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ACCESS is a prospective, multicenter phase II trial evaluating peripheral blood stem cell (PBSC) transplantation using 4-7/8 HLA-mismatched unrelated donors (MMUD) with post-transplant cyclophosphamide (PTCy), tacrolimus, and mycophenolate. Adults undergoing first HCT with myeloablative (MAC) or reduced-intensity/nonmyeloablative (RIC/NMA) conditioning were enrolled, with donors aged 18-35 years and matched at 4/8-7/8 HLA loci by high-resolution typing. This expanded analysis includes all enrolled adult PBSC recipients, including the protocol-specified RIC/NMA cohort expansion, to improve precision of outcome estimates and provide descriptive analyses by HLA match level. Among 268 adults, 183 received 7/8 and 85 received <7/8 MMUD grafts; 82.4% of the <7/8 cohort received 6/8 grafts. Median follow-up among survivors was 11.9 months. At 1-year, overall survival was 78.6% (95% CI, 71.9-83.9) in the 7/8 cohort and 85.6% (95% CI, 76.0-91.5) in the <7/8 cohort. One-year relapse, non-relapse mortality, and GVHD-free relapse-free survival were 17.1%, 13.7%, and 51.1% versus 22.8%, 8.4%, and 54.6%, respectively. The cumulative incidence of grade II-IV and grade III-IV acute GVHD by day 100 was 36.6% and 7.7% in the 7/8 cohort versus 28.3% and 5.9% in the <7/8 cohort. Moderate-to-severe chronic GVHD at 1 year was 11.3% versus 7.7%, respectively. Among adult ACCESS recipients treated on a uniform young-donor PBSC/PTCy platform, short-term outcomes with predominantly 6/8 MMUD transplantation were encouraging. Because donor match level was not prospectively assigned and between-group comparisons were exploratory, these findings are descriptive and should not be interpreted as establishing equivalence with 7/8 MMUD transplantation. (Registered as NCT04904588 at CT.gov)

In this retrospective cohort study at a quaternary referral hospital, 829 adult patients supported by extracorporeal membrane oxygenation (ECMO) between January 1, 2014, and October 31, 2024, were screened for ventilator-associated pneumonia (VAP). The incidence of VAP in ECMO-supported patients was 17.7 per 1,000 ECMO days (venoarterial [VA] ECMO, 22.1 per 1,000 ECMO days; venovenous [VV] ECMO, 13.8 per 1,000 ECMO days). Median time from ECMO cannulation to diagnosis of VAP was 4 (interquartile range [IQR], 3–8; range 1–84) days. Gram-negative bacteria comprised most respiratory pathogens. A significant increase in minimum ECMO sweep was noted from 2 days before to 1 day after VAP diagnosis (0.79 L/min increase, p = 0.004). Only 38 of 153 patients (24.8%) met National Healthcare Safety Network (NHSN) VAP definitions. After creating a modified VAP definition, which included an ECMO sweep increase of 0.5 L/min as evidence of worsening respiratory status, 78 (51.0%) met the modified definition. Those who met the modified VAP definition had worse in-hospital (60.3% vs. 28.0%, p < 0.001), 30 day (33.3% vs. 17.3%, p = 0.023), and 90 day (53.8% vs. 25.3%, p < 0.001) mortality compared with those who did not meet the modified VAP definition. The incorporation of ECMO parameters into diagnostic criteria may improve detection sensitivity, but further validation is necessary before implementation.

Importance Patients undergoing cardiac surgery with cardiopulmonary bypass often require platelet transfusions for bleeding. Platelets are routinely stored at room temperature (20-24 °C) for up to 5 to 7 days; however, cold storage (1-6 °C) may allow for increased storage duration without loss of hemostatic function. Objective To determine the maximum cold-storage duration, up to 21 days, for which cold-stored platelets (CSPs) are noninferior or superior in hemostatic efficacy to room-temperature platelets (RTPs) when transfused in actively bleeding patients undergoing cardiac surgery with cardiopulmonary bypass. Design, Setting, and Participants A phase 3, multicenter, randomized, partially blinded, adaptive, noninferiority, storage duration–ranging trial conducted in pediatric and adult patients undergoing cardiac surgery with planned cardiopulmonary bypass at 27 sites in the US and Australia from December 2021 to March 2025. Statistical analysis was conducted from September 9 to October 3, 2025. Intervention Patients were randomized 2:1 to receive CSPs with a maximum of 21 days of storage vs RTPs with a maximum of 7 days of storage. Main Outcomes and Measures The primary outcome was a hemostatic efficacy score with values ranging from 1 to 5 and higher values indicating greater bleeding. The noninferiority margin was 1 point. The success criterion was met if at least 1 cold-storage duration of 7 days or more had a posterior probability of noninferiority of at least 97.5%. The secondary outcome was 24-hour chest tube output. Results Of the 1000 patients who underwent platelet transfusion, 989 were included in the primary analysis (650 CSPs and 339 RTPs). The cohort had a mean (SD) age of 42.1 (30.1) years and 67.8% were male. CSPs were noninferior to RTPs for the primary outcome, with a probability of greater than 99.9% for all cold-storage durations. Pooled across storage durations, CSPs had a mean difference from RTPs of 0.09 (95% credible interval, −0.06 to 0.23). Median (IQR) chest tube output at 24 hours (8.9 mL/kg [5.2-15.4] for CSPs vs 8.4 mL/kg [5.5-15.9] for RTPs; difference in medians, 0.4 [95% CI, −1.0 to 1.5]) was not statistically different between study groups. In a post hoc analysis, as all storage durations were noninferior, considering the CSPs as a single group, the hemostatic efficacy score was similar between both groups: mean (SD) of 3.08 (1.15) CSPs vs 2.99 (1.10) RTPs. There were no differences in venous or arterial thrombotic events, transfusion-associated adverse events, acute respiratory distress syndrome, kidney failure, septic shock, and mortality between the study groups, except for increased reexploration rates in the CSP group. Conclusions and Relevance For patients undergoing cardiac surgery, CSPs stored up to 21 days are noninferior to RTPs for the control of active surgical bleeding. Use of CSPs may allow for increased availability of platelets by reducing wastage and shortages and may allow for incorporation of platelets into inventory at locations where platelets cannot be maintained due to the 5- to 7-day shelf life of RTPs. Trial Registration ClinicalTrials.gov Identifier: NCT04834414

This Viewpoint discusses the importance of and considerations for including benzodiazepines in airline emergency medical kits for treating patients who experience seizure during a flight.

Abstract Incretin‐based therapies, including glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) and dual incretin agonists, are increasingly used for the management of diabetes, obesity, and cardiometabolic disease. Although their systemic benefits are well established, uncertainty remains regarding their safety in patients with neuroendocrine neoplasms (NENs), a biologically heterogeneous group of tumors with diverse molecular profiles. Preclinical studies suggest that GLP‐1 receptor activation may promote tumor growth in select receptor‐expressing models, although receptor expression varies widely across NEN subtypes and is often absent in common tumors such as ileal neuroendocrine tumors. Population‐level and retrospective clinical data have not demonstrated a consistent increase in oncologic risk but are limited by methodological constraints. In this expert consensus statement, the authors synthesize current evidence and provide a practical framework for the use of incretin mimetics in patients with NENs. The authors emphasize individualized risk assessment, shared decision‐making, and multi‐disciplinary collaboration, balancing potential but unquantified oncologic risks against substantial cardiometabolic benefits. Until prospective data are available, careful patient selection, dose optimization, and close clinical and radiologic surveillance remain essential to guide safe and effective use of these agents in this population.

ABSTRACT Herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and varicella-zoster virus (VZV) are associated with a range of clinical manifestations depending on the anatomical site of infection. HSV and VZV lesions often exhibit similar phenotypical characteristics, making clinical differentiation challenging. Detection and differentiation of HSV-1, HSV-2, and VZV are essential for diagnosis and treatment management. An automated multiplex real-time PCR assay, Alinity m HSV 1 & 2/VZV assay, was developed to detect and differentiate HSV-1, HSV-2, and VZV. The assay was validated for use with cutaneous and mucocutaneous lesion swab specimens collected in commercial viral transport media from symptomatic patients. The assay demonstrated a limit of detection of 5.90 TCID 50 /mL for HSV-1, 2.07 TCID 50 /mL for HSV-2, and 0.055 TCID 50 /mL for VZV. Testing with clinical swab specimens demonstrated greater than 95% clinical sensitivity and specificity for all three analytes. The Alinity m HSV 1 & 2/VZV assay provides a reliable and accurate method for detection and differentiation of HSV-1, HSV-2, and VZV in lesion swab specimens for improved diagnostic accuracy and patient management. IMPORTANCE Herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and varicella-zoster virus (VZV) can cause skin and mucocutaneous lesions that often appear clinically similar, making accurate diagnosis difficult without laboratory testing. Rapid and reliable identification of the causative virus is important because patient counseling, treatment decisions, and infection management differ among these infections. In this multicenter study, a fully automated molecular assay was evaluated that simultaneously detects and differentiates HSV-1, HSV-2, and VZV from a single-lesion swab specimen. Testing of more than 1,200 clinical specimens demonstrated high sensitivity and specificity for all three viruses. The assay also offers a streamlined workflow with minimal hands-on time and rapid turnaround. These findings support the use of this multiplex assay as a practical diagnostic tool that can improve laboratory efficiency and provide clinicians with timely, accurate results to guide patient care.

ABSTRACT Background Percutaneous left atrial appendage occlusion (LAAO) is an alternative strategy for stroke prevention in patients with nonvalvular atrial fibrillation (AF) with contraindications to long‐term oral anticoagulation therapy. However, evidence comparing the long‐term outcomes of LAAO with those of direct oral anticoagulants (DOAC) remains limited. Methods A systematic search was conducted across PubMed, Scopus, and the Cochrane databases through April 2026. Co‐primary outcomes were major adverse cardiovascular and cerebrovascular events (MACCE; composite of cardiac death, stroke, or systemic embolism) and net adverse clinical events (NACE; composite of MACCE and non‐procedure‐related bleeding). Secondary endpoints included individual components of co‐primary endpoints, ischemic and hemorrhagic stroke, all‐cause death, major or clinically significant bleeding (procedure + non‐procedure related), and stroke or systemic embolism. The random‐effects model was used to generate risk ratios (RRs) and 95% CIs. Results Four randomized controlled trials comprising 5890 AF patients and a median follow‐up of 3 years were included. There was no significant difference between LAAO and DOAC therapy in the risk of MACCE (RR 1.17; 95%CI 0.96–1.41; I 2 = 0%) or NACE (RR 0.89; 95%CI 0.65–1.24; I 2 = 85%). Both LAAO and DOAC therapy were similar in risk of cardiac death, stroke, systemic embolism, hemorrhagic stroke, ischemic stroke, all‐cause mortality, stroke or systemic embolism, and pericardial effusion. LAAO was associated with a lower risk of non‐procedure‐related bleeding (RR 0.60; 95%CI 0.47–0.76; I 2 = 59%). Conclusion LAAO demonstrated efficacy comparable to DOAC therapy in reducing the risk of MACCE, NACE, and ischemic events, while significantly reducing the risk of non‐procedure‐related bleeding. Our findings support a tailored approach to stroke prevention in AF, wherein LAAO serves as an effective alternative for patients with contraindications to DOAC therapy.

The kinesin-5 motor protein KIF11 is crucial for mitotic spindle assembly, driving the separation of spindle poles through microtubule sliding. Src-family kinases phosphorylate KIF11 at multiple tyrosine residues within its motor domain, but the mechanistic consequences of these modifications remain unclear. Here, we dissect the role of phosphorylation at Y211 using phospho-mimetic (Y211E) and nonphosphorylatable mutants (Y211F) in biochemical, biophysical, and cellular assays. Optical trapping and Förster resonance energy transfer analyses reveal that Y211 phosphorylation slows neck-linker docking, reducing motor velocity and force generation under load. In human cells, Y211E expression impairs bipolar spindle formation and decreases spindle pole separation velocity, while Y211F shortens steady-state spindle length. Fluorescence recovery after photobleaching analyses show that Y211E accelerates motor turnover on spindle microtubules, consistent with the mutant motor’s heightened load sensitivity. Together, these findings support a model in which Src-mediated phosphorylation at Y211 acts as a rheostat to tune KIF11 mechanochemistry and spindle assembly dynamics, linking cancer-relevant kinase signaling to mitotic force generation.

Abstract Objectives To systematically evaluate the certainty of evidence for treatment strategies across age groups and mood phases in bipolar disorder, and develop an open access web platform to facilitate shared decision making. Design Living umbrella review, evaluation, analysis, and communication hub (U-REACH) project. Data sources PubMed, PsycInfo, and Cochrane library databases, from inception to 19 November 2024. Eligibility criteria for selecting studies Systematic reviews with network or pairwise meta-analyses of randomised controlled trials of pharmacological, nutraceutical, psychosocial, brain stimulation, or circadian rhythm based treatments, administered as monotherapy (without concurrent interventions), augmentation treatment (interventions added to an ongoing treatment regimen), or combination treatment (simultaneous initiation of two different interventions), examining any age group, bipolar disorder phase (ie, acute bipolar depression, mania or mixed episodes, or maintenance), treatment, control, or outcome. Results 77 studies met the inclusion criteria (21 network meta-analyses and 56 pairwise meta-analyses), including 116 unique pharmacological (n=74), brain stimulation (n=18), nutraceutical (n=13), psychosocial (n=8), and circadian rhythm based (n=3) treatments as monotherapy, augmentation, or combination therapy, along with five control interventions. These studies covered 133 unique outcomes (45 efficacy outcomes and 88 safety outcomes) resulting in 2510 meta-analyses with Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) ratings of the certainty of the evidence as high (n=236), moderate (n=827), low (n=986), and very low (n=461). A communication hub, the Evidence Based Interventions for Bipolar Disorder (EBI-BD) platform, was developed and the full results are freely available ( https://ebibd-database.org ), including the preference based tool (12 interventions and 17 safety outcomes). Interventions effective across outcomes varied by phases. For bipolar depression, effective interventions in adults were cariprazine, divalproex or valproate, fluoxetine, ketamine (augmentation), lamotrigine, lumateperone, lurasidone, olanzapine, olanzapine with fluoxetine, and quetiapine, whereas effective interventions in children and adolescents were lurasidone and olanzapine with fluoxetine. For mania episodes, effective interventions in adults were aripiprazole, asenapine, carbamazepine, cariprazine, divalproex or valproate, haloperidol, lithium, olanzapine, paliperidone, quetiapine (also augmentation), risperidone (also as augmentation), tamoxifen, and ziprasidone, whereas effective interventions in children and adolescents were aripiprazole, asenapine, olanzapine, quetiapine, and risperidone. For maintenance, interventions effective across outcomes in adults were aripiprazole (also the long acting injectable formulation), asenapine, divalproex or valproate, lithium, olanzapine, group psychoeducation (augmentation), quetiapine, and risperidone long acting injectable formulation. Interventions effective across phases were aripiprazole (also as augmentation and as a long acting injectable formulation), asenapine, cariprazine, cognitive behavioural therapy (augmentation), divalproex or valproate, lamotrigine, lithium, olanzapine (also as augmentation), paliperidone, quetiapine (also as augmentation), and risperidone (also as augmentation and the long acting injectable formulation) (adults). Treatment effects by neuroscience based nomenclature classes are also reported. Conclusions The EBI-BD tool can help clinicians make evidence based, personalised treatment decisions for bipolar disorder. This resource can inform clinical guidelines and provides a foundation for continuously improving bipolar disorder care as new evidence emerges. Trial registration Open Science Framework https://osf.io/pjmvn/ Readers’ note This is a living systematic review and may be updated in the next two years if additional evidence emerges.