Faculty Bibliography

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.

OBJECTIVES/OBJECTIVE:Sjögren's disease is an autoimmune disorder that can impact multiple organ systems, including the peripheral nervous system (PNS). PNS manifestations, which can exist concurrently, include mononeuropathies, polyneuropathies, and autonomic nervous system neuropathies. To help patients and providers in the decision-making process, we developed an evidence-based clinical practice guideline for the evaluation and management of peripheral nervous system manifestations in patients with Sjögren's disease. METHODS:A Topic Review Group (TRG), comprised of experts in rheumatology, neurology, and guideline methodology, developed Patient, Intervention, Comparison, and Outcome (PICO) questions and conducted a systematic review to identify current best evidence on management of PNS manifestations of Sjögren's disease. PubMed and Embase were searched for evidence published up to July 22, 2025. Literature screening, data extraction, and critical appraisal were performed in duplicate. Six case series, one retrospective cohort, and two prospective cohort studies lacking a comparison group met the inclusion criteria. RESULTS:We developed an aligned nomenclature of PNS terms that can be used across disciplines, 31 good practices for evaluation of suspected PNS manifestations, and 20 evidence-based treatment recommendations, the latter of which were rated as conditional or strong based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Due to the scarcity of high-level evidence, this guideline predominantly derives from expert opinion. CONCLUSION/CONCLUSIONS:This clinical practice guideline on PNS manifestations of Sjögren's disease provides clinicians a rigorous, evidence-based resource, developed through an expert consensus-based process, for the assessment, diagnosis, and treatment of peripheral neuropathy in Sjögren's patients. Recommendations were rated as strong when the benefits significantly outweighed potential harms, creating a scenario in which the majority of patients would prefer the advised action.

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.

BACKGROUND/UNASSIGNED:Movement of circulating lipids into tissues and arteries requires transfer across the endothelial cell (EC) barrier. This process allows the heart to obtain fatty acids, its chief source of energy, and apoB-containing lipoproteins to cross the arterial endothelial barrier, leading to cholesterol accumulation in the subendothelial space. Multiple studies have established elevated postprandial TRLs (triglyceride-rich lipoproteins) as an independent risk factor for cardiovascular disease. We explored how chylomicrons affect ECs and transfer their fatty acids across the EC barrier. METHODS/UNASSIGNED:C]oleate, we studied the uptake and release of this labeled by ECs. RESULTS/UNASSIGNED:]C labeled chylomicron triglycerides exited ECs primarily in phospholipids. EVs from chylomicron-treated versus untreated ECs were larger, more abundant, and contained specific microRNAs. Treatment of macrophages and naive ECs with media from chylomicron-treated ECs increased expression of inflammatory genes. CONCLUSIONS/UNASSIGNED:EC chylomicron metabolism produces EVs that increase macrophage inflammation and create LDs. Media containing these EVs also increases EC inflammation, illustrating an autocrine inflammatory process. Fatty acids within chylomicron triglycerides are converted to phospholipids within EVs. Thus, EC uptake of chylomicrons constitutes an important pathway for vascular inflammation and tissue lipid acquisition.

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.

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.

The cardiovascular-kidney-metabolic (CKM) syndrome consists of four progressive stages and is characterized by the interaction of metabolic risk factors, chronic kidney disease (CKD), and cardiovascular disease (CVD). We assessed the prevalence of hypertension in CKM and its role in progression to more advanced stages. We included 2118 Black adults from the Jackson Heart Study without a history of coronary heart disease, heart failure, stroke or stage 0 CKM (normal weight, no metabolic risk factors or CVD) at baseline. Participants were categorized into CKD stage: Stage 1: overweight/obesity, abdominal obesity or dysfunctional adipose tissue without metabolic risk factors or subclinical CVD; Stage 2: metabolic risk factors (hypertension, diabetes, hypertriglyceridemia, metabolic syndrome or CKD); or Stage 3: subclinical CVD. We used Cox proportional hazards regression to estimate the hazard ratio (HR) of developing stage 4 CKM, defined by a CVD event, in participants with hypertension and stages 2 and 3 CKM. At baseline, 20.2, 69.1 and 10.6% of participants had stage 1, 2 and 3 CKM, respectively. Hypertension was the most common metabolic risk factor in participants with stage 2 and 3 CKM with a prevalence of 80 and 95%, respectively. Incidence rates (95%CI) of stage 4 CKM per 1000 person-years were 1.4 (0.4, 2.4) for stage 1 CKM, 7.5 (6.1, 8.9) for stage 2 CKM with hypertension, and 26.6 (19.8, 33.3) for stage 3 CKM with hypertension. The HRs (95% CI) for developing stage 4 CKM were 3.25 (1.56, 6.80) and 5.11 (2.05,12.78) among participants with hypertension and stage 2 and 3 CKM versus stage 1 CKM, respectively. Hypertension was associated with an increased risk for progression to stage 4 CKM among Black adults.

BACKGROUND:Persistent chemotherapy-induced alopecia (pCIA) is a distressing side effect of antineoplastic agents, imposing significant psychological burdens on cancer survivors. Despite its impact, there are no standardized guidelines for diagnosis, prevention or management. OBJECTIVES/OBJECTIVE:To establish consensus-based definitions, diagnostic criteria, grading systems and management recommendations for pCIA. METHODS:A two-round Delphi method was conducted with 15 international experts in supportive oncodermatology and hair diseases from both Europe and the Americas. Statements were rated on a 5-point Likert scale, with a strong consensus defined as ≥75% agreement. Statements that did not achieve strong consensus in the first round were revised based on expert feedback and re-evaluated in a second-round survey. RESULTS:Strong consensus was reached on 47 statements (75.8%). pCIA was defined as non-scarring alopecia persisting beyond 6 months post-chemotherapy. Causes were attributed to the destruction of hair follicle stem cells, with taxanes, thiotepa and anthracyclines identified as key contributors. Consensus emphasized the importance of prevention of pCIA through scalp cooling devices, and the early intervention with topical or low-dose oral minoxidil was also recommended. Interestingly, the experts did not recommend the use of bicalutamide, oral finasteride and dutasteride (including in mesotherapy) for breast cancer patients with pCIA, citing potential safety concerns. CONCLUSIONS:This Delphi study established unified guidelines for pCIA, providing clinicians with a clear framework for diagnosis and treatment. Highlighting prevention through scalp cooling and timely interventions may improve outcomes for cancer survivors. Further research is necessary to assess new treatments and the long-term impact of chemotherapy on hair follicles.