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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

Abstract Purpose To assess if PSA density (PSAD) velocity is a predictor of clinically significant prostate cancer (csPCa). Methods Patients undergoing prostate MR for suspected csPCa between 2017 and 2023 were included. Of these, patients who underwent two or more MR exams within 0.3 to 2 years to each other and pathological confirmation within 1 year after the last MR were identified. PI-RADS score, patient age, screening or active surveillance (AS), PSA, PSAD, PSA-velocity and PSAD-velocity were assessed if they were predictor of csPCa. For univariate analysis, all variables were assessed using student t or chi-square tests. When variables were considered significant, variables were entered into multivariate logistic regression model. Results 23,244 MRs were performed (17,703 screening, 5,541AS). 1,174 patients (mean age: 65.9) met the inclusion criteria, and 550 patients (47%) were diagnosed with csPCa. On univariate analysis, PI-RADS score (p<.0001), age (67.0 vs 64.9, p<.0001), AS exam (67% vs 59%, p = 0.004), PSA (7.5 vs 6.6, p<.001 ), PSAD (0.16 vs 0.12, p<.0001) and PSAD-velocity (0.023 vs 0.012, p = 0.005 ) were predictors of csPCa but PSA-velocity (1.4 vs 1.2, p=.4) was not. On multivariate analysis, PI-RADS score (p<.0001), age (p<.0001), AS exam (p<.0001), PSA (p<.0001) and PSAD (p<.0001) remained significant predictors, but PSAD-velocity was not (p=.1). Conclusions Higher PSAD-velocity was associated with presence of csPCa on univariate analysis but not on multivariate analysis when combined with other predictors such PI-RADS score, age, and PSAD.

Background Randomized trials have shown equivocal outcomes between a direct aspiration as first-pass technique (ADAPT) and stent retriever (SR) stroke thrombectomy, yet whether specific patient subgroups benefit differentially from one technique over the other remains unknown. Methods In this retrospective multicenter cohort study, patients with large vessel occlusion were included, and those who underwent ADAPT versus SR first-pass thrombectomy (either as standalone or combined with aspiration) were compared. The primary outcome was a composite of first-pass effect (FPE, modified Thrombolysis In Cerebral Infarction (mTICI) 2c or better with one attempt) with no symptomatic intracranial hemorrhage (sICH). A causal forest model was used to estimate the conditional average treatment effect (CATE) for each patient, with larger CATEs indicating that ADAPT is expected to be more advantageous. Patients were stratified by CATEs, and outcomes were compared between treatment groups. Results Among 6700 included patients, ADAPT (n=3695, 55%) was associated with a higher rate of FPE with no sICH (39.9% vs 26.9%; adjusted OR (aOR) 2.07, 95% CI 1.77 to 2.41, P<0.001). The causal forest identified significant treatment effect heterogeneity (interaction P<0.001), where ADAPT was more advantageous in more recent years and among patients with M1 occlusions presenting in earlier time windows. Low-CATE patients showed no statistically significant difference between techniques (aOR 0.91, 95% CI 0.57 to 1.45, P=0.70), while medium- and high-CATE patients demonstrated progressively larger ADAPT advantages (aOR 2.06, 95% CI 1.67 to 2.55, and aOR 2.99, 95% CI 2.24 to 3.98, respectively, both P<0.001). Conclusions ADAPT may be superior to SR for a majority of patients, particularly in recent years, and among patients with M1 occlusions presenting in earlier time windows.

BACKGROUND. Survey research in critical care has dramatically increased over the past 25 years, and use of surveys within Delphi methods, which provide consensus definitions for heterogeneous disease states, has similarly expanded significantly. It is crucial for survey researchers to understand the nuances of survey development and expectations of information provided by surveys, to use them correctly. Few simple sources exist to guide development considerations to generate high-quality survey research. No studies to our knowledge exist that draw parallels between the principles of survey research as a guide within the Delphi process, as one potential conduit between a steering committee and expert panel. METHODS. We present a narrative review of and framework for rigorous design of survey research, highlighting the applicability to the design of surveys administered within Delphi methods. RESULTS AND CONCLUSIONS. The methodologic considerations presented for survey research and Delphi methods can inform high-quality critical care research.

INTRODUCTION: Recurrent Clostridioides difficile infection (rCDI) is associated with substantial morbidity, healthcare utilization, and costs. US FDA-approved microbiota-based therapies, fecal microbiota spores, live-brpk (VOS) and fecal microbiota, live-jslm (RBL), reduce recurrence risk, but cost-effective placement within the rCDI treatment pathway remains uncertain. METHODS: We performed a US payer-perspective cost-effectiveness analysis using decision-tree modeling according to CHEERS 2022 guidelines. Adults with rCDI entered the model after the first or second recurrence and were followed for <1 year. Effectiveness inputs were derived from ECOSPOR III/IV (VOS), PUNCH CD3/CD3-OLS (RBL) trials, and published literature for standard-of-care (SoC) comparators. Outcomes included costs (2025 USD), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Probabilistic and deterministic sensitivity analyses were performed using a willingness-to-pay threshold (WTP) of $150,000/QALY. ICERs were interpreted across $50,000, $100,000, $120,000, and $150,000/QALY. RESULTS: After the first recurrence, RBL was cost-effective vs SoC alone ($25,415/QALY). Early initiation remained favorable compared with delayed use for VOS ($27,239/QALY) and RBL ($26,704/QALY). After the second recurrence, VOS remained cost-effective vs SoC (ICER $53,983/QALY), whereas RBL exceeded the WTP threshold (ICER $171,496/QALY). Exploratory cross-trial VOS vs RBL comparisons yielded ICERs of $124,636/QALY after first recurrence and $137,350/QALY after second recurrence, indicating threshold-sensitive product-to-product comparisons. DISCUSSION: Earlier initiation of microbiota-based therapies after the first rCDI provides greater health benefits at acceptable cost-effectiveness thresholds compared with delayed use, supporting earlier integration into rCDI treatment strategies. VOS vs RBL comparisons should be interpreted as exploratory indirect comparisons pending comparative real-world or head-to-head data.

Abstract Recurrent Clostridioides difficile infection (CDI) is a clinical syndrome, a trial end point, and a surveillance construct. Epidemiologic and administrative datasets count repeat positive tests or coded episodes, but conflate colonization or test of cure with recurrence. Trials operationalize recurrent CDI with symptoms and testing, but have variable follow-up. Clinically, recurrent CDI requires response, and recurrent illness requires excluding postinfection bowel dysfunction and mimics. Relapse and reinfection remain difficult to distinguish without strain typing, which is more relevant for research. We propose a pragmatic lens: explicitly name the definition used, match it to the decision, and adjudicate clinical recurrence before escalating therapy.