Question: An 8-week-old boy presents with his mother to the pediatrician for a well visit. The patient has been breastfed since birth, and usually feeds for 30 minutes every 2-3 hours. The patient’s mother is concerned that her milk production is not keeping up with the patient’s nutritional requirements. She reports that about 2 weeks ago the patient began regurgitating breastmilk through his nose and mouth after some feeds. He seems mildly upset during the episodes of regurgitation but usually settles down quickly and is hungry again soon afterwards. His mother has already tried limiting the volume of each feed, which seems to have reduced the frequency of regurgitation. She denies any diarrhea, hematochezia, or family history of food allergies. Her older son had a similar problem with vomiting that resolved around 12 months of age. Four weeks ago, the patient’s height and weight were in the 40th and 34th percentiles, respectively. His height and weight are now respectively in the 37th and 36th percentiles. His temperature is 98.6°F (37°C), blood pressure is 72/49 mmHg, pulse is 121/min, and respirations are 32/min. On physical exam, the patient is cooing in his mother’s lap and smiles reciprocally with her. He lifts his head and shoulders off the examination table when placed in the supine position. His abdomen is soft, non-tender and non-distended. Bowel sounds are normoactive. Which of the following is the most appropriate next step in management?

Reassurance and counseling on positioning

Answer: Reassurance and counseling on positioning

Explanation:
This patient presents with regurgitation after feeding, appropriate appetite after episodes of regurgitation, and good weight gain, which suggests a diagnosis of uncomplicated gastroesophageal reflux. The most appropriate next step in management is reassurance and counseling on proper positioning.

Physiologic or uncomplicated gastroesophageal reflux usually presents in patients in the first few months of life with frequent regurgitation or vomiting, sustained appetite after regurgitation, and minimal irritability. The most appropriate first step in management is reassurance and counseling parents to position patients upright for 20-30 minutes after feeding. For patients with persistent symptoms, parents should be encouraged to provide lower volume feeds more frequently throughout the day, and consider a milk-free diet to address possible underlying cow’s milk allergy. Treatment with a proton pump inhibitor is reserved for intractable cases. For most patients, gastroesophageal reflux self-resolves by 1 year of age.

Chabra and Peeples review the evidence regarding the treatment of neonatal GERD. They discuss how alterations in the infant's environment and feeding pattern are effective in most cases. They recommend proton pump inhibitors if conservative treatments are not effective.

Incorrect Answers:
Answer A: Initiating a proton pump inhibitor is appropriate for infants with gastroesophageal reflux disease who have failed management with lifestyle changes. This patient has uncomplicated gastroesophageal reflux without any signs of feeding refusal, worsening irritability, or nutritional compromise.

Answer B: Obtaining an abdominal ultrasound would evaluate for pyloric stenosis, which presents with non-bilious, projectile vomiting rather than the regurgitation that this patient’s mother is describing. An abdominal ultrasound would be the appropriate next step in management for patients who present with a description of more forceful vomiting or have a classic “olive-shaped” mass in the epigastrium on physical exam.

Answer D: Recommending modification of the mother’s diet would be appropriate if this patient had more severe symptoms that were refractory to lifestyle changes. It would also be appropriate if the patient had signs of an underlying allergy to cow’s milk or soy protein, such as blood-streaked stools.

Answer E: Switching to a hydrolyzed formula would be appropriate for formula-fed patients with refractory symptoms of gastroesophageal reflux disease or signs of an allergy to cow’s milk or soy protein. Unless the patient has evidence of severe nutritional compromise, continued breastfeeding should be encouraged for breastfed patients with possible modification of the mother’s diet to eliminate cow’s milk or soy if an allergy is suspected.

Bullet Summary:
Uncomplicated gastroesophageal reflux in infants should be treated with reassurance and counseling to position the infant upright for 20-30 minutes after feeding.


Question: A 28-year-old G1P0 woman presents to initiate prenatal care after a positive home pregnancy test. The first day of her last menstrual period was 7 weeks prior to presentation. The patient has no medical conditions and takes no medications. Her temperature is 98.6°F (37.0°C), blood pressure is 110/70 mmHg, pulse is 64/min, and respirations are 17/min. Physical exam is notable for a nontender abdomen. Pelvic exam reveals a closed cervix with no adnexal or uterine tenderness. A urine pregnancy test is positive, and an intrauterine singleton pregnancy measuring approximately 9 weeks gestational age is visualized on transvaginal ultrasound. The patient asks if she should modify her current exercise regimen due to her pregnancy. She typically swims or uses an exercise bike for 45 minutes, 5 days a week, and plays in an office soccer league for 1 hour on 1 day per week. Which of the following is the most appropriate recommendation regarding exercise for this patient?

Avoid soccer during pregnancy, continue other activities

Limit moderate exercise to a maximum of 30 minutes per day during pregnancy

Reduce to walking only, beginning in the third trimester

Answer: Avoid soccer during pregnancy, continue other activities

Explanation:
This healthy primigravida woman presents to the clinic inquiring about her current exercise regimen involving 285 minutes of moderate to exercise weekly. With the exception of soccer, a contact sport, her exercise regimen is appropriate throughout her pregnancy.

The American College of Obstetricians and Gynecologists (ACOG), recommends that healthy pregnant women engage in moderate-intensity exercise for at least 30 minutes or more for 5-7 days weekly provided there are no contraindications to doing so (certain cardiac or pulmonary conditions, history of cerclage placement, multiple pregnancies, preeclampsia, or severe anemia). Highly active patients may continue their more vigorous pre-pregnancy regimens after consulting with a physician. Exercise in pregnancy can ease gastrointestinal symptoms and may decrease the risk of gestational diabetes, preeclampsia, and cesarean delivery. However, activities that may cause fetal or maternal injury, such as contact sports or activities with a significant fall risk should be avoided. Examples of contact sports include football, basketball, hockey, lacrosse, and wrestling.

Nascimento et al. review exercise in pregnancy. They note that exercise is beneficial in pregnancy and in the postpartum period and recommend engaging in appropriate exercise in this patient population.

Incorrect Answers:
Answer A: Avoiding exercise during pregnancy is not recommended, as at least 150 minutes of moderate exercise weekly is suggested during pregnancy for the health of the mother and the fetus.

Answer C: Continuing the current exercise regimen is not recommended, as soccer is a high-contact sport that could cause injury to the fetus or placenta.

Answer D: Limiting moderate exercise to 30 minutes per day maximum during pregnancy is not recommended, as 30 minutes daily is the minimum recommended time for moderate-exercise. There is no reason for healthy pregnant patients without high-risk pregnancies to significantly limit their exercise.

Answer E: Reducing to walking-only beginning in the third trimester is not necessary, as moderate activities are healthy throughout pregnancy.

Bullet Summary:
Healthy pregnant patients should perform at least 30 minutes of exercise 5-7 days per week and avoid high-contact sports or sports with fall risk.


Question: A 39-year-old man presents to his doctor for a wellness checkup. He is concerned about a rash that does not seem to be improving. He was recently exposed to his grandfather who has vesicular lesions on his skin and is being treated. He has a family history of skin cancer, colon cancer, and ovarian cancer. The patient has a medical history of asthma and seasonal allergies. His temperature is 98.6°F (37.0°C), blood pressure is 137/98 mmHg, pulse is 90/min, respirations are 14/min, and oxygen saturation is 98% on room air. Physical exam reveals the finding in Figure A. Which of the following describes this patient's most likely diagnosis?

Answer: Benign capillary proliferation

Explanation:
This patient who presents with red raised papules is presenting with a cherry angioma. These lesions are composed of benign capillary proliferations.

Cherry angiomas present with cherry red macules/papules that occur secondary to benign capillary and venule proliferation. The lesions are entirely benign and are cosmetic. These lesions are common in middle-aged adults. As the patient ages, more lesions will appear. In the absence of symptoms, observation and reassurance can be used for conservative management. They can be removed surgically if the patient desires.

Nazer et al. study the risk factors associated with the development of cherry angioma. They found that the use of clopidogrel and tamsulosin is associated with these lesions. They recommend ruling out underlying conditions.

Figure/Illustration A demonstrates cherry red macules/papules classically seen in patients with cherry angioma.

Incorrect Answers:
Answer B: Edema of the epidermis describes eczema or atopic dermatitis. This disease would present with pruritic, erythematous, and vesicular lesions. Topical creams and hygiene can be used for symptomatic management of these lesions.

Answer C: Healthy dermatologic development misses the diagnosis of a cherry angioma, which although benign, is a more accurate diagnosis for this case.

Answer D: Malignant blood vessel proliferation does not describe a cherry angioma which is benign and purely cosmetic. An angiosarcoma usually occurs in deep tissues and requires surgical excision.

Answer E: Viral infection describes herpes simplex virus which would present with vesicular lesions and neurogenic pain. These patients can be treated with valacyclovir as well as gabapentin for neuropathic pain.

Bullet Summary:
Cherry angiomas are benign capillary proliferations that appear as cherry red macules/papules.


Question: A 46-year-old man presents with his wife to his primary care provider for depression and strange movements. His wife reports that her husband has not been himself for the last 2 months. Whereas he was previously outgoing and “the life of the party,” the patient is now irritable and withdrawn. He is a partner at an accounting firm, but his colleagues are threatening to fire him if he continues to perform poorly at work. The patient cannot explain the recent changes to his mood and tearfully admits he fears there is something seriously wrong with him. His wife says that he is getting worse. The patient’s medical history is significant for hypertension, for which he takes lisinopril. His family history is unknown as he was adopted. The patient met his mother once and never knew his father but was told he died in his 50s. He drinks a few glasses of wine per week and has never smoked. His temperature is 98.6°F (37°C), blood pressure is 141/87 mmHg, pulse is 81/min, and respirations are 12/min. On physical exam, the patient has a flat affect with a facial grimace and sudden jerky movements of his upper extremities. Which of the following is most likely to be seen on further workup?

Alpha-synuclein aggregates on brain biopsy

Answer: Dorsal striatum atrophy on head CT

Explanation:
This patient presents with recent mood changes, jerky movements of the upper extremities, and a history of early death in his father, which suggests a diagnosis of Huntington disease. Huntington disease is characterized by atrophy of the caudate nucleus, which is a structure of the dorsal striatum.

Huntington disease (HD) is an autosomal dominant trinucleotide (CAG) repeat disorder located on chromosome 4. HD typically presents with mood changes and abnormal movements (particularly chorea or myoclonus) over weeks to months. Although executive function can be affected early on, memory is usually preserved until relatively late in the disease. Frontotemporal dementia, in contrast, usually presents with behavioral changes, and Alzheimer disease has memory impairment as an early sign. Caudate atrophy is typically seen on head imaging in Huntington disease. This disease cannot be cured but supportive treatment includes benzodiazepines and tetrabenazine for symptomatic relief of muscle spasms.

Walker presents a review of the evidence regarding the etiology of Huntington disease. He discusses that typically the onset of symptoms is in middle age after affected individuals have had children. He recommends a better understanding of the function of the mutant protein in this disease.

Incorrect Answers:
Answer A: Alpha-synuclein aggregates would be found on brain biopsy in Parkinson disease and Lewy body dementia. Lewy body dementia is characterized by parkinsonism and visual hallucinations. Patients would present with cogwheel rigidity, bradykinesia, and a resting tremor. Treatment is with dopamine agonists such as carbidopa/levodopa.

Answer C: Frontotemporal atrophy is consistent with a diagnosis of frontotemporal dementia. Frontotemporal dementia presents primarily with early behavioral changes, and it would not present with myoclonus. Treatment is supportive as there is no cure for this disease. Patients and their spouses may require psychiatric support for changes in behavior.

Answer D: Neurofibrillary tangles on brain biopsy would suggest a diagnosis of Alzheimer disease. This disease presents with a slowly progressive cognitive decline in elderly patients. Patients have early loss of memory but have maintained motor function and behavior until later in the course of the disease.

Answer E: A positive 14-3-3 CSF assay would confirm the diagnosis of Creutzfeldt-Jakob disease (CJD). Although CJD may also present with mood changes and myoclonus, CJD most prominently causes rapidly progressive dementia early in life. Treatment is supportive and death occurs quickly.

Bullet Summary:
Huntington disease is an autosomal dominant trinucleotide repeat disorder located on chromosome 4 that causes caudate atrophy and presents with mood changes, abnormal movements, and subcortical dementia.


Question: A 69-year-old man presents to the emergency department with shortness of breath. The patient has presented 3 times this month with similar complaints. He states his shortness of breath started when he was walking from his car to a local restaurant. He does not see a primary care physician and is not currently taking any medications. He drinks alcohol socially and does not smoke. His temperature is 99.5°F (37.5°C), pulse is 100/min, blood pressure is 130/90 mmHg, respirations are 18/min, and oxygen saturation is 96% on room air. On physical exam, he appears fatigued and the cardiovascular exam reveals an additional heart sound after S2. A pulmonary exam is notable for bilateral crackles and an abdominal exam reveals an obese abdomen without pain in any of the quadrants. Lower extremity pitting edema is noted bilaterally. Which of the sets of lab values shown in Figure A would most likely be seen in this patient?

Answer: C

Explanation:
This patient is presenting with symptoms of heart failure (CHF). The most likely laboratory abnormalities are elevated brain natriuretic peptide (BNP), high anti-diuretic hormone (ADH), low sodium, and low potassium.

Heart failure is characterized by the decreased performance of the cardiac ventricles resulting in ventricular dilation. As the ventricles dilate, they release BNP as a marker of stretching of myocardial tissue. BNP levels can therefore serve as a marker of CHF. The kidneys will also have decreased perfusion levels in this disease leading to several key physiologic changes. First, is the activation of the renin-angiotensin-aldosterone system, which serves to increase perfusion to the kidneys by increasing blood pressure. This system achieves increased blood pressure by maintaining sodium and fluid retention at the expense of decreased potassium (hypokalemia) and decreased hydronium ions (metabolic alkalosis). In addition, ADH is also increased to further increase perfusion, resulting in water retention, hemodilution, and hyponatremia.

Ma et al. studied the correlation between BNP levels and cardiovascular outcomes. They found that patients with CHF and high levels of BNP had increased rates of cardiovascular complications. They recommend assessing BNP levels in patients who are suspected of having CHF.

Figure A is a chart with changes in brain natriuretic peptide, anti-diuretic hormone, sodium, and potassium that would be seen in various diseases.

Incorrect Answers:
Answer A: High BNP, high ADH, high sodium, and high potassium does not reflect the changes that would be seen in CHF. Though aldosterone serves to retain sodium, it also absorbs water. Thus, hypernatremia would not be seen. This pattern could be seen in patients with heart failure who have high free water losses such as after a burn or in desert environments.

Answer B: High BNP, low ADH, normal sodium, and low potassium does not reflect the appropriate increase in ADH and subsequent decrease in sodium that would be seen in CHF. Patients who have diabetes insipidus can have low ADH in this setting resulting in loss of free water.

Answer D: Low BNP, high ADH, low sodium, and low potassium does not reflect the finding of elevated BNP that is classically found in the dilated ventricles of CHF. This pattern would be seen in patients with the syndrome of inappropriate ADH where excessive resorption of free water results in hemodilution.

Answer E: Low BNP, low ADH, normal sodium, and normal potassium reflect the findings in a healthy patient. This patient most likely has CHF, which would result in increased aldosterone and ADH function.

Bullet Summary:
Common lab findings in heart failure include elevated BNP, elevated ADH, low sodium, and low potassium.


Question: A 19-year-old woman presents to her primary care physician with headaches, blurry vision, and tinnitus over the past month. She started treatment for a skin condition with a new oral medication 2 months prior. She has not noticed any changes in her complexion as of yet. Her temperature is 98.2°F (36.8°C), blood pressure 100/65 mmHg, pulse 87/min, and respiratory rate 14/min. She is oriented to person, place, and time. Neurological exam reveals papilledema upon examination of both eyes. Skin examination is notable for the findings in Figure A. Which of the following is the most likely diagnosis?

Answer: Idiopathic intracranial hypertension

Explanation:
This young patient with severe nodulocytic acne who was started on a new oral medication (likely isotretinoin) is likely suffering from idiopathic intracranial hypertension, which can present with papilledema, headache, blurry vision, and diplopia.

Idiopathic intracranial hypertension is characterized by an increase in intracranial pressure without an identifiable cause. Patients often present with symptoms that include headache, blurry vision, and tinnitus. Fundoscopic examination typically reveals bilateral papilledema. Vision loss is a complication of this condition with high morbidity. While there is no identifiable cause, common associations include obesity or a recent increase in weight as well as medications such as isotretinoin - a vitamin A derivative that is often used in the management of severe nodulocystic acne vulgaris. Management should first involve imaging of the brain (CT or MRI) to exclude elevated cerebrospinal fluid pressure due to other causes such as brain tumor, dural sinus thrombosis, or hydrocephalus. The diagnosis is made via lumbar puncture revealing increased opening pressure. Lumbar puncture can also result in therapeutic relief. The specimen should be sent for gram stain, culture, and viral PCR to rule out other etiologies. Long term treatment is centered on weight loss and avoiding causative agents. Acetazolamide and serial lumbar punctures are other treatments.

Boyter reviews the clinical presentation and management of patients with idiopathic intracranial hypertension. They found the condition is most common among obese women in their 20's, but it also may occur in children, men, and older adults. They recommend referral for patients to see a neurologist for ongoing management of headaches and other symptoms, as well as an ophthalmologist or neuro-ophthalmologist for monitoring papilledema, given the risk of vision loss.

Figure/Illustration A: The figure depicts a patient with severe nodules and cysts (red arrows) consistent with severe inflammatory nodulocystic acne that would be suitable for treatment with isotretinoin.

Incorrect Answers:
Answer A: Cerebrovascular accidents can be embolic or hemorrhagic in nature and often result in persistent neurologic deficits or resolution of an acute neurologic deficit in a patient with cerebrovascular risk factors (diabetes, hypertension, hyperlipidemia). This young, healthy patient with intermittent headache and neurologic symptoms without a family history of hypercoagulable state is unlikely to have suffered from a cerebrovascular accident.

Answer B: Giant cell arteritis (GCA) is a vasculitis that is typically seen in elderly patients (>60 years of age) and presents with tenderness of the ipsilateral temple and elevated inflammatory markers. Many patients with GCA have one or more constitutional symptoms (weight loss, fever, fatigue, anorexia, malaise) in addition to symptoms such as new onset headache or jaw claudication.

Answer D: Meniere disease affects the inner ear and is characterized by severe episodes of vertigo, tinnitus, hearing loss, and fullness in the ear. Patients are often women between the ages of 40 and 60. Headaches and blurry vision are not a classic part of the clinical presentation.

Answer E: Migraines present with severe headaches that can be incapacitating with associated photophobia and phonophobia. In some cases, patients may present with an aura that precedes or occurs during the migraine. The presence of papilledema suggests elevated intracranial pressure and is not typically seen in migraines.

Bullet Summary:
Idiopathic intracranial hypertension may be a side effect of isotretinoin.


Question: A 52-year-old man presents to the emergency department by ambulance for evaluation of hematemesis. His wife states that he began vomiting bright red blood this evening while eating dinner, and has produced about 5 cups total. He has a history of alcohol use disorder and has vomited small streaks of blood in the past, but has never undergone formal medical workup for it. On exam, he has bright red blood in his mouth and pharynx, and also displays a distended abdomen with a fluid wave, jaundice, scattered spider angiomas, and multiple ecchymoses. His temperature is 98.4°F (36.9°C), blood pressure is 98/68 mmHg, pulse is 125/min, and respirations are 22/min. A rapid point-of-care hemoglobin and platelet count is 8.8 g/dL and 80,000/mm^3, respectively. The patient is given 1L of normal saline. Which of the following is the most appropriate initial step in management?

Answer: Octreotide

Explanation:
This patient with a history of alcohol use disorder and signs of liver failure (jaundice, ascites, spider angiomas, and ecchymoses) presents with acute hematemesis and hypovolemic shock (hypotension, tachycardia, tachypnea) most concerning for a variceal hemorrhage. The first step in the resuscitation of patients with variceal hemorrhage is rapid administration of intravenous (IV) fluids and octreotide.

Esophageal and gastric varices, most commonly seen in patients with cirrhosis, are abnormally distended veins that are a product of venous congestion from portal hypertension. As these varices can project into the gastrointestinal lumen, they are subject to rupture either spontaneously or by mechanical disruption (e.g., tearing by food particles). Variceal hemorrhage is a life-threatening complication of cirrhosis as it can quickly progress to hemorrhagic shock or airway loss (if profuse vomiting is present). Patients should immediately receive 2 large-bore peripheral IVs (or central IV access) with which to administer IV fluid boluses to increase circulating volume. Blood should be transfused as needed, and a massive transfusion protocol may be needed. Patients should also be given octreotide, a splanchnic vasoconstrictor, in an effort to divert blood away from the hemorrhaging varices. Other treatments that should be given include ceftriaxone (to reduce bacteremia and mortality), proton pump inhibitors, and possibly interventions such as tranexamic acid. Upper GI endoscopy and banding are the definitive therapy.

Stanley et al review the management of acute upper gastrointestinal bleeding with initial IV fluid resuscitation as the first measure to achieve hemodynamic stability. They also report that for patients with cirrhosis, vasoactive drugs such as octreotide should be started as soon as variceal hemorrhage is suspected. Red blood cell transfusion is indicated at a hemoglobin transfusion of 7.0-8.0 g/dL. Definitive therapy is endoscopy with variceal ligation.

Incorrect Answers:
Answer A: Balloon tamponade is often performed in the emergency department or intensive care unit as a temporizing measure to achieve hemostasis for patients with severe and persistent variceal hemorrhage. The balloon is inserted into the esophagus or stomach and inflated to apply direct pressure to the bleeding varices; this buys valuable time in the transition to definitive endoscopic management.

Answer B: Ceftriaxone is administered to patients with cirrhosis who present with an upper gastrointestinal bleed as a prophylactic measure against spontaneous bacterial peritonitis. This patient is hemodynamically unstable, and antibiotics should not delay initial intravenous fluid resuscitation as well as other measures to reduce and/or stop the bleeding. While this patient should receive ceftriaxone, it is more dire to first give fluids, blood, and octreotide.

Answer C: Nadolol or other nonselective beta-blocker therapy is indicated as secondary prophylaxis to prevent future bleeding episodes for patients with a history of variceal hemorrhage. Non-selective beta blockers such as nadolol decrease portal pressure, but are contraindicated in the acute setting as they could exacerbate hypovolemic shock by reducing cardiac output.

Answer D: Platelet transfusion is required for patients with variceal hemorrhage with an initial platelet count < 50,000/mm^3, and for those who receive a significant amount of blood products during their resuscitation (significant dilutional thrombocytopenia can occur after 10-12 units of transfused red blood cells). This patient's platelet count is above 50,000/mm^3, and he has not yet received blood products.

Bullet Summary:
The most appropriate initial step in the management of a cirrhosis patient with acute variceal hemorrhage is the rapid administration of intravenous fluids and octreotide, a splanchnic vasoconstrictor.


Question: A 38-year-old woman presents to the emergency department with difficulty eating. Over the past week, she has had increasing difficulty chewing her food and progressive pain in the left side of her jaw. This morning, she was unable to close her mouth for several minutes after taking a bite of her breakfast. Two months ago, the patient had a root canal on a left molar. Her medical history is significant for hyperlipidemia, mild intermittent asthma, and type 2 diabetes mellitus. She has never smoked and has 10-15 alcoholic drinks per week. She works as an aide at a nursing home. Her temperature is 100.8°F (38.2°C), blood pressure is 133/74 mmHg, pulse is 105/min, and respirations are 14/min. On physical exam, there is a bluish hue to the skin on the lower left side of the patient’s face. A 3x4 cm non-tender mass can be palpated inferior to the angle of the left mandible. Thick exudate is draining from an opening in the skin. The gram stain of the exudate can be seen in Figure A. Which of the following is the most appropriate treatment for this patient?

Answer: Penicillin

Explanation:
This patient presents with fever, trismus, and cutaneous drainage of sulfur granules in the setting of a recent dental procedure, which points to a diagnosis of cervicofacial actinomycosis. The most appropriate treatment for this disease is penicillin.

Actinomyces is a gram-positive, filamentous rod that causes a cervicofacial infection after direct inoculation during a dental procedure or trauma. It typically presents in an indolent fashion over a time course of weeks to months in which a hard, indurated mass evolves into multiple abscesses that drain through sinus tracts through the skin. The exudate is classically thick with small yellow “sulfur” granules, although it may also be serosanguinous. Since the infection spreads by direct extension, patients may complain of pain when the infection infiltrates or compresses nearby structures. Trismus may occur for the same reasons. The treatment of choice is penicillin.

Valour et al. review the evidence regarding the treatment of Actinomyces infection. They discuss how prolonged (6- to 12-month) high-dose penicillin or amoxicillin is required for the treatment of this disease. They recommend preventive measures such as improvement of dental hygiene to prevent this disease.

Figure/Illustration A demonstrates the histologic appearance of a basophilic “sulfur granule” (red circle). These granules are found in the draining exudate in patients with actinomycosis.

Incorrect Answers:
Answer A: Amphotericin B is the treatment of choice for fungal infections such as mucormycosis. This disease generally presents with a rapidly progressive soft tissue infection that can be fatal if left untreated. Patients would present with black fungal lesions generally in immunocompromised or diabetic hosts.

Answer B: Clindamycin may be used in the treatment of empyema as it has activity against many anaerobes. Although this patient has a substantial weekly alcohol intake and has a chief complaint of “difficulty eating,” she has no true pulmonary symptoms and her presentation is more likely related to her recent dental procedure.

Answer C: Metronidazole may be used in the treatment of empyema. Although this patient has a substantial weekly alcohol intake and has a chief complaint of “difficulty eating,” she has no true pulmonary symptoms and her presentation is more likely related to her recent dental procedure.

Answer E: Trimethoprim-sulfamethoxazole is the treatment of choice for Nocardiosis, which may cause cutaneous lesions in immunocompromised hosts. This disease more commonly causes pulmonary or central nervous system disease. Nocardia would not explain the granule seen in histology.

Bullet Summary:
Actinomyces is a gram-positive anaerobic rod that presents as an indurated mass with draining sinus tracts and should be treated with penicillin.


Question: A 3-year-old boy presents with his parents to a pediatrician for a new patient visit. The child was recently adopted and little is known about his medical or family history. The child seems to be doing well, but the patient is much larger than any of the other 3-year-olds in his preschool class. He eats a varied diet at home and with limited juice and snack foods. His temperature is 98.6°F (37°C), blood pressure is 101/67 mmHg, pulse is 110/min, and respirations are 24/min. On physical exam, the patient is in the 73rd percentile for weight, 99th percentile for height, and 86th percentile for head circumference. He appears mildly developmentally delayed. He has a fair complexion and tall stature with a prominent sternum. The patient also has joint hypermobility and hyperelastic skin. He appears to have poor visual acuity and is referred to an ophthalmologist, who finds downward lens subluxation of the right eye. This child is most likely to develop which of the following complications?

Answer: Thromboembolic stroke

Explanation:
This patient presents with Marfanoid habitus, joint hypermobility, hyperelastic skin, developmental delay, and downward lens subluxation, which suggests a diagnosis of homocystinuria. Homocystinuria predisposes to thromboembolic events such as stroke.

Although homocystinuria shares many features with Marfan syndrome, patients with homocystinuria also present with a fair complexion, intellectual disability, and downward subluxation of the lens (instead of the upward subluxation seen in Marfan syndrome). Patients with homocystinuria are also at an increased risk of thromboembolic events that disproportionally affect the cerebral vessels. Similar to Marfan syndrome, patients have phenotypic features of a Marfanoid habitus, including tall stature, long limbs, arachnodactyly, joint hypermobility, skin hyperelasticity, pectus deformity, and scoliosis. Treatment includes vitamin B6 supplementation.

Hasan et al. review the evidence regarding diseases associated with homocystinuria. They discuss how this disease is associated with cancer and Alzheimer disease. They recommend screening for this disease.

Incorrect Answers:
Answer A: Aortic dissection is a complication of Marfan syndrome, an autosomal dominant mutation of the fibrillin-1 gene. It is also associated with elevated homocysteine levels. Although Marfan syndrome shares many features with homocystinuria, the fair complexion, and intellectual disability seen in this patient are specific to homocystinuria. Treatment involves avoidance of contact sports and beta blockers.

Answer B: Medullary thyroid cancer is part of the syndrome of multiple endocrine neoplasia type 2B (MEN2B), which is caused by a mutation in the RET proto-oncogene. Patients with MEN2B present with Marfanoid habitus, but they do not present with the other features described in this vignette, including fair complexion, intellectual disability, and downward lens subluxation. Treatment is with surgical excision of tumors.

Answer C: Osteoarthritis is a complication of Ehlers-Danlos syndrome (EDS). Although patients with EDS may present with many of the phenotypic features of both Marfan syndrome and homocystinuria, patients are much less likely to have lens subluxation. Osteoarthritis may be seen with higher incidence in patients with homocystinuria. Treatment is with brace support of unstable joints.

Answer E: Wilms tumor is associated with Beckwith-Wiedemann syndrome (BWS), a pediatric overgrowth disorder usually caused by a mutation at chromosome 11p15. BWS presents with macrosomia (“gigantism”), which is defined as height and weight > 97th percentile. BWS additionally presents with omphalocele, hemihyperplasia, visceromegaly, neonatal hypoglycemia, and other embryonal tumors, including hepatoblastoma and neuroblastoma. Treatment is with surgical correction of defects.

Bullet Summary:
Homocystinuria presents with Marfanoid habitus, fair complexion, intellectual disability, downward lens subluxation, and an increased risk of thromboembolic events.


Question: A 67-year-old woman presents from a nursing home with altered mental status. She was last known to be normal the night before. The patient has dementia at baseline and is minimally interactive. This morning, she was found to be obtunded. No further history was provided from the nursing home, and the patient is unable to provide any history. Her temperature is 95.0°F (35.0°C), blood pressure is 84/54 mmHg, pulse is 50/min, respirations are 9/min, and oxygen saturation is 98% on room air. Physical exam reveals an obtunded woman who only withdraws her extremities to pain. Her skin is cool and pale, and her hair is thin. There are no signs of trauma noted on exam. Laboratory values are notable for a whole blood sodium of 120 mEq/L. The patient is given several intravenous boluses of fluids and her blood pressure improves to 100/60 mmHg. Which of the following is most likely to confirm the underlying cause of this patient's symptoms?

Obtain blood cultures and a serum lactate

Answer: Check serum TSH and free T4 levels

Explanation:
This patient is presenting with obtundation, bradycardia, hypotension, hypothermia, thinning of her hair, and hyponatremia, which are concerning for myxedema coma. A serum TSH and free T4 would be most informative in confirming this diagnosis.

Myxedema coma (decompensated hypothyroidism) is the most life-threatening manifestation of hypothyroidism. Key clinical features include hypothermia (often the temperature is <95.9°F (35.5°C)), bradycardia, hypotension, bradypnea (causing a respiratory acidosis), hypoxia, and obtundation. Immediate management is centered on warming the patient, warmed IV fluids, and protecting the patient's airway, if needed. If there is high clinical suspicion for myxedema coma, then IV levothyroxine can be given empirically. Otherwise, the TSH and free T4 should be checked, which will reveal an elevated TSH and a low free T4. Patients are often critically ill and require active rewarming and close monitoring in an ICU setting.

Wall reviews myxedema coma. Wall notes that myxedema coma is a life-threatening manifestation of hypothyroidism. She recommends that generally IV T4 (levothyroxine) is preferred over IV T3 in initial management.

Incorrect Answers:
Answer A: Administering glucagon would be appropriate in a beta-blocker overdose, which presents with bradycardia, hypotension, and altered mental status. There is no indication that this patient intentionally overdosed, and her hyponatremia and thinning hair supports a diagnosis of hypothyroidism. Other treatments that can be given in a beta-blocker overdose including epinephrine, calcium, insulin, dextrose, and lipid emulsion therapy.

Answer C: Obtaining blood cultures and a serum lactate is the appropriate management of sepsis/septic shock. Generally, patients with septic shock present with hypotension (refractory to fluid resuscitation), tachycardia, and fever or hypothermia. Though myocardial depression may happen in critically ill patients who are about to undergo cardiac arrest, hypothyroidism better explains this patient's constellation of symptoms. It would be appropriate to obtain cultures and a serum lactate in this patient while the differential is being narrowed.

Answer D: Performing a CT scan of the head would be indicated at some point in the workup of patients with altered mental status if there was a suspected central nervous system etiology such as a subdural hematoma. However, hemodynamically unstable patients should never be sent to the CT scanner prior to stabilization and resuscitation. A subdural hematoma is more common in older patients and patients with alcohol use disorder who experience head trauma as the atrophy of their brain makes the bridging veins more vulnerable.

Answer E: Performing an echocardiogram may show reduced cardiac function; however, it is unlikely to reveal the underlying cause of this patient's hypotension and bradycardia other than showing poor cardiac function.

Bullet Summary:
Myxedema coma presents as a critically ill, obtunded patient who is hypothermic, bradycardic, and hypotensive, and the diagnosis can be supported with a high TSH and a low free T4.


Question: A 43-year-old man presents to the emergency department acutely with altered mental status. He uses intravenous drugs and is unable to offer a history. He was found unconscious in a park. His temperature is 99.0°F (37.2°C), blood pressure is 80/40 mmHg, pulse is 156/min, and respirations are 26/min. Physical exam reveals an obtunded man covered in vomit, with track marks on his arm and several skin abscesses. The patient is given 4 liters of Ringer lactate and intravenous antibiotics. As the fourth liter of fluids is finishing, the patient is noted to have jugular venous distension and an oxygen saturation of 92% on nonrebreather. He is subsequently intubated. An ECG is obtained as seen in Figure A. The patient is started on norepinephrine, and his blood pressure is subsequently found to be 85/44 mmHg. Which of the following is the most appropriate next step in management?

Answer: Epinephrine

Explanation:
This patient who uses intravenous drugs with skin abscesses (the likely source of his infection) is hypotensive and tachycardic, with a blood pressure that is not responding to IV fluids; this is concerning for septic shock. Given his persistent hypotension, he should be started on vasopressors of which norepinephrine is first line and epinephrine is second line.

Septic shock is a life-threatening, systemic bacterial infection that leads to vasodilation and endothelial dysfunction. Early management is centered on IV fluids, blood cultures, broad-spectrum antibiotics, and workup to uncover the source. If the patient's blood pressure does not respond to IV fluids (by definition, their blood pressure will not respond to fluids in septic shock), vasopressors should be started with a goal mean arterial pressure > 65 mmHg. The first line vasopressor is norepinephrine, which can be titrated up for maximal effect. If this vasopressor fails to reach blood pressure goals, then the next vasopressor is either vasopressin or epinephrine (either is acceptable). If the second line vasopressor fails to increase blood pressure, then the third line vasopressor is vasopressin or epinephrine (whichever was not used as the second line pressor). Finally, the fourth line vasopressor for septic shock is phenylephrine.

Levy et al. review sepsis. They update the Surviving Sepsis campaign which gives the most up to date management guidelines of sepsis including adequate fluid resuscitation, broad-spectrum antibiotics, and vasopressors. They recommend early antibiotics and resuscitation to minimize morbidity and mortality.

Figure/Illustration A is an ECG demonstrating sinus tachycardia. Note the presence of P waves (red arrows highlighting several examples) that are present throughout all leads.

Incorrect Answers:
Answer A: Cardioversion would be appropriate in an unstable patient with unstable vital signs in the setting of atrial fibrillation with rapid ventricular response to convert the patient to normal sinus rhythm. Atrial fibrillation would present with an irregularly irregular rhythm without P waves. Cardioversion would not be indicated in sinus tachycardia.

Answer C: Hydrocortisone is a potent glucocorticoid that also has mineralocorticoid properties. While giving an IV steroid may have a permissive effect on blood pressure (via upregulating alpha-1 receptors on the vasculature) there is no reason that this patient would have a low cortisol level (such as in chronic steroid use). Epinephrine is a better answer in this case, though steroids can be considered. Steroids are typically reserved for patients failing at least 2 vasopressors (unless they have a known cortisol-deficient state).

Answer D: Normal saline is unlikely to benefit this patient as he has already been sufficiently fluid resuscitated. Moreover, it seems the patient may be developing pulmonary edema (hypoxia, jugular venous distension), a sign of fluid overload.

Answer E: Phenylephrine is the fourth line vasopressor and is an alpha-1 agonist. It is much less potent than norepinephrine and epinephrine, and would not be started in the management of septic shock until the patient has received epinephrine, norepinephrine, and vasopressin.

Bullet Summary:
In septic shock, the vasopressors given (in order) are norepinephrine, epinephrine/vasopressin, then phenylephrine.


Question: A 53-year-old man presents to the clinic with a non-tender mass in his right anterior neck. The mass has been slowly enlarging over the past 1 year. He reports no dysphagia, difficulty breathing, or changes to his voice. He also denies heat intolerance, palpitations, tremors, or diarrhea. He has hypertension and hyperlipidemia, for which he takes lisinopril and atorvastatin. He has never smoked cigarettes. His temperature is 37.1°C (98.8°F), blood pressure is 130/84 mmHg, pulse is 86/min, respirations are 12/min, and oxygen saturation is 99% on room air. Bedside ultrasound reveals a 1x2 cm hypoechogenic nodule with microcalcifications in the right thyroid lobe, which is biopsied. Pathology results are shown in Figure A. Which of the following is the most appropriate next step in management?

Thyroidectomy followed by radioactive iodine

Answer: Thyroidectomy followed by radioactive iodine

Explanation:
This patient who presents with a slowly enlarging neck mass has ultrasound (hypoechogenic nodule with microcalcifications) and histology findings (concentrically laminated calcifications called psammoma bodies) consistent with papillary thyroid carcinoma. The most appropriate next step in management would be thyroidectomy followed by radioiodine ablation.

Papillary thyroid carcinoma represents the majority of malignant thyroid cancers. They are slow-growing and are found in the hormone-producing follicular cells of the thyroid. Typically, these tumors are found incidentally on imaging. Risk factors for thyroid malignancy include a history of radiation exposure, female sex, and positive family history. Nodules with minimal uptake on radioactive iodine scan, firm and immobile solitary nodules, and rapidly growing nodules with associated hoarseness are more suggestive of thyroid malignancy. Findings on histology include empty-appearing nuclei with central clearing, psammoma bodies, and nuclear grooves. The treatment is thyroidectomy followed by radioactive iodine ablation of any remaining thyroid cells. Long-term care should include levothyroxine at a dose sufficient to suppress thyroid-stimulating hormone (TSH) release that may stimulate any remaining malignant cells.

Oakley et al. studied if relatives of patients diagnosed as having papillary thyroid carcinoma are at increased risk using a retrospective cohort study. The authors found first-degree relatives were at a 5-fold increased risk, and second-degree relatives were at a 2-fold increased risk. The authors recommend more research into optimal approaches to screening for thyroid cancers.

Figure/Illustration A is a histology section showing a psammoma body (blue circle), which are round, concentrically laminated calcifications that are formed after necrosis of papillary structures. Psammoma bodies and nuclei with central clearing (yellow circle) and nuclear grooves are common histology findings for papillary thyroid carcinoma.

Incorrect Answers:
Answer A: Levothyroxine would be the treatment of choice in hypothyroidism and is important in the long-term care of papillary thyroid carcinoma to suppress the TSH release that may stimulate any remaining malignant cells after treatment (thyroidectomy and radioactive iodine).

Answer B: Methimazole is an agent that blocks thyroid peroxidase, thus inhibiting the synthesis of thyroid hormones. It is used in the treatment of hyperthyroidism and does not have a role in the treatment of papillary thyroid carcinoma.

Answer C: Radioactive iodine is used as an adjunct after thyroidectomy in the treatment of papillary thyroid carcinoma in order to target any thyroid cells that may remain even after surgical excision. Surgery is the primary therapy for papillary thyroid carcinoma. Radioactive iodine is the primary method of therapy in cases of Grave disease, toxic adenoma, or multinodular goiter.

Answer D: Repeating an ultrasound in 6 months to assess the growth of the nodule or the development of suspicious characteristics is appropriate in cases where the ultrasound and biopsy findings are consistent with a benign thyroid nodule. The ultrasound findings of hypoechogenicity, microcalcifications, hypervascularity, and taller-than-wide nodules suggest malignancy, and together with a biopsy consistent with thyroid malignancy would warrant surgical treatment with subsequent radioactive iodine ablation.

Bullet Summary:
Papillary thyroid carcinoma is managed with thyroidectomy followed by radioactive iodine ablation and long-term levothyroxine to suppress thyroid-stimulating hormone stimulation of any remaining malignant cells.


Question: An 84-year-old man presents to the physician with numbness and tingling in the right hand for the last 6 months. He reports these symptoms started intermittently in the middle finger after returning from a golfing trip but has progressed to being nearly constant. The thenar eminence, thumb, and other digits are spared. He reports no other symptoms. His medical problems include hypertension, hyperlipidemia, hypothyroidism, and chronic neck pain for which he takes amlodipine, hydrochlorothiazide, atorvastatin, levothyroxine, and duloxetine. Surgical history consists of posterior lumbar fusion and elective left total hip arthroplasty. He has a 90-pack-year smoking history and quit 10 years ago. The patient’s temperature is 99.6°F (37.6°C), blood pressure is 134/80 mmHg, pulse is 90/min, and respirations are 16/min. Physical exam reveals 4/5 strength in elbow extension and wrist flexion on the right. He has 5/5 strength in the remainder of the motor exam on the right upper extremity and on the left upper extremity. The triceps reflex is 1+ on the right compared to 2+ on the left. There is no spasticity. His neck pain, which radiates down his right arm, is reproduced with axial loading during neck extension with simultaneous rightward rotation and lateral bending. Which of the following is the most likely diagnosis in this patient?

Answer: Cervical spondylosis

Explanation:
This patient presents with chronic middle finger paresthesia, weakness in elbow extension and wrist flexion, and a diminished triceps reflex in the setting of a positive Spurling test (pain with axial loading during neck extension, rotation, and lateral bending towards the affected side), indicative of C7 cervical radiculopathy. Cervical spondylosis is a common cause of cervical radiculopathy in elderly patients with chronic neck pain, especially in patients with findings suggestive of degenerative joint diseases (history of lumbar fusion and hip arthroplasty).

Cervical spondylosis is caused by degeneration of the intervertebral disc with possible disc herniation and facet joints with osteophyte formation. These osteophytes and cervical disc herniation can cause compression of exiting nerve roots, leading to radiculopathy. Radicular symptoms depend on the nerve root affected. For example, C6 radiculopathy causes weakness in wrist extension and a decreased brachioradialis reflex while C7 radiculopathy causes weakness in elbow extension and wrist flexion with a decreased triceps reflex. Sensory symptoms may be present depending on the dermatome affected. The diagnosis is confirmed with MRI. Treatment consists of non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, and/or corticosteroids for pain. Surgical treatments for severe or refractory cases include anterior cervical discectomy and fusion.

Young outlines the diagnosis and management of cervical spondylotic myelopathy. The discusses its pathophysiology, including osteophyte formation and spinal cord dysfunction. They recommend considering decompression and fusion operations in selected patients.

Incorrect Answers:
Answer A: Amyotrophic lateral sclerosis (ALS) is a motor neuron disease of the brain and spinal cord that leads to upper and lower motor neuron signs. ALS presents with hyperreflexia (as opposed to hyporeflexia), spasticity, weakness, and fasciculations. Treatment includes riluzole (to improve survival) and symptomatic management.

Answer B: Carpal tunnel syndrome is caused by compression of the median nerve as it travels through the carpal tunnel at the wrist. While the thenar eminence is typically spared due to take-off of the palmar cutaneous branch proximal to the carpal tunnel, the thumb and index finger are also affected. This patient’s symptoms primarily involve the middle finger, which is more indicative of a radiculopathy. Treatment is activity modification, splinting, and ultimately, surgical decompression of the carpal tunnel if refractory.

Answer D: Syringomyelia is caused by a fluid-filled cavity (syrinx) within the spinal cord that leads to central cord syndrome, characterized by weakness that is greater in the upper extremities compared to lower extremities and loss of pain and temperature sensation in a cape-like distribution in the upper back and upper extremities. This patient’s sensory loss is unilateral and in a dermatomal distribution. Treatment of syringomyelia can include surgical decompression.

Answer E: Transverse myelitis is characterized by segmental inflammation of the spinal cord that would present with acute, bilateral flaccid paresis based on the level affected and sensory loss within a sensory level. Autonomic symptoms such as incontinence may also be present. This patient’s symptoms are unilateral and localizable to nerve root compression as opposed to the spinal cord.

Bullet Summary:
Cervical spondylosis is caused by degeneration of cervical discs and facet joints with osteophyte formation and can present with symptoms of cervical radiculopathy or myelopathy in elderly patients with chronic neck pain.


Question: A 2-year-old boy is brought to the pediatrician’s office for a well-child visit. The parents have no concerns at this time and note he is starting to run around and speak in 3-word sentences. He has no remarkable medical history and his mother had an uncomplicated full-term pregnancy and delivery. He is appropriately meeting the developmental milestones for his age. The patient’s temperature is 98.4°F (36.9°C), blood pressure is 96/52 mmHg, pulse is 102/min, and respirations are 25/min. He is in the 55th percentile for height and 62nd percentile for weight, which is consistent with his documented growth curves. Fundoscopic exam shows the finding in Figure A. His pediatrician continues the ocular examination and further notes that the pupils are equal, round, and reactive, extraocular movements are full, and ocular alignment appears normal. Which of the following is the most appropriate next step in management?

Magnetic resonance imaging of the brain and orbits

Reevaluation at the next well-child visit

Answer: Ophthalmology referral

Explanation:
This otherwise healthy patient presents with leukocoria, or a white pupillary reflex, and requires an urgent referral to ophthalmology for further evaluation given the concern for retinoblastoma.

The differential diagnosis for leukocoria includes retinoblastoma, cataract, vitreous hemorrhage, retinal detachment, and other intraocular/systemic disease processes. Newly diagnosed leukocoria should be urgently referred to ophthalmology to exclude retinoblastoma. Retinoblastoma is the most common intraocular cancer of childhood caused by mutations in the RB1 tumor suppressor gene that encodes the retinoblastoma protein. Retinoblastoma typically presents as leukocoria in a child under the age of 3 with other signs including strabismus, nystagmus, or a red, inflamed eye. Treatment options include chemotherapy, laser photocoagulation, radiation, cryotherapy, and enucleation. Prompt diagnosis and treatment are important for optimal visual outcome and survival.

Francis et al. study the risk of extraocular extension in eyes with retinoblastoma that received intravitreous chemotherapy injections. The authors find that the risk of extraocular extension is small. The authors recommend the regular use of precautionary injection methods including lowering of intraocular pressure, cryotherapy, ocular surface irrigation, and ultrasonic biomicroscopy surveillance of the injection site.

Figure/Illustration A shows a child with leukocoria (blue circle) in the left eye.

Incorrect Answers:
Answer A: Biopsy of the eye is contraindicated in retinoblastoma due to the risk of tumor seeding.

Answer B: Genetic testing can be used to determine if a patient has the hereditary form of retinoblastoma, characterized by germline RB1 mutations, as opposed to the nonheritable form, which is associated with somatic RB1 mutations. An ophthalmological evaluation is required first to confirm the diagnosis.

Answer C: While magnetic resonance imaging of the brain and orbits should be performed in all children with suspected retinoblastoma to assess disease extent, an ophthalmological evaluation should be completed first.

Answer E: Reassurance or reevaluation at the next well-child visit is not appropriate management of newly diagnosed leukocoria given that undiagnosed retinoblastoma can be vision- and life-threatening.

Bullet Summary:
Leukocoria, or a white pupillary reflex, in a child requires urgent ophthalmologic referral to rule out retinoblastoma.


Question: A 17-year-old boy presents to the emergency department after a car accident. He drove his car into a pole while speeding at night. He has no past medical history and takes no medications. The patient is unable to offer a history and repetitively asks the nurses what happened. He knows his name and address and is able to remember other information about himself. He is complaining of a headache. His temperature is 97.6°F (36.4°C), blood pressure is 122/74 mmHg, pulse is 90/min, respirations are 12/min, and oxygen saturation is 98% of room air. Physical exam reveals a confused young man. Cranial nerves 2-12 are intact and the patient has normal strength and sensation. He demonstrates a stable gait. Throughout the exam, he continuously asks what happened to him. A head CT scan is ordered. Which of the following is the most likely diagnosis?

Answer: Concussion

Explanation:
This patient is presenting after a motor vehicle accident with confusion, repeated questioning, and a normal neurologic exam aside from his inability to remember the events that occurred. This constellation of symptoms is concerning for a concussion.

A concussion occurs after blunt trauma to the head and is common in athletics and motor vehicle collisions. Patients may present initially with symptoms including confusion, repeat questioning, repeating themselves, and amnesia surrounding the event. A thorough neurological exam is important as there should be no neurologic deficits in a concussion. Patients with a classic history and reassuring exam require rest from physical and cognitive activity. Post-concussive syndrome may present with chronic headaches, dizziness, trouble sleeping, trouble focusing, nausea, and difficulties with learning and concentrating. Mood changes such as depression and anxiety are common. Any patient with a concerning mechanism or symptoms should have a head CT to rule out other more severe diagnoses.

Pertab et al. review concussion and its presentation. They note that concussion can cause many symptoms including trouble focusing, mood changes, headaches, and also autonomic nervous system anomalies. They recommend reviewing the constellation of symptoms to make the diagnosis.

Incorrect Answers:
Answer A: Cerebral contusions are common after head trauma and may present with confusion, obtundation, neurologic deficits, and amnesia. While a severe concussion and a cerebral contusion have overlap, given this patient’s age, mechanism, and symptoms, concussion is more likely. A head CT would demonstrate contusion (hyperdense intraparenchymal lesion) with a possible contrecoup injury.

Answer C: Diffuse axonal injury occurs after a severe CNS injury with an obtunded patient who is typically unresponsive. CT imaging will show blurring of the gray-white interface with punctate hemorrhages. These patients have a very poor prognosis. They often are obtunded with minimal neurologic function.

Answer D: Epidural hematoma presents with trauma and the classic “talk and die” syndrome including a lucid interval followed by progressive obtundation and fixed, dilated pupils. Symptoms are rapidly progressive as this is an arterial bleed. CT scan would demonstrate a hyperdense lens-shaped lesion (composed of blood). A burr hole may relieve pressure and can be life-saving.

Answer E: Subarachnoid hemorrhage may present after trauma with a severe headache and meningeal signs. Patients may demonstrate focal neurologic deficits in severe cases. CT scan will demonstrate blood in the subarachnoid space and lumbar puncture would demonstrate blood in the CSF. A CTA may also localize the site of bleeding and if any aneurysm is present.

Bullet Summary:
A severe concussion can present with confusion, repeat questioning, and amnesia.


Question: A 47-year-old man presents to the emergency department with a headache. He suddenly developed a throbbing, bitemporal headache about 5 hours ago "out of nowhere." He has a history of migraine headaches, but he feels that this headache is significantly more painful than his typical migraines. The patient took his prescribed sumatriptan with no relief of his symptoms. He also endorses nausea and he reports that he vomited once before arrival in the emergency department. The patient denies any recent trauma to the head. His medical history is significant for migraines and hypertension. He has a 20-pack-year smoking history and a history of cocaine use. He drinks 5-6 beers per week. His temperature is 98.6°F (37°C), blood pressure is 147/91 mmHg, pulse is 62/min, and respirations are 12/min. On physical exam, he appears to be in moderate distress and has pain with neck flexion. He has no focal neurologic deficits. A head CT is performed and can be seen in Figure A. This patient’s condition affects the space in between which of the following brain layers?

Answer: Arachnoid mater and pia mater

Explanation:
This patient presents with a sudden, severe headache and a head CT showing bleeding in the subarachnoid space, which confirms a diagnosis of subarachnoid hemorrhage. The bleeding in a subarachnoid hemorrhage occurs between the arachnoid and pia mater.

Subarachnoid hemorrhages present with a sudden, severe headache referred to as a “thunderclap” headache. Patients typically complain that the headache is the "worst headache of their life." Some patients also present with symptoms of meningeal irritation such as nausea and vomiting, nuchal rigidity, or focal neurologic deficits. Although most cases of subarachnoid hemorrhage are secondary to trauma, patients with risk factors such as hypertension and cocaine use can have non-traumatic presentations. Patients with an expanding bleed or acute neurologic changes require surgical clipping or embolization of the bleeding vessels.

Macdonald and Schweizer review the evidence regarding the treatment of patients with subarachnoid hemorrhage. They discuss how survival rates have improved with early aneurysm repair, prescription of nimodipine, and advanced intensive care support. They recommend early diagnosis in order to improve outcomes in these patients.

Figure/Illustration A is an axial slice of a head CT showing hyperintensity in the basal cisterns (red circle). This finding is consistent with bleeding in the subarachnoid space.

Incorrect Answers:
Answer B: Bleeding between the dura and arachnoid mater describes a subdural hematoma. A subdural hematoma presents as a headache with progressive confusion. It appears as a crescent-shaped lesion on head CT. Patients with an expanding bleed will require surgical decompression to avoid herniation syndromes.

Answer C: Bleeding between the periosteum and galea aponeurosis describes a subgaleal hemorrhage. Subgaleal hemorrhages occur in newborns and are caused by vacuum-assisted deliveries. Treatment is usually supportive as the bleeding will resolve by itself. Some patients with severe bleeds may require transfusion due to excessive blood loss.

Answer D: Bleeding between the periosteum and skull describes a cephalohematoma. Cephalohematomas occur in newborns and are caused by rupture of the blood vessels crossing the periosteum. They are usually secondary to a prolonged second stage of labor. Treatment is supportive as the blood will resolve and be resorbed.

Answer E: Bleeding between the skull and dura mater describes an epidural hematoma. An epidural hematoma presents as a brief loss of consciousness followed by a lucid interval and then progressive confusion or somnolence. It appears as a biconvex lesion on head CT. Treatment is with urgent surgical decompression as patients will rapidly decompensate after the lucid interval.

Bullet Summary:
Subarachnoid hemorrhage classically presents as a thunderclap headache with a brief loss of consciousness and meningismus.


Question: An 82-year-old man with a history of atrial fibrillation presents to the emergency room complaining of sudden-onset, painless vision loss in his right eye starting 2 days ago. When it started, he felt like a “curtain was pulled down” over his right eye but wasn't able to seek care immediately because it was snowing outside and he didn't want to travel in inclement weather. A review of systems is significant for occasional palpitations and presyncope. The patient’s medications include aspirin and carvedilol. He reports that he is a smoker with a 50-pack-year history. The patient’s temperature is 99°F (37.2°C), blood pressure is 112/72 mmHg, pulse is 84/min, and respirations are 14/min with an oxygen saturation of 97% on room air. Physical exam reveals 20/800 vision in the right eye. A fundoscopic exam of the right eye is shown in Figure A. Physical and fundoscopic examinations of the left eye are unremarkable. Which of the following is the most appropriate next step in management?

Continue aspirin and start statin therapy

Answer: Continue aspirin and start statin therapy

Explanation:
This patient with a history of atrial fibrillation is presenting with acute-onset, painless, monocular vision loss and a fundoscopic exam positive for retinal whitening. This suggests a diagnosis of central retinal artery occlusion and management should focus on control of underlying risk factors given that he is 2 days out from the event.

Symptoms of central retinal artery occlusion (CRAO) include sudden, painless, complete, and normally unilateral vision loss. A fundoscopic exam can show pallor of the optic disc, diffuse ischemic whitening of the retina, cherry-red macula, retinal edema, and constricted/bloodless retinal arterioles. The center of the macula appears red because the photoreceptor layer at the fovea is perfused by the posterior choroidal vasculature rather than the central retinal artery. Treatment involves surgical decompression of the retinal anterior chamber, ideally within 1 hour of the occlusion. Tissue plasminogen activator should be administered if the patient presents within an acceptable time frame. If surgical intervention is not readily available, additional steps with minimal evidence to support their use include ocular massage (to dislodge the embolus) and either carbogen therapy or hyperbaric oxygen. Chronic management includes control of underlying risk factors with aspirin and statin therapy.

Dattilo et al. review the evidence regarding the treatment of central retinal artery occlusion. They discuss how treatments have not been particularly effective in the treatment of this disorder. They recommend engaging in secondary prevention of vascular events by controlling risk factors.

Figure/Illustration A is a fundoscopic photograph showing retinal pallor surrounding the superior temporal arcade (red circle). This finding is characteristically seen in central retinal artery occlusion.

Incorrect Answers:
Answer A: Administering ranibizumab is not appropriate because this medication is an anti-VEGF antibody, which can be used to treat wet age-related macular degeneration. Symptoms of wet age-related macular degeneration include acute visual distortion and loss of central vision that occurs over months. A fundoscopic exam would show neovascularization.

Answer B: Administration of tissue plasma activator has not been shown to be beneficial in central retinal artery occlusion if the event has occurred several days ago. This medication is used in patients who sustain an ischemic stroke within 4.5 hours of developing symptoms. A stroke in the posterior lobe can present with cortical hemianopsia.

Answer D: Retinal photocoagulation is used to treat diabetic retinopathy. In diabetic retinopathy, symptoms of painless vision loss present gradually. A retinal exam would show retinal hemorrhage and possibly neovascularization.

Answer E: Timolol is a beta-blocker used to treat glaucoma. Assessment of the optic disk would show an enlarged cup-to-disk ratio. Glaucoma can present with pain and pressure in the affected eye. Acute angle closure glaucoma would present with a rock-hard eye and may lead to permanent vision loss if not treated promptly.

Bullet Summary:
Chronic management of central retinal artery occlusion involves control of underlying risk factors with aspirin and statin therapy.


Question: A 34-year-old nulliparous woman presents to the clinic with 2 weeks of copper-colored discharge from her right nipple. Her breast has not been tender, and she has not noticed any changes to the skin. She is otherwise healthy and does not take any medications. Her temperature is 36.5°C (97.7°F), blood pressure is 110/82 mmHg, pulse is 68/min, respirations are 12/min, and oxygen saturation is 99% on room air. Exam of the right breast reveals no mass on palpation. Bloody discharge is expressed from the right nipple. There is no axillary lymphadenopathy. Which of the following is the most likely diagnosis?

Answer: Intraductal papilloma

Explanation:
This young patient who presents with non-painful unilateral bloody nipple discharge and no palpable mass on breast exam most likely has an intraductal papilloma.

Intraductal papilloma is a benign epithelial tumor that develops in the lactiferous ducts of the breast and is the most common cause of bloody nipple discharge in premenopausal women. Patients typically present with painless unilateral bloody nipple discharge, and often there is no mass palpable on breast exam. Ultrasound is the initial method for evaluation and may reveal an intraductal mass, but if results are inconclusive, further imaging with mammography is indicated. If the results of both still remain inconclusive, galactography (radiography after injecting radiopaque contrast into the duct system) is the most accurate imaging method for diagnosing intraductal papilloma. A core biopsy of the intraductal mass should be obtained, and if results show papilloma with atypia, treatment would be surgical excision of the involved duct to rule out a concomitant malignant neoplasm.

Khan et al. review the treatment of intraductal papilloma and note that in lesions with core biopsy showing papilloma with atypia, surgical excision revealed the diagnosis of a concomitant invasive or ductal in situ cancer is common. The authors also find that in patients whose core biopsies showed papilloma without atypia, the likelihood of cancer was much lower. The authors recommend that since the diagnosis of intraductal papilloma carries an increased risk of breast cancer compared to the general population, these patients should be monitored accordingly.

Incorrect Answers:
Answer A: Ductal carcinoma in situ (DCIS) is a neoplastic lesion confined to the breast duct that if untreated develops into invasive ductal carcinoma. Typically, patients are asymptomatic, and lesions are detected via screening mammography. Though it can sometimes present with nipple discharge, this is less common. Unilateral painless bloody nipple discharge is more likely to be due to intraductal papilloma, though no mass may be palpable for either diagnosis.

Answer C: Invasive ductal carcinoma is the most common type of breast cancer, which typically presents as a firm, immobile, painless lump in the breast, sometimes associated with nipple discharge, overlying skin changes, inverted nipple, and/or axillary lymphadenopathy. As with DCIS, nipple discharge may be present but is usually not bloody as in cases of intraductal papilloma.

Answer D: Mammary duct ectasia is a benign condition in which a milk duct in the breast widens and its walls thicken, leading to blockage and build-up of fluid in the duct. This is usually asymptomatic but can present with off-white or greenish nipple discharge. It may also result in infection of the affected duct, leading to periductal mastitis and a tender, erythematous breast. It tends to occur in perimenopausal women and often resolves without treatment, though if symptoms persist it can be treated with antibiotics and duct excision.

Answer E: Paget disease of the breast often presents as a scaly, raw, vesicular, or ulcerated lesion that begins on the nipple and then spreads to the areola, sometimes associated with bloody nipple discharge. Pain, burning, and pruritis are also common presenting symptoms. There is often an underlying breast carcinoma; thus, any patient with Paget disease should be evaluated with a mammogram. Although this patient has bloody nipple discharge, she does not present with a painful, scaly, raw, or vesiculated lesion that would be concerning for Paget disease of the breast.

Bullet Summary:
Intraductal papilloma often manifests in patients as painless unilateral bloody nipple discharge, and typically no mass is palpable on exam.


Question: A 21-year-old man presents to the emergency room with right lower quadrant pain that started this afternoon at his wrestling match. He also endorses loss of appetite and subjective fever. He has had vague, mild discomfort in the right upper quadrant since the start of this wrestling season. He endorses a history of unprotected sex with multiple partners and intravenous drug use during a recent vacation to Mexico but has no other significant medical history. He drinks socially and has never smoked. His temperature is 98.6°F (37°C), blood pressure is 119/72 mmHg, pulse is 102/min, and respirations are 12/min. Physical exam demonstrates pain on palpation of the right lower quadrant and mild pain in the right upper quadrant. He has significant acne on his face, chest, and back. A CT of the abdomen confirms appendicitis. The scan also shows a large liver mass measuring 6 cm as seen in Figure A. Aside from addressing his appendicitis, which of the following is the most appropriate next step in management?

Obtain follow-up CT of the abdomen in 3 months

Answer: Perform liver mass resection

Explanation:
This patient with a history of possible anabolic steroid use (wrestler with acne) who presents with right upper quadrant pain and an enhancing lesion in the liver most likely has a hepatic adenoma. The treatment of hepatic adenomas is surgical removal and discontinuation of precipitating agents.

Hepatic adenomas are benign epithelial tumors that typically arise in the right hepatic lobe. They are typically solitary masses but multiple lesions can be seen in patients with prolonged contraceptive or anabolic steroid use and those who have glycogen storage disorders. Patients present with abdominal pain that is localized in the epigastrium or in the right upper quadrant. Sudden, severe abdominal pain with hypotension suggests rupture of the hepatic adenoma into the peritoneum. The lesions can be confirmed on imaging such as ultrasound, CT, or MRI. For hepatic adenomas that are < 5 cm and asymptomatic, simply discontinuing the causative drug and observing are acceptable. Large or symptomatic lesions requiring surgical resection in addition to discontinuation of the offending agent. Because these tumors are highly vascular, failure to resect may result in rupture, hemoperitoneum, and shock. Biopsy is contraindicated to avoid rupturing the mass and causing hemorrhage.

Klompenhouwer et al. studied the current management strategies in patients with hepatocellular adenoma. They found that various molecular groups have been identified allowing for subtyping of these lesions. They recommend performing a CT scan to better characterize these lesions.

Figure/Illustration A is a CT with an enhancing mass with a hypoattenuating fatty component. This is characteristically seen in large hepatic adenomas, which are solitary well-marginated lesions.

Incorrect Answers:
Answer A: Metronidazole would be an effective treatment if this patient had contracted Entamoeba histolytica from contaminated food or water on his recent trip to Mexico. While this amoeba can lead to a liver abscess presenting as a mass on CT, it often also causes abdominal pain and dysentery due to intestinal involvement.

Answer B: Sofosbuvir is an antiviral medication used for hepatitis C. This patient does have risk factors for hepatitis C (risky sexual behavior and intravenous drug use). Although hepatitis C could lead to hepatocellular carcinoma and cause a liver mass, this patient’s presentation is not consistent with that diagnosis. Even if he did have hepatocellular carcinoma, treating hepatitis C alone without surgical resection or adjuvant therapies would be insufficient.

Answer C: Follow-up CT in 3 months would be dangerous for this man with a large hepatic adenoma. In the interim, the mass will likely continue to grow if he continues to use anabolic steroids, increasing the risk of rupture. Observation and repeat imaging may be suitable for asymptomatic hepatic lesions that are of uncertain but likely benign etiology.

Answer D: Biopsying the liver mass is appropriate if malignancy is suspected and there is no concern for hepatic adenoma. If an adenoma is on the differential, biopsy is contraindicated due to the risk of rupture and hemorrhage intraoperatively.

Bullet Summary:
Hepatic adenomas are benign, vascular liver masses associated with oral contraceptives and anabolic steroids that should be promptly resected if large and symptomatic.


Question: A 19-year-old man presents to his primary care physician. He is asymptomatic and has no acute complaints, has no medical problems, and takes no medications. He was born in the United States but moved to El Salvador at age 11 and has only recently moved back to the United States in the past year. He was up to date on his vaccinations prior to his move to El Salvador. He last received a diphtheria, tetanus, and acellular pertussis (DTaP) vaccine 14 years ago at age 5, the second dose of a meningococcal vaccine 3 years ago, and an influenza vaccine 2 months ago. The patient’s temperature is 98.2°F (36.8°C), blood pressure is 120/76 mmHg, pulse is 82/min, and respirations are 16/min. There are no rashes noted on physical exam. Which of the following vaccine regimens is indicated in this patient?

Tetanus, diphtheria, and acellular pertussis

Answer: Tetanus, diphtheria, and acellular pertussis

Explanation:
This patient has recently moved back to the United States after living in another country for several years and is behind on his tetanus, diphtheria, and pertussis vaccine series. The tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is indicated at least once in adults who have not previously received Tdap.

The standard vaccination schedule for tetanus, diphtheria, and pertussis includes a 5-dose childhood vaccine series consisting of DTaP at ages 2 months, 4 months, 6 months, 15-18 months, and 4-6 years. The first booster dose then consists of Tdap at age 11-12, with a tetanus and diphtheria (Td) vaccine every 10 years afterwards. In adults who have not previously received Tdap, a single Tdap dose should be administered regardless of time interval since the last dose of Td. Subsequent Td booster doses should then be given at 10-year intervals. Contraindications to Tdap include prior anaphylaxis after a tetanus, diphtheria, or pertussis vaccine or a history of seizures or encephalopathy within 7 days of receiving a previous pertussis-containing vaccine.

Kerr et al. studied the risk of major birth defects after administering the Tdap vaccine in pregnant patients. The authors found no increase in the risk of malformations in the offspring of pregnant patients that received the Tdap vaccine. The authors recommend the administration of Tdap during pregnancy.

Incorrect Answers:
Answer A: Influenza is incorrect because the influenza vaccine is recommended only once per flu season. This patient already received the flu vaccine during this flu season, so the influenza vaccine is not indicated.

Answer B: Tetanus and diphtheria only are incorrect because the Td vaccine booster is indicated every 10 years in adults who have already received a prior dose of Tdap. In adults who have never received a previous Tdap dose, Tdap is indicated unless contraindications exist.

Answer C: Tetanus, diphtheria, acellular pertussis, and influenza are incorrect because influenza vaccine is not indicated in this patient. This patient has already received a dose of the influenza vaccine during this flu season.

Answer E: Tetanus, diphtheria, and influenza are incorrect because neither the Td nor influenza vaccines are indicated in this patient. The Td vaccine is indicated every 10 years in adults who have already received a prior dose of Tdap. The influenza vaccine is only indicated once per flu season.

Bullet Summary:
The tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is usually administered to adolescents at age 11-12 and is indicated at least once in adults who have not previously received Tdap.


Question: A 7-week-old boy presents to the pediatrician for vomiting. Three weeks ago, the patient began vomiting after meals. The vomitus appears to be normal stomach contents without streaks of red or green. His parents have already tried repositioning him during mealtimes and switching his formula to eliminate cow’s milk and soy. Despite these adjustments, the vomiting has become more frequent and forceful. The patient is voiding about 4 times per day and his urine appears dark yellow. He has fallen 1 standard deviation off of the growth curve. The patient's mother reports that the pregnancy was uncomplicated other than an episode of sinusitis in the 3rd trimester, for which she was treated with azithromycin. The patient's temperature is 98.7°F (37.1°C), blood pressure is 58/41 mmHg, pulse is 166/min, and respirations are 16/min. On physical exam, the patient looks small for his age. His abdomen is soft, non-tender, and non-distended. Which of the following is the most appropriate next step in management?

Answer: Intravenous hydration

Explanation:
This patient presents with nonbilious, forceful vomiting, poor weight gain, signs of dehydration, and a history of exposure to azithromycin, which suggests a diagnosis of pyloric stenosis. The most appropriate next step in management is intravenous hydration.

Pyloric stenosis classically presents in a male infant between 4 to 6 weeks of age with nonbilious, projectile vomiting after meals. Risk factors for pyloric stenosis include bottle feeding and exposure to macrolide antibiotics in the patient or mother. Protracted vomiting frequently leads to hypochloremic, hypokalemic metabolic alkalosis. Patients should be resuscitated with intravenous hydration and evaluated for electrolyte abnormalities that require repletion. After a patient is adequately resuscitated, patients can undergo an ultrasound to confirm the diagnosis and then be treated surgically for definitive therapy.

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: Abdominal ultrasound is the test of choice to diagnose pyloric stenosis, but evaluation for electrolyte derangements and subsequent intravenous hydration and electrolyte repletion should be initiated first in this patient with signs of dehydration and malnutrition. Further evaluation is reserved after a patient is adequately resuscitated.

Answer B: MRI of the head would be appropriate if this patient had additional signs of a mass in the head, such as neurological changes or worsening of the vomiting in the morning. In the absence of these signs and the presence of a mass in the epigastrium, this patient is more likely to have pyloric stenosis.

Answer C: Pyloromyotomy is the definitive management of pyloric stenosis, but this patient should undergo fluid replacement and have any electrolyte derangements detected and managed before undergoing surgery. Surgical intervention can carry significant risks if patients are not adequately resuscitated.

Answer E: Thickening feeds are one of the techniques used to manage gastroesophageal reflux. In the setting of this patient’s epigastric mass and clinical picture, pyloric stenosis is the more likely etiology of his vomiting. Reflex presents with non-projectile vomiting that is dependent on position.

Bullet Summary:
Patients with pyloric stenosis should first undergo intravenous rehydration and electrolyte repletion, as protracted vomiting may lead to severe hypochloremic, hypokalemic metabolic alkalosis.


Question: A 34-year-old man presents to the emergency room with pain behind his eyes. He had a similar episode about 1 month ago which resolved after a few hours. The pain feels like a stabbing sensation behind his right eye. He denies any symptoms on the left side. The last time he had an episode like this, his eye was tearing. His temperature is 98.2°F (36.8°C), blood pressure is 120/90 mmHg, pulse is 110/min, and respirations are 12/min. Physical exam reveals a 2 mm pupil on the right and a 5 mm pupil on the left. Extraocular movements are intact bilaterally. The remainder of the neurologic exam is unremarkable. Which of the following is the most appropriate prophylactic treatment?

Answer: Verapamil

Explanation:
This patient with a history of retro-orbital pain, unilateral miosis (2 mm pupil on the right), and history of lacrimation during a similar episode is likely experiencing cluster headaches. Verapamil may be used as prophylaxis in the treatment of cluster headaches.

Cluster headaches occur more commonly in men and present with severe, unilateral, retro-orbital pain. Typical episodes last 15 minutes to 3 hours. Attacks may be associated with the circadian rhythm, as patients may notice that they get headaches at night. Because of the extreme pain, cluster headaches are sometimes colloquially referred to as "suicide" headaches. These headaches may present with autonomic symptoms, such as lacrimation and rhinorrhea. Horner syndrome may also occur, defined by a unilateral triad of ptosis, miosis, and anhidrosis. Acute management of cluster headaches includes administration of 100% oxygen. Other options include triptans. The first-line medication for prophylaxis of cluster headaches is verapamil. Studies have shown that lithium, topiramate, and ergotamine may also be effective as prophylaxis for cluster headaches; however, these therapies are less established than verapamil.

Blau and Engel review the use of medications for cluster headaches. They note that most of patients with episodic cluster headaches had complete suppression of attacks with the use of verapamil. It is recommended to give verapamil in this patient population.

Incorrect Answers:
Answer A: Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) that is used in the treatment of migraine and tension headaches. Migraine headaches present with unilateral, pulsating pain with photophobia and phonophobia, whereas tension headaches present with constant bilateral pain. Ibuprofen should not be used as prophylaxis for any type of headache as it has side effects including kidney dysfunction, ulcers, and even premature aging.

Answer B: Oxygen is first-line treatment for acute cluster headaches; however, it does not have any role in the prophylaxis of cluster headaches.

Answer C: Propranolol is a beta-blocker that is a prophylactic medication for migraine headaches. Migraines are more common in women and typically present as a unilateral headache with photophobia or phonophobia. They may also be associated with an aura, which presents as a visual, auditory, olfactory, or motor disturbance.

Answer D: Sumatriptan is a triptan that is used as an abortive treatment for migraine headaches and cluster headaches. It should not be used as prophylaxis for headaches.

Bullet Summary:
Verapamil may be used as prophylaxis for cluster headaches.


Question: A 65-year-old man presents to his primary care physician for a routine appointment. He has no concerns. His past medical history is significant for human immunodeficiency virus (HIV) infection, diagnosed 15 years ago. The patient is intermittently compliant with his antiretroviral therapy (ART). His temperature is 99.0°F (37.2°C), blood pressure is 130/84 mmHg, pulse is 92/min, and respirations are 11/min. His most recent lab work showed a cluster of differentiation CD4 count of 150 cells/µL. He received a dose of the 13-valent pneumococcal vaccine and a dose of the 23-valent pneumococcal vaccine 15 years ago, as well as a second dose of the 23-valent pneumococcal vaccine 10 years ago. In addition to encouraging greater compliance with his ART, which of the following is indicated in this patient?

Trimethoprim-sulfamethoxazole and pneumococcal vaccine

Trimethoprim-sulfamethoxazole and varicella vaccine

Trimethoprim-sulfamethoxazole and zoster vaccine

Answer: Trimethoprim-sulfamethoxazole and pneumococcal vaccine

Explanation:
This patient with HIV and a CD4 count of 150 cells/μL requires trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis and another dose of the 23-valent pneumococcal vaccine.

All HIV patients with a CD4 count < 200 cells/μL require TMP-SMX as prophylaxis against Pneumocystis jirovecci pneumonia. Patients with CD4 counts < 100 cells/μL also require TMP-SMX as prophylaxis against toxoplasmosis. HIV patients require a dose of the 23-valent pneumococcal vaccine at age 65. Patients should initially receive the 13-valent pneumococcal vaccine, followed by the 23-valent pneumococcal vaccine 8 weeks later, 5 years later, and at age 65. Compliance with ART is also critical in patients with HIV.

Kaplan et al. discuss recommendations for the prevention of opportunistic infections in HIV-infected adults. The authors find that daily prophylaxis with TMP-SMX is an appropriate regimen for the prevention of Pneumocystis pneumonia. The authors recommend dapsone, atovaquone, or pentamidine for patients that cannot receive TMP-SMX.

Incorrect Answers:
Answer A: Azithromycin is used as prophylaxis against Mycobacterium avium complex (MAC) in patients with a CD4 count < 50 cells/μL that has not been started on ART. Since this patient has a CD4 count of 150 cells/μL, azithromycin is not indicated at this time.

Answer B: Azithromycin is used as prophylaxis against Mycobacterium avium complex (MAC) in patients with a CD4 count < 50 cells/μL that has not been started on ART. This patient should not receive the zoster vaccine as it is a live vaccine and is contraindicated in immunocompromised patients.

Answer D: Although this patient does require TMP-SMX as prophylaxis against Pneumocystis pneumonia, he should not receive the varicella vaccine as it is a live vaccine and therefore contraindicated in immunocompromised patients.

Answer E: Although this patient does require TMP-SMX as prophylaxis against Pneumocystis pneumonia, he should not receive the zoster vaccine as it is a live vaccine and therefore contraindicated in immunocompromised patients.

Bullet Summary:
Patients with a CD4 count < 200 cells/μL require prophylaxis with TMP-SMX and all patients with HIV should receive a dose of the 23-valent pneumococcal vaccine at age 65.


Question: A 55-year-old woman is brought to the emergency department by her husband with a 1 hour history of an unremitting headache. The headache started suddenly while she was eating dinner and she says it feels like the “worst headache of my life.” An emergent CT scan of the head without contrast confirms the diagnosis, and a CT angiogram identifies the source of bleeding. The patient undergoes surgical management of her condition. On hospital day 3, she is found to be disoriented to person, place, and time. She also develops nausea and vomiting. Her medical problems consist of heart failure for which she takes furosemide, spironolactone, and metoprolol, which were continued at admission. Her temperature is 99.6°F (37.6°C), blood pressure is 100/60 mmHg, pulse is 112/min, and respirations are 16/min. Physical examination shows poor skin turgor. Capillary refill time is 4 seconds. Serum laboratory results are shown below: Na+: 120 mEq/L Cl-: 92 mEq/L K+: 3.9 mEq/L HCO3-: 26 mEq/L BUN: 32 mg/dL Creatinine: 1.0 mg/dL Serum osmolality is 265 mEq/L and urine osmolality is 340 mEq/L. Urine sodium is 44 mEq/L. Which of the following is the most likely diagnosis?

Answer: Cerebral salt wasting

Explanation:
This patient presents with a subarachnoid hemorrhage (“worst headache of my life”) which is treated and then subsequently develops nausea, vomiting, and altered mental status with reduced serum sodium concentration, indicative of symptomatic hyponatremia. In the setting of serum hypo-osmolality, urine hyper-osmolality, urine sodium concentration > 20 mEq/L, and hypovolemia (low blood pressure, decreased skin turgor, and prolonged capillary refill), this is indicative of cerebral salt wasting.

The mechanism of cerebral salt wasting is unclear, although some hypotheses point to increased release of brain natriuretic peptide after injury leading to suppression of renal sodium reabsorption, or sympathetic nervous system injury resulting in an impaired renin response. Patients classically present several days after cerebral injury or neurosurgery with hypovolemic hyponatremia and hypochloremia. Water retention results in serum hypo-osmolality, hyponatremia, and hypochloremia with urine hyper-osmolality and increased urine sodium excretion. In patients with prolonged cerebral salt wasting, hypokalemia can also occur (potassium may be normal in acute states). Treatment in mild or moderate cases consists of normal saline infusion to correct both volume status and hyponatremia. Treatment in severe cases consists of hypertonic saline. During correction, serum sodium must be monitored closely to prevent central pontine myelinolysis.

Cui et al. describe the differences between syndrome of inappropriate anti-diuretic hormone (SIADH) and cerebral salt wasting. They discuss how volume status serves as the key differentiator between these conditions. They recommend paying closer attention to total body electrolyte balance in understanding these conditions.

Incorrect Answers:
Answer A: Addison disease, also known as primary adrenal insufficiency, results in salt wasting due to decreased mineralocorticoid activity. Because of reduced aldosterone release, patients also have hyperkalemia and metabolic acidosis. In contrast, this patient’s potassium and bicarbonate levels are normal. Treatment is with steroids.

Answer C: Diuretic overuse is occasionally observed in patients using loop diuretics. Overuse of loop diuretics can cause hyponatremia, hypokalemia, and hypochloremia. Metabolic alkalosis is commonly seen due to volume contraction. Cerebral salt wasting is more likely in this patient presenting after a recent cerebral injury. Treatment is the cessation of the causative medication.

Answer D: Primary polydipsia can cause symptomatic hyponatremia. The urine would be maximally diluted (urine osmolality < 100 mEq/L) due to an appropriate physiological response to hyponatremia and excess free water intake. Treatment is cessation of excessive water consumption.

Answer E: Syndrome of inappropriate anti-diuretic hormone (SIADH) presents with identical findings as cerebral salt wasting with the exception of euvolemia as opposed to hypovolemia. An assessment of volume status is essential to differentiate. This patient has clear signs of hypovolemia. Treatment of SIADH is fluid restriction followed by ADH inhibitors, if needed.

Bullet Summary:
Cerebral salt wasting presents with hyponatremia, hypochloremia, and hypovolemia in the setting of recent cerebral injury or neurosurgery.