Faculty Bibliography

BACKGROUND & AIM/UNASSIGNED:Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing health issue. Identifying factors that prevent hepatic lipid accumulation could inform new MASLD prevention or treatment strategies. We previously demonstrated that adipocyte microsomal triglyceride transfer protein (MTP) regulates intracellular lipolysis by inhibiting adipose triglyceride lipase activity. The aim of this study was to investigate the impact of adipose MTP deficiency on MASLD. METHODS/UNASSIGNED: RESULTS/UNASSIGNED: CONCLUSION/UNASSIGNED:These findings highlight the importance of regulated FA flux from adipose tissue to the liver and the liver's adaptive capacity to utilize adipose-derived FAs in maintaining hepatic health. Modulation of adipocyte FA release may represent a therapeutic strategy to reduce hepatic steatosis. IMPACT AND IMPLICATIONS/UNASSIGNED:This study provides significant insights into the role of adipose-specific microsomal triglyceride transfer protein in regulating hepatic lipid metabolism and its potential implications for treating metabolic dysfunction-associated steatotic liver disease. By demonstrating that microsomal triglyceride transfer protein deficiency in adipose tissue leads to increased fatty acid oxidation and reduced hepatic steatosis through enhanced PPARα activation, the research underscores the importance of adipose-liver crosstalk in maintaining liver health. These findings suggest that targeting adipocyte fatty acid release could be a promising therapeutic strategy to mitigate hepatic lipid accumulation and combat metabolic dysfunction-associated steatotic liver disease, offering a novel approach to addressing this growing health issue.

DermGPT demonstrated strong potential for improving answer clarity and conciseness in dermatology-related queries, while ChatGPT provided more robust source citations, enhancing trust in evidence-based responses.

We compared outcomes of patients ≥ 70 years old undergoing allogeneic stem cell transplantation (alloSCT) with graft-vs-host disease (GvHD) prophylaxis regimens either including post-transplant cyclophosphamide (PTCy) or without cyclophosphamide (non-Cy). The primary endpoint was GvHD-free, relapse-free survival (GRFS) at one and five years; secondary endpoints included clinically significant acute (grade III-IV) and chronic (extensive) GvHD, relapse, overall survival (OS), and non-relapse mortality (NRM). Among 61 patients, 41 received PTCy and 20 received non-Cy prophylaxis. Unrelated donors accounted for 80 % of allografts; all non-Cy patients had 10/10 HLA matches, while PTCy patients had 64 % matched, 29 % haploidentical, and 7 % mismatched unrelated donors. Acute GvHD occurred in 5 % of PTCy vs 15 % of non-Cy patients (p = ns). One-year chronic GvHD incidence was lower with PTCy (12 % vs 30 %, p = 0.03). One-year GRFS was similar (34 % PTCy, 35 % non-Cy; p = ns). At five years, OS was 20 % vs 30 % and GRFS 21 % vs 15 % for PTCy and non-Cy, respectively (p = ns). We observed similar outcomes among patients receiving GvHD prophylaxis with PTCy compared to non-Cy. Importantly, non-Cy patients had HLA-matched donors, whereas mismatched donors were possible for the PTCy group. In this way, PTCy seems to have equalized outcomes for fully matched and mismatched alloSCT by yielding similar one and five-year GRFS. We also found no significant difference in relapse rate, NRM, OS, and five-year GRFS between patients aged 70-74 and ages 75 + , showing that numerical age should not be a contraindication to alloSCT.

BACKGROUND:Despite the goal of the 2018 revision to the heart allocation policy to reduce reliance on exception requests through improved granularity in status criteria, there has been a dramatic rise in exception requests. OBJECTIVES/OBJECTIVE:This study evaluated trends in exception use over the first 6 years of the updated policy, assessing associated clinical factors, temporal changes, and impact on waitlist outcomes. METHODS:This retrospective transplant registry analysis included all adult isolated heart transplant candidates from October 18, 2018, to September 30, 2024. Candidates were stratified by exception use, listing era, and region. Exception use was compared using Wilcoxon rank-sum and chi-squared tests, with multilevel logistic regression assessing independent associations. Trends over time and across UNOS (United Network for Organ Sharing) regions were evaluated, and a competing risks framework examined time to transplant and waitlist mortality. RESULTS:Among 26,330 candidates, 38.6% used exception requests, with a statistically significant increase over time, particularly in higher priority statuses. Exception use was more common among Black, non-Hispanic candidates, and candidates with blood type O, and less likely for patients with blood type A (P < 0.001). Additionally, pretransplant isolated durable left ventricular assist devices were less common in candidates who requested exceptions (19.0% vs 31.6%; P < 0.001). Overall, 39.9% of exception candidates were listed at status 1 or 2 compared to 29% of nonexception candidates, and 69.2% of exception candidates were removed from the waitlist at status 1 or 2 compared with 37% of nonexception candidates. CONCLUSIONS:The rising use of exceptions underscores ongoing limitations in allocation criteria, and disparities suggesting inequities in access to higher listing status. Policy refinements are needed to ensure a balance between medical urgency and equitable allocation.

Advocacy has long been at the core of the infectious diseases (ID) field, with clinicians and researchers advocating to ensure patients can access the care they need on an individual and global scale. The Infectious Diseases Society of America Training Program Directors' (PD) Committee met in 2024 and discussed ways that advocacy is and should be incorporated into fellowship training, as well as highlighted the role PDs play in advocating for their trainees. Policies with a negative impact on ID clinical care, public health, and research underscore the importance of mobilizing the field of ID to advocate for the patients and communities we serve, as well as for ourselves. This paper presents ideas generated at this meeting and is meant to serve as a reference for ID PDs, as well as the wider ID community, as a call to action for teaching and participating in advocacy work.

OBJECTIVE/UNASSIGNED:To assess the impact of laparoscopic treatment of endometriosis on pregnancy outcomes in women with infertility, performed either before or after failed fertility enhancement technology (FET). Secondary aims included evaluating the influence of age, body mass index (BMI), prior pregnancies, endometriosis stage, and the presence of endometriomas on reproductive outcomes. DESIGN/UNASSIGNED:Retrospective cohort study of 95 women aged 18-45 with primary or secondary infertility who underwent treatment of endometriosis laparoscopically with or without robotic assistance between January 2015 and January 2023. All surgeries were performed by a single gynecologic surgeon. Patients were grouped based on whether they had prior FET failure or no prior FET. Comparisons were made between pregnant and nonpregnant patients across both groups. MAIN OUTCOME MEASURES/UNASSIGNED:Postsurgical pregnancy rates (spontaneous vs assisted reproductive technology [ART]) and factors associated with pregnancy outcomes, including age, BMI, endometriosis stage, and presence of endometriomas. RESULTS/UNASSIGNED:= .011). Endometriosis stage did not significantly influence outcomes. Patients with endometriomas were more likely to be referred for surgery before FET. CONCLUSIONS/UNASSIGNED:Laparoscopic surgery for endometriosis is associated with high pregnancy rates, regardless of prior FET status. These findings support the role of surgery as a key component in fertility management for women with endometriosis, especially prior to initiating FET.

A cluster of Aspergillus fumigatus donor-derived infections (DDI) was rapidly diagnosed using plasma metagenomic next-generation sequencing (mNGS) among solid organ transplant recipients. The heart recipient, experiencing marginal hemodynamics, underwent an endomyocardial biopsy, which was concerning for a fungal infection on histopathology. Plasma mNGS was performed, identifying A. fumigatus two days prior to conventional diagnostics. This timely diagnosis enabled prompt nephrectomies in the kidney recipients, who survived. This report represents the first published use of mNGS in the diagnosis of Aspergillus fumigatus DDI, highlighting the utility of this novel, underutilized assay for early diagnosis of donor-derived infections.

INTRODUCTION/BACKGROUND:Excessive salt intake is a major risk factor for cardiovascular disease (CVD) and premature mortality in China and globally. A recent cluster randomized controlled trial demonstrated the effectiveness of home cook interventions in reducing salt intake and blood pressure among participants from six provinces in China. Yet, it remains unclear whether expanding these interventions across China would be cost-effective. METHODS:The China CVD Prevention Model, a validated microsimulation model that captures the development and consequences of CVD among adults 35 years or older in China, was used to estimate lifetime averted CVD events and deaths, direct medical costs (2022 international dollar, Int$), quality-adjusted life years (QALYs) gained, and the incremental cost-effectiveness ratio (ICER) of home cook interventions versus the status quo. Costs and QALYs were discounted at 3%. RESULTS:Compared to the status quo, home cook interventions were projected to avert 1.97 million coronary heart disease (CHD) events, 3.69 million stroke events, 0.77 million deaths due to CHD, and 1.29 million deaths due to stroke in women. The interventions would also avert 1.62 million CHD events, 3.8 million stroke events, 0.6 million deaths due to CHD, and 1.15 million deaths due to stroke in men. The interventions resulted in an ICER of Int$3552/QALY in women and Int$5445/QALY in men and, thus, were cost-effective considering a willingness-to-pay threshold of Int$21,318 (one-time the gross domestic product per capita). CONCLUSIONS:Public health policymakers in China should consider widely adopting home cook interventions to better prevent CVD and reduce health care costs.

Methotrexate (MTX) has improved survival for children with acute lymphoblastic leukemia, but is associated with a 3%-7% incidence of neurotoxicity. This retrospective study showed a higher incidence of MTX neurotoxicity (11.3%) with the classic presentations of stroke-like syndrome (17/19), seizures (2/19), and the majority (14/19) showing characteristic radiographic findings. Most cases occurred during the consolidation phase, a median of 6 days after MTX exposure. Older age, Hispanic ethnicity, greater body mass index, and National Cancer Institute high-risk status were predictors of neurotoxicity, with only ethnicity remaining significant in adjusted analyses. Prophylactic leucovorin after repeated intrathecal MTX doses may be protective.