Citations

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: Pancreatic ductal adenocarcinoma (PDAC) frequently recurs after neoadjuvant therapy (NT) and curative-intent resection. Although major pathologic response predicts favorable outcomes, most patients achieve only minor response with a heterogeneous recurrence risk. We asked whether the spatial organization of residual PDAC encodes clinically relevant biology beyond residual tumor burden. Experimental Design: In a retrospective cohort of 203 patients with resected PDAC treated with NT and restricted to minor pathologic response, routine hematoxylin and eosin (H&E) whole-slide images were segmented into cancer and stroma using an artificial intelligence–enabled pipeline. Spatial composition (patch density, edge density) and configuration (compactness/complexity, intermixing) were quantified and tested for associations with disease-free survival (DFS) using multivariable models adjusted for standard clinicopathologic factors. Results: Shorter DFS was associated with a fragmented, interface-rich tumor–stroma ecology featuring higher edge density and diversity and reduced homotypic aggregation, independent of clinicopathologic variables. Two spatial risk models were independently prognostic: (i) cancer mean shape index plus stromal shape index variability [adjusted hazard ratio (HR), 1.71; P = 0.003] and (ii) mean stromal patch area plus edge density (adjusted HR, 2.19; P = 0.002). Both models stratified outcomes in which pathologic response grading and residual cancer area did not. High-risk configurations were further associated with reduced intratumoral tumor-infiltrating lymphocyte (TIL) density and infiltration ratio, with relative TIL accumulation at the cancer periphery and within the stroma, consistent with an immune-excluded phenotype. Conclusions: Residual cancer–stroma topology quantified from standard H&E slides yields independent prognostic signals after NT in PDAC, provides a cellular immune correlate for spatial risk, and motivates prospective validation and spatially informed adjuvant strategies.

Abstract Clinical empathy is essential for patient care, but physicians need continually balance emotional warmth with factual precision under the cognitive and emotional constraints of clinical practice. This study investigates how large language models (LLMs) can function as empathy editors, refining physicians’ written responses to enhance empathetic tone while preserving underlying medical information. More importantly, we introduce novel quantitative metrics, an Empathy Ranking Score and a MedFactChecking Score to systematically assess both emotional and factual quality of the responses. Experimental results show that LLM-edited responses significantly increase perceived empathy while preserving factual accuracy compared with fully LLM-generated outputs. These findings suggest that using LLMs as editorial assistants, rather than autonomous generators , offers a safer, more effective pathway to empathetic and trustworthy AI-assisted healthcare communication.

Importance Anhydramnios from fetal kidney failure causes lethal pulmonary hypoplasia. Serial amnioinfusions have shown promise in mitigating pulmonary disease from bilateral renal agenesis, but efficacy and safety for other causes of fetal kidney failure are unproven. Objective To assess the efficacy of serial amnioinfusions initiated before 26 weeks’ gestation to mitigate lethal pulmonary hypoplasia in cases of anhydramnios due to fetal kidney failure. Design, Setting, and Participants Prospective, nonrandomized clinical trial conducted at 13 US fetal therapy centers from December 2018 to February 2025. Outcomes for maternal-fetal pairs with anhydramnios before 22 weeks’ gestation due to fetal kidney failure without bilateral renal agenesis are reported; data collection for surviving infants continued until February 13, 2026. Exposure Thirty-two participants underwent serial amnioinfusions with isotonic fluid beginning before 26 weeks’ gestation. Main Outcomes and Measures The primary end point was neonatal survival for 14 days or longer with dialysis access placement. Secondary outcome measures of survival to discharge home and kidney transplant are reported. Results Twenty-nine of 32 participants (91%) had a live birth, with a median (IQR) gestational age at delivery of 34 weeks 1 day (31 weeks 5 days to 34 weeks 6 days). All participants delivered before 37 weeks’ gestation. No unexpected serious maternal adverse events occurred, and the most common maternal complications were preterm prelabor rupture of membranes in 19 participants (56%) and chorioamniotic separation in 10 (29%). The primary outcome occurred in 19 (65.5%) of 29 live-born neonates (95% CI, 45.7%-82.1%). Factors associated with survival to the primary outcome included receiving more amnioinfusions (median [IQR], 14 [9-18] in survivors vs 7 [4-11] in nonsurvivors; P = .01), longer time interval from first amnioinfusion to preterm prelabor rupture of membranes (63.5 [60.5-74.5] days in survivors vs 29.0 [22.0-56.0] days in nonsurvivors; P = .01), gestational age greater than 32 weeks (79% of survivors vs 38% of nonsurvivors; P = .03), and higher birth weight (2029 [1770-2250] g in survivors vs 1635 [1185-1915] g in nonsurvivors; P = .01). Fourteen live-born infants (48%) survived to hospital discharge at a median (IQR) age of 4.7 (3.4-5.7) months. Of the 11 infants surviving to date, 7 (64%) have undergone kidney transplant between ages 2 years to 5 years. Conclusions and Relevance Serial amnioinfusions mitigated lethal pulmonary hypoplasia in neonates with anhydramnios due to fetal kidney failure. Significant neonatal morbidity and mortality independent of early lung function was noted. Factors associated with survival were consistent with the Renal Anhydramnios Fetal Therapy trial’s bilateral renal agenesis cohort, suggesting common mechanistic pathways for mitigating pulmonary hypoplasia. Trial Registration ClinicalTrials.gov Identifier: NCT03101891

Background Accreditation Council for Graduate Medical Education (ACGME) requires internal medicine (IM) residents to perform procedures considered “essential for the area of practice.” However, no guidelines or best practices exist for teaching these skills. To address this gap, a procedure training workshop (PTW) was developed. Methods IM residents attended a PTW where they practiced paracenteses, lumbar punctures (LPs), and central venous catheter (CVC) placement on ultrasound-compatible task trainers. The PTW was assessed using pre- and post-session tests and surveys. To evaluate translation into clinical practice, procedure volume, success rates, and immediate complications were tracked. Results Following implementation of the PTW, resident knowledge assessment scores increased from 67.4% to 84.1% (p < 0.001). More residents reported feeling “well-prepared” to perform or “teach others” procedures (CVC 69% from 31%, p < 0.01; LP 71% from 8%, p < 0.05; paracentesis 80% from 28%, p < 0.05) and able to perform all steps without assistance or model (CVC 54% from 28%; LP 49% from 17%, p < 0.01; paracentesis 66% from 25%, p < 0.01). Paracenteses increased from 71 (2020) to 119 (2021) to 143 (2024), while LPs increased from 87 (2020) to 156 (2021) to 135 (2024). Success rates remained stable across procedures: paracentesis (91.5% to 94.1% to 93.7%), LP (58.6% to 55.8% to 52.6%), and CVC placement (95.5% to 97.6% to 94.9%). Conclusions PTW is a valuable half-day session that equips early residents with essential procedural knowledge and hands-on practice that translates into sustained increases in bedside procedure volume.

Abstract Objective Ceribell Inc.'s point‐of‐care electroencephalographic (EEG) system and artificial intelligence‐based Automated Seizure Burden Estimator (ASBE; ClarityPro) have US Food and Drug Administration clearance for diagnosing electrographic status epilepticus (ESE). The AccuRASE study using ASBE version 6 (V6) showed high negative predictive value (NPV) but limited sensitivity and positive predictive value (PPV) at certain thresholds. Version 8 (V8) is the updated algorithm trained with additional EEG samples. Methods We tested V8 on the previously used rapid‐response EEG test dataset (not used to train V8). Sensitivity, specificity, PPV, and NPV were compared against blinded expert annotations. ESE, ESE and possible ESE (ESE/pESE), electrographic seizures (ESz), and Esz with highly epileptiform patterns (Esz/HEPs) at burden thresholds of >1%, >10%, >20%, >50%, and >90% were analyzed. Additionally, we evaluated the built‐in ESE and ESE/pESE alerts (≥90% over 5 min, ≥20% over 1 h, or ≥10 continuous minutes of seizure). Results V8 showed 100% sensitivity at lower thresholds (>10%–20%) for ESE (V6 .86), without a specificity loss (V8 .9 vs. V6 .85), and retained NPV (V8 1.0 vs. V6 .99). Sensitivity at 50% threshold was .86 for ESE (V6 .71), and specificity was .94 (V6 .91); PPV for ESE was 30% for ESE and 80% for ESE/pESE. The specificity for ESE remained high for 90% burden (V8 .96, V6 .97) but the sensitivity dropped (.29 vs. V6 .43). Sensitivity was lower for ESz/HEPs (.54 → .44 at >10% threshold), although the algorithm is not designed to detect HEPs. Built‐in alert analysis showed significantly improved sensitivity for ESE (.57 → .86); specificity and NPV remained high (>.94). Significance ASBE V8 showed meaningful improvements in sensitivity, continued excellent NPV, and improved built‐in alert accuracy for ESE and ESE/pESE. The best seizure burden threshold for ruling out ESE now is 20% (vs. 10% with V6) and that for ruling in ESE/pESE with reasonable certainty is 50% (vs. 90% with V6).

ABSTRACT First‐line therapy for mantle cell lymphoma (MCL) represents a critical opportunity for clinical benefit via sustained complete response. We conducted a phase 2 multicenter trial in the academic and community cancer research united (ACCRU) network, testing a multitargeted 1st line regimen. CARiBOU (ACCRU‐LY‐1804) employs alternating VR‐CAP and R‐cytarabine with continuous acalabrutinib, in six 21‐day cycles, for previously untreated MCL. The primary endpoint was complete metabolic response (CMR) rate. Secondary endpoints included safety, feasibility of stem cell collection, proportion proceeding to ASCT, and progression‐free (PFS) and overall survival (OS). Peripheral blood measurable residual disease (MRD) was tested using the ClonoSEQ assay (Adaptive Biotechnologies). Of 41 patients enrolled, 39 (95%) responded to therapy, including 37 patients achieving CMR (90%). Two nonresponders discontinued therapy for toxicity early, prior to study‐defined restaging, and received alternate therapy. Undetectable MRD at a 10 6 threshold was achieved in 26/33 tested patients (79%), and 94% at 10 5 . 18‐month estimated PFS is 79% (95% CI 64%–97%), and OS is 96% (95% CI 88%–100%). Toxicities were primarily hematologic (grade 3 hematologic AE in 32 patients, [78%]). Twelve required platelet transfusions, and one grade 3 bleeding event occurred. Febrile neutropenia occurred in 4 patients, and 6 (14%) experienced SAEs. There were no treatment‐related deaths. CARiBOU is an efficient, highly effective outpatient 1st line MCL regimen, employing intermediate‐dose cytarabine and continuous acalabrutinib for 6 cycles. This multitargeted regimen addresses the biologic heterogeneity of MCL and permits flexible MRD‐guided decisions on consolidation and maintenance. Trial Registration: ClinicalTrials.gov identifier: NCT04626791