Faculty Bibliography

IMPORTANCE/UNASSIGNED:Many patients are diagnosed with benign breast lesions; however, evidence- and consensus-based guidelines for the management of benign breast disease (BBD) are limited. OBSERVATIONS/UNASSIGNED:The American Society of Breast Surgeons (ASBrS) and the Society of Breast Imaging (SBI) developed guidelines for the management of benign fibroepithelial lesions (FELs) using a modified Delphi consensus methodology and public comment. There was strong consensus that core biopsy-proven concordant fibroadenomas without atypia only require excision if they were symptomatic, patient preferred, attained a certain size, or demonstrated substantive growth over time on clinical examination. There was strong consensus that when removing a fibroadenoma, complete excision without transection of the mass is recommended and surgeons should consider aesthetics, sensation, and other factors when selecting incision placement. Patients with core biopsy-proven concordant fibroadenomas do not require imaging follow-up and may return to age-appropriate screening. Many benign phyllodes tumors (BPTs) present as an FEL on core biopsy, and these lesions along with any lesions with suspicion of or concern for phyllodes tumors (PTs) require surgical excisional biopsy with complete excision of the mass. Re-excision of a BPT is not required for patients with a positive margin for BPT, but a margin re-excision may be considered if the mass was transected or there is concern of residual disease after excisional biopsy. Patients with BPT who have undergone excision do not require follow-up imaging and may return to age-appropriate screening. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Evidence-informed, consensus and expert opinion-based guidelines for the management of benign FELs of the breast were developed. These guidelines provide clarification on the controversial management of benign FELs of the breast. Any practicing clinicians who treat patients with benign FELs should integrate these guidelines into treatment of their patients.

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.

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.

BACKGROUND:There are risks associated with excessive intravenous fluid (IVF) administration in critically ill children. Previous efforts have described opportunities to reduce positive cumulative fluid balance (CFB) in this population but have not been widely implemented. In the wake of Hurricane Helene, a national IVF shortage led to the implementation of IVF conservation guidelines. We sought to determine if this was associated with a reduction in IVF use and CFB. METHODS:The present study is a four-site cohort study of critically ill children utilizing a federated data collection framework to extract patient age, sex, weight, and daily fluid intake/output for days 1-4 of all admissions 28 days prior to and 28 days after the implementation of IVF conservation guidelines. Guidelines were individualized per institution. Total fluid intake, total IVF intake, % intake from IVF, and % CFB were compared between pre- and post-IVF conservation groups. RESULTS:All sites had similar conservation recommendations. There were 633 patients admitted pre- and 619 patients admitted post-IVF conservation guideline implementation, with similar age and weight distributions. There was no significant difference in IVF use pre- and post-IVF conservation; 29-35% of patients had > 5% CFB on day 1 pre-IVF conservation while 27-39% did post-conservation, with increasing numbers on day 2. CONCLUSIONS:Even in the setting of a national IVF shortage, simple recommendations without structured change were insufficient to change IVF administration practices. This indicates additional practices will be needed to reduce IVF intake and % CFB in this vulnerable population.

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.

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 & 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.

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.

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.