Citations

Abstract Aims Infective endocarditis (IE) is a serious and potentially fatal complication of mitral valve (MV) intervention. There are limited data comparing the incidence of IE after MV repair compared with bioprosthetic MV replacement. The aim of this study was to analyse the incidence and timing of IE after MV repair compared with bioprosthetic valve replacement, in both surgical and transcatheter patient populations. Methods and results A literature search of Medline, Embase, and Cochrane Library (January 2000—September 2025) was conducted. Pooled IE incidence rates were derived using random-effects models. Eighty-two studies (80 939 patients, total follow-up 350 252 patient-years) were included. The overall incidence rate of IE was 0.97 per 100-patient-years (95% confidence interval [CI] 0.71–1.34). IE was more common after surgical MV replacement (SMVR) than surgical MV repair (SMVr): incidence rate 0.93 (95% CI 0.41–1.81) vs 0.39 (95% CI 0.25–0.62) per 100-patient-years, incidence rate ratio (IRR) 2.34 (95% CI 1.06–5.18), P = .035. The incidence of IE after transcatheter MV replacement (TMVR) was comparable to transcatheter MV repair (TMVr) (2.88 [95% CI 1.91–4.33] vs 1.70 [95% CI 0.84–3.43] per 100-patient-years), IRR 1.56 (95% CI 0.73–3.34), P = .250. The cumulative incidence of IE following SMVR was significantly higher than following SMVr at 1- and 2-years post-procedure, but not at 6 months. Conclusions IE is an infrequent complication of mitral valve intervention. The incidence of IE following SMVR is significantly higher than following SMVr, while the incidence of IE following TMVR is numerically but not significantly higher than following TMVr. Reducing IE risk after mitral intervention is a clinical and research priority.

Importance Transcatheter tricuspid valve replacement (TTVR) demonstrated superior outcomes over medical therapy in patients with severe tricuspid regurgitation (TR) in the Edwards EVOQUE Transcatheter Tricuspid Valve Replacement: Pivotal Clinical Investigation of Safety and Clinical Efficacy Using a Novel Device II (TRISCEND II) randomized clinical trial, and received regulatory approval in the US in 2024. Contemporary real-world data on its effectiveness and safety remain limited. Objective To evaluate 30-day clinical, echocardiographic, and health status outcomes of TTVR in real-world use. Design, Setting, and Population Retrospective cohort study of all consecutive patients who underwent TTVR in the US from February 2024 through March 2025 in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Patients had symptomatic, severe TR despite optimal medical therapy and TTVR was deemed appropriate by a heart team. Statistical analysis was conducted from September 2025 to February 2026. Exposure Device-enabled TTVR. Main Outcomes and Measures Thirty-day event rates (all-cause death, stroke, bleeding, new cardiac implantable electronic device [CIED] implantation, heart failure hospitalizations), TR reduction, and changes in health status (New York Heart Association [NYHA] functional class and Kansas City Cardiomyopathy Questionnaire Overall Summary [KCCQ-OS] score) are reported. Subgroup analyses examined the impact of baseline CIED status on outcomes. Results Among 1034 attempted procedures at 82 centers (mean [SD] age, 77.1 [10.6] years; 69.1% female; 73.2% NYHA functional class III/IV), a valve was successfully implanted in 1017 patients (98.4%). Mild or less TR was achieved in 98.4% of patients post procedure and in 97.7% at 30 days. At 30 days, all-cause mortality was 3.1%; stroke, 0.2%; bleeding, 7.9%; new CIED, 15.9% in CIED-naive patients; and heart failure hospitalization, 3.1%. There were significant improvements in NYHA functional class (class I/II, 82.7%; P < .001) and mean KCCQ-OS score (22.4 points; P < .001) from baseline to 30 days. There were no significant differences in 30-day mortality ( P = .47), heart failure hospitalization ( P > .99), and functional outcomes ( P = .55) when patients were stratified by baseline CIED status. Conclusions and Relevance Early US real-world experience with TTVR confirms safety and effectiveness in patients with severe TR. Thirty-day outcomes are consistent with the TRISCEND II pivotal trial, demonstrating acceptable safety, near-complete TR elimination, and significant health status improvements in an older, comorbid population. Rates of new CIED implantation and bleeding were lower than randomized clinical trial experience.

Abstract Background Immigrants to the United States often face challenges from limited healthcare access and less healthy environments which contribute to rising obesity and cardiovascular risk. Purpose To assess the feasibility and effectiveness of a community-based social network intervention for cardiovascular risk reduction among Hispanic and Somali adults. Methods A social network-informed, community-based participatory research-derived health promotion intervention was delivered by Hispanic and Somali lay health promoters (HPs) to members of their social networks over 1 year (12 biweekly sessions in months 0-6; 12 biweekly check-ins in months 7-12). Using a closed-cohort stepped wedge cluster randomized design, social networks were randomly assigned to receive the intervention immediately or after a delay of 1 year. Measurements at baseline, 6 months, and 12 months were derived from 6 of the American Heart Association’s “Life’s Simple 7”: BMI, blood pressure, fasting glucose, cholesterol, physical activity and dietary quality (range 0-12, with higher values indicating lower cardiovascular risk). Waist circumference and proportion of participants who achieved >5% body weight loss were also assessed. Results Four hundred seventy-five participants were enrolled among 51 HPs (29 Hispanic; 22 Somali). There was a statistically significant improvement in cardiovascular risk in the intervention group (n = 246) compared with controls (n = 229) at 6 months (0.4 [1.8] vs. −0.1 [1.7]; P = .03) that was not sustained at 12 months (0.5 [1.9] vs. 0.3 [1.8]; P = .38). There was a statistically significant higher proportion of participants who lost >5% of body weight in the intervention group compared with controls at 12 months (37% [15] vs. 18% [7.9]; P = .02). Reductions in weight and waist circumference in the intervention group compared with controls did not achieve statistical significance. Conclusion A social network intervention, delivered by lay HPs was feasible and resulted in a modest improvement of cardiovascular risk and clinically significant weight loss. Clinical Trial Identification Number NCT05136339.

Abstract Scientific foundation models learn high-dimensional representations from diverse data modalities, yet what they encode and how to extract that knowledge remain open questions. Here we show that probing the internal representations of Evo 2, a 7-billion-parameter genomic foundation model, enables accurate and interpretable genetic variant effect prediction. We introduce a covariance-based probe that captures second-order structure from Evo 2 sequence embeddings to predict variant pathogenicity across variant types and functional consequences, matching or exceeding specialized predictors within their domains. To ground these predictions in known biological mechanisms, we train a complementary panel of probes on existing annotations to detect which genomic properties are disrupted by a variant. This categorized evidence is then integrated with each variant’s genomic context through a language model to generate variant-specific mechanistic hypotheses. Our pathogenicity predictions correlate with experimental measures of variant function, clinical penetrance, and biobank disease associations while the mechanistic hypotheses are consistent with expert reviews, known mechanism classes, and downstream molecular readouts. We release pathogenicity scores, disruption profiles, and contextualized interpretations for 4.2 million variants from the ClinVar database as an open resource through the Evo Variant Effect Explorer (EVEE). More broadly, this structured probing approach offers a general framework for interrogating foundation models across scientific disciplines and grounding their outputs in existing domain concepts.

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Three patients with different neurologic diseases—amyotrophic lateral sclerosis, poliomyelitis, and idiopathic bilateral diaphragm paralysis—and with chronic ventilatory failure were successfully ventilated with negative pressure. This noninvasive ventilatory technique uses a chest cuirass and provides an alternative to tracheostomy and positive-pressure ventilation. As a result of the benefits that these three patients received, we conclude that the cuirass remains an acceptable method of ventilation for some patients with chronic neurologic disease.

ABSTRACT Background Quality of life and symptom burden of patients with myelofibrosis are well recognized and compounded in those with anemia; however, the effects of transfusion burden or anemia severity on quality of life have not been comprehensively characterized. This post hoc descriptive analysis explored the association between transfusion status or hemoglobin improvement and patient‐reported outcomes (PROs). Methods The analysis used pooled populations across treatment arms from 3 clinical trials (SIMPLIFY‐1, SIMPLIFY‐2, MOMENTUM); sample sizes for each PRO measure were dependent on the trials in which they were administered. Results At both baseline and week 24, transfusion independence was associated with umerically greater mean SF ‐36v2 and EORTC QLQ ‐ C30 scores than transfusion dependence; in the subgroup that was transfusion dependent at baseline, those who achieved transfusion independence at week 24 had greater PRO improvements than those who remained reliant on transfusions. Regardless of transfusion status, patients who achieved a hemoglobin improvement ≥ 1, ≥ 1.5, or ≥ 2 g/ dL from baseline also had clinically meaningful improvements in quality of life (assessed via mean EQ ‐ 5D ‐ 5L or SF ‐36v2 scores) and symptoms (assessed via PGIC or MPN ‐ SAF / MFSAF Total Symptom Score) at week 24 compared with those who did not. Conclusions Collectively, these results provide preliminary insights into the associations of transfusion status and anemia severity with quality of life in myelofibrosis; as current PRO measures do not directly evaluate the relationship between symptoms such as fatigue and anemia, development of new measures to more comprehensively capture the patient experience for those with anemia in myelofibrosis may be warranted. Trial Registration NCT01969838, NCT02101268, NCT04173494

The brain is a highly recurrent, nonlinear network hypothesized to remain near the edge of chaos for optimal performance. Excitation and inhibition must be balanced precisely within every neuron to ensure a consistent level of dynamical stability and rich dynamics during transition to chaos. However, analysis of biologically realistic synaptic weight matrices suggests that sparsity and low-dimensional structure interact such that there is no known synaptic balancing rule that constrains the stability (i.e., eigenvalues) of the network while also preserving computationally useful, low-dimensional structure. Further, even if a network were well-balanced, external stimuli interact with the nonlinear activation functions to unbalance the network in real time. Therefore, the brain must utilize dynamic, rather than static, mechanisms to actively regulate its level of stability. We propose that two specific adaptation mechanisms, spike frequency adaptation (SFA) and short-term synaptic depression (STD), continuously modulate the effective connectivity, keeping the brain near the edge of chaos and reducing dynamical fluctuations caused by stimuli. This theoretical framework links intrinsic and synaptic negative feedback mechanisms to network-level dynamics. This offers an explanation of why data-driven modeling of human brain signals, an exciting and useful method in epilepsy and anesthesiology research, seems to require linear time-varying (LTV) models which are refit every half second: difficult to observe adaptation processes interact with nonlinearities to make connectivity effectively dynamic at the macroelectrode scale. We suggest that compromised adaptation may underlie neurological conditions characterized by altered excitability, and that targeted brain stimulation could be used to probe the regulatory action of adaptation.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) provide recommendations for the treatment of patients with NSCLC, including diagnosis, primary disease management, surveillance, and subsequent treatment. The panel has updated the list of recommended targeted therapies based on recent FDA approvals and clinical data. This selection from the NCCN Guidelines for NSCLC focuses on treatment recommendations for advanced or metastatic NSCLC with actionable biomarkers.