Varsha K. Tanguturi

Promiscuous binding of extracellular peptides to cell surface class I MHC protein

Algorithms derived from measurements of short-peptide (8–10 mers) binding to class I MHC proteins suggest that the binding groove of a class I MHC protein, such as Kb, can bind well over 1 million different peptides with significant affinity (<500 nM), a level of ligand-binding promiscuity approaching the level of heat shock protein binding of unfolded proteins. MHC proteins can, nevertheless, discriminate between similar peptides and bind many of them with high (nanomolar) affinity. Some insights into this high-promiscuity/high-affinity behavior and its impact on immunodominant peptides in T-cell responses to some infections and vaccination are suggested by results obtained here from testing a model developed to predict the number of cell surface peptide–MHC complexes that form on cells exposed to extracellular (exogenous) peptides.

The Electrocardiographic Early Repolarization Pattern in Athletes

The clinical evaluation of athletes during symptom evaluation or pre-participation screening often involves interpretation of the 12-lead electrocardiogram (ECG). Differentiating abnormal ECG findings suggestive of underlying cardiovascular disease from benign findings caused by exercise-induced cardiac adaptations can be challenging, and recent clinical guidelines have been created for this purpose. One of the most common ECG findings in athletes is the early repolarization pattern (ERP), characterized by diffuse J-point elevation and concave ST-segment elevation, and long regarded as a normal variant. However, recently published data suggest that the ERP may be a marker of increased risk for sudden cardiac death (SCD) in the general population. The observation that the ERP can indicate increased SCD risk has important implications for the clinician charged with the care of athletes. This review will describe the evolving understanding of the ERP and will explore the relevance of the ERP for the care of athletes.

Variation in the Echocardiographic Surveillance of Primary Mitral RegurgitationCLINICAL PERSPECTIVE

Background— Clinical outcomes after surgical treatment of mitral regurgitation are worse if intervention occurs after deterioration of left ventricular size and function. Transthoracic echocardiographic (TTE) surveillance of patients with mitral regurgitation is indicated to avoid adverse ventricular remodeling. Overly frequent TTEs can impair patient access and reduce value in care delivery. This balance between timely surveillance and overutilization of TTE in valvular disease provides a model to study variation in the delivery of healthcare services. We investigated patient and provider factors contributing to variation in TTE utilization and hypothesized that variation was attributable to provider practice even after adjustment for patient characteristics. Methods and Results— We obtained records of all TTEs from 2001 to 2016 completed at a large echocardiography laboratory. The outcome variable was time interval between TTEs. We constructed a mixed-effects linear regression model with the individual physician as the random effect in the model and used intraclass correlation coefficient to assess the proportion of outcome variation because of provider practice. Our study cohort was 55 773 TTEs corresponding to 37 843 intervals ordered by 635 providers. The mean interval between TTEs was 12.4 months, 17.0 months, 18.3 months, and 17.4 months for severe, moderate, mild, and trace mitral regurgitation, respectively, with 20% of providers deemed overutilizers of TTEs and 25% underutilizers. Conclusions— We conclude that there is substantial variation in follow-up intervals for TTE assessment of mitral regurgitation, despite risk-adjustment for patient variables, likely because of provider factors.

Echocardiographic Surveillance of Valvular Heart Disease in Different Sociodemographic Groups

Substantial disparities in clinical outcomes exist for patients with valvular heart disease. Black patients with aortic stenosis receive aortic valve replacements (AVRs) less often than white patients, and women have greater mortality following valve surgery [(1,2)][1]. Although little is known