Faculty Bibliography

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:Porcine genome editing has revolutionized xenotransplantation, recently enabling the first pig-to-human heart xenotransplants. However, the xeno-immune response in heart xenografts remains largely unexplored. This study aimed to precisely characterize the xeno-immune response and injury in two heart xenografts, transplanted from 10-gene-edited pigs into brain-dead human recipients. METHODS:We analyzed xenograft biopsies at 66-hour post-reperfusion using a multimodal phenotyping approach combining: morphological evaluation, immunophenotyping, ultrastructural assessment, automated quantification of multiplex immunofluorescence staining and gene expression profiling. Xenografts before implantation and wild-type pig hearts with and without ischemia reperfusion injury and brain death were used as controls. RESULTS:Both xenografts showed evidence of endothelial activation and mild microvascular inflammation without capillary C4d deposition. Immune infiltrates were mainly composed of CD15+ and CD68+ innate immune cells. Ultrastructural assessment showed endothelial swelling with occasional intravascular leucocytes. Deep-learning based automated multiplex immunofluorescence analysis confirmed that microvascular inflammation was primarily associated with CD15+ and CD68+ innate immune cells. Both xenografts showed increased expression of genes and pathways associated with monocyte/macrophage activation, neutrophil activation, interferon-gamma response, natural killer cell burden, endothelial activation, apoptosis and injury repair. This phenotype was absent in all control pig hearts, independently from ischemia reperfusion injury and brain death. CONCLUSIONS:Multimodal phenotyping of pig-to-human heart xenografts revealed early signs of xeno-immune response, characterized by mild innate microvascular inflammation, endothelial activation, and molecular signature characteristic of antibody-mediated rejection. Developing such precision diagnostic system could improve graft monitoring in future clinical settings.

BACKGROUND:Bariatric surgery has long been established as an effective treatment option for obesity and diabetes [Kalainov et al. in J Am Acad Orthop Surg [32(10):427-438, 2025] and Ogden et al. in JAMA 311(8):806-806, 2025. 10.1001/jama.2014.732]. Recently, GLP-1 Receptor Agonists' (GLP-1RAs) use has expanded as an alternative therapy for weight loss and diabetes management. While GLP1RAs are known to be safe and effective, few have compared long term outcomes of GLP-1RAs versus the "gold standard" of bariatric surgery among Medicare/Medicaid patients, who make up the largest payer group in the U.S. [Kalainov et al. in J Am Acad Orthop Surg [32(10):427-438, 2025]. METHODS:This was a retrospective, multicenter study of obese, type-2 diabetic patients (T2D) ≥ 18 years old, who initiated weekly injectable semaglutide or tirzepatide or underwent bariatric surgery between January 1st, 2018 to July 31st, 2024. Patients with a baseline BMI ≤ 35, those with prior GLP1-RA use, or any prior bariatric procedure were excluded from analysis. The primary outcome of interest was % total body weight loss 3 months to 3 years post intervention among bariatrics surgery patients vs. GLP1-RA patients (any GLP1-RA prescription and 12 months continuous GLP1-RA prescription). RESULTS:7667 patients were included for analysis (7200 GLP1-RA, 467 bariatric surgery). Bariatric surgery patients were younger (median (IQR): 43 (34, 53) vs. 65 (54, 72); p < 0.001) and more likely to be female (67.5% vs. 60.8%; p < 0.01) and Hispanic (58.7% vs. 19.4%; p < 0.001) while GLP1-RA users were more likely to be white (58.5% vs. 10.7%; p < 0.001). In models adjusting for demographic and clinical characteristics, bariatric surgery was associated with a 22.9% total weight loss 3 years following surgery compared to 2.3% for patients with any GLP1-RA use, and 15.9% vs 2.4% for patients with 12 months consecutive GLP1-RA use (22.9 [21.0-24.8] vs 2.3 [0.5-4.1], 15.9 [6.9-24.9] vs. 2.4 [6.7-11.5]. CONCLUSIONS:Among obese, T2D, publicly insured patients, bariatric surgery was associated with greater weight loss than GLP1-RAs at all measured periods from 3 months to 3 years post op.

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.

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.

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.

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.