1. A 60-year-old man presents with fatigue and unintentional weight loss. Physical examination reveals painless lymphadenopathy. Laboratory tests show leukocytosis, and a peripheral blood smear reveals numerous small, mature-appearing lymphocytes which have been showed in the picture. Flow cytometry confirms a diagnosis. The patient is started on a monoclonal antibody therapy. Which of the following best describes the mechanism of action of this therapy?
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A 2-month-old infant presents with recurrent viral and fungal infections, seizures Physical examination reveals a small jaw and low-set ears. Which of the following CD markers is most likely absent in this patient? The picture of the patient is presented:
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A 61-year-old man presents with abdominal pain, fatigue, and weight loss. Physical exam reveals a pulsatile mass in the abdomen. CT angiography shows thickening of the abdominal aorta and periaortic fibrosis. A biopsy of the affected tissue demonstrates dense lymphoplasmacytic infiltrate, obliterative phlebitis, and "storiform" pattern of fibrosis. Which of the following is the most likely diagnosis?
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4. A 45-year-old farmer presents with a 2-week history of progressive fatigue, weight loss, fever, and a persistent dry cough. He works in the Ohio River Valley and frequently cleans barns with accumulated bird and bat droppings. A chest X-ray reveals multiple bilateral lung nodules and hilar lymphadenopathy. Sputum cultures at 37°C show no growth, but the patient’s urine antigen test is positive for a fungal infection. A GMS (Gomori methenamine silver stain) of a bronchoalveolar lavage sample shows small, intracellular yeast forms within macrophages. Which of the following organisms is the most likely cause of this patient's condition?
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5. A 26-year-old woman presents to the emergency department with a 4-day history of high fever, severe headache, retro-orbital pain, diffuse myalgia, and arthralgia. She also reports nausea and a skin rash that appeared yesterday. She recently returned from a 2- week vacation to Puerto Rico. On physical examination, her temperature is 39.2°C (102.6°F), and there is a petechial rash on her trunk and extremities. A positive tourniquet test is noted. Laboratory studies reveal the following: • Hemoglobin: 14.5 g/dL • Platelet count: 80,000/mm³ (normal: 150,000–450,000/mm³) • WBC count: 3,000/mm³ (normal: 4,000–11,000/mm³) • AST: 280 U/L (normal: 10–40 U/L) • ALT: 240 U/L (normal: 7–56 U/L) Which of the following complications is the patient most at risk for if the disease progresses?
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6. A 33-year-old man with a 5-year history of HIV infection presents to the clinic for a follow-up appointment. He reports fatigue, oral thrush, and a 10-pound unintentional weight loss over the past month. Laboratory studies reveal the following: • CD4+ T-cell count: 180 cells/mm³ (normal: 500–1,500 cells/mm³) • HIV viral load: 150,000 copies/mL The patient is diagnosed with AIDS. The physician decides to start antiretroviral therapy (ART) immediately. The regimen includes a combination of drugs targeting different stages of the HIV life cycle. Which of the following classes of antiretroviral medications includes a drug that inhibits the fusion of the virus with host CD4+ T-cells?
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7. A 32-year-old male agricultural worker from Egypt presents with fatigue, abdominal pain, and recurrent episodes of blood in his urine over the past year. He reports frequent exposure to freshwater canals for irrigation work. On examination, he has mild hepatosplenomegaly and no peripheral edema. Urinalysis reveals hematuria without proteinuria. Stool analysis shows no ova or parasites. A biopsy of the bladder shows granulomatous inflammation and calcifications. Which of the following is the primary mechanism behind the patient's symptoms?
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8. A private physician operates a clinic that typically closes at 5:00 PM. At 4:55 PM, two patients arrive seeking care for non-emergent issues: one has a rash that has persisted for a week, and the other reports mild knee pain after a recent strain. The physician feels tired and does not want to accept additional patients as they are about to close. What is the most appropriate action by the physician?
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9. A 27-year-old man is admitted to the hospital for a necrotizing skin and soft tissue infection caused by Clostridium perfringens. He is started on clindamycin and penicillin G. Despite initial improvement, he develops fever, jaundice, and petechiae after 10 days of therapy. Laboratory studies show the following: • Hemoglobin: 8.5 g/dL (normal: 13.5–17.5 g/dL) • Platelets: 40,000/mm³ (normal: 150,000–450,000/mm³) • Total bilirubin: 5.6 mg/dL (normal: 0.3–1.2 mg/dL) • Direct Coombs test: Positive Which of the following best explains the mechanism of action of the protein synthesis inhibitor likely contributing to this patient's condition?
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10. A 65-year-old man with non-Hodgkin lymphoma is treated with a chemotherapy regimen that includes an alkylating agent. After several cycles, his disease progresses, and the tumor is biopsied. Molecular analysis of the tumor cells reveals increased expression of MGMT (methylguanine-DNA methyltransferase). Which of the following drugs is most likely rendered ineffective by this resistance mechanism, and what is its primary mechanism of action?
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11. A 50-year-old man with acute myeloid leukemia (AML) is started on a chemotherapeutic regimen including cytarabine. After an initial response, the patient’s disease relapses, and further analysis reveals a mutation in the gene encoding deoxycytidine kinase. Which of the following best explains the effect of this mutation on cytarabine’s mechanism of action, and what additional drug would be least affected by this mutation while affecting pyrimidin pathway?
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12. A 63-year-old woman with metastatic non-small cell lung cancer (NSCLC) is being treated with pembrolizumab. Four months into therapy, she presents with progressive fatigue, diffuse muscle pain, and palpitations. Physical examination reveals mild proximal muscle weakness and a fine tremor. Laboratory results are as follows: • TSH:
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13. A 34-year-old man presents to the emergency department with profuse watery diarrhea for the past two days. He recently returned from a rural area in South Asia, where he consumed untreated water. On examination, he appears lethargic and severely dehydrated. Vital signs include: • Blood pressure: 88/50 mmHg • Heart rate: 120 bpm • Respiratory rate: 22/min • Temperature: 37.2°C (98.9°F) Laboratory findings are as follows: • Sodium (Na⁺): 135 mEq/L (normal: 135–145 mEq/L) • Potassium (K⁺): 2.8 mEq/L (normal: 3.5–5.0 mEq/L) • Chloride (Cl⁻): 110 mEq/L (normal: 98–107 mEq/L) • Bicarbonate (HCO₃⁻): 14 mEq/L (normal: 22–28 mEq/L) • Blood urea nitrogen (BUN): 28 mg/dL (normal: 7–20 mg/dL) • Creatinine: 1.4 mg/dL (normal: 0.6–1.2 mg/dL) Arterial blood gas (ABG) reveals: • pH: 7.32 (normal: 7.35–7.45) • PaCO₂: 30 mmHg (normal: 35–45 mmHg) What is the most likely cause of the acid-base disturbance in this patient?
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14. A 26-year-old woman presents with muscle weakness and cramping. Laboratory studies reveal the following serum electrolyte levels: • Sodium (Na⁺): 135 mEq/L (normal: 135–145 mEq/L) • Potassium (K⁺): 2.8 mEq/L (normal: 3.5–5.0 mEq/L) • Chloride (Cl⁻): 98 mEq/L (normal: 98–107 mEq/L) Her resting membrane potential is measured at -70 mV. The intracellular concentrations of sodium and potassium are 15 mEq/L and 150 mEq/L, respectively. The extracellular chloride concentration is 110 mEq/L. Assume the temperature is 37°C, and the permeability of the cell membrane to potassium is much higher than to sodium or chloride. Which of the following statements is correct regarding the equilibrium potential of the ions and the patient's resting membrane potential?
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15. A 45-year-old man undergoes an emergency appendectomy. During induction of anesthesia, the anesthesiologist chooses an agent with minimal cardiovascular effects due to the patient's history of severe coronary artery disease. The selected anesthetic provides rapid induction but is associated with adrenocortical suppression with prolonged use. Which of the following anesthetics was most likely used?
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16. A 27-year-old woman is diagnosed with focal epilepsy and started on an antiseizure medication. She returns for follow-up reporting improved seizure control but mild fatigue and dizziness. Her physician explains that the prescribed drug works by reducing neuronal excitability only through inhibition of voltage-gated sodium channels. Which of the following drugs was most likely prescribed, and what is its primary mechanism of action?
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17. . A 50-year-old woman presents with progressive muscle weakness that improves with rest but worsens throughout the day. She reports difficulty keeping her eyelids open and swallowing, especially in the evening. Physical examination reveals ptosis and fatigable weakness in the proximal muscles. Repetitive nerve stimulation test shows a decremental response in compound muscle action potentials. Which of the following best explains the mechanism of her condition, and how does it differ from botulinum toxin and Lambert-Eaton syndrome?
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18. A family medicine physician wants to support a local struggling artist by selling handmade pottery in their clinic’s waiting area. The physician is considering different approaches to ensure compliance with the American Medical Association (AMA) Code of Medical Ethics, which emphasizes avoiding conflicts of interest, maintaining professionalism, and ensuring patient autonomy. The physician contemplates the following possible approaches: 1. Selling the pottery at a modest price with no profit, ensuring that patients feel no pressure to buy. 2. Encouraging patients to buy the pottery while also holding a minority financial stake in the artist’s business. 3. Only offering the pottery to select patients at a special discount to promote fairness. 4. Earning a small commission on pottery sales but avoiding direct discussions with patients about it. 5. Informing patients that buying the pottery is strongly encouraged as part of a community support initiative. Which of the following combinations represents the most ethically appropriate approach according to the AMA Code of Medical Ethics?
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19. A 42-year-old man with a history of type 2 diabetes mellitus (T2DM) presents to the clinic for follow-up. His diabetes has been poorly controlled, with an HbA1c of 9.5% despite metformin therapy. He reports recent unintentional weight loss, polyuria, and fatigue. Physical examination shows thin extremities with a loss of subcutaneous fat, but his BMI remains elevated at 29 kg/m². Laboratory findings are as follows: • Fasting glucose: 210 mg/dL (↑) • C-peptide: Low • Autoantibodies to GAD (Glutamic Acid Decarboxylase): Positive • Serum ketones: Negative • Urine microalbumin: Elevated The patient’s physician considers changing his treatment regimen. Which of the following is the most appropriate next step in management
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20. A 32-year-old man with a history of type 1 diabetes mellitus (T1DM) presents to the emergency department with fatigue, confusion, and rapid breathing. His family states that he has not been taking his insulin for the past two days. On examination, he is tachypneic, his mucous membranes are dry, and his breath has a fruity odor. Laboratory findings: • Glucose: 480 mg/dL • Arterial pH: 7.21 • HCO₃⁻: 14 mEq/L • Serum ketones: Positive • Serum sodium: 130 mEq/L ( corrected: 137 mEq/L) • Serum potassium: 5.4 mEq/L • Anion gap: 18 Which of the following best describes the primary mechanism responsible for the severe hyperglycemia in this patient?
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21. A 32-year-old woman presents with a progressive decline in motor coordination and cognitive function. Her mother experienced similar symptoms, starting in her late 40s. Which of the following best describes the genetic phenomenon observed in this patient's family?
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22. A 65-year-old man undergoes aortic valve replacement surgery for severe aortic stenosis. Six weeks later, he presents with fever, fatigue, and shortness of breath. His temperature is 38.5°C (101.3°F), blood pressure is 110/70 mmHg, and a new diastolic murmur is heard over the right upper sternal border. Blood cultures grow gram-positive cocci in clusters that are catalase-positive, coagulase-negative, and novobiocin-sensitive. A transesophageal echocardiogram (TEE) reveals a large vegetation on the prosthetic aortic valve with mild perivalvular abscess formation. Which of the following is the most important virulence factor responsible for this organism's ability to cause infection in this patient?
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23. A 65-year-old hospitalized patient with a history of diabetes mellitus and chronic kidney disease develops pneumonia. Sputum culture reveals Klebsiella pneumoniae producing extended-spectrum beta-lactamases (ESBLs). Despite initial treatment with ceftriaxone, the patient’s condition worsens, and repeat cultures show continued bacterial growth. Which of the following mechanisms is MOST likely responsible for this bacterium’s resistance to ceftriaxone?
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24. A 72-year-old woman with a history of type 2 diabetes mellitus and chronic kidney disease presents to the emergency department with fever, dysuria, and flank pain. Urinalysis reveals leukocyte esterase, nitrites, and white blood cell casts. Urine culture grows Escherichia coli producing extended-spectrum beta-lactamases (ESBLs). Which of the following is the most appropriate first-line antibiotic for treating this infection?
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25. A 22-year-old woman presents to the clinic with facial swelling, foamy urine, and joint pain. She reports a history of photosensitive skin rash and oral ulcers. Vital signs show a BP of 145/90 mmHg. Physical exam reveals periorbital edema and bilateral knee tenderness without swelling. Laboratory studies reveal: • Serum creatinine: 2.1 mg/dL • Urinalysis: 3+ protein, RBC casts, hematuria • ANA: positive • Anti-dsDNA: positive • Serum complement C3 and C4: low A renal biopsy is performed and shows diffuse proliferative glomerulonephritis with wire loop lesions on light microscopy. Which of the following best explains the mechanism of her renal disease?
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26. . A 58-year-old man is diagnosed with colorectal adenocarcinoma. Genetic testing of the tumor reveals a point mutation in the KRAS gene resulting in a constitutively active GTP-bound form of the KRAS protein. Which of the following best describes the molecular consequence of this mutation? A) Failure of DNA mismatch repair leading to microsatellite instability B) Unregulated cell growth via constitutive activation of MAP kinase signaling C) Loss of heterozygosity of a tumor suppressor gene D) Decreased apoptosis due to p53 inactivation E) Impaired degradation of β-catenin leading to Wnt pathway activation 27. A 6-year-old boy with transfusion-dependent β-thalassemia undergoes genetic testing confirming a homozygous mutation in the HBB gene. He has been receiving regular red blood cell transfusions since infancy and has developed signs of secondary hemosiderosis. His parents are counseled on a recently approved gene therapy that may eliminate his need for future transfusions by allowing long-term production of functional β-globin. Which of the following best explains why this therapy is potentially curative?
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27. A 6-year-old boy with transfusion-dependent β-thalassemia undergoes genetic testing confirming a homozygous mutation in the HBB gene. He has been receiving regular red blood cell transfusions since infancy and has developed signs of secondary hemosiderosis. His parents are counseled on a recently approved gene therapy that may eliminate his need for future transfusions by allowing long-term production of functional β-globin. Which of the following best explains why this therapy is potentially curative?
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28. A 63-year-old man is diagnosed with high-risk polycythemia vera after presenting with headache, pruritus, and hematocrit of 54%. He is started on cytoreductive therapy with hydroxyurea. Over the next year, he develops painful oral ulcers and worsening anemia. His therapy is switched to a recombinant cytokine that suppresses the malignant JAK2-mutated clone and is safer in patients with cytopenias. Which of the following best describes the mechanism of this replacement therapy?
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29. A 58-year-old man presents to his primary care physician for a routine check-up. He has a history of hypertension and type 2 diabetes mellitus. He does not smoke. Physical exam is unremarkable. His lipid panel shows elevated LDL cholesterol. The physician orders a high-sensitivity C-reactive protein (hs-CRP) test, which is elevated. This finding supports the hypothesis that chronic inflammation is contributing to the development of his atherosclerosis. Which of the following cytokines is most directly responsible for stimulating hepatic production of this patient’s elevated marker?
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30. A newborn becomes cyanotic shortly after birth. Physical examination reveals tachypnea and a soft systolic murmur. Chest X-ray shows a markedly enlarged right atrium and right ventricle. Echocardiography confirms that the pulmonary veins drain into the superior vena cava instead of the left atrium. Which of the following conditions must be present for this newborn to survive?
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31. A 23-year-old man collapses during a college basketball game and is brought to the emergency department. He had no prior medical history. On examination, he is unresponsive, and resuscitation efforts are unsuccessful. Autopsy reveals massive asymmetric thickening of the interventricular septum without chamber dilation. Histology shows myofiber disarray. Which of the following best describes the underlying mechanism of his condition?
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32. A 26-year-old woman presents with chronic shortness of breath and wheezing. She has had frequent asthma exacerbations despite regular use of inhaled corticosteroids and long-acting beta agonists. Sputum cytology shows neutrophil-predominant inflammation with minimal eosinophils. Bronchoscopy biopsy reveals IL-17–producing T cells in the airway mucosa. Her condition is poorly responsive to corticosteroids. Which of the following best explains the pathogenesis of this patient’s asthma phenotype?
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33. A 52-year-old man presents with a 6-month history of intermittent diarrhea, weight loss, joint pain, and low-grade fever. He reports multiple episodes of non bloody, greasy stools and progressive fatigue. On examination, he has mild abdominal tenderness and bilateral knee effusions. No rash is present. Laboratory workup shows mild anemia and hypoalbuminemia. Colonoscopy is unremarkable, but duodenal biopsy reveals foamy macrophages in the lamina propria that stain positive with periodic acid–Schiff (PAS). Which of the following is the most likely explanation for the findings in this patient?
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34. A 67-year-old man comes to the clinic with a 3-month history of unintentional weight loss, vague upper abdominal discomfort, and dark urine. He has smoked one pack of cigarettes per day for the past 40 years. Physical examination reveals mild jaundice and a palpable gallbladder. CT scan shows a mass in the head of the pancreas with evidence of biliary obstruction. Despite the clinical suspicion of pancreatic cancer, serum CA 19-9 is within normal limits. Further testing shows that the patient is Lewis antigen–negative. Which of the following best explains the patient’s normal CA 19-9 level despite the presence of pancreatic cancer?
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35. A 62-year-old man with a 15-year history of type 2 diabetes mellitus and hypertension presents for evaluation of chronic fatigue and muscle weakness. His medications include insulin, lisinopril, and hydrochlorothiazide. Labs are as follows: • Na⁺: 138 mEq/L • K⁺: 5.8 mEq/L • Cl⁻: 113 mEq/L • HCO₃⁻: 17 mEq/L • Blood glucose: 156 mg/dL • Serum anion gap: Normal • Urine pH: 5.0 Which of the following is the most likely diagnosis?
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36. A 62-year-old man presents with chronic headaches and progressive double vision. MRI of the brain reveals a destructive midline mass at the base of the skull involving the clivus and compressing adjacent brainstem structures. Biopsy reveals a tumor composed of physaliphorous cells (cells with bubbly cytoplasm) in a myxoid matrix. This tumor most likely arises from remnants of which of the following embryologic structures?
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37. A 58-year-old woman presents for evaluation of progressive memory impairment. Her mother and two uncles were diagnosed with early-onset Alzheimer disease in their 50s. Genetic testing reveals a mutation in a gene located on chromosome 21 that increases production of amyloid precursor protein (APP). Which of the following best describes the protein product of this gene and its role in Alzheimer pathology?
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38. A 35-year-old man is undergoing a workup for premature coronary artery disease. His father had a myocardial infarction at age 42. Laboratory studies reveal: • Total cholesterol: 190 mg/dL • LDL: 110 mg/dL • HDL: 25 mg/dL (↓) • Triglycerides: 180 mg/dL (mildly elevated) Further testing reveals a mutation in a gene coding for an apolipoprotein that activates an enzyme responsible for esterifying cholesterol in HDL particles. Which of the following apolipoproteins is most likely deficient in this patient?
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39. A 62-year-old woman presents with a painless mass in her right breast that she noticed 3 weeks ago. She has no nipple discharge or skin changes. On examination, a firm, irregular, non-mobile mass is palpated in the upper outer quadrant. Mammography reveals a spiculated lesion with irregular borders. A core needle biopsy is performed, and histology shows malignant cells infiltrating fibrous stroma showed bellow in the slide, with desmoplastic reaction and preservation of E-cadherin expression. Which of the following is the most likely diagnosis?
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40. A 32-year-old man presents to the emergency department with severe abdominal pain, vomiting, and profuse diarrhea that began 6 hours after consuming wild mushrooms during a hiking trip. Laboratory tests reveal elevated liver enzymes and signs of acute liver failure. Which of the following cellular enzymes is most likely inhibited, leading to this patient’s symptoms?
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