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Data and Language Intelligence Lab 24

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A 55-year-old man presents to the emergency department with worsening dyspnea over the past 48 hours. He recently had a cold that kept him home from work for the past week. He has a past medical history of diabetes, obesity, and hypertension. He had his Achilles tendon repaired 4 weeks ago and he has been less mobile. His temperature is 99.2°F (37.3°C), blood pressure is 150/85 mmHg, pulse is 82/min, respirations are 16/min, and oxygen saturation is 100% on room air. Physical exam is notable for dyspnea provoked by walking short distances. Jugular venous distension is noted on exam. The patient’s blood pressure is 130/70 mmHg during inspiration. A bedside echocardiogram demonstrates impaired diastolic filling with normal ventricular contractility. An ECG is performed as seen in Figure A. Which of the following is the most likely diagnosis?

Cardiac tamponade

Constrictive pericarditis

Myocardial infarction

Pulmonary embolism

Restrictive cardiomyopathy

B

Constrictive pericarditis

This patient is presenting with a preceding viral illness, dyspnea, jugular venous distension, pulsus paradoxus (blood pressure drop from 150/85 to 130/70 mmHg during inspiration), an echocardiogram with impaired diastolic filling, and diffuse ST elevation with PR depression on ECG. This constellation of symptoms is concerning for constrictive pericarditis. Constrictive pericarditis occurs when the pericardium becomes thickened and fibrotic. In contrast to other types of pericarditis, in constrictive pericarditis, there is impaired diastolic filling and thus impaired cardiac function. There are many possible etiologies of constrictive pericarditis including infection, inflammatory conditions, or idiopathic. Patients will present with dyspnea, hypotension, tachycardia, a pericardial friction rub, and positional chest pain (usually worsened by laying back and relieved by leaning forward). Patients may also demonstrate jugular venous distension, lower extremity edema, worsening dyspnea, and congestive hepatopathy. ECG may demonstrate diffuse ST elevation with PR depression, and an echocardiogram will demonstrate impaired diastolic filling and may demonstrate a thickened pericardium. The diagnosis can be supported with pulsus paradoxus (a drop of blood pressure by > 10 mmHg during inspiration). Welch reviews constrictive pericarditis. He discusses constrictive pericarditis and how the inelastic pericardium inhibits cardiac filling possibly causing unexplained heart failure. Welch notes making the diagnosis is very challenging and requires meticulous echocardiograph assessment. Figure/Illustration A demonstrates diffuse ST elevation (blue arrows) with PR depression (black arrows). This is consistent with pericarditis. Incorrect Answers: Answer A: Cardiac tamponade can occur after trauma, in the setting of infection, or in the setting of autoimmune disease and is more likely to occur with a rapid accumulation of pericardial fluid. While pulsus paradoxus would be present in this condition, muffled heart sounds and electrical alternans would be more likely to be seen on ECG. Echocardiography would demonstrate an echogenic rim of fluid around the heart. Answer C: Myocardial infarction presents with chest pain, dyspnea, hypotension, tachycardia, and ST elevation in a vascular distribution. Note that this patient’s ST elevation is diffuse and there is no reciprocal ST depression. Moreover, the pattern of chest pain in myocardial infarction is typically exertional and not positional. Answer D: Pulmonary embolism may present with pleuritic chest pain, shortness of breath, tachycardia, hypoxia, hemoptysis, a history of hypercoagulability, and recent stasis or surgery (such as this patient’s recent Achilles tendon surgery). It can cause obstructive shock leading to hypotension and tachycardia. Note that right heart strain and sinus tachycardia would be seen on ECG. Answer E: Restrictive cardiomyopathy presents very similarly to restrictive pericarditis. Note that in restrictive cardiomyopathy, patients will also have impaired diastolic filling; however, it is due to a myocardium that will not expand rather than the pericardium impairing filling. It can occur secondary to conditions such as amyloidosis or hemochromatosis as well as other chronic inflammatory states. The ECG findings are nonspecific but may include low voltage QRS complexes, ST segment changes, T wave changes, bundle branch blocks, and pathologic Q waves (abnormally deep and wide Q waves). The diagnosis can be supported with an ultrasound demonstrating impaired diastolic filling and possible myocardial speckling if a protein (amyloid) is present and deposited in the myocardial wall. The diagnosis can only definitively be confirmed with a biopsy which is highly invasive. Bullet Summary: Restrictive pericarditis presents with chest pain that is positional, pulsus paradoxus, a friction rub, and diffuse ST elevation with PR depression on ECG.

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A 4-day-old neonate is brought to the pediatrician with vaginal discharge for the last 2 days. Her daughter has been feeding and voiding well. The neonate was delivered at 39 weeks gestation via an uncomplicated vaginal delivery and was discharged home after 2 days. The prenatal course was complicated by chlamydia in the mother during the first trimester, for which she and the partner were both treated with a confirmatory test of cure. The biological father is no longer involved in the patient's life, but her mother’s boyfriend has been caring for the baby whenever the mother rests. The neonate’s temperature is 98.5°F (36.9°C), blood pressure is 56/35 mmHg, pulse is 138/min, and respirations are 51/min. She appears comfortable, and cardiopulmonary and abdominal exams are unremarkable. There are no bruises or marks on her skin. Examination of the genitals reveals no vulvar irritation or skin changes but there is scant pink mucoid discharge at the introitus. Which of the following is the most appropriate next step in management?

Reassurance

Report to child protective services

Vaginal culture

Vaginal exam under anesthesia

Warm water irrigation of the vagina

A

Reassurance

This neonate presents with bloody vaginal discharge soon after birth without vulvar irritation, which is most consistent with physiologic neonatal vaginal discharge. Reassurance is the most appropriate next step in management. Vaginal discharge in a neonate that is bloody and/or mucoid is most commonly due to the rapid withdrawal of maternal hormones that cross the placenta. This results in a pink discharge that may be observed as “menses” in the perinatal period. This most commonly presents several days to 1 week after birth and will self-resolve. Without concerning red flags such as genital trauma, mucopurulent discharge, or surrounding skin changes, there is no need for work-up or treatment. Additional concerning findings should prompt a work-up for child abuse. Guritzky and Rudnitsky review the evidence regarding the work-up of a bloody neonatal diaper. They discuss how using an Apt test can be helpful in distinguishing between maternal and fetal blood. They recommend being aware of neonatal conditions that can cause bleeding to avoid missing pathologies. Incorrect Answers: Answer B: Reporting the case to child protective services would be necessary if child abuse were suspected. Although having an unrelated adult as a caregiver is traditionally a risk factor, there is no evidence that this neonate is being abused. Risk factors include vaginal trauma and bruising. Answer C: Vaginal culture may be indicated if an infectious etiology such as chlamydia or group A streptococcus is suspected; however, this would more commonly present with bloody and mucopurulent discharge with or without surrounding skin inflammation. Furthermore, the patient’s mother was successfully treated for chlamydia during pregnancy, making chlamydial infection unlikely. Answer D: Vaginal exam under anesthesia would be appropriate if a foreign body or trauma is suspected because prepubescent children should not undergo exams while awake. In a neonate with physiologic discharge, an exam is unnecessary. Foreign bodies would present with bloody discharge, pain, and potential purulence. Answer E: Warm water irrigation of the vagina may be helpful in locating a foreign body, which is the most common cause of vaginal bleeding and discharge in a prepubertal girl. This is unlikely in a neonate and there is no evidence of trauma or irritation in the perineum. Bullet Summary: Vaginal discharge in a neonate is most commonly due to the withdrawal of maternal hormones and will self-resolve.

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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?

Blinking after saline is applied to the cornea

Conjugate eye movement to the left with rotation of the head to the right

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

Grimacing after noxious stimulus to the arm

Spontaneous respiration 1 minute after disconnection from a ventilator

C

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

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.

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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?

Cauterization with silver nitrate

Fresh frozen plasma and intravenous phytonadione

Intravenous tranexamic acid

Placement of posterior nasal packing

Topical oxymetazoline

E

Topical oxymetazoline

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.

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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?

Albuterol and prednisone

Digoxin

Diltiazem

Intubation

Metoprolol

B

Digoxin

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.

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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?

Acute inflammatory demyelinating polyneuropathy

Cauda equina syndrome

L5/S1 disc herniation

Overflow incontinence

Spinal stenosis

B

Cauda equina syndrome

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.

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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?

Advanced sleep phase disorder

Chronic insomnia

Delayed sleep phase disorder

Normal aging

Obstructive sleep apnea

A

Advanced sleep phase disorder

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.

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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)?

A

B

C

D

E

C

C

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.

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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?

Cerebral toxoplasmosis

Glioblastoma multiforme

Hemorrhagic stroke

Metastatic brain tumor

Neurosarcoidosis

B

Glioblastoma multiforme

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.

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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?

Left ventricular hypertrophy

Non-ST elevation myocardial infarction

ST elevation myocardial infarction

Torsades des pointes

Wolff Parkinson White syndrome

A

Left ventricular hypertrophy

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.

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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?

Acetazolamide

High-flow oxygen

Sumatriptan

Topiramate

Verapamil

C

Sumatriptan

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.

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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?

Anterior cruciate ligament tear

Apophysitis of the tibial tubercle

Patellar fracture

Posterior dislocation of the knee

Tibial plateau fracture

E

Tibial plateau fracture

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.

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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?

Duodenal atresia

Hirschsprung disease

Intestinal malrotation

Jejunal atresia

Meconium ileus

C

Intestinal malrotation

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.

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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?

Acute lymphoblastic leukemia

Acute myelogenous leukemia

Chronic lymphocytic leukemia

Chronic myelogenous leukemia

Hairy cell leukemia

C

Chronic lymphocytic leukemia

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.

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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?

Laparoscopy to prevent detrimental effects on the fetus

Laparoscopy to remove a malignancy

Percutaneous umbilical blood sampling to determine prognosis

Reassurance

Spironolactone to treat hirsutism and acne

D

Reassurance

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.

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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?

Chalazion

Foreign body

Hordeolum

Ingrown eyelash follicle

Meibomian cell carcinoma

A

Chalazion

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.

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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?

Metronidazole

Nitrofurantoin

Topical clobetasol

Topical estrogen

Vaginal moisturizers

E

Vaginal moisturizers

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.

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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?

Karyotyping

Magnetic resonance imaging (MRI) of the brain with gadolinium

Radiograph of the hand and wrist

Reassurance with close follow-up

Testicular ultrasound

C

Radiograph of the hand and wrist

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).

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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

Anti-dsDNA antibodies

Anti-histone antibodies

Degenerated cartilage in weight bearing joints

IgM against parvovirus B19

B

Anti-dsDNA antibodies

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.

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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?

Aneuploidy

Neonatal hyperglycemia

Neural tube defect

Oligohydramnios

Post-term delivery

C

Neural tube defect

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.

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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?

Areflexia in all extremities

Digital clubbing

Inability to pass a nasogastric tube

Markedly decreased lung volume

Patent foramen ovale

C

Inability to pass a nasogastric tube

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.

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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?

First degree atrioventricular block

Second degree atrioventricular block, Mobitz type I

Second degree atrioventricular block, Mobitz type II

Sinus bradycardia

Third degree atrioventricular block

B

Second degree atrioventricular block, Mobitz type I

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.

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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?

CN VIII ablation

Epley maneuver

Low-salt diet

Meclizine

Thiamine

C

Low-salt diet

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.

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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?

Basal cell carcinoma

Keratoacanthoma

Molluscum contagiosum

Pyogenic granuloma

Verruca vulgaris

B

Keratoacanthoma

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.

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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?

Alzheimer disease

Mild cognitive impairment

Normal aging

Pseudodementia

Vascular dementia

E

Vascular dementia

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.

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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?

Acute lymphoblastic lymphoma

Chronic lymphocytic leukemia

Chronic myeloid leukemia

Leukemoid reaction

Multiple myeloma

D

Leukemoid reaction

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.

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A 65-year-old man presents to the emergency department with anxiety and intermittent palpitations. He began feeling the palpitations 3 days ago while eating dinner. He denies chest pain, shortness of breath, or loss of consciousness. He has a history of hypertension, major depressive disorder, Raynaud disease, and chronic obstructive pulmonary disease (COPD) on 2 liters of oxygen at home. Current medications include lisinopril, inhaled umeclidinium-vilanterol, and as-needed albuterol. He drinks 4 beers a day and has smoked 1 pack of cigarettes a day for 40 years. His temperature is 98.9° F (37.2° C), blood pressure is 130/85 mmHg, pulse is 125/min, and respirations are 16/min. Physical exam is notable for an irregular pulse and scattered end-expiratory wheezes. An echocardiogram performed 1 month ago showed a left ventricular ejection fraction of 60-65%. The patient requires 3 liters of oxygen today. An ECG is performed as seen in Figure A. Which of the following is the most appropriate treatment for the patient’s tachycardia?

Amiodarone

Clopidogrel

Digoxin

Metoprolol

Verapamil

E

Verapamil

This patient’s new-onset palpitations, irregularly irregular pulse, and absent p-waves on ECG are consistent with atrial fibrillation. In hemodynamically stable patients with a relative contraindication to β-blockers (COPD on home oxygen with increasing oxygen need), rate control with a non-dihydropyridine calcium channel blocker such as verapamil is preferred. Atrial fibrillation can present with palpitations, lightheadedness, or shortness of breath. ECG findings will be an irregularly irregular rhythm and absent P waves with an erratic baseline as shown in Illustration A. Treatment is centered on rate control. First-line agents for rate control include β1 selective blockers (metoprolol and esmolol) and non-dihydropyridine calcium channel blockers (verapamil and diltiazem). In patients with COPD, non-selective β-blockers (propranolol, timolol, and sotalol) can worsen bronchoconstriction by activating β2-adrenoreceptors. Other relative contraindications to β-blockers include Raynaud disease and depression (increased risk of fatigue and sexual dysfunction). In patients with relative contraindications to β-blockers, non-dihydropyridine calcium channel blockers are the preferred initial treatment option. Van Gelder et al. studied lenient (resting heart rate < 110 beats per minute) versus strict rate control (resting heart rate < 80 beats per minute) in patients with atrial fibrillation in a randomized control trial. The authors found that there was no difference in the primary composite outcome of death from cardiovascular causes, hospitalization for heart failure, stroke, bleeding, and life-threatening arrhythmias between the 2 groups. The authors recommend a lenient rate control strategy in patients with atrial fibrillation. Figure/Illustration A is an ECG lacking P waves (red arrows) and irregularly irregular RR intervals (red/blue lines), which are classic findings in atrial fibrillation. Incorrect Answers: Answer A: Amiodarone is an antiarrhythmic that can be used in patients to convert atrial fibrillation to sinus rhythm. It is often suitable to use in patients with depressed left ventricular function. Amiodarone has multiple multi-system adverse effects including pulmonary toxicity, and it is not used as a first-line agent. Answer B: Clopidogrel is an antiplatelet agent that can be used to reduce the risk of thrombosis. Although patients with atrial fibrillation are at increased risk of stroke, the preferred anticoagulation agents are warfarin or direct oral anticoagulants (apixaban). Answer C: Digoxin can be used as a rate control agent in atrial fibrillation as it directly suppresses atrioventricular nodal conduction. Due to its narrow therapeutic window and risk of toxicity, it is used as second-line therapy when first-line agents fail. Answer D: Metoprolol is a β-blocker that is a first-line agent for rate control in atrial fibrillation. In patients with contraindications to β-blockers, non-dihydropyridine calcium channel blockers are the treatment of choice. This patient has COPD with increasing oxygen needs making calcium channel blockers possibly a better choice. Bullet Summary: In hemodynamically stable patients with atrial fibrillation and relative contraindications to β-blockers, non-dihydropyridine calcium channel blockers are the treatment of choice.

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A 65-year-old man presents to the emergency department with sudden-onset altered mental status. He was last seen normal 1 hour ago. His wife noticed that he was confused, slurring his speech, and had notable weakness that caused him to drop his cup of coffee. The patient is confused and not able to answer any questions. Facial drooping of the left lower face is noted, and the patient cannot follow any commands. He has a past medical history of diabetes and atrial fibrillation and is currently taking warfarin. His other medications are not known. His temperature is 98.0°F (36.7°C), blood pressure is 150/90 mmHg, pulse is 115/min, and respirations are 17/min. The patient is not able to follow any commands for further neurologic evaluation but does not appear to be moving his right upper extremity. In addition to further physical exam, which of the following is the most appropriate next step in management?

Alteplase

CT head

Fingerstick blood glucose

Fresh frozen plasma and vitamin K

MRI brain

C

Fingerstick blood glucose

This patient is presenting with sudden onset confusion, slurred speech, asymmetric smile, and weakness in the setting of risk factors for stroke (atrial fibrillation, diabetes, and hypertension). The most important initial step in management in a patient with altered mental status and neurological deficits is to obtain a fingerstick blood glucose. The workup of stroke is first centered on a thorough history and physical and immediately calculating an NIH stroke scale (11-domain assessment of stroke severity involving patient consciousness level, orientation, ability to follow commands, degree of gaze palsy, degree of vision loss, ataxia, motor drift, sensation, inattention, language/speech) as well as ascertaining when the patient was last known to be neurologically normal. While performing the exam and NIH stroke scale, a fingerstick blood glucose should be performed in all patients as hypoglycemia may present identically to a stroke. Severe hypoglycemia may present with lethargy, confusion, focal or global weakness, nausea, vomiting, agitation, and even seizures. If the patient is hypoglycemic, dextrose can be given which will rapidly correct the patient's underlying deficits. Ohshita et al. review other possible causes of stroke-like symptoms. They note that hypoglycemia may mimic stroke and cause focal neurological signs with common findings being unilateral motor weakness with mild or moderate alteration of consciousness. They noted that all patients improved within 1 hour of glucose injection in this study, thus the recommendation to check a fingerstick blood glucose in all stroke patients. Incorrect Answers: Answer A: Alteplase would be indicated if a patient presented with disabling neurologic deficits from an ischemic stroke within 4.5 hours of symptom onset only after a CT scan of the head has ruled out an intracranial bleed. The patient must have no other contraindications to thrombolytics including but not limited to recent trauma, known intracranial hemorrhage, rapidly improving neurologic deficits (spontaneously), and no other clear reversible cause (among many other contraindications). Answer B: CT head is the most appropriate initial step in the management of an acute stroke; however, a rapid fingerstick blood glucose takes precedence as hypoglycemia can mimic a stroke and be immediately addressed thus removing the need for further workup if there is a complete resolution of symptoms with normoglycemia. While an exam is ongoing, a fingerstick blood glucose is being obtained, and neuroimaging is also often ordered to be performed immediately after. Answer D: Fresh frozen plasma and vitamin K would be indicated in this patient if he had a hemorrhagic stroke (a CT of the head would need to confirm this) to reverse his anticoagulation with warfarin. Factor concentrate can also be used to rapidly reverse anticoagulation with warfarin. Answer E: MRI brain would be indicated in the workup of a stroke or transient ischemic attack after all emergency interventions and labs including CT head, serum chemistries, CBC, and ECG. It delineates the extent of the stroke and gives useful prognostic and diagnostic information. It also may elucidate strokes missed on other forms of neuroimaging such as CT perfusion. Bullet Summary: A fingerstick blood glucose should be obtained immediately in all patients with stroke-like symptoms or altered mental status.

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A 35-year-old man presents to his primary care physician with pain along the bottom of his foot. The patient is a long-time runner but states that the pain has been getting worse recently. When running and at rest he has a burning and aching pain along the bottom of his foot that sometimes turns to numbness. Taking time off from training does not improve his symptoms. The patient has a medical history of surgical repair of his Achilles tendon, ACL, and medial meniscus. He is currently not taking any medications. The patient lives with his wife and they both practice a vegan lifestyle. His temperature is 98.6°F (37°C), blood pressure is 114/72 mmHg, pulse is 81/min, and respirations are 12/min. On physical exam, the patient states that he is currently not experiencing any pain in his foot but rather is experiencing numbness/tingling along the plantar surface of his foot. Strength is 5/5 and reflexes are 2+ in the lower extremities. Which of the following is the most likely diagnosis?

Common fibular nerve compression

Herniated disc

Plantar fasciitis

Tarsal tunnel syndrome

Vitamin B12 deficiency

D

Tarsal tunnel syndrome

This patient is presenting with pain, tingling, and numbness on the plantar surface of his foot that is not associated with exertion or rest suggesting a diagnosis of tarsal tunnel syndrome. Tarsal tunnel syndrome occurs due to compression of the tibial nerve as it travels through the tarsal tunnel. Compression of the nerve leads to symptoms along the plantar surface of the foot which can include pain, tingling, or numbness. These symptoms can be exacerbated/triggered by tapping on the tunnel, which lies posterior to the medial malleolus. In addition, the symptoms can occur at rest or during activity and are not improved with rest. Treatment is rest, NSAIDs, properly fitted shoes/orthotics, and in refractory cases, surgical release of the tarsal tunnel. Gould reviews the evidence regarding the diagnosis and treatment of tarsal tunnel syndrome. He discusses how this syndrome represents a collection of different entities including space-filling lesions and local inflammation. He recommends definitive diagnosis prior to surgical treatment given that the syndrome is often misdiagnosed. Incorrect Answers: Answer A: Common fibular nerve compression typically occurs when there is trauma/compression just inferior to the head of the fibula. This can occur when an individual wears work boots and after fractures of the fibular neck. Symptoms of common fibular nerve compression include foot drop and numbness on the dorsum of the foot. Treatment is with activity modification and a foot orthosis to prevent an equinus contracture. Answer B: Herniated disc presents with symptoms of radiculopathy including pain that travels down the leg through the toes. Symptoms are worsened with flexion of the leg such as during the straight leg raise test. Treatment is with NSAIDs and corticosteroid injections with surgical decompression of the disc in refractory cases. Answer C: Plantar fasciitis can present very similarly to tarsal tunnel syndrome with pain along the plantar surface of the foot. The pain is typically exacerbated by activity and improves with rest in contrast to this patient. In addition, there is an absence of burning, pain, and numbness that occur in tarsal tunnel syndrome. Tenderness will be at the medial insertion of the plantar fascia into the calcaneal tuberosity. Treatment is conservative with NSAIDs and activity modification. Answer E: Vitamin B12 deficiency could present with symptoms of peripheral neuropathy. This is possible given this patient's vegan diet. This patient has pain only in one of his feet and he does not have symptoms of anemia such as fatigue or pallor. Treatment is with the repletion of vitamin B12. Bullet Summary: Tarsal tunnel syndrome presents with pain, numbness, tingling, and aching along the plantar surface of the foot that is not associated with activity.

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A 25-year-old woman presents to her primary care physician complaining of recent hair growth along her jawline, now requiring her to shave every 2 days. She has not shaved in about a week. She has also gained about 10 pounds in the last several months, and her periods have become irregular over the last year. Her last menstrual period was 3 months ago. Her temperature is 98.6°F (37.0°C), pulse is 72/min, blood pressure is 136/86 mmHg, and respirations are 13/min. Her BMI is 26 kg/m^2. Her skin exam reveals hirsutism along the jawline and acanthosis nigricans in the axillary folds. Cardiopulmonary and abdominal exams are unremarkable. A pelvic exam reveals normal external genitalia, a mobile and non-tender 6-week-sized uterus, and no adnexal masses or tenderness. Transvaginal ultrasound is performed and shown in Figure A. This patient is at increased future risk of which of the following?

Endometrial carcinoma

Ovarian cancer

Ovarian cyst rupture

Type 1 diabetes mellitus

Virilization

A

Endometrial carcinoma

This patient presents with hirsutism, oligomenorrhea, and multiple follicles on pelvic ultrasound, which is most consistent with polycystic ovarian syndrome (PCOS). PCOS is associated with an increased risk of endometrial carcinoma. PCOS is an acquired endocrinopathy characterized by ovarian dysfunction and high rates of amenorrhea. Patients with PCOS are at risk for endometrial carcinoma due to unopposed estrogen exposure. Anovulation results in decreased progesterone, which prevents excessive endometrial build-up and thus increases the risk of endometrial hyperplasia and subsequent carcinoma. Increased adiposity in PCOS also increases estrogen, which is aromatized from testosterone in adipose cells, and further raises the risk for endometrial carcinoma. Treatment is with weight loss, metformin, and hormonal contraceptives. Khan et al. review the genetic basis underlying PCOS. They discuss how this disease is the most common endocrinopathy in reproductive-age women resulting in anovulatory infertility. They recommend using multimodal methods to treat this disease. Figure/Illustration A shows a transvaginal ultrasound of the ovary with many peripheral follicles (red circle). These findings are characteristic of PCOS. Incorrect Answers: Answer B: Ovarian cancer does not occur with increased incidence in patients with PCOS. They are at baseline risk and do not require additional screening. The rates of ovarian cancer increase with hereditary cancer syndromes such as BRCA mutation. Answer C: Ovarian cyst rupture is not a complication of PCOS, as PCOS does not actually cause cysts (despite the name). The cystic spaces seen on ultrasound are immature follicles rather than cysts. Recurrent infections can lead to cysts and rupture. Answer D: Type 1 diabetes mellitus is not associated with PCOS, but type 2 diabetes mellitus is. Type 2 diabetes can cause acanthosis nigricans via insulin resistance. Patients with recurrent bouts of pancreatitis are predisposed to diabetes mellitus. Answer E: Virilization is not seen in PCOS, as the testosterone levels are elevated but not to the degree necessary to produce frank masculinization. If there is evidence of virilization, such as voice deepening or clitoromegaly the differential should be broadened to other diagnoses. Bullet Summary: Patients with PCOS are at increased risk of endometrial carcinoma as a result of unopposed estrogen from anovulation as well as aromatization in adipose tissue.

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A 35-year-old man is brought into the emergency department by ambulance for a stab wound to the left leg near the inguinal ligament. The patient has no significant medical history, and takes no other medication. He was not stabbed or otherwise injured elsewhere. His temperature is 98.6°F (37.0°C), pulse is 130, blood pressure is 85/50, and respirations are 22. Primary and secondary survey and FAST exam are unremarkable for other associated injuries. Pressure is removed from the wound, and pulsatile bleeding from the wound is noted. Which of the following is the most appropriate next step in management?

Angiography of the left lower extremity

CT scan of the left lower extremity

Emergent surgical intervention

Observation

Wound closure

C

Emergent surgical intervention

This patient with pulsatile bleeding from a wound to the left thigh and hemodynamic instability has hard signs of vascular injury. Patients with penetrating wounds and hard signs of vascular injury should be managed with emergent surgical intervention. Vascular injury commonly occurs as a result of penetrating trauma, such as a stab wound as in this patient. Evaluation begins with a primary and secondary trauma survey to assess for other injuries. Hard signs of vascular injury include pulsatile bleeding, expanding hematoma, and absent pulses distal to the wound. For patients with suspected vascular injury that display either hard signs or hemodynamic instability, emergent surgical intervention is the most appropriate next step in management. For those with soft signs of vascular injury such as non-pulsatile bleeding or associated bony injury, the most appropriate next step in management is CT angiography of the affected limb. Ball et al. discuss penetrating trauma to the extremities. They state that extremity trauma is the most common source of vascular injury (51%), with femoral artery as the most frequently injured vessel (35%). They also state that though obtaining pulses is important, distal pulses can continue to be present in many limbs with arterial injuries and therefore may require confirmatory evaluation via doppler, CT scan, or even angiography. Incorrect Answers: Answer A: Angiography of the left lower extremity may be utilized if this patient did not present with hard signs of vascular injury. However, this patient's presentation warrants emergent surgical intervention. Answer B: CT scan of the left lower extremity may be utilized if this patient did not present with hard signs of vascular injury. This patient's presentation warrants emergent surgical intervention. Answer D: Observation may be appropriate if this patient was hemodynamically stable, and showed no hard or soft signs of vascular injury. Answer E: Wound closure may eventually be appropriate if this patient was hemodynamically stable, and showed no hard or soft signs of vascular injury. Bullet Summary: For patients with suspected vascular injury with hard signs of vascular injury the first step in management is emergent surgical intervention.

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A 67-year-old man presents to the emergency room with difficulty speaking for the past 1 hour. He was having dinner at home with his wife when he suddenly noticed he had difficulty eating and speaking. He also noticed a new-onset weakness on his left side. His medical history is significant for type 2 diabetes mellitus, hypertension, and hyperlipidemia. His current medications include metformin, atorvastatin, and lisinopril. His temperature is 98.6°F (37°C), blood pressure is 130/80 mmHg, pulse is 70/min, and respirations are 15/min. On examination, strength is 5/5 in the right upper and lower extremities and 3/5 in the left upper and lower extremities. On cranial nerve examination, his tongue deviates to the right side. There is also decreased sensation to light touch and vibration on the left side of his body. Which of the following arteries is most likely involved in this patient’s presentation?

Anterior inferior cerebellar artery

Anterior spinal artery

Lenticulostriate branches of the middle cerebral artery

Pontine perforators of the basilar artery

Posterior inferior cerebellar artery

B

Anterior spinal artery

This patient with hypertension, diabetes, hyperlipidemia, deviation of the tongue to the right, left-sided hemiparesis, and decreased sensation to light touch and vibration on the left side of his body most likely has a stroke of the right medial medulla. The medial medulla is supplied by paramedian branches of the vertebral arteries and the anterior spinal artery. Medial medullary syndrome (Dejerine syndrome) is usually caused by atherosclerotic occlusion of paramedian branches of the anterior spinal artery, vertebral arteries, or basilar artery which supply the medial medulla. Medial medullary structures include the lateral corticospinal tract, the medial lemniscus, and the hypoglossal nerve. Lesions to the lateral corticospinal tract lead to contralateral paresis of the upper and lower extremities. Lesions to the medial lemniscus lead to decreased vibration, proprioception, and light touch on the contralateral body. Ipsilateral hypoglossal nerve dysfunction leads to ipsilateral loss of function of the intrinsic and extrinsic muscles of the tongue including the genioglossus muscle, which protrudes the tongue forward from the root and is unopposed on the contralateral side. This pushes the tongue towards the side of the lesion, leading to ipsilateral tongue deviation. Treatment includes reperfusion via thrombolytics if the patient presents within 4.5 hours of the time last known well. Kim and Han present clinical findings, radiographic findings, angiographic data, and long-term outcomes from a case series of 86 patients with medial medullary infarction. The authors found that old age and severe motor dysfunction at admission were predictive factors portending poor prognosis. The authors recommend close follow-up of these patients for the development of central post-stroke pain. Incorrect Answers: Answer A: Anterior inferior cerebellar artery infarction leads to a lesion of the lateral pons, with damage to the facial nucleus, vestibular nuclei, spinothalamic tract, spinal trigeminal nucleus, sympathetic fibers, labyrinthine artery, and middle and inferior cerebellar peduncles. This presents with complete facial hemiparesis, vomiting, decreased pain and temperature sensation on the contralateral body and ipsilateral face, ipsilateral Horner syndrome, ipsilateral ataxia and dysmetria, and ipsilateral sensorineural deafness and vertigo. Answer C: Lenticulostriate branches of the middle cerebral artery supply the internal capsule. Strokes of the posterior limb of the internal capsule lead to contralateral hemiparesis. The findings of ipsilateral tongue deviation and sensory changes are not consistent with a lesion to the internal capsule. Answer D: Pontine perforators of the basilar artery supply the medial pons. Strokes of the medial pons lead to quadriplegia and loss of facial, mouth, and tongue movements with preserved sensorium. This patient’s findings of hemiparesis, ipsilateral tongue deviation, and changes in sensorium are more suggestive of a lesion to the medial medulla, not the medial pons. Answer E: Posterior inferior cerebellar artery infarction leads to a stroke of the lateral medulla (Wallenberg syndrome). This leads to lesions to the nucleus ambiguus, vestibular nuclei, lateral spinothalamic tract, spinal trigeminal nucleus, sympathetic fibers, and inferior cerebellar peduncle. Clinically this presents with dysphagia, hoarseness, decreased gag reflex, vomiting, vertigo, decreased pain and temperature sensation from the contralateral body and ipsilateral face, ipsilateral Horner syndrome, and ipsilateral ataxia. Bullet Summary: Occlusion of the anterior spinal artery can lead to medial medullary syndrome, which presents with ipsilateral deviation of the tongue, contralateral paresis of the upper and lower extremities, and contralateral loss of light touch and vibration sensation.

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A 26-year-old man presents to his primary care physician with a 6-month history of increasing lower back pain. He first felt the pain while lifting boxes at work but thought that he had just strained a muscle. The pain appears to be worse in the mornings and after rest. Exercise and physical activity appear to temporarily make the pain better. He has taken acetaminophen and ibuprofen for the pain. 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 exam, he is found to have limited flexion and extension of his spine as well as tenderness to palpation over the insertion of his patellar tendons bilaterally. Results from laboratory tests are shown below: Serum: Erythrocyte sedimentation rate (ESR): 61 mm/hr C-reactive protein (CRP): 36 mg/L (normal <10 mg/L) Which of the following is the most accurate test for this patient's condition?

Bone scan

Computed tomography

Magnetic resonance imaging

Radiograph

Ultrasound

C

Magnetic resonance imaging

This young man presents with low back pain that is relieved by physical activity, decreased spinal mobility, enthesitis of his patellar tendons, and elevated ESR/CRP values most likely has ankylosing spondylitis (AS). The most accurate diagnostic test for early ankylosing spondylitis is MRI. Multiple imaging tests can diagnose ankylosing spondylitis. Radiographs of the spine will show squaring of vertebrae with vertical or marginal syndesmophytes resulting in a "bamboo spine" appearance. The earliest radiographic sign is the erosion of the iliac side of the sacroiliac joint, but this finding is not sensitive in the early stages of the disease. MRI is sensitive in detecting sacroiliac inflammation, which makes this the best modality for early detection of ankylosing spondylitis in young patients. Initial therapy for ankylosing spondylitis includes lifestyle modifications (exercise, smoking cessation, physical therapy) and non-steroidal anti-inflammatory drugs (NSAIDs). Therapy for patients with inadequate response to NSAIDs includes tumor necrosis factor inhibitors (etanercept, infliximab, adalimumab) and interleukin 17 inhibitors (secukinumab, ixekizumab). Jung et al. studied whether signs of inflammation on MRI are correlated with bone quality in patients with ankylosing spondylitis. The authors find that bone marrow edema is negatively correlated with the trabecular bone score. The authors recommend control of active bone inflammation to prevent osteoporosis in patients with ankylosing spondylitis. Incorrect Answers: Answer A: Bone scan will show inflammation in the sacroiliac joints, but this study lacks specificity for this disease compared with other inflammatory forms of arthritis. Answer B: CT will show bony changes but not active inflammation, so it is most commonly used to diagnose cervical fractures in patients with ankylosing spondylitis. While it can support the diagnosis, it is less accurate than an MRI. Answer D: Radiographs will show erosion of the iliac side of the sacroiliac joint, but this finding is not sensitive in the early stages of the disease when bony ankylosis has not yet occurred. Radiographs may be an appropriate initial test. Answer E: Ultrasound is useful in evaluating muscle strains or tendon tears; however, it is not able to detect bony abnormalities and is therefore of limited use in ankylosing spondylitis. Bullet Summary: MRI is the most sensitive and accurate test for the early detection of ankylosing spondylitis.

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A 3-day-old boy is evaluated in the neonatal intensive care unit for failure to pass meconium. The patient is otherwise doing well and feeding every 2 hours. He is urinating 8-10 times per day. The patient has had 2 episodes of vomiting that were described as green in color. He was born at 39 weeks gestation to a 38-year-old G3P3 mother. The pregnancy was uncomplicated, and the patient’s mother received routine prenatal care. She declined prenatal testing. One of the patient’s older siblings has Down syndrome. The patient's temperature is 98.2°F (36.8°C), blood pressure is 48/32 mmHg, pulse is 164/min, and respirations are 48/min. On physical exam, the patient is in no acute distress. His abdomen is firm, non-tender, and distended with hypoactive bowel sounds. A digital rectal exam fails to relieve the obstruction. An abdominal radiograph is performed and the result can be seen in Figure A. Which of the following is the most appropriate next step in management?

Abdominal CT

Contrast enema

Rectal suction biopsy

Sweat testing

Upper gastrointestinal series

B

Contrast enema

This patient presents with delayed passage of meconium, bilious emesis, unsuccessful disimpaction on digital rectal exam, and dilated loops of bowel on abdominal radiograph which suggests a diagnosis of meconium ileus. The most appropriate next step in management is an enema with water-soluble contrast which may be both diagnostic and therapeutic. Meconium ileus presents with bilious emesis and failure to pass meconium in the first 48 hours of life. Abdominal radiography typically shows dilated loops of the small intestine proximal to the obstruction. Enema with water-soluble contrast (Gastrografin) is both diagnostic and therapeutic, as the contrast not only visualizes a microcolon but also relieves the obstruction via the osmotic pull of water into the lumen of the colon. Surgery may be necessary if the contrast enema fails. Patients should also be evaluated for underlying conditions such as cystic fibrosis. 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 demonstrating dilated loops of bowel and a “soap bubble” appearance of meconium mixed with bowel gas in the right lower quadrant (red circle). These findings are classically seen in patients with meconium ileus. Incorrect Answers: Answer A: An abdominal radiograph would be faster but less accurate than an abdominal CT. The use of CT should also be restricted in the pediatric population due to the radiation exposure involved. Answer C: Rectal suction biopsy is the most accurate test to diagnose Hirschsprung disease, which may present like meconium ileus with bilious vomiting, delayed passage of meconium, and dilated loops of bowel on an abdominal radiograph. A digital rectal exam typically temporarily relieves the intestinal obstruction in Hirschsprung disease and produces an expulsion of gas and stool called the “squirt sign.” Answer D: Sweat testing is used to diagnose cystic fibrosis, which is strongly associated with meconium ileus. An enema with water-soluble contrast would be the best next step to both confirm the diagnosis and relieve the obstruction. The patient should subsequently undergo sweat testing. Answer E: Upper gastrointestinal series is the diagnostic test of choice for intestinal malrotation which may also present with bilious vomiting. Malrotation is less likely to present with delayed passage of meconium, and an abdominal radiograph would more likely demonstrate a midgut volvulus. Treatment is with surgical derotation. Bullet Summary: Patients with meconium ileus should undergo an enema with water-soluble contrast (Gastrografin) to both confirm the diagnosis and relieve the obstruction.

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A 50-year-old man presents to the emergency department with chest pain. He states that the pain is dull in quality, started 30 minutes ago, has been gradually worsening, and is worse with exertion. He also endorses some shortness of breath. He also believes the pain is worse when leaning back and improved when leaning forward. His wife noticed he fainted after the pain started but regained consciousness shortly after. He has a medical history of diabetes and hypertension for which he is on metformin and losartan. His temperature is 99.2°F (37.3°C), blood pressure is 130/87 mmHg, pulse is 99/min, respirations are 22/min, and oxygen saturation is 100% on room air. Physical exam reveals an overweight man. A normal S1 and S2 are auscultated with clear breath sounds. An ECG is performed as seen in Figure A. Which of the following is the most likely diagnosis?

Hyperkalemia

Hypertrophic obstructive cardiomyopathy

Hypokalemia

Myocardial infarction

Pericarditis

D

Myocardial infarction

This patient is presenting with chest pain and an ECG demonstrating hyperacute T waves (leads V2-V6) which is an early finding concerning for a myocardial infarction. A myocardial infarction occurs when an atherosclerotic plaque ruptures causing occlusion of a coronary artery. Patients classically present with chest pain, dyspnea, and diaphoresis. Atypical manifestations of an acute myocardial infarction may include abdominal pain, nausea, reflux symptoms, and dizziness. The most important initial step in management is to administer aspirin as it lowers mortality and carries minimal risk. An ECG should then be performed. Classically, an ST-elevation myocardial infarction (STEMI) will demonstrate ST elevations in a vascular distribution. However, the progression to a STEMI is usually stepwise and may present with ST depressions, hyperacute T waves, pseudonormalization of the ST segment (a normal ST segment after a depression as it elevates), ST elevations, and finally tombstoning (a concave down wave that looks like a tombstone). If a STEMI is suspected after an ECG is performed, the patient should be started on a second antiplatelet agent (e.g., ticagrelor), heparin, and sent immediately to the cardiac catheterization laboratory. Nable et al. review the typical electrophysiologic changes found in STEMI. The authors note that T-wave inversions and ST-segment depression can before, during, or after the STEMI event. The authors recommend obtaining serial ECGs in patients with suspected STEMI. Figure/Illustration A demonstrates hyperacute T waves (blue arrows) that are only occurring in a vascular distribution (V2-V6). Incorrect Answers: Answer A: Hyperkalemia can present with peaked T waves; however, peaked T waves would be demonstrated in all leads. Other findings of hyperkalemia can include QRS widening. Immediate management of hyperkalemia with ECG changes should include calcium administration followed by drugs that shift potassium intracellularly such as insulin, albuterol, or sodium bicarbonate. Further management may include diuresis and/or dialysis. Answer B: Hypertrophic obstructive cardiomyopathy may demonstrate increased voltages throughout the ECG, in particular, in leads V2-V6 with deep Q waves in the septal leads. It may present with syncope upon exertion in a young patient (and in rare cases, sudden cardiac death). Ultrasound would show hypertrophy and left ventricular outflow tract obstruction. Management involves staying hydrated, avoiding strenuous activities, and beta blockers. Answer C: Hypokalemia can present initially on ECG with U waves and may progress to cardiac dysrhythmias. Repletion with potassium is the preferred treatment, and the magnesium level should be checked as low magnesium can lead to potassium wasting in the kidneys. Answer E: Pericarditis presents with chest pain worse by laying back and relieved by leaning forward. ECG may demonstrate diffuse ST elevations with PR depressions, and echocardiography may demonstrate a pericardial effusion. Management involves the administration of ibuprofen or colchicine and steroids in refractory cases. However, these therapies should not be used after myocardial infarction. Bullet Summary: Hyperacute T waves are an early finding that is concerning for myocardial infarction.

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A 31-year-old man presents to clinic for evaluation of a 3-year history of infertility. He has no significant medical history and takes no medications. He exercises twice a day, often with heavy weightlifting, and eats a high-protein diet. He reports occasional alcohol use and remote marijuana use. His temperature is 99.5°F (37.5°C), blood pressure is 148/90 mmHg, pulse is 84/min, and respirations are 15/min. He is sexually active with his wife and has no history of sexually transmitted infections. Physical exam reveals small testes and a receding hairline. He also has palpable tissue underneath his nipples bilaterally. His muscle tone is normal in his upper and lower extremities bilaterally. His laboratory values are below: Serum: Creatinine: 1.3 mg/dL Glucose: 110 mg/dL Total bilirubin: 0.8 mg/dL Aspartate aminotransferase (AST, GOT): 410 U/L Alanine aminotransferase (ALT, GPT): 275 U/L Hemoglobin: 12 g/dL Leukocyte count: 5,300/mm^3 Platelet count: 250,000/mm^3 Which of the following is the most likely cause of this patient’s infertility?

Anabolic steroid use

Cryptorchidism

Excess growth hormone use

Klinefelter syndrome

Myotonic dystrophy

A

Anabolic steroid use

This patient with infertility is presenting with decreased testicular size, receding hairline, gynecomastia (palpable breast tissue), and transaminitis. This is most likely due to exogenous testosterone from anabolic (androgenic) steroid use. Young people (especially athletes and heavy weightlifters) looking to improve their physical performance may rely on the use of anabolic steroids (testosterone, boldenone, and stanozolol). These steroids adversely impair endogenous testicular function, causing infertility secondary to decreased testicular size and sperm count. Furthermore, hepatic dysfunction and cardiac dysfunction can occur at high doses. Excess testosterone is converted to estradiol, leading to breast enlargement and signs of gynecomastia. Aggression and mood disturbances may also occur in patients with excessive anabolic steroid use. Finally, skin findings of anabolic steroid use include accelerated male pattern baldness and acne. Patients should be counseled on avoiding these agents. Van Wagoner et al. study the chemical composition of products marketed as selective androgen receptor modulators (SARMs). The authors find that less than half of the analyzed products contained compounds in the amount listed on the label. The authors recommend that clinicians counsel athletes and bodybuilders that these products are often mislabeled, are not regulated, and have not been shown to be safe or effective. Incorrect Answers: Answer B: Cryptorchidism is the failure of testicular descent into the scrotum and typically manifests in infancy. While uncorrected cryptorchidism can be a cause of infertility, this is an unlikely diagnosis in a man with palpable testes. Furthermore, cryptorchidism would not explain this patient’s receding hairline or gynecomastia. Answer C: Excess growth hormone use should be suspected because growth hormone can be taken exogenously to improve athletic performance and can present with hypertension. This typically also presents with hyperglycemia and enlarged hands and feet. Answer D: Klinefelter syndrome is an inherited disorder that also presents with infertility, gynecomastia, and decreased testicular size. This disorder also causes mental impairment and would not explain the patient’s elevated aminotransferases. Answer E: Myotonic dystrophy is a multi-system disorder that can also present with testicular atrophy, reduced fertility, and hair loss. Patients with myotonic dystrophy also have widespread muscular atrophy and weakness, as well as clinical features of myotonia (e.g., difficulty releasing a handshake). Bullet Summary: Anabolic steroid use in men can cause reduced fertility by suppressing endogenous testosterone activity, and presents with gynecomastia, testicular atrophy, accelerated male balding patterns, and hepatotoxicity.

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A 4-day-old girl is brought in by her mother for bilateral purulent eye discharge. Pregnancy and delivery were uncomplicated. The newborn had been sleeping regularly and feeding well. Then 1 day ago, the patient developed eyelid edema and eye redness. This morning, the newborn developed a thick yellow-white eye discharge. The mother denies that anyone in the house smokes. The family has a cat at home. The patient’s rectal temperature is 99°F (37.2°C), blood pressure is 80/50 mmHg, pulse is 134/min, and respirations are 34/min with an oxygen saturation of 98% O2 on room air. Figure A shows a photograph of one of the patient's eyes. The patient's physical exam is otherwise unrevealing. Which of the following most appropriately would have prevented this infant's condition?

Artificial tears

Intramuscular ceftriaxone

Oral erythromycin

Topical bacitracin

Topical erythromycin

E

Topical erythromycin

This patient is presenting with bilateral purulent eye discharge 4 days post-birth, suggesting the diagnosis of gonococcal conjunctivitis. Standard prophylaxis for this condition is topical erythromycin ointment. Neonatal gonococcal conjunctivitis is caused by Neisseria gonorrhea and presents in newborns that are 0-5 days old. Symptoms include purulent discharge and eye swelling. Standard prophylaxis for gonococcal conjunctivitis is erythromycin ointment. Silver nitrate drops can also be used as prophylaxis, but this treatment has been abandoned in most practices as it can cause chemical conjunctivitis. Treatment for gonococcal conjunctivitis includes intravenous or intramuscular ceftriaxone. All neonates with gonococcal conjunctivitis should also be treated for chlamydia. Franco and Hammerschlag prevent the current methods of providing prophylaxis against gonococcal conjunctivitis. They discuss how the development of macrolide resistance may make erythromycin ointment ineffective. They recommend screening and treatment of pregnant women to prevent the development of this disease. Figure/Illustration A shows a newborn's eye that is exhibiting eyelid swelling, redness, and purulent discharge (red circle). These findings are consistent with gonococcal conjunctivitis. Incorrect Answers: Answer A: Artificial tears can be used in the management of chemical conjunctivitis. The most common cause of neonatal chemical conjunctivitis is post-delivery use of silver nitrate drops. Symptoms usually present within the first 24 hours following birth/exposure as mild conjunctival injection and tearing without purulent discharge. Answer B: Intramuscular ceftriaxone is used as treatment, not prophylaxis, of neonatal gonococcal conjunctivitis. This disease would present with purulent discharge and eye swelling. The goal of prophylaxis is to prevent the development of this condition. Answer C: Oral erythromycin is used to treat neonatal chlamydial conjunctivitis. Symptoms of chlamydial conjunctivitis usually present 5-14 days post-birth with mild hyperemia and scant mucoid or watery discharge. Patients who are diagnosed with gonorrhea should also be treated empirically for chlamydia. Answer D: Topical bacitracin can be used as a treatment for gram-positive neonatal bacterial conjunctivitis. It would not be used as a prophylaxis. These patients would present with rapidly progressive infection associated with surrounding soft tissue cellulitis or abscess formation. Bullet Summary: Neonatal gonococcal conjunctivitis is treated with an intramuscular shot of ceftriaxone and standard prophylaxis to prevent this condition is with erythromycin ointment.

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A 69-year-old man presents to his primary care physician with hip and back pain. He states this weekend he had a barbecue. When he was lifting a heavy object, he suddenly felt pain in his lower back. He describes the pain as in his buttocks but states that at times it travels down his leg. He states that it feels electrical and burning in nature. The patient has a medical history of obesity, diabetes, depression, anxiety, diverticulosis, constipation, and a surgical repair of his anterior cruciate ligament. His current medications include metformin, insulin, lisinopril, fluoxetine, and sodium docusate. His temperature is 98.6°F (37°C), blood pressure is 131/82 mmHg, pulse is 82/min, and respirations are 14/min. On physical exam, he is found to have an intact motor and sensory function in his lower extremities bilaterally. No clonus or Babinski sign is appreciated. An exam of the cranial nerves is intact bilaterally. Which of the following is most likely to help confirm the diagnosis?

Flexion, abduction, and external rotation of the thigh

Internal rotation of the extended hip

Palpating the paraspinal muscles

Radiography

Straight leg raise

E

Straight leg raise

This patient is presenting with lower back pain that is electrical and travels down his legs after lifting an object suggesting a diagnosis of a herniated disc. The straight leg test can help confirm the diagnosis. A herniated disc classically presents in a middle-aged or older individual who was lifting a heavy object with improper form. They will typically experience lower back pain that can be described as radicular. The pain will typically travel down the legs or "shoot down" the legs and is typically described as feeling electrical. The straight leg test on physical exam supports the diagnosis without an MRI. When the individual raises their leg, this causes compression of the spinal nerve roots leading to an exacerbation of symptoms. The most appropriate initial step in management for these patients is limiting strenuous activity, physical therapy, and NSAIDs. Patients who have chronic symptoms that have failed conservative management can undergo surgical laminectomy. Camino and Piuzzi present the data regarding the diagnostic value of the straight leg raise test. They discuss how this test can exacerbate patients with radicular symptoms. They recommend all practitioners learn how to perform and interpret this test. Incorrect Answers: Answer A: Flexion, abduction, and external rotation of the thigh is referred to as the FABER test and is used to evaluate for sacroiliitis which can present with lower back pain and pain in the buttocks. This exam maneuver will cause intense pain in patients who have inflammation of the joint. Treatment is with physical therapy and NSAIDs. Answer B: Internal rotation of the extended hip is the Freiberg test which evaluates for piriformis syndrome. Piriformis syndrome presents with lower back pain similar to a herniated disc; however, is less likely to have occurred after a single lifting episode and does not typically present with electrical pain that originates in the buttocks. Answer C: Palpating the paraspinal muscles is a non-specific test that could further support a diagnosis of a muscle strain. It will likely not provide much information in the diagnosis of a herniated disc. Patients with muscle strain can be treated conservatively with relative rest and NSAIDs. Answer D: Radiography is unlikely to offer information regarding this patient's herniated disc. While it can detect bony abnormalities, the detail of this imaging modality will not depict a herniated disc. An MRI is required to offer the detail necessary to make the diagnosis and is the most accurate test for a herniated disc. Bullet Summary: A herniated disc typically presents with pain in the lower back that radiates down the legs and is exacerbated by the straight leg raise test.

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A 5-year-old boy presents to his primary care physician for recurrent colds, fatigue, and fussiness. Over the past several weeks, the child has been more fatigued and his parents state that “he always seems to be sick.” They state that sometimes he complains about his bones hurting and they note that he is less playful. He is up to date on his vaccinations. His temperature is 102°F (38.9°C), blood pressure is 92/60 mmHg, pulse is 115/min, respirations are 23/min, and oxygen saturation is 99% on room air. Physical exam is notable for diffuse non-tender lymphadenopathy. Abdominal exam reveals hepatosplenomegaly. Laboratory studies are ordered as seen below. Hemoglobin: 8.0 g/dL Hematocrit: 23% Leukocyte count: 27,500/mm^3 with 35% lymphoblasts Platelet count: 49,000/mm^3 Serum: Na+: 139 mEq/L Cl-: 101 mEq/L K+: 4.0 Eq/L HCO3-: 24 mEq/L BUN: 16 mg/dL Glucose: 100 mg/dL Creatinine: 0.7 mg/dL Which of the following is the most likely diagnosis?

Acute lymphoblastic leukemia

Acute myelogenous leukemia

Chronic myelogenous leukemia

Leukemoid reaction

Parvovirus B19 infection

A

Acute lymphoblastic leukemia

This pediatric patient is presenting with recurrent colds, fatigue, non-tender lymphadenopathy, hepatosplenomegaly, and leukocytosis with increased lymphoblasts, which are concerning for acute lymphoblastic leukemia (ALL). ALL is the most common hematologic cancer in pediatric patients. It initially presents with a vague constellation of symptoms including fatigue, fevers, easy bleeding/bruising, bone pain, lymphadenopathy, hepatosplenomegaly, and possibly testicular enlargement. The diagnosis is supported when the white blood cell count (which can be low, normal, or high) demonstrates increased lymphoblasts. Further confirmatory testing may include testing for the 12:21 translocation, which is more common with a better prognosis, or the 9:22 translocation (the Philadelphia chromosome), which is less common and denotes a poor prognosis. Onciu reviews ALL. He notes that ALL has a high cure rate with intensive chemotherapeutic regimens and that new research is improving outcomes in this very common condition. He recommends early treatment with these regimens for an improved prognosis. Incorrect Answers: Answer B: Acute myelogenous leukemia is a malignancy of myeloblasts and is more common in the elderly. Patients will present with systemic symptoms, weight loss, anorexia, leukocytosis, anemia (causing fatigue), thrombocytopenia (causing bleeding including gingival bleeding and bleeding from the gastrointestinal tract), and neutropenia (predisposing patients to life-threatening infection). Myeloblasts produce increased amounts of myeloperoxidase which can lead to the formation of Auer rods that can be seen on peripheral smear. Answer C: Chronic myelogenous leukemia is a neoplastic proliferation of myeloid stem cells and presents with a leukocyte count > 50,000/mm3. There are different presentations for this condition. Most patients present in the chronic phase with minimal symptoms (and a low blast count); however, they can also present with an accelerated phase and a blast phase which can lead to a hematologic emergency termed a blast crisis which may cause a hyperviscosity syndrome. Answer D: Leukemoid reaction is an overly robust immune reaction (often to infection) that resembles chronic myelogenous leukemia. However, the leukocyte alkaline phosphatase level is elevated. This elevated level indicates it is a robust immune response rather than increased cell levels from malignancy. Answer E: Parvovirus B19 infection presents with erythema infectiosum (fifth disease) which may include "slapped cheek" rash, fever, malaise, and possibly respiratory symptoms. In healthy patients, symptoms are usually minimal and self-limited. However, in patients with hemoglobinopathies (such as sickle cell disease), the transient halt in erythropoiesis that occurs in addition to hemolysis may lead to significant anemia requiring transfusion. Bullet Summary: Acute lymphoblastic leukemia presents in pediatric patients with pancytopenia, fatigue, repeat infections, easy bleeding, bone pain, lymphadenopathy, hepatosplenomegaly, and increased blast cells on peripheral smear.

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A 15-year-old boy presents to his pediatrician after an appendectomy 1 week ago. The patient denies any abdominal pain, fevers, chills, nausea, vomiting, diarrhea, or constipation. He eats solids and drinks liquids without difficulty. He is back to playing basketball for his school team without any difficulty. His urine appears more amber than usual but he suspects dehydration. His temperature is 98.6°F (37°C), blood pressure is 110/70 mmHg, pulse is 76/min, and respirations are 15/min. His physical exam is unremarkable. The laparoscopic incision sites are all clean without erythema. The pediatrician orders a urinalysis, which is notable for the following. Urine: Epithelial cells: Scant Glucose: Negative Protein: 3+ WBC: 3/hpf Bacteria: None Leukocyte esterase: Negative Nitrites: Negative The patient is told to return in 3 days for a follow-up appointment; however, his urinalysis at that time is similar. Which of the following is the most appropriate next step in management?

CT scan abdomen and pelvis with contrast

Renal biopsy

Repeat urinalysis

Urine dipstick in the morning and in the afternoon

Urine electrolytes and creatinine

D

Urine dipstick in the morning and in the afternoon

This patient is found to have proteinuria on urinalysis in the absence of clinical symptoms or signs of nephrotic syndrome. Given the likely diagnosis of transient proteinuria, the most appropriate next step is to repeat the urine dipstick in the morning and in the afternoon. Transient proteinuria can be due to febrile illnesses, seizures, strenuous exercise, emotional stress, serious illnesses like heart failure, and abdominal surgery. A detailed workup is not needed if the clinical story is clear, but an orthostatic test can be completed. One way to do this is to assess the urine dipstick in the morning and in the afternoon. Another way requires the patient to collect urine at multiple times throughout the day. A diagnosis is confirmed if the morning sample is protein-free but the evening sample contains protein. In general, pediatric patients with orthostatic proteinuria should have under 1 gram of protein in a full 24 hours. Treatment is with reassurance because this condition usually resolves by itself. Ingold and Bhatt review the evidence regarding the diagnosis and treatment of orthostatic proteinuria in patients. They discuss how this condition is benign and typically occurs in adolescents. They recommend reassurance and supportive treatment. Incorrect Answers: Answer A: A CT scan of the abdomen and pelvis with contrast could assess for any anatomic obstruction and a possible post-renal cause of kidney dysfunction. It would be more prudent to obtain basic labs and a timed urinalysis before exposing a pediatric patient to radiation. Answer B: Renal biopsy is indicated if the patient's clinical presentation is concerning for a glomerular or tubulointerstitial etiology for proteinuria. Patients will have edema, hematuria, or dysuria. Answer C: Repeat urinalysis will not change the presence of proteinuria. Generally, a patient who has proteinuria should have a repeat urinalysis performed to rule out transient proteinuria. If the repeat urinalysis demonstrates proteinuria (as in this patient), then the diagnosis is unlikely to be transient proteinuria, and further workup is needed. Answer E: Urine electrolytes and creatinine will assess the kidney's ability to concentrate urine and assess the etiology of acute kidney injury. Patients will present with oliguria or anuria. Bullet Summary: Consistent proteinuria in a child should by evaluated by performing a urinalysis in the morning and in the afternoon to see if proteinuria comes on toward the end of the day.

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A 24-year-old woman with no significant medical history presents to the emergency department for progressive shortness of breath. She endorses decreased exercise tolerance as well as intermittent palpitations. She returned from a recent missionary trip to South America 12 months prior where she endorsed eating a local delicacy as well as a period of fevers and eyelid swelling during her stay. Her temperature is 99.1°F (37.3°C), pulse is 95/min, blood pressure is 130/85 mmHg, respirations are 15/min, and oxygen saturation is 97% on room air. Physical exam is notable for a laterally displaced point of maximal impulse as well as a 2/6 diastolic murmur radiating to the axilla. A blood smear is shown in Figure A. Her laboratory results are: Leukocyte count and differential: Leukocyte count: 10,000/mm^3 Neutrophils: 57% Lymphocytes: 30% Monocytes: 3% Eosinophils: 9% Basophils: 1% Hemoglobin: 13.1 g/dL Platelet count: 420,000/mm^3 Which of the following is the most appropriate treatment?

Amphotericin B

Benznidazole

Erythromycin

Ganciclovir

Praziquantel

B

Benznidazole

This patient presents with symptoms of heart failure, eosinophilia, trypanosomes on peripheral smear, and a history of recent travel to South America consistent with the diagnosis of Chagas disease. Treatment options for Chagas disease include benznidazole and nifurtimox. Chagas disease is caused by the parasite Trypanosoma cruzi and is most commonly transmitted by the reduvvid (kissing) bug. The disease is endemic to South America and presents in an acute and chronic phase. The acute phase is characterized by fever, headaches, myalgias, and unilateral eyelid swelling (Romaña’ sign) where the infectious agent has been rubbed into the eye. The chronic phase of the disease is characterized by dilated apical cardiomyopathy leading to conduction abnormalities and valvular dysfunction, megacolon, and megaesophagus. Laboratory testing reveals a peripheral eosinophilia and a peripheral blood smear may reveal the infectious trypanosomes. Treatment is with benznidazole and/or nifurtimox. Perez-Molina and Molina present the data surrounding the diagnosis and treatment of Chagas disease. They discuss how many cases progress to a chronic state characterized by cardiomyopathy, arrhythmias, and organomegaly. They recommend prompt treatment of the disease to avoid end organ damage. Figure/Illustration A shows a peripheral blood smear with the trypomastigote form of Trypanosoma cruzi (red circle). Note the anterior location of the dense basophilic nucleus. Incorrect Answers: Answer A: Amphotericin B is a potent antifungal that has application in the treatment of multiple fungal infections. It is used as a first-line agent for mucormycosis and cryptococcal meningitis (in addition to flucytosine). Amphotericin B with sodium stibogluconate is used to treat visceral leishmaniasis, a protozoal infection most commonly caused by Leishmania donovani. Side effects can include nausea, vomiting, rigors, fever, hypertension or hypotension, renal dysfunction, and hypoxia. Answer C: Erythromycin is a macrolide antibiotic that is used in the treatment of bacterial infections. It has a pro-motility effect and can also be used as a gastric pro-motility agent. Potential side effects include gastrointestinal upset, prolonged QT interval, inhibition of the P450 system, and pyloric stenosis in infants. Answer D: Ganciclovir is a synthetic nucleoside analogue that is mainly used in the treatment of cytomegalovirus (CMV) infections. The most common side effects are bone marrow suppression (granulocytopenia, thrombocytopenia, and anemia) and gastrointestinal upset. Answer E: Praziquantel is an anti-helminthic used in the treatment of tapeworms and flukes including Echinococcus, Taenia solium (cysticerosis), Schistosoma sp., Clonorchis sinensis (liver fluke), and Paragonimus westermani (lung fluke). Side effects of praziquantel develop due to release of contents from dead parasites and can include gastrointestinal upset, elevated liver enzymes, and dizziness. Bullet Summary: Treatment of Chagas disease is with benznidazole or nifurtimox.

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A 27-year-old man presents for an appointment to establish care. He recently was released from prison. He has felt very fatigued and has had a cough. He has lost roughly 15 pounds over the past 3 weeks. He attributes this to intravenous drug use in prison. His temperature is 99.5°F (37.5°C), blood pressure is 127/68 mmHg, pulse is 100/min, respirations are 18/min, and oxygen saturation is 98% on room air. QuantiFERON gold testing is positive. The patient is started on appropriate treatment. Which of the following is the most likely indication to discontinue this patient's treatment?

Elevated liver enzymes

Hyperuricemia

Optic neuritis

Peripheral neuropathy

Red body excretions

A

Elevated liver enzymes

This patient is presenting with weight loss and cough with a positive quantiFERON gold test suggestive of tuberculosis and has been started on treatment. The most likely indication to discontinue tuberculosis therapy is elevation of liver enzymes. Tuberculosis typically presents with weight loss, cough, and night sweats usually in high-risk patients (prisoners or the immunosuppressed). It can be diagnosed using sputum samples as these organisms will be positive on an acid-fast test. These bacteria are slow to grow so cultures need to be held for an extended period of time. QuantiFERON gold testing can be used to make the diagnosis as well. Treatment for tuberculosis is RIPE therapy: Rifampin, Isoniazid, Pyrazinamide, and Ethambutol. The most common indication to alter or discontinue therapy is an elevation of liver enzymes 5 times greater than baseline. Tweed et al. review the evidence regarding liver injury in patients with RIPE therapy. They discuss how patients on HIV therapy are at higher risk. They recommend measuring liver enzymes to detect this potential side effect. Incorrect Answers: Answer B: Hyperuricemia is a side-effect of pyrazinamide; however, this is not the most common indication for discontinuing RIPE therapy. Patients can be treated with supportive therapy or with uric acid lowering agents in those with arthralgias. Answer C: Optic neuritis is a side-effect of ethambutol; however, it is not the most common indication for discontinuing RIPE therapy. Treatment is with discontinuation of ethambutol. Answer D: Peripheral neuropathy is a side-effect of isoniazid; however, it is typically not an indication to discontinue RIPE therapy. Treatment is with supplementation of vitamin B6. Answer E: Red body excretions are a side-effect of rifampin; however, this is a cosmetic concern rather than an indication to discontinue RIPE therapy. Patients should be counseled regarding this side effect prior to initiation of treatment. Bullet Summary: Elevation of liver enzymes 5 times above normal is the most common indication to alter or discontinue RIPE therapy when treating tuberculosis.

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A 37-year-old man presents to the emergency department for a persistent fever. The patient has felt unwell for the past week and has felt subjectively febrile. The patient has a medical history of a suicide attempt and alcohol abuse. He is not currently taking any medications. The patient admits to using heroin and cocaine and drinking 5-8 alcoholic drinks per day. His temperature is 103°F (39.4°C), blood pressure is 92/59 mmHg, pulse is 110/min, respirations are 20/min, and oxygen saturation is 96% on room air. Cardiopulmonary exam is notable for a systolic murmur heard best along the left sternal border. Dermatologic exam reveals scarring in the antecubital fossa. IV fluids are administered and the blood pressure is subsequently 120/70 mmHg. Which of the following is the most appropriate next step in management for the most likely underlying diagnosis?

Blood cultures

Chest radiograph

CT scan

Ultrasound

Vancomycin and gentamicin

A

Blood cultures

This patient is presenting with fever and a systolic murmur suggestive of bacterial endocarditis. The most appropriate initial step in management is to draw blood cultures. Bacterial endocarditis presents with fever, systemic symptoms (aches, myalgias, and fatigue), and a new murmur typically in a patient with intravenous drug use. These patients introduce bacteria intravenously which then flows to the right side of the heart and can cause right-sided endocarditis. The most appropriate initial step in management is to draw blood cultures. Once blood cultures have been drawn, broad-spectrum antibiotics can be started (vancomycin and gentamicin), and an ultrasound can be performed to further support the diagnosis (or rule out vegetations) and plan operative interventions if necessary. Wang et al. review the evidence regarding the diagnosis and treatment of infectious endocarditis. They discuss how echocardiogram and blood cultures are the mainstay of diagnosis. They recommend broad spectrum antibiotics. Incorrect Answers: Answer B: A chest radiograph may be performed in the workup for bacterial endocarditis; however, it is not the most appropriate initial step in management and is neither sensitive nor specific. Answer C: A CT scan would not be a very helpful confirmatory test in the diagnosis of bacterial endocarditis. A better confirmatory test would be an ultrasound. It may workup alternative causes of fever such as pneumonia. Answer D: Ultrasound (echocardiography) would be the imaging test of choice for bacterial endocarditis. It would be performed after blood cultures have been drawn and antibiotics had been started. Answer E: Vancomycin and gentamicin are the broad-spectrum antibiotics of choice for bacterial endocarditis. They would be started after blood cultures have been drawn and reduce mortality when given early in sepsis. Bullet Summary: The most appropriate initial step in the management of bacterial endocarditis after initial stabilization is to draw blood cultures.

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A 32-year-old woman presents to her primary care provider with pelvic pain. She reports that for the last several years, she has had chronic pain that is worse just before her menstrual period. Over the past 2 months, she has also had worsening pain during intercourse. She denies dysuria, vaginal discharge, or vaginal pruritus. The patient has never been pregnant and previously used a copper intrauterine device (IUD) for contraception, but she had the IUD removed 1 year ago because it worsened her menorrhagia. She has now been using combined oral contraceptive pills (OCPs) for nearly 1 year. The patient reports improvement in her menorrhagia on the OCPs but denies any improvement in her pain. Her medical history is otherwise unremarkable. Her temperature is 98.0°F (36.7°C), blood pressure is 124/73 mmHg, pulse is 68/min, and respirations are 12/min. The patient has pain with lateral displacement of the cervix on pelvic exam. A pelvic ultrasound shows no abnormalities, and a urine pregnancy test is negative. Which of the following is most likely to confirm the diagnosis?

Abdominal ultrasound

Hysterosalpingogram

Hysteroscopy

Laparoscopy

Pelvic MRI

D

Laparoscopy

This patient presents with chronic pelvic pain that is worse before her menstrual period, vaginal tenderness on physical exam, and lateral displacement of the cervix, which is consistent with a diagnosis of endometriosis. Since this patient has failed therapy with oral contraceptive pills (OCPs), she should undergo laparoscopy. Endometriosis classically presents with chronic pelvic pain and the “3 D symptoms” of dysmenorrhea, dyspareunia, and dyschezia. Since laparoscopy with biopsy is required for definitive diagnosis, patients with suspected endometriosis may be empirically managed with OCPs and NSAIDs. Most patients achieve symptom control on this regimen. If patients fail empiric therapy, have contraindications to hormonal therapy, or have severe symptoms they should undergo laparoscopy for both definitive diagnosis and treatment of the disease. Vercellini et al. review the evidence regarding the diagnosis and treatment of endometriosis. They discuss how the diagnosis of this disorder is carried out by direct visualization and histologic examination of lesions. They recommend medical treatment for symptomatic relief and surgical excision in refractory patients. Incorrect Answers: Answer A: Abdominal ultrasound is less accurate than a transvaginal ultrasound which has already been performed. Since there were no findings on transvaginal ultrasound, it is unlikely that abdominal ultrasound would reveal pathology. This modality would be effective for intra-abdominal disorders such as cholelithiasis or appendicitis (in pediatric and pregnant patients to avoid radiation exposure). Answer B: Hysterosalpingogram is more useful in the workup of infertility, particularly for patients with a history of pelvic inflammatory disease. It is not routinely used to diagnose endometriosis. Patients with pelvic inflammatory disease present with fever, purulent discharge, and cervical motion tenderness. Treatment is with antibiotics. Answer C: Hysteroscopy is used in the workup of abnormal uterine bleeding, fibroids, and endometrial thickening or polyps. Since endometriosis is defined as endometrial glands and stroma outside of the uterine cavity, a hysteroscopy is not particularly helpful in making the diagnosis. Treatment for polyps or fibroids is with surgical excision. Answer E: Pelvic MRI can be used to better characterize an abnormality seen on pelvic ultrasound or CT or to diagnose adenomyosis. It can aid in making the diagnosis of endometriosis but is not the most accurate/confirmatory test. A laparoscopy would both be diagnostic and therapeutic for this disorder. Bullet Summary: Patients with suspected endometriosis may be managed empirically with oral contraceptive pills and NSAIDs, but laparoscopy with biopsy is necessary for definitive diagnosis and management.

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A 27-year-old man presents to his primary care physician for a checkup. He has no health concerns and has not seen a physician in years. The patient has a medical history of depression treated with fluoxetine and lithium. His temperature is 99.5°F (37.5°C), blood pressure is 122/78 mmHg, pulse is 90/min, respirations are 13/min, and oxygen saturation is 98% on room air. Physical exam is notable for the finding in Figure A. Which of the following represents the most likely risk factor for this patient's presenting condition?

Alcohol consumption

Antibiotic use

Intravenous drug use

Poor dental hygiene

Sexual intercourse

A

Alcohol consumption

This patient is presenting with adherent white plaques on the inside of the cheek consistent with oral leukoplakia. Alcohol consumption is a risk factor for this disease. Oral leukoplakia presents with a white patch/plaque that occurs over the oral mucosa that is adherent and non-scrapable. Risk factors for this condition include the risk factors for squamous cell carcinoma such as consumption of alcohol and smoking. Though the cause of this lesion is largely idiopathic, any irritating substance can induce it. Other potential risk factors include candidiasis, vitamin deficiency, endocrine disturbances, and viral infections. A diagnosis can be made using a biopsy showing the degree of dysplasia. Treatment is with smoking and alcohol cessation as well as surgical removal for suspicious lesions. Mohammed and Fairozekhan review the evidence regarding the diagnosis and risk factors for leukoplakia. They discuss how this disease is associated with smoking and alcohol use. They recommend screening patients for these modifiable risk factors. Figure/Illustration A is a clinical photograph demonstrating adherent white plaques on the inside of the cheek (red circle). These findings are consistent with oral leukoplakia. Incorrect Answers: Answer B: Antibiotic use is a risk factor for candidiasis; however, this patient is not presenting with symptoms of candidiasis which is itself a risk factor for oral leukoplakia. Candidiasis presents with opaque white lesions that can be scraped off. Answer C: Intravenous drug use does make this patient riskier overall for many conditions; however, alcohol is a more direct risk factor for oral leukoplakia. Immunodeficiency conditions can cause widespread fungal and viral infections on the mucosal surfaces. Answer D: Poor dental hygiene may be found more often in patients with oral leukoplakia; however, it is not itself a direct cause. Answer E: Sexual intercourse would predispose this patient to infections and viruses (such as Epstein-Barr virus); however, it is a less likely risk factor than is alcohol consumption or smoking. These infections tend to present with ulcers more commonly than leukoplakia. Bullet Summary: Risk factors for oral leukoplakia and squamous cell carcinoma include alcohol consumption and smoking.

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A 32-year-old man presents to the emergency department for evaluation of headache. His symptoms started last night and have persisted. He occasionally has migraine headaches, but he has not had a headache like this in the past. He reports associated nausea, vomiting, fevers, and neck pain. He has a medical history of asthma. His temperature is 100.4°F (38.0°C), blood pressure is 110/60 mmHg, pulse is 95/min, respirations are 17/min, and oxygen saturation is 98% on room air. On physical exam, he appears uncomfortable. Neurologic exam reveals no focal deficits. There is pain with passive neck flexion. No edema or rashes are noted. Lungs are clear to auscultation bilaterally. Lumbar puncture is performed and CSF results are obtained as shown below. Cerebrospinal fluid (CSF): Cell count: 175/mm^3 RBCs: 0/mm^3 Cl-: 119 mEq/L Glucose: 49 mg/dL Pressure: 150 mmH2O Total protein: 55 mg/dL Based on these results, which of the following is the most appropriate treatment regimen for this patient?

Acyclovir

Amphotericin and 5-flucytosine

Ceftriaxone and vancomycin

Ceftriaxone, vancomycin and steroids

Supportive care and monitoring

E

Supportive care and monitoring

This patient with headache, fever, and neck stiffness has a presentation and CSF studies consistent with a diagnosis of viral or aseptic meningitis. Supportive care is the most appropriate management strategy for patients with viral meningitis. Aseptic (viral) meningitis presents similarly to bacterial meningitis with neck stiffness, photophobia, fever, malaise, and flu-like symptoms. Patients should be worked up and treated as if they have bacterial meningitis until proven otherwise. CSF findings in aseptic meningitis show an elevated cell count (though typically < 300/mm^3 in contrast to bacterial meningitis), a normal or elevated protein, and a normal glucose. CSF should be sent for Gram stain and culture to confirm the diagnosis and rule out bacterial meningitis. Once the diagnosis has been confirmed, management of viral meningitis consists of supportive care and monitoring for complications such as seizures, cerebral edema, or SIADH. Kohil et. al review viral meningitis. They discuss the pathophysiology, clinical manifestation and diagnosis. They recommend that most patients with viral meningitis be treated with supportive care. Incorrect Answers: Answer A: Acyclovir would be appropriate for suspected HSV or varicella encephalitis or meningitis. This patient with no RBCs in the CSF and no changes in mental status is not likely to have infection with HSV or varicella. Answer B: Amphotericin and 5-flucytosine followed by long-term fluconazole is the appropriate management of cryptococcal meningitis. Cryptococcal meningitis presents similarly to bacterial and viral meningitis, almost exclusively in immunocompromised patients. Answer C: Ceftriaxone and vancomycin would be appropriate if bacterial meningitis was suspected. Steroids are generally added if a bacterial source is likely. However, this patient has a presentation that is less concerning for bacterial meningitis, and CSF studies that are more consistent with aseptic meningitis. Answer D: Ceftriaxone, vancomycin and steroids are an appropriate initial regimen for bacterial meningitis. Dexamethasone reduces inflammatory injury while patients are being treated with antibiotics. Bullet Summary: Viral or aseptic meningitis is managed with supportive care and monitoring.

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A 23-year-old woman presents with a 7-day history of abdominal pain, and now bloody diarrhea that brings her to her primary care physician. Review of systems is notable for a 12-pound unintentional weight loss and intermittent loose stools. She has a family history notable for a father with coronary artery disease and a mother with primary sclerosing cholangitis. Her temperature is 37.2°C (98.9°F), blood pressure is 100/72 mmHg, pulse is 72/min, respirations are 12/min, and oxygen saturation is 100% on room air. Her abdomen is soft, mildly diffusely tender to deep palpation, and non-distended. She is found to have the finding on colonoscopy in Figure A. Serum perinuclear antineutrophil cytoplasmic antibodies (p-ANCA) are positive. Which of the following is most likely to be present in this patient?

Cobblestoning and skip lesions

Continuous lesion beginning in the rectum

Fistulae and stricture formation

Perianal disease

Worse disease severity near the ileocecal valve

B

Continuous lesion beginning in the rectum

This patient presents with features suggestive of inflammatory bowel disease (IBD), and her colonoscopic and serologic studies suggest ulcerative colitis (UC). UC typically begins in the rectum and progresses proximally towards the ileocecal valve in a continuous fashion. The diagnosis of IBD should always prompt further investigation to better delineate between UC, Crohn disease, or indeterminate colitis. Further delineation guides treatment and informs prognosis. UC has a peak incidence in the second and third decades of life. It is characterized by disease extending from the rectum proximally towards the ileocecal valve in a continuous fashion. UC presents as mucosal and submucosal inflammation, with characteristic crypt distortion and presence of crypt abscesses. P-ANCA is positive in most individuals with UC. Repeated mucosal injury can induce pseudopolyp formation, and pancolitis or disease in the descending colon warrants screening colonoscopy due to increased risk of colon cancer. On imaging, the colon can be dilated by edema, losing its haustral markings and giving it a "lead pipe" appearance. Gajendran et al. review the pathophysiology, diagnosis, and treatment of UC. They found that colonoscopy with biopsy is the best way to make a definitive diagnosis of UC. They recommend the Mayo scoring system as a commonly used method of assessing disease severity, guiding treatment options, and monitoring patients during therapy. Figure A is a colonoscopy image showing continuous colonic mucosal inflammation typical of ulcerative colitis. Incorrect Answer: Answer A: Cobblestoning and skip lesions refer to the patchy areas of inflammation noted in Crohn disease. In contrast, the inflammation seen in UC involves continuous stretches of colon mucosa. Answer C: Fistulae and stricture formation are features of Crohn disease, not UC. Fistulizing and stricture formation can affect the entire gastrointestinal tract in Crohn disease. Answer D: Perianal disease is a feature of Crohn disease. Although UC commonly affects the rectum, it tends to spare the anus. Answer E: Worse disease severity near the ileocecal valve is a feature of Crohn disease and not UC. UC tends to be characterized by more uniform disease severity spanning in continuous fashion from rectum towards the cecum. Bullet Summary: Ulcerative colitis is characterized by disease extending from the rectum proximally towards the ileocecal valve in a continuous fashion.

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A 71-year-old woman arrives to clinic with sudden vision loss. She was in her usual state of health until waking up this morning unable to see out of her right eye. She denies pain, but reports her right eye “feels funny.” The patient’s medical history is significant for a previous myocardial infarction, hypertension, and osteoporosis. Her current medications include aspirin, metoprolol, rosuvastatin, lisinopril, and alendronate. Her temperature is 98°F (36.7°C), blood pressure is 145/86 mmHg, pulse is 62/min, and respirations are 12/min with an oxygen saturation of 98% on room air. The patient's pupils are symmetric in size and equally reactive to light with accommodation. A fundoscopic exam of the right eye is shown in Figure A. The left optic fundus is unremarkable. Which of the following is the most likely diagnosis?

Central retinal artery occlusion

Closed angle glaucoma

Papilledema

Retinal detachment

Retinal vein occlusion

E

Retinal vein occlusion

This patient is presenting with sudden, painless, unilateral vision loss with a fundoscopic exam positive for venous dilation and retinal hemorrhage. These findings are consistent with the diagnosis of retinal vein occlusion. Retinal vein occlusion can occur in either central or branch retinal veins and is often caused by compression from nearby arterial atherosclerosis. It presents as acute onset, painless vision loss, normally in one eye. On fundoscopic exam, classic findings of this disease include venous engorgement, retinal hemorrhage, cotton wool exudates, and edema/swelling of the optic disk can be seen. There is no definitive treatment for this disorder but symptomatic treatment includes intravitreal glucocorticoid injections and retinal laser photocoagulation. Retinal vein occlusion may resolve spontaneously or progress to permanent vision loss. Robinson and Halpern present evidence regarding the treatment of retinal vein occlusion. They discuss how the treatments for the acute phase of this disease have been disappointing. They recommend managing long-term complications such as neovascularization with phototherapy. Figure/Illustration A is a fundoscopic exam showing engorged retinal veins, optic disk swelling, and widespread retinal hemorrhages (red circle). These findings are characteristic of central retinal vein occlusion. Incorrect Answers: Answer A: Central retinal artery occlusion can present as sudden onset, unilateral vision loss. Fundoscopic exam will show a “cherry-red” spot at the fovea and a “fuzzy” retina with attenuated vessels. Embolic sources may include carotid artery atherosclerosis or cardiac vegetation. Treatment is with risk factor control. Answer B: Closed-angle glaucoma presents as sudden, painful, vision loss caused by increased intraocular pressure. The eye will appear red and often feel “hard.” The optic disc will show characteristic cupping. Intraocular pressure will be levated and treatment is with acetazolamide, steroids, timolol, bromidine, and pilocarpine. Irodotomy is reserved for refractory cases. Answer C: Papilledema may present as an enlargement in the blind spot and is usually bilateral, as it is caused by increased intracranial pressure. On fundoscopic exam, there will be bilateral optic disk swelling, seen as an elevated optic disk and blurred margins. Patients should undergo a neurologic evaluation to determine the etiology of the papilledema. Answer D: Retinal detachment presents as monocular loss of vision, often described as a “curtain pulled down,” and preceded by “flashers” and “floaters.” On fundoscopic exam, crinkling of the retinal tissue and abrupt changes in vessel direction can be seen. Surgical reattachment of the retina is required to prevent loss of vision. Bullet Summary: Retinal vein occlusion presents with a sudden, monocular, painless loss of vision with optic disk swelling, dilated veins, cotton wool spots, and retinal hemorrhages.

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A 23-year-old woman presents to her psychiatrist concerned about her mood. She has felt tired and unwilling to engage in any activities lately. She states that her limbs feel heavy all the time and that completing any activity takes tremendous effort. She no longer finds any happiness in activities that she previously enjoyed. She struggles to sleep and at times can't sleep for several days. The patient is started on appropriate first-line therapy and sent home. She returns 1 week later stating that her symptoms have not improved. She is requesting help as her performance at work and school is suffering. Her temperature is 99.5°F (37.5°C), blood pressure is 115/72 mmHg, pulse is 60/min, respirations are 13/min, and oxygen saturation is 98% on room air. Which of the following is the most appropriate next step in management?

Add lithium to treatment regimen

Change treatment to duloxetine

Change treatment to lithium

Continue current therapy

Electroconvulsive therapy

D

Continue current therapy

This patient is presenting with depression and should be treated with a selective serotonin reuptake inhibitor (SSRI) for at least 4 weeks. Patients who have tried the therapy for a shorter duration of time may not yet have experienced the benefit of the medication. Depression presents with SIGE CAPS (Sleeplessness, Interest loss, Guilt, Energy decreased, Concentration abnormalities, Appetite changes, Psychomotor retardation, and Suicidal ideation). The most appropriate initial step in management is to treat the patient with an SSRI for at least 4 weeks since SSRI's take several weeks to reach their potential. If the treatment has failed after 4 weeks of use, altering the patient's medications could be appropriate. Treatment and side effects should be monitored by a physician. Kato et al. review the evidence regarding the treatment of depression with SSRI medications. They discuss how medications should be used for at least 4 weeks to determine treatment response. They recommend not allowing patients to switch between drug classes too early. Incorrect Answers: Answer A: Adding lithium to the treatment regimen could be an appropriate treatment if this patient had failed to respond to therapy after 4 weeks of using the drug. Lithium is an augmenting agent that could potentiate the effect of an SSRI. Answer B: Changing the treatment to duloxetine would be inappropriate as this patient has not taken the first-line SSRI for at least 4 weeks. Patients should try a full treatment course in order to determine if they may derive some benefit. Answer C: Changing the treatment to lithium would be appropriate if this patient's diagnosis was bipolar disorder, which would present with episodes of depression and mania. Altered sleep alone does not indicate mania. Answer E: Electroconvulsive therapy is the most effective treatment for depression; however, it is typically a last-line treatment. This therapy can be useful in refractory cases. Bullet Summary: SSRI medications are the most appropriate first-line agent for depression and should be tried for at least 4 weeks before changing therapy.

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A 72-year-old man presents to the clinic for his annual exam. For the past few months, he has pain in his chest with physical activity. The pain goes away after he takes a break. He reports no chest pain while he is resting, and the pain is not worsening. His past medical history is notable for hypertension, type 2 diabetes mellitus, and hyperlipidemia. His medications include amlodipine, atorvastatin, and metformin. His temperature is 36.5°C (97.7°F), blood pressure is 132/80 mmHg, pulse is 74/min, respirations are 14/min, and oxygen saturation is 98% on room air. He has a regular rate and rhythm, normal S1 and S2, and no murmurs, rubs, or gallops. His anterior, lateral, and posterior chest are non-tender to palpation. His electrocardiogram is shown in Figure A. Troponin I level is < 0.017 ng/mL. Which of the following is the most likely diagnosis?

Costochondritis

Non-ST elevation myocardial infarction

ST elevation myocardial infarction

Stable angina

Unstable angina

D

Stable angina

This patient who presents with exertional chest pain that is relieved with rest without increasing frequency or intensity of chest pain, a normal electrocardiogram (ECG), and normal troponin level most likely has stable angina. Angina pectoris is chest pain secondary to myocardial ischemia and is most commonly caused by atherosclerosis, though it can be caused by any etiology leading to narrowing of the coronary arteries. The pain tends to be substernal, dull, squeezing, or pressure-like and can also radiate to the neck or arm. It may also be associated with shortness of breath, dizziness, lightheadedness, nausea/vomiting, or diaphoresis. In stable angina, the chest pain is precipitated by exertion or stress and is consistently relieved with rest or nitroglycerin. ECG tends to be normal, and troponin I levels are not elevated. Treatment of stable angina includes beta blockers and nitrates (for episodes of pain), as well as therapy to prevent disease progression disease progression which may include antiplatelet therapy (aspirin), lipid-lowering medications, and glycemic control. Lifestyle measures are also the mainstay of therapy and may include smoking cessation, exercise, and dietary modification. Joshi and de Lemos review stable angina. They note the optimal management of this condition. They recommend lifestyle interventions, lipid-lowering therapy, and antiplatelets to reduce morbidity and mortality. Figure A shows an electrocardiogram with regular rate and rhythm. Every P wave is followed by a narrow QRS complex, which is consistent with normal sinus rhythm. Incorrect Answers: Answer A: Costochondritis presents with pain of the chest wall that can be sharp, aching, or pressure-like and typically worsens with cough or deep breathing. It is typically caused by injury to the chest, physical strain, or can be associated with inflammatory conditions such as arthritis. On exam, the pain can be reproduced with palpation of the chest wall, in particular, the costochondral junction. This patient's chest pain is associated with exertion and relieved with rest, and his pain is not reproduced upon palpation of the chest wall. Thus, he is unlikely to have costochondritis. Answer B: Non-ST elevation myocardial infarction presents similarly to unstable angina with substernal chest pain that is new-onset, accelerating, or occurring at rest, without ST elevations on ECG. However, ST depressions or T wave inversions may be present on ECG, and troponin I and creatine kinase-MB isoenzyme (CK-MB) would be elevated, indicating myocardial injury. Answer C: ST-elevation myocardial infarction presents with acute onset substernal chest pain that can radiate to the neck, arm, shoulders, or jaw and is sometimes associated with diaphoresis, nausea/vomiting, shortness of breath, lightheadedness, or anxiety. ECG shows ST elevations in a vascular distribution, and troponin I and CK-MB levels are elevated. This patient's ECG does not show ST elevations, and his symptoms are more consistent with stable angina. Answer E: Unstable angina is characterized by substernal chest pain occurring at rest or occurring with more severity, longer duration, or increasing frequency. ECG may be normal or show ST depression or T wave inversion, and the troponin level is not elevated. It is caused by incomplete coronary artery occlusion by a thrombus or atherosclerosis, commonly due to a ruptured plaque with subsequent clot formation. This patient's chest pain is exertional, does not occur at rest, and is consistently relieved with rest, and thus would be consistent with stable angina. Bullet Summary: Stable angina is characterized by exertional chest pain that is not changing in quality or quantity and is relieved with rest.

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A 49-year-old man presents with 3 months of generalized weakness. He has had a chronic cough and a 20 pound unintentional weight loss over the past 6 months. He has a medical history significant for high blood pressure, hyperlipidemia, and seasonal allergies with no prior surgical history. He has no history of tobacco use. He moved from India 7 years prior to presentation. He currently lives in Oregon and has not left the west coast since moving. His temperature is 99°F (37.2°C), blood pressure is 100/70 mmHg, pulse is 76/min, and respirations are 16/min. His physical exam is significant for hyperpigmentation of the oral mucosa and temporal muscle wasting. Radiography of the abdomen demonstrates bilateral adrenal calcifications. Laboratory values are as follows: Serum: Na+: 130 mEq/L Cl-: 96 mEq/L K+: 5.2 mEq/L HCO3-: 24 mEq/L Morning cortisol: 2 ug/dL 30-minute cortisol during cosyntropin test: 8 ug/dL (normal > 18 ug/dL) Morning adrenocorticotropic hormone (ACTH) concentration (serum): 80 pg/mL (normal 10-60 pg/mL) Which of the following is the most appropriate next step in management?

Bilateral adrenalectomy, prednisone, and fludrocortisone

Dexamethasone

Hydrocortisone and immunoglobulin therapy

Prednisone taper

Rifamycin, isoniazid, pyrazinamide, ethambutol, and hydrocortisone therapy

E

Rifamycin, isoniazid, pyrazinamide, ethambutol, and hydrocortisone therapy

This man from India presents with generalized weakness, chronic cough, unintentional weight loss, skin hyperpigmentation, hyponatremia, hyperkalemia, hypocortisolism, cosyntropin stimulation test failure, elevated ACTH, and bilateral adrenal calcifications on radiography. These symptoms and signs in this patient are most consistent with adrenal tuberculosis requiring RIPE therapy (rifamycin, isoniazid, pyrazinamide, ethambutol) as well as glucocorticoid and mineralocorticoid therapy. Adrenal insufficiency occurs when the adrenal glands do not produce enough cortisol and aldosterone. Primary adrenal insufficiency is due to dysfunction at the level of the adrenal glands themselves, as opposed to upstream factors such as the pituitary gland. Primary adrenal insufficiency in developed nations is most often caused by autoimmune disease. In developing nations, adrenal tuberculosis is a significant cause of primary adrenal insufficiency. Adrenal tuberculosis often presents with a history of tuberculosis or tuberculosis symptoms, as well as symptoms of adrenal insufficiency such as fatigue, unintentional weight loss, and hyperpigmentation. Patients often have hyponatremia, hyperkalemia, low morning cortisol, a failed cosyntropin test, and high ACTH concentrations. Radiography may demonstrate bilateral adrenal calcifications, and/or adrenal enlargement. Tuberculosis can infect all cortices of the adrenal glands bilaterally, and therefore treatment requires eradicating the infection with multi-drug therapy (RIPE therapy) as well as replacement of glucocorticoids and mineralocorticoids, which may be achieved by high-dose hydrocortisone or other combinations of steroids that together provide glucocorticoid and mineralocorticoid replacement. Vinnard and Blumberg outline the signs and symptoms, histopathology, lab results, imaging, differential diagnosis, and treatments associated with adrenal tuberculosis. They recommend early recognition and treatment. Incorrect Answers: Answer A: Bilateral adrenalectomy, prednisone therapy, and fludrocortisone therapy are incorrect because medical therapy should first be attempted to eradicate the infection before undergoing surgery. Bilateral adrenalectomy may be considered if there is suspicion of lung cancer with metastasis to the bilateral adrenal glands. Patients will require lifelong replacement therapy. Answer B: Dexamethasone alone is incorrect because this patient likely has tuberculosis and should be treated for it. Additionally, this patient has signs of mineralocorticoid deficiency (hyponatremia, hyperkalemia), and patients often require mineralocorticoid therapy or a high dose of a glucocorticoid with mineralocorticoid activity (e.g., hydrocortisone). Dexamethasone has minimal to absent mineralocorticoid activity. Answer C: Hydrocortisone therapy and immunoglobulin therapy are incorrect because this patient has adrenal tuberculosis. Although autoimmune adrenalitis can cause primary adrenal insufficiency, immunoglobulins are not used to treat this condition. Answer D: Prednisone taper would be appropriate for acute conditions such as an asthma or COPD exacerbation. While prednisone will treat the symptoms of primary adrenal insufficiency, it will not treat active tuberculosis infection. Primary adrenal insufficiency in developed nations is most often caused by autoimmune adrenalitis (Addison disease) and presents with fatigue, unintentional weight loss, abdominal pain, hyperpigmentation, and muscle weakness. In this condition, long-term steroid therapy is indicated. Bullet Summary: Patients with adrenal tuberculosis should be treated with rifamycin, isoniazid, pyrazinamide, ethambutol, as well as glucocorticoid and mineralocorticoid replacement.

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A 23-year-old man presents to the emergency department for altered mental status after a finishing a marathon. He has a medical history of obesity and anxiety and is not currently taking any medications. His temperature is 104°F (40°C), blood pressure is 147/88 mmHg, pulse is 200/min, respirations are 33/min, and oxygen saturation is 99% on room air. Physical exam reveals dry mucous membranes, hot flushed skin, and inappropriate responses to the physician's questions. Laboratory values are ordered as seen below. Hemoglobin: 15 g/dL Hematocrit: 44% Leukocyte count: 8,500/mm^3 with normal differential Platelet count: 199,000/mm^3 Serum: Na+: 165 mEq/L Cl-: 110 mEq/L K+: 4.0 mEq/L HCO3-: 20 mEq/L BUN: 30 mg/dL Glucose: 133 mg/dL Creatinine: 1.5 mg/dL Ca2+: 10.2 mg/dL AST: 12 U/L ALT: 10 U/L Which of the following is the most appropriate next step in management?

50% normal saline 50% dextrose

Dextrose solution

Hypotonic saline

Lactated ringer

Normal saline

D

Lactated ringer

This patient is presenting with hypernatremia and heat stroke for which the most appropriate next step in management is the administration of lactated ringer solution. Heat stroke presents with hot/flushed skin, fever, altered mental status, and hypernatremia secondary to loss of free water. Patients should immediately be cooled with external measures and started on fluids. Minor cases where the patient is cognitively intact can be treated with oral replacement with an electrolyte balanced solution (though this would be heat exhaustion and not heat stroke). Patients with altered mental status should be started on normal saline or lactated ringer, and sodium levels should be corrected slowly. Rapid correction of serum sodium or administration of hypotonic fluids can cause cerebral edema and seizures; however, this is more common in hypernatremia that has persisted for days as it has led to cerebral adaptations. Tinawi reviewed the evidence regarding the use of intravenous fluids in the hospital setting. He discusses how a large volume of normal saline can result in hypernatremia and hyperchloremia. He recommends considering the risks and benefits of colloid versus crystalloid usage. Incorrect Answers: Answers 1-3: 50% normal saline 50% dextrose, dextrose solution, and hypotonic saline are hypotonic solutions and would treat the hypernatremia too rapidly predisposing the patient to seizures. Answer E: Normal saline would be a reasonable option for this patient; however, it is less desirable given that this patient is suffering from hypernatremia, hyperchloremia, and a metabolic acidosis which could be worsened by normal saline given the large sodium and chloride load of this solution. Bullet Summary: Hypernatremia and dehydration should be treated with lactated ringer and sodium levels should be corrected no more rapidly than 1 mEq/L/hour.

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A 4-year-old boy is brought in by his grandmother for worsening seizure activity. She reports that occasionally he “suddenly drops” when running around the house. She says that his first seizure occurred 1 year ago. Since then, he has been on valproic acid but the seizure activity remains unchanged. He was recently enrolled in daycare because she could no longer care for him full-time. Since then, the seizure activity has increased and the daycare facility also noted concerns over his lack of response to voice commands. Family history is significant for a cousin who died suddenly at a young age. His temperature is 98.6°F (37°C), blood pressure is 105/52 mmHg, pulse is 110/min, and respirations are 25/min. A physical exam is significant for lack of response to auditory stimulation. An EEG is performed, which is unrevealing. An ECG is shown in Figure A. The patient is then startled when a door is closed quickly and he suddenly loses consciousness. An ECG is quickly performed and is shown in Figure B. An electrolyte panel is drawn with the following findings: Serum: Na+: 142 mEq/L Cl-: 88 mEq/dL K+: 3.4 mEq/L HCO3-: 24 mEq/L BUN: 11 mg/dL Glucose: 67 mg/dL Creatinine: 0.6 mg/dL Mg2+: 1.7 mg/dL Which of the following is the most appropriate next step in management?

Administer intravenous lorazepam

Implant a pacemaker

Replete potassium and magnesium and start a beta-blocker

Replete potassium and magnesium and start procainamide

Start ethosuximide

C

Replete potassium and magnesium and start a beta-blocker

The patient who presents with deafness and long QT syndrome that progressed to torsades de pointes most likely has Jervell and Lange-Nielsen syndrome. The most appropriate next step in management is to replete potassium and magnesium and then start a beta-blocker. Jervell and Lange-Nielsen syndrome is an autosomal recessive disorder caused by defective potassium ion channels. This causes abnormal function of the inner ear resulting in congenital sensorineural deafness as well as abnormal myocardial conduction resulting in long QT syndrome. A prolonged QT interval increases the risk of ventricular dysrhythmias, especially torsades de pointes, which may manifest as syncope, or sudden death. These episodes are usually triggered by exertion or by being startled. Management of symptomatic congenital long QT syndromes or torsades de pointes should involve the repletion of potassium and magnesium as well as the initiation of a beta-blocker medication. If symptoms are refractory to beta-blockers, a pacemaker can be implanted to avoid cardiac arrest. Adam et al. review the evidence regarding the diagnosis and treatment of Jervell and Lange-Nielsen syndrome. They discuss how a beta blocker medication should be used for medical control of this syndrome. They recommend pacemaker placement in refractory cases. Figure/Illustration A is an ECG showing a prolonged QT interval (blue lines). This interval can be prolonged due to certain medications such as ondansetron or it can be due to long QT syndrome, which may be acquired or congenital. Figure/Illustration B is an EKG showing a polymorphic ventricular tachycardia with varying QRS complex amplitudes over time (blue curve). This feature where the QRS complexes appear to “twist” around the isoelectric line is seen in torsades de pointes. Incorrect Answers: Answer A: IV lorazepam is the medical treatment for pediatric status epilepticus. Status epilepticus is a seizure that lasts for greater than 5 minutes or recurrent seizures with no return to baseline. This patient has an ECG showing torsades de pointes, which explains his sudden loss of consciousness as well as a normal EEG. Answer B: A pacemaker can be used to treat refractory dysrhythmias caused by Jervell and Lange-Nielsen syndrome, but would not be the initial step in management for this patient. Beta-blocker medications should be used prior to pacemaker placement. Answer D: While potassium and magnesium should be repleted, procainamide is a class 1A anti-arrhythmic medication that prolongs the QT interval. This class of medication is contraindicated in patients with long QT syndrome or torsades de pointes. Answer E: Ethosuximide is used to treat absence seizures. The loss of consciousness associated with Jervell and Lange-Nielsen syndrome can be mistaken for absence seizures, but the patient's prolonged QT interval on ECG makes Jervell and Lange-Nielsen syndrome the most likely diagnosis. Of note, valproic acid is also a medication for absence seizures. Bullet Summary: Jervell and Lange-Nielsen syndrome should be treated with repletion of potassium and magnesium as well as initiation of beta-blocker medication with pacemaker placement reserved for refractory cases.

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A 67-year-old man presents to the emergency room with a 2 day history of progressively worsening fatigue and shortness of breath. His past medical history is significant for previous myocardial infarction, a 30-pack-year smoking history, gastroesophageal reflux disease, and poorly controlled hypertension. The patient’s only home medication is omeprazole. His temperature is 98.6°F (37°C), blood pressure is 140/90 mmHg, pulse is 90/min, respirations are 30/min, and oxygen saturation is 88% on room air. Physical exam is significant for a jugular venous pressure of 15 cm, an S3 heart sound, bibasilar crackles, and 2+ pitting edema to the knees bilaterally. His abdomen is soft and non-tender. His neurological exam is nonfocal and he walks with a steady gait. An arterial blood gas shows the following: pH: 7.56 (normal 7.35-7.45) pCO2: 25 mmHg (normal 35-45 mmHg) HCO3: 29 mEq/L (normal 22-26 mEq/L) pO2: 62 mmHg (normal 80-100 mmHg) SaO2: 87% (normal 95-100%) Which of the following is the most appropriate treatment?

Furosemide

Ivabradine

Metoprolol

Sacubitril and valsartan

Spironolactone

A

Furosemide

This patient with multiple risk factors for heart failure (previous myocardial infarction, smoking history, hypertension), worsening fatigue, shortness of breath, respiratory alkalosis, and signs of fluid overload (S3 heart sound, elevated jugular venous pressure (JVP), bibasilar crackles, peripheral edema) most likely has acute decompensated heart failure (ADHF). The most appropriate initial management for patients in ADHF is a loop diuretic such as furosemide. Heart failure (HF) is a condition in which the heart does not pump effectively and can be due to either difficulty with relaxation in diastole or contraction in systole or a combination of both. Risk factors for this condition include myocardial infarction, diabetes mellitus, valvular disease, cigarette smoking, hypertension, and obesity. Left-sided HF leads to decreased forward flow into the systemic circulation and increased congestion in the pulmonary circulation which clinically manifests as shortness of breath, pulmonary edema, and crackles on lung exam. Early pulmonary edema leads to a ventilation/perfusion (V/Q) mismatch which causes hypoxia. Hypoxia leads to a compensatory increase in the respiratory rate, which leads to hypocapnia and respiratory alkalosis. The most appropriate initial treatment for patients in ADHF is a loop diuretic such as furosemide, which helps alleviate fluid overload. Other treatments for acute exacerbations may include nitroglycerin (in hypertensive patients) and BIPAP. Yancy et al. discuss the most recent ACC/AHA guidelines for the management of heart failure. They review current testing and treatment regimens. Acute episodes may be managed with loop diuretics to reduce volume overload and improve symptoms. Incorrect Answers: Answer B: Ivabradine inhibits the funny current, an electrical current that leads to spontaneous depolarization in pacemaker cells, leading to decreased heart rate. It reduces the risk of hospitalization in patients with chronic heart failure with reduced ejection fraction (HFrEF). However, it should not be started in ADHF due to lack of mortality benefit and should be held in ADHF patients with severe decompensation due to decreased heart rate leading to decreased cardiac output. Answer C: Metoprolol is a beta-blocker that reduces mortality when used in patients with chronic HFrEF. However, beta-blockers can worsen decompensated HFrEF due to negative inotropy and should not be started in ADHF. Answer D: Sacubitril and valsartan is a combination angiotensin receptor-neprilysin inhibitor (ARNI) that improves mortality in patients with chronic HFrEF. ARNIs, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) should not be started in ADHF due to concern for hypotension and worsening renal function. However, either an ARNI, ACE inhibitor or ARB should be started prior to discharge. Answer E: Spironolactone is a mineralocorticoid receptor antagonist that reduces mortality in chronic HFrEF. However, high-dose spironolactone does not improve outcomes as first-line therapy in ADHF (Anstrom et al. JAMA Cardiology 2017). Bullet Summary: Patients with acute decompensated heart failure present with fatigue, dyspnea, bibasilar crackles, respiratory alkalosis on arterial blood gas, edema, and other signs of fluid overload.

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A 71-year-old man arrives to the emergency room appearing cyanotic and having weak, shallow respirations. He is brought in by his home care nurse, who reports that the patient has a history of myasthenia gravis and frequent urinary tract infections. The patient was in his normal state of health until 5 days ago when he developed a urinary tract infection. He was receiving gentamicin infusions for his infections. This morning, he experienced poor grip strength and progressive difficulty breathing. The patient’s medications include pyridostigmine and aspirin, both of which he takes as prescribed. His temperature is 99.0°F (37.2°C), blood pressure is 128/78 mmHg, pulse is 92/min, and respirations are 28/min with an oxygen saturation of 86% O2 on room air. The patient has gray-blue skin, hypophonia, weak upper extremities, and normal leg strength. An arterial blood gas is drawn with results as shown below: PO2: 55 mmHg PCO2: 60 mmHg pH: 7.30 The patient is intubated. Which of the following is the most appropriate next step in management?

Atropine

Edrophonium

Neostigmine

Plasmapheresis

Thymectomy

D

Plasmapheresis

This patient is presenting with a history of myasthenia gravis, recent exposure to an aminoglycoside, and respiratory failure, suggesting a diagnosis of myasthenic crisis. The most appropriate initial step in management is intubation and plasmapheresis. Myasthenic crisis is an exacerbation of myasthenia gravis caused by under-dosing myasthenia gravis treatments or precipitated by infection, surgery, and certain medications such as aminoglycosides and beta-blockers. Symptoms include bulbar muscle weakness and type 2 respiratory failure (inadequate alveolar ventilation). The most appropriate initial step in management is to maintain adequate respiratory function by intubation. Plasmapheresis or IVIG is used to remove acetylcholine receptor antibodies from circulation, and steroids are started for long-term therapy. Avoiding risk factors and pre-medication before procedures with acetylcholinesterase inhibitors is important for preventing repeat occurrences. Rodrigues et al. review the evidence regarding the occurrence of myasthenic crisis in patients with COVID. They discuss how treatment with IVIG and plasma exchange were important in the care of these patients. They recommend also considering whether rituximab and tocilizumab may be effective in these cases. Incorrect Answers: Answer A: Atropine can be used in a cholinergic crisis. A cholinergic crisis is an acute exacerbation of muscle weakness due to over-medication with cholinergic anti-cholinesterases. This disease would present with diarrhea, sweating, miosis, bronchoconstriction, and bradycardia. It rarely occurs with proper dosing of pyridostigmine. Answer B: Edrophonium can be used in the diagnosis of myasthenia gravis. It is a cholinesterase inhibitor. In a positive test, a patient will exhibit temporary resolution of muscle weakness. In this patient’s case, the diagnosis of myasthenia gravis has already been made and he also had a recent exposure to a pharmaceutical known to precipitate myasthenic crisis. Answer C: Neostigmine is an acetylcholinesterase inhibitor used in the management of myasthenia gravis, but it is contraindicated in the initial treatment of myasthenic crisis. Acetylcholinesterase inhibitors may increase respiratory secretions, which can worsen respiratory failure. Answer E: Thymectomy is indicated in refractory cases of myasthenia gravis (and for increased risk of thymoma). In an unstable condition such as myasthenic crisis, thymectomy should be deferred. For patients over the age of 60, thymectomy is controversial. Bullet Summary: Myasthenic crisis can be precipitated by infection, surgery, and medications (aminoglycosides and beta-blockers) and should be managed with intubation followed by plasmapheresis or IVIG.

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A 2-year-old girl presents to the pediatrician with her mother for a routine well-child visit. Her mother is concerned that the patient is a picky eater and refuses to eat vegetables. She drinks milk with meals and has juice sparingly. She goes to sleep easily at night and usually sleeps for 11-12 hours. The patient has trouble falling asleep for naps but does nap for 1-2 hours a few times per week. She is doing well in daycare and enjoys parallel play with the other children. Her mother reports that she can walk downstairs with both feet on each step. She has a vocabulary of 10-25 words that she uses in the form of 1 word commands. She is in the 42nd percentile for height and 48th percentile for weight, which is consistent with her growth curves. Her temperature is 98.6°F (37°C), blood pressure is 92/56 mmHg, pulse is 106/min, and respirations are 23/min. On physical exam, she appears well nourished. She can copy a line and throw a ball. She can follow the command to “give me the ball and then close the door.” Which of the following is abnormal in this patient?

Expressive language skills

Fine motor skills

Gross motor skills

Social and receptive language skills

This child is developmentally normal

A

Expressive language skills

This child is meeting her milestones in every category but expressive language. By 2 years of age, a child should have a vocabulary of over 50 words and be using 2-word phrases. Assessing whether a child is meeting developmental milestones is important for identifying delays and enabling early intervention. In the gross motor category, a 2-year-old child should be able to jump and walk both up and down stairs with both feet on each step. In the fine motor category, a child should be able to copy a line and build a tower of 6 cubes. In the expressive language category, a child should have a vocabulary of over 50 words and be using 2-word phrases. In the social category, a child should participate in parallel play and be able to follow 2-step commands. Detecting a persistent developmental delay can be important as the first step in identifying a correctable condition such as hearing loss. Scharf et al. review the evidence regarding the use of developmental milestones in assessing children. They discuss how early identification of delays can allow for referral to required services. They recommend paying special attention to sensory function to avoid missing a correctable hearing deficit. Incorrect Answers: Answer B: This child's fine motor skills are appropriate, as she can copy a line. She may also be able to copy a circle and make a tower of 6 cubes at this age. Answer C: This child's gross motor skills are appropriate because she can walk downstairs with both feet on each step and throw a ball. She should also be able to jump and run at this age. Answer D: This child's social and receptive language skills are developing appropriately since she can follow 2-step commands and engages in parallel play. She should also be able to point to pictures, body parts, and pieces of clothing when named. Answer E: This child is not developmentally normal due to her deficits in expressive language. She should be using 2-word sentences and have a vocabulary of over 50 words. Her language should also be intelligible to strangers 50% of the time. Bullet Summary: By 2 years of age, a child should be able to walk up and down stairs, copy a line, follow a 2-step command, have a vocabulary of at least 50 words, and use 2-word phrases.

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A 52-year-old man presents to the clinic with a left foot ulcer that he noticed 6 days ago. He has a history of obesity, hypertension, type 2 diabetes mellitus, and depression. His current medications include metformin, aspirin, rosuvastatin, lisinopril, and fluoxetine. He has a 25-pack-year smoking history and drinks 1 glass of wine a day. 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 exam, he has a 1.2 x 1.7 cm ulcer on the plantar surface of his left metatarsal head. Which of the following tests will most appropriately assess this patient’s future risk of foot ulcers?

Ankle-brachial index

Capillary refill time

Contrast-enhanced foot magnetic resonance imaging

Knee reflex testing

Monofilament testing

E

Monofilament testing

This patient with a history of diabetes, hypertension, and obesity now presenting with a foot ulcer most likely has a diabetic foot ulcer. He should undergo monofilament testing to assess the subsequent risk of developing foot ulcers. Diabetic neuropathy is the most common underlying cause of diabetic foot ulcers. The pathophysiology of diabetic foot ulcers is thought to be the loss of pain and pressure sensation, which leads to muscular imbalance and foot deformities. This subsequently decreases microcirculation and impairs the integrity of the skin, leading to the formation of foot ulcers. Diabetic foot ulcers, like other neuropathic ulcers, occur commonly under bony prominences in the foot. During monofilament testing, a 10-g monofilament is placed on the plantar surface of the foot at a right angle, and pressure is applied until the patient can no longer tolerate it or the filament buckles. Patients with diabetic neuropathy have a higher-pressure threshold due to loss of sensation, and this is a useful predictor of the severity of diabetic neuropathy and future foot ulcer formation. The management of diabetic neuropathy consists of tight glycemic control, weight loss, blood pressure control, exercise, preventing complications, and pain management with pharmacotherapy (serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, or gabapentinoid antiseizure medications). Tesfaye et al. study the efficacy of various first-line medications for diabetic nephropathy including amitriptyline, duloxetine, pregabalin, or gabapentin. The authors found that there were no differences between any of the medications as monotherapy. The authors recommended adding combination pharmacotherapy for patients with painful diabetic neuropathy that do not respond to initial monotherapy. Incorrect Answers: Answer A: Ankle-brachial index is a calculation made in the assessment of peripheral arterial disease (PAD). While PAD can present with arterial ulcers, these are usually located at the tip of the toes and not the plantar surface. Furthermore, the ankle-brachial index does not accurately assess small vessel disease, which is associated with diabetic foot ulcers. Answer B: Capillary refill time, when delayed, may suggest decreased limb perfusion. This is a nonspecific test, as decreased limb perfusion can be caused by peripheral arterial disease, volume depletion, or hypotension. Answer C: Contrast-enhanced foot MRI is the most sensitive and specific test to identify soft tissue complications of acute osteomyelitis. This patient has no clinical features of osteomyelitis (fever, chills, or malaise, ulcer that probes to bone) and does not require imaging currently. Answer D: Knee reflex testing is not useful in assessing diabetic neuropathy. While diabetic neuropathy can affect large nerve fibers in the lower extremities, it typically impairs ankle reflexes while sparing knee reflexes. Bullet Summary: Preventative measures for diabetic foot ulcers should focus on regular foot exams with monofilament testing to assess for diabetic neuropathy.

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A 59-year-old man presents to the emergency department after a sudden onset of slurred speech and right upper extremity weakness. His symptoms lasted 20 minutes but by the time he arrived at the emergency department he was symptom-free. The patient denies any preceding symptoms. He has a history of diabetes, obesity, and hypertension but does not see a physician for his underlying conditions. His temperature is 99.2°F (37.3°C), blood pressure is 140/85 mmHg, pulse is 82/min, respirations are 16/min, and oxygen saturation is 100% on room air. Physical exam reveals normal vision, strength, and sensation with a stable gait. Finger-nose testing and tandem gait are unremarkable. A CT scan of the head is performed and is unremarkable. Which of the following is the most appropriate next step in management?

Aspirin

Atorvastatin

CTA head/neck

Labetalol

MRI brain

A

Aspirin

This patient is presenting with a transient episode of neurologic dysfunction (slurred speech and right upper extremity weakness) that has completely resolved, which is concerning for a transient ischemic attack. In the setting of his normal head CT, aspirin should be administered next. A transient ischemic attack (TIA) is a brief episode of focal neurologic dysfunction that completely resolves without any residual deficits. Patients with a TIA are at high risk for future TIAs and stroke. For this reason, management is immediately centered on a thorough neurological exam followed by a CT scan of the head to rule out a hemorrhage. Subsequently, aspirin should immediately be administered which reduces the incidence of future stroke. Patients will subsequently be discharged on aspirin in addition to other morbidity-lowering agents including a statin and tight blood pressure and glycemic control as well as a second antiplatelet agent in appropriate patients. Further workup for a TIA may include a CTA head/neck, an MRI brain, and an echocardiogram. Modification of risk factors is also critical in these patients including weight loss, smoking cessation, exercise, glycemic control, and blood pressure control. Clissold et al. review transient ischemic attacks. They note that transient ischemic attacks (TIA), if untreated, carry a high risk of early subsequent stroke. They recommend, after appropriate diagnostic workup, early administration of an antiplatelet agent. Incorrect Answers: Answer B: Atorvastatin is an important initial intervention in the management of patients who have TIA/stroke. However, this intervention takes weeks of consistent therapy in order to have a significant effect on morbidity, thus it would not be the most important next step in management when compared to aspirin, which is more important in reducing acute stroke risk. Further, a lipid panel is generally performed first to determine if a statin is needed. Answer C: CTA head/neck is a part of the workup of a TIA to rule out carotid stenosis/dissection/atherosclerosis as the cause of the patient's symptoms. It is more important to give aspirin early in TIA/stroke prior to obtaining further imaging (though this study would still be performed). Answer D: Labetalol and other blood pressure medications are important in risk factor modification to prevent future strokes/TIAs. Patients with diabetic nephropathy should be on an ACE inhibitor or angiotensin-receptor blocker which are nephroprotective. Of note, his blood pressure currently is not very elevated nor is it causing end-organ dysfunction. Answer E: MRI brain should be performed to further characterize whether there was any ischemic injury to the brain; however, this usually will occur after a CTA head/neck and certainly after the patient receives an aspirin. It can more accurately characterize if a stroke occurred, and the extent of the injury. Bullet Summary: The workup of a transient ischemic attack should be centered on a thorough neurological exam, a non-contrast CT scan of the head, and administration of aspirin assuming there is no intracranial bleed.

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A 2-month-old girl is brought to the pediatrician by her mother for a follow-up visit. The patient was born at 29 weeks gestation to a G1P1 mother. Her postnatal course was complicated by a prolonged neonatal intensive care unit stay for neonatal respiratory distress syndrome (NRDS). Since discharge from the hospital, her mother reports that the patient has been doing well without health problems. She has been gaining weight appropriately. Her temperature is 98.6°F (37.0°C), blood pressure is 80/50 mmHg, pulse is 120/min, and respirations are 25/min. The patient's mother asks the pediatrician about potentially delaying the 2-month vaccine doses due to the baby's medical history. Which of the following is the correct vaccination plan for this infant in terms of the vaccinations below? - Diphtheria, Tetanus, and acellular Pertussis - DTaP - Hepatitis A - HAV - Hepatitis B - HBV - Haemophilus influenzae type B conjugate - HiB - Pneumococcal conjugate - PCV 13

Administer DTaP, HAV, HBV, HiB, PCV 13, poliovirus, and rotavirus vaccines

Administer DTaP, HBV, HiB, PCV 13, and poliovirus vaccines

Administer DTaP, HBV, HiB, PCV 13, poliovirus, and rotavirus vaccines

Delay all vaccines for 2 months due to the infant's history of NRDS

Delay all vaccines for 2 months because the infant was born 2 months premature

C

Administer DTaP, HBV, HiB, PCV 13, poliovirus, and rotavirus vaccines

This 2-month-old girl has a history of prematurity (born at 29 weeks gestation) complicated by a NICU stay for NRDS but is healthy at this time. It is recommended that she receive all vaccines (DTaP, HBV, HiB, PCV 13, poliovirus, and rotavirus vaccines) as scheduled during this visit. Premature infants can safely be vaccinated on the regular schedule against serious infections. A history of both prematurity and respiratory disease makes a patient more at risk for these serious infections, increasing the importance of vaccinations. The regular vaccine schedule recommends the following vaccines at 2 months of age: DTaP (inactivated), HBV (subunit), HiB (inactivated), PCV 13 (inactivated), poliovirus (inactivated), and rotavirus (live-attenuated). The first dose of the HBV (subunit) vaccine is still given during the first 24 hours of life unless the child is born with a birth weight of < 2000 grams (4 pounds 6 ounces). Saari et al. discuss the recommendations of the American Academy of Pediatrics Committee on Infectious Diseases for the immunization of preterm infants. The authors find that preterm infants are less likely to receive recommended vaccines on time. The authors recommend also administering the influenza vaccine beginning at 6 months of age during the influenza season. Incorrect Answers: Answer A: Administering DTaP, HAV, HBV, HiB, PCV 13, poliovirus, and rotavirus vaccines is incorrect as this answer choice includes the vaccine for the hepatitis A virus. The first dose of this vaccine is given at 12-24 months of age. Answer B: Administering DTaP, HBV, HiB, PCV 13, and poliovirus vaccines is incorrect as this answer choice is missing the rotavirus vaccine. Despite being premature and having a history of NRDS, live vaccines are safe to administer on schedule to this infant. Answer D: Delaying all vaccines for 2 months due to the infant's history of NRDS is incorrect as while this child has a history of NRDS, she is currently healthy. It is safe to administer all vaccines on the regular schedule to this patient. Answer E: Delaying all vaccines for 2 months because the infant was born 2 months premature is incorrect as it is not recommended that previously premature infants, with or without a perinatal complication such as NRDS, delay vaccines to account for the discrepancy between gestational and chronologic age. Bullet Summary: Children born with a history of prematurity, with or without health complications in their early life secondary to their prematurity, should receive all recommended vaccines as scheduled.

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A 29-year-old woman is recovering on the obstetrics floor after the vaginal delivery of 8-pound twin boys born at 42 weeks gestation. The patient is fatigued but states that she is doing well. Currently, she is complaining that her vagina hurts. The next morning, the patient experiences chills and a light red voluminous discharge from her vagina. She states that she feels pain and cramps in her abdomen. The patient's medical history is notable for diabetes which was managed during her pregnancy with insulin. Her temperature is 99.5°F (37.5°C), blood pressure is 107/68 mmHg, pulse is 97/min, respirations are 16/min, and oxygen saturation is 98% on room air. Laboratory values are obtained and shown below. Hemoglobin: 12 g/dL Hematocrit: 36% Leukocyte count: 9,750/mm^3 with normal differential Platelet count: 197,000/mm^3 Serum: Na+: 139 mEq/L Cl-: 101 mEq/L K+: 4.2 mEq/L HCO3-: 23 mEq/L BUN: 20 mg/dL Glucose: 111 mg/dL Creatinine: 1.1 mg/dL Ca2+: 10.2 mg/dL AST: 12 U/L ALT: 10 U/L Which of the following is the most appropriate next step in treatment for this patient?

Cefoxitin and doxycycline

Clindamycin and gentamicin

Supportive therapy only

Vancomycin and clindamycin

Vancomycin and gentamicin

C

Supportive therapy only

This patient is presenting with a normal postpartum period which is managed with supportive therapy only. A normal postpartum period is associated with breast tenderness, chills, edema, and abdominal cramps from a contracting uterus. Vaginal discharge (lochia) is normal in this phase and progresses from a red color (lochia rubra) to a clear/fluid appearance (lochia serosa) to a white color (lochia alba). No management other than supportive therapy is needed during this period. Symptoms that indicate additional intervention may be necessary include fever, foul-smelling drainage, or hypotension. Fletcher et al. review the evidence regarding normal lochia after pregnancy. They discuss how this discharge can occur for up to 24-36 days after delivery. They recommend understanding normal discharge patterns to allow for the identification of pathologic conditions. Incorrect Answers: Answer A: Cefoxitin and doxycycline can be used to treat postpartum endometritis in which the suspected organism is Chlamydia trachomatis or Neisseria gonorrhoea. Suspect these organisms in a patient with risky sexual behavior. Answer B: Clindamycin and gentamicin offer broad-spectrum coverage for endometritis, which presents with fever, abdominal tenderness, and a foul-smelling vaginal discharge. This patient has no evidence of infection at this time. Answer D: Vancomycin and clindamycin is not a typical broad-spectrum antibiotic pair that is used routinely. Both of these agents are often effective against MRSA but are typically not used concurrently. Answer E: Vancomycin and gentamicin offer broad-spectrum antibiotic coverage and can be used for bacterial endocarditis which presents with fever and a new murmur in a high-risk individual (such as those who use IV drugs). Bullet Summary: A normal postpartum period presents with chills, abdominal cramps, and lochia (rubra, serosa, or alba) and is managed with supportive care.

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A 76-year-old woman is brought to a primary care physician by her daughter who is concerned about her mother's growing inability to take care of herself. Initially, she attributed her mother's forgetfulness and word-finding difficulties to normal aging, but over the past few years, her mother's memory has worsened, her mood has grown more irritable, and her mother has been found wandering the neighborhood unsure of how to get home. Her medical history includes type 2 diabetes mellitus which is well-controlled with metformin. On exam, her temperature is 98.2°F (36.8°C), blood pressure is 115/82 mmHg, pulse is 73/min, respirations are 12/min, and oxygen saturation is 99% on room air. Cardiopulmonary exam reveals normal S1 and S2, no murmurs, and clear lungs bilaterally. She scores 16/30 on the Montreal Cognitive Assessment (MoCA) test. Which of the following is the most likely diagnosis?

Alzheimer dementia

Creutzfeldt-Jakob disease

Frontotemporal dementia

Normal pressure hydrocephalus

Vascular dementia

A

Alzheimer dementia

This elderly patient who presents with slowly progressive memory loss, language difficulties, and progression to inability to care for herself most likely has Alzheimer dementia. Alzheimer dementia is a neurodegenerative disorder that is characterized by a gradual and progressive cognitive decline (memory loss, visuospatial and language deficits, impaired judgment), difficulties with executive function or carrying out activities of daily living, and sometimes psychiatric disturbances and behavioral changes (apathy, irritability, social isolation). It is the most common cause of dementia and its risk factors include increasing age, female gender, family history, and trisomy 21 (due to the amyloid precursor protein found on chromosome 21). This is a clinical diagnosis based on cognitive testing (such as the Montreal Cognitive Assessment or the mini-mental status exam) and ruling out other causes of dementia (vitamin B12 deficiency, depression, or hypothyroidism). Weller et al. review the current understanding of Alzheimer dementia pathophysiology. They discuss recent advances in clinical evaluation and treatment. They recommend having a high index of suspicion for the disease in elderly patients who appear to be regressing in their ability to take care of themselves. Incorrect Answers: Answer B: Creutzfeldt-Jakob disease is a rapidly progressive neurodegenerative disorder caused by a prion protein that is fatal, leading to death usually within 1 year of illness onset. Dementia progresses rapidly in this disease and is sometimes associated with startle myoclonus. Answer C: Frontotemporal dementia (FTD) is characterized primarily by disinhibition, apathy, or aphasia as a result of atrophy of the frontal and temporal lobes. It tends to occur at a younger age than does Alzheimer dementia. Behavioral changes are often the first noticeable symptom in FTD while they tend to occur later in Alzheimer disease progression. Problems with visuospatial orientation are more common in Alzheimer dementia than in FTD. Answer D: Normal pressure hydrocephalus (NPH) typically presents with a triad of dementia, gait instability (specifically magnetic gait, marked by an inability to lift feet off the floor), and urinary incontinence. In NPH, excess cerebrospinal fluid accumulates in the brain's ventricles, and treatment involves drainage of that fluid, usually via surgical placement of a shunt. Answer E: Vascular dementia typically presents as stepwise cognitive decline in the setting of stroke or brain injury and usually occurs in patients with the same risk factors as stroke, such as hypertension, hyperlipidemia, peripheral arterial disease, and smoking. This patient has neither hypertension nor stepwise decline. Bullet Summary: Alzheimer dementia presents with slowly progressive dementia, typically manifesting with memory loss, visuospatial and language difficulties, impaired judgment, and inability to care for oneself.

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A 33-year-old woman presents to the emergency department with foul-smelling vaginal discharge. She states that it started 1 day ago and has not improved with hygiene products. She is sexually active and uses condoms. She does not complain of any abdominal or pelvic pain but states she has some mild burning when urinating. Her temperature is 97.6°F (36.4°C), blood pressure is 111/74 mmHg, pulse is 81/min, respirations are 12/min, and oxygen saturation is 98% on room air. Physical exam is notable for thick, white discharge from the cervix. There is no cervical motion or adnexal tenderness or masses. Some whitish discharge is noted from the urethra. A urine pregnancy test is negative. Which of the following is the most appropriate treatment for this patient?

Azithromycin

Ceftriaxone

Ceftriaxone and azithromycin

Ceftriaxone and doxycycline

Metronidazole

D

Ceftriaxone and doxycycline

This nonpregnant woman is presenting with a thick, white cervical discharge, dysuria, and urethral discharge without cervical motion tenderness or adnexal tenderness which is concerning for urethritis without pelvic inflammatory disease. She should be treated with ceftriaxone and doxycycline to cover for the most common organisms. The most common bacterial sexually transmitted infections include Neisseria gonorrhoeae and Chlamydia trachomatis. They can cause urethritis, cervicitis, and pelvic inflammatory disease. The diagnosis is made clinically with the appropriate history (vaginal discharge, high-risk sexual behavior) and physical exam (purulent cervical discharge +/- cervical motion tenderness, adnexal tenderness). The diagnosis should be confirmed with PCR; however, this should not delay treatment. Treatment should be given empirically, and the preferred regimen is ceftriaxone and doxycycline in men and nonpregnant women. In pregnant women, ceftriaxone and azithromycin may be used. Metronidazole is added empirically to cover for Trichomonas vaginalis. Jennings and Krywko review pelvic inflammatory disease. They note that pelvic inflammatory disease is an inflammation of the upper genital tract due to an infection that can affect the uterus, fallopian tubes, and ovaries. They discuss the need for treatment and complications that can occur without treatment. They recommend timely diagnosis and treatment. Incorrect Answers: Answer A: Azithromycin is only indicated to cover chlamydia in pregnancy since doxycycline cannot be given to pregnant patients. Coverage for gonorrhea is also mandatory given this patient’s symptoms. Answer B: Ceftriaxone is insufficient coverage for chlamydia or gonorrhea as chlamydia requires treatment with doxycycline, and gonorrhea requires double coverage from ceftriaxone in addition to doxycycline. Answer C: Ceftriaxone and azithromycin is the preferred regimen to treat chlamydia and gonorrhea in pregnant patients since pregnant patients cannot receive doxycycline. Answer E: Metronidazole is an appropriate treatment for bacterial vaginosis which presents with a fishy odor, white/gray vaginal discharge, and positive clue cells on wet mount. Bullet Summary: The treatment of choice for urethritis is ceftriaxone and doxycycline in nonpregnant patients.

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A 64-year-old woman presents to the emergency room with whole-body itching. She noticed her symptoms while in the bathtub at home. She has never had symptoms like this before. Over the previous several months she has had episodes of joint swelling and pain in her hands as well as redness, burning pain, and swelling of her hands and feet. Her medical history is significant for type 2 diabetes mellitus, hypertension, and osteoporosis for which she takes metformin, enalapril, and alendronate. She was found to have a deep vein thrombosis of her left leg 3 months prior to presentation. Her temperature is 98.6°F (37.0°C), pulse is 80/min, blood pressure is 135/85 mmHg, and respirations are 13/min. Physical exam is notable for a woman in discomfort with excoriations over the skin on her forearms. Laboratory tests are shown below. Serum: Na+: 135 mEq/L Cl-: 100 mEq/L K+: 5.0 mEq/L HCO3-: 22 mEq/L BUN: 19 mg/dL Glucose: 130 mg/dL Creatinine: 1.0 mg/dL Hematocrit: 64% Leukocyte count: 19,000 cells/mm^3 with normal differential Platelet count: 900,000/mm^3 Which of the following is the most appropriate long-term treatment?

Cyclophosphamide

Diphenhydramine

Febuxostat

Hydroxyurea

Prednisone

D

Hydroxyurea

This patient presents with polycythemia, leukocytosis, and thrombocytosis in the setting of pruritus after bathing, as well as episodes suggestive of acute gout flares. These findings are consistent with polycythemia vera, which can be treated with hydroxyurea. Polycythemia vera is a malignancy of the bone marrow that results in the overproduction of red blood cells, platelets, and white blood cells. Classic symptoms include pruritus after hot baths as well as swelling, burning pain, and rubor of the hands and feet (erythromelalgia). Patients may also have gout due to increased cell turnover leading to hyperuricemia. Older patients (> 60 years old) and those with prior thrombosis should be treated with a myelosuppressive agent, most commonly hydroxyurea with or without aspirin. Therapeutic phlebotomy is often indicated on these patients. Stuart and Viera review the evidence regarding the diagnosis and treatment of polycythemia vera. They discuss how treatment includes phlebotomy with the possible addition of myelosuppressive agents. They recommend consultation with a hematologist for any patients with this syndrome. Incorrect Answers: Answer A: Cyclophosphamide is a chemotherapeutic agent that is used in the treatment of certain leukemias and lymphomas, as well as severe symptoms of autoimmune disease. A malignancy would present with vague systemic symptoms, weight loss, malaise, and abnormalities detected on CBC. Cyclophosphamide is not used in the treatment of polycythemia vera. Answer B: Diphenhydramine is a 1st-generation antihistamine that can be used to treat pruritus, but would not be indicated for the treatment of polycythemia vera which is the underlying condition. This treatment represents a symptomatic treatment versus an agent that addresses the underlying cause. Answer C: Febuxostat is a xanthine oxidase inhibitor that is used to reduce uric acid levels in the management of chronic gout. Gout would present with acute severe joint pain (typically the great toe) with risk factors of alcohol use, obesity, and thiazide use. It is not used in the acute management of gout or in polycythemia vera. Answer E: Prednisone is a glucocorticoid that is used in many different clinical situations but is not used in the management of polycythemia vera. It could be used in acute inflammatory conditions (like Crohn disease or granulomatosis with polyangiitis) or to reduce inflammation during a flare of asthma or COPD. Bullet Summary: Polycythemia vera presents with pruritus after bathing, erythromelalgia, and gout and should be treated with hydroxyurea with or without aspirin.

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A 17-year-old girl presents to the emergency department with a headache. The patient has had headaches in the past but this is the worst headache of her life. Her symptoms started yesterday and have been getting progressively worse. The patient states that the pain is mostly on the left side of her head. There has been a recent outbreak of measles at the patient’s school and the patient’s mother has been trying to give her daughter medicine to prevent her from getting sick. Her mother fears that her daughter may have caught measles. Her temperature is 98.6°F (37°C), blood pressure is 123/74 mmHg, pulse is 85/min, and respirations are 13/min. On exam, the patient is an obese girl who is clutching her head with the light in the room turned off. Her neurological exam is within normal limits. Fundoscopic exam reveals mild bilateral papilledema. An MRI of the head is obtained and reveals cerebral edema. A lumbar puncture reveals an increased opening pressure with a normal glucose level. Which of the following is the most likely diagnosis?

Bacterial meningitis

Fat-soluble vitamin overuse

Migraine headache

Subarachnoid hemorrhage

Viral meningitis

B

Fat-soluble vitamin overuse

This patient is presenting with headache, bilateral papilledema, obesity, and increased opening pressure on lumbar puncture suggesting a diagnosis of Idiopathic intracranial hypertension (IIH or pseudotumor cerebri). This disease is associated with hypervitaminosis A (a fat-soluble vitamin). Pseudotumor cerebri classically presents in an obese woman with symptoms of headache and double vision. Overuse of supplements containing vitamin A is a risk factor for developing idiopathic intracranial hypertension. Vitamin A is often used to decrease the duration and severity of a measles infection. On exam, patients will have bilateral papilledema, an increased CSF opening pressure, and cerebral edema. A lumbar puncture is the most accurate diagnostic test for this disease. Treatment is with cessation of offending agents and with carbonic anhydrase inhibitors such as acetazolamide to decrease the rate of cerebrospinal fluid production. Optic nerve sheath fenestration can also be performed in patients who fail medical management. Fuerst et al. present evidence regarding patients with hypervitaminosis A. They discuss how these patients can present with pseudotumor cerebri. They recommend being vigilant about vitamin A toxicity. Incorrect Answers: Answer A: Bacterial meningitis presents with a stiff neck, photophobia, fever, and a CSF finding of low glucose in contrast to this patient’s normal glucose. The most common causes of bacterial meningitis in young adults are N. meningitidis or S. pneumonia. Patients should be treated empirically with ceftriaxone and vancomycin because this is a medical emergency. Answer C: Migraine headache can present with a unilateral pulsing/pounding headache and photophobia; however, it would not present with physical exam findings of papilledema or cerebral edema. Acute migraines can be treated with NSAIDs and triptan medications. Chronic prophylaxis is with beta-blockers or calcium channel blockers. Answer D: Subarachnoid hemorrhage presents with the classic, “worst headache of my life,” as this patient has; however, there would be blood visible on MRI which was not described. In addition, there are no symptoms of meningeal irritation from a subarachnoid bleed. Patients may need surgical embolization or clipping of the bleeding vessel. Answer E: Viral meningitis would present with a stiff neck, photophobia, fever, and CSF that would only demonstrate lymphocytic pleocytosis. Though this patient’s CSF glucose is normal, her other symptoms do not point toward a diagnosis of meningitis. Treatment is either supportive or with antiviral agents depending on the causative organism. Bullet Summary: Hypervitaminosis A can cause pseudotumor cerebri, which typically presents in overweight women with headache, double vision, papilledema, and cerebral edema on MRI.

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A 45-year-old morbidly obese woman with a history of asthma and type 2 diabetes mellitus presents to her primary care physician for advice on weight loss. She thinks that her husband is having sex with other women because they have not had sex over the past year. She feels that her co-workers also disrespect her for her weight and constant sweat stains around her armpits and chest. She has noticed that the sweat stains get itchy and induce a burning sensation unless she showers or changes her shirt. She has been compliant with her medications, which include albuterol, metformin, glyburide, and atorvastatin. Her temperature is 98.6°F (37°C), blood pressure is 128/85 mmHg, pulse is 91/min, and respirations are 11/min. On physical exam, the patient has a flat affect, with moist oral mucosa and nasal polyps. She denies sinus tenderness. Her neck is thick with a posterior cervical fat pad. During cardiac auscultation, the finding in Figure A is noted below her breasts. What is the most appropriate next step in management for this finding?

Fluconazole

Prednisone

Topical clobetasol

Topical imiquimod

Topical nystatin

E

Topical nystatin

This patient has a rash consistent with candidal intertrigo given the location and history of a damp, pruritic rash. The most appropriate next step in management is topical nystatin powder. Intertrigo is caused by the Candida species and is characterized by pruritic, painful, and erythematous superficial patches surrounded by satellite lesions. They are commonly seen in intertriginous areas such as the breasts, groin, axilla, or abdominal pannus. Obesity and diabetes are significant risk factors. Initial management involves maintaining skin dryness along with medical treatment using topical nystatin, clotrimazole, or miconazole. Persistent lesions may require oral antifungal treatment. Nobles and Miller review the evidence regarding the diagnosis and treatment of intertrigo. They discuss how these lesions often become infected with Candida. They recommend the use of antifungal medications. Figure/Illustration A shows candidal intertrigo in the breast fold. Note the satellite lesions that surround the erythematous patch. Incorrect Answers: Answer A: Fluconazole is indicated for moderate to severe disease or if the rash is refractory to topical antifungals. Topical antifungal agents should be used before progressing to oral medications. Answer B: Prednisone is not indicated and would potentially worsen the rash through immunosuppression and exacerbation of the patient's diabetes mellitus. Answer C: Topical clobetasol is a high-potency corticosteroid. This would not be used because it can promote infection and lead to skin atrophy. Low-potency corticosteroids such as triamcinolone or hydrocortisone can be used as adjuncts for symptom control only. Answer D: Topical imiquimod is indicated for autoimmune skin diseases such as alopecia areata not for candidal intertrigo. This disease would present with segmental regions of hair loss Bullet Summary: The treatment of candidal intertrigo involves topical antifungals including nystatin, clotrimazole, and miconazole.

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A 6-hour-old newborn boy is noted to have a “lump on his head” by his mother. She denies that the lump was present at birth and is concerned about an infection. The child was born at 39 weeks gestation to a 34-year-old G2P2 mother by vacuum-assisted vaginal delivery after prolonged labor. His birth weight was 3.8 kg (8.4 lb) and his length and head circumference are at the 40th and 60th percentiles, respectively. The mother was diagnosed during this pregnancy with gestational diabetes mellitus and received prenatal care throughout. All prenatal screening was normal and the 20-week anatomy ultrasound was unremarkable. His temperature is 98.6°F (37°C), blood pressure is 65/42 mmHg, pulse is 131/min, and respirations are 36/min. On physical exam, the child is in no acute distress. He has a 3x3 cm fluctuant swelling over the right parietal bone that does not cross the midline. There is no discoloration of the overlying scalp. Laboratory testing is performed and reveals the following: Total bilirubin: 5.5 mg/dL Direct bilirubin: 0.7 mg/dL Which of the following is the most appropriate next step in management?

Incision and drainage

Intensive phototherapy

Neurosurgical decompression

Observation only

Red blood cell transfusion

D

Observation only

This patient presents with a fluctuant swelling of the scalp that is limited by suture lines, which is the classic description of a cephalohematoma. The majority of cases of cephalohematoma self-resolve, thus the most appropriate next step in management is observation. A cephalohematoma is a relatively common traumatic birth injury that occurs after prolonged labor or instrumentation due to rupture of the periosteal bridging veins. Because bleeding through these veins is slow, they typically present several hours after birth with a fluctuant swelling of the scalp that is limited by suture lines. The majority of cases self-resolve between 2 weeks to 3 months. In rare cases, the sequestration of blood in the cephalohematoma may cause an unconjugated hyperbilirubinemia that requires phototherapy but this is a rare complication. Treatment is with reassurance and outpatient monitoring. Raines et al. review the evidence regarding the diagnosis and treatment of cephalohematoma. They discuss how this injury presents gradually and does not cross suture lines. They recommend conservative treatment. Incorrect Answers: Answer A: An incision and drainage procedure is contraindicated in cephalohematoma without signs of infection, such as erythema of the skin overlying the swelling. In cases where the cephalohematoma is thought to be secondarily infected, patients should undergo incision and drainage to prevent osteomyelitis. Patients would present with increasing pain, erythema, and systemic findings such as fever. Answer B: Intensive phototherapy may be used to manage the unconjugated hyperbilirubinemia that may occur due to cephalohematoma, but the majority of cases resolve spontaneously. The unconjugated hyperbilirubinemia found in this patient does not necessitate phototherapy. Unconjugated bilirubin is produced due to the metabolism of hemoglobin. Answer C: Neurosurgical decompression may be necessary to manage other neonatal birth injuries, such as intracranial hemorrhages. Because a cephalohematoma involves bleeding between the periosteum and skull (i.e., outside of the skull), it does not require neurosurgical intervention. Intracranial hemorrhages would present with asymmetric reflexes or obtundation. Answer E: Red blood cell transfusions are sometimes necessary to manage intracranial hemorrhages in neonates with significant blood loss. They are not usually required to manage cephalohematoma as the bleeding in this condition is limited by the suture lines. Patients who are tachycardic or hypotensive may require transfusion. Bullet Summary: Most cases of cephalohematoma resolve spontaneously but can sometimes present with an unconjugated hyperbilirubinemia that requires treatment with phototherapy.

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A 24-year-old motorcyclist is involved in a head-on collision with a motor vehicle and suffers various traumatic injuries. She has no significant medical history, is up to date on all vaccinations, and her last tetanus shot was 3 years ago. On arrival, her temperature is 36.7°C (98°F), blood pressure is 82/63 mmHg, pulse is 120/min, respirations are 20/min, and oxygen saturation is 97% on 2L oxygen nasal cannula. On physical exam, there are extensive ecchymoses and abrasions along her left posterior ribs and left flank. A CT scan of the abdomen is obtained, which is shown in Figure A. After the appropriate surgical intervention is performed for the grade V splenic injury, which of the following is the most appropriate next step in management?

Insertion of a nasogastric tube

Insertion of a thoracostomy tube

Prophylactic intravenous antibiotics

Tetanus vaccination

Vaccination against Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae

E

Vaccination against Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae

This patient has an extensive splenic injury and hemodynamic instability requiring splenectomy, as evidenced by trauma to the left posterior ribs and left flank, low blood pressures with reflex tachycardia, and evidence of splenic rupture and hemoperitoneum on computed tomography imaging. Subsequently, this asplenic patient will require vaccination against encapsulated bacteria such as S. pneumoniae, N. meningitidis, and H. influenzae. The capsules of encapsulated bacteria serve as an antiphagocytic virulence factor. To clear these bacteria, opsonization and subsequent clearance by the spleen must occur. In the setting of asplenia, opsonization capability is significantly decreased and thus asplenic patients are at high risk of severe infections by encapsulated bacteria. As such, asplenic patients require vaccination against the encapsulated bacteria S. pneumoniae, N. meningitidis, and H. influenza. Patton et al. review recommendations for serogroup B meningococcal vaccination. The authors find that for patients aged 10 to 25 years old who are at increased risk for meningococcal disease (asplenic patients); 3 doses of the MenB-FHbp vaccine should be given. The authors recommend the administration of only 2 doses of the vaccine to patients that are not at elevated risk. Figure/Illustration A depicts a traumatic splenic rupture with perisplenic hemoperitoneum (red circle). Incorrect Answers: Answer A: Insertion of a nasogastric tube would be appropriate in a patient with bowel obstruction or significant post-operative ileus. There is no evidence that this patient is experiencing obstruction or ileus, which typically presents with nausea, vomiting, abdominal pain, bloating, and lack of flatus or bowel movements. Answer B: Insertion of a thoracostomy tube is not indicated in this patient as there is no evidence of pneumothorax or hemothorax. Patients with pneumothorax or hemothorax typically present with tachycardia, tachypnea, and decreased oxygen saturation. On exam, such patients may have decreased breath sounds. Ultrasonography may also reveal the absence of lung sliding. Answer C: Prophylactic intravenous antibiotics are not indicated in the immediate post-operative period for asplenic adults. However, daily oral antibiotic prophylaxis is indicated in asplenic patients with a history of another concurrent immunocompromising condition or a history of severe infection due to an encapsulated organism. Answer D: Tetanus vaccination is indicated every 10 years in patients who have previously received 3 doses of the tetanus vaccine and have clean or minor wounds. In patients with more extensive wounds who have previously received 3 doses of tetanus vaccine, re-vaccination is only necessary if their last tetanus vaccine was 5 or more years ago. This patient has extensive abrasions but is up to date on all vaccines and last received a tetanus vaccine 3 years ago, so a re-vaccination during this time is not indicated. Bullet Summary: Asplenic patients are at increased risk of severe infection by encapsulated bacteria; thus patients that undergo splenic removal require vaccination against Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae within 14 days of the procedure.

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A 17-year-old high school student was in shop class when he accidentally sawed off a portion of his right index finger. The teacher applied dressings and pressure to the patient's injured digit and immediately transported the patient to the emergency department. He arrived within 20 minutes of the accident. The patient has a medical history of asthma and his only medication is albuterol. His temperature is 98.0°F (36.6°C), blood pressure is 120/70 mmHg, pulse is 105/min, and respirations are 17/min. Exam was significant for pulsatile bleeding from a clean-cut wound on his right second finger. Radiography of the hand revealed a complete amputation of the right finger from the distal interphalangeal joint. The wound was cleaned, compression applied, analgesics administered, and the hand surgeons were notified. The teacher states that he left the amputated finger in the classroom, but the principal would be transporting it to the hospital. Which of the following is the correct method for transporting the amputated finger?

Rinse the finger in normal saline, wrap the finger in moist gauze, put in a plastic bag, and place the bag in ice water

Rinse the finger with hydrogen peroxide, wrap the finger in moist gauze, and place on ice

Submerge the finger in ice water

Wrap the finger in moist gauze and place in a plastic bag

Wrap the finger in moist gauze and place on ice

A

Rinse the finger in normal saline, wrap the finger in moist gauze, put in a plastic bag, and place the bag in ice water

This patient is presenting with a fingertip amputation with loss of pulp, nail, and bone (with a possibility for surgical reattachment and repair, efforts should be made to recover the severed tissue). The correct way to transport an amputated digit is to rinse the finger in normal saline to remove gross contaminants, wrap the appendage in gauze moistened by normal saline, place it in a plastic bag, and then place the bag in ice water. Amputation injuries are common with finger and thumb amputations being the most common. With rapid and proper transport of the patient and appendage, successful reattachment could be possible pending a surgical evaluation. It is important to know how to appropriately package the severed digit so as to optimize tissue viability. Cooling with ice water can slow the metabolic rate of the tissue and result in less tissue damage; however, there is a delicate balance. There must be proper barriers between the digit and ice water to avoid ice burns which could compromise the tissue. Patients should be given IV antibiotics to prevent infection as well. Zhang et al. note that once a finger amputation has occurred, ischemic tolerance times are 12 hours if warm and up to 24 hours if cold. For more proximal amputations, these times are halved due to the presence of muscle tissue, which can undergo irreversible changes after 6 hours of ischemia. Incorrect Answers: Answer B: Rinsing the amputated finger with hydrogen peroxide could damage the tissue decreasing the chances of salvageability. Avoiding the use of caustic solutions with amputated appendages preserves tissue. Answer C: Submerging the finger in ice water could lead to irreversible tissue damage and swelling making reattachment impossible. Answer D: Wrapping the finger in moist gauze and then placing in a plastic bag is not enough to optimize a severed finger for transport. Cooling further with ice water is necessary in order to slow down tissue metabolism and prevent further ischemic damage. Answer E: Wrapping the finger in moist gauze and placing it directly on ice could damage the finger by direct contact with ice rendering the amputated part non-viable. Bullet Summary: The correct handling of an amputated appendage is to first rinse it off with normal saline to remove any gross debris, wrap it in normal saline soaked gauze, put it in a plastic bag, and then place that bag in ice water.

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A 77-year-old man presents to the emergency department with a complaint of sudden onset weakness in his right upper extremity. At home, the patient thought he was simply dehydrated, but he rapidly began to have trouble speaking. When his wife noted this she brought him into the hospital. On arrival to the emergency department, the patient is not responding to verbal stimuli and only withdraws his left upper extremity and lower extremity to pain. His past medical history is notable for hypertension and atrial fibrillation treated with metoprolol, apixaban, and lisinopril. His temperature is 99.0°F (37.2°C), blood pressure is 170/100 mmHg, pulse is 95/min, and respirations are 16/min. The patient has a seizure and subsequently demonstrates agonal breathing. He no longer responds to painful stimuli. A fingerstick blood glucose is 122 mg/dL. Which of the following is the most likely etiology of this patient's symptoms?

Epidural hematoma

Intracerebral hemorrhage

Ischemic stroke

Subarachnoid hemorrhage

Subdural hematoma

B

Intracerebral hemorrhage

This patient with a medical history of hypertension on blood thinners (apixaban) is presenting with rapidly progressive neurologic symptoms. Initially, his symptoms are in his right upper extremity, which then progresses to affect his speech and cause altered mental status, obtundation, and seizures, which is suggestive of a left-sided intraparenchymal hemorrhage. Intraparenchymal (IPH) cerebral hemorrhages often present with sudden-onset focal neurologic deficits. A unique feature is that IPHs tend to present with progressive/worsening symptoms in contrast to ischemic strokes which often demonstrate stable or improving symptoms. It is not uncommon for a patient to present with focal neurologic deficits, which then progress to seizures and obtundation. Risk factors include older age, hypertension, and blood thinners. The prognosis is poor in intraparenchymal hemorrhages, and outcomes are dependent on the size and location of the bleed. Initial workup should be centered on obtaining a fingerstick blood glucose, securing the airway, and obtaining CNS imaging (often with a non-contrast CT scan). Further management is centered on elevating the head of the bed, reversing the patient's anticoagulation status, and possible neurosurgical intervention (though prognosis is very poor in general). Gross et al. review IPH. They note that IPH has very high morbidity and mortality even when treated. There is ongoing research into minimally invasive approaches for evacuation of primary IPH to optimize and improve outcomes, although immediate medical therapy is needed to reduce mortality which is recommended. Incorrect Answers: Answer A: Epidural hematomas present after trauma with the "talk and die" syndrome beginning with a period of unconsciousness, a lucid interval, and then progressive obtundation. A CT of the head would demonstrate a lens-shaped lesion, and a burr hole to drain the collection of blood is the treatment of choice. Acute epidural hematomas do not typically begin spontaneously. Answer C: Ischemic strokes present with sudden onset, focal neurologic deficits. Generally, after the initial ischemic event, patients will be stable or even note an improvement in their symptoms. It is less likely that this patient's progressive symptoms and seizures are caused by an ischemic stroke when compared to a hemorrhagic stroke or intraparenchymal hemorrhage. This diagnosis is certainly possible, and further workup with CT imaging and possibly MRI is needed to clarify the diagnosis and direct further care. Answer D: Subarachnoid hemorrhages generally present with a "thunderclap" headache with meningeal signs. It is possible that patients may present with obtundation and confusion with severe subarachnoid hemorrhages. Seizures are uncommon in subarachnoid hemorrhages and generally do not present with such focal neurologic deficits. CT will show blood in the subarachnoid space. The diagnosis can be supported with CTA or a lumbar puncture. Further management may involve nimodipine, neurosurgical intervention, and observation if the bleed is small and has stopped on its own. Answer E: Subdural hematomas are more common in the elderly patients and patients with alcohol use disorder and present after trauma with a gradual progression of altered mental status to obtundation. Note that large subdural hematomas may present with a rapid progression of symptoms. CT of the head will demonstrate a crescent-shaped lesion that crosses suture lines. Management may involve neurosurgical evacuation with large subdural hematomas causing mass effect. Bullet Summary: Intraparenchymal hemorrhages may occur spontaneously in the setting of hypertension and blood thinners and present with progressive neurologic deficits that get worse over time with possible seizures.

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A 44-year-old woman presents to the emergency department with fluctuating right upper quadrant abdominal pain. The pain was initially a 4/10 in severity but has increased recently to a 6/10 prompting her to come in. The patient has a medical history of type 2 diabetes mellitus, depression, anxiety, and irritable bowel syndrome. Her current medications include metformin, glyburide, escitalopram, and psyllium husks. Her temperature is 99.2°F (37.3°C), pulse of 95/min, blood pressure of 135/90 mmHg, respirations of 15/min with 98% oxygen saturation on room air. On exam, the patient is an obese woman with pain upon palpation of the right upper quadrant. Initial labs are are below: Na+: 140 mEq/L K+: 4.0 mEq/L Cl-: 100 mEq/L HCO3-: 24 mEq/L AST: 100 U/L ALT: 110 U/L Amylase: 30 U/L Alkaline phosphatase: 125 U/L Bilirubin Total: 2.5 mg/dL Direct: 1.8 mg/dL The patient is sent for a right upper quadrant ultrasound demonstrating an absence of stones, no pericholecystic fluid, a normal gallbladder contour and no abnormalities noted in the common bile duct. MRCP with secretin infusion is performed demonstrating patent biliary and pancreatic ductal systems. Her lab values and clinical presentation remain unchanged 24 hours later. Which of the following is the most appropriate next step in management?

Analgesics and await resolution of symptoms

Elective cholecystectomy

ERCP with manometry

Laparoscopy

MRI of the abdomen

C

ERCP with manometry

This patient is presenting with classic symptoms of acute cholecystitis or choledocholithiasis such as right upper quadrant pain and direct hyperbilirubinemia with ultrasound findings demonstrating the absence of gallstones. In this setting, sphincter of Oddi dysfunction should be suspected, and ERCP with manometry should be performed to confirm the diagnosis. Cholecystitis is inflammation of the gallbladder caused by irritation due to an intraluminal stone and possible bacterial translocation. The classic risk factors for this disease can be remembered as "fat, female, fertile and forty". Symptoms of acute cholecystitis are right upper quadrant pain that relapses and remits over time. Lab values will show elevated AST, ALT, alkaline phosphatase, and bilirubin which are also seen in patients where a stone is impacted in the common bile duct. A right upper quadrant ultrasound and MRCP can be used to confirm the diagnosis. Dysfunction of the Sphincter of Oddi should be suspected in patients with classic findings but negative imaging studies. In these cases, the most appropriate test is ERCP with manometry of the sphincter of Oddi. Ultimately, a sphincterotomy will be needed once the diagnosis is confirmed. Coucke et al. present the current evidence for the diagnosis and treatment of biliary obstruction. They discuss how the most common etiology of biliary obstruction is choledocholithiasis or gallstones. They recommend having a high index of suspicion for cholangitis as this condition can be rapidly fatal if untreated. Incorrect Answers: Answer A: Analgesics and await resolution of symptoms (in addition to NPO and IV fluids) would be appropriate management for pancreatitis. The diagnosis in this patient has not yet been confirmed (given the absence of findings on ultrasound) thus prompting another diagnostic test. Answer B: An elective cholecystectomy would be the most appropriate next step in management if the patient had cholecystitis. Answer D: Laparoscopy is an inappropriate and invasive method of diagnosing and treating disease of the biliary tree as there are better alternatives such as MRCP or ERCP. Laparoscopy would be effective in the treatment of intestinal tract disorders such as appendicitis. Answer E: An MRI of the abdomen would not confirm the diagnosis of sphincter of Oddi dysfunction. Though a CT scan could be performed as a more cost-effective alternative, given the absence of stones on ultrasound it is likely that a CT scan will not give more information. Bullet Summary: Sphincter of Oddi dysfunction can be diagnosed with ERCP and manometry.

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A 27-year-old man presents to the emergency department with altered mental status. He has become gradually more confused over the past several days. His wife also notes he has had diarrhea, nausea and vomiting, and abdominal pain for the past week. The patient has a history of depression and multiple suicide attempts. He takes fluoxetine as well as over-the-counter pain medications for a recent muscle strain. He works in a large industrial compound that manufactures semiconductors. He exercises regularly and recently has started making his own beer at home. His temperature is 98.3°F (36.8°C), blood pressure is 107/75 mmHg, pulse is 110/min, respirations are 22/min, and oxygen saturation is 99% on room air. Physical exam reveals a confused man with a garlic odor on his breath and the finding in Figure A. Cardiopulmonary exam reveals a rapid heart rate with no murmurs and clear breath sounds. Which of the following is the most likely etiology of this patient's symptoms?

Acetaminophen

Arsenic

Cyanide

Iron

Lead

B

Arsenic

This patient who works in the semiconductor industry and presents with confusion, hypotension, tachycardia, a garlic odor, and Mees lines (Figure A) most likely has arsenic poisoning. Arsenic poisoning can occur due to exposure to contaminated drinking water, industrial jobs, insecticides, and certain preservatives. Arsenic inhibits enzymes requiring lipoic acid as a cofactor; thus, it disrupts ATP production and causes oxidative stress. Signs and symptoms of arsenic poisoning include Mees lines (white horizontal/parallel lines on the nail beds), nausea, vomiting, abdominal pain, diarrhea, confusion, hypotension, tachycardia, and a garlic odor on the breath. Severe complications are more common with acute exposures and can include shock, pulmonary edema, rhabdomyolysis, and death. Findings consistent with chronic poisoning include anemia, neuropathy, ataxia, and somnolence. A urine arsenic level can support the diagnosis. The treatment of arsenic poisoning is chelating agents such as dimercaprol and supportive therapy. Dimercaprol is a nephrotoxic chelating agent with a narrow therapeutic index and should be used with care. Moon et al. study the association between low and moderate arsenic exposure and cardiovascular disease. The authors find that even low-dose exposure to arsenic increased the risk of cardiovascular disease, coronary artery disease, and stroke mortality. The authors recommend population-level interventions to decrease exposure to arsenic. Figure/Illustration A is the physical exam finding of Mees lines with multiple parallel white lines in the nail bed (blue arrows). Incorrect Answers: Answer A: Acetaminophen overdose has a spectrum of presentations, from non-specific symptoms which can include no symptoms at all to a toxic appearance with nausea, vomiting, jaundice, and altered mental status. Patients should have a 4-hour acetaminophen level drawn. If it falls above the treatment line on the Rummack Matthew nomogram, treatment with N-acetylcysteine should be started. Acetaminophen can cause fulminant liver failure and markedly elevated liver enzymes. Answer C: Cyanide inhibits complex IV in the electron transport chain. It can present after exposure to industrial fires. Patients may present with altered mental status and a profound lactic acidosis that does not respond to oxygen administration with rapid progression to death. The treatment involves the administration of hydroxocobalamin which combines with cyanide to form the non-toxic compound cyanocobalamin. Answer D: Iron overdose presents with nausea, vomiting, diarrhea (bloody), hemorrhagic gastritis, and lactic acidosis. A serum iron level should be ordered to aid in diagnosis. Treatment of acute overdose includes chelation therapy with deferoxamine. Answer E: Lead poisoning can present with constipation, irritability, lethargy, lead lines on radiography, and microcytic anemia with basophilic stippling. Treatment depends on the severity and can involve removal from exposure or chelating therapy with agents such as succimer. Bullet Summary: Arsenic poisoning presents with Mees lines, nausea, vomiting, abdominal pain, confusion, unstable vitals, and a classic “garlic odor.”

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A 6-week-old boy is referred to a pediatric hematologist-oncologist for further evaluation following an abnormal newborn hemoglobinopathy screening. The father’s brother died of sickle cell anemia at an early age. Parental studies reveal that both mother and father are carriers of the sickle cell gene. The patient's temperature is 98.6°F (37.0°C), blood pressure is 80/45 mmHg, pulse is 130/min, and respirations are 25/min. The physician decides to repeat testing for the patient and his 3-year-old sister. The results are shown in Figure A. The physician begins counseling the family. Which of the following is the most likely complication that the patient may have in the future?

Diabetes

Hematuria

Infection

Splenectomy

Stroke

B

Hematuria

Based on the presence of both hemoglobin (Hb) A and S on gel electrophoresis, this patient has sickle cell trait. Episodes of painless hematuria are commonly seen in these patients. Sickle cell trait is a condition that refers to carrying 1 normal and 1 abnormal beta-globin allele. On electrophoresis, this will present as 3 different bands consisting of about 50-60% HbA, 35-45% HbS, and < 2% HbF (fetal hemoglobin). HbF decreases significantly after the first 6 weeks of life. Individuals with sickle cell trait tend to be asymptomatic and do not have a decreased lifespan compared to the general population. However, they are at higher risk of some conditions. Patients are at increased risk of rhabdomyolysis during strenuous physical activity and may have episodic painless hematuria due to renal papillary necrosis. The hyperosmolar, acidotic, and hypoxic environment of the renal medulla is thought to trigger red cell sickling which results in ischemia and subsequent hematuria. Patients with sickle cell trait are managed similarly to the general population. These patients should receive reproductive counseling and use appropriate preventive measures to prevent dehydration during intensive exercise. Hulsizer et al. studied the association between sickle cell trait and common medical conditions using insurance claims data. The authors found that sickle cell trait is associated with increased risks of diabetes, hypertension, heart disease, chronic kidney disease, and retinopathy. The authors recommend further evaluation of these associations using prospective studies derived from clinical data. Figure/Illustration A shows gel electrophoresis with an example of a normal (95-98% HbA and < 2% HbF), sickle cell trait (50-60% HbA, 35-45% HbS, and < 2% HbF), and sickle cell anemia (85-95% HbS and 5-15% HbF) patient from left to right. Incorrect Answers: Answer A: Diabetes has not been associated with sickle cell trait in the majority of studies. Answer C: Infection is a complication of sickle cell anemia. Mechanisms include functional asplenism, reduced tissue perfusion during a sickle crisis, and chronic transfusions with an indwelling catheter. Common infections include bacteremia, meningitis, and pneumonia due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitis. Sickle cell trait is not clearly associated with an increased risk of infection and actually confers some protection against malaria. Answer D: Splenectomy from auto-infarction is often seen in sickle cell anemia, but it is rare with sickle cell trait. In sickle cell anemia, splenic sequestration of sickled red blood cells causes infarction, leading to progressive atrophy and functional hyposplenism. Most individuals with sickle cell disease are functionally asplenic by age 2 to 4. The spleen subsequently cannot phagocytose encapsulated organisms properly, which predisposes sickle cell patients to infection. Answer E: Stroke is a complication of sickle cell anemia but not sickle cell trait. This is due to the increased viscosity of the blood and reduced deformability of red cells in patients with sickle cell anemia. Bullet Summary: Sickle cell trait is associated with episodes of painless hematuria.

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A 69-year-old man presents to his primary care physician for a general checkup. Overall he is doing well. Since he retired, he has been working on projects at home and taking time to exercise every day. He eats a balanced diet and has been spending time with his wife every evening. Despite this, the patient claims that he feels less well-rested when he wakes up in the morning. The patient states that he used to sleep 9 hours a night in his youth and felt excellent. Now he sleeps 7 hours a night and doesn’t feel as well rested as he used to. The patient’s wife states that he seems to sleep peacefully. His medical history is significant for hypertension and diabetes for which he takes lisinopril and metformin. His temperature is 98.6°F (37°C), blood pressure is 131/85 mmHg, pulse is 71/min, and respirations are 12/min. His neurological exam is within normal limits. The patient is muscular and has a healthy weight with a pleasant demeanor. He denies feeling fatigued or tired currently. Which of the following physiological changes would most likely be seen in this patient?

Decreased melatonin

Decreased orexin

Increased acetylcholine

Increased dopamine

Increased norepinephrine

A

Decreased melatonin

This elderly patient is presenting with sleep that is sufficient but less refreshing than sleep was for him in his past suggesting a diagnosis of normal aging. Melatonin levels naturally decrease as patients age. Normal aging shortens most phases of sleep. It is normal for melatonin levels to decline during normal aging; however, this change is not responsible for all the symptoms associated with declining quality of sleep. Other changes that occur include decreased REM sleep, decreased stage N3 sleep, and a compensatory increase in stage N2 sleep. Patients will often complain of sleep that is less refreshing than it was in their youth, yet they are still functional and not excessively tired. Treatment is with sleep hygiene though some patients will also benefit from treatment with melatonin supplementation. Cardinali reviews the role of melatonin in aging. He discusses how natural levels of melatonin decrease in aging animals, which may have implications on the circadian clock. He recommends studies on whether melatonin supplementation may be beneficial to mitigate the effects of aging. Incorrect Answers: Answer B: Decreased orexin levels would be seen in patients with narcolepsy, which presents with sudden episodes of falling asleep. This tends to occur in younger patients and is also associated with cataplexy or sudden loss in muscle tone. Treatment of this disorder is with stimulant medications such as modafinil. Answer C: Increased acetylcholine levels would not be seen in patients as they age and would not explain the changes this patient is experiencing. Rather, acetylcholine levels tend to decline as we age. Drinking caffeinated drinks is associated with increased acetylcholine levels in the brain. Answer D: Increased dopamine would not be a principle change seen in age-related sleep changes. Higher dopamine levels would increase feelings of being awake as well as alertness. In contrast, decreased dopamine levels can be seen in patients with Parkinson disease, which would present with bradykinesia and a resting tremor. Answer E: Increased norepinephrine would result in increased wakefulness and potentially insomnia; however, it would not explain the changes seen in normal aging. This chemical is naturally produced during the fight or flight response and can be artificially increased by stimulant drugs such as cocaine. Bullet Summary: Normal aging results in a shortening of most phases of sleep as well as decreased melatonin levels and presents with sleep that is subjectively less restful.

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A 33-year-old man presents to the emergency department with dizziness. He states he has a constant sensation that the room is spinning. He is now having trouble walking and has been vomiting intermittently. He has no past medical history and takes no medications. His temperature is 98.0°F (36.7°C), blood pressure is 122/84 mmHg, pulse is 80/min, respirations are 16/min, and oxygen saturation is 98% on room air. Physical exam reveals a young man who is vomiting. His gait is ataxic and he exhibits rightward nystagmus. His dizziness is constant and unchanged with performance of the Dix-Hallpike maneuver. The head impulse test reveals a corrective saccade and there is no skew deviation. Which of the following is the most appropriate next step in management?

CT head

Epley maneuver

MRI brain

Prednisone

Tissue plasminogen activator

D

Prednisone

This young, healthy patient is presenting with constant vertigo, ataxia, vomiting, and a head impulse test revealing a corrective saccade, nystagmus, and test of skew (HINTS) exam, which suggests a peripheral etiology of vertigo, most likely vestibular neuritis. As the diagnosis can be made clinically, steroids are the only treatment needed. Differentiating peripheral (the vestibular system) versus central (the brain) vertigo is critical in management. Peripheral vertigo is commonly caused by benign paroxysmal positional vertigo, vestibular neuritis, and labyrinthitis. Vertigo that is constant is more consistent with vestibular neuritis or labyrinthitis but could also be a cerebellar stroke. To differentiate, age, risk factors, and onset of symptoms are critical. Moreover, the HINTS exam can point toward 1 cause of vertigo versus another. HINTS is a mnemonic for: Horizontal head impulse testing (Head Impulse), Direction-changing nystagmus in eccentric gaze (Nystagmus), and Vertical skew (Test of Skew). Findings that are suggestive of a peripheral cause of vertigo include a positive head impulse exam, positive nystagmus (also seen in stroke), and a negative test of skew. In the appropriate clinical context with appropriate risk factors, peripheral causes such as vestibular neuritis or labyrinthitis can be managed with steroids (which may improve outcomes) and meclizine (for symptom control). Kattah et al. discuss the HINTS exam. They note how it can be used to differentiate peripheral from central vertigo. It is recommended to perform this exam when differentiating central versus peripheral vertigo. Incorrect Answers: Answers 1 & 3: Head imaging such as a CT head or MRI brain is not necessary in patients with a clear peripheral cause of their vertigo/dizziness with a HINTS exam suggesting a peripheral etiology. Clinically, this patient has vestibular neuritis and can be treated accordingly. Imaging would be needed if the patient had an acute cerebellar stroke. Answer D: The Epley maneuver is only indicated in cases of benign paroxysmal peripheral vertigo, which presents with severe vertigo (with changes in head position) that diminish with time and keeping the head stationary. Note that this patient’s Dix-Hallpike maneuver is negative and that his vertigo is constant rather than intermittent or positional. Answer E: Tissue plasminogen activator is indicated within 4.5 hours in the setting of an ischemic stroke after a head CT rules out a head bleed, other reversible causes are treated, and assuming there are no contraindications to thrombolytics. Tissue plasminogen activator can be given in posterior circulation strokes. Bullet Summary: Peripheral causes of vertigo generally do not require head imaging, and causes such as labyrinthitis or vestibular neuritis can be treated with steroids.

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A 13-day-old boy is brought by his mother for eye redness and ocular discharge. The mother reports that the patient has developed a cough and nasal discharge. Pregnancy and delivery were uncomplicated but the mother had limited prenatal care during the third trimester. Immediately after delivery, the baby was given silver nitrate drops and vitamin K. His temperature is 99°F (37.2°C), blood pressure is 81/52 mmHg, pulse is 135/min, and respirations are 36/min with an oxygen saturation of 98% O2 on room air. Upon visual examination of the eyes, mucoid ocular discharge and eyelid swelling are noted. A fluorescein test is negative. On lung exam, scattered crackles are appreciated. A chest radiograph is performed that shows hyperinflation with bilateral infiltrates. Which of the following is the most appropriate pharmacotherapy?

Artificial tears

Intravenous acyclovir

Intravenous ceftriaxone

Oral erythromycin

Topical erythromycin

D

Oral erythromycin

This patient is presenting with mucoid ocular discharge around 2 weeks post-birth, suggesting the diagnosis of neonatal chlamydial conjunctivitis. The most appropriate treatment for this disease includes oral erythromycin. Neonatal chlamydial conjunctivitis is caused by Chlamydia trachomatis. It presents in newborns that are 5-14 days old. Symptoms include watery or mucoid discharge and eye swelling. The conjunctiva may be especially irritated. Diagnosis can be established by direct antibody testing or PCR. Treatment for chlamydial conjunctivitis includes both topical and oral erythromycin as there is likely dissemination of the infection. The most common complication of chlamydial conjunctivitis is pneumonia. Of note, all neonates with gonococcal conjunctivitis should also be treated for chlamydia. Smith-Norowitz et al. studied whether antibiotic prophylaxis was beneficial compared with silver nitrate for chlamydia conjunctivitis. They found that there was no benefit to topical antibiotic treatment compared with silver nitrate alone. They recommend testing infants for the disease if it is suspected so that oral antibiotics can be administered effectively. Incorrect Answers: Answer A: Artificial tears can be used in chemical conjunctivitis. The most common cause of neonatal chemical conjunctivitis is post-delivery silver nitrate drops. It usually presents within the first 24 hours following birth/exposure with mild conjunctival injection and tearing, and will spontaneously resolve within 2-4 days. Answer B: Intravenous acyclovir is used to treat conjunctivitis caused by herpes simplex virus. The newborn would present between 1-2 weeks post-birth with lid edema, conjunctival injection, and non-purulent serosanguineous discharge. Corneal involvement with microdendrites or ulcers may be seen with fluorescein stain. Answer C: Intravenous ceftriaxone is used to treat gonococcal conjunctivitis. Gonococcal conjunctivitis usually presents in newborns 0-5 days old with irritation or discharge. Patients with this disease will have very thick discharge with a purulent appearance. Answer E: Topical erythromycin would be used to treat chlamydial conjunctivitis in conjunction with oral erythromycin; however, it is insufficient on its own. Oral erythromycin is the best answer choice for this patient as the disease has likely disseminated. Topical erythromycin can also be used as prophylaxis for gonococcal conjunctivitis. Bullet Summary: Neonatal chlamydial conjunctivitis presents with watery or mucoid discharge as well as eye swelling and is treated with topical and oral erythromycin.

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A 70-year-old woman is brought to the emergency department by ambulance. She was found on the floor of her apartment after her neighbor called 911. She is confused and is unable to provide any history, but complains of generalized pain. Her temperature is 99.2°F (37.3°C), blood pressure is 129/64 mmHg, pulse is 63/min, respirations are 13/min, and oxygen saturation is 99% on room air. Physical exam reveals, a confused, ill-appearing woman. Lungs are clear to auscultation bilaterally. An electrocardiogram is obtained as shown in Figure A. Dipstick urinalysis is notable for 4+ blood and dark colored urine. Which of the following is the most appropriate next step in management?

Albuterol and IV fluid resuscitation

Calcium gluconate

Insulin, glucose, and IV fluid resuscitation

IV fluid resuscitation

Sodium polystyrene sulfonate

B

Calcium gluconate

This patient with confusion, dark urine, and peaked T waves on electrocardiogram in the setting of a prolonged time spent down likely has developed rhabdomyolysis with associated hyperkalemia. For patients with suspected hyperkalemia and electrocardiogram changes, the most appropriate next step in management is treatment with calcium gluconate Rhabdomyolysis occurs when muscle cells lyse and release their intracellular contents. This can occur secondary to intense athletics, seizures, stimulant drug use, or a prolonged period of immobility. Lysis of muscle cells leads to release of potassium, myoglobin, purines, and other intracellular contents. Release of large amounts of myoglobin can result in renal impairment and myoglobinuria. On dipstick urinalysis, myoglobin causes a positive result for blood. Renal impairment further increases the risk for development of hyperkalemia. On ECG, hyperkalemia manifests with a "peaked" appearance of T waves, especially in the precordial leads. As hyperkalemia worsens, electrocardiogram changes progress to loss of P waves, QRS complex widening, and eventual sine wave rhythm. For patients with suspected hyperkalemia and characteristic changes noted on the electrocardiogram, the most appropriate immediate step in management is treatment with intravenous calcium gluconate. Calcium gluconate acts to stabilize cardiac myocyte membranes and prevent development of life-threatening arrhythmias. Gupta et. al review rhabdomyolysis. They discuss the pathophysiology, clinical manifestations and diagnosis. They further detail complications that may arise such as hyperkalemia, and discuss respective management strategies. Figure A demonstrates an electrocardiogram with features characteristic of hyperkalemia. Note the peaked appearance of the T waves in the precordial leads. Incorrect Answers: Answer A: Albuterol and IV fluid resuscitation may eventually be appropriate. Albuterol (a beta agonist) will act to shift potassium to the intracellular compartment. This patient's electrocardiogram changes warrant immediate treatment with calcium gluconate in order to stabilize cardiac myocyte membranes. Answer C: Insulin, glucose, and IV fluid resuscitation are indicated in this patient. Insulin acts to shift potassium to the intracellular compartment, and fluid resuscitation is warranted for the patient's likely renal impairment. Calcium gluconate is the more immediate priority to prevent development of arrhythmia. Answer D: IV fluid resuscitation is indicated for this patient with likely renal impairment. However, calcium gluconate is the more immediate priority to address this patient's hyperkalemia and prevent development of arrhythmia. Answer E: Sodium polystyrene is an oral potassium binder that increases GI excretion of potassium. It may be appropriate to treat mild hyperkalemia in some patients. It takes a prolonged amount of time to have any significant effect. Bullet Summary: For patients with suspected hyperkalemia and characteristic changes noted on ECG, the most appropriate immediate step in management is treatment with intravenous calcium gluconate.

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A 17-year-old girl presents to the clinic reporting 7 months without a menstrual period. Menarche was at age 12 and she had regular periods up until 2 years ago. At that time, her periods became less regular until around 7 months ago when they ceased altogether. She is otherwise healthy, participates in multiple school sports teams, and has been training rigorously for upcoming competitions. She denies alcohol use, smoking, and recreational drugs. She is not sexually active and does not take oral contraceptives. Her temperature is 36.7°C (98°F), blood pressure is 121/80 mmHg, pulse is 62/min, respirations are 11/min, oxygen saturation is 100% on room air, and BMI is 20 kg/m^2. Her pelvic exam reveals an anteverted uterus, no adnexal masses, a normal-appearing cervix with no cervical motion tenderness, and normal vaginal anatomy. Which of the following is the most likely cause of this patient's amenorrhea?

Anorexia nervosa

Functional hypothalamic amenorrhea

Hypothyroidism

Polycystic ovarian syndrome

Pregnancy

B

Functional hypothalamic amenorrhea

This patient presenting with secondary amenorrhea (defined as 6 or more consecutive months without menstruation in women who have passed menarche) and a history of rigorous exercise most likely has functional hypothalamic amenorrhea. Functional hypothalamic amenorrhea is a condition in which relative caloric deficiency (whether through severe caloric restriction, increased energy expenditure, or increased stress) leads to functional disruption of the normal pulsatile release of gonadotropin-releasing hormone (GnRH). This in turn leads to decreased levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), disruption to estrogen levels, and amenorrhea. A common associated clinical presentation is known as the "female athlete triad", which includes decreased calorie availability or increased energy expenditure through exercise, decreased bone mineral density due to a decrease in estrogen levels, and menstrual dysfunction. Treatment includes increasing caloric intake, behavioral therapy as needed, and possible estrogen replacement therapy. Ackerman et al. reviews the role of estrogen replacement in improving bone mineral density in patients with functional hypothalamic amenorrhea. The authors find that spine and femoral neck bone mineral density z-scores significantly increased with estrogen replacement. The authors recommend the use of transdermal estradiol over 12 months in improving bone mineral density in patients with functional hypothalamic amenorrhea. Incorrect Answers: Answer A: Anorexia nervosa will often manifest with secondary amenorrhea in women. This patient has a normal BMI and no history of disordered eating. The mechanism of amenorrhea in the setting of anorexia nervosa relates to the same hypothalamic-pituitary-ovarian axis at play in functional hypothalamic amenorrhea wherein the state of energy deficiency from inadequate caloric intake disrupts normal pulsatile GnRH secretion, leading to decreased FSH, LH, estrogen levels, and subsequent amenorrhea. Answer C: Hypothyroidism is a cause of secondary amenorrhea wherein abnormal thyroid function can lead to altered levels of sex hormone-binding protein, prolactin, and gonadotropin-releasing hormone, thus causing menstrual dysfunction. This patient does not present with other signs of hypothyroidism, such as fatigue, sensitivity to cold, dry skin, muscle weakness, weight gain, constipation, joint stiffness, or thinning hair. Answer D: Polycystic ovary syndrome is a condition often associated with obesity in which hyperinsulinemia or insulin resistance is hypothesized to alter the hypothalamus feedback response, leading to the increased luteinizing hormone to follicle-stimulating hormone ratio, increased androgen levels, and decreased rate of follicular maturation leading to unruptured follicles. Patients will often present with amenorrhea or oligomenorrhea, hirsutism, acne, and decreased fertility. Answer E: Pregnancy is a cause of secondary amenorrhea that is less likely in this patient given her lack of sexual history and other associated symptoms such as decreased appetite, nausea, and insomnia. A beta-human chorionic gonadotropin (beta-hCG) test should always be part of the workup for secondary amenorrhea. Bullet Summary: Functional hypothalamic amenorrhea is a condition in which caloric restriction, increased energy expenditure through exercise, and/or increased stress leads to a disrupted pulsatile secretion of gonadotropin-releasing hormone with the downstream effect of amenorrhea.

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A 44-year-old homeless man presents to the emergency department after being stabbed multiple times in the abdomen. The patient is intoxicated and is unable to offer further history. His temperature is 97.5°F (36.4°C), blood pressure is 92/52 mmHg, pulse is 145/min, respirations are 33/min, and oxygen saturation is 90% on room air. He is intubated to protect his airway, given 2 units of packed red blood cells, and sent to the operating room for an exploratory laparotomy. The patient is subsequently admitted to the intensive care unit. He is extubated the next day and appears well. His vitals are within normal limits. Physical exam reveals sparse hair that is falling out throughout the patient’s body. He has a rash by the corners of his mouth. The patient has multiple loose bowel movements and on day 6 the patient’s surgical wound does not appear to be healing. It is held together only by the sutures with minimal underlying healing. Which of the following is most likely deficient in this patient?

Riboflavin

Thiamine

Vitamin C

Vitamin D

Zinc

E

Zinc

This homeless patient who likely has poor nutritional status presents with angular cheilitis, sparse hair that is falling out, diarrhea, and poor wound healing, all of which are suggestive of zinc deficiency. Zinc is involved in many physiologic processes and is an important mineral to include in the diet. Zinc deficiency is common in patients with poor nutritional status such as the homeless, individuals living in developing nations without access to food, and patients with eating disorders. Many malabsorptive conditions can cause zinc deficiency including steatorrhea and chronic pancreatitis. Zinc deficiency presents with impaired wound healing and impaired immune function. Other symptoms suggestive of zinc deficiency include xerosis, alopecia, stomatitis, oral ulceration, angular cheilitis, impaired vision (night blindness), impaired smell/taste, diarrhea, and anorexia. The treatment of zinc deficiency involves zinc supplementation and workup for any other nutritional deficiencies. Nagata etc al. study the incidence of zinc deficiency among younger patients with anorexia nervosa. The authors find that men and women are both equally likely to have zinc deficiency when admitted. The authors recommend screening all patients with eating disorders for zinc deficiency. Incorrect Answers: Answer A: Riboflavin deficiency may present with angular cheilitis, stomatitis, and a non-specific rash. The treatment involves supplementing or consuming foods with riboflavin; however, it is rare in the developed world to be riboflavin deficient (due to fortified foods) and would not cause such significant wound healing issues as in this patient. Answer B: Thiamine deficiency is common in alcoholics and can cause Wernicke-Korsakoff syndrome, which presents with ataxia, nystagmus, and ophthalmoplegia in addition to amnesia. The treatment involves the administration of high-dose thiamine. Answer C: Vitamin C deficiency causes scurvy, which presents with easy fractures, bleeding gums or loose teeth, delayed wound healing, and perifollicular hemorrhages. It is common in the homeless and alcoholics. Treatment involves vitamin C replacement or a diet rich in fruits and vegetables. Answer D: Vitamin D deficiency is common in the homeless, alcoholics, or those who suffer from steatorrhea (such as chronic pancreatitis or Crohn disease). It presents with weak, soft bones (osteomalacia/osteoporosis), and hypocalcemia which may present with paresthesias and tetany. Treatment involves replacement of vitamin D. Bullet Summary: Zinc deficiency presents with poor wound healing, hair loss, infertility, diarrhea, anorexia, and impaired immune function.

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A 51-year-old man presents to his primary care provider for intermittent shaking of his hands. For the last several years he has noticed this "shaking" when he brushes his teeth and prepares a cup of coffee in the morning. The shaking then gradually improves over the course of the day. His medical history is otherwise notable for hypertension and hyperlipidemia. His only home medication is pravastatin. The patient smokes half a pack per day of cigarettes and drinks 2-3 beers throughout the day. His family history is significant for Parkinson disease in his father. On physical exam, his temperature is 98.6°F (37.0°C), blood pressure is 159/84, pulse is 74/min, and respirations are 12/min. He has a high-frequency bilateral hand tremor elicited on finger-to-nose testing. His neurological exam is otherwise unremarkable. Which of the following medications should this patient be started on?

Alprazolam

Primidone

Propranolol

Topiramate

Trihexyphenidyl

C

Propranolol

This patient presents with a high frequency bilateral action tremor, which suggests a diagnosis of benign essential tremor. In light of his concomitant hypertension, the patient should be started on propranolol. Benign essential tremor usually presents as a bilateral tremor of the hands that is observed during fine motor movements. Patients present with worsening tremors with posturing and with voluntary movement and improve with alcohol and rest. First-line treatment includes propranolol and primidone, with propranolol being preferred for patients with hypertension or vascular risk factors. Refractory cases can be treated with deep brain stimulation which is often a last-line intervention. Shanker reviewed the diagnosis and treatment of patients with essential tremors. She discusses how this disease presents with an action tremor that lasts for at least 3 years. She recommends treatment with propranolol or primidone. Incorrect Answers: Answer A: Alprazolam is sometimes used as second-line therapy for essential tremor refractory to propranolol and primidone but would not be used as initial therapy in this patient. Benzodiazepines can be used in patients with panic disorders. Answer B: Primidone is a barbiturate that is another first-line treatment for essential tremor. For this patient, propranolol would be preferred to also treat this patient’s underlying hypertension. Primidone can be used in patients without other underlying comorbidities. Answer D: Topiramate is an antiepileptic that may be used as a second-line treatment option for essential tremor. It would not be used as initial drug therapy. Topiramate can be used in the treatment of patients with partial seizures that present with motor symptoms. Answer E: Trihexyphenidyl is an anticholinergic medication that is used to treat early Parkinson disease in which tremor is the predominant symptom. Despite this patient’s family history of Parkinson disease, the tremor in Parkinson disease usually presents as an asymmetric, “pill-rolling” resting tremor rather than an action tremor. Bullet Summary: Propranolol is the first-line treatment for benign essential tremor in patients with concomitant hypertension.

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A 1-hour-old newborn boy is evaluated in the delivery room. He was born at 37 weeks gestation to a 39-year-old G3P3 mother. The mother initially labored at home with a midwife but was transferred to the hospital for failure to progress. The infant was eventually delivered via Caesarean section. The mother declined all prenatal screening tests during this pregnancy. His temperature is 98.6°F (37°C), blood pressure is 63/41 mmHg, pulse is 133/min, and respirations are 39/min. His Apgar scores were 7 and 8 at 1 and 5 minutes, respectively. His weight is 3.0 kg (6.6 lb), and his height and his head circumference are in the 30th and 40th percentiles, respectively. On physical exam, he is found to have a 3 cm full-thickness defect in the abdominal wall to the right of the umbilicus with evisceration of a loop of the bowel. The abdominal defect is immediately covered in sterile saline dressings and an orogastric tube and 2 peripheral intravenous lines are placed. This condition is most likely associated with which of the following additional findings?

A normal cardiac exam

Bicuspid aortic valve

Endocardial cushion defect

Tetralogy of Fallot

Ventricular septal defect

A

A normal cardiac exam

This patient presents with a full-thickness defect in the abdominal wall lateral to the umbilicus with evisceration of the bowel, which suggests a diagnosis of gastroschisis. Gastroschisis is not associated with any cardiac defects. Gastroschisis and omphalocele are the most common abdominal wall defects found in infants and there are important differences between them. Whereas the eviscerated bowel in gastroschisis is not covered by a membrane, the exposed bowel in the omphalocele is covered by a membranous sac. The abdominal wall defect in gastroschisis is located lateral to the umbilicus, whereas in omphalocele the defect is midline. The distinction is also important for management, as omphalocele is commonly associated with other extraintestinal defects whereas fewer than 10% of cases of gastroschisis are associated with an extraintestinal abnormality. Treatment is with surgical correction of the abdominal wall defect. Skarsgard reviews the evidence regarding the diagnosis and treatment of gastroschisis. He discusses how this is one of the most common birth defects managed in the ICU setting. He recommends urgent surgical correction. Incorrect Answers: Answer B: A bicuspid aortic valve occurs in many cases of Turner syndrome. This disease presents with a webbed neck, short stature, low hairline, broad (“shield”) chest, bicuspid aortic valve, horseshoe kidney, and streak ovaries. Treatment is supportive with surgical fixation of cardiac defects and hormone supplementation with growth hormone. Answer C: Endocardial cushion defects are most commonly found in trisomy 21 (Down syndrome). Over a third of individuals with trisomy 21 have a complete atrioventricular septal defect, and another third have isolated ventricular septal defects. Infants with Down syndrome commonly present with the upslanting palpebral fissures, flat nasal bridge, transverse palmar crease, and hypotonia. Treatment is with supportive care of these deformities such as surgical correction of cardiac defects. Answer D: Tetralogy of Fallot is most often associated with trisomy 21 (Down syndrome) and 22q11 deletion syndromes. Infants with Down syndrome commonly present with upslanting palpebral fissures, flat nasal bridge, transverse palmar crease, and hypotonia. Treatment is with supportive care of these deformities such as surgical correction of cardiac defects. Answer E: Ventricular septal defects occur in several genetic syndromes, including trisomy 21 (Down syndrome) and trisomy 13 (Patau syndrome). Infants with trisomy 13 commonly present with cleft lip or palate, polydactyly, and severe intellectual disability. This disease is not compatible with survival past 1 year of age so treatment can involve termination of pregnancy or supportive care. Bullet Summary: Gastroschisis presents with an abdominal wall defect with evisceration of the bowel that is lateral to the umbilicus and is not usually associated with other birth defects.

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A 6-month-old boy is brought to the pediatrician by his parents for a routine visit. His parents report that he is feeding and stooling well and they have just started experimenting with solid foods. His parents are concerned because a few weeks ago he started rolling from back to front in addition to front to back, but he now struggles when placed on his back. The patient was noted to be developmentally appropriate for his age at his last visit 2 months ago. On physical exam, the patient seems well-nourished and has no dysmorphic features. His temperature is 98.6°F (37°C), blood pressure is 77/49 mmHg, pulse is 112/min, and respirations are 24/min. In the examination room, he is able to roll from front to back but cannot roll from back to front. He is not able to sit without support and makes no attempt at bouncing when supported in a standing position. The patient’s abdomen is non-tender and soft without hepatosplenomegaly. His patellar reflexes are 4+ bilaterally. He is found to have the ocular finding seen in Figure A. Accumulation of which of the following would most likely be found in this patient’s cells?

Cerebroside sulfate

Galactocerebroside

Glucocerebroside

GM2-ganglioside

Sphingomyelin

D

GM2-ganglioside

This 6-month-old boy who presents with developmental regression, a “cherry-red” macula, and hyperreflexia most likely has a diagnosis of Tay-Sachs disease. Tay-Sachs disease is caused by a deficiency of beta-hexosaminidase A that results in the accumulation of GM2-ganglioside. Tay-Sachs disease is a genetic disorder caused by an autosomal recessive deficiency of the beta-hexosaminidase A enzyme. This disease presents in infants aged 2-6 months with progressive neurodegeneration, hypotonia, feeding difficulties, and a “cherry red” spot on the macula. Tay-Sachs disease shares many features with Niemann-Pick disease; however, Niemann-Pick disease presents with the additional findings of hepatosplenomegaly and hyporeflexia whereas Tay-Sachs presents with hyperreflexia without hepatosplenomegaly. Both diseases are more common in the Ashkenazi Jewish population. There is no curative treatment for this disease so treatment is generally supportive. Solovyeva et al. review the evidence regarding the diagnosis and treatment of Tay-Sachs disease. They discuss how this disease normally presents with muscle weakness, ataxia, speech, and mental disorders. They recommend considering novel treatments such as substrate reduction therapy. Figure/Illustration A is a fundoscopic exam demonstrating a “cherry-red” spot on the macula (blue circle). This finding is seen in both Tay-Sachs disease and Niemann-Pick disease. Incorrect Answers: Answer A: Cerebroside sulfate accumulates in metachromic leukodystrophy, which is caused by an autosomal recessive deficiency in arylsufatase A. This disease presents with optic atrophy and seizures in childhood. Patients will later develop dementia, psychiatric disease, and neuropathy. There is no cure so treatment is supportive. Answer B: Galactocerebroside accumulates in Krabbe disease, which is caused by an autosomal recessive deficiency in galactocerebrosidase. Krabbe disease presents in early infancy with developmental regression, hypotonia, and areflexia. Treatment is supportive with musculoskeletal bracing as needed. Answer C: Glucocerebroside accumulates in Gaucher disease, which is caused by an autosomal recessive deficiency in glucocerebrosidase. Gaucher disease presents with pancytopenia and hepatosplenomegaly. “Gaucher cells,” or lipid-laden macrophages resembling crumpled tissue paper, can be seen on histology. Treatment is with enzyme replacement therapy. Answer E: Sphingomyelin accumulates in Niemann-Pick disease, an autosomal recessive sphingolipidosis caused by a deficiency in sphingomyelinase. Niemann-Pick disease presents with many of the same features as Tay-Sachs disease but has additional findings of hyporeflexia and hepatosplenomegaly. Bullet Summary: Tay-Sachs disease is caused by a deficiency of beta-hexosaminidase A resulting in the accumulation of GM2-ganglioside.

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A 25-year-old man presents to his primary care provider for a routine appointment. He feels well and has no complaints. His medical and surgical history is significant for the reconstruction of a torn anterior cruciate ligament in his right knee. His family history is significant for a mother with “thyroid problems” and a father with coronary artery disease. The patient is an information technology specialist at a local company. He is sexually active with men. His temperature is 98.6°F (37.0°C), blood pressure is 124/82 mmHg, pulse is 71/min, and respirations are 12/min. On physical exam, the patient is tall and slender with a BMI of 21 kg/m2. A single nodule can be palpated on the patient’s thyroid. He has palpable cervical lymphadenopathy. On cardiac exam, he has a normal S1/S2 with no murmurs, rubs, or gallops, and his lungs are clear bilaterally. His abdomen is soft and non-tender without hepatosplenomegaly. A physical exam of the perioral region can be seen in Figure A. Which of the following additional findings is most likely to be found in this patient?

Elevated plasma metanephrines

Elevated serum calcium level

Elevated serum prolactin level

Fasting hypoglycemia

Positive fecal occult blood test

A

Elevated plasma metanephrines

This patient presents with tall stature, mucosal neuromas of the lips and tongue, an isolated thyroid nodule, and a family history of thyroid disease, which suggests a diagnosis of multiple endocrine neoplasia type 2 (MEN2B). MEN2B is also associated with pheochromocytomas, which cause elevated plasma metanephrines. MEN2B is caused by a gain-of-function mutation in the RET proto-oncogene and presents with medullary carcinoma of the thyroid, pheochromocytoma, Marfanoid habitus, and mucosal neuromas. Medullary thyroid carcinoma (MTC) occurs in almost all patients with MEN2B and is often metastatic at the time of diagnosis. Patients should be screened for pheochromocytoma using plasma fractionated metanephrines at the time of diagnosis of MTC. Intestinal neuromas may also lead to intestinal manifestations such as chronic constipation and megacolon. Treatment is with surgical excision of malignant lesions and active screening for future development of tumors. Castinetti et al. review the evidence regarding the diagnosis and treatment of MEN2B. They discuss how often the first presentation of this disease involves the diagnosis of medullary thyroid carcinoma. They recommend developing techniques for earlier diagnosis of this disease in order to allow for better survival. Figure/Illustration A is a clinical photograph demonstrating mucosal neuromas, which are painless nodules on the lips or tongue (red circles). These findings are characteristically seen in multiple endocrine neoplasia type 2B. Incorrect Answers: Answer B: An elevated serum calcium level would suggest parathyroid hyperplasia, which is a feature of both type 1 and type 2A multiple endocrine neoplasia. Rather than hypercalcemia, this patient is likely to have an elevated serum calcitonin level due to his medullary thyroid carcinoma. Answer C: An elevated serum prolactin level would suggest the presence of a prolactinoma, which is a pituitary tumor that may be seen in type 1 multiple endocrine neoplasia (MEN1). Other findings in this disorder include parathyroid and pancreatic tumors. Treatment is with surgical excision of malignant lesions. Answer D: Fasting hypoglycemia would suggest the presence of an insulinoma, which is a less common pancreatic tumor that may be seen in MEN1. Other findings in this disorder include parathyroid and pancreatic tumors. Patients with an insulinoma require surgical excision in order to allow for proper glucose homeostasis. Answer E: A positive fecal occult blood test would raise suspicion for colorectal cancer, which is a feature of Peutz-Jeghers syndrome (PJS). The extraintestinal manifestations of PJS include mucocutaneous pigmented macules on the lips and perioral region. Treatment is with screening for colorectal cancer and surgical excision of malignant lesions. Bullet Summary: Multiple endocrine neoplasia type 2B presents with medullary thyroid carcinoma, pheochromocytoma, Marfanoid habitus, and mucosal neuromas.

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A 29-year-old woman comes to the emergency department complaining of painful genital ulcers that have been present for 4 days as well as low-grade fever and malaise. She denies any recent travel, new sexual partners, or antibiotic use. Physical examination reveals multiple clustered vesicles and shallow ulcers in the vulvar region. A Tzanck smear shows multinucleated giant cells. Which of the following medications is most appropriate for treating her condition?

Acyclovir

Amoxicillin

Fluconazole

Metronidazole

Trimethoprim-sulfamethoxazole

A

Acyclovir

The patient's painful genital ulcers coupled with the presence of multinucleated giant cells on a Tzanck smear are indicative of a herpes simplex virus type 2 (HSV-2) infection. Acyclovir is the treatment of choice. Herpes infections can present with painful genital ulcers and low-grade fever. The Tzanck smear showing multinucleated giant cells further confirms the diagnosis though the diagnosis is typically made on clinical grounds and treated empirically. Acyclovir is the drug of choice for treating HSV-2 as it inhibits viral DNA polymerase, preventing the virus from replicating. The drug can reduce the duration and severity of symptoms but does not eradicate the virus entirely. Groves (2016) emphasizes that genital herpes, caused by the herpes simplex virus (HSV), affects over 400 million people worldwide. The infection is lifelong, with vesicular outbreaks in genital areas that can ulcerate. While HSV-1 and HSV-2 are both culprits, the latter increases the risk of HIV acquisition. The polymerase chain reaction assay is the recommended diagnostic method. Nucleoside analogues are effective treatments, and pregnant women with the condition are advised antiviral prophylaxis from the 36th week until delivery to prevent neonatal complications. Incorrect Answers: Answer B: Amoxicillin is an antibiotic ineffective against viral infections like HSV-2. It is commonly used for bacterial infections such as streptococcal pharyngitis. Answer C: Fluconazole is an antifungal agent is used for treating fungal infections like Candida which may cause esophagitis or vaginitis. Answer D: Metronidazole is used primarily for anaerobic bacterial and protozoal infections. Answer E: Trimethoprim-sulfamethoxazole is used for bacterial infections like urinary tract infections and also offers MRSA coverage. Bullet Summary: Acyclovir is the drug of choice for treating herpes simplex virus infections.

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A 32-year-old G1P0 woman at 12 weeks gestation presents to her obstetrician for a follow-up appointment. She first presented 4 weeks ago with bilateral hand tremors. At that time, she was found to have a thyroid-stimulating hormone (TSH) concentration <0.01 mU/L and an elevated free T4. She was started on propranolol and propylthiouracil. The dosage of both medications has been titrated to the maximum dose. She reports mild improvement in her symptoms but continues to experience sweating and palpitations. She has a past medical history of polycystic ovary syndrome. Her family history is notable for hypothyroidism in her mother. She does not smoke cigarettes, stopped drinking alcohol prior to pregnancy, and does not use drugs. Her temperature is 97.6°F (36.4°C), blood pressure is 113/70 mmHg, pulse is 126/min, and respirations are 18/min. On physical exam, she appears anxious, mildly diaphoretic and has a non-tender prominence on her neck which is shown in Figure A. Which of the following is the most appropriate next step in management?

Continue routine prenatal care only

Methimazole

Oral iodinated contrast

Radioiodine ablation

Thyroidectomy in the 2nd trimester

E

Thyroidectomy in the 2nd trimester

This patient who initially presented with tremors, a suppressed TSH, and elevated T4 has Graves disease which was appropriately treated with propranolol and propylthiouracil. However, she has persistent symptoms (diaphoresis, palpitations, tachycardia, nontender goiter) despite maximum doses of these medications, which should then be treated with surgical thyroidectomy which can be performed safely in the 2nd trimester of pregnancy. Graves disease is caused by TSH receptor antibodies that activate the TSH receptor to synthesize thyroid hormone, leading to hyperthyroidism with suppressed TSH levels. The initial treatment for Graves disease is symptom control with a beta-blocker (e.g., propranolol) and inhibition of thyroid hormone synthesis with a thionamide (e.g., propylthiouracil or methimazole). In the 1st trimester of pregnancy, propylthiouracil is preferred to methimazole. In the 2nd and 3rd trimesters, methimazole is the preferred thionamide. The treatment of choice in pregnancy for Graves disease that is refractory to propranolol and a thionamide is thyroidectomy, which can safely be performed in the 2nd trimester. This is reserved only for more severe cases refractory to medical treatment. In nonpregnant patients, radioiodine ablation is the preferred treatment for refractory Graves disease but is contraindicated during pregnancy due to the risk of ablating the fetal thyroid. Davies et al. reviewed the pathogenesis, diagnosis, and treatment of Graves disease. They found that Graves disease is caused by autoantibodies to the TSH receptor, resulting in overactive thyroid hormone secretion. They recommend that Graves's disease be treated with antithyroid drugs, radioiodine ablation, or surgery depending on clinical characteristics. Figure A demonstrates goiter, a common finding in Graves disease that reflects thyroid growth in response to activation by TSH receptor antibodies. Incorrect Answers: Answer A: Continuing routine prenatal care does not address the symptoms of the patient's hyperthyroidism. Poorly-controlled hyperthyroidism can lead to spontaneous abortion, premature labor, low birth weight, heart failure, and preeclampsia in pregnant individuals. Therefore, Graves disease should be treated in pregnant individuals. Answer B: Methimazole is a thionamide that is an alternative to propylthiouracil in nonpregnant individuals. It is more potent than propylthiouracil. Methimazole is contraindicated during the 1st trimester of pregnancy due to its teratogenic effects on the fetus during organogenesis. Answer C: Oral iodinated contrast agents inhibit the peripheral conversion of T4 to T3 and may be used in thyroid storm in nonpregnant patients outside of the United States. Patients with thyroid storm present with tachycardia, arrhythmias, heart failure, and hyperpyrexia. Answer D: Radioiodine ablation is the preferred definitive treatment for Graves disease in nonpregnant individuals. It is contraindicated in pregnancy as fetal thyroid tissue has developed by 10-12 weeks of gestation and may be ablated alongside the maternal tissue. Bullet Summary: Initial treatment of Graves disease in pregnancy is propranolol and propylthiouracil, whereas severe symptoms that are refractory to medical management should be treated with thyroidectomy.

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A 54-year-old man presents to the clinic with 4 weeks of persistently worsening back pain. The pain is localized to 1 spot in his lower back and is worse with physical activity. His medical history is pertinent for intravenous drug use. He has no past surgical history. His temperature is 36.8°C (98.2°F), blood pressure is 118/90 mmHg, pulse is 92/min, respirations are 13/min, and oxygen saturation is 99% on room air. On physical exam, he has midline back tenderness to palpation at L2-L3. Laboratory workup reveals an erythrocyte sedimentation rate of 112 mm/h and C-reactive protein of 10 mg/dL. Which of the following is the most likely diagnosis?

Ankylosing spondylitis

Degenerative spine disease

Herniated disc

Metastatic tumor

Osteomyelitis

E

Osteomyelitis

This patient with a history of intravenous drug use who presents with worsening focal back pain and elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) most likely has vertebral osteomyelitis. Vertebral osteomyelitis typically occurs via three routes: hematogenous spread from a distant site (the most common mechanism), direct inoculation from spinal surgery or trauma, or contiguous spread from adjacent soft tissue infection. Patients usually present with back or neck pain, with or without fever, and the most common clinical finding is local tenderness to percussion over the involved posterior spinous process. Risk factors include injection drug use, degenerative spine disease, prior spinal surgery, infective endocarditis, diabetes mellitus, corticosteroid therapy, and other immunocompromised states. Vital signs may be normal, and laboratory evaluation commonly reveals an elevated white blood cell count, ESR, and CRP. An MRI of the spine is the most appropriate diagnostic test. In stable patients, antimicrobial therapy should be withheld until a microbiological diagnosis is confirmed; once the diagnosis is confirmed, pathogen-directed therapy should then be administered. Beronius et al. conducted a retrospective study on vertebral osteomyelitis in pursuit of diagnostic criteria to simplify the diagnosis and classification of vertebral osteomyelitis. The authors found that elevated ESR and CRP are found in most patients with vertebral osteomyelitis. The authors recommend clinicians have a high index of suspicion for vertebral osteomyelitis in order to avoid delayed diagnosis. Incorrect Answers: Answer A: Ankylosing spondylitis is an inflammatory arthritis of the spine and is often associated with one or more articular or periarticular extraspinal features, including synovitis, dactylitis, and enthesitis. Patients typically present with chronic back pain and loss of mobility before the age of 45. Answer B: Degenerative spine disease involves osteoarthritis of the spine and is associated with increasing age, presenting commonly as sharp or chronic pain in the neck or back. It typically does not result in radiculopathy, defined as irritation or injury of a nerve root, causing pain, weakness, numbness, or tingling in specific distributions depending on the location of the affected nerve root. Though it is certainly on the differential for this patient, his elevated ESR and CRP make osteomyelitis a more likely diagnosis. Answer C: Herniated disc can cause a variety of symptoms depending on the position and size of the herniation. If the herniated disk impinges on a nerve, patients may have radiculopathy. Answer D: Metastatic tumor is typically suspected in patients with back pain in the setting of a known malignancy. The most common primary cancers that metastasize to bone include breast, prostate, thyroid, lung, and renal cancer. Bullet Summary: Vertebral osteomyelitis typically presents as focal back pain, with or without fever, with an elevated erythrocyte sedimentation rate and C-reactive protein.

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A 55-year-old woman presents to the primary care clinic for her annual visit. She has no complaints and is asymptomatic. She has a history of hypertension, hyperlipidemia, and diabetes. Her medications are lisinopril, amlodipine, atorvastatin, and metformin. There is no family history of malignancy. She is a non-smoker and drinks 3-4 standard drinks per week. Her temperature is 98.2°F (36.8°C), blood pressure is 142/84 mmHg, pulse is 82/min, and respirations are 16/min. On physical exam, a solid, immobile neck mass is palpated inferior to the cricoid cartilage to the left of midline. An ultrasound is obtained and shows a 1.2 cm hypoechoic mass with microcalcifications. Serum thyroid-stimulating hormone (TSH) concentration is 7.2 µU/mL. Which of the following is the most appropriate next step in management?

Fine needle aspiration

Propylthiouracil

Radioiodine ablation

Surgical removal of the mass

Thyroid scintigraphy

A

Fine needle aspiration

This patient’s presentation with an asymptomatic thyroid nodule with suspicious ultrasound features (≥ 1 cm hypoechoic mass with microcalcifications) and elevated TSH is concerning for thyroid malignancy. The most appropriate next step in management is a fine needle aspiration (FNA). The first step in the diagnostic work-up of a thyroid nodule, which can be found incidentally in asymptomatic individuals or in the presence of obstructive or vocal symptoms, includes an ultrasound and measurement of serum TSH levels. If TSH is normal or elevated, this suggests a hypofunctioning (“cold”) nodule, which increases the risk of cancer. These nodules should undergo FNA if suspicious sonographic findings are present. Suspicious sonographic findings include irregular margins, microcalcifications, taller-than-wide shape, and rim calcifications in nodules ≥ 1 cm in diameter. If TSH is low, then thyroid scintigraphy (radioiodine scan) should be performed to confirm whether the nodule is hyperfunctioning (“hot”). Hyperfunctioning nodules are rarely cancerous, so these patients can often avoid FNA. Hyperfunctioning nodules such as toxic adenomas which cause overt hyperthyroid symptoms may warrant further treatment with radioiodine, surgery, or anti-thyroid medications. Durante et al. review the epidemiology and diagnostic approach to thyroid nodules. The authors find that nodules with suspicious sonographic patterns such as solid composition, hypoechogenicity, irregular margins, and microcalcifications should undergo cytological evaluation. The authors recommend molecular testing only in cases in which cytology is indeterminate. Incorrect Answers: Answer B: Propylthiouracil is a thionamide that inhibits thyroid peroxidase, thus preventing thyroid hormone synthesis. It can be used for the symptomatic control of hyperthyroidism in toxic adenomas prior to definitive surgical resection. It is not indicated for the treatment of a hypofunctioning nodule. Answer C: Radioiodine ablation can be used in the treatment of a toxic adenoma, which would take up the radioactive iodine. It is not indicated for the treatment of a hypofunctioning nodule, which would not exhibit radioiodine uptake. Answer D: Surgical removal of the mass is a treatment option for a malignant thyroid nodule. Although a hypofunctioning nodule is more likely to be malignant, an FNA should be performed first to confirm the diagnosis. Answer E: Thyroid scintigraphy is used for thyroid nodules with low TSH, which increases the probability of a hyperfunctioning nodule. Confirmation of a hyperfunctioning nodule can help prevent further invasive diagnostic work-up because hyperfunctioning nodules are unlikely to be malignant. Thyroid scintigraphy would not be appropriate in this patient with an elevated TSH. Bullet Summary: The next step in management for a thyroid nodule with suspicious sonographic features and an elevated TSH is fine needle aspiration.

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A 45-year-old man with a past medical history of obesity presents with a concern about his sexual performance. He has a history of depression which is well managed with fluoxetine. He states that since starting the medication, his sexual drive has increased, yet he is unable to achieve orgasm. As a result, he refuses to take the medication anymore. He has a past medical history of diabetes and notes that his home blood glucose readings have been higher lately. His temperature is 98.3°F (36.8°C), blood pressure is 127/82 mmHg, pulse is 88/min, respirations are 14/min, and oxygen saturation is 99% on room air. Physical exam reveals an obese man in no acute distress with a normal affect and non-focal neurologic exam. The physician agrees to change the patient’s antidepressant. Which of the following is the most appropriate treatment for this patient?

Bupropion

Electroconvulsive therapy

Escitalopram

Mirtazapine

Phenelzine

A

Bupropion

This patient is presenting with anorgasmia in the setting of treatment with a selective serotonin reuptake inhibitor (SSRI). Given his obesity, worsening home blood glucose levels, and desire for improved sexual performance, bupropion is an appropriate medication. Bupropion is an antidepressant that is not used first-line except in certain circumstances. Situations where bupropion is an appropriate agent for the management of depression include smoking cessation as it decreases smoking cravings. Bupropion is also weight neutral and is preferred in obese patients, patients who are gaining weight on other medications, and patients with poorly-managed diabetes. Finally, it does not have any sexual side effects in contrast to SSRIs. However, bupropion lowers the seizure threshold and should be avoided in patients at higher risk for seizures. Bupropion is sometimes given with other antidepressants for patients with persistent or refractory symptoms. Patel et al. review bupropion. They note the effectiveness of bupropion in managing depression and note that it can be given with other agents. They recommend its use, in particular, for smoking cessation or patients who need a more weight-neutral treatment. Incorrect Answers: Answer B: Electroconvulsive therapy is a highly effective therapy for depression; however, it is generally used in cases of severe suicidality, malnutrition due to food refusal secondary to depressive disorder, or last line when other medications have failed. This patient is primarily experiencing sexual side-effects and has gained weight, making bupropion a more viable initial alternative. Answer C: Escitalopram is merely a different SSRI that will lead to similar side effects. Thus, it would not be appropriate. Changing SSRIs is appropriate if the first SSRI does not work after an appropriate trial period of at least 4 weeks in the management of depression. Other changes when an SSRI fails to control symptoms include increasing the dose. Answer D: Mirtazapine is an antidepressant that increases appetite and leads to weight gain and would further worsen this patient’s obesity. It is preferred in conditions such as anorexia nervosa given weight gain is preferable in this population. Answer E: Phenelzine is a monoamine oxidase inhibitor and is usually used third-line (or later) in the management of depression given side-effects such as hypertensive crisis and the long washout period and interactions with other medications. Bupropion is a safer initial alternative. Bullet Summary: Patients with depression who experience sexual side effects or weight gain on SSRIs may be switched to bupropion.

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A 69-year-old patient presents to the emergency department with shortness of breath and substernal pain. The patient has a medical history of obesity, anxiety, and constipation. He is currently not taking any medications and has not filled his prescriptions for over 1 year. An ECG is obtained and is seen in Figure A. The patient is managed appropriately and is discharged on atorvastatin, metoprolol, aspirin, clopidogrel, and sodium docusate. The patient visits his primary care physician 4 weeks later and claims to be doing better. He has been taking his medications and resting. At this visit, his temperature is 99.5°F (37.5°C), blood pressure is 130/87 mmHg, pulse is 80/min, respirations are 11/min, and oxygen saturation is 96% on room air. The patient states he feels better since the incident. Which of the following is the most appropriate next step in management?

Add hydrochlorothiazide

Add lisinopril

Add nifedipine

Continue current medications and schedule follow up

Switch beta-blocker to carvedilol

B

Add lisinopril

This patient is presenting after a myocardial infarction for a follow-up appointment. The most appropriate next step in management is to start an angiotensin-converting enzyme (ACE) inhibitor such as lisinopril. When a patient experiences a myocardial infarction, there are certain medications that the patient should be started on that lower mortality. These medications include beta-blockers, aspirin, statins, other antiplatelet agents (clopidogrel), and ACE inhibitors. ACE inhibitors can reduce mortality after myocardial infarction by reducing afterload, allowing the damaged myocardium to maintain its ejection fraction. These medications also inhibit ventricular remodeling in this disease. ACE inhibitors most prominently reduce mortality if a patient's ejection fraction is reduced. Of note, ACE inhibitors also reduce mortality in diabetes by decreasing hyperfiltration damage to the glomeruli. Jering et al. hypothesized that using an angiotensin receptor neprilysin inhibitor would improve mortality in patients who have sustained a myocardial infarction. They discuss how an ACE inhibitor is the standard of care in patients currently. They recommend performing a randomized controlled trial comparing these treatment modalities. Figure/Illustration A demonstrates an ECG with ST elevation (red circles) in leads II, III, and AVF. These ST elevations are indicative of a STEMI. Incorrect Answers: Answer A: Hydrochlorothiazide can be used to manage this patient's blood pressure; however, this drug does not lower mortality like an ACE inhibitor. In the setting of patients with myocardial infarctions, inhibition of detrimental ventricular remodeling is key for lowering mortality. Answer C: Nifedipine is a calcium channel blocker that can be used to reduce blood pressure; however, it does not reduce mortality in patients who have experienced an MI. Calcium channel blockers tend to have few side effects and can be safely started in most patients. Answer D: Continuing current medications and scheduling a follow-up appointment misses the opportunity for the patient to be started on a mortality-lowering ACE inhibitor. In patients who are amenable to starting a new medication, an ACE inhibitor should be administered to all patients who have sustained an MI. Answer E: Switching to carvedilol would be unnecessary and not likely to benefit this patient as much as adding an ACE inhibitor. Metoprolol is the preferred beta blocker in patients who have sustained an MI. In the absence of idiosyncratic side effects, there is no indication to use another beta blocker. Bullet Summary: Patients who have experienced a myocardial infarction should be discharged on mortality-lowering drugs such as aspirin, beta-blockers, anti-platelet agents, and ACE inhibitors.

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A 67-year-old man presents to the emergency department with shortness of breath. His dyspnea began 1 hour ago while he was sitting in a chair watching television. He also endorses lightheadedness and fatigue but denies chest pain. Two weeks ago, he had a mitral valve repair for mitral insufficiency secondary to myxomatous degeneration. His medical history is otherwise significant for hypertension and diabetes mellitus, for which he takes metformin and lisinopril. His temperature is 98.8°F (37.1°C), blood pressure is 85/54 mmHg, pulse is 48/min, and respirations are 22/min. On physical exam, he appears to be in moderate distress. He has normal cardiac sounds with an irregular rhythm. His lungs are clear to auscultation bilaterally, and his electrocardiogram can be seen in Figure A. The patient is given an initial dose of atropine but this has no effect. Which of the following is the most appropriate next step in management?

Adenosine

Atropine

Cardioversion

Procainamide

Transvenous pacing

E

Transvenous pacing

This patient who presents with lightheadedness has an ECG consistent with a Mobitz type 2 2nd-degree heart block. Because the patient is symptomatic from his dysrhythmia and it did not respond to atropine, the most appropriate next step is transvenous pacing. Mobitz type 2 2nd-degree heart block can be distinguished from Mobitz type 1 (Wenckebach) by the length of the PR interval. Whereas the PR interval in Mobitz type 1 becomes progressively longer with each beat, the PR intervals in Mobitz type 2 are consistent in length and the QRS complexes drop suddenly. While Mobitz type 1 heart block is usually caused by atrioventricular (AV) node dysfunction, Mobitz type 2 is caused by dysfunction below the AV node in the His-Purkinje system. Patients with either type of heart block can present with lightheadedness or syncope. Since this pattern has a risk of progressing into 3rd-degree heart block, hemodynamic compromise, and asystole, Mobitz type 2 heart block is an indication for placement of a permanent pacemaker. Unstable patients who do not respond to atropine and/or other medical management should undergo transcutaneous or transvenous pacing. Clark and Prystowsky present the pathophysiology of heart block. They discuss how dysfunction at the infranodal level leads to type 2 2nd-degree heart block. They recommend pacing in symptomatic patients. Figure/Illustration A is an ECG that is characterized by consistent PR intervals (red lines) and sudden drops in the QRS complex. This pattern is classically seen with a Mobitz type 2 2nd-degree heart block. Incorrect Answers: Answer A: Adenosine can be used to terminate supraventricular tachycardia. These patients will present with tachycardia rather than bradycardia and will experience palpitations in addition to lightheadedness. The rhythm is rapid and regular with a narrow QRS complex. Answer C: Cardioversion can be used to convert atrial flutter, atrial fibrillation, stable monomorphic ventricular tachycardia, or recalcitrant supraventricular tachycardia (non-responsive to adenosine or vagal maneuvers) to sinus rhythm, but it is not used for 2nd-degree heart block. Answer B: Atropine can improve Mobitz type 1 2nd-degree heart block but tends not to be effective in Mobitz type 2 heart block in a stable patient. Atropine might be an appropriate treatment in symptomatic 3rd-degree heart block or Mobitz type 2 heart block; however, if it fails to improve a patient's symptoms, pacing is the most appropriate next step. Answer D: Procainamide is a class 1A antiarrhythmic medication used to treat Wolff-Parkinson-White syndrome. This would present with an upgoing delta wave that occurs prior to the QRS complex. This medication does not play a role in the management of 2nd-degree heart block. Bullet Summary: Hemodynamically unstable patients with Mobitz type 2 2nd-degree heart block should be managed with transvenous pacing followed by a permanent pacemaker.

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A 3-day-old boy is evaluated in the hospital nursery for the delayed passage of meconium. The patient is breastfed, has been feeding well every 2 hours, and is urinating over 8 times per day. He was born at 35 weeks gestation to a 27-year-old G4P4 mother. The patient is of Ashkenazi Jewish descent and the patient’s parents refused all prenatal genetic testing. The pregnancy was uncomplicated until the patient’s mother had a spontaneous rupture of membranes at 35 weeks of gestation. The patient’s 3 older siblings are all healthy. The patient’s temperature is 98.2°F (36.8°C), blood pressure is 48/32 mmHg, pulse is 164/min, and respirations are 48/min. On physical exam, he appears to be in moderate distress. He has no dysmorphic features, and his abdomen is distended and non-tender. Bowel sounds are absent. Which of the following is the most appropriate next step in management?

Abdominal CT

Abdominal radiograph

Contrast enema

Sweat testing

Upper gastrointestinal series

B

Abdominal radiograph

Delayed passage of meconium should be evaluated with an abdominal radiograph to rule out bowel perforation. Patients with a perforation require emergency surgery. All neonates should pass meconium in the first 48 hours of life. Patients that fail do to so should be evaluated with an abdominal radiograph to exclude the possibility of bowel perforation. If free air is seen on the abdominal radiograph, patients should be taken for emergent surgery to repair the perforation. If bowel perforation is ruled out, a workup should be done to determine the etiology of the delayed passage, which would most likely include a contrast enema to differentiate between meconium ileus and Hirschsprung disease. Treatment is with meconium removal or excision of the defective segment respectively. 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. Incorrect Answers: Answer A: An abdominal radiograph would be faster than an abdominal CT to rule out an indication for emergency surgery. The use of CT should also be restricted in the pediatric population due to the radiation exposure involved. Adult patients with unclear radiographic findings can be further assessed using a contrast CT scan. Answer C: Contrast enema is the test of choice to differentiate meconium ileus from Hirschsprung disease, but the most important first step is to rule out bowel perforation. Patients who do not have perforation can then undergo this test to determine the etiology of failure to pass meconium. Answer D: Sweat testing would aid in the diagnosis of cystic fibrosis, particularly in this patient who has had no prenatal screening. The first step in management should be an abdominal radiograph to rule out bowel perforation. Cystic fibrosis can be treated with pancreatic enzyme replacement and pulmonary therapy. Answer E: Upper gastrointestinal series is used to make the diagnosis of intestinal malrotation, which more commonly presents with bilious vomiting secondary to midgut volvulus rather than the delayed passage of meconium. Treatment is with surgical derotation. Bullet Summary: Neonates who fail to pass meconium in the first 48 hours of life should be urgently evaluated with an abdominal radiograph to rule out bowel perforation.

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A 25-year-old man presents to his primary care physician with anxiety and fatigue. During this past week, he has been unable to properly study and prepare for final exams because he is exhausted. He has been going to bed early but is unable to get a good night’s sleep. He admits to occasional cocaine and marijuana use. Otherwise, the patient has no significant medical history and is not taking any medications. His temperature is 98.6°F (37°C), blood pressure is 115/71 mmHg, pulse is 72/min, and respirations are 12/min. On physical exam, the patient is a tired and anxious appearing young man. His neurological exam is within normal limits. The patient states that he fears he will fail his courses if he does not come up with a solution. Which of the following is the most appropriate initial step in management?

Alprazolam

Melatonin

Polysomnography

Sleep hygiene education

Zolpidem

D

Sleep hygiene education

This patient is presenting with trouble sleeping without a known organic cause, for which the most appropriate initial step in management is to discuss sleep hygiene with the patient. In any patient that presents with a chief complaint of fatigue, it is always best to assess how they are sleeping. After a physical exam is performed in order to rule out signs or symptoms of a severe organic cause (neurologic deficits), the most appropriate initial step in management is to discuss sleep hygiene with the patient. Sleep hygiene includes discussing the patient’s exposure to light (eliminate exposure to blue light at night), altering diet (no large meals or caffeine before bed), and behavioral modification (only using the bed for sleep). Once a trial of proper sleep hygiene has been tried, then it would be appropriate to potentially move on to other interventions including pharmacological interventions. Horne presents evidence regarding the best sleep hygiene practices. He discusses how exercise and avoidance of caffeine near bedtime is beneficial to helping with insomnia. He recommends using these interventions prior to pharmacologic treatment. Incorrect Answers: Answer A: Alprazolam is a benzodiazepine that could be used to help with this patient’s anxiety and could help them sleep. However, benzodiazepines are potent drugs with addictive properties and would not be used as first-line treatment for insomnia. Lifestyle modifications should be tried first to determine if these will be effective in helping the patient sleep. Answer B: Melatonin is a supplement that is often used to improve sleep quality. Starting the patient on a supplement is plausible as an initial step in management, but it would not take precedence over educating the patient regarding sleep hygiene. These interventions often are very effective and have no side effects. Answer C: Polysomnography could be the most appropriate initial step in management if an organic cause for this patient’s sleep problems (such as obstructive sleep apnea) is suspected. There is nothing suggesting an organic cause for this patient’s sleep issues and it is highly likely that a college-age student near finals period would benefit from a discussion on sleep hygiene prior to an expensive diagnostic test such as polysomnography. Answer E: Zolpidem is a muscle relaxant and hypnotic with a similar mechanism of action to a benzodiazepine. Zolpidem has the potential to be addicting and would not be tried prior to sleep hygiene interventions. Some patients who are refractory to other interventions may benefit from the use of Zolpidem. Bullet Summary: Any patient that presents with fatigue and trouble sleeping without a clear organic cause should first be counseled in sleep hygiene habits prior to any other interventions or diagnostic tests.

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A 67-year-old man presents to the emergency room reporting sudden-onset abdominal and back pain that began 3 hours ago. He was eating dinner when he started feeling severe pain in his abdomen that made him lose his appetite. He denies any diarrhea or hematochezia and says the pain is not affected by movement. He has a history of hypertension, hyperlipidemia, and depression. He currently takes amlodipine and atorvastatin and is compliant with his medications. He has a 45-pack-year smoking history, but he does not drink alcohol or use any illicit drugs. His temperature is 98.6°F (37°C), his blood pressure is 110/64 mmHg, pulse is 97/min, and respirations are 15/min. Physical exam is notable for diffuse abdominal tenderness without rigidity or guarding. During evaluation, the patient becomes diaphoretic and pale and reports that he feels fatigued. Repeat blood pressure is 87/50 and pulse is 127. Intravenous fluid boluses are administered. Which of the following is the most likely diagnosis?

Acute pancreatitis

Aortic dissection

Ischemic colitis

Perforated viscus

Ruptured abdominal aortic aneurysm

E

Ruptured abdominal aortic aneurysm

This patient who presents with sudden-onset abdominal pain, hemodynamic instability (symptomatic hypotension with tachycardia), and significant history of hypertension and smoking most likely has a ruptured abdominal aortic aneurysm (AAA). Abdominal aortic aneurysms are dilations in the vessel wall that can predispose to rupture. Risk factors for AAA include advanced age (> 60 years), smoking history, male sex, and history of atherosclerosis. AAA can be asymptomatic or mildly symptomatic until it markedly expands or ruptures, leading to abdominal pain, back pain, or flank pain. The evaluation of suspected AAA depends on the hemodynamic stability of the patient and prior knowledge (or lack thereof) of the existence of an AAA. A hemodynamically unstable patient with a known history of AAA should be assumed to have a ruptured AAA and undergo surgical intervention without further workup (though bedside ultrasound can support the diagnosis). In an unstable patient without a known history, a bedside ultrasound to confirm the diagnosis should precede surgical intervention. In a hemodynamically stable patient with or without a known AAA history, an abdominal CTA is appropriate. Sakalihasan et al. present a review of the presentation and treatment of abdominal aortic aneurysms. They discuss how patients are often asymptomatic until catastrophic rupture occurs. They recommend immediate surgical repair of the aneurysm during ruptures to prevent death. Incorrect Answers Answer A: Acute pancreatitis also presents with abdominal pain and can present with hemodynamic instability in severe cases of hemorrhagic conversion of pancreatitis. This is a rare entity and is less likely in this patient. Treatment is immediate transcatheter arterial embolization for unstable patients with hemorrhagic pancreatitis. Answer B: Aortic dissection has similar risk factors to AAA (history of hypertension, advanced age) and also presents with acute onset back pain. Dissection normally occurs in the setting of hypertension. This diagnosis is possible but less likely in this man with a history of smoking. Answer C: Ischemic colitis can also present with abdominal pain in a patient with risk factors for atherosclerotic disease. It is associated with hematochezia and diarrhea and is unlikely to cause the level of hypotension in this patient. Treatment is with restoration of blood flow to the ischemic bowel segment or resection if this is not possible. Management is usually centered on medical optimization. Answer D: Perforated viscus is a surgical emergency that can also present acutely with hemodynamic instability and severe abdominal pain. However, signs of peritoneal irritation are usually present (guarding, rigidity). Treatment is with immediate surgical exploration and repair or resection. Bullet Summary: Patients with new-onset back and abdominal pain and a positive smoking history that progresses to hemodynamic instability should be suspected of having a ruptured abdominal aortic aneurysm.

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A 15-month-old boy presents with his mother for his well-child exam. His mother is concerned about his vision, as she noticed him squinting while watching television. The patient was born at 39 weeks of gestation via spontaneous vaginal delivery. He is up to date with routine vaccinations. He is able to walk alone, speak 3 words, and scribble with a crayon. His temperature is 98.6°F (37.0°C), blood pressure is 80/55 mmHg, pulse is 105/min, and respirations are 25/min. On exam, his pupils are round and reactive to light. A photograph of his eyes is shown in Figure A. When focusing on the pediatrician's penlight, the patient's left eye wanders. However, when the right eye is covered, the left eye refocuses on the light. The rest of his neurological exam, including extraocular movements, is within normal limits. Which of the following is the most appropriate next step in management for this patient?

Brain MRI

Head CT

Patch the left eye

Patch the right eye

Perform a Bielschowsky head tilt test

D

Patch the right eye

This patient, with a history that suggests decreased visual acuity, a positive cover test (refixation of the misaligned eye upon covering the appropriately aligned eye), and an asymmetric corneal light reflex in Figure A, is presenting with strabismus. Of the answer choices, only patching the sound eye (right eye) is an appropriate treatment. Strabismus occurs when a patient's eyes are not aligned properly. It often presents in children with one or both eyes turning inward, outward, upward, or downward. Patients will often tilt their heads or squint their eyes to correct this misalignment. Without proper treatment, there is a significant risk of developing amblyopia. Amblyopia is a developmental disorder in the visual cortex caused by abnormal visual stimuli. Untreated strabismus is the most common cause of amblyopia; it is secondary to visual loss from the deviated eye. The treatment of choice is wearing an eye patch over the appropriately tracking eye (sound eye), thereby encouraging the use of the deviated eye and preventing vision loss in this eye. Other treatments include surgical correction of strabismus, pharmacological penalization of the sound eye with atropine, and dichoptic movies and video games. Gopal et al. discuss the pathophysiology, prevention, and therapy for amblyopia as it relates to strabismus. The authors find that the earlier clinically refractive error and strabismus are detected and treated, the greater the likelihood of preventing amblyopia. The authors recommend treating amblyopia with the correction of refractive errors, patching, and pharmacologic treatments. Figure/Illustration A shows displacement of the light reflex from the center of the pupil in this patient's right eye, as indicated by the black arrow. This is known as an asymmetric corneal light reflex and is seen in strabismus. Incorrect Answers: Answer A: Brain MRI is part of the initial workup for retinoblastoma. Retinoblastoma typically presents in early childhood with visual loss, leukocoria, and an abnormal red reflex, which this patient does not have. Answer B: Head CT in a pediatric patient could be used to rule out hemorrhage following blunt head trauma. This patient has not experienced head trauma and has no symptoms of traumatic brain injury (abnormal neurologic exam, loss of consciousness seizures). CT scans are not preferred in pediatric patients to avoid radiation exposure. Answer C: Patching the left eye (the inappropriately tracking eye) would not treat this patient's strabismus and would likely increase his risk for amblyopia due to further decreasing his visual stimuli in this eye. Answer E: The Bielschowsky head tilt test is used to help diagnose trochlear nerve (CN IV) palsy. Patients with a unilateral trochlear nerve and subsequent superior oblique palsy experience double vision when tilting their head to one side, which is improved by tilting the head towards the shoulder on the unaffected side. A trochlear nerve palsy typically presents with difficulty looking down and a head tilt away from the side of the lesion, unlike this patient who appears to have a visual acuity deficit. Bullet Summary: Patching the appropriately aligned eye is the treatment of choice for strabismus to prevent progression to amblyopia.

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A 14-day-old girl is brought to the emergency department for diarrhea. Her mother reports that the patient began having “explosive” diarrhea 6 hours ago. The patient has little interest in feeding since leaving the hospital after her birth and has not yet regained her birth weight. Her immediate postnatal period was otherwise significant for 2 episodes of bilious vomiting that resolved with the temporary use of a nasogastric tube and expulsion of stool during a digital rectal exam. The patient passed meconium on the 3rd day of life. Her temperature is 101.8°F (38.8°C), blood pressure is 58/37 mmHg, pulse is 148/min, and respirations are 38/min. On physical exam, the patient appears to be in moderate distress. She has no dysmorphic features and she has a normal S1/S2 without any murmurs, rubs, or gallops. Her abdomen is firm and distended. A digital rectal exam reveals a tight anal sphincter and precipitates a release of gas and liquid stool. Her abdominal radiograph can be seen in Figure A. Which of the following is the most accurate test to diagnose this patient’s condition?

Contrast enema

Genetic testing

Intraoperative cholangiogram

Rectal suction biopsy

Upper gastrointestinal series

D

Rectal suction biopsy

This neonatal patient presents with bilious vomiting, failure to thrive, colonic distension on an abdominal radiograph, and new fever and tachycardia, which suggests a diagnosis of Hirschsprung disease complicated by enterocolitis. A rectal suction biopsy is the most accurate test to diagnose Hirschsprung disease. Hirschsprung disease presents in the neonatal period with bilious vomiting, failure to pass meconium in the first 48 hours of life, failure to thrive, and temporary relief of the intestinal obstruction by digital rectal exam. The most severe neonatal complication of Hirschsprung disease is Hirschsprung-associated enterocolitis, which presents in the first few weeks to months of life with explosive diarrhea, fever, and abdominal pain/distension. The most appropriate first step to diagnose Hirschsprung disease is a contrast enema, which may visualize a “transition zone” where the caliber of the intestine switches from the dilated proximal colon to the narrowed aganglionic segment. The most accurate test is a rectal suction biopsy, which will show a lack of ganglion cells. Surgical removal of the aganglionic portion of the colon is preferred management. Kessman reviews the evidence regarding the diagnosis and treatment of Hirschsprung disease. She discusses how the diagnosis can be made using a rectal suction biopsy. She recommends monitoring patients closely for enterocolitis for years after surgical treatment. Figure/Illustration A is an abdominal radiograph demonstrating diffuse proximal colonic distension (red circle) with a paucity of air in the rectosigmoid. This finding suggests a diagnosis of Hirschsprung disease. Incorrect Answers: Answer A: A contrast enema is both a diagnostic and therapeutic intervention for intussusception. It may also be used in the workup of bilious emesis to help differentiate between Hirschsprung disease and meconium ileus, but it is not the most accurate test. Answer B: Genetic testing would be used to diagnose cystic fibrosis, which is associated with meconium ileus. Although meconium ileus presents with delayed passage of meconium (> 48 hours of life), meconium ileus is not relieved by a digital rectal exam. Treatment is with irrigation and removal of the meconium. Answer C: Intraoperative cholangiogram is the gold standard for diagnosing biliary atresia. Biliary atresia presents with jaundice, pale stools or dark urine, and hepatomegaly over the first week to 2 months of life. Treatment is with urgent surgical intervention to prevent liver failure. Answer E: Upper gastrointestinal series is used to diagnose intestinal malrotation, as the ligament of Treitz can be visualized on the right side of the abdomen. Malrotation may present with bilious vomiting if the malrotation has been complicated by midgut volvulus, but it would not be relieved by digital disimpaction. Treatment is with surgical derotation of the volvulus. Bullet Summary: The most accurate test to diagnose Hirschsprung disease is a rectal suction biopsy to demonstrate the absence of ganglion cells.

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A 37-year-old woman presents to her physician for mood changes and recent falls over the course of 3 months. She feels more irritable with her husband and children and does not find pleasure in creating art anymore. Over the last 2 weeks, she has been sleeping approximately 5 hours a night and had a fall while walking in her home with the lights off. She denies any head trauma or loss of consciousness associated with the fall. She has a medical history of generalized anxiety disorder and hypothyroidism for which she takes escitalopram and levothyroxine. She had a Roux-en-Y gastric bypass 5 years ago. She has been in a monogamous relationship with her husband for the last 15 years and uses a copper intrauterine device. Physical examination is notable for a depressed affect. Pupils are equal, round, and reactive to light and accommodation. She has 4/5 strength in the bilateral lower extremities and brisk patellar reflexes. Which of the following is most likely the cause of this patient's symptoms?

Poor iron absorption

Prior Treponema pallidum exposure

Reduced central nervous system dopamine and serotonin

Reduced functional parietal cell count

Subtherapeutic levothyroxine dose

D

Reduced functional parietal cell count

This patient's mood changes and findings concerning for subacute combined degeneration (fall in the dark, impaired proprioception, weakness, and brisk patellar reflexes), and history of Roux-en-Y gastric bypass surgery are concerning for vitamin B12 deficiency. Roux-en-y gastric bypass reduces parietal cell count, leading to reduced intrinsic factor secretion, which is needed for vitamin B12 absorption. Roux-en-Y gastric bypass is a laparoscopic bariatric procedure that creates a small gastric pouch from the stomach with a gastrojejunal and jejunojejunal anastomosis. This causes small volumes of food to be consumed and decreases nutrient absorption. The small gastric pouch contains very few parietal cells, which decreases hydrochloric acid and intrinsic factor secretion. The reduced intrinsic factor secretion impairs the protection of vitamin B12 against HCl and reduces absorption in the ileum. Vitamin B12 deficiency can lead to neuropsychiatric changes (depressed mood, irritability, and insomnia) and subacute combined degeneration (weakness, sensory ataxia, peripheral neuropathy, and upper motor neuron signs). Patients who undergo Roux-en-Y gastric bypass must be given high doses of vitamin B12 (often intramuscularly) in order to prevent deficiency. Alexandrou et al. review long-term micronutrient deficiencies after sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB). The authors find that vitamin B12 deficiency was significantly higher in patients with RYGB compared with sleeve gastrectomy. The authors recommend adherence to supplemental iron and vitamin intake in all patients who undergo bariatric surgery. Incorrect Answers: Answer A: Poor iron absorption is a well-known complication of Roux-en-Y gastric bypass surgery due to bypass of the duodenum and proximal jejunum. Poor iron absorption leads to microcytic anemia from iron deficiency and presents with generalized fatigue and conjunctival pallor. Iron deficiency anemia would not present with brisk reflexes and impaired proprioception. Answer B: Prior Treponema pallidum exposure can result in tabes dorsalis, a neurological complication of syphilis, and is seen in patients with a history of multiple sexual partners who do not use barrier protection. The spirochete leads to disease in the posterior columns (vibration and proprioception sensation). Patients present with sensory ataxia (similar to subacute combined degeneration), lancinating pain (in the limbs, back, or face), and an Argyll-Robertson pupil (impaired pupillary constriction to light but intact pupillary constriction to accommodation). Answer C: Reduced central nervous system dopamine and serotonin are seen in patients with major depressive disorder which does not cause sensory ataxia with brisk reflexes. Answer E: Subtherapeutic levothyroxine dose would result in hypothyroidism, which can present with depressed mood, cold intolerance, bradycardia, and delayed relaxation of deep tendon reflexes. Roux-en-Y is an effective means of losing weight, and as the body mass decreases with weight loss, the required dose of levothyroxine is decreased. It would not present with the abnormal neurologic findings seen in this patient. Bullet Summary: Roux-en-Y bariatric surgery increases the risk of vitamin B12 deficiency via reduction of food intake, decreased functional parietal cell count, and reduced absorption of vitamin B12 (which may cause subacute combined degeneration).

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A 23-year-old man presents to the emergency department after he was rescued while hiking in Alaska. The patient was found on a mountain trail non-responsive. His temperature is 91°F (32.8°C), blood pressure is 103/61 mmHg, pulse is 60/min, respirations are 11/min, and oxygen saturation is 97% on room air. The patient is placed under a warm air circulator, and his extremities are bathed in warm water. An ECG is performed as seen in Figure A. Dark bullae are noted on the patient's extremities. His mental status rapidly improves with warming. Laboratory studies are ordered and are pending. Which of the following is most likely to be found in this patient?

Elevated troponin

Hypocalcemia

Hypomagnesemia

Hypophosphatemia

Red blood cells on urine microscopy

B

Hypocalcemia

This patient is presenting after being found outside with hypothermia and frostbite (dark bullae noted on the extremities in the setting of being out in the cold). Frostbite can lead to rhabdomyolysis, which may cause hyperkalemia (causing ECG changes including peaked T waves and QRS widening as seen in this patient) and hypocalcemia (the most common electrolyte finding in frostbite). Frostbite occurs when there is an extensive freezing injury to tissues and can cause benign swelling, erythema, and pain, all the way to insensate extremities with necrosis and permanent dysfunction. More severe forms of frostbite can cause rhabdomyolysis or breakdown of the muscles. Breakdown of the muscle cells leads to leakage of the intracellular contents. Common electrolyte derangements include hyperkalemia and hypophosphatemia. Hypocalcemia is the most common electrolyte derangement in rhabdomyolysis. It occurs due to the deposition of calcium in the necrotic muscle cells and the sequestration of calcium in the exposed sarcoplasmic reticulum. Note that hypocalcemia requires no treatment unless it is causing symptoms or ECG changes (such as QT prolongation). The management of rhabdomyolysis is centered on fluid administration to protect the kidney from myoglobin which is released from damaged muscles and is nephrotoxic. Zimmerman and Shen review rhabdomyolysis. They note that rhabdomyolysis can be commonly associated with myoglobinuria, hyperkalemia, hypocalcemia, and hyperphosphatemia. They suggest that an elevated creatine kinase level is indicated to support the diagnosis. Figure/Illustration A is an ECG demonstrating peaked T waves (blue arrows) which are associated with hyperkalemia. Incorrect Answers: Answer A: Elevated troponin may be seen in rhabdomyolysis. This is a non-cardiac cause of an elevated troponin; however, this is less common than hypocalcemia in rhabdomyolysis and is neither sensitive nor specific. Answer C: Hypomagnesemia is not a common electrolyte disturbance seen in rhabdomyolysis; however, hypomagnesemia may cause hypocalcemia (from impaired PTH release) and hypokalemia (from renal wasting of potassium). Note that this mechanism is separate from rhabdomyolysis. Answer D: Hypophosphatemia is common in refeeding syndrome and malnourished patients (such as those with alcohol use disorder) and presents with diffuse muscle weakness. Rather, hyperphosphatemia would be seen in rhabdomyolysis as it is released from damaged muscle cells. Answer E: Red blood cells on urine microscopy would be seen in a nephritic syndrome in addition to red blood cell casts. Note that the urine dipstick will be positive for red blood cells in rhabdomyolysis due to cross-reactivity with myoglobin; however, there are minimal/no red blood cells actually present. Bullet Summary: Frostbite can result in rhabdomyolysis which commonly causes hyperkalemia, hyperphosphatemia, and hypocalcemia (the most common derangement).

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An 8-year-old boy is brought to the emergency department by his parents for evaluation. He has had headache and fever for the last 2 days, and this morning he was confused and had difficulty answering questions. He also developed a rash this morning. He recently returned from summer camp. He has no significant medical history and takes no medications. His temperature is 104°F (40°C), pulse is 120/min, blood pressure is 105/60 mmHg, and respirations are 22/min. On exam, flexion of the neck causes flexion of the hips and knees. Fundoscopic exam reveals no papilledema. Examination of the patient's rash is shown in Figure A. Which of the following is the most appropriate next step in management?

Blood and urine cultures

Lumbar puncture, ceftriaxone, vancomycin, and methylprednisolone

MRI brain

Vancomycin and ceftriaxone

Vancomycin, ceftriaxone, and dexamethasone

B

Lumbar puncture, ceftriaxone, vancomycin, and methylprednisolone

This patient with fever, headache, signs of meningeal irritation, and a purpuric rash likely has bacterial meningitis. The most appropriate initial step in management is a lumbar puncture as well as ceftriaxone, vancomycin, and methylprednisolone. Meningitis classically presents with fever, neck stiffness or headache, and altered mental status. Specific physical exam findings that can suggest the diagnosis include meningeal signs such as a positive Kernig sign (inability to extend the knee while the hip is flexed) and Brudzinski sign (flexion of the neck results in flexion of lower extremities). Common causative agents include Streptococcus pneumoniae and Neisseria meningitidis. The latter of which is associated with the purpuric rash seen in this patient. The best initial step in management is a lumbar puncture followed promptly by IV broad spectrum antibiotics. Once the diagnosis/infectious agent is confirmed, the antibiotic agents can be refined. Other early steps in management include early blood cultures and fluid resuscitation. Steroids should be given in the setting of suspected Waterhouse-Friderichsen syndrome and concern for adrenal failure. Linder et. al review meningococcal meningitis. They discuss the pathophysiology, clinical manifestations, and diagnosis. They describe the association of purpuric rash with meningococcal infection, and note that this is indicative of disseminated intravascular coagulation. Figure A. demonstrates a purpuric rash over the lower extremities, which is classically associated with meningococcal meningitis. However, this can occur with meningitis or bacteremia from other infectious agents, as it is indicative of disseminated intravascular coagulation. Incorrect Answers: Answer A: Blood and urine cultures would be appropriate initial management for a fever of unknown origin and in this patient. Early antibiotics must be given as well to reduce mortality and improve outcomes. Answer C: MRI brain would not be appropriate in this setting. While CNS imaging is sometimes indicated prior to lumbar puncture if signs of increased intracranial pressure such as papilledema are present, CT imaging is typically preferred. Time required to obtain MR imaging is prohibitive and would delay definitive care for this patient. Answer D: Vancomycin and ceftriaxone are an appropriate initial antibiotic regimen for meningitis in children and adults. However, steroids are often added empirically. Lumbar puncture should be performed prior to administration of antibiotics (if possible) to avoid sterilization of the CSF. Answer E: Vancomycin, ceftriaxone, and prednisone are an appropriate initial regimen for meningitis in adults. Steroids have been shown to reduce inflammation and prevent neurologic sequelae. However, lumbar puncture should be performed prior to administration of antibiotics if possible to avoid sterilization of the CSF. Also, IV steroids are preferred rather than oral in ill patients. Bullet Summary: The best initial step in management for meningitis is a lumbar puncture followed by broad-spectrum antibiotics and steroids.

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A 55-year-old man presents to the emergency department with chest pressure and diaphoresis. His symptoms started at work when he was lifting boxes. He states that he currently feels crushing pressure over his chest. He is given aspirin and an ECG is performed in triage, as seen in Figure A. His past medical history is notable for diabetes and obesity. He has smoked 1 pack of cigarettes per day for the past 30 years. His temperature is 97.9°F (36.6°C), blood pressure is 155/99 mmHg, pulse is 110/min, respirations are 22/min, and oxygen saturation is 98% on room air. Physical exam reveals an uncomfortable, diaphoretic man. His heart and breath sounds are unremarkable. A repeat ECG in the emergency department is performed, also seen in Figure A. The patient’s chest pain is worse when the ECG in the emergency department is taken, compared to the one taken in triage. He is given nitroglycerin, with minimal improvement in his symptoms. A troponin level is drawn. Which of the following is the most appropriate next step in management?

Cardiac catheterization

Chest radiograph

CK-MB level

Heparin

Repeat ECG in 10 minutes

E

Repeat ECG in 10 minutes

This patient is presenting with a pattern of chest pain (pressure and diaphoresis) that is highly concerning for an acute myocardial infarction. This patient initially has ST depressions (in triage) followed by ST segment normalization and possibly hyperacute T waves which raises concern for an acute ST elevation myocardial infarction (STEMI) requiring frequent ECGs to determine if a STEMI evolves. A STEMI presents with crushing substernal chest pain, diaphoresis, chest pressure, nausea, vomiting, and abdominal pain among many other possible presentations. When a patient presents with symptoms concerning for a STEMI, aspirin should be administered and an ECG should be performed. Early in a myocardial infarction, ST depressions with hyperacute T waves may be present. As the infarction evolves, the T waves may become more acute and the ST segment will begin to elevate. There may be a brief period of pseudonormalization where the ST segment appears to be normal. If the patient appears better, this can be reassuring. However, ongoing chest pain in the setting of these findings raises concern for pseudonormalization of the ST segment (an ST segment that is going to continue to rise). Nitroglycerin can be administered to see if the patient can become chest pain-free, and serial ECGs should be performed to determine if a STEMI is present. If symptoms resolve and the ECG is stable, this is reassuring and medical optimization and an elective catheterization may be performed. If the ECG evolves into a STEMI, then cardiac catheterization is indicated emergently. Daga et al. discuss STEMI and its workup. They note the ECG manifestations, and the pathophysiology in addition to the appropriate workup of acute coronary syndrome. They recommend aspirin and catheterization in an acute STEMI. Figure/Illustration A demonstrates an initial ECG with ST depression (blue arrows) followed by pseudonormalization of the ST segment (green arrows) and possibly hyperacute T waves (black arrows), which are concerning for ischemia. Incorrect Answers: Answer A: Cardiac catheterization may be required in this patient; however, if the patient’s chest pain improves or if the troponin is negative, it is unlikely he is having an acute myocardial infarction requiring immediate catheterization. Repeating the ECG will allow for triaging of the patient and will aid in determining if emergency cardiac catheterization is needed. Answer B: Chest radiography is appropriate in the workup of chest pain as it can rule out diagnoses such as pneumothorax or may suggest diagnoses such as an aortic dissection (type A) if there is a widened mediastinum. In this patient, the ST segment changes and characteristic history make acute coronary syndrome a more likely diagnosis, and while a chest radiograph should be performed at some point, repeating the ECG is a more dire initial step in management. Answer C: CK-MB level could be helpful in determining if a myocardial infarction has occurred as it elevates rapidly and also decreases fairly rapidly. This makes it useful when diagnosing a new myocardial infarction after a recent infarction as the troponin may still be elevated from the previous infarction. This patient has no history of recent myocardial infarction, and a repeat ECG is more dire to determine if this patient needs emergent intervention. Of note, the decision for emergent catheterization should not wait on cardiac biomarkers. Answer D: Heparin should not be given empirically to patients in chest pain. It does not necessarily decrease mortality but does increase the risk of bleeding. It is often given to patients with an NSTEMI. Bullet Summary: Pseudonormalization occurs when an ST depression begins to elevate and appears normal in the setting of a myocardial infarction, requiring close monitoring and serial ECGs to ensure that a ST elevation myocardial infarction does not occur.

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A 47-year-old woman presents to the clinic with 3 weeks of increased thirst and urination. She has a history of obesity, hypertension, and depression for which she takes losartan and sertraline. She has smoked 1 pack of cigarettes per day for 30 years. Her temperature is 99.5°F (37.5°C), blood pressure is 148/90 mmHg, pulse is 84/min, and respirations are 15/min. Physical exam is unremarkable, including no costovertebral or suprapubic tenderness to palpation. Laboratory studies are performed and show: Serum: Na+: 140 mEq/L K+: 4.4 mEq/L HCO3-: 21 mEq/L Blood urea nitrogen (BUN): 38 mg/dL Creatinine: 1.1 mg/dL Glucose: 215 mg/dL Which of the following is the most appropriate screening test for nephropathy in this patient?

Creatinine clearance

Hemoglobin A1c

Oral glucose tolerance test

Urine albumin-to-creatinine ratio

Urine protein dipstick

D

Urine albumin-to-creatinine ratio

This patient with a history of obesity and hypertension presenting with polyuria and polydipsia in the setting of an elevated random blood glucose (> 200 mg/dL) likely has a new diagnosis of type 2 diabetes mellitus. The urine albumin-to-creatinine ratio is the most appropriate early test for diabetic nephropathy. Early detection of diabetic nephropathy is key to management, as the complication eventually leads to overt kidney disease and renal failure. The diagnosis of diabetic nephropathy is based on > 30 mg/g of albuminuria for > 3 months. Patients with type 2 diabetes mellitus should be screened annually with a random urine albumin-to-creatinine ratio starting at diagnosis. Elevation of urine albumin warrants treatment with ACE inhibitors or angiotensin receptor blockers. Blood pressure control slows the progression of diabetic nephropathy. Patients with type 2 diabetes mellitus and diabetic nephropathy should be started on a sodium-glucose cotransporter 2 (SGLT2) inhibitor. Patients with persistent albuminuria despite both ACE/ARB and SGLT2 inhibitor therapy should be started on the nonsteroidal selective mineralocorticoid receptor antagonist (MRA) finerenone. Bakris et al. study the efficacy of finerenone, a nonsteroidal selective MRA, in the treatment of patients with albuminuria in patients with chronic kidney disease (CKD) and type 2 diabetes. The authors found in a randomized control trial that finerenone reduced the incidence of a composite outcome of kidney failure. The authors recommend the use of finerenone in patients with persistent albuminuria despite optimal medical therapy to prevent risks of CKD progression and cardiovascular events. Incorrect Answers: Answer A: Creatinine clearance changes over the time course of diabetic nephropathy and can be normal or elevated (due to glomerular hyperfiltration) in early diabetic nephropathy. Therefore, it is an unreliable test for early diabetic nephropathy compared to the more sensitive urine albumin-to-creatinine ratio. Answer B: Hemoglobin A1c is a test that reflects the average blood glucose over the past 2 to 3 months. While this test provides information on a patient's glycemic control, it does not directly assess the presence or extent of diabetic nephropathy. Answer C: Oral glucose tolerance test is the test of choice for diagnosing gestational diabetes. It does not play a role in the detection of diabetic nephropathy. Answer E: Urine protein dipstick is a useful test to detect proteinuria. This test is insensitive to low levels of albumin. Therefore, it is considered an inferior test to urine albumin-to-creatinine ratio in the diagnosis of diabetic nephropathy. Bullet Summary: Urine albumin-to-creatinine ratio testing is the most sensitive test to detect moderately elevated levels of urinary albumin excretion, a known byproduct of diabetic nephropathy.

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A 60-year-old man presents to his primary care physician with weight gain. He states that ever since his wife died 4 months ago, he has been eating and sleeping more and no longer engages in any activities he once enjoyed such as hiking or fishing. He feels guilty for not spending more time with his wife before she died. He was recently fired for making several major bookkeeping mistakes at work as an accountant as he had trouble focusing. The patient is requesting oxycodone at this appointment as he states he has burning pain in his legs that feels worse now than it has in years past. The patient has a past medical history of obesity, poorly controlled diabetes, hypertension, and peripheral vascular disease. His temperature is 98.7°F (37.1°C), blood pressure is 129/82 mmHg, pulse is 83/min, respirations are 15/min, and oxygen saturation is 99% on room air. Physical exam reveals a stable gait and reduced sensation symmetrically over the lower extremities. He complains of electric pain when touching his lower extremities. His affect seems depressed. Which of the following is the most appropriate treatment for this patient?

Amitriptyline

Bupropion

Escitalopram

Phenelzine

Venlafaxine

E

Venlafaxine

This patient is presenting with sleep changes, interest loss, guilt, decrease in energy, and trouble concentrating for greater than 2 weeks concerning for major depressive disorder. In the setting of his diabetic neuropathy (lower extremity burning pain in the setting of poorly managed diabetes), a serotonin-norepinephrine reuptake inhibitor (SNRI) such as venlafaxine is the most appropriate initial treatment for this patient. Major depressive disorder should always initially be managed with cognitive behavioral therapy and often medication. Typically, the first-line medication is a selective serotonin reuptake inhibitor (SSRI). However, SNRIs such as venlafaxine and duloxetine are viable first-line options. They are particularly preferred in patients with diabetic neuropathy as they treat both diabetic neuropathy and depression. SNRIs are also generally considered to be less sedating than SSRIs. For this reason, SNRIs are often a better initial drug in depression than SSRIs in diabetic patients with peripheral neuropathy. Sansone and Sansone discuss SNRIs and their uses. They discuss how there are different efficacies and propensities of the different SNRIs. They recommend choosing an appropriate SNRI based on the patient's needs and comorbidities. Incorrect Answers: Answer A: Amitriptyline is a tricyclic antidepressant that can be used to treat depression in patients who also suffer from other neuropathic pain conditions or conditions such as fibromyalgia or irritable bowel syndrome. While it may also be used in diabetic neuropathy and depression, there is higher toxicity with this medication than SNRIs. For this reason, SNRIs are preferred. A TCA might be appropriate if the patient had already failed other first-line agents. Answer B: Bupropion is a weight-neutral antidepressant that can be used in smoking cessation and patients who are trying to avoid the sexual side effects of SSRIs (anorgasmia). It would not address this patient's diabetic neuropathy, though it could be beneficial for his obesity. Answer C: Escitalopram is an SSRI that could be used first-line for major depressive disorder. However, if a patient has a concomitant condition, it is better to choose a single agent that addresses both problems; thus, SNRIs are better first-line medications in this patient with diabetic neuropathy. Answer D: Phenelzine is a monoamine oxidase inhibitor that can be used in atypical depression or as a third-line or later agent in the management of depression. This agent can cause a hypertensive crisis in the setting of tyramine consumption, has many medication interactions, and a long washout period. Thus, it is not usually a first or second-line agent. However, it is highly effective in patients who have failed other first-line agents and should still be used in appropriate candidates. Bullet Summary: SNRIs are appropriate first-line agents for major depressive disorder in patients with diabetic neuropathy.