Faculty Bibliography

ABSTRACT/UNASSIGNED:Patients present to primary care physicians with musculoskeletal complaints more often than they do for upper respiratory infections, hypertension, or diabetes. Despite this, instruction in musculoskeletal medicine for internal medicine residents represents less than 1% of their total didactic and clinical education time. We recognize the immense breadth of knowledge and skill required to train residents in the practice of internal medicine. This curriculum guideline defines a recommended training strategy, and supplies relevant resources, to improve musculoskeletal education among internal medicine residents to optimize patient care. This curriculum guideline was created by internists who are sports medicine specialists. Sports medicine physicians promote overall health and well-being while providing expertise in acute and chronic musculoskeletal conditions, as well as how disease affects exercise and using exercise as medicine for people with chronic disease.

Early reports showed high mortality from coronavirus disease 2019 (COVID-19). Mortality rates have recently been lower; however, patients are also now younger, with fewer comorbidities. We explored 28-day mortality for patients hospitalized for COVID-19 in England over a 5-month period, adjusting for a range of potentially mitigating variables, including sociodemographics and comorbidities. Among 102,610 hospitalizations, crude mortality decreased from 33.4% (95% CI, 32.9-34.0) in March 2020 to 15.5% (95% CI, 14.1-17.0) in July. Adjusted mortality decreased from 33.4% (95% CI, 32.8-34.1) in March to 17.4% (95% CI, 11.3-26.9) in July. The relative risk of mortality decreased from a reference of 1 in March to 0.52 (95% CI, 0.34-0.80) in July. This demonstrates that the reduction in mortality is not solely due to changes in the demographics of those with COVID-19.

The landscape of HIV medicine dramatically changed with the advent of contemporary antiretroviral therapies (ART) which has allowed persons with HIV (PWH) to achieve good virologic control, essentially eliminating HIV-related complications and increasing life expectancy. As PWH are living longer, non-communicable diseases, such as cardiovascular disease (CVD), have become a leading cause of morbidity and mortality in PWH with rates that are 50-100% higher than in well-matched persons without HIV. In this review, we focus on disease of the coronary microvasculature and myocardium in HIV. We highlight a key hormonal system important to cardiovascular endocrinology, the renin-angiotensin-aldosterone system (RAAS), as a potential mediator of inflammatory driven-vascular and myocardial injury and consider RAAS blockade as a physiologically-targeted strategy to reduce CVD in HIV.

PURPOSE OF REVIEW/OBJECTIVE:The purpose of this review was to assess the prevalence of United States chronic kidney disease (CKD) health disparities, focusing on racial/ethnic groups, immigrants and refugees, sex or gender, and older adults. RECENT FINDINGS/RESULTS:There are major racial/ethnic disparities in CKD, with possible contributions from the social determinants of health, socioeconomics, and racial discrimination. Racial/ethnic minority patients experience faster progression to end-stage kidney disease (ESKD) and higher mortality predialysis, however, once on dialysis, appear to live longer. Similarly, men are quicker to progress to ESKD than women, with potential biological, behavioral, and measurement error factors. There is a lack of substantial evidence for intersex, nonbinary, or transgender patients. There are also strikingly few studies about US immigrants or older adults with CKD despite the fact that they are at high risk for CKD due to a variety of factors. SUMMARY/CONCLUSIONS:As providers and scientists, we must combat both conscious and unconscious biases, advocate for minority patient populations, and be inclusive and diverse in our treatment regimens and provision of care. We need to acknowledge that sufficient evidence exists to change treatment guidelines, and that more is required to support the diversity of our patient population.

In response to the COVID-19 global pandemic, recent research has proposed creating deep learning based models that use chest radiographs (CXRs) in a variety of clinical tasks to help manage the crisis. However, the size of existing datasets of CXRs from COVID-19+ patients are relatively small, and researchers often pool CXR data from multiple sources, for example, using different x-ray machines in various patient populations under different clinical scenarios. Deep learning models trained on such datasets have been shown to overfit to erroneous features instead of learning pulmonary characteristics -- a phenomenon known as shortcut learning. We propose adding feature disentanglement to the training process, forcing the models to identify pulmonary features from the images while penalizing them for learning features that can discriminate between the original datasets that the images come from. We find that models trained in this way indeed have better generalization performance on unseen data; in the best case we found that it improved AUC by 0.13 on held out data. We further find that this outperforms masking out non-lung parts of the CXRs and performing histogram equalization, both of which are recently proposed methods for removing biases in CXR datasets.

Limiting the metabolic competition in the tumor microenvironment (TME) may increase the effectiveness of immunotherapy. Because of its critical role in glucose metabolism of activated T cells, CD28 signaling has been proposed as a T-cell metabolic biosensor¹. Conversely, CTLA-4 engagement has been shown to down-regulate T-cell glycolysis¹. Here, we investigated the impact of CTLA-4 blockade on the metabolic fitness of intra-tumor T cells in relationship to the tumor glycolytic capacity. We found that CTLA-4 blockade promotes immune cell infiltration and metabolic fitness especially in glycolysis-low tumors. Accordingly, anti-CTLA-4 achieved better therapeutic outcomes in mice bearing glycolysis-defective tumors. Intriguingly, tumor-specific CD8⁺ T-cell responses correlated with phenotypic and functional destabilization of tumor-infiltrating regulatory T cells (Tregs) toward IFN-γ- and TNF-α-producing cells in glycolysis-defective tumors. By mimicking the highly and poorly glycolytic TME in vitro, we show that the effect of CTLA-4 blockade to promote Treg destabilization is dependent on Treg glycolysis and CD28 signaling. These findings indicate that decreasing tumor competition for glucose may facilitate the therapeutic activity of CTLA-4 blockade, thus supporting its combination with inhibitors of tumor glycolysis. Moreover, these results reveal a new mechanism through which anti-CTLA-4 interferes with Treg function in the presence of glucose.

A retrospective study was conducted to describe the impact of a molecular assay to detect the most common carbapenemase genes in carbapenem-resistant Enterobacterales isolates recovered in culture. Carbapenemases were detected in 69% of isolates, and assay results guided treatment modifications or epidemiologic investigation in 20% and 4% of cases, respectively.

PURPOSE OF REVIEW/OBJECTIVE:Several nontraditional risk factors have been the focus of research in an attempt to understand the disproportionately high cardiovascular morbidity and mortality in chronic kidney disease (CKD) and end-stage kidney disease (ESKD) populations. One such category of risk factors is cardiovascular autonomic dysfunction. Its true prevalence in the CKD/ESKD population is unknown but existing evidence suggests it is common. Due to lack of standardized diagnostic and treatment options, this condition remains undiagnosed and untreated in many patients. In this review, we discuss current evidence pointing toward the role of autonomic nervous system (ANS) dysfunction in CKD, building off of crucial historical evidence and thereby highlighting the areas in need for future research interest. RECENT FINDINGS/RESULTS:There are several key mediators and pathways leading to cardiovascular autonomic dysfunction in CKD and ESKD. We review studies exploring the mechanisms involved and discuss the current measurement tools and indices to evaluate the ANS and their pitfalls. There is a strong line of evidence establishing the temporal sequence of worsening autonomic function and kidney function and vice versa. Evidence linking ANS dysfunction and arrhythmia, sudden cardiac death, intradialytic hypotension, heart failure and hypertension are discussed. SUMMARY/CONCLUSIONS:There is a need for early recognition and referral of CKD and ESKD patients suspected of cardiovascular ANS dysfunction to prevent the downstream effects described in this review.There are many unknowns in this area and a clear need for further research.