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Which of the following patients should undergo prophylactic gonadectomy: a patient with 45,X; a patient with 46, XX type of pure gonadal dysgenesis; or a patient with 46,XY type of pure gonadal dysgenesis?

When confronted with this question on the test, it is important to recognize that the risk of gonadal malignancy is increased when a Y chromosome is present in the karyotype. Neither Turner syndrome nor the 46, XX type of pure gonadal dysgenesis appears to be associated with an increased risk of gonadal malignancy unless a Y chromosome is present in the mosaic forms.

Prophylactic gonadectomy is advised in the Y mosaic Turner syndrome because the risk of gonadoblastoma is estimated to be 12%. The 46,XY type of pure gonadal dysgenesis possesses a different problem because the bilateral streak go**ds carry a significant potential for malignancy. Nearly one third of patients develop a dysgerminoma or gonadoblastoma; therefore, gonadectomy becomes important as soon as the diagnosis is recognized followed by cyclic hormone replacement with estrogen and progestins. In addition to gonadoblastomas, seminomas, and embryonal cell carcinomas may develop. Early gonadectomy is recommended because tumors may arise in the first decade.

At USMLE Insider, we prep you comprehensively so that you can count on getting at least 90% of the questions on your test date from our course materials.

Which USMLE-favorite disease may be associated with a quintuple cadence on auscultation? Ebstein’s anomaly of the tricuspid valve, which results from downward displacement of the tricuspid valve towards the apex of the right ventricle.

This displacement causes “atrialization” of a portion of the morphologic right ventricle which is then contiguous with the right atrium leading to right atrial hypertrophy and right ventricular hypoplasia.

A quadruple rhythm (S3 and S4) associated with the systolic murmur of tricuspid regurgitation and a mid-diastolic murmur at the lower left sternal border suggests the diagnosis. The presence of right atrial hypertrophy and right ventricular conduction defects confirms the diagnosis.

50% of patients with Ebstein’s anomaly have the electrophysiological abnormality, Wolff-Parkinson-White syndrome, secondary to the atrialized right ventricular tissue. About 50% of individuals with Ebstein anomaly have an associated shunt between the right and left atria, either an atrial septal defect (ASD) or a patent foramen ovale.

A quintuple cadence on auscultation may be characteristic because the S1 is split and the usual presence of an ASD causes wide splitting of the S2. These sounds together with the S3 and S4 produce a quintuple cadence on auscultation.

An understanding of vaccinology or vaccine biology is so critical for USMLE success. And one important topic is the concept of recombinant vaccines. What are the currently available vaccines from this class?

Recombinant vaccines are the ones in which viral polypeptides are prepared from cloned genes using recombinant DNA technology. Genes encoding epitopes, which elicit protective immunity, are inserted into pro- or eukaryotic cells; large quantities of vaccine are produced rapidly. These vaccines are safe, noninfectious, and are feasible to prepare for viruses that cannot be cultured in vitro.

The hepatitis B vaccine was the first genetically engineered vaccine to be licensed for human use. Other recombinant DNA vaccines include the HPV vaccines, the Zoster Shingrix vaccine, the RSV vaccines, and the Ebola virus live vaccine, which is a recombinant vesicular stomatitis virus-Zaire ebolavirus (rVSV-ZEBOV; V920), that is a replication-competent viral vector vaccine.

Also, the recombinant influenza vaccine (influenza virus vaccine trivalent, recombinant), one of the four types of trivalent influenza vaccines available, contains recombinant HA proteins of strains of influenza virus specified by health authorities for inclusion in the annual seasonal vaccine. These proteins function as antigens, which induce a humoral immune response, measured by hemagglutination inhibition (HI) antibody.

This influenza vaccine was made with recombinant DNA methods to offer individuals with allergies to egg proteins an opportunity to evade such allergic responses that are associated with the regular trivalent influenza vaccine and the adjuvanted vaccine which are manufactured using an egg-based process.

Imagine an elderly patient with lipoproteinemia who has been stabilized on simvastatin for years. Let’s say this patient also has rheumatoid arthritis that has failed to respond to NSAIDs. One week after receiving a single 200 mg subcutaneous dose of a drug for arthritis, her plasma concentration of simvastatin is found to be markedly decreased. Which anti-arthritis medication could have caused this phenomenon?

You already know that simvastatin is a substrate of CYP450 3A4 and OATP 1B1. What may be difficult to understand is that plasma concentrations of drugs that are CYP450 substrates may decrease following the initiation of interleukin (IL) inhibitors, tumor necrosis factor (TNF) blockers, or interferon (IFN) inhibitors in patients with chronic inflammatory diseases, such as rheumatoid arthritis.

Normally, the formation of hepatic CYP450 enzymes is down-regulated during infection and chronic inflammation by increased levels of certain cytokines (e.g., interleukins-1, -6, and -10; tumor necrosis factor alpha; interferons). Consequently, treatment targeting these cytokines may restore or normalize CYP450 enzyme levels resulting in increased metabolism of these drugs.

Simvastatin systemic exposure is decreased by 45% by a single dose of sarilumab, an IL-6 inhibitor, in rheumatoid arthritis patients.

In fact, tocilizumab, another IL-6 inhibitor, has been found to impact expression of various CYP enzymes including CYP450 1A2, 2B6, 2C9, 2C19, 2D6, and 3A4.

Because no role for other interleukins such as IL-12, IL-17A, or IL-23 in the regulation of CYP450 enzymes has been established, risankizumab and tildrakizumab, both IL-23 antagonists, should not be answers to pick on the USMLE regarding this specific concept. This does not mean that risankizumab and tildrakizumab won’t be tested in other capacities; there are always questions testing their dermatologic applications and immunophysiologic mechanisms. But with regards to USMLE questions relating to hepatic microsomal enzymes and drug metabolism, always go with IL-1, IL-6, and IL-10 modulators (No IL-10 modulators are clinically available currently, so that leaves only IL-6 and IL-10).

Now, besides sarilumab and tocilizumab, which other IL-6 modulators can you name?

Drugs that cause progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that typically occurs in patients who are immunocompromised, and that usually leads to death or severe disability, is a big deal on the USMLE. PML is caused by JC virus and is one of the notorious adverse effects of natalizumab, an immunomodulating agent used for multiple sclerosis and Crohn’s disease.

Natalizumab, an α4-integrin antagonist, first received attention on the USMLE in 2009 when the FDA first issued a black box warning. It has been tested consistently on the exam since then. It has recently been joined by newer agents that have gained notoriety for causing PML: the sphingosine 1-phosphate (S1P) receptor modulators (fingolimod, ozanimod, and siponimod). The frequency of PML is as follows: fingolimod>>ozanimod>Siponimod.

Concomitant or recent use of immunosuppressant, immunomodulating, or antineoplastic agents in patients treated with natalizumab or S1P modulators may increase the risk of infections including PML. Be prepared to answer questions on this concept. The following should be your learning objectives:
Know:
 Natalizumab’s mechanism of action and why it works for multiple sclerosis (MS)
 Why natalizumab must be given only as monotherapy.
 Examples of drugs with which natalizumab is contraindicated.
 Mechanism of S1P modulators and why they work for MS.
 Why S1P modulators must be given monotherapy and examples of drugs with which these agents are contraindicated.
 How to diagnose PML, including characteristic histopathology and brain imaging findings as well as confirmatory test (i.e., the finding of anti-JCV antibodies in the CSF).
 The differential diagnoses of PML in an immunocompromised host (toxoplasmosis, CNS lymphoma, cryptococcal meningitis, etc.) and how to distinguish between them on CT)
 The virus that is responsible for PML and its morphology and characteristics.

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With regards to Pediatrics on USMLE Step 2 CK exam, no area of pediatrics is more important or high yield than Pediatric Orthopedics and Pediatric Urology. Mastery of the differential diagnosis of the limping child (Osgood-Schlatter disease, Legg-Calve-Perthes disease, slipped capital femoral epiphysis, child abuse, growing pains, osteomyelitis, transient synovitis, and septic arthritis of the hip), as well as scoliosis is so pivotal to success. As always, we are on top of our game; we offer the best prep course for the USMLE Step 2.

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When you take our USMLE class, we teach you "the 400 drug-drug interactions every physician must know," including the current trending topics tested on the exam. It may sound like an overkill, but it is so critical for mastery of clinical practice. One example is shown below; let us know what you think of this:

A 54-year-old woman who is infected with HIV is stabilized on triple antiretroviral therapy containing ritonavir. When she is diagnosed with severe migraine headaches, she is given a prescription for abortive therapy. A month after starting the antimigraine therapy, she presents with malaise, vague abdominal discomfort, leukocytosis with a leftward shift, claudication, and chest pain. Which of the following drugs was she most likely taking?

A. Eletriptan
B. Frovatriptan
C. Naratriptan
D. Rizatriptan
E. Sumatriptan
F. Zolmitriptan

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Neuroanatomy is our passion, and we teach it like no other person does it! The corticobulbar pathway is one of the most challenging concepts in Neuroanatomy, but we make it so easy to grasp with powerful illustrations and lecture. You also get to test yourself with some of our challenging questions on this concept.

The Corticobulbar Tract - USMLE Insider Blog At USMLE Insider Prep Course, we use powerful, illustrative imagery to teach you the challenging concepts that must be mastered for USMLE success. The corticobulbar tract is a poorly understood concept for most medical students. But we make this stuff ridiculously easy. This is what separates USMLE....