Faculty Bibliography

Improving long-term protective immunity elicited by prime-boost vaccinations requires a deeper understanding of the immunologic outcomes of different vaccine platforms. Given the variety of platforms used to develop vaccines against SARS-CoV-2, we reasoned that SARS-CoV-2 offered an opportunity to compare vaccine platforms in humans. We used flow cytometry and single-cell transcriptomics to explore the B cell response to different homologous and heterologous vaccine regimens. We found that an adenovirus vector prime followed by a messenger RNA (mRNA) vaccine boost showed the greatest short-term B cell expansion and preferentially elicited an activated atypical B cell subset that was associated with antibody binding titers against spike protein. In contrast, an mRNA primary series followed by homologous boost induced a different activated B cell subset with more proliferative potential and high frequencies of a long-lived resting memory subset. Moreover, immunoglobulin A (IgA)-expressing memory B cells had more somatic hypermutations than the predominant IgG-expressing B cell population. This heterogeneity in vaccine-elicited B cell responses underscores the potential of tailoring vaccine regimens that combine different platforms to achieve potent and durable protection against infectious diseases.

CONTEXT/BACKGROUND:More health systems are establishing outpatient palliative care (PC) programs, increasing demand for ambulatory PC clinicians. However, existing outpatient training during hospice and palliative medicine (HPM) fellowship remains limited and suboptimal. Little is known about the outpatient-specific knowledge and skills PC trainees should acquire for competent outpatient practice. OBJECTIVES/OBJECTIVE:To identify and prioritize outpatient-focused educational topics for HPM fellows and clinicians new to ambulatory practice. METHODS:A cross-sectional survey of United States (U.S.) outpatient PC clinicians (physicians, advanced practice practitioners [APPs]). Using a list of 51 educational topics, respondents selected a maximum of 20 topics they would prioritize as essential to prepare learners for outpatient practice. RESULTS:Of 247 clinicians, 136 (55%) responded, including 115 physicians and 21 APPs from all U.S. regions. Seven of 51 topics were prioritized by more than two-thirds of respondents (n = 92-119, 68%-86%). Four focused on outpatient application of core PC skills (pain management [n = 113, 83%], nonpain symptom management [n = 117, 86%], depression/anxiety [n = 107, 79%], goals of care [n = 92, 68%]). The remaining three covered discrete topics related to pain and opioid management, including best practices for caring for patients with comorbid pain and substance use disorder (n = 104, 76%). CONCLUSION/CONCLUSIONS:This national survey identified foundational outpatient-focused educational topics for HPM learners and suggests that outpatient curricula prioritize deliberate education on the unique application of core PC skills in outpatient settings. This prioritized list provides education leaders a roadmap to enhance existing curricula and informs the development of outpatient educational resources that can be shared across institutions.

VEXAS syndrome is a severe adult-onset autoinflammatory disease caused by somatic mutations in the UBA1 gene, disrupting cytoplasmic ubiquitin-activating enzyme E1 function in hematopoietic progenitors. Its pathogenesis remains poorly understood, particularly the mechanisms by which UBA1 mutations disrupt myeloid cell function in the context of inflammatory stimuli. Here, we combine a genetically engineered THP-1 monocytic model with ex vivo analyses of blood and tissue samples from VEXAS patients to investigate the consequences of the canonical UBA1M41V mutation. We show that UBA1-mutated monocytes exhibit TNF-α-induced cell death, characterized by RIPK1 phosphorylation, and MLKL- and caspase-8-mediated cell death. Importantly, we extend these findings to patient-derived CD14⁺ sorted cells, confirming that these cells undergo aberrant apoptotic and necroptotic cell death. Mechanistically, activation of these cell death pathways appears to be promoted by defective NF-κB-dependent transcriptional responses and reduced cFLIP(L) expression following TNF-α stimulation. UBA1-mutated monocytes also display blunted cytokine responses to Toll-like receptor (TLR) agonists despite preserved TLR expression, linked to an impaired NF-κB response. UBA1M41V-derived macrophages exhibit a pro-inflammatory transcriptional profile with increased chemokine secretion that promotes monocyte recruitment. In addition, these UBA1-mutated macrophages display impaired efferocytosis due to lysosomal dysfunction. Together, these findings reveal a pathogenic axis in VEXAS syndrome linking UBA1 loss of function and defective ubiquitination to RIPK1-mediated inflammatory cell death, impaired antimicrobial signaling, and defective resolution mechanisms. Our study provides novel mechanistic insights into the myeloid dysfunction underlying inflammation and cytopenia in VEXAS and supports the therapeutic targeting of inflammatory cell death pathways.

IMPORTANCE/UNASSIGNED:Asian language speakers with limited English proficiency (LEP) face significant barriers to accessing adequate mental health care. Despite worsening mental health outcomes for this population, there is limited research examining the availability of Asian language mental health treatment in the US. OBJECTIVE/UNASSIGNED:To quantify trends and analyze disparities in the geographic availability of Asian language mental health treatment from 2015 to 2024. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cross-sectional study of US mental health facilities from April 30, 2015, to December 9, 2024, used longitudinal data from the nationally representative Mental Health and Addiction Treatment Tracking Repository linked with county-level demographic data from the 2023 American Community Survey. Facilities were included if they completed the National Mental Health Services Survey or the National Substance Use and Mental Health Services Survey. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Primary outcomes included the annual proportion of mental health facilities offering Asian language services and the proportion of counties with at least 1 such facility. For 2024, facility-level characteristics associated with Asian language services were assessed and geographic mismatches between service availability and the proportion of Asian language-speaking individuals with LEP were mapped. RESULTS/UNASSIGNED:The study included 3847 mental health facilities. Of these, 214 facilities (5.6%) offered services in at least 1 Asian language in 2024 (including Arabic, Chinese, Farsi, Hindi, Hmong, Japanese, Korean, Tagolog, and Vietnamese). The proportion peaked at 265 facilities (6.9%) in 2021, then declined from 2022 to 2024. The number of counties with at least 1 facility with Asian language services was 98 (6.3%) in 2024. Facilities offering Asian language services were concentrated in metropolitan areas (208 [97.2%]), particularly in California (57 [26.6%]) and the Northeast (52 [24.3%]). Rural areas lacked such services (3 of 485 rural facilities [0.6%] in 2024), even in counties with substantial populations of Asian language-speaking individuals with LEP (0 of 5 facilities). CONCLUSIONS AND RELEVANCE/UNASSIGNED:This cross-sectional study found a persistent geographic mismatch between the mental health needs of Asian language-speaking individuals with LEP and the availability of appropriate linguistic services. The gap was pronounced in rural areas. The findings suggest that policies aimed at expanding the behavioral health workforce and increasing access to culturally and linguistically competent services to reduce ongoing disparities in mental health outcomes and access to care are urgently needed.

IMPORTANCE/UNASSIGNED:Overdose prevention centers (OPCs) are interventions to reduce overdose mortality and support health care engagement. In the US, concerns have been raised that OPCs may be associated with reduced economic activity in their surrounding neighborhoods. OBJECTIVE/UNASSIGNED:To evaluate changes in the local economic activity in New York City (NYC), measured by neighborhood-level foot traffic and consumer spending, following the opening of the first 2 publicly recognized OPCs in the US. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study used anonymized mobility and spending data from June 1, 2021, to June 13, 2022, for the areas surrounding the East Harlem and Washington Heights OPCs in NYC. These neighborhoods were defined using 5-minute and 10-minute walking buffers and Business Improvement Districts (BIDs). Synthetic control donors included walking buffers and BIDs around syringe service programs without OPCs and opioid treatment programs that were operational as of OPCs' opening. Analyses were conducted from February to July 2025. EXPOSURES/UNASSIGNED:Opening of the 2 NYC OPCs on November 30, 2021. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Primary outcomes were foot traffic and in-person consumer spending within 10-minute walking buffers. Secondary analyses considered 5-minute walking buffers and BIDs. Augmented synthetic control models were adjusted for neighborhood-level demographic and socioeconomic features, with fit assessed using root mean squared error before OPC opening. Permutation tests and conformal inference were used to assess significance. RESULTS/UNASSIGNED:A total of 27 biweekly observations (13 in pre-OPC and 14 in post-OPC periods) were analyzed. The 10-minute walking buffer analyses captured 1259 consumer spending sites and 7816 foot traffic sites across 2 treated buffers and 56 donor buffers. In East Harlem, the average treatment effect on the treated (ATT) estimate (SE) was -$21.96 ($40.53) for consumer spending (P = .16) and 1.28 (5.40) visits for foot traffic (P = .19). In Washington Heights, ATT (SE) estimates were $14.94 ($37.38) for consumer spending (P = .13) and 0.44 (3.54) visits for foot traffic (P = .97). Secondary analyses produced consistent results. No statistically significant results were observed at any post-OPC time point. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This cohort study found that OPC opening was not associated with significant changes in local economic activity. Given the absence of observed economic harms, policy debates should instead focus on the public health implications of OPCs.

BACKGROUND/UNASSIGNED:Lateral ankle sprains are the most common lower extremity injury in athletes, most often involving the anterior talofibular ligament (ATFL). Although ATFL repair outcomes are well studied, optimal management for patients with generalized ligamentous laxity (GLL) remains less understood. PURPOSE/UNASSIGNED:To (1) evaluate the radiographic findings, clinical measures, and complications in patients with GLL undergoing modified Broström-Gould repair and to (2) assess the role of suture augmentation in optimizing outcomes. STUDY DESIGN/UNASSIGNED:Systematic review; Level of evidence, 4. METHODS/UNASSIGNED:During July 2025, the PubMed, EMBASE, and Cochrane library databases were systematically searched to identify studies examining outcomes and complications in GLL patients who underwent modified Broström-Gould repair. RESULTS/UNASSIGNED:= .03). When suture augmentation was performed, no significant difference in complication rates existed between cohorts. CONCLUSION/UNASSIGNED:Patients with GLL experienced significantly higher rates of complication and failure following modified Broström-Gould repair compared with patients without ligamentous laxity. Suture augmentation may lower complication rates in GLL patients, but its effect on failure rates remains undetermined, as no studies directly compared augmented and nonaugmented GLL patients. Importantly, both GLL patients and patients without ligamentous laxity experienced clinical improvements from the modified Broström-Gould repair. While GLL increases the risk of mechanical complications, it should not be considered a contraindication to undergoing the modified Broström-Gould procedure. However, suture augmentation may be beneficial for GLL patients to reduce the risk of complications after undergoing ATFL repair. REGISTRATION/UNASSIGNED:CRD420251182303 (PROSPERO identifier).

INTRODUCTION/BACKGROUND:Postoperative urinary retention (POUR) is a common complication following inguinal hernia repair (IHR), and it can be influenced by the type of neuromuscular blockade reversal medication used, especially acetylcholinesterase inhibitors. Among the available options for neuromuscular blockade reversal, Sugammadex has gained significant popularity due to its effectiveness, speed, and safety profile. Additionally, some studies suggest that it prevents POUR compared to acetylcholinesterase inhibitors. We aimed to perform a systematic review and meta-analysis to assess the POUR rates with the use of Sugammadex after IHR. METHODS:PubMed, EMBASE, Cochrane, LILACS, and Web of Science databases were systematically searched without date or language restrictions from inception to October 2024. The databases were searched for studies comparing Sugammadex with other medications for neuromuscular blockade reversal after IHR. The primary outcome was POUR. RESULTS:< .001), with a relative risk reduction of 89%. CONCLUSION/CONCLUSIONS:Sugammadex is associated with a significantly lower risk of POUR following IHR when compared to other medications for neuromuscular blockade reversal following IHR. Despite its higher cost and decreased availability in some centers, the use of Sugammadex should be strongly considered as the preferred option to prevent POUR and minimize the need for hospital readmissions.

PURPOSE/OBJECTIVE:To describe the first successful whole eye transplantation (WET) in a human, performed with concurrent partial face transplantation, and to characterize postoperative outcomes. DESIGN/METHODS:Case report. PARTICIPANT/METHODS:A 46-year-old male with severe facial and ocular deficits following high-voltage electrical injury, including left eye enucleation and extensive soft tissue and aesthetic deformities. METHODS:Comprehensive preoperative evaluation, precise microsurgical techniques including vascular anastomosis and optic nerve coaptation, and serial postoperative assessments with optical coherence tomography (OCT), fluorescein angiography (FA), electroretinography (ERG), and visual evoked potentials (VEP). MAIN OUTCOME MEASURES/METHODS:Sustained globe viability, vascular perfusion, retinal structural integrity, and electrophysiological function. RESULTS:The transplanted globe demonstrated robust vascular perfusion and structural preservation over 12 months. Outer retinal function was maintained, as indicated by ERG, despite retinal nerve fiber layer loss and optic nerve transection. VEP confirmed absence of visual perception. The procedure achieved substantial aesthetic restoration. CONCLUSIONS:This study establishes the feasibility of WET in humans, with sustained globe viability and preserved outer retinal function. These findings serve as a critical step toward future exploration of ocular transplantation.