Supplement 3. Answers were generated by ChatGPT on 10 cases. Except the 10.2, all answers were generated on March 15, 2023 [Seoul time]. Ten cases were those in Supplement 2.

1. Asnwers on case 1 

1.1 What is a list of differential diagnosis of following case: In 2021, a 58-year-old woman presented to the emergency department with dyspnea and bilateral flank pain. She presented with pallor and clamminess and had a blood pressure of 170/120 mmHg, heart rate of 120 beats/min, body temperature of 38.2°C, respiration rate of 30 breaths/min, oxygen saturation of 89% on room air, and a body mass index of 25.1 kg/m2 (height, 148 cm; weight, 55 kg). She had no medical history or significant family history but had been taking phendimetrazine tartrate for weight loss for 5 years. On physical examination, crackles were heard in the right lung field upon auscultation and the abdomen was soft without tenderness.

Based on the given information, the differential diagnosis for this patient's symptoms may include:

Pulmonary embolism: This is a potentially life-threatening condition in which a blood clot travels to the lungs, causing shortness of breath, chest pain, and sometimes coughing up blood. The patient's dyspnea and crackles heard in the right lung field are suggestive of this condition.

Pneumonia: An infection of the lungs can cause symptoms like dyspnea, fever, cough, and crackles in the lung fields. The patient's fever and crackles heard in the right lung field could be indicative of this.

Acute respiratory distress syndrome (ARDS): ARDS is a severe lung condition that can occur as a complication of another illness or injury. It can cause shortness of breath, rapid breathing, and low oxygen levels. The patient's dyspnea and low oxygen saturation suggest this condition.

Renal colic: Flank pain could be indicative of a kidney stone, which can cause severe pain as it passes through the urinary tract. The patient's bilateral flank pain could be suggestive of this.

Acute coronary syndrome: Chest pain and shortness of breath are common symptoms of a heart attack or unstable angina, especially in patients with risk factors such as hypertension. The patient's elevated blood pressure and tachycardia put her at risk for this condition.

Sepsis: Infection in the body can cause sepsis, which can lead to organ failure and a drop in blood pressure. The patient's fever, tachycardia, and clamminess may suggest sepsis.

Drug-induced lung injury: The patient's use of phendimetrazine tartrate, a weight loss medication, for 5 years could potentially cause lung damage and lead to symptoms such as dyspnea and crackles in the lung fields.

It is important to note that this list is not exhaustive and further medical evaluation and testing would be necessary to confirm a diagnosis and develop an appropriate treatment plan for the patient.


1.2. What are list of differential diagnosis of following case?: In 2021, a 58-year-old woman presented to the emergency department with dyspnea and bilateral flank pain. She presented with pallor and clamminess and had a blood pressure of 170/120 mmHg, heart rate of 120 beats/min, body temperature of 38.2°C, respiration rate of 30 breaths/min, oxygen saturation of 89% on room air, and a body mass index of 25.1 kg/m2 (height, 148 cm; weight, 55 kg). She had no medical history or significant family history but had been taking phendimetrazine tartrate for weight loss for 5 years. On physical examination, crackles were heard in the right lung field upon auscultation and the abdomen was soft without tenderness.
Laboratory findings revealed elevated levels of inflammatory markers, including a CRP of 29.5 mg/dL and an erythrocyte sedimentation rate (ESR) of 120 mm/hr. Furthermore, leukocytosis (14.82×103/μL) and normocytic anemia (hemoglobin, 9.9 g/dL; mean corpuscular volume, 90.7 fL) were detected, and her platelet count was normal. Suspicious acute kidney injury (blood urea nitrogen, 25 mg/dL; creatinine, 1.66 mg/dL) and liver injury (aspartate aminotransferase, 179 IU/L; alanine aminotransferase, 106 IU/L) were observed (Table 1). Arterial blood gas analysis revealed mixed metabolic-respiratory acidosis with markedly elevated lactate levels (20 mmol/L). Chest radiography revealed bilateral diffuse infiltrations (Fig. 1A). Chest and abdominal computed tomography (CT) revealed a round mass lesion measuring 3.8 cm in length with heterogeneous contrast enhancement in the left paravertebral area (Fig. 2A, 2B). Fig. 1. 
(A) Chest X-ray performed at admission shows bilateral lung infiltrations. (B) Follow-up chest X-ray performed 24-hour after admission shows prominent resolution of the lung infiltrations.Fig. 2. 
(A) Abdominal CT scan demonstrates the presence of a 3.8 cm-long round mass originating from the left paravertebral area. Non-enhanced attenuation of the mass reaches more than 20 Hounsfield units (arrow). (B) In the arterial phase, the tumor is heterogeneously enhanced with partial cystic changes. (C) 18F-fluorodeoxyglucose PET-CT scan demonstrates increased uptake (arrow) in the mass originating in the left paravertebral area and no metastases. CT, computed tomography; PET, positron emission tomography.  Table 1.
Laboratory results at diagnosis and after surgery
Variable	At diagnosis	POD 4	Range
White blood cell (×103/μL)	14.8	7.0	4–10
Hemoglobin (g/dL)	9.9	10.2	12–16
Mean corpuscular volume (fL)	90.7	85.6	80–98
Platelets (×103/μL)	325	250	140–440
Hemoglobin A1c (%)	6.6	NA	4.4–6.3
C-reactive protein (mg/dL)	29.5	7.5	0–0.5
ESR (mm/hr)	120	NA	0–25
Interleukin-6 (pg/mL)	16.5	NA	0–7.0
Blood urea nitrogen (mg/dL)	37	13	5–20
Creatinine (mg/dL)	2.42	0.57	0.50–0.90
Aspartate aminotransferase (IU/L)	179	13	5–50
Alanine aminotransferase (IU/L)	106	8	5–50
Troponin-I (ng/mL)	0.841	0.006	0–0.041
Creatine kinase (ng/mL)	5.3	1.5	0.6–6.3
NT-proBNP (pg/mL)	35,000.0 	161.8	≤247.0
Catecholamines and metanephrines			
24-hr urinary metanephrine (mg/day)	2.12	0.25	0–0.71
Plasma norepinephrine (pg/mL)	1,588	462	70–150
Plasma epinephrine (pg/mL)	18	22	0–110
Plasma normetanephrine (nmol/L)	2.27	3.57	<0.90
Plasma metanephrine (nmol/L)	0.04	0.08	<0.50
POD, postoperative day; ESR, erythrocyte sedimentation rate; NA, not available; NT-proBNP, N-terminal prohormone of brain natriuretic peptide. Considering the sepsis of unknown origin and acute respiratory distress syndrome, the patient was sedated, intubated, and admitted to the intensive care unit. Within a 24-hour period of starting broad-spectrum antibiotics (vancomycin, meropenem, azithromycin) and mechanical ventilation, chest radiography showed rapid resolution of the lung infiltrations (Fig. 1B). However, the high fever and uncontrolled hypertension persisted in the patient. In addition, the patient’s troponin-I (0.841 ng/mL), creatinine kinase (5.3 ng/mL), and N-terminal prohormone of brain natriuretic peptide (NT-proBNP; 35,000 pg/mL) levels were elevated (Table 1). A bedside transthoracic echocardiogram showed hypokinetic mid inferior and apical segments and a reduced left ventricular ejection fraction of 38%; however, the echocardiogram could not explain the patient’s fever and paroxysmal hypertension.
The patient was referred to an endocrinologist for an incidentally discovered extra-adrenal mass and clinical signs and symptoms suggesting the likelihood of PPGL (such as pallor, palpitations, and tachycardia). In urinary and plasma catecholamine and metanephrine analysis, the 24-hour urinary metanephrine (2.12 mg/day; range, 0–0.71 mg/day), plasma norepinephrine (1,588 pg/mL; range, 70–150 pg/mL), and normetanephrine (2.27 nmol/L; range, <0.90 nmol/L) were elevated, whereas plasma epinephrine (18 pg/mL; range, 0–110 pg/mL), and metanephrine (0.04 nmol/L; range, <0.50 nmol/L) were normal (Table 1). In addition, the plasma IL-6 concentration appeared to be elevated (16.5 pg/mL; range, 0–7.0 pg/mL). Since somatostatin receptor positron emission tomography (PET)/CT was not available in our hospital, 18F-fluorodeoxyglucose PET/CT was the second choice, which showed increased uptake in the left paravertebral mass, without metastases (Fig. 2C).
The differential diagnosis for this case would include:

Sepsis: The patient presents with elevated levels of inflammatory markers, including CRP and ESR, leukocytosis, and a suspected acute kidney injury, suggesting the possibility of sepsis.
Acute respiratory distress syndrome (ARDS): The patient presents with dyspnea, bilateral infiltrates on chest radiography, and low oxygen saturation, indicating ARDS.
Pneumonia: The presence of crackles in the right lung field on auscultation and bilateral infiltrates on chest radiography suggest the possibility of pneumonia.
Pulmonary embolism: Dyspnea and bilateral infiltrates on chest radiography can also be a sign of pulmonary embolism.
Acute kidney injury (AKI): Elevated levels of blood urea nitrogen and creatinine suggest the possibility of AKI.
Liver injury: Elevated levels of liver enzymes suggest the possibility of liver injury.
Malignancy: The presence of a round mass lesion measuring 3.8 cm in length with heterogeneous contrast enhancement in the left paravertebral area on chest and abdominal CT scan suggests the possibility of malignancy.
Drug-induced injury: The patient had been taking phendimetrazine tartrate for weight loss for 5 years, which could have caused drug-induced injury to the liver and/or kidneys.


1.3. What are therapeutic modalities of functional paraganglioma? 
The treatment of functional paragangliomas depends on several factors, including the location and size of the tumor, its metastatic potential, and the presence or absence of symptoms. The following are the therapeutic modalities of functional paragangliomas:

Surgical resection: Surgical resection is the primary treatment for functional paragangliomas. The goal is to completely remove the tumor without damaging the surrounding structures. The surgery is usually performed by a specialized surgeon, and the success rate is high, especially if the tumor is small and localized.

Radiation therapy: Radiation therapy may be used to shrink or control the growth of the tumor if surgery is not an option, or if the tumor is not completely removed during surgery. It may also be used to relieve symptoms such as pain or bleeding.

Chemotherapy: Chemotherapy is rarely used to treat functional paragangliomas. However, it may be considered if the tumor has spread to other parts of the body and cannot be surgically removed.

Hormone therapy: Hormone therapy may be used to control the symptoms of functional paragangliomas that produce excessive amounts of hormones. This therapy may involve the use of medications that block the effects of hormones or reduce the production of hormones.

Surveillance: Regular monitoring of functional paragangliomas may be recommended to detect any changes in size or symptoms. This may involve regular imaging tests, such as CT scans or MRI scans, as well as blood tests to monitor hormone levels.

The choice of therapy depends on the individual case and requires a multidisciplinary approach involving an endocrinologist, oncologist, surgeon, and other specialists as needed.


2. Answers on case 2

2.1. What are a list of differential diagnoses of the following case: A 57-year-old man, 173 cm tall and weighing 99 kg, was scheduled for general anesthesia to undergo cardiac radiofrequency catheter ablation (RFCA) due to symptomatic persistent atrial fibrillation and flutter. The patient was diagnosed with hypertension but had no history of chest pain to suspect coronary disease. The echocardiography showed normal wall motion and ejection fraction with concentric left ventricular hypertrophy and mild diastolic dysfunction. The patient had no history of allergies, and the other preoperative laboratory tests were normal.

When the patient entered the cardiac angiography room, routine monitoring systems including non-invasive blood pressure, pulse oximetry, and electrocardiogram (ECG) were implemented. His initial vital signs were a blood pressure of 138/76 mmHg, pulse oxygen saturation of 97%, and heart rate of 114 beats/min with atrial fibrillation. General anesthesia was induced with 400 mg of thiopental and 90 mg of rocuronium. Endotracheal intubation was done, and anesthesia was maintained with 2–3% sevoflurane in 50% oxygen/air. Invasive arterial blood pressure was monitored continuously at the femoral artery from the femoral sheath for RFCA. His vital signs were maintained within a systolic blood pressure of 80–120 mmHg, pulse oxygen saturation of 98–100%, and heart rate of 70–130 beats/min during the procedure. An additional 50 mg of rocuronium was administered to maintain muscle relaxation, so the total dose of rocuronium was 140 mg.

The RFCA was completed uneventfully and took 3 h and 15 min. The ECG and other vital signs were normal. We stopped sevoflurane administration and gave him 400 mg of sugammadex (BridionⓇ, Merck and Co., USA). Within two minutes of the sugammadex administration, the ECG suddenly demonstrated ST elevation on the inferior leads, so an occlusion of the right coronary artery was strongly suspected (Fig. 1). His vital signs included a blood pressure of 80/57 mmHg, pulse oxygen saturation of 100%, and heart rate of 77 beats/min. There were no signs of hypersensitivity reactions, such as urticaria, wheals, swelling, or increased airway pressure.

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Based on the provided case description, some of the differential diagnoses could include:

Acute myocardial infarction: This is the most likely diagnosis given the sudden onset of ST elevation on the inferior leads of the ECG, and the suspicion of occlusion of the right coronary artery. The patient's age, hypertension, and history of atrial fibrillation could all be contributing risk factors for coronary artery disease.

Pulmonary embolism: Although less likely, pulmonary embolism can also cause ST segment changes on ECG and may occur during or after surgery. The patient's weight and surgery could also be contributing risk factors for pulmonary embolism.

Aortic dissection: Aortic dissection can present with chest pain and ECG changes, but the absence of chest pain makes it less likely.

Pericarditis: Acute pericarditis can also cause ECG changes similar to myocardial infarction, but it typically presents with chest pain, which is not present in this case.

Takotsubo cardiomyopathy: This is a stress-induced cardiomyopathy that can mimic acute myocardial infarction, but it typically presents with apical ballooning on echocardiogram, which is not present in this case.

Arrhythmia: Although less likely, a new arrhythmia could be responsible for the ECG changes.

It is important to note that a thorough evaluation, including a physical exam, laboratory tests, and imaging studies, would be needed to confirm the diagnosis and rule out other potential causes.


2.2. What is a list of differential diagnoses of the following case: A 57-year-old man, 173 cm tall and weighing 99 kg, was scheduled for general anesthesia to undergo cardiac radiofrequency catheter ablation (RFCA) due to symptomatic persistent atrial fibrillation and flutter. The patient was diagnosed with hypertension but had no history of chest pain to suspect coronary disease. The echocardiography showed normal wall motion and ejection fraction with concentric left ventricular hypertrophy and mild diastolic dysfunction. The patient had no history of allergies, and the other preoperative laboratory tests were normal.

When the patient entered the cardiac angiography room, routine monitoring systems including non-invasive blood pressure, pulse oximetry, and electrocardiogram (ECG) were implemented. His initial vital signs were a blood pressure of 138/76 mmHg, pulse oxygen saturation of 97%, and heart rate of 114 beats/min with atrial fibrillation. General anesthesia was induced with 400 mg of thiopental and 90 mg of rocuronium. Endotracheal intubation was done, and anesthesia was maintained with 2–3% sevoflurane in 50% oxygen/air. Invasive arterial blood pressure was monitored continuously at the femoral artery from the femoral sheath for RFCA. His vital signs were maintained within a systolic blood pressure of 80–120 mmHg, pulse oxygen saturation of 98–100%, and heart rate of 70–130 beats/min during the procedure. An additional 50 mg of rocuronium was administered to maintain muscle relaxation, so the total dose of rocuronium was 140 mg.

The RFCA was completed uneventfully and took 3 h and 15 min. The ECG and other vital signs were normal. We stopped sevoflurane administration and gave him 400 mg of sugammadex (BridionⓇ, Merck and Co., USA). Within two minutes of the sugammadex administration, the ECG suddenly demonstrated ST elevation on the inferior leads, so an occlusion of the right coronary artery was strongly suspected (Fig. 1). His vital signs included a blood pressure of 80/57 mmHg, pulse oxygen saturation of 100%, and heart rate of 77 beats/min. There were no signs of hypersensitivity reactions, such as urticaria, wheals, swelling, or increased airway pressure.

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Fig. 1.
Electrocardiogram (ECG). (A) At the end of radiofrequency catheter ablation, the ECG showed normal. (B) After sugammadex administration, it suddenly demonstrated ST elevation on the inferior leads.

Coronary angiography was initiated immediately, simultaneously with the infusion of norepinephrine at 16 μg/min and dopamine at 20 μg/kg/min. A little later, the patient’s heart rate gradually decreased, and the ECG showed pulseless electrical activity. Cardiac movement was not identified on X-ray fluoroscopy, so chest compressions were started immediately. Epinephrine (1 mg) was injected, and an external pacemaker was applied, but he did not respond. Chest compression was continued and an additional 1 mg of epinephrine was injected. At that time, coronary angiography demonstrated total collapse of the right coronary artery, and 0.2 mg of intra-coronary nitroglycerin was injected. The right coronary artery was partially dilated, and the ECG showed ventricular fibrillation. Cardioversion with 200 J was done, and the ECG returned to normal sinus rhythm. Additional intra-coronary nitroglycerin was injected, and the vasospasm of the right coronary artery was completely resolved (Fig. 2). Afterward, the patient underwent a left coronary artery angiogram, which revealed a normal pattern. His blood pressure became normal with the infusion of norepinephrine at 8 μg/min, dopamine at 10 μg/kg/min, and nitroglycerin at 10 μg/kg/min. However, because the echocardiography showed abnormal wall motion and low ejection fraction, extracorporeal membrane oxygenation was applied, and he was transferred to the intensive care unit.

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Fig. 2.
Left anterior oblique view on coronary angiography. (A) After cardiac arrest, the right coronary artery totally collapsed. (B) After the first injection of intra-coronary nitroglycerin, the right coronary artery was partially dilated. (C) After an additional injection of intra-coronary nitroglycerin, the vasospasm of the right coronary artery was completely resolved. Black arrow: right coronary artery.

On postoperative day 1, the patient’s trachea was extubated and extracorporeal membrane oxygenation was removed. On postoperative day 2, his vital signs remained stable without vasopressors and he was transferred to the general ward. There were no symptoms of chest pain, and there was no clinical basis to suspect coronary disease. The echocardiography showed normal wall motion and ejection fraction, and the ECG showed normal. He was discharged on postoperative day 5 without sequelae.  
Based on the information provided, the following are some possible differential diagnoses:

Coronary artery spasm: The sudden onset of ST elevation in the inferior leads on the ECG after sugammadex administration strongly suggests coronary artery spasm. This is a rare but potentially life-threatening complication of anesthesia and is more common in patients with underlying coronary artery disease or risk factors such as hypertension.

Acute coronary syndrome: Acute coronary syndrome, including acute myocardial infarction (AMI), is another potential diagnosis. Although the patient had no history of chest pain, AMI can occur without symptoms, especially in patients with diabetes or hypertension.

Hypotension and cardiac arrest: The patient's hypotension and subsequent cardiac arrest could be due to a number of causes, including hypovolemia, cardiogenic shock, pulmonary embolism, or arrhythmias. However, given the sudden onset and the ECG changes, coronary artery spasm or acute coronary syndrome are the most likely causes.

Anaphylaxis: Although the patient had no history of allergies and there were no signs of hypersensitivity reactions, anaphylaxis is always a potential diagnosis in any patient who undergoes general anesthesia.

Arrhythmia: The patient's preoperative diagnosis of persistent atrial fibrillation and flutter suggests that arrhythmia could be a contributing factor to the patient's cardiac arrest. However, it is unlikely that arrhythmia alone would cause the sudden onset of ST elevation on the ECG.

It is important to note that the definitive diagnosis would require further investigation, including laboratory tests, imaging studies, and clinical evaluation.


2.3. What are the therapeutic modalities of the total collapse of the right coronary artery caused by sugammadex hypersensitivity? 
The treatment for total collapse of the right coronary artery caused by sugammadex hypersensitivity includes immediate initiation of coronary angiography to evaluate the extent of the occlusion and administration of medications such as norepinephrine, dopamine, and nitroglycerin to support blood pressure and cardiac function. Intra-coronary nitroglycerin can be used to alleviate vasospasm of the coronary artery. Cardioversion with defibrillation may be necessary to treat ventricular fibrillation. Extracorporeal membrane oxygenation (ECMO) can be used to support cardiac function in cases of severe cardiac dysfunction. Ultimately, the management of the patient should be tailored to their individual condition and the expertise of the medical team.


3. Answers on case 3

3.1  What is a list of differential diagnoses of the following case: A 10-month-old female presented with eyelid edema and massive proteinuria and was admitted to an outside hospital in September 2007. She was born at a gestational age of 40 weeks and a birth weight of 2.94 kg, delivered vaginally without perinatal problems. The patient was the only child with no remarkable family history of renal disease. Upon admission, the patient was treated with a total dose of oral steroids for 4 weeks. Symptoms seemed to subside in the first 2 weeks, but edema and proteinuria worsened in the following 2 weeks. After 4 weeks of steroid treatment, the patient was transferred to our center.
The differential diagnoses of a 10-month-old female with eyelid edema and massive proteinuria who was admitted to an outside hospital include:

Minimal Change Disease (MCD)
Nephrotic Syndrome
Focal Segmental Glomerulosclerosis (FSGS)
Membranous Nephropathy
Systemic Lupus Erythematosus (SLE)
IgA Nephropathy
Henoch-Schönlein Purpura (HSP)
Acute Post-Streptococcal Glomerulonephritis (APSGN)
Alport Syndrome
Congenital Nephrotic Syndrome (CNS)
Further diagnostic tests such as kidney biopsy, serum and urine tests, and imaging studies can help to confirm the diagnosis.


3.2.  What is a list of differential diagnoses of the following case: A 10-month-old female presented with eyelid edema and massive proteinuria and was admitted to an outside hospital in September 2007. She was born at a gestational age of 40 weeks and a birth weight of 2.94 kg, delivered vaginally without perinatal problems. The patient was the only child with no remarkable family history of renal disease. Upon admission, the patient was treated with a total dose of oral steroids for 4 weeks. Symptoms seemed to subside in the first 2 weeks, but edema and proteinuria worsened in the following 2 weeks. After 4 weeks of steroid treatment, the patient was transferred to our center.When transferred, her height was 69.5 cm (3–10 p), and her weight was 7.7 kg (10–25 p). She showed mild periorbital swelling and abdominal distension. The initial laboratory findings were as follows. Serum albumin 1.6 g/dl, serum BUN/creatinine 4/0.4 mg/dl, serum cholesterol 712 mg/dl, IgG/A/M respectively 236/33/131 mg/dl, and C3/C4 103/16 mg/dl. Serological testing was negative for HBV, HCV, HIV, and RPR/VDRL. Urine dipstick examination showed albuminuria (3+) and a random urine protein/creatinine ratio of 27.47 mg/mg. Kidney ultrasonography findings were unremarkable, with no signs of increased echogenicity or renal cysts. A kidney biopsy was performed, and its pathology was consistent with focal segmental glomerulosclerosis (FSGS) of the perihilar type. Four of 101 glomeruli (3.9%) showed global sclerosis, three (2.9%) showed segmental sclerosis, and five (5.0%) showed small crescentic lesions. Focal GBM abnormalities were noted ultra-structurally, with widely effaced epithelial foot processes and a moth-eaten appearance. The patient did not show any remarkable extrarenal abnormalities. Upon admission in November 2007, at the age of 12 months, she was tested for known mutations in the NPHS2, WT1, and ACTN genes using Sanger sequencing, but all were negative.
The differential diagnoses for a 10-month-old female presenting with eyelid edema and massive proteinuria could include:

Focal segmental glomerulosclerosis (FSGS)
Minimal change disease (MCD)
Membranous nephropathy (MN)
IgA nephropathy (IgAN)
Henoch-Schonlein purpura (HSP)
Lupus nephritis (LN)
Alport syndrome
Congenital nephrotic syndrome
Congenital infections (e.g., toxoplasmosis, cytomegalovirus)
Post-infectious glomerulonephritis (PIGN)
Diabetes mellitus
Based on the patient's laboratory findings and kidney biopsy, the most likely diagnosis is FSGS. However, other possibilities cannot be ruled out and would need further investigation.

3. 3. What are the therapeutic modalities of infantile steroid-resistant nephrotic syndrome?
The therapeutic modalities of infantile steroid-resistant nephrotic syndrome (SRNS) depend on the underlying cause of the condition. Some possible treatments include:

Immunosuppressive therapy: Drugs such as cyclosporine, tacrolimus, mycophenolate mofetil, and rituximab may be used to suppress the immune system and reduce inflammation in the kidneys.

Plasma exchange or immunoadsorption: These procedures involve removing antibodies and other harmful substances from the blood to reduce inflammation in the kidneys.

Supportive therapy: This includes measures to control blood pressure and reduce proteinuria, such as ACE inhibitors or angiotensin receptor blockers.

Renal replacement therapy: In severe cases where kidney function is severely compromised, dialysis or kidney transplant may be necessary.

Novel therapies: Emerging treatments for SRNS include agents that target podocyte function, such as galactose-deficient IgA1 (Gd-IgA1) and anti-CD20 antibodies.

It is important to note that the choice of therapy will depend on the individual patient's case and should be determined by a specialist in pediatric nephrology.


4. Answers on case 4

4.1. What is a list of differential diagnoses of the following case: The patient was a 6‐year‐old Korean boy and the only child of nonconsanguineous healthy parents pregnant by in vitro fertilization. He was born appropriate for gestational age at full term. In addition, he was born through the elective cesarean section with normal Apgar scores and no perinatal complications. He was brought to medical attention because of fever and persistent jaundice at age of 2 months. In the physical examination, the patient was generally icteric. The liver and spleen were palpable 3 finger's breadth below the costal margin
Based on the information provided, the differential diagnoses for this case may include:

Neonatal hepatitis: Inflammation of the liver that occurs within the first 28 days of life. It can be caused by a viral infection, metabolic disorders, or exposure to drugs or toxins.

Biliary atresia: A rare disease of the liver and bile ducts that occurs in infants. It is characterized by the progressive destruction or absence of the extrahepatic bile ducts, leading to bile buildup and liver damage.

Choledochal cyst: A congenital abnormality of the biliary system that involves a dilation of the common bile duct. It can cause bile flow obstruction and may lead to liver damage.

Galactosemia: A rare genetic disorder that affects the body's ability to metabolize galactose, a sugar found in milk and dairy products. It can cause liver damage and other complications if left untreated.

Alpha-1 antitrypsin deficiency: A rare genetic disorder that can lead to liver disease and lung disease. It is caused by a deficiency of the alpha-1 antitrypsin protein, which normally protects the liver and lungs from damage.

Wilson's disease: A rare genetic disorder that causes copper to accumulate in the liver and other organs, leading to liver damage and other complications.

Hemolytic disease of the newborn: A condition that occurs when a baby's red blood cells break down faster than they can be replaced. It can be caused by a variety of factors, including blood group incompatibility between mother and baby.

Sepsis: A life-threatening condition caused by an infection in the bloodstream. It can lead to multiple organ failure, including liver failure.

Autoimmune hepatitis: A chronic inflammatory disorder of the liver in which the immune system attacks the liver cells, causing damage and scarring.

Congenital infections: Infections that are present at birth, such as cytomegalovirus, toxoplasmosis, or rubella, can cause liver damage and other complications.



4.2 What is a list of differential diagnoses of the following case: The patient was a 6‐year‐old Korean boy and the only child of nonconsanguineous healthy parents pregnant by in vitro fertilization. He was born appropriate for gestational age at full term. In addition, he was born through the elective cesarean section with normal Apgar scores and no perinatal complications. He was brought to medical attention because of fever and persistent jaundice at age of 2 months. In the physical examination, the patient was generally icteric. The liver and spleen were palpable 3 finger's breadth below the costal margin. Laboratory tests revealed anemia (Hb 8.5 g/dl); normal leukocyte and platelet counts; increased AST 214 IU/L (≤40 IU/L), ALT 95 IU/L (≤40 IU/L), γ‐GT 103 IU/L (8–61 IU/L), ALP 405 IU/L (40–120 IU/L); total bilirubin 10.0 mg/dl (0.2–1.2 mg/dl); direct bilirubin 7.9 mg/dl (≤0.5 mg/dl); PT 1.26 INR (0.8–1.3 INR); and aPTT 40.8 s (24–33 s). These laboratory tests suggest neonatal cholestatic liver disease. The total cholesterol 145 mg/dl (≤199 mg/dl), triglyceride 167 mg/dl (≤199 mg/dl), and HDL‐cholesterol 44 mg/dl (≥40 mg/dl) were normal. Tests for congenital infection, viral hepatitis, and metabolic screening were negative. Abdomen ultrasound and liver MRI showed marked hepatomegaly with multifocal nodularity and splenomegaly (Figure 1A,B). The liver biopsy demonstrated a giant cell transformation with ballooning degeneration, pinkish intracytoplasmic globules, and perisinusoidal fibrosis (Figure 1C). The whole‐exome sequencing was done and it revealed compound heterozygous missense mutations in NPC1 (c.338G>A:p.C113Y, c.2780C>T:p.A927V), confirming the diagnosis of NPC at age of 6 months. The Filipin test was positive in his skin fibroblasts. The concentration of the biomarker lyso‐SM‐509 was increased to 1.5 ng/ml (<0.9 ng/ml).

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FIGURE 1
Images and liver biopsy at diagnosis of NPC (at 6 months old, A–C) and HCC (at 6 years old, D–F). (A) Coronal T1‐weighted image of MRI, (B) coronal T2‐weighted image of MRI, (C) liver biopsy showing hepatitis with lipid‐laden macrophages and perisinusoidal fibrosis (hematoxylin and eosin [H&E], ×200), (D) abdominal CT scan showing liver cirrhosis with a large hypervascular mass and splenomegaly, (E) chest CT scan showing multiple pulmonary metastases, (F) liver biopsy confirming confirms HCC of Edmondson–Steiner grade 2 ([H&E], ×200)

Since then, he continued regular clinic visits every 6 months. Physical examination, developmental assessment, and laboratory tests were performed every visit. Annual abdominal ultrasound was carried out except for the previous visit. At that time, his parents canceled the scheduled test at their request. The clinical course and parameters were described in Table 1 and Figure 2. His height and weight were in the third percentile for age (Figure 2A). Regarding developmental milestones, he was just crawling at age 1 year and showed gross and fine motor delay. Miglustat (Zavesca®, Actelion Pharmaceuticals, Allschwil, Switzerland) treatment was initiated. He could walk alone at age 3 years. Otherwise, no further neurological sign was observed until the age of 6 years with normal intelligence. Systemic symptoms including cirrhotic liver with elevated transaminases and splenomegaly were stationary for a while (Figure 2B,C upper panel). Leaving a lot to be desired, the alpha‐fetoprotein (AFP) level was not checked for the last few years (Figure 2B lower panel).

TABLE 1
Clinical follow‐up data of the patient

Age	Height SDS	Weight SDS	Development	Hepatomegaly (FB)	Splenomegaly (FB)	AST (IU/L)	ALT (IU/L)	PT (INR)	AFP (ng/ml)	Abdomen ultrasonography
2m	0.29	0.13	Head control	3	3	214	95	1.26	65,700	Cirrhotic multinodular liver, splenomegaly (8.6 cm)
6m	0.27	−1.39	Roll over	3	3	196	156	1.17	18,800	Cirrhotic multinodular liver, splenomegaly (7.5 cm)
1y	−1.12	−1.54	Crawling (motor delay since then)	2	2	164	178	1.19	4660	Cirrhotic multinodular liver, splenomegaly (8.2 cm)
2y	−1.38	−1.88	Stand with support	2	2	219	177	1.16	NC	Cirrhotic multinodular liver, splenomegaly (8.3 cm)
3y	−2.3	−2.39	Walk alone	2	2	154	131	1.15	NC	Cirrhotic multinodular liver, splenomegaly (8.6 cm)
4y	−2.4	−2.68	Climb stairs with hand support	2	3	126	86	1.11	NC	Cirrhotic multinodular liver, splenomegaly (10.42 cm)
5y	−1.98	−2.47	Hop on one foot	2	3	126	80	1.13	NC	NA
6y	−1.72	−2.11	Apparently normal development	4	4	192	78	1.14	385,202	A large nodule with hyperechoic foci newly appeared in cirrhotic liver, severe splenomegaly (15.1 cm). HCC was identified.
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Abbreviations: FB, finger's breadth; NA, not available; NC, not checked.

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FIGURE 2
Clinical parameters and images of the patient. (A) Growth chart, (B) laboratory findings including transaminase, INR, and AFP, (C) liver ultrasound images showing cirrhotic liver with nodules at the last visit (upper panel), a large hyperechoic mass newly appeared at diagnosis of HCC (lower panel)

At the age of 6 years, he was brought to the emergency room with dizziness, sweating, and lethargy. Physical examination demonstrated enlarged liver in hard consistency, palpable 4 finger's breadth below the costal margin with the palpable spleen. The laboratory tests revealed severe hypoglycemia (serum glucose 28 mg/dl) and increased AST 192 IU/L, ALT 78 IU/L, ALP 206 IU/L, and PT 1.14 INR. An intravenous glucose infusion with a 10% dextrose was done and serum glucose level was raised to 144 mg/dl. He revisited the emergency room with the same symptoms on the following day. Serum glucose level was 27 mg/dl. Further laboratory tests at critical samples revealed low insulin 0.6 μIU/ml (0.9–8.5 μIU/ml), C‐peptide 0.10 μIU/ml (0.48–3.3 ng/ml), and β‐hydroxybutyrate 0.2 mmol/L (≤0.6 mmol/L), excluding hyperinsulinism. Serum growth hormone, cortisol, and thyroid hormone levels were normal. An abdominal ultrasound showed multiple hyperechoic nodules in the liver and splenomegaly (Figure 2C lower panel). Additional liver dynamic computed tomography (CT) demonstrated cirrhosis and there were multiple malignant hepatic tumors with a large vascularized mass of 10 cm diameter in the right liver (Figure 1D). A chest CT showed multiple lung metastases (Figure 1E).
The patient is a 6-year-old Korean boy who presented with fever and persistent jaundice at the age of 2 months. Laboratory tests showed anemia, increased AST, ALT, γ‐GT, ALP, total bilirubin, direct bilirubin, PT, and aPTT, suggesting neonatal cholestatic liver disease. Abdomen ultrasound and liver MRI showed marked hepatomegaly with multifocal nodularity and splenomegaly. The liver biopsy demonstrated giant cell transformation with ballooning degeneration, pinkish intracytoplasmic globules, and perisinusoidal fibrosis. The patient was diagnosed with NPC at the age of 6 months based on compound heterozygous missense mutations in NPC1 (c.338G>A:p.C113Y, c.2780C>T:p.A927V), positive Filipin test in his skin fibroblasts, and increased lyso-SM-509 biomarker concentration. The patient received regular clinic visits every 6 months, and annual abdominal ultrasound except for the previous visit, which was canceled at the parents' request. The patient's height and weight were in the third percentile for age. The developmental milestones showed gross and fine motor delay. The patient received miglustat treatment, could walk alone at the age of 3 years, and had normal intelligence until the age of 6 years. Systemic symptoms, including cirrhotic liver with elevated transaminases and splenomegaly, were stationary for a while. However, the alpha‐fetoprotein (AFP) level was not checked for the last few years. Differential diagnoses of the patient's condition may include other causes of neonatal cholestatic liver disease such as biliary atresia, alpha-1-antitrypsin deficiency, progressive familial intrahepatic cholestasis, Alagille syndrome, and cystic fibrosis. The patient's hepatomegaly and splenomegaly suggest liver cirrhosis, which may have been caused by chronic liver disease, metabolic disorders, or other causes. Finally, the possibility of liver cancer such as hepatocellular carcinoma should also be considered given the patient's history of chronic liver disease.



4.3. What are the therapeutic modalities of infantile hepatocellular carcinoma with advanced metastasis?
!
Infantile hepatocellular carcinoma (iHCC) is a rare form of liver cancer that occurs in children less than 3 years old. When iHCC is diagnosed at an advanced stage with metastasis, treatment options can be limited. However, several therapeutic modalities are available to manage iHCC with advanced metastasis, including:

Chemotherapy: Chemotherapy is often the first-line treatment for advanced iHCC. Chemotherapy drugs such as cisplatin, doxorubicin, and vincristine are commonly used to shrink tumors and slow their growth.

Liver transplantation: In some cases, a liver transplant may be recommended for children with advanced iHCC. This is an option if the tumor has not spread outside the liver and if the child is healthy enough to undergo surgery.

Radiation therapy: Radiation therapy is not commonly used for iHCC, but it may be an option if the tumor is not responding to other treatments. Radiation therapy uses high-energy radiation to destroy cancer cells.

Targeted therapy: Targeted therapy is a newer type of cancer treatment that targets specific genes or proteins that are involved in the growth and spread of cancer cells. There are currently no targeted therapies approved specifically for iHCC, but some clinical trials are investigating their effectiveness.

Palliative care: When iHCC has advanced to the point where a cure is not possible, palliative care can be used to manage symptoms and improve quality of life. Palliative care can include pain management, nutritional support, and other supportive treatments.

It's important to note that the treatment of advanced iHCC is complex and requires a multidisciplinary approach involving a team of healthcare professionals, including pediatric oncologists, hepatologists, surgeons, and radiation oncologists. The optimal treatment plan will depend on several factors,

5. Answers to case 5

5.1.What is a list of differential diagnoses of the following case: A 39-year-old woman without any other medical or family history presented to the emergency department of a hospital with uncontrolled fever, chills, and myalgia that had affected her intermittently for the previous 5 months. Upon an original examination at a local hospital, she was prescribed medication such as non-steroidal anti-inflammatory drugs, but her symptoms were not controlled. An evaluation at the local hospital 1 month earlier by transthoracic echocardiography (TTE), transesophageal echocardiography, and positron emission tomography resulted in a diagnosis of left atrial myxoma as the cause of her continued fever. Although surgery was planned 2 months later, she was referred to Asan Medical Center due to the aggravation of high temperature (over 38.3°C), headache, general pain, and myalgia.

A physical examination in the emergency room showed that her blood pressure was 111/69 mm Hg, her heart rate was 110 beats/min, her body temperature was 38.2°C, and her respiratory rate was 18/min.
There are many possible differential diagnoses for a 39-year-old woman with uncontrolled fever, chills, and myalgia that have affected her intermittently for the previous 5 months, and who has been diagnosed with left atrial myxoma. Here are some possibilities:

Infectious diseases: Various bacterial, viral, and parasitic infections can cause intermittent fever, chills, and myalgia, including tuberculosis, endocarditis, Lyme disease, Q fever, malaria, and others.

Autoimmune diseases: Autoimmune disorders such as lupus, rheumatoid arthritis, and vasculitis can cause persistent or recurrent fever, chills, and myalgia, especially if the patient has other symptoms such as joint pain, rashes, or fatigue.

Cancer: Certain types of cancer, such as lymphoma, leukemia, and renal cell carcinoma, can cause fevers, chills, and myalgia.

Drug reactions: Medications can sometimes cause fever and other flu-like symptoms, including non-steroidal anti-inflammatory drugs (NSAIDs).

Endocrine disorders: Thyroid disorders, adrenal insufficiency, and other hormonal imbalances can cause fever and other systemic symptoms.

Other cardiac abnormalities: In addition to left atrial myxoma, other cardiac conditions such as infective endocarditis, pericarditis, or myocarditis can cause fever, chills, and myalgia.

Neurological disorders: Some neurological conditions, such as multiple sclerosis, can cause intermittent fever and other systemic symptoms.

Systemic inflammatory response syndrome (SIRS): SIRS is a potentially life-threatening condition that can be caused by a variety of infections, injuries, or other medical conditions. Symptoms include fever, tachycardia, and increased respiratory rate.

Factitious fever: Factitious fever is a rare condition in which a patient deliberately falsifies symptoms of fever in order to gain attention or sympathy.

Environmental factors: Exposure to certain toxins, such as heavy metals or pesticides, can cause fever and other systemic symptoms.

It is important to note that this list is not exhaustive and other factors may also be present in the patient's history or physical exam that may point to other diagnoses. The patient's medical team will need to conduct further tests and examinations to arrive at an accurate diagnosis.


5.2 What is a list of differential diagnoses of the following case: A 39-year-old woman without any other medical or family history presented to the emergency department of a hospital with uncontrolled fever, chills, and myalgia that had affected her intermittently for the previous 5 months. Upon an original examination at a local hospital, she was prescribed medication such as non-steroidal anti-inflammatory drugs, but her symptoms were not controlled. An evaluation at the local hospital 1 month earlier by transthoracic echocardiography (TTE), transesophageal echocardiography, and positron emission tomography resulted in a diagnosis of left atrial myxoma as the cause of her continued fever. Although surgery was planned 2 months later, she was referred to Asan Medical Center due to the aggravation of high temperature (over 38.3°C), headache, general pain, and myalgia.

A physical examination in the emergency room showed that her blood pressure was 111/69 mm Hg, her heart rate was 110 beats/min, her body temperature was 38.2°C, and her respiratory rate was 18/min. Laboratory data showed a white blood cell count of 10,200/L, a hemoglobin concentration of 12.7 dg/L, a platelet count of 243,000/mL, and a serum C-reactive protein concentration of 4.55 mg/dL. Daily blood and urine cultures following admission were negative for growing bacteria. Chest X-rays and electrocardiography were normal. Computed tomography showed a mass in her left atrium, abutting the interatrial septum and suggesting a myxoma. TTE showed a huge echogenic mass with a stalk, with the mass having irregular surfaces and being hypermobile (Fig. 1). Based on TTE, there was a suspicion that the mass posed a high risk of embolic infarction because of its shape. Thus, we decided to proceed with an urgent operation. Three days passed from hospitalization to surgery. Although vancomycin was administered for 2 days before surgery, an infectious disease physician recommended the discontinuation of antibiotic treatment, which we agreed to.

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Fig. 1
Echocardiography results. (A) Preoperative transthoracic echocardiogram. Apical 4-chamber view showing the large left atrial myxoma, visible as a huge 3.7×3.1 cm echogenic mass with a stalk. (B) Preoperative transthoracic echocardiogram. Parasternal long-axis view, showing the mass in the left atrium. (C) Postoperative transthoracic echocardiogram. Parasternal long-axis view showing that the mass in the left atrium had been removed.

The mass was approached using a 5 cm lateral mini-thoracotomy through an incision in the right fourth intercostal space. Cardiopulmonary bypass was performed through the right femoral artery using Perclose-ProGlide (Abbot Laboratories, Chicago, IL, USA) and the right femoral vein. The operation included antegrade infusion through root cannulation under conditions of moderate hypothermia. The total cardiopulmonary bypass time was 62 minutes and the aortic cross-clamp time was 30 minutes. The excised mass measured 3×4 cm, was oval in shape, had a broad 1-cm stalk, abutted the interatrial septum, and was very fragile (Fig. 2). The tumor, including the atrial septum, was resected. The defect site was closed with 4-0 Prolene. To find the cause of the fever, we requested biopsy tissue from the Department of Laboratory Medicine, extracted DNA, and performed pan-bacterial PCR.

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Fig. 2
Gross finding. The excised mass had an oval shape with a 1-cm-long stalk and was very fragile.

The patient was transferred to an intensive care unit after surgery and extubated 6 hours later. She was moved to the general ward on postoperative day 2. TTE on postoperative day 4 showed no remnant mass with a normal-sized left ventricle and normal systolic function, including an ejection fraction of 60%. A pathologic examination of the surgically excised mass confirmed the diagnosis of left atrial myxoma.
Possible differential diagnoses for a 39-year-old woman presenting with uncontrolled fever, chills, and myalgia for 5 months, along with a diagnosis of left atrial myxoma, may include:

Infectious diseases: Infections such as endocarditis, sepsis, tuberculosis, and Lyme disease can cause prolonged fever and myalgia. Blood and urine cultures were negative in this case, but a biopsy was performed to investigate the possibility of an infectious etiology.

Autoimmune disorders: Systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other autoimmune disorders can cause fever and myalgia. However, a lack of other relevant symptoms or medical history would make autoimmune diseases less likely.

Neoplastic disorders: In addition to the myxoma found in this patient, other neoplastic disorders such as lymphoma and leukemia can cause prolonged fever and myalgia.

Drug-induced fever: Some medications, such as antibiotics, anticonvulsants, and antihistamines, can cause drug-induced fever, and may be a consideration in this case, given that non-steroidal anti-inflammatory drugs were prescribed initially.

Endocrine disorders: Thyroid disorders and adrenal insufficiency can cause prolonged fever and myalgia, but again, a lack of other relevant symptoms or medical history makes these less likely.

Psychiatric disorders: Psychiatric disorders such as depression and anxiety can manifest as physical symptoms such as fever and myalgia. However, given the diagnosis of left atrial myxoma, this seems unlikely.

Further investigations, such as a thorough medical history, imaging studies, and laboratory tests, may be needed to narrow down the list of differential diagnoses and arrive at an accurate diagnosis.


5.3 What are the therapeutic modalities of the Hemophilus parainfluenzae infected left atrial myxoma?
It is not mentioned in the case that the patient had a Hemophilus parainfluenzae infection. However, assuming that the patient has a Hemophilus parainfluenzae infection associated with left atrial myxoma, the appropriate treatment would depend on the severity of the infection and the extent of the disease. Treatment of Hemophilus parainfluenzae infection typically involves antibiotics that are effective against the bacterium. The choice of antibiotics would depend on the sensitivity of the bacterium to specific antibiotics, as determined by laboratory testing. In cases of severe infection, surgical intervention may be necessary to remove the infected tissue, in this case, the left atrial myxoma. In addition, supportive care may be needed to manage symptoms such as fever, pain, and inflammation. It is important to note that any treatment plan should be determined by a physician who has evaluated the patient and has access to their medical history and test results.

6. Answers on case 6.

6.1. What is a list of differential diagnoses of the following neonate case: :A 36-year-old multipara visited the hospital at 34 + 2 weeks of gestation with increased amniotic fluid index. The ultrasonographic examination revealed no abnormal fetal findings. The amniotic fluid index was 29, suggesting polyhydramnios. Laboratory tests, including viral study, showed no specific findings. The local hospital’s routine prenatal checkups, including aneuploidy screening test, ultrasonography, and screening for gestational diabetes mellitus, also revealed no specific findings.

Subsequently, the patient presented at the hospital with regular uterine contractions at 35 + 5 weeks of gestation. She underwent an emergent cesarean section and gave birth to a girl. The neonatal birth weight was 2200 g, and the Apgar scores at 1, and 5 minutes were 5 and 8, respectively. The blood acid-base status was 6.989.

The neonate cried feebly and exhibited cyanosis and very weak response to stimuli. Chest retraction and stridor were also observed.
Based on the information provided, some possible differential diagnoses for this neonate's condition could include:

Respiratory distress syndrome (RDS): RDS is a condition that occurs in premature infants due to immature lung development. Symptoms can include rapid, shallow breathing, grunting, chest retractions, and cyanosis.

Meconium aspiration syndrome (MAS): MAS occurs when a baby inhales meconium (fecal matter) while still in the uterus or during the birth process. Symptoms can include difficulty breathing, cyanosis, rapid breathing, and a weak cry.

Transient tachypnea of the newborn (TTN): TTN is a condition in which a newborn has difficulty clearing fluid from the lungs after birth, causing breathing difficulties. Symptoms can include rapid breathing, chest retractions, and grunting.

Congenital heart disease (CHD): CHD is a group of conditions that affect the heart and can be present at birth. Symptoms can vary depending on the specific type of CHD, but can include cyanosis, rapid breathing, and poor feeding.

Neonatal sepsis: Neonatal sepsis is a bacterial infection that occurs in newborns. Symptoms can include poor feeding, lethargy, fever, and rapid breathing.

Hypoglycemia: Hypoglycemia is a condition in which the baby's blood sugar levels are too low. Symptoms can include lethargy, poor feeding, and a weak cry.

It is important to note that this list is not exhaustive, and other conditions could also be considered depending on the specific clinical presentation of the neonate. A thorough medical evaluation by a healthcare professional is necessary to determine the underlying cause of the neonate's symptoms.



6.2. What is a list of differential diagnoses of the following neonate case:: A 36-year-old multipara visited the hospital at 34 + 2 weeks of gestation with increased amniotic fluid index. The ultrasonographic examination revealed no abnormal fetal findings. The amniotic fluid index was 29, suggesting polyhydramnios. Laboratory tests, including viral study, showed no specific findings. The local hospital’s routine prenatal checkups, including aneuploidy screening test, ultrasonography, and screening for gestational diabetes mellitus, also revealed no specific findings.

Subsequently, the patient presented at the hospital with regular uterine contractions at 35 + 5 weeks of gestation. She underwent an emergent cesarean section and gave birth to a girl. The neonatal birth weight was 2200 g, and the Apgar scores at 1, and 5 minutes were 5 and 8, respectively. The blood acid-base status was 6.989.

The neonate cried feebly and exhibited cyanosis and very weak response to stimuli. Chest retraction and stridor were also observed. Hence, nasal continuous positive airway pressure was applied immediately. However, the saturation pulse oxygen level decreased to 75% and the chest retraction worsened. Therefore, endotracheal intubation was performed, and a surfactant was administered.

Chest radiography revealed decreased diaphragm motion; therefore, ultrasonographic and fluoroscopic examinations were conducted. Nevertheless, no specific findings were noted. The stridor persisted; hence laryngoscopic examination was performed; it revealed no movement in both the vocal cords, and BVCP was diagnosed (Fig. ​(Fig.11).

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Figure 1.
Laryngoscopic examination. It shows no movement in both vocal cords.

The differential diagnoses of the neonate case with BVCP (bilateral vocal cord paralysis) include:

Arnold-Chiari malformation: a rare condition in which the brain tissue extends into the spinal canal, leading to neurological symptoms and breathing difficulties.

Neuromuscular disorders: conditions such as muscular dystrophy, myasthenia gravis, or spinal muscular atrophy can lead to muscle weakness and respiratory difficulties.

Trauma during delivery: the use of forceps or vacuum during delivery can lead to nerve damage, resulting in BVCP.

Idiopathic BVCP: In some cases, the cause of BVCP remains unknown.

Congenital laryngeal stridor: This is a common condition that occurs due to laryngeal or tracheal malformations.

Infections: In rare cases, infections such as diphtheria or herpes simplex can lead to BVCP.

Tumors: Rarely, tumors in the chest or neck can cause BVCP.

Neurological disorders: Disorders affecting the nervous system, such as cerebral palsy, can lead to BVCP.

It is important to note that some of these conditions are very rare, and the most common cause of BVCP in neonates is often idiopathic. A thorough evaluation and workup by a medical professional are necessary to determine the underlying cause of BVCP.


6.3. What are the therapeutic modalities of the neonate with congenital bilateral vocal cord paralysis?
The therapeutic modalities for a neonate with congenital bilateral vocal cord paralysis (BVCP) depend on the severity of the symptoms and the underlying cause. The management may include the following:

Supportive measures: These include positioning the baby in a slightly head-up position to prevent aspiration, providing oxygen therapy, and close monitoring of vital signs.

Airway management: In cases of severe respiratory distress, endotracheal intubation may be necessary to ensure adequate ventilation and oxygenation.

Surgical intervention: If the airway obstruction is severe and life-threatening, surgical interventions such as tracheostomy or cordotomy may be considered.

Speech therapy: Once the baby's airway is stabilized, speech therapy may be initiated to improve vocal cord movement and to assist with feeding and swallowing.

Medical management: In some cases, medications such as corticosteroids, botulinum toxin injections, or nerve stimulants may be used to improve vocal cord function.

Treatment of underlying cause: If the BVCP is caused by a specific underlying condition, such as a neurological disorder, treatment of the underlying cause may help improve vocal cord function.

The management of BVCP in neonates requires a multidisciplinary approach involving neonatologists, pediatricians, speech therapists, and pediatric surgeons to ensure optimal care and outcomes.

7. Answers on case 7
7.1. What is a list of differential diagnoses of the following case?: A 32-year-old man visited our emergency room because of right hemiparesis beginning approximately 6 hours and 30 minutes prior. At presentation, the patient’s vital signs were within normal ranges, except for high blood pressure of 155/114 mm Hg. The patient had no specific medical history. Neurological examination revealed dysarthria, right facial palsy, and right hemiparesis, classified as approximately Medical Council Research grade 4.
Possible differential diagnoses for the case of a 32-year-old man presenting with right hemiparesis, dysarthria, and right facial palsy include:

Ischemic stroke: A clot that blocks blood flow to the brain, causing a lack of oxygen and nutrients to brain cells.
Hemorrhagic stroke: A ruptured blood vessel in the brain that causes bleeding and damages brain cells.
Transient ischemic attack (TIA): A temporary blockage of blood flow to the brain that can cause stroke-like symptoms but usually resolves within minutes to hours.
Multiple sclerosis: A chronic autoimmune disorder that affects the central nervous system, causing damage to the myelin sheath that surrounds nerve fibers.
Brain tumor: A growth of abnormal cells in the brain that can cause pressure on surrounding tissues and neurological symptoms.
Traumatic brain injury: A sudden physical injury to the brain that can cause damage to brain cells and neurological symptoms.
Migraine with aura: A type of migraine headache that can cause temporary neurological symptoms, including weakness and visual disturbances, before the headache pain begins.
Guillain-Barré syndrome: An autoimmune disorder that affects the peripheral nervous system, causing muscle weakness and paralysis.
Bell's palsy: A condition that causes temporary paralysis of the muscles on one side of the face, often due to a viral infection.
Herpes simplex encephalitis: A viral infection of the brain that can cause neurological symptoms, including weakness and paralysis.



7.2 What is a list of differential diagnoses of the following case? A 32-year-old man visited our emergency room because of right hemiparesis beginning approximately 6 hours and 30 minutes prior. At presentation, the patient’s vital signs were within normal ranges, except for high blood pressure of 155/114 mm Hg. The patient had no specific medical history. Neurological examination revealed dysarthria, right facial palsy, and right hemiparesis, classified as approximately Medical Council Research grade 4.

Brain magnetic resonance image confirmed a diffusion-restricted lesion in the left pons. Stenosis or occlusion of the intracranial main artery was not detected on brain computed tomography angiography; no other brain lesions were found (Fig. ​(Fig.1).1). Laboratory tests revealed an elevated low-density lipoprotein level of 173 mg/dL and a triglyceride level of 348 mg/dL. All other laboratory tests performed showed normal results. The patient was diagnosed with acute infarction in the left pons and hospitalized for medical treatment with antiplatelet agents. Approximately 14 hours after the onset of the hemiparesis, the patient complained of monochorea in the right arm. Intermittent and irregular involuntary movements were observed in the distal right arm. These movements were unpredictable and random and were not observed in other body parts (Supplementary Video, Supplemental Digital Content, http://links.lww.com/MD/I349). The chorea improved spontaneously on day 5 without specific medical treatment. The patient was discharged on the ninth hospital day and was followed up at the outpatient department. Currently, the patient exhibits no choreatic movements, although mild right hemiparesis remains.

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Figure 1.
(A) Brain magnetic resonance image (MRI) reveals a diffusion restriction lesion in the left pons. (B) Brain computed tomography angiography shows no significant stenosis or occlusion in the major intracerebral arteries. (C and D) T2-fluid attenuated inversion recovery MRI reveals no other brain lesions in the basal ganglia, frontal cortex, and subcortex.
Possible differential diagnoses for this case include:

Ischemic stroke: The clinical presentation and the MRI findings are consistent with an acute ischemic stroke in the left pons, caused by the occlusion of a small branch of the basilar artery or one of its penetrating branches. The risk factors for stroke in this patient include hypertension, dyslipidemia, and possibly smoking, although the latter is not mentioned in the case.

Hemorrhagic stroke: Although the MRI shows a diffusion-restricted lesion, ruling out a hemorrhagic stroke, such as an intracerebral or subarachnoid hemorrhage, is important because the management of these conditions differs significantly from that of ischemic stroke.

Multiple sclerosis: This is less likely given the acute onset and the MRI findings, but a demyelinating plaque in the pons can cause similar symptoms and signs, such as hemiparesis and dysarthria. Additional MRI sequences, such as T2 and fluid-attenuated inversion recovery (FLAIR), may be helpful in detecting other lesions that are typical of multiple sclerosis.

Brainstem tumor: Although less common than stroke or demyelination, a brainstem tumor, such as a glioma or a metastasis, can cause similar symptoms and signs, especially if it compresses the corticospinal tracts or the cranial nerve nuclei. However, the absence of contrast enhancement on the MRI argues against this possibility.

Vasculitis: A systemic or isolated vasculitis, such as granulomatosis with polyangiitis or primary angiitis of the central nervous system, can cause ischemic or hemorrhagic strokes in young adults. However, this diagnosis requires specific laboratory tests, such as antineutrophil cytoplasmic antibodies (ANCA), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), as well as brain and systemic angiography.

Moyamoya disease: This is a rare, chronic, progressive vasculopathy that affects the major intracranial arteries, especially the distal internal carotid and the proximal middle cerebral arteries. Moyamoya disease can cause ischemic or hemorrhagic strokes in young adults, but it usually presents with bilateral or alternating symptoms, such as hemiparesis, dysarthria, and headache. The absence of stenosis or occlusion on the brain CT angiography makes this diagnosis less likely.

Others: Other rare or unusual causes of acute hemiparesis, such as mitochondrial disorders, metabolic encephalopathy, or paraneoplastic syndromes, should be considered if the clinical course or the laboratory findings suggest them. However, these conditions usually require specialized testing or consultation with a neurologist or a geneticist.


7.3 What are the therapeutic modalities of Monochorea after acute contralateral pontine infarction?
There is no specific therapy for monochorea after acute contralateral pontine infarction. In most cases, it resolves spontaneously within a few days to weeks without specific treatment. However, symptomatic treatment can be provided for patients who experience discomfort or functional impairment due to choreic movements. Such treatments may include benzodiazepines or antipsychotic medications to reduce involuntary movements. In some cases, physical therapy or occupational therapy may be recommended to improve motor control and reduce disability. Additionally, managing underlying risk factors such as high blood pressure, dyslipidemia, and smoking can help prevent future strokes and minimize the risk of recurrent symptoms.


8. Answers on case 8

8.1. What is a list of differential diagnoses of the following case?:
A 13-year-old female patient was admitted to the department of orthopaedic surgery outpatient clinic with a chief complaint of recurring swelling, burning sensation, and focal tenderness at the right great toe for the past 12 months with no history of trauma. Her symptoms had been well-controlled by NSAIDs but reappeared 4 months ago. The pain was more severe at night after long periods of walking or sports activities.

The physical examination revealed a slightly swollen great toe with focal tenderness at the interphalangeal joint area of the plantar aspect of the great toe. 
Possible differential diagnoses for the patient's symptoms include:

Gout: A common cause of toe pain, especially in the great toe. It occurs due to the buildup of uric acid crystals in the joint, causing swelling, redness, and severe pain.
Septic arthritis: An infection in the joint that causes swelling, pain, and fever. It can be caused by bacteria or other pathogens and is a medical emergency.
Osteoarthritis: A degenerative joint disease that causes pain, stiffness, and swelling in the joints. It is more common in older adults and can be aggravated by physical activity.
Rheumatoid arthritis: An autoimmune disorder that causes joint pain, swelling, and stiffness. It can affect multiple joints and can lead to joint damage and deformity over time.
Turf toe: An injury caused by hyperextension of the big toe, commonly seen in athletes who play on artificial turf. It causes pain, swelling, and limited movement of the joint.
Sesamoiditis: An inflammation of the sesamoid bones, which are small bones located beneath the big toe joint. It can cause pain, swelling, and difficulty in walking or running.
Morton's neuroma: A benign growth of nerve tissue between the toes, usually between the third and fourth toes. It can cause pain, burning sensation, and numbness in the toes.

8.2. What is a list of differential diagnoses of the following case?:A 13-year-old female patient was admitted to the department of orthopaedic surgery outpatient clinic with a chief complaint of recurring swelling, burning sensation, and focal tenderness at the right great toe for the past 12 months with no history of trauma. Her symptoms had been well-controlled by NSAIDs but reappeared 4 months ago. The pain was more severe at night after long periods of walking or sports activities.

The physical examination revealed a slightly swollen great toe with focal tenderness at the interphalangeal joint area of the plantar aspect of the great toe. The radiographs showed a 4-mm, round, radiolucent lesion with central mineralization and rim sclerosis at the head of the proximal phalanx of the great toe (Figure ​(Figure1).1). The complete blood analysis indicated no remarkable findings. With a clinical suspicion of subacute osteomyelitis, enhanced MRI indicated heterogeneously low signal intensity on T1-weighted images and low signal intensity in the center and higher signal intensity in the periphery on T2-weighted images at the same lesion seen on the simple radiograph. In addition, there were diffuse bone marrow edema and periosteal inflammatory change around the bony lesion along with thin enhancement at the periphery of the lesion (Figure ​(Figure2).2). CT revealed a radiolucent central nidus surrounded by a sclerotic rim (Figure ​(Figure3).3). Both MRI and CT findings were consistent with the diagnosis of OO in the head of the proximal phalanx of the great toe.
The possible differential diagnoses for this case include:

Subacute osteomyelitis
Osteoid osteoma (OO)
Enchondroma
Bone cyst
Chondroblastoma
Giant cell tumor of bone
Metastatic bone tumor
However, based on the radiographic findings and MRI and CT results, the final diagnosis was confirmed as osteoid osteoma (OO) in the head of the proximal phalanx of the great toe.


8.3. What are the therapeutic modalities of Osteoid osteoma? 
The treatment modalities for osteoid osteoma (OO) depend on the size and location of the lesion and the severity of symptoms. The following are some of the treatment options for OO:

Observation: Small OO lesions that are asymptomatic may not require any treatment and can be observed for spontaneous resolution.

Medications: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to relieve the pain and inflammation associated with OO. The use of NSAIDs may also lead to the spontaneous resolution of the lesion.

Radiofrequency ablation (RFA): RFA is a minimally invasive procedure that uses heat to destroy the lesion. This procedure is commonly used for the treatment of OO and has a high success rate.

Surgical excision: Surgery is recommended for large OO lesions or lesions that do not respond to other treatment modalities. The surgical procedure involves removing the entire lesion, along with a margin of healthy tissue.

CT-guided percutaneous drilling: This minimally invasive procedure involves drilling a hole through the center of the OO lesion, which can relieve the pain and allow for the spontaneous resolution of the lesion.

The choice of treatment depends on the location, size, and symptoms of the OO lesion, as well as the patient's age and overall health.

9. Answers on case 10
9.1. What is a list of differential diagnoses of the following case?:
A 64-year-old male patient had a history (2000 and 2017) of undergoing penetrating keratoplasty (PKP) for corneal opacity in his right and left eyes, respectively. In 2019, another PKP had been performed in his left eye due to graft rejection, which reoccurred 3 months after. Therefore, in 2020, he underwent Descemet stripping automated endothelial keratoplasty (DSAEK) and maintained a clear grafted cornea for 1 year (Fig. 1A).

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Object name is kjo-2022-0105f1.jpg
Fig. 1
Change in slit-lamp image and corneal endothelial cell count. (A) Slit-lamp image of a clear grafted cornea at the last follow-up before vaccination for several SARS-CoV-2. (B) Slit-lamp image at presentation on day 7 after vaccination with slight conjunctival injection and mild corneal edema. (C) Fine keratic precipitates found in the central cornea. (D) The corneal endothelial cell count was 1,320 cells/mm2 at the last visit before coronavirus disease vaccination. (E) Corneal endothelial cells were unmeasurable in numeric value, but the cell count, hexagonality, and size variation had increased 7 days after vaccination. (F) After treatment with topical and systemic steroids, the corneal endothelial cell count decreased to 1,086 cells/mm2. CCT = central corneal thickness; CD = cell density; CV = coefficient of variation; HEX = hexagonality; N = number of cells analyzed; MIN = minimum; MAX = maximum; AVG = average; SD = standard deviation; N/A = not available. In May 2021, he received the first dose of the ChAdOx1 vaccine. After 3 hours, he experienced a pressing sensation in the left eye; 2 days later, he experienced blurred vision
Based on the provided information, some possible differential diagnoses for the patient's symptoms could include:

Corneal edema or endothelial decompensation: This is a common complication after corneal transplantation, and the patient had a history of previous graft rejection and multiple surgeries. Corneal edema or endothelial decompensation can cause blurred vision and discomfort.

Graft rejection: The patient had a history of graft rejection in the past, and the symptoms appeared shortly after receiving the COVID-19 vaccine. Graft rejection can cause inflammation and damage to the transplanted cornea, resulting in decreased vision and discomfort.

Viral conjunctivitis: The patient experienced slight conjunctival injection after vaccination, which could be a sign of viral conjunctivitis. This can cause discomfort, redness, and blurred vision.

Uveitis: The fine keratic precipitates found in the central cornea could be a sign of uveitis, which is inflammation of the uvea, the middle layer of the eye. Uveitis can cause pain, redness, and blurred vision.

Acute angle-closure glaucoma: The pressing sensation in the left eye that the patient experienced after receiving the vaccine could be a sign of acute angle-closure glaucoma. This is a medical emergency that can cause severe eye pain, blurred vision, and nausea.

It's important to note that these are just some of the possible differential diagnoses, and further evaluation by an ophthalmologist would be necessary to make an accurate diagnosis.



9.2 What is a list of differential diagnoses of the following case?:   A 64-year-old male patient had a history (2000 and 2017) of undergoing penetrating keratoplasty (PKP) for corneal opacity in his right and left eyes, respectively. In 2019, another PKP had been performed in his left eye due to graft rejection, which reoccurred 3 months after. Therefore, in 2020, he underwent Descemet stripping automated endothelial keratoplasty (DSAEK) and maintained a clear grafted cornea for 1 year (Fig. 1A).

An external file that holds a picture, illustration, etc.
Object name is kjo-2022-0105f1.jpg
Fig. 1
Change in slit-lamp image and corneal endothelial cell count. (A) Slit-lamp image of a clear grafted cornea at the last follow-up before vaccination for several SARS-CoV-2. (B) Slit-lamp image at presentation on day 7 after vaccination with slight conjunctival injection and mild corneal edema. (C) Fine keratic precipitates found in the central cornea. (D) The corneal endothelial cell count was 1,320 cells/mm2 at the last visit before coronavirus disease vaccination. (E) Corneal endothelial cells were unmeasurable in numeric value, but the cell count, hexagonality, and size variation had increased 7 days after vaccination. (F) After treatment with topical and systemic steroids, the corneal endothelial cell count decreased to 1,086 cells/mm2. CCT = central corneal thickness; CD = cell density; CV = coefficient of variation; HEX = hexagonality; N = number of cells analyzed; MIN = minimum; MAX = maximum; AVG = average; SD = standard deviation; N/A = not available.

In May 2021, he received the first dose of the ChAdOx1 vaccine. After 3 hours, he experienced a pressing sensation in the left eye; 2 days later, he experienced blurred vision. At presentation, the uncorrected visual acuity was 20 / 50 and the intraocular pressure was 13 mmHg, unchanged compared with 6 months ago. Slit-lamp examination revealed slight conjunctival injection with mild corneal edema. Fine keratic precipitates were found in the central cornea, and a trace anterior chamber reaction was observed (Fig. 1B, 1C). Central corneal thickness had increased from 563 to 615 μm. The number of corneal endothelial cells and their degree of hexagonality decreased (Fig. 1D, 1E)
The differential diagnosis of this case may include:

Graft rejection: This patient has a history of graft rejection, and the symptoms and signs described in the case could be indicative of a recurrence of graft rejection.

Endothelial cell damage: The corneal endothelium is responsible for maintaining the hydration of the cornea, and damage to these cells can result in corneal edema. The increase in central corneal thickness and decrease in corneal endothelial cell count observed in this case could be indicative of endothelial cell damage.

Infection: Infection can cause conjunctival injection and anterior chamber reaction, which were observed in this case.

Glaucoma: Although the intraocular pressure was reported to be normal, glaucoma cannot be ruled out as a possible cause of the patient's symptoms.

Other vaccine-related complications: Although rare, other complications related to the ChAdOx1 vaccine have been reported, including ocular inflammation and thrombosis. These should be considered as a possibility in this case, especially given the timing of symptom onset after vaccination.

9.3. Not available

10. Answers on case 10
10.1. What is a list of differential diagnoses of the following case?: A 37-year-old male soldier presented to the ED complaining of worsening pain on his left buttock with fevers and chills despite ongoing oral antibiotics. The patient had seen his primary care physician (PCP) 6 days before ED presentation and was started on 100-mg doxycycline twice daily for diagnosed cellulitis at that time. He returned to his PCP for reevaluation 4 days later, who documented that the erythema extended to the perineum and scrotum, and switched him to 450-mg clindamycin three times daily. His surgical history included two left inguinal hernia repairs approximately 10 years before ED evaluation, but he denied other medical history and any family history of rheumatological or gastrointestinal disease. His initial vital signs included a rectal temperature of 97.6°F, blood pressure of 137/88 mm Hg, heart rate of 70 beats per minute, respiratory rate of 14 breaths per minute, and pulse oximetry of 100%. On examination, he could not sit secondary to pain, prompting examination in the prone position. An immense area of severe induration, erythema, and tense edema covered the medial half of his left buttock, including the perineum and scrotum, with severe tenderness, as well as several areas of palpable crepitus that did not extend into the anus or rectum
The possible differential diagnoses for the presented case include:

Necrotizing soft tissue infection (NSTI) - This is a serious and potentially life-threatening infection that rapidly destroys skin, subcutaneous tissue, fascia, and muscle. The symptoms of NSTI include severe pain, fever, chills, and edema. The presence of crepitus is a significant sign of NSTI.

Fournier's gangrene - This is a type of NSTI that affects the perineal and genital areas. It is characterized by severe pain, fever, and crepitus. It can lead to sepsis and organ failure if not treated promptly.

Abscess - An abscess is a localized collection of pus within the tissue. It can cause redness, swelling, pain, and fever. The history of recent cellulitis and the presence of edema suggest that an abscess could be a possible diagnosis.

Cellulitis - Cellulitis is a bacterial infection of the skin and subcutaneous tissue. It can cause redness, swelling, and pain. The patient has already been diagnosed with cellulitis, but the worsening symptoms suggest a possible treatment failure or progression to a more severe infection.

Deep vein thrombosis (DVT) - DVT is a blood clot that forms in a deep vein, usually in the legs. It can cause pain, swelling, and redness in the affected area. The patient's history of being a soldier could increase his risk for DVT.

Inflammatory bowel disease (IBD) - Although less likely, IBD can cause perineal and buttock pain and inflammation. However, the absence of other systemic symptoms, such as diarrhea, abdominal pain, and weight loss, makes IBD less likely in this case.


[2023. 3. 19. 20:11]
10.2. What is a list of differential diagnoses of the following case?: A 37-year-old male soldier presented to the ED complaining of worsening pain on his left buttock with fevers and chills despite ongoing oral antibiotics. The patient had seen his primary care physician (PCP) 6 days before ED presentation and was started on 100-mg doxycycline twice daily for diagnosed cellulitis at that time. He returned to his PCP for reevaluation 4 days later, who documented that the erythema extended to the perineum and scrotum, and switched him to 450-mg clindamycin three times daily. His surgical history included two left inguinal hernia repairs approximately 10 years before ED evaluation, but he denied other medical history and any family history of rheumatological or gastrointestinal disease. His initial vital signs included a rectal temperature of 97.6°F, blood pressure of 137/88 mm Hg, heart rate of 70 beats per minute, respiratory rate of 14 breaths per minute, and pulse oximetry of 100%. On examination, he could not sit secondary to pain, prompting examination in the prone position. An immense area of severe induration, erythema, and tense edema covered the medial half of his left buttock, including the perineum and scrotum, with severe tenderness, as well as several areas of palpable crepitus that did not extend into the anus or rectum. Laboratory findings included a white blood cell count (WBC) of 15,800/μL with 93% bands and C-reactive protein (CRP) of 7.8 mg/dL but were otherwise largely unremarkable (Table I). Bedside ultrasound found acoustic shadowing throughout hypoechoic areas, which correlated with palpable crepitus concerning FG. General surgery consultation requested computed tomography for further evaluation before admission, which revealed a 10 × 4cm collection of air extending from the left perianal area to the left perineum (Fig. 1) and anteriorly into the scrotum and left inguinal canal (Fig. 2). The radiologist also noted the possibility of a left-sided perianal fistula.

FIGURE 1.
Sagittal and transverse views of pelvic computed tomography revealing extensive subcutaneous air extending from buttock through perineum and into scrotum with additional spread to the left inguinal canal (arrows).
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Sagittal and transverse views of pelvic computed tomography revealing extensive subcutaneous air extending from buttock through perineum and into scrotum with additional spread to the left inguinal canal (arrows).

FIGURE 2.
Sagittal and transverse views of pelvic computed tomography revealing extensive subcutaneous air extending from buttock through perineum and into scrotum with additional spread to the left inguinal canal (arrows).
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Sagittal and transverse views of pelvic computed tomography revealing extensive subcutaneous air extending from buttock through perineum and into scrotum with additional spread to the left inguinal canal (arrows).


TABLE I.Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) Score Outline and Comparison to Case Patient Laboratory Values
Lab test	LRINEC value	LRINEC score	Patient value	Patient score
CRP (mg/dL) 	<15 	0 	7.8 	0 
 	≥15 	+4 	 	 
WBC (×10,000/µL) 	<15 	0 	15.8 	1 
 	15–25 	+1 	 	 
 	>25 	+2 	 	 
Hgb (g/dL) 	>13.5 	0 	15.3 	0 
 	11–13.5 	+1 	 	 
 	<11 	+2 	 	 
Sodium (mEq/L) 	≥135 	0 	143 	0 
 	<135 	+2 	 	 
Creatinine (mg/dL) 	≤1.6 	0 	0.92 	0 
 	>1.6 	+2 	 	 
Glucose (mg/dL) 	≤180 	0 	112 	0 
 	>180 	+1 	 	 
 	LRINEC score ≥6 prompts suspicion for NSTI 	Case patient score = 1 
Abbreviations: NSTI, necrotizing soft tissue infection; WBC, white blood cell count; CRP, C-reactive protein.

Based on the information provided, the following are possible differential diagnoses for the patient's symptoms:

Necrotizing fasciitis (NF) - This is a serious bacterial skin infection that spreads rapidly and destroys the body's soft tissue. The symptoms include pain, fever, chills, and skin that is red, swollen, and hot to the touch. The presence of crepitus (gas under the skin) is a red flag for NF.

Perianal abscess - This is a collection of pus that develops near the anus or rectum, usually caused by a bacterial infection. Symptoms include pain, swelling, redness, and tenderness in the affected area.

Anal fistula - This is a small tunnel that develops between the anus or rectum and the skin surrounding the anus. It can cause pain, swelling, and drainage of pus or stool.

Cellulitis - This is a bacterial skin infection that causes redness, swelling, and pain in the affected area. The patient's symptoms initially suggested cellulitis, but the progression of symptoms, lack of response to oral antibiotics, and the presence of crepitus suggest a more serious infection.

Fournier's gangrene - This is a rare and potentially life-threatening bacterial infection of the genital and perineal area. Symptoms include severe pain, swelling, and redness in the affected area, along with fever and chills.

Trauma or injury to the affected area - Although less likely given the progression of symptoms, it is important to consider any recent trauma or injury to the left buttock and perineal area that could have led to an infection.

Other bacterial infections - Other bacterial infections that can cause similar symptoms include staphylococcus aureus, streptococcus pyogenes, and pseudomonas aeruginosa infections.

It is important to note that the diagnosis of necrotizing fasciitis is a medical emergency that requires prompt diagnosis and treatment. The patient's symptoms and the presence of crepitus are highly concerning for this condition, and immediate surgical intervention is often necessary to prevent serious complications or even death.


10.3.What are the therapeutic modalities of the Abdominal Extension of Fournier Gangrene From Undiagnosed Crohn's Disease?
Fournier Gangrene is a rare but serious type of infection that affects the genital and perianal regions. It is a medical emergency that requires immediate treatment, and if left untreated, it can lead to sepsis and death. In the case of Fournier Gangrene from undiagnosed Crohn's disease, the therapeutic modalities may involve a combination of medical and surgical interventions, depending on the severity and extent of the infection.

Medical therapy may involve antibiotics to control the infection and anti-inflammatory medications to reduce the inflammation caused by Crohn's disease. Immunosuppressive medications such as corticosteroids and biologic agents may also be prescribed to manage the underlying Crohn's disease.

Surgical therapy is often necessary to remove the necrotic tissue and control the infection. The surgical approach may include debridement of the infected tissue, drainage of any abscesses or collections of pus, and reconstruction of the affected area. In severe cases, a colostomy or ileostomy may be required to divert the fecal stream and allow the affected area to heal.

In addition to medical and surgical interventions, supportive care such as wound care, pain management, and nutritional support may also be necessary to promote healing and prevent complications. It is essential to have a multidisciplinary team involved in the care of patients with Fournier Gangrene, including infectious disease specialists, gastroenterologists, surgeons, and wound care specialists.