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Importance Suicide is a leading cause of death among young people and an escalating public health crisis. Objective To assess the effectiveness and harms of available treatments for suicidal thoughts and behaviors among youths at heightened risk for suicide. Evidence Review A systematic review was conducted searching databases including MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, and various gray literature sources from January 1, 2000, to September 26, 2024. We included randomized clinical trials, comparative observational studies, and before-after studies of psychosocial interventions, pharmacologic interventions, neurotherapeutics, emerging therapies, and combination therapies. Eligible patients were youths (aged 5-24 years) with heightened risk for suicide, adolescents from racial and ethnic minority groups known to be at increased risk of suicide, or those exposed to crime or violence. Pairs of independent reviewers selected and appraised studies. Findings This review included 65 studies (33 randomized clinical trials, 13 comparative observational studies, and 19 before-after studies) reporting on 14 534 patients (median age, 15.1 years; 75.1% female patients). Psychosocial interventions comprised psychotherapy interventions (33 studies; cognitive behavioral therapy, dialectical behavioral therapy, collaborative assessment and management of suicidality, dynamic deconstructive psychotherapy, attachment-based family therapy, and family-focused therapy), acute (ie, 1-4 sessions or contacts) psychosocial interventions (19 studies; safety planning, family-based crisis management, motivational interviewing crisis interventions, continuity of care after crisis, and brief adjunctive treatments), and school- or community-based psychosocial interventions (13 studies; social network interventions, school-based skills interventions, suicide awareness or gatekeeper programs, and community-based, culturally tailored adjunct programs). Dialectical behavior therapy showed moderate strength of evidence for reducing suicidal ideation. Other categories of psychosocial treatments showed insufficient to low strength of evidence for reducing suicidal outcomes. None of the studies evaluated adverse events. The evidence base on pharmacologic treatment for youths at risk of suicide was largely nonexistent. Conclusions and Relevance This systematic review found that the current evidence on available interventions targeting youths at heightened risk of suicide is uncertain. Medication, neurotherapeutics, and emerging therapies remain unstudied among this population. The limited evidence base calls for the development of novel, developmentally and trauma-informed treatments, as well as multilevel interventions to target the increasing suicide risk among youths.

ABSTRACT Background Right bundle branch block (RBBB) has a high prevalence among heart transplant recipients and could influence outcomes. Crucially, the predictors of RBBB development after heart transplantation are not well‐established. Our study aims to evaluate the preoperative predictors and outcomes of RBBB following heart transplantation. Methods PubMed, Scopus, Web of Science, and Cochrane Library were searched up to November 15, 2024, to identify studies comparing heart transplant recipients with RBBB and without RBBB. Random‐effects models were used to estimate the pooled mean difference (MD) and risk ratios (RRs) with 95% confidence intervals (95% CIs). Results Nine studies incorporating 1507 patients were included. Patients who developed RBBB had higher graft ischemia time [MD: 10.0; 95% CI: 2.00–17.91; p = 0.01] and pulmonary vascular resistance (PVR) (MD: 0.44; 95% CI: 0.21–0.68; p < 0.001). There was no significant difference between RBBB and non‐RBBB patients in terms of pulmonary artery pressure (MD: 1.83; 95% CI: ‐0.86–4.53; p = 0.18) or donor age (MD: 1.51; 95% CI: ‐0.30– 3.31; p = 0.10). There was no significant difference in the prognosis of RBBB patients in terms of acute rejection (RR: 1.06; 95% CI: 0.70–1.61; p = 0.78), chronic rejection (RR: 0.92; 95% CI: 0.60–1.41; p = 0.70), or mortality (RR: 1.87; 95% CI: 0.81–4.31; p = 0.14). Conclusion Despite the association of RBBB with graft ischemia time and PVR, post‐transplant RBBB had no significant impact on mortality or graft rejection. Further research focusing on the identification period and applied definition of RBBB is recommended.

Importance The Implantable Neurostimulator for the Treatment of Parkinson’s Disease (INTREPID) trial was a randomized, double-blind, sham-controlled study of subthalamic nucleus (STN) deep brain stimulation (DBS) for the treatment of Parkinson disease (PD). Objective To evaluate the long-term (5-year) outcomes and safety of STN-DBS for PD. Design, Setting, and Participants This was a prospective, randomized (3:1), 12-week double-blind sham-controlled study at 23 movement disorder centers across the US with an open-label 5-year follow-up. Patients were implanted and followed up with the Vercise DBS system from May 2013 to December 2022. Eligibility required diagnosis of bilateral idiopathic PD with more than 5 years of motor symptoms, more than 6 hours per day of poor motor function, modified Hoehn and Yahr Scale scores higher than 2, Unified Parkinson’s Disease Rating Scale (UPDRS-III) score of 30 or higher (medication-off state), and 33% or higher improvement in UPDRS-III medication-on score. Intervention Bilateral STN-DBS for moderate to advanced PD. Main Outcomes and Measures Primary outcomes included changes in UPDRS and dyskinesia scores, quality-of-life measures, and safety assessments. Exploratory analyses included medication reduction and DBS association with motor signs. Results A total of 313 patients were enrolled with 191 receiving the DBS system, and 137 participants (72%) completed the study. The study population had a mean (SD) age of 60 (7.9) years, with 139 (73%) male participants. Motor function without medication as measured by UPDRS-III improved from a mean (SD) of 42.8 (9.4) to 21.1 (10.6) at year 1 (51%; 95% CI, 49%-53%; P &amp;lt; .001) and 27.6 (11.6) at year 5 (36%; 95% CI, 33%-38%; P &amp;lt; .001). Activities of daily living without medication as measured by UPDRS-II improved from a mean (SD) of 20.6 (6.0) to 12.4 (6.1) at year 1 (41%; 95% CI, 38%-42%; P &amp;lt; .001) and 16.4 (6.5) at year 5 (22%; 95% CI, 18%-23%; P &amp;lt; .001). Dyskinesia scores decreased from 4.0 (5.1) to 1.0 (2.1) at year 1 (75%; 95% CI, 73%-75%; P &amp;lt; .001) and to 1.2 (2.1) at year 5 (70%; 95% CI, 63%-75%; P &amp;lt; .001). The levodopa equivalent dose was reduced by 28% at year 1, remaining stable at year 5 (28%; 95% CI, 26%-31%; P &amp;lt; .001). The most common serious adverse event was infection (9 participants). Ten deaths were reported, none related to the study. Conclusions and Relevance Although STN-DBS outcomes declined slightly, possibly due to the progressive nature of the disease, patients with PD sustained significant improvement in motor and activities of daily living scores, along with a stable reduction in anti-parkinsonian medication over the 5-year follow-up period.

Wastewater treatment is evolving rapidly with the advent of advanced deep-learning AI, graph-based, and physics-informed approaches. This study integrates graph neural networks, physics-informed neural networks, and multi-agent reinforcement learning within a hybrid digital-twin framework, evaluated on multi-scale real-world datasets. The developed models achieved over 90% dissolved organic carbon removal and reduced aeration energy by up to 22% while maintaining process stability. The results demonstrate that graph–physics synergies not only boost operational efficiency but also reveal critical trade-offs between energy savings and hydraulic performance. Our findings establish a new benchmark for resilient, low-carbon wastewater treatment, highlighting the transformative role of data-driven system design.

Background and objectives Arteriovenous malformations (AVMs) with perinidal aneurysms and single draining vein are associated with an elevated risk of rupture and increased procedural complexity. The role of preoperative embolization in this high-risk anatomical subset remains unclear. This study aimed to evaluate the safety and efficacy of microsurgery with preoperative embolization, compared with microsurgery alone in patients with such AVMs. Methods We conducted a multicenter retrospective analysis of an AVM registry from the MISTA (Multicenter International Study for Treatment of Brain AVMs) consortium and included AVMs with perinidal aneurysms and a single draining vein. Baseline characteristics, angiographic outcomes, functional outcomes, and complication rates were compared. Propensity score weighting (PSW) using the covariate balancing method was applied to adjust for baseline differences. Results Out of a total of 1919 patients, 65 met the inclusion criteria; 45 patients underwent preoperative embolization followed by microsurgery, and 20 underwent microsurgery alone. After adjustment, complete obliteration rates were similar between groups (OR 0.87, 95% CI 0.04 to 16.33, P=0.92), as were rates of functional independence at discharge and follow-up. Overall complication, symptomatic complication, and mortality rates did not differ significantly between groups. However, permanent complications were significantly lower in patients with preoperative embolization (OR 0.06, 95% CI 0.004 to 0.84, P=0.03). Discussion In patients with AVMs featuring perinidal aneurysms and single draining vein, preoperative embolization followed by microsurgery was associated with fewer permanent complications and no increase in adverse outcomes compared with microsurgery alone. However, given the small number of events, this finding should be interpreted cautiously.

Abstract Clinical question What are the benefits and harms of medications for adults with type 2 diabetes at varied risks of cardiovascular and kidney related complications? Context Emerging clinical trials of novel medications have demonstrated benefits on cardiovascular, kidney, and weight related outcomes in people with type 2 diabetes. Dynamically updated practice guidelines adhering to standards of trustworthiness are necessary in response to a rapidly evolving evidence base and the availability of multiple medication alternatives. This living practice guideline incorporates the latest available medications and evidence and provides recommendations stratified by risks of cardiovascular and kidney complications to inform diabetes management. Recommendations The panel issued risk-stratified recommendations regarding four prioritised medications for adults with type 2 diabetes (SGLT-2 inhibitors, GLP-1 receptor agonists, finerenone and tirzepatide): • Lower risk (three or fewer cardiovascular risk factors without established cardiovascular disease (CVD) or chronic kidney disease (CKD)): weak recommendation against SGLT-2 inhibitors or GLP-1 receptor agonists. • Moderate risk (more than three cardiovascular risk factors without established CVD or CKD; or established CVD and/or CKD at lower risk of complications): weak recommendation in favour of SGLT-2 inhibitors or GLP-1 receptor agonists; and a weak recommendation against finerenone in adults with CKD. • Higher risk (established CVD and/or CKD at higher risk of complications, or established heart failure): strong recommendation in favour of SGLT-2 inhibitors or GLP-1 receptor agonists; and a weak recommendation in favour of finerenone in adults with CKD. • Across risk strata: weak recommendation in favour of tirzepatide in adults with obesity. About this guideline and how it was created An international panel including two patient partners, clinicians, and methodologists produced these recommendations. The panel followed standards for trustworthy guidelines and used the GRADE approach, explicitly considering the balance of benefits, harms and burdens of treatment from an individual patient perspective. Recommendations were informed by a linked living systematic review and network meta-analysis evaluating relative benefits and harms updated to 31 July 2024; and by linked systematic reviews addressing risk prediction models and values and preferences of adults with type 2 diabetes. Candidate therapeutics are prioritised based on availability of sufficient randomised trial data, relevance to a global audience and likelihood of changing practice. This is the first version of the living guideline. The guideline is part of the BMJ Rapid Recommendations series. MAGICapp displays the most recent version of the guideline and full content including evidence summaries and decision aids; major updates will be published in The BMJ . We encourage re-use, adaptation and translation of these living guidelines, and recognise that the lack of availability or high costs of some medications may be prohibitive and will impact on how these recommendations are implemented across different health care systems.

Abstract Glioblastoma is the most common type of malignant primary brain tumor and a major cause of morbidity and mortality. In 2021, the World Health Organization updated the classification of Central Nervous System (CNS) tumors to restrict glioblastomas to isocitrate dehydrogenase-wildtype (IDHwt) tumors, improving understanding of the prognosis and optimal therapy for these tumors. This revision also enables more homogeneous populations of patients to be enrolled in clinical trials, facilitating the evaluation of novel therapies. In this updated consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO), the current management of patients with glioblastoma is discussed. In addition, novel therapies such as immunotherapies, viral therapies, targeted molecular therapies, theranostics, and antibody–drug conjugates will be reviewed, as well as the current challenges and future directions for research.

In 2023, the VAS international working group on Buerger’s Disease (BD) recommended two diagnostic criteria based on a prior Delphi study: “definitive” and “suspected”. The “definitive” criteria are history of smoking, typical angiography, and typical histopathological features. All three features are mandatory to confirm a “definitive” diagnosis of BD. The conundrum is—what features should be considered typical of BD angiography? According to this review, segmental occlusion of infrapopliteal arteries, corkscrew collaterals that appear to continue the occluded arterial segment (Martorell’s sign) or bypass the segmental occlusion, absence of atherosclerotic plaque or aneurysm could differentiate BD from ASO. Hence, for “typical” BD angiography, these manifestations should certainly be considered. However, data for differentiating angiography patterns of BD from the small- and medium-sized vasculitis including Behcet’s disease, scleroderma, hepatitis associated vasculitis, and anti-phospholipid syndrome are limited. Further studies for investigating the angiography pattern in BD patients in early and late presentation of BD, particularly in the patients with long-term follow up, are highly recommended.