Citations

Abstract Rationale The impacts of COVID-19 vaccination and SAR-CoV-2 infection on brain tissues and structures remain controversial. This study examines whether COVID-19-related exposures are associated with measurable changes in structural magnetic resonance imaging (MRI) using data from the US general population-based Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study. Methods The C4R study is an observational meta-cohort study of 14 NIH-funded population-based cohorts, with directly measured data on COVID-19-related exposures, including vaccination and infection. For this analysis, we included participants with C4R data and paired brain MRI scans from both before and after the onset of the COVID-19 pandemic (defined as March 1, 2020) from two cohorts: the Atherosclerosis Risk in Communities study (ARIC) and Framingham Heart Study (FHS). MRI features examined as outcomes were white matter volume (WMV), gray matter volume (GMV), total brain volume (BV), hippocampal volume (HV), and white matter hyperintensity volume (WMH), a marker of microvascular disease. Exposures included SARS-CoV-2 infections identified via questionnaires, serosurveys, and medical record reviews from 2020-2025. Infections resulting in hospitalization were classified as severe. Time-to-recovery, symptoms of long COVID, and vaccination status were self-reported by questionnaire. Analysis of covariance (ANCOVA) estimated associations between COVID-19-related exposures and pandemic MRI-measured outcomes, with adjustment for: the corresponding pre-pandemic MRI measure, the time between the two MRI scans, age, sex, systolic blood pressure, diabetes, and cardiovascular disease. Results Of 270 participants with available data, mean (SD) age was 80.6 years (10.6); 43.0% were male; and the mean (SD) interval between paired MRI scans was 4.2 (2.0) years. Most (90%) were vaccinated (of whom 6.7% vaccinated before infection) and 7.9% reported SARS-CoV-2 infection (of which 13.6% were severe infections) prior to their pandemic MRI (conducted March 2020 - June 2022). In fully adjusted models, there was no statistically significant association for change in WMV, GMV, BV, HV, or WMH with SAR-CoV2 infection status, infection severity, vaccination status, or vaccination timing (Table, P > 0.05 for all comparisons). Self-reported symptoms of long COVID and vaccine manufacturer were also not associated with MRI outcomes. Conclusions Based on repeated (pre-pandemic and pandemic era) structural MRI scans, we found no evidence that SARS-CoV-2 infection or COVID-19 vaccination were associated with changes in brain structure or brain microvascular disease. These findings are consistent with prior data supporting COVID-19 vaccine safety and suggest resilience of brain structures following SARS-CoV-2 exposures. Nonetheless, further research is warranted using more sensitive measures and assessing longer term effects. This abstract is funded by: OT2HL156812

Abstract Background Tuberous sclerosis complex (TSC) is a multisystem genetic disorder frequently associated with lymphangioleiomyomatosis (LAM), a progressive cystic lung disease. The 2022 Updated International TSC Consensus guidelines recommend clinical assessment for LAM and chest CT in all females, and symptomatic males, 18 years or older. We aimed to evaluate pulmonary screening practices along with demographic, genetic and clinical characteristics of those with TSC-LAM in a large national TSC cohort. Methods We conducted a retrospective observational study using the TSC Alliance Natural History Database. Demographic, genetic, and clinical data were extracted. Screening rates for LAM were assessed, and clinical, genetic, and pulmonary characteristics of patients diagnosed with LAM were analyzed. Results Among 2,636 patients with TSC (1,301 females, 49%), molecular testing was performed in 1,591 (60%), identifying TSC1 mutations in 349 (21.9%) and TSC2 mutations in 978 (61.5%). Screening for LAM was reported by 312 patients (11.8%; 42 (13.5%) males), of whom 116 were diagnosed with LAM; 111 (95.7%) were female. Mean age at cohort characterization was 48 years (range 21-80, SD 12.9), and mean age at LAM diagnosis (available in 82 patients) was 33 years (range 14-69, SD 12.5). Among LAM patients, molecular testing was performed in 74 (64%), TSC1 mutations were present in 8 (6.9%), TSC2 in 47 (40.5%), and dual mutations in 2. Common clinical manifestations included renal angiomyolipomas (104, 89.7%), facial angiofibromas (90, 77.6%), epilepsy (70, 60.3%), and subependymal giant cell astrocytoma (27, 23.3%). Pulmonary function data were limited (mean FEV₁ 84.9% predicted, n = 43; mean DLCO 77.6% predicted, n = 27). Serum VEGF-D available in 10 patients, range 331-9,523 pg/mL). Chest CT was performed in 87 patients (75%) and biopsy in 4 (3%). Patient-reported respiratory complications included pneumothorax (14, 12.1%), chylothorax (3, 2.6%), and oxygen requirement (4, 3.4%). Treatments included mTOR inhibitors in 32 (27.6%) and lung transplantation in 1 patient. Conclusion Evaluation for LAM in patients with TSC appears to be underutilized in the U.S. LAM mainly affects women, is linked to TSC2 mutations, and is associated with high rates of renal and dermatologic manifestations. Although guidelines focus on females, LAM can occur in males, highlighting the need for awareness in all TSC patients. Limited lung function and biomarker data reveal gaps in evaluation, with some patients developing severe disease requiring oxygen or lung transplantation. These findings support standardized, genotype-informed surveillance for early detection and targeted care in TSC-related LAM. This abstract is funded by: None

Abstract Rationale Chronic bronchitis (CB), a common phenotype of chronic obstructive pulmonary disease (COPD), is characterized by pathologic mucus hypersecretion and is associated with substantial morbidity, impaired quality of life, and progressive functional decline, with prior studies demonstrating an average worsening of approximately one point/year on the COPD Assessment Test (CAT). Bronchial rheoplasty (BR) with RheOx® combines mechanical mucous plug disimpaction with pulsed electric field (PEF) energy to ablate and restore the airway mucosa. The RheSolve study was designed to provide evidence of safety and efficacy versus mechanical disimpaction alone. Primary endpoint results have been previously reported; final 2-year outcomes are reported here. Methods RheSolve was a prospective, randomized, double-blind study enrolling 273 patients with COPD and moderate-to-severe CB across 37 centers in the United States and Europe. Participants were randomized 2:1 to BR (n = 185) or a mechanical control procedure (n = 88). Following unblinding at 12 months, 75% of control patients crossed over to BR, precluding valid randomized comparisons beyond that time point; therefore, longer-term outcomes were evaluated using within-patient changes from baseline in the BR cohort. Outcomes included CAT, St George’s Respiratory Questionnaire (SGRQ), Cough and Sputum Assessment Questionnaire (CASA-Q), and pulmonary function tests (PFTs). Results Patients in the BR group represented a moderate to severe COPD CB phenotype at baseline (FEV1 60.9% predicted, emphysema (-950 HU) 11.0%, CAT 27.2 points, SGRQ 64.4) with most patients (93%) receiving a combination of ≥ 2 long-acting medications (LABA, LAMA, inhaled corticosteroids). The BR procedure was well-tolerated with no SAEs related to the device or procedure beyond 12 months. Both groups demonstrated clinically meaningful improvements in CAT, SGRQ, and CASA-Q at 12 months (P < 0.001), which were sustained in the BR group through 24 months. Follow-up was limited to 1 year in the mechanical control group, with outcomes demonstrating a modest regression towards baseline at 12 months (Figure). PFTs were also stable to improved in the BR group (changes from baseline to 24 months: FEV1 % Predicted 0.9 (±10.8) P = 0.319, FVC % Predicted 2.8% (±14.0) P = 0.02, FEV1/FVC -0.5% (±7.2) P = 0.449). Conclusions BR with RheOx® (e.g.,mechanical mucous plug disimpaction and PEF delivery) demonstrated clinically meaningful symptom improvement that was sustained through 24 months supporting BR as a therapeutic option for patients with persistent symptoms despite appropriate medical therapy. This abstract is funded by: Galvanize Therapeutics

Abstract Autoinflammatory syndromes are increasingly recognized as heterogeneous disorders of innate immune dysregulation, often overlapping in clinical and genetic features. Although pulmonary manifestations are uncommon, several autoinflammatory conditions such as VEXAS syndrome, juvenile rheumatoid arthritis, adult-onset Still’s disease, and Familial Mediterranean Fever can produce inflammatory pulmonary nodules that mimic metastatic malignancy. Recognition of these presentations is critical, as they can respond dramatically to immunosuppressive therapy once the correct diagnosis is established. We describe a diagnostically challenging case of a young adult male initially suspected to have metastatic lung cancer, whose evaluation ultimately suggested a previously uncharacterized autoinflammatory process. We present a 26-year-old previously healthy male with progressive dry cough, exertional dyspnea, diffuse myalgias, small joint arthritis involving the fingers, wrists, and ankles, tendonitis, a Gottron-like rash on the hands and lower extremities, low-grade fevers, and occasional bloody stools. Initial external workup revealed a right infrahilar mass, right lower lobe pleural thickening, small pleural effusion, and mediastinal and hilar lymphadenopathy on CT chest, with corresponding PET activity. Initially suspected to have metastatic lung cancer, he was informed his prognosis was poor. However, transbronchial, EBUS, and mediastinal lymph node biopsies showed only active inflammation without malignancy. On presentation to our facility, a broad differential was pursued, with suspicion for an autoinflammatory or autoimmune etiology. Pulmonary function testing was normal. Laboratory evaluation revealed ESR >100, elevated CRP, positive ANA (1:160), negative HLA-B27, normal ferritin, and negative S100 staining. Cytokine analysis showed elevated TNF, IL-6, MCP-1, IL-2, and IL-18. Targeted variant testing identified a UBA1 gene variant, c.123G>T p.(M41L), with low-level mosaicism (0.004%), and a heterozygous MEFV mutation. Although his ethnicity made Familial Mediterranean Fever unlikely, these findings raised the possibility of overlapping somatic and germline contributions to innate immune activation. He was treated empirically with immunosuppression for a presumed multisystem inflammatory disorder, resulting in resolution of symptoms and marked radiologic improvement. This case highlights the expanding spectrum of adult-onset autoinflammatory diseases that may present with pulmonary findings mimicking malignancy. The coexistence of low-level UBA1 mosaicism and MEFV mutation suggests a potential interaction between somatic and inherited variants in triggering inflammation. Similar to the recent discovery of VEXAS syndrome, this case may represent a novel subtype of autoinflammatory disease. Continued genomic and immunologic investigation is warranted, as timely recognition and immunosuppressive therapy can lead to dramatic recovery. This abstract is funded by: None

Abstract Introduction Inflammatory myofibroblastic tumor (IMT) constitutes 0.04 to 1% of all lung neoplasms, and endobronchial presentations are exceedingly uncommon.[1] We report a case in which a skin rash served as the sentinel sign of an occult endobronchial IMT. Case presentation A 58-year-old female was referred for evaluation of an incidental lung nodule. She initially presented with a diffuse erythematous rash. Skin biopsy revealed interstitial granulomatous dermatitis (IGD), a histologic pattern often associated with various systemic diseases. Workup to investigate potential underlying causes revealed a hypermetabolic endobronchial lesion (Figure 1). A subsequent flexible bronchoscopy demonstrated yellow nodular material occluding the anterior segment bronchus of the right upper lobe (RUL). An initial forceps biopsy resulted in fragmentation of necrotic tissue, which was successfully retrieved using a cryoprobe, revealing a patent distal airway (Figure 2). Histopathology confirmed an IMT harboring ALK gene rearrangement (Figure 3). Within the necrotic debris, rare acid-fast bacilli were observed, and bronchoalveolar lavage culture later grew Mycobacterium avium complex (MAC). A video-assisted thoracoscopic surgery (VATS) RUL lobectomy was performed, and final surgical pathology showed no residual tumor with negative bronchial margins and negative nodal involvement. At her four-week follow-up, she was free of any respiratory or dermatologic symptoms, and a structured five-year imaging surveillance plan was established. Discussion This case presents an intriguing clinical cascade. The pathophysiology we propose is a sequential, domino-like effect. The primary event was the development of an obstructive endobronchial IMT, impairing mucus clearance and creating a localized breeding environment for the second event-colonization and infection with MAC, an opportunistic pathogen known to exploit structural airway abnormalities.[2] Similar postobstructive nontuberculosis mycobacterial infections have been reported in association with endobronchial carcinoid and chondromatous tumors.[3-5] The subsequent systemic inflammatory response provides the most plausible trigger for the patient’s IGD, a subtype of reactive granulomatous dermatitis that can reflect remote immune activation and has been previously linked to MAC infection.[6] This case exemplifies an “endobronchial secret beneath the skin,” in which a concealed pulmonary neoplasm may have caused dermatologic manifestations through a sequence of tumor formation, obstruction, infection, and remote immune activation. The diagnostic process unfolded in reverse, beginning with a skin eruption that ultimately led to the unraveling of a rare endobronchial IMT. This case underscores the imperative of a multidisciplinary, system-wide approach when evaluating a nonspecific “umbrella diagnosis”. It also reminds clinicians of the sentinel role of the skin. Sometimes the surface tells the story first. This abstract is funded by: None

Abstract Background Immune checkpoint inhibitors (ICIs) improve outcomes across malignancies but can cause immune-related adverse events (irAEs), notably myocarditis, with case-fatality up to 50% Methods We retrospectively reviewed five patients with potential ICI-associated myocarditis treated at Mayo Clinic Florida (2019–2024) and summarize the existing literature. Cases were retrospectively categorized as definite, probable, or possible myocarditis according to cardiac magnetic resonance (CMR) findings and histopathology when available. Results The median age was 74 years, and four of the five patients were male. Myocarditis developed between 5 and 30 days after initiation of anti–PD-1 therapy. Presentations included dyspnea (three patients), chest pain (one patient), and asymptomatic troponin elevation detected on routine monitoring (one patient). Troponin T elevation above the 99th percentile was seen in all five cases (normal <= 15 ng/L). Electrocardiograms (ECG) demonstrated conduction abnormalities or ventricular ectopy in each patient. Left ventricular ejection fraction was preserved in four patients and severely reduced in one. CMR provided findings supportive of myocarditis in two of the five cases, while one endomyocardial biopsy (EMB) was performed and did not demonstrate active inflammation. Based on predefined criteria, one case was classified as definite myocarditis, one as probable, and three as possible ICI-associated myocarditis. All five patients received corticosteroid therapy. Two required escalation of immunosuppression. One patient developed concurrent myasthenia gravis, consistent with myocarditis–myositis–myasthenia (MMM) overlap, and underwent plasmapheresis for the neuromuscular component. Three patients recovered. Two patients died during follow-up; in both cases, myocarditis was considered a contributing factor, although direct causality could not be definitively established.

ABSTRACT Background The Academy for Women in Academic Emergency Medicine (AWAEM) within the Society for Academic Emergency Medicine was established to advance the recruitment, promotion, retention, and career satisfaction of women in academic emergency medicine (AEM). Despite progress, persistent gender disparities remain in several areas, including compensation, promotion, and leadership representation. Objective To better assess and evaluate current AWAEM programming, we developed a logic model to visually and systematically map AWAEM activities and initiatives with current and future metrics for evaluation. Methods The logic model was guided by AWAEM’s strategic plan and developed through an iterative process involving feedback from AWAEM members and leaders. Results The model outlines key inputs, describes activities categorized across five thematic areas, and identifies tangible outputs with corresponding metrics for those activities. The model concludes with short‐, intermediate‐, and long‐term outcomes that speak to the likely impact of AWAEM’s programming. Discussion The proposed logic model serves as a practical framework to align AWAEM’s efforts to outcomes while also embedding evaluation into ongoing programming. It provides a visual tool for identifying gaps and incorporating data‐driven modifications, as well as facilitating collaboration across the academy. While there are limitations to this logic model, it provides an initial roadmap and foundation for strategic planning and evaluation. It also provides an opportunity to periodically revise the model as AWAEM’s needs evolve to ensure continued relevance and alignment with the needs of the entire membership. Additionally, this model can serve as a framework for other professional development groups, academies, and societies external to SAEM.

Abstract Background/Purpose Diagnosing wrist ligament injuries is challenging; early detection and treatment are important to prevent osteoarthritis progression. Interosseous proximity maps, a proxy measure for joint space, can be generated from volumetric imaging data and may provide important information about wrist health. Artificial intelligence (AI) could enhance accuracy of noninvasive diagnosis based on imaging-derived metrics. This work demonstrates feasibility of AI training using synthetic proximity map data generated from finite element models (FEMs). Methods Personalized wrist FEMs for two asymptomatic participants were created from four-dimensional computed tomography-derived anatomic and kinematic data. Monte Carlo sampling varied 22 ligament material properties and simulated 7,500 unique injury scenarios generating 9,000,000 labeled red, green, and blue (RGB) images of interosseous proximity vector fields from FEM-derived motions. Images were associated with 17 descriptive metrics, including gross wrist angles and bone surface pairs, and used to develop mixed-input convolutional neural networks (CNNs). Model performance was evaluated for identifying specific ligament injuries. Results Average area under receiver operating characteristic curve (AUROC) for CNNs was 0.757 across all injury types and kinematics. In a subset with clinically-relevant functional angles, the average AUROC was 0.824. Best-performing individual ligament AUROCs ranged from 0.807 to 0.999. Sensitivities and specificities exceeded 0.99 for some ligament injury simulations under specific wrist angles and bone surface pairs. Conclusion This study demonstrates the feasibility of using synthetic data from FEMs to train AI models for classifying wrist ligament injuries. Proximity-based RGB images may be a relevant biomarker of ligamentous injury.

Abstract The Tau Global Conference 2025, hosted by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation, convened international experts from academia, industry, government, and philanthropy to explore advances and challenges in tauopathy research. The meeting highlighted progress across tau biology, including emerging models of tau regulation, degradation, and propagation; advances in biomarker development for the diagnosis and staging of tauopathies; and evolving therapeutic strategies targeting diverse aspects of tau pathophysiology. Discussions also emphasized the importance of cross‐sector collaboration, and global initiatives to address disparities in tau research. This report synthesizes key insights from the conference and underscores the critical role of interdisciplinary, biomarker‐driven, and globally inclusive approaches in accelerating the translation of tau research into effective clinical applications.

The discovery of genes encoding the volume-regulated anion channel (VRAC) has enabled detailed exploration of its cell type–specific roles in the brain. LRRC8A (SWELL1) is the essential VRAC subunit. We observed seizure-induced, subunit-specific changes in microglial VRAC expression and investigated its function using conditional KO (cKO) of LRRC8A in microglia. SWELL1 cKO mice exhibited a male-specific increase in kainate-induced seizure severity, yet showed paradoxical neuroprotection against seizure-associated neuronal loss. Mechanistically, SWELL1 deletion led to a cell-autonomous reduction in microglial density and decreased release of VRAC-permeable neuroactive metabolites, including taurine, GABA, and glutamate in culture. Additionally, impaired phagocytic kinetics and reduced lysosomal biogenesis contributed to the observed neuroprotection. These findings reveal potentially novel roles for microglial VRAC in regulating seizure outcomes and microglia-neuron interactions.