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NEJM_Reasoning_Subset_test

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NEJM_Reasoning_Subset0

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Natasha Merali Medicine: A 76-year-old woman was transferred to this hospital because of lethargy and altered mental status. The patient had been well until 2 months before this evaluation, when she was admitted to another hospital for community-acquired pneumonia. Empirical treatment with ceftriaxone and azithromycin was administered, and her condition partially improved. Two weeks later, the patient presented to the other hospital with recurrent dyspnea and lethargy. A partly loculated right pleural effusion was identified. Empirical treatment with vancomycin and piperacillintazobactam was administered intravenously. Thoracostomy placement of a chest tube for drainage was performed, and pleural fluid analysis revealed an exudative pleural effusion; Grams staining showed no neutrophils or microorganisms, culture showed no growth, and cytologic testing showed no malignant cells. After a 1-week admission, the dyspnea abated, and the patient was discharged with instructions to complete a 2-week course of antibiotic therapy. Two weeks before this evaluation, generalized weakness and lethargy developed, along with new diffuse headache. The patients family thought that she appeared somnolent and clumsy while walking. Four days later, her family took her to the other hospital for evaluation. A review of systems was notable for dys-pnea, leg edema, and hematochezia and no fever, chills, chest pain, cough, dysuria, hematuria, or melena. The temperature was 37.2C, the heart rate 74 beats per minute, the blood pressure 176101 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 99 while she was receiving oxygen through a nasal cannula at a rate of 2 liters per minute. The patient was alert and oriented but appeared to be confused when recalling recent events. She had jugular venous distention, diffuse lung rales, and 2 symmetric pitting edema of the lower legs up to the knees. The blood urea nitrogen level was 83 mg per deciliter 29.6 mmol per liter; reference range, 6 to 20 mg per deciliter 2.1 to 7.1 mmol per liter, the creatinine level 4.9 mg per deciliter 433 mol per liter; reference range, 0.4 to 1.1 mg per deciliter 35 to 97 mol per liter, and the hematocrit 26 reference range, 34 to 45. Other laboratory test results are shown in Table 1. Dr. R. Gilberto Gonzalez: Chest radiography re-vealed a small right pleural effusion and moderate interstitial pulmonary edema. Computed tomography CT of the head, performed without the administration of intravenous contrast material, revealed a chronic subcortical infarct of the right frontal lobe, as well as diffuse involutional changes and nonspecific white-matter hypoden-sities. Dr. Merali: Oral labetalol, clonidine, and hydra-lazine and intravenous furosemide were admin-istered to treat possible hypertensive emergency. During the next 2 days, the patients headache and anemia worsened and dizziness developed. On the seventh hospital day, there was an acute episode of nonbloody emesis, followed by a generalized tonicclonic seizure lasting 1 minute. The patient was transferred to the intensive care unit ICU of the other hospital. Dr. Gonzalez: Repeat CT of the head, performed without the administration of intravenous contrast material, revealed findings similar to those of the previous study. Magnetic resonance imaging MRI of the head Fig. 1, performed without the administration of intravenous contrast material, revealed two foci of restricted diffusion in the right frontal lobe and the left cerebellar hemisphere, each measuring 1 cm in diameter, with surrounding signal hyperintensity on T2-weighted and fluid-attenuated inversion recovery FLAIR images. In addition, there was diffuse ventricular enlargement, with surrounding smooth hyperintensity on T2-weighted and FLAIR images; this finding is suggestive of communicating hydrocephalus with transependymal flow of cerebrospinal fluid CSF. T2-weighted and FLAIR images also showed multiple foci of hyperintensity scattered throughout the deep white matter. Dr. Merali: Video electroencephalography revealed epileptiform discharges predominantly in the frontal lobe, with generalized slowing. Levetiracetam, vancomycin, and ceftazidime were administered; intermittent hemodialysis was initiated. During the next 3 days, the patient began to have a right gaze preference, left hemineglect, and aphasia. The temperature increased to 39.4C, and chills developed. Blood specimens were obtained for microbiologic culture. Lumbar puncture was deferred, pending additional imaging studies to rule out a space-occupying lesion. Empirical treatment with vancomycin, ceftazi-dime, ampicillin, metronidazole, and acyclovir was administered intravenously. At the request of her family, the patient was transferred to the ICU of this hospital. On arrival at this hospital, additional history was obtained from the patients family. Two years earlier, the patient had received a diagnosis of gastric adenocarcinoma, which was treated with fluorouracil, leucovorin, and oxaliplatin. Therapy was discontinued after three of six cycles because of ileus, renal injury, and neutropenic fever. Robotic subtotal gastrectomy and Roux-en-Y gastric bypass were then performed; histologic examination of the resected tissue revealed a nearly complete response of the adenocarcinoma. Five months before the current evaluation, CT with 18F-fluorodeoxyglucose FDGpositron-emission tomography performed at the other hospital revealed FDG avidity in nonenlarged lymph nodes in the mediastinum, retroperito-neum, porta hepatis, and right cervical region. Biopsy was offered, but the patient chose to undergo active surveillance. Additional medical history included hypertension, hyperlipidemia, type 2 diabetes mellitus, hypothyroidism, and stage 5 chronic kidney disease. Medications included torsemide, amlodipine, clonidine, hydrala-zine, hydrochlorothiazide, labetalol, rosuvastatin, insulin, levothyroxine, cholecalciferol, mirtazap-ine, and oxycodone. There were no known drug allergies. Four decades before the current admission, the patient had immigrated to the United States from an island off the west coast of Africa. She was widowed, had four children, and lived with a pet parrot in an urban area of New England. Two months before hospitalization, she had been independent in activities of daily living and had received minimal assistance, such as with buying groceries, from family members. The patient had traveled to her country of origin 8 years earlier and to South America and the Caribbean in the past year. She had had no sexual partners in the past three decades. She did not drink alcohol, smoke tobacco, or use illicit drugs. Her sister had received a diagnosis of pancreatic cancer at 60 years of age; there was no family history of rheumatologic, neurologic, cardiovascular, or renal disease. On examination, the temperature was 36.8C, the heart rate 93 beats per minute, the blood pressure 17092 mm Hg, the respiratory rate 12 breaths per minute, and the oxygen saturation 100 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 23.8. The patient was somnolent and variably oriented to self but not to situation, location, or time. She intermittently opened her eyes spontaneously but did not follow commands or reliably withdraw in response to noxious stimuli. Her face and pupils appeared symmetric; a right gaze preference and left hemineglect were present. There was no evidence of jugular venous distention, rales, or edema, and the abdominal examination was normal. Testing for human immunodeficiency virus HIV type 1 and type 2 antibodies and p24 an-tigen was nonreactive. A test for antitreponemal antibodies was positive, and a rapid plasma re-agin test was negative. Other laboratory test results are shown in Table 1. Dr. Gonzalez: Repeat CT of the head, performed without the administration of intravenous contrast material, revealed foci of hypoattenuation in the left superior cerebellar hemisphere and the right frontal lobe that corresponded to the foci of restricted diffusion on MRI observed at the other hospital. Dr. Merali: Empirical treatment with vancomy-cin, ceftriaxone, ampicillin, metronidazole, and acyclovir was administered intravenously. On the second hospital day, a lumbar puncture was performed. The opening pressure was 15 cm of water. The CSF was slightly yellow, with a glucose level of 18 mg per deciliter 1.0 mmol per liter; reference range, 50 to 75 mg per deciliter 2.8 to 4.2 mmol per liter and a protein level of 173 mg per deciliter reference range, 5 to 55. There were 236 nucleated cells per microliter reference range, 0 to 5, of which 69 were neutrophils, 19 lymphocytes, and 12 mono-cytes. Grams staining of the CSF showed abundant neutrophils and mononuclear cells; no organisms were identified. Transthoracic echo-cardiography revealed mild left ventricular hypo-kinesis and aortic sclerosis. On the fourth hospital day, new right esopho-ria developed and the patient was less responsive. The trachea was intubated and mechanical ventilation was initiated for airway protection. Dr. Gonzalez: Repeat MRI of the head Fig. 2, performed without the administration of intravenous contrast material, revealed enlargement of the previously observed lesions in the right frontal lobe and left cerebellum. There were additional foci of reduced diffusivity, with corresponding hyperintense signal abnormalities on T2-weighted and FLAIR images, involving both cerebral hemispheres, deep gray matter, the brain stem, and the cerebellum. Magnetic resonance angiography of the head, performed without the administration of intravenous contrast material, revealed multifocal narrowing of branches of the bilateral middle and posterior cerebral arteries. CT of the chest, abdomen, and pelvis, performed without the administration of intravenous contrast material, revealed small bilateral pleural effusions and no other abnormalities. Dr. Merali: Empirical treatment with methyl-prednisolone was started. The next day, repeat lumbar puncture was performed. The opening pressure was 16 cm of water. The CSF was slightly yellow, with a glucose level of 179 mg per deciliter 9.9 mmol per liter and a protein level of 181 mg per deciliter. There were 286 nucleated cells per microliter, of which 83 were neutrophils, 9 lymphocytes, and 8 monocytes. Grams staining of the CSF showed abundant neutrophils and moderate mononuclear cells; there were no organisms. A diagnostic test was performed. OUTPUT:

Mycobacterium tuberculosis meningitis.

NEJM_Reasoning_Subset1

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Naomi J. Serling-Boyd Medicine: A 48-year-old man was evaluated at this hospital because of transient vision loss. The patient had been in his usual state of good health until 1 hour before evaluation, when he noticed white sparkles flickering in the vision of the left eye, followed by sudden blurriness. He had no floaters or eye pain. During the next 2 minutes, the blurry vision worsened and became dark, such that the patient could not see a hand in front of his face when he covered the right eye. He presented to this hospital for evaluation, arriving 1 hour after the onset of vision symptoms. On presentation, the patient noted that the vision in the left eye was improving but remained blurry. The temperature was 36.7C, the blood pressure 12065 mm Hg, the heart rate 92 beats per minute, and the body-mass index the weight in kilograms divided by the square of the height in meters 24.2. Visual acuity was 2020 in the right eye and was limited to hand motions at 0.9 m 3.0 ft in the left eye; 2 hours later, visual acuity in the left eye was 2040 for distance vision and 2030 with correction for near vision. Results of the Ishihara color test were normal. The pupils were equal, round, and reactive to light, with no relative afferent pupillary defect. Extraocular movements were intact; visual fields were full in response to confrontation. Intraocular pressure and results of a slit-lamp examination of the anterior and posterior segments of the eye were normal bilaterally. There was severe ptosis of the left upper eyelid margin reflex distance, 4 mm in the right eye and 1 mm in the left eye. A dilated fundus examination revealed normal optic disks, maculae, and vessels. A nontender, irregular mass was palpable under the left superior orbital rim, but there was no proptosis. The temporal arteries were prominent bilaterally, more so on the right side than on the left side, with normal pulsations and no tenderness. There was no tenderness of the scalp or temporo-mandibular joints. The remainder of the physical examination was normal. A review of systems was notable for fatigue and weight loss of 4.5 kg in the past year, which the patient attributed to inactivity and decreased appetite. There was a 2-month history of bilateral jaw pain with chewing of firm foods but not with soft foods. There was lateral hip soreness in both hips after walking but no stiffness. There was a sensation of locking when flexing or extending the right first finger. Two days before evaluation, the patient had a temporal headache on the right side that resolved. He reported no numbness or weakness. The patient had a history of presbyopia. He had not undergone any surgeries, was not currently taking any medications, and had no known allergies. He was born and raised in a country in Eurasia and had lived in the United States for 20 years. He traveled internationally for his work as a university professor. He was divorced and lived with his two children in a house in New England. He had smoked a half pack of cigarettes for 5 years but had quit smoking 20 years earlier. He drank alcohol rarely and did not use illicit drugs. His parents were alive and well, both of his grandmothers had had breast cancer, and there was no family history of ocular or autoimmune disease. Laboratory evaluation revealed normocytic anemia and elevated levels of alanine amino-transferase, aspartate aminotransferase, and alkaline phosphatase. Results of tests of kidney and thyroid function were normal, as were blood levels of electrolytes, calcium, glucose, glycated hemoglobin, creatine kinase, homocysteine, and lipoproteina. Testing for antinuclear antibodies was negative, and levels of IgG subclasses were normal. Other laboratory test results are shown in Table 1. Aspirin was administered, along with empirical treatment with intravenous methylpred-nisolone, and the patient was admitted to the hospital. Dr. Hillary R. Kelly: Magnetic resonance imaging MRI of the head and orbits Fig. 1, performed before and after the administration of intravenous contrast material, revealed enlargement of the right medial rectus muscle with stranding of the adjacent extraconal fat, as well as an enhancing masslike lesion in the left anterior superior orbit, abutting the left lacrimal gland. The masslike lesion showed a hypointense signal on short-tau inversion recovery imaging. The brain parenchyma was normal. Magnetic resonance angiography of the head and neck was normal, as was ultrasonography of the temporal arteries. Ultrasonography of the abdomen revealed markedly heterogeneous liver paren-chyma and an enlarged periportal lymph node, measuring 2 cm in largest dimension. Computed tomography CT of the chest, abdomen, and pelvis Fig. 1, performed after the administration of intravenous contrast material, revealed multiple punctate calcifications throughout the liver and hypoattenuation of the right hepatic lobe, as well as diffuse coalescent mesenteric and retroperitoneal lymphadenopathy with coarse calcifications. There was a prominent right hilar lymph node, measuring 10 mm in diameter. The lung parenchyma was unremarkable. Dr. Serling-Boyd: On the second hospital day, diplopia occurred when the patient looked to the far right. On examination, there was mild limitation of abduction of the right eye. After a second dose of intravenous methylprednisolone was administered, the patient chose to leave the hospital against medical advice. After discharge, he took prednisone daily. During the next week, additional laboratory test results became available. Testing for antineutrophil cytoplasmic antibodies ANCAs was negative. Blood testing for blastomyces antigen, coccidioides antibodies, and histoplasma antibodies was negative, as was an interferon- release assay for Mycobacterium tuberculosis. A diagnostic test was performed. OUTPUT:

Systemic primary amyloidosis.

NEJM_Reasoning_Subset2

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Bart K. Chwalisz: A 65-year-old man was admitted to this hospital because of bilateral eye pain and decreased vision. The patient had been in his usual state of health until 8 days before this admission, when constant aching pain developed in the left eye and the left side of the head. During the next few days, the vision in the left eye gradually became blurry. Three days before this admission, redness developed in the right eye. The patient used tetrahydrozoline eye drops, but symptoms did not abate. One day before this admission, pain developed in the right eye that was similar to the pain in the left eye. The patient sought evaluation by his primary care physician, who recommended that he present to the emergency department of this hospital for further evaluation. On arrival, the patient rated the eye pain and headache at 2 on a scale of 0 to 10 with 10 indicating the most severe pain. The pain was not worse with eye movement or accompanied by flashing lights, floaters, or discharge. The patient reported no trauma but noted weight loss of 4.5 kg in the past 2 weeks, as well as pain with chewing food. He did not have scalp tenderness, fever, chills, nausea, vomiting, numbness, weakness, or slurred speech. The patient had a history of Waldenstroms macroglobulinemia, which had been diagnosed 2 years before this admission and treated with plasmapheresis, dexamethasone, and four cycles of bortezomib with discontinuation of bortezo-mib after 4 months because of peripheral neuropathy, as well as six cycles of bendamustine. During the 9 months that followed the completion of treatment with bendamustine, there was active surveillance of the blood IgM level. One month before this admission, the IgM level was 1001 mg per deciliter reference range, 53 to 334, and biopsy of the bone marrow revealed persistent disease. One week before this admission, the patient took his first dose of ibrutinib, which had been prescribed 3 months earlier. Other medical history included latent tuberculosis, depression, anxiety, prediabetes, folate deficiency, and seasonal allergies. Medications included ibrutinib, isoniazid, pyridoxine, sertra-line, citalopram, hydroxyzine, cetirizine, flutica-sone nasal spray, and a multivitamin. Rituximab had caused anaphylaxis. The patient did not smoke tobacco, use illicit drugs, or drink alcohol. He was originally from Central America and had immigrated to the United States 50 years earlier; 1 month earlier, he had moved from the West Coast to an urban area of New England. He lived in an apartment with his niece and cousins and worked in construction. His family history was unknown. On examination, the temperature was 36.3C, the blood pressure 10469 mm Hg, the pulse 60 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97 while the patient was breathing ambient air. Visual acuity was 2020 in the right eye and 20100 in the left eye with correction. On confrontation testing, visual fields in the left eye were deficient in the inferior temporal and nasal aspects. On the Ishi-hara color test, all plates were identified with the right eye but only the control plate was identified with the left eye. The pupils were symmetric and reactive to light; an afferent pupillary defect was present in the left eye. There was no propto-sis. Subconjunctival hemorrhage was present in the right eye; pterygia were present in both eyes. On funduscopic examination, the optic disk in the left eye was edematous. Results of tests of cranial nerve function, power, sensation, reflexes, coordination, and gait were normal. The blood hemoglobin level was 12.5 g per deciliter reference range, 13.5 to 17.5, the hema-tocrit 39.8 reference range, 41.0 to 53.0, the white-cell count 8090 per microliter reference range, 4500 to 11,000, and the platelet count 131,000 per microliter reference range, 150,000 to 400,000. The IgM level was 540 mg per deciliter; the level of IgM kappa M component in the gamma region was 0.36 g per deciliter. Blood levels of electrolytes were normal, as were the results of tests of kidney and liver function. Tests for Lyme disease, syphilis, toxoplasmosis, and bartonellosis were negative. Tests for human immunodeficiency virus HIV type 1 p24 antigen and antibodies to HIV types 1 and 2 were negative. Other laboratory test results are shown in Table 1. Dr. Javier M. Romero: Computed tomography CT of the head, performed with and without the administration of intravenous contrast material, revealed mild thickening and perineural enhancement along the entire length of the left optic nerve Fig. 1A and 1B. There was a deformity of the left lamina papyracea with medial deviation of the medial and superior rectus muscle, as well as postoperative changes in the sinuses. Magnetic resonance imaging MRI of the head and orbits, performed with and without the administration of contrast material, was limited by artifact but revealed increased signal intensity and possible focal enhancement within the retrobulbar segment of the left optic nerve Fig. 1C and 1D. Dr. Chwalisz: The patient was admitted to this hospital, and a diagnosis was made. OUTPUT:

Bing–Neel syndrome.

NEJM_Reasoning_Subset3

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Alexandra T. Lucas Pediatrics: A 19-year-old man was admitted to the pediatric intensive care unit PICU of this hospital because of shock, multiple organ failure, and rash. The patient had been well until 20 hours before this admission, when diffuse abdominal pain and nausea developed after he ate rice, chicken, and lo mein leftovers from a restaurant meal. Multiple episodes of emesis occurred, with vomitus that was either bilious or red-brown. The abdominal pain and vomiting were followed by the development of chills, generalized weakness, progressively worsening diffuse myalgias, chest pain, shortness of breath, headache, neck stiffness, and blurry vision. Five hours before this admission, purplish discoloration of the skin developed, and a friend took the patient to the emergency department of another hospital for evaluation. On arrival at the emergency department of the other hospital, 4.5 hours before this admission, the patient reported diffuse myalgias that he rated at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. On examination, he appeared pale, anxious, and moderately distressed; he answered questions appropriately and was oriented to person, place, time, and situation. The temperature was 37.4C, the pulse 147 beats per minute, the blood pressure 154124 mm Hg, the respiratory rate 24 breaths per minute, and the oxygen saturation 97 while he was breathing ambient air. The oral mucous membranes were dry. On auscultation of the heart, tachycardia was present with a regular rhythm. The radial pulses were normal. The lungs were clear, without crackles, rhonchi, or wheezes. The abdomen was soft and nondistended, without tenderness; the patient vomited yellow-green material during the examination. The skin was warm and dry and had a mottled appearance. Blood specimens were obtained and sent to the laboratory for culture, a complete blood count, and tests of renal function, liver function, and coagulation, as well as measurement of levels of electrolytes, glucose, lipase, lactic acid, and troponin. A urine specimen was sent for urinalysis and culture, and a nasopharyngeal swab was obtained for influenza virus nucleic acid testing. Approximately 40 minutes after the patients arrival at the other hospital, ondansetron, ceftriaxone, and a 2-liter bolus of 0.90 normal saline were administered intravenously. During the next 30 minutes, tachypnea worsened and labored breathing, hypoxemia, and cyanosis developed. Supplemental oxygen was administered through a nonrebreather face mask, resulting in an oxygen saturation of 83; then, oxygen was administered through a high-flow nasal cannula at a rate of 40 liters per minute. Intravenous doses of dexamethasone and vanco-mycin were given. During the following 40 minutes, the systolic blood pressure fell to 70 mm Hg and the dorsa-lis pedis pulses were noted to be weak. Approximately 110 minutes after the patients arrival at the other hospital, a triple-lumen central venous catheter was placed in the right femoral vein and a continuous intravenous infusion of norepineph-rine was initiated. After intravenous doses of midazolam, etomidate, and fentanyl were administered, tracheal intubation was performed and mechanical ventilation with pressure-regulated volume control was begun, with a tidal volume of 6 ml per kilogram of body weight, a rate of 24 breaths per minute, a positive end-expiratory pressure of 10 cm of water, and a fraction of inspired oxygen Fio2 of 100. A continuous infusion of propofol was begun. Hypotension persisted, and a diffuse purpu-ric rash developed. Approximately 2 hours after the patients arrival at the other hospital, a dose of piperacillintazobactam was administered, a 1-liter bolus of 0.45 normal saline with 150 meq of sodium bicarbonate was given, and a Foley catheter was inserted. Twenty minutes later, a continuous intravenous infusion of phenyleph-rine was added, followed 7 minutes later by a vasopressin infusion. The patient was transported by helicopter to the PICU of this hospital. On the patients admission to this hospital, additional history was obtained from family members. A friend who had eaten the same meal as the patient the evening before admission had vomited once shortly thereafter but had not become progressively ill. The patient had a history of anxiety and depression, as well as intermittent ear infections during childhood. He had no known drug allergies. He had reportedly received all routine childhood vaccinations. He smoked two packs of cigarettes weekly, smoked marijuana daily, and drank two alcoholic beverages approximately 2 times per week. He used dextromethorphan and diphenhydramine recre-ationally but did not use other illicit drugs. The patient lived in northern New England with his mother, brother, and three cats but had been staying with a friend for 5 days before admission, during which time he had visited a beach along the ocean and a music venue. He worked part-time at a restaurant; he had not traveled recently or had any other exposure to animals or ill persons. His father had coronary artery disease, his mother had hypothyroidism, and his brother had had viral meningitis at 6 weeks of age. On examination, the patient was pharmacologically sedated. The temperature was 40.8C, the pulse 166 beats per minute, the blood pressure 12053 mm Hg, the respiratory rate 28 breaths per minute, and the oxygen saturation 95 while he was receiving mechanical ventilation with an Fio2 of 50. He opened his eyes occasionally. The pupils were equal and reactive to light. The femoral pulses were palpable, but the peripheral pulses were not palpable and the digits were cold. There was diffuse anasarca and oozing from venipuncture sites and from the site of central venous catheter insertion. A diffuse reticular purpuric rash was present on the face, chest, abdomen, back, arms, and legs, sparing the palms and soles Fig. 1. A Foley catheter was in place, without urine output. Laboratory test results are shown in Table 1. Chest radiography revealed perihilar airspace and diffuse interstitial opacities and bilateral small, layering pleural effusions. Dr. Manuella Lahoud-Rahme: A transthoracic echo-cardiogram was obtained while the patient was receiving norepinephrine, epinephrine, and vaso-pressin. The left ventricle had moderate dysfunction with regional wall-motion abnormalities; septal motion was decreased, but apical motion appeared to be preserved. The right ventricle had mild-to-moderate dysfunction with underfilling. There was no pericardial effusion. Dr. Lucas: Approximately 7 hours after admission to this hospital, a diagnostic test result was received and additional management decisions were made. OUTPUT:

conduction system. The pacemaker was removed on hospital day 13. Dr. Lucas: This patient had a prolonged hospital course with many complications of fulminant meningococcemia, including necrosis of the arms Meningococcal purpura fulminans.

NEJM_Reasoning_Subset4

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Neil D. Fernandes Pediatrics: A 16-year-old boy was admitted to this hospital because of headache, nausea, vomiting, and abdominal pain. The patient had been well until 17 months before this admission, when he began to have episodes of headache and neck pain multiple times per week after an all-terrain vehicle ATV accident. Two months later, the patient collided with another adolescent while he was playing soccer, and the episodes of headache and neck pain worsened. He rated the pain at 8 on a scale of 0 to 10, with 10 indicating the most severe pain. Fifteen months before this admission, the patient was evaluated at the pediatric clinic of another hospital. On examination, the pulse was 95 beats per minute and the blood pressure 11778 mm Hg. There was mild tenderness in the area of the trapezius muscle. A radiograph of the cervical spine was normal. During the next 15 months, the patient was followed in the pediatric and neurology clinics of the other hospital. Ibuprofen, nortriptyline, sumatriptan, cyclobenzaprine, and diazepam were prescribed, but the headache did not abate. He underwent physical therapy, chiropractic adjustment, massage therapy, and acupuncture, but the symptoms persisted. Three months before this admission, nausea began to occur during the episodes of headache. The pain became more intense when the patient was lying down or was physically active, resulting in tunnel vision and vomiting; after he vomited, the pain became less intense. He was evaluated at the pediatric clinic of the other hospital. On examination, the pulse was 104 beats per minute and the blood pressure 12880 mm Hg. At the recommendation of his physicians, the patient stopped participating in all sports. Two days before this admission, the pain worsened and awoke the patient from sleep. The nausea was constant, and the vomiting occurred two times per day. The patient was unable to attend school because of the symptoms. His parents took him to the pediatric clinic of the other hospital. On examination, the temperature was 36.8C, the pulse 115 beats per minute, and the blood pressure 12064 mm Hg. The height was 183.6 cm, and the body-mass index BMI; the weight in kilograms divided by the square of the height in meters 27.0. The physical examination was normal. A probable diagnosis of mixed migraines and tension headaches was made. Prednisone, zolmitriptan, and ondansetron were prescribed, and the patient was sent home. On the day of this admission, the patient had new severe pain on the right side of the abdomen that awoke him from sleep. The headache, neck pain, and nausea were constant. The patient was taken to the emergency department of the other hospital. On examination, the temperature was 36.8C, the pulse 160 beats per minute, the blood pressure 239162 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 100 while he was receiving oxygen through a nasal cannula at a rate of 4 liters per minute. The white-cell count was 22,380 per microliter reference range at other hospital, 3800 to 10,500, the lactic acid level 2.7 mmol per liter 24 mg per deciliter; reference range, 0.5 to 2.2 mmol per liter 5 to 20 mg per deciliter, and the creatinine level 1.3 mg per deciliter 115 mol per liter; reference range, 0.6 to 1.3 mg per deciliter 53 to 115 mol per liter. An electrocardiogram ECG showed sinus tachycardia with increased R-wave and S-wave amplitudes in the precordial leads, as well as nonspecific repolarization abnormalities. One hour later, a repeat ECG showed an ectopic atrial rhythm with frequent premature ventricular contractions at a rate of 66 beats per minute. Intravenous hydromorphone, morphine, ondan-setron, metoclopramide, and lactated Ringers solution were administered. A nitroglycerin infusion was started, and the systolic blood pressure decreased to 143 mm Hg; the infusion was stopped, and the systolic blood pressure increased to 212 mm Hg. Intravenous labetalol was administered, and the systolic blood pressure decreased to 92 mm Hg. An esmolol infusion was started, and the patient was transferred to the pediatric intensive care unit PICU of this hospital, arriving 3 hours after presentation to the other hospital. Shortly after his arrival, the esmolol infusion was stopped. On admission to this hospital, additional history was obtained. The patient had played paint-ball a few days earlier but did not recall any direct trauma to the chest or abdomen. A review of systems was notable for heat intolerance and night sweats. He had a history of acne and had received a diagnosis of pneumonia involving the right upper lobe 10 months before this admission. He had normal growth and development and had received all routine childhood vaccines. His medications included doxycycline and topical tretinoin, clindamycin, and benzoyl peroxide, in addition to zolmitriptan and ondansetron; he had not started taking the recently prescribed pred-nisone. There were no known drug allergies. The patient lived in a suburban area of New England with his parents and younger brother. He performed well in high school. Before the recent progression of his symptoms, he had participated in soccer, basketball, and track. He did not smoke tobacco or use illicit drugs. He drank one or two alcoholic beverages per month. His father and paternal grandparents had hypertension, and his maternal aunts had migraines; his mother and brother were healthy. On examination, the temperature was 36.6C, the pulse 126 beats per minute, the blood pressure 9044 mm Hg, the respiratory rate 15 breaths per minute, and the oxygen saturation 100 while the patient was receiving oxygen through a nasal cannula at a rate of 4 liters per minute. He appeared tired, pale, and diaphoretic. He was in distress because of the pain; he spoke in brief sentences and had frequent hiccups. The abdomen was nondistended with marked tenderness in the right upper quadrant and right flank, with rebound and guarding. The skin was warm and clammy, and some inguinal hyperpigmentation was present. No cafe au lait spots were noted. The white-cell count was 27,140 per microliter reference range at this hospital, 4500 to 13,000, the lactic acid level 3.4 mmol per liter 31 mg per deciliter; reference range, 0.5 to 2.0 mmol per liter 5 to 18 mg per deciliter, the creatinine level 1.64 mg per deciliter 145 mol per liter; reference range, 0.60 to 1.50 mg per deciliter 53 to 133 mol per liter, and the high-sensitivity troponin T level 188 ng per liter reference range, 0 to 14. Additional laboratory test results are shown in Table 1. On hospital day 2, urinalysis revealed 1 blood, trace ketones, a pH of 5.0, and a specific gravity of 1.015; microscopic examination of the urinary sediment revealed squamous cells, crystals, and mucin, as well as 3 to 5 hyaline casts per high-power field, less than 10 white cells per high-power field, and no red cells. A diagnosis was made. OUTPUT:

Pheochromocytoma.

NEJM_Reasoning_Subset5

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. James W. Luccarelli Psychiatry: A 70-year-old man with bipolar disorder was evaluated at this hospital because of depressed mood, suicidal ideation, and gait disturbance. The patient had a long history of depressive episodes, with two previous hospitalizations for suicide attempts. Approximately two decades before the current admission, he was struck on the head with a beam while working at a construction site and had a 4-cm laceration. He presented to the emergency department of this hospital, where the wound was sutured but no further evaluation was conducted. Approximately 10 years before the current admission, around the time of his mothers death, the patient was evaluated at this hospital because of an episode of irritability, a reduced need for sleep, and grandiosity; he reported feelings of transcendence and being at one with God. He was admitted for 1 month to the psychiatry unit of a second hospital, where he was treated with lithium and elec-troconvulsive therapy. Thereafter, he received outpatient psychiatric treatment on a monthly basis, as well as therapy with valproic acid and fluoxetine. Approximately 9 years before the current admission, the patient fell on concrete stairs and had back pain with subsequent lower-leg weakness and urinary incontinence. He was evaluated at a third hospital, where magnetic resonance imaging MRI of the lumbar spine revealed multilevel degenerative changes, including L4L5 spinal stenosis and central disk protrusion. Acetaminophen and physical therapy were prescribed. Five years later 4 years before the current admission, the patient fell because of an unsteady gait and was evaluated at a fourth hospital. Neurologic examination revealed a memory deficit with an inability to recall any objects after 5 minutes on the three-item object-recall test and poor attention with an inability to perform serial sevens calculations, as well as action tremor in the arms and mildly unsteady gait, even with the use of a cane. The remainder of the physical examination was reportedly normal. The complete blood count, results of renal function tests, and levels of electrolytes, valproic acid, folate, vitamin B12, glycated hemoglobin, and thyrotropin were normal; serum and urine toxicologic panels were negative. MRI of the head reportedly revealed no evidence of an infarct, intracranial hemorrhage, or a mass but showed mild prominence of ventricles, sulci, and cisterns. The dose of fluoxetine was decreased, and the patient was discharged 3 days later. Additional falls occurred 2 months and 4 months later, and both times, the patient was evaluated at the fourth hospital. Two months after the most recent fall, he hit the car in front of him while driving. His psychiatrist noted that he had bilateral tremor at rest; the dose of val-proic acid was reduced, and he was referred to a neurologist. Two months after the car crash, he fell while walking and was evaluated at the fourth hospital. The evaluation was notable for nystagmus and a normal valproic acid level 89 g per milliliter; reference range, 50 to 100 despite the dose reduction; the doses of valproic acid and trazodone were reduced, and physical therapy was provided. During the next 5 months, gait instability was reduced but persisted. The patient was evaluated by two other neurologists after reporting a feeling of imbalance. Audiometry revealed mild-to-moderate high-frequency sensori-neural hearing loss. Medications were considered to be a contributor to his balance dysfunction. During the next 12 months, the dose of val-proic acid was tapered and fluoxetine was stopped; the patient underwent trials of escitalopram and then sertraline for the treatment of depressive symptoms. He reported to his psychiatrist symptoms of confusion, some difficulty with memory, and decreased leg coordination. The Montreal Cognitive Assessment score was 23 scores range from 0 to 30, with a score of 18 to 25 suggesting mild cognitive impairment. Dr. McKinley Glover: Fifteen months before the current admission, the patient began to have dizziness. MRI of the head Fig. 1, performed at this hospital, revealed an old infarct in the left corona radiata, features of mild small-vessel disease, mild diffuse brain parenchymal volume loss, and mild ventricular prominence. Dr. Luccarelli: Neuropsychiatric testing was performed, and the results did not suggest a neuro- OUTPUT:

Normal pressure hydrocephalus.

NEJM_Reasoning_Subset6

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. P. Connor Johnson Medicine: A 39-year-old woman presented to this hospital with fever, flank pain, and tender inguinal lymphadenopathy. The patient had been in her usual state of health until approximately 4 weeks before admission, when she noted tender bilateral inguinal swelling. Two days later, she began to have sharp, intermittent flank pain on the right side; she rated the pain at 5 on a scale of 0 to 10, with 10 indicating the most severe pain. During the next 3 days, she had nausea and a poor appetite. She noted foul-smelling urine but had no dysuria, urinary frequency, or hematuria. Three weeks before admission, the patient was evaluated by her primary care physician. On examination, the temperature was 36.6C, and she appeared well. There was costovertebral and abdominal tenderness on the right side, without rebound or guarding. The external genitalia were normal. Copious thin, white vaginal discharge was present; no cervical motion tenderness was noted, and the ovaries were normal on palpation. Multiple bilateral tender inguinal lymph nodes, measuring up to 2 cm in diameter, were noted on palpation. The remainder of the physical examination was normal. On microscopic examination of the vaginal discharge, clue cells were observed, but there were no fungal elements or trichomo-nads. Nucleic acid amplification tests of a cervical swab for Chlamydia trachomatis and Neisseria gonorrhoeae were negative. A blood test for IgM, IgG, and IgA antibodies to C. trachomatis serovars L1 and D through K was negative. Urinalysis revealed leukocyte esterase and nitrates; urine was obtained for culture. Vaginal metroni-dazole gel was prescribed. Two days later, the urine culture grew more than 100,000 colony-forming units CFU of Escherichia coli per milliliter and 10,000 to 100,000 CFU of Klebsiella pneu-moniae per milliliter. A 14-day course of trimethoprimsulfamethoxazole was prescribed. The inguinal swelling reportedly abated, but the flank pain and nausea persisted. Two days after the patient completed the prescribed course of trimethoprimsulfamethoxazole, fever and night sweats developed. After 3 days of fever with a temperature of up to 38.5C, she began vomiting and subsequently presented to the emergency department of this hospital for evaluation. In the emergency department, the patient reported ongoing flank pain, malaise, nausea, and poor appetite with weight loss of 2.3 kg during the past month. There was no sore throat, cough, or diarrhea. She had a history of hypothyroidism, asthma, bipolar disorder, dysmenorrhea, and migraines. She had had multiple urinary tract infections; pyelonephritis had been diagnosed 4 years before this presentation. A copper intrauterine device had been inserted 6 months before this presentation. Medications included albuterol, budesonideformoterol, divalproex, levothyroxine, loratadine, and sumatriptan as needed for migraines. The patient did not smoke tobacco, drink alcohol, or use illicit drugs. She had immigrated to the United States from Brazil 1 year earlier; she had been living in New England during the past year and had been working in a laboratory. She had recently spent 3 months in Brazil visiting her husband and had returned to New England shortly before she noted inguinal swelling. While in Brazil, she had remained in a large city and had not visited any remote locations. In New England, she lived alone with one kitten and one full-grown cat. There was no family history of cancer. An aunt had died from tuberculosis, but the patient had had only minimal contact with her aunt. On examination, the temperature was 36.6C, the blood pressure 10063 mm Hg, the heart rate 77 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 100 while the patient was breathing ambient air. The weight was 67.5 kg and the body-mass index the weight in kilograms divided by the square of the height in meters 24.4. The patient appeared ill. The right side of the abdomen was tender on palpation, without rebound or guarding. Hepatosplenomegaly was not present. Tender bilateral inguinal lymph nodes were noted. No palpable cervical, supraclavicular, infraclavicular, or axillary lymphadenopathy was noted. The remainder of the physical examination was normal. A urine test for human chorionic gonado-tropin was negative. Blood levels of glucose, electrolytes, creatine kinase, and lactate dehy-drogenase were normal, as were the results of liver-function and kidney-function tests. Blood tests for human immunodeficiency virus HIV type 1 p24 antigen and antibodies to HIV types 1 and 2 were negative, as was an interferon- release assay for Mycobacterium tuberculosis. Other laboratory test results are shown in Table 1. Imaging studies were obtained. Dr. Madeleine Sertic: Computed tomography CT of the abdomen and pelvis Fig. 1, performed without the administration of intravenous contrast material, revealed bilateral inguinal lymph-adenopathy, with the largest node, on the right side, measuring 2.6 cm in greatest dimension. A right pelvic sidewall lymph node measuring 1.3 cm in greatest dimension, a gastrohepatic lymph node measuring 0.9 cm in greatest dimension, and lymphadenopathy in the porta hepatis were also seen. Transvaginal ultrasonography revealed an intrauterine device in an appropriate position, normal ovaries, and trace free fluid in the pelvis. Dr. Johnson: Intravenous fluids and intramuscular ketorolac were administered, and the patient was admitted to the hospital. A diagnostic test was performed. OUTPUT:

Bartonella henselae infection (cat scratch disease).

NEJM_Reasoning_Subset7

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Carolina Chiou Ophthalmology: A 78-year-old man was admitted to this hospital because of a rash on the forehead and frontal scalp and edema of the left eyelids. The patient had been well until 3 days before presentation, when pressurelike pain developed in the left side of the forehead and frontal scalp and the bilateral maxillary sinuses and upper jaws. He described the pain as similar to previous episodes of sinusitis. He was evaluated in the primary care clinic of another hospital, and treatment with oral clindamycin was started for a presumed diagnosis of sinusitis. Two days before presentation, the patient noted erythema and small reddish-brown skin lesions on the left side of the forehead and frontal scalp. His barber had pointed out a similar spot on the top of his scalp 2 weeks earlier. The skin lesions were not painful or itchy, and he did not seek medical evaluation. On the day of presentation, the patient awoke from sleep and noted redness and swelling of the left eyelids. The skin lesions on the left side of the forehead and frontal scalp had increased in number, and some were covered with hemorrhagic crust. There was pain with movement of the left eye and blurry vision. Over the course of several hours, the swelling of the left eyelids worsened and the patient was unable to fully open the left eye. He presented to the emergency department of this hospital for evaluation. In the emergency department, the patient reported no ocular or nasal discharge, no changes in taste or hearing, and no jaw claudication. He had not recently changed his shampoo or been in a pool or hot tub. He had a history of recurrent sinus infection, allergic rhinitis, depression, benign prostatic hyperplasia, hypogonadism, and restless legs syndrome. He had received a diagnosis of rectal cancer 15 years earlier, which had led to partial colectomy, as well as a diagnosis of testicular cancer 50 years earlier, which had led to orchiectomy and radiation therapy. His ocular history included bilateral mild ptosis; he had undergone bilateral cataract extraction with intraocular lens implantation. Medications included finasteride, tamsu-losin, carbidopalevodopa, nasal azelastine and fluticasone, and topical testosterone. Levofloxacin, cefaclor, and sulfamethoxazoletrimethoprim had caused a rash. The patient was a retired engineer and lived with his wife in a coastal community of New England. He had previously smoked a pipe but had quit 30 years earlier. He drank a quarter glass of wine daily. His family history included skin cancer in his maternal grandmother and macular degeneration in his sister. On examination, the temperature was 38.1C, the blood pressure 12258 mm Hg, and the heart rate 74 beats per minute. The body-mass index the weight in kilograms divided by the square of the height in meters was 31.9. Visual acuity without glasses was 2040 in the right eye and 2050 in the left eye. Results of Ishihara color testing were normal. The pupils were equal, round, and reactive to light; there was no relative afferent pupillary defect. Extraocular movements were full. There was complete ptosis of the left upper eyelid, along with erythema and edema of left upper and lower lids. There was mild ptosis of the right upper lid. There was no proptosis. The intraocular pressure was 17 mm Hg in both eyes. Slit-lamp examination revealed diffuse con-junctival injection and inferior chemosis in the left eye. The corneas were clear, and no cells were visualized in the anterior chambers. Results of dilated fundoscopic examination were normal. There was prominent erythema affecting the forehead, left side of the anterior scalp, and left eyelids. Multiple coalescing erosions covered with hemorrhagic and serous crust were seen at sites of erythema, mainly affecting the left side of the forehead and extending to the midline, the frontal scalp, and the left upper eyelid. Erosions and erythema affected the right side of the forehead, as well, but to a much lesser extent. The remainder of the physical examination was normal. Laboratory evaluation revealed a blood sodium level of 125 mmol per liter reference range, 135 to 145. Results of kidney- and liver-function tests were normal. Tests for human immunodeficiency virus types 1 and 2 were negative. Other laboratory test results are shown in Table 1. Dr. Hillary R. Kelly: Computed tomography CT of the head and face Fig. 1, performed after the administration of intravenous contrast material, revealed marked swelling affecting the soft tissue over the left orbit and frontal sinus and extending superiorly along the superficial soft tissue of the frontal scalp, predominantly on the left side. The globe, orbit, and retrobulbar soft tissue were normal. The right maxillary sinus showed nearly complete opacification with wall thickening and sclerosis, findings consistent with chronic inflammation and sinusitis. There was a defect in the medial wall of the right maxillary sinus that was consistent with previous sinus surgery. The other paranasal sinuses, including the left maxillary sinus, ethmoid sinuses, and sphenoid sinuses, were well aerated. Dr. Chiou: Empirical treatment with valacyclo-vir, amoxicillinclavulanate, and topical bacitra-cinpolymyxin B was started. The next day, the edema and erythema of the left eyelids worsened, and there was new edema and erythema of the right eyelids. The patient was unable to open his eyes. He began to have visual hallucinations, and his wife noted that he was confused. The skin lesions on the left side of the forehead were unchanged, and new round punched-out erosions with overlying hemorrhagic crust were present on the right side of the forehead Fig. 2. Empirical treatment with intravenous vancomycin, cefepime, and acyclovir was started. A diagnostic test was performed. OUTPUT:

Varicella–zoster virus infection.

NEJM_Reasoning_Subset8

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Katherine A. Sparger: A newborn girl was admitted to the neonatal intensive care unit of this hospital after a planned delivery by cesarean section because of a neck mass. During pregnancy, the patients mother was 41 years old gravida 3, para 1 and received prenatal care at another hospital. At 7 weeks of gestation, vaginal bleeding occurred because of a subchorionic hematoma. At 10 weeks of gestation, the mothers blood thyrotropin level was 0.01 U per milliliter reference range, 0.40 to 5.00; levels of free thyroxine free T4 and total triiodothyronine total T3 were not obtained. At 19 weeks of gestation, the thyrotropin level was 0.44 U per milliliter and an ultrasonographic survey of the fetal anatomy was normal. During the third trimester, gestational diabetes was diagnosed; glycemic control was maintained with dietary changes. Four weeks before delivery, at 34 weeks 6 days of gestation, a routine transvaginal ultrasonographic survey of fetal growth revealed a new mass on the right side of the fetuss neck that measured 2.6 cm by 3.4 cm by 3.0 cm. The mother was referred to the obstetrics clinic of this hospital for further evaluation and treatment. Dr. Randheer Shailam: At 35 weeks 6 days of gestation, obstetrical ultrasonography performed at this hospital Fig. 1A confirmed the presence of a 4.6cm mass on the right side of the neck. The mass was hyperechoic and well circumscribed and had internal vascularity; the remainder of the survey of fetal anatomy was normal. Magnetic resonance imaging MRI of the fetus, performed without the intravenous administration of contrast material Fig. 1B, 1C, and 1D, revealed displacement of the trachea without compression. Dr. Sparger: For multiple weeks, the fetal biophysical profile score was 8 out of 8, indicating normal breathing motion, movement, tone, and amniotic fluid volume. The mother met with providers from MaternalFetal Medicine, Pediatric Surgery, OUTPUT:

Nodular follicular thyroid neoplasm with a so­matic NRAS mutation.

NEJM_Reasoning_Subset9

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Kathleen W. Miller Medicine: A 64-year-old woman was admitted to this hospital in early winter with fever and pancytopenia. The patient, who had multiple sclerosis, had been in her usual state of health until 7 months before admission, when nausea and fatigue developed. Over the next 2 months, these symptoms worsened, and in the context of severe nausea, two episodes of vasovagal syncope occurred. During an evaluation for syncope, anemia was noted. Five months before admission, the patient was evaluated by her primary care provider at another hospital. The weight was 87.6 kg, and the results of physical examination were normal. Blood levels of electrolytes, glucose, cobala-min, folate, iron, iron saturation, and total iron-binding capacity were normal, as were the results of kidney-function tests; other laboratory test results are shown in Table 1. Iron supplementation was prescribed. Nausea and fatigue persisted. Three months before admission, the patient was again evaluated by her primary care provider at the other hospital. The weight was 84.4 kg; the remainder of the examination was unchanged. Blood levels of electrolytes and glucose were normal, as were the results of kidney-function tests; other laboratory test results are shown in Table 1. Computed tomography CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed cholelithiasis and splenomegaly, with the spleen measuring 17 cm in the craniocaudal dimension normal value, 12 cm. Two and a half months before admission, the patient was evaluated in a hematology clinic affiliated with the other hospital. She reported persistent nausea and fatigue, poor appetite with reduced oral intake, and 2 weeks of dyspnea on exertion. There was no orthopnea or paroxysmal nocturnal dyspnea. The weight was 83.2 kg, and the spleen tip was palpable four fingerbreadths below the costal margin; the remainder of the physical examination was normal. A bone marrow biopsy was performed, and examination of the bone marrow specimen revealed mildly hypercel-lular marrow with maturing trilineage hematopoiesis and mild dyserythropoiesis. Treatment with prednisone and folic acid was begun. Ocrelizumab infusions for multiple sclerosis were stopped. Nausea and fatigue persisted, and fevers and sweats developed. After 3 weeks of treatment with prednisone, the anemia had not abated and the patient had temperatures as high as 39.0C. Testing for influenza A and B viruses was negative. Two units of packed red cells were transfused. The course of prednisone was tapered off over the next 18 days, and the patient was referred to a hematologist affiliated with this hospital. In the hematology clinic, the patient reported that the fevers had resolved but the fatigue, weakness, and poor appetite had worsened. She felt too fatigued to walk, and she had recently had a fall without loss of consciousness. The weight was 82.4 kg; splenomegaly was present, and the remainder of the examination was unchanged. The patient was admitted to this hospital for further evaluation and treatment. In addition to relapsingremitting multiple sclerosis, there was a history of trigeminal neuralgia, restless legs syndrome, vasovagal syncope when blood samples were obtained, and an elevated alkaline phosphatase level for 1 year without a clear cause. Medications included oxcar-bazepine, gabapentin, ropinirole, folic acid, and cholecalciferol. There were no known drug allergies. The patient had quit smoking 20 years earlier and did not drink alcohol or use illicit drugs. She lived in a suburban area of New England with her adult son and pet cat and dog. Her backyard adjoined a large wooded area where deer were often seen. She worked in health care administration. Her family history included diabetes in her mother, lung cancer in her father, and multiple sclerosis in her sister. On examination, the patient appeared pale but not unwell. The temperature was 38.3C, the blood pressure 9054 mm Hg, the heart rate 93 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 93 while she was breathing ambient air. The weight was 79.8 kg and the body-mass index the weight in kilograms divided by the square of the height in meters 32.2. The conjunctivae were pale. The heart rate was regular, with normal first and second heart sounds S1 and S2 and a soft systolic murmur. There was edema in the legs. The remainder of the examination was normal. Blood levels of homocysteine, methylmalonic acid, arsenic, cadmium, lead, and mercury were normal, as were the results of serum protein electrophoresis and coagulation tests; other laboratory test results are shown in Table 1. Blood cultures were obtained. Two units of packed red cells were transfused, and one dose of intravenous furosemide was administered. Intravenous methylprednisolone was administered daily for 3 days, and the patient reported a decrease in weakness and fatigue. Dr. Dexter P. Mendoza: On hospital day 4, CT of the chest, abdomen, and pelvis Fig. 1A revealed splenomegaly, with the spleen measuring 19 cm in the craniocaudal dimension. Concurrent positron-emission tomography with injection of 18F-fluorodeoxyglucose Fig. 1B revealed intense uptake in the spleen and diffuse uptake in the bone marrow throughout the axial and appen-dicular skeleton. Dr. Miller: On hospital day 5, the patient reported a recurrence of severe fatigue and generalized weakness. The temperature was 39.0C and the heart rate 130 beats per minute. The results of physical examination were otherwise unchanged. Laboratory test results are shown in Table 1. A diagnostic test result was received. OUTPUT:

Babesiosis.

NEJM_Reasoning_Subset10

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Arielle J. Medford: A 76-year-old woman with heart failure and type 2 diabetes mel-litus was admitted to this hospital with nausea, diarrhea, and acute kidney failure. The patient normally lived independently, but she had been staying in a skilled nursing facility for the past several weeks to recover from a recent humeral fracture. During her stay, nausea, abdominal cramps, and nonbloody diarrhea developed. The next day, the symptoms persisted, and she was transferred to the emergency department of this hospital. Approximately 3 months before the current admission, the patient was admitted to this hospital with respiratory failure due to an exacerbation of heart failure and pneumonia. She was treated with intravenous ceftriaxone and oral doxycycline for 5 days, and diuretic agents were adjusted during a 3-week hospitalization. Nine weeks before the current admission, the patients condition returned to baseline, and she was discharged home with instructions to continue a diuretic regimen of torsemide and spironolactone. The patients dry weight was 127 kg. Laboratory test results at the time of discharge are shown in Table 1. Four weeks before the current admission, the patient lost her balance while walking and fell onto her right side. She had no loss of consciousness, chest pain, or other symptoms. She was evaluated in the emergency department of this hospital and reported pain in her right arm. On examination, there were abrasions and bruising over the right elbow, with tenderness on palpation; the weight was 123 kg. The right radial pulse was normal, and sensation was intact in the arm and hand. Laboratory test results are shown in Table 1. Radiography of the right arm showed a mild transcondylar fracture of the right distal humerus. A splint was placed, and the patient was advised not to bear weight with the right arm. She was discharged to a skilled nursing facility for increased support with daily activities while she was recovering. Two weeks before the current admission, while the patient was staying in the skilled nursing facility, edema developed in both legs, and her weight increased by 5 kg. She attributed the weight gain to increased salt intake. Nine days before the current admission, oral metolazone was added to her diuretic regimen, and the leg edema resolved. At the time of the current admission, the patient reported nausea and abdominal cramps. She reported no fever, chills, cough, dyspnea, dysuria, flank pain, or vomiting. She had no known sick contacts. Her medical history included hypertension, atrial fibrillation, coronary artery disease, heart failure with reduced ejection fraction, type 2 diabetes mellitus, and obstructive sleep apnea, for which nightly treatment with continuous positive airway pressure had been prescribed. Medications included allopurinol, amiodarone, aspirin, atorvastatin, cyclobenzap-rine, enoxaparin, fluticasone, glipizide, loratadine, lorazepam, metformin, metolazone, metoprolol, sertraline, spironolactone, torsemide, warfarin, and zolpidem. The last doses of metolazone, spironolactone, and torsemide were taken more than 24 hours before admission. There were no known drug allergies. Before the recent humeral fracture, the patient had been living alone in an urban area of New England; she required assistance from home health services for bathing and chores and used a walker for ambulation. She did not smoke tobacco or drink alcohol. She had no recent history of travel, and her family history was unremarkable. On examination, the patient appeared well, without respiratory distress. The temperature was 36.7C, the blood pressure 13763 mm Hg, the heart rate 83 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 99 while she was breathing ambient air. The weight was 126 kg. The oral mucous membranes were dry. The heart sounds were normal, as were the breath sounds throughout both lung fields. There was no edema in the lower legs. The right arm was in a splint. The blood level of creatinine was 7.66 mg per deciliter 677 mol per liter; reference range, 0.60 to 1.50 mg per deciliter 53 to 133 mol per liter, and the level of lactic acid was 7.4 mmol per liter 67 mg per deciliter; reference range, 0.5 to 2.0 mmol per liter 4.5 to 18 mg per deciliter. Urinalysis by dipstick showed a pH of 5.0 reference range, 5.0 to 9.0 and a specific gravity of 1.012 reference range, 1.001 to 1.035, and no protein, blood, nitrites, leukocyte esterase, glucose, or ketones were present. Additional laboratory test results are shown in Table 1. Chest radiography revealed mild pulmonary interstitial edema. Ultrasonography of the kidneys and urinary tract revealed simple cysts in the left kidney, with no evidence of hydronephrosis or nephrolithiasis. Intravenous fluids were administered, and a diagnosis was made. OUTPUT:

Lactic acidosis due to toxic effects from metfor-min use.

NEJM_Reasoning_Subset11

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Adam Tanious Surgery: A 37-year-old woman was transferred to this hospital because of abdominal pain and aortic dilatation. The patient had been well until 3 weeks before the current admission, when she began to have pain in the right side of the abdomen that radiated to the back. She also had nausea, vomiting, fever, and chills. Approximately 2 weeks before the current admission, she sought evaluation at the emergency department of another hospital. Physical examination was notable for pain with palpation of all four quadrants. The pulses were normal, and the blood pressure did not differ substantially between the two arms or between the two legs. The white-cell count was 9800 per microliter reference range at the other hospital, 4800 to 10,000, the erythrocyte sedimentation rate 41 mm per hour reference range, 0 to 20, and the C-reactive protein level 44.0 mg per liter reference range, 0 to 10.0. Other laboratory test results are shown in Table 1. Blood specimens were obtained for two sets of bacterial cultures, with each set consisting of an aerobic bottle and an anaerobic bottle. Dr. Patrick D. Sutphin: Computed tomography CT of the abdomen and pelvis, performed without the intravenous administration of contrast material, revealed soft-tissue density adjacent to the infrarenal abdominal aorta and mild-to-moderate associated periaortic fat stranding Fig. 1A and 1B. These findings prompted CT angiography, performed 1 hour later, which more clearly delineated infrarenal abdominal aortic wall thickening at the level of the inferior mesenteric artery, with an aortic diameter of 2.3 cm Fig. 1C. Dr. Tanious: The patient was discharged from the emergency department of the other hospital on the same day, with a referral to the rheumatology clinic of that hospital and instructions to start treatment with prednisone. One day after discharge, one of the four culture bottles grew gram-positive bacilli, and the patient was admitted to the other hospital for investigation. After an evaluation, the positive culture was presumed to be contaminated. Additional blood specimens were obtained for culture, and the patient was discharged home on the second hospital day. The fever and chills resolved, and the abdominal pain abated initially but then gradually worsened. Eight days after discharge and 3 days before the current admission, the patient returned to the emergency department of the other hospital. On examination, the temperature was 36.8C, the pulse 50 beats per minute, and the blood pressure 14678 mm Hg. Physical examination was notable for diffuse abdominal tenderness, which was worse with deep palpation in all four quadrants. The white-cell count was 32,800 per microliter, the platelet count 565,000 per micro-liter reference range, 140,000 to 440,000, the erythrocyte sedimentation rate 18 mm per hour, and the C-reactive protein level 110.0 mg per liter. The urinalysis was normal; urine toxicologic screening was positive for amphetamines, canna-binoids, and opiates. Other laboratory test results are shown in Table 1. Dr. Sutphin: CT angiography revealed progression of aortic wall thickening and periaortic fat stranding and interval narrowing of the proximal segment of the inferior mesenteric artery, with an increase in the aortic diameter to 3.1 cm. Dr. Tanious: The patient was admitted to the other hospital for a second time. Intravenous fluids, methylprednisolone, and heparin were administered, as was empirical treatment with vancomycin and piperacillintazobactam. During the next 3 days, the patient remained afebrile. Consultations with the rheumatology, infectious diseases, and vascular surgery departments were requested. Dr. Sutphin: On the second hospital day, magnetic resonance angiography of the abdomen revealed an increase in aneurysmal dilatation of the infrarenal abdominal aorta aortic diameter, 3.6 cm with enhancement of the aortic wall. On the fourth hospital day, CT angiography of the abdomen and pelvis revealed a further increase in aneurysmal dilatation of the infrarenal abdominal aorta aortic diameter, 3.9 cm with increasing luminal irregularity and periaortic fat stranding. Dr. Tanious: The patient was transferred to this hospital for additional treatment. On evaluation, she reported abdominal pain that was worst in the right upper quadrant and radiated to the right lower quadrant, back, and chest. She rated the pain as 10 on a scale of 0 to 10, with 10 indicating the most severe pain. She also reported nausea but had not had fevers or chills since before the initial presentation. A review of systems was notable for the absence of fatigue, weight loss, night sweats, myalgias, joint pain, and rash; blue fingertips occurred with exposure to cold. Dr. Sutphin: CT angiography of the abdomen and pelvis revealed evidence of continued aneu-rysmal enlargement and increased luminal irregularity Fig. 1D, 1E, and 1F. Dr. Tanious: The patient had a history of poly-cystic ovary syndrome, depression, post-traumatic stress disorder, attention deficithyperactivity disorder, asthma, and Chiari I malformation, which had led to suboccipital craniectomy 3 years earlier. She had undergone cesarean section 5 years earlier. Medications included prednisone, cloni-dine, promethazine, dicyclomine, and inhaled albuterol; latex had caused a rash. The patient was White, lived in an urban area of New England, and had recently been homeless. She had injected heroin for the past 5 years; her last injection had been 3 weeks earlier. She had a history of marijuana use and reported no methamphetamine use. Sexual history was not obtained. She drank four alcoholic beverages and smoked one pack of cigarettes daily. Her sister had rheumatoid arthritis, her grandmother had tuberculosis, and several family members had hypermobility of the joints. On examination, the patient was uncomfortable because of the abdominal pain. The abdomen was soft, with diffuse tenderness that was worst in the right upper quadrant and both lower quadrants. She did not have any ulcers, rash, lymphadenopathy, or warmth, redness, or swelling of the joints; the elbows and metacar-pophalangeal joints were hyperextensible. The white-cell count was 27,710 per microliter reference range at this hospital, 4500 to 11,000, the platelet count 576,000 per microliter reference range, 150,000 to 400,000, the erythrocyte sedimentation rate 57 mm per hour reference range, 0 to 20, and the C-reactive protein level 60.6 mg per liter reference range, 0 to 8.0. Testing for human immunodeficiency virus types 1 and 2 was negative. Serologic testing for hepatitis C virus was positive. The blood-culture isolate detected at the other hospital was identified as bacillus species, and all other blood cultures performed at the other hospital showed no growth. Other laboratory test results are shown in Table 1. Management decisions were made. OUTPUT:

Staphylococcus aureus bacteremia and infection of a vascular graft.

NEJM_Reasoning_Subset12

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Vishwajith Sridharan Medicine: An 82-year-old woman was admitted to this hospital with pain, swelling, and ecchymosis of the left arm. The patient had been in her usual state of health until 4 days before admission, when she awoke from sleep with swelling and discoloration of the skin of the left arm above the elbow. There was no history of trauma to the arm. Over the next 2 days, the swelling and discoloration spread to the elbow and forearm and pain developed. The patient presented to the emergency department of another hospital for evaluation. On examination, the temperature was 36.9C, the blood pressure 15365 mm Hg, the pulse 59 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 98 while she was breathing ambient air. Ecchymosis extended from above the left elbow to the left wrist, and there was pain with palpation of the left forearm. The radial pulse was normal, as was range of motion in the left elbow and wrist. Radiographs of the left forearm showed diffuse osteopenia and degenerative changes of the wrist joint, without fractures or bone lesions. Blood levels of electrolytes and glucose were normal, as were results of kidney-function tests; other laboratory test results are shown in Table 1. Ibuprofen was administered, and the patient was given a shoulder sling for comfort and discharged home. Over the next 2 days, the pain in the left arm worsened and the ecchymosis spread to the left hand and digits. The pain did not abate with the use of ice packs or acetaminophen or with elevation of the arm. The patient presented to the emergency department of this hospital for further evaluation. In the emergency department, the patient reported pain in the left arm that occurred with supination or while she was making a fist. There was no numbness or tingling in the arm or hand or history of hemarthrosis, prolonged bleeding with dental procedures, or menorrhagia. The medical history was notable for hypertension, dyslipidemia, peripheral vascular disease, carotid artery stenosis, osteoporo-sis, chronic kidney disease, and obesity, as well as an episode of deep venous thrombosis 40 years earlier. Medications included aspirin, ator-vastatin, lisinopril, hydrochlorothiazide, and meto-prolol. The patient had smoked tobacco for 40 years but had quit 22 years earlier. She did not drink alcohol or use illicit drugs. She was widowed and lived alone but visited with her grown children regularly. Her father had had coronary artery disease. On examination, the temperature was 36.1C, the blood pressure 16977 mm Hg, the pulse 76 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 97 while the patient was breathing ambient air. The weight was 72.5 kg and the body-mass index the weight in kilograms divided by the square of the height in meters 32.3. There was discoloration of the left arm with sharp demarcation in the middle of the upper arm, proximal to the elbow, and uniform extension to the metacarpophalan-geal joints Fig. 1. There was tenderness with palpation of the forearm and dorsal wrist, passive range of motion of the wrist and elbow, and diffuse swelling and mild firmness of the forearm, without induration. Sensation to light touch was intact throughout the arm and hand. The radial pulse was normal, and the fingers were warm, with brisk capillary refill in all the digits. The remainder of the physical examination was normal. Blood levels of electrolytes and glucose were normal, as were results of kidney- and liver-function tests; other laboratory test results are shown in Table 1. Dr. Patrick D. Sutphin: Computed tomography CT of the left arm, performed after the administration of intravenous contrast material, revealed disproportionate enlargement of the brachiora-dialis muscle, a finding suggestive of intramuscular hematoma. There was hyperdense strand-ing in the subcutaneous fat centered over the elbow and forearm, a finding consistent with hemorrhage Fig. 2. CT angiography of the arteries revealed heavy, partially calcified plaque throughout the thoracic aorta. Focal heavy plaque in the left subclavian artery proximal to the vertebral artery resulted in approximately 70 to 80 stenosis Fig. 3. The arteries in the left arm were otherwise patent. There were no signs of active hemorrhage on arterial or delayed-phase images or findings that could lead to localization of an arterial injury, such as pseudoaneurysm or dissection. In addition, an enhancing mass was not identified. The visualized superficial and deep veins were patent on delayed-phase images. Dr. Sridharan: A diagnostic test was performed. OUTPUT:

Acquired factor VIII inhibitor.

NEJM_Reasoning_Subset13

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Matthew J. Emmett Medicine: An 81-year-old man was admitted to this hospital with fever, cough, and shortness of breath during the pandemic of coronavirus disease 2019 Covid-19, the disease caused by severe acute respiratory syndrome coronavirus 2 SARS-CoV-2. The patient had been in his usual state of health until 3 days before this admission, when fever and cough developed. On the morning of admission, he noted an abrupt onset of shortness of breath at rest and dyspnea on exertion. There was also substernal chest pain on the left side that worsened with deep breaths and when he lay down. The patients son called emergency medical services, and the patient was brought to the emergency department of this hospital for further evaluation. On arrival at the emergency department, the patient described ongoing chest pain and shortness of breath. The son reported that the patient had fallen at home 2 days before admission, but the patient did not remember falling and the son was not able to provide details about the nature or circumstances of the fall. The patient reported no pain in his abdomen, arms, legs, or groin and no headache. The patient had a history of hypertension. During a previous evaluation for cough, he was reportedly told that he had a lung disease that had caused the lung tissue to harden. Before the onset of his most recent symptoms, he had walked outside on a daily basis without limitation from shortness of breath. He took an unknown medication for hypertension. The patient did not smoke tobacco, use illicit drugs, or drink alcohol. He lived in an apartment with his wife. On examination, the temperature was 37.9C, the blood pressure 15795 mm Hg, the pulse 112 beats per minute, the respiratory rate 30 breaths per minute, and the oxygen saturation 91 while the patient was breathing ambient air. The respiratory rate decreased to 28 breaths per minute and the oxygen saturation improved to 96 with the administration of supplemental oxygen through a nasal cannula at a rate of 4 liters per minute. The body-mass index the weight in kilograms divided by the square of the height in meters was 22.8. Retractions were noted in the supraclavicular areas. Inspiratory crackles could be heard at the lung bases. The heart sounds were regular, with tachycardia but no murmur. There was no tenderness on palpation of the chest wall and no edema in the legs. Laboratory test results are shown in Table 1. Dr. Reece J. Goiffon: A single-view portable an-teroposterior radiograph of the chest showed bilateral patchy airspace opacities that were more extensive in the left lung than in the right lung, with predominance in the peripheral lower lung zones and with relative sparing of the peri-hilar regions Fig. 1. These opacities were superimposed on mild apical and bibasilar bron-chiectasis and bibasilar reticular opacities. A radiograph of the pelvis showed no fracture. Dr. Emmett: An electrocardiogram showed sinus tachycardia. Blood samples were obtained for culture, and a nasopharyngeal swab was submitted to test for SARS-CoV-2 RNA. Azithromycin and ceftriaxone were administered, and the patient was admitted to the hospital. On arrival at the medical floor, the patient was in respiratory distress, with a respiratory rate of 40 breaths per minute and an oxygen saturation of 86 while he was receiving supplemental oxygen through a nasal cannula at a rate of 4 liters per minute. The patient was restless and appeared uncomfortable, moving around in the bed and attempting to sit up; he reported severe pleuritic chest pain. The oxygen flow rate was adjusted to 5 liters per minute, and morphine was administered intravenously. A repeat electrocardiogram showed sinus tachycardia. A diagnostic test was performed. OUTPUT:

Pneumonia associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute pulmonary embolism.

NEJM_Reasoning_Subset14

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. David P. Bullis Behavioral Medicine, NewtonWellesley Hospital, Newton, MA: A 54-year-old man was evaluated by the neuropsychology service of this hospital because of irritability, confusion, and odd behaviors. The patient had been in his usual state of health until 9 months before the current evaluation, when he received a diagnosis of squamous-cell carcinoma of the tongue that had metastasized to the cervical lymph nodes. He underwent surgical dissection of the neck and resection of the tongue base on the right side, followed by adjuvant radiation therapy, which resulted in cancer remission. After treatment, neck pain and shoulder weakness developed and was attributed to postoperative neuropathy involving the right spinal accessory nerve. In the context of this illness and persistent pain, the patient sought care at the cancer center behavioral medicine clinic of this hospital and received a diagnosis of adjustment disorder with depression and anxiety. During the next 8 months, the patient was seen for psychotherapy approximately every 2 weeks. Treatment for the pain included physical therapy, occupational therapy, massage therapy, acupuncture, trigger-point injections, and the use of a scapular elevation brace. Therapy with oxycodone, methadone, gabapentin, tizanidine, and duloxetine was started. Four months before the current evaluation, a sural nerve graft was placed in the right spinal accessory nerve from the proximal, functioning portion to the distal portion, but the pain and weakness did not abate. Six weeks before the current evaluation, the patient did not respond to telephone calls for 24 hours. The police were called and found the patient unresponsive with prescription medication bottles nearby. Emergency medical services personnel arrived, and the initial evaluation, in the patients home, was notable for a severely decreased respiratory rate. Naloxone was administered, the trachea was intubated, and the patient was taken to a local hospital. In the emergency department, the patient was pulseless with ongoing electrocardiographic activity. Cardiopulmonary resuscitation was performed, and epinephrine was administered; after 4 minutes, spontaneous circulation was restored. The dose of methadone was decreased, and therapy with oxycodone, gaba-pentin, and tizanidine was stopped. During the subsequent 6 days, septic shock, aspiration pneumonia, acute kidney injury, and delirium occurred. When these problems resolved, the patient was discharged home. Five weeks before the current evaluation, the patient participated in a video follow-up evaluation at the behavioral medicine clinic. He expressed embarrassment and frustration related to his apparent accidental overdose. He described persistent depression, increased anxiety, and no other new symptoms. Two weeks before the current evaluation, the patient missed a routine video follow-up evaluation at the behavioral medicine clinic, and his family was called. For the preceding 2 weeks, they had noticed that the patient was uncharacteristically agitated, irritable, talking loudly, and verbally abusive. Odd behaviors were reported. The patient had gotten lost while driving to a friends house that he visited frequently, had been pulled over by police for driving erratically with normal results on a breathalyzer test, and on another occasion, had been found walking along the highway under an overpass. He called family members repeatedly in the middle of the night, and he would not answer when the calls were returned. When the family requested a police wellness check of the patient, the patient retaliated by requesting a police wellness check of the family members. After this incident, the family was advised to take the patient to a local hospital for admission. At the local hospital, the patient reported no symptoms and noted that he had stopped taking methadone because he was concerned about a medication overdose. The Montreal Cognitive Assessment score was 19, indicating cognitive impairment; scores range from 0 to 30, with higher scores indicating better cognitive function.1 Computed tomography CT of the head, performed without the administration of intravenous contrast material, revealed a nonspecific hypodensity in the centrum semiovale on the left side. The patient was told he had mild dementia. Visiting nurse services were arranged, and the patient was discharged home. One week before the current evaluation, the patients family reported that he had increased confusion and odd behaviors. He was unable to recall details of conversations that had happened minutes before. He could not operate the telephone or remote control and had emptied the trash can into the toilet. He had asked for his clothes to be cut off because he felt uncomfortable. Family members had been staying with the patient every night since his recent discharge because they were concerned about his safety. A neuropsychological evaluation was requested. Dr. Michael W. Parsons: The evaluation was conducted by the cancer center neuropsychology service of this hospital with the use of videoconferencing technology to reduce the risk of exposure to coronavirus disease 2019 Covid-19. The patient acknowledged only minimal cognitive changes and was dismissive of the familys concerns. A review of systems was notable for fatigue, moderate depression, mild anxiety, and difficulty sleeping and keeping track of time. Additional history obtained from the patients family included insomnia, lumbar disk herniation, olecranon bursitis, and an inguinal hernia that had led to surgical repair in early adulthood. He had had multiple concussions as a teenager, as well as a brief loss of consciousness during a motor vehicle collision 3 years earlier. After the collision, fatigue, headaches, difficulty concentrating, and impaired memory occurred; during the subsequent 2 years, occupational therapy was provided, and the symptoms gradually resolved. Medications at the time of evaluation included ibuprofen, acetaminophen, duloxetine, trazo-done, melatonin, polyethylene glycol, and multivitamins. There were no known drug allergies. The patient lived alone in a suburban area of New England with family members nearby. He had completed a masters degree and had had a successful career; he had taken a leave of absence from work 9 months earlier in anticipation of cancer treatment. After cancer treatment, he had been unable to return to work because of pain. He was athletic, walked 3 miles daily, and enjoyed golfing. He rarely drank alcohol and had never smoked tobacco or used illicit drugs. His family history included breast cancer and dementia in his mother, hearing loss and hypertension in his father, metastatic cancer with an unknown primary source in his paternal grandfather, glaucoma and alcohol use disorder in his maternal grandmother, and a brain tumor in a more distant relative. On video neuropsychological examination, the patient was in no distress and was adequately groomed, with normal-appearing hygiene. His affect was irritable, and the fact that he reported no symptoms suggested limited insight. His spontaneous speech was fluent and well articulated. His thoughts were tangential, and he was frequently forgetful and easily distracted; his information processing speed was slow. A formal neuropsychological assessment revealed impaired executive functioning, marked by disin-hibition and poor working memory, as well as deficits in recent memory, verbal fluency, and information processing speed. Dr. Bullis: A diagnostic test was performed. OUTPUT:

Delayed posthypoxic leukoencephalopathy.

NEJM_Reasoning_Subset15

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Claudio M. de Gusmao: A 69-year-old man was evaluated in the neurology clinic of this hospital because of progressively worsening ataxia. The patient had been well until 9 years before this evaluation, when abnormal gait and impaired coordination developed. He was unable to walk in a straight line; he bumped into walls when walking down a hallway. He also had difficulty reading traffic signs while driving and noted a change in the quality of his voice. The patient was evaluated at the neurology clinic of another hospital and began physical therapy. During the next several years, symptoms gradually worsened despite physical therapy. The patient was no longer able to drive or play golf, and he intermittently used a walker because of unsteadiness. He had frequent falls, including one that led to fractures in six ribs. His speech changes worsened, such that he could no longer sing. The patient was referred to the neurology clinic of this hospital for evaluation. In the neurology clinic, the patient reported frequent bowel movements, approximately 10 per day. He had no vertigo, lightheadedness, hearing loss, tremor, erectile dysfunction, disturbance of sleep, or urinary incontinence. He reported a sense of visual disorientation with head movement and with changes in the direction of gaze. He had a history of hyperlipidemia. Medications included atorvastatin, cetirizine, and a multivitamin; there were no known drug allergies. The patient had recently moved from an urban area in the southeastern United States to a suburban area of New England. He drank one glass of wine nightly; additional alcohol use caused worsening of ataxia and dysarthria. He had previously smoked five cigarettes daily but had quit smoking 30 years before this evaluation; he did not use illicit drugs. The patients mother had died of heart failure at an elderly age, and his father had died after a stroke and myocardial infarction at 70 years of age. The patient had two adult children, who were healthy. His two brothers and one of his sisters had celiac disease; the sister also reportedly had a shuffling gait. The sisters daughter had received a diagnosis of Turners syndrome and had been seen by a neurologist for a balance disturbance. A brothers grandson also had celiac disease and a gait disturbance Fig. 1. The temperature was 36.6C, the blood pressure 13688 mm Hg, and the pulse 72 beats per minute. The patient was alert, oriented, and attentive and provided a detailed history. He had moderate dysarthria, with impairment in the rate, rhythm, and clarity of speech. An oculomotor examination revealed complete and conjugate gaze in all directions; he had intact smooth pursuit movements but had slow, dysmetric saccades. Results of a head impulse test were abnormal, with corrective saccades noted bilaterally. Normal tone and full strength were present in all major muscle groups of the arms and legs. Reflexes were 2 and symmetric at the knees but absent at the ankles. Plantar responses were flexor bilaterally. Rapid tapping of the index fingers on the thumbs was dysrhythmic and uncoordinated. Fingernosefinger testing revealed mild intention tremor. Heel-to-shin testing revealed symmetric jerking movements with lateral movements across the shins. Vibration and joint-position senses in the legs were profoundly decreased: the patient was unable to sense vibration at the toes, had a decreased ability to sense vibration at the knees, and had difficulty discerning the position of his big toe with his eyes closed. There was sway in his stance, regardless of whether his eyes were open, and he could not stand with the feet together. The patient walked without support. He had a wide-based gait with considerable staggering and jerky, stiff movements of the legs. He was unable to maintain balance in a tandem stance or to walk with a tandem gait. The complete blood count and blood levels of electrolytes were normal, as were test results for kidney, liver, and thyroid function; antibodies to thyroid peroxidase and thyroglobulin were not detected. Blood levels of cyanocobalamin, methyl-malonic acid, vitamin E, and glycated hemoglobin were normal; antiglutamic acid decarboxylase antibodies and tissue transglutaminase antibodies were not detected. Results of serum protein electrophoresis were normal. Genetic testing revealed no mutations in genes associated with spinocerebellar ataxia types 1, 2, 3, 6, and 8. Clinical testing of otolith function revealed abnormal vestibular-evoked myogenic potentials on the left side. Nerve-conduction studies revealed absent or barely detectable responses in the bilateral sural nerves, left superficial peroneal nerve, left median nerve, left ulnar nerve, and right radial nerve. Results of motor nerve-conduction studies were normal, as were results of a modified barium-swallow evaluation. A previous workup at another hospital for chronic diarrhea had reportedly been normal, with no evidence of malabsorption. Dr. McKinley Glover: Magnetic resonance imaging MRI of the head Fig. 2, performed without the administration of intravenous contrast material, revealed mild diffuse parenchymal volume loss and prominent cerebellar volume loss, most notably involving the vermis and superior cerebellar hemispheres. There was mild flattening of the superior margin of the midbrain, and the ratio of midbrain to ventral pons was mildly reduced at 0.51 reference range, 0.52.1 The anteroposterior diameter of the midbrain was 8.90 mm reference range, 9.35.1 There was no abnormal signal in the pons, and the middle cerebellar peduncles were normal. There was a chronic lacunar infarct of the right thalamus. Dr. de Gusmao: Additional history was obtained, and a diagnosis was made. OUTPUT:

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome due to a biallelic expansion in RFC1.

NEJM_Reasoning_Subset16

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Kathy M. Tran: A 33-year-old pregnant woman with ulcerative colitis was admitted to this hospital during the summer at 10 weeks of gestation because of fever, nausea, vomiting, abdominal pain and tenderness, and headache. The patient had been in her usual state of health until 3 days before this admission, when fever, rigors, nausea, and vomiting developed. During the next 3 days, the symptoms worsened; the patient was unable to eat, drink, or take medications. She reported abdominal pain and cramping on the left side that she described as being similar to previous flares of ulcerative colitis; she also had nonbloody diarrhea. The patient called the obstetrics clinic and was instructed to seek evaluation in the emergency department of this hospital. A review of systems was notable for fatigue, mild headache, neck pain, and photophobia. The patient reported no hematochezia, pelvic pain, vaginal bleeding, dysuria, or joint pain. Ulcerative colitis had been diagnosed 11 years earlier; at the time of the diagnosis, she began treatment with azathioprine but stopped after 1 year because of severe fatigue. The patient had taken mesalamine and sulfasalazine intermittently for disease flares but typically stopped after a few months of treatment. Exacerbations of ulcerative colitis occurred approximately every year and were associated with fevers, rigors, nausea, vomiting, abdominal pain, and bloody diarrhea. Nine months before this admission, Clostridioides difficile colitis developed, and the patient was successfully treated with oral vancomycin. Three weeks before the current admission, she was admitted to this hospital for a flare of ulcerative colitis; intravenous methylprednisolone, hydromorphone, and ondansetron were administered, and mesalamine was restarted. Flexible sigmoidoscopy revealed mild erythema and friable mucosa with a decreased vascular pattern in the sigmoid colon. Dr. Craig R. Audin: A transvaginal ultrasound image obtained during that admission showed a single viable intrauterine pregnancy at 7 weeks of gestation and trace subchorionic hemorrhage. Dr. Tran: The patient was discharged after 7 days once most of the symptoms had abated, although nausea persisted. The patient had had two previous successful pregnancies that had resulted in cesarean deliveries at full term. The patient reported that she had received all the usual child-hood immunizations. Routine prenatal serologic screening during the current pregnancy showed immunity to varicella but not to rubella. Tests for syphilis, hepatitis B virus surface antigen, gonorrhea, chlamydia, and human immunodeficiency virus HIV were negative. Other history included anemia, chronic back pain, migraines, post-traumatic stress disorder, depression, and anxiety. At the time of the current admission, medications included prednisone, mesalamine, omepra-zole, ondansetron, hydromorphone, tramadol, cyclobenzaprine, sumatriptan, gabapentin, loraze-pam, sertraline, pyridoxine, cholecalciferol, and prenatal vitamins. There were no known drug allergies. The patient lived in an urban area of New England with her male partner, with whom she was monogamous, as well as her two children. She worked as an administrator. She did not eat sushi or rare or raw meat, and she did not consume unpasteurized milk or cheese. She had no known sick contacts or exposure to animals. The patient did not smoke tobacco, drink alcohol, or use illicit substances. Her mother had coronary artery disease, her father inflammatory bowel disease, and her sister depression. Her brother and two children were well. On examination, the temperature was 38.2C, the blood pressure 11861 mm Hg, the pulse 116 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100 while the patient was breathing ambient air. She appeared tired and uncomfortable. The abdominal examination was remarkable for a healed surgical scar; there was diffuse tenderness that was most painful in the lower quadrants. The remainder of the examination was normal. The hemoglobin level was 7.7 g per deciliter reference range, 12.0 to 16.0, which was similar to the patients baseline level. Urinalysis was normal. Blood specimens were obtained for micro-biologic culture. Other laboratory test results are shown in Table 1. Dr. Audin: Color Doppler ultrasonography of the abdomen revealed mild fullness in the pelvi-calyceal system on the right side Fig. 1A that is probably a physiologic finding in pregnancy. There was trace fluid in the right lower quadrant; however, the appendix was not visualized Fig. 1B. Dr. Tran: Intravenous fluids, ondansetron, acetaminophen, and hydromorphone were adminis-tered; mesalamine was continued, and a tapering of the prednisone dose was begun. The patient was admitted to the hospital for further evaluation and care. The next day, the abdominal pain persisted and was most severe in the right upper and right lower quadrants. The headache had increased in severity; it was pulsating in quality and was worst in the frontal region, with radiation to the occipital region and posterior neck. There was mild photophobia but no neck stiffness or limitation in the range of motion in the neck. Empirical treatment with intravenous ampicillin sulbactam and prophylaxis with oral vancomycin were started. On the third hospital day, the systolic blood pressure declined to 70 mm Hg; after intravenous fluids were administered, the systolic blood pressure increased to 100 mm Hg. Ultrasound images of the uterus obtained at the bedside confirmed a fetal heartbeat. A lumbar puncture was performed. The cerebrospinal fluid CSF was clear and colorless, with a glucose level of 63 mg per deciliter 3.5 mmol per liter; reference range, 50 to 75 mg per deciliter 2.8 to 4.2 mmol per liter and a protein level of 17 mg per deciliter reference range, 5 to 55. There were 0 nucleated cells per microliter reference range, 0 to 5. Grams staining of the CSF revealed no neutro-phils and very few mononuclear cells; no organisms were identified. Dr. Audin: Three days later, abdominal magnetic resonance imaging MRI Fig. 1C through 1F, performed without the administration of intravenous contrast material, revealed a normal gravid uterus. On T2-weighted imaging, there were rounded areas of myometrial thickening with low signal intensity that were consistent with focal myometrial contractions, as well as a thin band of low signal intensity surrounding the fetus that was consistent with chorioamniotic separation; both of these findings were considered to be normal in the first trimester. The appendix was normal, without wall thickening, dilatation, or adjacent inflammatory changes. Although evaluation of the bowel was limited in the absence of oral and intravenous contrast material, the rectum also appeared normal, without obvious signs of active or chronic inflammation. A diagnosis was made. OUTPUT:

Listeria monocytogenes bacteremia resulting in loss of fetus.

NEJM_Reasoning_Subset17

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Giovanna S. Manzano Neurology: A 64-year-old woman was admitted to this hospital with cognitive impairment, headache, and memory loss. The patient had been well until 6 weeks before admission, when respiratory symptoms developed. Testing of a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 RNA was negative. At around the same time, coworkers observed a decline in the patients performance at work. The patient noticed that she was having difficulty operating computers and was forgetting her personal passwords. The patient was evaluated at another hospital. Although she reported recent confusion and changes in cognitive performance, the examination at that time including a neurologic examination with assessment of orientation, speech, and memory recall after 5 and 20 minutes was unremarkable. The patient was referred for an outpatient neurologic evaluation. One week later 5 weeks before admission, severe headache developed suddenly, along with blurred vision, dizziness, and nausea. After the administration of ondansetron, the blurred vision, dizziness, and nausea resolved; after the administration of nonsteroidal antiinflammatory drugs, the headache became less severe, with mild pain and intermittent episodes of more severe pain. Three weeks before admission, the patient was seen in a neurology clinic affiliated with the other hospital. She had difficulty recalling the history of her symptoms. On examination, she was oriented to place and person only and was unable to perform serial sevens calculations or to spell world backward. The remainder of the examination was unremarkable. The complete blood count with differential count and test results for liver and kidney function were normal, as were blood levels of electrolytes, glucose, thiamine, and cobalamin. Tests for syphilis and human immunodeficiency virus infection were negative; other labora-tory test results are shown in Table 1. An electroencephalogram EEG showed no distinct epileptiform activity. Topiramate was prescribed for a working diagnosis of complex migraine. Imaging studies were obtained. Dr. R. Gilberto Gonzalez: Magnetic resonance imaging MRI of the head was performed. T2weighted fluid-attenuated inversion recovery FLAIR images showed diffusely scattered hy-perintensities in the periventricular, subcortical, and deep white matter and leptomeningeal enhancement. In addition, there was evidence of frontal superficial siderosis and a few scattered microhemorrhages. Dr. Manzano: Lumbar puncture was also performed. On cerebrospinal fluid CSF analysis, the white-cell count was 46 per microliter reference range, 0 to 5, with a lymphocyte count of 99 reference range, 40 to 80, the red-cell count was 35 per microliter reference value, 0, and the protein level was 221 mg per deciliter reference range, 13 to 40; other laboratory test results are shown in Table 1. Cultures of the CSF were negative. The administration of topiramate was stopped; treatment with oral doxycycline was started but then was stopped after 5 days, when results of a test for Borrelia burgdorferi were interpreted as negative. Over the next 3 weeks, intermittent headache persisted and cognitive impairment worsened. The patient presented to the emergency department of this hospital. She was unable to provide a history. According to the patients husband, the patient had stopped working and was no longer able to effectively care for herself, requiring assistance with daily activities such as bathing, dressing, and eating. She had difficulty planning and was unable to put on clothes in the correct sequence or to turn on the shower. Memory impairment persisted, conversation was tangential, and visual hallucinations frequently occurred. The patient had lost 6.8 kg in the past month. There was no fever, rash, or joint pain. The patient had a history of poliomyelitis in childhood, with residual mild weakness in the left leg; vitamin B12 deficiency, which had been corrected; and hypothyroidism. Medications included atorvastatin, levothyroxine, sertraline, vitamin B12, and cholecalciferol. She had a known allergy to amoxicillinclavulanate with an unknown reaction. She was a former smoker with a 40 pack-year history, and she had consumed four alcoholic beverages per week before the onset of the current illness. The patient worked in a health care clinic and lived with her husband in a suburban area of New England. She had not traveled outside the United States. She was an avid gardener; she had a dog but no other animal exposures. Her father had received a diagnosis of Alzheimers disease at 62 years of age. On examination, the patient was alert and interactive. The temperature was 36.7C, the blood pressure 10551 mm Hg, the heart rate 56 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 96 while she was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 32.4. The patient was oriented to time, place, and person. Her speech was fluent, with intact naming, repetition, and comprehension. She had impaired abstraction and mildly impaired attention. She was unable to recall three objects after a delay. Intermittently during the examination, she had visual hallucinations that she knew were not real. Cranial nerve examination was unremarkable. Strength was 55 throughout, except in the left leg 45. Reflexes were brisk throughout, including 3 reflexes in the arms and the right lower leg; pectoralis reflexes and a jaw jerk were present. No ankle clonus was noted. Examinations for tone, sensation, and cerebellar function were unremarkable. The remainder of the examination was normal. Laboratory test results are shown in Table 1. Dr. Gonzalez: MRI of the head was performed Fig. 1. FLAIR images showed slight progression of the diffuse subarachnoid hyperintensi-ties and leptomeningeal enhancement. Susceptibility-weighted images showed frontal superficial siderosis and scattered lobar microhemorrhages. Computed tomographic CT angiography of the head revealed patent cranial vessels, without evidence of aneurysm, arteriovenous malformation, or thrombosis. A CT scan of the chest and abdomen, obtained after the administration of intravenous contrast material, was normal. Dr. Manzano: Lumbar puncture was performed. On CSF analysis, the nucleated-cell count was 28 per microliter reference range, 0 to 5, the lymphocyte count 85, the red-cell count 53 per microliter, and the protein level 280 mg per deciliter. CSF was sent for culture and cytologic studies; other laboratory test results are shown in Table 1. An EEG was normal. The patient was admitted to this hospital, and intravenous ceftriaxone, acyclovir, and meth-ylprednisolone were administered. During the first 48 hours, the patient was agitated and impulsive. Visual hallucinations worsened, and olanzapine was administered. The CSF culture was negative, and the CSF cytologic studies showed no malignant cells. A diagnostic test was performed. OUTPUT:

Cerebral amyloid angiopathy–related inflammation.

NEJM_Reasoning_Subset18

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Matthew B. Roberts: A 41-year-old woman who had undergone renal transplantation was admitted to this hospital because of bloody stools and thrombocytopenia. The patient had been in her usual state of health until 3 weeks before this admission, when mild rectal discomfort and nonbloody diarrhea developed. The episodes of diarrhea occurred several times a day and were not associated with fever, chills, abdominal pain, nausea, or vomiting. Two weeks before this admission, the patient sought evaluation at this hospital. The abdominal and rectal examinations were normal. The hemoglobin level was 11.0 g per deciliter reference range, 14.0 to 18.0 and the platelet count 129,000 per microliter reference range, 150,000 to 450,000. Stool cultures and tests of the stool for Clostridioides difficile antigen and toxin and Shiga toxin were negative, as was examination of the stool for ova and parasites. Other laboratory test results are shown in Table 1. Treatment with docusate was stopped, treatment with topical rectal hydrocortisone cream was started, and a recommendation was made to increase the amount of fiber in the diet. During the next week, the episodes of diarrhea decreased in frequency to once a day; however, the rectal pain persisted. One week before this admission, the patient was evaluated by her primary care physician because the rectal pain had worsened; she was unable to sit down, and new tenesmus was present. A rectal examination revealed mild tenderness and thin yellow-brown liquid stool, with no evidence of blood or an external anal injury. A radiograph of the abdomen was normal. Docusate, senna, and topical lidocaine jelly were prescribed. Three days before this admission, bowel movements with tarry black and loose maroon stools and dark clots began to occur multiple times a day. When the episodes increased in frequency to every hour and there was bright-red blood per rectum, the patient presented to the emergency department of this hospital for evaluation. In the emergency department, the patient reported severe rectal pain and burn-ing, as well as fatigue, dizziness, and weakness. She did not report fever, chills, abdominal pain, hematemesis, hemoptysis, epistaxis, rash, bruising, hematuria, or menorrhagia. The patient was congenitally deaf. She had received a diagnosis of kidney disease 12 years earlier, when proteinuria and hypertension developed during pregnancy and did not resolve postpartum. Pathological examination of a renal biopsy specimen had reportedly revealed focal segmental glomerulosclerosis. The patient was presumed to have Alports syndrome; no genetic testing had been performed. Ten years before the current evaluation, the patient had discontinued all prescribed medications, including prednisone and labetalol, without talking to her doctors; 3 years later, she presented to this hospital with dyspnea on exertion and end-stage renal failure. Hemodialysis was started and continued until a deceased-donor renal transplantation was performed 6 months before the current evaluation. Routine pretransplantation serologic testing of the patient revealed IgG antibodies to Epstein Barr virus EBV and no antibodies to cytomega-lovirus CMV. Serologic testing of the donor also revealed IgG antibodies to EBV and no antibodies to CMV. Induction immunosuppressive therapy with antithymocyte globulin, belatacept, predni-sone, and everolimus was initiated; famciclovir was administered for 3 months after transplantation. Treatment with prednisone was stopped 2 months after transplantation, when diabetes developed. At the time of the current evaluation, medications included aspirin, linagliptin, trimethoprim sulfamethoxazole, and omeprazole, as well as cholecalciferol, docusate, senna, topical hydro-cortisone cream, and topical lidocaine jelly. The dose of everolimus had been decreased 1 month before this evaluation; belatacept had last been infused 2 weeks earlier. There were no known drug allergies. The patient lived with her male partner and young son in an urban area of New England. She had not traveled recently. She had previously worked part-time as a teacher. There had been no exposure to animals other than two pet dogs. She had never smoked tobacco and did not drink alcohol. Her sister was deaf and had a history of renal failure that had led to renal transplanta-tion. Her father had a history of diabetes and renal failure that required hemodialysis. On examination, the temperature was 37.2C, the blood pressure 8546 mm Hg, the pulse 130 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 100 while the patient was breathing ambient air. She appeared pale and unwell. There was no jaundice or lymphadenopathy. There were palatal petechiae and sublingual ecchymoses, but there was no bleeding from the gums or nose. There was a healed surgical incision in the right lower abdomen and no tenderness over the renal allo-graft. A rectal examination revealed tenderness and dark blood with clots. The hemoglobin level was 6.0 g per deciliter and the platelet count 0 per microliter. A peripheral-blood smear showed red cells that were generally normal in size and morphology, with few hypochromic cells and rare pencil cells; there were no schistocytes or platelets. A direct antiglobulin test was negative. Blood cultures were obtained. Other laboratory test results are shown in Table 1. Dr. Onofrio A. Catalano: Computed tomography CT of the abdomen and pelvis, performed without the administration of intravenous contrast material, revealed no bowel-wall thickening or distention. The spleen and liver were normal in size. The renal allograft was visible in the right lower quadrant Fig. 1. The transplanted kidney was enlarged and surrounded by extensive peri-nephric fat stranding. A small amount of free fluid was also present. There was moderate hydroureteronephrosis that extended up to the ureterovesical anastomosis. The renal collecting system, pelvis, and ureter contained spontaneously hyperdense material that was suggestive of blood breakdown products. No obstructing calculi were seen. Dr. Roberts: Intravenous fluids were administered, and the blood pressure increased to 9753 mm Hg. The patient was admitted to the hospital, and treatment with everolimus and trimethoprimsulfamethoxazole was stopped. During the next 24 hours, 4 units of packed red cells and 5 units of pooled platelets were transfused. On the second hospital day, the hemoglobin level was 11.0 g per deciliter and the platelet count 4 per microliter. A diagnostic test was performed. OUTPUT:

Cytomegalovirus-induced immune thrombocy-topenia.

NEJM_Reasoning_Subset19

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Jonathan R. Wing: A 48-year-old man was admitted to this hospital because of fatigue and swelling in both legs. The patient had been well until 8 months before the current admission, when fatigue and lethargy developed. He thought the fatigue was associated with alcohol consumption and reduced his intake to 12 beers weekly; before this, he had consumed 24 beers weekly for 15 years. Three months before the current admission, the patients weight had decreased by 9.1 kg. However, 3 weeks before this admission, the weight had increased by 9.6 kg and swelling developed in both legs. He thought the weight gain was related to diet changes, including consumption of pizza, pasta, and soup, during the coronavirus disease 2019 pandemic. One week before the current admission, the patient was evaluated by his primary care physician. He was instructed to elevate his legs, wear compression stockings, and decrease dietary sodium to 2 g daily. On the day of the current admission, the leg swelling had not abated and new abdominal distention occurred. He called the primary care clinic and was instructed to seek evaluation at the emergency department of this hospital. On evaluation, a review of systems was notable for fatigue, lethargy, decreased appetite, abdominal bloating, constipation, penile swelling, decreased libido, intolerance of cold temperatures, and ankle and knee pain in both legs that was worse when the patient was climbing stairs. There was no fever, shortness of breath, chest pain, or hematochezia. Sixteen months before the current evaluation, the patient had been admitted to this hospital with pneumonia involving the right upper and middle lobes that was due to Mycoplasma pneumoniae. During that admission, he received diagnoses of diabetes and normocytic anemia. After discharge from the hospital, laboratory evaluation revealed a glycated hemoglobin level of 6.1 reference range, 4.3 to 6.4. Metformin was prescribed, and follow-up evaluation was recommended; however, the patient had not returned to the primary care clinic before the current illness. CME The patient had not started taking metformin until 3 weeks before the current evaluation; he took no other medications and had no known drug allergies. He lived with his wife and two children in an urban area of New England. He did not smoke tobacco or use illicit drugs. His mother had Parkinsons disease and dementia; he did not know the health of his father or paternal half-siblings. On examination, the temperature was 36.6C, the blood pressure 9854 mm Hg, the heart rate 64 beats per minute, and the oxygen saturation 100 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 27.3. The patient did not have jaundice, scleral icterus, or spider angiomas. He had jugular venous distention and an S3 gallop; there were no rales. The abdomen was distended, with dullness on percussion of the flanks; there was no hepatosplenomegaly. There was 2 symmetric pitting edema in the lower legs up to the knees. Mild palmar erythema was present; there was no asterixis. The blood glucose level was 402 mg per deciliter 22.3 mmol per liter; reference range, 70 to 110 mg per deciliter 3.9 to 6.1 mmol per liter; the glycated hemoglobin level was 11.6. The platelet count was 82,000 per microliter reference range, 150,000 to 400,000. Other laboratory test results are shown in Table 1. Dr. Reece J. Goiffon: Radiography of the chest revealed new elevation of the right hemidiaphragm and atelectasis in the lower lobes. Ultrasonogra-phy with Doppler analysis of the abdomen revealed mild thickening of the gallbladder wall, coarsened liver echotexture, moderate ascites, and mild splenomegaly; the portal veins were patent. Duplex ultrasonography revealed nonocclusive deep-vein thrombosis of the right popliteal vein. Dr. Wing: Paracentesis was performed with ultrasonographic guidance, and 50 ml of peritoneal fluid was drained. Results of peritoneal fluid analysis are shown in Table 1; cytologic examination of the fluid revealed no malignant cells. Electrocardiography revealed normal sinus rhythm with occasional premature atrial complexes, left axis deviation, and T-wave inversions in leads I and aVL. Insulin and enoxaparin were administered subcutaneously, and the patient was admitted to the hospital. A diagnostic test was performed. OUTPUT:

Hereditary hemochromatosis.

NEJM_Reasoning_Subset20

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Reuben A. Hendler Psychiatry: A 37-year-old woman was admitted to this hospital because of fever, shortness of breath, and suicidal ideation in March 2020, during the pandemic of coronavirus disease 2019 Covid-19. Ten days before this admission, fever, fatigue, sore throat, cough, and myalgias developed. The symptoms did not abate after the patient took aspirin and acetaminophen. Five days before this admission, she sought evaluation at the urgent care clinic of this hospital because Covid-19 had been diagnosed in two coworkers. A test for Covid-19 was not performed because of limited test availability; tests for influenza A and B viruses and respiratory syncytial virus were not performed because of a statewide shortage of nasopharyngeal swabs. The patient was instructed to quarantine at home. During the next 5 days, the patient quarantined in a room in her apartment. Her husband periodically brought food to the door of the room. The fever, fatigue, sore throat, cough, and myalgias persisted; new shortness of breath and anosmia developed. She had decreased appetite, and she consumed minimal food and drink. One day before this admission, nausea, vomiting, and diarrhea developed, and the patient sought evaluation at the emergency department of another hospital. Intravenous fluid, ondansetron, and ketorolac were administered, and she was discharged home with instructions to continue to quarantine. On the day of admission, the patient had dizziness while standing, as well as shortness of breath, and she returned to the urgent care clinic of this hospital. The temperature was 38.7C, the heart rate 127 beats per minute, the respiratory rate 38 breaths per minute, and the oxygen saturation 97 while she was breathing ambient air. The patient was anxious and tearful. The lungs were clear on auscultation. Intravenous fluid, ondansetron, and oral acetaminophen were administered. The dizziness resolved, and the fever, shortness of breath, and anxiety decreased. The patient was advised to return home to quarantine; however, she disclosed that if she were sent home, she planned to overdose on medications to die by suicide because of her anxiety and feelings of sadness and loneliness. Owing to concern about the patients risk of harming herself, an order authorizing temporary involuntary hospitalization was implemented. Emergency medical services were called, and the patient was brought to the emergency department. On evaluation in the emergency department, the patient reported anxiety, palpitations, and shortness of breath and noted that her anxiety and feelings of isolation and loneliness had developed during quarantine. She also reported poor sleep, decreased energy, and anhedonia. The patient described that she felt like a burden to her husband and was terrified that she would transmit severe acute respiratory syndrome coro-navirus 2 SARS-CoV-2 to her children, including her 4-year-old son, who had been born prematurely and had a congenital pulmonary condition. In addition, the patient reported a 1-week history of new, recurring nightmares in which she would see herself playing with her own severed body parts; these nightmares occurred more frequently during periods of high fever. She intermittently had the sensation that someone was in the room with her while she was awake, even though she was aware that she was alone. She disclosed that, on the previous day, she had had new suicidal ideation associated with fear of transmitting SARS-CoV-2 to her family and that she had taken five aspirinparacetamolcaffeine pills at once. There had been no history of suicidal ideation or attempt, self-harm, or homicidal ideation. The patient had a history of depression and panic attacks when she was a teenager and had been treated for less than 1 year with a medication that she could not recall; the symptoms had resolved by 19 years of age, and there had been no mental health follow-up. She also had a history of migraines, which occurred four times per week. She took aspirin, acetaminophen, and aspirinparacetamolcaffeine as needed; there were no known drug allergies. The patient was born in Central America and had been living in the United States for 19 years. She lived with her husband, four children, and mother-in-law in an urban area of New England in a community that was predominantly Latinx and that had a high rate of Covid-19related infections and deaths. The patient did not complete high school while she was living in Central America and was currently employed full time in a food-production factory. She reported that she enjoyed her job but that she had been reluctant to work during the Covid-19 pandemic because of concern about becoming ill; however, she described that she felt obligated to work to support her family. The patient did not smoke cigarettes, drink alcohol, or use illicit drugs. Her mother had died from cancer. On examination, the temperature was 38.2C, the blood pressure 14884 mm Hg, the heart rate 110 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 97 while the patient was breathing ambient air. She appeared well-groomed and fatigued, and she was tearful with a depressed and dysphoric mood. Her behavior was described as sullen, and there was limited eye contact and reduced psychomotor activity. Her speech, in Spanish, was fluent but was slow and mumbling, with reduced prosody. She had no derailment of thought, delusions, or obsessions, but she ruminated on her nightmares. She stated that she had no current suicidal ideation but that she might attempt suicide if she had to return to her children and expose them to SARS-CoV-2 again. Nucleic acid testing of a nasopharyngeal swab for SARS-CoV-2 RNA was positive. Additional laboratory test results are shown in Table 1. Radiography of the chest revealed ground-glass opacities in the right middle and lower lobes and in the left lower lobe. Intravenous ceftriaxone, oral azithromycin, atorvastatin, and hydroxychlo-roquine were administered, and the patient was admitted to the hospital. Management decisions were made. OUTPUT:

Fear associated with coronavirus disease 2019 (Covid-19), causing suicidal ideation.

NEJM_Reasoning_Subset21

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: CME at NEJM.org Dr. Emma C. Materne Pediatrics: A 12-month-old boy with Hirschsprungs disease was admitted to this hospital because of fever. Fifteen days before the current admission, the patient had a temperature of 39.7C. His parents noticed that he was fussy and less active than usual and that he had a decreased appetite along with several episodes of spitting up; there was no vomiting or diarrhea. During the next 5 days, fever occurred daily and abated with the administration of acetaminophen or ibuprofen. Ten days before the current admission, a bowel movement with watery, nonbloody, foul-smelling, mustard-yellow stool occurred. The patient was brought to the emergency department of this hospital. On examination, the patient was irritable. The abdomen was soft and non-tender. There were well-circumscribed, erythematous, edematous plaques on the abdomen, legs, feet, and forearms. The alanine aminotransferase level was 131 U per liter reference range, 10 to 55, the aspartate aminotransferase level 250 U per liter reference range, 9 to 80, the ferritin level 3826 g per liter reference range, 30 to 300, and the d-dimer level 3218 ng per milliliter reference range, 500. The erythrocyte sedimentation rate was 40 mm per hour reference range, 0 to 15; the white-cell count was normal. Other laboratory test results are shown in Table 1. A radiograph of the abdomen showed gas-filled loops of bowel. The rectum was irrigated, and intravenous piperacillintazobactam was administered. On the third hospital day, the patient was afebrile and able to take formula, and the diarrhea abated. He was discharged home with a prescription for a course of metro-nidazole. During the next 2 days, the patient had no fever or diarrhea. However, 4 days before the current admission, a day-care worker observed that the patient appeared tired. During the subsequent 3 days at home, fever again developed, with chills and a decreased appetite. The day before the current admission, the patient cried through the night. He was brought to the emergency department of this hospital for evaluation. The parents reported that the patient was fussy and had poor sleep and generalized weakness; there was no diarrhea or new rash. The parents did not think that the patient was in pain. Additional history was obtained from the parents. The patient had met developmental milestones until 1 month earlier, when he had stopped crawling. He had previously been able to pull his body into a standing position, but he no longer attempted this maneuver. If he was placed in a standing position, he collapsed; if he was placed in a sitting position, he was able to stay upright. He had previously passed objects from hand to hand, but he had a new preference of holding objects with the left hand. Two days before this evaluation, the parents had noticed that the patient no longer walked with support; he seemed to dislike having his hands held. The patient had cornea plana and a history of Hirschsprungs disease, for which he had undergone laparoscopic sigmoid colectomy and an anal pull-through procedure at 2 months of age. Four months before the current evaluation, an intermittent diffuse rash on the trunk, arms, and legs had developed. The rash was characterized by purplish and pinkish plaques that appeared and varied in intensity of color throughout the day; it did not seem to be itchy or painful and usually resolved within 24 hours without treatment. Immunizations were up to date. Medications included metronidazole, acetaminophen, ibuprofen, and cetirizine, as well as carboxymethylcel-lulose eye drops; there were no known allergies to medications. The patient lived with his mother, father, and pet dog in a small town in New England, and he attended day care 5 days per week. His mother was healthy, and his father had irritable bowel syndrome and Poland syndrome congenital aplasia of unilateral chest-wall muscles. His paternal grandmother had hypothyroidism, his maternal great-grandfather had had pancreatic cancer, his paternal great-grandfather had had breast cancer, a maternal second cousin had autism, and multiple maternal family members had Raynauds phenomenon. On examination, the temperature was 38.3C, the blood pressure 11352 mm Hg, the heart rate 166 beats per minute normal range for age, 80 to 160, and the respiratory rate 30 breaths per minute normal range for age, 30 to 60. The patient was diaphoretic and irritable, and he cried during the examination. He had rhinorrhea. The abdomen was not distended or tender. There was limited extension of the wrists and knees, as well as limited inversion and eversion of the feet. The ankles were mildly stiff, and the feet were mildly swollen. There were erythematous plaques on the abdomen, back, arms, and legs Fig. 1. The ferritin and d-dimer levels remained elevated, and the aspartate aminotransferase and alanine aminotransferase levels were normal. The erythrocyte sedimentation rate was 75 mm per hour, the white-cell count 26,820 per microliter reference range, 6000 to 17,500, and the platelet count 682,000 per microliter reference range, 150,000 to 400,000. Blood cultures and urinalysis were normal. Testing of a nasopharyngeal swab for severe acute respiratory syndrome coro-navirus 2 SARS-CoV-2 RNA was negative. Other laboratory test results are shown in Table 1. Dr. Randheer Shailam: A radiograph of the chest and abdomen was normal. Ultrasonography of the abdomen revealed cholelithiasis and prominent lymph nodes in the right lower quadrant. Ultrasonography of the legs revealed a small amount of joint fluid in the hips and knees Fig. 2; the amount of fluid appeared to be within the normal range. Computed tomography CT of the abdomen, performed after the administration of intravenous contrast material, revealed a gallstone in the neck of the gallbladder, without gallbladder distention. There were a few prominent lymph nodes in the paraaortic, iliac, and inguinal regions Fig. 2. Transtho-racic echocardiography showed normal coronary arteries. Dr. Materne: The empirical administration of intravenous vancomycin, cefepime, and metroni-dazole was begun. During the next 3 days, the fever continued and the white-cell count remained elevated. On the seventh hospital day, the fever, leukocytosis, and elevation in levels of inflammatory markers persisted. The administration of antibiotic agents was stopped. A diagnostic test was performed. OUTPUT:

Systemic juvenile idiopathic arthritis.

NEJM_Reasoning_Subset22

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. David M. Dudzinski: A 47-year-old right-handed man was evaluated at this hospital because of pain on the left side of the head and neck. Six years before the current evaluation, the patient was admitted to this hospital with 1 week of headache, pain on the left side of the neck, numbness on the left side of the face, and dizziness. The pain was not relieved with the use of ibuprofen and had previously been evaluated and treated by a chiropractor. A neu-rologic examination revealed a slight decrease in taste and in sensation to touch and temperature on the left side of the face; a gait evaluation revealed a subtle leftward sway. Imaging studies were obtained. Dr. Byung C. Yoon: Computed tomography CT of the head, performed after the administration of intravenous contrast material, revealed subtle foci of hypoden-sity in the left cerebellum, a finding suggestive of infarction. There was no evidence of arterial dissection, aneurysm, stenosis, or thrombotic occlusion. Magnetic resonance imaging MRI of the head, performed before and after the administration of intravenous contrast material, confirmed the presence of a left medial cerebellar infarct and a small left lateral medullary infarct Fig. 1A, 1B, and 1C. Dr. Dudzinski: The patient had normal results on cerebrospinal fluid CSF analysis, echocardiography, and a hypercoagulability panel, except for a mildly elevated level of anticardiolipin IgM 18.9 IgM phospholipid units; reference range, 0 to 15. During the hospital admission, lesions with a vesicular appearance developed on the left side of the lips and oral cavity, and the patient was treated with famciclo-vir. He was discharged home while receiving aspirin, with a follow-up visit scheduled in the neurology clinic. One month later in the neurology clinic, the patient reported partial resolution of headache, persistent neck pain and ear pain with balance difficulty, and perioral paresthesia. There was diminished sensation on the left side of the face similar to that observed during the previous examination. No oropharyngeal lesions were visible. An evaluation of gait and balance was normal. Dr. Yoon: Magnetic resonance angiography of the head and neck, performed before and after the administration of intravenous contrast material, revealed expected evolution of the left cerebellar infarct and no new infarction. The left posterior inferior cerebellar artery was not visualized, possibly because of occlusion or slow blood flow. Dr. Dudzinski: Repeat CSF analysis showed normal protein and glucose levels and 14 white cells per microliter reference range, 0 to 5, of which 94 were lymphocytes. Grams staining showed no organisms. CSF tests for borrelia and varicella DNA and for cytomegalovirus and herpes simplex virus antibodies were negative. Two days later, cerebral angiography revealed mild narrowing of the origin of the left vertebral artery. Tests for antinuclear antibodies, antineutro-phil cytoplasmic antibodies, and anti-La and anti-Ro antibodies were negative, as was a rapid plasma reagin test. The patient received follow-up care at another hospital until the current evaluation, when he presented to the emergency department of this hospital with 3 days of severe pain on exertion that affected the left side of the neck and left temporo-occipital region. The symptoms were similar to those he had reported in the past and were not relieved with the use of ibuprofen or marijuana. The head pain was described as pulsating and pounding, and it worsened when he was in the supine position. The patient reported right flank pain; the onset of this pain had occurred with lifting of a heavy object and had just preceded the onset of headache. He also reported a tendency to bruise. The review of systems was otherwise normal. His medical history was notable for dyslipidemia. He had undergone repair of meniscus tears in both knees and repair of a traumatic dislocation of the right shoulder. Medications included rosu-vastatin and gemfibrozil, as well as acetaminophen as needed. There were no known adverse reactions to medications. The patient was a self-employed laborer and lived with his wife and children in a suburb of Boston. He smoked cigars and marijuana occasionally, and he drank up to eight beers per day on weekends. His family history was notable for hypertension and dyslipid-emia in both of his parents, as well as early-onset dementia in his father. The temperature was 36.7C, the blood pressure 176119 mm Hg in both arms, the heart rate 72 beats per minute, and the oxygen saturation 98 while the patient was breathing ambient air. A neurologic examination revealed a mild decrease in coordination in the left hand but was otherwise normal. Blood levels of electrolytes, troponin T, C-reactive protein, lipoproteina, and glycated hemoglobin were normal, as were the prothrombin time, partial-thromboplastin time, and results of renal function tests. Urinalysis was also normal; other laboratory test results are shown in Table 1. Dr. Yoon: CT angiography of the head and neck, performed after the administration of intravenous contrast material, revealed dissection of the left vertebral artery, extending from the origin of the artery to the proximal V3 upper cervical segment, with a 2-mm pseudoaneurysm at the C2C3 level Fig. 1D and 1E. There was no evidence of acute ischemia. MRI of the head, performed before and after the administration of intravenous contrast material, did not reveal any evidence of infarction or a perfusion abnormality. However, a T1-weighted image showed a focus of intrinsic hyperintensity along the left vertebral artery, a finding consistent with hemorrhage within the vessel wall from the dissection Fig. 1F. Dr. Dudzinski: The patient was admitted to the neurology service. Control of the blood pressure required multiple medications. Echocardiography showed no cardiac, valvular, or aortic structural abnormality. Right flank pain recurred. Urinalysis showed 5 to 10 red cells per high-power field but was otherwise normal. Dr. Yoon: CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed dissection of the right renal artery, extending from the origin of the artery to subsegmental renal arteries. Perinephric fat stranding was present on the right side, and there were areas of diminished enhancement in the right kidney. These findings were suggestive of infarction Fig. 2. Additional diagnostic tests were performed. OUTPUT:

Vascular Ehlers–Danlos syndrome.

NEJM_Reasoning_Subset23

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Philippe-Antoine Bilodeau Medicine: A 21-year-old man presented to this hospital with a sore throat, epistaxis, and petechiae of the oropharynx. One week before the current presentation, blood-filled blisters developed inside the patients mouth, on the buccal mucosa. He had occasional bleeding from the mouth that resolved spontaneously. He consulted with his dentist, who was concerned about the possibility of impacted wisdom teeth. Two days before the current presentation, a sore throat developed. There was no difficulty with swallowing. On the day of the current presentation, epistaxis developed and did not resolve over a period of 2 hours. The patient presented to another hospital for evaluation. On examination, the temperature was 37.1C, the blood pressure 14276 mm Hg, the pulse 98 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 99 while he was breathing ambient air. He had blood in the nares and petechiae on the soft palate. There was a large ecchymosis on the left forearm that the patient attributed to carrying heavy boxes several days earlier. The remainder of the examination was normal. Laboratory testing revealed a hemoglobin level of 9.8 g per deciliter reference range, 13.5 to 17.5, a platelet count of 1000 per microliter reference range, 150,000 to 450,000, and a white-cell count of 670 per microliter reference range, 4000 to 11,000. The absolute neutrophil count was 50 per micro-liter reference range, 1800 to 7000. Blood levels of electrolytes and glucose were normal, as were results of tests for coagulation, renal function, and liver function. Other laboratory test results are shown in Table 1. The nose was packed to control the bleeding, and 1 unit of platelets was transfused. The patient was transferred to this hospital for additional evaluation and treatment. In the emergency department of this hospital, the patient reported a mild sore throat but no other symptoms; epistaxis had resolved with nasal packing. There was no fever, weight loss, rash, nausea, vomiting, or diarrhea. The patient had a history of sickle cell trait. He took no medications and had no known allergies. He had been living with his parents and younger brother since he had left his col-lege campus at the start of the coronavirus disease 2019 Covid-19 pandemic. He worked in a grocery store, and his only known sick contact was his mother, who had been infected with severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 2 months earlier. She had been isolated in a room in their home during her illness. The patient did not have any symptoms associated with Covid-19 and had never been tested for SARS-CoV-2 infection. His father and brother had been well. The family lived adjacent to a wooded region, and the patient had been hiking in northern New England 2 months before the current presentation. He had not noticed any tick bites. He had no animal contacts. The patient was born in Central America and had moved to a suburban region of New England at 3 years of age. He had previously traveled to Mexico and Canada. He was sexually active with female partners only. He did not smoke tobacco, drink alcohol, or use illicit drugs. His father had hypertension and hyperlipidemia, and paternal family members had sickle cell disease. On examination, the patient appeared well. There were petechiae on the soft palate Fig. 1. There was no scleral icterus, lymphadenopathy, or hepatosplenomegaly. A large ecchymosis was present on the left forearm. The remainder of the examination was normal. Blood levels of folate and cobalamin were normal, as were results of serum protein electrophoresis and the ratio of free kappa to lambda light chains. Other laboratory test results are shown in Table 1. A radio-graph of the chest and an ultrasound image of the upper abdomen were normal, without sple-nomegaly. Testing of a specimen obtained from the nasopharynx was positive for SARS-CoV-2 RNA; the patient was admitted to the hospital and placed in enhanced isolation. Examination of thick and thin peripheral-blood smears for babesia was negative. A second unit of platelets was transfused, and a diagnostic test was performed. OUTPUT:

Severe acquired aplastic anemia after infection with severe acute respiratory syndrome corona-virus 2.

NEJM_Reasoning_Subset24

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: CME Dr. Austin Be Surgery: A 14-year-old girl was admitted to this hospital because of swelling of the left jaw. The patient had been well until 6 weeks before this admission, when she noticed a lump in the left lower jaw; there was no pain, tenderness, or discomfort in the jaw. She was evaluated in a primary care clinic of another hospital and was told that a salivary gland may be obstructed. Treatment with sialagogues, increased oral hydration, warm compresses, and massage of the salivary glands were recommended. During the next 3 weeks, the lump in the left jaw increased in size, and swelling of the left side of the face and neck developed. Three weeks before this admission, she returned to the primary care clinic; treatment with cephalexin was started. Eighteen days before this admission, the patient was evaluated in the otolaryngol-ogy clinic of the other hospital. The temperature was 37.2C, the blood pressure 13290 mm Hg, the heart rate 86 beats per minute, and the body-mass index the weight in kilograms divided by the square of the height in meters 21.0. There was swelling in the left mandibular and submandibular areas, with no erythema, fluc-tuance, or palpable salivary stones. Dr. Hillary R. Kelly: Computed tomography CT of the face and neck was performed after the administration of intravenous contrast material. CT of the face Fig. 1 revealed a 3.7-cm mass in the left mandibular body, with lytic and expansile features and numerous internal wavy septations. Areas of marked thinning and obliteration were noted in the buccal and lingual cortexes of the mandible, and extension of the mass among the roots of the first molar, second molar, and premolar was observed. No fluidfluid or bloodfluid levels were seen within the lesion. There was no lymphadenopathy. The patient was referred to the otolaryngol-ogy clinic at this hospital. Dr. Be: Fifteen days before this admission, the patient reported numbness and tingling in the lower lip and chin on the left side. She had had no fatigue, fever, chills, or redness and no pain in her face, jaw, or neck. On examination, she appeared well but had obvious facial asymmetry with swelling of the left mandible Fig. 2. There was a firm, mildly tender mass in the body of the left man-dible that extended to the mandibular angle. Orthodontic braces were in place and dentition and jaw occlusion were normal. The remainder of the ear, nose, and throat examination was normal. The overlying skin was normal, and no anterior or posterior submandibular or supraclavicular lymphadenopathy was present. The blood levels of sodium, potassium, and chloride were normal, as were the complete blood count and the results of tests of coagulation and renal function. The calcium level was 11.8 mg per deciliter 3.0 mmol per liter; reference range, 8.5 to 10.5 mg per deciliter 2.1 to 2.6 mmol per liter, and the albumin level was 4.1 g per deciliter reference range, 3.3 to 5.0. Radiography of the chest was normal. Dr. Vania Nose: An intraoral biopsy of the left mandibular mass was performed. Pathological examination Fig. 3C of the biopsy specimen revealed that the lesion was partially surrounded by reactive bone trabeculae, was hemorrhagic, and contained numerous osteoclast-type giant cells around extravasated red cells, findings that were consistent with a central giant-cell lesion or a central giant-cell granuloma. Dr. Be: Ten days before this admission, the patient was seen in the oral and maxillofacial surgical clinic of this hospital, and admission for the excision of the left mandibular mass was planned. On admission to this hospital, additional history was obtained. The patient had normal growth and development and had reportedly received all routine childhood vaccinations. She had finished the prescribed course of cephalexin and had taken no other medications; penicillin had caused fever and hives early in childhood. She lived in a suburban area of New England with her mother, stepfather, and two cats; she frequently stayed in another suburban area of New England with her father. The patient performed well in high school and participated in theater. She did not smoke tobacco, use illicit drugs, or drink alcohol. Her mother had hypothyroidism; her father had obstructive sleep apnea. Her maternal grandmother had a history of hypothyroidism, parathyroid ad-enoma, breast cancer, and colon cancer; her paternal grandfather had died from colon cancer. The temperature was 36.6C, the blood pressure 12885 mm Hg, and the heart rate 111 beats per minute. The physical examination was unchanged. The left mandibular mass was excised. Pathological examination of the surgical specimen revealed abundant giant cells. On the second hospital day, the calcium level was 12.6 mg per deciliter 3.2 mmol per liter and the parathyroid hormone PTH level was 396 pg per milliliter reference range, 10 to 60. A diagnosis was made. OUTPUT:

Primary hyperparathyroidism and brown tumor.

NEJM_Reasoning_Subset25

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: CME Dr. Ian D. Cooley Medicine: A 68-year-old man was admitted to this hospital because of painful mouth ulcers and weight loss. The patient had been well until 6 weeks before the current admission, when painful mouth ulcers and neck pain developed. He was evaluated at an urgent care center. He had reduced range of motion of the neck due to pain with flexion, extension, and rotation, but there was no spinal tenderness. There were small ulcers on the lower lip and gingivae. Cyclobenzaprine and acyclovir were prescribed. Five weeks before the current admission, the patient was evaluated by his primary care physician in a clinic at this hospital. He reported that neck pain on the right side and oral ulcers had persisted and that several new oral ulcers had developed. He had no rash, eye pain, joint pain or swelling, dysuria or genital lesions, abdominal pain, or diarrhea. The examination was notable for several large ulcers on the lips and tongue Fig. 1A. Treatment with acyclovir was continued. A direct immunofluorescence assay of a swab of an oral ulcer was negative for herpes simplex virus HSV types 1 and 2 and for varicellazoster virus. Blood tests were negative for human immunodeficiency virus HIV types 1 and 2 and for syphilis; other laboratory test results are shown in Table 1. The patient was referred to the dermatology clinic for further evaluation of the oral ulcers. Before the patient could be evaluated in the dermatology clinic, his mouth ulcers and pain worsened. Four weeks before the current admission, he presented to the emergency department of this hospital. Erythema and watering of the left eye had developed, as had new skin lesions on the trunk and upper face. The examination revealed multiple ulcers on the lips and tongue Fig. 1B and two pink crusted papules with hemorrhage on the right temple. There were scattered pustules on the lower back and right flank. An ophthalmologic examination revealed a pinguecula on the nasal side of the right eye with mild surrounding inflammation but was otherwise normal. Blood levels of electrolytes and glucose were normal, as were results of kidney- and liver-function tests. HLA typing was positive for the HLA-B51 allele; other laboratory test results are shown in Table 1. The patient was evaluated by the rheumatol-ogy and dermatology services. The decision was made to pursue a skin biopsy before an oral biopsy. A biopsy of a pustule on the patients back was performed, and examination of the specimen revealed mild spongiosis, neutrophilic granulomatous inflammation, and a superficial perivascular lymphohistiocytic infiltrate with neutrophils and occasional eosinophils. Colchi-cine was prescribed, along with oxycodone and lidocaine oral solution, for the treatment of a working diagnosis of Behcets disease. Outpatient follow-up with the rheumatology service was arranged. Three days after discharge from the emergency department, the patient reported that the oral ulcers had not abated. Treatment with predni-sone was started, and colchicine was continued. Two weeks before the current admission, the patient was evaluated in the rheumatology clinic of this hospital. Prednisone treatment had led to only transient healing of the oral ulcers. The patient had pain with eating and speaking and had lost 10 kg of body weight in 3 weeks. The neck pain, the eye watering, and several skin lesions had resolved. The examination revealed extensive ulceration of the upper and lower labial mucosa and of the ventrolateral surface of the tongue on both sides, as well as two focal ulcerations, measuring 0.5 cm in diameter, involving the soft palate on the left side Fig. 1C and 1D. There were multiple purple-red, scaly papules involving the skin of the arms and lower legs. There was no evidence of a joint abnormality. Laboratory test results are shown in Table 1. Prednisone was switched to oral methylpredniso-lone, and treatment with amoxicillinclavulanate was started for possible bowel-associated derma-tosisarthritis syndrome. Omeprazole, which the patient had taken for many years, was stopped because of peripheral eosinophilia. An evaluation in the oral medicine clinic at an affiliated hospital was arranged, with plans for oral and skin biopsies. One week before the current admission, a biopsy of lower labial mucosa revealed squamous mucosa and parenchyma of the minor salivary glands, with mild nonspecific chronic inflammation. A skin biopsy was notable for epidermal ulceration with impetiginization and associated folliculitis. Dexamethasone oral rinses were prescribed, as was trimethoprimsulfamethoxa-zole for prophylaxis against Pneumocystis jiroveci infection. During the next 7 days, the ulcers worsened and the patient had ongoing pain that was unresponsive to oxycodone. He was unable to eat and was admitted to this hospital for pain control and further evaluation. The patients medical history included gastro-esophageal reflux disease. Medications included methylprednisolone, colchicine, amoxicillin clavulanate, trimethoprimsulfamethoxazole, lorazepam, and oxycodone, as well as dexa-methasone oral rinses. The patient was allergic to clarithromycin, which had caused a rash. He had quit smoking 30 years earlier, and he consumed 10 alcoholic drinks per week. There was no illicit drug use. The patient lived with his wife in a suburban area of New England. He had traveled to Western Europe, Mexico, and the Caribbean. He was employed part-time as a contractor. His family history included prostate cancer in his father and type 2 diabetes mellitus in his mother. On examination, the temperature was 35.8C, the blood pressure 13456 mm Hg, the heart rate 70 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 96 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 26.4. The patient looked uncomfortable, with an edematous tongue and multiple oral ulcers. There was no cervical lymphadenopa-thy or joint abnormality. Skin examination revealed a slightly raised pustule, measuring 2 mm in diameter, on the anterior aspect of the thigh. The remainder of the examination was normal. Laboratory test results are shown in Table 1. Dr. Markus Y. Wu: Computed tomography CT of chest and abdomen, performed after the administration of intravenous contrast material, revealed subtle centrilobular ground-glass opacities in the upper lobes of the lungs, as well as prominent right hilar and left supraclavicular lymph nodes, each measuring 1 cm in diameter Fig. 2. Dr. Cooley: A diagnostic procedure was performed. OUTPUT:

Eosinophilic leukemia.

NEJM_Reasoning_Subset26

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Luke A. Stevens Emergency Medicine: A 38-year-old man was evaluated at this hospital because of altered mental status and a seizure. The patient had been in his usual state of health until the night before the current evaluation. His wife reported that he fell out of bed at approximately 4 a.m. and was on the floor shaking. He appeared confused and was speaking gibberish. Police were called to the patients apartment, and emergency medical services were activated. On evaluation at the patients home, a fingerstick blood glucose measurement was 110 mg per deciliter 6.1 mmol per liter. The patient was combative and disoriented, and he actively resisted being placed in the ambulance. On arrival at the emergency department, he had a witnessed generalized tonicclonic seizure, lasting 2 minutes, for which lorazepam was administered intravenously. A limited history was obtained from the patients wife, brother, and sister-in-law. The patient had not been ill recently and had no history of seizures or cardiovascular, respiratory, gastrointestinal, genitourinary, or neurologic disorders. His medical history was notable for a laparoscopic appendectomy. The patient took no medications and had no known adverse reactions to medications. He worked in environmental maintenance at a local business. He lived with his wife, daughter, and son. He had immigrated to Boston from a rural area of Guatemala approximately 20 years earlier. He rarely drank alcohol and did not use tobacco or illicit drugs. There was no known family history of seizure disorder or other neurologic disease. The temperature was 36.4C, the heart rate 120 beats per minute, the blood pressure 17190 mm Hg, the respiratory rate 22 breaths per minute, and the oxygen saturation 95 while the patient was using a nonrebreather mask. His eyes were open, and an involuntary upward gaze was noted; the pupils were 4 mm, symmetric, and reactive to light. He did not verbally respond to questions or follow commands. Gag and cough reflexes were normal. He withdrew his arms and legs in response to pain, and a jerking motion of the head was noted. The score on the Glasgow Coma Scale was 6 on a scale of 3 to 15, with lower scores indicating greater alteration of consciousness. The neck was supple. Peripheral reflexes were normal. The toes were downgoing bilaterally. Scant blood was observed in the mouth, without visible lacerations. The remainder of the examination was normal. Blood levels of albumin, globulin, calcium, phosphorus, magnesium, lipase, N-terminal pro B-type natriuretic peptide, and troponin T were normal, as were the prothrombin time, partial-thromboplastin time, and results of liver-function tests; other laboratory test results are shown in Table 1. A blood specimen was obtained to test for strongyloides antibodies. An electrocardiogram showed sinus tachycardia at a rate of 114 beats per minute but was otherwise normal. Seven minutes after the first dose, a second dose of lorazepam was administered intravenously for suspected continued seizure activity. The patient remained confused and agitated, and an endotracheal tube was placed for airway protection. A chest radiograph was normal, with the endotracheal tube in an appropriate position. A diagnosis was made. OUTPUT:

Seizure from neurocysticercosis.

NEJM_Reasoning_Subset27

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Mubeen A. Shakir Medicine: A 50-year-old woman was admitted to this hospital because of pain in the left upper quadrant and hypoxemia. The patient had been in her usual state of health until 1 year before this admission, when fatigue and weight loss developed and she had abnormal results on liver-function tests after undergoing cholecystectomy for presumed acalculous cholecystitis. Computed tomography CT of the abdomen, which was performed as part of the evaluation to determine the cause of the abnormal liver-function test results, revealed hepatosplenomegaly Fig. 1A. Seven months before this admission, a submandibular mass and swelling developed; 1 month later, examination of a biopsy specimen of the mass revealed granulomatous sialadenitis. A liver biopsy was performed to investigate the patients abdominal distention, poor appetite, and persistently abnormal liver-function test results, which were suggestive of cholestasis. The liver-biopsy specimen showed evidence of granulomatous hepatitis; portal and periportal nonnecrotizing granulomatous inflammation that was associated with multinucleated giant cells, lymphocytes, and some plasma cells; and stage 1 to 2 portal and periportal fibrosis. Special stains for organisms acid-fast and Grocott methenaminesilver stains were negative. CT of the chest revealed minimal bibasilar atelectasis and a trace left pleural effusion. An interferon- release assay for Mycobacterium tuberculosis was negative. Tests for histoplasma species, blastomyces species, cryptococcus species, coccidioides species, the human immunodeficiency virus HIV, and hepatitis A, B, and C viruses were all negative, as was testing for antinuclear antibodies, antimitochondrial antibodies, and antismooth muscle antibodies. A diagnosis of sarcoidosis was made on the basis of the biopsy results of the submandibular gland and liver and the presence of hypercalcemia and an elevated angiotensin-convertingenzyme level. Four months before this admission, prednisone therapy was initiated at a dose of 40 mg per day; subsequently, there was a marked reduction in the patients abdominal distention and marked improvement in her appetite. Liver-function test results also improved. Methotrexate therapy was started at a dose of 15 mg per week, with plans to taper the dose of prednisone. Three months before this admission, the patient stopped prednisone therapy because of irritability and insomnia. One month later, routine monitoring of the patients liver function revealed worsening liver-function test results in a cholestatic pattern. This finding was attributed to undertreatment of sarcoidosis, but the patient declined to restart prednisone; the dose of metho-trexate was increased to 25 mg per week. During the next month, the patient noted fatigue, slowly progressive dyspnea on exertion, and cough, without fever or chills. She was evaluated by her primary care physician 1 month before this admission, and a chest radiograph showed bilateral, perihilar, diffuse, symmetric ground-glass opacities with scattered patchy opacities at the lung bases Fig. 1B and 1C. Levo-floxacin was administered. Three weeks before this admission, CT of the abdomen and pelvis revealed worsening hepato-splenomegaly. Prednisone therapy was started at a dose of 20 mg per day. On the morning of admission, the patient was awakened from sleep by severe, sharp pain in the left upper quadrant. The pain was not worse with eating, and she reported no nausea, vomiting, or diarrhea. Because of persistent pain throughout the day, she presented to the emergency department of this hospital for evaluation. In the emergency department, the patient reported progressive dyspnea on exertion and being unable to climb stairs in her home. There was no chest pain, edema in the legs, weight gain, or orthopnea. She had a cough that was productive of clear sputum but had no fevers or chills. The patient had a history of preeclampsia, Helicobacter pylori infection, cholecystectomy, and papillary thyroid cancer for which she had undergone hemithyroidectomy 9 years before this admission. In addition to methotrexate and pred-nisone, her medications included omeprazole and trazodone. Her father had hypertension and hy-perlipidemia, and one son had ulcerative colitis. Both maternal grandparents had had tuberculosis, but the patient had not had contact with them; her mother had latent tuberculosis. The patient had no known drug allergies. She worked as an administrative assistant and lived with her husband and children in a suburb of Boston. She had never smoked tobacco, did not use illicit drugs, and previously drank one glass of wine per week before her diagnosis of sarcoidosis. She had not traveled outside the United States in the past 5 years. On examination, the temperature was 36.7C, the blood pressure 11256 mm Hg, the pulse 128 beats per minute, the respiratory rate 22 breaths per minute, and the oxygen saturation 85 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 21. The patient was awake and alert but appeared fatigued. The first and second heart sounds S1 and S2 were normal, without murmurs; the jugular venous pressure, which was measured from the approximate midpoint of the right atrium, was 6 cm of water. Crackles were present in the middle and lower lung fields bilaterally. Normal bowel sounds were present, and the abdomen was soft and nondistended, with tenderness in the left upper quadrant. The liver edge was palpable 3 cm below the right costal margin; the spleen tip was also palpable. There was no edema in the legs. Supplemental oxygen was administered through a nasal cannula at a rate of 3 liters per minute, and the oxygen saturation increased to 93. The blood levels of electrolytes, glucose, and lactate were normal, as were the results of kidney-function tests. The level of alanine aminotrans-ferase was 38 IU per liter reference range, 7 to 33, and the levels of aspartate aminotransferase and total bilirubin were normal. The blood level of alkaline phosphatase was 268 IU per liter reference range, 30 to 100. Streptococcus pneu-moniae and Legionella pneumophila antigens were not detected in the urine. The blood level of 1,3--d-glucan was less than 31 pg per milliliter reference value, 60; other laboratory test results are shown in Table 1. Dr. Victorine V. Muse: CT of the abdomen and pelvis Fig. 2A and 2B, performed after the administration of intravenous contrast material, revealed hepatosplenomegaly with a hypodense wedge-shaped region in the midpole of the spleen. A portable anteroposterior chest radio-graph Fig. 2C showed progressive coalescing consolidations in the middle and lower lobes with diffuse ground-glass opacities. CT of the chest Fig. 2D, performed after the administration of intravenous contrast material, revealed new mediastinal and hilar lymphadenopathy and confirmed the presence of multifocal confluent areas of airspace consolidation, with a background of diffuse ground-glass opacities. There was no evidence of pulmonary embolism or pleural effusions. Dr. Shakir: The patient was admitted to the hospital. Treatment with prednisone, methotrex-ate, and omeprazole was stopped, and trazodone was continued. On hospital day 2, the temperature rose to 39.1C, the respiratory rate increased to 32 breaths per minute, and the oxygen saturation decreased to 89 while she was receiving supplemental oxygen through a nasal cannula at a rate of 3 liters per minute. Supplemental oxygen was increased to a rate of 5 liters per minute, and the oxygen saturation increased to 93. Cultures of the blood were obtained. A diagnostic test was performed. OUTPUT:

Pneumocystis jirovecii pneumonia.

NEJM_Reasoning_Subset28

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: CME at NEJM.org Dr. Marisa L. Winkler: A 22-year-old man was admitted to this hospital because of pain and rapidly spreading erythema of the left hand. The patient had been well until the day of admission, when he awoke with pain and swelling of the left hand that involved the distal interphalangeal joint of the second finger and the proximal interphalangeal joint of the fourth finger. Over a period of several hours, the pain progressed and bullae began to form. He began to have pain with movement of the second and fourth fingers, and the bullae turned dark purple; these changes prompted the patient to present to the emergency department of this hospital. In the emergency department, the patient reported pain of the left hand that worsened with movement of the second and fourth fingers. There was no lethargy, fatigue, headache, dyspnea, cough, or pain elsewhere. The patient had no notable medical history and had been well before the day of presentation. On examination, the patient appeared well. The temperature was 38.6C, the blood pressure 12663 mm Hg, the heart rate 101 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 100 while he was breathing ambient air. There were two violaceous, tender bullae on the dorsal aspect of the left hand one on the distal interphalangeal joint of the second finger and one on the proximal interphalangeal joint of the fourth finger, each measuring 7 mm by 3 mm Fig. 1. In addition, there was nontender, streaking erythema spreading across the dorsal aspect of the left hand, the volar aspect of the left forearm, and the medial aspect of the left upper arm into the axilla. There was no axillary lymphadenopathy. On further examination of the left arm, the soft-tissue compartments were soft and compressible, without evidence of crepitus. Finger flexion and extension were intact but limited by pain and swelling in the second and fourth fingers. Results of motor and sensory examinations were normal. The hand was warm. The radial pulse was palpable, and the capillary refill was brisk. The remainder of the overall physical examination was unremarkable. A blood specimen was obtained for cul-ture, a complete blood count, and a metabolic panel. Initial laboratory test results are shown in Table 1. Dr. Arvin Kheterpal: Computed tomography CT of the left hand and arm, performed after the administration of intravenous contrast material, revealed focal soft-tissue swelling overlying the distal interphalangeal joint of the second finger and the proximal interphalangeal joint of the fourth finger on the dorsal aspect of the left hand Fig. 2. There was no evidence of osseous erosion, periosteal reaction, fracture, joint effusion, fluid collection, or subcutaneous air. The left forearm had a normal appearance on imaging. Dr. Winkler: While the patient was in the emergency department, additional history was obtained. The patient was not taking any medications and had no known allergies to medications. He had recently graduated from college and was seeking employment. He lived with his parents in a suburban area of New England. There was no history of recent travel or sick contacts. He rarely drank alcohol and did not smoke cigarettes or use illicit drugs. There was no notable family history. The patient had recently begun practicing taxidermy as a new hobby. Four days before presentation, he received a frozen deer hide from a friend, which he began to prepare for tanning. When he first received the deer hide, he scraped the skin and fur to remove numerous ticks. On the day before presentation, he kneaded the hide with his hands and massaged into it a mixture of deer brain and tap water that had been prepared the day before and left to stand overnight. While the patient was working with the animal hide, he did not wear protective clothing or gloves. His mother had assisted in part of the process but remained well. Intravenous fluid, ceftriaxone, and vancomy-cin were administered, and the patient was admitted to the hospital. Consultants from the orthopedic hand service, dermatology, and infectious diseases evaluated the patient. A diagnostic test was performed. OUTPUT:

Erysipelothrix rhusiopathiae infection.

NEJM_Reasoning_Subset29

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: CME at NEJM.org Dr. Zoe N. Memel Medicine: A 60-year-old man presented to this hospital because of fevers, fatigue, arthralgias, a mouth ulcer, and a rash. The patient had been in his usual state of health until 1 month before the current presentation, when sore throat, fever, and fatigue developed while he was visiting relatives in the Southwest region of the United States. The symptoms persisted despite regular use of acetaminophen. Two weeks before the current presentation, the patient was evaluated in the emergency department of a local hospital in the Southwest, where a test for severe acute respiratory syndrome coro-navirus 2 SARS-CoV-2 was reportedly negative. Oral amoxicillinclavulanic acid and doxycycline were prescribed, and the patient was discharged home. Ten days before the current presentation, a tongue ulcer developed, along with dry scaly nodules on the face and hands and migratory arthralgias in the wrists, fingers, elbows, and shoulders. Because of worsening symptoms, the patient returned home to Boston by airplane. When he landed in Boston, the patient felt too weak to stand, and an ambulance was called to transport him to this hospital. In the emergency department, the patient reported ongoing fevers, fatigue, arthralgias, and sore throat. He had lost 4.5 kg over a 1-month period. He had no eye redness or pain, genital ulcers, shortness of breath, cough, nausea, vomiting, diarrhea, or headache. There was no notable medical history, and the patient had not been taking any regular medications before this illness. He had completed a course of oral amoxicillinclavulanic acid and doxycycline the day before presentation, and he had been taking acetaminophen for the past month. There were no known drug allergies. The patient was born in China and had immigrated to the United States 20 years earlier. He lived with his wife in Boston. He had not traveled internationally for more than 10 years. The patient had previously worked in environmental maintenance but was retired. He had no history of exposure to animals or fresh water and no sick contacts. He had not been sexually active for several years. He was a smoker with a 30-pack-year history, and he drank alcohol socially; there was no injection-drug use. His family history included colon cancer in his father, lung cancer in his mother, pancreatic cancer in his sister, and hepa-tocellular carcinoma in his brother. On examination, the temperature was 37.8C, the blood pressure 11869 mm Hg, the heart rate 78 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 96 while the patient was breathing ambient air. The weight was 59 kg and the body-mass index the weight in kilograms divided by the square of the height in meters 19.2. The patient appeared unwell. There was no conjunctival injection. Oral mucous membranes were dry. There was a circular shallow ulcer on the lateral aspect of the tongue on the left side, as well as white plaque on the dorsal aspect of the tongue. There was no cervical, axillary, or inguinal lymphadenopathy. The abdomen was soft and nontender, without hepatosplenomegaly. Strength was 45 in both shoulders. The remainder of the neurologic examination was normal. There were several small scaly nodules with a rim of patchy erythema on the fingers, an erosion with serosanguineous crust on the left elbow, and two erythematous and mildly violaceous nodules on the forehead Fig. 1. There were no genital lesions. Testing of a nasopharyngeal specimen for SARS-CoV-2 RNA was negative. The ferritin level was 3089 g per liter reference range, 20 to 300 and the creatine kinase level 505 U per liter reference range, 60 to 400. Urinalysis showed 2 ketones and 1 protein. Additional laboratory test results are shown in Table 1. Dr. Karen Rodriguez: Chest radiography performed in the emergency department revealed bibasilar patchy opacities. Computed tomography CT of the chest, performed after the administration of intravenous contrast material, revealed dependent reticular opacities throughout the lower lobes of the lungs Fig. 2. CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed a left adrenal nodule, measuring 1.2 cm in diameter. Dr. Memel: The patient was admitted to the hospital. Intravenous fluid and oral fluconazole were administered. Biopsies of skin lesions on the left elbow and left side of the forehead were performed. During the next 5 days, the fatigue, arthralgias, skin lesions, and mouth pain continued, and daily fevers with temperatures of up to 38.8C were recorded. The mouth lesion did not abate with the use of fluconazole, which was being administered for presumptive oral candi-diasis, and the agent was discontinued. Dr. Samantha N. Champion: Histopathological examination of the biopsy specimen of the forehead lesion revealed vacuolar interface dermatitis with hyperkeratosis, dyskeratosis, pigment incontinence, and sparse perivascular chronic inflammation. Similar findings were observed on histopathological examination of the biopsy specimen of the elbow lesion. Dr. Memel: Cough developed, and pain in the left shoulder increased. On the fifth hospital day, the creatine kinase level was 906 U per liter. Other laboratory test results are shown in Table 1. The next day, imaging studies of the left shoulder were obtained. Dr. Rodriguez: Magnetic resonance imaging MRI of the left shoulder, performed on hospital day 6, revealed patchy mild intramuscular edema that was most pronounced in the trape-zius and deltoid, a finding compatible with myo-sitis Fig. 2. There was no focal or organized fluid collection. Dr. Memel: On hospital day 10, biopsy of the left deltoid was performed with the patient under general anesthesia. In the 24 hours after the muscle biopsy, hypoxemia developed, and the patient received 3 liters of supplemental oxygen through a nasal cannula to maintain an oxygen saturation of more than 93. The next day, the patient received 8 liters of supplemental oxygen through a nasal cannula. Additional laboratory test results are shown in Table 1. Imaging studies of the chest were obtained. Dr. Rodriguez: Repeat chest radiography revealed progressive patchy opacities at the lung bases. Repeat CT of the chest revealed progressive peribronchovascular and peripheral ground-glass and consolidative opacities predominantly involving the lower lobes, a finding consistent with organizing pneumonia Fig. 2. In addition, new small left and trace right pleural effusions were present. Dr. Memel: A diagnostic test was performed. OUTPUT:

Anti–melanoma differentiation–associated protein 5 (anti–MDA-5) dermatomyositis.

NEJM_Reasoning_Subset30

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: CME at NEJM.org Dr. Gabrielle K. Bromberg: A 76-year-old woman was admitted to this hospital because of abdominal pain, anorexia, weight loss, memory impairment, and suicidal ideation. The patient had been in her usual state of health until 2 months before this admission, when she began having epigastric pain and anorexia associated with new constipation. Findings on upper and lower endoscopy were reportedly normal, as were the results of serologic testing for celiac disease. Fifteen days before this admission, the abdominal pain worsened. Ten days before this admission, the patient was admitted to another hospital because of diffuse abdominal pain associated with nausea and poor oral intake. On examination, the patient appeared pale. The abdomen was soft and nontender. The patient was alert and oriented to time, place, and person but had difficulty with word finding. Initial laboratory test results were notable for normocytic anemia and an elevated bilirubin level; other laboratory test results are shown in Table 1. Dr. Ryan Chung: On admission to the other hospital, computed tomography CT of the abdomen and pelvis Fig. 1A and 1B was performed after the administration of intravenous contrast material. There was evidence of a previous cholecys-tectomy, the common bile duct measured 7 mm in diameter reference range, 10 mm after cholecystectomy, and there was mild anasarca with diffuse mesenteric edema. On magnetic resonance cholangiopancreatography Fig. 1C and 1D, the common bile duct again measured 7 mm in diameter; findings were otherwise normal. Dr. Bromberg: After admission to the other hospital, 1 unit of packed red cells was transfused, and the hemoglobin level remained stable thereafter. On the third hospital day, the patient could eat small amounts of food. On further questioning, the patient expressed suicidal ideation and reported a history of prolonged domestic abuse; she was evaluated by the psychiatry service. A diagnosis of post-traumatic stress disorder was made, and lorazepam was administered. The suicidal ideation resolved, but she was noted to need substantial assistance with self-care. While plans were being made for the patients discharge to an assisted-living facility, the constipation worsened, and her oral intake decreased. On the seventh hospital day, vomiting developed, and the laboratory evaluation was notable for hyponatremia, with a blood sodium level of 120 mmol per liter reference range, 135 to 145. A nasogastric tube was placed, and 3 hypertonic saline was administered intravenously. On the eighth day at the other hospital, additional imaging studies were obtained. Dr. Chung: Repeat CT of the abdomen and pelvis Fig. 1E and 1F, performed after the administration of intravenous contrast material, revealed multiple dilated, fluid-filled loops of small bowel that measured up to 4 cm in diameter and the presence of airfluid levels and an abrupt transition point in the right lower quadrant. Dr. Bromberg: Urine specimens had been sent for measurement of urinary porphyrin levels at the time of admission to the other hospital; the resulting levels were elevated Table 1, and the patient was transferred to this hospital for further evaluation. On admission to this hospital, the patient reported persistent abdominal pain, constipation, and anorexia. The vomiting had resolved after insertion of the nasogastric tube. She reported weight loss of 18 kg over the course of the previous 4 months while she was following a limited diet. In an effort to improve the patients overall health, the patients daughter had provided her with supplements and recommended a ketogenic diet consisting of protein and cooked vegetables. The patient also reported that she had been having difficulty with memory for 2 months before this admission. The patient had a history of type 2 diabetes mellitus, hypertension, and glaucoma. Her surgical history included remote cholecystectomy and hysterectomy. Medications included panto-prazole, ondansetron, and calcium carbonate in combination with cholecalciferol. The patient was allergic to ampicillin, penicillin, trimethoprim sulfamethoxazole, doxycycline, tetracycline, eryth-romycin, nitrofurantoin, and nortriptyline all with unknown reactions. She lived with her sister in suburban New England and reported that she was recently separated from her husband owing to long-standing domestic abuse. The patient had two children. She did not have contact with her son, and her daughter lived in India but visited regularly. Her mother had died from breast cancer. Her father and son both had bipolar affective disorder. The patient did not smoke tobacco, drink alcohol, or use illicit drugs. On examination, the temperature was 36.1C, the heart rate 95 beats per minute, the blood pressure 12555 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 97 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 18.5. The patient appeared cachec-tic. There was a nasogastric tube in place. The conjunctivae were pale. The abdomen was soft and diffusely tender, without guarding, rigidity, or rebound tenderness. There was no rash. The patient was alert but inconsistently oriented to time, place, and person. Her speech was tangential, and she was unable to recite days of the week backward. The remainder of the examination was normal. The hemoglobin level was 9.1 g per deciliter reference range, 12.0 to 16.0. Additional laboratory test results are shown in Table 1. A peripheral-blood smear showed normochromic red cells with occasional burr cells and no schistocytes. Reticulocytes, basophilic stippling, and rare nucleated red cells were present; there were no blasts, and the white cells were morphologically normal. Dr. Chung: Ultrasonography of the right upper quadrant revealed mildly increased echogenicity and mild coarsening of the liver parenchyma Fig. 2. The common bile duct measured 5 mm in diameter. Dr. Bromberg: Intravenous fluids and hemin were administered. On the third hospital day, the volume of output from the nasogastric tube remained elevated. The patient underwent surgical exploration for possible small-bowel obstruction. Dilated loops of small bowel with a transition point near the terminal ileum were observed; there was a loop of small bowel tethered underneath an adhesion band around which the cecum had volvulized. The adhesion was lysed, and the loop of small bowel released. There was no mass or stricture. A diagnosis was made. OUTPUT:

Lead poisoning.

NEJM_Reasoning_Subset31

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: CME at NEJM.org Dr. Viral S. Shah: A 26-year-old woman was transferred to this hospital because of respiratory failure and altered mental status. The patient had been in her usual state of health until 3 days before the current admission, when she underwent elective abdominoplasty and liposuction at an ambulatory surgery center. During the procedure, anesthetic agents included intravenous propofol, fentanyl, midazolam, and ketamine, as well as local lidocaine injections. During recovery after the procedure, medications included intravenous cefazolin, enoxaparin, and ondansetron; oral oxycodone, tramadol, and gabapen-tin; and transdermal scopolamine. The patient was lethargic after the procedure but was able to be discharged home after a period of observation. Later that day, the patient was instructed by telephone to take a lower dose of postoperative oxycodone. The next day, on evaluation at the surgical center, she was found to be somnolent but arousable and able to answer questions with effort; the scopolamine patch was removed. Several hours after the patient returned home, her family noticed that she had increased respiratory effort and minimal responsiveness. She was taken by ambulance to the emergency department of a local hospital. In the emergency department, the temperature was 37.7C, the heart rate 130 beats per minute, the blood pressure 12177 mm Hg, the respiratory rate 30 breaths per minute, and the oxygen saturation 83 while the patient was breathing ambient air. She was lethargic, moaned intermittently, and responded with one-word answers; symmetric movement in the arms and legs was observed. Intravenous naloxone was administered, with minor improvement in her condition. Levels of electrolytes and results of kidney- and liver-function tests were normal; other laboratory test results are shown in Table 1. An electrocardiogram showed sinus tachycardia, rightward axis deviation, and nonspecific STT-wave changes. Dr. Dexter P. Mendoza: A chest radiograph showed diffuse confluent opacities in both lungs Fig. 1A. Computed tomography CT of the chest, performed after the administration of intravenous contrast material as part of a pulmonary-embolism protocol, ruled out pulmonary embolism but revealed diffuse mixed ground-glass and consolidative opacities involving all lobes of the lungs, with relative sparing of the subpleural lung Fig. 1B. CT of the abdomen revealed postoperative changes. CT of the head, performed without the administration of contrast material, revealed mild effacement of the cerebral sulci and cisterns on both sides, a finding suggestive of mild diffuse cerebral edema Fig. 1C and 1D. There was also a small hypodensity in the left globus pal-lidus, a finding suggestive of infarction. Dr. Shah: Noninvasive bilevel positive airway pressure was initiated, and the patient was admitted to the intensive care unit ICU at the other hospital. Intravenous vancomycin, piperacil-lintazobactam, levofloxacin, and oseltamivir were administered empirically, and a triple-lumen central venous catheter was inserted. The next morning, the findings on a repeat chest radiograph appeared to be unchanged, but the patient had progressive lethargy, so intubation was performed and mechanical ventilation was initiated. Pink frothy secretions were noted. Intravenous methylprednisolone, propofol, and norepinephrine were administered. A nucleic acid test for severe acute respiratory syndrome coro-navirus 2 SARS-CoV-2 was negative. The tropo-nin I level increased to 4.31 ng per milliliter reference range, 0.029. The thyrotropin, car-boxyhemoglobin, and lipase levels were normal, and tests for Legionella pneumophila and Streptococcus pneumoniae urinary antigens were negative. Later that afternoon, the patient was transferred to the ICU at this hospital. A review of systems was unavailable because intubation was performed on arrival. Medical history that was obtained from family members included iron-deficiency anemia, anxiety disorder, insomnia, and two normal spontaneous vaginal deliveries. Regular medications included lorazepam as needed for sleep; postoperative medications included tramadol, gabapentin, and oxycodone as needed for pain. There were no known adverse reactions to medication. The patient had attended college and worked in an office. She lived with her husband and children. She drank alcohol intermittently and did not use tobacco or other substances. There was no family history of cardiopulmonary or neurologic disorders. The temperature was 36.6C, the heart rate 88 beats per minute, and the blood pressure 11878 mm Hg while the patient was receiving norepinephrine at a rate of 8 g per minute. The height was 168 cm and the body-mass index the weight in kilograms divided by the square of the height in meters 27.8. The oxygen saturation was 99 while the patient was receiving oxygen through a mechanical ventilator in volume-control mode tidal volume, 320 ml; positive end-expiratory pressure, 12 cm of water; respiratory rate, 18 breaths per minute; fraction of inspired oxygen, 1.0. The pupils were 2 mm and symmetrically reactive. The lung sounds were coarse. The abdominal incision was well approximated and without drainage; abdominal drains were in place on both sides. A neurologic examination with interruption of sedation showed spontaneous eye-opening but an inability to visually track and to follow commands. Brain-stem reflexes were intact. The legs withdrew equally and briskly in response to pain. The remainder of the examination was normal. A chest radiograph showed diffuse opacities in both lungs. Levels of electrolytes, urea nitrogen, creatinine, calcium, alanine aminotransfer-ase, bilirubin, creatine kinase, lipase, and ammonia were normal; other laboratory test results are shown in Table 1. Urine human chorionic gonadotropin was undetectable. Urine toxico-logic screening was negative except for the presence of opiates. Specimens of blood and urine were obtained for microbiologic culture. An electrocardiogram including posterior leads showed sinus rhythm, rightward axis deviation, diminutive Q waves, and minor nonspecific STT-wave abnormalities. An abdominal radiograph showed a nonspecific bowel gas pattern, subcutaneous emphysema, and surgical drains over the pelvis. On bedside cardiac ultrasonography, the left ventricle could not be visualized clearly, but right ventricular dilatation did not appear to be present. Intravenous vancomycin, cefepime, and metroni-dazole were administered. Dr. Mendoza: CT of the head, performed without the administration of contrast material, revealed hypodensities in the left basal ganglia and right cerebellum that were suggestive of infarcts; the previously described cerebral edema had reduced slightly. A CT angiogram of the head and neck was normal. CT of the chest, performed after the administration of intravenous contrast material, revealed a reduction in ground-glass opacities but an increase in consolidations, particularly in the lower lobes. CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed a small anterior abdominal hematoma and diffuse subcutaneous emphysema. Dr. Shah: A neurology consultation was obtained; aspirin and atorvastatin were administered. On hospital day 2, the findings on neuro-logic examination worsened, with only sluggish eye-opening and no motor responses to noxious stimuli. Intravenous mannitol at a dose of 1 g per kilogram of body weight was administered. Dr. Mendoza: Repeat CT of the head, performed without the administration of contrast material, revealed a hypodensity in the left glo-bus pallidus that had not changed from the previous study, as well as a hypodensity in the right cerebellum that was not definitive and was probably an artifact. Magnetic resonance imaging MRI of the head showed infarcts within the globi pallidi and smaller punctate infarcts in the cerebral white matter. There were also innumerable diffuse microhemorrhagic foci affecting the cerebral white matter, including the corpus cal-losum Fig. 2. Dr. Shah: Bronchoscopy revealed bloody mucus in the distal trachea Fig. 3. Serial bronchoal-veolar lavage BAL performed in the right upper lobe revealed increasingly erythematous effluent. Lupus anticoagulant and anticardiolipin antibodies were not detected. Levels of C3 and C4 were normal. Tests for antinuclear antibodies and antineutrophil cytoplasmic antibodies were negative. Tests for legionella, streptococcus, and galactomannan urinary antigens and antitrepo-nemal antibodies were negative, as was a repeat nucleic acid test for SARS-CoV-2. Dr. Yasmin Aghajan: On hospital day 3, the pa-tient underwent continuous electroencephalographic monitoring. The study was abnormal because of generalized rhythmic delta activity at a frequency of 1 Hz, which occasionally evolved to generalized periodic discharges superimposed on a disorganized background with irregular delta and theta slowing. There were no epilepti-form abnormalities. Although generalized rhythmic delta activity and generalized periodic discharges are on the ictalinterictal continuum, there were no features suggestive of seizures. The electroencephalographic findings were consistent with encephalopathy and the effects of propofol. A diagnosis was made. OUTPUT:

Fat embolism syndrome.

NEJM_Reasoning_Subset32

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Sagar M. Raju Pediatrics: A 9-year-old boy was transferred to this hospital because of transient weakness and facial droop on the left side and slurred speech. The patient had been well until 5 hours before this evaluation, when his parents observed that he had a facial droop on the left side and slurred speech. In addition, the patient noticed that his left arm and leg felt limp. When he moved to get out of his bed, he could not stand on his own or grip using the left hand. There was no confusion, loss of consciousness, shaking in the arms or legs, urinary or fecal incontinence, headache, nausea, vomiting, recent illness, or trauma. The symptoms lasted approximately 2 minutes and then resolved completely. Emergency medical services were called, and the patient was taken to the emergency department of another hospital. At the other hospital, the physical examination was reportedly normal. The complete blood count, erythrocyte sedimentation rate, prothrombin time, partial-thromboplastin time, and blood levels of electrolytes, glucose, and troponin were normal, as were the results of tests of renal, liver, and thyroid function. The patient was transferred to this hospital for further evaluation. On arrival at this hospital, additional history was obtained from the patients parents. Earlier in the day, the patient had become upset while visiting his grandfather, who was dying of esophageal cancer. He then played a game of hockey with a sibling; no falls or head trauma occurred. At the time that his parents observed the new neurologic symptoms, he had been lying in bed and crying profusely and inconsolably for an extended period. His parents noticed that he was gasping for air and hiccupping while crying. The patient had been born by normal spontaneous vaginal delivery at full term. He had met normal developmental milestones and had received routine childhood vaccinations. He had chronic gastrointestinal upset that had been attributed to anxiety. Two years earlier, he had been evaluated at the neurology clinic of another hospital because of episodes of shaking in the arms and legs, which occurred multiple times a day. The shaking occurred more frequently when the patient was excited or emotional. He was aware of the shaking; he felt an urge before each episode, and the urge was relieved after the shaking occurred. His parents were told that the shaking was stereotypy, and no diagnostic tests were performed. The patient took no medications and had no known drug allergies. He lived with his parents and two siblings in a suburban area of New England. He attended elementary school and performed well academically, although he received tutoring for mild difficulties with reading and phonology. In addition to the history of esophageal cancer in his paternal grandfather, his father had ulcerative colitis, his mother had received a diagnosis of large-B-cell lymphoma in childhood, his sister had asthma, and his maternal grandfather had died of acute coronary syndrome at 30 years of age. On evaluation, the patient appeared well developed and mildly anxious. The temperature was 37.2C, the blood pressure 11664 mm Hg, the pulse 91 beats per minute, the respiratory rate 26 breaths per minute, and the oxygen saturation 100 while he was breathing ambient air. The face was symmetric, with normal forehead wrinkling, blinking, smiling, and cheek puffing. An evaluation of other cranial-nerve functions, sensation, power, bulk, tone, coordination, and gait was normal. A diagnostic test result was reviewed, and a diagnosis was made. OUTPUT:

Moyamoya disease.

NEJM_Reasoning_Subset33

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Suma Babu: A 67-year-old man was evaluated in the sleep clinic at this hospital because of odd behaviors during sleep, daytime sleepiness, and apnea detected on a home sleep study. Three years before the current evaluation, the patients wife noticed that the patient had vocalizations, including talking and yelling, while sleeping. He also had thrashing movements while sleeping; he fell out of bed more than once and inadvertently hit his wife during these movements. Two years before the current evaluation, the patients wife noticed that the patient had prolonged episodes of daytime sleepiness. During the episodes, he appeared to fall asleep while sitting up and was unresponsive to shaking and loud voices; several hours later, he returned to normal interaction without any intervention. The daytime sleepiness was intermittent and fluctuated in severity. Four months before the current evaluation, the patient fell asleep while washing dishes. This resulted in a fall and unstable C1 spinal fracture, which required urgent surgical repair. After the surgical repair, melatonin and trazodone were prescribed for insomnia, and abnormal movements during sleep abated. However, vocalizations during sleep including singing, talking, and expression of fear and anger in the context of upsetting dreams continued and were most prominent in the early morning hours. The patient also had a motor neurologic syndrome that had started before the onset of sleep symptoms, approximately 3.5 years before the current evaluation. Symptoms included progressive gait imbalance with falls, hand clumsiness, hoarse voice, and dysphagia. Serial neurologic examinations, performed over a 3-year period by multiple neuromuscular specialists, revealed slow progression of generalized fasciculations and the development of bulbar hyperreflexia, postural instability, and hypophonia, although strength in the arms and legs remained intact. Serial electromyography revealed progressive and widespread involvement of muscles showing chronic reinnervation changes, including eventual involvement of craniobulbar muscles tongue and masseter muscles. CME at NEJM.org Dr. Brian Zhao: One year before the current evaluation, magnetic resonance imaging MRI of the cervical spine revealed moderate neural foraminal narrowing at the level of C3C4 bilaterally and no central canal stenosis. Four months before the current evaluation, MRI of the head revealed a punctate subacute infarct in the left posterior centrum semiovale, chronic infarcts in the left middle frontal gyrus and right cerebellum, and nonspecific moderate-to-severe white-matter changes Fig. 1. Dr. Babu: Blood tests for paraneoplastic, nutritional, and paraproteinemic causes of the patients neurologic syndrome were unrevealing. A diagnosis of slowly progressive motor neuron disease was made, and therapy with riluzole was begun. A videofluoroscopic swallowing study revealed severe oropharyngeal dysphagia with laryngeal penetration and silent aspiration; a gastrostomy tube was placed, and tube feeding was initiated. The patient underwent a home sleep-apnea test, which showed sleep-disordered breathing with an apneahypopnea index of 20 events per hour; hypoxemia was present at rest while he was breathing ambient air. Severe oxygen de-saturation occurred with frequent respiratory events while he was asleep in the supine position. The patient was then referred to the sleep clinic for an initial evaluation. On evaluation in the sleep clinic, the patient reported that obstructive sleep apnea had been diagnosed on the basis of a home sleep study performed 1 year earlier. Multiple attempts at treatment with continuous positive airway pressure CPAP had been unsuccessful; there had been difficulty in finding a mask that fit comfortably. In addition to the sleep and motor neurologic syndrome described previously, the patients symptoms included snoring, difficulty with sleep initiation, forgetfulness, poor judgment regarding his ability to safely complete physical tasks, urinary urgency and frequency, and night sweats. He had a history of type 2 diabetes mellitus, which was well controlled with insulin and had been complicated by mild, stable, length-dependent sensory polyneuropathy; other history included hyperlipidemia, a heterozygous factor V Leiden mutation, depression, orthostatic hypotension, and gastroesophageal reflux disease. Medications included alprazolam, bupropion, fenofibrate, insulin, melatonin, metformin, riluzole, sertraline, and trazodone; there were no known drug allergies. The patient lived in New England with his wife. He was a retired engineer. He drank two alcoholic beverages per day. He did not smoke tobacco or use illicit drugs. His mother had died from an unknown cause at an elderly age; his father had died from trauma. One of his brothers had cerebrovascular disease, and another had schizophrenia. On examination, the temperature was 36.6C, the blood pressure 11260 mm Hg, the pulse 83 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 96 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 24.2. The patient was awake, alert, and oriented, although his attention was somewhat diminished. He could recall two words out of three. Naming and repetition were intact. The pupils were equally reactive to light and accommodation. Extraocular movements were intact, and visual fields were full. Facial sensation and strength were normal. Speech was hypophonic and mildly slurred. Elevation of the palate was symmetric, and movement of the tongue was normal. Shoulder shrug was symmetric. Strength was 55 in all muscle groups. Deep-tendon reflexes were brisk in the arms, with mild spasticity in the legs. Plantar responses were normal. Vibratory sensation in the legs was mildly diminished. Results of finger-to-nose and heel-to-shin testing were normal. There were mild myoclonic movements in both hands. Alternating movements were mildly clumsy. Tone was slightly increased in the legs. The gait was on a narrow base and was unsteady; the patient was unable to walk with a tandem gait. The Rom-berg test showed truncal titubation. A sleep study to determine the appropriate positive airway pressure PAP therapy was performed. In CPAP mode, there was good control of respiratory events. Electromyographic signals revealed elevated muscle tone during rapid-eye-movement REM sleep, but there were no abnormal behaviors. Two weeks later, during a follow-up visit in the neuromuscular clinic, the patient became unresponsive to sternal rub; the vital signs and blood glucose level were normal. He was transported to the emergency department, where he returned to a normal level of consciousness without intervention. Electroencephalography EEG revealed frequent intermittent diffuse polymorphic delta slowing of the background, often with bifrontal predominance, but showed no epileptiform abnormalities. The patient was fitted with a mask for CPAP, and treatment was initiated. Several weeks after the initiation of treatment, download of CPAP data revealed good effectiveness and adherence. However, episodes of unresponsiveness increased in frequency and lasted up to 3 hours at a time. During the episodes, the patients wife was unable to arouse him despite performing a sternal rub. Modafinil was prescribed, but the episodes did not abate. The patient was admitted to the epilepsy monitoring unit for long-term monitoring and EEG. During the admission, two episodes of unresponsiveness occurred, during which the patient had a normal blood pressure, heart rate, and glucose level and EEG revealed findings consistent with sleep. A diagnostic test was performed. OUTPUT:

Anti-IgLON5 IgG–associated neurologic disorder.

NEJM_Reasoning_Subset34

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Cory A. Perugino: A 70-year-old man was evaluated in the rheumatology clinic of this hospital because of a recurrent left pleural effusion. Five years before this presentation, the patient had pain in the shoulders and proximal muscles of the arms and legs. The pain was worse in the morning and was associated with fatigue. There was no associated stiffness. The erythrocyte sedimentation rate and the C-reactive protein level were elevated. Prednisone was initiated for the treatment of a working diagnosis of polymyalgia rheumatica, and symptoms abated quickly. During the next year, attempts to discontinue predni-sone led to recurrent myalgias, as well as elevations in the erythrocyte sedimentation rate and the C-reactive protein level. Three years before this presentation, swelling, erythema, and pain developed in the cartilaginous portion of the left ear, sparing the earlobe Fig. 1. There was no reduction in these symptoms after empirical antibacterial therapy was initiated for the treatment of presumed cellulitis. The dose of prednisone was increased, and the symptoms involving the ear resolved; however, they recurred when the dose of prednisone was tapered. Biopsy of the left auricle revealed perichondrial inflammation and degenerative changes in the cartilage. The dose of prednisone was increased for a presumed diagnosis of relapsing polychondritis. The symptoms involving the ear resolved, and weekly therapy with methotrexate was initiated. During the next 6 months, attempts to taper the prednisone dose were associated with worsening inflammatory joint and cartilage symptoms, along with elevations in the erythrocyte sedimentation rate and the C-reactive protein level. The erythrocyte sedimentation rate was as high as 89 mm per hour reference range, 0 to 13 and the C-reactive protein level as high as 73.6 mg per liter reference value, 8.0. Two years before this presentation, the patient began treatment with tocilizu-mab for fatigue, markedly elevated C-reactive protein level, and elevated erythrocyte sedimentation rate, all of which persisted despite treatment with prednisone and methotrexate. The administration of tocilizumab allowed for the tapering of prednisone to a lower dose without causing an exacerbation of inflammatory joint and cartilage symptoms. Two weeks after the patient began receiving tocilizumab therapy, and upon tapering of the prednisone dose, pain and swelling developed in the right leg; ultrasound examination revealed a distal deep-vein thrombosis in the right posterior tibial vein. Repeat ultrasonogra-phy of the leg performed 2 weeks later did not show propagation of the deep-vein thrombosis, and the pain and swelling resolved with the continued use of a compression stocking and elevation of the right leg. However, 2 months later, when further tapering of the prednisone dose was started, inflammatory joint and cartilage symptoms recurred, and pain and swelling developed in the left leg. Ultrasound examination revealed deep-vein thromboses in the left popliteal and left calf veins and in the right femoral vein; therapy with rivaroxaban was initiated. The development of recurrent deep-vein thromboses was attributed to the underlying inflammatory disease. The dose of prednisone was increased, methotrexate was continued, and tocilizumab was replaced with infliximab therapy. During the next 6 months, the inflammatory joint and cartilage symptoms worsened when attempts were made to taper the prednisone dose, and these conditions abated only when the dose of prednisone was increased. Blood tests for antineutrophil cytoplasmic antibodies ANCAs, rheumatoid factor, and anticyclic citrullinated peptide antibodies were negative. Fifteen months before this presentation, treatment with rituxi-mab was initiated. However, after an attempt to taper the dose of prednisone, bilateral scleritis developed Fig. 1; the dose of prednisone was increased again, which resulted in resolution of the ocular pain and redness. During the next 3 months, attempts to taper the prednisone dose resulted in recurrent episodes of scleritis and inflammatory joint and cartilage symptoms; additional rituximab treatment was not administered. One year before the current presentation, treatment with low-dose cyclophosphamide was initiated, but the use of this medication was complicated by severe neutropenia, which did not allow for the dose to be escalated. Nine months before this presentation, treatment with cyclophosphamide was stopped, and intravenous tocilizumab was restarted, given its previous efficacy in this patient. However, the use of tocilizu-mab also resulted in moderate but transient neutropenia after each infusion. Seven months before this presentation, pleu-ritic chest pain on the lower left side developed, along with dyspnea on exertion and a dry cough. Chest radiography revealed a moderate left pleural effusion Fig. 2A and 2B. Thoracentesis was performed, and 1 liter of straw-colored pleural fluid was removed; laboratory test results are shown in Table 1. Grams staining of the pleural fluid revealed abundant polymorphonuclear cells but no organisms; bacterial, fungal, and myco-bacterial cultures were without growth. Cytologic examination of the pleural fluid revealed no malignant cells. Computed tomography CT of the chest performed after the pleural fluid was drained showed a small left pleural effusion, a trace right pleural effusion, and bibasilar dependent atelectasis without consolidation, nodules, or lymphadenopathy Fig. 2C. The pleural effusions were attributed to ongoing inflammatory disease. The dose of prednisone was increased, and the pleurisy and dyspnea resolved. Five months before this presentation, tocilizumab therapy was stopped, and tofacitinib was initiated. One week before this presentation, the patient had sudden onset of back pain on the left side. Imaging studies were performed. Dr. Vincent V. Dinculescu: CT of the chest and abdomen, performed 6 months after the first CT of the chest, revealed a small left pleural effusion that was larger than it had been on the first chest CT Fig. 2D. A punctate stone in the lower pole of the left kidney was also observed, with no evidence of hydronephrosis. Dr. Perugino: The patient presented to the rheu-matology clinic for further evaluation. He had no dyspnea, cough, or fever. On examination, the temperature was 36.7C, the heart rate 64 beats per minute, the blood pressure 14575 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 99 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 29.2. There was no scleral redness or erythema of the helix of the ear. The heart sounds were regular. Breath sounds were decreased at the base of the left lung. There was no leg edema, joint swelling or tenderness, pur-pura, petechiae, or deficits in motor strength. The patient had a history of mucinous adeno-carcinoma of the cecum, which had been diagnosed 10 years before this presentation and had been treated with laparoscopic colectomy of the right side of the colon and with oxaliplatin therapy, without evidence of recurrence. Other history included peripheral neuropathy attributed to the oxaliplatin therapy, hypothyroidism, and monoclonal gammopathy of undetermined significance. Macrocytic anemia had been present for 3 years before this presentation, with normal blood levels of cobalamin and folate. The patient also had a history of leukopenia and neutropenia; these conditions had occurred intermittently over the course of the 10 years preceding this presentation but were most pronounced after treatment with cyclophosphamide and tocilizumab. Medications included alendro-nate, atorvastatin, cholecalciferol, folic acid, levo-thyroxine, methotrexate, omeprazole, prednisone, rivaroxaban, trimethoprimsulfamethoxazole, and tofacitinib. The patient drank alcohol occasionally; he did not smoke tobacco or use illicit drugs. He lived in New England and was retired. There was no family history of autoimmune disease. The blood levels of electrolytes, glucose, and thyrotropin were normal, as were the results of liver-function and kidney-function tests. Testing for antinuclear antibodies was negative. Other laboratory test results are shown in Table 1. A diagnostic test was performed, and management decisions were made. OUTPUT:

VEXAS (vacuoles, E1 enzyme, X-linked, autoin-flammatory, somatic) syndrome.

NEJM_Reasoning_Subset35

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Micaela Atkins Pediatrics: A 14-year-old boy was admitted to this hospital because of fatigue, fever, joint pain, abdominal cramping, and diarrhea. The patient had been well until 2 weeks before this admission, when fatigue and fever developed on his final day of summer camp. He was taken to the primary care clinic at another hospital and was told that he had a viral infection. Nine days before this admission, new mild sore throat developed, and the patient returned to the primary care clinic. A throat culture for group A beta-hemolytic streptococcus was reportedly negative. The patient was told that he had possible sinusitis, and treatment with amoxicillinclavulanate was started. During the next 3 days, the sore throat abated, but fatigue and fever persisted. Six days before this admission, new pain in the right shoulder and left knee developed, and the patient again returned to the primary care clinic. The white-cell count and erythrocyte sedimentation rate were reportedly elevated; a blood test for Lyme disease was performed. On the day of admission, the joint pain progressed to involve the shoulders and knees on both sides, and the temperature increased to 39.4C. The patient was given ibuprofen and brought to the emergency department at this hospital. On evaluation, the patient described aching pain in the shoulders and knees, which was worst in his right shoulder and left knee. He rated the pain at 7 on a scale of 0 to 10, with 10 indicating the most severe pain. He had not noticed redness, swelling, or stiffness of the joints. A review of systems was notable for chills, intermittent night sweats, headache, myalgias, and lightheadedness when he stood up from a sitting position. He had no weight loss, rash, vision changes, or respiratory symptoms. He had mild abdominal cramping, decreased appetite, and intermittent nausea. During the past week, there had been a few episodes of nonbloody emesis and watery diarrhea. There had been no hematemesis, hematochezia, or melena. The patient had autism spectrum disorder, with an early delay in speech development that had resolved after speech therapy. He had met milestones for gross CME at NEJM.org and fine motor skills and growth. He had reportedly received all routine childhood vaccinations. Other history included asthma, seasonal rhinosinusitis, and allergies to peanuts and tree nuts; there were no known drug allergies. He had undergone a tonsillectomy in early childhood. Medications included amoxicillinclavula-nate, inhaled fluticasone, and ibuprofen and inhaled albuterol as needed. At the time of admission, the patient was on his summer break before entering high school. Earlier in the summer, he had gone on vacation to a coastal area of New England. He had also attended camp in a rural area of New England, where he camped and hiked in wooded areas and swam in fresh water. He had seen a tick on his clothing but did not recall any bites. Two weeks before this admission, the patient had returned to his home in a suburban area of New England, where he lived with his mother who was a veterinarian, father, sister, and pet dog. His sister had recently had an acute gastrointestinal illness that resolved after several days. The patient was not sexually active and did not use alcohol, drugs, or tobacco. His mother had hypothyroidism, and his maternal uncle had rheumatoid arthritis; there was no other known family history of autoimmune diseases. On examination, the temperature was 36.1C, the blood pressure 12858 mm Hg, the heart rate 107 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 27.2. The patient appeared to be well developed and well nourished, but he looked tired. The conjunctivae were normal. The mucous membranes were dry, and there was an aphthous ulcer on the right buccal mucosa. The lungs were clear on auscultation. There was tenderness on palpation of the epigastric and periumbilical abdomen. There was no erythema, warmth, swelling, or crepitus of the large and small joints. There was tenderness on palpation, as well as pain with movement, of the right shoulder and knees; range of motion in these joints was not decreased. The patient had no rash or lymph-adenopathy. The white-cell count was 12,950 per micro-liter reference range, 4500 to 13,000, the erythrocyte sedimentation rate 48 mm per hour reference range, 0 to 13, the C-reactive protein level 207.6 mg per liter reference range, 0.0 to 8.0, and the lipase level 82 U per liter reference range, 13 to 60. Laboratory test results are shown in Table 1. While the patient was in the emergency department, the temperature increased to 39.2C. Intravenous fluids were administered, and empirical treatment with doxycycline was started. The patient was admitted to the hospital. During the next 2 days, the fever resolved, but the joint pain, abdominal cramping, and diarrhea worsened in severity. On the third hospital day, fever recurred. The white-cell count was 15,190 per microliter, the C-reactive protein level 178.3 mg per liter, and the lipase level 145 U per liter. A fecal occult blood test was positive. A plain film of the right shoulder was normal. A diagnostic test was performed. OUTPUT:

Inflammatory bowel disease (Crohn’s disease).

NEJM_Reasoning_Subset36

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Mia Y. Bothwell Medicine: A 55-year-old man was evaluated in the rheumatol-ogy clinic of this hospital because of bilateral hearing loss and eye redness. The patient had been in his usual state of health until 8 weeks before the current evaluation, when a headache involving the left temple developed. A similar headache had occurred during an episode of shingles 15 years earlier. He received a prescription for a 1-week course of valacyclovir for the treatment of presumed shingles. No skin lesions developed, and the headache resolved. Four weeks before the current evaluation, hearing loss in the left ear developed during an airplane flight. The hearing loss persisted after the flight, and the patient began to have intermittent tinnitus in the left ear and redness in both eyes. He was evaluated by an otolaryngologist at a clinic affiliated with this hospital. He reported no vertigo, otorrhea, rhinitis, or sore throat. On examination, there was redness in both eyes. The right and left auricles and external auditory canals were normal, as was the right tympanic membrane. The left tympanic membrane was retracted; there was no middle-ear effusion. Results of the Weber test were inconsistent. The Rinne test was positive bilaterally, with air conduction greater than bone conduction. There was no sinus tenderness. Nasopharyngoscopy revealed midseptal deviation to the left; the posterior aspect of the nasopharynx was normal. The remainder of the examination, including a cranial nerve examination, was normal. An audiogram showed sloping mild-to-severe sensorineural hearing loss in both ears. Results were asymmetric at low frequencies, with more severe hearing loss in the left ear than in the right ear from 125 to 2000 Hz Fig. 1A. Word recognition was 96 with the right ear and 84 with the left ear reference range, 80 to 100. Results of tympanometry were normal in both ears. The patient received a prescription for a 12-day tapering course of oral prednisone. Magnetic resonance imaging MRI of the head, performed with and without the administration of intravenous contrast material, revealed no abnormal findings. CME at NEJM.org Four weeks later, the patient was evaluated by a different otolaryngologist at the clinic affiliated with this hospital. Hearing loss had progressed. Eye redness had initially decreased after prednisone therapy was started but had subsequently recurred after prednisone therapy was stopped. On examination, there was redness in both eyes. There was no spontaneous nystagmus or gait ataxia. Sinusoidal gaze tracking was normal. The head-thrust test to the left was positive, a finding that indicates vestibular hypofunction on the left side. Results of the Romberg test were normal. The Fukuda step test was positive, with the patient rotated to the left, a finding that also indicates vestibular hypo-function on the left side. A repeat audiogram showed worsening of sensorineural hearing loss and reduction of word recognition to 90 with the right ear and 64 with the left ear Fig. 1B. Results of tympanometry were normal. The patient was referred for an urgent rheumatologic evaluation. Three days later, in the rheumatology clinic at this hospital, the patient reported ongoing hearing loss in both ears and redness in both eyes, as well as the recent onset of imbalance. He also reported that he had had fatigue and intermittent body aches for 2 months and that he had lost 5 kg of weight over a 6-month period. There was no history of oral or genital lesions; 6 weeks earlier, a nonpruritic patchy rash had developed on his torso after he received the influenza vaccine and had rapidly resolved with the use of an oral antihistamine. There was a history of irritable bowel syndrome, diverticulosis, gastritis, allergic rhinitis, and asthma. Medications included intranasal and inhaled fluticasone, vita-min B12, and omeprazole. There were no known drug allergies. The patient lived with his wife in an urban area of New England. For the past 12 years, he had been sexually active with his wife only. He was a retired construction worker. He was a nonsmoker, drank alcohol rarely, and did not use illicit drugs. On examination, the patient appeared well. The temperature was 36.9C, the blood pressure 11579 mm Hg, the heart rate 95 beats per minute, the respiratory rate 15 breaths per minute, and the oxygen saturation 100 while he was breathing ambient air. There was redness in both eyes. The finger-rub test revealed grossly reduced hearing in both ears. The Romberg test was positive when the patients eyes were open, a finding that indicates vestibular or cerebellar hypofunction. The remainder of the examination, including skin, joint, and neurologic assessments, was normal. Blood levels of electrolytes and glucose were normal, as were results of liver-function and kidney-function tests. The complete blood count with differential count was normal. The erythrocyte sedimentation rate was 55 mm per hour reference range, 0 to 13, and the C-reactive protein level 12.3 mg per liter reference value, 8.0. The patient was referred for an urgent ophthalmologic evaluation at this hospital, which was to take place on the same day. On ophthalmologic evaluation, the patient reported no blurred vision, floaters, eye pain, itching, or photophobia. He wore contact lenses, which he changed daily. On examination, visual acuity was normal in both eyes. The right cornea had trace pinpoint epithelial deposits, a peripheral ring of punctate epithelial erosions, and several small confluent areas of punctate epithelial erosions centrally, with no infiltrate. The left cornea had a peripheral ring of punctate epithelial erosions and several confluent areas of punctate epithelial erosions centrally, with no infiltrate. There was evidence of anterior uveitis, with 7 cells per high-power field in the right anterior chamber and 6 to 7 cells per high-power field in the left anterior chamber. There was trace flare in both eyes. A diagnostic test was performed. OUTPUT:

Neurosyphilis.

NEJM_Reasoning_Subset37

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Adith Sekaran Medicine: A 68-year-old man with metastatic melanoma was evaluated in the oncology clinic of this hospital because of fatigue and weight loss. Six years before the current evaluation, the patient received a diagnosis of superficial spreading melanoma of the left shoulder. He was treated with a wide local excision; a biopsy of the sentinel lymph node was negative for melanoma. One year before the current evaluation, the patient began to have slurred speech and weakness in the left hand. Imaging revealed a mass lesion in the parietal lobe of the brain and another mass in the hilum of the left lung. Craniotomy with resection of the brain mass was performed; pathological examination of the resected specimen revealed findings consistent with melanoma, as did a biopsy of the lung mass. Seizures developed postoperatively, and treatment with levetiracetam was initiated. Further treatment included radiation therapy targeting the parietal resection cavity and the administration of pembrolizumab. Four months before the current evaluation, after seven cycles of pembrolizu-mab, the blood thyrotropin level was 9.4 IU per milliliter reference range, 0.4 to 5.0 and the free thyroxine level 0.9 ng per deciliter 12 pmol per liter; reference range, 0.9 to 1.8 ng per deciliter 12 to 23 pmol per liter; treatment with levothy-roxine was initiated. Three months before the current evaluation, after eight cycles of pembrolizumab, exertional angina developed, and the patient underwent coronary catheterization with placement of two drug-eluting stents. Pembrolizumab treatment was resumed 1 month later. When the patient presented to the oncology clinic for a planned infusion of pembrolizumab, he reported a 3-week history of fatigue and a 2-week history of increased thirst and nocturia, with a need to urinate as many as three times each night. Although there was no change in appetite or eating habits, he had lost 5 kg of weight in the previous 3 weeks. There was no headache or change in vision. On examination, the temperature was 36.4C, the heart rate 75 beats per minute, the blood pressure 12866 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 100 while the patient was breathing ambient air. The CME at NEJM.org body-mass index the weight in kilograms divided by the square of the height in meters was 29.0. Heart sounds were regular, with no murmur. Lung sounds were normal. There was no leg edema. Muscle bulk was normal, as was strength in the arms and legs. There was no rash, bruising, or change in skin tone. Other history included hyperlipidemia, hypothyroidism, and coronary artery disease. Medications included aspirin, atorvastatin, clopidogrel, levetiracetam, levothyroxine, metoprolol, and pembrolizumab. He did not smoke tobacco, drink alcohol, or use illicit drugs. The patient lived in New England and was a retired police officer. His father, sister, and brother had had melanoma. There was no family history of diabetes. A complete blood count, the results of liver-function tests, and the blood thyrotropin level were normal. The blood glucose level was 505 mg per deciliter 28.03 mmol per liter; reference range, 70 to 110 mg per deciliter 3.89 to 6.11 mmol per liter. Other laboratory test results are shown in Table 1. The patient was sent to the emergency department of this hospital, and management decisions were made. OUTPUT:

Immune checkpoint inhibitor–induced diabetes.

NEJM_Reasoning_Subset38

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Diana L. Stern Psychiatry: A 65-year-old woman was admitted to this hospital because of depression, recurrent falls, and difficulty caring for herself. Four years before the current admission, the patient received a diagnosis of depression that was precipitated by psychosocial stressors. She was treated with bupropion, citalopram, and cognitive behavioral therapy. The depression was well controlled until 1 year before the current admission, when she began to have an-hedonia, decreased energy, sadness, and poor concentration. She resumed cognitive behavioral therapy, but her symptoms worsened during the next 4 months, and she had suicidal ideation. The dose of bupropion was increased, and treatment with trazodone was started. Fourteen weeks before the current admission, the patient was in a motor vehicle accident that was attributed to her falling asleep while driving. After the accident, she reported increased sadness, low energy, and inability to perform her usual activities. One week later, she fell and struck her head, and she was evaluated in the emergency department of this hospital. She reported that, before her fall, she had been feeling unsteady because of weakness in the left leg. A physical examination was normal. Computed tomography CT of the head, performed without the administration of intravenous contrast material, revealed hypodensi-ties involving the subcortical and periventricular white matter, findings consistent with chronic small-vessel disease. The patient was referred to the neurology clinic of this hospital and was discharged home. During the next week, the patient had balance difficulties and began using a walker. When she was evaluated in the neurology clinic, she reported imbalance and occasional nausea. On examination, she had a depressed affect. Strength was assessed as 55 in the proximal and distal muscles of the arms and legs. Reflexes were 1 and symmetric at the biceps, triceps, and patellar tendons and were CME at NEJM.org absent at the ankles, with downgoing toes. The gait was wide-based and unsteady, with mild dragging of the left leg. A diagnosis of post-concussive syndrome was considered, and treatment with ondansetron was started for nausea. Additional tests were performed. Magnetic resonance imaging MRI of the head, performed after the administration of intravenous contrast material, revealed increased signal intensity in the pons and in a periventricu-lar distribution on T2-weighted imaging, without associated contrast enhancement. There was a region of decreased signal intensity in the right corona radiata on a map of the apparent diffusion coefficient. Results of electroencephalography were normal, as were results of electromyography and nerve-conduction studies of the left leg. Physical therapy was recommended, and repeat MRI was planned for 6 weeks later. Over the next 6-week period, during sessions of cognitive behavioral therapy, the patient was noted to be less talkative, with slow processing, impaired recall, and mild inattention. Repeat MRI with angiography performed 6 weeks after the first study revealed patchy hyperintensity involving the centrum semiovale, corona radiata, internal capsule, and corticospinal tract bilaterally on T2-weighted fluid-attenuated inversion recovery FLAIR imaging, without contrast enhancement; the cerebral vasculature was normal. The patient had recurrent falls without loss of consciousness and began using a wheelchair. She reported worsening sadness, anxiety, and anhedonia, and treatment with buspirone was started. On evaluation in the neurology clinic 6 weeks before the current admission, testing of leg strength yielded inconsistent results, but strength in both legs was assessed as 55 with maximum effort. Dragging of the left leg was also noted to be inconsistent. There were concerns that her depression might be contributing to her neurologic changes, and further follow-up with the psychiatric service was recommended. Five weeks before the current admission, the patients husband brought her to the emergency department of this hospital for an evaluation of worsening memory impairment, poor self-care, and frequent falls. The patient had stopped participating in physical therapy and was spending most of the day in bed. She reported that she had lost 14 kg during the previous 4 months. Other medical history included hypertension, diabetes, and osteoarthritis of the knees. There was a history of postpartum depression 27 years earlier that had lasted for several months. Medications included amlodipine, buspirone, bupro-pion, cholecalciferol, citalopram, metformin, and trazodone. There were no known drug allergies. The patient lived with her husband in a suburb of Boston and worked as a teacher. She was a lifelong nonsmoker, drank alcohol only occasionally, and did not use illicit drugs. Her mother had a history of anxiety and depression in her seventh decade of life. Her sister had a history of stroke. On examination, the patient appeared tired and disheveled, with psychomotor retardation. Strength in both legs was assessed as 55. She had a monoplegic gait, with buckling of the left leg, when walking down a hallway, but she had a normal gait when walking on a treadmill. Her score on the Montreal Cognitive Assessment was 25, indicating mild cognitive impairment; scores range from 0 to 30, with higher scores indicating better cognitive function. The complete blood count, results of liver-function and kidney-function tests, and blood levels of cobalamin, thyrotropin, and electrolytes were normal. Screening for syphilis, Lyme disease, and the human immunodeficiency virus was negative, as was urine toxicologic screening. After an evaluation by a neurology consultant, the patient was voluntarily admitted to the inpatient psychiatric unit. While the patient was in the hospital, the dose of citalopram was tapered, and treatment with desvenlafaxine and amphetaminedextro-amphetamine was started; her levels of attention and wakefulness increased. She participated in group psychotherapy, cognitive behavioral therapy, and occupational and physical therapy. She continued to have variable weakness in the left leg and had three witnessed falls, during which she reportedly had fatigue and lowered herself to the ground. On hospital day 11, the patient reported being unable to use her left arm because of weakness. Although her left arm rested across her chest for most of the day, she was observed holding her husbands hand with her left hand when saying goodbye. On evaluation by a neurology consultant, strength in the left arm was assessed as 55. The working diagnosis was functional neurologic disorder. On hospital day 12, the patient was discharged to a rehabilitation center. At the rehabilitation center, the patient received physical, occupational, and speech therapy, as well as medications to treat depression. During the first week, she made progress toward independence in bathing, toileting, and grooming but had limited attention, memory, and problem solving. During the second week, she became more withdrawn. There was a paucity of speech with hypophonia, decreased attention, and less eye contact with visitors who sat on her left side than with visitors who sat on her right side. During the third week, the patient stopped answering questions and following commands. She was evaluated again in the emergency department of this hospital. On examination, the temperature was 36.7C, the blood pressure 14190 mm Hg, the pulse 98 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 99 while the patient was breathing ambient air. She was withdrawn and minimally interactive. She was able to state her name but not the date or location. She did not blink in response to threat on the left side and did not track the examiners finger past the midline to the left. There was flattening of the left nasolabial fold. The left arm was hypertonic and held in flexion; there was no spontaneous movement of the left arm or leg, and she declined to participate in a strength examination. She did not withdraw the left arm in response to nail-bed pressure; she withdrew the left foot with antigravity movement in response to tactile stimulation. The white-cell count was 12,940 per micro-liter reference range, 4500 to 11,000, with a normal differential count. The remainder of the complete blood count was normal, as were the results of liver-function and kidney-function tests and blood levels of electrolytes. A diagnostic test was performed. OUTPUT:

Diffuse large B-cell lymphoma.

NEJM_Reasoning_Subset39

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Neelam A. Phadke: A 54-year-old woman with a history of episodic swelling of the arms, hands, and feet was evaluated in the emergency department of this hospital because of abdominal pain, nausea, and vomiting. Twenty-three years before the current presentation, swelling of the left hand developed after the patient sustained a human bite. The swelling was associated with mild pruritus, erythema, and warmth. The swelling was well demarcated, involved only the left hand, and resolved after 3 days without specific treatment. Twenty-two years before the current presentation, the patient had epigastric pain that radiated to her back, with associated nausea. Results of an upper gastrointestinal series, computed tomography CT of the abdomen, hepatobiliary scintig-raphy, and esophagogastroduodenoscopy were reportedly normal. The abdominal pain resolved, but two similar self-limited episodes occurred during the next year. No cause for the abdominal pain was identified. During the next 3 years, episodes of self-limited swelling occurred once per year; one episode involved the right foot, one the left hand, and one the right hand. There were no clear triggers for the episodes, although they tended to occur after exposure to cold or after minor trauma, such as scratching. Eighteen years before the current presentation, episodes of swelling of the hands and feet began to occur on a monthly basis, and the patient was evaluated at another hospital after an episode of swelling of the left hand. A skin-biopsy specimen reportedly showed sparse superficial dermal perivascular and interstitial mixed inflammatory infiltrate and stromal edema. Treatment with prednisone was initiated. The swelling of the left hand resolved after 3 days, and the patient was referred to the allergy clinic of this hospital. Laboratory test results are shown in Table 1. A diagnosis of acquired C1 inhibitor deficiency was made on the basis of low levels of C1 esterase inhibitor, C4, and C1q. Results of serum protein electrophoresis were normal, and tests for antinuclear antibodies were negative. The patient was evaluated in the allergy clinic of a third hospital, and treatment with CME at NEJM.org daily danazol was initiated. The episodes of swelling of the hands and feet resolved. Ten years before the current presentation, episodes of swelling of the eyelids and upper lip occurred with associated pruritus. The episodes began with a sensation of facial flushing, pruri-tus of the scalp, and a raised pruritic rash on the face and chest; at times, these episodes were accompanied by shortness of breath, chest tightness, itchy throat, and red eyes. The patient was evaluated in the allergy clinic of the third hospital. Laboratory test results are shown in Table 1. The dose of danazol was increased, and the patient was instructed to take hydroxyzine as needed during episodes of swelling that were associated with pruritus. The swelling episodes associated with pruritus occurred with variable frequency several times per week to once every few months but resolved within 30 minutes after the administration of hydroxyzine. Cetirizine was substituted for hydroxyzine for acute episodes. Treatment with daily loratadine and ranitidine was initiated, and the episodes of swelling with pruritus decreased in frequency. Four months before the current presentation, swelling of the right arm developed after veni-puncture. There was no associated pruritus. The patient was evaluated in the emergency department of this hospital. Ultrasonography of the arm showed no evidence of deep-vein thrombo-sis, and the patient was discharged from the emergency department. The swelling resolved after 3 days. Two weeks before the current presentation, nausea, vomiting, and diarrhea developed. The patient attributed her symptoms to food poisoning, since her daughter had similar symptoms; the symptoms resolved after 3 days. One week before the current presentation, epigastric pain developed; the pain was burning in character, worsened with consumption of food, and abated with the use of nonsteroidal anti-inflammatory drugs NSAIDs. The patient was evaluated at a fourth hospital, where CT of the abdomen reportedly revealed inflammation of the duodenum and jejunum. A proton-pump inhibitor was administered, and the abdominal pain decreased. The patient was instructed not to take NSAIDs and was discharged home. However, during the next week, abdominal pain recurred, along with new symptoms of poor appetite and early satiety. She presented to the emergency department of this hospital for further care. Other history included hypertension, low-back pain, and osteoporosis; she had undergone previous appendectomy and cesarean section. The patient also had a subepithelial duodenal mass, measuring 7 mm in diameter, that had been stable in size during the past 5 years; ultrasono-graphic images had shown that the mass was consistent with a benign stromal cell neoplasm. Medications included amlodipine, calcium carbonate, cholecalciferol, omeprazole, ranitidine, loratadine, and danazol, as well as cetirizine as needed. The patient had no known medication allergies but was allergic to iodinated contrast material. She was originally from Bangladesh and now lived with her husband and two children in a suburban community in New England and worked as a teacher. She did not smoke tobacco, drink alcohol, or use illicit drugs. Her mother had hypertension. The patient reported no similar episodes of swelling in either of her parents. On examination, the temperature was 36.8C, the blood pressure 10681 mm Hg, the pulse 74 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 99 while the patient was breathing ambient air. The abdomen was mildly distended with normal bowel sounds and diffuse tenderness on palpation, without rebound or involuntary guarding. The remainder of the physical examination was normal. The complete blood count was normal, as were blood levels of lipase, bilirubin, alkaline phosphatase, troponin, and thyrotropin. The alanine aminotransferase level was 49 IU per liter reference range, 7 to 33, and the aspartate aminotransferase level was 52 IU per liter reference range, 9 to 32. Dr. Ravi Gottumukkala: CT of the abdomen and pelvis, performed without the administration of oral or intravenous contrast material, revealed long-segment marked circumferential thickening of the jejunal wall with associated mesen-teric edema and small-volume free intraperito-neal fluid. The remainder of the small bowel and colon showed no abnormalities Fig. 1. Dr. Phadke: Diagnostic tests were performed, and treatment decisions were made. OUTPUT:

Hereditary angioedema with C1 inhibitor deficiency and chronic spontaneous urticaria.

NEJM_Reasoning_Subset40

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: CME Dr. Alison C. Castle: A 56-year-old woman was admitted to this hospital in the spring of 2020, during the initial surge of the coronavirus disease 2019 Covid-19 pandemic in Boston, because of fever, myalgias, diarrhea, and a dry cough. Six weeks before this admission, the patient had contact with a person with confirmed severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 infection. At that time, she did not have any symptoms compatible with Covid-19 and was not tested for SARS-CoV-2. Four weeks before this admission, in accordance with statewide recommendations from the Department of Public Health, the patient began isolating at home with her teenage son, working from home, and having groceries delivered. Two weeks before this admission, she and her son left home for a few hours to eat outdoors and spend time in a wooded area; they otherwise remained at home. Six days before this admission, fever, chills, and myalgias developed. The next day, watery diarrhea occurred. The patients temperature measured at home was 38.3C; fever persisted despite the intermittent administration of acetaminophen. Three days before this admission, a frontal headache developed, along with a dry cough that was associated with a self-limited episode of chest pain. The patients son had had no symptoms, except for a self-limited episode of diarrhea 2 weeks before the patients symptoms developed. On the day of admission, the patient continued to have fever, so she presented to the emergency department of this hospital for evaluation. In the emergency department, the patient reported ongoing myalgias, headache, and cough. There was no nausea, vomiting, rash, shortness of breath, or anosmia. She had no notable medical history and took no medications. She was allergic to amoxicillin, with an unknown reaction. She did not smoke tobacco and drank alcohol rarely; she did not use illicit drugs. The patient lived in an urban area of New England and had traveled to Canada 6 months before this admission. She had a pet cat; there was no other animal contact. On examination, the patient appeared anxious, but breathing was unlabored. The temperature was 38.9C, the blood pressure 12164 mm Hg, the heart rate 124 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 95 at rest and 98 during ambulation, both while she was breathing ambient air. The patient was alert and oriented to time, place, and person. There were no focal neurologic deficits. There was no meningism. The mucous membranes were dry. The first and second heart sounds were normal, without additional sounds or murmurs. There were vesicular breath sounds. The abdomen was soft and nontender, without hepatosplenomegaly. There was no rash. Laboratory test results are shown in Table 1. Dr. Patrick P. Bourgouin: Chest radiography revealed low lung volumes, without evidence of pneumonia or pulmonary edema. Dr. Castle: SARS-CoV-2 nucleic acid testing of a nasopharyngeal specimen was negative, as was testing for adenovirus, human metapneumovirus, influenza virus types A and B, parainfluenza virus types 1 through 4, respiratory syncytial virus, human rhinovirus and enterovirus, Bordetella pertussis, B. parapertussis, Chlamydia pneumoniae, and Mycoplasma pneumoniae. Blood cultures were negative. Urinalysis was negative for leukocyte esterase and nitrites. The procalcitonin level was 0.36 ng per milliliter reference range, 0.00 to 0.08. Intravenous fluids and acetaminophen were administered, and the heart rate decreased to 93 beats per minute. The patient was admitted to this hospital because of concerns that she had Covid-19. On the second hospital day, the patient had ongoing diarrhea, headache, and cough, along with fatigue. The temperature was 40.2C, the blood pressure 11564 mm Hg, the heart rate 89 beats per minute, and the oxygen saturation 96 while she was breathing ambient air. The administration of intravenous fluids was continued. SARS-CoV-2 nucleic acid testing of a second nasopharyngeal specimen was negative. Laboratory test results are shown in Table 1. On the third hospital day, the temperature was 38.7C. Dr. Bourgouin: Computed tomography CT of the chest, performed without the administration of intravenous contrast material, revealed interlobular septal thickening, mild ground-glass opacities at the lung bases, and small bilateral pleural effusions Fig. 1. Dr. Castle: During the next 3 days, the patient had ongoing myalgias, headache, and cough. Fever persisted, and the oxygen saturation remained normal. Urine antigen testing for legion-ella and Streptococcus pneumoniae antigens was negative, as was screening for human immunodeficiency virus HIV types 1 and 2 and nucleic acid testing of a blood specimen for cytomega-lovirus and EpsteinBarr virus. Blood cultures remained negative. On the seventh hospital day, diarrhea resolved, but fever, myalgias, headache, and cough persisted. The physical examination was unchanged, with a normal oxygen saturation during ambulation. Dr. Bourgouin: Chest radiography revealed no evidence of pneumonia. Dr. Castle: The procalcitonin level was 0.57 ng per milliliter; other laboratory test results are shown in Table 1. Levofloxacin was administered. On the eighth hospital day, fever resolved but headache and fatigue persisted. A diagnostic test was performed. OUTPUT:

Anaplasmosis.

NEJM_Reasoning_Subset41

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: CME at NEJM.org Dr. David M. Dudzinski: A 78-year-old man was evaluated in the cardiology clinic of this hospital because of biventricular myocardial wall thickening, progressive mi-tral regurgitation, and ventricular arrhythmias. The patient had been a distinguished multisport athlete in high school and college. However, in his 20s, he found that he was unable to perform competitively, and he noticed that he did not sweat as much as his teammates. After an episode of sports-related exertional dizziness, he was evaluated by a physician, and a diagnosis of hypertrophic cardiomyopathy was considered. Twenty-five years before the current evaluation, a transthoracic echocardiogram TTE reportedly showed a symmetric left ventricular wall thickness of 19 mm reference value, 11, a left ventricular ejection fraction of 74 reference range, 50 to 75, mitral valve thickening, and trace mitral regurgitation, with no left ventricular outflow gradient. An electrocardiogram showed sinus rhythm, incomplete right bundle-branch block, precordial J-point elevation, and QRS voltage that met the electrocardiographic criteria for left ventricular hypertrophy Fig. 1A. The patients blood pressure was 16090 mm Hg, and he started treatment with meto-prolol succinate and then also with amlodipine for elevated blood pressure. During the next 10 years, the patient had intermittent chest discomfort, exer-tional dyspnea, and leg edema. The chest discomfort and exertional dyspnea were most likely to occur when he was walking or after he had eaten a meal. He was evaluated by three cardiologists; treatment with metoprolol succinate and amlo-dipine was continued, treatment with enalapril was started, and triamterene hydrochlorothiazide was administered as needed for leg edema. A repeat TTE reportedly showed a symmetric left ventricular wall thickness of 20 mm, a normal left ventricular ejection fraction, right ventricular wall thickening, left atrial enlargement, mitral valve thickening, mild-to-moderate mitral regurgitation, aortic valve thickening, and mild ascending aortic dilatation 39 mm, with no evidence of left ventricular outflow tract obstruction and no evidence of systolic anterior motion of the mitral valve. An exercise stress test followed by OUTPUT:

Fabry’s disease.

NEJM_Reasoning_Subset42

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Leontios Pappas Medicine: An 80-year-old woman was admitted to this hospital because of pancytopenia and the identification of schistocytes on a peripheral-blood smear. Six weeks before admission to this hospital, nausea, vomiting, and diarrhea developed, along with chills and subjective fever. The symptoms resolved after 4 days without specific intervention, but then intermittent dysphagia with solid foods and early satiety developed. During the next 4 weeks, the patient had gradually progressive fatigue and light-headedness. The fatigue progressed to the point that she could no longer stay at work for more than a few hours; she presented to another hospital for evaluation. At the other hospital, the patient reported that she had ongoing fatigue and had lost 6 kg of weight over a 5-week period. On examination, the temperature was 38.9C, the weight 55.5 kg, and the body-mass index the weight in kilograms divided by the square of the height in meters 21.9. Laboratory studies revealed pancytopenia, and examination of a peripheral-blood smear revealed schistocytes. Blood levels of glucose and electrolytes were normal, as were the results of kidney-function and liver-function tests; other laboratory test results are shown in Table 1. Imaging studies were obtained. Dr. Ranjodh S. Dhami: A chest radiograph was normal. Computed tomography CT of the abdomen and pelvis, performed after the administration of intravenous and oral contrast material, revealed a small hiatal hernia, multiple simple cysts in the right kidney, and indeterminate bilateral pelvic masses measuring 4.8 cm in diameter on the right side and 6.3 cm in diameter on the left side Fig. 1. Dr. Pappas: Intravenous fluids were administered, and the patient was admitted to the other hospital. On hospital day 2, the hemoglobin level decreased to 6.6 g per deciliter, and two units of packed red cells were transfused. Esophagogastro-duodenoscopy revealed diffuse esophageal inflammation with white exudates throughout the esophagus; examination of brushings revealed yeast consistent with candida, and treatment with fluconazole was initiated. During the next 3 hospital days, the patient continued to feel unwell, with persistent fever and limited oral intake due to odynophagia, and the administration of intravenous fluids was continued. Blood and urine cultures showed no growth. On hospital day 5, empirical therapy with doxycycline was started because of concerns about a possible tickborne illness. On hospital day 6, the oxygen saturation decreased to 89 while the patient was breathing ambient air and then increased to 94 when oxygen was delivered through a nasal cannula at a rate of 3 liters per minute. CT of the chest, performed after the administration of intravenous contrast material, revealed ground-glass opacities and interlobular septal thickening, findings consistent with pulmonary edema, along with bilateral pleural effusions of a small to moderate size. The administration of intravenous fluids was stopped, and one dose of intravenous furosemide was provided. On hospital day 7, fever resolved but pancyto-penia persisted. Examination of a peripheral-blood smear revealed a moderate amount of schistocytes, severe anisocytosis, large platelets, and an increased amount of bands without blasts. Direct and indirect Coombs tests were negative, as were nucleic acid tests for babesiosis and anaplasmosis. Blood levels of electrolytes, glucose, cobalamin, folate, homocysteine, and anticardiolipin IgG and IgM were normal, as were the results of kidney-function and liver-function tests. The results of serologic tests for EpsteinBarr virus were consistent with previous infection. Flow cytometry of the peripheral blood showed phenotypically normal myeloid cells; there was an increased amount of atypical CD34 myeloblasts, which accounted for less than 1 of leukocytes and were of unclear clinical significance. A tunneled catheter was placed in the right internal jugular vein, and plasma exchange was initiated for the treatment of possible thrombotic thrombocytopenic purpura TTP. Total parenteral nutrition was also initiated, because oral intake was still limited by odynophagia. On hospital day 8, oral intake of soft foods and liquids increased. A transthoracic echocar-diogram showed normal left ventricular size and function, as well as a mildly thickened aortic valve with no stenosis or regurgitation; there was trace mitral and tricuspid regurgitation. On hospital day 9, the patient underwent additional plasma exchange and was transferred to this hospital for further care. On evaluation in this hospital, the patient reported that her energy level had increased. She recalled that she had felt mildly confused at the other hospital, but the confusion had since resolved. She had had no gum bleeding or blood in the stool or urine. Other medical history included hypertension and dyslipidemia. Surgical history included hysterectomy at 40 years of age, with no vaginal bleeding since the procedure. One year earlier, routine laboratory testing had revealed mild thrombocytopenia and anemia. A bone marrow biopsy performed at that time had revealed slightly hypercellular marrow with maturing trilineage hematopoiesis but with some erythroid abnormalities and occasional hyper-chromatic megakaryocytes; cytogenetic analysis had shown a loss of chromosomes 3 and 5 and a gain of chromosome 8 in 65 of the cells. Thereafter, blood counts monitored every 4 months, including 4 months before this presentation, had remained stable; laboratory test results are shown in Table 1. Medications included amlodipine, atorvastatin, and hydrochlorothiazide. There were no known drug allergies. The patient drank alcohol occasionally and did not use illicit drugs. She had smoked tobacco for 50 years but had quit 5 years before this presentation. She was widowed and lived alone in New England; her work involved cleaning a church several days a week. Her sister had had breast cancer at 30 years of age, and a brother had had testicular cancer at a young age and liver cancer at 55 years of age. On examination, the temperature was 36.8C, the blood pressure 15065 mm Hg, the pulse 72 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97 while oxygen was administered through a nasal cannula at a rate of 2 liters per minute. The patient was alert and oriented, and she did not appear ill. There were no petechiae. There was no bleeding at the site of tunneled catheter placement in the right internal jugular vein. The first and second heart sounds were normal; a grade 26 systolic murmur was heard at the left lower sternal border. The remainder of the physical examination was normal. Examination of a peripheral-blood smear revealed schistocytes, anisocytosis, and a low platelet count, with large platelets present; the white cells appeared normal, and there were no blasts Fig. 2. The results of serum protein electrophoresis were normal. The levels of serum free kappa and lambda light chains were increased, with a normal ratio. Screening for human immunodeficiency virus infection was negative. Urinalysis showed 2 urobilinogen, without bilirubin, blood, glucose, ketones, protein, or nitrates; the specific gravity and pH were normal. Consultation was obtained from the gyne-cology service regarding the bilateral pelvic masses noted on CT of the abdomen and pelvis. Blood levels of CA 125, CA 19-9, and carcinoem-bryonic antigen were normal, and follow-up in the gynecology clinic was recommended for further evaluation after discharge. Other laboratory test results are shown in Table 1. A diagnostic test was performed, and management decisions were made. OUTPUT:

Myelodysplastic syndrome.

NEJM_Reasoning_Subset43

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Jacquelyn M. Nestor Medicine: A 41-year-old woman with transient dysarthria and facial droop was transferred to this hospital for evaluation of masses on the mitral valve. Three weeks before this presentation, the patient presented to the emergency department of another hospital because of concerns about heavy vaginal bleeding that had developed 1 week earlier and was associated with crampy abdominal pain, fatigue, dyspnea, and lightheadedness. Examination was notable for a heart rate of 91 beats per minute, a blood pressure of 13079 mm Hg, and an oxygen saturation of 100 while she was breathing ambient air; the examination was otherwise reportedly normal, although a gynecologic examination was not performed. Laboratory results were notable for a hemoglobin level of 8.2 g per deciliter reference range, 12.0 to 16.0; previous level 1 year earlier, 9.1, a mean corpuscular volume of 71.3 fl reference range, 80 to 94, and a platelet count of 148,000 per microliter reference range, 150,000 to 450,000. Urine human chorionic gonadotropin was undetectable. Normal saline was administered intravenously, and a 5-day course of medroxyprogesterone acetate was prescribed. Eleven days after the patient completed the therapy with medroxyprogesterone acetate 9 days before this presentation, heavy vaginal bleeding and dyspnea recurred. An additional 3-day course of medroxyprogesterone acetate was prescribed. The evening after the patient finished the second course of treatment, within 1 hour after she had been seen and had appeared to be well, her husband noted that she had facial droop on the right side and slurred speech; he called emergency medical services. When she arrived at the emergency department of a second hospital, within 1 hour after the onset of symptoms, her examination was notable for a heart rate of 91 beats per minute, a blood pressure of 17383 mm Hg, and an oxygen saturation of 99 while she was breathing ambient air. She was noted to have facial droop on the right side and unintelligible speech. Dr. Sandra P. Rincon: Computed tomography CT of the head Fig. 1A revealed no evidence of acute infarction or intracranial hemorrhage. Small chronic infarcts were seen in the right thalamus and right cerebellar hemisphere. A CT angiogram CTA of the head and neck did not show high-grade stenosis or large-vessel occlusion. Dr. Nestor: A neurology consultation was obtained; aspirin and atorvastatin were administered. Blood levels of electrolytes, albumin, low-density lipoprotein cholesterol, and glycated hemoglobin were normal, as were the white-cell count and differential count and the results of liver-function and kidney-function tests. Urine human chorionic gonadotropin was undetectable, and urinalysis showed 3 blood, no protein, and no casts. Additional laboratory test results are shown in Table 1. Within 45 minutes after the patient arrived at the emergency department of the second hospital, the facial asymmetry and dysarthria resolved. The patient was admitted to the medical unit of the second hospital. Dr. Rincon: The next day, magnetic resonance imaging MRI and angiography of the head and neck again revealed old lacunar infarcts in the right thalamus Fig. 1B and right cerebellar hemisphere Fig. 1C. There was no evidence of an acute infarction Fig. 1D, intracranial hemorrhage, or cerebrovascular occlusion Fig. 1E and 1F. Dr. Nestor: Two units of packed red cells were transfused. Post-transfusion laboratory test results are shown in Table 1. A transthoracic echocar-diogram Fig. 2A and 2B and Video 1, available with the full text of this article at NEJM.org showed thickened mitral valve leaflets and mild-to-moderate mitral regurgitation, with an estimated right ventricular systolic pressure of 48 mm Hg. Dr. Evin Yucel: On the third hospital day, a trans-esophageal echocardiogram Fig. 2C and Videos 2 and 3 showed multiple echodensities on the atrial side of the mitral valve leaflets at the closure lines that were consistent with vegetations. Cultures of blood were obtained, and heparin was administered intravenously. Dr. Nestor: On the fourth hospital day, the rate of heparin infusion was decreased at 6-hour intervals when the partial-thromboplastin time exceeded 150 seconds, until the infusion was stopped. Laboratory test results are shown in Table 1; complement levels C3 and C4 were normal. Additional cultures of blood were obtained. Dr. Rincon: Repeat CT of the head revealed no acute abnormality. CT of the chest showed clustered nodules in the lower lobes that were probably related to aspiration, and CT of the abdomen and pelvis Fig. 2D, 2E, and 2F revealed an enlarged heterogeneous uterus with multiple fibroids. Dr. Nestor: The next day, the patient was transferred to this hospital. On a review of systems, she reported no recurrence of dysarthria or facial droop and noted no other neurologic symptoms. She reported that she had had heavy menstrual bleeding and exertional dyspnea in the weeks preceding this presentation; pruritic, macular rashes on the trunk, scalp, arms, and legs with associated photosensitivity that had persisted for many weeks; new Raynauds phenomenon in the past 10 months; and a long history of dry eyes and seasonal allergies. Medical history was notable for sickle cell trait, vitamin B12 deficiency, iron deficiency resulting in past iron infusions, uterine fibroids, anxiety, and hyperten-sion. Surgical history included multiple laparos-copies and two laparotomies, including salpingo-oophorectomy for endometriosis. Owing to infertility, she had undergone in vitro fertilization; she had a first-trimester spontaneous abortion at 25 years of age. During her second pregnancy at 33 years of age, a screening rapid plasma reagin RPR test was positive at 1:8; however, a treponemal-specific confirmatory test for syphilis was negative. Pregnancy-induced hypertension developed, followed by placental ab-ruption at 30 weeks, which resulted in a cesarean delivery. Medications included amlodipine, cyano-cobalamin, ferrous sulfate, and medroxyproges-terone acetate. She had no known medication allergies. The patient lived in eastern Massachusetts with her husband and child. She did not drink alcohol or smoke tobacco. Her mother had rheumatoid arthritis, hypertension, and a history of spontaneous abortion. One grandmother had diabetes and the other grandmother had had a stroke. An aunt had had leukemia and later breast cancer. Her child has psoriasis. The temperature was 36.8C, the heart rate 74 beats per minute, the blood pressure 15598 mm Hg, and the oxygen saturation 99 while the patient was breathing ambient air. The height was 175 cm, the weight 107 kg, and the body-mass index the weight in kilograms divided by the square of the height in meters 34.9. There were several small, circular macules on her back Fig. 3. There was a grade 26 holosystolic murmur at the left sternal border and apex. She had no lymphadenopathy, petechiae, nail changes, or evidence of arthritis. The remainder of the examination was normal, as was a neurologic examination. Laboratory test results are shown in Table 1. All the blood cultures obtained at the second hospital showed no growth. An electrocardiogram was normal. Diagnostic test results were received, and management decisions were made. OUTPUT:

Systemic lupus erythematosus with antiphospho-lipid syndrome.

NEJM_Reasoning_Subset44

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Shaan Khurshid: A 56-year-old man presented to this hospital in early autumn with a 1-month history of myalgias and fever. Approximately 4 weeks before the current presentation, the patient began to have generalized myalgias and arthralgias, which were worst in the shoulders, proximal arms, and upper back. He had fever with temperatures of up to 38.2C, along with chills and diaphoresis. He took naproxen, and the next day, he presented to an urgent care clinic affiliated with this hospital. The temperature was 37.2C, the heart rate 72 beats per minute, the blood pressure 17595 mm Hg, and the oxygen saturation 100 while he was breathing ambient air; the remainder of the physical examination was normal. A test for severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 RNA was negative. Symptoms abated after 3 days, but then fever with temperatures of up to 38.3C and fatigue occurred. The patient stopped consuming alcohol. Three weeks later, the patient had episodes of mild dyspnea with coughing fits and presented to a second urgent care clinic affiliated with this hospital. The temperature was 37.2C, the heart rate 59 beats per minute, the blood pressure 13875 mm Hg, and the oxygen saturation 98 while he was breathing ambient air. He appeared fatigued, but the remainder of the physical examination was normal. Another test for SARS-CoV-2 RNA was negative, and the results of urinalysis and chest radiography were normal. The next day, the patient was evaluated by his primary care physician at another hospital. He reported a 1-month history of stabbing back pain between his shoulders, which was worst at the end of the day and was not relieved with the use of naproxen or a heating pad. The temperature was 36.7C, the heart rate 48 beats per minute, the blood pressure 12272 mm Hg, and the oxygen saturation 100 while he was breathing ambient air. There was tenderness on palpation of the left thoracic paraspinal area, but the remainder of the physical examination was normal. Radiographic images of the thoracic spine were reportedly normal. Laboratory test results obtained at that time are shown in Table 1, alongside routine test results obtained 6 months earlier. The patient was referred to the emergency department of this hospital. On the systems review, the patient reported that he had recently measured heart rates of 40 to 50 beats per minute on his home pulse oximeter; his baseline heart rate was 80 to 90 beats per minute. He also reported a history of dysuria that was attributed to chronic prostatitis, as well as pain in the left wrist and knee that was attributed to gout. He reported no weight loss, sweats, palpitations, dyspnea, dizziness, lightheadedness, chest discomfort, joint swelling or redness, rash, headache, focal neurologic symptoms, nausea, vomiting, diarrhea, or rectal bleeding. The patients medical history was notable for sickle cell trait, hypertension with mild left ventricular hypertrophy, palpitations, unprovoked pulmonary embolism, obstructive sleep apnea, hyperuricemia, latent tuberculosis, malaria, chronic hepatitis B virus infection, Helicobacter pylori infection, colonic schistosomiasis, prostatism, and thrombocytopenia. His last dental procedure had taken place more than 2 years earlier. Medications included aspirin, metoprolol, and losartan, as well as sildenafil as needed. He had received two vaccines for coronavirus disease 2019 Covid-19, with the second vaccine administered 7 months before the current evaluation. There were no known adverse reactions to medication. The patient grew up in equatorial Central Africa. He had immigrated to the United States 20 years earlier and had not returned to Africa for more than 5 years. He was employed at a local university and occasionally had contact with college students. He lived with his family in a suburb of Boston. During the summer months, he had visited islands in Massachusetts and coastal wooded areas to hike, camp, and swim. The patient reported that he had encountered many ticks but had not received a tick bite. He had been scratched by cats; there were no other animal exposures. In the past, he had consumed two or three beers daily, but he had stopped all alcohol intake during the previous month. He had never used tobacco or illicit substances. His family history was notable for atherosclerotic coronary disease. On examination, the temperature was 36.5C, the heart rate 46 beats per minute, the blood pressure 14165 mm Hg, and the oxygen saturation 100 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 34.4. He appeared comfortable. Auscultation of the chest revealed a bradycardic heart rate. There was tenderness on palpation of the left infrascapular area. A prostate examination revealed a nontender hemorrhoid. There was no rash or lymphadenopathy, and the remainder of the examination was normal. Blood levels of calcium, total protein, and thyrotropin were normal, as were the results of liver-function tests. Other laboratory test results are shown in Table 1. Blood cultures were obtained. Electrocardiograms were notable for sinus rhythm with first-degree and second-degree 2:1 atrioventricular block with intermittent right bundle-branch block Fig. 1A, alternating with sinus rhythm with third-degree complete atrio-ventricular block and junctional escape rhythm with intraventricular conduction delay Fig. 1B. Computed tomography CT of the chest, abdomen, and pelvis, performed after the administration of intravenous contrast material, was negative for pulmonary embolism. Intravenous ceftriaxone, naproxen, acetaminophen, and oxycodone were administered. The patient was evaluated by an electrophysiologist and admitted to the cardiology unit of this hospital. The next day, the heart rate remained at approximately 40 beats per minute, and the maximum temperature was 37.8C. Oxycodone and topical lidocaine were administered. Dr. Alex L. Huang: Transthoracic echocardiogra-phy TTE revealed normal biventricular systolic function, with no regional left ventricular wall-motion abnormalities. There was mild diastolic mitral and tricuspid regurgitation Fig. 1C, a finding consistent with atrioventricular block.1 There was no evidence of valvular vegetations. Dr. Khurshid: The blood level of high-sensitivity troponin was 63 ng per liter. Urinalysis was negative, as were blood tests for Lyme disease antibodies, anti-rickettsia IgM, ehrlichia and ana-plasma DNA, human immunodeficiency virus types 1 and 2, and babesia. On the third hospital day, tests for SARS-CoV-2, Bartonella henselae and B. quintana antibodies, and anti-treponemal antibodies were negative. An interferon- release assay for Mycobacterium tuberculosis was positive. Dr. Borek Foldyna: The patient underwent cardiac CT with electrocardiographic gating, including contrast-enhanced CT angiography and delayed imaging. Epicardial fat and a thickened interatrial septum abutting the noncoronary sinus of the aortic valve showed increased radioden-sity on delayed imaging Fig. 2A and 2B; these findings are suggestive of inflammatory changes and may indicate evolving abscess. The tricus-pid aortic valve had mildly thickened leaflets, but there was no evidence of focal valvular vegetations, thrombi, or calcifications. Dr. Khurshid: Oral doxycycline was administered. On the fourth hospital day, the ventricular rate measured between 30 and 40 beats per minute, and the maximum temperature was 37.9C. OUTPUT:

Regional myocarditis due to infection with Liste-ria monocytogenes.

NEJM_Reasoning_Subset45

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Amiko M. Uchida Medicine: A 57-year-old man was evaluated in the gastroen-terology clinic of this hospital because of new ascites. Twenty years before the current presentation, the patient began to have swelling of the legs, which initially occurred only after airplane trips. During the fifth decade of life, the leg swelling was present on a daily basis. Thirteen years before the current presentation, the patient began to have frequent bowel movements up to four per day with loose malodorous stools and increased flatus. He was evaluated in the gastroenterology clinic of this hospital. On examination, the abdomen was soft and nontender, with no evidence of organomegaly. There was pitting edema in both legs. The blood level of total protein was 5.5 g per deciliter reference range, 6.0 to 8.3, and the blood albumin level was 3.1 g per deciliter reference range, 3.3 to 5.0. Results of other liver-function tests, including liver enzyme levels, were normal. The protein level in a 24-hour urine sample was normal. The blood alpha1-antitrypsin level was 173 mg per deciliter reference value, 54. Blood levels of IgG, IgA, and IgM were low. Serologic tests for antitissue trans-glutaminase antibodies and anti-giardia antibodies were negative. Dr. Mark A. Anderson: Computed tomographic CT enterography of the abdomen and pelvis, performed after the administration of intravenous and oral contrast material, revealed diffuse mural thickening and hyperenhancement of the small bowel, with no evidence of stricturing or obstruction Fig. 1A and 1B. In addition, there was trace ascites Fig. 1B. Dr. Uchida: Esophagogastroduodenoscopy EGD and colonoscopy revealed no visible abnormalities. A random biopsy specimen of the duodenum showed a focal area with more than 70 eosinophils per high-power field; a biopsy specimen of the gastric antrum showed scattered eosinophils in the lamina propria. A working diagnosis of protein-losing enteropathy was made, although neither a 2-week course of oral prednisone nor a 6-week course of oral budesonide led to a decrease in the number of bowel movements or leg edema. No further treatment was pursued. Eleven years before the current presentation, the patient was evaluated in the gastroenterology clinic of this hospital. There had been no weight loss or recurrent infections, but leg edema persisted. Repeat EGD revealed no visible abnormalities, and a random biopsy specimen of the duodenum showed fewer eosinophils than the previous specimen, with no epithelial damage. CT enterography revealed diffuse wall thickening of the entire small bowel and trace ascites. Treatment for protein-losing enteropathy which included limiting salt intake, increasing dietary protein, and wearing compression stockings was recommended. During the next 10 years, the leg edema was stable and was occasionally treated with diuretic agents, which did not lead to substantial improvement. Six months before the current presentation, the patient began to have dyspnea on exertion. Three months before this presentation, abdominal distention developed. The patient initially attributed the dyspnea and abdominal distention to weight gain due to reduced physical activity during quarantine for the coronavirus disease 2019 Covid-19 pandemic. Six weeks before this presentation, the patient was evaluated by his primary care physician in a video conference. On the basis of this evaluation, laboratory and imaging studies were obtained. The blood level of total protein was 4.5 g per deciliter updated reference range, 6.4 to 8.3, and the blood albumin level was 2.1 g per deciliter. The complete blood count, blood levels of electrolytes and glucose, and results of liver-function and kidney-function tests were normal. Dr. Anderson: CT of the chest, performed after the administration of intravenous contrast material, revealed multiple small pulmonary nodules, enlarged subcarinal and upper mesenteric lymph nodes, and moderate-volume ascites in the upper abdomen. Dr. Uchida: Three weeks later, paracentesis was performed, and 3.1 liters of milky-appearing ascitic fluid were removed. Results of the ascitic fluid analysis are shown in Table 1. Cytologic examination of the ascitic fluid revealed no malignant cells. The patient was referred to the gastroenterology clinic of this hospital for further evaluation. On the current presentation, the patient reported that he was having bowel movements with normally formed stools and no abdominal pain. His wife had noticed that he appeared to be moving slowly when performing activities of daily living and that he had lost muscle mass in his arms. There was no history of abdominal surgery or trauma to the abdomen. Other medical history included type 2 diabetes mellitus, psoriasis, osteoarthritis, and hypogammaglobu-linemia. There was no history of recurrent infections, asthma, or atopic dermatitis. Medications included aspirin, insulin glargine, and metfor-min. There were no known drug allergies. The patient lived with his wife in a suburb of Boston and worked in an office. He was a lifelong nonsmoker, drank alcohol occasionally, and did not use illicit drugs. His mother had colon cancer. The physical examination was limited, because the evaluation was done in a video conference in the context of the Covid-19 pandemic. Imaging studies were obtained. Dr. Anderson: CT of the abdomen and pelvis, performed after the administration of intravenous and oral contrast material, revealed multiple new hypoenhancing lesions throughout the right and left hepatic lobes, diffuse small-bowel wall thickening, moderate-volume ascites, upper abdominal varices, and enlarged upper abdominal and pelvic nodes Fig. 1C, 1D, and 1E. The only liver lesions that were large enough for reliable percutaneous sampling were at the far cranial aspect of the hepatic dome, where respiratory motion and crossing the diaphragm would have made an attempt at CT-guided or ultrasono-graphically guided biopsy very challenging, if not prohibitive. CT of the chest revealed tree-in-bud and clustered nodules, predominantly in the dependent lower lobes, and right hilar and subcari-nal lymphadenopathy Fig. 1F. Dr. Uchida: Tests for hepatitis C virus antibodies and for hepatitis B virus surface antibodies, surface antigen, and core antibodies were negative. Repeat paracentesis was performed, and 3.2 liters of milky-appearing ascitic fluid were removed. Results of the ascitic fluid analysis are shown in Table 1. An acid-fast stain of a concentrated specimen of ascitic fluid was negative. Cytologic examination of the ascitic fluid revealed no malignant cells. A fluoroscopically guided transjugular liver biopsy was also performed. The hepatic venous pressure gradient HVPG was 2 mm Hg normal value, 5; the right atrial pressure was 7 mm Hg, the wedged hepatic venous pressure 11 mm Hg, and the free hepatic venous pressure 9 mm Hg. Dr. Megan J. Fitzpatrick: Histologic examination of the liver-biopsy specimen revealed mild mixed portal inflammation and grade 1 steatosis without steatohepatitis. A trichrome stain showed mild portal tract edema but no fibrosis. Dr. Uchida: Mycobacterial cultures of the as-citic fluid were negative. A diagnostic test was performed. OUTPUT:

High-grade B-cell lymphoma, not otherwise specified.

NEJM_Reasoning_Subset46

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: CME at NEJM.org Dr. Molly Wolf Medicine and Pediatrics: A 17-year-old boy was admitted to the pediatric intensive care unit ICU of this hospital, before the coronavirus disease 2019 Covid-19 pandemic, because of chest pain, syncope, electrocardiographic ECG abnormalities, and elevated blood levels of creatine kinase and troponin T. The patient had been well until 5 days before this admission, when fever, nausea, diarrhea, muscle aches, and chest pain developed. The chest pain radiated to the left shoulder and was worse when he took deep breaths or was lying flat. One episode of nonbloody, nonbilious emesis occurred. On the second day of illness, the patient presented to his primary care clinic at another hospital, where a viral illness was diagnosed. An intramuscular glucocorticoid injection was administered, nebulized albuterol was prescribed, and the patient was advised to take ibuprofen and acetaminophen. During the next 3 days, fever and diarrhea resolved, but chest pain, muscle aches, and nausea persisted and were accompanied by decreased appetite and cold, pale fingers. On the morning of admission, lightheadedness developed. When the patient stood to get a drink of water, he felt unsteady, his vision faded, and syncope occurred. He regained consciousness within 1 minute. Emergency medical services were called, and on arrival they found that the patient was alert and the vital signs were normal. The peripheral blood glucose level, obtained by fingerstick testing, was 24 mg per deciliter 1.3 mmol per liter; reference range, 70 to 110 mg per deciliter 3.9 to 6.1 mmol per liter. Thiamine and 50 ml of a 50 dextrose solution were administered intravenously, and the patient was transported by ambulance to the emergency department of the other hospital. On arrival at the other hospital, the patient reported pleuritic left parasternal chest pain, which he rated at 4 on a scale of 0 to 10, with 10 indicating the most severe pain. The temperature was 36.9C, the pulse 106 beats per minute, the blood pressure 12672 mm Hg, the respiratory rate 23 breaths per minute, and the oxygen saturation 93 while he was receiving supplemental oxygen through a nasal cannula at a flow rate of 2 liters per minute. The pulse oximeter plethysmographic waveform was noted to be of low amplitude, and the oxygen saturation was difficult to obtain. The weight was 95.3 kg and the body-mass index the weight in kilograms divided by the square of the height in meters 32. The fingers were cool, with a capillary refill time of 3 to 4 seconds. Blood levels of alkaline phosphatase, bilirubin, and lactic acid were normal; other laboratory test results are shown in Table 1. Serum toxicologic screening was negative. Chest radiography revealed a borderline enlarged cardiac silhouette. ECG and echocardiography were performed. Dr. Oscar J. Benavidez: An ECG showed normal sinus rhythm at a rate of 100 beats per minute Fig. 1. ST-segment elevation and PR-segment depression were present in leads I and II and the lateral precordial leads. There was no atrial or ventricular ectopy. A transthoracic echocardiogram showed mild concentric left ventricular hypertrophy and normal left ventricular volume and systolic function, with a left ventricular ejection fraction of 63; there were no wall-motion abnormalities. The right ventricular volume and systolic function were normal. There was no mitral valve prolapse, but mild mitral regurgitation was present. The aortic dimensions were within normal limits, and there was no pericardial effusion. Doppler imaging revealed normal systolic and diastolic velocities. Dr. Wolf: Three hours after arrival, the patient was transferred by ambulance to the pediatric ICU of this hospital. On admission, he reported that he had intentionally lost 45 kg of weight during the previous year. He took no medications, herbal remedies, or nutritional supplements and had no known allergies. His immunizations were reportedly current. The patient lived with his mother and younger brother. He played sports; he had no known exposure to sick persons and was not sexually active. He did not smoke tobacco, drink alcohol, or use illicit drugs. His mother had hypertension, unspecified heart disease, and a history of recurrent miscarriages. A brother had died at 56 days of age from sudden infant death syndrome. His maternal grandmother had hypertension and diabetes, and a maternal aunt had systemic lupus erythematosus SLE with nephritis. On examination, the patient appeared well. The temperature was 37.6C, the pulse 111 beats per minute, the blood pressure 14872 mm Hg, the respiratory rate 23 breaths per minute, and the oxygen saturation 100 while he was receiving supplemental oxygen through a nasal can-nula at a flow rate of 2 liters per minute. The fingers were cold and pale. Examination of the skin revealed striae on the abdomen. The remainder of the physical examination was normal. Tests for influenza virus, respiratory syncy-tial virus, parainfluenza virus, adenovirus, and human immunodeficiency virus HIV were negative. Urinalysis showed a specific gravity of 1.031, a pH of 6.0, and 1 protein. Intravenous fluids, ibuprofen, and famotidine were administered, and supplemental oxygen was discontinued. During the next 24 hours, the chest pain and ECG abnormalities abated and the blood levels of creatine kinase, troponin T, alanine amino-transferase, and aspartate aminotransferase decreased. The patient was discharged home; he was advised to take acetaminophen and ibuprofen as needed for pain, and a follow-up appointment with a pediatric cardiologist was scheduled. Ten days later, in the cardiology clinic, the patient reported that the chest pain had resolved. He appeared well. The pulse was 86 beats per minute and the blood pressure 15177 mm Hg. The remainder of the examination was unchanged. Results of laboratory tests performed in the patients primary care clinic 3 days earlier are shown in Table 1. ECG was performed. Dr. Benavidez: An ECG showed normal sinus rhythm at a rate of 82 beats per minute Fig. 1. There were nonspecific ST-segment changes in leads III and aVF; ST-segment elevation and PR-segment depression were no longer present. Dr. Wolf: Ultrasonographic examination of the kidneys was normal. Amlodipine was prescribed, and follow-up appointments with a pediatric ne-phrologist and a medical geneticist were scheduled but not kept by the patient. Results of laboratory tests performed in the primary care clinic 6 weeks after discharge are shown in Table 1. Approximately 9.5 months after admission to the pediatric ICU, the patient presented to the emergency department of the other hospital with a 15-hour history of fever, malaise, nausea, vomiting, diarrhea, midsternal chest pain, and light-headedness. He rated the chest pain at 6 out of 10. The temperature was 39.3C, the pulse 119 beats per minute, the blood pressure 13461 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 98 while he was breathing ambient air. On examination, the capillary refill time in the fingers was 3 to 4 seconds. ECG and imaging studies were performed. Dr. Benavidez: An ECG showed sinus tachycardia at a rate of 126 beats per minute Fig. 1. There were frequent premature atrial and ventricular contractions, along with diffuse flattening of T waves. Dr. Sjirk J. Westra: Frontal and lateral chest radiography revealed cardiomegaly, as characterized by an increased cardiothoracic ratio, with predominant enlargement of the left atrium Fig. 2. Pulmonary vascular congestion with mild interstitial pulmonary edema and a small left pleural effusion were detected; these findings are suggestive of congestive heart failure. Dr. Wolf: The patient was again transferred by ambulance to the pediatric ICU of this hospital. On admission, he reported that the chest pain had abated. He appeared to be in no distress. The temperature was 38.8C, the pulse 134 beats per minute, the blood pressure 12949 mm Hg, the respiratory rate 27 breaths per minute, and the oxygen saturation 98 while he was breathing ambient air. The weight was 83.9 kg. On auscultation of the heart, the rhythm was irregular; the remainder of the examination was normal. Laboratory test results are shown in Table 1. Urinalysis showed a specific gravity of 1.027, a pH of 5.0, and 1 protein. Intravenous fluids, magnesium sulfate, sodium phosphate, amlodipine, famotidine, ondansetron, acetaminophen, and ibuprofen were administered. During the next 2 days, fever and intermittent chest pain persisted and hypertension developed, with blood-pressure measurements as high as 18797 mm Hg. Hydralazine and labetalol were administered, and the dose of amlodipine was increased. On examination, strength in the proximal muscles of the arms and legs was graded as 4 out of 5, with 5 indicating normal muscular contraction against full resistance. There were episodes during which the fingers were cold and pale; no nailfold capillary abnormalities were seen. The remainder of the examination was unchanged. The blood level of troponin T decreased to 0.57 ng per milliliter and the blood level of cre-atine kinase MB isoenzyme decreased to 50.2 ng per milliliter, whereas the blood level of creatine kinase increased to 8336 U per liter; the urine level of myoglobin was 283 g per liter reference value, 21. The results of thyroid-function tests were normal. Some peripheral blood glucose measurements, obtained by fingerstick testing, were as low as 22 mg per deciliter 1.2 mmol per liter, despite a regular diet and the administration of dextrose-containing intravenous fluids. These values were not verified by concurrent central venous blood glucose measurements. Additional test results were received, and a diagnosis was made. OUTPUT:

Undifferentiated autoimmune rheumatic disease.

NEJM_Reasoning_Subset47

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: CME at NEJM.org Dr. Daryl J. Selen: A 29-year-old woman was admitted to this hospital because of recurrent bone fractures and hypophosphatemia. The patient had been well until 19 months before admission, when pain in the right midfoot developed during a vacation in Europe. On her return to the United States, she was evaluated by her primary care physician at a clinic affiliated with another hospital; an orthotic device was recommended, but the foot pain did not decrease with use of the device. Three months later, the pain in the right foot increased in severity after a second vacation in Europe. Radiography of the right foot reportedly revealed no fracture; physical therapy was recommended. During the subsequent 8 months, the pain continued to gradually increase in severity, was worse when the patient stood upright or walked, and was relieved with the administration of ibuprofen. Eight months before admission, the patient tripped, and the severity of pain in the right foot increased suddenly. She was evaluated in the orthopedic clinic of this hospital. On examination, the height was 173 cm, the weight 115 kg, and the body-mass index the weight in kilograms divided by the square of the height in meters 38.6. There was tenderness over the right third metatarsal. Imaging studies were obtained. Dr. Rene Balza: Radiography of the right foot Fig. 1A revealed a fracture of the third metatarsal shaft. Magnetic resonance imaging MRI of the right foot revealed a nondisplaced, incompletely healed transverse fracture of the third metatarsal shaft, as well as subchondral sclerosis and bone marrow edema within the distal navicular bone and in the calcaneocuboid joint. Bone stimulation was recommended, but the patients pain did not abate after these treatments. Dr. Selen: Seven months before admission, the patient had increased pain in the right foot after a fall while walking on ice. Additional imaging studies were obtained. Dr. Balza: Radiography of the right foot Fig. 1B revealed fractures of the distal fourth and fifth metatarsals. Dr. Selen: Five months before admission, the second metatarsal region of the right foot was tender on palpation after the patient had walked up a flight of stairs. However, no evidence of a fracture was seen on radiography. Four months before admission, the patient was evaluated in the endocrinology clinic affiliated with the other hospital. The calcium level was 9.5 mg per deciliter 2.4 mmol per liter; reference range, 8.5 to 10.5 mg per deciliter 2.1 to 2.6 mmol per liter, the 25-hydroxyvitamin D level 26 ng per milliliter 65 nmol per liter; reference range, 20 to 80 ng per deciliter 50 to 200 nmol per liter, and the parathyroid hormone level 45 pg per milliliter reference range, 10 to 60; other laboratory test results are shown in Table 1. Dual-energy x-ray absorptiometry, performed for the assessment of bone mineral density, revealed normal bone mass in the lumbar spine z score, 0.0; reference range, 1.9 to 1.9 and in the femoral neck z score, 0.4; reference range, 1.9 to 1.9. Calcium and vitamin D supplementation and weight loss were recommended. The pain in the right foot persisted, and additional imaging studies were obtained. Dr. Balza: Three months before admission, MRI of the right foot Fig. 1C and 1D showed a non-displaced fracture of the second metatarsal metadiaphysis with associated bone and soft-tissue edema, a nondisplaced fracture of the medial cuneiform, and healing fractures of the third, fourth, and fifth metatarsals. A controlled ankle motion walking boot and crutches were recommended for ambulation. Dr. Selen: During the next 3 months, the pain in the right foot persisted, and new pain developed in the left foot. The patient was seen in the pain medicine and podiatry clinics affiliated with the other hospital. Diagnoses of plantar fasciitis, Achilles tendinitis, and sinus tarsi syndrome were considered. Treatment with methyl-prednisolone and celecoxib was initiated, and the patient was referred to the rheumatology clinic of this hospital. On evaluation in the rheumatology clinic, the patient reported bilateral foot and ankle pain and swelling that was greater in the right foot and ankle than in the left, as well as stiffness and warmth in the ankles. There was lower back pain and bilateral hip pain, which was greater on the right side than on the left side. The patient reported that the back and hip pain had been present since she was a teenager but had gradually increased in severity during the previous year. Fatigue and generalized weakness had developed and worsened during the previous month. There was no fever, weight loss, or change in diet. Menarche had occurred when the patient was 11 years of age, and menstrual cycles had been regular since then. There was a history of fractures of the left wrist in childhood. Other medical history included obesity, hyperlipidemia, anxiety, nephrolithiasis, biliary dyskinesia which had led to cholecystectomy 1 year before this admission, and nonalcoholic fatty liver disease diagnosed on the basis of a liver biopsy. Medications included celecoxib, ergocalciferol, citalopram, and lorazepam; she had no known drug allergies. The patient lived alone in a suburban area of New England and had previously worked as a nurse; however, she was unable to work during the previous 8 months because of pain and difficulty with ambulation. She did not smoke cigarettes, drink alcohol, or use illicit drugs. Her mother had osteopenia; her mother, father, and sister had psoriasis; her father had psoriatic arthritis; and her brother had the Williams syndrome, a rare genetic and developmental disorder. On examination, the temperature was 36.9C, the blood pressure 12178, and the heart rate 94 beats per minute. Dentition was normal, and the gait was antalgic. Proximal muscle strength was intact in both arms 55 and slightly reduced in the legs 45. There was tenderness over the lumbar spine and sacroiliac joints that was more pronounced on the right side than on the left side. The FABER test in which the leg is flexed and the thigh is abducted and externally rotated elicited pain in both hips. There was tenderness over the right midfoot and warmth and swelling of the ankles. No musculoskeletal deformities, bowing of the legs, lymphadenopa-thy, skin lesions, or rashes were noted. The blood level of phosphorus was 1.0 mg per deciliter 0.3 mmol per liter; reference range, 2.6 to 4.5 mg per deciliter 0.8 to 1.5 mmol per liter; other laboratory test results are shown in Table 1. The patient was instructed to go to the emergency department of this hospital. Intravenous sodium phosphate and oral potassium phosphate were administered. Additional imaging studies were obtained. Dr. Balza: Radiography of the lumbar spine, pelvis, hips, and ankles revealed anterolisthesis of L4 and L5 with a defect in the pars interarticu-laris; there were no fractures. On radiography of the right foot, a fracture in the third metatarsal was initially identified 8 months before admission Fig. 1A, followed by the development of fractures in the fourth and fifth metatarsals 1 month later Fig. 1B. Subsequently, T2-weighted MRI of the sacrum with fat suppression performed on admission Fig. 1E and 1F revealed vertically oriented hypointense bands in the bilateral sacral alae and a horizontally oriented hypoin-tense band in S2, as well as bone marrow edema adjacent to the fracture lines; the combination of these findings was consistent with an H-shaped sacral insufficiency fracture. Dr. Selen: The patient was admitted to the hospital. A diagnostic test was performed. OUTPUT:

Phosphaturic mesenchymal tumor causing osteo-malacia.

NEJM_Reasoning_Subset48

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Jon S. DuBois: A 29-year-old woman was evaluated in the gastroenterology clinic of this hospital for the management of a soft-tissue mass in the head of the pancreas. The patient had been well until 7 weeks before this presentation, when progressive pruritus throughout the body developed, along with nausea, bloating, and watery mustard-colored diarrhea. She had eaten sushi for dinner the previous night. She was evaluated in an urgent care clinic in the southeastern United States; she had recently moved there from New England. An injection of methylpredniso-lone was administered, and hydroxyzine and diphenoxylateatropine were prescribed. During the next 3 weeks, the symptoms did not abate and jaundice developed, along with new discomfort in the right upper quadrant of the abdomen, decreased appetite, and amber-colored urine. Four weeks before this presentation, the patient was evaluated in the emergency department of a local hospital. The alanine aminotransferase level was 327 U per liter reference range, 1 to 33, the aspartate aminotransferase level 104 U per liter reference range, 1 to 32, and the total bilirubin level 5.8 mg per deciliter reference range, 0.1 to 1.2. The carbohydrate antigen 19-9 CA 19-9 level was 73 U per milliliter reference range, 0 to 35. Additional laboratory test results are shown in Table 1. Imaging studies were obtained. Computed tomography CT of the abdomen, performed after the intravenous administration of contrast material, reportedly revealed a distended gallbladder with sludge, as well as dilated hepatic and pancreatic ducts. The patient was admitted to the local hospital. On the second hospital day, results of liver-function tests improved, and she was discharged home with plans for an outpatient evaluation with a gastroenterologist. However, the next day, the patient flew back to New England and presented to the emergency department of a second hospital for further evaluation. On evaluation, she described persistent diffuse pruritus, nausea, right upper abdominal CME at NEJM.org pain, and mustard-colored diarrhea. She also reported fatigue, unintentional weight loss of 3.2 kg during the past month, and poor sleep. The patient had a history of anxiety and depression. She took no medications and had no known drug allergies. Aside from her recent move to the southeastern United States and trip back to New England, there was no recent travel. She worked seasonally as an official at sporting events. She smoked cigarettes occasionally, drank alcohol rarely, and did not use illicit drugs. Her family history included colon cancer in her maternal grandmother, maternal grandfather, and paternal grandmother; breast cancer in her maternal aunt and paternal aunt; and thyroid cancer in her father. In addition, her maternal grandmother had diabetes, and both grandmothers had coronary artery disease. On examination, the temperature was 36.9C, the blood pressure 15582 mm Hg, the pulse 94 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 100 while the patient was breathing ambient air. She was thin and appeared jaundiced, with scleral icterus. She had diffuse excoriations from scratching. The bowel sounds were normal. There was mild tenderness in the right upper abdomen on palpation, but masses and hepatosplenomegaly were not detected. The remainder of the examination was normal. The alanine aminotransferase level was 85 U per liter, the aspartate aminotransferase level 267 U per liter, and the total bilirubin level 6.7 mg per deciliter. The CA 19-9 level was 79 U per milliliter. Additional laboratory test results are shown in Table 1. The abdominal CT images obtained at the first hospital were reviewed, and additional imaging studies were obtained. Dr. Avinash Kambadakone: CT of the abdomen Fig. 1A and 1B, performed after the intravenous administration of contrast material, revealed diffuse dilatation of the intrahepatic and extra-hepatic biliary ducts, as well as dilatation of the pancreatic ducts. The dilated ducts terminated abruptly in the pancreatic head. There was a hypodense pancreatic mass at the site of duct obstruction. Magnetic resonance cholangiopan-creatography Fig. 1C and 1D also revealed dilatation of the biliary and pancreatic ducts, which narrowed abruptly at the level of the pancreatic head, with a heterogeneously enhancing mass at the site of obstruction. Dr. DuBois: The patient was admitted to the second hospital. Endoscopic retrograde cholan-giopancreatography revealed a stricture in the bile duct at the level of the mass, and a stent was placed. The bilirubin level initially decreased, but pruritus and diarrhea persisted. By the seventh hospital day, the bilirubin level had increased to 12.6 mg per deciliter and the CA 19-9 level had increased to 959 U per milliliter. Additional diagnostic testing was performed. Dr. Kambadakone: Endoscopic ultrasonography Fig. 1E revealed a hypoechoic mass in the pancreatic head. Fine-needle aspiration was performed. Dr. DuBois: The aspirate showed variably atypical epithelium, but the quantity and quality of the findings were insufficient for definitive diagnosis. Given the uncertain diagnosis and the possibility of cancer, a surgical consultation was obtained. Surgical removal of the mass was recommended to establish the definitive diagnosis, but the patient declined surgery. Prednisone was administered, and the pruritus and diarrhea abated. On the 20th hospital day, the patient was discharged with plans for an outpatient followup evaluation with a gastroenterologist. Three days after discharge from the second hospital, the patient was evaluated in the gastro-enterology clinic of this hospital. At that time, her symptoms had resolved, the results of liver-function tests were normal, and the CA 19-9 level had decreased to 80 U per milliliter. IgG levels total and subclasses were normal, and tests for antinuclear antibodies ANA were negative. The possibility of cancer was explained to the patient, and surgical removal of the mass was again recommended, but the patient declined surgery owing to multiple issues related to her work and personal life. A management plan that was acceptable to the patient was adopted during the next 6 months. The patient was closely monitored, and biliary stents were changed when they became occluded. Additional diagnostic procedures were performed, and management decisions were made. OUTPUT:

Pancreatic ductal adenocarcinoma.

NEJM_Reasoning_Subset49

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Annabelle Anandappa Medicine: A 25-year-old man with a history of B-cell acute lymphoblastic leukemia was evaluated in the emergency department of this hospital because of vision changes. Ten months before this presentation, the patient was evaluated for fatigue and dyspnea on exertion. Laboratory testing revealed a hemoglobin level of 3.5 g per deciliter reference range, 13.5 to 17.5 and a white-cell count of 23,450 per micro-liter reference range, 4000 to 11,000, with 81 lymphocytes and 4 blasts. A bone marrow biopsy was performed. Dr. Judith A. Ferry: Examination of the bone marrowbiopsy specimen Fig. 1 revealed markedly hypercellular marrow with a loss of normal elements. There were sheets of blasts, including larger cells with oval-to-irregular nuclei, fine chromatin, distinct nucleoli, and scant cytoplasm, as well as more mature-appearing lymphocyte-like blasts with more condensed chromatin. Cytogenetic analysis revealed an abnormal karyotype: 46,XY,t9;22q34;q11.21546,idem,t2;12 p13;p13,?del10p13346,idem,del6p21,add7p132. On next-generation sequencing, SNaPshot analysis identified a RUNX1 mutation, and gene fusion analysis was positive for BCR-ABL1 e13a2. A diagnosis of B-cell acute lymphoblastic leukemia with BCR-ABL1 was made. Dr. Anandappa: Induction chemotherapy with vincristine, doxorubicin, metho-trexate, cytarabine, and prednisone was administered, along with dasatinib and intrathecal cytarabine, methotrexate, and hydrocortisone. One month later, examination of a bone marrowbiopsy specimen revealed 7 blasts. Treatment with blinatumomab was started, and dasatinib was continued. Seven months before this presentation, examination of a bone marrowbiopsy specimen revealed a complete hematologic response. BCR-ABL1 was undetectable by means of reverse-transcriptasepolymerase-chain-reaction testing. Five months before this presentation, the patient underwent allogeneic hemato-poietic-cell transplantation HCT from a matched, unrelated donor after myeloab-lative conditioning with cyclophosphamide and total-body irradiation. Early post-transplantation complications included severe mucositis and febrile neutropenia. Two months before this presentation, examination of a bone marrowbiopsy specimen revealed a complete hematologic response, no BCR-ABL1 rearrangement, and full donor chime-rism. Dasatinib was continued as maintenance therapy. During the next 2 months, the patient had worsening anemia, and dasatinib was stopped. Two days before this presentation, the patient noticed large black blobs that looked like shadows in the periphery of the visual fields of both eyes. There were also intermittent episodes of blurry vision in both eyes that resolved after 10 minutes. Two days later, the patient sought an evaluation in the oncology clinic of this hospital and was transferred to the emergency department for further evaluation. In the emergency department, the patient reported ongoing vision symptoms but no eye pain, flashing lights, or floaters. He also reported 3 weeks of night sweats, areas of swelling in the neck and groin, and a pruritic rash on the upper chest, upper back, and both arms. He had a history of chronic daily migraine headaches, which had frequently been associated with eye pain and photophobia but had not been associated with vision changes. Other medical history included depression and obesity. Medications included tacrolimus, trimethoprimsulfamethoxazole, fam-ciclovir, omeprazole, and escitalopram, as well as vitamin D and magnesium supplementation. There were no known drug allergies. The patient lived in a coastal town in New England with his mother. He had previously worked in the food-service industry. He had never smoked tobacco or used illicit drugs; he drank three cans of beer weekly. His family history included breast cancer and headaches in his maternal grandmother, prostate cancer in his paternal grandfather, and hypertension in his father. On examination, the temperature was 36.9C, the blood pressure 13688 mm Hg, the pulse 104 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 100 while the patient was breathing ambient air. Visual acuity was 2025 in both eyes with correction, and visual fields were full on confrontation testing. The pupils were symmetric and reactive to light. There was no proptosis. Slit-lamp examination revealed few cells in the anterior chamber, and funduscopic examination was normal. Test results for cranial nerve function, strength, sensation, reflexes, coordination, and gait were normal. There was palpable lymphadenopathy in the cervical, clavicular, axillary, and inguinal regions. Discrete papules were present on both arms, and diffuse xerosis and an eczematous rash were present on the upper back and chest. Laboratory testing revealed a platelet count of 47,000 per microliter reference range, 150,000 to 400,000. Blood testing for cytomegalovirus, EpsteinBarr virus EBV, varicellazoster virus, and human herpesvirus 8 HHV-8 DNA was negative. Screening for human immunodeficiency virus, syphilis, and Lyme disease was also negative. Examination of a peripheral-blood smear confirmed the presence of anemia and thrombo-cytopenia; there were no schistocytes. Additional laboratory test results are shown in Table 1. Imaging studies were obtained. Dr. Karen Rodriguez: Magnetic resonance imaging MRI of the head was performed. T2-weighted, fluid-attenuated inversion recovery images Fig. 2A and 2B showed multiple new hyperintense lesions, measuring up to 11 mm in greatest dimension, within the supratentorial and infratentorial regions of the brain. Images obtained after the administration of contrast material showed faint enhancement of the lesions. These foci appeared to be centered within the juxtacortical and peri-ventricular white matter and could reflect areas of demyelination, graft-versus-host disease GVHD involving the central nervous system CNS, acute lymphoblastic leukemia with CNS involvement, or an infectious process. There was no abnormal enhancement of the optic nerves or the orbital structures. 18F-fluorodeoxyglucose FDGpositron-emission tomography PET and computed tomography CT was also performed. The PET-CT scans Fig. 2C through 2H showed moderate-to- intense FDG uptake associated with widespread lymphadenopathy, including bilateral cervical, axillary, external iliac, and inguinal lymph nodes. There was also abnormal uptake in the spleen. Dr. Anandappa: The patient was admitted to this hospital, and lumbar puncture was performed. Cerebrospinal fluid analysis revealed a total protein level of 147 mg per deciliter reference range, 5 to 55 and a glucose level of 49 mg per deciliter 2.7 mmol per liter; reference range, 50 to 75 mg per deciliter 2.8 to 4.2 mmol per liter. The white-cell count was 21 per microliter reference range, 0 to 5, with 61 lymphocytes, 27 neutrophils, and 3 eosinophils; the red-cell count was 16,000 per microliter reference range, 0 to 5, with xanthochromia present. Grams staining of cerebrospinal fluid showed a moderate amount of mononuclear cells and no organisms. Cytologic studies were notable for increased lymphocytes and plasma cells. A diagnostic test was performed. OUTPUT:

Plasma-cell myeloma post-transplantation lym-phoproliferative disorder.

NEJM_Reasoning_Subset50

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Samantha D. Martin Pediatrics: A 17-year-old girl was admitted to this hospital during the coronavirus disease 2019 Covid-19 pandemic because of fever and cough. The patient had been well until 10 days before admission, when fever and cough that was productive of clear sputum developed. She also had fatigue, eye redness, sore throat, nasal congestion, rhinorrhea, and myalgias. Seven days before this admission, the patient was evaluated in the urgent care clinic of another hospital. On examination, there was conjunctival injection in both eyes. The lungs were clear on auscultation, and the remainder of the physical examination was reportedly normal. Testing of a nasopharyngeal specimen for severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 RNA was negative. Treatment with acetaminophen and dextromethorphan was recommended. During the next 2 days, the fever decreased but did not resolve with the use of acetaminophen. New mild chest discomfort occurred with coughing. An expectorated sputum specimen contained flecks of blood, and the patient returned to the urgent care clinic. The physical examination was unchanged, and rapid antigen testing for influenza types A and B was negative. Additional treatment with ibuprofen, benzonatate, and guaifenesin was recommended. Three days before this admission, the patient had persistent symptoms and was unable to sleep because of the fever and cough. New shortness of breath developed. She was evaluated by a primary care physician at the other hospital in a telehealth visit. Empirical treatment with amoxicillin was started, and close monitoring was recommended. During the next 3 days, the shortness of breath increased in severity, and the patient was instructed to present to the emergency department of this hospital. On evaluation, the patient reported cough that was worse with exertion and deep breathing, improved with rest, and was associated with pain in the chest and back on the left side. The sputum had streaks of bright red blood. Other symptoms included fatigue, sore throat, nasal congestion, rhinorrhea, myalgias, and pain in both knees when walking. The eye redness had resolved, but there was mild soreness of the right eye. There was no headache, ear pain, difficulty swallowing, abdominal pain, nausea, vomiting, diarrhea, or rash. The patient had a history of developmental dysplasia of the hip and was otherwise healthy. She had normal growth and development and had received all routine childhood vaccinations. Medications included amoxicillin, acetaminophen, ibuprofen, benzonatate, guaifenesin, and dextro-methorphan. There were no known drug allergies. The patient was born in New England and lived in a suburban area of New England with her mother, father, and brother. She performed well in high school, which she was attending remotely because of the Covid-19 pandemic; she had no known sick contacts. She had traveled to a Caribbean island 1 year earlier. She was a vegetarian and did not drink alcohol, smoke tobacco, or use illicit drugs. Her parents and brother were healthy. On examination, the temperature was 38.5C, the heart rate 124 beats per minute, the blood pressure 14262 mm Hg, the respiratory rate 30 breaths per minute, and the oxygen saturation 97 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 35.9. The patient appeared pale, and she coughed and sniffled frequently. She did not use accessory muscles while breathing, and breath sounds in the lower lung fields were decreased. There was no conjunctival injection, lymphade-nopathy, joint swelling or tenderness, or rash; the remainder of the physical examination was normal. The creatinine level was 2.00 mg per deciliter 177 mol per liter; reference range, 0.60 to 1.50 mg per deciliter 53 to 133 mol per liter and the C-reactive protein level 77.5 mg per liter reference value, 8.0. The hemoglobin level was 6.7 g per deciliter reference range, 12.0 to 16.0, the hematocrit 21.1 reference range, 36.0 to 46.0, the white-cell count 11,890 per microliter reference range, 4500 to 13,000, and the platelet count 526,000 per microliter reference range, 150,000 to 450,000. Urinalysis revealed 3 blood and 2 protein; microscopic examination of the urinary sediment revealed more than 100 red cells per high-power field reference range, 0 to 2 and 10 to 20 white cells per high-power field reference value, 10, as well as mixed granular casts and red-cell casts. Nucleic acid testing of a nasopharyngeal specimen for SARS-CoV-2, influenza types A and B, and respiratory syncytial virus was negative. An interferon- release assay for Mycobacterium tuberculosis was performed, and blood cultures were obtained. Other laboratory test results are shown in Table 1. Dr. Randheer Shailam: Chest radiography Fig. 1A and 1B revealed prominent patchy opacities in the lower lung zones. Computed tomography CT of the chest Fig. 1C through 1F, performed without the administration of intravenous contrast material, revealed peripheral patchy ground-glass opacification with greater involvement of the lower lobes than of the upper lobes, the lingula left lung, and the middle lobe right lung. There were also areas of normal-appearing lung. These findings are not specific and can be seen with infectious causes such as bacterial pneumonia and Covid-19, as well as with noninfectious causes such as aspiration, pulmonary hemorrhage, and less likely, alveolar proteinosis. Dr. Martin: Ceftriaxone, azithromycin, and intravenous fluids were administered. A diagnostic test was performed. OUTPUT:

Granulomatosis with polyangiitis.

NEJM_Reasoning_Subset51

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Theodore R. Pak Medicine: A 34-year-old woman was admitted to this hospital with hypercortisolism in the context of a metastatic pancreatic neuroendocrine tumor. The patient had been well until 4 years before this presentation, when abdominal pain, diarrhea, and ascites developed. A pancreatic neuroendocrine tumor with metastases to the liver and spleen was ultimately diagnosed, and treatment with octreotide and everolimus was initiated. Three years before this presentation, treatment with peptide receptor radionuclide therapy was initiated; four cycles were completed over the course of the next 2 years. Eight months before this presentation, the patient decided to stop taking everolimus because of fatigue. Seven months before this presentation, the patient was evaluated at another hospital because of weight gain, hyperglycemia, and changes in mood. She was found to have elevated blood levels of corticotropin and elevated salivary and urinary levels of cortisol. Dr. Adina Haramati: Magnetic resonance imaging MRI of the head revealed a pituitary lesion measuring 1.3 cm in greatest dimension. A specimen of blood obtained from the inferior petrosal sinus identified a pituitary source of cortico-tropin secretion. Dr. Pak: Treatment with octreotide was discontinued, and 3 months before this presentation, transsphenoidal resection of the pituitary lesion was performed. After the surgery, the cortisol and corticotropin levels remained elevated. Repeat MRI of the head revealed a residual pituitary lesion. Transsphenoidal resection of the residual lesion was performed 2 months before this presentation. After the second surgery, the cortisol and corticotropin levels decreased but did not normalize. Pathological evaluation of a resected pituitary specimen revealed normal anterior pituitary architecture that was not consistent with a corticotroph adenoma. At a follow-up appointment in the endocrinology clinic after the patient was discharged, the 24-hour urinary free corti-sol level was again elevated, and treatment with pasireotide was initiated. Ten days before this presentation, the patient began to have confusion, urinary incontinence, and recurrent falls. She was evaluated in the emergency department of another hospital. Her husband noted atypical impulsive behaviors, such as online shopping and excessive eating. Dr. Haramati: MRI of the head revealed a small focus of decreased enhancement within the left inferior aspect of the sella turcica, a finding that was consistent with postsurgical changes or residual adenoma. Dr. Pak: A morning blood level of cortisol was 80 g per deciliter 2207 nmol per liter; reference range, 4 to 23 g per deciliter 110 to 635 nmol per liter, and the blood level of corticotropin was 519 pg per milliliter 114 pmol per liter; reference range, 7.2 to 63 pg per milliliter 1.6 to 14 pmol per liter. The 24-hour urinary free cortisol level was 9450 g 26,069 nmol per liter; reference range, 3.5 to 45 g 10 to 124 nmol per liter. Dr. Haramati: MRI of the abdomen revealed an exophytic mass on the pancreatic tail that broadly abutted the left adrenal gland, thickening of both adrenal glands, retroperitoneal metastases on the left side, and extensive hepatic metastases with chronic cavernous transformation of the portal vein. Dr. Pak: Treatment with pasireotide was discontinued, and treatment with ketoconazole was initiated, in addition to potassium supplementation and spironolactone for hypokalemia. On the tenth day at the other hospital, the patient was transferred to this hospital for further treatment. On evaluation at this hospital, the patient reported fatigue but no fever, chills, night sweats, or weight loss. She had no cough, hemop-tysis, or chest pain; no rheumatologic symptoms; and no history of dysphagia or gastro-esophageal reflux disease. Her medical history included asthma and portal-vein thrombosis complicated by ascites, as well as hypothyroidism and central diabetes insipidus after she had undergone transsphenoidal resection of the pituitary lesions. Medications included atovaquone, cholecalciferol, desmopressin, ketoconazole, levo-thyroxine, metformin, pantoprazole, spironolac-tone, and potassium chloride. She had no known drug allergies. She did not drink alcohol or use tobacco or vaping products; she smoked marijuana occasionally. She lived with her husband in Vermont and had previously worked in a health care facility. The patient reported that she had had several skin tests for Mycobacterium tuberculosis owing to her work in the health care setting, and none had been positive. Before her illness, she had frequently gardened and hiked locally. She had traveled to Canada but otherwise had not traveled outside New England. A paternal aunt had had ovarian cancer. On examination, the temperature was 36.9C, the blood pressure 15287 mm Hg, the pulse 77 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 24.0. The patient was alert and oriented and answered questions appropriately. Her face was rounded, and acne and hair thinning were present. The abdomen had increased adiposity and palpable striae. There were several bruises on her arms and legs. A chest radiograph obtained on admission to this hospital showed an implanted venous access device and a patchy opacity in the right upper lung zone. Treatment with octreotide was reinitiated, and treatment with the other medications that the patient had been receiving was continued. The hypercortisolism was thought to be due to secretion of corticotropin from the metastatic pancreatic neuroendocrine tumor. Bilateral adrenalec-tomy was planned, but on the second hospital day, the patient became withdrawn and would not speak, take any oral medications, or consume any food. She was transferred to the intensive care unit, and an etomidate infusion was initiated; the dose was adjusted to attain a blood level of cortisol between 10 and 20 g per deciliter. Subsequent treatment with intravenous lora-zepam resulted in marked improvement in the patients mental status such that she was following commands and responding appropriately to questions. On the sixth hospital day, bilateral adrenalectomy was performed. Treatment with intravenous hydrocortisone was initiated postoperatively, and on the seventh hospital day, the patient was transferred to the medicine unit of this hospital for further care. Dr. Haramati: On the eighth hospital day, sinus tachycardia developed. Computed tomography CT of the chest, performed after the administration of intravenous contrast material according to a pulmonary embolism protocol Fig. 1, revealed a patchy consolidation in the right upper lobe with areas of cavitation and adjacent tree-in-bud opacities, as well as small bilateral pleural effusions. There was no evidence of pulmonary embolism. Although previous imaging was not available for review, clinical notes indicated that positron-emission tomographyCT performed at another hospital 8 months before this presentation had revealed a new cavitary nodule in the right upper lobe that measured 7 mm in diameter. Dr. Pak: A sputum culture showed few squamous epithelial cells, rare polymorphonuclear leukocytes, and few mixed gram-positive and gram-negative organisms with no specific type predominating; no acid-fast bacilli were observed on a mycobacterial smear of an induced sputum sample. Urine tests for Legionella pneumophila and Streptococcus pneumoniae antigens were negative, as was a blood test for cryptococcal antigen. The blood level of 1,3--d-glucan was less than 31 pg per milliliter reference value, 60, and the blood galactomannan index was 0.05 reference range, 0 to 0.49. Other laboratory test results are shown in Table 1. On the ninth hospital day, bronchoscopy was performed; bronchial washings and bronchoal-veolar-lavage BAL samples were obtained, and no purulent secretions were observed. Grams staining of the BAL fluid revealed few mixed gram-positive and gram-negative organisms, and no organisms were seen on an acid-fast bacilli smear or on a modified acid-fast bacilli smear. Examination of the BAL fluid for Pneumocystis jirovecii was negative. On the 11th hospital day, culture of the BAL fluid showed growth of few methicillin-sensitive Staphylococcus aureus organisms. Treatment with intravenous vancomycin, cefepime, and metroni-dazole was initiated. On the 12th hospital day, a urine test for histoplasma antigen was positive, at a level of 2.25 ng per milliliter reference ranges, 0.00 to 0.10 negative; 0.11 to 1.10 indeterminate; 1.11 positive. Management decisions were made, and results of a diagnostic test were received. OUTPUT:

Infection with Blastomyces dermatitidis.

NEJM_Reasoning_Subset52

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: CME at NEJM.org Dr. Mollie Sands Medicine: A 49-year-old man was admitted to this hospital because of hypoglycemia. The patient had been well until 3 hours before this admission, when altered mental status developed while he was at work. During a meeting, his colleagues noticed that he was not paying attention or participating in the conversation, which was atypical of the patient. Instead, he was fidgeting and mumbling as though talking to another person. When his mobile telephone rang, he allowed it to continue ringing. Two hours before this admission, the patient was found by colleagues on the floor of a conference room. His eyes were open, but he was obtunded and making nonpurposeful movements. Emergency medical services were called. On evaluation, a fingerstick glucose measurement was 39 mg per deciliter 2.2 mmol per liter; reference range, 70 to 109 mg per deciliter 3.9 to 6.1 mmol per liter. Intravenous dextrose was administered, and the patient was brought to the emergency department of this hospital for further evaluation. On arrival at the emergency department, the patient was obtunded and did not react to sternal rub. Additional intravenous dextrose was administered, and a dextrose infusion was started. The patients mental status improved, and he was able to provide additional history. That morning, he had felt that he was in a dreamlike state; there were no other symptoms. The altered mental status had resolved, but he could not recall most events of the morning, including the meeting that had taken place 3 hours before admission. Review of symptoms was notable for unintentional weight gain of one pant size during the past 3 months, as well as intermittent morning dizziness during the past 3 years, which would resolve after the patient ate candy or breakfast. He reported no recent illness, depression, anxiety, change in activity or exercise, or change in intake of food or drink. On a typical day, he had breakfast at 5 a.m., a second breakfast at 10 a.m., lunch at 1 p.m., dinner at 6 p.m., and a snack at 8 p.m. The patient had last eaten approximately 7 hours before presentation to the emergency department. Two years earlier, the patient had had an episode of drooping and decreased sensation of the left side of the face and difficulty enunciating words, which occurred while he was at work. He presented to the emergency department of this hospital. The blood glucose level was 64 mg per deciliter 3.6 mmol per liter, and testing for Lyme disease was negative. He received a diagnosis of Bells palsy and was treated with pred-nisone and acyclovir; the symptoms resolved. Two months later, the patient established care in the primary care clinic of this hospital. Routine laboratory testing revealed a blood glucose level of 46 mg per deciliter 2.6 mmol per liter. The patient took vitamin B12 and vitamin D supplements. He took no other medications and had no known drug allergies. He drank alcohol rarely and did not smoke tobacco or use illicit drugs. Sixteen years earlier, he had immigrated to the United States from Southeast Asia and now lived alone in an urban area of New England. He worked as a registered nurse. His father and brother had type 2 diabetes and used insulin. On examination, the temperature was 35.7C, the heart rate 82 beats per minute, the blood pressure 14676 mm Hg, and the respiratory rate 14 breaths per minute. The body-mass index the weight in kilograms divided by the square of the height in meters was 27.6. The patient appeared well. He had no hepatosplenomegaly or skin hyperpigmentation, and the remainder of the physical examination was normal. On arrival at the emergency department, the blood glucose level was 36 mg per deciliter 2.0 mmol per liter; after the administration of dextrose, a fingerstick glucose measurement was 158 mg per deciliter 8.8 mmol per liter. The complete blood count and blood electrolyte levels were normal, as were the results of liver-function and kidney-function tests. The glycated hemoglobin level was 5.4 reference range, 4.3 to 6.4. Serum and urine toxicologic panels were negative. Laboratory test results are shown in Table 1. The patient was admitted to this hospital. A diagnostic test was performed. OUTPUT:

Well-differentiated pancreatic insulin-secreting neuroendocrine tumor (insulinoma).

NEJM_Reasoning_Subset53

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Vivian De Oliveira Rodrigues Gama Medicine: A 31-year-old man was admitted to this hospital because of perianal and penile ulcers, rectal pain, and vesiculopustu-lar rash. The patient had been in his usual state of health until 9 days before this admission, when he noticed several itchy white bumps around the anus that subsequently evolved into ulcerative lesions. The next day, he sought evaluation at a primary care clinic of another hospital. Tests for human immunodeficiency virus HIV, syphilis, gonorrhea, and chlamydia were performed. An injection of penicillin G benzathine was administered, and treatment with valacyclovir was started. During the next 5 days, the perianal ulcers did not abate, and the patient stopped taking valacyclovir. Painful proctitis with rectal bleeding and malodorous, mucopurulent discharge developed, along with fever, chills, drenching sweats, and new tender swelling in the groin. Three days before this admission, a new painless ulcer appeared on the penis that was similar in appearance to the perianal ulcers. Two days before this admission, new scattered vesicular lesions appeared on the arms and legs, and the patient presented to the infectious disease clinic of this hospital for evaluation. Additional history was obtained from the patient. Fourteen years before this evaluation, sore throat and upper body rash developed; he received a diagnosis of secondary syphilis and was treated with penicillin G benzathine. He also had a history of recurrent oral herpes simplex virus HSV infection, for which he was treated intermittently with valacyclovir. He took daily oral emtricitabine and teno-fovir for HIV preexposure prophylaxis PrEP. There were no known drug allergies. The patient lived in a suburban area of Massachusetts with two roommates and a cat. Two weeks before this evaluation, he had traveled to an urban area of southeastern Canada. During this trip, he had had sex with male partners without the use of barrier protection. There was no other recent travel. The patient did not smoke cigarettes or use illicit drugs; he drank alcohol rarely. CME at NEJM.org On examination, the temperature was 36.5C, the blood pressure 13086 mm Hg, the pulse 75 beats per minute, and the oxygen saturation 98 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 23.9. There were six tender perianal ulcers, measuring less than 1 cm in diameter, with raised, firm margins. There was also one ulcer on the dorsum of the penile shaft, measuring 7 mm in diameter, with raised borders Fig. 1. Painful bilateral inguinal lymphadenopa-thy was present. The perianal skin was weeping, and there was proctitis with severe tenderness that precluded digital rectal examination. In addition, there were approximately 12 papulovesicu-lar lesions scattered across the chest, back, arms, and legs. The lesions measured 2 mm in diameter, were filled with clear fluid, and had surrounding erythema Fig. 2A and 2B. Blood levels of electrolytes and glucose were normal, as were the results of kidney-function and liver-function tests. A blood test for trepo-nemal antibodies was positive; a rapid plasma reagin RPR test was reactive at a dilution of 1:1. A blood test for HIV was nonreactive, and tests of urine and rectal specimens for Neisseria gonorrhoeae and Chlamydia trachomatis nucleic acids were negative. A test of a specimen obtained from a perianal ulcer for HSV nucleic acids was performed, and a blood sample was obtained for bacterial culture. An injection of ceftriaxone was administered, and treatment with valacyclovir and doxycycline was started. During the next 2 days, the ulcers did not abate and the rectal pain worsened, such that the patient was not able to sit, sleep, or have bowel movements. Additional skin lesions appeared. The patient returned to the infectious disease clinic for evaluation. Anoscopy revealed intense rectal and anal inflammation with shallow ulcerations and purulent exudate, findings consistent with proctitis Fig. 3. The patient was admitted to this hospital. On examination, the patient appeared uncomfortable because of rectal pain. Skin lesions that had become pustular with an erythematous base were scattered across the scalp, chest, back, legs, and arms, including one on the palm Fig. 2C. There were no lesions in the mouth. Multiple tender, enlarged inguinal lymph nodes, measuring more than 1 cm in diameter, were present. The perianal and penile ulcers were tender and had heaped margins around a central dry base. The complete blood count and the white-cell differential count were normal. Swabs from a perianal ulcer and a chest skin lesion were obtained for bacterial culture. Treatment with intravenous acyclovir was started, and doxycycline was continued; stool softeners and hydromorphone were administered. A blood test for HIV type 1 RNA was performed. A diagnostic test was performed. OUTPUT:

Infection with monkeypox virus, West African clade.

NEJM_Reasoning_Subset54

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Victoria Clark Neurosurgery: A 25-year-old woman with a history of migraines was admitted to this hospital with progressively worsening headaches and photo-phobia during the previous 6 weeks and a 1-week history of nausea, vomiting, and blurred vision. Six weeks before this admission, the patient began to have headaches that were not characteristic of her previous migraines. She described these headaches as discomfort in the middle of her head that was associated with photophobia, phono-phobia, and tinnitus. She reported that she was occasionally awakened from sleep because of headache and that the headache was always present on awakening in the morning. The headache was worse with coughing and abated with standing; treatment with ibuprofen did not reduce the discomfort. One week before admission, nausea and vomiting developed, along with blurred vision when the patient looked to the left. She also reported occasional episodes of total vision loss that lasted for several seconds. When she was unable to eat food because of worsening nausea and vomiting, she presented to another hospital for evaluation. Computed tomography CT of the head revealed dilatation of the lateral and third ventricles with hypodensity that involved the dorsal brain stem and cerebellar hemispheres Fig. 1A; a possible soft-tissue mass in the region of the fourth ventricular outlet was also observed. The patient was transferred to the emergency department of this hospital for further evaluation. On arrival, the patient reported ongoing headache and nausea. Other medical history included obesity and opioid use disorder, which was treated with oral bu-prenorphinenaloxone and was complicated by relapses with injection of heroin; she last injected heroin 1 month before admission. Other medications included ibuprofen as needed. She had no known allergies. She smoked a half pack of cigarettes daily and did not drink alcohol. The patient lived in a wooded area of New England with four cats and one dog. She spent time outside, although she had become less active owing to headache. She was sexually active with one male partner and had no history of sexually transmitted infections. She had not traveled outside of New Eng-CME at NEJM.org OUTPUT:

Chronic Candida albicans meningitis.

NEJM_Reasoning_Subset55

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: CME Dr. Esra D. Gumuser Medicine: A 48-year-old woman was admitted to this hospital because of multiple lung and liver lesions identified during an evaluation for abdominal pain. The patient had been in her usual state of health until 10 days before this admission, when burning epigastric pain developed after she ate a meal. Nausea and vomiting occurred 1 hour later; there was no diarrhea. After the pain persisted for 8 hours, she presented to the emergency department of another hospital for evaluation. On examination, the temperature was 36.8C, the blood pressure 13694 mm Hg, the pulse 80 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 99 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 25.8. The abdomen was soft but distended; there was diffuse mild tenderness on palpation, without rebound or guarding. The white-cell count was 12,800 per micro-liter reference range, 4500 to 11,000 and the blood lipase level 147 U per liter reference range, 13 to 60; other laboratory test results are shown in Table 1. The pain did not resolve after treatment with intravenous famotidine and oral simethicone. Imaging studies were obtained. Dr. Melissa C. Price: A chest radiograph showed faint nodular opacities in the lungs, predominantly in the upper lobes. Computed tomography CT of the abdomen, performed after the administration of intravenous contrast material, revealed multiple fluid-filled small-bowel loops with associated mild mesenteric edema and trace ascites. There was no biliary dilatation. In addition, there were numerous hypoattenuating hepatic lesions with peripheral enhancement. Dr. Gumuser: The patient was admitted to the other hospital with a diagnosis of possible small-bowel obstruction and pneumonia. Treatment with intravenous fluids and ceftriaxone, oral doxycycline, and bowel rest was initiated. On the second hospital day, additional imaging studies of the liver were obtained. Dr. Price: Magnetic resonance imaging MRI of the abdomen Fig. 1, performed with and without the administration of intravenous contrast material, revealed bilobar hepatic lesions with peripheral enhancement, high T2 signal, and diffusion restriction. Dr. Gumuser: Blood was obtained for microbio-logic culture, and treatment with intravenous metronidazole was initiated. On the third hospital day, the abdominal pain had resolved, and the patient began drinking clear fluids. On the fourth hospital day, ultrasound-guided liver biopsy was performed. While the results of the liver biopsy were pending, the patient resumed a normal diet, with no recurrence of abdominal pain. Treatment with oral doxycycline and intravenous ceftriax-one and metronidazole was continued. Dr. Price: On the sixth hospital day, CT of the chest Fig. 1, performed without the administration of intravenous contrast material, revealed numerous irregular cysts and cavitary nodules in the lungs, which were most pronounced in the upper lobes, as well as solid and subsolid paren-chymal nodules that measured less than 1.0 cm in diameter. There were multiple nodules in the thyroid gland, measuring up to 2.8 cm in diameter in the inferior left thyroid lobe. There was a 1.7-cm nodule with soft-tissue attenuation in the right breast. Dr. Gumuser: On the eighth hospital day, bron-choscopy was performed. The airways were inspected to the segmental level, and no abnormalities were visualized. Transbronchial biopsy and bronchoalveolar lavage BAL were performed in the right upper lobe. Examination of the BAL fluid revealed 321 white cells per microliter reference range, 94 to 175. Grams staining and examination of an acid-fast bacilli smear of the BAL fluid were negative. On the ninth hospital day, results of the liver biopsy became available, showing extensive eo-sinophilic infiltration of the liver parenchyma with associated moderate steatosis. Staining of the biopsy specimen for microorganisms, including mycobacteria, was negative. Cultures of blood obtained on the second hospital day showed no growth. The patient was transferred to this hospital for further care. On arrival, the patient reported a mild sore throat that had developed after bronchoscopy, but there was no abdominal pain. She had lost 2 kg of weight before the hospitalization, in the context of dietary changes. She had no history of fever but reported a several-year history of mild shortness of breath with walking that she attributed to smoking. Her surgical history included cholecystectomy and cesarean section. Results of a Papanicolaou test performed 3 months before this presentation had been normal; the patient had not undergone mammography or colonoscopy. She took no medications and had no known drug allergies. The patient lived in an urban area of New England. She was born in Portugal and had immigrated to the United States 40 years earlier. She had not traveled recently; her last trip had been to Portugal 25 years before this admission. The patient was divorced, lived alone, and worked in a medical laboratory. She had no known exposure to chemicals or dust; a coworker at a previous office job had had an atypical infection attributed to mold in the workplace. She had smoked one pack of cigarettes per day for the past 30 years. She drank alcohol three times a week and did not use illicit drugs. Her mother had died from colon cancer at 43 years of age. On examination, the temperature was 36.2C, the blood pressure 13064 mm Hg, the pulse 65 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 99 while the patient was breathing ambient air. The physical examination was normal. A diagnosis was made. OUTPUT:

Langerhans-cell histiocytosis of the lung and liver.

NEJM_Reasoning_Subset56

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Javier A. Suarez Neurology: A 32-year-old man was admitted to this hospital after 2 weeks of confusion and headache and 2 days of fever. The patient had been in his usual state of health until 1 month before admission, when his wife noted that he began to have behavior suggestive of anxiety. Two weeks before admission, his wife noted that he began to have confusion; for example, he was unable to recall the ages of his children or to correctly identify the date. At that time, headache and neck stiffness developed. Two days before admission, fever developed. On the day of admission, the patient had worsening confusion and somnolence, and his wife brought him to the emergency department of this hospital for evaluation. On presentation, the patient was not able to provide any history but was accompanied by his wife, who described his recent symptoms. His medical record showed a 10-year history of Behcets disease, which had initially been complicated by oral and genital ulcers and intermittent fever. During the following decade, flares of Behcets disease had been associated with various manifestations: pulmonary embolism, iliac artery aneurysm and dissection, bilateral renal vein thrombosis, erythema nodosum, deep venous thrombosis, uveitis, an inferior vena cava clot complicated by superior vena cava syndrome that led to thrombectomy, and renal infarction. The flares of Behcets disease had usually included oral ulcers, genital ulcers, uveitis, or fever. Past treatment for Behcets disease had included azathioprine, cyclosporine, and prednisone. Two years before this presentation, treatment with azathioprine and cyclosporine was discontinued and adalimumab initiated. Attempts to taper the dose of prednisone resulted in flares of genital and oral ulcers. The frequency of adalimumab administration was increased to weekly, but genital and oral ulcers persisted. Thirteen months before this presentation, treatment with adalimumab was stopped and infliximab initiated. Diffuse arthralgias developed that were attributed to infliximab. Twelve months before this presentation, treatment with infliximab was stopped and golimumab initiated. CME at NEJM.org Other medical history included an episode of lymphocyte-predominant meningitis, which had been diagnosed during an evaluation for headache, fever, and neck pain 17 months before this presentation. During the episode, there was a 72-hour delay in performing lumbar puncture for cerebrospinal fluid CSF analysis because the patient had been taking apixaban for the treatment of venous thromboembolism. While he was awaiting lumbar puncture, broad-spectrum antibiotic agents were administered, and the headache, fever, and neck pain resolved. CSF analysis revealed normal levels of glucose and total protein, no red cells, and a nucleated-cell count of 88 per microliter reference range, 0 to 5, with 97 lymphocytes and 3 monocytes. Nucleic acid amplification testing for herpes simplex virus type 1 and type 2 DNA was negative, and Grams staining revealed no organisms. Antimicrobial therapy was discontinued, and the patient was discharged home. There was also a history of coronavirus disease 2019, which had been diagnosed 16 months before this presentation. Current medications included golimumab, apixaban, prednisone, and trimethoprimsulfamethoxazole. There were no known allergies. The patient lived with his wife and four children. He had previously worked in construction; he had been released from prison 3 months before this presentation and was not currently working. He had a remote history of smoking tobacco; he did not drink alcohol or use illicit drugs. His grandmother had hypertension. On examination in the emergency department, the patient was somnolent but arose in response to verbal stimuli. His level of alertness fluctuated, he was only intermittently able to answer simple questions, and he could not provide a coherent history of his illness. The temperature was 39.5C, the blood pressure 12271 mm Hg, the heart rate 81 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 96 while he was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 29.7. He was oriented to person and place but not to time. There was no neck stiffness. Mild injection in the left eye was present, but there were no oral or skin lesions. The patient was not able to participate fully in a neuro-logic examination, but he was able to move his arms and legs; no focal neurologic findings were noted on observation. The remainder of the examination was normal. Blood levels of glucose and electrolytes were normal, as were results of liver-function, kidney-function, and coagulation tests. Other laboratory test results are shown in Table 1. Urinalysis revealed trace ketones but was otherwise normal. The blood acetaminophen level was less than 5.0 g per milliliter reference range, 0.0 to 25.0; blood testing for ethanol was negative. Testing of a nasopharyngeal swab specimen for respiratory viral pathogens was positive for human rhinovirus or enterovirus. Blood specimens were obtained for culture. Imaging studies were obtained. Dr. Pamela W. Schaefer: A chest radiograph was normal. Computed tomography CT of the head revealed mucosal thickening with layering fluid levels in both maxillary sinuses, but the study was otherwise normal. CT angiography of the head and neck, performed with and without the administration of intravenous contrast material, revealed normal arterial and venous vasculature. Dr. Suarez: Treatment with vancomycin, ceftri-axone, ampicillin, and acyclovir was initiated. The patient was admitted to the hospital. Treatment with apixaban was stopped and heparin administered intravenously in anticipation of performing a lumbar puncture. Fever and headache abated, but the patients mental status did not improve. Blood cultures showed no growth. On the fourth hospital day, a lumbar puncture was performed. The opening pressure was not obtained. CSF analysis revealed a normal total protein level, a glucose level of 40 mg per deciliter 2.2 mmol per liter; reference range, 50 to 75 mg per deciliter 2.8 to 4.2 mmol per liter, a red-cell count of 2 per microliter reference range, 0 to 5, and a nucleated-cell count of 284 per microliter reference range, 0 to 5, with 72 lymphocytes, 13 neutrophils, 11 monocytes, and 4 unclassified cells. Nucleic acid amplification testing for herpes simplex virus type 1 and type 2 DNA was negative, and Grams staining revealed no organisms. No acid-fast bacilli were observed on a mycobacterial smear, and no fungi were seen on examination of a fungal wet preparation. Testing of the CSF for cryptococcal antigen and enterovirus RNA was negative. Additional diagnostic testing was performed, and a diagnosis was made. OUTPUT:

Encephalitis due to Behçet’s disease.

NEJM_Reasoning_Subset57

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: CME at NEJM.org Dr. John H. Stone: A 59-year-old man was evaluated in the rheumatology clinic of this hospital because of headache and progressive neurologic dysfunction. Ten months before this evaluation, daily fever with a temperature of up to 38.9C, chills, myalgias, drenching night sweats, and pressure and pain in both cheeks and ears developed. The patient was evaluated by his primary care physician. He reported rhinorrhea and fatigue but no headache, pharyngitis, or dyspnea, and he had no sick contacts. On examination, the temperature was 37.8C, the heart rate 100 beats per minute, the blood pressure 11264 mm Hg, and the oxygen saturation 98 while he was breathing ambient air. He was ill-appearing, and the maxillary sinuses were tender on palpation; the remainder of the examination was normal. Blood levels of electrolytes, calcium, total protein, albumin, and globulin were normal, as were the results of kidney-function tests. The platelet count was 463,000 per microliter reference range, 140,000 to 400,000; the remainder of the complete blood count and the differential count were normal. Amoxicillinclavulanate was prescribed. During the next 2 weeks, fever, night sweats, and sinus and facial pain continued. Diffuse headache developed, along with jaw soreness, scalp tenderness, and hip and shoulder stiffness. The patient was evaluated again by his primary care physician. He reported weight loss of 2 kg, episodic double vision, and hip pain that caused difficulty in standing and climbing stairs. The physical examination was unchanged. Urinalysis was normal. A test for heterophile antibody and an interferon- release assay for Mycobacterium tuberculosis were negative, as were screening tests for human immunodeficiency virus and Lyme disease. Chest radiography and computed tomography of the sinuses were normal. The patient was referred to a rheumatologist at another hospital. On evaluation, the patient reported persistent fever and frontal, temporal, and maxillary headache. There were palpable temporal artery pulses without tender-ness; the remainder of the examination was normal, including the absence of bruits on auscultation of large vessels. The erythrocyte sedimentation rate was 108 mm per hour reference range, 0 to 20, the blood level of C-reactive protein greater than 100 mg per liter reference value, 8.0, the blood level of rheumatoid factor 24 IU per milliliter reference value, 14, and the blood level of aldolase 8.4 IU per milliliter reference value, 8.1. Biopsy of the right temporal artery was performed. Histologic examination of the biopsy specimen reportedly showed no granulomas, but evidence of chronic inflammation of the temporal artery and fibrinoid necrosis of an adjacent small vessel were noted. A diagnosis of giant-cell arteritis was made, and treatment with prednisone was started. Within a few days after initiation of treatment, headache, fever, jaw pain, and joint stiffness abated. The next month, an attempt to lower the predni-sone dose resulted in recurrent severe headache with scalp tenderness, jaw pain, and hip stiffness. The erythrocyte sedimentation rate was 55 mm per hour and the C-reactive protein level 84 mg per liter. Treatment with weekly subcutaneous administration of tocilizumab was initiated. During the next 6 weeks, another attempt was made to taper the prednisone dose. After 1 week of treatment at a lower prednisone dose, and 5 months after the development of initial symptoms 5 months before the current evaluation, the patient reported headache that he described as the worst headache of my life, with associated jaw pain and diplopia. The pain was worst at the right frontal and maxillary areas, but the entire right side of the face, including the scalp and neck, was affected. The patient returned to the other hospital for evaluation. He was found to have palsies of the third and sixth cranial nerves on the right side. The patient was admitted to the neurology service at the other hospital. Antineutrophil cytoplasmic antibody ANCA testing revealed a slightly elevated myeloperoxi-dase antibody level, at 1.9 U reference value, 1.0, but antibodies to proteinase 3 were not detected. Blood levels of IgG subclasses were normal. Imaging studies were obtained. Dr. Otto Rapalino: Magnetic resonance imaging MRI of the head Fig. 1A and 1B, performed after the administration of intravenous contrast material, revealed abnormal expansion and en-hancement of the right cavernous sinus that extended into the right superior orbital fissure and right pterygopalatine fossa, as well as abnormal pachymeningeal thickening and enhancement of the adjacent right middle cranial fossa. MRI of the cervical spine Fig. 1C and 1D showed mass-like pachymeningeal thickening and enhancement in the upper cervical spinal canal at C2C4 with an anterior predominance as well as more circumferentially at the cervicothoracic junction C6T3 with a posterior predominance, with resultant canal narrowing and mild cord compression at C7T2. There was no spinal cord edema. Dr. John Stone: A lumbar puncture was performed; an opening pressure was not recorded. The cerebrospinal fluid CSF glucose level was 65 mg per deciliter 3.6 mmol per liter; reference range, 50 to 80 mg per deciliter 2.8 to 4.4 mmol per liter, and the protein level was 126 mg per deciliter reference range, 15 to 45, with 2 red cells per microliter and 8 white cells per micro-liter of which 79 were lymphocytes. Grams staining and cultures of the CSF were negative. Tests for CSF myelin basic protein, angiotensin-converting enzyme, cryptococcal antigen, cysti-cercosis IgG, mycobacterial DNA, EpsteinBarr virus DNA, and borrelia DNA were negative, as was a Venereal Disease Research Laboratory test. Cytologic analysis of the CSF showed a mixed population of mononuclear cells with rare plasma cells. The CSF immunoglobulin level was 19 mg per deciliter reference range, 0 to 6, with 5 oligo-clonal bands. On the eighth hospital day, a meningeal biopsy was performed. Treatment with high-dose prednisone was started, and the patient was discharged home. During the next 2 weeks, the patient continued taking the prednisone, but the facial and head pain worsened. He was readmitted to the other hospital to receive 3 days of treatment with parenteral pulse-dose methyl-prednisolone. Pathological examination of the meningeal biopsy specimen revealed a densely fibrotic, chronically inflamed dura mater with large numbers of CD68 macrophages and CD3 T lymphocytes and with focal collections of CD20 B lymphocytes. There was a large number of poly-clonal plasma cells with more than 100 IgG4 plasma cells per high-power field. Storiform fi-brosis was present, and elastin staining revealed obliterative venulitis. Some of the inflammatory foci were angiocentric, but no vasculitis was present. There were rare foci of fibrinoid necrosis and some neutrophils, with rare giant cells but no granulomas. A diagnosis of IgG4-related disease was made, and rituximab was administered. Two days after the first rituximab dose, a pulmonary embolism was diagnosed, and treat-ment with apixaban was initiated. Two weeks later, repeat imaging was obtained to evaluate the treatment response. Dr. Rapalino: Repeat MRI of the head Fig. 2A and 2B, performed after the administration of intravenous contrast material, revealed increased abnormal enhancement in the right cavernous sinus and right middle cranial fossa and new abnormal enhancement in the left cavernous sinus and adjacent left middle cranial fossa. MRI of the cervical spine Fig. 2C and 2D also showed progression in the extent and thickness of the ventral and dorsal pachymeningeal thickening and enhancement. There was also progression of the canal stenosis, which had become severe, and cord compression at the C7 level. There was no cord signal abnormality. fusion of rituximab, as well as treatment with oral dexamethasone. Three weeks later, and 7 months after the development of initial symptoms 3 months before the current evaluation, the patient was admitted to the other hospital because of worsening headache, nausea, and vomiting. Examination was notable for new sensorineural hearing loss in the right ear and deviation of the tongue to the left. A ventriculoperitoneal shuntDr. John Stone: The patient received a second in-was placed. Treatment with dexamethasone was continued, and the patient was discharged home. Three weeks after placement of the ventriculo-peritoneal shunt, the patient was admitted again to the other hospital because of streptococcal infection. Two months after discharge, and 10 months after the development of initial symptoms, he was seen in the rheumatology clinic of this hospital for additional evaluation. The patient had a history of migraines, hypertension, and a heterozygous factor V Leiden mutation. Medications included apixaban, ba-clofen, dexamethasone, furosemide, gabapentin, lisinopril, and metoprolol. He was a retired businessman and lived with his wife. He drank one glass of wine weekly and had quit smoking more than 40 years before the current evaluation. His maternal grandfather had died from a ruptured aortic aneurysm. The temperature was 36.5C, the heart rate 88 beats per minute, the blood pressure 11879 mm Hg, and the oxygen saturation 97 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 25.8. The scalp hair was thin. He had cushingoid facies; acne on the face, back, and chest; striae on the flanks; and proximal muscle weakness of the arms and legs. There was no scalp or temporal tenderness. He had no tongue lesions or oral ulcers, and the nasal examination showed no crusting. Extra-ocular movements were intact. There was no arthritis. The chest, abdominal, and neurologic examinations were normal. The complete blood count and the differential count were normal, as was a urinalysis. The erythrocyte sedimentation rate was 52 mm per hour and the C-reactive protein level 5 mg per liter. Serum protein electrophoresis revealed an IgM level of 22 mg per deciliter reference range, 53 to 334 and normal levels of IgG and IgA. ANCA testing was negative. A diagnosis and management decisions were made. OUTPUT:

Granulomatosis with polyangiitis.

NEJM_Reasoning_Subset58

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: CME Dr. Dilara Hatipoglu Medicine: A 33-year-old man was evaluated in the gastroenter-ology clinic of this hospital because of relapsing chronic diarrhea and a diagnosis of autoimmune enteropathy. Diarrhea had initially developed in the patient during infancy. When the patient was 2 months of age, he had poor growth and frequent bowel movements with loose stools. When he began to eat solid foods, diarrhea continued, and a hydrolyzed-protein diet was started. His parents were instructed to remove dairy, soy, and gluten from his diet, but diarrhea did not abate. Allergy skin-prick testing with cows milk and soy antigens was negative. When the patient was 10 months of age, failure to thrive and diarrhea persisted, and generalized edema and nephrotic syndrome developed. Esophagogas-troduodenoscopy EGD was performed, and histopathological examination of a small-intestinal biopsy specimen reportedly revealed villous atrophy, crypt hyperplasia, and diffuse inflammation. Transmission electron microscopy reportedly showed mild degenerative changes of the surface epithelium and mild focal micro-villous atrophy; there were no immune deposits, and the basement membrane was normal. Renal biopsy was also performed, and histopathological examination of a renal biopsy specimen revealed glomeruli with diffuse thickening of the basement membrane; there was no proliferation of cells or mesangial matrix. Transmission electron microscopy showed total effacement of the epithelial cell foot processes and an irregularly thickened glomerular basement membrane with numerous subepi-thelial and intramembranous electron-dense deposits. The patient received a working diagnosis of nephrotic syndrome due to membranous glomerulonephritis, and treatment with prednisone was started. Diarrhea abated, proteinuria and generalized edema resolved, and growth resumed. However, during the next 2 years, intermittent relapses of diarrhea and nephrotic syndrome occurred when the dose of prednisone was decreased. When the patient was 3 years of age, treatment with chlorambucil was started for recurrent membranous glomerulonephritis, and there were no relapses for 1 year. When the patient was 4 years of age, there was a recurrence of diarrhea associated with fever and hemolytic anemia. Stool culture, stool testing for Clostridioides difficile toxin, and examination of the stool for ova and parasites were all negative. EGD was performed, and histopatho-logical examination of a small-intestinal biopsy specimen reportedly revealed villous atrophy, crypt hyperplasia, and active enteritis. The blood IgE level was 501 IU per milliliter reference range, 0 to 100. The blood level of endomysial antibodies was not elevated, but antiepithelial cell antibodies were detected. The patient received a diagnosis of autoimmune enteropathy, and treatment with intravenous glucocorticoids and cyclosporine was begun. After several months, treatment with gluco-corticoids and cyclosporine was stopped, and tacrolimus was begun. Tacrolimus was stopped after several years, when the patients symptoms resolved. From 5 to 13 years of age, he had no enteropathy, anemia, or nephropathy. Beginning at 13 years of age, the patient was hospitalized for recurrences of diarrhea and ne-phropathy every 2 to 4 years during the 20 years before this evaluation. Six years before this evaluation, EGD and colonoscopy were performed, and the duodenal and colonic mucosa appeared diffusely edematous. Biopsy specimens were obtained. Dr. Stuti G. Shroff: Examination of a duodenal biopsy specimen Fig. 1 revealed marked villous blunting, an increase in lymphoplasmacytic inflammatory cells in the lamina propria known as lymphoplasmacytic expansion of the lamina propria, and a patchy increase in intraepithelial lymphocytes. Examination of a colonic biopsy specimen revealed mild focal active colitis that spared the rectum. Dr. Hatipoglu: Treatment with intravenous methylprednisolone was begun, and diarrhea abated. For the next 2 years, relapses of diarrhea and nephrotic syndrome were treated with intravenous methylprednisolone or oral prednisone in combination with cyclosporine, tacrolimus, and mycophenolate mofetil. Four years before this evaluation, antibodies against the M-type phospholipase A2 receptor were not detected. Renal biopsy was performed, and histopathological examination of a renal biopsy specimen again revealed evidence of membranous glomerulonephritis. Treatment was changed to prednisone, budesonide, and abata-cept, and symptoms abated. After 2 years, the patient stopped taking abatacept. After another 2 years, diarrhea recurred, and the patient was referred to the gastroenterology clinic of this hospital. In the gastroenterology clinic, additional history was obtained. There was a history of hypertension, gallstones, and rosacea. Eczema had developed when the patient was 10 months of age and had occurred intermittently into adulthood; it had abated with the administration of immunosuppressive agents. Anaphylactic shock had occurred when the patient was 2 years of age after he had been exposed to uncooked egg. At that time, allergy testing was performed, and the patients parents were instructed to remove eggs, tree nuts, peanuts, fish, and shellfish from his diet, in addition to removing dairy, soy, and gluten. Current medications included prednisone, budesonide, and losartan. There were no known drug allergies. The patient lived in a Mid-Atlantic state and worked as a salesperson. He did not smoke tobacco and drank beer rarely. His family history included ovarian cancer in his mother and skin cancer in his father; his brother was healthy. On examination, the temperature was 37.0C, the blood pressure 13194 mm Hg, the heart rate 106 beats per minute, and the oxygen saturation 97 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 24.1. The patient had short stature and diffuse erythema of the face and neck. There was mild tenderness in the left lower abdomen. The results of a lactulose breath test were normal, as was the fecal calprotectin level. Testing for antibodies to tissue transglutamin-ase was negative. Other laboratory test results are shown in Table 1. EGD and colonoscopy were performed, and the findings were consistent with duodenitis, gastritis, and atrophy of the colon. Biopsy specimens were obtained. Dr. Shroff: Histopathological examination of ileal and duodenal biopsy specimens Fig. 1 revealed villous blunting, lymphoplasmacytic expansion of the lamina propria, and intraepithe-lial lymphocytosis. Dr. Hatipoglu: A diagnostic test was performed. OUTPUT:

Immune dysregulation, polyendocrinopathy, en-teropathy, X-linked (IPEX) syndrome.

NEJM_Reasoning_Subset59

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Numa P. Perez Surgery: A newborn girl was transferred to the neonatal intensive care unit ICU of this hospital because of hypoglycemia. The patients mother was a 27-year-old woman gravida 1, para 1 who had received prenatal care at another hospital. At 34 weeks of gestation, an ultrasono-graphic survey of the fetal anatomy had reportedly revealed an avascular intraab-dominal cystic mass that was located near the bladder and measured 3.7 cm by 2.1 cm by 2.0 cm. A sacral dimple was noted. The patients mother was referred to the maternalfetal medicine clinic of the other hospital; she declined follow-up imaging and amniocentesis. At 37 weeks 6 days of gestation, premature labor occurred, and the patients mother was taken to a second hospital. A fetal heart tracing was noted to be nonreactive with minimal variability. The fetal biophysical profile score was 4 out of 8, indicating decreased breathing motion and body movement but normal tone and amniotic fluid volume. An emergency cesarean section was performed. On delivery, the newborn had limp tone and poor respiratory effort. The birth weight was 2963 g 19th percentile, the length 48 cm 20th percentile, and the head circumference 35 cm 77th percentile. The Apgar scores at 1 minute and 5 minutes were 7 and 9, respectively. The patient was transferred to the newborn nursery. In the nursery, the patient was noted to be jittery. Oxygen therapy was administered through a low-flow nasal cannula. The blood glucose level was reportedly less than 10 mg per deciliter 0.6 mmol per liter; reference range, 70 to 110 mg per deciliter 3.9 to 6.1 mmol per liter and the bilirubin level 16.0 mg per deciliter 274 mol per liter; reference range, 2.0 to 15.0 mg per deciliter 34 to 257 mol per liter. A chest radiograph showed a normal cardiac shadow and findings indicative of retained fetal lung fluid. The newborn was fed, and a bolus of dextrose was administered; however, a repeat blood glucose level was 2 mg per deciliter 0.1 mmol per liter. A continuous infusion of dextrose was started. Phototherapy and empirical treatment with ampicillin and gentamicin were administered. During the next 3 days, the patients blood glucose level remained low, with a maximum level of 61 mg per deciliter 3.4 mmol per liter, even though the glucose infusion rate was increased and enteral feeding with formula was initiated. On the fourth day of life, she was transferred to the neonatal ICU of this hospital for further treatment. On admission to the neonatal ICU, additional history was obtained. Before the ultrasono-graphic survey at 34 weeks of gestation, the pregnancy had been normal. The patients mother had taken prenatal vitamins. Prenatal maternal screening had been negative for gonorrhea, chlamydia, and syphilis, as well as human immunodeficiency virus, hepatitis B virus, and group B streptococcal infections; there was evidence of immunity to rubella virus. The maternal ABO blood type was AB, Rh positive. The newborns parents had immigrated to the United States from the Caribbean and now lived in a suburb in New England. The patients mother, father, and half brother were healthy. On examination, the patient was alert and appeared comfortable. The temperature was 36.9C, the heart rate 148 beats per minute, the blood pressure 7945 mm Hg, the respiratory rate 49 breaths per minute, and the oxygen saturation 98 while she was breathing ambient air. The anterior and posterior fontanelles were flat and soft. The lungs were clear on auscultation. The abdomen was soft without distention, tenderness, or palpable masses. Two sacral dimples with visible bases were noted. The female genitalia appeared normal, but the anus was displaced anteriorly. The blood glucose level was 60 mg per deciliter 3.3 mmol per liter while the patient was receiving dextrose at a glucose infusion rate of 10.5 mg per kilogram of body weight per minute. The total bilirubin level was 20.4 mg per deciliter 349 mol per liter. Other laboratory test results are shown in Table 1. Dr. Sjirk J. Westra: A chest radiograph showed clear lungs. Abdominal and pelvic ultrasonogra-phy Fig. 1 revealed a large solidcystic mass anterior to the sacrum that measured 2.7 cm by 3.0 cm by 5.7 cm, with the rectum passing anteriorly to the mass. Results of spinal ultrasonog-raphy were normal, as were results of cranial ultrasonography performed through the anterior fontanelle. In addition, magnetic resonance im-aging MRI of the abdomen, pelvis, and spine Fig. 2 showed a presacral solidcystic mass that measured 2.7 cm by 2.8 cm by 5.9 cm, with a small extension into the ischiorectal fossa on the right side. There was no evidence of abdominal lymphadenopathy or involvement of the sacral spine. Dr. Perez: During the next few days, the patient continued to receive dextrose at a high glucose infusion rate to maintain normoglycemia. At 5 days of life, a small bowel movement occurred. The blood lactate dehydrogenase level was 1173 U per liter reference range, 110 to 210 and the beta human chorionic gonadotropin level 10.7 mIU per milliliter reference range, 1.1. A diagnostic test was performed. OUTPUT:

Neonatal hypoglycemia due to biologically active teratoma and the Sotos syndrome.

NEJM_Reasoning_Subset60

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Yousef R. Badran: A 72-year-old man was transferred to this hospital because of heartburn, nausea, and the inability to eat solid and liquid food. The patient had a history of gastroesophageal reflux disease. The symptoms had been well controlled with the use of daily omeprazole therapy until 11 months before this admission, when heartburn recurred despite treatment. At that time, the patient also noticed nausea after eating and early satiation. During the next 9 months, the heartburn and nausea slowly increased in severity. To help manage his symptoms, the patient adjusted his diet from solid food to soft solid food. Two months before this admission, the patient sought evaluation at the gastro-enterology clinic of another hospital. The glycated hemoglobin level was 6.1 reference range, 4.3 to 5.6. Esophagogastroduodenoscopy EGD was performed. Although the patient had not eaten food for 24 hours before the procedure, the stomach could not be adequately visualized because there was a large amount of residual food; no intraluminal masses were seen. A scintigraphy study of gastric emptying was performed. During the study, 88 of the gastric contents were retained at 1 hour, 88 at 2 hours, 81 at 3 hours, and 80 at 4 hours. In a patient with normal gastric emptying, less than 60 of the gastric contents would be retained at 2 hours and less than 10 at 4 hours. Thus, the results were consistent with severely delayed gastric emptying. The patient was told that he had idiopathic gastroparesis and underwent trials of several medications. Ondansetron caused constipation, erythromycin caused burning while swallowing and abdominal cramping, and metoclopramide and scopolamine did not lead to a decrease in the patients symptoms. During the 2 months after the evaluation in the gastroenterology clinic, the patient adjusted his diet from soft solid food to blended solid food. Two weeks before this admission, he adjusted his diet to primarily liquid food, such as nutritional supplement drinks, protein shakes, and ice cream. When the patient was no longer able to drink liquids, he sought evaluation at the emergency department of the other hospital. CME at NEJM.org On evaluation, the patient described epigas-tric burning and nausea after eating. He had lost 13.6 kg of weight in the preceding year, including 5.4 kg in the past 2 weeks. He had no recent history of illness, night sweats, vomiting, dysphagia, odynophagia, abdominal pain, or diarrhea. Dr. David A. Rosman: Computed tomography CT of the chest, abdomen, and pelvis, performed after the administration of intravenous contrast material, revealed a patulous esophagus, along with wall thickening in scattered areas of the upper and lower segments of the esophagus. There was abnormal circumferential wall thickening 13 mm in the stomach, particularly at the antrum, incisura, and pyloric canal Fig. 1. The antrum was decompressed or nonexpansile, and the rest of the stomach was distended. There were multiple bilateral pulmonary nodules 5 mm in diameter and multiple hepatic hypodensities 10 mm in diameter, as well as a pancreatic cyst 5 mm in diameter and an exophytic renal lesion 8 mm in diameter. Dr. Badran: A nasogastric tube was inserted. Treatment with intravenous pantoprazole was started, and intravenous lorazepam was administered for nausea. The patient was admitted to the other hospital. During the subsequent week, the patient received vitamin and mineral supplements for severe malnutrition. He remained unable to drink liquids. On the 7th hospital day, a peripherally inserted central catheter was placed, and total parenteral nutrition was administered. The patient was monitored for refeeding syndrome. On the 15th hospital day, he was transferred to this hospital for further treatment. On transfer to this hospital, additional history was obtained. The patient had a history of prediabetes, hypertension, dyslipidemia, divertic-ulosis, glaucoma, and basal cell carcinoma of the ear that had been resected. Five years before this admission, EGD had revealed a widely patent Schatzkis ring, an irregular-appearing Z line, and a few gastric polyps; examination of an esophageal biopsy specimen had revealed no abnormalities. Colonoscopy had shown two tubular adenomas. The patient had undergone orthognathic surgery, but there was no history of abdominal surgery. Medications included omeprazole, lisinopril, atorvastatin, vitamin D supplements, and bimatoprost and bromonidine eye drops. Sulfa drugs had caused a rash. The patient lived with his wife in a rural area of New England. He had previously served in the military and currently worked as a biotechnologist. He had never smoked tobacco, and he drank alcohol rarely. His mother and paternal aunt had died of colon cancer, his father of lung cancer, his maternal grandmother of breast cancer, and his maternal grandfather of prostate cancer. His two children and two grandchildren were healthy. On examination, the temperature was 37.7C, the blood pressure 12876 mm Hg, the pulse 105 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97 while the patient was breathing ambient air. He was thin and had a nasogastric tube in place. He had normal mood, affect, and insight. The abdomen was flat, soft, and nondistended, with mild tenderness in the epigastrium on palpation. There was no palpable lymphadenopathy. Distal sensory and motor function were normal. Laboratory test results are shown in Table 1. A diagnostic test was performed. OUTPUT:

Linitis plastica (invasive gastric adenocarcinoma).

NEJM_Reasoning_Subset61

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: CME at NEJM.org Dr. David M. Dudzinski: A 76-year-old man was evaluated in the intensive care unit of this hospital for persistent postoperative cardiogenic shock and new diffuse rash after undergoing mitral-valve replacement. Two months before this evaluation, the patient was admitted to another hospital with anorexia, generalized weakness, fatigue, and edema. Examination of the lungs was notable for decreased breath sounds and basilar crackles. The level of N-terminal proB-type natriuretic peptide was 15,895 pg per milliliter reference value, 1500. Dr. Matthew T. Stib: A chest radiograph Fig. 1A showed a mildly enlarged cardiac silhouette, as well as evidence of pulmonary edema and bilateral pleural effusions. Dr. Dudzinski: At the other hospital, intravenous furosemide was administered. Blood cultures obtained at the time of admission grew methicillin-sensitive Staphylococcus aureus MSSA in four of four bottles. Transesophageal echocardiography TEE reportedly revealed moderate-to-severe mitral regurgitation and a 7-mm vegetation on the anterior leaflet of the mitral valve. Treatment with intravenous oxacillin was initiated; a 4-week course of treatment was planned, after which the patient was scheduled for follow-up in the cardiac surgery clinic at this hospital. However, 3 weeks after discharge, the patient reported dyspnea on exertion, fatigue, progressive edema of the legs, and weight gain of 7 kg. He was admitted to this hospital for further evaluation and treatment. Medical history was notable for hypertension, right bundle-branch block, hypothyroidism, and prostatism, as well as atrial fibrillation, for which the patient had undergone cardioversion. Surgical history included tooth extraction for a painful dental abscess 6 weeks before admission to the other hospital, appendectomy, arthroplasty of the left hip after a fall 3 years earlier, and repair of a meniscus tear in the left knee. Medications included oxacillin administered intravenously every 4 hours and oral furo-semide, sotalol, rivaroxaban, levothyroxine, and tamsulosin. He had had no known adverse drug reactions. The patient was retired and lived with his spouse. He reported that, before his admission to the other hospital, he had been riding a bicycle a few miles several times per week. He had previously smoked cigarettes but had quit 30 years earlier; he consumed one beer weekly and used no other substances. His family history was notable for atrial fibrillation. The temperature was 36.7C, the heart rate 83 beats per minute, the blood pressure 12072 mm Hg, and the oxygen saturation 96 while the patient was breathing ambient air. He appeared fatigued. The jugular venous pressure was elevated, at 15 cm of water. The cardiac impulse was discrete and was not displaced. Auscultation of the chest revealed an irregularly irregular cardiac rhythm, with a grade 36 holo-systolic murmur at the left sternal border and apex that did not change with respiration, and bibasilar crackles. There was 2 pitting edema in the legs. A peripherally inserted central catheter was present in the right arm. The blood levels of calcium, magnesium, albumin, lipase, glycated hemoglobin, alkaline phosphatase, and bilirubin were normal, and a screening test for human immunodeficiency virus antigen and antibodies was negative. Other laboratory test results are shown in Table 1. Cultures of blood were obtained. An electrocardiogram Fig. 1B showed atrial fibrillation, multifocal ventricular premature beats, and right bundle-branch block. Dr. Stib: A chest radiograph Fig. 1C showed bilateral pulmonary edema, which was more prominent in the right lung than in the left lung, as well as pleural effusions and left atrial enlargement. The tip of a peripherally inserted central catheter was appropriately positioned in the lower superior vena cava. Dr. Dudzinski: Treatment with intravenous oxa-cillin and furosemide was continued. TEE Fig. 1D and transthoracic echocardiography TTE revealed a normal-sized left ventricle with an ejection fraction of 61, dilatation of the right ven-tricle with normal function, dilatation of both atria, mitral-valve perforation and thickening, severe mitral regurgitation due to mitral-valve perforation, and moderate tricuspid regurgitation with a right ventricular systolic pressure of 48 mm Hg also see Videos 1 and 2, available with the full text of this article at NEJM.org. Coronary angiography revealed 70 stenosis in the proximal left anterior descending coronary artery and 90 stenosis in the middle right coronary artery. On hospital day 11, cardiac surgery was performed. The patient underwent bioprosthetic mitral-valve replacement, along with two-vessel coronary-artery bypass grafting and amputation of the left atrial appendage. TEE performed after the surgical procedure revealed a well-seated mitral prosthesis with trace central regurgitation, as well as mild biventricular systolic dysfunction. Subsequently, on transfer to the intensive care unit, the blood pressure was 10852 mm Hg and the cardiac index 3.0 liters per minute per square meter of body-surface area while the patient was receiving epinephrine at a rate of 2 g per minute, norepineph-rine 10 g per minute, and vasopressin 0.04 U per minute. An electrocardiogram Fig. 1E showed atrial fibrillation, right bundle-branch block, and ventricular premature beats. During postoperative day 1, the patient had increased ventricular ectopy and a 25-beat run of ventricular tachycardia. Laboratory and hemody-namic data are shown in Table 1. Dr. Stib: An anteroposterior chest radiograph Fig. 1F showed left atrial enlargement, bilateral pulmonary edema, and basilar atelectasis, along with sternotomy wires, an endotracheal tube, a catheter in the right main pulmonary artery, bilateral chest tubes, and a mediastinal drain. Dr. Dudzinski: Treatment with intravenous ami-odarone was started, and the epinephrine infusion was discontinued. On postoperative day 2, the trachea was extu-bated, and mechanical ventilation was discontinued. The cardiac index had decreased to less than 2.0 liters per minute per square meter, and intravenous milrinone was initiated. The next day, a 35-beat run of ventricular tachycardia occurred. On postoperative day 4, given that the cardiac index was less than 1.9 liters per minute per square meter, intravenous dopamine was started. On postoperative day 5, deep-vein thrombosis was identified in the right lower leg, and treatment with warfarin was started. A truncal macular rash was noted. TTE revealed a left ventricular ejection fraction of 32, right ventricular dysfunction, atrial dilatation, trace central prosthetic mitral regurgitation with a mean transmitral gradient of 5 mm Hg measured at 70 beats per minute, and moderate-to-severe tricuspid regurgitation see Video 3. There was also worsening renal function. Milrinone was stopped and epinephrine initiated. On postoperative day 8, microbiologic cultures obtained during the surgical procedure showed no growth; the patients oxacillin treatment was switched to cefazolin. During the next few days, the rash became more confluent and extended to the face, back, arms, and neck in addition to the trunk, but there was no mu-cosal involvement. Examination of the joints was normal, and there was no lymphadenopa-thy or hepatosplenomegaly. The arms and legs were cool, and urine output had decreased, despite continued therapy with intravenous epi-nephrine, norepinephrine, and dopamine. Laboratory test results are shown in Table 1. Repeat TTE on postoperative day 13 revealed borderline left ventricular dilatation with an ejection fraction of 37, right ventricular dilatation and dysfunction, and moderate-to-severe tricuspid regurgitation. Additional diagnostic tests were performed, and management decisions were made. OUTPUT:

Eosinophilic myocarditis and drug reaction with eosinophilia and systemic symptoms (DRESS).

NEJM_Reasoning_Subset62

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: CME Dr. Natalie A. Diacovo Pediatrics: An 11-year-old girl was evaluated in the rheuma-tology clinic of this hospital because of redness of the eyes. The patient had been well until 8 weeks before the current evaluation, when she noticed mild eye redness, which was worse in the right eye than in the left eye. There was intermittent swelling of the eyelids but no photophobia, itching, pain, tearing, or discharge. The patients parents administered naphazoline hydrochloride and glycerin eye drops, but the eye redness did not abate. When the eye redness had persisted for 2 weeks, the patient was taken to the pediatrics clinic of another hospital. She was given a 7-day course of an oral antibiotic agent as empirical treatment for possible preseptal cellulitis. Five weeks before the current evaluation, the eye redness persisted despite treatment, and the patient was referred to the ophthalmology clinic of the other hospital. The blood pressure was not measured during this evaluation. The visual acuity with correction was 2020 in the right eye and 2025 in the left eye. The pupils were symmetric and reactive to light, with no relative afferent pupillary defect. Slit-lamp examination revealed abundant white cells in the anterior chamber of both eyes, with a greater amount in the right eye than in the left eye. There were also keratic precipitates, posterior synechiae, and rare iris nodules in the right eye. Funduscopic examination was notable for optic-disk swelling and peripheral retinal hemorrhages in both eyes, as well as perivascular exudates in the right eye. Cyclopentolate eye drops in the right eye and prednisolone eye drops in both eyes were prescribed. During the subsequent 3 weeks, additional tests were performed in the pediatrics clinic of the other hospital. Screening blood tests for human immunodeficiency virus HIV types 1 and 2, syphilis, and Lyme disease were negative. An interferon- release assay for Mycobacterium tuberculosis was indeterminate. Other laboratory test results are shown in Table 1. Radiography of the chest revealed hilar fullness. Dr. Maria G. Figueiro Longo: Computed tomography CT of the chest and abdomen Fig. 1A and 1B, performed after the administration of intravenous contrast material, showed a normal-appearing thymus. However, diffuse lymphadenopathy was detected in the mediastinum, upper abdomen, and axillae, with the largest lymph node measuring 2.0 cm by 1.3 cm by 1.8 cm. Dr. Diacovo: Two weeks before the current evaluation, the patient was asked to present to the emergency department of the other hospital for an expedited workup. On evaluation, she described eye redness that had persisted but decreased in severity. She reported no fever, weight loss, night sweats, rash, headache, cough, shortness of breath, or joint pain. On examination, the temperature was 37.0C, the blood pressure 9661 mm Hg, the heart rate 95 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 100 while she was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 18.3. The patient appeared well, with no oral lesions or rash. The visual acuity was unchanged. Slit-lamp examination revealed keratic precipitates and white cells in the anterior chamber of both eyes, with a greater amount in the right eye than in the left eye. There were extensive posterior synechiae in the right eye. Funduscopic examination Fig. 2 showed vitreous white cells, optic-disk swelling, perivascular exudates, peripheral retinal hemorrhages, and cotton-wool spots in both eyes. The lungs were clear on auscultation. Urinalysis was normal. Other laboratory test results are shown in Table 1. Methylprednisolone was administered, and the patient was admitted to the other hospital. During the next 4 days, additional tests were performed, and sputum specimens were obtained for an acid-fast bacilli smear and culture. Optical coherence tomography revealed optic-disk swelling but no cystoid macular swelling. Fluorescein angiography revealed optic-disk leakage with areas of peripheral retinal nonperfusion and some vessel leakage. Dr. Figueiro Longo: Magnetic resonance imaging MRI of the head Fig. 1C, performed before and after the administration of intravenous con- OUTPUT:

Sarcoidosis.

NEJM_Reasoning_Subset63

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Michael D. Kritzer: A 57-year-old woman with major depressive disorder and coro-navirus disease 2019 Covid-19 was evaluated at a hospital affiliated with this hospital because she was having delusions that she was dead. The patient had been in her usual state of health until 2 weeks before this presentation, when myalgias, cough, sore throat, nausea, and vomiting developed. She sought evaluation at the primary care clinic of an academic medical center affiliated with this hospital the two hospitals are part of the same health care system. Nucleic acid testing of a nasopharyngeal swab was positive for severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 RNA, and the patient was instructed to quarantine at home. She lived with her father and assisted him with activities of daily living; he also received a diagnosis of Covid-19. During the following week, the patients cough persisted, and new shortness of breath developed. Her symptoms worsened; she felt that she was unable to take care of her father. Emergency medical services were called, and the patient and her father were taken to the emergency department of the other hospital, where they were both admitted for worsening Covid-19 pneumonia. The patient was treated with supplemental oxygen, remdesivir, and dexamethasone. Treatment with rem-desivir was stopped on hospital day 4 when the blood aminotransferase levels increased to three times the upper limit of the normal range. During the hospitalization, the patient was noted to have intermittent anxiety, particularly when discharge planning for her father was discussed. She and her brother declined to have their father discharged to a rehabilitation center and instead planned for him to eventually return home to quarantine with the patient. On hospital day 6, the patients oxygen saturation was normal while she was breathing ambient air, and the blood aminotransferase levels had improved. She was discharged home with instructions to quarantine and continue taking dexa-methasone. One day after discharge, the patients brother spoke to her on the telephone. CME at NEJM.org He thought that she seemed to be confused and unable to take care of herself, and he asked her to return to the emergency department of the other hospital. On evaluation in the emergency department, the patient explained that she was unsure why her brother had asked her to return to the hospital, and she said that she wanted to go home. She also expressed that she felt anxious about being home alone after discharge and overwhelmed about needing to care for her father at home once he was discharged from the hospital. The myalgias, cough, and shortness of breath had abated; she had no fevers, visual or auditory hallucinations, or suicidal or homicidal ideation. The patient had a history of major depressive disorder, which had been diagnosed during the second decade of life. At the time of diagnosis, she had been admitted to a psychiatric hospital and had received electroconvulsive therapy; thereafter, she had been discharged to a partial hospital program. She had been hospitalized for psychiatric symptoms twice since then, once for major depressive disorder and once for a mixed bipolar episode that was due to insomnia and anxious distress. The latter episode was associated with catatonic features and was treated with electroconvulsive therapy. The patient had no history of suicidal or homicidal ideation or attempts and no history of violence. She had hypertension, diabetes, obesity, and gastroesophageal reflux disease. Medications included dexamethasone, bupropion, fluoxetine, olanzapine, losartan, metformin, and pantoprazole. Sulfa drugs had caused angio-edema, and lisinopril had caused cough. The patient was born in the Caribbean and had emigrated four decades earlier, first to southwestern Europe and then to the United States 2 years later. She lived in an apartment in an urban area of New England with her father, who had mild dementia. She did not drink alcohol, smoke cigarettes, or use illicit substances. On examination, the temperature was 37.2C, the pulse 97 beats per minute, the blood pressure 15395 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 93 while the patient was breathing ambient air. The patient was alert and oriented but guarded, with a flat affect. She appeared to be more anxious than she had been during the previous hospitalization. She paced around the room and perseverated about the care of her father. The remainder of the examination was normal. The blood levels of electrolytes and glucose were normal, as were the results of liver-function and kidney-function tests. The white-cell count was 11,490 per microliter reference range, 4000 to 11,000, with neutrophil predominance; the complete blood count with differential count was otherwise normal. Urinalysis and a radio-graph of the chest were normal. Treatment with dexamethasone was stopped, and the patient was admitted to the hospital to facilitate discharge to a rehabilitation center for continued care. On hospital day 3, the patient was noted to be more withdrawn, and she began responding to questions with one-word answers or silence. When she was encouraged to speak more, she continued to perseverate about the care of her father. When she was asked to elaborate on her concerns, she stated, He is dead. I am dead. The patient appeared disheveled, sullen, and anxious. She laid in bed motionless with her eyes open and looking forward, and she responded briefly to questions in a quiet voice with slowed speech. Her thoughts were persev-erative and tangential. There was no evidence that she had loosening of associations, hallucinations, or suicidal or homicidal ideation. She had poor insight and judgment. Memory, attention, concentration, abstract reasoning, and fund of knowledge were normal. When her arms and legs were lifted against gravity and released, they fell to the bed without resistance; with encouragement, she was able to move them. Muscle tone was normal, with no rigidity or waxy flexibility. Imaging studies were obtained. Dr. Aaron B. Paul: Computed tomography CT of the head Fig. 1, performed without the administration of intravenous contrast material, revealed no evidence of an acute territorial infarct, intracranial mass, or hemorrhage. There was nonspecific moderate confluent hypoattenu-ation involving the supratentorial white matter. Dr. Kritzer: Clonazepam was administered, and the dose of olanzapine was increased. Admission to an inpatient psychiatric unit was recommended. During the next week, while awaiting placement in an inpatient psychiatric unit, the patient continued to show signs of anxiety and a depressed mood. She said, I am dead. I do not exist. I am not real. She also believed that her father and brother, as well as her nurses and doctors, were dead. The patient was selectively mute and motionless, but she talked and moved with encouragement. She expressed that she felt directly responsible for the Covid-19 pandemic and asked to be thrown out of the window. She had the sensation that her bladder was gone and that she could not urinate, although she had been observed urinating independently. She felt that she could not eat, although she had been observed eating breakfast daily. On hospital day 9, the patient was transferred to the inpatient psychiatric unit of the other hospital. A diagnosis and management decisions were made. OUTPUT:

Cotard’s syndrome, catatonia, depression, and seizure after coronavirus disease 2019.

NEJM_Reasoning_Subset64

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: CME at NEJM.org Dr. Bart K. Chwalisz: A 30-year-old woman was evaluated in the neuro-ophthalmology clinic at a hospital affiliated with this hospital because of monocular vision loss. Two months before the current presentation, during the third trimester of the patients first pregnancy, headache and decreased vision in the right eye developed. The patient thought that the headache felt like previous migraines, which had been infrequent. However, decreased vision had not been a typical feature of her migraines. Colors appeared dim, and light perception was decreased. There was soreness in the right eye but no pain with eye movement. Five days later, the patient was evaluated by an optometrist. She reported that she could see only shapes and movements. On a visual field test, there was a normal response in the left eye but no response in the right eye. The patient was instructed to seek evaluation in an emergency department of another hospital. In the emergency department, magnetic resonance imaging MRI of the head, which was performed without the administration of intravenous contrast material because of the pregnancy, revealed marked enlargement of the intraorbital right optic nerve. The nerve appeared isointense as compared with the extraocular muscles on the T1-weighted sequences but appeared bright on the T2-weighted sequence; the globes appeared normal, and the extraocular muscles were not enlarged. The results of magnetic resonance venography of the head were normal. The patient was admitted to the hospital, and treatment with intravenous methyl-prednisolone was initiated for a working diagnosis of optic neuritis. During the hospitalization, her ability to see colors improved slightly, but her vision did not improve; she could see only hand motions. On the fifth hospital day, she was discharged home with instructions to schedule follow-up appointments with a neurologist and an optometrist. One month after discharge from the other hospital and 2 weeks before the current presentation, the patient was again evaluated by her optometrist. The vision in the right eye had worsened; she was no longer able to see shadows or movements. The patient was referred for evaluation by a neuro-ophthalmologist. On the current presentation to the neuro-ophthalmology clinic of a hospital affiliated with this hospital, the patient reported no improvement in vision and ongoing soreness in the right eye. There was a history of Lyme disease, which had been diagnosed during the second trimester of pregnancy and had been treated with amoxi-cillin. Medications included prenatal vitamins and ferrous sulfate. The patient lived with her husband in New England and worked in health care. She had never smoked tobacco and did not drink alcohol or use illicit drugs. A brother had a history of childhood epilepsy, and her mother had macular degeneration. On examination, the visual acuity was 2015 in the left eye, and there was no light perception in the right eye. The pupils were symmetric and reactive to light, although the response in the right pupil was sluggish; an afferent pupillary defect was present in the right eye. On the Ishi-hara color test, all plates were identified with the left eye. On a visual field test, there was a normal response in the left eye. The Ishihara color test and the visual field test could not be performed on the right eye because of poor vision. The results of a slit-lamp examination were normal, with no cells identified in the anterior chamber or vitreous. On a funduscopic examination Fig. 1A and 1B, the optic disk in the right eye was swollen and had temporal pallor; there was a small area of hypopigmentation close to the macula in the left eye. Optical coherence tomography revealed increased thickness of the retinal nerve fiber layer and circumferential thinning of the ganglion cell complex of the right eye; no abnormalities were noted in the left eye. The blood creatinine level was 0.56 mg per deciliter 50 mol per liter; reference range, 0.60 to 1.50 mg per deciliter 53 to 133 mol per liter and the blood alkaline phosphatase level 147 U per liter reference range, 30 to 100. The results of other kidney-function and liver-function tests were normal, as were the blood levels of electrolytes, the complete blood count, and the results of coagulation tests. The blood C-reactive protein level was 15 mg per liter reference value, 8 and the erythrocyte sedimentation rate 34 mm per hour reference range, 0 to 20. A blood test for antinuclear antibodies was positive at a titer of 1:40 with a speckled pattern. Tests for antibodies against aquaporin-4 and myelin oligo-dendrocyte glycoprotein MOG were negative. A diagnosis of atypical optic neuritis was considered. Because the patient was near delivery, further treatment was delayed until after the birth of her child, which occurred 3 days later. Six days after delivery of the baby, the patient was admitted to this hospital, and additional studies were obtained. Lumbar puncture was performed. On cerebrospinal fluid CSF analysis, there were no nucleated cells, and the levels of protein, glucose, albumin, and IgG were normal. There was no oligoclonal banding after concentration of the CSF. Testing of the CSF was negative for syphilis antibodies and for antibodies against aquaporin-4. Dr. Benjamin M. Kozak: MRI of the head Fig. 2, performed before and after the administration of intravenous contrast material, revealed prominent fusiform enlargement of a segment of the intraorbital right optic nerve with associated enhancement, as well as associated hyperintensity on the T2-weighted short-tau inversion recovery STIR sequence. There was no evidence of associated orbital edema or other orbital abnormalities. There was a punctate hyperintense focus within the left parietal subcortical white matter on the T2-weighted fluid-attenuated inversion recovery sequence, without associated enhancement or restricted diffusion. Dr. Chwalisz: Treatment with intravenous methyl-prednisolone and daily plasmapheresis was administered. On the fourth hospital day, the soreness in the right eye had resolved, and there was light perception in the right eye. On the fifth hospital day, treatment with intravenous methylprednisolone was changed to oral predni-sone. On the ninth hospital day, rituximab was administered, and the patient was discharged home with a prescription for a 7-week tapering course of prednisone. During the next 3 weeks, treatment with rituximab was administered weekly. Two weeks after the last rituximab infusion, the patient was evaluated in the neuro-ophthalmology clinic at the hospital affiliated with this hospital. She reported no eye pain and only occasional headache, but she noted that the vision in the right eye had worsened. Examination revealed no light perception in the right eye, with an afferent pu-pillary defect. The results of a visual field test and the Ishihara color test were unchanged from the previous evaluation in the neuro-ophthalmology clinic. On a funduscopic examination Fig. 1C, the optic disk in the right eye was swollen and had more pronounced temporal pallor; optociliary shunt vessels were also newly present. Additional imaging studies were obtained. Dr. Kozak: Follow-up MRI of the head Fig. 2 revealed no radiologically significant change in the segmental enlargement of the intraorbital right optic nerve, with persistent enhancement as well as hyperintensity on the T2-weighted STIR sequence. No new orbital abnormalities were present. In addition, the punctate lesion in the left parietal subcortical white matter was unchanged. Dr. Chwalisz: A diagnostic procedure was performed. OUTPUT:

Meningioma, meningothelial type, World Health Organization grade 1.

NEJM_Reasoning_Subset65

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: CME at NEJM.org Dr. Jarone Lee: A 55-year-old man was admitted to this hospital 7 months after kidney transplantation because of fatigue, weight loss, and new pulmonary nodules. The patient had been in his usual state of health until 1 week before this admission, when severe fatigue and generalized weakness developed. He had lost 4.5 kg in the past month after making healthier dietary choices; however, he had also noticed abdominal discomfort and a decrease in appetite. During the next week, the patient was able to eat and drink very little and lost an additional 4.5 kg. The fatigue and weakness worsened, and he mostly stayed in bed. He had several episodes of lightheadedness, gait instability, and falls while he was walking to the bathroom. There was new odynophagia, dysphagia, and nausea. On the day of admission, the patient was evaluated at the transplant nephrol-ogy clinic of this hospital before a scheduled infusion of belatacept. The temperature was 37.3C, the blood pressure 7050 mm Hg, the heart rate 98 beats per minute, the respiratory rate 35 breaths per minute, and the oxygen saturation 96 while he was breathing ambient air. He appeared cachectic and lethargic. He was transported by ambulance from the clinic to the emergency department of this hospital. In the emergency department, the patient reported malaise and feeling like he had no energy or strength. The lightheadedness and gait instability persisted. A review of systems was notable for shortness of breath, dark urine, and continued anorexia, nausea, odynophagia, dysphagia, and abdominal discomfort. He reported no chills, night sweats, cough, chest pain, vomiting, hematochezia, melena, or dysuria. The patient had a history of sarcoidosis. Nine years before this admission, nephrocalcinosis caused end-stage kidney disease. Hemodialysis was started, and this treatment was continued until a deceased-donor kidney transplantation was performed 7 months before this admission. Routine serologic testing performed before transplantation was positive for EpsteinBarr virus EBV IgG and cytomega-lovirus CMV IgG. An interferon- release assay for Mycobacterium tuberculosis was negative. Serologic testing in the donor was also positive for EBV IgG but was negative for CMV IgG. Induction immunosuppressive therapy with antithymocyte globulin was initiated; maintenance therapy included prednisone, mycopheno-late mofetil, and tacrolimus. Six months before the current admission, pathological examination of a biopsy specimen from the transplanted kidney revealed vascular disease of donor origin and acute tubular injury but no evidence of T-cellmediated or antibody-mediated rejection. Treatment with tacrolimus was stopped and belatacept started; prednisone and mycophenolate mofetil therapy was continued. One month before the current admission, pathological examination of another biopsy specimen from the transplanted kidney revealed focal infiltrates that were vaguely granulomatous and were associated with ruptured tubules and interstitial TammHorsfall protein also known as uromodulin. There was no evidence of allograft rejection. Two weeks before the current admission, laboratory tests revealed a blood creatinine level of 2.31 mg per deciliter 204.2 mol per liter; reference range, 0.60 to 1.50 mg per deciliter 53.0 to 132.6 mol per liter; routine laboratory tests had revealed similar creatinine levels during the previous 6 months. Other laboratory test results are shown in Table 1. The patient also had a history of hypertension, hyperlipidemia, and gout. Current medications included aspirin, atorvastatin, labetalol, nifedip-ine, trimethoprimsulfamethoxazole, valganci-clovir, prednisone, mycophenolate mofetil, and belatacept. There were no known drug allergies. The patient lived with his mother in an urban area of New England and had never traveled outside the region. He worked as an administrator and had never been homeless or incarcerated. He had no sexual partners and did not smoke tobacco, use illicit drugs, or drink alcohol. On the day of evaluation in the emergency department, the temperature was 36.7C, the blood pressure 8050 mm Hg, the heart rate 100 beats per minute, the respiratory rate 24 breaths per minute, and the oxygen saturation 92 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 20.5. The patient was lethargic and spoke in sentences of three or four words. The mucous membranes were dry, and the throat could not be evaluated because of nausea. There was no cervical lymph-adenopathy. Auscultation of the lungs revealed diffuse inspiratory crackles. Neurologic examination was limited but was notable for 45 motor strength in the arms and legs. The blood level of creatinine was 5.05 mg per deciliter 446.4 mol per liter, the calcium level 13.1 mg per deciliter 3.3 mmol per liter; reference range, 8.5 to 10.5 mg per deciliter 2.1 to 2.6 mmol per liter, the lactic acid level 4.4 mmol per liter 39.6 mg per deciliter; reference range, 0.5 to 2.0 mmol per liter 4.5 to 18.0 mg per deciliter, and the hemoglobin level 6.6 g per deciliter reference range, 13.5 to 17.5. Cultures of blood were obtained. Other laboratory test results are shown in Table 1. Dr. Mark C. Murphy: Computed tomography CT of the chest, abdomen, and pelvis was performed without the administration of intravenous contrast material. CT of the chest Fig. 1 revealed innumerable bilateral miliary pulmonary nodules that were new relative to a CT scan that had been obtained 6 months earlier. The nodules were in a random distribution that was suggestive of a hematogenous origin. Trace bilateral pleural effusions were present, as was calcified mediastinal and bilateral hilar lymphadenopathy; the lymphadenopathy appeared unchanged from previous imaging. CT of the spleen Fig. 2 revealed new splenomegaly. There was new mild dilatation of the renal collecting system of the transplanted kidney in the right lower quadrant of the abdomen. Dr. Lee: While the patient was being evaluated in the emergency department, the temperature increased to 39.6C. Intravenous fluids and intravenous infusion of phenylephrine were administered. Empirical treatment with vancomycin, ce-fepime, metronidazole, levofloxacin, doxycycline, and micafungin was started; trimethoprimsul-famethoxazole and valganciclovir were continued. Treatment with prednisone and mycophenolate mofetil was discontinued, and hydrocortisone therapy was started. The patient was admitted to the intensive care unit. Within 24 hours after admission, the oxygen saturation had decreased to 84 while the patient was breathing ambient air; supplemental oxygen was administered through a nasal cannula at a rate of 2 liters per minute, and the oxygen saturation increased to 94. Continuous intra-venous infusion of phenylephrine was continued, and norepinephrine was added to maintain a mean arterial blood pressure above 65 mm Hg. Two units of packed red cells were transfused. The creatinine level decreased to 3.82 mg per deciliter 337.7 mol per liter, the lactic acid level to 1.6 mmol per liter 14.4 mg per deciliter, and the calcium level to 8.9 mg per deciliter 2.2 mmol per liter. Treatment with levofloxacin and micafungin was stopped; isavuconazole was started. A diagnostic test was performed. OUTPUT:

Disseminated Mycobacterium tuberculosis infection.

NEJM_Reasoning_Subset66

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Kathy M. Tran Medicine: A 21-year-old woman was evaluated at this hospital because of fatigue, weight gain, and abdominal pain. The patient had been well until 4 months before the current evaluation, when an episode of dull, aching pain in the right lower quadrant occurred. The pain lasted for a few hours before resolving spontaneously. During the next 4 months, episodes of abdominal pain continued to occur and increased in duration, frequency, and severity. The patient sought evaluation in the gynecology clinic of this hospital. On evaluation, the patient described the pain as variable, rating it between 3 and 8 on a scale of 0 to 10, with 10 indicating the most severe pain. The episodes of pain occurred daily and lasted for up to 20 hours. The pain decreased with sitting or lying down and did not increase with movement; it was not associated with her menstrual period. The patient also reported fatigue, irritability, and weight gain of 4.5 kg in the previous 4 months despite increased exercise and decreased food intake. There was a history of hypothyroidism, anxiety, irritable bowel syndrome, and migraines. The patient had never been pregnant and had no known history of sexually transmitted infections or abnormal results on screening tests for cervical cancer. She had previously been sexually active with male partners, but she reported no current sexual activity. She had taken oral contraceptives for 2 years but had stopped taking them 6 months before this evaluation, when a levonorgestrel-releasing intrauterine device IUD was placed. Other medications included levo-thyroxine, citalopram, and multivitamins; there were no known drug allergies. The patient lived with roommates in an urban area of New England. She was a former athlete and worked as a research scientist. She did not smoke cigarettes, drink alcohol, or use illicit drugs. Her family history included hypothyroidism in her mother, coronary artery disease and hyperlipidemia in her father, breast cancer and diabetes in her paternal grandmother, and lung cancer in her paternal grandfather. CME at NEJM.org On examination, the blood pressure was 11973 mm Hg and the heart rate 62 beats per minute. The body-mass index the weight in kilograms divided by the square of the height in meters was 28.4. The thyroid was firm on palpation, with a small nodule noted on the right side. The abdomen was nondistended, soft, and nontender. A small hernia with a thrill was noted at the right inguinal ring. A speculum examination of the vagina and cervix was normal; IUD strings were visible at the cervical os. The complete blood count was normal, as were blood levels of electrolytes and glucose and results of tests for kidney, liver, and thyroid function. Screening tests for gonorrhea, chlamydia, human immunodeficiency virus, and syphilis were negative. Imaging studies were obtained. Dr. Madeleine Sertic: Transabdominal and trans-vaginal ultrasonography of the abdomen and pel-vis revealed a mass measuring 4.8 cm by 5.0 cm by 3.9 cm along the posterior aspect of the right hepatic lobe Fig. 1A. The uterus, ovaries, and adnexa were normal. There was no free fluid in the pelvis, and the IUD was in an appropriate position. Magnetic resonance imaging of the abdomen, performed before and after the administration of intravenous contrast material, revealed a right adrenal mass measuring 4.5 cm by 4.7 cm by 4.0 cm that was T2 isointense Fig. 1B and T1 hypointense. The mass had diffusion restriction Fig. 1C, as well as early enhancement with washout, which refers to the temporal reduction in the enhancement of a lesion. The features were indeterminate and were not definitively diagnostic of adrenal adenoma or another adrenal lesion, such as pheochromocytoma or adre-nocortical carcinoma. Computed tomography CT of the abdomen and pelvis again revealed a right adrenal mass, which had a density of 33 Hounsfield units HU before the administration of contrast material Fig. 1D, 74 HU during the portal-venous phase Fig. 1E, and 45 HU during the 15-minute delayed phase Fig. 1F. The absolute washout was calculated as 71. The absolute washout is calculated by dividing the difference between the portal-venousphase density and the delayed-phase density by the difference between the portal-venousphase density and the unenhanced density and then converting the result to a percentage: HU portal-venous phase HU delayed phase HU portal-venous phase HU unen-hanced 100. Adrenal adenomas tend to wash out faster than other adrenal lesions, and an absolute washout of more than 60 is highly suggestive of an adrenal adenoma. However, lesions larger than 4 cm are likely to be malignant, regardless of the washout characteristics.1 There was also a thin-walled cyst measuring 3.3 cm in diameter in the lower lobe of the left lung. Dr. Tran: The patient was referred to the endocrinology clinic of this hospital. Additional laboratory tests were performed to further evaluate the adrenal mass. Blood levels of renin and aldo-sterone were normal, as were urinary levels of catecholamines and metanephrines. An overnight, low-dose dexamethasone suppression test was performed. The baseline blood corticotropin level was 3 pg per milliliter 0.7 pmol per liter; reference range, 6 to 76 pg per milliliter 1.3 to 16.7 pmol per liter. At 11 p.m., dexamethasone 1 mg was administered; at 8 a.m., the blood cortisol level was 9.1 g per deciliter 251 nmol per liter; reference value, 1.8 g per deciliter 50 nmol per liter, and the concurrent blood dexamethasone level was 631 ng per deciliter reference range, 140 to 295. The 24-hour urinary free cortisol level was 31.0 g reference range, 3.5 to 45.0; the blood levels of dehydro-epiandrosterone and dehydroepiandrosterone sulfate were normal. Management decisions were made. OUTPUT:

Adrenocortical carcinoma.

NEJM_Reasoning_Subset67

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Megan E. Bunnell Obstetrics and Gynecology: A 31-year-old woman was admitted to this hospital 15 days after the birth of her first child because of abdominal pain and fever. The patient had received routine prenatal care at this hospital. Serologic screening during the pregnancy showed immunity to rubella. Rectovaginal culture was positive for group B streptococcus. Tests for syphilis, hepatitis B virus surface antigen, gonorrhea, chlamydia, and human immunodeficiency virus were negative. Sixteen days before this admission, the patient went into labor at 38 weeks 1 day of gestation. She was admitted to this hospital. The white-cell count was 13,800 per microliter reference range, 4500 to 11,000, and the hemoglobin level was 14.0 g per deciliter reference range, 12.0 to 16.0; treatment with intravenous penicillin was started. On hospital day 2, an epidural anesthetic agent was administered. Artificial rupture of the membranes revealed clear, odorless fluid, and infusion of oxytocin was started. Six hours after artificial rupture of the membranes, the patient gave birth to a healthy baby by vaginal delivery. Three minutes later, the placenta was delivered intact. Immediately after delivery, hemorrhage due to uterine atony occurred; there was an estimated blood loss of 500 ml. Bimanual massage of the uterus was performed, and oxytocin and methylergonovine were administered; hemostasis was subsequently achieved. A perineal laceration was repaired. The patient began breast-feeding, and on postpartum day 1, she was discharged. Six days before the current admission, on postpartum day 9, pain in the left upper quadrant developed. The pain was dull, radiated to the left flank and back, and was worse with movement and deep breathing. The patient presented to a local urgent care clinic; urine was obtained for culture, and empirical treatment with amoxicillinclavulanate was started. Five days before this admission, on postpartum day 10, abdominal pain persisted, and a fever with a temporal temperature of 38.3C developed. The patient sought evaluation in the emergency department of this hospital. She rated the abdominal pain at 10 on a scale of 0 to 10, with 10 indicating the most severe CME at NEJM.org pain. A review of systems was notable for nausea and minimal lochia; there was no diarrhea, constipation, dysuria, hematuria, or breast tenderness. On examination, the abdomen was soft, and there was mild tenderness on palpation of the left upper quadrant, the uterine fundus, the supra-pubic region, and the left costovertebral angle. Pelvic examination, including examination with the use of a speculum, revealed no dehiscence, drainage, or hematoma at the site of the peri-neal laceration repair and no discharge from the cervical os; there was mild cervical motion tenderness. The white-cell count was 20,700 per microliter. The level of hemoglobin was 11.4 g per deciliter. Blood cultures were obtained. The urine culture obtained at the urgent care clinic was positive for group B streptococcus. Other laboratory test results are shown in Table 1. Treatment with ceftriaxone was started, and the patient was admitted to the hospital for presumed pyelonephritis. On hospital day 3, when the fever and abdominal pain resolved, the patient was discharged home to complete a course of amoxicillin. During the subsequent 2 days, the patient continued to take amoxicillin at home, but fever and abdominal and flank pain returned. On postpartum day 15, when the pain did not abate after she took acetaminophen, she returned to the emergency department of this hospital. The patients medical history included high-grade cervical dysplasia that had led to a loop electrosurgical excision procedure 5 years earlier, as well as a ruptured ovarian cyst 3 years earlier and nephrolithiasis on the left side 5 months earlier. The patient had not been pregnant before the recent pregnancy; before this pregnancy, she had taken oral contraceptives for 12 years. She took prenatal vitamins, as well as polyethylene glycol, docusate, acetaminophen, and ibuprofen as needed. She had no known drug allergies. She lived with her husband and newborn infant in an urban area of New England and worked as an office manager. She did not smoke tobacco, drink alcohol, or use illicit drugs. Her mother had multiple sclerosis and her father had coronary artery disease; her brother was healthy. On examination, the abdomen was soft, and there was mild tenderness in the left upper quadrant and at the left costovertebral angle. There was no tenderness on palpation of the uterine fundus or the suprapubic region and no cervical motion tenderness. The white-cell count was 10,330 per microliter. The hemoglobin level was 11.2 g per deciliter, the alanine aminotrans-ferase ALT level 153 U per liter reference range, 7 to 33, the aspartate aminotransferase AST level 44 U per liter reference range, 9 to 32, and the alkaline phosphatase level 194 U per liter reference range, 30 to 100. Other laboratory test results are shown in Table 1. The patient was admitted to this hospital. The next day, the hemoglobin level decreased to 9.7 g per deciliter. Additional studies were performed, and a diagnosis was made. OUTPUT:

Hepatic adenoma.

NEJM_Reasoning_Subset68

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: CME at NEJM.org Dr. J. Sawalla Guseh: A 38-year-old man was evaluated at the cardiology clinic of this hospital because of exertional chest discomfort. The patient had been a competitive athlete in the past and had remained an avid runner. Approximately 15 years before the current evaluation, while he was running, he had episodes of flushing with diffuse cutaneous swelling involving the face, lips, hands, and trunk, along with hives on the abdomen and legs and associated dyspnea. The first episode occurred in autumn and the second episode the following summer. After the second episode, he lost consciousness while sitting on a bench. The next day, he was evaluated at an urgent care center. A Holter monitor was placed, and a transthoracic echocardiogram TTE was reportedly normal. The patient consulted with an allergist, who made a diagnosis of food-related exercise-induced anaphylaxis with reactions to soybeans, chickpeas, and tahini, on the basis of the foods he had eaten before these episodes and the results of radioallergosorbent testing. An epinephrine autoinjector was prescribed for use during future episodes, but the anaphylaxis symptoms did not recur. Approximately 4 months before the current evaluation, during a routine 5-mile jog, the patient had a new sensation that he described as my heart beating out of my chest. He rested, and the symptom subsided; he completed his run. One month later, during a bicycle ride, he had crampy discomfort in the anterior chest, which abated when he stopped cycling. Two weeks before the current evaluation, during a jog of several miles, he had cramping pain in the anterior chest on the left side that gradually escalated over a 5-minute period. He started walking, and the pain abated; he ran for an additional 20 minutes without a recurrence of pain. He sought an evaluation in the cardiology clinic of this hospital to determine the cause of his symptoms and the safety of continued vigorous exercise. On evaluation in the cardiology clinic, a review of systems was negative for dyspnea, recent syncope, orthopnea, edema, cough, hemoptysis, and recent allergic symptoms. The patient ran or cycled four times per week and had previously completed a marathon. His medical history included attention deficithyperactivity disorder. Five years earlier, an episode of syncope had occurred in the context of multiple episodes of nonbloody diarrhea, abdominal discomfort, and chills. His surgical history included two colonic polypectomies, one 6 years before this evaluation and the other 1 month before this evaluation; pathological examination of the polyps had revealed lymphoid aggregates and hyperplastic polyps. The patient took no medications and reported no adverse reactions to medications. The patient worked in the financial sector and lived with his wife and children. He did not use tobacco, alcohol, or other substances. Multiple maternal relatives had had colon cancer, and an older brother had had colonic polyps removed in his fourth decade of life. There was a family history of hypertension. On examination, the blood pressure was 12284 mm Hg measured in both arms, the heart rate 54 beats per minute, and the oxygen saturation 99 while the patient was breathing ambient air. There were mild expiratory wheezes; the remainder of the examination was normal. An electrocardiogram ECG showed sinus bradycardia and anterior T-wave abnormalities, findings that had been observed on tracings obtained 5 years earlier during an evaluation for presyncope; a TTE obtained at that time had been normal. Sinus bradycardia and anterior T-wave abnormalities had not been observed on tracings obtained 15 years earlier Fig. 1A, 1B, and 1C. The white-cell count and platelet count were normal, as were blood levels of hemoglobin, electrolytes, calcium, and thyrotropin and results of renal-function tests. The high-sensitivity troponin level was 10 ng per liter reference range, 0 to 14. Plasma metanephrines were undetectable, and the normetanephrine level was normal. The next day, a TTE showed no abnormalities of cardiac chamber size and function and no evidence of valvular dysfunction. An ambulatory patch heart monitor, applied to evaluate cardiac rhythm over a 2-week period, revealed sinus rhythm without arrhythmia. A cardiopulmonary exercise stress test was performed; the patient exercised for 19 minutes 17 seconds according to a treadmill protocol that increased incrementally to maximal effort with a respiratory exchange ratio of 1.12 and a maximum heart rate of 181 beats per minute 99 of the age-predicted maximum. At peak effort, the stress test did not reproduce symptoms, and he stopped because of leg fatigue. An ECG showed 0.5-mm horizontal ST-segment depression in leads III, aVF, V3, and V6, along with isolated premature ventricular contractions. The ventila-tory efficiency was normal. Additional diagnostic testing was performed, and management decisions were made. OUTPUT:

Cardiac paraganglioma with a germline mutation in the gene encoding succinate dehydroge-nase subunit C (SDHC).

NEJM_Reasoning_Subset69

As a meticulous physician, your task is to provide at least 10 accurate and distinct differential diagnoses for patients based on the input case report. Ensure that you list each diagnosis on a separate line and cover a wide range of unique possibilities. Follow the guideline for generation: Guideline: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Note: Ensure to provide at least 10 diagnoses in order of likelihood, with the most likely diagnosis listed first. We need to calculate the accuracy of all the top 10 performance of the output. Let’s think step by step. ***Output format***: Differential diagnosis: 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. INPUT: Dr. Peiyun Ni (Medicine): A 63-year-old woman was admitted to this hospital because of fever, headache, sore throat, and confusion. The patient had been well until 2 weeks before this admission, when fever, chills, myalgias, and headache developed. She also had sore throat, odynophagia, and the feeling of a “lump” in the neck. The patient was concerned that she had coronavirus disease 2019 (Covid-19) and sought evaluation at an urgent care clinic of another hospital. Testing of a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was negative, and she was instructed to quarantine at home. Five days before this admission, the patient returned to the clinic of the other hospital because of persistent symptoms, including daily fevers. The temperature was 37.2°C, and the remainder of the physical examination was reportedly normal. Testing of another nasopharyngeal swab for SARS-CoV-2 RNA was negative, as was testing of an oropharyngeal swab for the rapid detection of streptococcal antigen. On the day of admission, the patient’s sister visited the patient and noticed that she had difficulty with word finding and performing basic tasks at home. Emergency medical services were called, and the patient was transported to the emergency department of this hospital. On evaluation, the patient reported fevers, chills, myalgias, fatigue, generalized weakness, headaches, sore throat, and odynophagia. She acknowledged that she had mild confusion and “mental slowness” of 2 weeks’ duration. A review of systems was notable for a lump in the neck, poor appetite, unintentional weight loss of 3 kg in the past 2 weeks, and anosmia for the past year, with onset before the beginning of the Covid-19 pandemic. There was no neck stiffness, photophobia, cough, dyspnea, abdominal pain, diarrhea, or dysuria. The patient had hypertension for which she took amlodipine and lisinopril; there were no known drug allergies. She was born in South America and had im-migrated to the United States two decades earlier. She lived in an urban area of New England with her mother and son. Her son had a brain injury and was seen by visiting nurses daily; one nurse had had a positive SARS-CoV-2 test 4 days before this evaluation. There were no other sick contacts. The patient worked in management and enjoyed gardening as a hobby. She had no recent insect bites or travel. Although she had not been sexually active for several years, she had had an episode of unprotected sexual intercourse with a new male partner 3 weeks before this evaluation. She smoked four cigarettes daily and had done so for 40 years. She did not drink alcohol or use illicit drugs. Her mother had Alzheimer’s disease. The temperature was 38.9°C, the blood pressure 160/80 mm Hg, the pulse 96 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 97% while the patient was breathing ambient air. The body-mass index (the weight in kilograms divided by the square of the height in meters) was 29.9. The patient appeared fatigued and was alert and oriented. She was unable to perform simple calculations, to list the days of the week in reverse order, or to follow two-step commands. The mucous membranes were dry, and a small non-tender lymph node was palpable in the posterior neck on the left side. The white-cell count was 3700 per microliter (reference range, 4500 to 11,000); the aspartate aminotransferase level was 280 U per liter (reference range, 9 to 32) and the alanine aminotransferase level 235 U per liter (reference range, 7 to 33). Additional laboratory test results are shown in Table 1. Urinalysis revealed the presence of ketones, nitrites, and protein; there were fewer than 10 white cells per high-power field (reference range, <10). Testing of a third nasopharyngeal swab for SARS-CoV-2 RNA was negative, and blood specimens were obtained for culture. Dr. William A. Mehan: A radiograph of the chest was normal. Ultrasonography of the abdomen showed gallbladder sludge. Computed tomography (CT) of the abdomen, performed after the intravenous administration of contrast material, showed prominent gastrohepatic, periportal, peri-aortic, and inguinal lymph nodes, the largest measuring 1.4 cm in diameter. CT of the head, performed without the intravenous administration of contrast material, showed mild scattered hypodensities in the peri-ventricular and subcortical white matter of the cerebral hemispheres. Magnetic resonance imaging (MRI) of the head, performed before and after the intravenous administration of contrast material, was notable for multifocal patchy hyper-intensities throughout the juxtacortical and deep white matter of the cerebral hemispheres on fluid-attenuated inversion recovery images, without corresponding restricted diffusion or abnor-mal enhancement (Fig. 1). The findings were unchanged from MRI findings obtained 3 months before presentation. Dr. Ni: Empirical treatment with intravenous ceftriaxone and acyclovir was started, and the patient was admitted to the hospital. A lumbar puncture was performed. The opening pressure was 24 cm of water; the cerebrospi-nal fluid (CSF) was clear and colorless. On CSF analysis, the total protein level was 201 mg per deciliter (reference range, 5 to 55) and the glucose level 43 mg per deciliter (2.4 mmol per liter; reference range, 50 to 75 mg per deciliter [2.8 to 4.2 mmol per liter]). There were 73 white cells per microliter (reference range, 0 to 5), of which 65% were lymphocytes, 29% plasma cells, and 6% monocytes. Gram’s staining showed abundant mononuclear cells and no organisms. The intravenous administration of ceftriaxone and acyclovir was stopped. A diagnostic test was performed. OUTPUT:

Acute human immunodeficiency virus type 1 infection.