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Abstract Background Implantable cardioverter-defibrillator (ICD) is a well-established therapeutic option associated with decreased mortality in patients with ischemic and non-ischemic cardiomyopathies. However, the indications for patients with chronic Chagas cardiomyopathy (CCC) are not well established since these patients were underrepresented in the trials validating ICD use. Purpose This systematic review and single-arm meta-analysis aims to synthetize the available evidence in the literature on the role and outcomes of ICD in CCC. Methods A systematic search of PubMed, Web of Science, Cochrane, and LILACS registries was performed following PRISMA guidelines. Studies evaluating the response to ICD in CCC were included. There were no language restrictions. Data were collected and synthesized using a meta-analysis of proportions with Freeman-Tukey double-arcsine transformation as needed. Results We included 14 observational studies and 1 randomized clinical trial (RCT), comprising 1315 patients with CCC. Mean age at ICD implantation was 58.2 ± 11.8, 65% were male, and 77% received an ICD for secondary prevention. During a mean follow up of 37.3 ± 37.0 months, the all-cause death rate was 22% (95% CI 15 to 29%; Figure 1A), the cardiovascular death rate was 16% (95% CI 11 to 22%; Figure 1B), the sudden cardiac death rate was 3% (95% CI 2 to 5%), and the non-cardiovascular death rate was 7% (95% CI 2 to 5%). In addition, 55% (95% CI 43 to 67%; Figure 1C) of patients received ≥1 appropriate ICD therapy (shocks or antitachycardia pacing), 8% (95% CI 5 to 12%) received inappropriate ICD shocks, and 23% (95% CI 11 to 37%) experienced electrical storms. Conclusion Despite ICD, the mortality rate in patients with CCC remains unacceptably high, primarily driven by cardiovascular causes, with frequent appropriate ICD therapies and electrical storms. Further studies are needed to better delineate the benefits and risks of ICD therapy in patients with CCC.Figure 1

Abstract Purpose To evaluate alcohol intake trends and identify demographic, clinical, lifestyle and socioeconomic factors associated with alcohol consumption in late survivorship among breast cancer survivors. Methods Individuals diagnosed with stage 0–3 breast cancer enrolled in the Mayo Clinic Breast Disease registry between 2014 to 2022 reported their average weekly alcohol intake at baseline (time of diagnosis) and at approximately four years post-diagnosis. Alcohol intake was divided into four categories and cross-sectional associations with demographic, clinical, and lifestyle factors were examined using Monte Carlo-based Fisher exact tests and multivariable multinomial logistic regression. Changes in alcohol consumption from baseline to Year 4 were evaluated using Bowker’s test of symmetry and multinomial models. Results Among 719 participants, alcohol intake 4 years post diagnosis closely resembled baseline patterns, with 30.2% of patients reporting no alcohol use and 48.8% of patients consuming 1–4 drinks per week. Younger age and current smoking status were strongly associated with higher intake at Year 4. Exercise and better physical health were associated with higher alcohol intake in univariable models, however not in adjusted models. From time of diagnosis to Year 4, 15.6% of patients decreased their alcohol intake, 10.2% increased alcohol intake, and 74.3% reported no change. Higher levels of mild intensity exercise were associated with an elevation in alcohol intake over time. Conclusion Alcohol consumption remained stable in late survivorship, in contrast to the initial decline in alcohol use during early survivorship seen in this cohort. Younger age and smoking were key associations with higher alcohol intake.

Background: High-grade intracranial atherosclerosis (ICAS) is associated with an elevated risk of recurrent ischemic stroke, particularly in patients with severe stenosis (70–99%). Identifying predictors of early recurrence can inform risk stratification and guide treatment strategies. Methods: The Biomarkers and Recurrence Risk in Symptomatic Intracranial Arterial Stenosis (BIORISK-ICAS) study is a multicenter, international, retrospective cohort analysis pooling data from 35 comprehensive stroke centers. We included hospitalized adult patients with symptomatic ICAS, defined as 50–99% stenosis of an intracranial artery (intracranial vertebral, basilar, distal ICA, or M1 MCA), confirmed by vascular imaging and associated with a qualifying ischemic event. Patients with only high-grade stenosis (70-99%) were included in this analysis. The primary outcome was to determine predictors of recurrent ischemic stroke in the territory of the symptomatic artery within 90 days of the index event. Baseline demographic, clinical, and imaging characteristics were recorded. Multivariable Cox proportional hazards regression with stepwise selection (p < 0.1) was used to identify independent predictors of recurrence; model discrimination was assessed using Harrell’s C-statistics. Results: Among 2,050 patients, 1,476 had high-grade (70-99%) symptomatic ICAS. The mean age was 67 ± 12.5 years, and 767 (55%) were male. Most patients were non-Hispanic (90.1%), taking dual antiplatelet therapy (77.8%), and statins (94.5%). Recurrent stroke occurred in 160 patients (10.8%) within 90 days. In multivariable Cox model, independent predictors of recurrence included atrial fibrillation (HR 2.05; 95% CI, 1.26–3.33; p = 0.004), hyperlipidemia (HR 1.57; 95% CI, 1.10–2.24; p = 0.014), diabetes mellitus (HR 1.36; 95% CI, 0.98–1.88; p = 0.064), and home use of dual antiplatelet therapy (HR 1.60; 95% CI, 1.01–2.54; p = 0.043)(Harrell’s C-statistic=0.62). In patients who underwent perfusion(n=402), mistmatch >10seconds were associated with increased recurrence (HR 1.80; 95% CI 0.95-3.38, p=0.07) and atrial fibrillation (HR 2.06: 95% CI 0.03-4.60, p=0.78) though did not reach statistical significance. Conclusion: In this population, diabetes, hyperlipidemia, atrial fibrillation, and prior use of dual antiplatelet therapy were associated with increased risk of 90-day recurrent ischemic stroke. Perfusion imaging may help identify high-risk patients who could benefit from intensified secondary prevention.

OBJECTIVE The minimal important difference (MID) and minimal important change (MIC) are two metrics that bridge the gap between statistical significance and clinical relevance and are critical to managing clinical decisions and conducting clinical research. The objective of this study was to define MIDs to evaluate cross-sectional differences among groups and to define MICs to evaluate longitudinal within-patient changes for the Mayo Clinic Vestibular Schwannoma Quality of Life (VSQOL) Index. METHODS Anchor-based methods were used to define MIDs and MICs for the VSQOL Index domain scores, which range from 0 to 100 points, for a national cohort of 1050 patients with sporadic vestibular schwannoma, 644 of whom completed the VSQOL Index twice approximately 1 year apart. RESULTS The median of the MID estimates for the VSQOL Index domains were: hearing problems (17, IQR 12.5–21); dizziness and imbalance (21, IQR 18–23); pain, discomfort, and tinnitus (19.5, IQR 15–23.5); problems with face or eyes (18, IQR 17–28); impact on physical, emotional, and social well-being (19.5, IQR 14.5–23.5); difficulty with thinking and memory (23.5, IQR 18.5–28.5); global quality of life (12, IQR 8–16); and satisfaction or regret (13.5, IQR 7–17). MIC estimates for the hearing problems and satisfaction and regret domains were not obtained because the correlations between these domain scores and their associated anchors were not sufficiently strong. The MIC estimates (minimum and maximum) for the remaining domains were: dizziness and imbalance (7.2 and 8.3); pain, discomfort, and tinnitus (8.3 and 8.5); problems with face or eyes (7.0 and 7.4); impact on physical, emotional, and social well-being (2.1 and 8.0); and difficulty with thinking and memory (12.9 and 15.0). The median of the MIC estimates for global quality of life was 5.2 (IQR 3.7–5.6). CONCLUSIONS The MIDs and MICs reported herein provide a framework to interpret quality-of-life benefit or harm cross-sectionally among groups and longitudinally within patients. Moving forward, these values should be considered when interpreting studies using the VSQOL Index to assess disease-specific quality of life in patients with sporadic vestibular schwannoma.

Background: Running often elicits stress urinary incontinence (SUI) in parous athletes. While cadence retraining improves running biomechanics, its impact on incontinence is unclear. This feasibility study assessed the implementation and preliminary effects of a 6-week cadence retraining program in parous female runners with SUI. Methods: A total of 8 participants with self-reported SUI and a preferred running cadence ≤ 170 steps/minute underwent treadmill testing before and after the intervention. The program involved a 6-week cadence retraining program using a Garmin Forerunner 55 watch. Feasibility was assessed across 6 domains. Running outcome measures included cadence and vertical oscillation. SUI outcome measures included the Questionnaire for Urinary Incontinence Diagnosis and Urinary Distress Inventory-6 scores. Paired t-tests were conducted (α = .05). Results: Following the 6-week program, feasibility outcomes supported the viability of study procedures and high adherence. Statistically significant increases in cadence ( P = .016) and decreases in vertical oscillation ( P = .019) and concomitant decreases in Questionnaire for Urinary Incontinence Diagnosis ( P = .013) and Urinary Distress Inventory-6 ( P = .042) scores were observed. Discussion: This study demonstrated the feasibility and acceptability of a 6-week cadence retraining program for parous runners with SUI. Given the growing movement to foster athleticism after pregnancy, these findings will appeal to physical therapists searching for acceptable treatment options for SUI in parous runners. Preliminary running mechanics and SUI symptoms warrant a larger randomized controlled trial. A power analysis estimated a sample size of 66 participants for a future full-scale efficacy study.

Abstract Background: As with most Sub-Saharan African countries, Nigeria has a rising incidence of cancer, with disproportionate mortality rates. The financial burden of cancer care often results in catastrophic healthcare spending, leading to treatment refusal, disruption, and discontinuation. This is particularly significant in Nigeria, where nearly all patients are uninsured, and out-of-pocket costs often exceed households’ ability to pay. Financial Navigation Programs (FNPs) have been shown to mitigate treatment-related financial toxicity in cancer care and reduce treatment abandonment, but there is a paucity of high-quality data on this intervention in resource-constrained settings. Here, we present a randomized controlled trial to evaluate the impact of a novel FNP in Nigeria. Methods: We designed the COST-FIN trial, a multi-site pragmatic single-blinded randomized controlled trial of newly diagnosed (<6 weeks from diagnosis) adults (≥18 years) with breast, colorectal, or prostate cancer at two tertiary cancer centers in Nigeria. Participants (n=200) will be randomized (1:1) to either the intervention (FNP) or the control arm and followed for 12 months. Data on key individual, treatment, and financial parameters will be collected via structured interviews and chart abstraction at baseline, 3, 6, and 12-month follow-up. In addition, participants randomized to the FNP will receive a tailored financial literacy assessment, financial planning support, and enhanced access to resources by trained financial navigators. Primary and secondary outcomes are Financial Catastrophe (FC) and Financial Distress (FD), respectively. Exploratory outcomes will include cost-related non-adherence and cost-effectiveness of the program. An interim analysis will be conducted when 50% of the estimated accruals reach 6 months of follow-up, with crossover if compelling evidence of benefit is demonstrated at that time point. All participants will be followed for 12 months from recruitment. Discussion: This first-of-its-kind study will provide evidence on the role of FNP in potentially eliminating financial barriers to cancer care in Nigeria. Given the country’s renewed interest in cancer control through the passage of the National Cancer Control Plan, findings from this study have the potential to influence policy reform and set the stage for further studies to evaluate the scalability and implementation of similar interventions in resource-limited settings. Trial registration : ClinicalTrials.gov NCT06630962. Oct 8, 2024 (https://clinicaltrials.gov/study/NCT06630962)

Abstract Motivation: Epilepsy is a diverse group of neurological disorders affecting over 50 million people worldwide. While common epilepsy types are well studied, rare epilepsies—often severe and genetically complex—pose significant challenges in diagnosis, research, and treatment. Accurate and interoperable etiology and disease classifications are critical for improving data sharing, supporting clinical decision-making, and advancing rare disease research. Results: To enhance the accuracy of epilepsy-related disease concept representation within the Mondo Disease Ontology (Mondo), we conducted a series of expert-driven workshops in collaboration with the team from the Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP). Specialists in epileptology, genetics, neurodevelopment, biomedical ontology, and patient community advocates systematically reviewed and revised the epilepsy hierarchy in Mondo, aligning it with the International League Against Epilepsy (ILAE) classification system. These updates include reclassification of epilepsy subtypes, including syndromes, age-related epilepsies, and developmental epileptic encephalopathies, resulting in a more granular, standardized, and clinically relevant structure. Mondo now offers an enhanced framework for integrating epilepsy data across resources, enabling improved interoperability and facilitating rare disease research and data curation, with continued efforts underway to further refine and expand this integration.

Background Tumor-derived small extracellular vesicles were shown to contribute to immunosuppression in various cancer types, including head and neck squamous cell carcinoma. Dendritic cells, major regulators of specific anti-tumor immune response, are often impaired in their function in the context of cancer. Methods Monocyte-derived dendritic cells were incubated with isolated small extracellular vesicles during or after maturation. Cell surface markers and antigen processing machinery were assessed by flow cytometry. Vesicle-treated dendritic cells were tested for interleukin 12p70 production by ELISA, and differences in uptake of labeled vesicles were shown by confocal microscopy. Results Small extracellular vesicles derived from HPV(+) tumor cell lines increased maturation and activation of immature dendritic cells, priming them for more rapid phagocytosis. Immature dendritic cells co-incubated with vesicles had lower levels of antigen presenting machinery components and produced less IL12p70 than controls, while similarly co-incubated mature dendritic cells remained unaffected. Vesicles in plasma of patients with head and neck cancer inhibited functions of mature dendritic cells by downregulating expression of antigen presenting machinery components. Conclusion Our results uncover mechanisms through which tumor-derived small extracellular vesicles modulate dendritic cell functions locally and systemically. These mechanisms may also affect dendritic cell-based vaccine efficacy.

567 Background: IDH2 mutation is rare (1%) in patients (pts) with cholangiocarcinoma and there are no data on prognosis in these pts and response to first line (1L) chemotherapy or off-label IDH2 inhibitor enasidenib. Methods: This IRB approved retrospective study included consecutive pts 18 years or older with IDH2 mutated biliary cancer identified between 2010-2024 at 4 large academic centers. Pt characteristics, systemic therapy(ies), next-generation sequencing (NGS) and survival data were obtained via review of electronic medical records. Survival probabilities were estimated using the product-limit method of Kaplan-Meier using SAS (v9.4, Cary, NC). Results: In 40 pts who met criteria, 9 (22.5%) underwent curative intent resection/ ablation, 34 (85%) had recurrent or de novo locally advanced or metastatic stage and of them 33 (82.5%) received any therapy for advanced cancer. Of these 33 pts, 25 (75.7%) were female, 29 (87.9%) non-Hispanic White and 32 (97%) had intrahepatic subtype with a median (range) age of 65 (28-82) years. NGS on tissue (51.5%), plasma (21.2%) or both tissue and plasma (27.3%) identified IDH2 R172* in 28 (84.8%), I98T in 1 (3%), F278fs in 1 (3%) pts and not reported/missing in 1 (3%) pt. Most common co-altered genes included TP53 (27.5%), ARID1A (17.5%), PBRM1 (12.5%), CDKN2A (10%), BAP1 (10%). FGFR2 fusion or N/KRAS mutation was present in 2 (5%) pts each. Of 33 pts with advanced stage, 1L therapy was gemcitabine/platinum +/- devimistat or durvalumab in 84.9%. Median (95% CI) progression-free survival (PFS) on 1L chemotherapy and overall survival were 6.6 (4.1-7.8) and 16.3 (12.1-28.9) months, respectively. Eight of 33 (24.2%) pts with advanced stage received off label enasidenib as Nth line therapy with median PFS (95% CI) 3.9 (1.1-5.1) months. Conclusions: Most pts with IDH2 mutation had advanced ds with median survival similar to those with IDH1 mutated advanced cholangiocarcinoma. Off label enasidenib had modest benefit in this rare subset of pts and should be investigated further.

Abstract Background Stigma associated with tuberculosis (TB) and TB diagnosis is a major social factor in delay of diagnosis and non-adherence to TB treatment among Asian American and Pacific Islander (AAPI) populations. Main sources of stigma include misconceptions regarding TB transmission and lack of knowledge about symptoms or treatment.Figure 1.Respondent demographicsBreakdown of respondent demographics by age, gender, and AAPI subgroup.Figure 2.Demographic breakdown of TB awarenessTB awareness by AAPI subgroup, age, and gender. Methods A cross-sectional survey of 666 AAPI individuals analyzed TB symptom recognition, transmission misconceptions, and awareness in two AAPI community centers. Data were segmented by AAPI subgroup, metropolitan area (Seattle/Tacoma vs. Las Vegas), age, and gender.Figure 3.TB transmission beliefs.Figure 4.TB treatment, curability, and latent TB infection awareness. Results Overall, 76.6% of respondents reported TB awareness, varying by AAPI subgroup. Awareness was highest among Korean (95%) and Filipino (91%) participants, and lowest among Vietnamese (52%) and Cambodian (50%) respondents. Regionally, TB awareness was similar between Tacoma (76%) and Las Vegas (79%). Age and gender significantly impacted awareness. Respondents under 18 had the lowest TB awareness (59%), while those aged 18-34 had the highest (84%). Females reported higher TB awareness (79%) and symptom recognition (61%) than males (74% and 46%, respectively). Symptom knowledge varied. 55% were aware of TB symptoms, but only 16% were able to recognize five common TB symptoms. Misconceptions about transmission also persisted broadly. Out of the 71% of respondents who were aware that TB is transmissible, many incorrectly believed TB spread via shaking hands (35%), sharing food/drinks (50%), or touching items in public areas (37%). The 45-64 and 65+ age groups were most prone to misconceptions about transmission. While 72% of respondents were aware that TB could be treated, only 57% knew TB could be cured. 30% of respondents were aware of latent TB infection. Conclusion Significant disparities in TB awareness exist in AAPI communities. Females demonstrated greater TB awareness perhaps due to cultural differences (“caretaker role”), while TB transmission misconceptions were prevalent among older individuals. Limited knowledge on LTBI and TB treatment represent significant barriers to effective TB control. Tailored educational efforts will be required to improve TB awareness and reduce misconceptions within AAPI communities. Disclosures All Authors: No reported disclosures