Reimagining a pass/fail clinical core clerkship: a US residency program director survey and meta-analysis.

Pass/fail (P/F) grading has emerged as an alternative to tiered clerkship grading. Systematically evaluating existing literature and surveying program directors (PD) perspectives on these consequential changes can guide educators in addressing inequalities in academia and students aiming to improve their residency applications. In our survey, a total of 1578 unique PD responses (63.1%) were obtained across 29 medical specialties. With the changes to United States Medical Licensure Examination (USMLE), responses showed increased importance of core clerkships with the implementation of Step 2CK cutoffs. PDs believed core clerkship performance was a reliable representation of an applicant's preparedness for residency, particularly in Accreditation Council for Graduate Medical Education's (ACGME)Medical Knowledge and Patient Care and Procedural Skills. PDs disagreed with P/F core clerkships because it more difficult to objectively compare applicants. No statistically significant differences in responses were found in PD preferential selection when comparing applicants from tiered and P/F core clerkship grading systems. If core clerkships adopted P/F scoring, PDs would further increase emphasis on narrative assessment, sub-internship evaluation, reference letters, academic awards, professional development and medical school prestige. In the meta-analysis, of 6 studies from 2,118 participants, adjusted scaled scores with mean difference from an equal variance model from PDs showed residents from tiered clerkship grading systems overall performance, learning ability, work habits, personal evaluations, residency selection and educational evaluation were not statistically significantly different than from residents from P/F systems. Overall, our dual study suggests that while PDs do not favor P/F core clerkships, PDs do not have a selection preference and do not report a difference in performance between applicants from P/F vs. tiered grading core clerkship systems, thus providing fertile grounds for institutions to examine the feasibility of adopting P/F grading for core clerkships.

Antibody-Drug Conjugates (ADCs) Derived from Interchain Cysteine Cross-Linking Demonstrate Improved Homogeneity and Other Pharmacological Properties over Conventional Heterogeneous ADCs.

Conventional antibody-drug conjugates (ADCs) are heterogeneous mixtures of chemically distinct molecules that vary in both drugs/antibody (DAR) and conjugation sites. Suboptimal properties of heterogeneous ADCs have led to new site-specific conjugation methods for improving ADC homogeneity. Most site-specific methods require extensive antibody engineering to identify optimal conjugation sites and introduce unique functional groups for conjugation with appropriately modified linkers. Alternative nonrecombinant methods have emerged in which bifunctional linkers are utilized to cross-link antibody interchain cysteines and afford ADCs containing four drugs/antibody. Although these methods have been shown to improve ADC homogeneity and stability in vitro, their effect on the pharmacological properties of ADCs in vivo is unknown. In order to determine the relative impact of interchain cysteine cross-linking on the therapeutic window and other properties of ADCs in vivo, we synthesized a derivative of the known ADC payload, MC-MMAF, that contains a bifunctional dibromomaleimide (DBM) linker instead of a conventional maleimide (MC) linker. The DBM-MMAF derivative was conjugated to trastuzumab and a novel anti-CD98 antibody to afford ADCs containing predominantly four drugs/antibody. The pharmacological properties of the resulting cross-linked ADCs were compared with analogous heterogeneous ADCs derived from conventional linkers. The results demonstrate that DBM linkers can be applied directly to native antibodies, without antibody engineering, to yield highly homogeneous ADCs via cysteine cross-linking. The resulting ADCs demonstrate improved pharmacokinetics, superior efficacy, and reduced toxicity in vivo compared to analogous conventional heterogeneous ADCs.

Assessing readiness: the impact of an experiential learning entrustable professional activity-based residency preparatory course.

As medical schools move to integrate the Core Entrustable Professional Activities for Entering Residency (EPAs) into curricula and address the transition from student to resident, residency preparatory courses have become more prevalent. The authors developed an experiential learning EPA-based capstone course for assessment to determine impact on learner self-assessed ratings of readiness for residency and acquisition of medical knowledge. All fourth-year students from the classes of 2018-2020 completed a required course in the spring for assessment of multiple EPAs, including managing core complaints, performing basic procedures, obtaining informed consent, and providing patient handoffs. Learners selected between three specialty-based parallel tracks - adult medicine, surgery, or pediatrics. Students completed a retrospective pre-post questionnaire to provide self-assessed ratings of residency preparedness and comfort in performing EPAs. Finally, the authors studied the impact of the course on knowledge acquisition by comparing student performance in the adult medicine track on multiple choice pre- and post-tests. Four hundred and eighty-one students were eligible for the study and 452 (94%) completed the questionnaire. For all three tracks, there was a statistically significant change in learner self-assessed ratings of preparedness for residency from pre- to post-course (moderately or very prepared: adult medicine 61.4% to 88.6% [p-value < 0.001]; surgery 56.8% to 81.1% [p-value < 0.001]; pediatrics 32.6% to 83.7% [p-value 0.02]). A similar change was noted in all tracks in learner self-assessed ratings of comfort from pre- to post-course for all studied EPAs. Of the 203 students who participated in the adult medicine track from 2019-2020, 200 (99%) completed both the pre- and post-test knowledge assessments. The mean performance improved from 65.0% to 77.5% (p-value < 0.001). An experiential capstone course for the assessment of EPAs can be effective to improve learner self-assessed ratings of readiness for residency training and acquisition of medical knowledge.

Neutrophil-to-lymphocyte ratio and prognosis in patients undergoing percutaneous coronary intervention for acute coronary syndrome.

OBJECTIVE: The purpose of this study was to characterize Acute Coronary Syndrome (ACS)-associated inflammation by investigating correlates of the neutrophil-to-lymphocyte ratio (NLR), a surrogate marker of inflammation, and its relation to 1-year mortality in a cohort of patients undergoing percutaneous coronary intervention (PCI) for ACS at a single institution. METHODS: We performed a single-institution, retrospective, observational study of all-comer ACS patients who underwent PCI and were discharged home before the COVID-19 pandemic between September 23, 2011 and July 31, 2017 for who outcomes data were available. RESULTS: NLRhigh group tended to be older, white patients, less likely to smoke, more likely to have a history of heart failure and cardiac arrest, higher creatinine values, lower LVEF, and higher CK-MB (a surrogate for infarct size). Linear regression model demonstrated a strong correlation between increasing NLR and white race (B = 1.103, p = 0.001, hemoglobin (B = -0.30, p < 0.001), peak CK-MB (B = 0.004, p = 0.02), LVEF (B = -0.048, p < 0.001), and serum creatinine (B = 0.47, p = 0.03). There were a total of 87 deaths at one year. NLR > 3.4 was associated with worse one-year survival post-PCI (91.4 % vs. 95.4 %, log-rank p < 0.004), which was confirmed on multivariate analysis. CONCLUSION: Our data confirm the independent prognostic significance of inflammation to mortality after ACS and may provide some insight into the putative benefits of inflammation modulation.

Challenge in Diagnosis and Management of a Patient With Myocardial Bridge and Coronary Artery Spasm.

Positive ischemia by noninvasive imaging studies often results in nonobstructive disease in cardiac catheterization. In this case, we observed ischemia by nuclear stress test in only the anteroseptal area, and the apex is free of ischemia. Coronary angiogram findings were unremarkable, but intravascular ultrasound confirmed the long length of the myocardial bridge. Further testing with spasm provocation and microvascular testing showed diffuse epicardial spasm in this area of myocardial bridge without microvascular dysfunction. We observed the myocardial bridge but no microvascular dysfunction. This case illustrates the coexistence of spasm in the area of a myocardial bridge and the challenges in the medical management of these patients. (Level of Difficulty: Advanced.).

Risk factors for cardiogenic shock in thyroid storm: a retrospective and case-series study.

Aim: Thyroid storm (TS) occurs in 10% of thyrotoxicosis patients and 1% of TS patients experience cardiogenic shock (CS), which is associated with poor prognosis. Methods: This is a single institution, retrospective study in which 56 patients with TS were evaluated. Results: BMI (p = 0.002), history of heart failure (OR 8.33 [1.91, 36.28]; p = 0.004), pro-BNP elevation (p = 0.04), chest x-ray showing interstitial edema (OR 3.33 [1.48, 7.52]; p = 0.01) and Burch-Wartofsky score (62.5 vs 40; p = 0.004) showed association with CS. CS patients had increased length of stay (16.5 vs 4 days; p = 0.01) and higher in-hospital mortality (OR 24.5 [2.90, 207.29]; p < 0.001). Conclusion: These risk factors are useful to risk stratify TS patients on admission, institute therapy in a timely manner and decrease mortality.

The Relationship of Duffy Gene Polymorphism, High Sensitivity C-Reactive Protein, and Long-term Outcomes.

Background: Black adults have higher incidence of all-cause death and worse cardiovascular outcomes when compared to other populations. The Duffy chemokine receptor is not expressed in a large majority of Black adults and the clinical implications of this are unclear. Methods: Here, we investigated the relationship of Duffy receptor status, high-sensitivity C-reactive protein (hs-CRP), and long-term cardiovascular outcomes in Black members of two contemporary, longitudinal cohort studies (the Jackson Heart Study and Multi-Ethnic Study of Atherosclerosis). Data on 4,307 Black participants (2,942 Duffy null and 1,365 Duffy receptor positive, as defined using Single Nucleotide Polymorphism (SNP) rs2814778) were included in this analysis. Results: Duffy null was not independently associated with elevated levels of serum hs-CRP levels once conditioning for known CRP locus alleles in linkage disequilibrium with the Duffy gene. Duffy null status was not found to be independently associated with higher incidence of all-cause mortality or secondary outcomes after adjusting for possible confounders in Black participants. Conclusions: These findings suggest that increased levels of hs-CRP found in Duffy null individuals is due to co-inheritance of CRP alleles known to influence circulating levels hs-CRP and that Duffy null status was not associated with worse adverse outcomes over the follow-up period in this cohort of well-balanced Black participants.

Relation of Left Ventricular Hypertrophy Subtype to Long-Term Mortality in Those With Subclinical Cardiovascular Disease (from the Multiethnic Study of Atherosclerosis [MESA]).

The clinical and biochemical profile of differing Left ventricular hypertrophy phenotypes and its effect on long-term outcomes is ill-defined. The study investigated the differences in risk profiles and prognostic effect of concentric (CH) and eccentric hypertrophy (EH) on long-term adverse outcomes in a contemporary, ethnically diverse cohort. We analyzed follow-up data over 15 years from the Multiethnic Study of Atherosclerosis study. A total of 4,979 participants with cardiac magnetic resonance performed at baseline enrollment were included. Descriptive statistics, Kaplan-Meier curves, and regression models were applied. Independent variables associated with CH were black and Hispanic race/ethnicity, systolic blood pressure, and metabolic syndrome. Independent variables associated with EH were systolic blood pressure and urine creatinine, whereas serum creatinine had an inverse association. The primary end point of all-cause death (n = 1,137, 22.8%) occurred in 21.7%, 47.4%, and 56.6% of participants with no, CH, or EH, respectively (p- < 0.001). Age (hazard ratio [HR] per year = 1.10 [1.09 to 1.11], p <0.001), male gender (HR = 1.48 [1.29 to 1.69], p <0.001), black race (HR = 1.17 [1.005 to 1.36], p = 0.04), fasting glucose (HR = 1.005 [1.003 to 1.007], p <0.001), baseline creatinine (HR per mg/100 ml = 1.29 [1.15 to 1.46], p <0.001), left ventricular ejection fraction (HR per 1% = 0.98 [0.98 to 0.99], p = 0.005), IL-6 (HR per pg/ml = 1.17 [1.12 to 1.22], p <0.001), CH (HR = 1.84 [1.41 to 2.41], p <0.001), and EH (HR = 2.58 [1.77 to 3.76], p <0.001) were significant predictors of all-cause mortality. In conclusion, CH and EH are 2 distinct clinical phenotypes of left ventricular hypertrophy with differing gender and racial predisposition, both of which are associated with worse long-term adverse outcomes.

Clinical variables for predicting type-1 and type-2 non-ST segment elevation myocardial infarction in those presenting with ischemic symptoms.

Introduction: The accuracy of detecting myocardial infarction (MI) has greatly improved with the advent of more sensitive assays, and this has led to etiologic subtyping. Distinguishing between type 1 and type 2 non-ST-segment elevation myocardial infarction (NSTEMI) early in the clinical course allows for the most appropriate advanced diagnostic procedures and most efficacious treatments. The purpose of this study was to investigate the predictive effect of demographic and clinical variables on predicting NSTEMI subtypes in patients presenting with ischemic symptoms. Material and methods: We performed a single institution retrospective cohort study of patients who presented to the emergency department (ED) with ischemic signs and symptoms consistent with non-ST-segment myocardial infarction, for whom results of coronary angiography were available. We analyzed demographic, laboratory, echocardiography and angiography data to determine predictors of NSTEMI sub-types. Results: Five hundred and forty-six patients were enrolled; 426 patients were found on coronary angiography to have type 1 acute MI (T1AMI), whereas 120 patients had type 2 acute MI (T2AMI). Age (OR per year = 1.03 (1.00, 1.05), p = 0.03), prior MI (OR = 3.50 (1.68, 7.22), p = 0.001), L/H > 2.0 (OR = 1.55 (1.12, 2.13), p = 0.007), percentage change in troponin I > 25% (OR = 2.54 (1.38, 4.69), p = 0.003), and regional wall motion abnormalities (RWMA) (OR = 3.53 (1.46, 8.54), p = 0.004) were independent predictors of T1AMI, whereas sex, race, body mass index, hypertension, end-stage renal disease (ESRD), heart failure, family history (FH) of coronary artery disease (CAD), HbA1c, and left ventricular ejection fraction (LVEF) were not. Conclusions: Key clinical variables such as age, prior MI, L/H ratio, percentage change in troponin I, and presence of RWMA on echocardiogram may be utilized as significant predictors of T1AMI in patients presenting with ischemic symptoms to the ED.

Staphylococcus Auricularis Endocarditis: A Rare Cause of Subacute Prosthetic Valve Endocarditis with Severe Aortic Stenosis.

Prosthetic valve endocarditis (PVE) represents 20% of all cases of endocarditis. Herein, we present a rare cause of PVE by Staphylococcus auricularis (S. auricularis) exhibiting features of subacute endocarditis causing severe aortic stenosis and acute myocardial infarction.

Eccentric hypertrophy predicts adverse events in patients undergoing percutaneous coronary intervention for acute coronary syndrome.

INTRODUCTION: The effect of the type of left ventricular hypertrophy in patients presenting with an acute coronary syndrome (ACS) on long-term outcomes is ill-defined. The purpose of this study was to investigate the prognostic effect of concentric (CH) or eccentric hypertrophy (EH) on adverse outcomes in patients presenting with ACS undergoing percutaneous coronary intervention (PCI). MATERIAL AND METHODS: We analyzed 1-year follow-up data from a single-institution, retrospective, observational study that enrolled 1,153 patients who presented with ACS and were treated with PCI, for whom echocardiographic data were available. RESULTS: Normal geometry was observed in 718 (62.3%) patients, while 27.2% had CH and 10.5% had EH. The primary endpoint of all-cause death (n = 90, 7.8%) occurred in 6.4%, 8.0%, and 14.9% of patients with no, concentric, or eccentric hypertrophy, respectively (p = 0.005). Major adverse cardiac events (MACE - all-cause death, non-fatal myocardial infarction or stroke or hospitalization for bleeding) occurred in 13.9%, 17.8%, 30.6%, respectively (p < 0.001). Age (HR per year = 1.04 (1.02, 1.05), p < 0.001), female gender (HR = 1.56 (1.12, 2.16), p = 0.008), diabetes (HR = 1.49 (1.07, 2.06), p = 0.02), eccentric hypertrophy (HR = 1.58 (1.006, 2.47), p = 0.047), peak troponin I (HR per 1 ng/ml = 1.004 (1.001, 1.006), p = 0.004) and left ventricular ejection fraction < 50% (HR = 1.57 (1.12, 2.20), p < 0.008) were significant predictors of MACE. CONCLUSIONS: The presence of eccentric hypertrophy in ACS patients undergoing PCI is an independent predictor of adverse outcomes at 1 year.

The effect of cardiac geometry variation according to sex and race on outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

INTRODUCTION: The prevalence and long-term consequences of differences in baseline cardiac geometry (as a result of hypertension) in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) are ill-defined. The primary purpose of this study was to clarify whether there were differences among sexual and racial groups in echocardiographic findings reflecting cardiac geometry and adaptation in patients undergoing PCI for ACS and whether this could explain the differences in outcomes seen between these groups. MATERIAL AND METHODS: We analyzed 1-year follow-up data from a single institution, a retrospective, observational study that enrolled 1,153 patients who presented with ACS and were treated with PCI, for whom echocardiographic data were available. RESULTS: Normal, concentric hypertrophy, and eccentric hypertrophy in males vs. females were observed as follows: 29% vs. 19% (p = 0.001), 25% vs. 31% (p = 0.02), and 8% vs. 14% (p = 0.004), respectively. The primary endpoint of all-cause death (n = 89, 7.7%) occurred in 48 (10.5%) females and in 41 (8.2%) males, p = 0.03. Major adverse cardiac events and bleeding (MACE-B - all-cause death, non-fatal myocardial infarction, stroke or hospitalization for bleeding) was higher among women than men (21.6% vs. 13.5%, p = 0.0002). Males with eccentric hypertrophy (EH) had similar MACE-B outcomes as females with EH 1-year post-PCI (29% vs. 32%, respectively, p = 0.77). CONCLUSIONS: Females undergoing PCI for ACS are at higher risk for worse outcomes because they are more likely to express the eccentric hypertrophy phenotype; however, it did not account for the difference in adverse outcomes observed between sexes.

Non-ischemic Cardiomyopathy Secondary to Left Ventricular Hypertrophy due to Long-term Anabolic-androgenic Steroid Use in a Former Olympic Athlete.

Currently, the cardiovascular risk associated with the use of anabolic steroids is not well documented. Recent studies have shown that its use may potentiate the development of cardiac dysfunction in the short term. This case report describes an encounter that supports a causal link between anabolic-androgenic steroid use (AAS) and cardiomyopathy later in life. We herein present a case study of a 73-year-old prior Olympic athlete who had misused AAS for 20 years and subsequently was found to have developed a systolic and diastolic cardiomyopathy, presumably due to long-standing left ventricular hypertrophy. A 73-year-old man presented to our medical center with symptoms of lightheadedness and palpitations. He was found to be in ventricular tachycardia and was converted to sinus rhythm with medical pharmacotherapy. Further workup with two-dimensional trans-thoracic echocardiogram and cardiac catheterization showed severe left ventricular (LV) hypertrophy in the absence of hypertension and a combined systolic and diastolic heart failure with reduced ejection fraction in the absence of significant coronary artery disease or dilated cardiac chambers. The patient denies any family or personal history of cardiac issues until the time of presentation. By exclusion, he was diagnosed with a non-ischemic cardiomyopathy secondary to his prior regimented use of anabolic steroids. Although causality can only be inferred, this case presents a potentially delayed long-term cardiac consequences of extreme AAS use over many years. Notably, our patient had remained asymptomatic, until the development of arrhythmias, eventuating in ventricular tachycardia and contributing to heart failure with reduced ejection fraction. Physicians should caution users about the risk of possible long-term cardiac complications linked with AAS use.