Faculty Bibliography

In a previous study, heart xenografts from 10-gene-edited pigs transplanted into two human decedents did not show evidence of acute-onset cellular- or antibody-mediated rejection. Here, to better understand the detailed molecular landscape following xenotransplantation, we carried out bulk and single-cell transcriptomics, lipidomics, proteomics and metabolomics on blood samples obtained from the transplanted decedents every 6 h, as well as histological and transcriptomic tissue profiling. We observed substantial early immune responses in peripheral blood mononuclear cells and xenograft tissue obtained from decedent 1 (male), associated with downstream T cell and natural killer cell activity. Longitudinal analyses indicated the presence of ischemia reperfusion injury, exacerbated by inadequate immunosuppression of T cells, consistent with previous findings of perioperative cardiac xenograft dysfunction in pig-to-nonhuman primate studies. Moreover, at 42 h after transplantation, substantial alterations in cellular metabolism and liver-damage pathways occurred, correlating with profound organ-wide physiological dysfunction. By contrast, relatively minor changes in RNA, protein, lipid and metabolism profiles were observed in decedent 2 (female) as compared to decedent 1. Overall, these multi-omics analyses delineate distinct responses to cardiac xenotransplantation in the two human decedents and reveal new insights into early molecular and immune responses after xenotransplantation. These findings may aid in the development of targeted therapeutic approaches to limit ischemia reperfusion injury-related phenotypes and improve outcomes.

BACKGROUND:Recent data suggest patients with graft failure had better access to repeat kidney transplantation (re-KT) than transplant-naive dialysis accessing first KT. This was postulated to be because of better familiarity with the transplant process and healthcare system; whether this advantage is equitably distributed is not known. We compared the magnitude of racial/ethnic disparities in access to re-KT versus first KT. METHODS:Using United States Renal Data System, we identified 104 454 White, Black, and Hispanic patients with a history of graft failure from 1995 to 2018, and 2 357 753 transplant-naive dialysis patients. We used adjusted Cox regression to estimate disparities in access to first and re-KT and whether the magnitude of these disparities differed between first and re-KT using a Wald test. RESULTS:Black patients had inferior access to both waitlisting and receiving first KT and re-KT. However, the racial/ethnic disparities in waitlisting for (adjusted hazard ratio [aHR] = 0.77; 95% confidence interval [CI], 0.74-0.80) and receiving re-KT (aHR = 0.61; 95% CI, 0.58-0.64) was greater than the racial/ethnic disparities in first KT (waitlisting: aHR = 0.91; 95% CI, 0.90-0.93; Pinteraction = 0.001; KT: aHR = 0.68; 95% CI, 0.64-0.72; Pinteraction < 0.001). For Hispanic patients, ethnic disparities in waitlisting for re-KT (aHR = 0.83; 95% CI, 0.79-0.88) were greater than for first KT (aHR = 1.14; 95% CI, 1.11-1.16; Pinteraction < 0.001). However, the disparity in receiving re-KT (aHR = 0.76; 95% CI, 0.72-0.80) was similar to that for first KT (aHR = 0.73; 95% CI, 0.68-0.79; Pinteraction = 0.55). Inferences were similar when restricting the cohorts to the Kidney Allocation System era. CONCLUSIONS:Unlike White patients, Black and Hispanic patients with graft failure do not experience improved access to re-KT. This suggests that structural and systemic barriers likely persist for racialized patients accessing re-KT, and systemic changes are needed to achieve transplant equity.

INTRODUCTION:Intensive weight management programs are effective but often have low enrollment and high attrition. Lack of motivation is a key psychological barrier to enrollment, engagement, and weight loss. Mental Contrasting with Implementation Intentions (MCII) is a unique imagery technique that increases motivation for behavior change. We describe our study protocol to assess the efficacy and implementation of MCII to enhance the effectiveness of VA's MOVE! or TeleMOVE! weight management programs using a procedure called "WOOP" (Wish, Outcome, Obstacle, Plan) for Veterans. We hypothesize that WOOP+MOVE! or TeleMOVE! (intervention) will lead to greater MOVE!/TeleMOVE! program engagment and consequently weight loss than MOVE!/TeleMOVE! alone (control). METHOD:Veterans are randomized to either the intervention or control. Both arms receive the either MOVE! or TeleMOVE! weight management programs. The intervention group receives an hour long WOOP training while the control group receives patient education. Both groups receive telephone follow up calls at 3 days, 4 weeks, and 2 months post-baseline. Eligible participants are Veterans (ages 18-70 years) with either obesity (BMI ≥ 30 kg/m2) or overweight (BMI ≥ 25 kg/m2) and an obesity-associated co-morbidity. At baseline, 6 and 12 months, we assess weight, diet, physical activity in both groups. The primary outcome is mean percent weight change at 6 months. Secondary outcomes include changes in waist circumference, diet, physical activity, and dieting self-efficacy and engagement in regular physical activity. We assess implementation using the RE-AIM framework. CONCLUSION:If WOOP VA is found to be efficacious, it will be an important tool to facilitate weight management and improve weight outcomes. CLINICAL TRIAL REGISTRATION:NCT05014984.

IMPORTANCE/UNASSIGNED:Anabolic androgenic steroids (AAS) are disproportionately used by sexual minority men, with the physical and mental health implications of AAS use incompletely understood. OBJECTIVE/UNASSIGNED:To understand the reasons for use and health care needs of gay, bisexual, and queer cisgender men using AAS. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This qualitative study was conducted from November 2021 to May 2023 using self-administered questionnaires and semistructured interviews that were transcribed and coded using reflexive thematic analysis. Participants were recruited through convenience and snowball sampling from lesbian, gay, bisexual, transgender, and queer clinical centers in New York, New York, as well as through online platforms. All patients self-identified as cisgender and gay, bisexual, or queer. EXPOSURES/UNASSIGNED:History of nonprescribed AAS use for a minimum of 8 consecutive weeks was required. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcomes were reasons for and health implications of AAS use and interactions with health care practitioners, as determined through interviews. Interview transcripts were collected and analyzed. RESULTS/UNASSIGNED:Thematic saturation was reached after interviews with 12 male participants (mean [SD] age, 44 [11] years), with the majority of participants identifying as gay (10 participants [83%]), White non-Hispanic (9 participants [75%]), being in their 30s and 40s (9 participants [75%]), holding a bachelor's degree or higher (11 participants [92%]), and having used steroids for a mean (SD) of 7.5 (7.1) years. One participant (8%) self-identified as Black, and 2 (17%) identified as Hispanic. Seven men (58%) met the criteria for muscle dysmorphia on screening. Nine overarching themes were found, including internal and external motivators for initial use, continued use because of effectiveness or fear of losses, intensive personal research, physical and emotional harms experienced from use, using community-based harm reduction techniques, frustration with interactions with the medical community focused on AAS cessation, and concerns around the illegality of AAS. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this qualitative study, AAS use among cisgender gay, bisexual, and queer men was found to be associated with multifactorial motivators, including a likely AAS use disorder and muscle dysmorphia. Despite all participants experiencing harms from use, men seeking medical help found insufficient support with practitioners insistent on AAS cessation and, thus, developed their own harm reduction techniques. Further research is needed to assess the utility of practitioner education efforts, the safety and efficacy of community-developed harm reduction methods, and the impact of AAS decriminalization on health care outcomes for this patient population.

PURPOSE/UNASSIGNED:The Professional Identity Essay (PIE) is a theory and evidence-based Medical Professional Identity Formation (MPIF) measure. We describe trajectories of PIE-measured MPIF over a 4-year US medical school curriculum. METHODS/UNASSIGNED:Students write PIEs at medical school orientation, clinical clerkships orientation, and post-advanced (near graduation) clerkship. A trained evaluator assigns an overall stage score to narrative responses to nine PIE prompts (inter-rater ICC 0.83, 95% CI [0.57 - 0.96], intra-rater ICC 0.85). Distribution of PIE stage scores across time points were analyzed in the aggregate and individual students were classified as Increase, Stable (no score change) or Decrease based on the trajectories of PIE stage scores over time. RESULTS/UNASSIGNED: CONCLUSIONS/UNASSIGNED:Medical students' PIE stage scores increase over time with three distinctive trajectories. Further study is needed to explore the utility of this method for formative assessment, program evaluation, and MPIF research.

The risk of arrhythmia and its management become increasingly complex as kidney disease progresses. This presents a multifaceted clinical challenge. Our discussion addresses these specific challenges relevant to patients as their kidney disease advances. We highlight numerous opportunities for enhancing the current standard of care within this realm. Additionally, this review delves into research concerning early detection, prevention, diagnosis, and treatment of various arrhythmias spanning the spectrum of kidney disease.

BACKGROUND:Non-fatal overdose is a leading predictor of subsequent fatal overdose. For individuals who are incarcerated, the risk of experiencing an overdose is highest when transitioning from a correctional setting to the community. We assessed if enrollment in jail-based medications for opioid use disorder (MOUD) is associated with lower risk of non-fatal opioid overdoses after jail release among individuals with opioid use disorder (OUD). METHODS:This was a retrospective, observational cohort study of adults with OUD who were incarcerated in New York City jails and received MOUD or did not receive any MOUD (out-of-treatment) within the last three days before release to the community in 2011-2017. The outcome was the first non-fatal opioid overdose emergency department (ED) visit within 1 year of jail release during 2011-2017. Covariates included demographic, clinical, incarceration-related, and other characteristics. We performed multivariable cause-specific Cox proportional hazards regression analysis to compare the risk of non-fatal opioid overdose ED visits within 1 year after jail release between groups. RESULTS:MOUD group included 8660 individuals with 17,119 incarcerations; out-of-treatment group included 10,163 individuals with 14,263 incarcerations. Controlling for covariates and accounting for competing risks, in-jail MOUD was associated with lower non-fatal opioid overdose risk within 14 days after jail release (adjusted HR=0.49, 95% confidence interval=0.33-0.74). We found no significant differences 15-28, 29-56, or 57-365 days post-release. CONCLUSION/CONCLUSIONS:MOUD group had lower risk of non-fatal opioid overdose immediately after jail release. Wider implementation of MOUD in US jails could potentially reduce post-release overdoses, ED utilization, and associated healthcare costs.

The frequency of burnout is rising among cardiologists, affecting not only their well-being but also the quality of patient care. Computerization of practice, bureaucracy, excessive workload, lack of control/autonomy, hostile and hectic work environments, insufficient income, and work life imbalance are the main categories listed as contributing factors to cardiologists' burnout. Organization- and physician-directed interventions can be impactful; however, the effectiveness and feasibility of these interventions have rarely been assessed in cardiology. This review summarizes recent publications on burnout in cardiology, discusses the contributing factors and implications of burnout on physicians' health and patient safety, and explores possible interventions.