ITE Internal Medicine In-Training Exam — Questions and Answers

Question 1: A 35-year-old man has hypertension, hypokalemia, and metabolic alkalosis. Plasma renin activity is markedly elevated, as is aldosterone. CT shows a 3 cm right renal artery mass. What is the most likely diagnosis?

Primary hyperaldosteronism (Conn syndrome)
Pheochromocytoma
Adrenocortical carcinoma
Juxtaglomerular cell tumor (reninoma) (Correct answer)

Correct answer: Juxtaglomerular cell tumor (reninoma)

A juxtaglomerular cell tumor (reninoma) secretes renin autonomously, causing secondary hyperaldosteronism with high renin; in primary hyperaldosteronism, renin would be suppressed.

Question 2: A 29-year-old man with no significant medical history presents with a 2-day history of fever (39.2°C), sore throat, and diffuse maculopapular rash involving the palms and soles. He has painless, shallow oral ulcers and painless bilateral inguinal lymphadenopathy. RPR is reactive at 1:128; FTA-ABS is positive. He reports unprotected receptive anal intercourse 6 weeks ago with a new male partner. He denies HIV-risk factors but HIV-1/2 antigen/antibody combination assay returns positive. HIV-1 RNA PCR returns at 1,200,000 copies/mL with CD4 count pending. What is the MOST appropriate next step?

Perform LP to rule out neurosyphilis before initiating any treatment
Treat syphilis with benzathine penicillin G 2.4 million units IM × 1 dose and initiate ART immediately (Correct answer)
Treat syphilis with benzathine penicillin G 2.4 million units IM × 3 doses (weekly) and defer ART for 2 weeks
Initiate ART immediately and defer syphilis treatment pending neurosyphilis evaluation

Correct answer: Treat syphilis with benzathine penicillin G 2.4 million units IM × 1 dose and initiate ART immediately

This presentation is classic for secondary syphilis (palmoplantar rash, mucous patches, lymphadenopathy) occurring during acute HIV infection (high viral load, acute retroviral syndrome symptoms overlap). Secondary syphilis without neurologic symptoms is treated with benzathine penicillin G 2.4 million units IM as a single dose — not 3 doses (which is reserved for latent syphilis >1 year duration or unknown duration). LP for neurosyphilis is not required unless neurologic or ocular symptoms are present. Current guidelines (DHHS, IDSA) strongly recommend immediate ART initiation regardless of CD4 count, including during acute HIV infection, due to benefits in reducing reservoir establishment, transmission, and inflammation. Deferring ART is not indicated.

Question 3: A 35-year-old man with sickle cell disease presents with gradual onset renal insufficiency, isosthenuria, hematuria, and inability to concentrate urine. Urinalysis shows no casts. What is the most likely renal complication?

Renal papillary necrosis
Sickle cell nephropathy with focal segmental glomerulosclerosis (Correct answer)
Membranoproliferative glomerulonephritis
Renal cortical necrosis

Correct answer: Sickle cell nephropathy with focal segmental glomerulosclerosis

Sickle cell nephropathy progresses from early tubular defects (hyposthenuria) to FSGS-pattern glomerular disease from hyperfiltration in surviving nephrons.

Question 4: A 70-year-old nursing home resident with type 2 DM is found unresponsive. Labs show glucose 1,350 mg/dL, Na 152, osmolality 385 mOsm/kg, pH 7.35, bicarbonate 22. What is the diagnosis?

Mixed DKA and HHS
Hyperosmolar hyperglycemic state (HHS) (Correct answer)
Severe DKA with hyperosmolality
Lactic acidosis

Correct answer: Hyperosmolar hyperglycemic state (HHS)

HHS is characterized by extreme hyperglycemia (>600 mg/dL), hyperosmolality (>320 mOsm/kg), and absent or minimal ketoacidosis (pH >7.3, bicarb >18).

Question 5: A 45-year-old woman develops acute respiratory distress syndrome (ARDS) after septic shock. P/F ratio is 95. Which ventilator strategy has the strongest mortality benefit?

Pressure-controlled ventilation targeting RR <12 breaths/min
High tidal volume ventilation at 10 mL/kg IBW
Low tidal volume ventilation at 6 mL/kg IBW with plateau pressure <30 cmH2O (Correct answer)
High PEEP strategy with FiO2 titration only

Correct answer: Low tidal volume ventilation at 6 mL/kg IBW with plateau pressure <30 cmH2O

The ARDSNet trial demonstrated that low tidal volume ventilation (6 mL/kg IBW) with plateau pressure <30 cmH2O reduces mortality by 22% compared to higher tidal volumes.

Question 6: A 55-year-old man with type 2 diabetes on metformin, empagliflozin, and insulin glargine presents with nausea, vomiting, and abdominal pain. Glucose is 198 mg/dL, bicarbonate 11 mEq/L, pH 7.19, anion gap 24, beta-hydroxybutyrate 4.8 mmol/L, and urine ketones 3+. Which factor most directly explains why euglycemic diabetic ketoacidosis (euDKA) occurs with SGLT2 inhibitors?

SGLT2 inhibitors directly inhibit beta-cell insulin secretion, causing absolute insulin deficiency
Empagliflozin competes with ketone bodies for renal tubular reabsorption, falsely elevating serum ketone measurements
SGLT2 inhibition causes volume depletion, triggering stress-hormone-mediated lipolysis independently of insulin levels
SGLT2 inhibition increases renal glucose excretion, lowering plasma glucose while glucagon-mediated ketogenesis is simultaneously upregulated (Correct answer)

Correct answer: SGLT2 inhibition increases renal glucose excretion, lowering plasma glucose while glucagon-mediated ketogenesis is simultaneously upregulated

SGLT2 inhibitors cause euDKA through a two-pronged mechanism: (1) they increase urinary glucose excretion, which lowers plasma glucose and reduces the insulin-to-glucagon ratio (lower glucose → less insulin secretion → relative glucagon excess); (2) SGLT2 inhibitors directly increase glucagon secretion via an alpha-cell mechanism, driving ketogenesis from free fatty acids. The result is ketoacidosis without significant hyperglycemia. SGLT2 inhibitors do not directly inhibit beta-cell insulin secretion. They do not interfere with ketone measurement assays. While volume depletion and stress hormones can contribute, the primary mechanism is the glucose-lowering effect uncoupling the usual signal that suppresses ketogenesis, combined with direct glucagonotropic effects.

Question 7: A 70-year-old man presents with dysphagia to solids progressively worsening over 3 months with a 15-pound weight loss. What is the most appropriate initial evaluation?

Esophageal manometry
Upper endoscopy (Correct answer)
Barium swallow
CT chest/abdomen

Correct answer: Upper endoscopy

Upper endoscopy (EGD) is the preferred initial test for progressive dysphagia with alarm features because it allows direct visualization and biopsy to evaluate for malignancy.

Question 8: A 58-year-old man with newly diagnosed acute myeloid leukemia (AML) with FLT3-ITD mutation begins induction chemotherapy with 7+3 (cytarabine + daunorubicin). On day 14 bone marrow biopsy, there is aplasia with no residual blasts. Which maintenance strategy is most appropriate following complete remission and consolidation with high-dose cytarabine?

Allogeneic hematopoietic stem cell transplantation in first complete remission (Correct answer)
Observation alone without further therapy
Autologous stem cell transplantation followed by azacitidine maintenance
Midostaurin maintenance for 12 months

Correct answer: Allogeneic hematopoietic stem cell transplantation in first complete remission

FLT3-ITD mutation in AML confers high risk of relapse, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission is the preferred consolidation/curative strategy for eligible patients. While midostaurin is used as part of induction (with 7+3) and as maintenance post-transplant (per some protocols), it does not replace allo-HSCT as definitive therapy. Autologous SCT is generally reserved for AML patients without a suitable donor or with favorable-risk cytogenetics. Observation alone is insufficient for FLT3-ITD AML given the high relapse risk.

Question 9: A 35-year-old person who injects drugs presents with a fever of 38.8°C (101.8°F) and a new holosystolic murmur. Blood cultures are drawn, and an echocardiogram is ordered. According to the modified Duke criteria, which of the following findings constitutes a major criterion for the diagnosis of infective endocarditis?

Fever >38.0°C
Presence of Janeway lesions
Positive blood culture for *Staphylococcus epidermidis* from a single sample
Echocardiogram showing an oscillating intracardiac mass on a valve (Correct answer)

Correct answer: Echocardiogram showing an oscillating intracardiac mass on a valve

The modified Duke criteria classify findings into major and minor categories. The major criteria include: (1) positive blood cultures typical for infective endocarditis and (2) evidence of endocardial involvement. Evidence of endocardial involvement on an echocardiogram includes an oscillating intracardiac mass (vegetation), abscess, or new partial dehiscence of a prosthetic valve. Fever, vascular phenomena (like Janeway lesions), and immunologic phenomena are all minor criteria. A single positive blood culture with a common skin contaminant like *S. epidermidis* does not meet the major criterion for blood cultures.

Question 10: A 34-year-old woman returns from a 2-week safari in sub-Saharan Africa. She presents with cyclic fevers every 72 hours, splenomegaly, and thrombocytopenia. Peripheral smear shows large ring forms and occasional banana-shaped gametocytes. Parasite density is 6% of RBCs infected. Which management strategy is most appropriate?

Oral atovaquone-proguanil as outpatient therapy
Oral chloroquine given the 72-hour fever cycle suggesting P. malariae
IV artesunate with close monitoring for post-artesunate delayed hemolysis (Correct answer)
IV quinidine gluconate plus doxycycline with cardiac monitoring

Correct answer: IV artesunate with close monitoring for post-artesunate delayed hemolysis

The 72-hour fever cycle plus banana-shaped gametocytes indicates Plasmodium falciparum (the 72-hour cycle reflects schizogony timing, not tertian malaria; gametocytes are pathognomonic for P. falciparum). With >5% parasitemia, this meets criteria for severe malaria requiring IV artesunate, now the preferred first-line treatment over quinidine gluconate in the US (CDC emergency protocol). Post-artesunate delayed hemolysis (PADH) occurs weeks later in high-burden patients and requires monitoring. Quinidine gluconate is no longer readily available and carries significant cardiac toxicity risk. Oral therapy is inappropriate for severe/high-density malaria.

Question 11: A patient with a mechanical mitral valve prosthesis becomes pregnant. Which anticoagulation strategy is associated with the lowest risk of valve thrombosis?

Unfractionated heparin throughout pregnancy
Aspirin monotherapy throughout pregnancy
Low-molecular-weight heparin throughout pregnancy
Warfarin throughout pregnancy (Correct answer)

Correct answer: Warfarin throughout pregnancy

Warfarin throughout pregnancy offers the most reliable anticoagulation for mechanical valves and the lowest thrombosis risk, though it carries fetal risks (especially in the first trimester).

Question 12: A 61-year-old woman with a 25 pack-year smoking history (quit 8 years ago) undergoes low-dose CT lung cancer screening. The scan reveals a 7 mm pure ground-glass nodule (GGN) in the right upper lobe. No solid component is identified. Which of the following management strategies is most consistent with current Lung-RADS and Fleischner Society guidelines for this finding?

Surgical resection given size >6 mm in a high-risk patient (former smoker)
PET-CT scan to evaluate metabolic activity, as GGNs >6 mm have significant malignant potential
CT follow-up at 3 and 5 years; if stable, no further follow-up needed
CT follow-up at 6 months to assess for interval growth or development of a solid component (Correct answer)

Correct answer: CT follow-up at 6 months to assess for interval growth or development of a solid component

Per Fleischner Society 2017 guidelines for incidental pulmonary nodules and Lung-RADS 2022 for screening-detected nodules, a pure ground-glass nodule (GGN) of 7 mm in a screening patient (high-risk by definition) is categorized as Lung-RADS 3 (probable benign) and warrants 6-month CT follow-up. The rationale: pure GGNs grow slowly and represent adenocarcinoma spectrum lesions (AIS, MIA, or invasive adenocarcinoma). PET-CT (answer B) is inappropriate — pure GGNs are typically FDG-negative even when malignant due to their indolent metabolic activity, making PET non-diagnostic. Answer C (3 and 5 year follow-up) is appropriate for GGNs <6 mm in low-risk patients per Fleischner (or for GGNs ≥6 mm in low-risk patients per some protocols), but in a screening context with a 7 mm GGN, 6-month follow-up per Lung-RADS takes precedence. Answer D (surgical resection) is not indicated without evidence of growth or solid component development — pure GGNs have a protracted natural history and immediate resection would represent overtreatment.

Question 13: A 44-year-old woman presents with a 3-week history of pleuritic chest pain, facial rash worsened by sun, and joint pain. ANA is 1:640. Which antibody is most specific for systemic lupus erythematosus?

Anti-Scl-70 antibody
Anti-dsDNA antibody (Correct answer)
Anti-SSA (Ro) antibody
Anti-CCP antibody

Correct answer: Anti-dsDNA antibody

Anti-dsDNA antibodies are highly specific for SLE (>95%) and correlate with disease activity and lupus nephritis.

Question 14: A 40-year-old woman has chronic diarrhea, flushing, and wheezing. Urinary 5-HIAA is markedly elevated. Which imaging study is most appropriate to localize the primary tumor?

PET scan with FDG
Octreotide scan (somatostatin receptor scintigraphy) (Correct answer)
MRI liver
CT abdomen with contrast

Correct answer: Octreotide scan (somatostatin receptor scintigraphy)

Somatostatin receptor scintigraphy (octreotide scan or Ga-68 DOTATATE PET/CT) is the preferred functional imaging modality to localize carcinoid tumors expressing somatostatin receptors.

Question 15: A 55-year-old woman with obesity and type 2 diabetes has AST 78 and ALT 92. Ultrasound shows echogenic liver. Which histologic finding distinguishes NASH from simple steatosis?

Lobular inflammation and hepatocyte ballooning (Correct answer)
Macrovesicular fat deposits
Portal fibrosis only
Bile duct proliferation

Correct answer: Lobular inflammation and hepatocyte ballooning

NASH is distinguished from simple steatosis by the presence of lobular inflammation and hepatocyte ballooning injury, which drive fibrosis progression and risk of cirrhosis.

Question 16: A 44-year-old woman presents with episodic epigastric pain, diarrhea, and multiple duodenal ulcers despite PPI therapy. Fasting gastrin level is 1200 pg/mL (normal <100). What is the most appropriate next diagnostic step?

H. pylori testing
Secretin stimulation test (Correct answer)
CT scan of the abdomen
Repeat endoscopy

Correct answer: Secretin stimulation test

The secretin stimulation test is the gold standard for diagnosing Zollinger-Ellison syndrome; paradoxical rise in gastrin >200 pg/mL after secretin injection confirms gastrinoma.

Question 17: A 72-year-old woman with permanent atrial fibrillation and prior TIA is on warfarin with INR 2.5. She develops hematuria. Cystoscopy is negative for malignancy. What is the most appropriate next step in anticoagulation management?

Reduce warfarin dose targeting INR 1.5–2.0
Switch to aspirin alone for anticoagulation
Continue warfarin; bleeding risk outweighs stroke risk (Correct answer)
Stop warfarin permanently due to bleeding risk

Correct answer: Continue warfarin; bleeding risk outweighs stroke risk

In AF with prior TIA, stroke risk is high; warfarin should be continued because the annual stroke risk far exceeds the bleeding risk from hematuria with a negative workup.

Question 18: A 34-year-old woman returning from a 3-week trip to sub-Saharan Africa presents with 5 days of fever, rigors, myalgias, and headache. Thick and thin blood smears show Plasmodium falciparum with 6% parasitemia. She is alert, oriented, and tolerating oral intake. Serum creatinine is 1.1 mg/dL, bilirubin 2.8 mg/dL, blood glucose 88 mg/dL. Which treatment is most appropriate?

IV artesunate followed by oral artemisinin-based combination therapy upon tolerating PO (Correct answer)
Oral quinine sulfate plus doxycycline for 7 days
IV quinidine gluconate plus doxycycline with telemetry monitoring
Oral atovaquone-proguanil

Correct answer: IV artesunate followed by oral artemisinin-based combination therapy upon tolerating PO

Parasitemia ≥5% in Plasmodium falciparum infection meets the CDC definition of severe malaria regardless of the absence of classic organ failure criteria, mandating IV artesunate as first-line therapy. IV artesunate is now the preferred agent over IV quinidine (which is no longer commercially available in the US) due to superior efficacy and safety. After clinical improvement and ability to tolerate oral medications, transition to a full course of oral ACT (e.g., artemether-lumefantrine) is required to complete treatment. Oral-only regimens are insufficient for parasitemia at this level.

Question 19: A 42-year-old individual with HIV is found to have a CD4+ T-cell count of 85 cells/µL and is seropositive for Toxoplasma gondii. According to the CDC and NIH guidelines, which of the following prophylactic medications is indicated?

Trimethoprim-sulfamethoxazole (Correct answer)
Valganciclovir
Itraconazole
Azithromycin

Correct answer: Trimethoprim-sulfamethoxazole

Trimethoprim-sulfamethoxazole is indicated for primary prophylaxis against both *Pneumocystis jirovecii* pneumonia (PJP) and toxoplasmosis in this patient. Prophylaxis for PJP should be initiated when the CD4 count is <200 cells/µL, and prophylaxis for toxoplasmosis should be initiated in seropositive patients when the CD4 count is <100 cells/µL. Trimethoprim-sulfamethoxazole is the preferred agent for both conditions. Azithromycin is used for *Mycobacterium avium* complex (MAC) prophylaxis when the CD4 count is <50 cells/µL. Valganciclovir and Itraconazole are not indicated for primary prophylaxis in this scenario.

Question 20: A 65-year-old asymptomatic woman is found to have a serum calcium of 11.4 mg/dL (normal range 8.6-10.3 mg/dL) on routine labs. A repeat level confirms hypercalcemia. Subsequent workup reveals an elevated intact PTH of 110 pg/mL (normal 15-65 pg/mL) and a 24-hour urine calcium of 350 mg. Her eGFR is 75 mL/min, and a DEXA scan shows a T-score of -1.8 at the lumbar spine. According to the guidelines from the International Workshop on Asymptomatic Primary Hyperparathyroidism, which of the following is a clear indication for parathyroidectomy in this patient?

24-hour urine calcium of 350 mg/day
DEXA scan T-score of -1.8
Age of 65 years
Serum calcium level >1.0 mg/dL above the upper limit of normal (Correct answer)

Correct answer: Serum calcium level >1.0 mg/dL above the upper limit of normal

The patient has asymptomatic primary hyperparathyroidism. The current guidelines for recommending parathyroidectomy include several criteria. One major criterion is a serum calcium level 1.0 mg/dL or more above the upper limit of the normal range. In this case, the upper limit is 10.3 mg/dL, so a level ≥11.3 mg/dL is an indication for surgery. Her level of 11.4 mg/dL meets this criterion. The other options are incorrect: the age criterion is for patients <50 years old, the bone density criterion is a T-score of ≤ -2.5 (osteoporosis), and the hypercalciuria criterion is typically >400 mg/day.

Question 21: A 24-year-old female with a known history of intermittent asthma presents to the urgent care clinic with complaints of wheezing and shortness of breath for the past two days. She uses her albuterol inhaler 4-5 times a day with partial relief. She has no daily controller medication. According to the 2024 GINA guidelines, which of the following is the most appropriate long-term management plan to initiate?

Prescribe a daily long-acting beta-agonist (LABA) inhaler
Continue with as-needed short-acting beta-agonist (SABA) only
Prescribe as-needed low-dose inhaled corticosteroid (ICS)-formoterol (Correct answer)
Prescribe a daily low-dose inhaled corticosteroid (ICS) and continue SABA as needed

Correct answer: Prescribe as-needed low-dose inhaled corticosteroid (ICS)-formoterol

The 2024 Global Initiative for Asthma (GINA) guidelines strongly recommend against treatment with a short-acting beta-agonist (SABA) alone due to safety concerns. The preferred approach (Track 1) for patients with mild asthma (symptoms less than daily) is to use an as-needed low-dose inhaled corticosteroid (ICS)-formoterol combination inhaler. This strategy provides both rapid symptom relief from the formoterol and anti-inflammatory action from the ICS, reducing the risk of severe exacerbations compared to SABA-only treatment.

Question 22: A 62-year-old man with known acromegaly has a post-surgical IGF-1 still 2.5× the upper limit of normal. MRI shows no residual tumor. What is the most appropriate next step in management?

Repeat surgery
Pituitary radiation
Pegvisomant monotherapy
Somatostatin receptor ligand (octreotide LAR or lanreotide) (Correct answer)

Correct answer: Somatostatin receptor ligand (octreotide LAR or lanreotide)

When post-surgical IGF-1 remains elevated without visible residual tumor, somatostatin receptor ligands are first-line medical therapy; pegvisomant is reserved for those not responding to or intolerant of somatostatin analogues.

Question 23: A 58-year-old man with COPD presents with acute hypercapnic respiratory failure. ABG shows pH 7.28, PaCO2 72 mmHg, PaO2 58 mmHg on room air. Which intervention is MOST appropriate as first-line therapy?

Heliox administration
High-flow nasal cannula at 40 L/min
Non-invasive positive pressure ventilation (NIPPV) (Correct answer)
Immediate endotracheal intubation

Correct answer: Non-invasive positive pressure ventilation (NIPPV)

NIPPV (BiPAP) is the first-line intervention for acute hypercapnic respiratory failure in COPD, reducing intubation rates, mortality, and hospital length of stay.

Question 24: A 28-year-old man has recurrent episodes of jaundice after fasting and during illness. All liver enzymes are normal except indirect bilirubin of 3.5 mg/dL. What is the most likely diagnosis?

Rotor syndrome
Crigler-Najjar syndrome type I
Gilbert syndrome (Correct answer)
Dubin-Johnson syndrome

Correct answer: Gilbert syndrome

Gilbert syndrome presents with isolated unconjugated hyperbilirubinemia triggered by fasting, stress, or illness, with otherwise normal liver function and benign prognosis.

Question 25: A 40-year-old man is admitted to the ICU with septic shock from pneumonia. After 6 hours of resuscitation with 4 L of crystalloid, he remains hypotensive with MAP 58 mmHg. He is on norepinephrine 0.18 mcg/kg/min. Point-of-care echo shows hyperdynamic LV function with IVC collapsibility >50%. What intervention is MOST appropriate?

Begin hydrocortisone 200 mg/day for refractory septic shock
Add vasopressin 0.03 units/min to norepinephrine
Start dobutamine for cardiogenic shock
Administer an additional 2 L of IV fluid bolus (Correct answer)

Correct answer: Administer an additional 2 L of IV fluid bolus

IVC collapsibility >50% indicates volume responsiveness; additional fluid resuscitation is appropriate when dynamic indices suggest ongoing hypovolemia in distributive shock.

Question 26: A 58-year-old man with alcoholic cirrhosis develops confusion and asterixis. Ammonia level is elevated. Which treatment is most appropriate?

Rifaximin
Neomycin
Zinc supplementation
Lactulose (Correct answer)

Correct answer: Lactulose

Lactulose is first-line therapy for hepatic encephalopathy, reducing ammonia absorption by acidifying colonic contents and promoting excretion.

Question 27: A 58-year-old male with a bicuspid aortic valve is found to have severe chronic aortic regurgitation (AR) on a routine echocardiogram. He is completely asymptomatic. His LVEF is 52% and his LV end-diastolic dimension is 72 mm. Blood pressure is 130/50 mmHg. According to the most recent guidelines, which of the following is the strongest indication for aortic valve replacement in this patient?

The presence of a bicuspid aortic valve.
The left ventricular ejection fraction. (Correct answer)
The wide pulse pressure.
The severe degree of regurgitation.

Correct answer: The left ventricular ejection fraction.

The 2020 ACC/AHA guidelines lowered the threshold for intervention in asymptomatic severe aortic regurgitation. Aortic valve replacement is recommended for asymptomatic patients with severe AR if the LVEF is 55% or less. This patient's LVEF is 52%, which is a clear indication for surgery to prevent irreversible left ventricular dysfunction. While the bicuspid valve is the etiology and the wide pulse pressure is a physical finding, the LVEF is the key parameter guiding the timing of intervention in this asymptomatic patient.

Question 28: A 34-year-old woman with a history of lithium therapy for bipolar disorder presents with polyuria, polydipsia, and a serum sodium of 148 mEq/L. Her urine osmolality after 8 hours of water deprivation is 185 mOsm/kg. After administration of desmopressin (DDAVP), urine osmolality rises to 210 mOsm/kg. Which pathophysiologic mechanism best explains this blunted response to exogenous ADH?

Upregulation of cyclooxygenase-2 leading to prostaglandin-mediated vasoconstriction of vasa recta
Competitive inhibition of ADH at V2 receptors in the renal medulla
Destruction of posterior pituitary magnocellular neurons by lithium nephrotoxicity
Downregulation of aquaporin-2 channels in the collecting duct due to impaired cAMP-mediated signaling (Correct answer)

Correct answer: Downregulation of aquaporin-2 channels in the collecting duct due to impaired cAMP-mediated signaling

Lithium causes nephrogenic diabetes insipidus by entering principal cells via ENaC channels and inhibiting adenylyl cyclase, reducing cAMP generation downstream of the V2 receptor. This impairs PKA-mediated phosphorylation and insertion of aquaporin-2 (AQP2) water channels into the apical membrane. The post-DDAVP rise in urine osmolality from 185 to 210 mOsm/kg (< 50% increase) confirms nephrogenic DI — partial response occurs because some residual AQP2 expression remains. Lithium does not destroy pituitary neurons, does not competitively antagonize V2 receptors, and COX-2 upregulation is not the primary mechanism of concentrating defect.

Question 29: A 72-year-old man with a history of alcoholism is brought to the emergency department with a 24-hour history of high fever, severe headache, nuchal rigidity, and confusion. A lumbar puncture is planned but will be delayed for a CT scan of the head. Which of the following empiric antimicrobial regimens should be administered immediately?

Ceftriaxone plus ampicillin
Vancomycin, ceftriaxone, and ampicillin (Correct answer)
Vancomycin plus ceftriaxone
Meropenem monotherapy

Correct answer: Vancomycin, ceftriaxone, and ampicillin

For adults over the age of 50 with suspected bacterial meningitis, empiric therapy must cover the most common pathogens, including *Streptococcus pneumoniae*, *Neisseria meningitidis*, and *Listeria monocytogenes*. The combination of vancomycin (for resistant pneumococcus), a third-generation cephalosporin like ceftriaxone (for pneumococcus and meningococcus), and ampicillin (for *Listeria*) is the recommended regimen. Omitting ampicillin would leave the patient vulnerable to *Listeria*, which has increased incidence in older adults, pregnant women, and the immunocompromised.

Question 30: A 38-year-old with Crohn's disease on azathioprine develops a perianal fistula that fails to close with antibiotics. What biologic therapy is FDA-approved for fistulizing Crohn's disease?

Vedolizumab
Natalizumab
Infliximab (Correct answer)
Ustekinumab

Correct answer: Infliximab

Infliximab is the only biologic with FDA approval specifically for fistulizing Crohn's disease, demonstrated in the landmark ACCENT II trial to induce and maintain fistula closure.

Question 31: A 29-year-old man is referred for evaluation of hematuria and proteinuria (1.2 g/day). He has a family history of end-stage renal disease in his maternal grandfather and sensorineural hearing loss diagnosed at age 12. Renal biopsy electron microscopy shows thinning and splitting of the glomerular basement membrane (GBM) with a characteristic 'basket-weave' pattern. Genetic testing confirms a heterozygous pathogenic variant in COL4A5. Which statement about his prognosis and management is MOST accurate?

ACE inhibitor therapy initiated before proteinuria exceeds 0.5 g/day has been shown to delay ESKD by approximately 13 years in retrospective studies (Correct answer)
His sensorineural hearing loss confirms autosomal recessive inheritance, requiring testing of both parents before estimating ESKD risk
Rituximab therapy targeting podocyte autoantibodies should be considered given the proteinuria level
As a heterozygous carrier of X-linked Alport syndrome, he is unlikely to progress to ESKD and requires only annual monitoring

Correct answer: ACE inhibitor therapy initiated before proteinuria exceeds 0.5 g/day has been shown to delay ESKD by approximately 13 years in retrospective studies

COL4A5 mutations cause X-linked Alport syndrome (XLAS). Males with XLAS are hemizygous and almost invariably progress to ESKD, typically by age 20-30 without treatment. Retrospective data from the European Alport Registry (Gross et al.) demonstrated that ACE inhibitor therapy started at the stage of microhematuria alone (before proteinuria develops) delayed ESKD by approximately 13 years compared to treatment started at the proteinuria stage, and by about 13 years compared to no treatment. This supports early nephroprotective intervention. Males with COL4A5 mutations are NOT mild carriers — that term applies to heterozygous females, who have variable expression. The basket-weave GBM is the EM hallmark of Alport syndrome regardless of inheritance pattern.

Question 32: A 38-year-old woman with Crohn's disease on azathioprine and infliximab develops right lower quadrant pain, fever, and a palpable mass. CT imaging shows a phlegmon involving the terminal ileum with an adjacent 4 cm abscess. She has no peritonitis. The optimal initial management is:

Increase infliximab dose to induce remission and resolve the abscess
CT-guided percutaneous drainage plus antibiotics, with infliximab held (Correct answer)
Colonoscopy with balloon dilation of any associated stricture
Emergent surgical resection of the terminal ileum

Correct answer: CT-guided percutaneous drainage plus antibiotics, with infliximab held

In Crohn's disease complicated by an intra-abdominal abscess, the standard of care is source control first — percutaneous drainage (if technically feasible) plus broad-spectrum antibiotics — before any escalation of immunosuppression. Anti-TNF agents (infliximab) are contraindicated in the setting of undrained abscess because immunosuppression worsens septic outcomes. Emergent surgery is reserved for peritonitis, failure of drainage, or inaccessible abscesses. Colonoscopy and stricture dilation are not appropriate in the acute septic phase.

Question 33: A 61-year-old man with type 2 diabetes and an eGFR of 28 mL/min/1.73m² presents for medication review. His HbA1c is 8.9%. Current medications include metformin 1000 mg BID, glipizide 10 mg BID, and linagliptin 5 mg daily. His blood pressure is 148/92 mmHg and urine albumin-to-creatinine ratio is 620 mg/g. Which change to his diabetes regimen has the strongest evidence for reducing risk of kidney disease progression at this stage?

Discontinue metformin and glipizide; initiate a GLP-1 receptor agonist with demonstrated nephroprotective outcomes data
Continue current regimen; add empagliflozin 10 mg daily given its EMPA-REG outcomes benefit
Discontinue metformin; add finerenone to the existing regimen
Discontinue metformin and linagliptin; initiate an SGLT2 inhibitor titrated to the lowest approved dose for kidney protection (Correct answer)

Correct answer: Discontinue metformin and linagliptin; initiate an SGLT2 inhibitor titrated to the lowest approved dose for kidney protection

At eGFR 28, metformin is contraindicated (hold at eGFR < 30) due to lactic acidosis risk. SGLT2 inhibitors — specifically canagliflozin (CREDENCE, eGFR ≥ 20) and dapagliflozin (DAPA-CKD, eGFR ≥ 25) — have robust RCT evidence for reducing CKD progression, cardiovascular events, and ESKD in patients with diabetic kidney disease and elevated albuminuria, and can be used at reduced eGFR (down to ~20–25) primarily for kidney protection even when glycemic effect is minimal. Linagliptin should be discontinued if an SGLT2 inhibitor is added to avoid therapeutic overlap without additive organ-protection benefit. GLP-1 RAs (semaglutide — FLOW trial) show nephroprotection but do not replace SGLT2 inhibitors at this eGFR. Finerenone requires concurrent RAAS blockade and is added to — not a replacement for — SGLT2 inhibitor therapy. Empagliflozin at eGFR 28 with urine ACR > 200 is appropriate per EMPA-KIDNEY trial data (eGFR 20–45 enrolled), making option C more complete and mechanistically accurate.

Question 34: A 29-year-old man with known cystic fibrosis (CF) has FEV1 that has declined to 25% predicted despite maximal inhaled therapy. He is listed for lung transplantation. His most recent sputum grows Burkholderia cepacia complex. How does this organism affect transplant candidacy?

It is a relative contraindication requiring additional workup
It requires pre-transplant eradication with IV antibiotics before listing
It is not a contraindication to transplantation
It is an absolute contraindication at most transplant centers (Correct answer)

Correct answer: It is an absolute contraindication at most transplant centers

Burkholderia cepacia complex (especially genomovar III/cenocepacia) is considered an absolute contraindication to lung transplantation at most centers due to dramatically increased post-transplant mortality.

Question 35: A 45-year-old patient from the Ohio River Valley presents with fever, weight loss, and mediastinal lymphadenopathy. BAL reveals intracellular yeast within macrophages. What is the treatment for severe disseminated histoplasmosis?

Liposomal amphotericin B followed by itraconazole (Correct answer)
Voriconazole 200mg BID
Echinocandin plus itraconazole
Fluconazole 400mg daily x 12 months

Correct answer: Liposomal amphotericin B followed by itraconazole

Severe or disseminated histoplasmosis is treated with liposomal amphotericin B for induction (1-2 weeks) followed by step-down to itraconazole for 12 months.

Question 36: A 61-year-old man with alcoholic cirrhosis (albumin 1.8 g/dL) and type 1 diabetes presents with 3 days of vomiting. Labs: Na 136, Cl 104, HCO₃ 18 mEq/L, glucose 415 mg/dL, pH 7.29, large urinary ketones. A resident calculates an anion gap of 14 mEq/L and concludes the acidosis is non-gap and DKA is unlikely. Which response best corrects this reasoning?

The anion gap of 14 mEq/L is truly normal; the ketonuria reflects starvation ketosis, not DKA
Hypoalbuminemia raises the calculated anion gap, so a gap of 14 actually underestimates the degree of alkalosis
The albumin-corrected anion gap is approximately 19.5 mEq/L, revealing a masked elevated anion gap consistent with DKA (Correct answer)
The anion gap should only be adjusted for albumin when the albumin is below 1.0 g/dL; otherwise 14 is reassuringly normal

Correct answer: The albumin-corrected anion gap is approximately 19.5 mEq/L, revealing a masked elevated anion gap consistent with DKA

Albumin is the principal unmeasured anion contributing to the normal anion gap. When albumin is low, the baseline anion gap falls, masking an elevated anion gap acidosis. The correction formula is: corrected AG = calculated AG + 2.5 × (4 − patient albumin g/dL). Here: 14 + 2.5 × (4 − 1.8) = 14 + 5.5 = 19.5 mEq/L — clearly elevated and consistent with DKA. Failing to correct the AG in hypoalbuminemic patients (common in cirrhosis, malnutrition, nephrotic syndrome) is a high-yield pitfall on the ITE.

Question 37: A 52-year-old man with type 2 diabetes on metformin and a GLP-1 receptor agonist presents with an HbA1c of 8.9%. He has an eGFR of 28 mL/min/1.73m² and urine albumin-to-creatinine ratio of 420 mg/g. He has no history of bladder cancer or recurrent UTIs. Which agent is most appropriate to add for cardiorenal protection?

Finerenone (Correct answer)
Pioglitazone
Insulin glargine
SGLT2 inhibitor

Correct answer: Finerenone

Finerenone, a non-steroidal mineralocorticoid receptor antagonist, has demonstrated cardiorenal protection in CKD with type 2 diabetes (FIDELIO-DKD and FIGARO-DKD trials) and is approved for use down to eGFR ≥25 mL/min/1.73m². SGLT2 inhibitors are generally not recommended when eGFR <30 mL/min/1.73m² for glycemic benefit, though some (empagliflozin, dapagliflozin) have cardiorenal indications down to eGFR ≥20-25 for CKD protection — however, at eGFR 28 with significant albuminuria on a GLP-1 agonist already, finerenone provides additive benefit and is the guideline-preferred addition in this scenario. Pioglitazone carries fluid retention risk at this CKD stage.

Question 38: A patient with HHS has a serum osmolality of 345 mOsm/kg and blood glucose of 1100 mg/dL. Which IV fluid is most appropriate for initial resuscitation?

Lactated Ringer's solution
0.9% NaCl (isotonic saline) (Correct answer)
0.45% NaCl (hypotonic saline)
D5W (5% dextrose in water)

Correct answer: 0.9% NaCl (isotonic saline)

Isotonic normal saline (0.9% NaCl) is used first in HHS to restore circulating volume before transitioning to hypotonic fluids for free water replacement.

Question 39: A 61-year-old man with compensated cirrhosis (Child-Pugh A) due to NASH is found to have a 2.2 cm arterially enhancing hepatic lesion with washout on portal venous phase on contrast-enhanced MRI. He undergoes curative-intent resection. Three months post-resection, surveillance MRI shows a new 1.8 cm lesion in the contralateral lobe with identical enhancement pattern. Which statement regarding his candidacy for liver transplantation is most accurate?

He can be downstaged with locoregional therapy and listed if within Milan criteria for ≥6 months (Correct answer)
He exceeds Milan criteria and should be referred for systemic therapy only
Recurrence post-resection is an absolute contraindication to liver transplantation
He meets UCSF criteria and may be listed after demonstrating 6 months of stable disease

Correct answer: He can be downstaged with locoregional therapy and listed if within Milan criteria for ≥6 months

Post-resection HCC recurrence does NOT absolutely preclude transplantation. UNOS/OPTN policy supports downstaging of HCC outside Milan criteria using locoregional therapies (TACE, ablation, TARE). If the tumor burden is reduced to within Milan criteria (single lesion ≤5 cm, or up to 3 lesions each ≤3 cm) and maintained for ≥6 months with AFP response, patients can be listed. The new 1.8 cm lesion alone is within Milan and the prior resected lesion is no longer present — this patient may be evaluated for transplant after downstaging and disease stability confirmation. UCSF criteria (single ≤6.5 cm or ≤3 lesions with largest ≤4.5 cm and total ≤8 cm) are used by some centers but UNOS policy is based on Milan.

Question 40: A 67-year-old woman is intubated for hypoxemic respiratory failure. On assist-control volume-targeted ventilation: TV 420 mL (6 mL/kg IBW), RR 24, PEEP 12, FiO2 0.7. P/F ratio is 96 (severe ARDS). Peak pressure is 38 cmH2O, plateau pressure is 34 cmH2O. She is paralyzed with cisatracurium. An esophageal balloon is placed: end-expiratory esophageal pressure is +18 cmH2O. What does the transpulmonary plateau pressure calculation reveal, and what is the appropriate ventilator adjustment?

Transpulmonary plateau = 16 cmH2O; current plateau is safe, increase PEEP to titrate by transpulmonary PEEP (Correct answer)
Transpulmonary plateau = 52 cmH2O; decrease tidal volume to 4 mL/kg IBW
Transpulmonary plateau = 34 cmH2O; plateau pressure is safe and no adjustment is indicated
Transpulmonary plateau = 16 cmH2O; current driving pressure is acceptable, no change needed

Correct answer: Transpulmonary plateau = 16 cmH2O; current plateau is safe, increase PEEP to titrate by transpulmonary PEEP

Transpulmonary pressure (PL) = airway pressure − esophageal pressure (as a surrogate for pleural pressure). Transpulmonary plateau = 34 (plateau) − 18 (esophageal pressure) = 16 cmH2O, which is within the safe range (<25 cmH2O). This means the elevated plateau pressure (34 cmH2O, above the conventional 30 cmH2O threshold) is explained by a high chest wall elastance (e.g., obesity, abdominal hypertension, pleural effusions), not by dangerous overdistension of the lungs. The appropriate action is to use transpulmonary PEEP titration — titrate PEEP to achieve a positive end-expiratory transpulmonary pressure (PEEP − esophageal EEP > 0) to maintain alveolar recruitment, rather than reflexively lowering PEEP because of the high airway plateau. The transpulmonary plateau of 16 cmH2O does NOT indicate a need to reduce TV further, as lung stress is already safe.

Question 41: A 44-year-old man is found to have a 2.5 cm hepatic lesion on ultrasound done for elevated liver enzymes. He has no cirrhosis and no known liver disease. MRI shows a well-demarcated lesion with arterial phase hyperenhancement, peripheral nodular enhancement, and progressive centripetal fill-in on delayed phases. The most likely diagnosis and appropriate next step are:

Cholangiocarcinoma — ERCP with brushings
Hepatic hemangioma — reassurance and no further workup needed (Correct answer)
Hepatocellular carcinoma — proceed to thermal ablation
Focal nodular hyperplasia — confirmatory hepatobiliary contrast MRI phase assessment

Correct answer: Hepatic hemangioma — reassurance and no further workup needed

The described MRI pattern — peripheral nodular arterial enhancement with progressive centripetal fill-in ('light bulb' sign on T2, scalloped margins) — is pathognomonic for a hepatic cavernous hemangioma. In a non-cirrhotic patient without risk factors, this classic pattern on MRI is sufficient for diagnosis; no biopsy or further invasive workup is needed. HCC would show washout appearance in a cirrhotic liver. FNH shows a central scar and homogeneous arterial blush. Cholangiocarcinoma would show different ductal features.

Question 42: A 44-year-old woman has a TSH of 0.02 mIU/L and free T4 of 2.8 ng/dL. She takes levothyroxine 150 mcg/day for hypothyroidism. She is asymptomatic. DEXA shows T-score −2.1 at lumbar spine. What is the most important reason to adjust her levothyroxine?

Exogenous subclinical hyperthyroidism accelerates bone loss (Correct answer)
Risk of thyroid storm
Risk of Afib from subclinical hyperthyroidism
Suppressed TSH causes pituitary enlargement

Correct answer: Exogenous subclinical hyperthyroidism accelerates bone loss

Exogenous subclinical hyperthyroidism (suppressed TSH) accelerates bone turnover and exacerbates osteoporosis, making dose reduction important in this patient with already reduced bone density.

Question 43: A 52-year-old woman with systemic lupus erythematosus on mycophenolate mofetil and prednisone 20 mg/day develops progressive dyspnea and dry cough over 3 weeks. CT chest shows bilateral ground-glass opacities in a perihilar distribution. Bronchoalveolar lavage fluid reveals silver-stain-positive cysts and trophozoites. She was NOT on Pneumocystis jirovecii pneumonia (PJP) prophylaxis. Her LDH is 520 U/L (ULN 250), PaO2 on room air is 58 mmHg, and A-a gradient is 48 mmHg. Which adjunctive therapy is MOST indicated alongside TMP-SMX?

Adjunctive corticosteroids are contraindicated in immunosuppressed patients with PJP
Methylprednisolone 1 g IV daily for 3 days (pulse therapy) for underlying SLE flare
Inhaled pentamidine to augment anti-Pneumocystis coverage
Prednisone 40 mg PO twice daily for 5 days, then taper over 21 days (Correct answer)

Correct answer: Prednisone 40 mg PO twice daily for 5 days, then taper over 21 days

Adjunctive corticosteroids are indicated in moderate-to-severe PJP (defined as PaO2 <70 mmHg on room air or A-a gradient >35 mmHg), as they reduce inflammation-mediated hypoxemia and decrease mortality. The standard regimen is prednisone 40 mg PO twice daily for days 1–5, 40 mg daily for days 6–10, then 20 mg daily for days 11–21. Pulse methylprednisolone (1 g/day) is for SLE nephritis or other autoimmune crises — not PJP. The misconception that corticosteroids are contraindicated in immunosuppressed patients is incorrect; the benefit is well-established in HIV and non-HIV PJP. Inhaled pentamidine has no adjunctive role in established PJP.

Question 44: A 72-year-old man with CKD stage 3 and a porcine aortic valve replacement (6 years ago) is diagnosed with Enterococcus faecalis endocarditis (blood cultures, 4/4 bottles positive). MIC of ampicillin is 0.25 µg/mL; gentamicin MIC is 500 µg/mL (high-level aminoglycoside resistance, HLAR); no beta-lactamase detected. What is the MOST appropriate antibiotic regimen?

Daptomycin monotherapy for 6 weeks
Ampicillin plus gentamicin for 4–6 weeks
Vancomycin plus gentamicin for 6 weeks
Ampicillin plus ceftriaxone for 6 weeks (Correct answer)

Correct answer: Ampicillin plus ceftriaxone for 6 weeks

This is a pivotal nuance: the organism has high-level aminoglycoside resistance (HLAR, defined as gentamicin MIC ≥500 µg/mL), which abolishes the synergistic bactericidal effect of ampicillin-aminoglycoside. In HLAR enterococcal endocarditis, the recommended regimen is ampicillin plus ceftriaxone (double beta-lactam therapy), which achieves synergy via saturation of different penicillin-binding proteins. This is particularly important in patients with CKD where aminoglycosides pose nephrotoxicity risk. Vancomycin (choice C) is inappropriate because the organism is ampicillin-susceptible. Daptomycin monotherapy (choice D) is not guideline-endorsed as sole therapy for endocarditis.

Question 45: A 28-year-old man presents with genital ulcers and painful inguinal lymphadenopathy (buboes). He recently returned from a trip to Africa. The ulcers are soft and painful. What is the most likely diagnosis and treatment?

Syphilis; benzathine penicillin G IM
Chancroid; azithromycin 1g single dose (Correct answer)
LGV; doxycycline 100mg BID x 21 days
Genital herpes; acyclovir 400mg TID

Correct answer: Chancroid; azithromycin 1g single dose

Chancroid (Haemophilus ducreyi) presents with painful soft ulcers and suppurative buboes; azithromycin 1g PO single dose is one of the recommended treatments.

Question 46: A 48-year-old woman with type 2 diabetes on metformin and linagliptin develops worsening renal function (eGFR now 22 mL/min). Which medication adjustment is most appropriate?

Discontinue both metformin and linagliptin
Switch linagliptin to sitagliptin
Discontinue metformin; continue linagliptin (Correct answer)
Continue both at reduced doses

Correct answer: Discontinue metformin; continue linagliptin

Metformin is contraindicated when eGFR <30 mL/min; linagliptin, unlike other DPP-4 inhibitors, is primarily excreted via bile and requires no renal dose adjustment even in severe CKD.

Question 47: A 34-year-old woman with systemic sclerosis presents with 6 months of progressive dyspnea. PFTs show TLC 62% predicted, DLCO 38% predicted, FVC/FEV1 ratio 0.82. Right heart catheterization reveals mPAP 42 mmHg, PCWP 9 mmHg, PVR 6.8 Wood units, and cardiac output 4.1 L/min. She is WHO functional class III. Which of the following is the most appropriate initial therapy?

Combination oral ambrisentan plus tadalafil (Correct answer)
IV epoprostenol infusion
Oral sildenafil monotherapy
Oral bosentan plus inhaled iloprost

Correct answer: Combination oral ambrisentan plus tadalafil

This patient has Group 1 pulmonary arterial hypertension (PAH) associated with systemic sclerosis, WHO FC III. The AMBITION trial demonstrated that upfront combination therapy with an ERA (ambrisentan) plus a PDE5 inhibitor (tadalafil) reduced the risk of clinical failure events by 50% compared to monotherapy in treatment-naive patients. Current guidelines (ESC/ERS 2022, ACC/AHA 2022) recommend upfront oral combination therapy as preferred initial strategy for FC II–III PAH. IV epoprostenol is preferred for FC IV or rapidly deteriorating patients. Bosentan is preferred over ambrisentan in scleroderma-associated PAH with ILD due to liver safety concerns, but the ambrisentan/tadalafil combination has the strongest evidence for initial combination therapy.

Question 48: A 40-year-old woman has an incidentally discovered 2.5 cm adrenal mass on CT for kidney stones. She has no hypertension or symptoms. Hormonal workup shows: normal aldosterone/renin ratio, normal 24-hour urine catecholamines, and 1 mg overnight dexamethasone suppression test shows cortisol of 3.8 mcg/dL. What is the next step?

PET scan to rule out malignancy
Adrenalectomy
Repeat imaging in 6–12 months and reassay hormones annually (Correct answer)
Salivary cortisol testing

Correct answer: Repeat imaging in 6–12 months and reassay hormones annually

An adrenal incidentaloma <4 cm that is hormonally inactive (cortisol suppresses to <5 mcg/dL on 1 mg DST) should be followed with repeat imaging at 6–12 months and annual hormonal reassessment per guidelines.

Question 49: A 52-year-old woman with rheumatoid arthritis on methotrexate 20 mg/week and folic acid presents with macrocytic anemia (MCV 108 fL), hypersegmented neutrophils, and a serum B12 of 310 pg/mL (normal >200). Serum folate is 3.2 ng/mL (normal >4). Which finding would most specifically confirm that methotrexate — rather than dietary folate deficiency — is the primary etiology?

Rapid response to increased dietary folate supplementation alone
Low red blood cell (RBC) folate with normal serum folate
Elevated serum homocysteine with normal methylmalonic acid (MMA) (Correct answer)
Elevated serum homocysteine with elevated methylmalonic acid (MMA)

Correct answer: Elevated serum homocysteine with normal methylmalonic acid (MMA)

Methotrexate inhibits dihydrofolate reductase, impairing conversion of folate to its active tetrahydrofolate form — a functional folate deficiency even when serum folate stores appear adequate. Both dietary folate deficiency and methotrexate toxicity impair the folate-dependent step in homocysteine methylation, elevating homocysteine. However, MMA elevation is specific to B12 deficiency (B12 is required for the MMA→succinyl-CoA reaction). A pattern of elevated homocysteine with normal MMA points to folate pathway dysfunction (as seen with methotrexate) rather than true B12 deficiency.

Question 50: A 30-year-old man presents with polyuria, polydipsia, and a serum sodium of 148 mEq/L. Urine osmolality is 110 mOsm/kg after water deprivation, rising to 680 mOsm/kg after desmopressin (DDAVP). What is the diagnosis?

Nephrogenic diabetes insipidus
Primary polydipsia
Central (neurogenic) diabetes insipidus (Correct answer)
Syndrome of inappropriate ADH

Correct answer: Central (neurogenic) diabetes insipidus

A markedly concentrated urine response to exogenous DDAVP after failure to concentrate with water deprivation indicates central diabetes insipidus, where ADH is deficient but the kidney can respond normally.

Question 51: A 55-year-old man with no prior GI history has a positive fecal immunochemical test (FIT). What is the most appropriate next step?

Flexible sigmoidoscopy
Colonoscopy (Correct answer)
Repeat FIT in 1 year
CT colonography

Correct answer: Colonoscopy

A positive FIT requires diagnostic colonoscopy to evaluate for colorectal cancer or adenomatous polyps; no alternative testing is appropriate after a positive non-invasive screen.

Question 52: Which physical examination finding is most specific for cardiac tamponade?

Distant heart sounds
Pulsus paradoxus >10 mmHg (Correct answer)
Pericardial friction rub
Elevated JVP with Kussmaul's sign

Correct answer: Pulsus paradoxus >10 mmHg

Pulsus paradoxus (>10 mmHg drop in systolic BP during inspiration) is the most specific physical finding for cardiac tamponade.

Question 53: A 62-year-old man undergoes colonoscopy showing a 1.5 cm sessile serrated lesion in the ascending colon. When should surveillance colonoscopy be performed?

3 years (Correct answer)
5 years
10 years
1 year

Correct answer: 3 years

Sessile serrated lesions ≥10 mm or with dysplasia warrant 3-year surveillance colonoscopy per current ACG guidelines due to their malignant potential.

Question 54: A 50-year-old woman with systemic lupus erythematosus presents with dyspnea, elevated JVP, and an echocardiogram showing a thickened pericardium with respiratory variation in mitral inflow >25%. What is the diagnosis?

Pulmonary arterial hypertension
Dilated cardiomyopathy
Constrictive pericarditis (Correct answer)
Restrictive cardiomyopathy

Correct answer: Constrictive pericarditis

Constrictive pericarditis presents with elevated JVP, Kussmaul's sign, and exaggerated respiratory variation in Doppler inflow velocities, and is a known complication of SLE.

Question 55: A 35-year-old African American woman presents with bilateral hilar lymphadenopathy, erythema nodosum, and polyarthritis. Serum ACE is elevated. Bronchoscopy with BAL shows lymphocytosis with CD4:CD8 ratio of 5:1. What is the MOST likely diagnosis?

Berylliosis
Lymphoma with pulmonary involvement
Sarcoidosis (Correct answer)
Hypersensitivity pneumonitis

Correct answer: Sarcoidosis

Löfgren syndrome (bilateral hilar adenopathy, erythema nodosum, and arthritis) combined with elevated ACE and high BAL CD4:CD8 ratio is pathognomonic for sarcoidosis.

Question 56: A 61-year-old lung transplant recipient (18 months post-transplant) on tacrolimus, mycophenolate, and prednisone presents with subacute sinusitis and new right-sided proptosis. CT shows opacification of the right ethmoid and sphenoid sinuses with bony erosion into the right orbital apex. Biopsy of sinus tissue reveals broad, aseptate hyphae with right-angle branching. Serum galactomannan is negative; beta-D-glucan is negative. What is the SINGLE most important initial management step beyond antifungal therapy?

Emergent surgical debridement of necrotic tissue (Correct answer)
Initiation of granulocyte colony-stimulating factor (G-CSF) to restore neutrophil function
Reduction of immunosuppression, particularly mycophenolate
Addition of adjunctive hyperbaric oxygen therapy

Correct answer: Emergent surgical debridement of necrotic tissue

This presentation is classic for invasive mucormycosis (Mucorales — broad aseptate hyphae with wide-angle branching, contrasting with Aspergillus which has septate hyphae with acute-angle branching). The negative galactomannan and beta-D-glucan are consistent since Mucorales do not produce these biomarkers. While reduction of immunosuppression is important, the SINGLE most critical initial step in rhino-orbital-cerebral mucormycosis is aggressive surgical debridement of all necrotic tissue — this is a surgical emergency that determines survival. Antifungal therapy (liposomal amphotericin B) without surgery has very high mortality. Hyperbaric oxygen (choice C) is adjunctive and unproven. G-CSF (choice D) is useful in neutropenic mucormycosis, not transplant-associated disease.

Question 57: A 45-year-old woman with stage IIIA Hodgkin lymphoma achieves complete remission after ABVD chemotherapy. A PET scan performed after cycle 2 shows a Deauville score of 3. What is the most appropriate management?

Add rituximab to the remaining ABVD cycles
Continue standard ABVD for the planned total course (Correct answer)
Escalate to BEACOPPescalated immediately
Consolidate with autologous stem cell transplant

Correct answer: Continue standard ABVD for the planned total course

A Deauville score of 3 on interim PET (after 2 cycles of ABVD) is considered a negative scan per the Lugano criteria and indicates an adequate early response. Current evidence (RATHL trial) supports continuing standard ABVD without escalation for interim PET-negative patients with classic Hodgkin lymphoma. Escalation to BEACOPPescalated is reserved for PET-positive patients (Deauville 4–5). ASCT is for relapsed/refractory disease. Rituximab is not active in Hodgkin lymphoma (which is CD20-negative on Reed-Sternberg cells).

Question 58: A 48-year-old man is found to have an LDL of 310 mg/dL despite high-intensity statin therapy. Genetic testing confirms heterozygous familial hypercholesterolemia. What is the most appropriate add-on therapy?

Niacin 2g daily
Ezetimibe plus a PCSK9 inhibitor (Correct answer)
Omega-3 fatty acids 4g daily
Cholestyramine 8g twice daily

Correct answer: Ezetimibe plus a PCSK9 inhibitor

Ezetimibe plus a PCSK9 inhibitor (evolocumab or alirocumab) provides additive LDL lowering and is recommended for FH patients not at goal on maximally tolerated statins.

Question 59: A 35-year-old woman with lupus nephritis class IV on mycophenolate and prednisone has a serum creatinine rise from 1.1 to 2.4 mg/dL over 3 months with worsening proteinuria. What is the best next step?

Switch mycophenolate to cyclophosphamide
Repeat kidney biopsy (Correct answer)
Add hydroxychloroquine
Add belimumab

Correct answer: Repeat kidney biopsy

A repeat kidney biopsy in lupus nephritis is essential to determine whether the class has transformed, activity has increased, or chronic scarring has developed before changing therapy.

Question 60: A 34-year-old woman presents with hypertension, hypokalemia, and suppressed plasma renin activity. Aldosterone-to-renin ratio is markedly elevated. CT abdomen shows bilateral adrenal hyperplasia. Adrenal vein sampling reveals a lateralization ratio of 1.8 (left:right). Which is the most appropriate next step?

Proceed with left adrenalectomy based on lateralization ratio
Start mineralocorticoid receptor antagonist therapy and avoid surgery
Order 11-deoxycortisol levels to evaluate for 11β-hydroxylase deficiency
Repeat adrenal vein sampling with cosyntropin stimulation (Correct answer)

Correct answer: Repeat adrenal vein sampling with cosyntropin stimulation

A lateralization ratio <2.0 without cosyntropin stimulation is indeterminate. Current Endocrine Society guidelines recommend adrenal vein sampling with cosyntropin (ACTH) stimulation to maximize cortisol secretion, correct for dilution, and improve selectivity index reliability. A selectivity index ≥3:1 post-stimulation confirms successful cannulation. Surgery should only be considered with a clear lateralization ratio ≥4:1 on stimulated sampling. Without confirming lateralization, proceeding to unilateral adrenalectomy risks persistent hypertension and unnecessary surgery.

Question 61: A 45-year-old woman presents with palpitations, tremor, and a painless diffuse goiter. TSH is 0.01 mIU/L, free T4 is 3.2 ng/dL. TSH receptor antibodies are positive. She wants the most definitive long-term cure. What is the best option?

Beta-blocker monotherapy
Methimazole for 12–18 months
Radioactive iodine ablation
Total thyroidectomy (Correct answer)

Correct answer: Total thyroidectomy

Total thyroidectomy provides the most immediate and definitive cure for Graves' disease and is preferred when the patient desires rapid, definitive resolution; RAI is effective but slower and may worsen ophthalmopathy.

Question 62: A 30-year-old woman with recurrent UTIs asks about post-coital prophylaxis. She has 3 UTIs per year, all temporally related to sexual intercourse. Which regimen is appropriate?

Single-dose TMP-SMX SS taken within 2 hours of intercourse (Correct answer)
Cranberry extract 500mg daily
Daily TMP-SMX DS continuously for 6 months
Nitrofurantoin 100mg nightly for 12 months

Correct answer: Single-dose TMP-SMX SS taken within 2 hours of intercourse

Post-coital single-dose TMP-SMX or nitrofurantoin is effective prophylaxis for women whose UTIs are clearly linked to sexual activity.

Question 63: A 52-year-old man presents with increased hat and shoe size over 5 years, jaw prominence, and hyperhidrosis. Random GH is 12 ng/mL. What is the confirmatory test for acromegaly?

Insulin tolerance test (ITT)
24-hour urine GH
GH after oral glucose tolerance test (OGTT) (Correct answer)
IGF-1 level alone

Correct answer: GH after oral glucose tolerance test (OGTT)

In acromegaly, GH fails to suppress to <1 ng/mL after 75 g oral glucose load (OGTT); this is the gold-standard confirmatory test because random GH levels fluctuate.

Question 64: A 45-year-old HIV-positive man (CD4 180, not on ART) is diagnosed with PCP pneumonia. His PaO2 on room air is 58 mmHg. In addition to TMP-SMX, what adjunctive therapy should be started?

Inhaled pentamidine
Systemic corticosteroids (prednisone 40mg BID) (Correct answer)
Adjunctive atovaquone
G-CSF support

Correct answer: Systemic corticosteroids (prednisone 40mg BID)

Adjunctive corticosteroids are indicated for PCP when PaO2 < 70 mmHg or A-a gradient > 35 mmHg, as they reduce mortality by preventing inflammatory deterioration.

Question 65: A 42-year-old woman presents with several months of progressive fatigue, weight loss, nausea, and orthostatic dizziness. On examination, her blood pressure is 90/60 mmHg, and she has hyperpigmentation of her palmar creases. Laboratory studies reveal hyponatremia and hyperkalemia. A baseline 8 AM serum cortisol level is 2.8 µg/dL (low). Which of the following tests is the most appropriate next step to confirm the diagnosis of primary adrenal insufficiency?

24-hour urine free cortisol measurement
High-dose (250 mcg) ACTH (cosyntropin) stimulation test (Correct answer)
Metyrapone test
CRH stimulation test

Correct answer: High-dose (250 mcg) ACTH (cosyntropin) stimulation test

The clinical presentation and initial laboratory findings are highly suggestive of primary adrenal insufficiency (Addison's disease). The standard and most definitive diagnostic test is the high-dose (250 mcg) ACTH stimulation test. A failure of serum cortisol to rise to an adequate level (typically >18-20 µg/dL) after cosyntropin administration confirms the diagnosis. A 24-hour urine free cortisol is used to screen for cortisol excess (Cushing's syndrome). The CRH stimulation test is used to differentiate between secondary (pituitary) and tertiary (hypothalamic) adrenal insufficiency. The metyrapone test is rarely used.

Question 66: A 52-year-old man with diabetes presents with serum creatinine rising from 1.0 to 1.8 mg/dL after starting lisinopril. Renal artery duplex shows elevated resistive indices bilaterally with post-stenotic turbulence. What should be done?

Continue lisinopril at reduced dose and recheck creatinine in 2 weeks
Discontinue lisinopril and pursue further imaging to assess for bilateral renal artery stenosis (Correct answer)
Add amlodipine and continue lisinopril
Discontinue lisinopril and arrange renal artery stenting urgently

Correct answer: Discontinue lisinopril and pursue further imaging to assess for bilateral renal artery stenosis

A >30% rise in creatinine after ACE inhibitor initiation suggests bilateral renal artery stenosis or stenosis in a solitary kidney; ACE inhibitor should be stopped and vascular imaging pursued.

Question 67: A 28-year-old woman presents with fever, rash on palms and soles, and headache after camping in North Carolina in May. Peripheral smear shows no parasites but thrombocytopenia and hyponatremia are present. What is the treatment?

Chloramphenicol 500mg QID
Azithromycin 500mg daily
Ciprofloxacin 500mg BID
Doxycycline 100mg BID (Correct answer)

Correct answer: Doxycycline 100mg BID

Rocky Mountain Spotted Fever (Rickettsia rickettsii) is treated empirically with doxycycline 100mg BID, which should not be delayed awaiting confirmatory testing.

Question 68: A 17-year-old girl with obesity, short stature, and shortened 4th and 5th metacarpals has labs showing Ca2+ 7.1 mg/dL, PO4 6.3 mg/dL, PTH 310 pg/mL, and TSH 9.1 mIU/L with normal free T4. Exogenous PTH infusion fails to raise urinary cAMP or phosphate excretion. Her father has the same body habitus but has normal calcium, PTH, and TSH. A GNAS mutation is found in the family. Which mechanism explains why the father is phenotypically similar but metabolically normal?

Tissue-specific maternal imprinting of GNAS means only the maternally inherited allele is expressed in kidney and pituitary (Correct answer)
Penetrance of GNAS mutations is age-dependent and his phenotype will emerge after age 40
The father carries an X-linked recessive allele that requires hemizygosity for full expression
The father has a somatic mosaic mutation with low variant allele frequency

Correct answer: Tissue-specific maternal imprinting of GNAS means only the maternally inherited allele is expressed in kidney and pituitary

Pseudohypoparathyroidism type 1a (PHP1a) requires a maternally inherited GNAS mutation because Gsα is expressed only from the maternal allele in the kidney, pituitary, and other key tissues due to genomic imprinting. The father carries the same GNAS mutation and has Albright's hereditary osteodystrophy (AHO) phenotype — short stature, brachydactyly, subcutaneous ossifications — but because the paternal GNAS allele is silenced in hormone-responsive tissues, he has no PTH or TSH resistance. This paternal inheritance pattern is called pseudopseudohypoparathyroidism (PPHP).

Question 69: A 61-year-old man with alcohol-related cirrhosis (Child-Pugh B) and a history of variceal bleeding is on nadolol. He develops refractory ascites requiring large-volume paracentesis every 2 weeks despite maximal diuretic therapy. Creatinine is 1.0 mg/dL, sodium is 128 mEq/L. He is listed for liver transplant. What is the most appropriate next intervention?

Place a transjugular intrahepatic portosystemic shunt (TIPS) (Correct answer)
Switch from nadolol to carvedilol for better portal pressure reduction
Add midodrine and octreotide to improve renal perfusion
Initiate terlipressin for hyponatremia

Correct answer: Place a transjugular intrahepatic portosystemic shunt (TIPS)

TIPS is the most appropriate intervention for refractory ascites in a transplant candidate with preserved renal function (creatinine 1.0) and Child-Pugh B (not C, where benefit is less clear). TIPS reduces portal hypertension, eliminates or dramatically reduces the need for paracentesis, and can bridge patients to transplant. Midodrine/octreotide is used for hepatorenal syndrome, not refractory ascites. Terlipressin targets HRS-AKI, not hyponatremia per se. Carvedilol switch does not address the mechanical ascites problem. Contraindications to TIPS (hepatic encephalopathy, cardiac dysfunction) are not present here.

Question 70: A 68-year-old former shipyard worker presents with progressive dyspnea and pleural plaques on chest CT. Pulmonary function testing shows FVC 68%, FEV1 70%, FEV1/FVC 0.82, DLCO 55% predicted. What type of pattern is present and what is the MOST likely diagnosis?

Restrictive pattern due to asbestosis (Correct answer)
Obstructive pattern due to asbestos-related COPD
Normal spirometry with isolated DLCO reduction from pulmonary vascular disease
Mixed pattern due to mesothelioma

Correct answer: Restrictive pattern due to asbestosis

A reduced FVC with preserved FEV1/FVC ratio (restrictive pattern) combined with reduced DLCO and occupational asbestos exposure indicates asbestosis (interstitial fibrosis from asbestos).

Question 71: A 55-year-old man has low serum testosterone (180 ng/dL), LH 0.8 mIU/mL (low), and FSH 1.0 mIU/mL (low). MRI pituitary is normal. He takes opioids chronically for back pain. What is the diagnosis?

Opioid-induced hypogonadotropic hypogonadism (Correct answer)
Klinefelter syndrome
Primary hypogonadism
Idiopathic hypogonadotropic hypogonadism

Correct answer: Opioid-induced hypogonadotropic hypogonadism

Chronic opioid use suppresses GnRH pulsatility, reducing LH and FSH secretion and resulting in secondary (hypogonadotropic) hypogonadism with low testosterone.

Question 72: A 50-year-old woman with morbid obesity develops sudden-onset severe abdominal pain after bariatric surgery 3 years ago. CT shows dilated small bowel loops with mesenteric swirling. What is the most likely diagnosis?

Dumping syndrome
Marginal ulcer
Internal hernia with small bowel obstruction (Correct answer)
Adhesive bowel obstruction

Correct answer: Internal hernia with small bowel obstruction

Internal hernia through mesenteric defects created during Roux-en-Y gastric bypass is a well-recognized complication presenting with small bowel obstruction and the CT finding of 'mesenteric swirl.'

Question 73: A 28-year-old man presents with episodic severe headaches, diaphoresis, and palpitations. BP is 210/115 mmHg during an episode. 24-hour urine metanephrines are markedly elevated. Prior to surgical resection, which medication should be initiated FIRST?

ACE inhibitor (lisinopril)
Alpha-blocker (phenoxybenzamine) (Correct answer)
Beta-blocker (propranolol)
Calcium channel blocker (amlodipine)

Correct answer: Alpha-blocker (phenoxybenzamine)

Alpha-blockade must be established before beta-blockade in pheochromocytoma to prevent unopposed alpha-adrenergic stimulation and hypertensive crisis.

Question 74: What is the most common cause of community-acquired pneumonia (CAP) in adults?

Streptococcus pneumoniae (Correct answer)
Haemophilus influenzae
Legionella pneumophila
Mycoplasma pneumoniae

Correct answer: Streptococcus pneumoniae

Streptococcus pneumoniae is consistently identified as the most common bacterial cause of community-acquired pneumonia (CAP) in adults. This pathogen is responsible for a significant portion of pneumonia cases, often presenting with classic symptoms like fever, cough, and pleuritic chest pain. Vaccination against S. pneumoniae is an important preventive measure.

Question 75: A 50-year-old woman on long-term prednisone for rheumatoid arthritis develops disseminated Strongyloides infection. What is the treatment?

Mebendazole 500mg single dose
Albendazole 400mg BID x 7 days
Praziquantel 20mg/kg TID x 1 day
Ivermectin 200mcg/kg daily x 2 days (Correct answer)

Correct answer: Ivermectin 200mcg/kg daily x 2 days

Ivermectin is the drug of choice for Strongyloides stercoralis; in disseminated disease, it is given daily until stool exams are negative for 2 consecutive weeks.

Question 76: A 70-year-old man with ischemic cardiomyopathy (EF 25%) has a fasting blood glucose of 115 mg/dL. Which antidiabetic agent has demonstrated cardiovascular mortality benefit in patients with heart failure with reduced EF?

Empagliflozin (SGLT2 inhibitor) (Correct answer)
Sitagliptin (DPP-4 inhibitor)
Metformin
Liraglutide (GLP-1 agonist)

Correct answer: Empagliflozin (SGLT2 inhibitor)

SGLT2 inhibitors like empagliflozin and dapagliflozin reduce cardiovascular death and heart failure hospitalizations in HFrEF, even in patients without diabetes.

Question 77: A 57-year-old man with compensated cirrhosis (Child-Pugh A, MELD-Na 12) due to NASH is found on surveillance ultrasound to have a 1.8 cm arterially enhancing hepatic nodule with washout appearance on gadoxetate-enhanced MRI (LI-RADS 5). AFP is 18 ng/mL. He has no extrahepatic disease. Which treatment modality offers the best long-term survival benefit for this patient?

Liver transplantation within Milan criteria (Correct answer)
Radiofrequency ablation (RFA)
Stereotactic body radiation therapy (SBRT)
Transarterial chemoembolization (TACE)

Correct answer: Liver transplantation within Milan criteria

For a patient with cirrhosis and a single HCC ≤2 cm (well within Milan criteria: single lesion ≤5 cm or ≤3 lesions each ≤3 cm), liver transplantation provides the only curative treatment for both the HCC and the underlying cirrhosis, offering the best long-term survival and lowest recurrence rates (~10–15% at 5 years vs. ~50–70% after ablation). With a MELD-Na of 12 and Child-Pugh A status, this patient is an excellent transplant candidate. RFA achieves excellent local control for small HCC but does not address the cirrhotic liver field defect, leading to high intrahepatic recurrence. TACE is palliative for intermediate-stage HCC and is not the preferred modality for early-stage resectable/transplantable disease.

Question 78: A 70-year-old woman presents with proximal muscle weakness, difficulty rising from a chair, bilateral shoulder and hip girdle aching, an ESR of 95 mm/hr, and a CRP of 4.2 mg/dL. She has no muscle enzyme elevation and normal EMG. What is the most likely diagnosis?

Polymyositis
Hypothyroid myopathy
Polymyalgia rheumatica (PMR) (Correct answer)
Fibromyalgia

Correct answer: Polymyalgia rheumatica (PMR)

PMR presents in patients >50 with bilateral proximal girdle stiffness/aching, markedly elevated inflammatory markers, but normal CK and EMG — distinguishing it from inflammatory myopathy. Polymyositis has elevated CK and abnormal EMG. Fibromyalgia does not cause elevated ESR. Hypothyroid myopathy may elevate CK and TSH would be abnormal.

Question 79: A 44-year-old man with alcoholic cirrhosis (Child-Pugh C) presents with worsening abdominal distension and fever. Diagnostic paracentesis reveals PMN count of 320 cells/µL. He is initiated on cefotaxime. Blood cultures return with Escherichia coli susceptible to all agents tested. On hospital day 3, his creatinine rises from 0.9 to 2.7 mg/dL despite IV fluid hydration. Which intervention has the strongest evidence for preventing this complication at the TIME OF SBP DIAGNOSIS?

Terlipressin 1 mg IV every 4 hours initiated when creatinine exceeds 1.5 mg/dL
Norepinephrine infusion titrated to MAP ≥65 mmHg to maintain renal perfusion
Midodrine plus octreotide plus albumin (triple therapy) beginning at diagnosis
Albumin 1.5 g/kg IV on day 1 and 1 g/kg on day 3 of antibiotic therapy (Correct answer)

Correct answer: Albumin 1.5 g/kg IV on day 1 and 1 g/kg on day 3 of antibiotic therapy

Spontaneous bacterial peritonitis (SBP) triggers systemic inflammation that precipitates hepatorenal syndrome (HRS) in susceptible cirrhotics. The landmark Sort et al. trial (NEJM 1999) demonstrated that albumin infusion at 1.5 g/kg on day 1 and 1 g/kg on day 3 of antibiotic initiation significantly reduced the incidence of HRS and improved 3-month survival compared to antibiotics alone. This is the standard of care per AASLD and EASL guidelines and is initiated AT THE TIME OF DIAGNOSIS, not after creatinine rises. Terlipressin is used for established HRS-AKI. Midodrine/octreotide/albumin is used for HRS management, not SBP prophylaxis. Norepinephrine is a vasopressor without evidence in this preventive role.

Question 80: A 32-year-old pregnant woman (20 weeks) is diagnosed with Graves' disease. TSH is suppressed, free T4 is 3.4 ng/dL. Which antithyroid drug is preferred during the second trimester?

Methimazole (Correct answer)
Propylthiouracil (PTU)
Radioactive iodine (RAI)
Beta-blocker monotherapy

Correct answer: Methimazole

Methimazole is preferred after the first trimester; PTU is preferred in the first trimester due to methimazole's teratogenicity risk early in pregnancy, and RAI is absolutely contraindicated in pregnancy.

Question 81: A patient in the ICU on mechanical ventilation has the following ABG: pH 7.50, PaCO2 30 mmHg, PaO2 95 mmHg, HCO3 23 mEq/L. Current settings: TV 500 mL, RR 18, PEEP 5, FiO2 0.40. What is the MOST appropriate ventilator adjustment?

Decrease FiO2 to 0.21
Increase PEEP to improve oxygenation
Increase tidal volume to increase minute ventilation
Decrease respiratory rate to correct respiratory alkalosis (Correct answer)

Correct answer: Decrease respiratory rate to correct respiratory alkalosis

The ABG shows respiratory alkalosis (low PaCO2, elevated pH) with adequate oxygenation; decreasing respiratory rate reduces minute ventilation and corrects hypocapnia.

Question 82: A 58-year-old man with HIV (CD4 count 45 cells/µL) on antiretroviral therapy presents with 3 weeks of progressive dyspnea, fever, and bilateral infiltrates. BAL reveals Pneumocystis jirovecii. He is started on TMP-SMX but worsens on day 3 with PaO2 of 58 mmHg on room air. Which adjunctive intervention is most appropriate at this point?

Add adjunctive caspofungin for possible co-infection
Initiate mechanical ventilation before continuing PCP therapy
Switch to IV pentamidine and add corticosteroids
Add corticosteroids (prednisone 40 mg twice daily) (Correct answer)

Correct answer: Add corticosteroids (prednisone 40 mg twice daily)

Adjunctive corticosteroids are indicated in PCP pneumonia when PaO2 < 70 mmHg on room air or A-a gradient > 35 mmHg, and are most beneficial when started within 72 hours of anti-PCP therapy. Prednisone 40 mg BID for 5 days, then tapered, reduces inflammation-driven respiratory failure and mortality. Switching to pentamidine is reserved for TMP-SMX failure after an adequate trial (≥5-7 days), not on day 3. Caspofungin has no role here, and mechanical ventilation is not the priority before optimizing medical management.

Question 83: A 55-year-old man with newly diagnosed type 2 diabetes has an HbA1c of 7.8%, BMI 36 kg/m², no cardiovascular disease, and normal renal function. What is the most appropriate pharmacotherapy beyond lifestyle modification?

Sulfonylurea alone
Metformin + GLP-1 receptor agonist (Correct answer)
Metformin alone
Insulin glargine

Correct answer: Metformin + GLP-1 receptor agonist

Current ADA guidelines favor early combination therapy in patients with HbA1c >1.5–2% above goal; adding a GLP-1 agonist to metformin also promotes weight loss, which is beneficial in this obese patient.

Question 84: A patient with long-standing hypertension presents with an aortic dissection beginning just distal to the left subclavian artery (Type B). Blood pressure is 165/95 mmHg and he is pain-free. What is the preferred initial management?

Emergency surgical repair
Medical management with IV beta-blockers targeting HR <60 and SBP 100-120 mmHg (Correct answer)
Thoracic endovascular aortic repair (TEVAR)
Anticoagulation with heparin to prevent thrombosis

Correct answer: Medical management with IV beta-blockers targeting HR <60 and SBP 100-120 mmHg

Uncomplicated Type B (Stanford) aortic dissections are initially managed medically with heart rate and blood pressure control using IV beta-blockers.

Question 85: A 72-year-old man with CLL has a rising lymphocyte count and new lymphadenopathy. Biopsy shows transformation to DLBCL with loss of CD5 expression and elevated LDH. What is this transformation called?

Richter transformation (Correct answer)
Accelerated phase CLL
Prolymphocytic transformation
Blastic transformation

Correct answer: Richter transformation

Richter transformation refers to the development of aggressive lymphoma (most commonly DLBCL) in a patient with CLL, carrying a poor prognosis.

Question 86: A 62-year-old woman with known pulmonary arterial hypertension presents with worsening dyspnea and right heart failure. Echocardiogram shows RV dilation and septal bowing. Which hemodynamic finding on right heart catheterization confirms WHO Group 1 PAH?

Mean PAP >20 mmHg with PCWP >15 mmHg
Systolic PAP >50 mmHg with normal PVR
Mean PAP >20 mmHg with PCWP ≤15 mmHg and PVR ≥3 Wood units (Correct answer)
Mean PAP >25 mmHg with elevated cardiac output

Correct answer: Mean PAP >20 mmHg with PCWP ≤15 mmHg and PVR ≥3 Wood units

Updated 2022 ESC/ERS guidelines define PAH (Group 1) as mean PAP >20 mmHg with PCWP ≤15 mmHg and PVR ≥3 Wood units on right heart catheterization.

Question 87: A 68-year-old man on hemodialysis develops bacteremia with MSSA. TEE shows no vegetation. What is the recommended duration of antibiotic therapy for uncomplicated MSSA bacteremia?

28 days
14 days (Correct answer)
42 days
7 days

Correct answer: 14 days

Uncomplicated S. aureus bacteremia (no endocarditis, no metastatic focus, clinical improvement by 72h) requires 14 days of IV anti-staphylococcal therapy.

Question 88: A 48-year-old woman with rheumatic mitral stenosis (MVA 1.2 cm²) develops symptomatic dyspnea. Echo shows pliable leaflets, no significant MR, and no left atrial thrombus. What is the preferred intervention?

Percutaneous mitral balloon commissurotomy (PMBC) (Correct answer)
Open surgical commissurotomy
Medical therapy with diuretics only
Mitral valve replacement with bioprosthesis

Correct answer: Percutaneous mitral balloon commissurotomy (PMBC)

PMBC is the procedure of choice for symptomatic moderate-severe MS with favorable valve morphology (pliable leaflets, minimal calcification, no significant MR, no LA thrombus).

Question 89: A 48-year-old man presents with massive pleural effusion. Thoracentesis reveals exudative fluid (LDH 380 U/L, protein 4.2 g/dL, pH 7.15, glucose 42 mg/dL). Gram stain is negative, but culture grows Streptococcus milleri. What is the MOST appropriate next management step?

Thoracoscopy with decortication
Intrapleural tPA plus DNase
IV antibiotics alone with repeat thoracentesis in 48 hours
Chest tube drainage plus IV antibiotics (Correct answer)

Correct answer: Chest tube drainage plus IV antibiotics

A complicated parapneumonic effusion with pH <7.20 and glucose <60 mg/dL with positive culture (empyema) requires chest tube drainage combined with IV antibiotics.

Question 90: A 72-year-old woman with stage 4 CKD is found to have serum bicarbonate of 18 mEq/L. Which intervention has been shown to slow CKD progression in addition to correcting the acidosis?

Sodium bicarbonate supplementation (Correct answer)
Furosemide to reduce sodium load
Dietary protein restriction alone
Calcium carbonate as a phosphate binder

Correct answer: Sodium bicarbonate supplementation

Alkali therapy with oral sodium bicarbonate has been shown in multiple trials to slow GFR decline in CKD patients with metabolic acidosis.

Question 91: A 62-year-old man presents with episodic headaches, palpitations, and diaphoresis. Blood pressure is 185/110 mmHg during an episode. 24-hour urine metanephrines are elevated. What is the most appropriate initial treatment before surgery?

Beta-blocker alone
Alpha-blocker (phenoxybenzamine) followed by beta-blocker (Correct answer)
ACE inhibitor alone
Calcium channel blocker alone

Correct answer: Alpha-blocker (phenoxybenzamine) followed by beta-blocker

Alpha-blockade must be established before beta-blockade in pheochromocytoma to prevent paradoxical hypertension from unopposed alpha stimulation.

Question 92: A 60-year-old with known achalasia undergoes esophageal manometry showing aperistalsis and incomplete lower esophageal sphincter relaxation. Which treatment has the lowest risk of GERD as a complication?

Per-oral endoscopic myotomy (POEM)
Pneumatic dilation
Botulinum toxin injection
Heller myotomy with fundoplication (Correct answer)

Correct answer: Heller myotomy with fundoplication

Heller myotomy combined with partial fundoplication (Dor or Toupet) reduces post-procedural GERD compared to myotomy alone or POEM, which disrupts the anti-reflux barrier without fundoplication.

Question 93: A 44-year-old woman with a prosthetic mitral valve (implanted 8 months ago) presents with 6 weeks of low-grade fever and fatigue. Blood cultures grow Enterococcus faecalis susceptible to ampicillin (MIC 2 µg/mL) and gentamicin (MIC 128 µg/mL via high-level aminoglycoside resistance screen). Echocardiogram confirms vegetation on the prosthetic valve without abscess. Which treatment regimen is preferred?

Linezolid monotherapy for 8 weeks given prosthetic valve involvement
Ampicillin plus ceftriaxone for 6 weeks (Correct answer)
Ampicillin plus gentamicin for 6 weeks
Vancomycin plus gentamicin for 6 weeks

Correct answer: Ampicillin plus ceftriaxone for 6 weeks

High-level aminoglycoside resistance (HLAR) — defined as gentamicin MIC ≥500 µg/mL by high-level screen — eliminates synergistic benefit of ampicillin-gentamicin, the traditional combination for enterococcal endocarditis. A MIC of 128 µg/mL via screen indicates HLAR. The IDSA guidelines now recommend ampicillin plus ceftriaxone as an equivalent alternative with superior safety profile (no nephrotoxicity/ototoxicity), particularly for E. faecalis with HLAR — based on the GAMES cohort and subsequent validation. This regimen works through distinct PBP binding and is effective regardless of aminoglycoside resistance. Vancomycin plus gentamicin is inferior and still faces the HLAR issue. Linezolid lacks bactericidal activity and is not guideline-supported for enterococcal endocarditis.

Question 94: A 44-year-old woman is found to have a serum calcium of 11.6 mg/dL on routine labs. PTH is 78 pg/mL (normal 15–65). 24-hour urine calcium is 95 mg/24h (reference > 200 mg for hypercalcemia). Her calcium-to-creatinine clearance ratio (CCCR) is 0.008. She has no symptoms and her DEXA scan shows Z-score of −1.0 at the lumbar spine. Her sister was recently diagnosed with the same condition. What is the most appropriate management?

Obtain sestamibi scan and neck ultrasound to localize a parathyroid adenoma prior to surgery
Initiate cinacalcet to normalize serum calcium and reduce fracture risk
Reassure and monitor without intervention; refer for genetic testing for CaSR or AP2S1 mutation (Correct answer)
Refer for parathyroidectomy given symptomatic primary hyperparathyroidism meeting surgical criteria

Correct answer: Reassure and monitor without intervention; refer for genetic testing for CaSR or AP2S1 mutation

This presentation is classic for Familial Hypocalciuric Hypercalcemia (FHH), an autosomal dominant condition caused by loss-of-function mutations in the calcium-sensing receptor (CaSR) gene, or less commonly AP2S1 or GNA11. Key features: mild-moderate hypercalcemia, inappropriately normal-to-elevated PTH, markedly low 24-hour urine calcium (< 100 mg/day), and CCCR < 0.01 (the diagnostic threshold). Family history of similar calcium levels strongly supports FHH. FHH is benign — parathyroidectomy does not normalize calcium and is not indicated. Cinacalcet may lower calcium temporarily but is not standard of care for FHH. Genetic testing confirms the diagnosis and prevents unnecessary surgical intervention. DEXA Z-score of −1.0 does not meet criteria for parathyroidectomy even if primary hyperparathyroidism were confirmed.

Question 95: A 55-year-old man has serum calcium of 11.4 mg/dL, PTH of 95 pg/mL (normal 15–65), and normal renal function. Urine calcium-to-creatinine clearance ratio is 0.005. What is the most likely diagnosis?

Vitamin D toxicity
Malignancy-associated hypercalcemia
Primary hyperparathyroidism
Familial hypocalciuric hypercalcemia (Correct answer)

Correct answer: Familial hypocalciuric hypercalcemia

A urine calcium-to-creatinine clearance ratio <0.01 with hypercalcemia and elevated PTH indicates familial hypocalciuric hypercalcemia (FHH), not primary hyperparathyroidism.

Question 96: A 58-year-old man with HIV (CD4 count 45 cells/µL, viral load 120,000 copies/mL) presents with 3 weeks of headache, fever, and confusion. CSF analysis reveals: opening pressure 320 mmHg, WBC 8 cells/µL (lymphocyte-predominant), glucose 45 mg/dL, protein 78 mg/dL, India ink positive. Cryptococcal antigen titer is 1:2048. After initiating liposomal amphotericin B plus flucytosine, what is the most critical determinant of 10-week mortality in this patient?

Adequacy of serial therapeutic lumbar punctures to control intracranial pressure (Correct answer)
Baseline CSF cryptococcal antigen titer
Time to CSF culture sterilization
CD4 count at time of diagnosis

Correct answer: Adequacy of serial therapeutic lumbar punctures to control intracranial pressure

In cryptococcal meningitis, elevated intracranial pressure (ICP) is the primary driver of early mortality. Serial therapeutic lumbar punctures (targeting opening pressure <200 mmHg) are the cornerstone of ICP management and have been shown in multiple studies — including the COAT trial — to be the most critical intervention affecting 10-week survival. While antifungal therapy addresses the underlying infection, uncontrolled ICP causes herniation and death before sterilization occurs. Baseline antigen titers and CD4 count are prognostic but not as actionable in the acute setting.

Question 97: A 45-year-old man with hepatitis B (HBsAg positive, HBeAg positive, HBV DNA 8 log IU/mL, ALT 180) has liver biopsy showing moderate inflammation and bridging fibrosis. Which treatment is most appropriate?

Tenofovir disoproxil fumarate (Correct answer)
Lamivudine
Interferon-alpha monotherapy
Monitor without treatment

Correct answer: Tenofovir disoproxil fumarate

Tenofovir (TDF or TAF) is the preferred first-line treatment for chronic hepatitis B with significant disease activity and fibrosis due to its potency, high barrier to resistance, and safety profile.

Question 98: A medical ICU patient with septic shock from gram-negative bacteremia has been on norepinephrine 0.35 mcg/kg/min and vasopressin 0.03 units/min for 18 hours. MAP is 62 mmHg. Bedside echocardiography reveals: EF 15%, severely dilated left ventricle, TAPSE 12 mm, dilated RV with septal flattening in systole. CVP is 22 mmHg. ScvO2 is 58%. Lactate is 6.2 mmol/L trending upward. Which hemodynamic intervention is MOST appropriate at this time?

Administer 1L crystalloid bolus to optimize preload before adding inotropes
Add phenylephrine to increase SVR and improve coronary perfusion pressure
Add epinephrine infusion and prepare for intra-aortic balloon pump (Correct answer)
Begin dobutamine infusion at 5 mcg/kg/min

Correct answer: Add epinephrine infusion and prepare for intra-aortic balloon pump

This patient has septic cardiomyopathy with biventricular failure (EF 15%, TAPSE 12 mm, RV dilation with septal D-sign in systole), refractory shock (MAP 62 on dual vasopressors), and worsening end-organ perfusion (rising lactate, low ScvO2). The CVP of 22 mmHg indicates the patient is already volume overloaded, making fluid administration contraindicated and potentially harmful. Dobutamine alone may worsen hypotension through vasodilation in an already vasoplegic state. Phenylephrine (pure alpha agonist) would increase afterload against a failing LV and RV, worsening cardiac output. Epinephrine provides inotropic support (beta-1) while maintaining vasoconstriction (alpha), and in biventricular failure refractory to norepinephrine + vasopressin, it is the preferred next agent. IABP should be prepared given the severity of LV failure and refractory shock — it reduces LV afterload and augments diastolic coronary perfusion, providing a bridge to recovery or escalation.

Question 99: A 48-year-old woman is found to have a 1.8 cm thyroid nodule incidentally on a carotid ultrasound. Her TSH level is normal. A dedicated thyroid ultrasound is performed and describes the nodule as solid, markedly hypoechoic, with a taller-than-wide shape and microcalcifications. Based on these high-risk features, which of the following is the most appropriate next step in management?

Measurement of serum thyroglobulin
Reassurance and repeat ultrasound in 12 months
Trial of levothyroxine suppression therapy
Fine-needle aspiration (FNA) biopsy (Correct answer)

Correct answer: Fine-needle aspiration (FNA) biopsy

According to the American Thyroid Association (ATA) and ACR TI-RADS guidelines, a nodule >1 cm with high-suspicion sonographic features warrants a fine-needle aspiration (FNA) biopsy. The features described (solid, markedly hypoechoic, taller-than-wide, microcalcifications) place this nodule in the highest risk category for malignancy (TI-RADS 5). Reassurance would be inappropriate. Levothyroxine suppression is not recommended for the management of thyroid nodules. Serum thyroglobulin is primarily used as a tumor marker for surveillance after thyroidectomy, not for the initial diagnosis of a nodule.

Question 100: A 32-year-old woman with no prior medical history presents with fever, myalgias, and rash one week after tick removal in New England. CBC shows leukopenia and thrombocytopenia. What is the most likely diagnosis?

Lyme disease
Babesiosis
Rocky Mountain Spotted Fever
Anaplasmosis (Anaplasma phagocytophilum) (Correct answer)

Correct answer: Anaplasmosis (Anaplasma phagocytophilum)

Anaplasmosis (formerly HME/HGA) presents with fever, leukopenia, thrombocytopenia, and elevated transaminases after Ixodes tick bite in the Northeast; treated with doxycycline.

Question 101: A 47-year-old woman with type 1 diabetes is 8 hours into treatment for DKA. Her admission phosphate was 2.6 mg/dL. Repeat labs now show phosphate 1.1 mg/dL, potassium 3.7 mEq/L, glucose 220 mg/dL. She is asymptomatic with no respiratory distress, normal cardiac rhythm, and no signs of hemolysis. Which statement most accurately describes the role of phosphate replacement in her management?

Routine phosphate replacement is standard of care in DKA and should be initiated for any phosphate below 2.0 mg/dL based on multiple RCTs demonstrating improved outcomes
Hypophosphatemia in DKA is entirely driven by osmotic diuresis and corrects spontaneously with IV fluids, eliminating any need for supplementation
Routine phosphate replacement has not demonstrated clinical benefit in RCTs; replacement may be considered for severe hypophosphatemia (< 1.0–1.5 mg/dL) complicated by cardiac dysfunction, respiratory muscle weakness, or hemolytic anemia (Correct answer)
Phosphate replacement is contraindicated in DKA because IV phosphate salts invariably cause symptomatic hypocalcemia

Correct answer: Routine phosphate replacement has not demonstrated clinical benefit in RCTs; replacement may be considered for severe hypophosphatemia (< 1.0–1.5 mg/dL) complicated by cardiac dysfunction, respiratory muscle weakness, or hemolytic anemia

Phosphate levels fall during DKA treatment as insulin drives phosphate intracellularly. However, randomized controlled trials have consistently failed to show that routine phosphate replacement improves clinical outcomes. The ADA therefore does not recommend routine replacement. The exception is severe hypophosphatemia (generally < 1.0–1.5 mg/dL) in the presence of specific complications where it becomes clinically relevant: cardiac dysfunction (phosphate-dependent myocardial contractility), respiratory muscle weakness (risk of ventilatory failure), or hemolytic anemia. At 1.1 mg/dL without symptoms or organ dysfunction, this patient is borderline but does not yet meet the threshold for mandatory replacement. Hypocalcemia is a real concern with phosphate infusion but is not an absolute contraindication.

Question 102: A 52-year-old man with primary sclerosing cholangitis (PSC) and ulcerative colitis presents with a 6-week history of progressive jaundice, weight loss, and a dominant biliary stricture on MRCP. CA 19-9 is 450 U/mL. Brush cytology of the stricture is negative for malignancy. What is the most appropriate next step in management?

Perform endoscopic ultrasound-guided fine needle aspiration of the stricture
Repeat brush cytology with fluorescence in situ hybridization (FISH) (Correct answer)
Proceed directly to orthotopic liver transplantation evaluation
Start ursodeoxycholic acid at 28–30 mg/kg/day and repeat MRCP in 3 months

Correct answer: Repeat brush cytology with fluorescence in situ hybridization (FISH)

In PSC with a dominant stricture, a single negative brush cytology does not exclude cholangiocarcinoma (CCA). FISH detects chromosomal polysomy and has significantly higher sensitivity (~40–60%) than routine cytology alone (~20%) for CCA in PSC. FISH is the recommended adjunct when cytology is negative but clinical suspicion remains high. High-dose UDCA is not recommended (and may be harmful in PSC). EUS-FNA is technically difficult for proximal bile duct strictures and carries seeding risk. OLT evaluation is premature without confirmed CCA diagnosis via established Mayo criteria.

Question 103: A 78-year-old man is admitted to the hospital with radiographically confirmed community-acquired pneumonia (CAP). He is clinically stable with normal vital signs, mental status, and oral intake. According to the most recent American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) guidelines, which of the following is an appropriate duration of antibiotic therapy for this patient?

A fixed 10-day course of antibiotics
Antibiotic therapy for at least 14 days
A course of 3-5 days, provided he has achieved clinical stability (Correct answer)
Antibiotic treatment until the C-reactive protein level normalizes

Correct answer: A course of 3-5 days, provided he has achieved clinical stability

Recent updates to the ATS/IDSA guidelines for community-acquired pneumonia recommend a shorter duration of antibiotic therapy for patients who are clinically stable. For both outpatients and inpatients with non-severe CAP who achieve clinical stability (resolution of vital sign abnormalities, ability to eat, normal mentation), a course of antibiotics as short as 3-5 days is now conditionally recommended. This is a shift from previous recommendations of longer, fixed-duration courses and aims to reduce antibiotic exposure and resistance.

Question 104: A 50-year-old man with type 2 diabetes and a recent MI (6 weeks ago) has HbA1c 8.5%. He is on metformin and a sulfonylurea. Which agent should be added given his cardiovascular history?

Empagliflozin or liraglutide (Correct answer)
Pioglitazone
Sitagliptin
Alogliptin

Correct answer: Empagliflozin or liraglutide

SGLT-2 inhibitors (empagliflozin, dapagliflozin) and GLP-1 agonists (liraglutide, semaglutide) have demonstrated cardiovascular mortality reduction in patients with established ASCVD and are preferred add-on agents.

Question 105: A 22-year-old college student presents with fever, pharyngitis, cervical lymphadenopathy, and splenomegaly. Heterophile antibody test is positive. Which complication requires activity restriction?

Splenic rupture risk (Correct answer)
Airway obstruction
Thrombocytopenia
Hepatitis

Correct answer: Splenic rupture risk

Splenic rupture is a rare but life-threatening complication of infectious mononucleosis; patients should avoid contact sports and strenuous activity for at least 3-4 weeks.

Question 106: A 75-year-old man with COPD (FEV1 38% predicted) and hypoxemia at rest (PaO2 55 mmHg) has been started on long-term oxygen therapy. What is the minimum daily duration of supplemental oxygen recommended to improve survival?

8 hours per day
24 hours per day
12 hours per day
15 hours per day (Correct answer)

Correct answer: 15 hours per day

The NOTT trial established that continuous oxygen (>15 hours/day) improves survival in COPD with severe resting hypoxemia, with the greatest benefit at 24 hours.

Question 107: A 40-year-old woman from Southeast Asia presents with fever, night sweats, weight loss, and a productive cough for 3 months. AFB smear is positive. She starts RIPE therapy. After 2 months, cultures show full susceptibility. What is the total treatment duration?

6 months total (Correct answer)
4 months total
9 months total
12 months total

Correct answer: 6 months total

Drug-susceptible pulmonary tuberculosis is treated with 2 months of RIPE followed by 4 months of rifampin and isoniazid, for a total of 6 months.

Question 108: A 38-year-old man undergoes capsule endoscopy for obscure gastrointestinal bleeding. The study identifies a solitary 1.2 cm subepithelial lesion in the mid-jejunum with a central umbilication. Histology reveals spindle cells positive for CD117 (c-KIT) and DOG1, with a mitotic rate of 8 per 50 HPF. What feature most critically determines the malignant potential classification of this tumor?

Tumor size alone (>2 cm)
Tumor location in the small bowel rather than stomach
Combination of tumor size and mitotic rate (Correct answer)
CD117 positivity

Correct answer: Combination of tumor size and mitotic rate

Gastrointestinal stromal tumors (GISTs) are risk-stratified using BOTH tumor size AND mitotic rate (per 50 HPF), along with tumor site, per the Modified NIH Consensus Criteria and AFIP criteria. This jejunal GIST at 1.2 cm with 8 mitoses/50 HPF falls into a high-risk category because of the elevated mitotic rate despite small size. Location (small bowel vs. gastric) also modifies risk but does not replace the size+mitotic rate combination. CD117 positivity confirms diagnosis but does not classify malignant potential. Size alone is insufficient.

Question 109: A 48-year-old woman with ulcerative colitis develops worsening right upper quadrant pain, jaundice, and pruritus. MRCP shows multifocal strictures and dilations of intrahepatic and extrahepatic bile ducts. What is the most likely diagnosis?

Primary sclerosing cholangitis (Correct answer)
Choledocholithiasis
Primary biliary cholangitis
IgG4-related cholangiopathy

Correct answer: Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is strongly associated with ulcerative colitis and presents with the characteristic 'beaded' appearance of multifocal biliary strictures on MRCP.

Question 110: A 25-year-old man presents with a painless penile ulcer with indurated borders and bilateral inguinal lymphadenopathy. Dark-field microscopy confirms the diagnosis. What is the treatment of choice?

Azithromycin 1g PO single dose
Ceftriaxone 250mg IM single dose
Doxycycline 100mg BID x 14 days
Benzathine penicillin G 2.4 million units IM single dose (Correct answer)

Correct answer: Benzathine penicillin G 2.4 million units IM single dose

Primary syphilis is treated with benzathine penicillin G 2.4 million units IM as a single dose, which is curative for early syphilis.

Question 111: A 45-year-old woman is evaluated for amenorrhea and galactorrhea. MRI shows a 6 mm pituitary microadenoma. Prolactin level is 210 ng/mL. She is started on cabergoline. After 12 months, her prolactin normalizes and repeat MRI shows tumor resolution. She desires to discontinue cabergoline. Which of the following factors is most strongly associated with sustained remission after dopamine agonist withdrawal?

Normalization of prolactin for at least 2 years and radiological tumor disappearance (Correct answer)
Female sex and microadenoma size < 5 mm
Absence of cabergoline side effects during treatment
Prolactin nadir below 5 ng/mL during therapy

Correct answer: Normalization of prolactin for at least 2 years and radiological tumor disappearance

The Endocrine Society guidelines recommend that dopamine agonist withdrawal may be attempted after at least 2 years of therapy if prolactin has normalized and the tumor is no longer visible on MRI. Studies show that radiological disappearance of the adenoma and sustained normoprolactinemia for ≥2 years are the strongest predictors of durable remission after withdrawal. Approximately 21–31% of patients achieve lasting remission after cabergoline discontinuation under these criteria. The prolactin nadir during therapy and patient sex are not validated predictors of remission. The absence of side effects is clinically useful but not predictive of remission.

Question 112: A 26-year-old normotensive woman presents with recurrent muscle cramps and fatigue. Labs: K+ 2.8 mEq/L, HCO3- 31 mEq/L, Mg2+ 1.2 mg/dL (low), spot urine Ca/Cr ratio 0.04 (hypocalciuria). She takes no medications. Urine chloride and potassium are inappropriately elevated. Which molecular defect best explains this constellation of findings?

Gain-of-function mutation in CaSR causing hypercalciuria and hypomagnesemia
Inactivating mutation in NCC in the distal convoluted tubule (Correct answer)
Inactivating mutation in ROMK causing neonatal salt wasting then hypokalemia
Inactivating mutation in NKCC2 in the thick ascending limb of Henle

Correct answer: Inactivating mutation in NCC in the distal convoluted tubule

This is Gitelman syndrome, caused by loss-of-function mutations in SLC12A3 encoding NCC (the thiazide-sensitive Na-Cl cotransporter) in the distal convoluted tubule. The DCT is responsible for Mg reabsorption via TRPM6 channels and calcium reabsorption — NCC dysfunction causes hypomagnesemia and hypocalciuria (the same effect as chronic thiazide use). Bartter syndrome (types 1/2/3 affecting NKCC2, ROMK, or CLCNKB in the TAL) causes hypercalciuria, not hypocalciuria. The triad of hypokalemic metabolic alkalosis + hypomagnesemia + hypocalciuria is pathognomonic for Gitelman.

Question 113: A 55-year-old man with alcohol-associated hepatitis (AH) has a Maddrey Discriminant Function (MDF) of 48 and a Model for End-Stage Liver Disease (MELD) score of 26. He is started on prednisolone 40 mg daily. On day 7, his Lille score is calculated at 0.48. What is the most appropriate next step in management?

Add N-acetylcysteine to ongoing prednisolone therapy for synergistic benefit
Discontinue prednisolone and transition to pentoxifylline
Continue prednisolone for a full 28-day course
Discontinue prednisolone and refer for early liver transplant evaluation at experienced center (Correct answer)

Correct answer: Discontinue prednisolone and refer for early liver transplant evaluation at experienced center

The Lille score predicts corticosteroid response at day 7. A Lille score ≥0.45 indicates steroid non-response (predicts ~75% 6-month mortality). In non-responders, continuing prednisolone confers no survival benefit and increases infection risk — it should be stopped. Pentoxifylline has not been shown to rescue steroid non-responders and is no longer recommended as salvage. N-acetylcysteine as adjunct (ATTIR trial data) showed no 6-month mortality benefit. Early liver transplantation (LT) for severe AH without a 6-month abstinence period is performed at select experienced centers, and landmark trials (Mathurin et al., ACCELERATE-AH) demonstrate improved survival in carefully selected patients with first-episode severe AH and strong psychosocial support.

Question 114: A 58-year-old man with chronic hypersensitivity pneumonitis is evaluated for lung transplant candidacy. His PFTs show FVC 48% predicted, DLCO 32% predicted. He is started on antifibrotic therapy. Six months later, his FVC has declined by 12% absolute. Which finding on high-resolution CT would MOST strongly suggest accelerated progression requiring urgent transplant re-evaluation?

New mosaic attenuation with air trapping on expiratory views
Enlarged mediastinal lymph nodes measuring 1.2 cm short axis
New basilar honeycombing with traction bronchiectasis
Bilateral ground-glass opacities superimposed on fibrotic background (Correct answer)

Correct answer: Bilateral ground-glass opacities superimposed on fibrotic background

Bilateral ground-glass opacities superimposed on a fibrotic background in a patient with chronic hypersensitivity pneumonitis represent an acute exacerbation (AE-HP), which carries a mortality exceeding 50% and constitutes a medical emergency requiring urgent re-evaluation for transplant listing. AE-HP is analogous to acute exacerbations of IPF and is distinct from progressive fibrosis. New honeycombing represents chronic progression but not acute decompensation. Mosaic attenuation with air trapping is a feature of HP itself (small airways involvement) and is not an acute finding. Mediastinal lymphadenopathy is a nonspecific finding in HP and does not signal urgent deterioration.

Question 115: A mechanically ventilated patient with ARDS (P/F ratio 90) is being managed with prone positioning and neuromuscular blockade. After 18 hours prone, the nurse notes plateau pressure has risen from 28 to 38 cmH2O with no change in PEEP or tidal volume. SpO2 is 84%. The MOST likely cause requiring immediate intervention is:

Selective right mainstem intubation due to ETT migration
Ventilator-induced pneumothorax
Abdominal compartment syndrome causing increased chest wall elastance (Correct answer)
Auto-PEEP from secretion plugging in the dependent airways

Correct answer: Abdominal compartment syndrome causing increased chest wall elastance

Prone positioning increases intra-abdominal pressure and can unmask or worsen abdominal compartment syndrome (ACS), which raises chest wall (not lung) elastance, causing a rise in plateau pressure. In prone patients, ACS is a critical and often overlooked cause of acute plateau pressure rise. ETT migration is possible but would cause asymmetric breath sounds. Pneumothorax would cause sudden desaturation often with hemodynamic compromise. Secretion plugging would more likely raise peak airway pressure without proportionally raising plateau pressure.

Question 116: A 34-year-old woman presents with hypertension, hypokalemia, and suppressed plasma renin activity. Aldosterone-to-renin ratio is markedly elevated. CT abdomen shows bilateral adrenal hyperplasia. She undergoes adrenal vein sampling (AVS), which demonstrates a lateralization ratio of 1.8 (right:left). Which of the following is the most appropriate next step?

Proceed with right adrenalectomy based on lateralization ratio
Order 11C-metomidate PET scan to identify unilateral adenoma
Treat with mineralocorticoid receptor antagonist (spironolactone) rather than surgery (Correct answer)
Repeat AVS with cosyntropin stimulation to improve accuracy

Correct answer: Treat with mineralocorticoid receptor antagonist (spironolactone) rather than surgery

A lateralization ratio of ≥4:1 (or ≥3:1 with cosyntropin stimulation) is generally required to confirm unilateral disease and proceed with adrenalectomy. A ratio of 1.8 is non-lateralizing, indicating bilateral hyperplasia rather than a unilateral adenoma. In bilateral adrenal hyperplasia causing primary aldosteronism, the treatment of choice is medical management with a mineralocorticoid receptor antagonist such as spironolactone or eplerenone, not surgery. Proceeding with adrenalectomy based on an inadequate lateralization ratio would likely result in surgical failure without biochemical cure.

Question 117: A 67-year-old man with CLL develops sudden onset of anemia (Hgb 6.8 g/dL), elevated indirect bilirubin, LDH 920 U/L, and a positive direct antiglobulin test (DAT) with IgG and complement positivity. His peripheral smear shows spherocytes. His CLL has been managed with ibrutinib for 14 months. What is the most likely diagnosis and appropriate initial therapy?

Richter transformation; perform lymph node biopsy and initiate R-CHOP
Ibrutinib-induced hemolysis; discontinue ibrutinib and observe
Cold agglutinin disease; start rituximab and avoid cold exposure
Warm autoimmune hemolytic anemia; initiate corticosteroids (Correct answer)

Correct answer: Warm autoimmune hemolytic anemia; initiate corticosteroids

Warm AIHA (IgG-mediated, complement-activating) is a well-recognized complication of CLL and can occur even during BTK inhibitor therapy. The DAT positivity with IgG and complement, spherocytes, and indirect hyperbilirubinemia confirm warm AIHA. First-line treatment is systemic corticosteroids (prednisone 1 mg/kg/day). Cold agglutinin disease typically shows IgM on DAT and is exacerbated by cold. Richter transformation presents as rapidly enlarging nodes, B symptoms, and elevated LDH disproportionate to anemia. Ibrutinib does not directly cause DAT-positive hemolysis.

Question 118: A 65-year-old immunocompetent man presents with fever, altered mental status, and CSF pleocytosis with lymphocyte predominance, elevated protein, and normal glucose. HSV-1 encephalitis is suspected. What test confirms the diagnosis?

CSF culture for HSV
Brain biopsy for Cowdry type A inclusions
Serum HSV IgM antibodies
CSF HSV PCR (Correct answer)

Correct answer: CSF HSV PCR

CSF HSV PCR is the diagnostic test of choice for HSV encephalitis, with sensitivity >95% and specificity >99%, replacing brain biopsy as the gold standard.

Question 119: A 32-year-old man presents with low back pain and stiffness for 8 months, worse in the morning and improving with exercise, not rest. He is HLA-B27 positive. Sacroiliac joint MRI shows bone marrow edema. Which of the following is the most appropriate initial therapy?

Systemic corticosteroids
Anti-TNF biologic therapy
A nonsteroidal anti-inflammatory drug (NSAID) at full therapeutic dose (Correct answer)
Methotrexate 15 mg weekly

Correct answer: A nonsteroidal anti-inflammatory drug (NSAID) at full therapeutic dose

NSAIDs at full doses are first-line therapy for axial spondyloarthritis (ankylosing spondylitis) per ASAS and ACR guidelines. Methotrexate is not effective for axial disease. Anti-TNF biologics are indicated only after failure of at least two NSAIDs. Systemic corticosteroids are not recommended for axial disease.

Question 120: A 70-year-old man on mechanical ventilation develops sudden hemodynamic instability with decreased breath sounds on the left, tracheal deviation to the right, and rising peak airway pressures. What is the immediate management?

Increase PEEP to recruit atelectatic lung
Chest X-ray to confirm diagnosis
Bronchoscopy to assess for mucus plugging
Needle decompression of the left hemithorax (Correct answer)

Correct answer: Needle decompression of the left hemithorax

Tension pneumothorax is a clinical diagnosis requiring immediate needle decompression at the 2nd intercostal space midclavicular line before imaging.

Question 121: A 34-year-old male with a history of alcohol abuse presents to the emergency department with severe, constant epigastric pain radiating to the back, nausea, and vomiting for the past 12 hours. His serum lipase is 2500 U/L. Vital signs are stable, and there are no signs of organ failure. According to the 2024 ACG guidelines, which of the following is the most critical initial management step?

Moderately aggressive intravenous fluid resuscitation with Lactated Ringer's solution (Correct answer)
Placement of a nasogastric tube for gastric decompression
Administration of prophylactic broad-spectrum antibiotics
Immediate ERCP to assess for biliary obstruction

Correct answer: Moderately aggressive intravenous fluid resuscitation with Lactated Ringer's solution

The cornerstone of initial management for acute pancreatitis is fluid resuscitation to support intravascular volume and maintain end-organ perfusion. The 2024 ACG guidelines suggest moderately aggressive, goal-directed fluid resuscitation. Lactated Ringer's solution is preferred over normal saline as it has been associated with a reduced systemic inflammatory response. Prophylactic antibiotics are not recommended in the absence of infected necrosis, and ERCP is only indicated if there is evidence of acute cholangitis.

Question 122: A 58-year-old male is admitted to the ICU with sepsis and develops acute respiratory distress syndrome (ARDS). He is intubated and placed on mechanical ventilation. His height is 178 cm (5'10") and his ideal body weight is 75 kg. According to the ARDSNet protocol and current clinical practice guidelines, which of the following represents the most appropriate initial ventilator settings?

Tidal volume of 450 mL, PEEP of 10 cm H₂O, and plateau pressure < 30 cm H₂O (Correct answer)
Tidal volume of 750 mL, PEEP of 5 cm H₂O, and plateau pressure < 40 cm H₂O
Tidal volume of 600 mL, PEEP of 5 cm H₂O, and permissive hypercapnia is strictly avoided
Tidal volume of 300 mL, PEEP of 15 cm H₂O, and respiratory rate of 35 breaths/min

Correct answer: Tidal volume of 450 mL, PEEP of 10 cm H₂O, and plateau pressure < 30 cm H₂O

The cornerstone of mechanical ventilation in ARDS is a lung-protective strategy to minimize ventilator-induced lung injury. This involves using a low tidal volume, typically 4-8 mL/kg of ideal body weight. For this 75 kg patient, 450 mL (6 mL/kg) is an appropriate initial tidal volume. Additionally, maintaining a plateau pressure (the pressure in the alveoli at the end of inspiration) below 30 cm H₂O is crucial to prevent barotrauma. An adequate level of PEEP (Positive End-Expiratory Pressure) is also used to prevent alveolar collapse and improve oxygenation. A PEEP of 10 cm H₂O is a reasonable starting point in moderate-to-severe ARDS.

Question 123: A 67-year-old man presents with bone pain, fatigue, and recurrent pneumonias. Labs show calcium 12.2 mg/dL, creatinine 2.3 mg/dL, Hgb 9.1 g/dL, and total protein 10.2 g/dL. Serum protein electrophoresis reveals an M-spike. What is the most likely diagnosis?

Waldenstrom macroglobulinemia
Multiple myeloma (Correct answer)
Monoclonal gammopathy of undetermined significance (MGUS)
Chronic lymphocytic leukemia

Correct answer: Multiple myeloma

Multiple myeloma classically presents with the CRAB criteria (hyperCalcemia, Renal insufficiency, Anemia, Bone pain) along with a monoclonal spike on SPEP.

Question 124: A 30-year-old presents with crampy abdominal pain, bloody diarrhea, and fever after eating at a barbecue. Stool culture grows Shiga toxin-producing E. coli O157:H7. Which treatment should be avoided?

Electrolyte monitoring
Fluid replacement
Rest
Antibiotics (Correct answer)

Correct answer: Antibiotics

Antibiotics are contraindicated in STEC O157:H7 infection because they may increase Shiga toxin release, raising the risk of hemolytic uremic syndrome (HUS).

Question 125: Which medication class is the preferred initial treatment for heart failure with reduced ejection fraction (HFrEF) to reduce mortality?

Digoxin
Loop diuretics
Beta-blockers and ACE inhibitors (Correct answer)
Calcium channel blockers

Correct answer: Beta-blockers and ACE inhibitors

Beta-blockers (carvedilol, metoprolol succinate, bisoprolol) and ACE inhibitors/ARBs are proven to reduce mortality in HFrEF and are the cornerstone of therapy.

Question 126: What is the goal LDL cholesterol level for a high-risk patient with cardiovascular disease?

<70 mg/dL (Correct answer)
<130 mg/dL
<50 mg/dL
<100 mg/dL

Correct answer: <70 mg/dL

For high-risk patients with established cardiovascular disease, the goal LDL cholesterol level is typically less than 70 mg/dL. Aggressive lowering of LDL cholesterol in this population has been shown to significantly reduce the risk of recurrent cardiovascular events. In some very high-risk cases, even lower targets may be considered.

Question 127: Which of the following is the most common cause of acute pancreatitis in the United States?

Alcohol
Medications
Gallstones (Correct answer)
Hypertriglyceridemia

Correct answer: Gallstones

Gallstones (biliary pancreatitis) account for approximately 40% of acute pancreatitis cases in the US, making it the most common etiology.

Question 128: A 63-year-old man with Stage IV NSCLC (adenocarcinoma) is found to have an EGFR exon 19 deletion on molecular testing. He has good performance status and no brain metastases. Which first-line treatment provides the longest progression-free survival?

Erlotinib 150 mg daily
Carboplatin/pemetrexed plus pembrolizumab
Gefitinib 250 mg daily
Osimertinib 80 mg daily (Correct answer)

Correct answer: Osimertinib 80 mg daily

Osimertinib (3rd generation EGFR TKI) demonstrated superior PFS and OS over 1st generation TKIs in the FLAURA trial and is the preferred first-line agent for EGFR-mutated NSCLC.

Question 129: A 44-year-old woman with HIV (CD4 count 38 cells/µL, not on ART) presents with 3 weeks of progressive dyspnea and nonproductive cough. CXR shows bilateral perihilar infiltrates. BAL silver stain is positive for Pneumocystis jirovecii. She is started on TMP-SMX and prednisone. On day 5, she develops worsening hypoxemia with new unilateral consolidation and pleural effusion. Pleural fluid analysis: pH 7.18, glucose 28 mg/dL, LDH 2,400 U/L, protein 5.1 g/dL, 85% neutrophils. The MOST appropriate next step is:

Increase prednisone dose and reassess in 48 hours
Chest tube drainage and add antibiotics targeting Staphylococcus aureus (Correct answer)
Chest tube drainage and add empiric antifungal therapy
Add empiric vancomycin and piperacillin-tazobactam and repeat BAL

Correct answer: Chest tube drainage and add antibiotics targeting Staphylococcus aureus

This pleural fluid has pH <7.20, glucose <40 mg/dL, and LDH >1,000 U/L — criteria for a complicated parapneumonic effusion or frank empyema requiring chest tube drainage. The clinical context (severely immunocompromised HIV patient on PCP treatment with worsening on day 5) raises concern for a secondary bacterial superinfection. Staphylococcus aureus (including MRSA) is a particularly important pathogen in this context because PCP itself predisposes to pneumatocele formation and subsequent Staph superinfection. Vancomycin (targeting MRSA) plus a beta-lactam broad-spectrum agent is appropriate, but the pleural fluid characteristics mandate drainage first, making option C (drainage + Staph-directed coverage) more precisely correct. Increasing steroids alone would be inappropriate given an infected pleural space. Adding antifungal therapy without drainage does not address the empyema.

Question 130: A 47-year-old previously healthy man is admitted with 4 days of fever, myalgias, and progressive hypoxemia. CXR shows bilateral interstitial infiltrates. BAL reveals: negative bacterial cultures, negative Legionella/Pneumococcal urinary antigens, negative respiratory viral panel (influenza, RSV, parainfluenza, adenovirus), negative PCP DFA. CD4 count is 620 cells/µL. Serum β-D-glucan is 478 pg/mL (normal <60). BAL galactomannan index is 0.6 (normal <0.5). He has no known immunosuppression. The most likely diagnosis is:

Pneumocystis jirovecii pneumonia with false-negative DFA
Disseminated histoplasmosis
Cryptogenic organizing pneumonia
Invasive pulmonary aspergillosis (Correct answer)

Correct answer: Invasive pulmonary aspergillosis

Invasive pulmonary aspergillosis (IPA) best explains this presentation. While classic IPA occurs in neutropenic hosts, it is well-recognized in non-classically immunocompromised patients, including those with viral pneumonias, ICU patients, and those with occult immune defects. The BAL galactomannan index ≥0.5 is highly specific for IPA in BAL (sensitivity ~70%, specificity ~90%). The elevated β-D-glucan (>80 pg/mL is significant; 478 is markedly elevated) further supports a fungal etiology. PCP DFA false negatives occur but would be unusual with a β-D-glucan this markedly elevated without PCP; moreover, the CD4 count of 620 makes PCP unlikely. Histoplasmosis would typically require urine/serum Histoplasma antigen and does not elevate galactomannan. COP is non-infectious and would not elevate these fungal biomarkers.

Question 131: A 58-year-old man on hemodialysis for 8 years presents with bone pain and a serum calcium of 11.2 mg/dL, phosphorus of 5.8 mg/dL, and intact PTH of 850 pg/mL. What is this condition called and what surgical intervention may be needed?

Tertiary hyperparathyroidism; parathyroidectomy if refractory to cinacalcet (Correct answer)
Primary hyperparathyroidism; single-gland parathyroidectomy
Secondary hyperparathyroidism; parathyroidectomy if refractory to cinacalcet
Adynamic bone disease; bisphosphonate therapy

Correct answer: Tertiary hyperparathyroidism; parathyroidectomy if refractory to cinacalcet

Tertiary hyperparathyroidism occurs in long-term dialysis patients when autonomous PTH hypersecretion persists and may require parathyroidectomy if calcimimetics fail.

Question 132: A 48-year-old woman with obesity (BMI 38) presents with daytime somnolence, morning headaches, and an AHI of 42 events/hour with SpO2 nadir of 78% on polysomnography. What is the MOST appropriate first-line treatment?

Uvulopalatopharyngoplasty (UPPP)
Continuous positive airway pressure (CPAP) (Correct answer)
Bilevel positive airway pressure (BiPAP)
Supplemental oxygen via nasal cannula at night

Correct answer: Continuous positive airway pressure (CPAP)

CPAP is the first-line treatment for moderate-to-severe obstructive sleep apnea, effectively eliminating apneic events and improving symptoms.

Question 133: A patient with cirrhosis develops spontaneous bacterial peritonitis (SBP). After treatment, which prophylactic antibiotic is recommended to prevent recurrence?

Cephalexin
Amoxicillin-clavulanate
Metronidazole
Norfloxacin (Correct answer)

Correct answer: Norfloxacin

Norfloxacin (or trimethoprim-sulfamethoxazole as an alternative) is recommended for long-term secondary prophylaxis after a first episode of SBP to reduce recurrence risk.

Question 134: Which anticoagulation regimen is recommended for a patient with a bileaflet mechanical aortic valve prosthesis with no additional risk factors?

Warfarin with INR target 2.0-3.0 (Correct answer)
Dabigatran 150 mg twice daily
Warfarin with INR target 2.5-3.5
Aspirin 325 mg daily alone

Correct answer: Warfarin with INR target 2.0-3.0

For a bileaflet mechanical AVR with no additional thromboembolic risk factors, warfarin with INR target 2.0-3.0 is recommended; higher targets are needed for additional risk factors.

Question 135: A 29-year-old man presents with polyuria (6 L/day), polydipsia, and a serum sodium of 148 mEq/L. A water deprivation test is performed: after 8 hours of water deprivation, urine osmolality plateaus at 195 mOsm/kg. After desmopressin (DDAVP) administration, urine osmolality rises to 620 mOsm/kg. Which diagnosis best explains these findings?

Partial nephrogenic diabetes insipidus
Central diabetes insipidus (Correct answer)
Nephrogenic diabetes insipidus
Primary polydipsia (psychogenic)

Correct answer: Central diabetes insipidus

The water deprivation test shows failure to concentrate urine adequately (plateau of 195 mOsm/kg, well below the normal >600–800 mOsm/kg), confirming diabetes insipidus. The robust response to exogenous DDAVP (rise from 195 to 620 mOsm/kg, representing >50% increase) indicates that the kidneys are capable of responding to ADH — distinguishing central from nephrogenic DI. In nephrogenic DI, the kidneys fail to respond to DDAVP. In primary polydipsia, baseline urine osmolality during deprivation typically rises above 300–400 mOsm/kg (though may be blunted by chronic medullary washout). This pattern is diagnostic of complete central DI.

Question 136: Which of the following is an established indication for intervention in a patient with asymptomatic severe primary mitral regurgitation?

Age greater than 75 years.
Pulmonary artery systolic pressure (PASP) at rest of 55 mmHg. (Correct answer)
Left ventricular end-systolic dimension (LVESD) of 38 mm.
Left ventricular ejection fraction (LVEF) of 65%.

Correct answer: Pulmonary artery systolic pressure (PASP) at rest of 55 mmHg.

For asymptomatic patients with severe primary mitral regurgitation and preserved LV function (LVEF >60% and LVESD <40 mm), surgery is indicated if new-onset atrial fibrillation or pulmonary hypertension (pulmonary artery systolic pressure >50 mmHg at rest) develops. An LVEF of 65% and LVESD of 38 mm are within the normal range and would not trigger intervention on their own. Advanced age is a factor in risk assessment but not a primary indication for surgery.

Question 137: A 50-year-old immunocompromised patient presents with fever, pleuritic chest pain, and a pulmonary nodule with halo sign on CT. Galactomannan antigen returns elevated. What is the most appropriate initial antifungal?

Micafungin 150mg IV daily
Voriconazole 6mg/kg IV q12h x 2 doses, then 4mg/kg q12h (Correct answer)
Fluconazole 400mg IV daily
Liposomal amphotericin B 3mg/kg/day

Correct answer: Voriconazole 6mg/kg IV q12h x 2 doses, then 4mg/kg q12h

Voriconazole is the preferred first-line treatment for invasive pulmonary aspergillosis based on superior efficacy demonstrated in landmark clinical trials.

Question 138: A mechanically ventilated patient with ARDS (P/F ratio 88) on volume-control ventilation develops sudden worsening hypoxemia and decreased lung compliance. Trachea is midline, breath sounds are equal bilaterally, and the chest X-ray shows new bilateral opacities that were not present 6 hours ago. Plateau pressure has increased from 28 to 36 cmH2O. Which of the following is the most likely cause?

Auto-PEEP with dynamic hyperinflation
Right mainstem intubation
Ventilator-associated pneumonia
Worsening ARDS with disease progression (Correct answer)

Correct answer: Worsening ARDS with disease progression

The scenario describes sudden deterioration with new bilateral opacities, increased plateau pressure, and preserved symmetric breath sounds — this constellation is most consistent with worsening ARDS (disease progression). Right mainstem intubation would cause unilateral changes (decreased breath sounds on left, unilateral opacity) and tracheal deviation. Auto-PEEP causes increased peak pressures but plateau pressure elevation suggests decreased compliance, and dynamic hyperinflation would be associated with obstructive physiology and would not produce new bilateral opacities. VAP typically develops over 48+ hours with gradual changes and fever/leukocytosis, not acute bilateral deterioration within 6 hours without systemic signs, making it less likely to be the acute precipitant here.

Question 139: A 30-year-old woman presents with dysuria and urinary frequency. Urine culture grows >100,000 CFU/mL of E. coli sensitive to all agents. She is 10 weeks pregnant. What is the appropriate antibiotic?

Nitrofurantoin 100mg BID x 5 days (Correct answer)
Trimethoprim-sulfamethoxazole DS BID x 7 days
Doxycycline 100mg BID x 7 days
Ciprofloxacin 500mg BID x 3 days

Correct answer: Nitrofurantoin 100mg BID x 5 days

Nitrofurantoin is safe in the second trimester and is first-line for uncomplicated UTI in pregnancy; TMP-SMX and fluoroquinolones are avoided due to fetal risks.

Question 140: Which finding on ECG is most consistent with hyperkalemia in a patient with chronic kidney disease?

ST segment depression
Prolonged QT interval
Tall peaked T waves (Correct answer)
Prominent U waves

Correct answer: Tall peaked T waves

Hyperkalemia classically produces tall, narrow, peaked T waves as one of the earliest ECG manifestations.

Question 141: A 35-year-old man with a dog bite to his hand 8 hours ago presents for evaluation. He is up to date on tetanus and the wound has been thoroughly irrigated. What organism most commonly causes infection in dog bites?

Staphylococcus aureus
Pasteurella multocida (Correct answer)
Capnocytophaga canimorsus
Eikenella corrodens

Correct answer: Pasteurella multocida

Pasteurella multocida is the most common pathogen isolated from dog and cat bite wounds, typically causing rapid-onset cellulitis within 24 hours.

Question 142: A 58-year-old man with IPF is admitted with acute respiratory failure requiring mechanical ventilation after a 2-week history of worsening dyspnea without identifiable trigger. BAL shows no infection. Despite lung-protective ventilation, he deteriorates. Which of the following has demonstrated a mortality benefit in acute exacerbation of IPF?

Veno-venous ECMO as a bridge to lung transplantation (Correct answer)
Cyclosporine A added to corticosteroids
Rituximab plus plasma exchange
High-dose methylprednisolone 1g IV daily for 3 days

Correct answer: Veno-venous ECMO as a bridge to lung transplantation

Acute exacerbations of IPF carry an extremely poor prognosis with in-hospital mortality exceeding 50-80%. No pharmacological intervention (steroids, rituximab, cyclosporine) has shown consistent mortality benefit in randomized trials. VV-ECMO as a bridge to lung transplantation is the only strategy with evidence of survival benefit in carefully selected patients who are transplant-eligible. High-dose steroids are commonly used but lack RCT evidence of benefit and carry significant harm risk.

Question 143: A 40-year-old woman presents with two episodes of unilateral optic neuritis over 2 years plus a history of transient bilateral leg weakness that resolved completely. MRI of the brain and spine shows periventricular white matter lesions disseminated in space and time. CSF shows oligoclonal bands. What is the most likely diagnosis?

Acute disseminated encephalomyelitis (ADEM)
CNS vasculitis
Neuromyelitis optica spectrum disorder (NMOSD)
Relapsing-remitting multiple sclerosis (RRMS) (Correct answer)

Correct answer: Relapsing-remitting multiple sclerosis (RRMS)

The presentation of relapsing neurological episodes with lesions disseminated in space and time, periventricular MRI lesions, and CSF oligoclonal bands satisfies McDonald criteria for RRMS. NMOSD typically involves longitudinally extensive spinal cord lesions and AQP4-IgG positivity. CNS vasculitis and ADEM are typically monophasic or have distinct features.

Question 144: A 70-year-old man with osteoporosis has a T-score of −3.1 at the hip. He has been on alendronate for 7 years. He now reports right thigh pain and X-ray shows cortical thickening of the subtrochanteric femur. What is the best next step?

Switch to denosumab
Continue alendronate and add calcium/vitamin D
Refer for prophylactic hip nailing
Discontinue bisphosphonate and consider teriparatide (Correct answer)

Correct answer: Discontinue bisphosphonate and consider teriparatide

Atypical femoral fractures are a recognized complication of prolonged bisphosphonate use; the drug should be discontinued and anabolic therapy with teriparatide may promote healing.

Question 145: A 57-year-old woman undergoes upper endoscopy for dysphagia. Biopsies from the mid-esophagus show ≥15 eosinophils per high-power field, with no response to an 8-week course of twice-daily proton pump inhibitor therapy. She has no peripheral eosinophilia. Which statement about her subsequent management is most accurate?

Endoscopic dilation should be avoided due to high risk of esophageal perforation exceeding 10%
Topical swallowed fluticasone or budesonide is first-line pharmacologic therapy after PPI failure (Correct answer)
Systemic prednisone is required because topical steroids do not penetrate the esophageal mucosa adequately
Elimination diet (six-food elimination) is contraindicated in adults with confirmed eosinophilic esophagitis

Correct answer: Topical swallowed fluticasone or budesonide is first-line pharmacologic therapy after PPI failure

After failure of PPI therapy (which itself can treat PPI-responsive esophageal eosinophilia and is required to confirm the EoE diagnosis), topical swallowed corticosteroids — fluticasone propionate (swallowed from an MDI) or budesonide oral suspension — are first-line pharmacologic treatment for eosinophilic esophagitis (EoE). Systemic steroids are not routinely used due to side effects. Six-food elimination diet (milk, wheat, egg, soy, nuts, seafood) is a validated non-pharmacologic option in adults. Endoscopic dilation is safe and effective for fibrostenotic EoE; perforation risk is low (<1%), not >10%.

Question 146: A 45-year-old returning traveler from sub-Saharan Africa presents with fever, myalgia, and headache 5 days after return. Blood smear shows 14% parasitemia with P. falciparum. He is alert but tachycardic and his creatinine is 2.1 mg/dL (baseline 0.9). IV artesunate is initiated. Forty-eight hours later, parasitemia has fallen to 0.3%, he is afebrile and clinically improved. Which complication should be MOST carefully monitored for over the next 2–6 weeks?

Artemisinin partial resistance emergence and treatment failure
Post-artesunate delayed hemolysis (PADH) (Correct answer)
Artesunate-induced QTc prolongation and arrhythmia
Immune reconstitution inflammatory syndrome (IRIS)

Correct answer: Post-artesunate delayed hemolysis (PADH)

Post-artesunate delayed hemolysis (PADH) is an increasingly recognized complication occurring 1–6 weeks after IV artesunate treatment, particularly in patients with initial high parasitemia (>5%). The mechanism involves clearance of pRBCs followed by delayed destruction of the 'once-infected' RBCs that were transiently spared. Patients may develop significant anemia requiring transfusion despite apparent clinical cure. QTc prolongation (choice B) is associated with quinine/quinidine, not artesunate. IRIS (choice C) does not apply here. Artemisinin resistance (choice D) is a concern in Southeast Asia, not the primary monitoring concern in the immediate post-treatment period.

Question 147: A 55-year-old woman with class II obesity presents for cardiovascular risk assessment. Her 10-year ASCVD risk is 8%. LDL is 125 mg/dL. What is the most appropriate initial intervention?

Refer to cardiology before any therapy
Start fibrate therapy for triglycerides
Start high-intensity statin immediately
Lifestyle modification with shared decision-making about statin therapy (Correct answer)

Correct answer: Lifestyle modification with shared decision-making about statin therapy

A 10-year ASCVD risk of 7.5–10% is considered borderline; guidelines recommend shared decision-making about statin initiation after lifestyle modification counseling.

Question 148: A 60-year-old man is diagnosed with diffuse large B-cell lymphoma (DLBCL), Ann Arbor stage II, IPI score 2. What is the standard first-line chemotherapy regimen?

R-CHOP (Correct answer)
CHOP alone
Bendamustine-rituximab
R-CVP

Correct answer: R-CHOP

R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) is the standard first-line treatment for DLBCL regardless of stage.

Question 149: A 55-year-old man who recently started allopurinol presents with widespread erythema, skin sloughing affecting >30% of body surface area, mucosal involvement, and fever. Skin biopsy shows full-thickness epidermal necrosis. What is this condition?

Pemphigus vulgaris
Toxic epidermal necrolysis (TEN) (Correct answer)
Stevens-Johnson syndrome (SJS)
Staphylococcal scalded skin syndrome (SSSS)

Correct answer: Toxic epidermal necrolysis (TEN)

TEN is defined by epidermal detachment affecting >30% BSA with full-thickness epidermal necrosis on biopsy, commonly drug-induced (allopurinol, sulfonamides, anticonvulsants). SJS involves <10% BSA detachment. SSSS affects mainly children and involves superficial epidermal cleavage from staph exotoxin. Pemphigus vulgaris presents with flaccid blisters from autoantibodies, not drug-induced.

Question 150: A 34-year-old woman with SLE on hydroxychloroquine and low-dose prednisone develops fever, rigors, and altered mental status 10 days after a camping trip in Missouri. Blood smear shows intraerythrocytic ring forms with occasional multiple rings per cell and 'Maltese cross' (tetrad) forms. Parasitemia is 6%. Which of the following is the MOST appropriate treatment?

Quinine plus doxycycline for 7 days
Chloroquine 1g followed by 500 mg at 6, 24, and 48 hours
Atovaquone plus azithromycin for 7–10 days (Correct answer)
Atovaquone-proguanil for 3 days

Correct answer: Atovaquone plus azithromycin for 7–10 days

Maltese cross (tetrad) forms are pathognomonic for Babesia microti, not Plasmodium. This patient has babesiosis, which is endemic in the upper Midwest and Northeast. The treatment of choice is atovaquone plus azithromycin for 7–10 days (or up to 6 weeks in severe/immunocompromised cases). Exchange transfusion should be considered when parasitemia exceeds 10%, in cases of severe hemolysis, or end-organ compromise. Chloroquine (choice C) treats only chloroquine-sensitive Plasmodium. Quinine plus doxycycline (choice B) is an alternative for babesiosis but is second-line due to toxicity. Atovaquone-proguanil (choice D) is for malaria prophylaxis/treatment, not babesiosis.

Question 151: Which echocardiographic parameter is most useful for determining surgical timing in asymptomatic chronic severe mitral regurgitation?

Left atrial size
Left ventricular end-diastolic diameter
Left ventricular end-systolic diameter (LVESD) (Correct answer)
Pulmonary artery systolic pressure alone

Correct answer: Left ventricular end-systolic diameter (LVESD)

LVESD ≥40-45 mm in severe chronic MR is the key echocardiographic threshold that prompts surgical intervention even in asymptomatic patients.

Question 152: A 72-year-old woman with a history of breast cancer treated 8 years ago presents with back pain and a serum protein electrophoresis showing an M-spike of 1.1 g/dL (IgG kappa). Bone marrow biopsy shows 7% plasma cells. Serum free light chain ratio is 2.4 (normal). She has no lytic lesions, anemia, hypercalcemia, or renal insufficiency. What is the correct diagnosis and initial management?

MGUS; reassure and monitor annually
Multiple myeloma; initiate VRd (bortezomib, lenalidomide, dexamethasone)
Smoldering multiple myeloma; initiate lenalidomide to prevent progression
Smoldering multiple myeloma; observation with monitoring every 3–6 months (Correct answer)

Correct answer: Smoldering multiple myeloma; observation with monitoring every 3–6 months

This patient meets criteria for smoldering multiple myeloma (SMM): M-spike ≥1 g/dL (IgG), bone marrow plasma cells 10–59% or M-spike meeting threshold, but ABSENCE of CRAB criteria (hyperCalcemia, Renal insufficiency, Anemia, Bone lesions) or SLiM criteria. Note: 7% plasma cells technically falls below the 10% SMM threshold, making this a borderline case; however, the M-spike of 1.1 g/dL IgG satisfies SMM M-protein criterion per IMWG 2014. Standard care is observation. Lenalidomide was studied in QUIREDEX trial for high-risk SMM only, and is not standard of care. MGUS requires M-spike <3 g/dL AND <10% plasma cells AND no end-organ damage — the M-spike threshold alone can differentiate.

Question 153: A 45-year-old asymptomatic man is found to have severe aortic regurgitation on routine echocardiography. LVEF is 58%, LV end-systolic dimension is 48 mm, and LV end-diastolic dimension is 72 mm. He exercises regularly without symptoms. What is the most appropriate next step?

Exercise stress testing to unmask symptoms before deciding on surgery
Aortic valve replacement now based on LV end-diastolic dimension
Serial echocardiography every 6–12 months with continued observation
Aortic valve replacement based on LV end-systolic dimension threshold (Correct answer)

Correct answer: Aortic valve replacement based on LV end-systolic dimension threshold

According to ACC/AHA guidelines, aortic valve replacement is indicated in asymptomatic severe AR when LVEF falls below 55% OR when LV end-systolic dimension (LVESD) exceeds 50 mm (Class I). This patient's LVESD is 48 mm — just below the threshold — and LVEF is 58%. However, a LVESD of 50 mm is the cutoff; at 48 mm, surgery is not yet mandated. Importantly, LVESD ≥50 mm is the key threshold, not LVEDD. The LVEDD of 72 mm alone is not a Class I surgical indication (threshold would be >65 mm as a lower-evidence indicator). Close follow-up every 6–12 months is appropriate here.

Question 154: A patient with Burkitt lymphoma develops oliguria, creatinine rising to 3.1 mg/dL, potassium of 6.8 mEq/L, phosphorus of 8.2 mg/dL, calcium of 7.1 mg/dL, and uric acid of 14 mg/dL 24 hours after starting chemotherapy. What is the most likely complication?

Cisplatin-induced nephrotoxicity
Septic acute tubular necrosis
Contrast-induced nephropathy
Tumor lysis syndrome (Correct answer)

Correct answer: Tumor lysis syndrome

Tumor lysis syndrome occurs when massive tumor cell death releases intracellular contents, causing hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia with acute kidney injury.

Question 155: A 72-year-old woman has a 2.4 cm solid pulmonary nodule discovered incidentally on CT. She has a 40 pack-year smoking history and stopped 5 years ago. PET scan shows SUV of 4.8 in the nodule. CT-guided biopsy shows adenocarcinoma. Staging workup reveals no metastatic disease. What is the preferred management for Stage IA NSCLC in a patient with FEV1 70% predicted?

Concurrent chemoradiation
Surgical resection with anatomic lobectomy (Correct answer)
Wedge resection due to borderline lung function
Stereotactic body radiation therapy (SBRT)

Correct answer: Surgical resection with anatomic lobectomy

Anatomic lobectomy is the standard of care for resectable Stage I NSCLC in operable patients; FEV1 70% predicted is sufficient for lobectomy, making surgery preferable to SBRT.

Question 156: A patient with long-standing Crohn's disease develops right lower quadrant pain and fever. CT shows a 4 cm fluid collection adjacent to the terminal ileum. What is the best next step?

Colonoscopy
Emergent surgery
IV antibiotics alone
Percutaneous drainage plus antibiotics (Correct answer)

Correct answer: Percutaneous drainage plus antibiotics

A walled-off abscess in Crohn's disease is best managed with percutaneous drainage plus antibiotics, avoiding emergent surgery and allowing inflammation to subside before elective resection if needed.

Question 157: A 67-year-old man with type 2 diabetes and CKD (eGFR 28 mL/min/1.73m²) undergoes elective knee arthroplasty. On post-operative day 5, he develops fever to 38.9°C and knee pain. Arthrocentesis yields 85,000 WBCs/µL (95% PMNs), glucose 20 mg/dL (serum 110 mg/dL), and cultures grow oxacillin-susceptible Staphylococcus aureus. TEE is negative for endocarditis. What is the MINIMUM recommended duration of IV antibiotic therapy before considering oral step-down?

4–6 weeks of IV therapy without oral step-down option for prosthetic joint infections (Correct answer)
2 weeks IV followed by chronic oral suppressive therapy
6 weeks regardless of clinical response
2 weeks, with oral step-down permissible after clinical improvement and bacteremia clearance

Correct answer: 4–6 weeks of IV therapy without oral step-down option for prosthetic joint infections

Prosthetic joint infections (PJI) due to Staphylococcus aureus require prolonged IV antibiotic therapy. Per IDSA guidelines for PJI managed with debridement and implant retention (DAIR), the recommended regimen is 2–6 weeks of IV therapy followed by oral rifampin-based combination therapy (e.g., rifampin plus a fluoroquinolone) for 3–6 months. However, for retained hardware with S. aureus PJI, oral step-down to rifampin + ciprofloxacin after initial IV therapy is guideline-supported. The critical distinction here is that the question asks about minimum IV duration before step-down — which is 2 weeks IV (not 4–6 weeks of exclusive IV). Option B is a common misconception. IDSA supports oral rifampin-based step-down after initial IV induction.

Question 158: A 38-year-old woman with Graves' disease has been on methimazole 10 mg daily for 18 months. Her free T4 and TSH are now normal. She is eager to pursue definitive therapy. She is 10 weeks pregnant. Her TRAb titer is 4.2 IU/L (reference < 1.75). Which statement best guides clinical decision-making regarding fetal and neonatal thyroid risk?

Elevated maternal TRAb at > 3× upper limit of normal in the third trimester predicts fetal/neonatal hyperthyroidism and warrants fetal surveillance with Doppler thyroid vascularity and fetal heart rate monitoring (Correct answer)
Methimazole should be switched to propylthiouracil for the remainder of the pregnancy to eliminate teratogenic risk
Neonatal Graves' disease risk is determined by maternal free T4 level at delivery, not by TRAb titer
TRAb does not cross the placenta in the first trimester, so current titer has no fetal implications until after 20 weeks

Correct answer: Elevated maternal TRAb at > 3× upper limit of normal in the third trimester predicts fetal/neonatal hyperthyroidism and warrants fetal surveillance with Doppler thyroid vascularity and fetal heart rate monitoring

TRAb (TSH receptor antibodies) are IgG immunoglobulins that cross the placenta from the first trimester onward and can stimulate the fetal thyroid (which becomes responsive to TSH at ~20 weeks). Maternal TRAb > 3× ULN (here 4.2 vs ULN 1.75, ratio ~2.4 — borderline) in the second and especially third trimester identifies fetuses at risk for fetal and neonatal hyperthyroidism. Guidelines (ATA, ETA) recommend fetal surveillance (Doppler thyroid vascularity, fetal heart rate, growth) in women with elevated TRAb. TRAb does cross the placenta from the first trimester. Neonatal Graves' disease risk is primarily predicted by TRAb titer, not free T4. Regarding drug choice: PTU is preferred in the FIRST trimester (lower teratogenic risk), and methimazole is generally acceptable after 16 weeks — the instruction to switch PTU for the remainder of pregnancy is incorrect; PTU has its own risk profile (hepatotoxicity) and the switch timing guidance is the reverse of current recommendations.

Question 159: A 66-year-old male with a history of COPD presents to the emergency department with increased dyspnea, cough, and sputum production. He has a history of two exacerbations in the past year. His blood eosinophil count is 350 cells/µL. According to the 2024 GOLD report, which of the following is the most appropriate initial pharmacologic management for this patient's chronic condition?

A combination of a long-acting beta-agonist (LABA) and a long-acting muscarinic antagonist (LAMA)
A combination of an inhaled corticosteroid (ICS), a long-acting beta-agonist (LABA), and a long-acting muscarinic antagonist (LAMA) (Correct answer)
A short-acting beta-agonist (SABA) as needed with no maintenance therapy
A long-acting muscarinic antagonist (LAMA) monotherapy

Correct answer: A combination of an inhaled corticosteroid (ICS), a long-acting beta-agonist (LABA), and a long-acting muscarinic antagonist (LAMA)

According to the 2024 GOLD guidelines, for a patient with a history of frequent exacerbations (≥2 in the past year) and a blood eosinophil count ≥300 cells/µL, initial therapy with a triple combination of ICS/LABA/LAMA is recommended. This approach targets bronchoconstriction with the dual bronchodilators (LABA/LAMA) and airway inflammation with the ICS, which is particularly beneficial in patients with eosinophilic features.

Question 160: A 38-year-old woman is found to have a 2.8 cm hepatic adenoma on imaging done for right upper quadrant pain. She takes oral contraceptive pills (OCPs). Biopsy demonstrates β-catenin mutation subtype. She desires future pregnancy. What is the most appropriate management?

Discontinue OCPs and repeat MRI in 6 months; proceed to resection regardless of size change
Immediate surgical resection given β-catenin mutation subtype (Correct answer)
Arterial embolization followed by MRI surveillance
Discontinue OCPs and repeat MRI in 6 months; resect only if adenoma grows >5 cm

Correct answer: Immediate surgical resection given β-catenin mutation subtype

Hepatocellular adenomas with β-catenin activation mutations carry a significantly elevated risk of malignant transformation to hepatocellular carcinoma (estimated 10–fold higher than other subtypes). Current guidelines recommend resection for β-catenin–mutated adenomas regardless of size because of this malignant potential, particularly in a patient who desires future pregnancy (which increases rupture and growth risk). The standard size threshold of 5 cm applies to non-β-catenin subtypes. Embolization is reserved for hemorrhagic or symptomatic adenomas not amenable to resection.

Question 161: A 38-year-old woman presents with hypertension, hypokalemia, and metabolic alkalosis. Plasma aldosterone-to-renin ratio is markedly elevated. CT abdomen shows a 1.8 cm right adrenal adenoma. What is the definitive treatment?

Fludrocortisone suppression test and observation
Bilateral adrenalectomy
Lifelong spironolactone therapy
Laparoscopic right adrenalectomy (Correct answer)

Correct answer: Laparoscopic right adrenalectomy

A unilateral aldosterone-producing adenoma confirmed by adrenal vein sampling is best treated with laparoscopic unilateral adrenalectomy, which is curative in most cases.

Question 162: A mechanically ventilated patient with ARDS has refractory hypoxemia (P/F ratio 65) despite optimized ventilator settings and prone positioning for 18 hours. Which rescue therapy should be considered next?

Partial liquid ventilation with perfluorocarbon
Venovenous extracorporeal membrane oxygenation (VV-ECMO) (Correct answer)
High-frequency oscillatory ventilation (HFOV)
Inhaled nitric oxide

Correct answer: Venovenous extracorporeal membrane oxygenation (VV-ECMO)

VV-ECMO is the rescue therapy for severe refractory ARDS when conventional strategies including prone positioning have failed, as supported by the CESAR and EOLIA trials.

Question 163: A 45-year-old man presents with acute oliguric kidney injury, hemoptysis, and pANCA positivity. Kidney biopsy shows pauci-immune crescentic glomerulonephritis. What is the most appropriate induction therapy?

Rituximab alone
High-dose glucocorticoids plus cyclophosphamide or rituximab (Correct answer)
Mycophenolate mofetil plus prednisone
Plasmapheresis alone

Correct answer: High-dose glucocorticoids plus cyclophosphamide or rituximab

ANCA-associated vasculitis with rapidly progressive GN requires induction with high-dose glucocorticoids combined with either cyclophosphamide or rituximab.

Question 164: A 29-year-old woman with Crohn's disease on azathioprine and adalimumab presents with 3 weeks of right upper quadrant pain. Labs show ALT 340 U/L, AST 290 U/L, ALP 188 U/L, total bilirubin 2.1 mg/dL. She is ANA positive (1:160), anti-smooth muscle antibody negative, serum IgG 2,100 mg/dL (ULN 1,700). Liver biopsy shows interface hepatitis with lymphoplasmacytic infiltrate, rosette formation, and emperipolesis. Which statement about her diagnosis and management is most accurate?

Azathioprine is the most likely causative agent and should be stopped; liver biopsy alone cannot distinguish drug-induced liver injury from AIH
Her histology confirms AIH type 1; azathioprine can serve dual purpose as immunosuppression for both IBD and AIH after steroid induction
This is de novo autoimmune hepatitis (AIH) associated with TNF-α inhibitor therapy; steroids should be initiated and adalimumab discontinued (Correct answer)
This represents adalimumab-induced drug hepatotoxicity and the biologic should be stopped immediately

Correct answer: This is de novo autoimmune hepatitis (AIH) associated with TNF-α inhibitor therapy; steroids should be initiated and adalimumab discontinued

De novo autoimmune hepatitis (AIH) is a well-documented immune-mediated adverse effect of TNF-α inhibitors (adalimumab, infliximab, etanercept). It presents with AIH histology (interface hepatitis, rosettes, emperipolesis), positive ANA, elevated IgG, and often ASMA negative — mimicking classic AIH type 1. Management requires discontinuation of the offending TNF inhibitor AND initiation of corticosteroids (prednisone ± azathioprine). Simply stopping the drug without immunosuppression often leads to incomplete resolution. Azathioprine can cause hepatotoxicity (nodular regenerative hyperplasia, peliosis hepatis) but not this histologic pattern. While azathioprine can treat AIH, the TNF inhibitor must be stopped given its likely causative role, and an alternative biologic for IBD (e.g., vedolizumab or ustekinumab) should be considered.

Question 165: A 52-year-old man with hepatitis C-related cirrhosis has a 2.5 cm liver lesion showing arterial enhancement and washout on multiphasic MRI. What is the most appropriate next step?

Proceed with treatment per LI-RADS 5 criteria (Correct answer)
Repeat MRI in 3 months
Liver biopsy
Alpha-fetoprotein measurement only

Correct answer: Proceed with treatment per LI-RADS 5 criteria

A LI-RADS 5 lesion (arterial hyperenhancement with washout and capsule in a cirrhotic patient) is diagnostic for hepatocellular carcinoma; biopsy is not required before treatment planning.

Question 166: A 67-year-old man on warfarin (INR 2.4) for atrial fibrillation develops a massive pulmonary embolism with hemodynamic instability. He had a hemorrhagic stroke 8 weeks ago. Which management strategy is most appropriate?

Anticoagulation dose escalation with unfractionated heparin and vasopressors
Catheter-directed therapy (mechanical thrombectomy or pharmacomechanical CDT) (Correct answer)
Surgical embolectomy via sternotomy
Systemic thrombolysis with alteplase 100 mg IV over 2 hours after reversing INR

Correct answer: Catheter-directed therapy (mechanical thrombectomy or pharmacomechanical CDT)

Systemic thrombolysis is an absolute contraindication within 3 months of hemorrhagic stroke. Anticoagulation alone with UFH is insufficient for a massive PE with hemodynamic instability. Surgical embolectomy is appropriate but requires cardiothoracic surgery availability and carries high operative risk. Catheter-directed therapy (CDT) — including aspiration thrombectomy — offers a middle ground: it achieves rapid thrombus debulking with much lower thrombolytic drug doses (or no thrombolytics at all in mechanical CDT), making it the preferred advanced reperfusion strategy when systemic thrombolysis is contraindicated.

Question 167: A 28-year-old woman is referred for evaluation of amenorrhea and galactorrhea. Serum prolactin is 340 ng/mL. MRI shows a 9 mm pituitary lesion. She desires pregnancy in the next year. She is started on cabergoline 0.5 mg twice weekly. After 6 months, prolactin normalizes and the lesion shrinks to 4 mm. She now asks about stopping cabergoline prior to conception. What is the most appropriate recommendation?

Switch to bromocriptine before conception since it has a longer safety record in pregnancy
Continue cabergoline throughout pregnancy to prevent tumor regrowth
Stop cabergoline once pregnancy is confirmed, as tumor enlargement risk is low with microadenoma (Correct answer)
Obtain visual field testing monthly during pregnancy regardless of lesion size

Correct answer: Stop cabergoline once pregnancy is confirmed, as tumor enlargement risk is low with microadenoma

For prolactinoma microadenomas (<10 mm), the risk of clinically significant tumor enlargement during pregnancy is very low (~2-3%). The standard approach is to discontinue dopamine agonist therapy once pregnancy is confirmed, as cabergoline's safety data in first-trimester exposure is reassuring but not as extensive as bromocriptine. Importantly, cabergoline should be stopped — not continued — during pregnancy in microadenoma patients. Monthly visual fields are unnecessary for microadenomas; surveillance is reserved for macroadenomas. Switching to bromocriptine before conception is a valid historical approach but is not mandatory — cabergoline is acceptable and has sufficient safety data in early pregnancy.

Question 168: A 61-year-old man with a history of neck irradiation for Hodgkin lymphoma 25 years ago is found to have a 2.2 cm thyroid nodule on incidental imaging. Fine-needle aspiration returns Bethesda Category III (atypia of undetermined significance). Repeat FNA after 3 months again returns Bethesda III. Molecular testing shows a TERT promoter mutation without RAS or BRAF mutations. What is the most appropriate next step?

Radioactive iodine ablation
Active surveillance with repeat ultrasound in 12 months
Surgical resection (Correct answer)
Repeat FNA a third time in 6 months

Correct answer: Surgical resection

TERT promoter mutations are associated with aggressive thyroid malignancy, dedifferentiation, and increased risk of recurrence and mortality — even when found in isolation. In the context of a persistently Bethesda III nodule with TERT promoter mutation, plus a history of prior therapeutic neck irradiation (a major risk factor for thyroid malignancy), surgical resection is the appropriate next step. Current ATA guidelines support surgery for Bethesda III nodules with high-risk molecular markers. Active surveillance or repeat FNA would be inappropriate given the combined risk profile. RAI is not used for initial management of indeterminate nodules.

Question 169: A 63-year-old woman with known coronary artery disease presents with an acute inferior STEMI. Primary PCI is performed successfully to the right coronary artery. Post-procedure, she develops hypotension (BP 78/50) with clear lung fields, elevated JVP, and a new pansystolic murmur loudest at the left lower sternal border. ECG shows sinus bradycardia. What is the most likely diagnosis?

Ventricular septal rupture (Correct answer)
Acute mitral regurgitation due to papillary muscle rupture
Cardiac tamponade from free wall rupture
Right ventricular infarction with tricuspid regurgitation

Correct answer: Ventricular septal rupture

Post-MI ventricular septal rupture (VSR) classically presents 3–5 days after MI (though can be earlier) with sudden hemodynamic deterioration and a new harsh pansystolic murmur at the left lower sternal border, reflecting left-to-right shunting. Inferior MI commonly causes posterior VSR. Right ventricular infarction causes hypotension with clear lungs and elevated JVP but does not produce a new pansystolic murmur. Acute MR from papillary muscle rupture produces a murmur, but it is often apical/radiating to the axilla. Cardiac tamponade causes muffled heart sounds and pulsus paradoxus, not a new murmur.

Question 170: A 45-year-old man with recurrent sinopulmonary infections since age 25 is found to have serum IgG of 280 mg/dL (normal 700–1600), IgA of 15 mg/dL, and IgM of 40 mg/dL. He has normal T cell counts but markedly reduced B cell numbers. What is the most appropriate long-term management?

Bone marrow transplantation
Prophylactic trimethoprim-sulfamethoxazole
Subcutaneous interferon-gamma injections
Intravenous immunoglobulin (IVIG) replacement therapy (Correct answer)

Correct answer: Intravenous immunoglobulin (IVIG) replacement therapy

Common variable immunodeficiency (CVID) is characterized by low IgG, IgA, and IgM with normal T cells and recurrent bacterial infections in adults. The mainstay of treatment is IVIG (or SCIG) replacement to prevent infections. TMP-SMX prophylaxis is used for PCP in T cell deficiencies, not antibody deficiencies. BMT is reserved for SCID. Interferon-gamma is used for chronic granulomatous disease.

Question 171: A 58-year-old woman on long-term lithium therapy presents with fatigue and a calcium of 10.8 mg/dL. PTH is 72 pg/mL (high-normal). What is the most likely mechanism of her hypercalcemia?

Lithium induces ectopic PTH production
Lithium-induced autonomous parathyroid adenoma
Lithium raises the calcium set-point for PTH suppression (Correct answer)
Lithium causes vitamin D toxicity

Correct answer: Lithium raises the calcium set-point for PTH suppression

Lithium elevates the calcium threshold for PTH suppression (shifts the set-point), resulting in inappropriately elevated PTH and mild hypercalcemia; this is usually reversible upon lithium discontinuation.

Question 172: A 58-year-old man with newly diagnosed acute promyelocytic leukemia (APL) is started on ATRA and arsenic trioxide. On day 4, he develops fever to 39.2°C, weight gain of 3 kg, and new bilateral pulmonary infiltrates. His WBC has risen from 2,000 to 18,000/µL. Which of the following is the most appropriate next step?

Initiate broad-spectrum antibiotics and hold ATRA pending cultures
Discontinue ATRA immediately and start idarubicin
Add dexamethasone 10 mg IV twice daily and continue ATRA (Correct answer)
Perform bronchoscopy with BAL before any treatment changes

Correct answer: Add dexamethasone 10 mg IV twice daily and continue ATRA

This presentation is classic differentiation syndrome (formerly retinoic acid syndrome), which occurs in APL patients receiving ATRA or arsenic trioxide due to rapid differentiation and cytokine release from maturing promyelocytes. Management is high-dose corticosteroids (dexamethasone 10 mg IV BID) while continuing ATRA unless severe respiratory compromise requires temporary interruption. Discontinuing ATRA outright without steroids is incorrect; the syndrome is not infectious in origin, making antibiotics alone insufficient; and delaying treatment for bronchoscopy would be dangerous.

Question 173: A 30-year-old woman is diagnosed with moderate-to-severe ulcerative colitis affecting the left side of her colon. She has failed to respond to a 4-week course of high-dose oral and rectal 5-aminosalicylic acid (5-ASA) agents. Which of the following medication classes is an appropriate next step to induce remission?

Cholestyramine
Oral corticosteroids (Correct answer)
Loperamide
Long-term broad-spectrum antibiotics

Correct answer: Oral corticosteroids

For patients with moderate-to-severe ulcerative colitis who do not respond to first-line 5-ASA therapy, systemic corticosteroids (e.g., oral prednisone) are the next step to induce remission. Biologic agents like TNF-alpha inhibitors (e.g., infliximab) or other advanced therapies are options for corticosteroid-refractory or dependent disease, or as first-line therapy in severe cases, but a course of corticosteroids is a standard intermediate step. Loperamide is for symptomatic control and should be used with caution, while antibiotics and cholestyramine are not standard induction therapies for UC.

Question 174: A 60-year-old man with a history of atrial fibrillation on warfarin is started on methimazole for Graves' disease. After 6 weeks his TSH normalizes. Which lab change is most expected regarding his anticoagulation?

Methimazole directly inhibits warfarin metabolism
INR will decrease as hyperthyroidism resolves (Correct answer)
INR is unaffected by thyroid status
INR will increase as hyperthyroidism resolves

Correct answer: INR will decrease as hyperthyroidism resolves

Hyperthyroidism accelerates clotting factor catabolism, increasing INR; as thyroid function normalizes with treatment, clotting factor turnover slows and INR decreases, requiring warfarin dose adjustment upward.

Question 175: A 35-year-old woman with diarrhea, bloating, and weight loss has anti-tissue transglutaminase IgA antibodies. Duodenal biopsy shows villous atrophy and crypt hyperplasia. What is the first-line treatment?

Mesalamine
Azathioprine
Prednisone
Gluten-free diet (Correct answer)

Correct answer: Gluten-free diet

Celiac disease is treated with strict adherence to a gluten-free diet, which leads to mucosal healing and resolution of symptoms in the majority of patients.

Question 176: A 52-year-old woman with type 2 diabetes has an HbA1c of 9.2% on metformin 1000 mg twice daily. She has CKD stage 3a (eGFR 52 mL/min). Which medication is CONTRAINDICATED in this patient?

Empagliflozin
Sitagliptin
Glipizide
Metformin 2000 mg twice daily (Correct answer)

Correct answer: Metformin 2000 mg twice daily

Metformin is contraindicated when eGFR falls below 30, but at eGFR 52 it can be continued at current dose; however, doubling to 2000 mg twice daily (4000 mg/day) exceeds the maximum recommended dose of 2550 mg/day and is not indicated.

Question 177: A 44-year-old female never-smoker develops cough and hemoptysis. Bronchoscopy reveals a polypoid endobronchial lesion in the right lower lobe. Biopsy shows carcinoid features with 3 mitoses/10 HPF and focal necrosis. What is the diagnosis?

Typical carcinoid tumor
Small cell lung carcinoma
Large cell neuroendocrine carcinoma
Atypical carcinoid tumor (Correct answer)

Correct answer: Atypical carcinoid tumor

Atypical carcinoid is defined by 2–10 mitoses/10 HPF and/or foci of necrosis, distinguishing it from typical carcinoid (<2 mitoses/10 HPF, no necrosis); both differ from high-grade neuroendocrine tumors.

Question 178: A 38-year-old male marathon runner collapses during a race. He is resuscitated from ventricular fibrillation. ECG after resuscitation shows epsilon waves and T-wave inversions in leads V1–V4. Cardiac MRI reveals fibrofatty infiltration of the right ventricular free wall. Genetic testing confirms a desmoplakin mutation. Which of the following is the most important determinant guiding ICD implantation in this condition?

Inducibility of ventricular tachycardia on EP study
Presence of a pathogenic desmosomal mutation alone
History of sustained ventricular arrhythmia or aborted sudden cardiac death (Correct answer)
Right ventricular ejection fraction below 45%

Correct answer: History of sustained ventricular arrhythmia or aborted sudden cardiac death

In arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D), ICD implantation is a Class I indication for survivors of sustained VT/VF or aborted sudden cardiac death — this patient clearly qualifies. While RVEF <45%, desmosomal mutations, and EP inducibility are risk factors used in risk stratification for primary prevention, a prior cardiac arrest is the strongest and most definitive indication for ICD regardless of other variables. Mutation alone without documented arrhythmia is insufficient for Class I ICD indication.

Question 179: A 72-year-old woman presents with acute onset of bright red blood per rectum, crampy left lower quadrant pain, and tenesmus without systemic symptoms. CT shows segmental colonic wall thickening at the splenic flexure. What is the most likely diagnosis?

Colorectal cancer
Diverticular hemorrhage
Ischemic colitis (Correct answer)
Ulcerative colitis flare

Correct answer: Ischemic colitis

Ischemic colitis classically affects watershed areas like the splenic flexure in older patients and presents with acute crampy pain and bloody diarrhea; segmental distribution on CT is characteristic.

Question 180: A 32-year-old woman presents with a 9-month history of amenorrhea and milky breast discharge. Her serum prolactin level is 150 ng/mL (normal <25 ng/mL). An MRI of the pituitary reveals a 7 mm microadenoma. Visual field testing is normal. What is the most appropriate initial treatment for this condition?

Observation with serial MRIs
Transsphenoidal surgery
Cabergoline (Correct answer)
Stereotactic radiosurgery

Correct answer: Cabergoline

The patient has a symptomatic prolactin-secreting microadenoma (prolactinoma). The first-line treatment for virtually all prolactinomas, regardless of size, is medical therapy with a dopamine agonist. Cabergoline is generally preferred over bromocriptine due to its higher efficacy and better side-effect profile. Dopamine agonists are highly effective at normalizing prolactin levels, restoring gonadal function (and thus menses), and shrinking the tumor. Surgery is considered second-line for patients who are intolerant of or resistant to medical therapy. Observation is not appropriate for a symptomatic patient. Radiation is a third-line option for aggressive or refractory tumors.

Question 181: A 62-year-old man with decompensated alcoholic cirrhosis undergoes a diagnostic paracentesis for new-onset ascites. His medical history is negative for prior spontaneous bacterial peritonitis (SBP). The ascitic fluid analysis reveals a total protein of 1.1 g/dL, a serum-ascites albumin gradient (SAAG) of 1.8 g/dL, and an absolute neutrophil count (ANC) of 80 cells/mm³. His serum creatinine is 1.4 mg/dL and total bilirubin is 3.5 mg/dL. According to current AASLD guidelines, which of the following is the most appropriate next step regarding SBP prophylaxis?

Initiate prophylaxis only if the ascitic fluid culture becomes positive.
Administer a one-time dose of intravenous ceftriaxone and discharge.
No prophylaxis is needed as he has never had an episode of SBP.
Initiate long-term prophylaxis with a daily oral fluoroquinolone or trimethoprim-sulfamethoxazole. (Correct answer)

Correct answer: Initiate long-term prophylaxis with a daily oral fluoroquinolone or trimethoprim-sulfamethoxazole.

Primary prophylaxis for SBP is indicated in patients with cirrhosis and ascites if the ascitic fluid protein is <1.5 g/dL along with evidence of advanced liver failure (e.g., Child-Pugh score ≥9 and bilirubin ≥3 mg/dL) or renal dysfunction (creatinine ≥1.2 mg/dL). This patient meets the criteria with an ascitic fluid protein of 1.1 g/dL, creatinine of 1.4 mg/dL, and bilirubin of 3.5 mg/dL. Lifelong daily oral prophylaxis, typically with ciprofloxacin or trimethoprim-sulfamethoxazole, is the standard of care.

Question 182: A 52-year-old man undergoes surgical resection of a 3 cm pancreatic neuroendocrine tumor. Post-operatively, he develops persistent hypoglycemia with glucose nadir of 38 mg/dL during a 72-hour fast. Insulin level is 18 µU/mL, C-peptide is 4.2 ng/mL, and proinsulin is 22 pmol/L (normal <5). Urine sulfonylurea screen is negative. Which additional test would most definitively differentiate nesidioblastosis from occult insulinoma recurrence?

Selective arterial calcium stimulation with hepatic venous sampling (Correct answer)
68Ga-DOTATATE PET/CT scan
Glucagon stimulation test with C-peptide measurement
Repeat endoscopic ultrasound of the pancreatic remnant

Correct answer: Selective arterial calcium stimulation with hepatic venous sampling

Selective arterial calcium stimulation with hepatic venous sampling (ASVS) is the gold standard for localizing focal insulin hypersecretion. In nesidioblastosis (diffuse beta-cell hyperplasia), calcium stimulation causes a diffuse, non-localizing insulin response from multiple arterial territories. In a focal insulinoma, a stepwise dominant response is seen from the specific artery supplying that region. 68Ga-DOTATATE is ideal for somatostatin receptor-positive NETs but insulinomas often have low SSTR2 expression. Endoscopic ultrasound may miss small recurrences. Glucagon stimulation tests cannot differentiate focal from diffuse disease.

Question 183: Which of the following best describes the mechanism of action of ursodeoxycholic acid (UDCA) in primary biliary cholangitis?

Inhibition of TNF-alpha synthesis
Bile acid synthesis inhibition
Immunosuppression of autoreactive T cells
Displacement of toxic bile acids and hepatoprotection (Correct answer)

Correct answer: Displacement of toxic bile acids and hepatoprotection

UDCA works by replacing toxic hydrophobic bile acids, stimulating bile secretion, and providing cytoprotection to cholangiocytes, slowing disease progression in PBC.

Question 184: A 50-year-old man with type 2 diabetes has an HbA1c of 9.2% despite maximum metformin. He has established atherosclerotic cardiovascular disease. Which agent should be added next according to current guidelines?

Thiazolidinedione
GLP-1 receptor agonist with proven CV benefit (Correct answer)
Sulfonylurea
DPP-4 inhibitor

Correct answer: GLP-1 receptor agonist with proven CV benefit

ADA guidelines prioritize GLP-1 receptor agonists with proven cardiovascular benefit (liraglutide, semaglutide) or SGLT-2 inhibitors in patients with established ASCVD.

Question 185: A 55-year-old patient develops fever and diarrhea 4 days after starting clindamycin for a skin infection. Stool testing is positive for C. difficile toxin. She has her first episode. What is the preferred treatment?

Fidaxomicin 200mg BID x 10 days (Correct answer)
Metronidazole 500mg TID x 10 days
Rifaximin 400mg TID x 10 days
Oral vancomycin 125mg QID x 10 days

Correct answer: Fidaxomicin 200mg BID x 10 days

Current IDSA guidelines recommend fidaxomicin as preferred first-line therapy for initial C. difficile infection due to lower recurrence rates compared to vancomycin.

Question 186: A 58-year-old man with severe COPD (FEV1 28% predicted) is admitted for hypercapnic respiratory failure. After 2 hours of BiPAP, his ABG shows pH 7.29, PaCO2 72 mmHg, PaO2 68 mmHg on FiO2 0.40. His mental status is declining. Which of the following is the most appropriate next step in management?

Initiate invasive mechanical ventilation with volume-control mode (Correct answer)
Increase BiPAP IPAP to 20 cmH2O and reassess in 2 hours
Add high-flow nasal cannula at 40 L/min in combination with BiPAP
Administer IV doxapram as a respiratory stimulant to avoid intubation

Correct answer: Initiate invasive mechanical ventilation with volume-control mode

This patient has failed a trial of noninvasive ventilation (NIV) — defined by worsening ABG, declining mental status, and inability to cooperate — after an adequate trial period (≥1–2 hours). NIV failure mandates prompt transition to invasive mechanical ventilation to prevent respiratory arrest. Increasing BiPAP settings is unlikely to help when the patient is already deteriorating on NIV. Combining HFNC with BiPAP is not a validated rescue strategy and would delay definitive airway management. Doxapram is rarely used in modern practice, not recommended in guidelines for COPD exacerbation, and is not appropriate when mental status is declining.

Question 187: A patient with severe acute pancreatitis is being managed in the ICU. CT shows 40% pancreatic necrosis without infection. When should nutritional support be initiated?

Early enteral nutrition via nasojejunal tube within 24-48 hours (Correct answer)
Oral clear liquids when amylase normalizes
Bowel rest until pain resolves
Parenteral nutrition within 24 hours

Correct answer: Early enteral nutrition via nasojejunal tube within 24-48 hours

Early enteral nutrition via nasojejunal (or nasogastric) tube within 24-48 hours is preferred in severe pancreatitis to maintain gut barrier function and reduce infectious complications compared to TPN.

Question 188: A 70-year-old nursing home resident develops fever, productive cough, and hypoxia. Urinary antigen is positive. She has sulfa allergy. CXR shows lobar consolidation. What is the most likely pathogen and first-line treatment?

Streptococcus pneumoniae; ceftriaxone
Klebsiella pneumoniae; piperacillin-tazobactam
Legionella pneumophila; azithromycin or fluoroquinolone (Correct answer)
Staphylococcus aureus; vancomycin

Correct answer: Legionella pneumophila; azithromycin or fluoroquinolone

Positive urinary antigen in pneumonia diagnoses Legionella; first-line treatment is a macrolide (azithromycin) or respiratory fluoroquinolone (levofloxacin).

Question 189: A 62-year-old woman with polycythemia vera (JAK2 V617F positive) controlled on hydroxyurea presents with a 3-month history of increasing spleen size, constitutional symptoms, and worsening anemia requiring transfusions (hemoglobin 7.8 g/dL). Bone marrow biopsy shows >20% blasts. Cytogenetics reveal del(17p) and complex karyotype. What is the most appropriate diagnosis and management strategy?

Post-PV myelofibrosis progressing to accelerated phase; start ruxolitinib and defer transplant evaluation
Myelofibrosis with myeloid metaplasia; initiate fedratinib as second-line JAK inhibitor therapy
Blast-phase transformation of PV (secondary AML); consider venetoclax + azacitidine and evaluate for allogeneic SCT (Correct answer)
Hydroxyurea-induced myelodysplasia; stop hydroxyurea and transition to anagrelide

Correct answer: Blast-phase transformation of PV (secondary AML); consider venetoclax + azacitidine and evaluate for allogeneic SCT

Blast phase (blast crisis) of polycythemia vera — defined as ≥20% blasts in bone marrow or peripheral blood — represents transformation to secondary AML, a recognized complication of MPN. This is distinct from post-PV myelofibrosis or accelerated phase (10–19% blasts). The complex karyotype including del(17p) (TP53 locus) confers very high-risk cytogenetics. Standard AML induction has poor outcomes; venetoclax + azacitidine (HMA/ven) is increasingly used for TP53-mutated or complex-karyotype secondary AML in older/unfit patients, with allo-HSCT in CR1 as the only potentially curative option. Ruxolitinib addresses myelofibrosis symptoms but is not appropriate for blast-phase disease. The blast count of >20% definitively excludes the MF accelerated phase designation.

Question 190: A 29-year-old woman presents with weakness, hyperpigmentation, salt craving, and orthostatic hypotension. Labs show Na 128 mEq/L, K 5.8 mEq/L, and glucose 62 mg/dL. ACTH stimulation test shows a peak cortisol of 10 mcg/dL at 60 minutes. What is the most likely diagnosis?

Secondary adrenal insufficiency
Cushing syndrome
Primary adrenal insufficiency (Addison's disease) (Correct answer)
Congenital adrenal hyperplasia (non-classic)

Correct answer: Primary adrenal insufficiency (Addison's disease)

Primary adrenal insufficiency (Addison's disease) is characterized by loss of both cortisol and aldosterone, causing hyponatremia, hyperkalemia, hyperpigmentation (elevated ACTH), and a blunted cortisol response to ACTH stimulation.

Question 191: A 58-year-old male with acute myeloid leukemia is undergoing induction chemotherapy. He develops a fever of 39.2°C (102.6°F) and his absolute neutrophil count is 150 cells/mm³. He is hemodynamically stable with no clear source of infection on initial examination. According to IDSA guidelines, which of the following is the most appropriate initial empiric antibiotic regimen?

Vancomycin plus Cefepime
Metronidazole plus Ciprofloxacin
Ceftriaxone
Piperacillin-tazobactam (Correct answer)

Correct answer: Piperacillin-tazobactam

In high-risk febrile neutropenia, empiric monotherapy with an anti-pseudomonal beta-lactam is the standard of care. Piperacillin-tazobactam, cefepime, meropenem, or imipenem-cilastatin are all appropriate first-line choices. Ceftriaxone lacks reliable Pseudomonas aeruginosa coverage. Vancomycin is not recommended for routine initial empiric therapy unless specific indications are present, such as suspected catheter-related infection, pneumonia, hemodynamic instability, or known MRSA colonization. Metronidazole would only be added if an anaerobic source, like an intra-abdominal infection, is suspected.

Question 192: A 67-year-old renal transplant recipient on tacrolimus develops culture-confirmed Candida glabrata fungemia. He is hemodynamically stable with no ophthalmologic involvement. Susceptibility testing shows elevated MIC to fluconazole (MIC 16 µg/mL). Which is the most appropriate definitive antifungal strategy?

High-dose fluconazole (800 mg/day) given stable clinical status
Micafungin for a minimum of 14 days after last positive blood culture (Correct answer)
Voriconazole due to its superior bioavailability over echinocandins
Amphotericin B liposomal formulation to avoid echinocandin resistance

Correct answer: Micafungin for a minimum of 14 days after last positive blood culture

Candida glabrata (now reclassified as Nakaseomyces glabrata) frequently demonstrates reduced fluconazole susceptibility, with MIC ≥8 µg/mL classified as dose-dependent susceptible or resistant. Echinocandins (micafungin, anidulafungin, caspofungin) are first-line for C. glabrata candidemia per IDSA guidelines. Duration is at minimum 14 days from the first negative blood culture in non-neutropenic patients. Fluconazole at high dose is inappropriate for an MIC of 16 µg/mL (resistant by EUCAST criteria). Voriconazole is not preferred for Candida candidemia and has significant interactions with tacrolimus. Amphotericin B carries nephrotoxicity risk especially in a transplant patient and is reserved for refractory cases.

Question 193: A 35-year-old woman with systemic lupus erythematosus (SLE) presents with acute dyspnea and hemoptysis. Chest X-ray shows bilateral alveolar infiltrates. Bronchoscopy with BAL returns progressively bloodier returns from all lobes. ANA titer is 1:640. Anti-dsDNA is markedly elevated. Urinalysis shows RBC casts. What is the MOST likely diagnosis?

Granulomatosis with polyangiitis (GPA)
Diffuse alveolar hemorrhage (DAH) from SLE (Correct answer)
Microscopic polyangiitis (MPA)
Goodpasture syndrome (anti-GBM disease)

Correct answer: Diffuse alveolar hemorrhage (DAH) from SLE

Diffuse alveolar hemorrhage in the setting of active SLE (elevated anti-dsDNA, lupus nephritis with RBC casts) is most consistent with SLE-associated DAH, a life-threatening complication.

Question 194: A 71-year-old man with known pulmonary arterial hypertension (WHO Group 1) on ambrisentan and tadalafil presents with acute decompensation. RHC reveals: RAP 18 mmHg, mPAP 62 mmHg, PCWP 8 mmHg, CO 2.1 L/min, PVR 25.7 Wood units. Exam shows cool extremities, JVD, RV gallop, and moderate ascites. Which of the following treatment strategies is MOST likely to cause acute clinical deterioration in this patient?

Starting IV epoprostenol while weaning oral therapies
IV diuresis with furosemide 40 mg
Inhaled nitric oxide at 20 ppm
Aggressive IV fluid resuscitation with 2L normal saline (Correct answer)

Correct answer: Aggressive IV fluid resuscitation with 2L normal saline

In acute decompensated pulmonary arterial hypertension with right ventricular failure, the RV is severely afterloaded (PVR 25.7 Wood units) and preload-dependent but has a very limited ability to handle additional volume. The RV in this setting operates on the flat or descending portion of its Starling curve. Aggressive IV fluid resuscitation will cause RV overdistension, which shifts the interventricular septum leftward via ventricular interdependence, compresses the LV, reduces LV filling and cardiac output, and precipitates hemodynamic collapse. Inhaled nitric oxide selectively reduces PVR and is a first-line rescue therapy. Gentle IV diuresis offloads the congested RV and is appropriate given RAP of 18 and clinical signs of RV failure. Transitioning to IV epoprostenol in decompensated PAH is an evidence-based escalation strategy that can be lifesaving. Fluids are contraindicated unless there is clear evidence of hypovolemia.

Question 195: A 74-year-old man with EF of 25% is on optimal HFrEF therapy. He has NYHA class III symptoms. His ICD was implanted 2 years ago. QRS is 110 ms. What additional therapy should be considered to reduce hospitalization?

SGLT2 inhibitor (dapagliflozin or empagliflozin) (Correct answer)
Hydralazine-nitrate combination
Nesiritide infusion
Digoxin titrated to 1.5 ng/mL

Correct answer: SGLT2 inhibitor (dapagliflozin or empagliflozin)

SGLT2 inhibitors (dapagliflozin, empagliflozin) reduce HF hospitalization and cardiovascular death in HFrEF independent of diabetes status.

Question 196: A 67-year-old man with GOLD Stage III COPD (FEV1 38% predicted) is admitted for a moderate exacerbation. He is on triple inhaled therapy (LAMA/LABA/ICS). Arterial blood gas on admission: pH 7.32, PaCO2 58 mmHg, PaO2 54 mmHg, HCO3 29 mEq/L. He is started on high-flow nasal cannula at 40 L/min, FiO2 0.40. After 90 minutes, repeat ABG: pH 7.30, PaCO2 64 mmHg, PaO2 88 mmHg. He remains alert and cooperative. What is the most appropriate next intervention?

Reduce FiO2 to 0.28 to avoid oxygen-induced hypercapnia and repeat ABG in 60 minutes
Increase HFNC flow rate to 60 L/min and FiO2 to 0.60 to improve oxygenation further
Proceed to immediate endotracheal intubation given worsening hypercapnia
Initiate non-invasive positive pressure ventilation (NIV/BiPAP) (Correct answer)

Correct answer: Initiate non-invasive positive pressure ventilation (NIV/BiPAP)

This patient has acute hypercapnic respiratory failure with worsening respiratory acidosis (pH 7.30, PaCO2 64) despite HFNC. NIV (BiPAP) is the indicated next step for COPD exacerbations with hypercapnic failure (pH 7.25–7.35) and is supported by strong evidence to reduce intubation rates and mortality. HFNC has not been shown to be equivalent to NIV in hypercapnic COPD exacerbations. While the PaO2 improved with HFNC, the rising PaCO2 and worsening acidosis indicate ventilatory failure requiring pressure support. Intubation is premature in an alert, cooperative patient who has not yet failed NIV. Reducing FiO2 alone will not address the ventilatory failure.

Question 197: A 62-year-old patient with cirrhosis develops spontaneous bacterial peritonitis (SBP). Ascitic fluid PMN count is 350 cells/µL. What is the empiric antibiotic of choice?

Vancomycin plus piperacillin-tazobactam
Amoxicillin-clavulanate PO
Cefotaxime 2g IV q8h (Correct answer)
Metronidazole plus ciprofloxacin

Correct answer: Cefotaxime 2g IV q8h

Cefotaxime (or ceftriaxone) is the empiric antibiotic of choice for SBP, providing excellent gram-negative coverage without nephrotoxicity in an already vulnerable population.

Question 198: A 65-year-old man with type 2 diabetes presents with burning pain, numbness, and tingling in both feet in a 'stocking' distribution. Nerve conduction studies show reduced amplitude and slowed conduction velocity in distal sensory nerves bilaterally. Which of the following is MOST appropriate for neuropathic pain control?

Amitriptyline 150 mg at bedtime
Celecoxib 200 mg twice daily
Gabapentin plus opioids as first-line combination
Duloxetine or pregabalin (Correct answer)

Correct answer: Duloxetine or pregabalin

Duloxetine and pregabalin are FDA-approved first-line agents for diabetic peripheral neuropathic pain with strong evidence and favorable risk profiles. Opioids are not first-line. High-dose amitriptyline (150 mg) carries significant anticholinergic and cardiac risk; low doses may be used but are not first-line. NSAIDs do not address neuropathic pain mechanisms.

Question 199: A 35-year-old woman is found to have latent tuberculosis infection (LTBI) with a positive IGRA. She has no active TB symptoms. She is not pregnant and has no liver disease. What is the preferred LTBI treatment regimen?

Isoniazid 300mg daily for 9 months
Rifampin 600mg daily for 4 months
Isoniazid 300mg daily for 6 months
Isoniazid plus rifapentine weekly for 12 weeks (3HP) (Correct answer)

Correct answer: Isoniazid plus rifapentine weekly for 12 weeks (3HP)

The 3HP regimen (weekly isoniazid plus rifapentine for 12 weeks) is preferred for LTBI due to superior completion rates compared to 9-month isoniazid monotherapy.

Question 200: A 29-year-old woman presents with 5 days of fever, sore throat, and cervical lymphadenopathy. Monospot test is negative. EBV VCA IgM is positive. Three weeks later she develops high fevers, ferritin 42,000 ng/mL, splenomegaly, cytopenia (neutrophils 0.8 × 10⁹/L, platelets 68 × 10⁹/L), elevated triglycerides, and fibrinogen 150 mg/dL. Bone marrow biopsy shows hemophagocytosis. Which finding would MOST strongly indicate that this is EBV-driven hemophagocytic lymphohistiocytosis (HLH) versus secondary HLH from another trigger?

Bone marrow biopsy showing CD8+ T-cell infiltration with hemophagocytosis
Homozygous PRF1 (perforin) mutation on genetic testing (Correct answer)
Elevated EBV DNA in peripheral blood by PCR with markedly elevated sNK cell activity
Ferritin level greater than 50,000 ng/mL

Correct answer: Homozygous PRF1 (perforin) mutation on genetic testing

While EBV is a common trigger of secondary HLH, the discovery of a homozygous PRF1 (perforin-1) mutation definitively identifies primary/familial HLH (FHL2), which typically presents in early adulthood triggered by viral infections (especially EBV). This distinction is critical: primary HLH requires hematopoietic stem cell transplantation as definitive therapy, while secondary HLH may remit with immunosuppression and treatment of the trigger. Elevated EBV PCR (choice A) confirms viral trigger but doesn't distinguish primary from secondary. Ferritin >50,000 (choice B) increases HLH specificity but doesn't differentiate primary vs. secondary. CD8+ infiltration (choice D) is a histologic feature seen in both.

Question 201: A 72-year-old woman sustains a hip fracture after a fall from standing height. A subsequent DEXA scan reveals a T-score of -2.8 at the femoral neck. She has no contraindications to oral medications and her renal function is normal. Which of the following is the most appropriate initial long-term pharmacologic therapy?

Denosumab
Oral alendronate (Correct answer)
Teriparatide
Raloxifene

Correct answer: Oral alendronate

This patient has established, severe osteoporosis, defined by the presence of a fragility fracture. According to major clinical guidelines (AACE/ACE), oral bisphosphonates such as alendronate are the recommended first-line therapy for most postmenopausal women with osteoporosis. They are effective at reducing both vertebral and hip fractures, are cost-effective, and have an extensive safety record. Denosumab is also a first-line option but is often used in those who cannot tolerate oral bisphosphonates. Teriparatide, an anabolic agent, is typically reserved for very high-risk patients or those who fail bisphosphonate therapy. Raloxifene is less potent and is not proven to reduce the risk of hip fractures.

Question 202: A 58-year-old man with HIV (CD4 count 45 cells/µL, viral load 120,000 copies/mL) presents with 3 weeks of progressive headache and altered mentation. CSF analysis shows: opening pressure 28 cmH₂O, WBC 8 cells/µL (lymphocytes), glucose 42 mg/dL (serum 90 mg/dL), protein 65 mg/dL, India ink positive. Cryptococcal antigen titer is 1:2048. After starting liposomal amphotericin B plus flucytosine, what is the MOST critical monitoring parameter during the first two weeks of induction therapy?

Renal function and electrolytes for amphotericin B nephrotoxicity
Weekly serum cryptococcal antigen titers
Daily CBC to monitor flucytosine-induced bone marrow suppression
Serial CSF opening pressures via therapeutic lumbar punctures (Correct answer)

Correct answer: Serial CSF opening pressures via therapeutic lumbar punctures

Elevated intracranial pressure (ICP) is the leading cause of early morbidity and mortality in cryptococcal meningitis. The IDSA guidelines mandate serial therapeutic lumbar punctures to maintain opening pressure below 20 cmH₂O; failure to manage ICP aggressively causes blindness, herniation, and death. While amphotericin B nephrotoxicity (choice D) is important and monitored, and flucytosine-related myelosuppression (choice C) is relevant, neither is the 'most critical' determinant of early outcome. Serum CrAg titers (choice B) are not useful for short-term monitoring.

Question 203: A 60-year-old man undergoes right heart catheterization. Results: RA pressure 18 mmHg, RV 55/20 mmHg, PA 55/28 mmHg (mean 38), PCWP 24 mmHg, cardiac output 3.8 L/min. What is the MOST likely diagnosis?

Pulmonary hypertension due to lung disease (Group 3)
Chronic thromboembolic pulmonary hypertension (CTEPH)
Idiopathic pulmonary arterial hypertension
Pulmonary hypertension due to left heart disease (Group 2) (Correct answer)

Correct answer: Pulmonary hypertension due to left heart disease (Group 2)

Elevated PCWP (>15 mmHg) with elevated mean PAP indicates post-capillary (Group 2) pulmonary hypertension due to left heart disease, not pre-capillary PAH.

Question 204: A 52-year-old woman is admitted to the ICU with septic shock from urosepsis. On day 3, she is improving, with vasopressors being weaned. Labs show Na 131 mEq/L (was 139 mEq/L on admission). She is euvolemic on exam. Urine sodium is 48 mEq/L, urine osmolality 520 mOsm/kg, serum osmolality 272 mOsm/kg. She received 3 L of D5W over 24 hours and is on empiric vancomycin and piperacillin-tazobactam. Which mechanism MOST contributes to her hyponatremia?

SIADH from pain and stress response causing inappropriate ADH secretion
Hypotonic fluid administration compounded by non-osmotic ADH release from hemodynamic recovery (Correct answer)
Cerebral salt wasting triggered by hemodynamic instability
Reset osmostat syndrome from malnutrition and critical illness

Correct answer: Hypotonic fluid administration compounded by non-osmotic ADH release from hemodynamic recovery

This patient received 3 L of D5W (a hypotonic fluid) in the context of improving septic shock. As hemodynamic instability resolves, the baroreceptor-mediated non-osmotic ADH stimulus diminishes, but transitioning to hypotonic fluids during a phase when ADH levels are still relatively elevated causes iatrogenic hyponatremia. This is a classically under-recognized ICU scenario. While SIADH from stress exists, the history points to a primarily iatrogenic hypotonic fluid contribution. Reset osmostat maintains serum Na at a new lower set point without ongoing natriuresis. Cerebral salt wasting requires a CNS insult and presents with hypovolemia and urinary sodium loss, not euvolemia.

Question 205: A 50-year-old woman with rheumatoid arthritis on methotrexate presents with new onset dyspnea and bilateral ground-glass opacities on CT chest. BAL shows eosinophilia. Lung biopsy reveals organizing pneumonia pattern. Which statement about this drug-induced lung injury is TRUE?

The organizing pneumonia pattern from methotrexate typically responds to corticosteroids (Correct answer)
High-dose cyclophosphamide is the treatment of choice
Methotrexate-induced lung disease carries a >50% mortality rate
Methotrexate must be permanently discontinued and can never be restarted

Correct answer: The organizing pneumonia pattern from methotrexate typically responds to corticosteroids

Methotrexate-induced organizing pneumonia typically responds well to discontinuation of methotrexate and systemic corticosteroids, with most patients recovering fully.

Question 206: A 45-year-old man with known bicuspid aortic valve and moderate aortic regurgitation has an aortic root diameter of 4.8 cm and ascending aorta of 4.3 cm. He is asymptomatic with EF of 62% and LVESD of 42 mm. Which is the most appropriate management?

Refer for surgery only when EF drops below 55% or LVESD exceeds 50 mm
Observation with annual imaging; surgery threshold in BAV patients is aortic diameter ≥5.0 cm
Refer for surgery now given aortic root ≥4.5 cm in a bicuspid aortic valve patient with additional risk modifier (Correct answer)
Initiate beta-blocker therapy to slow aortic root dilation and defer surgery

Correct answer: Refer for surgery now given aortic root ≥4.5 cm in a bicuspid aortic valve patient with additional risk modifier

In bicuspid aortic valve (BAV) disease, the threshold for prophylactic aortic surgery is lower than in tricuspid valves. Current AHA/ACC guidelines recommend surgery at ≥5.5 cm for tricuspid valves but ≥5.0 cm for BAV. However, surgery is reasonable at ≥4.5 cm in BAV patients who have an additional risk modifier — such as a family history of aortic dissection, a rapid growth rate (>0.5 cm/year), or planned cardiac surgery for another indication. At 4.8 cm root with BAV, the threshold is met if any risk modifier exists; this patient warrants surgical referral evaluation. Beta-blockers alone do not change the aortopathy trajectory sufficiently to defer needed intervention.

Question 207: A 68-year-old woman with osteoporosis and a T-score of −3.0 at the hip has been on denosumab for 3 years. She asks about stopping therapy. What is the most important risk to counsel her about?

Development of monoclonal gammopathy
Jaw osteonecrosis upon stopping
Rebound hypercalcemia
Rapid bone loss and increased vertebral fracture risk upon discontinuation (Correct answer)

Correct answer: Rapid bone loss and increased vertebral fracture risk upon discontinuation

Denosumab discontinuation causes a rebound increase in bone turnover markers and rapid bone loss, significantly increasing vertebral fracture risk; transition to a bisphosphonate is recommended before stopping.

Question 208: Which of the following features most strongly differentiates papillary thyroid carcinoma from follicular thyroid carcinoma on fine needle aspiration?

Colloid abundance
Nuclear grooves, pseudoinclusions, and Orphan Annie eye nuclei (Correct answer)
Hurthle cell metaplasia
Psammoma bodies in follicular architecture

Correct answer: Nuclear grooves, pseudoinclusions, and Orphan Annie eye nuclei

Papillary thyroid carcinoma is diagnosed by characteristic nuclear features: grooves, pseudo-inclusions, and pale (Orphan Annie eye) nuclei on cytology.

Question 209: A 55-year-old man with diabetes presents with right lower extremity cellulitis and fever. He was treated with cephalexin for 5 days without improvement. What additional coverage should be empirically added?

Piperacillin-tazobactam
Clindamycin alone
Metronidazole
TMP-SMX or doxycycline (MRSA coverage) (Correct answer)

Correct answer: TMP-SMX or doxycycline (MRSA coverage)

Failure to improve on beta-lactam therapy for cellulitis should prompt consideration of MRSA, and empiric MRSA coverage with TMP-SMX or doxycycline should be added.

Question 210: A 28-year-old woman presents with a one-year history of intermittent abdominal cramping, bloating, and chronic diarrhea. She reports unintentional weight loss of 10 lbs. Laboratory studies reveal a microcytic anemia with a hemoglobin of 10.5 g/dL. She is currently consuming a regular diet. According to the American College of Gastroenterology (ACG), which of the following is the most appropriate initial serologic test for celiac disease?

Anti-gliadin IgG antibody
Tissue transglutaminase (tTG) IgA antibody plus total serum IgA (Correct answer)
HLA-DQ2 and HLA-DQ8 genetic testing
Anti-Saccharomyces cerevisiae antibodies (ASCA)

Correct answer: Tissue transglutaminase (tTG) IgA antibody plus total serum IgA

The ACG guidelines recommend IgA anti-tissue transglutaminase (tTG-IgA) antibody as the preferred single test for the initial detection of celiac disease in adults. It is highly sensitive and specific. It is crucial to measure total serum IgA concurrently to rule out selective IgA deficiency, which is more common in patients with celiac disease and can cause a false-negative tTG-IgA result. If IgA deficiency is present, IgG-based tests (e.g., tTG-IgG) should be performed.

Question 211: A 34-year-old woman with systemic lupus erythematosus presents with nephrotic-range proteinuria (4.8 g/day), serum creatinine 1.9 mg/dL, and complement levels showing low C3 and C4. Kidney biopsy reveals mesangial and subendothelial immune deposits with 'wire-loop' lesions on light microscopy and no tubuloreticular inclusions on electron microscopy. Which ISN/RPS class of lupus nephritis is this, and what is the most appropriate induction therapy?

Class II mesangial; hydroxychloroquine plus ACE inhibitor only
Class IV diffuse proliferative; high-dose mycophenolate mofetil plus glucocorticoids (Correct answer)
Class V membranous; tacrolimus monotherapy
Class III focal proliferative; azathioprine plus low-dose prednisone

Correct answer: Class IV diffuse proliferative; high-dose mycophenolate mofetil plus glucocorticoids

Wire-loop lesions on light microscopy reflect large subendothelial deposits and are hallmark of Class IV (diffuse proliferative) lupus nephritis — the most severe and most common form requiring aggressive induction. Tubuloreticular inclusions are often seen in lupus but their absence does not exclude it. Induction with high-dose mycophenolate mofetil (2–3 g/day) plus corticosteroids is now preferred over cyclophosphamide in most patients, per current KDIGO and ACR guidelines, with equivalent efficacy and a better tolerability profile, especially for preservation of fertility.

Question 212: A 40-year-old man presents with hematuria, flank pain, and a palpable abdominal mass. Imaging shows bilateral enlarged kidneys with multiple cysts. His father had the same condition and died from a ruptured intracranial aneurysm. Which gene mutation is most likely responsible?

PKD2
TSC1
PKD1 (Correct answer)
VHL

Correct answer: PKD1

PKD1 mutations account for approximately 85% of autosomal dominant polycystic kidney disease cases and are associated with more severe disease and earlier ESRD.

Question 213: A 29-year-old nurse undergoes routine employee health screening and is found to have a positive tuberculin skin test (15 mm induration). She is asymptomatic and her chest X-ray is negative for active disease. According to current CDC guidelines, which of the following is a preferred short-course regimen for treating latent tuberculosis infection (LTBI)?

Levofloxacin daily for 6 months
Isoniazid and rifapentine once weekly for 3 months (Correct answer)
Isoniazid daily for 9 months
Ethambutol daily for 12 months

Correct answer: Isoniazid and rifapentine once weekly for 3 months

The CDC preferentially recommends short-course, rifamycin-based regimens for the treatment of LTBI due to higher completion rates and similar efficacy compared to the older 9-month isoniazid regimen. The preferred regimens include once-weekly isoniazid plus rifapentine for 3 months (3HP), daily rifampin for 4 months (4R), or daily isoniazid plus rifampin for 3 months (3HR). While 9 months of daily isoniazid is still an acceptable alternative, it is no longer the sole preferred regimen. Ethambutol and levofloxacin are not first-line agents for treating LTBI.

Question 214: A 45-year-old male traveler develops profuse watery diarrhea, nausea, and vomiting 2 days after returning from India. Stool cultures show Vibrio cholerae. What is the primary treatment priority?

IV fluid resuscitation with Ringer's lactate (Correct answer)
Ciprofloxacin 1g single dose
Doxycycline 300mg single dose
Azithromycin 1g single dose

Correct answer: IV fluid resuscitation with Ringer's lactate

Aggressive fluid and electrolyte replacement is the cornerstone of cholera treatment, as severe dehydration causes most deaths; antibiotics are adjunctive.

Question 215: What is the first-line treatment for acute exacerbation of chronic obstructive pulmonary disease (COPD)?

Bronchodilators and leukotriene antagonists
Inhaled corticosteroids and beta-blockers
Antihistamines and nasal decongestants
Systemic corticosteroids and antibiotics (Correct answer)

Correct answer: Systemic corticosteroids and antibiotics

The first-line treatment for acute exacerbation of chronic obstructive pulmonary disease (COPD) typically involves systemic corticosteroids and antibiotics. Corticosteroids reduce airway inflammation, while antibiotics are often prescribed to cover potential bacterial infections, which frequently trigger exacerbations. Bronchodilators are also crucial for symptom relief.

Question 216: A 25-year-old woman is found to have BP of 170/100 mmHg on routine exam. Labs show hypokalemia, suppressed plasma renin activity, and elevated aldosterone. CT shows no adrenal mass. What is the best next diagnostic step?

Adrenal vein sampling (Correct answer)
MRI of the pituitary
24-hour urine metanephrines
Renal artery Doppler ultrasound

Correct answer: Adrenal vein sampling

Adrenal vein sampling is the gold standard for differentiating unilateral aldosterone-producing adenoma from bilateral adrenal hyperplasia when CT is non-diagnostic.

Question 217: A 38-year-old man with multiple endocrine neoplasia type 1 (MEN1) undergoes surveillance imaging and is found to have a 1.8 cm non-functioning pancreatic neuroendocrine tumor (pNET). His serum calcium is 11.4 mg/dL, PTH is 142 pg/mL, and gastrin is normal. He is otherwise asymptomatic. In MEN1, what is the correct sequence of surgical management when both hyperparathyroidism and a pNET require surgery?

The pNET should be treated with somatostatin analogues first to shrink it before surgical planning
Address both simultaneously with a single operative session to minimize anesthetic risk
Perform parathyroidectomy first, as hypercalcemia stimulates gastrin and may unmask latent gastrinoma (Correct answer)
Resect the pNET first to reduce the risk of Zollinger-Ellison syndrome

Correct answer: Perform parathyroidectomy first, as hypercalcemia stimulates gastrin and may unmask latent gastrinoma

In MEN1 patients with concurrent hyperparathyroidism and pNETs, parathyroidectomy should be performed first. Hypercalcemia potentiates gastrin secretion and exacerbates acid hypersecretion in gastrinoma (Zollinger-Ellison syndrome), making hypercalcemia correction essential before pancreatic surgery. Normalization of calcium can unmask true gastrin levels and improve control of ZES. The recommended operation for MEN1-related hyperparathyroidism is subtotal (3.5-gland) parathyroidectomy or total parathyroidectomy with autotransplantation. Performing pancreatic surgery first does not address the hormonal milieu driving gastric acid secretion and may complicate postoperative management.

Question 218: A 45-year-old woman presents with jaundice, pruritus, and elevated alkaline phosphatase. AMA is positive. What is the most likely diagnosis?

Choledocholithiasis
Primary sclerosing cholangitis
Autoimmune hepatitis
Primary biliary cholangitis (Correct answer)

Correct answer: Primary biliary cholangitis

Anti-mitochondrial antibody (AMA) positivity with cholestatic pattern strongly suggests primary biliary cholangitis, a chronic autoimmune bile duct disease predominantly affecting middle-aged women.

Question 219: A 65-year-old man with severe COPD (FEV1/FVC 0.52, FEV1 32% predicted) has symptoms despite maximal bronchodilator therapy. CT shows heterogeneous emphysema predominantly in the upper lobes with low exercise capacity. Which intervention has demonstrated mortality benefit in this population?

Lung volume reduction surgery (LVRS) (Correct answer)
Inhaled triple therapy (LABA/LAMA/ICS)
Azithromycin prophylaxis 250 mg daily
Bronchoscopic lung volume reduction with endobronchial valves

Correct answer: Lung volume reduction surgery (LVRS)

The NETT trial demonstrated that LVRS reduces mortality and improves exercise capacity in COPD patients with upper-lobe predominant emphysema and low baseline exercise capacity.

Question 220: An ICU patient develops ventilator-associated pneumonia (VAP) on day 8. Endotracheal cultures grow Pseudomonas aeruginosa. Which antibiotic combination should be used empirically given concern for multidrug-resistant (MDR) Pseudomonas?

Cefepime plus tobramycin (Correct answer)
Ceftazidime-avibactam plus colistin
Meropenem plus ceftolozane-tazobactam
Piperacillin-tazobactam monotherapy

Correct answer: Cefepime plus tobramycin

For MDR Pseudomonas VAP, combination therapy with an antipseudomonal beta-lactam plus an aminoglycoside (e.g., cefepime plus tobramycin) is recommended pending susceptibilities.

Question 221: A 52-year-old woman with primary biliary cholangitis (PBC) on ursodeoxycholic acid presents with worsening pruritus, fatigue, and a rising alkaline phosphatase despite 12 months of therapy. Her ALP remains >1.67× the upper limit of normal. Which second-line agent has demonstrated reduction in ALP and improved transplant-free survival in this setting?

Rifampin
Bezafibrate
Obeticholic acid (Correct answer)
Cholestyramine

Correct answer: Obeticholic acid

Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, is FDA-approved as second-line therapy in PBC for patients with inadequate response to UDCA. In the POISE trial, OCA significantly reduced ALP and total bilirubin, and long-term data suggest improved transplant-free survival. Cholestyramine treats pruritus but does not alter disease progression. Rifampin is used off-label for pruritus only. Bezafibrate (a PPAR agonist) shows promise and is approved in some countries but is not FDA-approved for this indication.

Question 222: A 55-year-old diabetic woman presents with right facial pain, black eschar on the palate, and periorbital edema. CT shows sinus involvement extending to the orbit. What is the likely pathogen?

Mucor/Rhizopus species (Correct answer)
Candida albicans
Fusarium solani
Aspergillus fumigatus

Correct answer: Mucor/Rhizopus species

Rhinocerebral mucormycosis caused by Mucorales (Mucor/Rhizopus) classically occurs in diabetic ketoacidosis, presenting with black necrotic eschar and rapid orbital/CNS spread.

Question 223: A 72-year-old female is brought to the emergency department from a nursing home with a fever of 39.1°C (102.4°F), a respiratory rate of 28 breaths/min, and confusion. Her blood pressure is 85/50 mmHg despite receiving a 1L bolus of normal saline. A chest X-ray confirms a right lower lobe pneumonia. According to the Surviving Sepsis Campaign guidelines, which of the following interventions is the highest priority within the first hour of recognition?

Initiating vasopressor therapy with norepinephrine
Administering a 30 mL/kg crystalloid fluid bolus
Obtaining blood cultures and administering broad-spectrum antibiotics (Correct answer)
Measuring serum lactate level

Correct answer: Obtaining blood cultures and administering broad-spectrum antibiotics

The Surviving Sepsis Campaign guidelines emphasize the immediate initiation of treatment in patients with sepsis and septic shock. The 'Hour-1 Bundle' includes several critical actions. While fluid resuscitation (30 mL/kg crystalloid for hypotension) and measuring lactate are essential, the highest priority is to obtain blood cultures *before* administering broad-spectrum antibiotics, with the goal of starting antibiotics within the first hour of recognition. Delayed antibiotic administration is associated with increased mortality.

Question 224: A patient with stage 5 CKD presents to the emergency department with altered mental status. Which of the following findings represents the most urgent indication to initiate hemodialysis?

Blood urea nitrogen (BUN) of 120 mg/dL
Refractory peripheral edema
Uremic pericarditis with a friction rub (Correct answer)
Serum creatinine of 9.0 mg/dL

Correct answer: Uremic pericarditis with a friction rub

While elevated BUN and creatinine, and fluid overload are indications for dialysis, the most urgent, life-threatening indications are remembered by the mnemonic AEIOU (Acidosis, Electrolytes, Intoxication, Overload, Uremia). Uremic pericarditis is a life-threatening complication of uremia that can lead to pericardial effusion and tamponade. It is an absolute and urgent indication for initiating hemodialysis.

Question 225: A 50-year-old man with known esophageal varices presents with hematemesis. He is hemodynamically stable after resuscitation. What is the most appropriate endoscopic treatment?

Coagulation therapy
Hemostatic clips
Band ligation (Correct answer)
Sclerotherapy

Correct answer: Band ligation

Endoscopic variceal band ligation (EVL) is the preferred endoscopic treatment for acute esophageal variceal bleeding due to its superior efficacy and lower complication rate compared to sclerotherapy.

Question 226: A 45-year-old woman is found to have a serum calcium of 11.4 mg/dL and PTH of 88 pg/mL (normal 15–65). She is asymptomatic. Bone density shows T-score of −2.0 at lumbar spine. Which is the best next step?

Start bisphosphonate therapy alone
Refer for parathyroidectomy (Correct answer)
Start cinacalcet
Reassure and recheck calcium in 6 months

Correct answer: Refer for parathyroidectomy

Asymptomatic primary hyperparathyroidism with a T-score ≤ −2.5 or other surgical criteria warrants parathyroidectomy, which is curative.

Question 227: A 52-year-old woman with type 2 diabetes on empagliflozin, metformin, and lisinopril presents with 2 days of vomiting and decreased oral intake. She is tachypneic with Kussmaul breathing. Labs: glucose 181 mg/dL, Na 138, Cl 102, HCO₃ 9 mEq/L, pH 7.16, beta-hydroxybutyrate 4.4 mmol/L. Which mechanism best explains her ketoacidosis despite a near-normal glucose?

Type 4 renal tubular acidosis precipitated by lisinopril in the setting of volume depletion
Ketosis-prone type 2 diabetes triggered by volume depletion, independent of SGLT2 inhibitor effects
Lactic acidosis from metformin accumulation in the setting of acute kidney injury
Relative insulin deficiency with glucagon excess driving ketogenesis, while SGLT2 inhibition promotes urinary glucose excretion and lowers the renal threshold for glycosuria (Correct answer)

Correct answer: Relative insulin deficiency with glucagon excess driving ketogenesis, while SGLT2 inhibition promotes urinary glucose excretion and lowers the renal threshold for glycosuria

SGLT2 inhibitors can cause euglycemic DKA (euDKA) by increasing the glucagon-to-insulin ratio (promoting ketogenesis) while simultaneously lowering the renal threshold for glucose excretion. Blood glucose remains near-normal despite true DKA because glucosuria is markedly enhanced. Clinicians must maintain a high index of suspicion for euDKA in patients on SGLT2 inhibitors, especially during fasting, surgery, or intercurrent illness. Metformin-associated lactic acidosis is possible but would show an elevated lactate rather than elevated ketones. Type 4 RTA causes a non-anion gap hyperchloremic acidosis.

Question 228: A 40-year-old man presents for a routine health evaluation. He is asymptomatic but reports that his father was diagnosed with colon cancer at age 48. He has no other personal or family history of cancer. According to current U.S. Preventive Services Task Force (USPSTF) and ACG guidelines, what is the most appropriate recommendation for colorectal cancer screening for this patient?

Begin screening now with a stool-based test (FIT).
No screening is necessary until he develops symptoms.
Begin screening with colonoscopy at age 50.
Begin screening now with colonoscopy. (Correct answer)

Correct answer: Begin screening now with colonoscopy.

For individuals with a first-degree relative diagnosed with colorectal cancer before the age of 60, screening guidelines recommend initiating colonoscopy at age 40, or 10 years younger than the age at which the relative was diagnosed, whichever comes first. In this case, 10 years before his father's diagnosis at age 48 would be age 38. Since the patient is now 40, he should begin screening with colonoscopy immediately.

Question 229: Phentolamine is administered before surgical resection of a pheochromocytoma. What is its primary purpose?

Reduce catecholamine synthesis
Lower perioperative cortisol levels
Block alpha-adrenergic receptors to prevent hypertensive crisis (Correct answer)
Prevent tachyarrhythmias during induction

Correct answer: Block alpha-adrenergic receptors to prevent hypertensive crisis

Alpha-blockade with phentolamine (or phenoxybenzamine) is essential to prevent severe hypertension from catecholamine release during tumor manipulation.

Question 230: A 55-year-old man with metastatic non-small cell lung adenocarcinoma is found to have an EGFR exon 20 insertion mutation. His oncologist initially considers osimertinib. Which of the following statements is most accurate regarding this mutation?

EGFR exon 20 insertions are generally resistant to first-, second-, and third-generation EGFR TKIs including osimertinib (Correct answer)
Exon 20 insertions are functionally identical to exon 19 deletions and respond equally to erlotinib
Osimertinib is the preferred first-line therapy for exon 20 insertions due to superior CNS penetration
Amivantamab is approved for exon 20 insertions as first-line therapy regardless of prior treatment

Correct answer: EGFR exon 20 insertions are generally resistant to first-, second-, and third-generation EGFR TKIs including osimertinib

EGFR exon 20 insertion mutations represent approximately 4–10% of EGFR mutations and are notably resistant to standard EGFR TKIs (erlotinib, afatinib, dacomitinib, and osimertinib) due to steric hindrance preventing drug binding at the active site. FDA-approved agents specifically for exon 20 insertions include amivantamab (EGFR/MET bispecific antibody) and mobocertinib, both approved for platinum-pretreated patients (not first-line). Osimertinib is the standard of care for exon 19 deletions and exon 21 L858R mutations, NOT for exon 20 insertions.

Question 231: A 55-year-old man is being weaned from mechanical ventilation after 10 days for ARDS. He passes a spontaneous breathing trial (SBT) using PSV 5/PEEP 5 for 30 minutes with stable vitals and adequate oxygenation. What is the NEXT most important assessment before extubation?

Echocardiogram to rule out cardiac dysfunction
Assessment of airway patency, cough strength, and secretion management (Correct answer)
24-hour sedation holiday before attempting extubation
Repeat ABG to confirm PaO2 >80 mmHg

Correct answer: Assessment of airway patency, cough strength, and secretion management

After a successful SBT, the primary determinant of extubation success is the ability to protect and maintain the airway, including adequate cough strength and secretion clearance.

Question 232: A 44-year-old nonsmoking woman presents with progressive dyspnea and diffuse cystic lung disease on CT. She also has recurrent pneumothoraces and chylothorax. Serum VEGF-D is markedly elevated. What is the MOST likely diagnosis?

Birt-Hogg-Dubé syndrome
Pulmonary emphysema
Pulmonary Langerhans cell histiocytosis
Lymphangioleiomyomatosis (LAM) (Correct answer)

Correct answer: Lymphangioleiomyomatosis (LAM)

LAM presents in women of childbearing age with diffuse thin-walled cysts, chylothorax, recurrent pneumothorax, and markedly elevated serum VEGF-D (>800 pg/mL is diagnostic).

Question 233: A 30-year-old pregnant woman at 32 weeks develops BP of 158/102 mmHg, 3+ proteinuria, and a platelet count of 82,000/µL with elevated LDH. What is the most appropriate next step?

IV magnesium only and recheck labs in 24 hours
Oral nifedipine and close outpatient monitoring
Emergent delivery after maternal stabilization (Correct answer)
IV labetalol and expectant management until 37 weeks

Correct answer: Emergent delivery after maternal stabilization

HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) at ≥32 weeks warrants delivery after maternal stabilization with magnesium and antihypertensives.

Question 234: A 45-year-old woman with rheumatic mitral stenosis (MVA 1.1 cm², mean gradient 12 mmHg) presents 32 weeks pregnant with worsening dyspnea (NYHA Class III). Echo shows pliable leaflets, no significant MR, and Wilkins score 6. She has no left atrial thrombus on TEE. Which intervention is most appropriate?

Optimize heart rate control with beta-blocker, deliver at 36–37 weeks, and perform PMBC postpartum
Percutaneous mitral balloon commissurotomy (PMBC) under fluoroscopic guidance (Correct answer)
Cesarean delivery followed by mitral valve replacement postpartum
Closed surgical mitral commissurotomy

Correct answer: Percutaneous mitral balloon commissurotomy (PMBC) under fluoroscopic guidance

Percutaneous mitral balloon commissurotomy (PMBC) is the procedure of choice for symptomatic mitral stenosis in pregnancy when valve anatomy is favorable (Wilkins score ≤8, pliable leaflets, no significant MR, no LA thrombus). At 32 weeks with NYHA Class III symptoms, medical therapy alone is unlikely to suffice until delivery, and waiting carries significant maternal and fetal risk. PMBC can be performed safely in the second and third trimester with abdominal shielding to minimize fetal radiation exposure. Surgical commissurotomy carries significant maternal and fetal mortality. Mitral valve replacement during pregnancy carries fetal mortality of 20–30% with mechanical valves and anticoagulation risks.

Question 235: Which of the following is a common first-line treatment for stable angina?

Calcium channel blockers and statins
Aspirin and nitrates (Correct answer)
ACE inhibitors and diuretics
Beta-blockers and anticoagulants

Correct answer: Aspirin and nitrates

Aspirin and nitrates are common first-line treatments for stable angina. Aspirin helps prevent clot formation and reduces the risk of myocardial infarction, while nitrates provide rapid relief of anginal symptoms by causing vasodilation and reducing myocardial oxygen demand. This combination addresses both symptom management and cardiovascular event prevention.

Question 236: A 61-year-old man with a 20-year history of well-controlled Crohn's disease on azathioprine presents with painless jaundice, pruritus, and a 12 kg weight loss over 4 months. CT scan shows a 3.5 cm hypodense mass in the pancreatic head and dilated intrahepatic ducts. CA 19-9 is 9 U/mL (normal). Serum IgG4 is 620 mg/dL (normal <140). What is the most critical next step before proceeding to Whipple resection?

Initiate a 2–4 week steroid trial and reassess imaging to exclude IgG4-related disease (Correct answer)
Check serum IgG subclass panel and repeat IgG4 in 4 weeks
Order EUS-FNA of the pancreatic mass to confirm pancreatic adenocarcinoma
Proceed to surgery; IgG4 elevation in the context of mass lesion is likely spurious

Correct answer: Initiate a 2–4 week steroid trial and reassess imaging to exclude IgG4-related disease

A markedly elevated IgG4 (>2× upper limit of normal, here ~4.4× ULN) in the context of obstructive jaundice and a pancreatic mass raises serious concern for type 1 autoimmune pancreatitis (AIP), which can mimic pancreatic adenocarcinoma on imaging. AIP is dramatically steroid-responsive; a short empirical steroid trial (prednisone 40 mg/day for 2–4 weeks) with repeat imaging is an established diagnostic maneuver recommended by international consensus (HISORt criteria). If the mass resolves or significantly decreases, AIP is confirmed and surgery is avoided. Proceeding directly to Whipple risks unnecessary major surgery for a benign, treatable condition. EUS-FNA has poor sensitivity for AIP and may not be conclusive.

Question 237: A patient on warfarin for atrial fibrillation presents with INR of 8.4 but has no active bleeding. What is the most appropriate management?

Hold warfarin and administer IV vitamin K plus fresh frozen plasma
Continue warfarin and recheck INR in 24 hours
Hold warfarin and administer oral vitamin K (Correct answer)
Administer 4-factor prothrombin complex concentrate (PCC)

Correct answer: Hold warfarin and administer oral vitamin K

For supratherapeutic INR without active bleeding, holding warfarin and giving oral vitamin K to gradually lower the INR is the appropriate management.

Question 238: A 66-year-old woman is started on amiodarone for persistent atrial fibrillation. Six months later she presents with dyspnea and is found to have bilateral pleural effusions and a diffuse interstitial infiltrate on CT chest. PFTs show a restrictive pattern with DLCO 52% predicted. Bronchoscopy with BAL shows foamy macrophages. Which of the following is the most appropriate next step?

Discontinue amiodarone, switch to an alternative antiarrhythmic, and initiate corticosteroids (Correct answer)
Reduce amiodarone dose to 100 mg daily and repeat PFTs in 3 months
Continue amiodarone and add high-dose prednisone 60 mg daily
Discontinue amiodarone only; corticosteroids are not indicated for amiodarone pulmonary toxicity

Correct answer: Discontinue amiodarone, switch to an alternative antiarrhythmic, and initiate corticosteroids

Amiodarone pulmonary toxicity (APT) is a life-threatening complication occurring in 1-5% of patients. The combination of new restrictive physiology, reduced DLCO, bilateral infiltrates, and foamy macrophages on BAL (pathognomonic phospholipidosis from drug accumulation) confirms the diagnosis. Management requires: (1) discontinuation of amiodarone — dose reduction is insufficient as the drug's half-life is 40-55 days and tissue accumulation persists; (2) initiation of corticosteroids (prednisone 40-60 mg/day) because inflammation-mediated injury responds to steroids and untreated APT has >10% mortality; (3) substitution with an alternative rhythm control agent (e.g., dofetilide, dronedarone, or rate control strategy). Continuing amiodarone even with steroids allows ongoing pulmonary injury. Corticosteroids ARE indicated given the severity of presentation.

Question 239: A 45-year-old man with HIV (CD4 50 cells/µL) presents with fever, headache, and neck stiffness. CSF shows elevated protein, low glucose, and India ink positive organisms. What is the first-line treatment?

Liposomal amphotericin B plus flucytosine (Correct answer)
Micafungin IV
Voriconazole IV
Fluconazole 400mg daily

Correct answer: Liposomal amphotericin B plus flucytosine

Cryptococcal meningitis in HIV patients is treated with induction therapy using liposomal amphotericin B plus flucytosine for 2 weeks, followed by fluconazole consolidation.

Question 240: A 55-year-old man with type 2 diabetes and chronic kidney disease (eGFR 28 mL/min) has a recent STEMI with residual EF of 35%. He is initiated on guideline-directed medical therapy. Which agent from the following list provides BOTH cardiovascular mortality reduction AND slowing of CKD progression in this patient population, independent of glycemic control?

Sitagliptin (DPP-4 inhibitor)
Empagliflozin (SGLT2 inhibitor) (Correct answer)
Exenatide (GLP-1 receptor agonist)
Pioglitazone (thiazolidinedione)

Correct answer: Empagliflozin (SGLT2 inhibitor)

SGLT2 inhibitors (e.g., empagliflozin, dapagliflozin) have demonstrated cardiovascular mortality reduction in patients with HFrEF (EMPEROR-Reduced, DAPA-HF) and nephroprotective effects (EMPA-KIDNEY, CREDENCE) independent of glucose lowering. They are now guideline-recommended in HFrEF with or without diabetes. Sitagliptin showed neutral CV effects (TECOS) with no renal benefit. GLP-1 agonists reduce MACE but lack robust HF and CKD benefit in this specific population. Pioglitazone causes fluid retention and worsens HF — it is contraindicated in this setting.

Question 241: A 55-year-old woman undergoes laparoscopic right adrenalectomy for a 3.4 cm adrenal incidentaloma. Preoperative workup showed post-1 mg DST cortisol of 4.1 mcg/dL (subclinical autonomous cortisol secretion), normal urine metanephrines, and normal aldosterone/renin ratio. On postoperative day 1 she develops fatigue, nausea, and hypotension unresponsive to 2L IV normal saline. Her plasma ACTH is undetectable. What is the most appropriate immediate next step?

Administer IV hydrocortisone 100 mg immediately (Correct answer)
Start fludrocortisone 0.1 mg daily for mineralocorticoid deficiency alone
Perform a high-dose cosyntropin stimulation test before initiating steroids
Obtain a morning serum cortisol before any intervention

Correct answer: Administer IV hydrocortisone 100 mg immediately

This patient is in adrenal crisis due to HPA axis suppression by the chronically autonomous cortisol production of the resected adenoma. Even subclinical hypercortisolism suppresses the contralateral adrenal cortex and the hypothalamic-pituitary axis. Postoperative hypotension, nausea, and undetectable ACTH in this context represent an endocrine emergency. Treatment must not be delayed for diagnostic testing — IV hydrocortisone should be given immediately. After stabilization, a cosyntropin stimulation test can assess recovery of the contralateral adrenal.

Question 242: A patient with AML achieves complete remission after induction chemotherapy. Cytogenetics show inv(16). Which post-remission strategy is preferred?

Autologous stem cell transplant
Allogeneic stem cell transplant
High-dose cytarabine consolidation (Correct answer)
Maintenance azacitidine

Correct answer: High-dose cytarabine consolidation

Inv(16) is a favorable-risk cytogenetic abnormality in AML; high-dose cytarabine consolidation achieves excellent outcomes without the added toxicity of transplant.

Question 243: A 55-year-old woman with recently diagnosed hypersensitivity pneumonitis (HP) is found to have a pet cockatiel at home. After antigen avoidance, symptoms persist and DLCO is 52% predicted. Which finding on surgical lung biopsy would indicate chronic fibrotic HP rather than subacute HP?

Diffuse alveolar damage with hyaline membranes
Non-caseating granulomas with giant cells
Eosinophilic infiltrates with mucous plugging
Peribronchiolar fibrosis with architectural distortion and honeycombing (Correct answer)

Correct answer: Peribronchiolar fibrosis with architectural distortion and honeycombing

Chronic fibrotic HP is characterized by peribronchiolar fibrosis, bronchiolocentricity, and architectural distortion (including honeycombing), distinguishing it from subacute HP which shows granulomas without fibrosis.

Question 244: A 32-year-old woman presents to the ICU with status asthmaticus unresponsive to nebulized bronchodilators, systemic corticosteroids, and magnesium sulfate. She is becoming fatigued. ABG: pH 7.32, PaCO2 50 mmHg. What does the rising PaCO2 indicate in this context?

Adequate compensation for metabolic acidosis
Hyperventilation-induced hypocapnia returning to baseline
Successful bronchodilation reducing dynamic hyperinflation
Impending respiratory failure requiring preparation for intubation (Correct answer)

Correct answer: Impending respiratory failure requiring preparation for intubation

In an asthmatic who was initially hyperventilating (low PaCO2), normalization or rising PaCO2 indicates muscle fatigue and impending respiratory failure requiring intubation preparation.

Question 245: A 49-year-old woman with scleroderma-associated interstitial lung disease (ILD) develops progressive dyspnea over 3 months. HRCT shows new bilateral ground-glass opacities predominantly in the upper and mid-lung zones overlying a background of subpleural reticulation with honeycombing at the bases. PFTs show a rapid decline: FVC dropped from 72% to 54% predicted over 6 months. Anti-topoisomerase I (Scl-70) antibody is strongly positive. Bronchoscopic BAL shows 38% lymphocytes. Which of the following management decisions is BEST supported by current evidence?

Perform surgical lung biopsy to distinguish UIP from NSIP pattern before initiating any treatment
Initiate rituximab, as anti-Scl-70 positivity with BAL lymphocytosis defines a rituximab-responsive phenotype
Start nintedanib given the rapid FVC decline, recognizing it slows progression in SSc-ILD regardless of inflammatory activity (Correct answer)
Start high-dose methylprednisolone 1 mg/kg/day, given the BAL lymphocytosis suggesting an inflammatory, steroid-responsive process

Correct answer: Start nintedanib given the rapid FVC decline, recognizing it slows progression in SSc-ILD regardless of inflammatory activity

Nintedanib is FDA-approved for SSc-ILD based on the SENSCIS trial, which demonstrated a significant reduction in FVC decline rate regardless of background immunosuppression. This patient has an alarming 18% absolute FVC decline in 6 months (severe progression), which is a clear indication to escalate therapy with an antifibrotic. High-dose corticosteroids in SSc-ILD carry substantial risks (including scleroderma renal crisis) and are not supported by evidence as a first-line or high-dose therapy — mycophenolate or low-dose prednisone are the immunosuppressive backbone. BAL lymphocytosis in the setting of SSc is a nonspecific finding and does not reliably predict steroid responsiveness. While rituximab has emerging evidence in SSc-ILD, it is not defined by anti-Scl-70 positivity specifically, and there is no validated biomarker-based indication. Surgical biopsy is high-risk and not needed when HRCT + clinical context are diagnostic of SSc-ILD, especially with active progression requiring urgent treatment.

Question 246: A 28-year-old woman presents with amenorrhea, galactorrhea, and a serum prolactin of 340 ng/mL. MRI reveals a 1.8 cm pituitary macroadenoma. She is started on cabergoline 0.5 mg twice weekly. After 6 months, prolactin normalizes and the tumor shrinks 60%, but she reports new-onset compulsive gambling and hypersexuality. What is the most appropriate next step?

Discontinue cabergoline and initiate bromocriptine (Correct answer)
Reduce cabergoline dose and add bromocriptine
Refer for transsphenoidal surgery immediately
Add an SSRI and continue cabergoline at the same dose

Correct answer: Discontinue cabergoline and initiate bromocriptine

Impulse control disorders (ICDs) — including pathological gambling, hypersexuality, binge eating, and compulsive shopping — are a recognized class effect of dopamine agonists, particularly cabergoline, due to stimulation of mesolimbic D3/D4 receptors. When ICDs develop, cabergoline should be discontinued. Bromocriptine has a lower affinity for extrastriatal dopamine receptors and a substantially lower risk of ICD and is the preferred alternative. Simply reducing cabergoline may not eliminate the risk and may compromise tumor control. Surgery is indicated for dopamine agonist resistance or intolerance, not as the first step when an alternative agonist is available. Adding an SSRI does not address the dopaminergic mechanism driving the ICD.

Question 247: A 55-year-old man with idiopathic pulmonary fibrosis (IPF) has FVC 65% predicted and DLCO 48% predicted. Honeycombing is present on HRCT. Which medication has been shown to slow FVC decline in IPF?

Azathioprine 150 mg/day
Nintedanib 150 mg twice daily (Correct answer)
N-acetylcysteine 600 mg three times daily
Prednisone 60 mg/day

Correct answer: Nintedanib 150 mg twice daily

Nintedanib (and pirfenidone) are the only FDA-approved antifibrotic agents that slow FVC decline in IPF; corticosteroids and azathioprine increase mortality in IPF.

Question 248: A 58-year-old woman with rheumatic mitral stenosis presents with progressive dyspnea. Echocardiography shows a mitral valve area of 1.3 cm², mean gradient of 7 mmHg, and a Wilkins score of 6. She has mild mitral regurgitation and no left atrial thrombus on TEE. Which intervention is most appropriate?

Medical management with beta-blockers and anticoagulation
Mitral valve replacement with mechanical prosthesis
Percutaneous mitral balloon commissurotomy (PMBC) (Correct answer)
Mitral valve repair via open commissurotomy

Correct answer: Percutaneous mitral balloon commissurotomy (PMBC)

PMBC is indicated for symptomatic severe mitral stenosis (MVA ≤1.5 cm²) when valve morphology is favorable (Wilkins score ≤8), there is no significant MR (mild is acceptable), and no left atrial thrombus. This patient meets all criteria. A Wilkins score of 6 indicates excellent valve pliability, with expected good procedural outcomes. Surgical options are reserved for patients with unfavorable anatomy (Wilkins >8), significant MR (≥moderate), or left atrial thrombus.

Question 249: A 45-year-old man with a history of dyspepsia undergoes an upper endoscopy which reveals a 1.5 cm duodenal ulcer. A biopsy is positive for Helicobacter pylori. The patient has no known drug allergies. The local clarithromycin resistance rate is known to be over 20%. Which of the following is the most appropriate first-line eradication therapy?

A proton pump inhibitor (PPI) and amoxicillin for 10 days
A proton pump inhibitor (PPI), bismuth subsalicylate, metronidazole, and tetracycline for 14 days (Correct answer)
A proton pump inhibitor (PPI), clarithromycin, and amoxicillin for 14 days
A proton pump inhibitor (PPI), metronidazole, and amoxicillin for 14 days

Correct answer: A proton pump inhibitor (PPI), bismuth subsalicylate, metronidazole, and tetracycline for 14 days

In regions where the clarithromycin resistance rate is high (>15-20%), standard clarithromycin-based triple therapy is no longer recommended as first-line treatment due to low eradication rates. The American College of Gastroenterology (ACG) guidelines recommend bismuth quadruple therapy (a PPI, bismuth, metronidazole, and tetracycline) for 14 days as a preferred first-line option in this scenario.

Question 250: A 48-year-old woman has fatigue, weight gain, constipation, and bradycardia. TSH is 48 mIU/L and free T4 is undetectable. She takes no medications. What is the most appropriate initial treatment?

Levothyroxine 1.6 mcg/kg/day
Levothyroxine 25 mcg/day with gradual titration (Correct answer)
Desiccated thyroid extract
Liothyronine (T3) alone

Correct answer: Levothyroxine 25 mcg/day with gradual titration

In severe hypothyroidism, especially in older adults or those with cardiac risk, levothyroxine should be started at a low dose (25–50 mcg/day) and titrated slowly to avoid precipitating cardiac ischemia or arrhythmia.

Question 251: A 65-year-old man with cirrhosis and ascites develops acute kidney injury. Creatinine rises from 1.0 to 2.6 mg/dL over 48 hours despite albumin infusion and diuretic discontinuation. Urine sodium is <10 mEq/L. What is the most likely diagnosis?

Contrast nephropathy
Prerenal azotemia
Hepatorenal syndrome (Correct answer)
Acute tubular necrosis

Correct answer: Hepatorenal syndrome

Hepatorenal syndrome (HRS) is characterized by functional renal failure in cirrhotic patients with very low urine sodium (<10), absence of improvement with volume expansion, and no intrinsic renal disease.

Question 252: During rounds in the medical ICU, you review a patient's ventilator waveforms. The flow-time scalar shows flow not returning to zero before the next breath is delivered, and the pressure-time scalar shows an initial negative deflection at the start of each breath followed by a rapid pressure rise. The patient is on volume-assist control. Which of the following best explains these findings and their clinical consequence?

Patient-ventilator dyssynchrony from flow starvation causing breath stacking and dynamic hyperinflation
Double-triggering due to neural inspiratory time exceeding set ventilator inspiratory time
Auto-PEEP from intrinsic PEEP causing ineffective triggering and increased work of breathing (Correct answer)
Reverse triggering: ventilator-initiated breaths entraining diaphragmatic contractions, increasing VILI risk

Correct answer: Auto-PEEP from intrinsic PEEP causing ineffective triggering and increased work of breathing

The flow-time waveform showing flow not returning to zero indicates gas trapping (auto-PEEP). The negative pressure deflection at breath onset reflects the patient's effort needed to overcome auto-PEEP before the ventilator triggers, dramatically increasing work of breathing. This is distinct from reverse triggering (which occurs in deeply sedated patients without spontaneous respiratory drive) and flow starvation (which causes a 'scooped' pressure waveform, not a negative deflection). Double-triggering produces two pressure spikes in rapid succession. Auto-PEEP must be measured with an expiratory hold maneuver and addressed by reducing respiratory rate, increasing expiratory time, or adjusting PEEP settings.

Question 253: A 52-year-old man with a 35 pack-year smoking history presents with a 3 cm right upper lobe mass. CT-PET shows hypermetabolic activity in the mass (SUV 12) and a single ipsilateral mediastinal node at station 4R (SUV 4.1). Endobronchial ultrasound-guided biopsy (EBUS) of station 4R is performed and cytology shows no malignant cells. Pulmonary function is adequate for resection. What is the most appropriate next step?

Proceed directly to surgical resection with mediastinal lymph node dissection, as EBUS was negative
Mediastinoscopy to further sample station 4R before any surgical resection (Correct answer)
Initiate concurrent chemoradiotherapy as this is unresectable Stage IIIA disease
Repeat PET-CT in 3 months to assess for interval change before proceeding

Correct answer: Mediastinoscopy to further sample station 4R before any surgical resection

A PET-positive mediastinal node with a negative EBUS creates a discordant result. Per ACCP and ESTS guidelines, a PET-positive node that is EBUS/EUS-negative requires surgical staging (mediastinoscopy or VATS) before proceeding to resection, because false-negative EBUS rates can reach 20–30% in this scenario. Proceeding directly to resection risks incomplete staging and potentially leaving behind N2 disease that would change the treatment plan. Mediastinoscopy remains the gold standard for confirming or excluding N2 disease when less invasive methods are negative in the setting of a PET-positive node. Chemoradiotherapy without confirmed N2 disease would be premature.

Question 254: A 45-year-old woman presents with episodic hypertension, diaphoresis, and palpitations. 24-hour urine shows elevated normetanephrine but normal metanephrine. Plasma normetanephrine is 3.2× the upper limit of normal. MRI adrenals are unremarkable. What is the next most appropriate imaging study?

¹²³I-MIBG scintigraphy
CT chest/abdomen/pelvis with contrast
¹⁸F-FDOPA PET/CT (Correct answer)
⁶⁸Ga-DOTATATE PET/CT

Correct answer: ¹⁸F-FDOPA PET/CT

This presentation is consistent with a paraganglioma (extra-adrenal pheochromocytoma), given the predominant normetanephrine elevation and negative adrenal MRI. ¹⁸F-FDOPA PET/CT has the highest sensitivity for detecting head-and-neck and thoracic paragangliomas, and is the preferred functional imaging for biochemically confirmed pheochromocytoma/paraganglioma when conventional imaging is negative. ¹²³I-MIBG has lower sensitivity (~80%) and is less useful for head-and-neck paragangliomas. ⁶⁸Ga-DOTATATE is preferred for metastatic or SDHB-related paragangliomas. CT is less sensitive than functional imaging for occult lesions.

Question 255: Which of the following valvular conditions most commonly causes a late-peaking systolic murmur heard best at the right upper sternal border that radiates to the carotids?

Mitral valve prolapse
Hypertrophic obstructive cardiomyopathy
Aortic stenosis (Correct answer)
Pulmonary stenosis

Correct answer: Aortic stenosis

Severe aortic stenosis produces a harsh, late-peaking crescendo-decrescendo systolic murmur at the right upper sternal border radiating to the carotids; the later the peak, the more severe the stenosis.

Question 256: A 38-year-old woman presents with dyspnea and is found to have a systolic BP of 160/90 in both arms and diastolic murmur over the back. CXR shows rib notching. What is the diagnosis?

Coarctation of the aorta (Correct answer)
Essential hypertension
Renal artery stenosis
Marfan syndrome with aortic regurgitation

Correct answer: Coarctation of the aorta

Coarctation of the aorta presents with upper extremity hypertension, a diastolic murmur over the back from collaterals, and rib notching from intercostal artery enlargement.

Question 257: A 60-year-old male with long-standing GERD and Barrett's esophagus develops a dry cough and progressive dyspnea. HRCT shows basal-predominant reticulation with traction bronchiectasis and honeycombing. The BAL shows 6% lymphocytes. What is the most likely diagnosis?

Hypersensitivity pneumonitis
NSIP associated with GERD
Idiopathic pulmonary fibrosis (IPF) (Correct answer)
Cryptogenic organizing pneumonia

Correct answer: Idiopathic pulmonary fibrosis (IPF)

The HRCT pattern of bibasilar honeycombing with traction bronchiectasis represents UIP pattern, most consistent with IPF, even in the context of GERD; low BAL lymphocytes also favor IPF over HP.

Question 258: A 35-year-old competitive athlete collapses during a basketball game. Resuscitation is successful. ECG shows deep T-wave inversions in V1–V4 and left axis deviation. His father died suddenly at age 40. What is the most likely diagnosis?

Long QT syndrome
Coronary artery vasospasm
Hypertrophic cardiomyopathy (HCM)
Arrhythmogenic right ventricular cardiomyopathy (ARVC) (Correct answer)

Correct answer: Arrhythmogenic right ventricular cardiomyopathy (ARVC)

ARVC characteristically presents with T-wave inversions in right precordial leads, ventricular arrhythmias triggered by exercise, and a family history of sudden death.

Question 259: A 65-year-old patient is mechanically ventilated in the ICU for pneumonia. The clinical team is discussing the sedation strategy. Which of the following approaches has been associated with improved clinical outcomes, including shorter duration of mechanical ventilation and ICU length of stay?

Using daily sedation interruptions combined with a protocol targeting light sedation (RASS 0 to -2) (Correct answer)
Administering continuous high-dose benzodiazepines without a daily awakening trial
Maintaining deep sedation (RASS -4 to -5) to ensure patient comfort and prevent ventilator recall
Avoiding all sedation and analgesia to promote rapid extubation

Correct answer: Using daily sedation interruptions combined with a protocol targeting light sedation (RASS 0 to -2)

Maintaining a light level of sedation (e.g., Richmond Agitation-Sedation Scale [RASS] 0 to -2) in critically ill, mechanically ventilated patients is associated with better outcomes. Studies have shown that strategies combining daily interruptions of sedative infusions ('sedation vacations') with protocols that target light sedation lead to a shorter duration of mechanical ventilation, reduced ICU length of stay, and decreased incidence of delirium without increasing psychological stress. Deep sedation is associated with adverse outcomes, while avoiding all sedation may not be feasible or safe for all patients.

Question 260: A 29-year-old woman presents with recurrent episodes of severe epigastric pain, nausea, and elevated lipase (peak 1,800 U/L) over the past 2 years. She has no gallstones, drinks no alcohol, takes no medications, and has normal triglycerides. Genetic testing reveals a heterozygous SPINK1 N34S variant and a heterozygous CFTR F508del variant. MRCP is normal. What is the pathophysiologic basis for her recurrent pancreatitis?

SPINK1 mutations directly activate trypsinogen, triggering autodigestion
The CFTR F508del variant causes exocrine pancreatic insufficiency that secondarily activates inflammatory cascades
Compound heterozygosity creates a threshold effect that overwhelms pancreatic trypsin inhibitor capacity (Correct answer)
CFTR mutations alone cause ductal obstruction sufficient to trigger recurrent acute pancreatitis

Correct answer: Compound heterozygosity creates a threshold effect that overwhelms pancreatic trypsin inhibitor capacity

SPINK1 encodes the pancreatic secretory trypsin inhibitor (PSTI), which serves as a fail-safe by inhibiting prematurely activated trypsin. The N34S variant reduces PSTI inhibitory capacity but alone is insufficient to cause disease (present in ~2% of the general population). CFTR mutations impair ductal bicarbonate secretion and fluid flow, increasing pancreatic juice viscosity and acinar cell stress. The combination (compound heterozygosity) creates a threshold effect: each variant independently provides a modest susceptibility, but together they overwhelm compensatory mechanisms — a 'two-hit' model. SPINK1 does not directly activate trypsinogen; it inhibits trypsin. CFTR mutations alone rarely cause recurrent acute pancreatitis without additional modifiers. F508del does cause exocrine insufficiency in cystic fibrosis, but this is not the mechanism driving acute pancreatitis.

Question 261: A 52-year-old woman with massive hemoptysis (>600 mL in 24 hours) from a left lower lobe cavitary lesion is hemodynamically stable. What is the MOST appropriate immediate management?

Bronchial artery embolization
Position patient with left side down and consult interventional radiology (Correct answer)
Rigid bronchoscopy with Fogarty balloon tamponade
Emergent left pneumonectomy

Correct answer: Position patient with left side down and consult interventional radiology

In massive hemoptysis, positioning the bleeding lung in the dependent (down) position protects the unaffected lung and is the immediate stabilizing maneuver before definitive treatment.

Question 262: A 52-year-old woman with primary biliary cholangitis (PBC) on ursodeoxycholic acid presents with pruritus, fatigue, and an alkaline phosphatase that remains 3× the upper limit of normal after 12 months of therapy. LFTs show ALT 55 U/L, bilirubin 1.1 mg/dL. Which second-line agent is most appropriate to add?

Cholestyramine
Obeticholic acid (Correct answer)
Rifampin
Fibrate (bezafibrate)

Correct answer: Obeticholic acid

Obeticholic acid (OCA), a farnesoid X receptor agonist, is FDA-approved as second-line therapy for PBC in patients with inadequate response to UDCA, defined as alkaline phosphatase ≥1.67× ULN and/or elevated bilirubin after 12 months. Cholestyramine and rifampin target pruritus symptomatically but do not alter disease progression. Fibrates (bezafibrate/fenofibrate) are used off-label in some European guidelines but are not FDA-approved for PBC. OCA is the guideline-endorsed add-on in this scenario.

Question 263: A 62-year-old male with a 10-year history of type 2 diabetes mellitus and a prior myocardial infarction has an HbA1c of 7.8% on metformin monotherapy. His eGFR is 65 mL/min/1.73m². According to the most recent American Diabetes Association (ADA) guidelines, which of the following medications would be the most appropriate addition to his regimen?

Sitagliptin
Pioglitazone
Empagliflozin (Correct answer)
Glipizide

Correct answer: Empagliflozin

For patients with type 2 diabetes and established atherosclerotic cardiovascular disease (ASCVD), guidelines strongly recommend adding an agent with proven cardiovascular benefit. Empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, has demonstrated a significant reduction in major adverse cardiovascular events, cardiovascular mortality, and hospitalization for heart failure in this patient population. Glipizide (a sulfonylurea) increases insulin secretion but carries a risk of hypoglycemia and is cardiovascular neutral. Sitagliptin (a DPP-4 inhibitor) is also weight and cardiovascular neutral. Pioglitazone (a thiazolidinedione) can cause weight gain and fluid retention, and should be used with caution in patients at risk for heart failure.

Question 264: A 40-year-old HIV-positive man (CD4 40) on antiretrovirals develops vision loss. Fundoscopic exam shows yellow-white perivascular exudates with hemorrhage ('pizza pie' appearance). What is the diagnosis and treatment?

Ocular histoplasmosis; itraconazole
CMV retinitis; IV ganciclovir or oral valganciclovir (Correct answer)
Cryptococcal chorioretinitis; fluconazole
Toxoplasma retinitis; pyrimethamine plus sulfadiazine

Correct answer: CMV retinitis; IV ganciclovir or oral valganciclovir

CMV retinitis in advanced AIDS presents with the classic 'pizza pie' fundoscopic appearance and is treated with valganciclovir 900mg BID for induction followed by maintenance therapy.

Question 265: A 70-year-old man undergoes hip arthroplasty and develops fever and wound drainage at day 14. Joint aspiration grows MRSA. What is the antibiotic of choice for MRSA prosthetic joint infection?

Linezolid 600mg BID
Daptomycin 6mg/kg IV daily
Cefazolin 2g IV q8h
Vancomycin IV dosed to trough 15-20 mcg/mL (Correct answer)

Correct answer: Vancomycin IV dosed to trough 15-20 mcg/mL

Vancomycin IV remains the standard of care for MRSA prosthetic joint infections, typically combined with rifampin for biofilm penetration in device-associated infections.

Question 266: A 52-year-old man undergoes selective inferior petrosal sinus sampling (IPSS) for suspected Cushing's disease. Basal central-to-peripheral ACTH ratio is 1.8. After CRH stimulation, the ratio rises to 2.4 on the right side and 1.6 on the left. MRI of the pituitary is unremarkable. What is the most appropriate next step in management?

Diagnose ectopic ACTH syndrome and proceed with CT chest/abdomen/pelvis
Repeat IPSS with simultaneous bilateral sampling under strict catheter position verification
Order repeat 24-hour urine free cortisol and late-night salivary cortisol to confirm hypercortisolism
Proceed with right-sided selective transsphenoidal exploration targeting the right hemipituitary (Correct answer)

Correct answer: Proceed with right-sided selective transsphenoidal exploration targeting the right hemipituitary

An IPSS central-to-peripheral ACTH ratio ≥ 2 basal or ≥ 3 post-CRH confirms pituitary-source Cushing's disease with ~95% sensitivity and specificity. Here the post-CRH ratio is 2.4 on the right (≥ 2 is sufficient for lateralization when ≥ 3 threshold is not reached, though many centers use ≥ 1.4 lateralization ratio). Since pituitary source is confirmed (post-CRH ratio 2.4 > 2.0) and lateralization favors the right, right-sided hemipituitary exploration is appropriate even with a negative MRI — approximately 40–60% of corticotroph adenomas are MRI-occult. Ectopic ACTH is excluded by the central-to-peripheral gradient. Repeating biochemical confirmation is unnecessary after IPSS confirmation. Repeating IPSS is not indicated when the procedure was technically successful.

Question 267: During management of a patient with massive hemoptysis (>600 mL/24 hrs) due to a right-sided cavitary lesion, the patient is intubated with a standard ETT and placed in the lateral decubitus position. After initial bronchoscopy confirms bleeding from the right upper lobe, the patient becomes hypoxic (SpO2 72%) and hemodynamic status deteriorates. Which of the following interventions is most immediately appropriate to stabilize oxygenation?

Insert a bronchial blocker into the right mainstem bronchus via the current ETT
Initiate veno-venous ECMO for refractory hypoxemia
Advance the ETT into the left mainstem bronchus to isolate and protect the non-bleeding lung (Correct answer)
Place a rigid bronchoscope and apply endobronchial tamponade to the right upper lobe

Correct answer: Advance the ETT into the left mainstem bronchus to isolate and protect the non-bleeding lung

In the acute setting of massive hemoptysis with hemodynamic compromise and severe hypoxemia, the most immediately life-saving maneuver is isolation of the non-bleeding (left) lung by advancing the ETT into the left mainstem bronchus. This prevents aspiration of blood into the good lung and allows oxygenation to continue from the unaffected side. A bronchial blocker (option D) is also a valid approach but requires bronchoscopic guidance and takes more time to position correctly — advancing the ETT into the left mainstem can be done rapidly and blindly in extremis. Rigid bronchoscopy with tamponade is an excellent definitive intervention but requires additional setup time and personnel. VV-ECMO is not appropriate as the first-line emergency maneuver when simpler airway maneuvers can rapidly restore oxygenation.

Question 268: A 25-year-old woman with type 1 diabetes uses an insulin pump. She is found unconscious by her roommate. Glucometer reads 28 mg/dL. IV access cannot be obtained. What is the immediate treatment?

Oral glucose gel under the tongue
Dextrose 50% sublingual
Glucagon 1 mg intramuscularly (Correct answer)
Halt the insulin pump only

Correct answer: Glucagon 1 mg intramuscularly

Glucagon IM (or subcutaneously) is the appropriate treatment for severe hypoglycemia when IV access is unavailable and the patient cannot safely take oral glucose.

Question 269: A 48-year-old woman presents with progressive proximal muscle weakness and difficulty rising from a chair. CK is 3500 U/L. ANA is positive. What is the most likely diagnosis?

Myasthenia gravis
Multiple sclerosis
Polymyositis (Correct answer)
Fibromyalgia

Correct answer: Polymyositis

Polymyositis presents with symmetric proximal muscle weakness, elevated CK, and positive ANA; EMG and muscle biopsy confirm the diagnosis.

Question 270: A 49-year-old man with newly diagnosed hepatocellular carcinoma (HCC) has a single lesion measuring 3.8 cm in a cirrhotic liver (Child-Pugh A, ECOG 0). No vascular invasion or extrahepatic spread is seen on imaging. He is placed on the transplant waitlist (Milan criteria met). While awaiting transplant, locoregional therapy is being considered. Which statement best reflects current evidence regarding bridging therapy?

Transarterial chemoembolization (TACE) is the preferred bridging modality and has been shown in randomized trials to improve post-transplant survival compared to no treatment
Stereotactic body radiation therapy (SBRT) is contraindicated as bridging for HCC in cirrhosis due to high rates of radiation-induced liver disease
Bridging therapy is recommended to reduce dropout risk from waitlist progression, though no randomized trial has proven a post-transplant survival benefit over no bridging (Correct answer)
Thermal ablation (RFA/MWA) should not be used for lesions >3 cm because complete ablation is uniformly unachievable

Correct answer: Bridging therapy is recommended to reduce dropout risk from waitlist progression, though no randomized trial has proven a post-transplant survival benefit over no bridging

Bridging locoregional therapy (TACE, ablation, SBRT, Y-90) for HCC while awaiting transplant is widely recommended to prevent waitlist dropout due to tumor progression beyond Milan criteria. However, no randomized controlled trial has demonstrated a statistically significant improvement in post-transplant recurrence-free or overall survival compared to observation alone — the benefit is in reducing dropout, not necessarily improving post-transplant outcomes. SBRT is an accepted bridging modality in cirrhosis when technically appropriate. RFA/MWA can achieve complete ablation for lesions 3–5 cm, particularly with microwave technology, though rates are lower than for <3 cm lesions.

Question 271: A 29-year-old woman with obesity (BMI 41) and no other comorbidities presents with excessive daytime sleepiness, morning headaches, and bilateral papilledema on fundoscopic exam. Polysomnography shows AHI 52 events/hour, mean SaO2 88%, with prolonged periods of hypoventilation. Arterial blood gas while awake shows pH 7.37, PaCO2 52 mmHg, PaO2 62 mmHg, HCO3 30 mEq/L. Serum bicarbonate elevation is consistent with chronic compensation. Which diagnostic criterion BEST supports a diagnosis of Obesity Hypoventilation Syndrome (OHS) rather than OSA with nocturnal hypoventilation alone?

Awake daytime hypercapnia (PaCO2 ≥45 mmHg) in the absence of other causes of hypoventilation (Correct answer)
BMI greater than 35 kg/m² with Epworth Sleepiness Scale score above 10
AHI greater than 30 events/hour on polysomnography
Nocturnal SaO2 nadir below 85% on polysomnography

Correct answer: Awake daytime hypercapnia (PaCO2 ≥45 mmHg) in the absence of other causes of hypoventilation

The cardinal diagnostic criterion for Obesity Hypoventilation Syndrome (OHS) is awake daytime hypercapnia (PaCO2 ≥45 mmHg) in an obese patient (BMI ≥30) after excluding other causes of hypoventilation (e.g., COPD, neuromuscular disease, chest wall deformity, hypothyroidism). This patient's awake PaCO2 of 52 mmHg with elevated bicarbonate confirms chronic daytime CO2 retention. OSA alone — even with severe nocturnal desaturation — does not cause daytime hypercapnia in the absence of impaired ventilatory control. The AHI, nocturnal SaO2 nadir, BMI threshold, and ESS score are not diagnostic of OHS; they suggest OSA but cannot distinguish it from OHS without the daytime gas exchange criterion.

Question 272: A 52-year-old man with cirrhosis presents with fever, altered mental status, and nuchal rigidity. CSF shows: WBC 1,800 cells/µL (95% PMNs), glucose 28 mg/dL (serum glucose 110 mg/dL), protein 380 mg/dL. Blood and CSF cultures are pending. He has a severe penicillin allergy (anaphylaxis). Which empiric antibiotic regimen is most appropriate?

Trimethoprim-sulfamethoxazole plus vancomycin plus dexamethasone
Chloramphenicol plus rifampin plus dexamethasone
Aztreonam plus vancomycin plus dexamethasone
Meropenem plus vancomycin plus dexamethasone (Correct answer)

Correct answer: Meropenem plus vancomycin plus dexamethasone

This presentation is consistent with bacterial meningitis requiring empiric coverage for S. pneumoniae, N. meningitidis, and in a cirrhotic patient (immunocompromised), Listeria monocytogenes. Standard therapy (ceftriaxone + vancomycin + ampicillin) cannot be used given anaphylaxis to penicillin. Meropenem is the preferred carbapenem alternative — it has excellent CNS penetration and covers all three pathogens including Listeria (unlike aztreonam, which has no gram-positive or Listeria coverage). Vancomycin covers penicillin-resistant pneumococcus. Dexamethasone should be given with or before the first antibiotic dose. Aztreonam lacks gram-positive coverage entirely. Chloramphenicol has poor activity against Listeria and significant toxicity. TMP-SMX does not cover pneumococcus adequately in this acute setting.

Question 273: A 40-year-old man returns from a trip to sub-Saharan Africa with fever, chills, and headache starting 10 days after return. Peripheral blood smear shows ring forms in >5% of RBCs with multiple rings per cell. What is the treatment?

Atovaquone-proguanil plus doxycycline
IV artesunate (Correct answer)
Quinine plus doxycycline
Chloroquine 600mg base then 300mg at 6h, 24h, 48h

Correct answer: IV artesunate

Severe falciparum malaria (parasitemia >5%) requires IV artesunate, which is now available in the US and superior to IV quinine for severe disease.

Question 274: A 58-year-old woman with hypertrophic obstructive cardiomyopathy (HOCM) presents with worsening dyspnea and near-syncope. Echocardiography shows a resting LVOT gradient of 55 mmHg. She is currently on metoprolol 100 mg daily. Which of the following is the most appropriate next step?

Add disopyramide to her current regimen (Correct answer)
Add a loop diuretic to reduce preload
Refer for alcohol septal ablation
Discontinue metoprolol and start verapamil

Correct answer: Add disopyramide to her current regimen

Disopyramide is a Class IA antiarrhythmic with significant negative inotropic properties, making it highly effective for reducing LVOT obstruction in HOCM when added to a beta-blocker. The combination of metoprolol + disopyramide is guideline-recommended for symptomatic patients with persistent gradients despite beta-blocker monotherapy. Loop diuretics reduce preload and would worsen obstruction. Verapamil is an alternative to beta-blockers, not an add-on. Septal reduction therapy (ablation or myectomy) is reserved for patients who fail maximal medical therapy.

Question 275: A 29-year-old MSM presents with painful genital ulcers, tender inguinal lymphadenopathy, and a reactive RPR 1:64 with confirmatory TPPA. He reports a prior syphilis infection treated 3 years ago with benzathine penicillin G, with documented fourfold RPR decline to 1:4. His current neurological exam is normal, and LP is deferred. Which treatment is most appropriate?

Benzathine penicillin G 2.4 million units IM once (primary syphilis) (Correct answer)
Aqueous crystalline penicillin G IV for 10-14 days (neurosyphilis coverage)
Benzathine penicillin G 2.4 million units IM weekly for 3 doses (late latent protocol)
Doxycycline 100 mg orally twice daily for 28 days (late latent alternative)

Correct answer: Benzathine penicillin G 2.4 million units IM once (primary syphilis)

This patient has secondary syphilis (painful ulcer at primary site plus lymphadenopathy plus RPR 1:64 representing a fourfold or greater rise from documented nadir of 1:4). Secondary syphilis represents early syphilis (<1 year duration) and is treated with a single dose of benzathine penicillin G 2.4 million units IM — not the 3-dose regimen, which is reserved for late latent or latent syphilis of unknown duration. The 1:64 titer compared to a documented nadir of 1:4 (fourfold rise = 1:16 → 1:64) confirms reinfection rather than treatment failure. With a normal neurological exam and no ocular symptoms, LP is not required. IV penicillin is reserved for confirmed neurosyphilis.

Question 276: A 44-year-old woman is referred for evaluation of refractory ascites. She has no history of liver disease, alcohol use, or malignancy. Paracentesis reveals: total protein 4.2 g/dL, LDH 320 U/L, glucose 78 mg/dL, SAAG 0.8 g/dL, cytology negative. Right heart catheterization shows: PCWP 28 mmHg, right atrial pressure 24 mmHg, pulmonary artery pressure 42/20 mmHg. What is the most likely diagnosis?

Tuberculous peritonitis
Hepatic sinusoidal obstruction syndrome
Budd-Chiari syndrome
Constrictive pericarditis (Correct answer)

Correct answer: Constrictive pericarditis

The key findings are a low SAAG (<1.1 g/dL), exudative ascites (high protein), and right heart catheterization demonstrating elevated right atrial pressure equal to PCWP — a hallmark of constrictive pericarditis (equalization of diastolic pressures). Constrictive pericarditis causes elevated venous pressures that transude protein-rich fluid into the peritoneum, but because there is no portal hypertension, SAAG is low. Budd-Chiari syndrome produces high-SAAG ascites (>1.1) from hepatic venous obstruction. Sinusoidal obstruction syndrome also causes high-SAAG ascites and typically follows bone marrow transplant or hepatotoxin exposure. Tuberculous peritonitis produces exudative, low-SAAG ascites but would not explain the cardiac catheterization findings.

Question 277: A 65-year-old man with a mechanical aortic valve develops fever, positive blood cultures for viridans streptococcus, and a new perivalvular abscess on TEE. What does the abscess finding indicate?

Empiric switch to vancomycin is required
Repeat TEE in 2 weeks is the next step
Cardiac surgery consultation is required (Correct answer)
Outpatient antibiotic therapy is sufficient

Correct answer: Cardiac surgery consultation is required

Perivalvular abscess is a class I indication for urgent cardiac surgery in prosthetic valve endocarditis, as medical therapy alone is insufficient.

Question 278: A 25-year-old woman has elevated transaminases, Kayser-Fleischer rings, and neuropsychiatric symptoms. Serum ceruloplasmin is low. Which test best confirms the diagnosis of Wilson's disease?

Genetic testing for ATP7B mutation
Liver biopsy with quantitative copper (Correct answer)
24-hour urine copper
Serum copper level

Correct answer: Liver biopsy with quantitative copper

Liver biopsy with quantitative hepatic copper content >250 mcg/g dry weight is the gold standard for confirming Wilson's disease when clinical criteria are equivocal.

Question 279: A 45-year-old man is found to have WBC 90,000/μL with predominantly mature neutrophils and myelocytes, low leukocyte alkaline phosphatase score, and splenomegaly. BCR-ABL fusion gene is detected on PCR. What is the first-line treatment?

Allogeneic stem cell transplant upfront
Hydroxyurea alone
Cytarabine and daunorubicin induction chemotherapy
Imatinib (a BCR-ABL tyrosine kinase inhibitor) (Correct answer)

Correct answer: Imatinib (a BCR-ABL tyrosine kinase inhibitor)

CML driven by the BCR-ABL fusion (Philadelphia chromosome) is treated with BCR-ABL tyrosine kinase inhibitors such as imatinib as first-line therapy.

Question 280: A 44-year-old woman presents with recurrent episodes of abdominal pain, nausea, and watery diarrhea for 3 years. Colonoscopy shows normal mucosa; random colonic biopsies reveal a subepithelial collagen band measuring 18 µm with surface epithelial damage and mixed inflammatory infiltrate in the lamina propria. Stool cultures and Clostridioides difficile testing are negative. Which medication, if recently started, is the most common pharmacologic cause of this finding?

Olmesartan
Metformin
Lansoprazole (Correct answer)
Sertraline

Correct answer: Lansoprazole

Collagenous colitis (collagen band >10 µm) is strongly associated with proton pump inhibitor use, particularly lansoprazole (and to a lesser extent omeprazole and other PPIs), as well as NSAIDs, SSRIs, and ranitidine. Among PPIs, lansoprazole has the highest association with collagenous colitis, with an odds ratio significantly elevated in multiple case-control studies. Olmesartan is classically associated with olmesartan-induced enteropathy (sprue-like) affecting the small bowel, not collagenous colitis. Metformin and sertraline have weaker associations. The collagen band of 18 µm confirms collagenous colitis.

Question 281: A 62-year-old woman is evaluated for recurrent bilateral pleural effusions. Thoracentesis reveals: protein 2.1 g/dL (serum 7.0 g/dL), LDH 88 U/L (serum LDH 210 U/L), glucose 88 mg/dL, pH 7.42, WBC 240 cells/µL (85% lymphocytes), triglycerides 210 mg/dL. Which of the following is the most likely diagnosis?

Yellow nail syndrome
Chylothorax (Correct answer)
Hepatic hydrothorax
Lymphoma-associated exudative effusion

Correct answer: Chylothorax

A pleural fluid triglyceride level >110 mg/dL is diagnostic of chylothorax, regardless of other parameters. This is the pathognomonic finding here. Hepatic hydrothorax is a transudate (low protein, low LDH by Light's criteria) not an exudate, and triglycerides would not be elevated. Lymphoma can cause exudative lymphocytic effusions but would not elevate triglycerides unless there is associated chylothorax from thoracic duct obstruction — in that case the etiology is still chylothorax. Yellow nail syndrome causes exudative effusions with lymphocytosis but does not cause elevated triglycerides. The triglyceride level of 210 mg/dL is the discriminating finding that makes chylothorax the definitive diagnosis.

Question 282: A 45-year-old man with a history of neck irradiation for Hodgkin lymphoma at age 20 is found to have a 1.2 cm thyroid nodule. Fine-needle aspiration returns Bethesda IV (follicular neoplasm). Molecular testing shows a PAX8-PPARγ rearrangement. Which statement most accurately characterizes the significance of this molecular finding?

It is diagnostic of papillary thyroid carcinoma and mandates central neck dissection
It predicts radioiodine resistance but does not differentiate benign from malignant follicular lesions
It confirms benign adenoma and lobectomy can be avoided entirely
It is highly specific for follicular thyroid carcinoma and supports proceeding directly to total thyroidectomy (Correct answer)

Correct answer: It is highly specific for follicular thyroid carcinoma and supports proceeding directly to total thyroidectomy

PAX8-PPARγ rearrangement is found in approximately 30–40% of follicular thyroid carcinomas (FTC) and only rarely in follicular adenomas. Unlike BRAF V600E (which is diagnostic of malignancy in PTC), PAX8-PPARγ is not 100% specific but significantly increases the probability of malignancy in a Bethesda IV nodule, typically guiding surgeons toward total thyroidectomy rather than diagnostic lobectomy alone. It is not a feature of PTC and does not mandate central neck dissection, which is reserved for PTC with high-risk features. The presence of this rearrangement does not confirm benignity. While some FTCs show radioiodine resistance, this is not the primary clinical implication of PAX8-PPARγ — the malignancy risk stratification is.

Question 283: A 25-year-old man presents with bilateral testicular germ cell tumor markers showing elevated AFP and beta-hCG. Staging CT shows retroperitoneal lymph nodes up to 3 cm but no visceral metastases. What is the first-line treatment?

Orchiectomy and retroperitoneal lymph node dissection only
Orchiectomy followed by radiation alone
BEP chemotherapy without surgery
Orchiectomy followed by BEP chemotherapy (Correct answer)

Correct answer: Orchiectomy followed by BEP chemotherapy

For intermediate or high-risk nonseminomatous GCT with elevated markers and lymph node involvement, orchiectomy followed by BEP (bleomycin, etoposide, cisplatin) is standard.

Question 284: A 38-year-old woman presents with pleuritic chest pain, dyspnea, and hemoptysis 2 weeks after a total knee replacement. CT pulmonary angiography confirms bilateral pulmonary emboli without RV dysfunction. She has no contraindications to anticoagulation. What is the MOST appropriate treatment?

Systemic thrombolysis with IV alteplase
Catheter-directed thrombolysis
Surgical embolectomy
Anticoagulation with rivaroxaban or apixaban (Correct answer)

Correct answer: Anticoagulation with rivaroxaban or apixaban

Submassive PE without hemodynamic compromise or severe RV dysfunction is treated with anticoagulation alone; DOACs (rivaroxaban or apixaban) are preferred for low-risk PE.

Question 285: A 65-year-old woman presents with exertional dyspnea and a harsh systolic crescendo-decrescendo murmur at the right upper sternal border radiating to the carotids. Echocardiogram shows an AVA of 0.7 cm². What is the next step?

Referral for aortic valve replacement (Correct answer)
Cardiac catheterization to confirm
Exercise stress test
Medical management with ACE inhibitor

Correct answer: Referral for aortic valve replacement

An AVA <0.8 cm² with symptoms defines severe symptomatic aortic stenosis, which requires valve replacement as definitive treatment.

Question 286: A 68-year-old man with atrial fibrillation and hypertension presents 90 minutes after sudden onset right-sided weakness and aphasia. CT head is negative for hemorrhage. His INR is 1.1 (not on anticoagulation). What is the most appropriate immediate intervention?

Emergency carotid endarterectomy
IV alteplase (tPA) if no contraindications (Correct answer)
Heparin drip with target aPTT 60–80 seconds
Aspirin 325 mg orally immediately

Correct answer: IV alteplase (tPA) if no contraindications

IV tPA within 4.5 hours of ischemic stroke symptom onset is the standard of care when contraindications are absent. Aspirin is appropriate but is secondary to thrombolysis in the acute window. Carotid endarterectomy is for symptomatic carotid stenosis, not acute treatment. IV heparin is not recommended in acute ischemic stroke.

Question 287: A 58-year-old man with newly diagnosed acute promyelocytic leukemia (APL) is started on ATRA and arsenic trioxide. On day 4, he develops fever, weight gain of 3 kg, and new bilateral pulmonary infiltrates. His WBC has risen from 2,000 to 18,000/µL. Which of the following is the most appropriate next step?

Perform bronchoscopy with BAL to rule out infection before treating
Add dexamethasone 10 mg IV twice daily and continue ATRA (Correct answer)
Discontinue ATRA immediately and initiate idarubicin
Start hydroxyurea to control leukocytosis

Correct answer: Add dexamethasone 10 mg IV twice daily and continue ATRA

This presentation is classic for differentiation syndrome (formerly ATRA syndrome), occurring in ~25% of APL patients treated with ATRA or arsenic trioxide. It is characterized by fever, weight gain, pulmonary infiltrates, and rising WBC. The correct management is to add high-dose dexamethasone (10 mg IV BID) while continuing ATRA — discontinuation is reserved only for severe cases with renal failure or respiratory failure requiring mechanical ventilation. Early steroid intervention is life-saving and ATRA should not be stopped empirically.

Question 288: A 44-year-old man with alcohol use disorder presents with acute kidney injury. Urine microscopy shows muddy brown granular casts and renal tubular epithelial cells. FENa is 3.2%. What is the most likely diagnosis?

Pre-renal azotemia from volume depletion
Rhabdomyolysis-induced AKI
Acute interstitial nephritis
Acute tubular necrosis (Correct answer)

Correct answer: Acute tubular necrosis

Muddy brown granular casts and RTECs on urinalysis with FENa >2% are the hallmark of acute tubular necrosis.

Question 289: A 60-year-old man with COPD is hospitalized with healthcare-associated pneumonia. He has no prior antibiotic exposure. What empiric coverage is most appropriate?

Levofloxacin monotherapy
Ceftriaxone plus azithromycin
Azithromycin monotherapy
Piperacillin-tazobactam plus vancomycin (Correct answer)

Correct answer: Piperacillin-tazobactam plus vancomycin

Healthcare-associated pneumonia requires broad-spectrum coverage for MRSA and Pseudomonas, making piperacillin-tazobactam plus vancomycin the appropriate empiric regimen.

Question 290: According to the 2021 IDSA and SHEA focused update, which of the following is the preferred first-line agent for an initial episode of non-severe Clostridioides difficile infection?

Oral Metronidazole
Fecal Microbiota Transplantation
Oral Fidaxomicin (Correct answer)
Oral Vancomycin

Correct answer: Oral Fidaxomicin

The 2021 IDSA/SHEA guidelines conditionally recommend oral fidaxomicin as the preferred agent over oral vancomycin for an initial episode of C. difficile infection (CDI). This preference is based on evidence showing fidaxomicin has a lower rate of CDI recurrence compared to vancomycin. Oral metronidazole is no longer recommended as a first-line agent for even mild-to-moderate disease. Fecal microbiota transplantation is reserved for patients with multiple recurrent episodes.

Question 291: A patient with type 1 DM develops DKA during pregnancy at 28 weeks gestation. Which unique consideration applies to DKA management in pregnancy?

Fetal distress resolves only after delivery, not with maternal treatment
Target glucose of 200-250 mg/dL to avoid hypoglycemia in fetus
Insulin should be avoided in first trimester DKA
DKA may occur at lower glucose levels (as low as 200 mg/dL) in pregnancy (Correct answer)

Correct answer: DKA may occur at lower glucose levels (as low as 200 mg/dL) in pregnancy

Pregnant patients are at risk for 'euglycemic DKA' with lower glucose thresholds due to altered metabolism, increased insulin resistance, and decreased buffering capacity.

Question 292: Which scoring system is used to prioritize liver transplant allocation in the United States?

MELD score (Correct answer)
APACHE II
King's College Criteria
Child-Pugh score

Correct answer: MELD score

The MELD (Model for End-stage Liver Disease) score, based on bilirubin, INR, and creatinine, is used by UNOS to prioritize patients for liver transplant allocation.

Question 293: What is the most appropriate initial insulin bolus regimen for moderate-to-severe DKA in an adult?

IM regular insulin 10 units every 2 hours
IV infusion at 0.14 units/kg/hr without a bolus (Correct answer)
IV bolus of 0.1 units/kg followed by infusion at 0.1 units/kg/hr
Subcutaneous rapid-acting insulin 0.3 units/kg immediately

Correct answer: IV infusion at 0.14 units/kg/hr without a bolus

Current ADA guidelines recommend starting IV insulin at 0.14 units/kg/hr without a bolus as an alternative to the bolus-then-infusion approach, showing equal efficacy.

Question 294: A patient is found to have H. pylori infection on urea breath test after completing a PPI plus clarithromycin-based triple therapy. What is the best next step?

Bismuth quadruple therapy (Correct answer)
Metronidazole monotherapy
Endoscopy with biopsy culture
Repeat the same triple therapy regimen

Correct answer: Bismuth quadruple therapy

After failure of clarithromycin-based triple therapy, bismuth quadruple therapy (PPI + bismuth + tetracycline + metronidazole) is recommended as salvage treatment.

Question 295: A 44-year-old woman has recurrent syncopal episodes during emotional stress. ECG shows a prolonged QTc of 520ms. She is started on nadolol. Which additional measure is most important for preventing sudden death?

Potassium supplementation to maintain K+ >4.5 mEq/L
Avoidance of all QT-prolonging medications (Correct answer)
Implantable cardioverter-defibrillator placement
Left cardiac sympathetic denervation

Correct answer: Avoidance of all QT-prolonging medications

Avoidance of QT-prolonging drugs (antiarrhythmics, antibiotics, antiemetics, antipsychotics) is critical in congenital long QT syndrome to prevent torsades de pointes.

Question 296: A 44-year-old woman with systemic sclerosis presents with progressive exertional dyspnea. PFTs show FVC 68% predicted, TLC 70% predicted, DLCO 38% predicted. Right heart catheterization reveals mPAP 29 mmHg, PAWP 10 mmHg, PVR 3.2 WU. Which of the following most accurately characterizes her hemodynamic profile and guides management?

Borderline pre-capillary PH; exercise RHC needed before initiating PAH therapy (Correct answer)
Pulmonary hypertension due to ILD alone; PAH-specific therapy offers no benefit
Combined pre- and post-capillary PH; phosphodiesterase-5 inhibitors are contraindicated
Pre-capillary PAH meeting WHO/ESC criteria; initiate dual oral combination therapy

Correct answer: Borderline pre-capillary PH; exercise RHC needed before initiating PAH therapy

Per 2022 ESC/ERS guidelines, PAH is defined by mPAP >20 mmHg, PAWP ≤15 mmHg, and PVR ≥2 WU at rest. This patient meets the mPAP and PAWP criteria but PVR is 3.2 WU (borderline). Crucially, her mPAP of 29 mmHg is below the old threshold of 25 mmHg but above the new 20 mmHg threshold — however, with borderline values, exercise RHC may unmask significant exercise-induced PH and better delineate whether PAH-specific therapy is warranted before committing to combination therapy. Immediate dual therapy initiation would be premature given the borderline hemodynamics.

Question 297: A 26-year-old woman with type 1 diabetes presents with recurrent DKA episodes despite good outpatient compliance. She has celiac antibodies positive on screening. How does undiagnosed celiac disease contribute to DKA in type 1 diabetes?

Celiac increases glucagon secretion
Malabsorption leads to unpredictable glucose-insulin matching (Correct answer)
Celiac disease causes insulin resistance
Celiac destroys beta cells directly

Correct answer: Malabsorption leads to unpredictable glucose-insulin matching

Celiac disease-related malabsorption causes erratic carbohydrate absorption, making glucose-insulin matching unpredictable and precipitating hypoglycemia or hyperglycemia and DKA.

Question 298: A 22-year-old woman with Turner syndrome (45,X) presents for routine evaluation. Which endocrine complication is she at highest risk for?

Primary hyperparathyroidism
Prolactinoma
Primary hypothyroidism (Hashimoto's) (Correct answer)
Cushing syndrome

Correct answer: Primary hypothyroidism (Hashimoto's)

Women with Turner syndrome have a significantly increased prevalence of autoimmune thyroid disease, particularly Hashimoto's thyroiditis and primary hypothyroidism.

Question 299: A 67-year-old man with Stage IIIA non-small cell lung cancer (NSCLC) and ECOG performance status 1 has a PD-L1 expression of 85%. He has no driver mutations (EGFR/ALK negative). Which treatment approach is MOST appropriate?

Cisplatin/pemetrexed chemotherapy alone
Concurrent chemoradiation followed by durvalumab (Correct answer)
EGFR-targeted therapy with osimertinib
Pembrolizumab monotherapy

Correct answer: Concurrent chemoradiation followed by durvalumab

For unresectable Stage III NSCLC, concurrent chemoradiation followed by consolidation durvalumab (PACIFIC trial) is the standard of care regardless of PD-L1 expression.

Question 300: A 28-year-old man with severe hemophilia A (factor VIII activity <1%) presents with rapidly expanding knee hemarthrosis after a fall. What is the first-line treatment?

Fresh frozen plasma infusion
Cryoprecipitate infusion
Factor VIII concentrate replacement therapy (Correct answer)
Desmopressin (DDAVP)

Correct answer: Factor VIII concentrate replacement therapy

Hemophilia A is treated with specific factor VIII concentrate replacement, which is preferred over non-specific blood products for efficacy and safety.

ITE Internal Medicine In-Training Exam

The ITE Internal Medicine In-Training Exam is an annual assessment for internal medicine residents covering cardiovascular disease, pulmonary and critical care, gastroenterology, infectious disease, and endocrinology to benchmark clinical knowledge.

300

Questions

360 min

Time Limit

60%

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