Citations

ABSTRACT Recent advances in the diagnosis and management of reflux disease were the central focus of the inaugural Gatherings in Esophagology (GiE), which convened experts across gastroenterology, surgery, otolaryngology, pulmonology, and basic research. The sessions highlighted innovations in reflux monitoring—including high‐resolution manometry, wireless pH monitoring, and novel salivary biomarkers—while critically evaluating their diagnostic accuracy and clinical utility. Presentations explored the limitations of traditional proton‐pump inhibitor therapy, the emergence of potassium‐competitive acid blockers as a new class of acid suppressants, and the evolving role of adjunctive treatments such as mucosal protectants, reflux reducers, and neuromodulators for refractory symptoms. The discourse extended to advanced interventional procedures, including transoral incisionless fundoplication, magnetic sphincter augmentation, and the RefluxStop device, with discussion of patient selection, efficacy, and complication management. Discussants emphasized the pathophysiology and management of extraesophageal manifestations of reflux, the interplay between reflux and pulmonary disease, and the diagnostic challenges in pediatric populations. The meeting also addressed the integration of behavioral therapies, the role of the microbiome, and the application of artificial intelligence in reflux diagnostics. Collectively, these insights underscore a shift toward precision medicine in reflux disease, emphasizing individualized diagnostic strategies and tailored therapeutic approaches to improve patient outcomes.

Background: Long COVID, the chronic sequela of SARS-CoV-2 infection, has affected millions of people worldwide. However, its pathogenesis and treatment remain unknown. To address this critical gap, the National Institutes of Health (NIH) developed the Researching COVID to Enhance Recovery (RECOVER) Initiative that included the Viral Persistence and Reactivation, and Immune Dysregulation (RECOVER-VITAL) study as one of the first of five NIH-sponsored, integrated platform protocols to support the rigorous and rapid investigation of potential interventions for Long COVID. Methods: Experts across academia, the NIH, and the community of patients and caregivers were brought together to design the RECOVER-VITAL protocol. We present the challenges and rationale underpinning critical components of this protocol and provide evidence for use of the platform for efficient execution of current and future Long COVID clinical trials. Facets of the RECOVER-VITAL protocol, including inclusion criteria, intervention groups, study procedures, investigation of biomarkers, and endpoints, were carefully crafted to advance the current and future science and operations of Long COVID clinical trials, particularly in the absence of existing data. The initial trial within the RECOVER-VITAL platform evaluated two durations of an antiviral drug, nirmatrelvir/ritonavir, to test the proposed etiology of viral persistence on the Long COVID symptom clusters of autonomic dysfunction, cognitive dysfunction, and exercise intolerance. The primary outcome measures were patient-reported, and secondary outcomes included performance-based measures for each of the symptom clusters of interest. Conclusions: The RECOVER-VITAL platform protocol has substantial implications for the design and conduct of future Long COVID clinical trials.

Abstract Introduction: Accurate detection and prioritization of tumor-specific somatic variants is foundational to the development of personalized immunotherapies. Traditional pipelines for neoepitope identification rely heavily on short-read next-generation sequencing (NGS) and DNA-based variant calling, followed by RNA expression filtering and HLA-binding prediction. However, this approach is limited by time-intensive workflows, potential false positives from DNA-only calls, and poor capture of complex isoforms or RNA-level editing. Moreover, the accuracy of neoepitope prediction is constrained by conventional sequence-based HLA binding algorithms that do not account for structural and biophysical features of peptide-MHC interactions, particularly across underrepresented HLA alleles. Methods: To overcome these limitations, we developed a streamlined, sequencing-to-vaccine framework that leverages long-read RNA sequencing for direct detection of expressed somatic variants, including fusions, indels, and single nucleotide variants. Using Oxford Nanopore Technologies’ cDNA-PCR approach, we enable comprehensive, full-length transcript characterization from both fresh and frozen breast tumor samples. Our bioinformatic pipeline, NeoTarget, integrates alignment, variant calling, and neoepitope inference from tumor RNA in a single, modular workflow. A core innovation of this pipeline is HLA-Inception, a deep convolutional neural network trained to predict peptide-MHC class I binding using features derived from molecular dynamics-based modeling of electrostatic potential at the peptide-HLA interface, enhancing generalizability across diverse HLA subtypes. Results: Expanding on previous results, the current NeoTarget pipeline identifies, evaluates, and prioritizes single nucleotide variants, indels, and fusions. To validate this system, we used a set of 9 human breast cancer tumors benchmarked with short read sequencing. Identified neoantigens included most variants shown by clinical short read sequencing and also novel structural variants (i.e., fusions) only revealed with long read sequencing with high confidence. Conclusion: Here, we describe the design and performance of the NeoTarget pipeline, and show proof-of-concept feasibility of applying this fast and cost-effective workflow for HLA-restricted epitope discovery in breast tumors using long-read RNA sequencing. Overall, these methods can be applied to rapidly identify and prioritize neoantigens for personalized neoantigen-based immune therapies. Citation Format: F. Batalini, S. Henry, Y. Zhang, R. Foster, J. M. Gayton, A. Hostal, E. A. Wilson, A. Singharoy, M. Gustafson, B. Pockaj, J. Park, K. S. Anderson. Somatic variant detection using long read RNA sequencing reveals HLA-restricted targets for immunotherapy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-06-08.

Abstract Background: Breast cancer (BC) chemoprevention with selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) remains underutilized among high-risk women. Improving knowledge about BC risk and chemoprevention among high-risk patients and their healthcare providers may enhance informed decision-making about this BC risk reduction strategy. Methods: We conducted a cluster randomized controlled trial to evaluate the effectiveness of web-based patient and provider decision support, RealRisks and BNAV, to improve chemoprevention informed choice among women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS). Thirty-one sites, including academic and community practices across the U.S., were randomized to standard patient educational materials alone or combined with RealRisks and BNAV. A total of 412 patients and 210 healthcare providers were enrolled. Patient surveys were administered at baseline, 6 and 12 months. The primary outcome at 6 months was chemoprevention informed choice, defined as adequate chemoprevention knowledge and attitudes congruent with decision. Secondary endpoints included BC risk perceptions, worry, chemoprevention knowledge, decision conflict and chemoprevention decision. Assuming 10% loss to follow up (LTFU), roughly equal accrual across sites, and an intraclass coefficient (ICC) of 0.02, we had 90% power to detect a 15% absolute difference in informed choice if the event rate in the control arm was 10%. Results: Among 24 evaluable sites, 14 were randomized to the intervention arm and 10 to the control arm. Among 210 enrolled providers, median age was 46 (range, 28-83) and 78% were female; 75% physicians and 25% advanced practice providers/nurses; 53% medical oncologists, 29% surgeons, and 10% gynecologists/family practitioners/internists; and 83% had previously prescribed chemoprevention. Among 412 enrolled patients, median age was 53 (range, 35-74), including 77% White, 8% Black, and 10% Asian race, and 14% Hispanic ethnicity. In terms of BC risk factors, 77% had AH and 23% LCIS, 34% had a first-degree family history of BC, and 65% had heterogeneously or extremely dense breasts on mammography. Thirty percent were unevaluable for the primary endpoint (1% ineligible, 26% LTFU, 3% missing data). Among 288 evaluable patients (148 at intervention sites, 140 at control sites), the proportion of patients exercising informed choice at 6 months in the intervention and control arms was 35% vs. 27%, respectively (odds ratio [OR]=1.44, 95% confidence interval [CI]=0.84-2.46, p=0.19; observed ICC=0.006). Compared to patients in the control arm at 6 months, those in the intervention arm were more likely to have accurate BC risk perceptions (OR=1.80, 95% CI=1.11-2.91) and adequate chemoprevention knowledge (OR=1.62, 95% CI=1.00-2.61). We observed no significant differences in BC worry, decision conflict, or chemoprevention decision between study arms. At 6 months, 49% of women in the control arm and 51% in the intervention arm decided to take a SERM or AI for BC chemoprevention (p=0.58), a rate higher than anticipated. Conclusions: We did not observe a significant increase in informed choice among patients and providers assigned to chemoprevention decision support compared to standard educational materials alone. Among women with AH or LCIS seen mainly by breast specialists who prescribed chemoprevention, about half decided to take a SERM or AI. Therefore, relatively high chemoprevention uptake may be achieved among women with high-risk breast lesions managed by breast specialists. Chemoprevention decision support may improve decision antecedents, such as accurate BC risk perceptions and chemoprevention knowledge, but may have a limited role in changing health behaviors. Citation Format: K. D. Crew, G. L. Anderson, K. B. Arnold, A. Michel, M. T. DeLucie, C. W. Law, S. Pruthi, A. C. Sandoval Leon, R. Shirley, M. T. Grosse Perdekamp, S. V. Colonna, S. L. Krisher, T. King, L. D. Yee, T. J. Ballinger, C. Braun-Inglis, D. A. Mangino, K. B. Wisinski, C. A. DeYoung, M. Ross, J. D. Floyd, A. Kaster, L. VanderWalde, T. Saphner, C. Zarwan, S. Lo, C. Graham, A. K. Conlin, K. J. Yost, D. M. Agnese, C. Jernigan, D. L. Hershman, M. L. Neuhouser, J. A. Zell, B. Arun, R. Kukafka. Making informed choices on incorporating chemoprevention into care (MiCHOICE): Cluster randomized controlled trial of decision support for breast cancer chemoprevention, SWOG 1904 [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-01-15.

Abstract Purpose: There are limited prospective data on the efficacy, tolerability, and functional impact of treatments for older and frail adults with HER2+ early breast cancer. We report the first-ever, US-based adjuvant trial dedicated to this population. Methods: We conducted a single arm, phase II, multicenter, investigator-initiated study of adjuvant ado-trastuzumab emtansine (T-DM1) in patients aged 60 and older with stage I-III HER2+ breast cancer who either declined standard adjuvant therapy or were deemed by their physician not to be candidates for standard treatment for any reason. Protocol therapy included postoperative administration of T-DM1 (3.6 mg/kg) every 21 days for one year (17 cycles). The primary endpoint was 5-year invasive disease-free survival (iDFS) with a 2-sided 90% confidence interval. Secondary endpoints presented here are toxicity and 3-year iDFS, invasive breast cancer-free survival (iBCFS), and overall survival (OS). All survival analyses were evaluated using Kaplan Meier methods and began at the time of C1D1 of T-DM1. Results: ATOP enrolled 111 evaluable patients during 2015-2020; median follow-up is 4.9 years (IQR 4.2-5.5). The median age was 71 (range 60-88); 50.4% were aged >70 and 11.7% were aged >80. Overall, 69.4% had stage I, 26.1% had stage II, and 4.5% had stage III disease; 70.3% had hormone receptor-positive tumors. The 5-year iDFS = 84.2% (90% CI 77.1-92.0%). The 3-year iDFS = 91.2% (90% CI 85.9%, 96.9%) and iBCFS = 94.1% (90% CI 89.7-98.8%) (see Table for event details); 3-year OS = 96.1% (90% CI 92.4-99.9%). In total, there were 3 distant recurrences and 2 breast cancer-related deaths. Overall, 82% reported grade 2+ toxicity during treatment; the most common grade 2+ events were fatigue (30.6%) and peripheral sensory neuropathy (19.8%). The most frequent grade 3 events were liver function abnormality, anemia, decreased neutrophil count, and neuropathy (<5% for each); one patient (0.9%) had grade 4 thrombocytopenia. Sixty-five (58.6%) completed all 17 cycles of protocol therapy; 27 (24.3%) completed 10-16 cycles, and 19 (17.1%) completed 1-9 cycles. Reasons for early treatment discontinuation in the remaining 41.4% included toxicity (28.8%), patient withdrawal (6.3%), other (3.6%), disease progression (0.9%), death on study (0.9%, deemed unrelated to treatment), and other complicating disease (0.9%). Conclusions: The ATOP trial demonstrated a favorable 5-year iDFS and manageable toxicity among older adults with early stage HER2+ breast cancer. Although iDFS was numerically worse than historical controls (i.e., 5-year iDFS in the ‘ATEMPT’ trial by Tolaney et al. J Clin Oncol, 2024 was 97% [95% 95.2-98.7]), ATOP’s participants had higher-risk cancers, advanced age, and more competing non-breast cancer events. Future endpoints will include in-depth analyses of patient-reported outcomes, biomarkers of aging, and longitudinal functional status. Citation Format: R. A. Freedman, H. Heiling, K. J. Ruddy, L. Rogak, M. Sedrak, A. Dueck, H. Liu, A. Fraettarelli, S. Atanasov, M. DeMeo, P. Lange, A. Perilla Glen, S. Sinclair, D. Dillon, J. Mortimer, M. Fenton, J. Walsh, L. Spring, H. Muss, N. Sinclair, E. Hamilton, C. Dang, S. Giordano, M. Faggen, S. Lo, C. Kuzma, S. Lemke, P. Stella, R. Mowat, M. Wilkinson, J. Rauch, N. Tayob, E. Winer. Adjuvant Ado-Trastuzumab Emtansine (T-DM1) for Older Patients with HER2+ Breast Cancer - Results from the ATOP Study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-11-04.

ABSTRACT Background One in five emergency department (ED) visits is by older adults aged 65+ years. Clinical practice guidelines are needed to optimize patient care by translating the best available evidence into actionable recommendations to guide person‐centered management for this medically complex and growing patient population. Our objective was to understand contributors' experiences and share best practices to inform other guideline working groups. Methods We conducted a qualitative study based on thematic analysis with an interpretivist paradigm in June–July 2025, using semi‐structured interviews of Geriatric Emergency Department (GED) Guidelines 2.0 contributors to understand their experiences. Interviews were transcribed, independently reviewed by team members, and reflexively coded to identify themes. Results We interviewed 18 participants. Four main themes emerged: (1) motivations for participation, (2) varying opportunities to be involved, (3) personal benefits, and (4) challenges for improvement. Participants contrasted the strengths of shared learning and development with the burdens of organization and coordination. Conclusion Contributors to the GED Guidelines 2.0 reported a positive experience. They joined because they wanted to contribute to better care of older patients and to achieve personal and professional goals. Many cited that their roles aligned with their strengths and expertise. They also gained skills and knowledge on systematic reviews and benefited from networking. Future groups planning a similar process should consider having multiple levels of leadership, experts in systematic reviews, regular reminders, and creative incentives to improve the process and foster improved networking opportunities within their disciplines.

Abstract The demand for high-quality faculty development in medical education is more acute than ever. Faculty developers’ responsibilities are growing exponentially as they are called upon to help medical faculty maintain expertise in an evolving array of content domains, curricular and assessment strategies, education technologies, and active learning methods. Faculty development has a long history of supporting medical education colleagues in times of change. More recently expectations for faculty developers are expanding due to (1) increasing enrollment of learners, (2) emphasis on learner-centered teaching practices and competency-based assessment methods, and (3) heightened accreditation standards for training faculty. Yet, faculty development in medical education lacks the conventional structures of a profession, such as an adopted set of competencies. In 2023, a series of sessions at regional, national, and international medical education conferences were held to generate ideas and collect examples of faculty developer competencies from over 100 stakeholders. More than 500 responses were gathered from prompts such as “What are the competencies faculty developers need?” and “What is one of the most valuable faculty developer competencies today?” This perspective offers both a rationale for establishing faculty development in medical education as a profession and a path forward through the provision and broad promotion of clearly defined core competencies. The competencies outlined are intended to help inform those entering or currently working in the profession, recruiters of faculty developers, medical education leaders, institutional partners, those conducting performance appraisals of faculty developers, and the broader medical education community. The aim of this work is to generate discussion among vested medical education and faculty development stakeholders who seek to provide structure, clarify roles, and further define medical education faculty development as a profession.

Ultrasound‐guided nerve blocks (USGNBs) are increasingly used in the emergency department (ED) as a safe and effective part of multimodal pain management. Their use has been shown to reduce reliance on opioids and procedural sedation, improve pain scores, and enhance functional outcomes for patients. Additionally, USGNBs in the ED have a complication rate of 0.4%, markedly lower than procedural sedation (4–11%), and they significantly reduce opioid requirements, which is critical considering the current opioid epidemic and the risks of persistent opioid use and overdose. Despite these benefits, relevant concerns about medicolegal liability, informed consent, evolving standards of care, may still influence the adoption of USGNBs in clinical practice. To address these issues, this review examines the legal risks associated with USGNBs by drawing on current clinical literature, closed claims data, and case law. We highlight common adverse events such as peripheral nerve injury and local anesthetic systemic toxicity and assess their legal implications. Potential legal risk including liability related to alternatives like opioid use and procedural sedation, are discussed. While the risk of litigation remains low when best practices are followed, failing to offer a USGNB when clearly indicated may increasingly be viewed as a liability if preventable complications occur. This article aims to provide a practical, interdisciplinary framework, including legal risk assessment, training, credentialing, and risk mitigation, to help clinicians, educators, and hospital administrators safely and confidently integrate USGNBs into ED practice.