenatal period, or by trauma. This condition is characterised by epileptic seizures. This condition may also present with ... --PARENT--> [LA05.5] Abnormal neuronal migration Def: Any condition caused by abnormal migration of neuronal cells during the antenatal period. These conditions may present with poor muscle tone and motor function, seizures, developmental delays, mental ... --EXCLUDES--> [?] Syndromes with lissencephaly as a major feature Def: The term lissencephaly covers a group of rare malformations sharing the common feature of anomalies in the appearance of brain convolutions (characterised by simplification or absence of folding) asso... --- Walk 3 --- [8E7Y] Other specified diseases of the nervous system --PARENT--> [08] Diseases of the nervous system Def: This is a group of conditions characterised as being in or associated with the nervous system.... --CHILD--> [?] Disorders with neurocognitive impairment as a major feature --- Walk 4 --- [8E7Y] Other specified diseases of the nervous system --PARENT--> [08] Diseases of the nervous system Def: This is a group of conditions characterised as being in or associated with the nervous system.... --RELATED_TO--> [?] Syndromes with central nervous system anomalies as a major feature --- Walk 5 --- [8B26.Y] Other specified vascular syndromes of brain in cerebrovascular diseases --PARENT--> [8B26] Vascular syndromes of brain in cerebrovascular diseases --CHILD--> [8B26.1] Cerebellar stroke syndrome --- Walk 6 --- [8B26.Y] Other specified vascular syndromes of brain in cerebrovascular diseases --PARENT--> [8B26] Vascular syndromes of brain in cerebrovascular diseases --PARENT--> [?] Cerebrovascular diseases Def: This is a group of brain dysfunctions related to disease of the blood vessels supplying the brain. This includes “stroke”, which includes the following entities: Intracerebral haemorrhage; Subarachnoi...	[ "[LA05.51] Cortical dysplasia\n Def: A condition caused by failure of the cortex to correctly develop during the antenatal period, or by trauma. This condition is characterised by epileptic seizures. This condition may also present with ...\n --PARENT--> [LA05.5] Abnormal neuronal migration\n Def: Any condition caused by abnormal migration of neuronal cells during the antenatal period. These conditions may present with poor muscle tone and motor function, seizures, developmental delays, mental ...\n --CHILD--> [LA05.5Y] Other specified abnormal neuronal migration", "[LA05.51] Cortical dysplasia\n Def: A condition caused by failure of the cortex to correctly develop during the antenatal period, or by trauma. This condition is characterised by epileptic seizures. This condition may also present with ...\n --PARENT--> [LA05.5] Abnormal neuronal migration\n Def: Any condition caused by abnormal migration of neuronal cells during the antenatal period. These conditions may present with poor muscle tone and motor function, seizures, developmental delays, mental ...\n --EXCLUDES--> [?] Syndromes with lissencephaly as a major feature\n Def: The term lissencephaly covers a group of rare malformations sharing the common feature of anomalies in the appearance of brain convolutions (characterised by simplification or absence of folding) asso...", "[8E7Y] Other specified diseases of the nervous system\n --PARENT--> [08] Diseases of the nervous system\n Def: This is a group of conditions characterised as being in or associated with the nervous system....\n --CHILD--> [?] Disorders with neurocognitive impairment as a major feature", "[8E7Y] Other specified diseases of the nervous system\n --PARENT--> [08] Diseases of the nervous system\n Def: This is a group of conditions characterised as being in or associated with the nervous system....\n --RELATED_TO--> [?] Syndromes with central nervous system anomalies as a major feature", "[8B26.Y] Other specified vascular syndromes of brain in cerebrovascular diseases\n --PARENT--> [8B26] Vascular syndromes of brain in cerebrovascular diseases\n --CHILD--> [8B26.1] Cerebellar stroke syndrome", "[8B26.Y] Other specified vascular syndromes of brain in cerebrovascular diseases\n --PARENT--> [8B26] Vascular syndromes of brain in cerebrovascular diseases\n --PARENT--> [?] Cerebrovascular diseases\n Def: This is a group of brain dysfunctions related to disease of the blood vessels supplying the brain. This includes “stroke”, which includes the following entities: Intracerebral haemorrhage; Subarachnoi..." ]	LA05.51	Cortical dysplasia	[ { "from_icd11": "9C43", "icd10_code": "H47619", "icd10_title": "Cortical blindness, unspecified side of brain" }, { "from_icd11": "9C43", "icd10_code": "H47611", "icd10_title": "Cortical blindness, right side of brain" }, { "from_icd11": "9C43", "icd10_code": "H47612", "icd10_title": "Cortical blindness, left side of brain" }, { "from_icd11": "9C43", "icd10_code": "H476", "icd10_title": "Disorders of visual cortex" }, { "from_icd11": "QF2Z", "icd10_code": "Z7389", "icd10_title": "Other problems related to life management difficulty" }, { "from_icd11": "QF2Z", "icd10_code": "Z7382", "icd10_title": "Dual sensory impairment" }, { "from_icd11": "QF2Z", "icd10_code": "Z742", "icd10_title": "Need for assistance at home and no other household member able to render care" }, { "from_icd11": "QF2Z", "icd10_code": "Z602", "icd10_title": "Problems related to living alone" }, { "from_icd11": "QF2Z", "icd10_code": "Z748", "icd10_title": "Other problems related to care provider dependency" }, { "from_icd11": "QF2Z", "icd10_code": "Z73", "icd10_title": "Problems related to life management difficulty" }, { "from_icd11": "QF2Z", "icd10_code": "Z738", "icd10_title": "Other problems related to life management difficulty" }, { "from_icd11": "QF2Z", "icd10_code": "Z739", "icd10_title": "Problem related to life management difficulty, unspecified" }, { "from_icd11": "QF2Z", "icd10_code": "Z74", "icd10_title": "Problems related to care provider dependency" }, { "from_icd11": "QF2Z", "icd10_code": "Z749", "icd10_title": "Problem related to care provider dependency, unspecified" }, { "from_icd11": "6A05.Z", "icd10_code": "F902", "icd10_title": "Attention-deficit hyperactivity disorder, combined type" } ]	H47619	Cortical blindness, unspecified side of brain
This case describes a young male horse presenting severe gait deficits. Cervical vertebral stenotic myelopathy (CVSM), aberrant parasite migration and equine degenerative myeloencephalopathy (EDM) were considered in the differential diagnostics. Due to the geographic location, equine protozoal meningitis (EPM) was excluded. The histological lesions and the results of the examinations excluded other diseases, such as EDM or a nematode infection. EDM affects animals that are genetically predisposed to the disease, that have disorders of vitamin E absorption, limited access to pasture or excess exposure to insecticides, all of which were excluded in the presented case . The histological lesions visible in the course of EDM affect the dorsal grey column, while those in CVSM affect the white matter. EDM features neuroaxonal dystrophy with axonal-dendritic edema and neuronal atrophy, which results from lipofuscin accumulation. The histological findings in the case of chronic, eosinophilic encephalomyelitis caused by nematodes from the Protostrongylidae family are characteristic . Most migration routes are present in the white matter or on the border between the grey and white matter and lead to hemorrhagic lesions, large eosinophilic infiltrations and infiltrations of multinucleated giant cells, lymphocytes and hemosiderin-laden macrophages. Adult parasites are found mainly in the brain, while larvae are present in the thoracic and lumbar spinal cord and are located mainly in the dorsal grey columns . Cellular vacuolization and axonal spheroids indicate cellular lesions and occur in various neurological diseases. Parasytoses caused by cerebrospinal nematodes such as Parelaphostrongylus tenuis lead to dorsal grey column and lateral white column lesions, but are not reported in our geographical region. Our results indicated a significant reduction in the functionality of the spinal cord nerve tissue following loss of neurons which is similar to some other diseases. At the same time the lack of haemorrhagic lesions, lipofuscin deposits or hemosiderin-laden cells excludes those diseases. The presence of neuronal degeneration, numerous microglial cells and unmyelinated dysfunctional so-called “spongy structure” areas all suggest CVSM, which was confirmed in the radiological findings. Most studies reporting age and breed correlations of CVSM describe the condition in young fast-growing males . The latest research indicates that the traditional 50% reduction of DMC rule is ineffective in diagnosing CVSM, particularly in the flexed neck position . Other studies report the principle of diagnosis based on comparing the intra- and intervertebral ratio measured on cervical spine lateral radiographic projections. However, such measurements are limited due to observer bias. Nevertheless, static and dynamic CVSM are distinguished . A 70% DMC reduction instead of a 50% one has already been proposed to avoid false positive results . Therefore, radiographs and myelograms should be evaluated with caution and always in correlation with the results of the clinical examinations. Moreover, the lateral view is useful only in detecting dorso-ventral compression . In the described stallion, the compression, understood as a reduction of the DMC equal or higher than 50%, was only detected at the C3/C4 level. The measured DMC reduction in this colt was 67%, which is thought to be responsible for the clinical symptoms. A 20% DD reduction has been described as potentially significant enough to reflect dural sac narrowing due to vertebral canal malformation . In the presented study, the obtained DD reduction was 64% at the C3/C4 level. Contrary to hypothetic results based on the radiographs, the post-mortem measurements revealed a 44% diameter reduction of the vertebral canal. These measurements were taken in a neutral position of the spine. It is clear that the measurements taken post mortem are more accurate than the radiographic analysis as they were collected in a neutral position of the cervical spine following confirmation of dynamic changes. Interestingly, the percentage reduction was lower than CVSM gold standard value, while the clinical symptoms were described as moderate to strong. Hence we expected a higher reduction rate based on measurements performed on anatomical sections. The intra- and intervertebral ratio in the C4/C5 section should be taken into account with reference to the available literature . We focused on the C3/C4 compression due to the lowest intravertebral ratio at this site with a simultaneous reduction of the DD and DMC as well as measurements carried out macroscopically. Despite the fact that the value of the intravertebral ratio at the C4/C5 site was lower than 48.5%, and that the intervertebral ratio considered more specific was lower than at C3/C4, which, based on the cited study, could have high diagnostic value, was not confirmed in the measurements performed during the myelography . This may have been caused by differences in the assessment of the cervical radiographs . However, myelography is considered an important intravital diagnostic tool that enables the qualification of patients for cervical vertebral stabilisation surgery, therefore our study focused on the C3/C4 analysis. CSF analysis which is also a valuable tool concerning protozoal or verminous infection has not been performed due to its high costs and low diagnostic value in the case of suspected CVSM . CT and MR are also valuable tools that enable the analysis of the cervical spine. Due to technical constraints, MR can be currently used to assess only the cranial section of the cervical spine and enables high quality soft tissue analysis of the studied area. Computed tomography and myelo-CT are valuable diagnostic methods but require an appropriate gantry size . Unfortunately, high-field imaging of the cervical spine using MR or appropriate CT is not available in Poland. We decided to carry out a histologic study, which is thought to be the most appropriate tool in the diagnosis of CVSM although it is not applicable in in vivo studies. The typical histologic changes described in horses with CVSM are observed within the white matter . Commonly described primary changes consist of an increased number of macrophages, perivascular collagen , the presence of “digestive chambers” partial/total loss of myelin, axonal degeneration and gliosis . Our results were slightly different as they did not include some of the commonly described histologic changes such as the formation of a glial scar or spheroids characteristic of CVSM (only oedematose axons were found). This may result from an early NSAIDs therapy, which inhibited the inflammatory process, the age of the animal or the relatively short interval between symptom recognition and euthanasia. The results of the immunohistochemical study, which was not performed by other authors, did not confirm inflammation. In the case of CD68, the lack of reaction may indicate non-specificity of the used antibody or the occurrence of a very weak reaction at the limit of detection , which is difficult to interpret. However, the negative TNFα reaction indicates an absence of the tumor necrosis factor representative of inflammation, produced by the activated tissue macrophages . As a result of the administration of anti-inflammatory drugs, the inflammatory reaction was suppressed or the histologic changes did not develop sufficiently due to a rapid diagnosis of the disease as evidenced by the lack of gliosis. Nevertheless, it would be useful to collect a sample from the spinal cord both above and below the place of the compression while performing a histologic examination. However, a complete histological and immunohistochemical analysis of the entire cervical spinal cord is very difficult technically. An analysis of spinal cord samples above and below the described lesion may have been performed to confirm or exclude co-existing diseases. In addition, a wider sample analysis may have facilitated the identification of an area with lesions typical of CVSM and an analysis of their severity depending on their distance from the site of greatest compression.	4.394531	0.811523	sec[2]/p[0]	en	0.999996	31416466	https://doi.org/10.1186/s12917-019-2047-x	[ "cvsm", "which", "reduction", "cervical", "that", "lesions", "measurements", "spine", "this", "diseases" ]	[ { "code": "BD50.41", "title": "Abdominal aortic aneurysm with rupture" }, { "code": "EK91", "title": "Dermatoses which may presage cutaneous lymphoma" }, { "code": "MH12.1", "title": "Death occurring less than 24 hours from onset of symptoms, not otherwise explained" }, { "code": "8A44.3", "title": "Certain specified leukodystrophies" }, { "code": "GC79", "title": "Disorders of breast reduction" }, { "code": "LB9A.Z", "title": "Reduction defects of lower limb, unspecified" }, { "code": "LB99.Z", "title": "Reduction defects of upper limb, unspecified" }, { "code": "LB9Z", "title": "Structural developmental anomalies of the skeleton, unspecified" }, { "code": "LB9A.Y", "title": "Other specified reduction defects of lower limb" }, { "code": "GA04", "title": "Cervicitis" } ]	=== ICD-11 CODES FOUND === [BD50.41] Abdominal aortic aneurysm with rupture Also known as: Abdominal aortic aneurysm with rupture \| abdominal aorta aneurysm rupture \| abdominal aorta aneurysm ruptured \| abdominal aortic aneurysm which has ruptured \| ruptured AAA [EK91] Dermatoses which may presage cutaneous lymphoma Definition: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature. Also known as: Dermatoses which may presage cutaneous lymphoma [MH12.1] Death occurring less than 24 hours from onset of symptoms, not otherwise explained Also known as: Death occurring less than 24 hours from onset of symptoms, not otherwise explained \| died without sign of disease \| Death known not to be violent or instantaneous for which no cause can be discovered \| death known not to be violent or instantaneous, cause unknown \| Death without sign of disease Includes: Death known not to be violent or instantaneous for which no cause can be discovered \| Death without sign of disease [8A44.3] Certain specified leukodystrophies Also known as: Certain specified leukodystrophies \| CACH syndrome \| Vanishing white matter disease \| Childhood ataxia with central nervous system hypomyelination \| Congenital or early infantile CACH syndrome [GC79] Disorders of breast reduction Also known as: Disorders of breast reduction [LB9A.Z] Reduction defects of lower limb, unspecified Also known as: Reduction defects of lower limb, unspecified \| Reduction defects of lower limb \| lower extremities underdeveloped [LB99.Z] Reduction defects of upper limb, unspecified Also known as: Reduction defects of upper limb, unspecified \| Reduction defects of upper limb [LB9Z] Structural developmental anomalies of the skeleton, unspecified Also known as: Structural developmental anomalies of the skeleton, unspecified \| Abnormal bone development \| skeletal anomaly NOS [LB9A.Y] Other specified reduction defects of lower limb Also known as: Other specified reduction defects of lower limb [GA04] Cervicitis Also known as: Cervicitis \| inflammation of cervix \| inflammation of cervix uteri \| Ulcer of cervix with cervicitis \| Acute cervicitis === GRAPH WALKS === --- Walk 1 --- [BD50.41] Abdominal aortic aneurysm with rupture --PARENT--> [BD50.4] Abdominal aortic aneurysm --PARENT--> [BD50] Aortic aneurysm or dissection Def: Aortic aneurysm is a term for any swelling (dilation or aneurysm) of the aorta to greater than 1.5 times normal, usually representing an underlying weakness in the wall of the aorta at that location. ... --- Walk 2 --- [BD50.41] Abdominal aortic aneurysm with rupture --PARENT--> [BD50.4] Abdominal aortic aneurysm --CHILD--> [BD50.41] Abdominal aortic aneurysm with rupture --- Walk 3 --- [EK91] Dermatoses which may presage cutaneous lymphoma Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature.... --CHILD--> [EK91.0] Large plaque parapsoriasis Def: Large plaque parapsoriasis is a chronic skin disorder characterised by the indolent development over years or decades of scaly patches or slightly elevated plaques which may be clinically indistinguis... --PARENT--> [EK91] Dermatoses which may presage cutaneous lymphoma Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature.... --- Walk 4 --- [EK91] Dermatoses which may presage cutaneous lymphoma Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature.... --PARENT--> [?] Disorders of the skin of uncertain or unpredictable malignant potential --CHILD--> [EK91] Dermatoses which may presage cutaneous lymphoma Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature.... --- Walk 5 --- [MH12.1] Death occurring less than 24 hours from onset of symptoms, not otherwise explained --PARENT--> [MH12] Other sudden death, cause unknown --CHILD--> [MH12.Y] Other specified sudden death, cause unknown --- Walk 6 --- [MH12.1] Death occurring less than 24 hours from onset of symptoms, not otherwise explained --PARENT--> [MH12] Other sudden death, cause unknown --CHILD--> [MH12.1] Death occurring less than 24 hours from onset of symptoms, not otherwise explained	[ "[BD50.41] Abdominal aortic aneurysm with rupture\n --PARENT--> [BD50.4] Abdominal aortic aneurysm\n --PARENT--> [BD50] Aortic aneurysm or dissection\n Def: Aortic aneurysm is a term for any swelling (dilation or aneurysm) of the aorta to greater than 1.5 times normal, usually representing an underlying weakness in the wall of the aorta at that location. ...", "[BD50.41] Abdominal aortic aneurysm with rupture\n --PARENT--> [BD50.4] Abdominal aortic aneurysm\n --CHILD--> [BD50.41] Abdominal aortic aneurysm with rupture", "[EK91] Dermatoses which may presage cutaneous lymphoma\n Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature....\n --CHILD--> [EK91.0] Large plaque parapsoriasis\n Def: Large plaque parapsoriasis is a chronic skin disorder characterised by the indolent development over years or decades of scaly patches or slightly elevated plaques which may be clinically indistinguis...\n --PARENT--> [EK91] Dermatoses which may presage cutaneous lymphoma\n Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature....", "[EK91] Dermatoses which may presage cutaneous lymphoma\n Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature....\n --PARENT--> [?] Disorders of the skin of uncertain or unpredictable malignant potential\n --CHILD--> [EK91] Dermatoses which may presage cutaneous lymphoma\n Def: Dermatoses which may represent the earliest stages of cutaneous lymphoma but where it is not possible to confirm their neoplastic nature....", "[MH12.1] Death occurring less than 24 hours from onset of symptoms, not otherwise explained\n --PARENT--> [MH12] Other sudden death, cause unknown\n --CHILD--> [MH12.Y] Other specified sudden death, cause unknown", "[MH12.1] Death occurring less than 24 hours from onset of symptoms, not otherwise explained\n --PARENT--> [MH12] Other sudden death, cause unknown\n --CHILD--> [MH12.1] Death occurring less than 24 hours from onset of symptoms, not otherwise explained" ]	BD50.41	Abdominal aortic aneurysm with rupture	[ { "from_icd11": "BD50.41", "icd10_code": "I713", "icd10_title": "Abdominal aortic aneurysm, ruptured" }, { "from_icd11": "EK91", "icd10_code": "L989", "icd10_title": "Disorder of the skin and subcutaneous tissue, unspecified" }, { "from_icd11": "MH12.1", "icd10_code": "R961", "icd10_title": "" }, { "from_icd11": "LB9A.Z", "icd10_code": "Q7292", "icd10_title": "Unspecified reduction defect of left lower limb" }, { "from_icd11": "LB9A.Z", "icd10_code": "Q72891", "icd10_title": "Other reduction defects of right lower limb" }, { "from_icd11": "LB9A.Z", "icd10_code": "Q72899", "icd10_title": "Other reduction defects of unspecified lower limb" }, { "from_icd11": "LB9A.Z", "icd10_code": "Q72", "icd10_title": "Reduction defects of lower limb" }, { "from_icd11": "LB9A.Z", "icd10_code": "Q728", "icd10_title": "Other reduction defects of lower limb" }, { "from_icd11": "LB9A.Z", "icd10_code": "Q729", "icd10_title": "Unspecified reduction defect of lower limb" }, { "from_icd11": "LB99.Z", "icd10_code": "Q71892", "icd10_title": "Other reduction defects of left upper limb" }, { "from_icd11": "LB99.Z", "icd10_code": "Q71899", "icd10_title": "Other reduction defects of unspecified upper limb" }, { "from_icd11": "LB99.Z", "icd10_code": "Q7192", "icd10_title": "Unspecified reduction defect of left upper limb" }, { "from_icd11": "LB99.Z", "icd10_code": "Q71", "icd10_title": "Reduction defects of upper limb" }, { "from_icd11": "LB99.Z", "icd10_code": "Q718", "icd10_title": "Other reduction defects of upper limb" }, { "from_icd11": "LB99.Z", "icd10_code": "Q719", "icd10_title": "Unspecified reduction defect of upper limb" } ]	I713	Abdominal aortic aneurysm, ruptured

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