Question: A 47-year-old man is brought in after a motor vehicle accident. He was driving under the influence of alcohol when he sustained a crash against a pole. His medical history is significant for hypertension but he does not take any medications. His temperature is 98.6°F (37.0°C), blood pressure is 110/80 mmHg, pulse is 60/min, and respirations are 12/min on a ventilator. His Glasgow coma score (GCS) on presentation is 6. Initial urine toxicology is negative. The patient is admitted to the intensive care unit and appropriate care is initiated. One week later, the patient’s GCS score is now 3. Laboratory studies do not show significant electrolyte, acid-base, or endocrine disturbances. Sedative and paralytic agents are withdrawn. Which of the following findings on physical exam would be compatible with brain death?

Flexion of the thigh, leg, and foot upon noxious stimulation of the foot

Grimacing after noxious stimulus to the arm

Answer: Flexion of the thigh, leg, and foot upon noxious stimulation of the foot

Explanation:
This patient with a Glasgow coma score (GCS) of 3 and a known mechanism of injury due to motor vehicle accident trauma is normothermic, normotensive, not on sedatives, and without laboratory abnormalities so they are appropriate for examination of brain death. Cortical and brain stem function must be absent in brain death; however, spinal cord reflexes such as triple flexion (flexion of the thigh, leg, and foot upon noxious stimulation of the foot) may remain intact in patients with brain death.

The clinical brain death exam may be performed in patients with evidence of irreversible central nervous system catastrophe after a known mechanism of trauma or medical injury. The patient must not have other causes for obtundation, and should be euthermic, not on sedative or paralytic agents, not be intoxicated due to drugs or poisoning, and not have other severe electrolyte, acid-base, or endocrine disturbances. In brain death, there must be no cerebral motor response such as moaning or grimacing to pain in all extremities and the face. Brain stem reflexes such as the pupillary light reflex, corneal reflex, oculocephalic reflex, vestibulo-ocular reflex, gag reflex, and apnea test should also be absent in brain death. Spinal cord and deep tendon reflexes may still be present in brain death. Complex movements mediated by the spinal cord such as triple flexion and the Lazarus sign (raising the arms and dropping them crossed on the chest after noxious stimulus) do not preclude a diagnosis of brain death.

Greer et al. review neurologic criteria for the determination of brain death. They discuss how to clinically differentiate spinal motor responses from brain-mediated motor responses. They recommend understanding these distinctions in order to properly examine patients with brain death.

Incorrect Answers:
Answer A: Blinking after saline is applied to the cornea indicates a positive corneal reflex. In the corneal reflex, the ophthalmic branch of the trigeminal (V1) nerve senses stimulus to the cornea, and bilateral temporal branches of the facial nerve (VII) activate the orbicularis oculi muscles to blink. Brainstem reflexes must be absent in brain death, so the presence of a corneal reflex is not compatible with a diagnosis of brain death.

Answer B: Conjugate eye movement to the left with rotation of the head to the right describes the oculocephalic reflex. In this reflex, movement of the head stimulates endolymph in the horizontal semicircular canal to rotate, causing the firing of the ipsilateral vestibulocochlear (VIII) nerve. This leads to activation or inhibition of the contralateral abducens (VI) and oculomotor (III) nerves. Brainstem reflexes must be absent in brain death, so the presence of an oculocephalic reflex is not compatible with a diagnosis of brain death.

Answer D: Grimacing after the noxious stimulus of the arm indicates some residual cortical function. Grimacing is not a spinal cord reflex and requires some cortical processing of sensory information. All cortical function must be absent in brain death, so grimacing to pain would not be compatible with brain death.

Answer E: Spontaneous respiration 1 minute after disconnection from a ventilator in a patient without diabetes insipidus and with normal blood gas values and systolic blood pressure above 90 mmHg indicates a negative apnea test. The apnea test assesses respiratory control system reflexes in the brainstem. Apnea testing is an important component of the brain death exam, and a negative apnea test is incompatible with brain death.

Bullet Summary:
Although brain death criteria universally include the absence of cortical and brainstem function, spinal cord and deep tendon reflexes may be preserved in patients with brain death.


Question: A 55-year-old man presents to the emergency department with epistaxis for the past hour. He has never had epistaxis before and has been unable to control it with pressure, head elevation, and ice. The patient has a past medical history of atrial fibrillation and is currently taking metoprolol and warfarin. His temperature is 98.5°F (36.9°C), blood pressure is 123/81 mmHg, pulse is 90/min, respirations are 13/min, and oxygen saturation is 97% on room air. Physical exam reveals a comfortable man in no distress. Inspection reveals active bleeding in the anterior nares. There is not a clear, single bleeding vessel. Which of the following is the most appropriate initial step in management?

Answer: Topical oxymetazoline

Explanation:
This patient on warfarin is presenting with epistaxis from the anterior nares (and is currently hemodynamically stable) suggesting anterior epistaxis. Prior to more invasive measures, topical therapy with oxymetazoline should be tried as it is very successful in reducing or resolving epistaxis.

Epistaxis can be a benign or life-threatening presentation. For anterior epistaxis, the management is centered on compression of the anterior nares as most cases are caused by bleeding from Kiesselbach plexus. If this fails, the next step in management is having the patient blow their nose to remove any clots, followed by vigorous application of topical oxymetazoline which vasoconstricts the vessels in the nares and is highly effective in treating epistaxis. If this fails, other topical agents include topical tranexamic acid, and thrombogenic foams. If pressure and topical therapy fail to resolve epistaxis, then anterior nasal packing (such as nasal tampons) may be used.

Kucik and Clenney review treatments for epistaxis. They note that the first-line treatment of anterior epistaxis is compression of the anterior nares. If this fails, they recommend other measures such as topical vasoconstrictors, cautery, and packing.

Incorrect Answers:
Answer A: Cauterization with silver nitrate is appropriate for anterior epistaxis, but generally should be reserved for patients who have failed initial medical therapy with topical agents. It may also be appropriate first-line therapy in patients with recurrent epistaxis from a clear, single bleeding vessel (which is not present in this patient).

Answer B: Fresh frozen plasma and intravenous phytonadione is the appropriate reversal agent for warfarin. While this may stop the patient's epistaxis, he is hemodynamically stable and the bleeding is not life-threatening; thus, the risk of thrombus from atrial fibrillation is likely greater than the risk of bleeding in this case of epistaxis. Less invasive medical therapy should be started/tried first.

Answer C: Intravenous tranexamic acid would be appropriate in an acutely hemorrhaging patient to reduce bleeding in the setting of hemorrhagic shock. Topical (not intravenous) tranexamic acid may be an appropriate first-line agent for anterior epistaxis.

Answer D: Placement of posterior nasal packing would be indicated if there was persistent bleeding in the setting of posterior epistaxis (often from bleeding from the sphenopalatine artery), which presents with more profuse bleeding that may threaten the airway. This patient's bleeding is clearly anterior as it can easily be visualized in the anterior nares; thus, this intervention is not needed.

Bullet Summary:
Topical oxymetazoline and other topical agents such as tranexamic acid are appropriate first-line agents in the management of epistaxis if pressure alone fails to resolve symptoms.


Question: A 66-year-old man presents to the emergency department with shortness of breath. He typically has poor exercise tolerance and is only able to walk from his house to his mailbox before becoming dyspneic. He now has shortness of breath even at rest. He had a cold recently but has no new medical problems. His past medical history is notable for a myocardial infarction 7 years ago, COPD, heart failure with a left ventricular ejection fraction of 22%, obesity, diabetes, and peripheral vascular disease. His temperature is 97.7°F (36.5°C), blood pressure is 124/82 mmHg, pulse is 140/min, respirations are 32/min, and oxygen saturation is 78% on room air. Physical exam reveals an uncomfortable man with increased work of breathing. He demonstrates bilateral crackles and wheezing on pulmonary exam. The patient is started on BiPAP, and his oxygen saturation improves to 94%. An ECG is performed, as seen in Figure A, and a chest radiograph is performed, as seen in Figure B. Which of the following is the most appropriate next step in management?

Answer: Digoxin

Explanation:
This patient with a history of heart failure with reduced ejection fraction is presenting with respiratory distress (increased work of breathing, hypoxia, wheezes, and crackles) in the setting of atrial fibrillation (ECG with irregularly irregular rhythm without P waves) with rapid ventricular response and pulmonary edema on chest radiograph. Digoxin is an appropriate medication that can both control the heart rate in atrial fibrillation and increase cardiac contractility and potentially improve respiratory symptoms in this decompensated patient with heart failure.

Atrial fibrillation presents on ECG with an irregularly irregular rhythm without discernible P waves. The initial management of atrial fibrillation with rapid ventricular response is rate control. If the patient is stable, possible first-line agents include beta-blockers (e.g., metoprolol) or calcium channel blockers (e.g., diltiazem). These agents may reduce cardiac contractility and worsen complications such as pulmonary edema in the setting of heart failure with reduced ejection fraction when the patient is in a decompensated state. If the patient has a reduced ejection fraction and requires rate control, then digoxin is a highly effective medication that blocks the AV node and increases cardiac contractility. Any hemodynamically unstable patient with atrial fibrillation with rapid ventricular response should immediately be cardioverted.

Moskowitz et. al review the management of atrial fibrillation. They note that in the management of atrial fibrillation with rapid ventricular response, metoprolol is commonly used in the intensive care setting, is more successful than amiodarone, and had better rate control when compared to diltiazem.

Ehle et. al note that digoxin is approved to control ventricular response in patients with chronic atrial fibrillation and is the only oral agent with positive inotropic effects approved for the management of mild to moderate heart failure.

Figure/Illustration A is an ECG demonstrating an irregularly irregular rate/rhythm (note the spacing of the blue arrows indicating the QRS complexes) without P waves, which is suggestive of atrial fibrillation. Figure B is a chest radiograph demonstrating bilateral, hazy interstitial infiltrates, which are concerning for pulmonary edema.

Incorrect Answers:
Answer A: Albuterol and prednisone would be appropriate management of a COPD flare, which presents in a patient with a history of smoking with dyspnea, wheezing, increased work of breathing, and a barrel chest. While this patient’s wheezing may be secondary to his COPD, it is much more likely to be a cardiac wheeze given his chest radiograph findings including pulmonary edema. Treating his atrial fibrillation is more likely to alleviate his pulmonary symptoms. Other treatments in COPD include ipratropium and BiPAP.

Answer C: Diltiazem would be an appropriate rate control agent for atrial fibrillation with rapid ventricular response, particularly in the setting of a COPD flare as it will not impair the mechanism of albuterol (which should be given as a nebulizer in COPD flares). In this patient, further impairing cardiac contractility with a calcium channel blocker may worsen his underlying pulmonary edema (given his reduced ejection fraction).

Answer D: Intubation would be indicated if this patient’s respiratory status were worsening, including failure to oxygenate, failure to ventilate, or impending respiratory failure. This patient’s respiratory status has improved on BiPAP; thus intubation is not needed.

Answer E: Metoprolol, like diltiazem, would reduce cardiac contractility and may worsen pulmonary edema, in particular, in a patient with a reduced ejection fraction. It also may cause COPD symptoms to emerge, as beta-2 blockade may cause bronchoconstriction (even though metoprolol is beta-1 selective). It would be indicated as outpatient rate control for a patient with atrial fibrillation who can tolerate a beta-blocker, and is preferred in patients with a history of acute coronary syndrome, as it reduces mortality.

Bullet Summary:
Patients with atrial fibrillation with rapid ventricular response with a reduced ejection fraction may be optimally managed with digoxin, which blocks the AV node and increases cardiac contractility.


Question: A 65-year-old man presents to the emergency department with low back pain. The pain started 6 hours ago when he was gardening and carrying a heavy bag. The pain is rated as 10/10 in severity and radiates down the posterior aspect of the right thigh. He reports no fevers or chills. His only medical problem is hypertension for which he takes amlodipine. The patient is a non-smoker, uses alcohol infrequently, and has never used illicit drugs. His temperature is 99.6°F (37.6°C), blood pressure is 140/70 mmHg, pulse is 90/min, and respirations are 20/min. Physical examination reveals 3/5 strength to hip extension, knee flexion and extension, and plantar flexion bilaterally. Sensation to pinprick is diminished over the posterolateral legs and lateral aspects of both feet. Ankle and knee reflexes are absent bilaterally. The patient’s underwear is wet and a bladder scan reveals 800 mL of urine. Which of the following is the most likely underlying diagnosis?

Answer: Cauda equina syndrome

Explanation:
This patient presenting with acute, severe, radiating low back pain with sensorimotor deficits (3/5 strength in hip extension, knee flexion/extension, plantar flexion, reduced sensation to pinprick) in multiple nerve root distributions (L3-S5), lower motor neuron signs, urinary incontinence (wet underwear), and acute urinary retention (bladder scan showing 800 mL of urine) most likely has cauda equina syndrome.

Cauda equina syndrome is characterized by deficits in 2 or more nerve roots that comprise the cauda equina of the spinal cord. It has multiple etiologies, including disc herniation, epidural abscess, tumor, or lumbar spine spondylosis. Cauda equina syndrome presents with severe low back pain radiating into the legs, flaccid paralysis or lower extremity weakness which can be symmetric or asymmetric (often asymmetric), bladder and/or rectal sphincter paralysis, impotence/erectile dysfunction, sensory loss in affected dermatomes, and saddle anesthesia (sensory loss in the perineum). Urinary retention occurs due to bladder paralysis. Diagnosis is aided by emergency magnetic resonance imaging. Cauda equina syndrome is a surgical emergency; the goal of surgical treatment is to decompress the cauda equina to prevent permanent neurological injury, such as with a lumbar laminectomy. This can be differentiated from conus medullaris syndrome, which has perianal numbness without numbness through other dermatomes (down the leg in the S1 or S2 patterns), less severe pain (cauda equina presents with more severe pain), and hyperreflexia in the knees (cauda equina presents with lower motor neuron signs in the legs which lead to decreased reflexes - though conus medullaris may present with absent ankle reflexes, the knees are typically hyperreflexic).

Gardner et al. review the symptoms, diagnosis, and medico-legal landscape of cauda equina syndrome. They discuss how the most frequent etiology is a large central lumbar disc herniation. They recommend being vigilant for urinary retention in patients who may have compression as many patients have urinary retention on presentation.

Incorrect Answers:
Answer A: Acute inflammatory demyelinating polyneuropathy, also known as Guillain-Barre syndrome, occurs after respiratory or gastrointestinal infections and presents with ascending paralysis and diminished reflexes. While bladder dysfunction can occur, back pain is not typical. Guillain-Barre syndrome can be treated with intravenous immunoglobulin.

Answer C: L5/S1 disc herniation affects the traversing S1 nerve root. S1 radiculopathy presents with posterolateral leg and dorsolateral foot sensory loss and absence of the ankle reflex. Typically, bowel/bladder symptoms are not present. Treatment includes decompression of the affected nerve root.

Answer D: Overflow incontinence is caused by either bladder outlet obstruction or poor bladder tone. While this could explain this patient’s urinary retention, it does not account for his back pain or sensorimotor deficits. Isolated overflow incontinence can be treated with catheterization.

Answer E: Spinal stenosis presents with lower extremity claudication, characterized by pain with standing or ambulation. The pain of neurogenic claudication is characteristically relieved by spinal flexion (“shopping cart sign”). Sensory loss and motor weakness can be present; however, bladder dysfunction is atypical. Treatment includes surgical decompression of the area of stenosis.

Bullet Summary:
Cauda equina syndrome is characterized by impingement of 2 or more nerve roots of the cauda equina, resulting in radicular pain, bilateral lower extremity weakness, lower motor neuron signs, sensory loss in affected dermatomes, bowel/bladder dysfunction, and saddle anesthesia.


Question: A 69-year-old man presents to his primary care physician for trouble sleeping. He recently retired from working the day shift at a cemetery. When the patient retired, his goal was to finally be able to go out with his wife; however, he finds that he is unable to stay awake past 6 pm in the evening. His wife is disappointed that they cannot do any activities in the evening together. The patient has tried drinking caffeine but finds that it does not help. The patient’s wife claims that the patient seems to sleep peacefully, and the patient states he feels rested when he awakes. The patient has a medical history of irritable bowel syndrome which is managed with fiber supplements. His temperature is 98.6°F (37°C), blood pressure is 125/83 mmHg, pulse is 87/min, and respirations are 11/min. The patient’s neurological exam is within normal limits. Which of the following is the most likely diagnosis?

Answer: Advanced sleep phase disorder

Explanation:
This patient is presenting with difficulty staying awake in the early evening suggesting a diagnosis of advanced sleep phase disorder (also known as advanced sleep phase syndrome).

Advanced sleep phase disorder can present in patients of all ages. Patients will experience difficulty staying awake in the early evening (5 to 8 pm); however, they will typically sleep a normal quantity of hours. These patients generally feel well rested in the morning and are able to function normally during the day. This condition can impair social activities that occur in the evening, which can cause distress to the patient. The diagnosis of advanced sleep phase disorder can be made when these symptoms are present in addition to an absence of another organic cause (such as obstructive sleep apnea). Treatment is with bright light visual stimulation therapy and reconditioning of circadian rhythms.

Yaremchuk reviews the diagnosis and treatment of patients with sleep phase disorder. She discusses how sleep disorders such as advanced sleep phase disorder should be distinguished from normal aging. She recommends intervening when sleep quality is compromised as it reduces quality of life in the elderly.

Incorrect Answers:
Answer B: Chronic insomnia will present with trouble falling asleep or staying asleep, often alternating with other sleep pathologies. This patient does not claim to have any trouble falling or staying asleep. He also feels well rested in the morning so his sleep quality is adequate. Treatment of insomnia may include melatonin and sleep hygiene.

Answer C: Delayed sleep phase disorder typically presents in younger patients with difficulty falling asleep early. These patients will often fall asleep very late and struggle to wake up early for obligations such as school or work. Treatment is with melatonin and sleep hygiene interventions.

Answer D: Normal aging presents with patients claiming that their sleep is less restful in the absence of an organic cause (such as obstructive sleep apnea). As patients age, it is natural for all phases of their sleep to shorten. However, it is not normal for this patient to have such difficulty staying awake in the early evening, so advanced sleep phase disorder is a more likely diagnosis.

Answer E: Obstructive sleep apnea presents with fatigue, morning headaches, and non-restful sleep. Patients will typically snore loudly and typically are overweight. This patient does not have any of these risk factors or symptoms in his history. Treatment is with positive airway pressure machines and weight loss.

Bullet Summary:
Advanced sleep phase disorder presents with difficulty staying awake in the early evening that impairs social functioning.


Question: A 25-year-old G1P0 woman presents to her physician for a prenatal visit. She is at 12 weeks gestational age and has not received prior prenatal care. She has mild morning sickness but no other symptoms. She has no known medical problems and takes only a prenatal multivitamin. She has unprotected sexual intercourse with 3 male partners. Her temperature is 98.6°F (37.0°C), blood pressure is 118/70 mmHg, pulse is 80/min, and respirations are 18/min. Physical exam reveals a well-appearing woman in no acute distress. There are no lesions appreciated on skin exam. Cardiopulmonary exam is unremarkable. An antibody test for human immunodeficiency virus (HIV)-1/2 is positive. The patient is started on an appropriate treatment regimen. Assuming that her HIV viral load is undetectable by the time of delivery, which of the following maternal regimens is she most likely receiving and what neonatal prophylaxis is indicated (Figure A)?

Answer: C

Explanation:
This pregnant patient presents with a positive HIV antibody test in the setting of unprotected sexual intercourse. An appropriate maternal HIV treatment regimen is abacavir, lamivudine, and raltegravir; prophylaxis in the infant consists of zidovudine alone if maternal HIV viral load is suppressed to < 50 copies/mL.

All pregnant women should be screened for HIV as early as possible during pregnancy. Maternal treatment for HIV should be initiated as early as possible (before pregnancy if possible) with highly-active anti-retroviral therapy (HAART) consisting of 2 nucleoside reverse transcriptase inhibitors (NRTIs) such as abacavir/lamivudine, plus an integrase inhibitor (e.g., raltegravir) or a protease inhibitor (e.g., ritonavir/atazanavir). Regimens for prophylaxis in infants of HIV-positive mothers depends on the HIV viral load at the time of delivery. If the viral load is < 50 copies/mL, infant prophylaxis with zidovudine alone for 4 weeks is sufficient. If the viral load is ≥ 50 copies/mL or the mother did not receive HAART during pregnancy, infant prophylaxis should consist of the 3-drug regimen of: zidovudine, lamivudine, and either nevirapine or raltegravir for 6 weeks.

Harris et al. reviewed the treatment of HIV infection in pregnancy. They found that although anti-retroviral therapy during pregnancy significantly reduces mother-to-child transmission of HIV, it is still associated with certain perinatal complications such as low birthweight and preterm delivery. Despite these risks, they recommend anti-retroviral therapy during pregnancy and during breastfeeding to prevent transmission.

Figure A shows the answer choices.

Incorrect Answers:
Answer A: Maternal treatment with abacavir/lamivudine/raltegravir and no neonatal treatment is inappropriate because all infants of HIV-positive mothers should receive zidovudine (if maternal viral load < 50 copies/mL at delivery). Lamivudine and raltegravir would be added if maternal viral load is ≥ 50 copies/mL at delivery.

Answer B: Maternal treatment with abacavir/lamivudine/raltegravir and neonatal prophylaxis with zidovudine/lamivudine/raltegravir would be appropriate if the maternal viral load were ≥ 50 copies/mL at delivery. The HIV viral load in this patient was assumed to be undetectable at delivery.

Answer D: Maternal treatment with raltegravir/ritonavir/atazanavir and neonatal prophylaxis with zidovudine/lamivudine/raltegravir is inappropriate because raltegravir is an integrase inhibitor and ritonavir/atazanavir are protease inhibitors. HAART must include 2 NRTIs. Atazanavir is often co-administered with ritonavir to increase the former’s bioavailability. Additionally, zidovudine/lamivudine/raltegravir is the neonatal regimen for infants whose mothers have a viral load ≥ 50 copies/mL at delivery.

Answer E: Maternal treatment with raltegravir/ritonavir/atazanavir and neonatal prophylaxis with zidovudine only is inappropriate because HAART for the mother must include 2 NRTIs.

Bullet Summary:
Maternal HIV infection should consist of highly-active anti-retroviral therapy consisting of 2 nucleoside reverse transcriptase inhibitors plus either an integrase inhibitor or protease inhibito, while neonatal prophylaxis consists of zidovudine only for infants of mothers with viral load < 50 copies/mL at delivery.


Question: A 66-year-old woman presents to the emergency room after experiencing a tonic-clonic seizure. She has been having worsening headaches and intermittent nausea over the past 5 months. The headaches are constant and dull, and they typically worsen when she sneezes or laughs. Recently, she has become increasingly nauseous and has vomited twice in the past 10 days. Her medical history is significant for type 2 diabetes mellitus and hypertension for which she takes metformin and losartan. Her temperature is 98.6°F (37.0°C), blood pressure is 115/70 mmHg, pulse is 70/min, and respirations are 12/min. She is noted to have papilledema on fundoscopy, but physical exam is otherwise normal. Her CT scan findings are presented in Figure A. Which of the following is the most likely diagnosis?

Answer: Glioblastoma multiforme

Explanation:
This patient is presenting with symptoms of increased intracranial pressure (i.e., positional headaches, nausea, vomiting, and papilledema). Combined with her CT finding of a space-occupying butterfly-shaped lesion, the most likely diagnosis is glioblastoma multiforme.

Glioblastoma multiforme is the most common malignant primary nervous system cancer, most commonly occurring in adults above the age of 65. The tumor arises from the cerebral hemispheres and classically crosses the corpus callosum, producing a butterfly appearance on CT/MRI. Pseudopalasading necrosis is seen on biopsy, and tissue biopsy is usually glial fibrillary acidic protein (GFAP) positive. It has an unfavorable prognosis with a life expectancy of 6 months to 1 year. Management of glioblastoma includes surgical resection and palliative radiotherapy/chemotherapy.

Stupp et al. studied the role of electrical field therapy (TTFields) in conjunction with temozolomide in the treatment of glioblastoma multiforme. The authors found that combination therapy improved median progression-free survival (6.7 vs. 4.0 months, p < 0.001). The authors recommend that clinicians consider the use of TTFields to treat selected patients with glioblastoma multiforme.

Figure/Illustration A demonstrates a non-contrast axial head CT showing the classic butterfly lesion characteristic of glioblastoma multiforme (red arrow).

Incorrect Answers:
Answer A: Cerebral toxoplasmosis presents on imaging with multiple ring-enhancing lesions and is most common in patients with acquired immunodeficiency syndrome (AIDS), especially with CD4 T-cell counts of less than 100 cells/mm^3. This patient has no signs of infection or ring-enhancing lesions.

Answer C: Hemorrhagic stroke presents acutely with hemiparesis, altered mental status, slurred speech, or sensorimotor symptoms. CT imaging would reveal a hemorrhage.

Answer D: Metastatic brain tumor often presents with imaging findings of multiple well-circumscribed lesions with surrounding edema. These lesions are generally found at the highly vascularized gray-white junction. In a patient with no smoking history, a single brain lesion, and no other extra-cranial symptoms, this is a less likely diagnosis.

Answer E: Neurosarcoidosis can be caused by infiltrative sarcoidosis and often presents with bitemporal hemianopsia due to infiltration of the pituitary gland. Patients with sarcoidosis typically also present with pulmonary symptoms (e.g., wheezing and coughing) which are absent in this patient.

Bullet Summary:
Glioblastoma multiforme should be suspected in patients presenting with symptoms of increasing intracranial pressure and classic CT/MRI findings of a butterfly shaped lesion with central necrosis.


Question:
A 55-year-old man presents to the emergency department after feeling lightheaded then fainting while he was carrying boxes upstairs. The patient works on a farm and does not see a doctor often. He has a history of hypertension but does not take medications routinely. He has not had any chest pain, dyspnea, or weakness during this time frame and currently feels at his baseline. He smokes cigarettes occasionally. His temperature is 98.1°F (36.7°C), blood pressure is 152/93 mmHg, pulse is 86/min, respirations are 15/min, and oxygen saturation is 98% on room air. Physical exam is unremarkable and the patient walks with a stable gait and no focal weakness. An ECG is performed as seen in Figure A. Laboratory studies are ordered as seen below.

Hemoglobin: 12 g/dL
Hematocrit: 36%
Leukocyte count: 6,500/mm^3 with normal differential
Platelet count: 197,000/mm^3

Serum:
Na+: 140 mEq/L
Cl-: 102 mEq/L
K+: 4.3 mEq/L
HCO3-: 24 mEq/L
BUN: 20 mg/dL
Glucose: 139 mg/dL
Creatinine: 1.1 mg/dL
Troponin: < 0.01 ng/mL

Which of the following is the most likely diagnosis?

Answer: Left ventricular hypertrophy

Explanation:
This patient with chronic untreated hypertension is presenting with syncope and an ECG demonstrating large voltages in leads V1-V6 and a left ventricular strain pattern (ST depressions in V5/V6 and aVL), which are concerning for left ventricular hypertrophy.

Left ventricular hypertrophy occurs secondary to chronic hypertension or conditions that increase afterload such as aortic stenosis. This leads to an increase in the mass of the left ventricle. There are many possible criteria on ECG for left ventricular hypertrophy including left axis deviation, large R waves, a large S wave in aVR, or ST segment depression and T wave inversion in the left heart leads (referred to as left ventricular strain). A more simple method of recalling left ventricular hypertrophy is very large voltages in the ECG leads that serve the left ventricle. Left ventricular hypertrophy should be considered in presentations such as syncope. Note that while ECG findings suggest left ventricular hypertrophy, the diagnosis must be supported with echocardiography. Management involves treating the underlying cause (most commonly, this is hypertension).

Artham et al. discuss left ventricular hypertrophy. They note that it is a risk factor for future cardiac events and increased mortality. They recommend early diagnosis and management to improve outcomes.

Figure/Illustration A is an ECG with very large voltages (red arrows) and ST segment depressions/T wave inversions (blue arrows, a more classic left ventricular strain pattern), concerning for left ventricular hypertrophy.

Incorrect Answers:
Answer B: Non-ST elevation myocardial infarction would present with nonspecific ST segment and T wave changes with an elevated troponin. While this patient does demonstrate ST depressions in the lateral leads, the troponin level is normal.

Answer C: ST elevation myocardial infarction would present with ST elevation in a vascular distribution on ECG in the setting of chest pain, diaphoresis, and an elevated troponin level. Note that this patient’s lack of symptoms (pain) and normal troponin in the setting of the ST elevation in leads V1-V3 make this unlikely to be ST elevation myocardial infarction and more likely to be left ventricular hypertrophy.

Answer D: Torsades des pointes occurs in patients with a prolonged QT interval that evolves into twisting of the QRS complexes around an isoelectric baseline. It may cause syncope or cardiac arrest. Note there is no QT prolongation on this patient’s ECG that would predispose him to this condition.

Answer E: Wolff Parkinson White syndrome presents with a delta wave on ECG (a slurred upstroke into the QRS complex) and may undulate with supraventricular or ventricular tachycardia. There is no delta wave in this patient’s ECG supporting this diagnosis. Ablation is the most effective long-term treatment.

Bullet Summary:
Left ventricular hypertrophy can be associated with syncope and presents with large voltages in the leads that serve the left ventricle and a left ventricular strain pattern.


Question: A 28-year-old woman presents to her primary care provider with a headache. Every few weeks she has an episode of a right-sided, throbbing headache. The episodes began several years ago and are accompanied by nausea and bright spots in her vision. The headache usually subsides if she lies still in a dark, quiet room for several hours. The patient denies any weakness, numbness, or tingling during these episodes. Her medical history is significant for acne, hypothyroidism, obesity, and endometriosis. Her home medications include levothyroxine, oral contraceptive pills, and topical trans-retinoin. Her temperature is 98.6°F (37°C), blood pressure is 125/81 mmHg, pulse is 64/min, and respirations are 11/min. She has 2 glasses of wine with dinner several nights a week and has never smoked. She works as a receptionist at a marketing company. On physical exam, the patient has no focal neurologic deficits. A CT of the head is performed and shows no acute abnormalities. Which of the following is the most appropriate treatment for this patient during these episodes?

Answer: Sumatriptan

Explanation:
This patient presents with episodic, unilateral throbbing headaches with photophobia, which suggests a diagnosis of migraine. The most appropriate treatment during these episodes is an abortive medication such as sumatriptan.

Migraines present with unilateral, "throbbing" pain and are associated with nausea and vomiting, photophobia, and phonophobia. Migraines can occur after exposure to specific triggers or they can occur idiopathically. Patients may also endorse visual auras such as bright lines or shapes in the visual field and sensory auras such as paresthesias. Medications like NSAIDs or sumatriptan are usually used as abortive treatment during acute episodes of migraine. Patients with recurrent migraines can be managed with prophylactic medications like topiramate, beta-blockers, or amitriptyline.

Mayans and Walling present evidence regarding the treatment of migraines. They discuss how acetaminophen, nonsteroidal anti-inflammatory drugs, triptans, antiemetics, ergot alkaloids, and combination analgesics are effective against this disease. They recommend providing these treatments in order to mitigate symptoms.

Incorrect Answers:
Answer A: Acetazolamide is used to treat idiopathic intracranial hypertension (IIH). IIH is most commonly seen in obese women of childbearing age and can be caused by medications such as oral isotretinoin (not topical tretinoin, as in this case) and tetracyclines. The initial symptom is usually a pulsatile headache that worsens with lying down and improves upon standing.

Answer B: High-flow oxygen is an abortive treatment for cluster headaches. Cluster headaches typically present in male patients with unilateral pain around the eye that is worse at night. Associated symptoms include spasms of the unilateral face as well as tearing and visual abnormalities in the eye.

Answer D: Topiramate can be used as prophylaxis for migraines but is not commonly used as an abortive medication. Chronic prophylactic medications generally function by decreasing spasms of the cranial blood supply in order to prevent a migraine from developing. They have minimal effectiveness after a migraine has already developed.

Answer E: Verapamil is a prophylactic medication used for cluster headaches. In addition to presenting in the peri-orbital region, cluster headaches are typically accompanied by lacrimation, rhinorrhea, and focal findings such as ptosis. It would not be effective in terminating a migraine.

Bullet Summary:
Triptans are used as an abortive treatment for migraines, which present as unilateral, throbbing headaches that may be associated with nausea and/or vomiting, photophobia, phonophobia, and aura.


Question: A 27-year-old man presents to the emergency department after he developed pain in his right leg after landing off a ski jump. The patient is otherwise healthy and does not take any medications. He states his pain is 10/10. He is requesting medications and is crying out in pain. His temperature is 98.7°F (37.1°C), blood pressure is 149/85 mmHg, pulse is 103/min, respirations are 15/min, and oxygen saturation is 99% on room air. Physical exam reveals swelling over his right leg and knee. The patient cries out in pain with passive motion of the foot at the ankle. A radiograph is performed as seen in Figure A. Which of the following is the most likely diagnosis?

Answer: Tibial plateau fracture

Explanation:
This patient is presenting after an axial load on his lower extremity (landing off a ski jump) with severe pain, a fracture on radiography, and severe pain with passive range of motion. This suggests compartment syndrome in the setting of a tibial plateau fracture.

Tibial plateau fractures occur as a result of an axial load, where the femur forcefully impacts the tibia, leading to intense pain in the proximal tibia region. One potential complication of this type of fracture is compartment syndrome, which presents with exquisite pain out of proportion to exam with passive motion of the lower extremity. While radiography can aid in diagnosing tibial plateau fractures, a negative radiograph should prompt further investigation with a CT scan in patients with a high suspicion of this type of fracture. Treatment involves performing a fasciotomy if compartment syndrome is present. Surgical repair is warranted if there is evidence of neurovascular compromise or a significantly displaced fracture. Otherwise, immobilizing the knee and providing outpatient orthopedic follow-up care is deemed appropriate for certain less severe fractures.

Schneiderman et al. studied compartment syndrome in high-energy tibial plateau fractures. The authors found that younger patients aged 12-29 years old are more likely to develop compartment syndrome, likely due to increased muscle mass and thicker fascial tissue. The risk of deep surgical site infection remains high at 20-25% of cases. The authors recommend that clinicians should be aware of factors associated with increased risk for compartment syndrome, including young age, male gender, and a high-energy mechanism of injury.

Figure/Illustration A is a radiograph demonstrating a tibial plateau fracture with the red arrows demonstrating a fracture of the tibial plateau.

Incorrect Answers:
Answer A: Anterior cruciate ligament tear would present with a sudden popping sensation of the knee with swelling, knee instability, and laxity to anterior traction when force is applied to the tibia causing anterior displacement of the tibia relative to the femur. Management involves assessment with MRI and surgical repair in complete tears or immobilization in partial tears.

Answer B: Apophysitis of the tibial tubercle (Osgood-Schlatter disease) is common in pediatric patients and presents after exertion (such as basketball or jumping) with pain and tenderness over the tibial tubercle. It is caused by repeated microtrauma or microavulsion, separation of the proximal patellar tendon from the tibial tubercle, and subsequent callous deposition at the tibial tubercle. Management involves rest, ice, and nonsteroidal anti-inflammatory drugs.

Answer C: Patellar fracture would present with tenderness over the patella with a fracture line on the patella. Treatment of non-displaced fractures includes rest and immobilization in a straight-leg knee immobilizer.

Answer D: Posterior dislocation of the knee presents with sudden trauma to the knee with pain, swelling, and a loss of pulses in the extremity when the popliteal artery is compromised. Radiography is diagnostic and will show a knee dislocation. Treatment involves immediate reduction to avoid permanent injury to the popliteal artery.

Bullet Summary:
Tibial plateau fractures present after trauma with severe lower extremity pain and are highly associated with compartment syndrome.


Question: A 4-day-old girl presents with her parents to the pediatrician for a routine visit. She was feeding well until this morning when she had several episodes of vomiting. The parents describe the vomitus as “bright green” and the patient has shown little interest in feeding since then. She was born at 36 weeks gestation to a 37-year-old G2P2 mother. The pregnancy was complicated by gestational diabetes, and all prenatal testing was unremarkable. The patient has not yet regained her birth weight and is in the 46th percentile for height and the 36th percentile for weight. The patient’s temperature is 99.2°F (37.3°C), blood pressure is 68/46 mmHg, pulse is 132/min, and respirations are 32/min. On physical exam, the patient is in mild distress. She has no dysmorphic features. Her abdomen is distended and firm without guarding. Bowel sounds are hypoactive. The patient’s abdominal radiograph can be seen in Figure A and the patient’s upper gastrointestinal series can be seen in Figure B. Which of the following is the most likely etiology of this patient’s condition?

Answer: Intestinal malrotation

Explanation:
This patient presents with bilious vomiting and an upper gastrointestinal series demonstrating the “corkscrew” appearance of the distal duodenum and proximal jejunum, which is consistent with a diagnosis of intestinal malrotation.

Intestinal malrotation most commonly presents in newborns with bilious emesis. This condition increases the risk of midgut volvulus where the intestines create a closed loop. Abdominal radiographs are rarely diagnostic but are useful in excluding bowel perforation. An upper gastrointestinal series is the diagnostic test of choice and demonstrates an abnormally placed duodenum with a ligament of Treitz on the right side of the abdomen and a “corkscrew” appearance of the distal duodenum and proximal jejunum. Treatment is with surgical derotation of the bowel or exploratory laparotomy if perforation has occurred.

Adams and Stanton review the evidence regarding the diagnosis and treatment of neonatal bowel obstruction. They discuss how malrotation, jejunoileal atresia, duodenal atresia, and colonic atresia are common causes of this finding. They recommend surgical management of these conditions.

Figure/Illustration A is an abdominal radiograph showing a paucity of air in the abdomen (red circle). These findings are consistent with nonspecific findings of intestinal malrotation.

Figure/Illustration B is an upper gastrointestinal series showing a right-sided ligament of Treitz and a “corkscrew” appearance of the distal duodenum (red circle). These are classic findings of intestinal malrotation.

Incorrect Answers:
Answer A: Although duodenal atresia presents with bilious vomiting, the “double bubble” sign would be seen on an abdominal radiograph, which reflects air trapping in both the stomach and the 1st portion of the duodenum. Treatment is with surgical repair of the obstructed segment.

Answer B: Hirschsprung disease may also cause bilious vomiting, but an abdominal radiograph would demonstrate proximal colonic distension with little air in the rectosigmoid colon. Hirschsprung disease is also well visualized on contrast enema, on which a transition point can be seen between the proximal dilated colon and the narrow sigmoid. Treatment is with excision of the defective segment.

Answer D: Jejunal atresia can also lead to bilious vomiting, although a “triple bubble” sign would be seen on an abdominal radiograph with air additionally filling the proximal jejunum. Treatment is with excision of the atretic segment and anastomosis of the bowel lumen.

Answer E: Meconium ileus may present with bilious emesis, but multiple dilated loops of bowel would be seen on an abdominal radiograph. Meconium ileus is better characterized by contrast enema, on which a microcolon can be visualized. Treatment is with the removal of the meconium and treatment of the underlying cystic fibrosis, if present.

Bullet Summary:
Intestinal malrotation presents in newborns with bilious emesis, an upper gastrointestinal series demonstrating a misplaced duodenum, and a “corkscrew” appearance of the distal duodenum and proximal jejunum.


Question:
A 72-year-old man presents to his primary care physician for a general checkup. He states that he has been a bit more fatigued lately but believes it is secondary to poor sleep at his new house. The patient is otherwise healthy and takes no medications. His temperature is 98.0°F (36.7°C), blood pressure is 141/90 mmHg, pulse is 82/min, respirations are 16/min, and oxygen saturation is 98% on room air. Physical exam is notable only for minor pallor but is otherwise unremarkable. Basic laboratory studies are ordered as seen below.

Hemoglobin: 10 g/dL
Hematocrit: 30%
Leukocyte count: 67,500/mm^3
Platelet count: 119,000/mm^3

Serum:
Na: 141 mEq/L
Cl: 103 mEq/L
K: 4.0 Eq/L
HCO3-: 24 mEq/L
BUN: 22 mg/dL
Glucose: 109 mg/dL
Creatinine: 1.2 mg/dL
Ca: 10.0 mg/dL

Which of the following is the most likely diagnosis?

Answer: Chronic lymphocytic leukemia

Explanation:
This elderly patient is presenting with minor fatigue, anemia, thrombocytopenia, and a leukocyte count >50,000/mm^3, which is most likely caused by chronic lymphocytic leukemia (CLL).

CLL is a monoclonal proliferation of incompetent mature B-cells. It is common in elderly men and is the most common form of leukemia in the United States. Patients are often asymptomatic when the diagnosis is made or may present with vague constitutional symptoms including fatigue, malaise, and weight loss. It is important to note that symptoms may be subtle or absent. Other findings include non-tender lymphadenopathy and splenomegaly. The diagnosis is supported when the white blood cell count is >50,000/mm^3 and can be supported with a peripheral smear which will show smudge cells. The cells in CLL may be CD5, CD20, and CD23 positive. The most common cause of death in this population is infection given the lack of competent B-cells.

Hallek reviews CLL. They discuss updated guidelines on the diagnosis and management of CLL. They recommend the use of targeted agents in initial therapy and acknowledge the need for further clinical trials to guide therapy.

Incorrect Answers:
Answer A: Acute lymphoblastic leukemia (ALL) is a common malignancy seen in children and presents with pancytopenia, anemia, fatigue, leukopenia (leading to recurrent infections), and thrombocytopenia (leading to bleeding). Other findings may include fever, bone pain, lymphadenopathy, splenomegaly, and hepatomegaly. Translocations in ALL include: t(12:21) which is the most common and denotes a favorable prognosis and t(9:22) (the Philadelphia chromosome) which is less common and denotes a poor prognosis

Answer B: Acute myelogenous leukemia occurs secondary to the proliferation of myeloblasts and presents in older patients. Patients will present with fatigue, malaise, weight loss, anorexia, fever, leukocytosis, anemia, thrombocytopenia, and neutropenia. Auer rods are frequently present on a blood smear.

Answer D: Chronic myelogenous leukemia is a neoplastic proliferation of myeloid stem cells and presents with a leukocyte count often >50,000/mm3. The increased myeloid lines include red blood cells, granulocytes, monocytes, and platelets. Many patients present in the chronic phase with minimal symptoms; however, the blast phase can lead to a hematologic emergency termed a blast crisis which may cause a hyperviscosity syndrome. This condition is more symptomatic and less common than CLL.

Answer E: Hairy cell leukemia occurs when there is a neoplastic proliferation of mature B cells with abundant cytoplasm with “hairy” cytoplasmic processes. The cells are tartrate-resistant acid phosphatase positive. Patients will present with splenomegaly, pancytopenia, weakness, and fatigue. This is a more rare diagnosis when compared to CLL.

Bullet Summary:
Chronic lymphocytic leukemia (CLL) presents in elderly patients with malaise, fatigue, and other nonspecific signs (but can also be asymptomatic), with anemia, thrombocytopenia, and a white blood cell count often >50,000/mm^3.


Question: A 27-year-old G1P0000 woman presents to her obstetrician’s office at 24 weeks gestation complaining of new hair growth on her upper lip. She now needs to shave her face every day or else thick hair appears. She also has worsening acne that started several weeks ago. Her pregnancy thus far has been complicated by gestational diabetes, which is managed by diet and exercise. She has a male fetus based on her 20 week anatomy ultrasound. The patient has a medical history of polycystic ovary syndrome. The patient’s temperature is 98.5°F (36.9°C), blood pressure is 121/76 mmHg, pulse is 70/min, and respirations are 13/min. The cardiopulmonary exam is normal, and the patient’s abdomen has a fundal height of 31 cm. A pelvic exam reveals an unremarkable closed cervix and a right-sided adnexal mass without tenderness. Transvaginal ultrasound is performed and shown in Figure A. Which of the following is the most appropriate next step in management?

Answer: Reassurance

Explanation:
This patient presents with hirsutism and acne, symptoms of hyperandrogenism, as well as a solid pelvic mass on ultrasound, most consistent with a luteoma. The most appropriate next step in management is reassurance as the mass tends to self-resolve after pregnancy.

Luteomas are ovarian tumors that arise during pregnancy and produce androgens, causing maternal and sometimes fetal virilization. They appear as solid masses on ultrasound and are not malignant. The likelihood of virilizing the fetus increases if the luteoma arises in the 1st trimester and affected female fetuses present with clitoromegaly or labioscrotal fusion. Male fetuses are not affected. Treatment is supportive as the masses tend to resolve after pregnancy.

Wang et al. review the evidence regarding the diagnosis and treatment of luteomas. They discuss how this is a rare tumor that primarily affects women who have had multiple pregnancies. They recommend early diagnosis of this condition in order to inform treatment options.

Figure/Illustration A shows a transvaginal ultrasound with a solid mass on the right ovary (red circle). This appearance is consistent with a luteoma.

Incorrect Answers:
Answer A: Laparoscopy to prevent detrimental effects on the fetus is not considered a treatment option for luteomas. In this patient, the exposure to high androgen levels is late in pregnancy and the fetus is a male, making it especially unnecessary to perform surgery.

Answer B: Laparoscopy to remove a malignancy is not indicated for luteomas, which are benign tumors and self-regress after delivery. Malignancies that can cause virilization in or outside of pregnancy include Sertoli-Leydig cell tumors and Krukenberg tumors.

Answer C: Percutaneous umbilical blood sampling to determine prognosis may be performed in women who have early virilization and female fetuses. High androgen levels in the umbilical cord are required for the virilization of the fetus, whereas high androgen levels in the mother’s peripheral blood may not predict this outcome.

Answer E: Spironolactone to treat hirsutism and acne is used outside of pregnancy in women with polycystic ovary syndrome. However, because it is an anti-androgen, spironolactone should not be used in pregnancy as it can cause feminization of male fetuses.

Bullet Summary:
Luteomas generally do not require treatment as they regress after pregnancy.


Question: A 37-year-old machinist presents to his primary care physician with eye problems. He has felt a mass in his eye that has persisted for the past month. The patient has a medical history of blepharitis treated with eye cleansing and squamous cell carcinoma of the skin treated with Mohs surgery. His temperature is 99.5°F (37.5°C), blood pressure is 157/102 mmHg, pulse is 90/min, respirations are 17/min, and oxygen saturation is 98% on room air. Physical exam is notable for a firm and rubbery nodule palpable inside the patient's left eyelid. Physical exam does not elicit any pain. Which of the following is the most likely diagnosis?

Answer: Chalazion

Explanation:
This patient presenting with a painless firm and rubbery nodule has symptoms that are suggestive of a chalazion.

Chalazion presents with a hard and painless eyelid nodule. This pathology occurs secondary to granulomatous inflammation of the Meibomian gland. The lesion can be treated with simple excision; however, recurrent lesions are concerning for Meibomian cell carcinoma. The most important differential diagnosis to consider in these patients is a hordeolum which presents with a firm and painful lid nodule (in contrast to painless). Treatment is with warm compresses followed by incision and curettage in refractory cases.

Li et al. review the evidence regarding the diagnosis and treatment of chalazion. They discuss how gland loss is a possible sequelae from this disorder. They recommend using warm compresses for symptomatic relief.

Incorrect Answers:
Answer B: Foreign body is a possible diagnosis given this patient's occupation as a machinist; however, this would typically present with pain over the patient's cornea with a sudden onset of symptoms. Treatment is with removal of the foreign body.

Answer C: Hordeolum presents with a hard and painful lid nodule in contrast to a hard and painless lid nodule. Treatment is with warm compresses and possible debridement in refractory cases.

Answer D: Ingrown eyelash follicle could present with a firm lid nodule; however, it would be located near the margin of the eyelid and would likely be inflamed and tender. Treatment is with warm compresses and possible debridement in refractory cases.

Answer E: Meibomian cell carcinoma is a possible diagnosis but is epidemiologically less common than a chalazion. This diagnosis would be more likely if the lesion was recurrent despite excision. Treatment is with wide excision of the lesion.

Bullet Summary:
Chalazion presents with a firm and painless eyelid nodule.


Question: A 59-year-old woman comes to the clinic due to a 3-month history of “always feeling the urge to urinate” as well as vaginal pruritis. She states that she has had involuntary loss of urine about 4 times each day over the past 3 months. It is not associated with coughing or sneezing. Menopause occurred at age 52. She has a history of chlamydial infection in her 20's and has had 3 urinary tract infections over the past year. The patient has not been sexually active with her husband due to pain with intercourse. She has no other significant medical history and does not take any medications. Her temperature is 98.6°F (37.0°C), blood pressure is 115/70 mmHg, pulse is 70/min, and respirations are 12/min. On physical examination, the vulvar skin is pale and atrophic with reduced elasticity and multiple areas of petechiae. The vaginal mucosa also has a loss of rugae and several areas of friable irritation. There is minimal clear vaginal discharge. Urinalysis is normal and fecal occult blood test is negative. Pelvic ultrasound reveals a small, retroverted uterus. Which of the following is the most appropriate next step in management?

Answer: Vaginal moisturizers

Explanation:
This postmenopausal patient is presenting with vulvovaginal dryness and irritation, dyspareunia, urinary incontinence, and recurrent urinary tract infections, likely due to genitourinary syndrome of menopause (GSM). The most appropriate initial treatment is symptomatic relief with vaginal moisturizers and lubricants.

Reduced estrogen levels after menopause lead to vulvovaginal atrophy by causing reduced blood flow and collagen content in vulvovaginal tissues. Patients typically have thin vulvar skin and loss of vaginal tissue pliability. The bladder and urethral epithelium may also atrophy leading to dysuria and urinary frequency. Atrophic tissue becomes thin, dry, and susceptible to injury. The first line of treatment is vaginal moisturizers and lubricants. If this does not improve symptoms, the next step in treatment is vaginal estrogen to help restore blood flow in vulvovaginal tissues. Finally, hormone replacement therapy is indicated if symptoms are refractory to all other modalities.

Bhupathiraju et al. studied the association between vaginal estrogen and chronic disease risk. The authors found no association between low-dose vaginal estrogen and cardiovascular disease, cancer, and hip fractures over an 18-year period. The authors recommended that low-dose vaginal estrogen can be used indefinitely without concomitant progestin therapy.

Incorrect Answers:
Answer A: Metronidazole is the treatment for trichomoniasis or bacterial vaginosis. While patients with trichomoniasis can present with cervical petechiae and punctate hemorrhages, they typically also have frothy green discharge (absent in this patient). While patients with bacterial vaginosis can also have vaginal discharge, the discharge is typically malodorous and symptoms of pruritis are generally absent.

Answer B: Nitrofurantoin is the treatment of choice for urinary tract infections. While this patient has increased urinary frequency and a history of recurrent urinary tract infections, her normal urinalysis makes the diagnosis of urinary tract infection unlikely.

Answer C: Topical clobetasol cream is the treatment for lichen sclerosis. While lichen sclerosis can present with pain with intercourse and vulvar pruritis, patients often have plaques that disrupt the normal vulvar architecture. Lichen sclerosis does not affect the vaginal tissues.

Answer D: Topical estrogen is the treatment of choice for cases of vulvovaginal atrophy resistant to treatment with vaginal moisturizers and lubricants. This patient should first be trialed on vaginal moisturizers and lubricants.

Bullet Summary:
Vulvovaginal atrophy is initially treated with vaginal moisturizers and lubricants.


Question: A 16-year-old boy presents to his primary care physician for a routine follow-up visit. He feels disappointed because his voice has not changed. He is concerned that he is not as tall as his classmates. He denies any headache, vision changes, nausea, or vomiting. He recently started playing for his high school basketball team and generally eats healthy food. He has no significant medical history and takes no medications. His temperature is 98.6°F (37.0°C), blood pressure is 115/70 mmHg, pulse is 70/min, and respirations are 12/min. On physical examination, the patient does not have facial hair or acne. His height is 60 inches and his arm span is 50 inches. His visual fields are full and he has no cranial nerve abnormalities. His strength is 5/5 in bilateral upper and lower extremities. Chest palpation and abdominal examination are unremarkable. He has no pubic hair and his testicles are symmetric with a volume of 3 mL. Which of the following is the most appropriate next step in management?

Answer: Radiograph of the hand and wrist

Explanation:
This patient is greater than 14 years of age without the development of secondary sex characteristics (e.g., testicular volume < 4 mL), which is concerning for delayed puberty. The patient should have a radiograph of the hand and wrist to evaluate for discrepancies between bone age and chronological age.

Delayed puberty in boys is defined as the absence or incomplete development of secondary sexual characteristics (increased testicular volume and pubic hair) at 14 years or older. It has a variety of etiologies including chromosomal abnormalities, gonadotropin-releasing hormone (GnRH) deficiencies, and constitutional delay of puberty. In addition to obtaining a history and physical examination, initial diagnostic studies used to work up delayed puberty includes a radiograph of the hand and wrist to determine bone age, and serum studies (complete blood count, complete metabolic panel, follicular-stimulating hormone [FSH], luteinizing hormone [LH], and testosterone). Radiography can compare the patient's bone age to the chronological age (as constitutional delay presents with delayed bone age), and serum endocrine studies can help distinguish between primary causes of hypogonadism (high FSH and LH) and secondary causes of hypogonadism (low to normal FSH and LH). Treatment in cases with a specific cause of delayed puberty is aimed at the underlying cause. For male patients with presumed constitutional delay of puberty, therapy can include hormone replacement with testosterone.

Saengkaew et al. discuss the genetics of pubertal delay. The authors find that pathologic mechanisms that may underlie constitutional delay of puberty are largely related to GnRH neuronal development and biology. The authors recommend further study of GnRH neuronal biology and network functionality to provide the opportunity for improved therapies for patients with disorders of puberty.

Incorrect Answers:
Answer A: Karyotyping is a useful diagnostic study in patients with Klinefelter syndrome, which would demonstrate 47, XXY. Patients would present with a eunuchoid habitus (arm span at least 5 cm longer than height), gynecomastia, and testicular atrophy.

Answer B: Magnetic resonance imaging (MRI) of the brain with gadolinium is a useful diagnostic study in patients with neurological symptoms in addition to hypogonadism. These symptoms would suggest that the patient has a prolactinoma causing impingement of the optic chiasm leading to bitemporal hemianopsia and sometimes a headache. Laboratory studies consistent with a prolactinoma include elevated serum prolactin with low to normal FSH and TSH.

Answer C: Reassurance with close follow-up would be appropriate in some patients with constitutional delay of puberty, which is the most common cause of delayed puberty. It is believed to be caused by a transient defect in the production of GnRH. Patients typically have a family history of "late bloomers," characterized as family members having a late growth spurt or late puberty.

Answer E: Testicular ultrasound would be appropriate in patients with asymmetric testicles since gonadal tumors can occur in a number of intersex disorders (e.g., androgen insensitivity syndrome) and present with impaired sexual maturation.

Buller Summary:
Delayed puberty in boys is defined as a lack of testicular enlargement by age 14 and initial diagnostic evaluation should include radiography of the hand and wrist as well as serum testing (FSH, LH, and testosterone).


Question: A 27-year-old woman presents to her primary care physician with pain in her hands, shoulders, and knees. The pain has lasted for several months but seems to have worsened recently. Any activity such as opening jars, walking, or brushing her teeth is painful. The patient has a medical history of a suicide attempt in college, constipation, anxiety, depression, and a sunburn associated with surfing which was treated with aloe vera gel. Her temperature is 99.5°F (37.5°C), blood pressure is 137/78 mmHg, pulse is 92/min, respirations are 14/min, and oxygen saturation is 98% on room air. Laboratory values are obtained and shown below. Hemoglobin: 9 g/dL Hematocrit: 33% Leukocyte count: 2,500/mm^3 with normal differential Platelet count: 107,000/mm^3 Serum: Na+: 139 mEq/L Cl-: 102 mEq/L K+: 4.4 mEq/L HCO3-: 24 mEq/L BUN: 21 mg/dL Glucose: 90 mg/dL Creatinine: 1.0 mg/dL Ca2+: 10.2 mg/dL AST: 12 U/L ALT: 10 U/L Which of the following findings is the most likely to be positive in this patient?

Anti-cyclic citrullinated peptide antibodies

Answer: Anti-dsDNA antibodies

Explanation:
This patient is presenting with arthralgias, pancytopenia, possible malar rash, and a history of depression/abnormal behavior. Epidemiologically, the most likely diagnosis is systemic lupus erythematosus (SLE) which is associated with anti-dsDNA antibodies.

SLE is an autoimmune disorder that most commonly occurs in young adult women. It presents with at least 4 criteria from SOAP BRAIN MD - Serositis, Oropharyngeal ulcers, Anti-nuclear antibodies, Photosensitivity, Blood disorders (pancytopenia and hemolytic anemia), Renal abnormalities (proteinuria), Arthralgias, Immune disease (hemolytic anemia and anti-dsDNA), Neurologic (psychosis, stroke, and seizure), Malar rash, and Discoid rash. The most common presenting symptoms for SLE can often be just arthralgias/arthritis with vague other symptoms suggestive of a rheumatologic disorder. Anti-nuclear antibodies are very sensitive for this pathology and anti-dsDNA antibodies are very specific. Treatment may include hydroxychloroquine as well as other immunomodulators and management of end-organ dysfunction.

Wang and Xia review the evidence regarding double stranded DNA in patients with SLE. They discuss how these antibodies are a very specific finding in this disease. They recommend measuring these levels.

Incorrect Answers:
Answer A: Anti-cyclic citrullinated peptide is associated with rheumatoid arthritis which is a possible diagnosis in this patient, but it is less likely epidemiologically given her age and other symptoms of pancytopenia and a history of sunburn (which is likely a malar rash or photosensitivity). Treatment is with methotrexate.

Answer C: Anti-histone antibodies would be found in drug-induced lupus. This patient's medication history is not known; however, this is a less likely diagnosis compared to SLE. Treatment is with discontinuation of the offending medication.

Answer D: Degenerated cartilage in weight bearing joints describes osteoarthritis which tends to affect the knees and hips in older patients. Treatment is with conservative management or with total joint replacement.

Answer E: IgM against parvovirus B19 describes a parvovirus B19 infection which commonly presents with arthralgias; however, her other symptoms point towards a diagnosis of SLE. Treatment is supportive.

Bullet Summary:
Arthritis/arthralgias are often the most common presenting symptom for SLE.


Question: A 31-year-old woman presents to her obstetrician for her first prenatal visit after having a positive home pregnancy test 1 week ago. Her last menstrual period was 8 weeks ago. The patient has a medical history of type 1 diabetes mellitus since childhood and her home medications include insulin. Her hemoglobin A1c 2 weeks ago was 13.7%. At that time, she was also found to have microalbuminuria on routine urinalysis. Her primary care provider prescribed lisinopril but the patient has not yet started taking it. The patient’s brother is autistic but her family history is otherwise unremarkable. Her temperature is 98.6°F (37.0°C), blood pressure is 124/81 mmHg, pulse is 75/min, and respirations are 14/min. A physical exam is unremarkable. This fetus is most likely at increased risk for which of the following complications?

Answer: Neural tube defect

Explanation:
This patient has type 1 diabetes mellitus and presents in early pregnancy with a markedly elevated hemoglobin A1c, suggesting poor glycemic control. Poor glycemic control increases the risk of a neural tube defect in the fetus.

Infants of diabetic mothers (IDM) are at increased risk of many congenital malformations as well as postnatal complications. These risks are more likely if there is poor maternal glycemic control, especially in the periconceptional period. Poorly controlled hemoglobin A1c and microalbuminuria on urinalysis indicate long-standing poor glycemic control and indicate a poor prognosis. The most common anomalies in IDM are cardiovascular defects such as septal defects and transposition of the great arteries as well as neural tube defects such as anencephaly and spina bifida. Sacral agenesis, or a poorly developed caudal spine and spinal cord, as well as small left colon syndrome due to a meconium plug, are other common malformations seen in IDM. General complications in IDM include prematurity, intrauterine growth restriction or macrosomia, and miscarriage. Risk is minimized by tight glycemic control throughout pregnancy.

Dean et al. summarize the evidence surrounding micronutrients and obesity in pregnancy. They found that patients with diabetes had a higher risk of having infants with a neural tube or a congenital heart defect. They recommend using folic acid supplementation in all patients to reduce the risk of neural tube defects.

Incorrect Answers:
Answer A: Aneuoploidy risk is not increased in IDM. This complication is associated with advanced maternal age. This patient is at baseline risk since she is below the “advanced maternal age” cutoff of 35 years. Some of the values used in aneuploidy screening (maternal serum alphafetoprotein, estriol, and inhibin A) are generally lower in women with diabetes. Guidelines specific to this patient population should be used for the aneuploidy screen so as to avoid false positive results.

Answer B: Neonatal hyperglycemia is not seen in IDM. Patients may experience hypoglycemia. This is due to the crossing of glucose from the mother to the fetus via the placenta and subsequent hyperinsulinemia and ß-cell hyperplasia from the fetus. After delivery, the high insulin levels cause hypoglycemia because there is no longer an overabundant source of glucose. Hyperglycemia in infants is much less common and can be due to glucose infusion or sepsis.

Answer D: Oligohydramnios is not specifically associated with maternal hyperglycemia. Instead, patients may experience polyhydramnios. The mechanism for increased amniotic fluid is unclear, though some speculate that fetal hyperglycemia results in polyuria and thus polyhydramnios. Severe oligohydramnios can cause pulmonary hypoplasia and clubfoot as well as cord compression, while polyhydramnios is associated with cord prolapse, placental abruption, and prematurity.

Answer E: Post-term delivery occurs after 42 weeks gestation. Maternal diabetes typically causes prematurity. Post-term delivery is associated with fetal malnutrition, hypoxemia, and oligohydramnios due to suboptimal functioning of the placenta. The risk of meconium aspiration increases as gestational age increases. Induction of labor is generally performed at 42 weeks to avoid these complications.

Bullet Summary:
Maternal hyperglycemia from diabetes mellitus is associated with congenital heart defects, neural tube defects, and small left colon syndrome.


Question: A 32-year-old G1P0 woman delivers a boy at 40 weeks and 3 days of gestation. The delivery is uncomplicated and the neonate has Apgar scores of 9 and 9 at 1 and 5 minutes respectively. After 15 minutes, he attempts to nurse for the 1st time. His mother notices that his face, chest, and extremities turn dusky blue during nursing. She also notes that he seems to be snoring loudly and breathing very quickly. When she removes him from her breast, he begins to cry and his color improves. The neonate’s prenatal course was unremarkable, and his mother has a medical history of asthma with occasional albuterol inhaler use. As the infant is resting, vital signs are taken. His temperature is 98.2°F (36.7°C), pulse is 130/min, respirations are 45/min, and oxygen saturation is 97% on room air. A physical exam demonstrates well-perfused skin but is notable for the facial features shown in Figure A. Which of the following is most likely to be observed in this neonate?

Answer: Inability to pass a nasogastric tube

Explanation:
This neonate presents with central cyanosis upon feeding, resolution with crying, and midface hypoplasia on exam, most consistent with choanal atresia. A nasogastric (NG) tube would not pass through the nasal canal.

Choanal atresia is caused by failed recanalization of the nasal fossae during fetal development. This disease typically presents with noisy breathing, cyanosis when feeding, and improvement with crying and the use of the mouth for breathing. Cyanosis in this condition affects the entire body as opposed to just the hands and feet. Bilateral atresia often presents early in life. Clinical suspicion of choanal atresia should prompt an attempt to pass an NG tube, which will meet resistance at the posterior part of the nasal canal. Treatment is with the surgical creation of the nasal passages.

Lesciotto et al. review the diagnosis and pathophysiology of patients with choanal atresia. They discuss how this condition is often comorbid with craniosynostosis. They recommend a better understanding of how these patients develop decreased nasal airway volume.

Figure/Illustration A is a clinical photograph showing midface hypoplasia with a poorly developed nasal bone (red circle). These findings are consistent with a diagnosis of choanal atresia.

Incorrect Answers:
Answer A: Areflexia in all extremities may be seen in spinal muscular atrophy, a genetic condition that causes loss of motor neurons. This condition may cause difficulty feeding due to weakness of the oropharyngeal and glossopharyngeal muscles, but it typically does not cause cyanosis. Treatment is with steroid use and nusinersen.

Answer B: Digital clubbing can result from chronic hypoxemia, as seen in conditions such as cystic fibrosis. It would be unexpected for a neonate to have clubbing as the characteristic finger appearance depends on the long-term deposition of platelet-derived growth factor and would not develop within minutes. This patient also does not have cyanosis at baseline. Treatment of cystic fibrosis is with enzyme repletion and respiratory therapy.

Answer D: Markedly decreased lung volume can occur in congenital diaphragmatic hernia, in which the abdominal contents herniate into the chest cavity and cause pulmonary hypoplasia. Infants may present with cyanosis due to respiratory failure, but there would be no association with feeding or improvement with crying. Vital signs would also be abnormal. Treatment is with surgical repair of the diaphragm.

Answer E: A patent foramen ovale occurs when the connection between the left and right atria does not close soon after birth. It does not result in cyanosis and is typically asymptomatic, though it may cause paradoxical embolism and stroke later in life. Treatment of a symptomatic patent foramen ovale is surgical closure of the defect.

Bullet Summary:
Choanal atresia presents with cyanosis and respiratory distress that worsens with feeding and improves with crying associated with failure to pass a nasogastric tube.


Question: A 24-year-old woman presents to clinic for a routine annual exam. She has generally been feeling well, but notes feeling intermittent palpitations over the past few months. Her past medical history is unremarkable and she is not currently taking any medications. She denies drinking alcohol, smoking cigarettes, or using recreational drugs. She attributes her palpitations to recently drinking more caffeine, but would like to obtain an electrocardiogram since her symptoms are worrisome and affecting her ability to concentrate on her career as a fitness instructor. Her temperature is 36.9°C (98.4°F), blood pressure is 116/76 mmHg, pulse is 55/min, respirations are 12/min, and oxygen saturation is 98% on room air. Her electrocardiogram is shown in Figure A. Which of the following is the most likely diagnosis?

Second degree atrioventricular block, Mobitz type II

Answer: Second degree atrioventricular block, Mobitz type I

Explanation:
This patient's progressively increasing PR intervals until a P wave is not followed by a QRS complex on ECG is consistent with second degree atrioventricular (AV) block, Mobitz type I, also referred to as Wenckebach phenomenon.

Second degree AV block, Mobitz type I can occur in a variety of settings, such as in the context of digoxin, beta blockers, calcium channel blockers, or increased vagal tone. On ECG, there is progressive lengthening of the PR intervals until a P wave is not followed by a QRS complex (a dropped beat); then, the PR interval resets. Patients are typically asymptomatic, but should undergo evaluation for an underlying etiology of the dysrhythmia, such as electrolyte imbalances, medication side effect, or structural heart disease, as well as a follow-up ECG to evaluate for any progression. If the dysrhythmia is caused by medication, the offending agent should be discontinued, but otherwise there are no specific treatments necessary for asymptomatic patients. Patients who are symptomatic and hemodynamically stable can undergo telemetry monitoring and receive atropine with limited efficacy. Patients who are hemodynamically unstable and not responsive to atropine may need cardiac pacing. Generally, there is a low risk of progression to third degree AV block, and a pacemaker is rarely required (in contrast to second degree heart block type II).

Barold and Hayes review second-degree heart block. They note the changes in AV node conduction time on ECG in this condition. They recommend using the correct definition of the different heart blocks for the correct underlying treatment.

Figure/Illustration A is an ECG showing PR intervals that gradually prolong until a P wave is seen not followed by a QRS complex (note the blue bars that show the progressive lengthening of the PR intervals until the dropped beat).

Incorrect Answers:
Answer A: First degree AV block is seen on ECG with prolonged PR intervals greater than 0.2 sec, but a consistent 1:1 ratio of P waves to QRS complexes. This finding is typically found in younger patients with increased vagal tone or in athletes, and does not require treatment.

Answer C: Second degree AV block, Mobitz type II is seen with fixed PR intervals and occasional dropped QRS complexes. Patients with Mobitz II sometimes present with syncope and frequently progress to third degree AV block. This finding may be associated with fibrotic changes to the conduction system or from acute, subacute, or prior myocardial infarction, and should be treated with placement of a pacemaker in most cases.

Answer D: Sinus bradycardia findings on ECG include normal sinus rhythm with a ventricular rate of less than 60 beats per minute. Patients with sinus bradycardia may be asymptomatic, but may also present with syncope, lightheadedness, chest pain, or hypotension. No treatment is required if the patient is asymptomatic, but atropine may be given to increase the heart rate in symptomatic cases. Pacemaker placement is required for patients with chronic symptoms.

Answer E: Third-degree AV block occurs when the atria and ventricles depolarize independently on ECG. There is no relationship between P waves and QRS complexes. Patients may present with syncope, dizziness, acute heart failure, or hypotension. The treatment is pacemaker placement.

Bullet Summary:
Second degree atrioventricular block, Mobitz type I, is characterized by progressively lengthening PR intervals until a P wave is not followed by a QRS complex.


Question: A 59-year-old man presents accompanied by his wife with nausea and dizziness. He is unsure when his symptoms started, but they have been affecting him for “a while.” It began as episodes of “unsteadiness” that progressed to a feeling of “spinning.” He cannot tell if his symptoms change with position but reports that if he does not lie down he will become nauseous. He also has worsening hearing loss worse on his right side. The patient’s medical history is significant for hypertension, alcohol use disorder, and chronic obstructive pulmonary disease. His medications include aspirin, amlodipine, and fluticasone-salmeterol. He drinks a glass of red wine every night with dinner and smokes a cigar on the weekends. His temperature is 98.6°F (37°C), blood pressure is 135/91 mmHg, pulse is 72/min, and respirations are 12/min. Examination shows delayed horizontal nystagmus. Which of the following is the most appropriate treatment for this patient's condition?

Answer: Low-salt diet

Explanation:
This patient is presenting with chronic vertigo, hearing loss, and horizontal nystagmus, which is suggestive of Meniere disease. The most appropriate initial step in the management of this disease is a low-salt diet.

Meniere disease is caused by an abnormal accumulation of endolymph within the inner ear. Symptoms will include chronic relapsing and remitting episodes of vertigo, sensorineural hearing loss, tinnitus, and nausea. Physical exam, audiometry, and vestibular testing can be performed to confirm the diagnosis. First-line treatment is a thiazide diuretic as well as lifestyle modifications including a low-salt diet as well as avoidance of alcohol, nicotine, and caffeine. If symptoms persist, additional therapy may involve vestibular nerve ablation or a labyrinthectomy.

Tassinari et al. review the evidence regarding the treatment of Meniere disease. They discuss how vertigo, low-pitched tinnitus, and hearing loss are characteristic of this disease. They recommend creating a database to allow for better research into this disease.

Incorrect Answers:
Answer A: CN VIII ablation can be used to treat Meniere disease that is uncontrolled by diet modifications or thiazide diuretics. Patients usually respond to conservative care so a complete course of these treatments should be trialed first.

Answer B: The Epley maneuver can be used to treat benign paroxysmal positional vertigo (BPPV). Patients will present with vertigo that changes with the patient's position without hearing loss or tinnitus. This maneuver functions by dislodging otoliths from the semicircular canals.

Answer D: Meclizine can be used to treat other types of vertigo such as BPPV or viral labyrinthitis. Labyrinthitis can present with similar symptoms to the symptoms of Meniere disease, but they will be acute and self-limited. There will also be inflammation of the cochlear portion of the inner ear.

Answer E: Thiamine can be used for Wernicke-Korsakoff syndrome. A history of chronic heavy alcohol use, confusion with confabulation, ataxia, memory loss, and nystagmus are all concerning signs that may indicate thiamine deficiency.

Bullet Summary:
Meniere disease should be treated initially with a low-salt diet, avoidance of triggers, and thiazide diuretics.


Question: A 66-year-old man presents to the clinic for evaluation of a skin lesion on his hand. The lesion has grown rapidly over the previous 2 weeks. He endorses trauma to the area when he accidentally scraped his hand against a window and notes that there was some bleeding. His medical history is significant for chronic renal failure for which he received a renal transplant 5 years prior, as well as multiple surgeries for skin cancer. His current medications include aspirin, atorvastatin, prednisone, tacrolimus, and mycophenolate mofetil. His temperature is 98.6°F (37°C), blood pressure is 136/91 mmHg, pulse is 82/min, and respirations are 11/min. Physical exam is notable for a 2 x 2.5 cm nodular lesion of the dorsal hand as seen in Figure A. Which of the following is the most likely diagnosis?

Answer: Keratoacanthoma

Explanation:
This patient presents with a rapidly enlarging, well-circumscribed, volcano-like papule with a central keratotic core consistent with the diagnosis of keratoacanthoma.

Keratoacanthomas represent a well-differentiated variant of cutaneous squamous cell carcinoma. They present as a rapidly enlarging skin lesion with a characteristic hyperkeratotic core. Most lesions occur on the sun-exposed areas of the body, especially the head, neck, and extremities. Risk factors for developing a keratoacanthoma include immunosuppression, arsenic exposure, old scars or burns, xeroderma pigmentosum, or exposure to high levels of ionizing radiation. Most keratoacanthomas tend to involute within several months after initial onset; however, surgical excision can be performed because of the histologic similarity to squamous cell carcinoma. Biopsy of lesions with malignant transformation will show atypical keratinocytes and malignant cells, invasion into dermis, and keratin “pearls” on histology.

Kwiek and Schwartz present a review of keratoacanthoma diagnosis and treatment. They discuss how these lesions characteristically exhibit spontaneous regression after rapid growth. They recommend surgical excision as first-line therapy for the lesion.

Figure/Illustration A is a clinical photograph showing a well-circumscribed, dome-shaped papule with a hyperkeratotic core (red circle) consistent with keratoacanthoma.

Incorrect Answers:
Answer A: Basal cell carcinoma is the most common skin cancer in humans. It most commonly presents as a pearly pink papule or ulcer with telangiectasias and a rolled border. Compared to keratoacanthoma, basal cell carcinomas are slow-growing and are only locally invasive. Surgical excision is the treatment of choice for most basal cell carcinomas.

Answer C: Molluscum contagiosum is a common viral infection caused by a poxvirus that is most frequently seen in children. It presents with solitary or multiple umbilicated papules and is spread by person-to-person contact. Immunosuppressed individuals, such as those with HIV/AIDS, may have disseminated molluscum contagiosum, which is highly recalcitrant to treatment.

Answer D: Pyogenic granulomas are vascular proliferations that present as rapidly growing, pink to red, friable papules that are prone to bleeding with minor trauma. They are most commonly seen in children and pregnant women. The oral mucosa is a common area of presentation, although pyogenic granulomas may present in any skin location. Treatment is through mechanical removal via surgical excision, laser ablation, or electrical curettage.

Answer E: Verruca vulgaris is a common viral infection of the skin caused by several subtypes of human papilloma virus (HPV). They present as rough-textured or filiform papules. Close examination may reveal pinpoint areas of red/black, which represent thrombosed blood vessels within the wart. Treatment options for common warts include salicylic acid or cryotherapy; however, recurrence after treatment is common.

Bullet Summary:
Keratoacanthomas presents as rapidly enlarging, well-circumscribed, volcano-like papules with a central hyperkeratotic core.


Question: A 72-year-old man with a history of type 2 diabetes mellitus, hypertension, and hyperlipidemia presents to his primary care provider for concerns about his cognitive decline. His wife has noticed that he has a worsening ability to organize, plan, and exhibit impulse control over the last month. The patient states that he is able to complete his activities of daily living without assistance, but has some weakness of his left upper and lower extremities that began 3 months prior. He needs reminders from his wife about daily tasks to complete. He enjoys spending time with his spouse, playing cards with his friends, and taking daily walks around his neighborhood. His temperature is 98.2°F (36.8°C), blood pressure is 149/87 mmHg, pulse is 87/min, and respirations are 12/min. Physical exam reveals an elderly man who is oriented to person, place, and time. He has 4/5 left-sided weakness of the upper and lower extremities and associated pronator drift of the left upper extremity. A mini-mental status exam reveals he is able to remember 2 out of 3 words after 4 minutes. He is able to appropriately draw a clock. A magnetic resonance imaging study of the brain is shown in Figure A. Which of the following is the most likely diagnosis?

Answer: Vascular dementia

Explanation:
This patient with cardiovascular risk factors (hypertension, type 2 diabetes mellitus, hyperlipidemia) who presents with sudden cognitive decline of executive function and neurologic symptoms consistent with vasculopathy and possible prior stroke given his neurologic exam likely has vascular dementia, which can be corroborated with magnetic resonance imaging revealing white matter focal involvement consistent with vascular infarcts.

Vascular dementia is a form of dementia that results from compromise of blood supply to the brain, such as minor strokes or microinfarcts to the white matter. These insults lead to worsening cognitive abilities and presents classically as a stepwise decline (sudden/sharp declines in cognitive function that occur at distinct periods of time, not gradually) in cognitive function (thinking, planning, self-control, flexibility in thought). This is often associated with neurologic deficits as byproducts of these strokes. Unlike other forms of dementia, this presentation is step-wise. Treatment involves optimizing medical management to treat underlying medical comorbidities (managing cardiovascular risk factors such as hypertension, type 2 diabetes mellitus, hyperlipidemia), physical therapy/rehab for stroke symptoms, and caregiver support at home. Magnetic resonance imaging reveals focal white matter changes consistent with small vascular infarcts.

Khan et al. review the diagnosis and management of vascular dementia while including commentary on recent updates in the literature. They found that risk factors for vascular diseases such as stroke, high blood pressure, high cholesterol, and smoking also raise the risk of vascular dementia. They thus recommend medical management of underlying medical comorbidities such as hypertension, diabetes mellitus, or hyperlipidemia as treatments for vascular dementia.

Figure/Illustration A shows magnetic resonance imaging with white matter small vessel ischemic changes (red arrows) characteristic of vascular dementia within a background of diffuse generalized atrophy.

Incorrect Answers:
Answer A: Alzheimer disease is a form of dementia that presents with progressive forgetfulness as the first and most jarring clinical symptom, followed by worsening visual/spatial recognition, and then worsening behavioral function. It is most common in patients over the age of 75. It is not associated with focal deficits or weakness on neurological exam.

Answer B: Mild cognitive impairment is a stage between the expected cognitive decline of normal aging and forms of dementia. Patients and family members may notice problems with memory, thinking, or judgment, but they are not significant enough to cause interference with activities of daily living.

Answer C: Normal aging does not involve a noticeable decline in cognition and does not involve neurologic deficits. Declines are present, but are infrequent and do not impede activities of daily living.

Answer D: Pseudodementia is the result of untreated depression, which can present as forgetfulness in the elderly. This etiology can be distinguished by screening for signs or symptoms of depression, which might include sleep disturbance, anhedonia, lack of energy, increased or decreased appetite, fatigue, and/or loss of concentration. These symptoms are absent in this case.

Bullet Summary:
Vascular dementia presents with a step-wise decline in executive cognitive function and neurologic deficits in a patient with cardiovascular risk factors and is associate with MRI findings including white matter changes consistent with vascular infarcts.


Question: A 59-year-old man presents to his primary care physician for fatigue. In general, he has been in good health; however, he recently has experienced weight loss, abdominal pain, and general fatigue. He has a medical history of anxiety, diabetes, a fracture of his foot sustained when he tripped, and a recent cold that caused him to miss work for 1 week. His current medications include metformin, insulin, buspirone, vitamin D, calcium, and sodium docusate. His temperature is 99.5°F (37.5°C), blood pressure is 150/100 mmHg, pulse is 90/min, respirations are 18/min, and oxygen saturation is 98% on room air. Physical exam reveals a calm gentleman. A mild systolic murmur is heard in the left upper sternal region. The rest of the physical exam is within normal limits. Laboratory values are ordered as seen below. Hemoglobin: 12 g/dL Hematocrit: 36% Leukocyte count: 66,500/mm^3 with normal differential Platelet count: 177,000/mm^3 Leukocyte alkaline phosphatase: elevated Serum: Na+: 139 mEq/L Cl-: 100 mEq/L K+: 4.3 mEq/L BUN: 20 mg/dL Glucose: 120 mg/dL Creatinine: 1.1 mg/dL Ca2+: 10.9 mEq/L AST: 12 U/L ALT: 10 U/L Which of the following is the most likely diagnosis?

Answer: Leukemoid reaction

Explanation:
This patient is presenting with leukocytosis and an elevated leukocyte alkaline phosphatase suggestive of a leukemoid reaction.

A leukemoid reaction typically presents with a drastically elevated leukocyte count (typically > 50,000/mm^3) in the setting of an elevated leukocyte alkaline phosphatase score (LAP). This reaction typically occurs after a major infection and is an immunologic response to the pathogen that caused the illness. In contrast, chronic myeloid leukemia presents with a similar elevation in leukocytes but a low LAP score in addition to symptoms of general malaise, fatigue, and weight loss. The LAP score is the critical differentiating factor when comparing these 2 pathologies. Treatment for a leukemoid reaction is by addressing the underlying pathology.

Portich and Faulhaber review the evidence regarding the diagnosis of leukemoid reaction. They discuss how the most common cause is infection. They recommend considering paraneoplastic syndromes in patients without evidence of infection.

Incorrect Answers:
Answer A: Acute lymphoblastic lymphoma presents in a pediatric patient with pallor, fatigue, easy bruising, fever, bone pain, hepatomegaly, and splenomegaly. Treatment is with combination chemotherapy.

Answer B: Chronic lymphocytic leukemia can present similarly to a leukemoid reaction with non-specific systemic symptoms and lymphadenopathy but is a less likely diagnosis in this patient given his age and LAP score. Treatment is with ibrutinib and rituximab as well as other agents.

Answer C: Chronic myeloid leukemia presents with systemic symptoms, fatigue, malaise, weight loss, and abdominal pain with an elevated leukocyte count (typically > 50,000/mm^3) but a depressed LAP score. Treatment is with tyrosine kinase inhibitors.

Answer E: Multiple myeloma presents with systemic symptoms, weight loss, pathologic fractures, and hypercalcemia. It is not associated with an elevated leukocyte score and an elevated LAP score. Treatment is with steroids and chemotherapy.

Bullet Summary:
Both a leukemoid reaction and chronic myeloid leukemia present with an elevated leukocyte count (> 50,000/mm^3), but an elevated leukocyte alkaline phosphatase score is suggestive of a leukemoid reaction.