Faculty Bibliography

BACKGROUND/UNASSIGNED:During the last 20 years, the novel and highly visible nature of facial transplantation (FT) has posed a dual and potentially conflicting obligation for FT programs: to disseminate findings for scientific advancement while respecting recipients' preferences for privacy, given the significant public and media attention. The individually identifying nature of FT is not present in other forms of vascularized composite allotransplantation, making it unique. Despite extensive ethical discourse on FT, implications for privacy are largely absent from ethical analyses. METHODS/UNASSIGNED:This conceptual analysis assesses the complex ethical implications associated with privacy in FT and offers guidance to FT programs for navigating concerns related to donors, recipients, and their families. A literature review was performed and supplemented by our institutional experience. RESULTS/UNASSIGNED:Ethical approaches to privacy require balancing the conflicting ethical principles at the center of this dual obligation. Patient-centered strategies should include comprehensive psychological screening to understand patients' goals for care, informed consent that clearly addresses the dissemination of information and media involvement, and control of media coverage until the recipient is ready and willing. Public relations support for recipients has been helpful in our institution's experience. Additional community-based strategies include educational outreach interventions to satisfy public curiosity. CONCLUSIONS/UNASSIGNED:Findings from published reports alongside our institution's experience suggest that a nuanced, multifaceted approach is essential to navigate the ethical complexities of privacy in FT. Aligning key stakeholders to support FT recipients' well-being while maintaining scientific integrity reflects the ethical tension between duties to patients and obligations to advance transplant science.

BACKGROUND:Clinical practice guidelines (CPGs) were developed to standardize and optimize cancer care delivery in low- and middle-income countries (LMICs). The aim of this scoping review is to identify implementation science (IS) frameworks and strategies to promote CPG adoption and adherence in LMICs. METHODS:We identified studies that describe, develop, reference, or utilize IS frameworks or strategies to deliver or evaluate adoption of oncology CPGs in LMICs. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), we searched Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), African Journals Online, Latin American and Caribbean Health Sciences Literature, Scopus, Web of Science, and PsycINFO on 3/21/2022, 12/20/2022, 01/26/2024, and 10/03/2025. Publications in all languages and of all study types were eligible for inclusion. Titles, abstracts, and full text were screened by two reviewers with conflicts resolved by a third reviewer. Excluded studies did not use an IS framework or strategy, did not focus on cancer care, or were conducted in a high-income country. RESULTS:Searches identified 17,806 unique publications for title/abstract screening. 182 studies met criteria for full-text review; 35 were included. Twenty-four studies were country-specific, most commonly India (n = 5) and Nigeria (n = 5). The most frequent CPGs referenced were national/country-specific guidelines (n = 13) and Breast Health Global Initiative (BHGI) guidelines (n = 9). Only 16 full-text publications described original research to promote or evaluate evidence-based CPG interventions in LMICs. Established IS frameworks used in more than one study were the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework (n = 2) and Consolidated Framework for Implementation Research (CFIR) (n = 2). CONCLUSIONS:There is limited research utilizing IS frameworks and strategies to promote CPG adoption and adherence in LMICs and substantial heterogeneity in reporting. Greater utilization of IS frameworks, strengthening implementation capacity and improving consistency in reporting, are needed to improve CPG uptake in LMICs. SYSTEMATIC REVIEW REGISTRATION/BACKGROUND:Open Science Framework (https://osf.io/nb75s).

BACKGROUND:The optimal number of pulsed field ablation (PFA) applications during atrial fibrillation (AF) ablation is unclear. We hypothesized that the number of PFA applications would predict atrial tachyarrhythmia (ATA) recurrence rates. OBJECTIVE:To determine whether higher numbers of PFA applications would decrease ATA recurrence rates. METHODS:We studied cases of patients with AF undergoing first-time ablation with PFA between 5/6/24 and 10/7/24. All patients underwent pulmonary vein and posterior wall isolation. The primary outcome was ATA recurrence. Additional outcomes included stroke, post-procedural acute kidney injury (AKI), total procedure time, and major periprocedural complications. Univariable and multivariable analyses were performed to determine if the number of PFA applications predicted ATA recurrence. RESULTS:In a cohort consisting of 177 patients, univariable and multivariable analysis showed that the number of PFA applications split at the smallest quartile (< 57 applications) versus the largest three quartiles (≥ 57 applications) was the strongest predictor of ATA recurrence (p = 0.03). ATA recurrence at 1 year (29% vs. 8%; p < 0.01) and AF burden on continuous monitor (4% vs. 0%; p < 0.01) was higher with the standard (< 57 applications) vs higher (≥ 57 applications) PFA dose groups. When comparing the standard versus higher PFA dose groups, there was no difference in total procedure time (106 vs. 107 min; p = 0.77), major periprocedural complications (0% vs. 2%; p = 0.33), or post-procedural AKI (2% vs. 2%; p = 0.69). CONCLUSION/CONCLUSIONS:Increasing number of PFA applications is associated with reduced ATA recurrence. A higher number of PFA applications may decrease ATA recurrence without affecting procedure times or complication rate.

Squamous cell carcinomas (SCCs) are common epithelial malignancies frequently associated with EZH2 upregulation, which correlates with aggressive growth and poor prognosis. EZH2 functions as the catalytic subunit of Polycomb repressive complex 2 (PRC2), which deposits the repressive H3K27me3 histone mark, yet PRC2 function in SCC pathogenesis remains unresolved. Here, we uncover a paradox: although EZH2 is elevated, the PRC2-catalyzed H3K27me3 is profoundly reduced in human SCC and complementary murine models. Mechanistically, we identify that oncogenic Ras signaling causes degradation of the PRC2 subunit EED, destabilizing PRC2 and depleting H3K27me3. Loss of EED reprograms keratinocytes into an aggressive tumor-specific cell state and induces paracrine factors that remodel the tumor microenvironment, driving metastasis. Remarkably, reintroducing EED suppresses tumor growth via restoring PRC2 integrity and H3K27me3 levels, revealing the reversibility of this epigenetic collapse. These findings link oncogenic signaling to epigenetic reprogramming and uncover PRC2 reconstitution as a potential therapeutic option in epithelial cancers.

BACKGROUND:Benefits from clinical guidelines often only exceed harms after 10 years (payoff time). Based on population norms, guidelines are often discontinued at 75 years of age, but survival likely differs for those with complex chronic disease. We compare estimates based on age alone versus the physiologically based Veterans Ageing Cohort Study-Charlson Comorbidity Index (VACS-CCI) among all patients in care, and among patients with diabetes or HIV. METHODS:Estimates for patients in care within the US Veterans Health Administration (VHA) with a clinic visit in 2007-17 (followed thru 2021) were compared using C-statistics, Brier Scores, and calibration curves. "Physiological age" was defined as the chronological age at which median VACS-CCI matched US population survival estimates. Among those with 10-year follow-up, we compared percent correctly classified using age ≥75 years vs. VACS-CCI score of ≥42. FINDINGS/RESULTS:Among 6.6 million (51.4% ≥ 65 years; 25.2% with diabetes; 0.5% with HIV) VACS-CCI improved discrimination over age (Overall C-statistic: 0.81 vs. 0.74; Brier Score 0.239 vs. 0.262). Among 65-year-old males-females, "physiological age" exceeded chronological age by 4.6-3.1 years overall; 8.6-7.8 years for diabetes; and 13.5-11.6 years for HIV. Compared to age ≥75 years, VACS-CCI improved correct classification of survival for 1 in 13.3 overall; 1 in 7.8 with diabetes; and 1 in 6.4 with HIV. INTERPRETATION/CONCLUSIONS:Compared to chronological age alone, VACS-CCI offers an improved method to identify those likely to reach minimum payoff time, especially for those with complex chronic diseases. Use of clinical data to assess "physiological age" could improve healthcare value. FUNDING/BACKGROUND:This work was supported by National Institutes of Health NIAAA: P01 AA029545, U24 AA020794 and the Emory Center for AIDS Research (P30AI050409).

IMPORTANCE/UNASSIGNED:Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) lacks proven relapse-preventive therapies. While clinical trials are ongoing, safety data may be limited and approved drugs are costly. Studies of interleukin 6 receptor blocker (IL-6RB) in MOGAD are limited by small numbers and no comparative studies, contributing to low use. OBJECTIVE/UNASSIGNED:To evaluate the impact of IL-6RB therapy on relapse rates in MOGAD and compare relapse frequency with intravenous immunoglobulin (IVIG). DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This international, multicenter, retrospective cohort study (January 1, 2015, through December 31, 2025) included a historical IVIG-treated cohort of varying doses. The study took place across sites in North and South America (US, Canada, Mexico, Argentina, Brazil, Chile, Colombia, and Peru). Patients with MOGAD (n = 116, no excluded patients) who received at least 1 dose of an IL-6RB were included. These data were analyzed in January 2026. EXPOSURES/UNASSIGNED:Tocilizumab or satralizumab. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Annualized relapse rate (ARR) during IL-6RB therapy, time to next relapse after treatment initiation, and adverse events. Outcomes were compared with the IVIG cohort using inverse probability of treatment weighting (IPTW) adjusted for age, sex, prior ARR, and concomitant therapies. RESULTS/UNASSIGNED:A total of 116 patients with MOGAD (89% relapsing) receiving IL-6RB (tocilizumab, 104 [90%] and satralizumab, 12 [10%]) were included; overall, 60.3% were female, 39.7% were male, and 18% were younger than 18 years. The median (IQR) IL-6RB treatment follow-up was 1.4 (0.7-2.5) years and 23 relapses occurred during 241.8 person-years of IL-6RB therapy. The ARR decreased from 0.64 (95% CI, 0.58-0.70) for relapsing MOGAD before IL-6RB to 0.09 (95% CI, 0.06-0.14) during IL-6RB treatment (incidence rate ratio, 0.08; 95% CI, 0.04-0.16). Adverse events occurred in 58 patients (50%), most commonly mild infections, although 10 (9%) had severe infections. In the IVIG cohort (n = 59), 30 relapses occurred over 133.8 person-years (ARR, 0.22; 95% CI, 0.15-0.32). After IPTW, IL-6RB was associated with a lower hazard ratio (HR) than the group who underwent IVIG therapy less than 1 g/kg every 4 weeks (HR, 4.5; 95% CI, 2.0-9.8), with no significant difference vs the group who underwent IVIG 1 g/kg or more every 4 weeks (HR, 2.0; 95% CI, 0.8-4.5). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this multicenter observational cohort, IL-6RB use in MOGAD was associated with low relapse rates and a favorable safety profile, though severe infections occurred occasionally. Relapse rates were lower than the group who underwent IVIG less than 1 g/kg every 4 weeks but not significantly different from the group who underwent IVIG 1 g/kg or more every 4 weeks. This supports IL-6RB as a potential relapse-prevention therapy in MOGAD; the wide availability and relative affordability of tocilizumab may enable broad global use.