U World 3/25

Absolute risk reduction

Risk control - risk treatment

This patient's intracranial hemorrhage was likely treated with andexanet alfa, a biologic agent that shares homology with factor Xa but has no proteolytic effect. It is administered to patients who have life-threatening bleeding while on a factor Xa inhibitor (eg, ____, ____). The similarity of andexanet to factor Xa allows it to function as a decoy that binds to factor Xa inhibitors. This restores intravascular coagulation by increasing the availability of endogenous factor Xa, which converts prothrombin to thrombin and generates fibrin clots. Andexanet is reserved for life-threatening bleeding because it is associated with a significant risk of thrombosis

rivaroxaban, apixaban

negative predictive value =

true negative/ total number of negative tests

Number needed to treat

1/ARR arr = risk control - risk treatment

D. Inhibition of transpeptidase and bacterial cell wall cross-linking (%) Syphilis is caused by the corkscrew-shaped organism Treponema pallidum. Secondary syphilis develops in untreated patients weeks or months after the initial infection, and presents with a diffuse, macular rash and generalized lymphadenopathy. First-line treatment is penicillin, which blocks the last step in bacterial cell wall synthesis (transpeptidation)

28-year-old man comes to the office due to a rash. He has a history of seizure disorder and has been taking phenytoin for 6 years. Examination shows a diffuse, macular rash and lymphadenopathy. Biopsy of a lymph node is shown in the exhibit. Treatment of this patient's condition is most likely to involve which of the following? A. Blockade of viral reverse transcriptase and integrase (%) B. Diminished type IV delayed hypersensitivity reaction (%) C. Inhibition of bacterial DNA gyrase and topoisomerase (%) D. Inhibition of transpeptidase and bacterial cell wall cross-linking (%) E. Reduced production of dihydrofolic acid and tetrahydrofolic acid (%)

A 35-year-old man comes to the office for a routine health maintenance evaluation. After separating from his wife, the patient recently moved to "make a fresh start" and start a new job. He has no chronic medical conditions and has had no surgeries. The patient is sexually active and has had 6 lifetime partners. When completing the rest of the sexual history, which of the following questions is most appropriate for the physician to ask? A. "What are the genders of your current and previous sexual partners?" (%) B. "Can you tell me about your previous romantic relationships?" (%) C. "Did you have other sexual partners while you were married?" (%) D. "Do you identify as heterosexual, homosexual, or bisexual?" (%) E. "Have you ever had sexual intercourse with a man?" (%)

A. "What are the genders of your current and previous sexual partners?" (%) When asking about sexual partners, the physician should avoid using labels or making assumptions about patients or their partners' sexual orientation or gender identity. Asking an open-ended question about all sexual partners allows patients to describe their sexual partners and behavior in terms that they are familiar with and that reflect their gender identity. After inquiring about the gender of sexual partners (including trans, nonbinary), the physician can ask about pertinent types of sex (eg, vaginal, oral, anal) with each partner in order to make testing recommendations for sexually transmitted infections (eg, HIV) and discuss risk-reduction strategies. Another possible formulation is, "What is/are the sex and gender of your sexual partner(s)?

A 45-year-old man is brought to a rural emergency department due to severe chest pain, sweating, and nausea. The symptoms began suddenly an hour ago. He has no significant medical history. His father died at age 50 after experiencing sudden-onset chest pain. The patient smokes a pack of cigarettes daily. He does not take any medications and has no known drug allergies. Examination shows normal heart sounds and breath sounds. ECG shows sinus tachycardia with ST segment elevation in leads II, III, and aVF. Medical management for the patient's acute condition is initiated. After initial treatment, the chest pain decreases in intensity and a reperfusion complex ventricular arrhythmia emerges. The arrhythmia is asymptomatic and resolves spontaneously. Which of the following drugs is most likely responsible for rapid reperfusion in this patient? A. Alteplase (%) B. Apixaban (%) C. Argatroban (%) D. Aspirin (%) E. Heparin (%) F. Prasugrel (%) G. Rosuvastatin (%)

A. Alteplase (%) This patient had an ST-elevation myocardial infarction (STEMI) and, following medical treatment, experienced symptomatic improvement and reperfusion-related arrhythmia; this is most likely the result of fibrinolytic (thrombolytic) therapy. Fibrinolytic agents (eg, alteplase) are indicated in patients with acute STEMI who cannot receive percutaneous coronary intervention in a timely manner. Administration of these agents leads to breakdown of fibrin clot and often restoration of myocardial perfusion; some patients develop a self-limiting reperfusion-related arrhythmia (most commonly an accelerated idioventricular rhythm).

A. BCL-2 overexpression (%)

A. BCL-2 overexpression (%) B. BCR-ABL rearrangement (%) C. C-MYC overexpression (%) D. Constitutive tyrosine kinase activation (%) E. N-MYC overexpression (%)

62-year-old hospitalized man is evaluated for new-onset renal failure. The patient was admitted 3 days ago due to precordial chest pain. He was found to have an elevated troponin I level but no ST-segment elevation on ECG. Percutaneous catheterization revealed 3-vessel coronary artery disease, and no coronary interventions were performed. The patient has continued to receive medical treatment while awaiting coronary artery bypass graft surgery. Today, he was noted to have elevated blood urea nitrogen and serum creatinine levels. The patient has had no fever, and blood pressure and heart rate have been within normal limits. Physical examination shows no new findings. Which of the following pathologic findings is most likely present in this patient? A. Diffuse necrosis of the proximal tubular cells (%) B. Extensive crescents in the glomeruli (%) C. Fibrin-like material lining the arteriolar walls (%) D. Mononuclear cell infiltrate in the interstitium (%) E. Needle-shaped clefts in the arterioles (%)

A. Diffuse necrosis of the proximal tubular cells (%) This patient developed acute kidney injury after undergoing percutaneous catheterization, a procedure that uses contrast material to evaluate the patency of the coronary arteries. In a patient with normal vital signs, this presentation suggests contrast-induced nephropathy (CIN). Patients with CIN typically have an acute rise in creatinine and blood urea nitrogen within 24-48 hours of contrast administration, followed by a gradual return to baseline. The etiology of CIN remains unclear but is likely multifactorial and includes: Direct cytotoxicity causing acute tubular necrosis, resulting in diffuse necrosis of the proximal tubular cells visible on histologic specimens and muddy brown casts on urinalysis Renal vasoconstriction causing medullary ischemia

A 60-year-old man comes to the office with a 6-month history of exertional chest pain that remits with rest. His other medical conditions include hypertension, diabetes mellitus, and hypercholesterolemia. An exercise stress test is positive for inducible ischemia. Cardiac catheterization shows 80% occlusion of the right coronary artery and 60% occlusion of the left coronary artery. The first step in the pathogenesis of this patient's coronary artery disease most likely involved which of the following cell types? A. Endothelial cells (%) B. Interstitial fibroblasts (%) C. Macrophages (%) D. Mast cells (%) E. Pericytes (%) F. Platelets (%) G. Smooth muscle cells (%)

A. Endothelial cells (%) Atherosclerosis is initiated by repetitive endothelial cell injury, which leads to a chronic inflammatory state in the underlying intima of large elastic arteries as well as in large- and medium-sized muscular arteries.

26-year-old man is brought to the emergency department due to fever and lethargy. His girlfriend says the patient abruptly began experiencing fever, chills, vomiting, and diarrhea several hours ago, which were quickly followed by lightheadedness and lethargy. He has no prior medical conditions other than an episode of epistaxis after a bar fight 3 days ago. The patient does not smoke cigarettes or use injection drugs. There is no history of exposure to sick contacts, and he has not eaten anything out of the ordinary. Temperature is 38.9 C (102 F), blood pressure is 90/60 mm Hg, and pulse is 120/min. Physical examination shows a diffuse, erythematous rash. There is an anterior nasal packing in the left nostril, removal of which shows mild mucosal erythema with a purulent discharge. Cardiopulmonary and abdominal examinations reveal no abnormalities, and signs of meningeal irritation are absent. Which of the following processes is most essential in pathogenesis of this patient's current condition? A. Activation of toll-like receptors by bacterial components (%) B. Binding of T-cell receptors by bacterial secretory products (%) C. Bridging of cell-bound IgE by multivalent antigens (%) D. Phagocytosis of bacteria in the blood by neutrophils (%) E. Presentation of processed antigens by dendritic cells (%)

B. Binding of T-cell receptors by bacterial secretory products (%)

A 34-year-old man is brought to the emergency department after a motor vehicle collision. He has blunt abdominal trauma and bilateral femur fractures. The patient has no significant medical history and takes no medications. He does not smoke but drinks 8-12 alcoholic beverages a day. Blood pressure is 80/40 mm Hg and pulse is 110/min. Immediate resuscitation efforts are initiated, during which he receives transfusion of several units of packed red blood cells. During transport to the intensive care unit, the patient reports a tingling sensation in his fingers and toes. Serum ionized calcium level is 4 mg/dL (normal: 4.8-5.5). Which of the following is the most likely cause of this patient's current symptoms? A. Antibody-mediated red blood cell membrane damage (%) B. Calcium chelation by a substance in the transfused blood (%) C. Electrolyte leakage from red blood cells during pretransfusion storage (%) D. Increased renal tubular excretion of calcium (%) E. Release of intracellular contents from injured muscle (%)

B. Calcium chelation by a substance in the transfused blood (%) Citrate anticoagulants in high-volume blood transfusion can chelate plasma calcium, leading to hypocalcemia which causes peripheral neuromuscular excitability (eg, paresthesia, muscle spasms). This is most common with very rapid transfusion rates, but it can also be seen at lower rates in patients with hepatic insufficiency because citrate is metabolized by the liver

A 48-year-old man comes to the office due to several hours of severe right knee pain. The patient has a history of peptic ulcer disease and gastroesophageal reflux disease. His right knee is swollen, erythematous, and tender. Arthrocentesis is performed and synovial fluid analysis shows needle-shaped, negatively birefringent crystals with many neutrophils. The medication given to this patient selectively binds to an interleukin-1 inducible enzyme that is highly expressed by inflammatory cells and undetectable in the surrounding normal tissue. Which of the following is most likely the drug used in this patient's treatment? A. Aspirin (%) B. Celecoxib (%) C. Colchicine (%) D. Infliximab (%) E. Prednisone (%)

B. Celecoxib (%) (Choice A) Like other NSAIDs, aspirin nonselectively inhibits both COX-1 and COX-2. Aspirin irreversibly modifies these enzymes; therefore, restoration of enzymatic activity requires synthesis of new enzymes. (Choice C) Colchicine binds to tubulin, which inhibits microtubule formation. This results in impaired neutrophil mitosis and decreased neutrophil chemotaxis. (Choice D) Infliximab is a monoclonal antibody that irreversibly binds to and inhibits TNF-α, a cytokine involved in the inflammatory response. TNF-α is an intercellular signaling protein, not an enzyme. (Choice E) Glucocorticoids (eg, prednisone) bind to cytoplasmic receptors that then translocate to the nucleus where the expression of anti-inflammatory peptides is upregulated. Glucocorticoids decrease COX-2 transcription but do not bind to COX-2 directly. Educational objective:Cyclooxygenase-2 (COX-2) is an inducible enzyme upregulated during inflammation by interleukin-1 and TNF-α. Selective COX-2 inhibitors (eg, celecoxib) decrease inflammation by inhibiting COX-2 production of pro-inflammatory arachidonic acid metabolites. Because they do not affect COX-1, they have minimal gastroduodenal toxicity.

Researchers are interested in the association between colorectal carcinoma and nonsteroidal anti-inflammatory drug use. They first interview a group of patients with biopsy-proven colorectal carcinoma and then interview a group consisting of the patients' neighbors who are of similar age and race. The analysis is based on comparing the results of pairs of individuals (one from each of the 2 groups) who have similar characteristics. This design technique best helps address which of the following potential problems with this study? A. Ascertainment bias (%) B. Confounding (%) C. Observer bias (%) D. Recall bias (%) E. Selection bias (%)

B. Confounding (%) Matching is a method generally used in the design stage of case-control studies to control confounding (ie, when a perceived association between an exposure and an outcome is actually explained by a confounding variable associated with both the exposure and the outcome). The initial step in matching involves selecting variables that could be confounders (eg, age, race). Cases and controls are then selected based on the matching variables so that both groups have a similar distribution in accordance with the variables. In this scenario, the "cases" (patients with colorectal cancer) were matched with neighborhood "controls" of similar age and race. Selecting neighbors as controls has another advantage of matching the cases to controls by variables that are difficult to measure (eg, socioeconomic status, environmental factors). Gender and smoking status are other common confounders A. Ascertainment bias (%) B. Confounding (%) C. Observer bias (%) D. Recall bias (%) E. Selection bias (%) Observer bias and ascertainment bias result from mislabeling exposed/unexposed or cases/controls. Recall bias could be a limitation of this study as the interviewed participants with colorectal cancer may be more likely to recall certain exposures. Selection bias is a potential problem in this study because the controls selected may not reflect the exposure experience of the general population. However, although these biases may be present, matching best addresses confounding rather than any of these biases

A 43-year-old man comes to the emergency department due to a 3-day history of persistent headaches. The patient has a history of hypertension and has had poor medical follow-up. Blood pressure is 224/115 mm Hg and pulse is 67/min. He appears mildly confused during the physical examination, but no focal neurologic deficits are noted. Funduscopic examination shows bilateral papilledema. Serum creatinine is 1.4 mg/dL. An intravenous medication is initiated that causes arteriolar dilation while also improving renal perfusion and increasing natriuresis. Which of the following agents is most likely being used in this patient? A. Esmolol (%) B. Fenoldopam (%) C. Hydralazine (%) D. Nitroglycerin (%) E. Phenylephrine (%)

B. Fenoldopam (%) Fenoldopam is a short-acting, selective, peripheral dopamine-1 receptor agonist with little to no effect on alpha- or beta-adrenergic receptors. Dopamine-1 receptor stimulation activates adenylyl cyclase and raises intracellular cyclic AMP, resulting in vasodilation of most arterial beds with a corresponding decrease in systemic blood pressure. Renal vasodilation is particularly prominent and leads to increased renal perfusion, increased urine output, and natriuresis (ie, sodium excretion). This makes fenoldopam especially beneficial in patients with hypertensive emergency and renal insufficiency.

A 7-year-old boy is admitted to the hospital after his adoptive parents brought him to the emergency department due to fatigue and pallor. Laboratory evaluation reveals pancytopenia with an absolute neutrophil count consistent with severe neutropenia. Bone marrow examination reveals signs of aplastic anemia, and subsequent genetic testing reveals a congenital genomic defect in DNA repair leading to chromosomal instability. A bone marrow transplant is required for treatment. The patient's only living relatives are an identical twin brother and older sister who were both adopted by the same parents. He also has stored umbilical stem cells that were harvested after birth. Which of the following is the best bone marrow transplantation method for this patient? A. Freshly harvested autologous transplant (%) B. Matched unrelated donor (%) C. Stored umbilical cord stem cells from the patient (%) D. Twin sibling syngenetic transplant (%) E. Unmatched sibling allogeneic transplant (%)

B. Matched unrelated donor (%) Donor sources are generally categorized as follows: Autologous: Stem cells harvested from the patient or banked from the patient's cord blood at birth are transplanted to reconstitute the patient's bone marrow. However, autologous transplants cannot be used for congenital genetic disorders because the genetic mutation will be present in all cells harvested from the patient (Choices A and C) . Syngenetic: Identical twins have the same genome; therefore, cells transplanted from one identical twin to the other will be an exact HLA match and will not cause graft rejection or graft-versus-host disease. However, syngenetic transplants are not helpful for congenital genetic conditions because any congenital mutation present in one twin will be present in the other (Choice D). Allogeneic donors: Donors who do not have the same genome as the patient are classified as related or unrelated. Related donors: Because HLA alleles are encoded on chromosome 6, each nonidentical sibling has a 25% chance of being an exact HLA match (HLA identical), a 50% chance of sharing half the HLA alleles (haploidentical), and a 25% chance of sharing none of the HLA alleles (HLA mismatch). Therefore, siblings often are tested first for HLA matching because there is a 1:4 chance they will be an exact match. However, unmatched siblings usually are not used for donation because their HLA alleles are not the same as the patient's (Choice E). Unrelated donors: Unrelated donors do not have the same genome as the patient but can have perfect or near-perfect HLA matching; however, extensive searching is often required. Matched unrelated donors generally are best for congenital genetic conditions because the genomic error that leads to the patient's condition will not usually be present in an unrelated individual.

A 16-year-old boy comes to the office for an annual health maintenance visit. He has no medical conditions and feels well. The patient plays football for his high school team and states he is planning to increase his physical workouts to prepare for the upcoming season. He indicates that last season he was often fatigued during the second half of games, and he plans to focus on endurance training. Physical examination shows no abnormalities. Which of the following is most likely to increase in this patient's large skeletal muscle groups after a prolonged period of regular training? A. Anaerobic glycolytic enzymes (%) B. Mitochondrial content (%) C. Number of motor endplates per fiber (%) D. Proportion of type II (fast-twitch) fibers (%) E. Total quantity of myocytes (%)

B. Mitochondrial content (%) Targeted physical training stimulates specific phenotypic adaptations in skeletal muscle fibers to improve skeletal muscle function. Endurance training (eg, distance running, sustained light-to-moderate weightlifting) promotes the characteristics of type I fibers (eg, increased size and quantity of mitochondria) and also increases capillary density. In contrast, resistance training (eg, heavy weightlifting) amplifies the characteristics of type II fibers while also stimulating increased muscle mass.

A study to assess spironolactone's efficacy in patients with heart failure is performed. 450 patients receive either spironolactone or placebo for two years. Neither the patients nor physicians are aware of who takes the drug or placebo. The study setup described above is most effective in preventing: A. Beta error (2%) - the probability that a test says there isn't an association when there actually is one B. Recall bias (2%) C. Observer bias (75%) D. Effect modification (7%) E. Selection bias (12%) (Choice B) Recall bias results from the inaccurate recall of past exposure by subjects. It applies mostly to case-control studies. (Choice D) Effect modification is not a bias and should not be controlled. (pretty sure this is like when a drug has different effects in men and women) (Choice E) Selection bias results from the manner in which people are selected for the study, or from the selective losses from follow-up. Educational Objective:The main purpose of blinding is to prevent patient or researcher expectancy from interfering with an outcome.

C. Observer bias (75%)

8-year-old boy is brought to the office due to acute facial puffiness. His mother reports that for the preceding 24 hours he has been easily fatigued and has had dark urine. The patient was treated for a skin infection 3 weeks ago but has no chronic medical conditions. Temperature is 36.1 C (97 F) and blood pressure is 140/94 mm Hg. Physical examination shows periorbital edema and mild pitting edema along the ankles. The remainder of the examination shows no abnormalities. A representative renal biopsy sample is shown in the below image. The fluorescent areas on the slide most likely indicate the presence of which of the following substances? A. Albumin (%) B. C1q (%) C. C3 (%) D. Fibrin (%) E. IgE (%) F. M protein (%)

C. C3 (%) Poststreptococcal glomerulonephritis is most common in children and presents with nephritic syndrome (eg, renal failure, hypertension, hematuria with red blood cell casts) 2-4 weeks after an infection with group A beta-hemolytic Streptococcus. Immunofluorescence microscopy shows granular deposits of IgG, IgM, and C3 in the mesangium and basement membranes. M protein is a component of the streptococcal cell wall that acts as an antiphagocytic virulence factor. The cross-reactivity of antibodies directed against M protein within myocardial cells may be responsible for rheumatic heart disease. However, M protein has not been isolated in the immune complexes in PSGN.

A 54-year-old previously healthy man comes to the office due to several weeks of leg swelling. He has had no fever, chest pain, or dyspnea. The patient has a 40-pack-year smoking history but does not use alcohol or illicit drugs. He is afebrile and vital signs are within normal limits. On physical examination, there is symmetric pitting edema of the lower extremities bilaterally. The abdomen is soft and nondistended. A mobile left flank mass can be palpated. There are several vertically oriented tortuous veins on the lower abdominal wall. Item 1 of 2 Which of the following structures is most likely obstructed in this patient? A. Femoral veins (%) B. Iliac veins (%) C. Inferior vena cava (%) D. Portal vein (%) E. Saphenous veins (%)

C. Inferior vena cava (37%) This patient's symmetric bilateral lower extremity pitting edema and tortuous abdominal veins are concerning for an inferior vena cava (IVC) obstruction, which, in the setting of a left-sided flank mass, suggests renal cell carcinoma (RCC) with extension into the IVC. RCC accounts for >90% of all malignancies arising in the kidney and is highly associated with smoking. Patients with RCC classically have a triad of flank pain, palpable mass, and hematuria, although many remain asymptomatic until the disease is advanced. RCC is a highly vascular tumor that invades the renal vein in up to 25% of cases. IVC obstruction can occur due to intraluminal extension and thrombus formation, rather than mass effect from the tumor itself. The obstruction can occur acutely or gradually over time. In chronic cases, collateral venous circulation may develop based on the site of the obstruction. Prominent abdominal wall collateral veins, as in this patient, suggest obstruction of the upper segment of the IVC. (Choice D) Obstruction of the portal vein is most commonly associated with severe hepatic cirrhosis. Affected patients have shunting of blood through portocaval anastomoses, leading to hemorrhoids, esophageal varices, and caput medusae about the umbilicus. They may also have ascites.

32-year-old man comes to the emergency department due to sudden onset of severe right flank pain that radiates toward the groin. He also has gross hematuria but no fever or dysuria. The patient has no significant medical conditions and has never experienced similar symptoms. He takes no medications. Temperature is 36.7 C (98.1 F), blood pressure is 120/80 mm Hg, and pulse is 88/min. The right flank is tender to palpation. There is no costovertebral angle tenderness. Imaging shows a stone in the middle of the right ureter. Which of the following is most likely to be seen on laboratory evaluation of this patient? A. Hypercalcemia, hypercalciuria (%) B. Hyperuricemia, hyperuricosuria (%) C. Normocalcemia, hypercalciuria (%) D. Normocalcemia, hyperoxaluria (%) E. Normouricemia, hyperuricosuria (%)

C. Normocalcemia, hypercalciuria (%) In most patients, the hypercalciuria is idiopathic. Factors can include increased gastrointestinal absorption, increased mobilization of calcium from bone, or decreased renal tubular calcium reabsorption. However, in the absence of an underlying metabolic disorder (eg, hyperparathyroidism), most patients remain normocalcemic due to regulation of plasma calcium levels by vitamin D and parathyroid hormone.

A 34-year-old man is admitted to the intensive care unit due to fever, chills, shortness of breath, and altered mental status. His symptoms began 3 days ago and have progressively worsened over the last 24 hours. His past medical history is significant for a motor vehicle accident 2 years ago in which he sustained blunt abdominal trauma and required emergency laparotomy due to internal bleeding. His blood pressure is 81/44 mm Hg and pulse is 122/min. He is started on broad-spectrum antibiotics, intravenous fluids, and vasopressors. His condition continues to deteriorate and he dies in the hospital several hours later despite extensive resuscitation efforts. Blood cultures obtained on admission grow Streptococcus pneumoniae. Impairment of which of the following mechanisms most likely contributed to the severity of this patient's infection? A. Complement production (%) B. Immediate hypersensitivity (%) C. Intracellular killing (%) D. Systemic bacterial clearance (%) E. Type I interferon release (%)

D. Systemic bacterial clearance (%) This patient likely experienced traumatic splenic rupture 2 years ago with the splenic remnants removed during laparotomy (spleen is the most commonly injured organ with blunt abdominal trauma). He subsequently experienced overwhelming asplenic sepsis, a condition that carries a 50% mortality risk. The spleen is a part of the systemic lymphoid system and receives roughly 6% of the cardiac output. Many of the splenic capillaries are open-ended and sinusoidal, permitting whole blood to flow into the red pulp cords. These cords form a reticular meshwork that acts as a fine sieve with spaces as small as 1 micron in diameter. Large numbers of macrophages line the red pulp cords and sinusoids and ingest any particulate matter that becomes trapped. The splenic red pulp is important for: Destroying aged and abnormal erythrocytes (eg, spherocytes) and serving as an emergency store of blood cells and platelets that can be delivered into the circulation when needed. Clearance of circulating bacteria that become lodged in the cords. Macrophages then present captured antigens to the B- and T-cells residing in the splenic white pulp to generate an active immune response. Nearly half of the body's total immunoglobulins are produced by splenic B-lymphocytes. Splenic opsonizing antibody is of particular importance in the clearance of encapsulated species, as the capsule allows them to resist innate phagocytosis. Vaccination against encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis is recommended for all asplenic patients

A 35-year-old man is admitted to the hospital after sustaining multiple injuries in a motor vehicle accident. He undergoes surgery for an open fracture of the tibia and a spiral fracture of the humerus. The tibial repair is successful, but the surgeon operates on the wrong arm. Which of the following procedures would be most effective in preventing a similar error? A. Confirm the correct site with the patient (%) B. Have the anesthesiologist and surgeon verify the surgical site together (%) C. Have the head nurse verify the surgical site (%) D. Have the nurse and surgeon verify the surgical site independently (%) E. Have the operating physician verify the surgical site (%)

D. Have the nurse and surgeon verify the surgical site independently (52%) According to The Joint Commission's sentinel event statistics, wrong-site surgery is the most frequently reported serious adverse event. Emergency operations, failure to mark the surgical site, poor communication, and surgeon fatigue are contributing factors. As in this case, multiple procedures on the same patient and multiple surgeons will also increase the risk of operating at the wrong site. Therefore, a preoperative verification process is important to decrease this risk. In addition to marking the operative site, independent verification of the patient, procedure, and site by 2 health care workers (eg, a nurse and physician) should be performed. The "dual identifiers" must perform the verification independently because 2 clinicians verifying identifiers together can result in replicating an error. The Joint Commission recommends use of a "surgical timeout" immediately prior to the procedure in order to conduct a final verification of the patient, procedure, and site

A 56-year-old man with chronic kidney disease is seen for a routine follow-up visit. The patient also has type 2 diabetes, hypertension, and hyperlipidemia. His serum creatinine level has been increasing over the past 2 years. Blood pressure is 144/90 mm Hg and pulse is 88/min. Weight is 80 kg (176 lb). Physical examination is normal except for trace pitting ankle edema. Serum creatinine level is 1.8 mg/dL; 1 year ago, serum creatinine was 1.4 mg/dL. Serum calcium and phosphorus levels are in the normal range. Which of the following is most likely responsible for maintaining the serum phosphorus within normal range despite declining renal function? A. Elevated serum thyrotropin (%) B. Hypocalcemia (%) C. Hypomagnesemia (%) D. Increased serum fibroblast growth factor 23 level (%) E. Suppressed serum parathyroid hormone level (%)

D. Increased serum fibroblast growth factor 23 level (40%) Patients with chronic kidney disease (CKD) can develop hyperphosphatemia due to decreased filtration of phosphate. Fibroblast growth factor 23 (FGF23) is secreted in response to hyperphosphatemia and lowers plasma phosphate by reducing intestinal absorption and renal reabsorption of phosphate. FGF23 levels are useful as an early marker of abnormal phosphate metabolism in patients with CKD.

A 65-year-old man dies while hospitalized for severe breathing difficulty. The patient had several prior episodes of dyspnea and cough requiring hospitalization. He had a history of hypertension and chronic kidney disease. The patient smoked a pack of cigarettes daily for 38 years and immigrated to the United States 20 years ago. Autopsy is performed, and microscopic examination of the lungs reveals alveolar macrophages containing aggregates of golden-brown cytoplasmic granules that turn dark blue with Prussian blue staining. Which of the following conditions is most likely associated with this patient's microscopic findings? A. Airway hyperreactivity (%) B. Coal particle inhalation (%) C. Granulomatous microbial infection (%) D. Left ventricular dysfunction (%) E. Pulmonary arterial hypertension (%) F. Pulmonary thromboembolism (%)

D. Left ventricular dysfunction (%) This patient most likely had heart failure due to left ventricular dysfunction. Impaired forward pumping by the left ventricle causes increased pulmonary capillary pressure that can lead to pulmonary edema and dyspnea. The rise in hydrostatic pressure also disrupts the integrity of the pulmonary capillaries, leading to extravasation of red blood cells and alveolar hemorrhage. The red blood cells are eventually phagocytosed by macrophages, and the iron from hemoglobin is converted to hemosiderin. Prussian blue stain detects ferric iron stores (eg, ferritin and hemosiderin). In the Prussian blue reaction, colorless potassium ferrocyanide is converted by iron to blue-black ferric ferrocyanide. Macrophages containing golden-brown cytoplasmic granules that turn blue with Prussian blue staining represent hemosiderin-laden macrophages (siderophages). These cells may be found in any tissue where macrophages encounter extravasated red blood cells; in the alveolar parenchyma, they are often called "heart failure cells."

For a case-control study designed to investigate a possible association between endometriosis and systemic lupus erythematosus (SLE), 1,040 women with SLE and 1,260 women without SLE are selected. The investigators inquire about a history of endometriosis in both groups of women. Among women with SLE, 240 had a history of endometriosis; among women without SLE, 210 had a history of endometriosis. Which of the following is the estimated odds ratio of endometriosis in women with SLE compared to women without SLE? A. 0.1 (%) B. 0.7 (%) C. 0.8 (%) D. 1.2 (%) E. 1.5 (%)

E. 1.5 (%) The odds of endometriosis in women with SLE and women without SLE are: Odds of endometriosis in cases: a/c = 240/800 = 0.3 Odds of endometriosis in controls: b/d = 210/1,050 = 0.2 Therefore, the OR of endometriosis in women with SLE compared to women without SLE is: OR = (odds of endometriosis in cases) / (odds of endometriosis in controls) = (a/c) / (b/d) = 0.3/0.2 = 1.5

A 30-year-old Caucasian male presents to your office with fatigue, muscle weakness and occasional headaches. His blood pressure is 180/110 mmHg and his heart rate is 80/min. Laboratory evaluation reveals low serum potassium, severely depressed plasma renin activity, and a CT scan demonstrates a right-sided adrenal mass. After treatment for several weeks, the patient's symptoms resolve, his blood pressure is decreased to 130/70 mmHg and his heart rate is 75/min. Which of the following drugs was most likely used in this patient? A. Clonidine (%) B. Propranolol (%) C. Captopril (%) D. Hydrochlorothiazide (%) E. Eplerenone (%) F. Verapamil (%) G. Amlodipine (%) H. Isosorbide dinitrate (%)

E. Eplerenone (%) This patient is suffering from an aldosterone secreting tumor (adenoma) leading to primary hyperaldosteronism (Conn's Syndrome). Presenting signs of hyperaldosteronism most commonly include hypertension, hypokalemia, metabolic alkalosis and decreased plasma renin activity. Aldosterone causes resorption of sodium and water and wasting of potassium and hydrogen ions (acid) at the distal portion of the nephron, leading to hypokalemia and alkalosis. Additionally, inappropriately high aldosterone will suppress renin activity as part of a feedback inhibition loop. The treatment for a unilateral adenoma secreting aldosterone, as is found in this patient, can be either by surgical resection or by medical therapy with aldosterone antagonists. Spironolactone is the most frequently used first-line drug, and eplerenone is a new aldosterone antagonist that has fewer side effects than spironolactone and is often used in those that can not tolerate spironolactone. The most frequently mentioned side effect of these medications is their ability to cause gynecomastia (approximately 1% with eplerenone, 9% with spironolactone). Other drugs mentioned in the other choices are not commonly used in Conn's syndrome

A 22-year-old woman comes to the office due to several years of persistent facial blemishing that has failed to respond to over-the-counter treatment. The patient has no other medical conditions. She does not use tobacco, alcohol, or illicit drugs. Skin examination findings are shown in the image below: Which of the following most likely contributed to the pathogenesis of this patient's skin condition? A. Androgen-induced involution of sebaceous glands (%) B. Bacterial degradation of apocrine gland secretions (%) C. Estrogen-stimulated secretory function of sebaceous glands (%) D. Increased desquamation of follicular epithelial cells (%) E. Proliferation of lipid-utilizing bacteria within pilosebaceous follicles (%)

E. Proliferation of lipid-utilizing bacteria within pilosebaceous follicles (%) This patient's red papules and pustules on the face are consistent with inflammatory acne. The pathogenesis of acne involves the following: Hyperkeratinization due to abnormal epithelial growth and differentiation of corneocytes leads to keratin plug formation in the pilosebaceous follicles. These blocked follicles are referred to as comedones (ie, whiteheads and blackheads). In response to androgen stimulation (eg, during pubertal adrenarche), sebaceous glands enlarge (not involute) and increase production of sebum, a lipid-rich substance that facilitates obstruction of pilosebaceous follicles (Choice A). Cutibacterium acnes, an anaerobic bacteria that relies on sebum as a nutrient source, proliferates in occluded follicles, triggering an inflammatory response that results in the red papules and pustules characteristic of nodulocystic acne. (Choice B) Bacterial metabolism of apocrine secretions contributes to body odor. Bromhidrosis is a condition characterized by excessive and offensive body odor.

A 55-year-old man comes to the office for evaluation of chronic muscle weakness. Over the past several months, he has had increasing difficulty walking up stairs and lately has had trouble removing objects out of the overhead cabinets in his kitchen. Temperature is 36.7 C (98 F), blood pressure is 125/80 mm Hg, and pulse is 78/min. On examination, the patient has symmetric proximal muscle weakness and mild muscle tenderness. There is no rash. Muscle biopsy reveals an endomysial mononuclear infiltrate and patchy muscle fiber necrosis. An autoantibody directed against which of the following antigens is most likely to be seen in this patient? A. Acetylcholine receptor (%) B. Cardiolipin (%) C. Desmoglein (%) D. Mitochondria (%) E. Presynaptic calcium channel (%) F. tRNA synthetase (%) G. Smooth muscle (%)

F. tRNA synthetase (%) Polymyositis and dermatomyositis are characterized by symmetric proximal muscle weakness and are associated with antinuclear and anti-tRNA synthetase (anti-Jo-1) autoantibodies. Biopsy in polymyositis shows patchy endomysial inflammatory infiltrate (ie, direct invasion of individual muscle fibers), whereas dermatomyositis causes perifascicular inflammation (ie, localized around blood vessels and the septa between muscle fascicles).

Hematologic stem cell transplantation (HCT) requires identification of a donor with similar human leukocyte antigens (HLAs), polymorphic proteins expressed on the surface of every cell. The most important HLA proteins to match are _____, which form major histocompatibility complex class I molecules, and _____ which form major histocompatibility complex class II molecules. Because these HLAs play a vital role in the differentiation between self and nonself, recipients who receive well-matched donor cells have lower rates of graft rejection (ie, host cells attack the donor) and graft-versus-host disease (ie, donor cells attack the host)

HLA-A, B, and C (class I) HLA-DP, DQ, and DR, Class II (two letters!)

C. Improved quality of care (%) ncidence and prevalence are important concepts for evaluating the impact of disease on a population. Incidence corresponds to the number of new cases of a disease diagnosed in a population at risk over a given period. Prevalence refers to the total number of diseased individuals in the population at a particular point; it is dependent on incidence and the average duration of the disease (ie, time from diagnosis to cure or death): Prevalence = (Incidence) x (Duration of disease) A simplified diagram compares incidence and prevalence to adding new drops (incident cases) to a sink collecting water (prevalent cases). The above graph shows that the incidence of type II diabetes mellitus has been constant for the last 30 years (Choice F), but that prevalence is rising. Because this is a steady-state population with little migration, a constant incidence rate should result in a nearly stable disease prevalence, unless there is some additional factor affecting the duration of the condition. Factors that prolong disease duration can increase disease prevalence even when the incidence is unchanged because diseased individuals live longer on average. In this case, improved quality of care likely led to a lower mortality rate in diabetics over time, resulting in a higher prevalence of the disease in the population (Choice B)

Which of the following is the most likely explanation for the change in disease prevalence seen in the graph? A. Decreased hospitalization rate (%) B. High mortality in diabetics (%) C. Improved quality of care (%) D. Increased accuracy of diagnostic testing (%) E. Increased exposure to risk factors (%) F. Increased number of new diabetes cases (%) G. Selective survival bias (%)

43-year-old man comes to the office due to joint pain and stiffness in both hands for the past 6 months. He sometimes awakens with hand pain at night. Over the last year, the patient also has had chronic fatigue and poor sexual performance. He has no history of serious illness and takes no medications. The patient rarely sees a physician. He does not smoke tobacco or drink alcohol. Blood pressure is 126/80 mm Hg and pulse is 80/min. BMI is 25 kg/m2. Hand radiographs reveal bilateral erosions and joint deformities involving the second and third metacarpophalangeal joints. Which of the following is the most likely diagnosis? A. Chronic gouty arthritis (19%) B. Hereditary hemochromatosis (36%) C. Multiple myeloma (9%) D. Reactive arthritis (28%) E. Rheumatic fever (6%) Choice A) Gouty arthritis may occasionally present as a chronic arthritis of the small joints of the hands and feet, superficially resembling rheumatoid arthritis. X-ray often shows associated bony erosions. However, most patients have a history of acute gout attacks, and gout would not explain this patient's fatigue and sexual dysfunction. (Choice C) Multiple myeloma usually occurs in older patients and is rare at age <50. Characteristic x-ray findings include scattered osteolytic lesions that typically involve the axial skeleton. (Choice D) Reactive arthritis typically presents with asymmetric oligoarthritis, enthesitis (ie, inflammation at tendon/ligament insertion sites), and dactylitis (ie, sausage digit). It is often associated with extraarticular symptoms, including conjunctivitis, uveitis, and urethritis. Symptoms usually resolve within a few months and would not be chronic. (Choice E) Rheumatic fever is an immune-mediated complication of streptococcal infections characterized by migratory arthritis, carditis, subcutaneous nodules, rash (erythema marginatum), and chorea. It is most common at age 5-15 and presents acutely 2-4 weeks after an episode of untreated pharyngitis.

hereditary hemochromatosis

Hemoglobin S (HbS) contains valine in place of glutamic acid at the sixth amino acid position of the beta globin chain. This promotes

hydrophobic interaction among Hb molecules and results in HbS polymerization and erythrocyte sickling.

T-lymphocytes, or thymocytes, are produced in the bone marrow and undergo maturation in the thymus during the first trimester of gestation. In the thymus the processes of T-cell receptor (TCR) gene rearrangement, positive selection, negative selection and expression of extracellular membrane markers and co-stimulatory molecules occur. Pro-T cells arrive at the thymus as "double negative" cells - cells that lack both CD4 and CD8 antigens. Next, the process of TCR gene rearrangement begins first with rearrangement of the b chain genes. Synthesis of a productive rearrangement of the b chain of the TCR leads to stimulation of production of BOTH CD4 and CD8 antigens with simultaneous expression of BOTH CD4 and CD8. These cells are referred to as "double positive" T cells or immature T-lymphocytes (Choice A). Subsequently, the process of rearrangement of the a chain of the TCR occurs followed by positive selection in the ____ and negative selection in the _____. Once these processes are complete, the final step in maturation of the T-lymphocytes is loss of either the CD4 or the CD8 antigen so that the mature thymocytes only express one or the other of these antigens.

positive selection- thymic cortex negative selection- thymic medulla