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NEJM_Reasoning_Subset0 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: Dr. Shaan Khurshid: A 56-year-old man presented to this hospital in early autumn with a 1-month history of myalgias and fever. Approximately 4 weeks before the current presentation, the patient began to have generalized myalgias and arthralgias, which were worst in the shoulders, proximal arms, and upper back. He had fever with temperatures of up to 38.2C, along with chills and diaphoresis. He took naproxen, and the next day, he presented to an urgent care clinic affiliated with this hospital. The temperature was 37.2C, the heart rate 72 beats per minute, the blood pressure 17595 mm Hg, and the oxygen saturation 100 while he was breathing ambient air; the remainder of the physical examination was normal. A test for severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 RNA was negative. Symptoms abated after 3 days, but then fever with temperatures of up to 38.3C and fatigue occurred. The patient stopped consuming alcohol. Three weeks later, the patient had episodes of mild dyspnea with coughing fits and presented to a second urgent care clinic affiliated with this hospital. The temperature was 37.2C, the heart rate 59 beats per minute, the blood pressure 13875 mm Hg, and the oxygen saturation 98 while he was breathing ambient air. He appeared fatigued, but the remainder of the physical examination was normal. Another test for SARS-CoV-2 RNA was negative, and the results of urinalysis and chest radiography were normal. The next day, the patient was evaluated by his primary care physician at another hospital. He reported a 1-month history of stabbing back pain between his shoulders, which was worst at the end of the day and was not relieved with the use of naproxen or a heating pad. The temperature was 36.7C, the heart rate 48 beats per minute, the blood pressure 12272 mm Hg, and the oxygen saturation 100 while he was breathing ambient air. There was tenderness on palpation of the left thoracic paraspinal area, but the remainder of the physical examination was normal. Radiographic images of the thoracic spine were reportedly normal. Laboratory test results obtained at that time are shown in Table 1, alongside routine test results obtained 6 months earlier. The patient was referred to the emergency department of this hospital. On the systems review, the patient reported that he had recently measured heart rates of 40 to 50 beats per minute on his home pulse oximeter; his baseline heart rate was 80 to 90 beats per minute. He also reported a history of dysuria that was attributed to chronic prostatitis, as well as pain in the left wrist and knee that was attributed to gout. He reported no weight loss, sweats, palpitations, dyspnea, dizziness, lightheadedness, chest discomfort, joint swelling or redness, rash, headache, focal neurologic symptoms, nausea, vomiting, diarrhea, or rectal bleeding. The patients medical history was notable for sickle cell trait, hypertension with mild left ventricular hypertrophy, palpitations, unprovoked pulmonary embolism, obstructive sleep apnea, hyperuricemia, latent tuberculosis, malaria, chronic hepatitis B virus infection, Helicobacter pylori infection, colonic schistosomiasis, prostatism, and thrombocytopenia. His last dental procedure had taken place more than 2 years earlier. Medications included aspirin, metoprolol, and losartan, as well as sildenafil as needed. He had received two vaccines for coronavirus disease 2019 Covid-19, with the second vaccine administered 7 months before the current evaluation. There were no known adverse reactions to medication. The patient grew up in equatorial Central Africa. He had immigrated to the United States 20 years earlier and had not returned to Africa for more than 5 years. He was employed at a local university and occasionally had contact with college students. He lived with his family in a suburb of Boston. During the summer months, he had visited islands in Massachusetts and coastal wooded areas to hike, camp, and swim. The patient reported that he had encountered many ticks but had not received a tick bite. He had been scratched by cats; there were no other animal exposures. In the past, he had consumed two or three beers daily, but he had stopped all alcohol intake during the previous month. He had never used tobacco or illicit substances. His family history was notable for atherosclerotic coronary disease. On examination, the temperature was 36.5C, the heart rate 46 beats per minute, the blood pressure 14165 mm Hg, and the oxygen saturation 100 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 34.4. He appeared comfortable. Auscultation of the chest revealed a bradycardic heart rate. There was tenderness on palpation of the left infrascapular area. A prostate examination revealed a nontender hemorrhoid. There was no rash or lymphadenopathy, and the remainder of the examination was normal. Blood levels of calcium, total protein, and thyrotropin were normal, as were the results of liver-function tests. Other laboratory test results are shown in Table 1. Blood cultures were obtained. Electrocardiograms were notable for sinus rhythm with first-degree and second-degree 2:1 atrioventricular block with intermittent right bundle-branch block Fig. 1A, alternating with sinus rhythm with third-degree complete atrio-ventricular block and junctional escape rhythm with intraventricular conduction delay Fig. 1B. Computed tomography CT of the chest, abdomen, and pelvis, performed after the administration of intravenous contrast material, was negative for pulmonary embolism. Intravenous ceftriaxone, naproxen, acetaminophen, and oxycodone were administered. The patient was evaluated by an electrophysiologist and admitted to the cardiology unit of this hospital. The next day, the heart rate remained at approximately 40 beats per minute, and the maximum temperature was 37.8C. Oxycodone and topical lidocaine were administered. Dr. Alex L. Huang: Transthoracic echocardiogra-phy TTE revealed normal biventricular systolic function, with no regional left ventricular wall-motion abnormalities. There was mild diastolic mitral and tricuspid regurgitation Fig. 1C, a finding consistent with atrioventricular block.1 There was no evidence of valvular vegetations. Dr. Khurshid: The blood level of high-sensitivity troponin was 63 ng per liter. Urinalysis was negative, as were blood tests for Lyme disease antibodies, anti-rickettsia IgM, ehrlichia and ana-plasma DNA, human immunodeficiency virus types 1 and 2, and babesia. On the third hospital day, tests for SARS-CoV-2, Bartonella henselae and B. quintana antibodies, and anti-treponemal antibodies were negative. An interferon- release assay for Mycobacterium tuberculosis was positive. Dr. Borek Foldyna: The patient underwent cardiac CT with electrocardiographic gating, including contrast-enhanced CT angiography and delayed imaging. Epicardial fat and a thickened interatrial septum abutting the noncoronary sinus of the aortic valve showed increased radioden-sity on delayed imaging Fig. 2A and 2B; these findings are suggestive of inflammatory changes and may indicate evolving abscess. The tricus-pid aortic valve had mildly thickened leaflets, but there was no evidence of focal valvular vegetations, thrombi, or calcifications. Dr. Khurshid: Oral doxycycline was administered. On the fourth hospital day, the ventricular rate measured between 30 and 40 beats per minute, and the maximum temperature was 37.9C.
OUTPUT:
| Regional myocarditis due to infection with Listeria monocytogenes. |
NEJM_Reasoning_Subset1 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: Dr. Suma Babu: A 67-year-old man was evaluated in the sleep clinic at this hospital because of odd behaviors during sleep, daytime sleepiness, and apnea detected on a home sleep study. Three years before the current evaluation, the patients wife noticed that the patient had vocalizations, including talking and yelling, while sleeping. He also had thrashing movements while sleeping; he fell out of bed more than once and inadvertently hit his wife during these movements. Two years before the current evaluation, the patients wife noticed that the patient had prolonged episodes of daytime sleepiness. During the episodes, he appeared to fall asleep while sitting up and was unresponsive to shaking and loud voices; several hours later, he returned to normal interaction without any intervention. The daytime sleepiness was intermittent and fluctuated in severity. Four months before the current evaluation, the patient fell asleep while washing dishes. This resulted in a fall and unstable C1 spinal fracture, which required urgent surgical repair. After the surgical repair, melatonin and trazodone were prescribed for insomnia, and abnormal movements during sleep abated. However, vocalizations during sleep including singing, talking, and expression of fear and anger in the context of upsetting dreams continued and were most prominent in the early morning hours. The patient also had a motor neurologic syndrome that had started before the onset of sleep symptoms, approximately 3.5 years before the current evaluation. Symptoms included progressive gait imbalance with falls, hand clumsiness, hoarse voice, and dysphagia. Serial neurologic examinations, performed over a 3-year period by multiple neuromuscular specialists, revealed slow progression of generalized fasciculations and the development of bulbar hyperreflexia, postural instability, and hypophonia, although strength in the arms and legs remained intact. Serial electromyography revealed progressive and widespread involvement of muscles showing chronic reinnervation changes, including eventual involvement of craniobulbar muscles tongue and masseter muscles. CME at NEJM.org Dr. Brian Zhao: One year before the current evaluation, magnetic resonance imaging MRI of the cervical spine revealed moderate neural foraminal narrowing at the level of C3C4 bilaterally and no central canal stenosis. Four months before the current evaluation, MRI of the head revealed a punctate subacute infarct in the left posterior centrum semiovale, chronic infarcts in the left middle frontal gyrus and right cerebellum, and nonspecific moderate-to-severe white-matter changes Fig. 1. Dr. Babu: Blood tests for paraneoplastic, nutritional, and paraproteinemic causes of the patients neurologic syndrome were unrevealing. A diagnosis of slowly progressive motor neuron disease was made, and therapy with riluzole was begun. A videofluoroscopic swallowing study revealed severe oropharyngeal dysphagia with laryngeal penetration and silent aspiration; a gastrostomy tube was placed, and tube feeding was initiated. The patient underwent a home sleep-apnea test, which showed sleep-disordered breathing with an apneahypopnea index of 20 events per hour; hypoxemia was present at rest while he was breathing ambient air. Severe oxygen de-saturation occurred with frequent respiratory events while he was asleep in the supine position. The patient was then referred to the sleep clinic for an initial evaluation. On evaluation in the sleep clinic, the patient reported that obstructive sleep apnea had been diagnosed on the basis of a home sleep study performed 1 year earlier. Multiple attempts at treatment with continuous positive airway pressure CPAP had been unsuccessful; there had been difficulty in finding a mask that fit comfortably. In addition to the sleep and motor neurologic syndrome described previously, the patients symptoms included snoring, difficulty with sleep initiation, forgetfulness, poor judgment regarding his ability to safely complete physical tasks, urinary urgency and frequency, and night sweats. He had a history of type 2 diabetes mellitus, which was well controlled with insulin and had been complicated by mild, stable, length-dependent sensory polyneuropathy; other history included hyperlipidemia, a heterozygous factor V Leiden mutation, depression, orthostatic hypotension, and gastroesophageal reflux disease. Medications included alprazolam, bupropion, fenofibrate, insulin, melatonin, metformin, riluzole, sertraline, and trazodone; there were no known drug allergies. The patient lived in New England with his wife. He was a retired engineer. He drank two alcoholic beverages per day. He did not smoke tobacco or use illicit drugs. His mother had died from an unknown cause at an elderly age; his father had died from trauma. One of his brothers had cerebrovascular disease, and another had schizophrenia. On examination, the temperature was 36.6C, the blood pressure 11260 mm Hg, the pulse 83 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 96 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 24.2. The patient was awake, alert, and oriented, although his attention was somewhat diminished. He could recall two words out of three. Naming and repetition were intact. The pupils were equally reactive to light and accommodation. Extraocular movements were intact, and visual fields were full. Facial sensation and strength were normal. Speech was hypophonic and mildly slurred. Elevation of the palate was symmetric, and movement of the tongue was normal. Shoulder shrug was symmetric. Strength was 55 in all muscle groups. Deep-tendon reflexes were brisk in the arms, with mild spasticity in the legs. Plantar responses were normal. Vibratory sensation in the legs was mildly diminished. Results of finger-to-nose and heel-to-shin testing were normal. There were mild myoclonic movements in both hands. Alternating movements were mildly clumsy. Tone was slightly increased in the legs. The gait was on a narrow base and was unsteady; the patient was unable to walk with a tandem gait. The Rom-berg test showed truncal titubation. A sleep study to determine the appropriate positive airway pressure PAP therapy was performed. In CPAP mode, there was good control of respiratory events. Electromyographic signals revealed elevated muscle tone during rapid-eye-movement REM sleep, but there were no abnormal behaviors. Two weeks later, during a follow-up visit in the neuromuscular clinic, the patient became unresponsive to sternal rub; the vital signs and blood glucose level were normal. He was transported to the emergency department, where he returned to a normal level of consciousness without intervention. Electroencephalography EEG revealed frequent intermittent diffuse polymorphic delta slowing of the background, often with bifrontal predominance, but showed no epileptiform abnormalities. The patient was fitted with a mask for CPAP, and treatment was initiated. Several weeks after the initiation of treatment, download of CPAP data revealed good effectiveness and adherence. However, episodes of unresponsiveness increased in frequency and lasted up to 3 hours at a time. During the episodes, the patients wife was unable to arouse him despite performing a sternal rub. Modafinil was prescribed, but the episodes did not abate. The patient was admitted to the epilepsy monitoring unit for long-term monitoring and EEG. During the admission, two episodes of unresponsiveness occurred, during which the patient had a normal blood pressure, heart rate, and glucose level and EEG revealed findings consistent with sleep. A diagnostic test was performed.
OUTPUT:
| Anti-IgLON5 IgG-associated neurologic disorder |
NEJM_Reasoning_Subset2 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: Dr. Amiko M. Uchida Medicine: A 57-year-old man was evaluated in the gastroen-terology clinic of this hospital because of new ascites. Twenty years before the current presentation, the patient began to have swelling of the legs, which initially occurred only after airplane trips. During the fifth decade of life, the leg swelling was present on a daily basis. Thirteen years before the current presentation, the patient began to have frequent bowel movements up to four per day with loose malodorous stools and increased flatus. He was evaluated in the gastroenterology clinic of this hospital. On examination, the abdomen was soft and nontender, with no evidence of organomegaly. There was pitting edema in both legs. The blood level of total protein was 5.5 g per deciliter reference range, 6.0 to 8.3, and the blood albumin level was 3.1 g per deciliter reference range, 3.3 to 5.0. Results of other liver-function tests, including liver enzyme levels, were normal. The protein level in a 24-hour urine sample was normal. The blood alpha1-antitrypsin level was 173 mg per deciliter reference value, 54. Blood levels of IgG, IgA, and IgM were low. Serologic tests for antitissue trans-glutaminase antibodies and anti-giardia antibodies were negative. Dr. Mark A. Anderson: Computed tomographic CT enterography of the abdomen and pelvis, performed after the administration of intravenous and oral contrast material, revealed diffuse mural thickening and hyperenhancement of the small bowel, with no evidence of stricturing or obstruction Fig. 1A and 1B. In addition, there was trace ascites Fig. 1B. Dr. Uchida: Esophagogastroduodenoscopy EGD and colonoscopy revealed no visible abnormalities. A random biopsy specimen of the duodenum showed a focal area with more than 70 eosinophils per high-power field; a biopsy specimen of the gastric antrum showed scattered eosinophils in the lamina propria. A working diagnosis of protein-losing enteropathy was made, although neither a 2-week course of oral prednisone nor a 6-week course of oral budesonide led to a decrease in the number of bowel movements or leg edema. No further treatment was pursued. Eleven years before the current presentation, the patient was evaluated in the gastroenterology clinic of this hospital. There had been no weight loss or recurrent infections, but leg edema persisted. Repeat EGD revealed no visible abnormalities, and a random biopsy specimen of the duodenum showed fewer eosinophils than the previous specimen, with no epithelial damage. CT enterography revealed diffuse wall thickening of the entire small bowel and trace ascites. Treatment for protein-losing enteropathy which included limiting salt intake, increasing dietary protein, and wearing compression stockings was recommended. During the next 10 years, the leg edema was stable and was occasionally treated with diuretic agents, which did not lead to substantial improvement. Six months before the current presentation, the patient began to have dyspnea on exertion. Three months before this presentation, abdominal distention developed. The patient initially attributed the dyspnea and abdominal distention to weight gain due to reduced physical activity during quarantine for the coronavirus disease 2019 Covid-19 pandemic. Six weeks before this presentation, the patient was evaluated by his primary care physician in a video conference. On the basis of this evaluation, laboratory and imaging studies were obtained. The blood level of total protein was 4.5 g per deciliter updated reference range, 6.4 to 8.3, and the blood albumin level was 2.1 g per deciliter. The complete blood count, blood levels of electrolytes and glucose, and results of liver-function and kidney-function tests were normal. Dr. Anderson: CT of the chest, performed after the administration of intravenous contrast material, revealed multiple small pulmonary nodules, enlarged subcarinal and upper mesenteric lymph nodes, and moderate-volume ascites in the upper abdomen. Dr. Uchida: Three weeks later, paracentesis was performed, and 3.1 liters of milky-appearing ascitic fluid were removed. Results of the ascitic fluid analysis are shown in Table 1. Cytologic examination of the ascitic fluid revealed no malignant cells. The patient was referred to the gastroenterology clinic of this hospital for further evaluation. On the current presentation, the patient reported that he was having bowel movements with normally formed stools and no abdominal pain. His wife had noticed that he appeared to be moving slowly when performing activities of daily living and that he had lost muscle mass in his arms. There was no history of abdominal surgery or trauma to the abdomen. Other medical history included type 2 diabetes mellitus, psoriasis, osteoarthritis, and hypogammaglobu-linemia. There was no history of recurrent infections, asthma, or atopic dermatitis. Medications included aspirin, insulin glargine, and metfor-min. There were no known drug allergies. The patient lived with his wife in a suburb of Boston and worked in an office. He was a lifelong nonsmoker, drank alcohol occasionally, and did not use illicit drugs. His mother had colon cancer. The physical examination was limited, because the evaluation was done in a video conference in the context of the Covid-19 pandemic. Imaging studies were obtained. Dr. Anderson: CT of the abdomen and pelvis, performed after the administration of intravenous and oral contrast material, revealed multiple new hypoenhancing lesions throughout the right and left hepatic lobes, diffuse small-bowel wall thickening, moderate-volume ascites, upper abdominal varices, and enlarged upper abdominal and pelvic nodes Fig. 1C, 1D, and 1E. The only liver lesions that were large enough for reliable percutaneous sampling were at the far cranial aspect of the hepatic dome, where respiratory motion and crossing the diaphragm would have made an attempt at CT-guided or ultrasono-graphically guided biopsy very challenging, if not prohibitive. CT of the chest revealed tree-in-bud and clustered nodules, predominantly in the dependent lower lobes, and right hilar and subcari-nal lymphadenopathy Fig. 1F. Dr. Uchida: Tests for hepatitis C virus antibodies and for hepatitis B virus surface antibodies, surface antigen, and core antibodies were negative. Repeat paracentesis was performed, and 3.2 liters of milky-appearing ascitic fluid were removed. Results of the ascitic fluid analysis are shown in Table 1. An acid-fast stain of a concentrated specimen of ascitic fluid was negative. Cytologic examination of the ascitic fluid revealed no malignant cells. A fluoroscopically guided transjugular liver biopsy was also performed. The hepatic venous pressure gradient HVPG was 2 mm Hg normal value, 5; the right atrial pressure was 7 mm Hg, the wedged hepatic venous pressure 11 mm Hg, and the free hepatic venous pressure 9 mm Hg. Dr. Megan J. Fitzpatrick: Histologic examination of the liver-biopsy specimen revealed mild mixed portal inflammation and grade 1 steatosis without steatohepatitis. A trichrome stain showed mild portal tract edema but no fibrosis. Dr. Uchida: Mycobacterial cultures of the as-citic fluid were negative. A diagnostic test was performed.
OUTPUT:
| High-grade B-cell lymphoma, not otherwise specified. |
NEJM_Reasoning_Subset3 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: Dr. Cory A. Perugino: A 70-year-old man was evaluated in the rheumatology clinic of this hospital because of a recurrent left pleural effusion. Five years before this presentation, the patient had pain in the shoulders and proximal muscles of the arms and legs. The pain was worse in the morning and was associated with fatigue. There was no associated stiffness. The erythrocyte sedimentation rate and the C-reactive protein level were elevated. Prednisone was initiated for the treatment of a working diagnosis of polymyalgia rheumatica, and symptoms abated quickly. During the next year, attempts to discontinue predni-sone led to recurrent myalgias, as well as elevations in the erythrocyte sedimentation rate and the C-reactive protein level. Three years before this presentation, swelling, erythema, and pain developed in the cartilaginous portion of the left ear, sparing the earlobe Fig. 1. There was no reduction in these symptoms after empirical antibacterial therapy was initiated for the treatment of presumed cellulitis. The dose of prednisone was increased, and the symptoms involving the ear resolved; however, they recurred when the dose of prednisone was tapered. Biopsy of the left auricle revealed perichondrial inflammation and degenerative changes in the cartilage. The dose of prednisone was increased for a presumed diagnosis of relapsing polychondritis. The symptoms involving the ear resolved, and weekly therapy with methotrexate was initiated. During the next 6 months, attempts to taper the prednisone dose were associated with worsening inflammatory joint and cartilage symptoms, along with elevations in the erythrocyte sedimentation rate and the C-reactive protein level. The erythrocyte sedimentation rate was as high as 89 mm per hour reference range, 0 to 13 and the C-reactive protein level as high as 73.6 mg per liter reference value, 8.0. Two years before this presentation, the patient began treatment with tocilizu-mab for fatigue, markedly elevated C-reactive protein level, and elevated erythrocyte sedimentation rate, all of which persisted despite treatment with prednisone and methotrexate. The administration of tocilizumab allowed for the tapering of prednisone to a lower dose without causing an exacerbation of inflammatory joint and cartilage symptoms. Two weeks after the patient began receiving tocilizumab therapy, and upon tapering of the prednisone dose, pain and swelling developed in the right leg; ultrasound examination revealed a distal deep-vein thrombosis in the right posterior tibial vein. Repeat ultrasonogra-phy of the leg performed 2 weeks later did not show propagation of the deep-vein thrombosis, and the pain and swelling resolved with the continued use of a compression stocking and elevation of the right leg. However, 2 months later, when further tapering of the prednisone dose was started, inflammatory joint and cartilage symptoms recurred, and pain and swelling developed in the left leg. Ultrasound examination revealed deep-vein thromboses in the left popliteal and left calf veins and in the right femoral vein; therapy with rivaroxaban was initiated. The development of recurrent deep-vein thromboses was attributed to the underlying inflammatory disease. The dose of prednisone was increased, methotrexate was continued, and tocilizumab was replaced with infliximab therapy. During the next 6 months, the inflammatory joint and cartilage symptoms worsened when attempts were made to taper the prednisone dose, and these conditions abated only when the dose of prednisone was increased. Blood tests for antineutrophil cytoplasmic antibodies ANCAs, rheumatoid factor, and anticyclic citrullinated peptide antibodies were negative. Fifteen months before this presentation, treatment with rituxi-mab was initiated. However, after an attempt to taper the dose of prednisone, bilateral scleritis developed Fig. 1; the dose of prednisone was increased again, which resulted in resolution of the ocular pain and redness. During the next 3 months, attempts to taper the prednisone dose resulted in recurrent episodes of scleritis and inflammatory joint and cartilage symptoms; additional rituximab treatment was not administered. One year before the current presentation, treatment with low-dose cyclophosphamide was initiated, but the use of this medication was complicated by severe neutropenia, which did not allow for the dose to be escalated. Nine months before this presentation, treatment with cyclophosphamide was stopped, and intravenous tocilizumab was restarted, given its previous efficacy in this patient. However, the use of tocilizu-mab also resulted in moderate but transient neutropenia after each infusion. Seven months before this presentation, pleu-ritic chest pain on the lower left side developed, along with dyspnea on exertion and a dry cough. Chest radiography revealed a moderate left pleural effusion Fig. 2A and 2B. Thoracentesis was performed, and 1 liter of straw-colored pleural fluid was removed; laboratory test results are shown in Table 1. Grams staining of the pleural fluid revealed abundant polymorphonuclear cells but no organisms; bacterial, fungal, and myco-bacterial cultures were without growth. Cytologic examination of the pleural fluid revealed no malignant cells. Computed tomography CT of the chest performed after the pleural fluid was drained showed a small left pleural effusion, a trace right pleural effusion, and bibasilar dependent atelectasis without consolidation, nodules, or lymphadenopathy Fig. 2C. The pleural effusions were attributed to ongoing inflammatory disease. The dose of prednisone was increased, and the pleurisy and dyspnea resolved. Five months before this presentation, tocilizumab therapy was stopped, and tofacitinib was initiated. One week before this presentation, the patient had sudden onset of back pain on the left side. Imaging studies were performed. Dr. Vincent V. Dinculescu: CT of the chest and abdomen, performed 6 months after the first CT of the chest, revealed a small left pleural effusion that was larger than it had been on the first chest CT Fig. 2D. A punctate stone in the lower pole of the left kidney was also observed, with no evidence of hydronephrosis. Dr. Perugino: The patient presented to the rheu-matology clinic for further evaluation. He had no dyspnea, cough, or fever. On examination, the temperature was 36.7C, the heart rate 64 beats per minute, the blood pressure 14575 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 99 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 29.2. There was no scleral redness or erythema of the helix of the ear. The heart sounds were regular. Breath sounds were decreased at the base of the left lung. There was no leg edema, joint swelling or tenderness, pur-pura, petechiae, or deficits in motor strength. The patient had a history of mucinous adeno-carcinoma of the cecum, which had been diagnosed 10 years before this presentation and had been treated with laparoscopic colectomy of the right side of the colon and with oxaliplatin therapy, without evidence of recurrence. Other history included peripheral neuropathy attributed to the oxaliplatin therapy, hypothyroidism, and monoclonal gammopathy of undetermined significance. Macrocytic anemia had been present for 3 years before this presentation, with normal blood levels of cobalamin and folate. The patient also had a history of leukopenia and neutropenia; these conditions had occurred intermittently over the course of the 10 years preceding this presentation but were most pronounced after treatment with cyclophosphamide and tocilizumab. Medications included alendro-nate, atorvastatin, cholecalciferol, folic acid, levo-thyroxine, methotrexate, omeprazole, prednisone, rivaroxaban, trimethoprimsulfamethoxazole, and tofacitinib. The patient drank alcohol occasionally; he did not smoke tobacco or use illicit drugs. He lived in New England and was retired. There was no family history of autoimmune disease. The blood levels of electrolytes, glucose, and thyrotropin were normal, as were the results of liver-function and kidney-function tests. Testing for antinuclear antibodies was negative. Other laboratory test results are shown in Table 1. A diagnostic test was performed, and management decisions were made.
OUTPUT:
| VEXAS (vacuoles, E1 enzyme, X-linked, autoin- flammatory, somatic) syndrome |
NEJM_Reasoning_Subset4 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: Dr. Micaela Atkins Pediatrics: A 14-year-old boy was admitted to this hospital because of fatigue, fever, joint pain, abdominal cramping, and diarrhea. The patient had been well until 2 weeks before this admission, when fatigue and fever developed on his final day of summer camp. He was taken to the primary care clinic at another hospital and was told that he had a viral infection. Nine days before this admission, new mild sore throat developed, and the patient returned to the primary care clinic. A throat culture for group A beta-hemolytic streptococcus was reportedly negative. The patient was told that he had possible sinusitis, and treatment with amoxicillinclavulanate was started. During the next 3 days, the sore throat abated, but fatigue and fever persisted. Six days before this admission, new pain in the right shoulder and left knee developed, and the patient again returned to the primary care clinic. The white-cell count and erythrocyte sedimentation rate were reportedly elevated; a blood test for Lyme disease was performed. On the day of admission, the joint pain progressed to involve the shoulders and knees on both sides, and the temperature increased to 39.4C. The patient was given ibuprofen and brought to the emergency department at this hospital. On evaluation, the patient described aching pain in the shoulders and knees, which was worst in his right shoulder and left knee. He rated the pain at 7 on a scale of 0 to 10, with 10 indicating the most severe pain. He had not noticed redness, swelling, or stiffness of the joints. A review of systems was notable for chills, intermittent night sweats, headache, myalgias, and lightheadedness when he stood up from a sitting position. He had no weight loss, rash, vision changes, or respiratory symptoms. He had mild abdominal cramping, decreased appetite, and intermittent nausea. During the past week, there had been a few episodes of nonbloody emesis and watery diarrhea. There had been no hematemesis, hematochezia, or melena. The patient had autism spectrum disorder, with an early delay in speech development that had resolved after speech therapy. He had met milestones for gross CME at NEJM.org and fine motor skills and growth. He had reportedly received all routine childhood vaccinations. Other history included asthma, seasonal rhinosinusitis, and allergies to peanuts and tree nuts; there were no known drug allergies. He had undergone a tonsillectomy in early childhood. Medications included amoxicillinclavula-nate, inhaled fluticasone, and ibuprofen and inhaled albuterol as needed. At the time of admission, the patient was on his summer break before entering high school. Earlier in the summer, he had gone on vacation to a coastal area of New England. He had also attended camp in a rural area of New England, where he camped and hiked in wooded areas and swam in fresh water. He had seen a tick on his clothing but did not recall any bites. Two weeks before this admission, the patient had returned to his home in a suburban area of New England, where he lived with his mother who was a veterinarian, father, sister, and pet dog. His sister had recently had an acute gastrointestinal illness that resolved after several days. The patient was not sexually active and did not use alcohol, drugs, or tobacco. His mother had hypothyroidism, and his maternal uncle had rheumatoid arthritis; there was no other known family history of autoimmune diseases. On examination, the temperature was 36.1C, the blood pressure 12858 mm Hg, the heart rate 107 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 27.2. The patient appeared to be well developed and well nourished, but he looked tired. The conjunctivae were normal. The mucous membranes were dry, and there was an aphthous ulcer on the right buccal mucosa. The lungs were clear on auscultation. There was tenderness on palpation of the epigastric and periumbilical abdomen. There was no erythema, warmth, swelling, or crepitus of the large and small joints. There was tenderness on palpation, as well as pain with movement, of the right shoulder and knees; range of motion in these joints was not decreased. The patient had no rash or lymph-adenopathy. The white-cell count was 12,950 per micro-liter reference range, 4500 to 13,000, the erythrocyte sedimentation rate 48 mm per hour reference range, 0 to 13, the C-reactive protein level 207.6 mg per liter reference range, 0.0 to 8.0, and the lipase level 82 U per liter reference range, 13 to 60. Laboratory test results are shown in Table 1. While the patient was in the emergency department, the temperature increased to 39.2C. Intravenous fluids were administered, and empirical treatment with doxycycline was started. The patient was admitted to the hospital. During the next 2 days, the fever resolved, but the joint pain, abdominal cramping, and diarrhea worsened in severity. On the third hospital day, fever recurred. The white-cell count was 15,190 per microliter, the C-reactive protein level 178.3 mg per liter, and the lipase level 145 U per liter. A fecal occult blood test was positive. A plain film of the right shoulder was normal. A diagnostic test was performed.
OUTPUT:
| Inflammatory bowel disease (Crohn’s disease) |
NEJM_Reasoning_Subset5 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: Dr. Mia Y. Bothwell Medicine: A 55-year-old man was evaluated in the rheumatol-ogy clinic of this hospital because of bilateral hearing loss and eye redness. The patient had been in his usual state of health until 8 weeks before the current evaluation, when a headache involving the left temple developed. A similar headache had occurred during an episode of shingles 15 years earlier. He received a prescription for a 1-week course of valacyclovir for the treatment of presumed shingles. No skin lesions developed, and the headache resolved. Four weeks before the current evaluation, hearing loss in the left ear developed during an airplane flight. The hearing loss persisted after the flight, and the patient began to have intermittent tinnitus in the left ear and redness in both eyes. He was evaluated by an otolaryngologist at a clinic affiliated with this hospital. He reported no vertigo, otorrhea, rhinitis, or sore throat. On examination, there was redness in both eyes. The right and left auricles and external auditory canals were normal, as was the right tympanic membrane. The left tympanic membrane was retracted; there was no middle-ear effusion. Results of the Weber test were inconsistent. The Rinne test was positive bilaterally, with air conduction greater than bone conduction. There was no sinus tenderness. Nasopharyngoscopy revealed midseptal deviation to the left; the posterior aspect of the nasopharynx was normal. The remainder of the examination, including a cranial nerve examination, was normal. An audiogram showed sloping mild-to-severe sensorineural hearing loss in both ears. Results were asymmetric at low frequencies, with more severe hearing loss in the left ear than in the right ear from 125 to 2000 Hz Fig. 1A. Word recognition was 96 with the right ear and 84 with the left ear reference range, 80 to 100. Results of tympanometry were normal in both ears. The patient received a prescription for a 12-day tapering course of oral prednisone. Magnetic resonance imaging MRI of the head, performed with and without the administration of intravenous contrast material, revealed no abnormal findings. CME at NEJM.org Four weeks later, the patient was evaluated by a different otolaryngologist at the clinic affiliated with this hospital. Hearing loss had progressed. Eye redness had initially decreased after prednisone therapy was started but had subsequently recurred after prednisone therapy was stopped. On examination, there was redness in both eyes. There was no spontaneous nystagmus or gait ataxia. Sinusoidal gaze tracking was normal. The head-thrust test to the left was positive, a finding that indicates vestibular hypofunction on the left side. Results of the Romberg test were normal. The Fukuda step test was positive, with the patient rotated to the left, a finding that also indicates vestibular hypo-function on the left side. A repeat audiogram showed worsening of sensorineural hearing loss and reduction of word recognition to 90 with the right ear and 64 with the left ear Fig. 1B. Results of tympanometry were normal. The patient was referred for an urgent rheumatologic evaluation. Three days later, in the rheumatology clinic at this hospital, the patient reported ongoing hearing loss in both ears and redness in both eyes, as well as the recent onset of imbalance. He also reported that he had had fatigue and intermittent body aches for 2 months and that he had lost 5 kg of weight over a 6-month period. There was no history of oral or genital lesions; 6 weeks earlier, a nonpruritic patchy rash had developed on his torso after he received the influenza vaccine and had rapidly resolved with the use of an oral antihistamine. There was a history of irritable bowel syndrome, diverticulosis, gastritis, allergic rhinitis, and asthma. Medications included intranasal and inhaled fluticasone, vita-min B12, and omeprazole. There were no known drug allergies. The patient lived with his wife in an urban area of New England. For the past 12 years, he had been sexually active with his wife only. He was a retired construction worker. He was a nonsmoker, drank alcohol rarely, and did not use illicit drugs. On examination, the patient appeared well. The temperature was 36.9C, the blood pressure 11579 mm Hg, the heart rate 95 beats per minute, the respiratory rate 15 breaths per minute, and the oxygen saturation 100 while he was breathing ambient air. There was redness in both eyes. The finger-rub test revealed grossly reduced hearing in both ears. The Romberg test was positive when the patients eyes were open, a finding that indicates vestibular or cerebellar hypofunction. The remainder of the examination, including skin, joint, and neurologic assessments, was normal. Blood levels of electrolytes and glucose were normal, as were results of liver-function and kidney-function tests. The complete blood count with differential count was normal. The erythrocyte sedimentation rate was 55 mm per hour reference range, 0 to 13, and the C-reactive protein level 12.3 mg per liter reference value, 8.0. The patient was referred for an urgent ophthalmologic evaluation at this hospital, which was to take place on the same day. On ophthalmologic evaluation, the patient reported no blurred vision, floaters, eye pain, itching, or photophobia. He wore contact lenses, which he changed daily. On examination, visual acuity was normal in both eyes. The right cornea had trace pinpoint epithelial deposits, a peripheral ring of punctate epithelial erosions, and several small confluent areas of punctate epithelial erosions centrally, with no infiltrate. The left cornea had a peripheral ring of punctate epithelial erosions and several confluent areas of punctate epithelial erosions centrally, with no infiltrate. There was evidence of anterior uveitis, with 7 cells per high-power field in the right anterior chamber and 6 to 7 cells per high-power field in the left anterior chamber. There was trace flare in both eyes. A diagnostic test was performed.
OUTPUT:
| Neurosyphilis |
NEJM_Reasoning_Subset6 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: CME at NEJM.org Dr. Molly Wolf Medicine and Pediatrics: A 17-year-old boy was admitted to the pediatric intensive care unit ICU of this hospital, before the coronavirus disease 2019 Covid-19 pandemic, because of chest pain, syncope, electrocardiographic ECG abnormalities, and elevated blood levels of creatine kinase and troponin T. The patient had been well until 5 days before this admission, when fever, nausea, diarrhea, muscle aches, and chest pain developed. The chest pain radiated to the left shoulder and was worse when he took deep breaths or was lying flat. One episode of nonbloody, nonbilious emesis occurred. On the second day of illness, the patient presented to his primary care clinic at another hospital, where a viral illness was diagnosed. An intramuscular glucocorticoid injection was administered, nebulized albuterol was prescribed, and the patient was advised to take ibuprofen and acetaminophen. During the next 3 days, fever and diarrhea resolved, but chest pain, muscle aches, and nausea persisted and were accompanied by decreased appetite and cold, pale fingers. On the morning of admission, lightheadedness developed. When the patient stood to get a drink of water, he felt unsteady, his vision faded, and syncope occurred. He regained consciousness within 1 minute. Emergency medical services were called, and on arrival they found that the patient was alert and the vital signs were normal. The peripheral blood glucose level, obtained by fingerstick testing, was 24 mg per deciliter 1.3 mmol per liter; reference range, 70 to 110 mg per deciliter 3.9 to 6.1 mmol per liter. Thiamine and 50 ml of a 50 dextrose solution were administered intravenously, and the patient was transported by ambulance to the emergency department of the other hospital. On arrival at the other hospital, the patient reported pleuritic left parasternal chest pain, which he rated at 4 on a scale of 0 to 10, with 10 indicating the most severe pain. The temperature was 36.9C, the pulse 106 beats per minute, the blood pressure 12672 mm Hg, the respiratory rate 23 breaths per minute, and the oxygen saturation 93 while he was receiving supplemental oxygen through a nasal cannula at a flow rate of 2 liters per minute. The pulse oximeter plethysmographic waveform was noted to be of low amplitude, and the oxygen saturation was difficult to obtain. The weight was 95.3 kg and the body-mass index the weight in kilograms divided by the square of the height in meters 32. The fingers were cool, with a capillary refill time of 3 to 4 seconds. Blood levels of alkaline phosphatase, bilirubin, and lactic acid were normal; other laboratory test results are shown in Table 1. Serum toxicologic screening was negative. Chest radiography revealed a borderline enlarged cardiac silhouette. ECG and echocardiography were performed. Dr. Oscar J. Benavidez: An ECG showed normal sinus rhythm at a rate of 100 beats per minute Fig. 1. ST-segment elevation and PR-segment depression were present in leads I and II and the lateral precordial leads. There was no atrial or ventricular ectopy. A transthoracic echocardiogram showed mild concentric left ventricular hypertrophy and normal left ventricular volume and systolic function, with a left ventricular ejection fraction of 63; there were no wall-motion abnormalities. The right ventricular volume and systolic function were normal. There was no mitral valve prolapse, but mild mitral regurgitation was present. The aortic dimensions were within normal limits, and there was no pericardial effusion. Doppler imaging revealed normal systolic and diastolic velocities. Dr. Wolf: Three hours after arrival, the patient was transferred by ambulance to the pediatric ICU of this hospital. On admission, he reported that he had intentionally lost 45 kg of weight during the previous year. He took no medications, herbal remedies, or nutritional supplements and had no known allergies. His immunizations were reportedly current. The patient lived with his mother and younger brother. He played sports; he had no known exposure to sick persons and was not sexually active. He did not smoke tobacco, drink alcohol, or use illicit drugs. His mother had hypertension, unspecified heart disease, and a history of recurrent miscarriages. A brother had died at 56 days of age from sudden infant death syndrome. His maternal grandmother had hypertension and diabetes, and a maternal aunt had systemic lupus erythematosus SLE with nephritis. On examination, the patient appeared well. The temperature was 37.6C, the pulse 111 beats per minute, the blood pressure 14872 mm Hg, the respiratory rate 23 breaths per minute, and the oxygen saturation 100 while he was receiving supplemental oxygen through a nasal can-nula at a flow rate of 2 liters per minute. The fingers were cold and pale. Examination of the skin revealed striae on the abdomen. The remainder of the physical examination was normal. Tests for influenza virus, respiratory syncy-tial virus, parainfluenza virus, adenovirus, and human immunodeficiency virus HIV were negative. Urinalysis showed a specific gravity of 1.031, a pH of 6.0, and 1 protein. Intravenous fluids, ibuprofen, and famotidine were administered, and supplemental oxygen was discontinued. During the next 24 hours, the chest pain and ECG abnormalities abated and the blood levels of creatine kinase, troponin T, alanine amino-transferase, and aspartate aminotransferase decreased. The patient was discharged home; he was advised to take acetaminophen and ibuprofen as needed for pain, and a follow-up appointment with a pediatric cardiologist was scheduled. Ten days later, in the cardiology clinic, the patient reported that the chest pain had resolved. He appeared well. The pulse was 86 beats per minute and the blood pressure 15177 mm Hg. The remainder of the examination was unchanged. Results of laboratory tests performed in the patients primary care clinic 3 days earlier are shown in Table 1. ECG was performed. Dr. Benavidez: An ECG showed normal sinus rhythm at a rate of 82 beats per minute Fig. 1. There were nonspecific ST-segment changes in leads III and aVF; ST-segment elevation and PR-segment depression were no longer present. Dr. Wolf: Ultrasonographic examination of the kidneys was normal. Amlodipine was prescribed, and follow-up appointments with a pediatric ne-phrologist and a medical geneticist were scheduled but not kept by the patient. Results of laboratory tests performed in the primary care clinic 6 weeks after discharge are shown in Table 1. Approximately 9.5 months after admission to the pediatric ICU, the patient presented to the emergency department of the other hospital with a 15-hour history of fever, malaise, nausea, vomiting, diarrhea, midsternal chest pain, and light-headedness. He rated the chest pain at 6 out of 10. The temperature was 39.3C, the pulse 119 beats per minute, the blood pressure 13461 mm Hg, the respiratory rate 20 breaths per minute, and the oxygen saturation 98 while he was breathing ambient air. On examination, the capillary refill time in the fingers was 3 to 4 seconds. ECG and imaging studies were performed. Dr. Benavidez: An ECG showed sinus tachycardia at a rate of 126 beats per minute Fig. 1. There were frequent premature atrial and ventricular contractions, along with diffuse flattening of T waves. Dr. Sjirk J. Westra: Frontal and lateral chest radiography revealed cardiomegaly, as characterized by an increased cardiothoracic ratio, with predominant enlargement of the left atrium Fig. 2. Pulmonary vascular congestion with mild interstitial pulmonary edema and a small left pleural effusion were detected; these findings are suggestive of congestive heart failure. Dr. Wolf: The patient was again transferred by ambulance to the pediatric ICU of this hospital. On admission, he reported that the chest pain had abated. He appeared to be in no distress. The temperature was 38.8C, the pulse 134 beats per minute, the blood pressure 12949 mm Hg, the respiratory rate 27 breaths per minute, and the oxygen saturation 98 while he was breathing ambient air. The weight was 83.9 kg. On auscultation of the heart, the rhythm was irregular; the remainder of the examination was normal. Laboratory test results are shown in Table 1. Urinalysis showed a specific gravity of 1.027, a pH of 5.0, and 1 protein. Intravenous fluids, magnesium sulfate, sodium phosphate, amlodipine, famotidine, ondansetron, acetaminophen, and ibuprofen were administered. During the next 2 days, fever and intermittent chest pain persisted and hypertension developed, with blood-pressure measurements as high as 18797 mm Hg. Hydralazine and labetalol were administered, and the dose of amlodipine was increased. On examination, strength in the proximal muscles of the arms and legs was graded as 4 out of 5, with 5 indicating normal muscular contraction against full resistance. There were episodes during which the fingers were cold and pale; no nailfold capillary abnormalities were seen. The remainder of the examination was unchanged. The blood level of troponin T decreased to 0.57 ng per milliliter and the blood level of cre-atine kinase MB isoenzyme decreased to 50.2 ng per milliliter, whereas the blood level of creatine kinase increased to 8336 U per liter; the urine level of myoglobin was 283 g per liter reference value, 21. The results of thyroid-function tests were normal. Some peripheral blood glucose measurements, obtained by fingerstick testing, were as low as 22 mg per deciliter 1.2 mmol per liter, despite a regular diet and the administration of dextrose-containing intravenous fluids. These values were not verified by concurrent central venous blood glucose measurements. Additional test results were received, and a diagnosis was made.
OUTPUT:
| Undifferentiated autoimmune rheumatic disease. |
NEJM_Reasoning_Subset7 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: CME at NEJM.org Dr. Daryl J. Selen: A 29-year-old woman was admitted to this hospital because of recurrent bone fractures and hypophosphatemia. The patient had been well until 19 months before admission, when pain in the right midfoot developed during a vacation in Europe. On her return to the United States, she was evaluated by her primary care physician at a clinic affiliated with another hospital; an orthotic device was recommended, but the foot pain did not decrease with use of the device. Three months later, the pain in the right foot increased in severity after a second vacation in Europe. Radiography of the right foot reportedly revealed no fracture; physical therapy was recommended. During the subsequent 8 months, the pain continued to gradually increase in severity, was worse when the patient stood upright or walked, and was relieved with the administration of ibuprofen. Eight months before admission, the patient tripped, and the severity of pain in the right foot increased suddenly. She was evaluated in the orthopedic clinic of this hospital. On examination, the height was 173 cm, the weight 115 kg, and the body-mass index the weight in kilograms divided by the square of the height in meters 38.6. There was tenderness over the right third metatarsal. Imaging studies were obtained. Dr. Rene Balza: Radiography of the right foot Fig. 1A revealed a fracture of the third metatarsal shaft. Magnetic resonance imaging MRI of the right foot revealed a nondisplaced, incompletely healed transverse fracture of the third metatarsal shaft, as well as subchondral sclerosis and bone marrow edema within the distal navicular bone and in the calcaneocuboid joint. Bone stimulation was recommended, but the patients pain did not abate after these treatments. Dr. Selen: Seven months before admission, the patient had increased pain in the right foot after a fall while walking on ice. Additional imaging studies were obtained. Dr. Balza: Radiography of the right foot Fig. 1B revealed fractures of the distal fourth and fifth metatarsals. Dr. Selen: Five months before admission, the second metatarsal region of the right foot was tender on palpation after the patient had walked up a flight of stairs. However, no evidence of a fracture was seen on radiography. Four months before admission, the patient was evaluated in the endocrinology clinic affiliated with the other hospital. The calcium level was 9.5 mg per deciliter 2.4 mmol per liter; reference range, 8.5 to 10.5 mg per deciliter 2.1 to 2.6 mmol per liter, the 25-hydroxyvitamin D level 26 ng per milliliter 65 nmol per liter; reference range, 20 to 80 ng per deciliter 50 to 200 nmol per liter, and the parathyroid hormone level 45 pg per milliliter reference range, 10 to 60; other laboratory test results are shown in Table 1. Dual-energy x-ray absorptiometry, performed for the assessment of bone mineral density, revealed normal bone mass in the lumbar spine z score, 0.0; reference range, 1.9 to 1.9 and in the femoral neck z score, 0.4; reference range, 1.9 to 1.9. Calcium and vitamin D supplementation and weight loss were recommended. The pain in the right foot persisted, and additional imaging studies were obtained. Dr. Balza: Three months before admission, MRI of the right foot Fig. 1C and 1D showed a non-displaced fracture of the second metatarsal metadiaphysis with associated bone and soft-tissue edema, a nondisplaced fracture of the medial cuneiform, and healing fractures of the third, fourth, and fifth metatarsals. A controlled ankle motion walking boot and crutches were recommended for ambulation. Dr. Selen: During the next 3 months, the pain in the right foot persisted, and new pain developed in the left foot. The patient was seen in the pain medicine and podiatry clinics affiliated with the other hospital. Diagnoses of plantar fasciitis, Achilles tendinitis, and sinus tarsi syndrome were considered. Treatment with methyl-prednisolone and celecoxib was initiated, and the patient was referred to the rheumatology clinic of this hospital. On evaluation in the rheumatology clinic, the patient reported bilateral foot and ankle pain and swelling that was greater in the right foot and ankle than in the left, as well as stiffness and warmth in the ankles. There was lower back pain and bilateral hip pain, which was greater on the right side than on the left side. The patient reported that the back and hip pain had been present since she was a teenager but had gradually increased in severity during the previous year. Fatigue and generalized weakness had developed and worsened during the previous month. There was no fever, weight loss, or change in diet. Menarche had occurred when the patient was 11 years of age, and menstrual cycles had been regular since then. There was a history of fractures of the left wrist in childhood. Other medical history included obesity, hyperlipidemia, anxiety, nephrolithiasis, biliary dyskinesia which had led to cholecystectomy 1 year before this admission, and nonalcoholic fatty liver disease diagnosed on the basis of a liver biopsy. Medications included celecoxib, ergocalciferol, citalopram, and lorazepam; she had no known drug allergies. The patient lived alone in a suburban area of New England and had previously worked as a nurse; however, she was unable to work during the previous 8 months because of pain and difficulty with ambulation. She did not smoke cigarettes, drink alcohol, or use illicit drugs. Her mother had osteopenia; her mother, father, and sister had psoriasis; her father had psoriatic arthritis; and her brother had the Williams syndrome, a rare genetic and developmental disorder. On examination, the temperature was 36.9C, the blood pressure 12178, and the heart rate 94 beats per minute. Dentition was normal, and the gait was antalgic. Proximal muscle strength was intact in both arms 55 and slightly reduced in the legs 45. There was tenderness over the lumbar spine and sacroiliac joints that was more pronounced on the right side than on the left side. The FABER test in which the leg is flexed and the thigh is abducted and externally rotated elicited pain in both hips. There was tenderness over the right midfoot and warmth and swelling of the ankles. No musculoskeletal deformities, bowing of the legs, lymphadenopa-thy, skin lesions, or rashes were noted. The blood level of phosphorus was 1.0 mg per deciliter 0.3 mmol per liter; reference range, 2.6 to 4.5 mg per deciliter 0.8 to 1.5 mmol per liter; other laboratory test results are shown in Table 1. The patient was instructed to go to the emergency department of this hospital. Intravenous sodium phosphate and oral potassium phosphate were administered. Additional imaging studies were obtained. Dr. Balza: Radiography of the lumbar spine, pelvis, hips, and ankles revealed anterolisthesis of L4 and L5 with a defect in the pars interarticu-laris; there were no fractures. On radiography of the right foot, a fracture in the third metatarsal was initially identified 8 months before admission Fig. 1A, followed by the development of fractures in the fourth and fifth metatarsals 1 month later Fig. 1B. Subsequently, T2-weighted MRI of the sacrum with fat suppression performed on admission Fig. 1E and 1F revealed vertically oriented hypointense bands in the bilateral sacral alae and a horizontally oriented hypoin-tense band in S2, as well as bone marrow edema adjacent to the fracture lines; the combination of these findings was consistent with an H-shaped sacral insufficiency fracture. Dr. Selen: The patient was admitted to the hospital. A diagnostic test was performed.
OUTPUT:
| Phosphaturic mesenchymal tumor causing osteomalacia. |
NEJM_Reasoning_Subset8 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: Dr. Jon S. DuBois: A 29-year-old woman was evaluated in the gastroenterology clinic of this hospital for the management of a soft-tissue mass in the head of the pancreas. The patient had been well until 7 weeks before this presentation, when progressive pruritus throughout the body developed, along with nausea, bloating, and watery mustard-colored diarrhea. She had eaten sushi for dinner the previous night. She was evaluated in an urgent care clinic in the southeastern United States; she had recently moved there from New England. An injection of methylpredniso-lone was administered, and hydroxyzine and diphenoxylateatropine were prescribed. During the next 3 weeks, the symptoms did not abate and jaundice developed, along with new discomfort in the right upper quadrant of the abdomen, decreased appetite, and amber-colored urine. Four weeks before this presentation, the patient was evaluated in the emergency department of a local hospital. The alanine aminotransferase level was 327 U per liter reference range, 1 to 33, the aspartate aminotransferase level 104 U per liter reference range, 1 to 32, and the total bilirubin level 5.8 mg per deciliter reference range, 0.1 to 1.2. The carbohydrate antigen 19-9 CA 19-9 level was 73 U per milliliter reference range, 0 to 35. Additional laboratory test results are shown in Table 1. Imaging studies were obtained. Computed tomography CT of the abdomen, performed after the intravenous administration of contrast material, reportedly revealed a distended gallbladder with sludge, as well as dilated hepatic and pancreatic ducts. The patient was admitted to the local hospital. On the second hospital day, results of liver-function tests improved, and she was discharged home with plans for an outpatient evaluation with a gastroenterologist. However, the next day, the patient flew back to New England and presented to the emergency department of a second hospital for further evaluation. On evaluation, she described persistent diffuse pruritus, nausea, right upper abdominal CME at NEJM.org pain, and mustard-colored diarrhea. She also reported fatigue, unintentional weight loss of 3.2 kg during the past month, and poor sleep. The patient had a history of anxiety and depression. She took no medications and had no known drug allergies. Aside from her recent move to the southeastern United States and trip back to New England, there was no recent travel. She worked seasonally as an official at sporting events. She smoked cigarettes occasionally, drank alcohol rarely, and did not use illicit drugs. Her family history included colon cancer in her maternal grandmother, maternal grandfather, and paternal grandmother; breast cancer in her maternal aunt and paternal aunt; and thyroid cancer in her father. In addition, her maternal grandmother had diabetes, and both grandmothers had coronary artery disease. On examination, the temperature was 36.9C, the blood pressure 15582 mm Hg, the pulse 94 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 100 while the patient was breathing ambient air. She was thin and appeared jaundiced, with scleral icterus. She had diffuse excoriations from scratching. The bowel sounds were normal. There was mild tenderness in the right upper abdomen on palpation, but masses and hepatosplenomegaly were not detected. The remainder of the examination was normal. The alanine aminotransferase level was 85 U per liter, the aspartate aminotransferase level 267 U per liter, and the total bilirubin level 6.7 mg per deciliter. The CA 19-9 level was 79 U per milliliter. Additional laboratory test results are shown in Table 1. The abdominal CT images obtained at the first hospital were reviewed, and additional imaging studies were obtained. Dr. Avinash Kambadakone: CT of the abdomen Fig. 1A and 1B, performed after the intravenous administration of contrast material, revealed diffuse dilatation of the intrahepatic and extra-hepatic biliary ducts, as well as dilatation of the pancreatic ducts. The dilated ducts terminated abruptly in the pancreatic head. There was a hypodense pancreatic mass at the site of duct obstruction. Magnetic resonance cholangiopan-creatography Fig. 1C and 1D also revealed dilatation of the biliary and pancreatic ducts, which narrowed abruptly at the level of the pancreatic head, with a heterogeneously enhancing mass at the site of obstruction. Dr. DuBois: The patient was admitted to the second hospital. Endoscopic retrograde cholan-giopancreatography revealed a stricture in the bile duct at the level of the mass, and a stent was placed. The bilirubin level initially decreased, but pruritus and diarrhea persisted. By the seventh hospital day, the bilirubin level had increased to 12.6 mg per deciliter and the CA 19-9 level had increased to 959 U per milliliter. Additional diagnostic testing was performed. Dr. Kambadakone: Endoscopic ultrasonography Fig. 1E revealed a hypoechoic mass in the pancreatic head. Fine-needle aspiration was performed. Dr. DuBois: The aspirate showed variably atypical epithelium, but the quantity and quality of the findings were insufficient for definitive diagnosis. Given the uncertain diagnosis and the possibility of cancer, a surgical consultation was obtained. Surgical removal of the mass was recommended to establish the definitive diagnosis, but the patient declined surgery. Prednisone was administered, and the pruritus and diarrhea abated. On the 20th hospital day, the patient was discharged with plans for an outpatient followup evaluation with a gastroenterologist. Three days after discharge from the second hospital, the patient was evaluated in the gastro-enterology clinic of this hospital. At that time, her symptoms had resolved, the results of liver-function tests were normal, and the CA 19-9 level had decreased to 80 U per milliliter. IgG levels total and subclasses were normal, and tests for antinuclear antibodies ANA were negative. The possibility of cancer was explained to the patient, and surgical removal of the mass was again recommended, but the patient declined surgery owing to multiple issues related to her work and personal life. A management plan that was acceptable to the patient was adopted during the next 6 months. The patient was closely monitored, and biliary stents were changed when they became occluded. Additional diagnostic procedures were performed, and management decisions were made.
OUTPUT:
| Pancreatic ductal adenocarcinoma. |
NEJM_Reasoning_Subset9 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: Dr. Adith Sekaran Medicine: A 68-year-old man with metastatic melanoma was evaluated in the oncology clinic of this hospital because of fatigue and weight loss. Six years before the current evaluation, the patient received a diagnosis of superficial spreading melanoma of the left shoulder. He was treated with a wide local excision; a biopsy of the sentinel lymph node was negative for melanoma. One year before the current evaluation, the patient began to have slurred speech and weakness in the left hand. Imaging revealed a mass lesion in the parietal lobe of the brain and another mass in the hilum of the left lung. Craniotomy with resection of the brain mass was performed; pathological examination of the resected specimen revealed findings consistent with melanoma, as did a biopsy of the lung mass. Seizures developed postoperatively, and treatment with levetiracetam was initiated. Further treatment included radiation therapy targeting the parietal resection cavity and the administration of pembrolizumab. Four months before the current evaluation, after seven cycles of pembrolizu-mab, the blood thyrotropin level was 9.4 IU per milliliter reference range, 0.4 to 5.0 and the free thyroxine level 0.9 ng per deciliter 12 pmol per liter; reference range, 0.9 to 1.8 ng per deciliter 12 to 23 pmol per liter; treatment with levothy-roxine was initiated. Three months before the current evaluation, after eight cycles of pembrolizumab, exertional angina developed, and the patient underwent coronary catheterization with placement of two drug-eluting stents. Pembrolizumab treatment was resumed 1 month later. When the patient presented to the oncology clinic for a planned infusion of pembrolizumab, he reported a 3-week history of fatigue and a 2-week history of increased thirst and nocturia, with a need to urinate as many as three times each night. Although there was no change in appetite or eating habits, he had lost 5 kg of weight in the previous 3 weeks. There was no headache or change in vision. On examination, the temperature was 36.4C, the heart rate 75 beats per minute, the blood pressure 12866 mm Hg, the respiratory rate 18 breaths per minute, and the oxygen saturation 100 while the patient was breathing ambient air. The CME at NEJM.org body-mass index the weight in kilograms divided by the square of the height in meters was 29.0. Heart sounds were regular, with no murmur. Lung sounds were normal. There was no leg edema. Muscle bulk was normal, as was strength in the arms and legs. There was no rash, bruising, or change in skin tone. Other history included hyperlipidemia, hypothyroidism, and coronary artery disease. Medications included aspirin, atorvastatin, clopidogrel, levetiracetam, levothyroxine, metoprolol, and pembrolizumab. He did not smoke tobacco, drink alcohol, or use illicit drugs. The patient lived in New England and was a retired police officer. His father, sister, and brother had had melanoma. There was no family history of diabetes. A complete blood count, the results of liver-function tests, and the blood thyrotropin level were normal. The blood glucose level was 505 mg per deciliter 28.03 mmol per liter; reference range, 70 to 110 mg per deciliter 3.89 to 6.11 mmol per liter. Other laboratory test results are shown in Table 1. The patient was sent to the emergency department of this hospital, and management decisions were made.
OUTPUT:
| Immune checkpoint inhibitor–induced diabetes |
NEJM_Reasoning_Subset10 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: Dr. Annabelle Anandappa Medicine: A 25-year-old man with a history of B-cell acute lymphoblastic leukemia was evaluated in the emergency department of this hospital because of vision changes. Ten months before this presentation, the patient was evaluated for fatigue and dyspnea on exertion. Laboratory testing revealed a hemoglobin level of 3.5 g per deciliter reference range, 13.5 to 17.5 and a white-cell count of 23,450 per micro-liter reference range, 4000 to 11,000, with 81 lymphocytes and 4 blasts. A bone marrow biopsy was performed. Dr. Judith A. Ferry: Examination of the bone marrowbiopsy specimen Fig. 1 revealed markedly hypercellular marrow with a loss of normal elements. There were sheets of blasts, including larger cells with oval-to-irregular nuclei, fine chromatin, distinct nucleoli, and scant cytoplasm, as well as more mature-appearing lymphocyte-like blasts with more condensed chromatin. Cytogenetic analysis revealed an abnormal karyotype: 46,XY,t9;22q34;q11.21546,idem,t2;12 p13;p13,?del10p13346,idem,del6p21,add7p132. On next-generation sequencing, SNaPshot analysis identified a RUNX1 mutation, and gene fusion analysis was positive for BCR-ABL1 e13a2. A diagnosis of B-cell acute lymphoblastic leukemia with BCR-ABL1 was made. Dr. Anandappa: Induction chemotherapy with vincristine, doxorubicin, metho-trexate, cytarabine, and prednisone was administered, along with dasatinib and intrathecal cytarabine, methotrexate, and hydrocortisone. One month later, examination of a bone marrowbiopsy specimen revealed 7 blasts. Treatment with blinatumomab was started, and dasatinib was continued. Seven months before this presentation, examination of a bone marrowbiopsy specimen revealed a complete hematologic response. BCR-ABL1 was undetectable by means of reverse-transcriptasepolymerase-chain-reaction testing. Five months before this presentation, the patient underwent allogeneic hemato-poietic-cell transplantation HCT from a matched, unrelated donor after myeloab-lative conditioning with cyclophosphamide and total-body irradiation. Early post-transplantation complications included severe mucositis and febrile neutropenia. Two months before this presentation, examination of a bone marrowbiopsy specimen revealed a complete hematologic response, no BCR-ABL1 rearrangement, and full donor chime-rism. Dasatinib was continued as maintenance therapy. During the next 2 months, the patient had worsening anemia, and dasatinib was stopped. Two days before this presentation, the patient noticed large black blobs that looked like shadows in the periphery of the visual fields of both eyes. There were also intermittent episodes of blurry vision in both eyes that resolved after 10 minutes. Two days later, the patient sought an evaluation in the oncology clinic of this hospital and was transferred to the emergency department for further evaluation. In the emergency department, the patient reported ongoing vision symptoms but no eye pain, flashing lights, or floaters. He also reported 3 weeks of night sweats, areas of swelling in the neck and groin, and a pruritic rash on the upper chest, upper back, and both arms. He had a history of chronic daily migraine headaches, which had frequently been associated with eye pain and photophobia but had not been associated with vision changes. Other medical history included depression and obesity. Medications included tacrolimus, trimethoprimsulfamethoxazole, fam-ciclovir, omeprazole, and escitalopram, as well as vitamin D and magnesium supplementation. There were no known drug allergies. The patient lived in a coastal town in New England with his mother. He had previously worked in the food-service industry. He had never smoked tobacco or used illicit drugs; he drank three cans of beer weekly. His family history included breast cancer and headaches in his maternal grandmother, prostate cancer in his paternal grandfather, and hypertension in his father. On examination, the temperature was 36.9C, the blood pressure 13688 mm Hg, the pulse 104 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 100 while the patient was breathing ambient air. Visual acuity was 2025 in both eyes with correction, and visual fields were full on confrontation testing. The pupils were symmetric and reactive to light. There was no proptosis. Slit-lamp examination revealed few cells in the anterior chamber, and funduscopic examination was normal. Test results for cranial nerve function, strength, sensation, reflexes, coordination, and gait were normal. There was palpable lymphadenopathy in the cervical, clavicular, axillary, and inguinal regions. Discrete papules were present on both arms, and diffuse xerosis and an eczematous rash were present on the upper back and chest. Laboratory testing revealed a platelet count of 47,000 per microliter reference range, 150,000 to 400,000. Blood testing for cytomegalovirus, EpsteinBarr virus EBV, varicellazoster virus, and human herpesvirus 8 HHV-8 DNA was negative. Screening for human immunodeficiency virus, syphilis, and Lyme disease was also negative. Examination of a peripheral-blood smear confirmed the presence of anemia and thrombo-cytopenia; there were no schistocytes. Additional laboratory test results are shown in Table 1. Imaging studies were obtained. Dr. Karen Rodriguez: Magnetic resonance imaging MRI of the head was performed. T2-weighted, fluid-attenuated inversion recovery images Fig. 2A and 2B showed multiple new hyperintense lesions, measuring up to 11 mm in greatest dimension, within the supratentorial and infratentorial regions of the brain. Images obtained after the administration of contrast material showed faint enhancement of the lesions. These foci appeared to be centered within the juxtacortical and peri-ventricular white matter and could reflect areas of demyelination, graft-versus-host disease GVHD involving the central nervous system CNS, acute lymphoblastic leukemia with CNS involvement, or an infectious process. There was no abnormal enhancement of the optic nerves or the orbital structures. 18F-fluorodeoxyglucose FDGpositron-emission tomography PET and computed tomography CT was also performed. The PET-CT scans Fig. 2C through 2H showed moderate-to- intense FDG uptake associated with widespread lymphadenopathy, including bilateral cervical, axillary, external iliac, and inguinal lymph nodes. There was also abnormal uptake in the spleen. Dr. Anandappa: The patient was admitted to this hospital, and lumbar puncture was performed. Cerebrospinal fluid analysis revealed a total protein level of 147 mg per deciliter reference range, 5 to 55 and a glucose level of 49 mg per deciliter 2.7 mmol per liter; reference range, 50 to 75 mg per deciliter 2.8 to 4.2 mmol per liter. The white-cell count was 21 per microliter reference range, 0 to 5, with 61 lymphocytes, 27 neutrophils, and 3 eosinophils; the red-cell count was 16,000 per microliter reference range, 0 to 5, with xanthochromia present. Grams staining of cerebrospinal fluid showed a moderate amount of mononuclear cells and no organisms. Cytologic studies were notable for increased lymphocytes and plasma cells. A diagnostic test was performed.
OUTPUT:
| Plasma-cell myeloma post-transplantation lymphoproliferative disorder. |
NEJM_Reasoning_Subset11 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: Dr. Diana L. Stern Psychiatry: A 65-year-old woman was admitted to this hospital because of depression, recurrent falls, and difficulty caring for herself. Four years before the current admission, the patient received a diagnosis of depression that was precipitated by psychosocial stressors. She was treated with bupropion, citalopram, and cognitive behavioral therapy. The depression was well controlled until 1 year before the current admission, when she began to have an-hedonia, decreased energy, sadness, and poor concentration. She resumed cognitive behavioral therapy, but her symptoms worsened during the next 4 months, and she had suicidal ideation. The dose of bupropion was increased, and treatment with trazodone was started. Fourteen weeks before the current admission, the patient was in a motor vehicle accident that was attributed to her falling asleep while driving. After the accident, she reported increased sadness, low energy, and inability to perform her usual activities. One week later, she fell and struck her head, and she was evaluated in the emergency department of this hospital. She reported that, before her fall, she had been feeling unsteady because of weakness in the left leg. A physical examination was normal. Computed tomography CT of the head, performed without the administration of intravenous contrast material, revealed hypodensi-ties involving the subcortical and periventricular white matter, findings consistent with chronic small-vessel disease. The patient was referred to the neurology clinic of this hospital and was discharged home. During the next week, the patient had balance difficulties and began using a walker. When she was evaluated in the neurology clinic, she reported imbalance and occasional nausea. On examination, she had a depressed affect. Strength was assessed as 55 in the proximal and distal muscles of the arms and legs. Reflexes were 1 and symmetric at the biceps, triceps, and patellar tendons and were CME at NEJM.org absent at the ankles, with downgoing toes. The gait was wide-based and unsteady, with mild dragging of the left leg. A diagnosis of post-concussive syndrome was considered, and treatment with ondansetron was started for nausea. Additional tests were performed. Magnetic resonance imaging MRI of the head, performed after the administration of intravenous contrast material, revealed increased signal intensity in the pons and in a periventricu-lar distribution on T2-weighted imaging, without associated contrast enhancement. There was a region of decreased signal intensity in the right corona radiata on a map of the apparent diffusion coefficient. Results of electroencephalography were normal, as were results of electromyography and nerve-conduction studies of the left leg. Physical therapy was recommended, and repeat MRI was planned for 6 weeks later. Over the next 6-week period, during sessions of cognitive behavioral therapy, the patient was noted to be less talkative, with slow processing, impaired recall, and mild inattention. Repeat MRI with angiography performed 6 weeks after the first study revealed patchy hyperintensity involving the centrum semiovale, corona radiata, internal capsule, and corticospinal tract bilaterally on T2-weighted fluid-attenuated inversion recovery FLAIR imaging, without contrast enhancement; the cerebral vasculature was normal. The patient had recurrent falls without loss of consciousness and began using a wheelchair. She reported worsening sadness, anxiety, and anhedonia, and treatment with buspirone was started. On evaluation in the neurology clinic 6 weeks before the current admission, testing of leg strength yielded inconsistent results, but strength in both legs was assessed as 55 with maximum effort. Dragging of the left leg was also noted to be inconsistent. There were concerns that her depression might be contributing to her neurologic changes, and further follow-up with the psychiatric service was recommended. Five weeks before the current admission, the patients husband brought her to the emergency department of this hospital for an evaluation of worsening memory impairment, poor self-care, and frequent falls. The patient had stopped participating in physical therapy and was spending most of the day in bed. She reported that she had lost 14 kg during the previous 4 months. Other medical history included hypertension, diabetes, and osteoarthritis of the knees. There was a history of postpartum depression 27 years earlier that had lasted for several months. Medications included amlodipine, buspirone, bupro-pion, cholecalciferol, citalopram, metformin, and trazodone. There were no known drug allergies. The patient lived with her husband in a suburb of Boston and worked as a teacher. She was a lifelong nonsmoker, drank alcohol only occasionally, and did not use illicit drugs. Her mother had a history of anxiety and depression in her seventh decade of life. Her sister had a history of stroke. On examination, the patient appeared tired and disheveled, with psychomotor retardation. Strength in both legs was assessed as 55. She had a monoplegic gait, with buckling of the left leg, when walking down a hallway, but she had a normal gait when walking on a treadmill. Her score on the Montreal Cognitive Assessment was 25, indicating mild cognitive impairment; scores range from 0 to 30, with higher scores indicating better cognitive function. The complete blood count, results of liver-function and kidney-function tests, and blood levels of cobalamin, thyrotropin, and electrolytes were normal. Screening for syphilis, Lyme disease, and the human immunodeficiency virus was negative, as was urine toxicologic screening. After an evaluation by a neurology consultant, the patient was voluntarily admitted to the inpatient psychiatric unit. While the patient was in the hospital, the dose of citalopram was tapered, and treatment with desvenlafaxine and amphetaminedextro-amphetamine was started; her levels of attention and wakefulness increased. She participated in group psychotherapy, cognitive behavioral therapy, and occupational and physical therapy. She continued to have variable weakness in the left leg and had three witnessed falls, during which she reportedly had fatigue and lowered herself to the ground. On hospital day 11, the patient reported being unable to use her left arm because of weakness. Although her left arm rested across her chest for most of the day, she was observed holding her husbands hand with her left hand when saying goodbye. On evaluation by a neurology consultant, strength in the left arm was assessed as 55. The working diagnosis was functional neurologic disorder. On hospital day 12, the patient was discharged to a rehabilitation center. At the rehabilitation center, the patient received physical, occupational, and speech therapy, as well as medications to treat depression. During the first week, she made progress toward independence in bathing, toileting, and grooming but had limited attention, memory, and problem solving. During the second week, she became more withdrawn. There was a paucity of speech with hypophonia, decreased attention, and less eye contact with visitors who sat on her left side than with visitors who sat on her right side. During the third week, the patient stopped answering questions and following commands. She was evaluated again in the emergency department of this hospital. On examination, the temperature was 36.7C, the blood pressure 14190 mm Hg, the pulse 98 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 99 while the patient was breathing ambient air. She was withdrawn and minimally interactive. She was able to state her name but not the date or location. She did not blink in response to threat on the left side and did not track the examiners finger past the midline to the left. There was flattening of the left nasolabial fold. The left arm was hypertonic and held in flexion; there was no spontaneous movement of the left arm or leg, and she declined to participate in a strength examination. She did not withdraw the left arm in response to nail-bed pressure; she withdrew the left foot with antigravity movement in response to tactile stimulation. The white-cell count was 12,940 per micro-liter reference range, 4500 to 11,000, with a normal differential count. The remainder of the complete blood count was normal, as were the results of liver-function and kidney-function tests and blood levels of electrolytes. A diagnostic test was performed.
OUTPUT:
| Diffuse large B-cell lymphoma. |
NEJM_Reasoning_Subset12 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: Dr. Neelam A. Phadke: A 54-year-old woman with a history of episodic swelling of the arms, hands, and feet was evaluated in the emergency department of this hospital because of abdominal pain, nausea, and vomiting. Twenty-three years before the current presentation, swelling of the left hand developed after the patient sustained a human bite. The swelling was associated with mild pruritus, erythema, and warmth. The swelling was well demarcated, involved only the left hand, and resolved after 3 days without specific treatment. Twenty-two years before the current presentation, the patient had epigastric pain that radiated to her back, with associated nausea. Results of an upper gastrointestinal series, computed tomography CT of the abdomen, hepatobiliary scintig-raphy, and esophagogastroduodenoscopy were reportedly normal. The abdominal pain resolved, but two similar self-limited episodes occurred during the next year. No cause for the abdominal pain was identified. During the next 3 years, episodes of self-limited swelling occurred once per year; one episode involved the right foot, one the left hand, and one the right hand. There were no clear triggers for the episodes, although they tended to occur after exposure to cold or after minor trauma, such as scratching. Eighteen years before the current presentation, episodes of swelling of the hands and feet began to occur on a monthly basis, and the patient was evaluated at another hospital after an episode of swelling of the left hand. A skin-biopsy specimen reportedly showed sparse superficial dermal perivascular and interstitial mixed inflammatory infiltrate and stromal edema. Treatment with prednisone was initiated. The swelling of the left hand resolved after 3 days, and the patient was referred to the allergy clinic of this hospital. Laboratory test results are shown in Table 1. A diagnosis of acquired C1 inhibitor deficiency was made on the basis of low levels of C1 esterase inhibitor, C4, and C1q. Results of serum protein electrophoresis were normal, and tests for antinuclear antibodies were negative. The patient was evaluated in the allergy clinic of a third hospital, and treatment with CME at NEJM.org daily danazol was initiated. The episodes of swelling of the hands and feet resolved. Ten years before the current presentation, episodes of swelling of the eyelids and upper lip occurred with associated pruritus. The episodes began with a sensation of facial flushing, pruri-tus of the scalp, and a raised pruritic rash on the face and chest; at times, these episodes were accompanied by shortness of breath, chest tightness, itchy throat, and red eyes. The patient was evaluated in the allergy clinic of the third hospital. Laboratory test results are shown in Table 1. The dose of danazol was increased, and the patient was instructed to take hydroxyzine as needed during episodes of swelling that were associated with pruritus. The swelling episodes associated with pruritus occurred with variable frequency several times per week to once every few months but resolved within 30 minutes after the administration of hydroxyzine. Cetirizine was substituted for hydroxyzine for acute episodes. Treatment with daily loratadine and ranitidine was initiated, and the episodes of swelling with pruritus decreased in frequency. Four months before the current presentation, swelling of the right arm developed after veni-puncture. There was no associated pruritus. The patient was evaluated in the emergency department of this hospital. Ultrasonography of the arm showed no evidence of deep-vein thrombo-sis, and the patient was discharged from the emergency department. The swelling resolved after 3 days. Two weeks before the current presentation, nausea, vomiting, and diarrhea developed. The patient attributed her symptoms to food poisoning, since her daughter had similar symptoms; the symptoms resolved after 3 days. One week before the current presentation, epigastric pain developed; the pain was burning in character, worsened with consumption of food, and abated with the use of nonsteroidal anti-inflammatory drugs NSAIDs. The patient was evaluated at a fourth hospital, where CT of the abdomen reportedly revealed inflammation of the duodenum and jejunum. A proton-pump inhibitor was administered, and the abdominal pain decreased. The patient was instructed not to take NSAIDs and was discharged home. However, during the next week, abdominal pain recurred, along with new symptoms of poor appetite and early satiety. She presented to the emergency department of this hospital for further care. Other history included hypertension, low-back pain, and osteoporosis; she had undergone previous appendectomy and cesarean section. The patient also had a subepithelial duodenal mass, measuring 7 mm in diameter, that had been stable in size during the past 5 years; ultrasono-graphic images had shown that the mass was consistent with a benign stromal cell neoplasm. Medications included amlodipine, calcium carbonate, cholecalciferol, omeprazole, ranitidine, loratadine, and danazol, as well as cetirizine as needed. The patient had no known medication allergies but was allergic to iodinated contrast material. She was originally from Bangladesh and now lived with her husband and two children in a suburban community in New England and worked as a teacher. She did not smoke tobacco, drink alcohol, or use illicit drugs. Her mother had hypertension. The patient reported no similar episodes of swelling in either of her parents. On examination, the temperature was 36.8C, the blood pressure 10681 mm Hg, the pulse 74 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 99 while the patient was breathing ambient air. The abdomen was mildly distended with normal bowel sounds and diffuse tenderness on palpation, without rebound or involuntary guarding. The remainder of the physical examination was normal. The complete blood count was normal, as were blood levels of lipase, bilirubin, alkaline phosphatase, troponin, and thyrotropin. The alanine aminotransferase level was 49 IU per liter reference range, 7 to 33, and the aspartate aminotransferase level was 52 IU per liter reference range, 9 to 32. Dr. Ravi Gottumukkala: CT of the abdomen and pelvis, performed without the administration of oral or intravenous contrast material, revealed long-segment marked circumferential thickening of the jejunal wall with associated mesen-teric edema and small-volume free intraperito-neal fluid. The remainder of the small bowel and colon showed no abnormalities Fig. 1. Dr. Phadke: Diagnostic tests were performed, and treatment decisions were made.
OUTPUT:
| Hereditary angioedema type I due to heterozy- gous deletion of exons 5 and 6 in SERPING1. |
NEJM_Reasoning_Subset13 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: CME Dr. Alison C. Castle: A 56-year-old woman was admitted to this hospital in the spring of 2020, during the initial surge of the coronavirus disease 2019 Covid-19 pandemic in Boston, because of fever, myalgias, diarrhea, and a dry cough. Six weeks before this admission, the patient had contact with a person with confirmed severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 infection. At that time, she did not have any symptoms compatible with Covid-19 and was not tested for SARS-CoV-2. Four weeks before this admission, in accordance with statewide recommendations from the Department of Public Health, the patient began isolating at home with her teenage son, working from home, and having groceries delivered. Two weeks before this admission, she and her son left home for a few hours to eat outdoors and spend time in a wooded area; they otherwise remained at home. Six days before this admission, fever, chills, and myalgias developed. The next day, watery diarrhea occurred. The patients temperature measured at home was 38.3C; fever persisted despite the intermittent administration of acetaminophen. Three days before this admission, a frontal headache developed, along with a dry cough that was associated with a self-limited episode of chest pain. The patients son had had no symptoms, except for a self-limited episode of diarrhea 2 weeks before the patients symptoms developed. On the day of admission, the patient continued to have fever, so she presented to the emergency department of this hospital for evaluation. In the emergency department, the patient reported ongoing myalgias, headache, and cough. There was no nausea, vomiting, rash, shortness of breath, or anosmia. She had no notable medical history and took no medications. She was allergic to amoxicillin, with an unknown reaction. She did not smoke tobacco and drank alcohol rarely; she did not use illicit drugs. The patient lived in an urban area of New England and had traveled to Canada 6 months before this admission. She had a pet cat; there was no other animal contact. On examination, the patient appeared anxious, but breathing was unlabored. The temperature was 38.9C, the blood pressure 12164 mm Hg, the heart rate 124 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 95 at rest and 98 during ambulation, both while she was breathing ambient air. The patient was alert and oriented to time, place, and person. There were no focal neurologic deficits. There was no meningism. The mucous membranes were dry. The first and second heart sounds were normal, without additional sounds or murmurs. There were vesicular breath sounds. The abdomen was soft and nontender, without hepatosplenomegaly. There was no rash. Laboratory test results are shown in Table 1. Dr. Patrick P. Bourgouin: Chest radiography revealed low lung volumes, without evidence of pneumonia or pulmonary edema. Dr. Castle: SARS-CoV-2 nucleic acid testing of a nasopharyngeal specimen was negative, as was testing for adenovirus, human metapneumovirus, influenza virus types A and B, parainfluenza virus types 1 through 4, respiratory syncytial virus, human rhinovirus and enterovirus, Bordetella pertussis, B. parapertussis, Chlamydia pneumoniae, and Mycoplasma pneumoniae. Blood cultures were negative. Urinalysis was negative for leukocyte esterase and nitrites. The procalcitonin level was 0.36 ng per milliliter reference range, 0.00 to 0.08. Intravenous fluids and acetaminophen were administered, and the heart rate decreased to 93 beats per minute. The patient was admitted to this hospital because of concerns that she had Covid-19. On the second hospital day, the patient had ongoing diarrhea, headache, and cough, along with fatigue. The temperature was 40.2C, the blood pressure 11564 mm Hg, the heart rate 89 beats per minute, and the oxygen saturation 96 while she was breathing ambient air. The administration of intravenous fluids was continued. SARS-CoV-2 nucleic acid testing of a second nasopharyngeal specimen was negative. Laboratory test results are shown in Table 1. On the third hospital day, the temperature was 38.7C. Dr. Bourgouin: Computed tomography CT of the chest, performed without the administration of intravenous contrast material, revealed interlobular septal thickening, mild ground-glass opacities at the lung bases, and small bilateral pleural effusions Fig. 1. Dr. Castle: During the next 3 days, the patient had ongoing myalgias, headache, and cough. Fever persisted, and the oxygen saturation remained normal. Urine antigen testing for legion-ella and Streptococcus pneumoniae antigens was negative, as was screening for human immunodeficiency virus HIV types 1 and 2 and nucleic acid testing of a blood specimen for cytomega-lovirus and EpsteinBarr virus. Blood cultures remained negative. On the seventh hospital day, diarrhea resolved, but fever, myalgias, headache, and cough persisted. The physical examination was unchanged, with a normal oxygen saturation during ambulation. Dr. Bourgouin: Chest radiography revealed no evidence of pneumonia. Dr. Castle: The procalcitonin level was 0.57 ng per milliliter; other laboratory test results are shown in Table 1. Levofloxacin was administered. On the eighth hospital day, fever resolved but headache and fatigue persisted. A diagnostic test was performed.
OUTPUT:
| Anaplasmosis. |
NEJM_Reasoning_Subset14 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
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INPUT: CME at NEJM.org Dr. David M. Dudzinski: A 78-year-old man was evaluated in the cardiology clinic of this hospital because of biventricular myocardial wall thickening, progressive mi-tral regurgitation, and ventricular arrhythmias. The patient had been a distinguished multisport athlete in high school and college. However, in his 20s, he found that he was unable to perform competitively, and he noticed that he did not sweat as much as his teammates. After an episode of sports-related exertional dizziness, he was evaluated by a physician, and a diagnosis of hypertrophic cardiomyopathy was considered. Twenty-five years before the current evaluation, a transthoracic echocardiogram TTE reportedly showed a symmetric left ventricular wall thickness of 19 mm reference value, 11, a left ventricular ejection fraction of 74 reference range, 50 to 75, mitral valve thickening, and trace mitral regurgitation, with no left ventricular outflow gradient. An electrocardiogram showed sinus rhythm, incomplete right bundle-branch block, precordial J-point elevation, and QRS voltage that met the electrocardiographic criteria for left ventricular hypertrophy Fig. 1A. The patients blood pressure was 16090 mm Hg, and he started treatment with meto-prolol succinate and then also with amlodipine for elevated blood pressure. During the next 10 years, the patient had intermittent chest discomfort, exer-tional dyspnea, and leg edema. The chest discomfort and exertional dyspnea were most likely to occur when he was walking or after he had eaten a meal. He was evaluated by three cardiologists; treatment with metoprolol succinate and amlo-dipine was continued, treatment with enalapril was started, and triamterene hydrochlorothiazide was administered as needed for leg edema. A repeat TTE reportedly showed a symmetric left ventricular wall thickness of 20 mm, a normal left ventricular ejection fraction, right ventricular wall thickening, left atrial enlargement, mitral valve thickening, mild-to-moderate mitral regurgitation, aortic valve thickening, and mild ascending aortic dilatation 39 mm, with no evidence of left ventricular outflow tract obstruction and no evidence of systolic anterior motion of the mitral valve. An exercise stress test followed by
OUTPUT:
| Fabry’s disease. |
NEJM_Reasoning_Subset15 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: Dr. Leontios Pappas Medicine: An 80-year-old woman was admitted to this hospital because of pancytopenia and the identification of schistocytes on a peripheral-blood smear. Six weeks before admission to this hospital, nausea, vomiting, and diarrhea developed, along with chills and subjective fever. The symptoms resolved after 4 days without specific intervention, but then intermittent dysphagia with solid foods and early satiety developed. During the next 4 weeks, the patient had gradually progressive fatigue and light-headedness. The fatigue progressed to the point that she could no longer stay at work for more than a few hours; she presented to another hospital for evaluation. At the other hospital, the patient reported that she had ongoing fatigue and had lost 6 kg of weight over a 5-week period. On examination, the temperature was 38.9C, the weight 55.5 kg, and the body-mass index the weight in kilograms divided by the square of the height in meters 21.9. Laboratory studies revealed pancytopenia, and examination of a peripheral-blood smear revealed schistocytes. Blood levels of glucose and electrolytes were normal, as were the results of kidney-function and liver-function tests; other laboratory test results are shown in Table 1. Imaging studies were obtained. Dr. Ranjodh S. Dhami: A chest radiograph was normal. Computed tomography CT of the abdomen and pelvis, performed after the administration of intravenous and oral contrast material, revealed a small hiatal hernia, multiple simple cysts in the right kidney, and indeterminate bilateral pelvic masses measuring 4.8 cm in diameter on the right side and 6.3 cm in diameter on the left side Fig. 1. Dr. Pappas: Intravenous fluids were administered, and the patient was admitted to the other hospital. On hospital day 2, the hemoglobin level decreased to 6.6 g per deciliter, and two units of packed red cells were transfused. Esophagogastro-duodenoscopy revealed diffuse esophageal inflammation with white exudates throughout the esophagus; examination of brushings revealed yeast consistent with candida, and treatment with fluconazole was initiated. During the next 3 hospital days, the patient continued to feel unwell, with persistent fever and limited oral intake due to odynophagia, and the administration of intravenous fluids was continued. Blood and urine cultures showed no growth. On hospital day 5, empirical therapy with doxycycline was started because of concerns about a possible tickborne illness. On hospital day 6, the oxygen saturation decreased to 89 while the patient was breathing ambient air and then increased to 94 when oxygen was delivered through a nasal cannula at a rate of 3 liters per minute. CT of the chest, performed after the administration of intravenous contrast material, revealed ground-glass opacities and interlobular septal thickening, findings consistent with pulmonary edema, along with bilateral pleural effusions of a small to moderate size. The administration of intravenous fluids was stopped, and one dose of intravenous furosemide was provided. On hospital day 7, fever resolved but pancyto-penia persisted. Examination of a peripheral-blood smear revealed a moderate amount of schistocytes, severe anisocytosis, large platelets, and an increased amount of bands without blasts. Direct and indirect Coombs tests were negative, as were nucleic acid tests for babesiosis and anaplasmosis. Blood levels of electrolytes, glucose, cobalamin, folate, homocysteine, and anticardiolipin IgG and IgM were normal, as were the results of kidney-function and liver-function tests. The results of serologic tests for EpsteinBarr virus were consistent with previous infection. Flow cytometry of the peripheral blood showed phenotypically normal myeloid cells; there was an increased amount of atypical CD34 myeloblasts, which accounted for less than 1 of leukocytes and were of unclear clinical significance. A tunneled catheter was placed in the right internal jugular vein, and plasma exchange was initiated for the treatment of possible thrombotic thrombocytopenic purpura TTP. Total parenteral nutrition was also initiated, because oral intake was still limited by odynophagia. On hospital day 8, oral intake of soft foods and liquids increased. A transthoracic echocar-diogram showed normal left ventricular size and function, as well as a mildly thickened aortic valve with no stenosis or regurgitation; there was trace mitral and tricuspid regurgitation. On hospital day 9, the patient underwent additional plasma exchange and was transferred to this hospital for further care. On evaluation in this hospital, the patient reported that her energy level had increased. She recalled that she had felt mildly confused at the other hospital, but the confusion had since resolved. She had had no gum bleeding or blood in the stool or urine. Other medical history included hypertension and dyslipidemia. Surgical history included hysterectomy at 40 years of age, with no vaginal bleeding since the procedure. One year earlier, routine laboratory testing had revealed mild thrombocytopenia and anemia. A bone marrow biopsy performed at that time had revealed slightly hypercellular marrow with maturing trilineage hematopoiesis but with some erythroid abnormalities and occasional hyper-chromatic megakaryocytes; cytogenetic analysis had shown a loss of chromosomes 3 and 5 and a gain of chromosome 8 in 65 of the cells. Thereafter, blood counts monitored every 4 months, including 4 months before this presentation, had remained stable; laboratory test results are shown in Table 1. Medications included amlodipine, atorvastatin, and hydrochlorothiazide. There were no known drug allergies. The patient drank alcohol occasionally and did not use illicit drugs. She had smoked tobacco for 50 years but had quit 5 years before this presentation. She was widowed and lived alone in New England; her work involved cleaning a church several days a week. Her sister had had breast cancer at 30 years of age, and a brother had had testicular cancer at a young age and liver cancer at 55 years of age. On examination, the temperature was 36.8C, the blood pressure 15065 mm Hg, the pulse 72 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97 while oxygen was administered through a nasal cannula at a rate of 2 liters per minute. The patient was alert and oriented, and she did not appear ill. There were no petechiae. There was no bleeding at the site of tunneled catheter placement in the right internal jugular vein. The first and second heart sounds were normal; a grade 26 systolic murmur was heard at the left lower sternal border. The remainder of the physical examination was normal. Examination of a peripheral-blood smear revealed schistocytes, anisocytosis, and a low platelet count, with large platelets present; the white cells appeared normal, and there were no blasts Fig. 2. The results of serum protein electrophoresis were normal. The levels of serum free kappa and lambda light chains were increased, with a normal ratio. Screening for human immunodeficiency virus infection was negative. Urinalysis showed 2 urobilinogen, without bilirubin, blood, glucose, ketones, protein, or nitrates; the specific gravity and pH were normal. Consultation was obtained from the gyne-cology service regarding the bilateral pelvic masses noted on CT of the abdomen and pelvis. Blood levels of CA 125, CA 19-9, and carcinoem-bryonic antigen were normal, and follow-up in the gynecology clinic was recommended for further evaluation after discharge. Other laboratory test results are shown in Table 1. A diagnostic test was performed, and management decisions were made.
OUTPUT:
| Myelodysplastic syndrome. |
NEJM_Reasoning_Subset16 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: Dr. Jacquelyn M. Nestor Medicine: A 41-year-old woman with transient dysarthria and facial droop was transferred to this hospital for evaluation of masses on the mitral valve. Three weeks before this presentation, the patient presented to the emergency department of another hospital because of concerns about heavy vaginal bleeding that had developed 1 week earlier and was associated with crampy abdominal pain, fatigue, dyspnea, and lightheadedness. Examination was notable for a heart rate of 91 beats per minute, a blood pressure of 13079 mm Hg, and an oxygen saturation of 100 while she was breathing ambient air; the examination was otherwise reportedly normal, although a gynecologic examination was not performed. Laboratory results were notable for a hemoglobin level of 8.2 g per deciliter reference range, 12.0 to 16.0; previous level 1 year earlier, 9.1, a mean corpuscular volume of 71.3 fl reference range, 80 to 94, and a platelet count of 148,000 per microliter reference range, 150,000 to 450,000. Urine human chorionic gonadotropin was undetectable. Normal saline was administered intravenously, and a 5-day course of medroxyprogesterone acetate was prescribed. Eleven days after the patient completed the therapy with medroxyprogesterone acetate 9 days before this presentation, heavy vaginal bleeding and dyspnea recurred. An additional 3-day course of medroxyprogesterone acetate was prescribed. The evening after the patient finished the second course of treatment, within 1 hour after she had been seen and had appeared to be well, her husband noted that she had facial droop on the right side and slurred speech; he called emergency medical services. When she arrived at the emergency department of a second hospital, within 1 hour after the onset of symptoms, her examination was notable for a heart rate of 91 beats per minute, a blood pressure of 17383 mm Hg, and an oxygen saturation of 99 while she was breathing ambient air. She was noted to have facial droop on the right side and unintelligible speech. Dr. Sandra P. Rincon: Computed tomography CT of the head Fig. 1A revealed no evidence of acute infarction or intracranial hemorrhage. Small chronic infarcts were seen in the right thalamus and right cerebellar hemisphere. A CT angiogram CTA of the head and neck did not show high-grade stenosis or large-vessel occlusion. Dr. Nestor: A neurology consultation was obtained; aspirin and atorvastatin were administered. Blood levels of electrolytes, albumin, low-density lipoprotein cholesterol, and glycated hemoglobin were normal, as were the white-cell count and differential count and the results of liver-function and kidney-function tests. Urine human chorionic gonadotropin was undetectable, and urinalysis showed 3 blood, no protein, and no casts. Additional laboratory test results are shown in Table 1. Within 45 minutes after the patient arrived at the emergency department of the second hospital, the facial asymmetry and dysarthria resolved. The patient was admitted to the medical unit of the second hospital. Dr. Rincon: The next day, magnetic resonance imaging MRI and angiography of the head and neck again revealed old lacunar infarcts in the right thalamus Fig. 1B and right cerebellar hemisphere Fig. 1C. There was no evidence of an acute infarction Fig. 1D, intracranial hemorrhage, or cerebrovascular occlusion Fig. 1E and 1F. Dr. Nestor: Two units of packed red cells were transfused. Post-transfusion laboratory test results are shown in Table 1. A transthoracic echocar-diogram Fig. 2A and 2B and Video 1, available with the full text of this article at NEJM.org showed thickened mitral valve leaflets and mild-to-moderate mitral regurgitation, with an estimated right ventricular systolic pressure of 48 mm Hg. Dr. Evin Yucel: On the third hospital day, a trans-esophageal echocardiogram Fig. 2C and Videos 2 and 3 showed multiple echodensities on the atrial side of the mitral valve leaflets at the closure lines that were consistent with vegetations. Cultures of blood were obtained, and heparin was administered intravenously. Dr. Nestor: On the fourth hospital day, the rate of heparin infusion was decreased at 6-hour intervals when the partial-thromboplastin time exceeded 150 seconds, until the infusion was stopped. Laboratory test results are shown in Table 1; complement levels C3 and C4 were normal. Additional cultures of blood were obtained. Dr. Rincon: Repeat CT of the head revealed no acute abnormality. CT of the chest showed clustered nodules in the lower lobes that were probably related to aspiration, and CT of the abdomen and pelvis Fig. 2D, 2E, and 2F revealed an enlarged heterogeneous uterus with multiple fibroids. Dr. Nestor: The next day, the patient was transferred to this hospital. On a review of systems, she reported no recurrence of dysarthria or facial droop and noted no other neurologic symptoms. She reported that she had had heavy menstrual bleeding and exertional dyspnea in the weeks preceding this presentation; pruritic, macular rashes on the trunk, scalp, arms, and legs with associated photosensitivity that had persisted for many weeks; new Raynauds phenomenon in the past 10 months; and a long history of dry eyes and seasonal allergies. Medical history was notable for sickle cell trait, vitamin B12 deficiency, iron deficiency resulting in past iron infusions, uterine fibroids, anxiety, and hyperten-sion. Surgical history included multiple laparos-copies and two laparotomies, including salpingo-oophorectomy for endometriosis. Owing to infertility, she had undergone in vitro fertilization; she had a first-trimester spontaneous abortion at 25 years of age. During her second pregnancy at 33 years of age, a screening rapid plasma reagin RPR test was positive at 1:8; however, a treponemal-specific confirmatory test for syphilis was negative. Pregnancy-induced hypertension developed, followed by placental ab-ruption at 30 weeks, which resulted in a cesarean delivery. Medications included amlodipine, cyano-cobalamin, ferrous sulfate, and medroxyproges-terone acetate. She had no known medication allergies. The patient lived in eastern Massachusetts with her husband and child. She did not drink alcohol or smoke tobacco. Her mother had rheumatoid arthritis, hypertension, and a history of spontaneous abortion. One grandmother had diabetes and the other grandmother had had a stroke. An aunt had had leukemia and later breast cancer. Her child has psoriasis. The temperature was 36.8C, the heart rate 74 beats per minute, the blood pressure 15598 mm Hg, and the oxygen saturation 99 while the patient was breathing ambient air. The height was 175 cm, the weight 107 kg, and the body-mass index the weight in kilograms divided by the square of the height in meters 34.9. There were several small, circular macules on her back Fig. 3. There was a grade 26 holosystolic murmur at the left sternal border and apex. She had no lymphadenopathy, petechiae, nail changes, or evidence of arthritis. The remainder of the examination was normal, as was a neurologic examination. Laboratory test results are shown in Table 1. All the blood cultures obtained at the second hospital showed no growth. An electrocardiogram was normal. Diagnostic test results were received, and management decisions were made.
OUTPUT:
| Systemic lupus erythematosus with antiphospho- lipid syndrome. |
NEJM_Reasoning_Subset17 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: CME at NEJM.org Dr. Emma C. Materne Pediatrics: A 12-month-old boy with Hirschsprungs disease was admitted to this hospital because of fever. Fifteen days before the current admission, the patient had a temperature of 39.7C. His parents noticed that he was fussy and less active than usual and that he had a decreased appetite along with several episodes of spitting up; there was no vomiting or diarrhea. During the next 5 days, fever occurred daily and abated with the administration of acetaminophen or ibuprofen. Ten days before the current admission, a bowel movement with watery, nonbloody, foul-smelling, mustard-yellow stool occurred. The patient was brought to the emergency department of this hospital. On examination, the patient was irritable. The abdomen was soft and non-tender. There were well-circumscribed, erythematous, edematous plaques on the abdomen, legs, feet, and forearms. The alanine aminotransferase level was 131 U per liter reference range, 10 to 55, the aspartate aminotransferase level 250 U per liter reference range, 9 to 80, the ferritin level 3826 g per liter reference range, 30 to 300, and the d-dimer level 3218 ng per milliliter reference range, 500. The erythrocyte sedimentation rate was 40 mm per hour reference range, 0 to 15; the white-cell count was normal. Other laboratory test results are shown in Table 1. A radiograph of the abdomen showed gas-filled loops of bowel. The rectum was irrigated, and intravenous piperacillintazobactam was administered. On the third hospital day, the patient was afebrile and able to take formula, and the diarrhea abated. He was discharged home with a prescription for a course of metro-nidazole. During the next 2 days, the patient had no fever or diarrhea. However, 4 days before the current admission, a day-care worker observed that the patient appeared tired. During the subsequent 3 days at home, fever again developed, with chills and a decreased appetite. The day before the current admission, the patient cried through the night. He was brought to the emergency department of this hospital for evaluation. The parents reported that the patient was fussy and had poor sleep and generalized weakness; there was no diarrhea or new rash. The parents did not think that the patient was in pain. Additional history was obtained from the parents. The patient had met developmental milestones until 1 month earlier, when he had stopped crawling. He had previously been able to pull his body into a standing position, but he no longer attempted this maneuver. If he was placed in a standing position, he collapsed; if he was placed in a sitting position, he was able to stay upright. He had previously passed objects from hand to hand, but he had a new preference of holding objects with the left hand. Two days before this evaluation, the parents had noticed that the patient no longer walked with support; he seemed to dislike having his hands held. The patient had cornea plana and a history of Hirschsprungs disease, for which he had undergone laparoscopic sigmoid colectomy and an anal pull-through procedure at 2 months of age. Four months before the current evaluation, an intermittent diffuse rash on the trunk, arms, and legs had developed. The rash was characterized by purplish and pinkish plaques that appeared and varied in intensity of color throughout the day; it did not seem to be itchy or painful and usually resolved within 24 hours without treatment. Immunizations were up to date. Medications included metronidazole, acetaminophen, ibuprofen, and cetirizine, as well as carboxymethylcel-lulose eye drops; there were no known allergies to medications. The patient lived with his mother, father, and pet dog in a small town in New England, and he attended day care 5 days per week. His mother was healthy, and his father had irritable bowel syndrome and Poland syndrome congenital aplasia of unilateral chest-wall muscles. His paternal grandmother had hypothyroidism, his maternal great-grandfather had had pancreatic cancer, his paternal great-grandfather had had breast cancer, a maternal second cousin had autism, and multiple maternal family members had Raynauds phenomenon. On examination, the temperature was 38.3C, the blood pressure 11352 mm Hg, the heart rate 166 beats per minute normal range for age, 80 to 160, and the respiratory rate 30 breaths per minute normal range for age, 30 to 60. The patient was diaphoretic and irritable, and he cried during the examination. He had rhinorrhea. The abdomen was not distended or tender. There was limited extension of the wrists and knees, as well as limited inversion and eversion of the feet. The ankles were mildly stiff, and the feet were mildly swollen. There were erythematous plaques on the abdomen, back, arms, and legs Fig. 1. The ferritin and d-dimer levels remained elevated, and the aspartate aminotransferase and alanine aminotransferase levels were normal. The erythrocyte sedimentation rate was 75 mm per hour, the white-cell count 26,820 per microliter reference range, 6000 to 17,500, and the platelet count 682,000 per microliter reference range, 150,000 to 400,000. Blood cultures and urinalysis were normal. Testing of a nasopharyngeal swab for severe acute respiratory syndrome coro-navirus 2 SARS-CoV-2 RNA was negative. Other laboratory test results are shown in Table 1. Dr. Randheer Shailam: A radiograph of the chest and abdomen was normal. Ultrasonography of the abdomen revealed cholelithiasis and prominent lymph nodes in the right lower quadrant. Ultrasonography of the legs revealed a small amount of joint fluid in the hips and knees Fig. 2; the amount of fluid appeared to be within the normal range. Computed tomography CT of the abdomen, performed after the administration of intravenous contrast material, revealed a gallstone in the neck of the gallbladder, without gallbladder distention. There were a few prominent lymph nodes in the paraaortic, iliac, and inguinal regions Fig. 2. Transtho-racic echocardiography showed normal coronary arteries. Dr. Materne: The empirical administration of intravenous vancomycin, cefepime, and metroni-dazole was begun. During the next 3 days, the fever continued and the white-cell count remained elevated. On the seventh hospital day, the fever, leukocytosis, and elevation in levels of inflammatory markers persisted. The administration of antibiotic agents was stopped. A diagnostic test was performed.
OUTPUT:
| Systemic juvenile idiopathic arthritis. |
NEJM_Reasoning_Subset18 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: Dr. David M. Dudzinski: A 47-year-old right-handed man was evaluated at this hospital because of pain on the left side of the head and neck. Six years before the current evaluation, the patient was admitted to this hospital with 1 week of headache, pain on the left side of the neck, numbness on the left side of the face, and dizziness. The pain was not relieved with the use of ibuprofen and had previously been evaluated and treated by a chiropractor. A neu-rologic examination revealed a slight decrease in taste and in sensation to touch and temperature on the left side of the face; a gait evaluation revealed a subtle leftward sway. Imaging studies were obtained. Dr. Byung C. Yoon: Computed tomography CT of the head, performed after the administration of intravenous contrast material, revealed subtle foci of hypoden-sity in the left cerebellum, a finding suggestive of infarction. There was no evidence of arterial dissection, aneurysm, stenosis, or thrombotic occlusion. Magnetic resonance imaging MRI of the head, performed before and after the administration of intravenous contrast material, confirmed the presence of a left medial cerebellar infarct and a small left lateral medullary infarct Fig. 1A, 1B, and 1C. Dr. Dudzinski: The patient had normal results on cerebrospinal fluid CSF analysis, echocardiography, and a hypercoagulability panel, except for a mildly elevated level of anticardiolipin IgM 18.9 IgM phospholipid units; reference range, 0 to 15. During the hospital admission, lesions with a vesicular appearance developed on the left side of the lips and oral cavity, and the patient was treated with famciclo-vir. He was discharged home while receiving aspirin, with a follow-up visit scheduled in the neurology clinic. One month later in the neurology clinic, the patient reported partial resolution of headache, persistent neck pain and ear pain with balance difficulty, and perioral paresthesia. There was diminished sensation on the left side of the face similar to that observed during the previous examination. No oropharyngeal lesions were visible. An evaluation of gait and balance was normal. Dr. Yoon: Magnetic resonance angiography of the head and neck, performed before and after the administration of intravenous contrast material, revealed expected evolution of the left cerebellar infarct and no new infarction. The left posterior inferior cerebellar artery was not visualized, possibly because of occlusion or slow blood flow. Dr. Dudzinski: Repeat CSF analysis showed normal protein and glucose levels and 14 white cells per microliter reference range, 0 to 5, of which 94 were lymphocytes. Grams staining showed no organisms. CSF tests for borrelia and varicella DNA and for cytomegalovirus and herpes simplex virus antibodies were negative. Two days later, cerebral angiography revealed mild narrowing of the origin of the left vertebral artery. Tests for antinuclear antibodies, antineutro-phil cytoplasmic antibodies, and anti-La and anti-Ro antibodies were negative, as was a rapid plasma reagin test. The patient received follow-up care at another hospital until the current evaluation, when he presented to the emergency department of this hospital with 3 days of severe pain on exertion that affected the left side of the neck and left temporo-occipital region. The symptoms were similar to those he had reported in the past and were not relieved with the use of ibuprofen or marijuana. The head pain was described as pulsating and pounding, and it worsened when he was in the supine position. The patient reported right flank pain; the onset of this pain had occurred with lifting of a heavy object and had just preceded the onset of headache. He also reported a tendency to bruise. The review of systems was otherwise normal. His medical history was notable for dyslipidemia. He had undergone repair of meniscus tears in both knees and repair of a traumatic dislocation of the right shoulder. Medications included rosu-vastatin and gemfibrozil, as well as acetaminophen as needed. There were no known adverse reactions to medications. The patient was a self-employed laborer and lived with his wife and children in a suburb of Boston. He smoked cigars and marijuana occasionally, and he drank up to eight beers per day on weekends. His family history was notable for hypertension and dyslipid-emia in both of his parents, as well as early-onset dementia in his father. The temperature was 36.7C, the blood pressure 176119 mm Hg in both arms, the heart rate 72 beats per minute, and the oxygen saturation 98 while the patient was breathing ambient air. A neurologic examination revealed a mild decrease in coordination in the left hand but was otherwise normal. Blood levels of electrolytes, troponin T, C-reactive protein, lipoproteina, and glycated hemoglobin were normal, as were the prothrombin time, partial-thromboplastin time, and results of renal function tests. Urinalysis was also normal; other laboratory test results are shown in Table 1. Dr. Yoon: CT angiography of the head and neck, performed after the administration of intravenous contrast material, revealed dissection of the left vertebral artery, extending from the origin of the artery to the proximal V3 upper cervical segment, with a 2-mm pseudoaneurysm at the C2C3 level Fig. 1D and 1E. There was no evidence of acute ischemia. MRI of the head, performed before and after the administration of intravenous contrast material, did not reveal any evidence of infarction or a perfusion abnormality. However, a T1-weighted image showed a focus of intrinsic hyperintensity along the left vertebral artery, a finding consistent with hemorrhage within the vessel wall from the dissection Fig. 1F. Dr. Dudzinski: The patient was admitted to the neurology service. Control of the blood pressure required multiple medications. Echocardiography showed no cardiac, valvular, or aortic structural abnormality. Right flank pain recurred. Urinalysis showed 5 to 10 red cells per high-power field but was otherwise normal. Dr. Yoon: CT of the abdomen and pelvis, performed after the administration of intravenous contrast material, revealed dissection of the right renal artery, extending from the origin of the artery to subsegmental renal arteries. Perinephric fat stranding was present on the right side, and there were areas of diminished enhancement in the right kidney. These findings were suggestive of infarction Fig. 2. Additional diagnostic tests were performed.
OUTPUT:
| Vascular Ehlers–Danlos syndrome. |
NEJM_Reasoning_Subset19 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: Dr. Philippe-Antoine Bilodeau Medicine: A 21-year-old man presented to this hospital with a sore throat, epistaxis, and petechiae of the oropharynx. One week before the current presentation, blood-filled blisters developed inside the patients mouth, on the buccal mucosa. He had occasional bleeding from the mouth that resolved spontaneously. He consulted with his dentist, who was concerned about the possibility of impacted wisdom teeth. Two days before the current presentation, a sore throat developed. There was no difficulty with swallowing. On the day of the current presentation, epistaxis developed and did not resolve over a period of 2 hours. The patient presented to another hospital for evaluation. On examination, the temperature was 37.1C, the blood pressure 14276 mm Hg, the pulse 98 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 99 while he was breathing ambient air. He had blood in the nares and petechiae on the soft palate. There was a large ecchymosis on the left forearm that the patient attributed to carrying heavy boxes several days earlier. The remainder of the examination was normal. Laboratory testing revealed a hemoglobin level of 9.8 g per deciliter reference range, 13.5 to 17.5, a platelet count of 1000 per microliter reference range, 150,000 to 450,000, and a white-cell count of 670 per microliter reference range, 4000 to 11,000. The absolute neutrophil count was 50 per micro-liter reference range, 1800 to 7000. Blood levels of electrolytes and glucose were normal, as were results of tests for coagulation, renal function, and liver function. Other laboratory test results are shown in Table 1. The nose was packed to control the bleeding, and 1 unit of platelets was transfused. The patient was transferred to this hospital for additional evaluation and treatment. In the emergency department of this hospital, the patient reported a mild sore throat but no other symptoms; epistaxis had resolved with nasal packing. There was no fever, weight loss, rash, nausea, vomiting, or diarrhea. The patient had a history of sickle cell trait. He took no medications and had no known allergies. He had been living with his parents and younger brother since he had left his col-lege campus at the start of the coronavirus disease 2019 Covid-19 pandemic. He worked in a grocery store, and his only known sick contact was his mother, who had been infected with severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 2 months earlier. She had been isolated in a room in their home during her illness. The patient did not have any symptoms associated with Covid-19 and had never been tested for SARS-CoV-2 infection. His father and brother had been well. The family lived adjacent to a wooded region, and the patient had been hiking in northern New England 2 months before the current presentation. He had not noticed any tick bites. He had no animal contacts. The patient was born in Central America and had moved to a suburban region of New England at 3 years of age. He had previously traveled to Mexico and Canada. He was sexually active with female partners only. He did not smoke tobacco, drink alcohol, or use illicit drugs. His father had hypertension and hyperlipidemia, and paternal family members had sickle cell disease. On examination, the patient appeared well. There were petechiae on the soft palate Fig. 1. There was no scleral icterus, lymphadenopathy, or hepatosplenomegaly. A large ecchymosis was present on the left forearm. The remainder of the examination was normal. Blood levels of folate and cobalamin were normal, as were results of serum protein electrophoresis and the ratio of free kappa to lambda light chains. Other laboratory test results are shown in Table 1. A radio-graph of the chest and an ultrasound image of the upper abdomen were normal, without sple-nomegaly. Testing of a specimen obtained from the nasopharynx was positive for SARS-CoV-2 RNA; the patient was admitted to the hospital and placed in enhanced isolation. Examination of thick and thin peripheral-blood smears for babesia was negative. A second unit of platelets was transfused, and a diagnostic test was performed.
OUTPUT:
| Severe acquired aplastic anemia after infection with severe acute respiratory syndrome corona- virus 2. |
NEJM_Reasoning_Subset20 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: CME Dr. Austin Be Surgery: A 14-year-old girl was admitted to this hospital because of swelling of the left jaw. The patient had been well until 6 weeks before this admission, when she noticed a lump in the left lower jaw; there was no pain, tenderness, or discomfort in the jaw. She was evaluated in a primary care clinic of another hospital and was told that a salivary gland may be obstructed. Treatment with sialagogues, increased oral hydration, warm compresses, and massage of the salivary glands were recommended. During the next 3 weeks, the lump in the left jaw increased in size, and swelling of the left side of the face and neck developed. Three weeks before this admission, she returned to the primary care clinic; treatment with cephalexin was started. Eighteen days before this admission, the patient was evaluated in the otolaryngol-ogy clinic of the other hospital. The temperature was 37.2C, the blood pressure 13290 mm Hg, the heart rate 86 beats per minute, and the body-mass index the weight in kilograms divided by the square of the height in meters 21.0. There was swelling in the left mandibular and submandibular areas, with no erythema, fluc-tuance, or palpable salivary stones. Dr. Hillary R. Kelly: Computed tomography CT of the face and neck was performed after the administration of intravenous contrast material. CT of the face Fig. 1 revealed a 3.7-cm mass in the left mandibular body, with lytic and expansile features and numerous internal wavy septations. Areas of marked thinning and obliteration were noted in the buccal and lingual cortexes of the mandible, and extension of the mass among the roots of the first molar, second molar, and premolar was observed. No fluidfluid or bloodfluid levels were seen within the lesion. There was no lymphadenopathy. The patient was referred to the otolaryngol-ogy clinic at this hospital. Dr. Be: Fifteen days before this admission, the patient reported numbness and tingling in the lower lip and chin on the left side. She had had no fatigue, fever, chills, or redness and no pain in her face, jaw, or neck. On examination, she appeared well but had obvious facial asymmetry with swelling of the left mandible Fig. 2. There was a firm, mildly tender mass in the body of the left man-dible that extended to the mandibular angle. Orthodontic braces were in place and dentition and jaw occlusion were normal. The remainder of the ear, nose, and throat examination was normal. The overlying skin was normal, and no anterior or posterior submandibular or supraclavicular lymphadenopathy was present. The blood levels of sodium, potassium, and chloride were normal, as were the complete blood count and the results of tests of coagulation and renal function. The calcium level was 11.8 mg per deciliter 3.0 mmol per liter; reference range, 8.5 to 10.5 mg per deciliter 2.1 to 2.6 mmol per liter, and the albumin level was 4.1 g per deciliter reference range, 3.3 to 5.0. Radiography of the chest was normal. Dr. Vania Nose: An intraoral biopsy of the left mandibular mass was performed. Pathological examination Fig. 3C of the biopsy specimen revealed that the lesion was partially surrounded by reactive bone trabeculae, was hemorrhagic, and contained numerous osteoclast-type giant cells around extravasated red cells, findings that were consistent with a central giant-cell lesion or a central giant-cell granuloma. Dr. Be: Ten days before this admission, the patient was seen in the oral and maxillofacial surgical clinic of this hospital, and admission for the excision of the left mandibular mass was planned. On admission to this hospital, additional history was obtained. The patient had normal growth and development and had reportedly received all routine childhood vaccinations. She had finished the prescribed course of cephalexin and had taken no other medications; penicillin had caused fever and hives early in childhood. She lived in a suburban area of New England with her mother, stepfather, and two cats; she frequently stayed in another suburban area of New England with her father. The patient performed well in high school and participated in theater. She did not smoke tobacco, use illicit drugs, or drink alcohol. Her mother had hypothyroidism; her father had obstructive sleep apnea. Her maternal grandmother had a history of hypothyroidism, parathyroid ad-enoma, breast cancer, and colon cancer; her paternal grandfather had died from colon cancer. The temperature was 36.6C, the blood pressure 12885 mm Hg, and the heart rate 111 beats per minute. The physical examination was unchanged. The left mandibular mass was excised. Pathological examination of the surgical specimen revealed abundant giant cells. On the second hospital day, the calcium level was 12.6 mg per deciliter 3.2 mmol per liter and the parathyroid hormone PTH level was 396 pg per milliliter reference range, 10 to 60. A diagnosis was made.
OUTPUT:
| Primary hyperparathyroidism and brown tumor. |
NEJM_Reasoning_Subset21 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: Dr. Samantha D. Martin Pediatrics: A 17-year-old girl was admitted to this hospital during the coronavirus disease 2019 Covid-19 pandemic because of fever and cough. The patient had been well until 10 days before admission, when fever and cough that was productive of clear sputum developed. She also had fatigue, eye redness, sore throat, nasal congestion, rhinorrhea, and myalgias. Seven days before this admission, the patient was evaluated in the urgent care clinic of another hospital. On examination, there was conjunctival injection in both eyes. The lungs were clear on auscultation, and the remainder of the physical examination was reportedly normal. Testing of a nasopharyngeal specimen for severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 RNA was negative. Treatment with acetaminophen and dextromethorphan was recommended. During the next 2 days, the fever decreased but did not resolve with the use of acetaminophen. New mild chest discomfort occurred with coughing. An expectorated sputum specimen contained flecks of blood, and the patient returned to the urgent care clinic. The physical examination was unchanged, and rapid antigen testing for influenza types A and B was negative. Additional treatment with ibuprofen, benzonatate, and guaifenesin was recommended. Three days before this admission, the patient had persistent symptoms and was unable to sleep because of the fever and cough. New shortness of breath developed. She was evaluated by a primary care physician at the other hospital in a telehealth visit. Empirical treatment with amoxicillin was started, and close monitoring was recommended. During the next 3 days, the shortness of breath increased in severity, and the patient was instructed to present to the emergency department of this hospital. On evaluation, the patient reported cough that was worse with exertion and deep breathing, improved with rest, and was associated with pain in the chest and back on the left side. The sputum had streaks of bright red blood. Other symptoms included fatigue, sore throat, nasal congestion, rhinorrhea, myalgias, and pain in both knees when walking. The eye redness had resolved, but there was mild soreness of the right eye. There was no headache, ear pain, difficulty swallowing, abdominal pain, nausea, vomiting, diarrhea, or rash. The patient had a history of developmental dysplasia of the hip and was otherwise healthy. She had normal growth and development and had received all routine childhood vaccinations. Medications included amoxicillin, acetaminophen, ibuprofen, benzonatate, guaifenesin, and dextro-methorphan. There were no known drug allergies. The patient was born in New England and lived in a suburban area of New England with her mother, father, and brother. She performed well in high school, which she was attending remotely because of the Covid-19 pandemic; she had no known sick contacts. She had traveled to a Caribbean island 1 year earlier. She was a vegetarian and did not drink alcohol, smoke tobacco, or use illicit drugs. Her parents and brother were healthy. On examination, the temperature was 38.5C, the heart rate 124 beats per minute, the blood pressure 14262 mm Hg, the respiratory rate 30 breaths per minute, and the oxygen saturation 97 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 35.9. The patient appeared pale, and she coughed and sniffled frequently. She did not use accessory muscles while breathing, and breath sounds in the lower lung fields were decreased. There was no conjunctival injection, lymphade-nopathy, joint swelling or tenderness, or rash; the remainder of the physical examination was normal. The creatinine level was 2.00 mg per deciliter 177 mol per liter; reference range, 0.60 to 1.50 mg per deciliter 53 to 133 mol per liter and the C-reactive protein level 77.5 mg per liter reference value, 8.0. The hemoglobin level was 6.7 g per deciliter reference range, 12.0 to 16.0, the hematocrit 21.1 reference range, 36.0 to 46.0, the white-cell count 11,890 per microliter reference range, 4500 to 13,000, and the platelet count 526,000 per microliter reference range, 150,000 to 450,000. Urinalysis revealed 3 blood and 2 protein; microscopic examination of the urinary sediment revealed more than 100 red cells per high-power field reference range, 0 to 2 and 10 to 20 white cells per high-power field reference value, 10, as well as mixed granular casts and red-cell casts. Nucleic acid testing of a nasopharyngeal specimen for SARS-CoV-2, influenza types A and B, and respiratory syncytial virus was negative. An interferon- release assay for Mycobacterium tuberculosis was performed, and blood cultures were obtained. Other laboratory test results are shown in Table 1. Dr. Randheer Shailam: Chest radiography Fig. 1A and 1B revealed prominent patchy opacities in the lower lung zones. Computed tomography CT of the chest Fig. 1C through 1F, performed without the administration of intravenous contrast material, revealed peripheral patchy ground-glass opacification with greater involvement of the lower lobes than of the upper lobes, the lingula left lung, and the middle lobe right lung. There were also areas of normal-appearing lung. These findings are not specific and can be seen with infectious causes such as bacterial pneumonia and Covid-19, as well as with noninfectious causes such as aspiration, pulmonary hemorrhage, and less likely, alveolar proteinosis. Dr. Martin: Ceftriaxone, azithromycin, and intravenous fluids were administered. A diagnostic test was performed.
OUTPUT:
| Granulomatosis with polyangiitis. |
NEJM_Reasoning_Subset22 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: Dr. Theodore R. Pak Medicine: A 34-year-old woman was admitted to this hospital with hypercortisolism in the context of a metastatic pancreatic neuroendocrine tumor. The patient had been well until 4 years before this presentation, when abdominal pain, diarrhea, and ascites developed. A pancreatic neuroendocrine tumor with metastases to the liver and spleen was ultimately diagnosed, and treatment with octreotide and everolimus was initiated. Three years before this presentation, treatment with peptide receptor radionuclide therapy was initiated; four cycles were completed over the course of the next 2 years. Eight months before this presentation, the patient decided to stop taking everolimus because of fatigue. Seven months before this presentation, the patient was evaluated at another hospital because of weight gain, hyperglycemia, and changes in mood. She was found to have elevated blood levels of corticotropin and elevated salivary and urinary levels of cortisol. Dr. Adina Haramati: Magnetic resonance imaging MRI of the head revealed a pituitary lesion measuring 1.3 cm in greatest dimension. A specimen of blood obtained from the inferior petrosal sinus identified a pituitary source of cortico-tropin secretion. Dr. Pak: Treatment with octreotide was discontinued, and 3 months before this presentation, transsphenoidal resection of the pituitary lesion was performed. After the surgery, the cortisol and corticotropin levels remained elevated. Repeat MRI of the head revealed a residual pituitary lesion. Transsphenoidal resection of the residual lesion was performed 2 months before this presentation. After the second surgery, the cortisol and corticotropin levels decreased but did not normalize. Pathological evaluation of a resected pituitary specimen revealed normal anterior pituitary architecture that was not consistent with a corticotroph adenoma. At a follow-up appointment in the endocrinology clinic after the patient was discharged, the 24-hour urinary free corti-sol level was again elevated, and treatment with pasireotide was initiated. Ten days before this presentation, the patient began to have confusion, urinary incontinence, and recurrent falls. She was evaluated in the emergency department of another hospital. Her husband noted atypical impulsive behaviors, such as online shopping and excessive eating. Dr. Haramati: MRI of the head revealed a small focus of decreased enhancement within the left inferior aspect of the sella turcica, a finding that was consistent with postsurgical changes or residual adenoma. Dr. Pak: A morning blood level of cortisol was 80 g per deciliter 2207 nmol per liter; reference range, 4 to 23 g per deciliter 110 to 635 nmol per liter, and the blood level of corticotropin was 519 pg per milliliter 114 pmol per liter; reference range, 7.2 to 63 pg per milliliter 1.6 to 14 pmol per liter. The 24-hour urinary free cortisol level was 9450 g 26,069 nmol per liter; reference range, 3.5 to 45 g 10 to 124 nmol per liter. Dr. Haramati: MRI of the abdomen revealed an exophytic mass on the pancreatic tail that broadly abutted the left adrenal gland, thickening of both adrenal glands, retroperitoneal metastases on the left side, and extensive hepatic metastases with chronic cavernous transformation of the portal vein. Dr. Pak: Treatment with pasireotide was discontinued, and treatment with ketoconazole was initiated, in addition to potassium supplementation and spironolactone for hypokalemia. On the tenth day at the other hospital, the patient was transferred to this hospital for further treatment. On evaluation at this hospital, the patient reported fatigue but no fever, chills, night sweats, or weight loss. She had no cough, hemop-tysis, or chest pain; no rheumatologic symptoms; and no history of dysphagia or gastro-esophageal reflux disease. Her medical history included asthma and portal-vein thrombosis complicated by ascites, as well as hypothyroidism and central diabetes insipidus after she had undergone transsphenoidal resection of the pituitary lesions. Medications included atovaquone, cholecalciferol, desmopressin, ketoconazole, levo-thyroxine, metformin, pantoprazole, spironolac-tone, and potassium chloride. She had no known drug allergies. She did not drink alcohol or use tobacco or vaping products; she smoked marijuana occasionally. She lived with her husband in Vermont and had previously worked in a health care facility. The patient reported that she had had several skin tests for Mycobacterium tuberculosis owing to her work in the health care setting, and none had been positive. Before her illness, she had frequently gardened and hiked locally. She had traveled to Canada but otherwise had not traveled outside New England. A paternal aunt had had ovarian cancer. On examination, the temperature was 36.9C, the blood pressure 15287 mm Hg, the pulse 77 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 97 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 24.0. The patient was alert and oriented and answered questions appropriately. Her face was rounded, and acne and hair thinning were present. The abdomen had increased adiposity and palpable striae. There were several bruises on her arms and legs. A chest radiograph obtained on admission to this hospital showed an implanted venous access device and a patchy opacity in the right upper lung zone. Treatment with octreotide was reinitiated, and treatment with the other medications that the patient had been receiving was continued. The hypercortisolism was thought to be due to secretion of corticotropin from the metastatic pancreatic neuroendocrine tumor. Bilateral adrenalec-tomy was planned, but on the second hospital day, the patient became withdrawn and would not speak, take any oral medications, or consume any food. She was transferred to the intensive care unit, and an etomidate infusion was initiated; the dose was adjusted to attain a blood level of cortisol between 10 and 20 g per deciliter. Subsequent treatment with intravenous lora-zepam resulted in marked improvement in the patients mental status such that she was following commands and responding appropriately to questions. On the sixth hospital day, bilateral adrenalectomy was performed. Treatment with intravenous hydrocortisone was initiated postoperatively, and on the seventh hospital day, the patient was transferred to the medicine unit of this hospital for further care. Dr. Haramati: On the eighth hospital day, sinus tachycardia developed. Computed tomography CT of the chest, performed after the administration of intravenous contrast material according to a pulmonary embolism protocol Fig. 1, revealed a patchy consolidation in the right upper lobe with areas of cavitation and adjacent tree-in-bud opacities, as well as small bilateral pleural effusions. There was no evidence of pulmonary embolism. Although previous imaging was not available for review, clinical notes indicated that positron-emission tomographyCT performed at another hospital 8 months before this presentation had revealed a new cavitary nodule in the right upper lobe that measured 7 mm in diameter. Dr. Pak: A sputum culture showed few squamous epithelial cells, rare polymorphonuclear leukocytes, and few mixed gram-positive and gram-negative organisms with no specific type predominating; no acid-fast bacilli were observed on a mycobacterial smear of an induced sputum sample. Urine tests for Legionella pneumophila and Streptococcus pneumoniae antigens were negative, as was a blood test for cryptococcal antigen. The blood level of 1,3--d-glucan was less than 31 pg per milliliter reference value, 60, and the blood galactomannan index was 0.05 reference range, 0 to 0.49. Other laboratory test results are shown in Table 1. On the ninth hospital day, bronchoscopy was performed; bronchial washings and bronchoal-veolar-lavage BAL samples were obtained, and no purulent secretions were observed. Grams staining of the BAL fluid revealed few mixed gram-positive and gram-negative organisms, and no organisms were seen on an acid-fast bacilli smear or on a modified acid-fast bacilli smear. Examination of the BAL fluid for Pneumocystis jirovecii was negative. On the 11th hospital day, culture of the BAL fluid showed growth of few methicillin-sensitive Staphylococcus aureus organisms. Treatment with intravenous vancomycin, cefepime, and metroni-dazole was initiated. On the 12th hospital day, a urine test for histoplasma antigen was positive, at a level of 2.25 ng per milliliter reference ranges, 0.00 to 0.10 negative; 0.11 to 1.10 indeterminate; 1.11 positive. Management decisions were made, and results of a diagnostic test were received.
OUTPUT:
| Infection with Blastomyces dermatitidis. |
NEJM_Reasoning_Subset23 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: CME at NEJM.org Dr. Mollie Sands Medicine: A 49-year-old man was admitted to this hospital because of hypoglycemia. The patient had been well until 3 hours before this admission, when altered mental status developed while he was at work. During a meeting, his colleagues noticed that he was not paying attention or participating in the conversation, which was atypical of the patient. Instead, he was fidgeting and mumbling as though talking to another person. When his mobile telephone rang, he allowed it to continue ringing. Two hours before this admission, the patient was found by colleagues on the floor of a conference room. His eyes were open, but he was obtunded and making nonpurposeful movements. Emergency medical services were called. On evaluation, a fingerstick glucose measurement was 39 mg per deciliter 2.2 mmol per liter; reference range, 70 to 109 mg per deciliter 3.9 to 6.1 mmol per liter. Intravenous dextrose was administered, and the patient was brought to the emergency department of this hospital for further evaluation. On arrival at the emergency department, the patient was obtunded and did not react to sternal rub. Additional intravenous dextrose was administered, and a dextrose infusion was started. The patients mental status improved, and he was able to provide additional history. That morning, he had felt that he was in a dreamlike state; there were no other symptoms. The altered mental status had resolved, but he could not recall most events of the morning, including the meeting that had taken place 3 hours before admission. Review of symptoms was notable for unintentional weight gain of one pant size during the past 3 months, as well as intermittent morning dizziness during the past 3 years, which would resolve after the patient ate candy or breakfast. He reported no recent illness, depression, anxiety, change in activity or exercise, or change in intake of food or drink. On a typical day, he had breakfast at 5 a.m., a second breakfast at 10 a.m., lunch at 1 p.m., dinner at 6 p.m., and a snack at 8 p.m. The patient had last eaten approximately 7 hours before presentation to the emergency department. Two years earlier, the patient had had an episode of drooping and decreased sensation of the left side of the face and difficulty enunciating words, which occurred while he was at work. He presented to the emergency department of this hospital. The blood glucose level was 64 mg per deciliter 3.6 mmol per liter, and testing for Lyme disease was negative. He received a diagnosis of Bells palsy and was treated with pred-nisone and acyclovir; the symptoms resolved. Two months later, the patient established care in the primary care clinic of this hospital. Routine laboratory testing revealed a blood glucose level of 46 mg per deciliter 2.6 mmol per liter. The patient took vitamin B12 and vitamin D supplements. He took no other medications and had no known drug allergies. He drank alcohol rarely and did not smoke tobacco or use illicit drugs. Sixteen years earlier, he had immigrated to the United States from Southeast Asia and now lived alone in an urban area of New England. He worked as a registered nurse. His father and brother had type 2 diabetes and used insulin. On examination, the temperature was 35.7C, the heart rate 82 beats per minute, the blood pressure 14676 mm Hg, and the respiratory rate 14 breaths per minute. The body-mass index the weight in kilograms divided by the square of the height in meters was 27.6. The patient appeared well. He had no hepatosplenomegaly or skin hyperpigmentation, and the remainder of the physical examination was normal. On arrival at the emergency department, the blood glucose level was 36 mg per deciliter 2.0 mmol per liter; after the administration of dextrose, a fingerstick glucose measurement was 158 mg per deciliter 8.8 mmol per liter. The complete blood count and blood electrolyte levels were normal, as were the results of liver-function and kidney-function tests. The glycated hemoglobin level was 5.4 reference range, 4.3 to 6.4. Serum and urine toxicologic panels were negative. Laboratory test results are shown in Table 1. The patient was admitted to this hospital. A diagnostic test was performed.
OUTPUT:
| Well-differentiated pancreatic insulin-secreting neuroendocrine tumor (insulinoma). |
NEJM_Reasoning_Subset24 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: Dr. Vivian De Oliveira Rodrigues Gama Medicine: A 31-year-old man was admitted to this hospital because of perianal and penile ulcers, rectal pain, and vesiculopustu-lar rash. The patient had been in his usual state of health until 9 days before this admission, when he noticed several itchy white bumps around the anus that subsequently evolved into ulcerative lesions. The next day, he sought evaluation at a primary care clinic of another hospital. Tests for human immunodeficiency virus HIV, syphilis, gonorrhea, and chlamydia were performed. An injection of penicillin G benzathine was administered, and treatment with valacyclovir was started. During the next 5 days, the perianal ulcers did not abate, and the patient stopped taking valacyclovir. Painful proctitis with rectal bleeding and malodorous, mucopurulent discharge developed, along with fever, chills, drenching sweats, and new tender swelling in the groin. Three days before this admission, a new painless ulcer appeared on the penis that was similar in appearance to the perianal ulcers. Two days before this admission, new scattered vesicular lesions appeared on the arms and legs, and the patient presented to the infectious disease clinic of this hospital for evaluation. Additional history was obtained from the patient. Fourteen years before this evaluation, sore throat and upper body rash developed; he received a diagnosis of secondary syphilis and was treated with penicillin G benzathine. He also had a history of recurrent oral herpes simplex virus HSV infection, for which he was treated intermittently with valacyclovir. He took daily oral emtricitabine and teno-fovir for HIV preexposure prophylaxis PrEP. There were no known drug allergies. The patient lived in a suburban area of Massachusetts with two roommates and a cat. Two weeks before this evaluation, he had traveled to an urban area of southeastern Canada. During this trip, he had had sex with male partners without the use of barrier protection. There was no other recent travel. The patient did not smoke cigarettes or use illicit drugs; he drank alcohol rarely. CME at NEJM.org On examination, the temperature was 36.5C, the blood pressure 13086 mm Hg, the pulse 75 beats per minute, and the oxygen saturation 98 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 23.9. There were six tender perianal ulcers, measuring less than 1 cm in diameter, with raised, firm margins. There was also one ulcer on the dorsum of the penile shaft, measuring 7 mm in diameter, with raised borders Fig. 1. Painful bilateral inguinal lymphadenopa-thy was present. The perianal skin was weeping, and there was proctitis with severe tenderness that precluded digital rectal examination. In addition, there were approximately 12 papulovesicu-lar lesions scattered across the chest, back, arms, and legs. The lesions measured 2 mm in diameter, were filled with clear fluid, and had surrounding erythema Fig. 2A and 2B. Blood levels of electrolytes and glucose were normal, as were the results of kidney-function and liver-function tests. A blood test for trepo-nemal antibodies was positive; a rapid plasma reagin RPR test was reactive at a dilution of 1:1. A blood test for HIV was nonreactive, and tests of urine and rectal specimens for Neisseria gonorrhoeae and Chlamydia trachomatis nucleic acids were negative. A test of a specimen obtained from a perianal ulcer for HSV nucleic acids was performed, and a blood sample was obtained for bacterial culture. An injection of ceftriaxone was administered, and treatment with valacyclovir and doxycycline was started. During the next 2 days, the ulcers did not abate and the rectal pain worsened, such that the patient was not able to sit, sleep, or have bowel movements. Additional skin lesions appeared. The patient returned to the infectious disease clinic for evaluation. Anoscopy revealed intense rectal and anal inflammation with shallow ulcerations and purulent exudate, findings consistent with proctitis Fig. 3. The patient was admitted to this hospital. On examination, the patient appeared uncomfortable because of rectal pain. Skin lesions that had become pustular with an erythematous base were scattered across the scalp, chest, back, legs, and arms, including one on the palm Fig. 2C. There were no lesions in the mouth. Multiple tender, enlarged inguinal lymph nodes, measuring more than 1 cm in diameter, were present. The perianal and penile ulcers were tender and had heaped margins around a central dry base. The complete blood count and the white-cell differential count were normal. Swabs from a perianal ulcer and a chest skin lesion were obtained for bacterial culture. Treatment with intravenous acyclovir was started, and doxycycline was continued; stool softeners and hydromorphone were administered. A blood test for HIV type 1 RNA was performed. A diagnostic test was performed.
OUTPUT:
| Infection with monkeypox virus, West African clade. |
NEJM_Reasoning_Subset25 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: Dr. Victoria Clark Neurosurgery: A 25-year-old woman with a history of migraines was admitted to this hospital with progressively worsening headaches and photo-phobia during the previous 6 weeks and a 1-week history of nausea, vomiting, and blurred vision. Six weeks before this admission, the patient began to have headaches that were not characteristic of her previous migraines. She described these headaches as discomfort in the middle of her head that was associated with photophobia, phono-phobia, and tinnitus. She reported that she was occasionally awakened from sleep because of headache and that the headache was always present on awakening in the morning. The headache was worse with coughing and abated with standing; treatment with ibuprofen did not reduce the discomfort. One week before admission, nausea and vomiting developed, along with blurred vision when the patient looked to the left. She also reported occasional episodes of total vision loss that lasted for several seconds. When she was unable to eat food because of worsening nausea and vomiting, she presented to another hospital for evaluation. Computed tomography CT of the head revealed dilatation of the lateral and third ventricles with hypodensity that involved the dorsal brain stem and cerebellar hemispheres Fig. 1A; a possible soft-tissue mass in the region of the fourth ventricular outlet was also observed. The patient was transferred to the emergency department of this hospital for further evaluation. On arrival, the patient reported ongoing headache and nausea. Other medical history included obesity and opioid use disorder, which was treated with oral bu-prenorphinenaloxone and was complicated by relapses with injection of heroin; she last injected heroin 1 month before admission. Other medications included ibuprofen as needed. She had no known allergies. She smoked a half pack of cigarettes daily and did not drink alcohol. The patient lived in a wooded area of New England with four cats and one dog. She spent time outside, although she had become less active owing to headache. She was sexually active with one male partner and had no history of sexually transmitted infections. She had not traveled outside of New Eng-CME at NEJM.org
OUTPUT:
| Chronic Candida albicans meningitis. |
NEJM_Reasoning_Subset26 | Your task is to provide at least 10 accurate and distinct patient diagnoses based on the input case report. Key points: 1) Diagnoses are confirmed by clinical or anatomic pathology tests, or sometimes by clinical criteria or expert opinion. 2) You will be informed at the end of the case description if diagnostic tests are being ordered to confirm the diagnosis. Ensure that you provide at least 10 most likely diagnoses, listed in order of likelihood, and cover a wide range of unique possibilities.
Follow the guidelines for a generation: 1. Each diagnosis should be precise and unique, ensuring a variety of at least 10 possibilities. 2. List one diagnosis per line. 3. Generate at least 10 differential diagnoses related to the input case report. Think step by step.
***Output format***:Differential diagnosis: 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
INPUT: CME Dr. Esra D. Gumuser Medicine: A 48-year-old woman was admitted to this hospital because of multiple lung and liver lesions identified during an evaluation for abdominal pain. The patient had been in her usual state of health until 10 days before this admission, when burning epigastric pain developed after she ate a meal. Nausea and vomiting occurred 1 hour later; there was no diarrhea. After the pain persisted for 8 hours, she presented to the emergency department of another hospital for evaluation. On examination, the temperature was 36.8C, the blood pressure 13694 mm Hg, the pulse 80 beats per minute, the respiratory rate 16 breaths per minute, and the oxygen saturation 99 while the patient was breathing ambient air. The body-mass index the weight in kilograms divided by the square of the height in meters was 25.8. The abdomen was soft but distended; there was diffuse mild tenderness on palpation, without rebound or guarding. The white-cell count was 12,800 per micro-liter reference range, 4500 to 11,000 and the blood lipase level 147 U per liter reference range, 13 to 60; other laboratory test results are shown in Table 1. The pain did not resolve after treatment with intravenous famotidine and oral simethicone. Imaging studies were obtained. Dr. Melissa C. Price: A chest radiograph showed faint nodular opacities in the lungs, predominantly in the upper lobes. Computed tomography CT of the abdomen, performed after the administration of intravenous contrast material, revealed multiple fluid-filled small-bowel loops with associated mild mesenteric edema and trace ascites. There was no biliary dilatation. In addition, there were numerous hypoattenuating hepatic lesions with peripheral enhancement. Dr. Gumuser: The patient was admitted to the other hospital with a diagnosis of possible small-bowel obstruction and pneumonia. Treatment with intravenous fluids and ceftriaxone, oral doxycycline, and bowel rest was initiated. On the second hospital day, additional imaging studies of the liver were obtained. Dr. Price: Magnetic resonance imaging MRI of the abdomen Fig. 1, performed with and without the administration of intravenous contrast material, revealed bilobar hepatic lesions with peripheral enhancement, high T2 signal, and diffusion restriction. Dr. Gumuser: Blood was obtained for microbio-logic culture, and treatment with intravenous metronidazole was initiated. On the third hospital day, the abdominal pain had resolved, and the patient began drinking clear fluids. On the fourth hospital day, ultrasound-guided liver biopsy was performed. While the results of the liver biopsy were pending, the patient resumed a normal diet, with no recurrence of abdominal pain. Treatment with oral doxycycline and intravenous ceftriax-one and metronidazole was continued. Dr. Price: On the sixth hospital day, CT of the chest Fig. 1, performed without the administration of intravenous contrast material, revealed numerous irregular cysts and cavitary nodules in the lungs, which were most pronounced in the upper lobes, as well as solid and subsolid paren-chymal nodules that measured less than 1.0 cm in diameter. There were multiple nodules in the thyroid gland, measuring up to 2.8 cm in diameter in the inferior left thyroid lobe. There was a 1.7-cm nodule with soft-tissue attenuation in the right breast. Dr. Gumuser: On the eighth hospital day, bron-choscopy was performed. The airways were inspected to the segmental level, and no abnormalities were visualized. Transbronchial biopsy and bronchoalveolar lavage BAL were performed in the right upper lobe. Examination of the BAL fluid revealed 321 white cells per microliter reference range, 94 to 175. Grams staining and examination of an acid-fast bacilli smear of the BAL fluid were negative. On the ninth hospital day, results of the liver biopsy became available, showing extensive eo-sinophilic infiltration of the liver parenchyma with associated moderate steatosis. Staining of the biopsy specimen for microorganisms, including mycobacteria, was negative. Cultures of blood obtained on the second hospital day showed no growth. The patient was transferred to this hospital for further care. On arrival, the patient reported a mild sore throat that had developed after bronchoscopy, but there was no abdominal pain. She had lost 2 kg of weight before the hospitalization, in the context of dietary changes. She had no history of fever but reported a several-year history of mild shortness of breath with walking that she attributed to smoking. Her surgical history included cholecystectomy and cesarean section. Results of a Papanicolaou test performed 3 months before this presentation had been normal; the patient had not undergone mammography or colonoscopy. She took no medications and had no known drug allergies. The patient lived in an urban area of New England. She was born in Portugal and had immigrated to the United States 40 years earlier. She had not traveled recently; her last trip had been to Portugal 25 years before this admission. The patient was divorced, lived alone, and worked in a medical laboratory. She had no known exposure to chemicals or dust; a coworker at a previous office job had had an atypical infection attributed to mold in the workplace. She had smoked one pack of cigarettes per day for the past 30 years. She drank alcohol three times a week and did not use illicit drugs. Her mother had died from colon cancer at 43 years of age. On examination, the temperature was 36.2C, the blood pressure 13064 mm Hg, the pulse 65 beats per minute, the respiratory rate 18 breaths per minute, and the oxygen saturation 99 while the patient was breathing ambient air. The physical examination was normal. A diagnosis was made.
OUTPUT:
| Langerhans-cell histiocytosis of the lung and liver. |
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