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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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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 diagnoses for patients based on the input case report. This is part of an experiment comparing your diagnoses with those of human experts, using cases from the New England Journal of Medicine. Note that you are not treating any patients. Key points: 1) Usually, there is a single definitive diagnosis known to exist in humans. 2) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 3) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Provide the top 10 most likely diagnoses, listed in order of likelihood and being as specific as possible. Think step by step: Read the input case report, noting key symptoms, history, and test results. Identify the most likely diagnosis. Consider alternative diagnoses. Ensure each diagnosis is precise and distinct. Rank the diagnoses by likelihood. Generation guidelines: Each diagnosis should be precise and unique, with at least 10 possibilities. List one diagnosis per line. Provide the diagnoses in order of likelihood, with the most likely first. 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.