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This cross-sectional study investigates rates of incident pericardial effusion or cardiac tamponade in patients receiving Bruton tyrosine kinase inhibitors.

Abstract Context Menstrual irregularities have been associated with cardiovascular disease (CVD) risk, but underlying etiologies may confer distinct risk profiles. Functional hypothalamic amenorrhea (FHA) has not been evaluated as a separate risk phenotype. Objective To assess the association between FHA phenotype and incident CVD and cardiometabolic risk factors. Design Prospective cohort study with biennial follow-up from 1993 to 2019. Setting Nurses’ Health Study II cohort. Participants The sample included 52,655 premenopausal women free of CVD in 1993. FHA phenotype was defined as irregular or absent cycles without PCOS traits combined with low body mass index and/or high physical activity. Intervention None Main Outcome Measures Incident CVD (coronary heart disease [CHD; myocardial infarction or coronary revascularization] and stroke) and incident elevated cholesterol, hypertension, and type 2 diabetes (T2DM). Results During up to 26 years of follow-up, 1,007 CVD events occurred. Among women who developed CVD, the median time to the first CVD event was 17.0 years (IQR, 11.3-21.0). FHA phenotype in mid-adulthood was associated with a 62% higher risk of CVD (95% confidence interval [CI]: 1.01–2.59), driven by an almost two-fold higher risk of CHD (hazard ratio [HR] = 1.91; 95% CI: 1.11–3.27), compared with women with regular cycles. FHA was also associated with T2DM (HR = 1.86; 95% CI: 1.41–2.47), but not hypertension or elevated cholesterol. Non-FHA menstrual irregularity was associated with elevated cholesterol, hypertension, and T2DM, but not CVD. FHA in early adulthood was not associated with outcomes. Conclusions FHA phenotype in mid-adulthood was associated with increased CHD risk independent of traditional risk factors. Menstrual history may serve as an early marker of cardiometabolic risk.

Objectives: Psychological health changes are known to occur during perimenopause, but the extent to which these differ from premenopause remains unclear. This study aimed to assess psychological symptoms during perimenopause compared with premenopause and evaluate differences by country. Methods: Flo app users aged 35 years or above not taking hormonal contraception or hormone therapy were included. The psychological domain of the Menopause Rating Scale (range 0-16) and symptoms within this domain of depressive mood, irritability, anxiety, and exhaustion (range 0-4 each) were evaluated. Participants in perimenopause were compared with those in premenopause (self-reported not in perimenopause or postmenopause). Results: A total of 7,975 women were included, with 2,353 in perimenopause (mean age 45 years [SD±4.5]) and 5,622 in premenopause (39 y [SD±4.0]). Psychological Menopause Rating Scale scores in the perimenopause group were significantly higher (7.3 [SD±3.56]) than in the premenopause group (4.8 [SD±3.56]; P <0.001). The individual symptoms of depressive mood, irritability, anxiety, and exhaustion were also higher in the perimenopause group ( P <0.001, for all respectively), with the largest difference being exhaustion. These findings remained after adjusting for known confounders, including an existing diagnosis of anxiety or depression. Geographic analysis included 20 countries across 6 continents, with significant differences identified between countries for the overall psychological symptom domain score and all individual symptoms. Conclusion: Significantly greater psychological symptom burden was identified in the perimenopause group compared with the premenopause group, with the greatest difference noted for the individual symptom of exhaustion. Differences in symptom burden were also identified by country.

Objectives Comparing clinical outcomes after cardiopulmonary bypass with hemodsorption (HA) versus cardiopulmonary bypass without HA in patients undergoing cardiac surgery in terms of mortality and major complications. Methods PubMed, Scopus, and Web of Science databases were searched for relevant randomized control trials (RCTs) that compared postoperative clinical outcomes between patients receiving intraoperative HA with cardiopulmonary bypass versus patients receiving cardiopulmonary bypass without intraoperative HA in cardiac surgery. Results Sixteen RCTs with 851 patients (433 in the HA group and 418 in the control group), were included in our meta-analysis. Our meta-analysis found no significant differences between the intraoperative HA group and the control group in patients undergoing cardiac surgery in terms of 30-days/in-hospital mortality, new-onset atrial fibrillation, stroke or cerebrovascular events, postoperative delirium, renal failure/acute kidney injury, need for renal replacement, postoperative liver dysfunction, thrombocytopenia, bleeding, volume of blood loss, pneumonia, sepsis, respiratory insufficiency, duration of postoperative ventilation, distributive/septic shock, pericardial tamponade, need for extracorporeal membrane oxygenation (ECMO) support, sequential organ failure assessment (SOFA) score at ICU admission, plasma-free hemoglobin levels, and fibrinogen levels. However, the pooled analysis showed a significant association between HA and decreased albumin at ICU admission (MD = − 0.28, 95% CI [0.55 to 0.01], p -value = 0.04), decreased length of ICU stay (MD = −0.66, 95% CI [−1.24 to 0.08], p -value = 0.03), and decreased length of hospital stay (MD = −0.99, 95% CI [−1.88 to −0.10], p -value = 0.03). Conclusion Our findings suggest that there is not enough evidence to endorse the role of routine intraoperative HA during cardiopulmonary bypass in improving clinical outcomes after cardiac surgery. Factors such as patient risk profile, procedure complexity, and cost implications should be taken into account when considering this adjunct therapy.

Introduction To assess and compare the accuracy, readability, and overall performance of large language models (LLMs) in answering questions about functional hypothalamic amenorrhea (FHA) for patients and healthcare professionals. Methods A total of 11 patient-level and 15 clinician-level FHA-related questions were entered separately into four LLMs: ChatGPT 3.5 (free version), ChatGPT 4.0 (updated, paid subscription), Gemini, and OpenEvidence. OpenEvidence was used only for clinician-based questions. Responses were evaluated by three expert reviewers blinded to the LLM used who rated them as accurate and complete, accurate but incomplete, or inaccurate. A fourth reviewer resolved discordant scores. Readability for patient-level questions was assessed using the Flesch Reading Ease Score (FRES) and word count. Lower FRES scores indicate more difficult reading. Accuracy and completeness were compared using odds ratios (95% CI) with ChatGPT 3.5 as the reference model, and differences in readability were analyzed using Friedman’s test. Results LLM performance varied across question types. For patient-level questions, ChatGPT 4.0 achieved the highest accuracy (9 of 11; 82%), followed by ChatGPT 3.5 and Gemini (each 8 of 11; 73%), with no statistically significant differences. Among clinician-level questions, OpenEvidence demonstrated perfect accuracy (15 of 15; 100%), compared with 93% for and 80% for ChatGPT 4.0 and Gemini. Completeness followed similar patterns, with OpenEvidence providing the most complete clinician responses (93%) and ChatGPT 4.0 the most complete patient-level responses (89%). Readability differed significantly among models ( p = 0.012), with Gemini producing the most readable patient-level content (median FRES 43.5 [IQR 36.8–53.4]) compared with ChatGPT 3.5 (30.6 [16.8–48.4]) and ChatGPT 4.0 (28.8 [22.1–37.6]). Word counts did not differ significantly ( p = 0.39). Discussion LLMs demonstrated good overall performance in answering FHA-related questions but often provided incorrect or incomplete information. Fine tuning field-specific data, engineered prompts, and obtaining human-in-the-loop feedback may help improve the accuracy of these models.

TPS2673 Background: The main challenge for developing CAR T therapies for solid tumors is the lack of targets that distinguish tumor from normal cells, resulting in on-target, off-tumor toxicity. Tmod logic-gated CAR T therapy addresses this challenge by incorporating 2 CARs on the same T cell: an activator targeting a marker on both tumor and normal cells, and a blocker targeting HLA-A*02 that inhibits CAR T activity against normal cells while allowing activation against tumor cells (with HLA-A*02 LOH), improving tumor selectivity and decreasing toxicity. Early safety results from 3 ongoing phase 1/2 clinical trials of logic-gated, Tmod CAR T therapy (EVEREST-1, EVEREST-2, and DENALI-1) have demonstrated manageable safety and tolerability in patients with advanced solid tumors (Grierson et al, SITC , 2024; Ward et al, SITC 2025; Specht et al, SABCS , 2025). Early efficacy results include the first ever reported complete response in a patient with non-small cell lung cancer following treatment with a CAR T-cell therapy (A2B694). A2B543 is an autologous Tmod CAR T therapy that contains the same Tmod construct as A2B694 with an added membrane-tethered IL-12 (memIL12) booster. Specifically, A2B543 is comprised of autologous Tmod cells transduced with 2 lentiviral vectors: one expressing both the HLA-A*02-targeted blocker and the mesothelin-targeted CAR activator; and a second expressing the memIL12 booster. Interleukin 12 (IL-12) is a potent, pro-inflammatory cytokine that plays a crucial role in inducing antitumor immune responses; however, systemic IL-12 can be prohibitively toxic (Jia et al, Front Immunol , 2022). In A2B543, expression of the memIL12 cassette is under the control of an NFAT promoter and is induced during antigen engagement or T cell activation. This inducible memIL12 is designed to reduce the toxicity associated with systemic IL-12 while enhancing the long-term potency and persistence of Tmod (Zhang et al, J Immunother Cancer , 2025). Methods: EVEREST-2 (NCT06051695) is a phase 1/2, open-label, nonrandomized study evaluating the safety and efficacy of A2B543 in adults with recurrent/metastatic mesothelin-expressing cancers with tumor-associated HLA-A*02 LOH, including mesothelioma, colorectal, non-small cell lung, pancreatic, or ovarian cancer. Patients are enrolled through BASECAMP-1 (NCT04981119), a master prescreening study that identifies patients with HLA LOH via next-generation sequencing and cryopreserves leukapheresis product. Upon progression, A2B543 is manufactured and then administered after lymphodepletion. The phase 1 primary objective is to evaluate the safety and tolerability of A2B543 and identify a recommended phase 2 dose (RP2D). The phase 2 primary objective is to assess overall response rate. Clinical trial information: NCT06051695 .

e16535 Background: RMC is a rare and highly aggressive malignancy that predominantly affects young individuals with sickle hemoglobinopathies. Due to its rarity, no validated prognostic models exist to guide clinical decision-making. We aimed to develop and internally validate a prognostic model for patients with RMC using routinely available clinical and laboratory variables. Methods: We analyzed a single-institution cohort of patients with RMC. Candidate variables were identified based on biological plausibility and represented in a directed acyclic graph. Missing data were handled via multiple imputation by chained equations ( m = 50). Variables were ranked using elastic net Cox regression ( α = 0.5, λ = λ min ) with stability selection derived from 100 bootstrap resamples per imputed dataset. Predictors achieving > 60% selection frequency were retained for a nested parsimony analysis. Bootstrap internal validation ( B = 2000) estimated optimism-corrected discrimination and calibration performance, with the calibration slope applied as global shrinkage to penalize final coefficients for overfitting. Clinical utility was evaluated via decision curve analysis (DCA) at 18- and 24-month horizons. Results: Among 180 patients (median age 29; IQR 23–37), 142 deaths occurred with a median follow-up of 12.4 months. The final model included four predictors (Table). The optimism-corrected c-index was 0.667 (optimism = 0.009), and the calibration slope was 0.964, indicating minimal overfitting. Calibration plots showed excellent predicted-observed agreement at 12, 18, 24, and 36 months. DCA showed net benefit across threshold probabilities of 10%–75% at 18 months and 10%–80% at 24 months compared to default strategies. In sensitivity analysis, inclusion of TP53 mutation status improved discrimination ( c -index 0.686) and model fit ( ΔAIC −10.6). An interactive web-based risk calculator was developed to facilitate clinical implementation. Conclusions: This study presents the first internally validated prognostic model for RMC, demonstrating acceptable discrimination and excellent calibration using routinely available variables. By stratifying patients into distinct risk groups, this model may inform treatment intensity—guiding escalation to multi-agent regimens or sequential chemotherapy cycling in high-risk patients, while identifying lower-risk patients who may benefit from de-escalation strategies such as metastasis-directed therapy for oligometastatic disease or consideration of cytoreductive nephrectomy. External validation is warranted. Variable Time Ratio 95% CI p value ECOG performance status 0.64 0.53–0.77 <0.001 Distal (non-retroperitoneal) lymph node metastases 0.69 0.52–0.92 0.011 Neutrophil-to-lymphocyte ratio 0.98 0.94–1.02 0.25 Corrected calcium (mg/dL) 0.77 0.56–1.06 0.10 Sensitivity Analysis Only TP53 Mutation 0.63 0.36-1-10 0.10

Abstract Aims To characterize global variation in cardiac rehabilitation (CR) staffing, indications, and prescribed dose by country income classification and compare findings with the International Council of Cardiovascular Prevention and Rehabilitation’s 2016 Global Audit. Methods and results Cross-sectional REDCap survey of Phase II/post-discharge CR programmes (May–September 2025). Outcomes were multidisciplinary team size/composition, accepted cardiac and non-cardiac indications, and centre-based CR dose. Comparisons were made across World Bank country income classifications and Audit decade (2016 vs. 2025). Of 7025 programmes identified globally, 1505 (median programme response rate = 62%/country) initiated a survey, from 90/113 (80%) countries with CR. CR was delivered by a multidisciplinary team of 7 (median; P25–P75 = 5–8; nurses, physiotherapists, cardiologists, and dietitians most common); teams were smaller in low-income countries (median = 4; P &lt; 0.001), and physician specialty varied. Non-low-income programmes consistently accepted (≥90%) patients with acute coronary syndrome, with programmes in low-income countries less often accepting related interventions (e.g. surgery: low-income 0% vs. high-income 97%; P &lt; 0.01), but non-cardiac indications were more frequently accepted (e.g. primary prevention, diabetes, and lung disease). Acceptance of heart failure increased compared with the previous Audit (70% vs. 87%; P &lt; 0.001). Centre-based programmes prescribed a median of 20 h (P25–P75 = 12–30), typically two sessions/week over 8 weeks. Globally, 65 (72%) countries prescribed a median ≥12 sessions/programme. Programmes in upper-middle-income countries prescribed more sessions (median = 24, P25–P75 = 12–36; P &lt; 0.001). Dose did not differ meaningfully between Audits (P = 0.07). Conclusion CR programmes globally are offered by small, but multidisciplinary teams. They accept guideline-indicated patients, with applicable variation by context. Insufficient dose in one-quarter of countries underscores investment need.

9567 Background: Resected stage IIB/C and microscopic stage IIIA/B/C/D melanoma presents a significant risk of recurrence risk of 37 to 62% at 5 years (yrs). While 1 year of adjuvant PD1 therapy reduces this risk by approximately half, the individual patient’s baseline risk without treatment and their specific benefit from adjuvant PD1 remain unknown. We aimed to generate two separate predictive models for recurrence – one for untreated and one for treated pts - to calculate the individualised benefit of adjuvant PD1. Methods: Pts with resected stage IIB/C or microscopic stage IIIA/B/C/D melanoma, either treated with adjuvant PD1 or untreated at 13 major melanoma centres, and with at least 2 years of follow-up from surgery were included. We analysed pts demographics, disease characteristics, blood parameters, pathological and imaging data at baseline, and clinical outcomes. Propensity scores were estimated using logistic regression with covariates associated with treatment in univariate screening (p<0.05). Separate penalised multivariable logistic regression models were built to predict recurrence for treated and untreated pts. A tool based on these models was created to calculate the individual patient benefit from adjuvant PD1. Results: A total of 3560 pts was included, divided into untreated (discovery n=2384 and validation n=597) and treated (discovery n=404 and validation n=175) cohorts. The model for untreated pts included age, gender, primary site, histological subtype, Breslow thickness, ulceration, mitosis, number and site of regional lymph nodes (LN), mutation status and LDH (AUC 0.70 in discovery, 0.69 in validation). The model for treated pts included age, gender, Breslow thickness, site of regional LN, and mutation status (AUC 0.69 in discovery, 0.61 in validation). ADAPT-M (ADjuvant Anti-PD-1 Tool for Melanoma) calculates the individualized benefit of adjuvant PD1. For example, patient A, a woman ≤45 years old with a primary head & neck melanoma (superficial spreading, thickness >1-2 mm, no ulceration, 1 mitosis/mm 2 ), 2 clinically occult LN metastases in the neck, NRAS mutant, and normal LDH, has a 12-month recurrence risk of 21.9% untreated vs 2.3% treated (benefit 19.6%), and a 24-month risk of 41.1% untreated vs 6.4% treated (benefit 34.7%). While, patient B, a man ≤45 years old with a primary melanoma in the lower limb (nodular, thickness >1-2 mm, no ulceration, 1 mitosis/mm 2 ), 2 clinically occult LN metastases in the groin, BRAF V600 mutant, and normal LDH, has a 12-month recurrence risk of 14.2% untreated vs 11.8% treated (benefit 2.5%), and a 24-month risk of 28.0% untreated vs 30.1% treated (no benefit). Conclusions: ADAPT-M, a clinical tool that estimate individualized recurrence risks with and without adjuvant anti-PD1 therapy, quantifies the absolute benefit of treatment for pts with high-risk resected melanoma, facilitating personalized adjuvant therapy decisions.