Faculty Bibliography

OBJECTIVES/OBJECTIVE:The gut microbiome plays a crucial role in regulating systemic immunity and has been implicated in several chronic inflammatory diseases. Intestinal expansions of Ruminococcus gnavus (RG), a dominant gut commensal, correlate with disease flares in lupus nephritis (LN), but the underlying mechanism remains unknown. METHODS:In a Pilot cohort of patients with biopsy-proven LN, subsetted by gut microbiota community, immune status was characterised using bulk-blood RNA sequencing libraries, serum levels of representative host proteins, and levels of immunoglobulin (Ig)G antibodies to the novel lipoglycan (LG) produced by pathogenic RG strains. A Validation LN cohort was evaluated for blood transcriptomic profiles and levels of anti-LG antibodies. In murine models, mechanistic hypotheses were tested after RG gut colonisation or after intraperitoneal injection with an LG preparation, with outcomes determined by transcriptomic analyses, platelet functional readouts, and tissue histology. RESULTS:In a Pilot cohort of patients with LN, RG gut expansions were associated with high-level platelet, neutrophil, and monocyte activation. Serum levels of platelet factor 4 and release of neutrophil extracellular traps (NETs) were significantly higher in patients with high serum IgG antibody against the novel RG-specific LG, a marker of in vivo immune exposure. An LN Validation cohort confirmed these correlates and showed that anti-LG antibodies serve as a surrogate for thromboinflammatory profile in this LN-associated endotype. In mice, gut colonisation with LG-producing RG strains or a single LG injection caused megakaryocytosis and platelet activation; RG colonisation with LG-producing strains induced tubulointerstitial injury with NETosis. In vivo responses to LG toxin were Toll-like receptor 2-dependent. CONCLUSIONS:Gut expansions of the RG pathobiont may contribute to autoimmune pathogenesis through the LG toxin and cause LN flares through thromboinflammatory mechanisms in this previously unrecognised LN endotype.

We present MelOD (Melanoma Omics Dashboard), a free, web-based interactive platform integrating preprocessed data from 16 melanoma studies, including eight bulk transcriptomics, six single-cell RNA-seq, and two proteomics datasets. MelOD provides user-friendly visualization and analysis tools, differential expression, dimensionality reduction, clustering, correlation, and survival analysis without requiring local computational resources. Several datasets include annotations for immunotherapy response, facilitating exploration of resistance and response signatures. Built on RShiny with optimized handling of large datasets, MelOD supports real-time hypothesis generation, cross-study validation, and community dataset contributions. Freely accessible online, MelOD lowers barriers to multi-omics research in melanoma and related fields.

Poly(A) tails are present on most cellular and viral mRNAs, providing a platform for poly(A)-binding proteins that stimulate translation and regulate the deadenylation and stability of transcripts in the cytoplasm. Here we leverage nanopore direct RNA sequencing to analyse the distribution of poly(A) tail lengths on cellular and viral mRNAs across Herpesviridae and other DNA and RNA virus infections. We find that herpesvirus mRNA poly(A) tails are consistently longer than those on cellular and other viral transcripts, presenting a previously unrecognized yet widespread mechanism to potentially advantage herpesviral gene expression. This contrasts with the templated poly(A) tails on coronavirus RNAs and those on cytoplasmically transcribed poxviral mRNAs, which are more similar in length to those on host mRNAs. Herpesviral noncoding RNAs display differential poly(A) tailing patterns while individual herpesviral mRNAs also show variation in the extent to which their poly(A) tail lengths change during the virus lifecycle, suggestive of additional uncharacterised layers of poly(A) tail length regulation. Importantly, while we detect non-adenosine nucleotides within herpesviral poly(A) tails, which are known to oppose deadenylase activity, this "mixed tailing" is not at sufficient frequency to explain the widespread extended tails of herpesvirus mRNAs.

Sickle cell disease (SCD) has been documented for more than 115 years, yet its scientific and clinical history extends far deeper, beginning with African physicians such as Dr. James Africanus Horton, who described symptoms consistent with SCD decades before its formal recognition in Western medicine. The first modern clinical report, published by Dr. James B. Herrick in 1910, initiated a century of discovery that transformed SCD into the first fully elucidated "molecular disease." Advances in diagnostics, especially newborn screening, comprehensive care, and treatments, including penicillin, prophylaxis hydroxyurea, stem cell transplant and gene therapies, have transformed hematology and improved survival and quality of life. However, access to these advances remains uneven, reflecting persistent inequities that disproportionately impact SCD communities domestically and globally. Against this backdrop, the SCD 115 Years Later Symposium, held November 12, 2025, explored three interconnected pillars shaping the future of SCD care: research, collaboration, and policy. Four sessions illuminated structural and clinical challenges across the lifespan, emphasizing poor access to care, the need for more holistic care models, the importance of engaging community-based organizations, optimizing and expanding SCD surveillance systems, and stronger policy alignment at state and federal levels. Central themes included unified advocacy, improved care transitions, expansion of multidisciplinary care models, improved access to emerging therapies, and the integration of mental health and psychosocial support into clinical practice. Collectively, the symposium-derived priorities connected scientific progress, policy innovation, and community leadership to improve outcomes for all individuals living with SCD and their families.

The American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee provides reviews of existing, new, or emerging endoscopic technologies that have an impact on the practice of GI endoscopy. Evidence-based methodology is used, with a MEDLINE literature search to identify pertinent clinical studies on the topic and a MAUDE (U.S. Food and Drug Administration Center for Devices and Radiological Health) database search to identify the reported adverse events of a given technology. Both are supplemented by accessing the "related articles" feature of PubMed and by scrutinizing pertinent references cited by the identified studies. Controlled clinical trials are emphasized, but in many cases, data from randomized, controlled trials are lacking. In such cases, large case series, preliminary clinical studies, and expert opinions are used. Technical data are gathered from traditional and Web-based publications, proprietary publications, and informal communications with pertinent vendors. Technology Status Evaluation Reports are drafted by 1 or 2 members of the ASGE Technology Committee, reviewed and edited by the committee as a whole, and approved by the Governing Board of the ASGE. When financial guidance is indicated, the most recent coding data and list prices at the time of publication are provided. For this review, the MEDLINE database was searched through August 2024 for articles related to endoscopic submucosal dissection. Technology Status Evaluation Reports are scientific reviews provided solely for educational and informational purposes. Technology Status Evaluation Reports are not rules and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment or payment for such treatment.

BACKGROUND:Transcatheter aortic valve replacement (TAVR) has become a cornerstone in the management of aortic valve disease. However, delayed complications after hospital discharge and readmission remain in an issue following TAVR. We aimed to evaluate the impact of remote monitoring systems on clinical outcomes after TAVR. METHODS:All patients who underwent TAVR from September 2014 through January 2019 were included retrospectively. Additionally, all patients, clinically indicated for TAVR from 9/1/2018 through 8/30/2021, were screened, and patients who agreed were prospectively enrolled. Medtronic Care Management Service (MCMS) was used to monitor patients following TAVR after discharge (Medtronic, Minneapolis, MN). RESULTS:A total of 1078 patients were included. Among them, 843 (78.2 %) patients were discharged with MCMS (MCMS group) and 235 (21.8 %) patients were discharged without (non-MCMS group). Overall, the mean age was 81.5 years, and mean STS-PROM was 5.53 %. Baseline conduction defect was observed in 427 (39.6 %). Peripheral artery disease was more common in the MCMS group while a history of myocardial infarction was more likely seen in the non-MCMS group. After propensity-score matching, length of hospital stays was significantly shorter in the MCMS group (1.42 days vs. 1.82 days in the non-MCMS group, p < 0.001). Readmission rates and new permanent pacemaker insertion rates were similar between the two groups. All-cause mortality, 30-day and 90-day mortality were comparable between the groups. CONCLUSIONS:MCMS was easily applicable to a clinical practice and may reduce length of hospital stays in patients undergoing TAVR without increasing readmission or mortality.

The academic promotion process is best navigated from a mindset that emphasizes individual control in reaching the many landmarks along the way. Drawing on the established psychological theories of locus of control and self-efficacy, the authors propose parallels in concepts that faculty members seeking academic promotion should consider. By marking these points on their individual paths, faculty members can control their efforts to achieve academic promotion.

INTRODUCTION/BACKGROUND:Immune checkpoint inhibitors (ICI) have transformed the treatment landscape for triple-negative breast cancer (TNBC), but their efficacy in older adults remains unclear. The objective of this systematic review is to evaluate the efficacy of ICI in patients with TNBC aged ≥65 years. MATERIALS AND METHODS/METHODS:We conducted a systematic review of randomized controlled trials (RCTs) between January 2013 and September 2023 using searches of Medline, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform. RESULTS:Eighteen full-text articles representing 11 unique RCTs were identified. Only four RCTs reported efficacy outcomes for patients ≥65 years: KEYNOTE 355, KEYNOTE 522, IMpassion130, and IMpassion131. Across these trials, 602 of 3215 patients (18.7%) were 65 and older. The overall risk of bias was low to intermediate, but heterogeneity in trial design and endpoints precluded meta-analysis. Pembrolizumab, the only FDA-approved ICI in TNBC, showed a nonsignificant trend toward improved pathological complete response and event-free survival among older adults with early-stage TNBC (KEYNOTE-522). In the metastatic setting, pembrolizumab may improve overall survival in older patients with PD-L1 combined positive score ≥ 10 (KEYNOTE-355). All studies enrolled few older patients, and none prespecified age-stratified analyses. DISCUSSION/CONCLUSIONS:These findings highlight a major evidence gap and underscore the need for further research evaluating ICI outcomes in older adults with TNBC.

INTRODUCTION/UNASSIGNED:Medicaid spent over 129 billion dollars on home- and community-based services (HCBS) in 2022. However, complex financing structures obscure which services are used, who uses them, and how use varies across states. METHODS/UNASSIGNED:Using 100% of national Medicaid claims data from 2021, we characterize HCBS use among dual-eligible adults aged 65 and older, distinguishing between direct care services (services that provide hands-on assistance with functional needs) and non-direct care services (eg, transportation and case management), which are often grouped together in the literature. RESULTS/UNASSIGNED:We find that 38% of older duals used any Medicaid-funded HCBS in 2021, and 26% used direct care, with direct care users being older, sicker, and more likely to have dementia than non-users. We also find that the share of older duals using direct care varies more than 4-fold between the lowest and highest utilization states, with states that finance personal care as a State Plan benefit, rather than exclusively through waiver programs, generally having greater utilization. CONCLUSION/UNASSIGNED:In light of potential funding cuts, our findings highlight the large but uneven role that Medicaid plays in financing direct care for a vulnerable population of older adults, which can be critical for them to remain in their homes and communities.