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

This study examines the patient- and hospital-level variation in time to initiation of inpatient management among patients admitted to general medical services.

Mesothelioma is a rare cancer that originates from the mesothelial surfaces of certain sites within the body. Pleural mesothelioma is the most common type and represents approximately 85% of mesotheliomas. The NCCN Guidelines for Mesothelioma: Pleural provide recommendations for evaluation and treatment in patients with pleural mesothelioma. The NCCN Guidelines will continue to be updated annually based on available clinical evidence and panel consensus.

Abstract Aim To confirm or refute recent pilot studies showing unexpectedly high rates of undetected heart failure (HF) in cardiology patients. Methods We assessed the prevalence, characteristics, and outcome of undetected HF in a large prospective cohort study of patients referred for non-invasive coronary artery disease (CAD) work-up with cardiac positron emission tomography computed tomography. HF presence and phenotype were centrally adjudicated by an independent cardiologist according to clinical practice guidelines requiring three mandatory criteria: symptoms, elevated natriuretic peptides, and structural/functional cardiac abnormalities. The endpoint was a composite of cardiovascular death and acute HF (AHF) hospitalization through 2-year of follow-up. Results Among 1738 eligible patients (median age 67 years, 30% women), 138 patients (7.9%) had known HF, and 534 of 1600 patients (33.4%) without known HF had adjudicated undetected HF, resulting in a ratio of undetected HF to known HF of 3.9 (95%CI, 3.2–4.7)-to-1 and a number needed to screen to detect one patient with undetected HF of 3.0 (95%CI, 2.9-3.1). In undetected HF, left ventricular ejection fraction (LVEF) was preserved in 72.3%, mildly reduced in 16%, and reduced in 11.7%. Older age, known CAD, atrial fibrillation, previous pacemaker implantation, and ECG abnormalities were associated with a higher likelihood for undetected HF. Undetected HF was associated with an increased cumulative incidence of the composite endpoint (adjusted subdistribution hazard ratio 7.37 [95%CI, 3.87-14.06], p<0.001, versus no HF). Conclusion One-out-of three patients referred for CAD work-up had undetected HF, which was associated with cardiovascular death and AHF hospitalization.

This article describes clinical, serologic, and histopathologic features of the first North American cohort of patients with positive anti-p200 serology identified at Mayo Clinic, Rochester, Minnesota, USA and Beutner Laboratories, Buffalo, New York, USA. Forty-seven patients were identified with positive p200 laminin beta 4 autoantibodies, detected with either immunoglobulin (Ig)G or IgG4 modified indirect immunofluorescence on HEK293 cells transfected with recombinant laminin beta.

The effect of induced hypertension (iHTN) on functional outcomes in noncardioembolic acute ischemic stroke (AIS) with early neurological deterioration remains unclear. We performed a systematic review and meta-analysis evaluating the safety and efficacy of iHTN vs medical management. A literature search of PubMed/MEDLINE, Web of Science, Ovid Embase, and Scopus from inception through November 6th, 2025. The protocol was registered in PROSPERO (CRD420261282211). Studies evaluating iHTN within 72 h of AIS onset and reporting 90-day functional independence (modified Rankin Scale [mRS] 0-2) were included. Safety outcome was hemorrhagic transformation. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using random-effects model based on Restricted Maximum-Likelihood (REML) methods. Three studies were included, comprising 366 patients (iHTN, n = 180; control, n = 186). Mean age was 65.8 ± 11.8 years, 60.9% were men, and the mean initial NIHSS was 5.4 ± 3.5. Target systolic blood pressure (SBP) was a 15-25% increase from baseline SBP using phenylephrine. Functional independence at 90-days occurred more often in the iHTN group than in controls (68.8% vs 50.5%; RR = 1.37; 95% CI, 1.09-1.73; P = 0.007). Hemorrhagic transformation was uncommon and did not differ significantly between groups (3.3% vs 0.5%; RR = 2.08; 95% CI, 0.05-88.07; P = 0.70). In our study, phenylephrine-induced hypertension was associated with greater 90-day functional independence in selected AIS subtypes,without a significant increase in hemorrhagic transformation. However, the limited studies, predominance of retrospective designs, exclusively Asian cohorts, and heterogeneity in treatment protocols and populations warrant cautious interpretation and underscore the need for larger multicenter RCTs.

ABSTRACT Introduction The insula is an increasingly important target for functional neurosurgery given its involvement in a range of neurological and neuropsychiatric disorders, including epilepsy and chronic pain. As this practice evolves, optimal targeting will require standardized outcome measures that relate electrode or laser trajectory to postprocedural outcome. Traditional whole- brain registration approaches fail to capture the substantial person-to-person variability in insular gyral configuration, including the relative internal rotation of the insular gyri with respect to standard stereotactic space. Objective We propose and validate a stereotactic coordinate system based on local anatomical landmarks to facilitate surgical planning and standardized outcome assessment within the insular cortex. Methods Our approach transforms brain MRI first into standard AC-PC space, and then into an insular-specific space defined by five anatomical landmarks: four points along the central sulcus of the insula and one point at the middle cerebral artery (MCA) bifurcation (at the limen insulae). The system calculates two angles - θ (axial) and φ (sagittal) - between the AC-PC line and the insular axis, and the brain volume undergoes sequential rotation through these angles followed by translation to place the coordinate system’s origin along the insular axis. Results In a sample of 32 patients, the angle between the AC-PC line and the insular axis ranged from -17° to 17° in the axial plane (θ) and 31° to 69° in the sagittal plane (φ). In the resulting coordinate system, the insular axis defines z = 0 and the MCA turning point defines y = 0. We developed a custom, open-access MATLAB graphical interface that allows intuitive implementation of this system for both surgical planning and postoperative analysis; implanted electrodes, laser fiber position, and ablation geometry can each be localized within this common space. As a demonstration of its utility for pooling data across subjects, we applied the transformation to a previously acquired intracranial electrophysiology dataset and found that anatomically consistent, effector-specific motor representations emerged across 18 subjects once electrode positions were expressed in insular-specific coordinates. Conclusion As stereotactic surgery for insular targets becomes more common with expanding scientific inquiry, an insular-specific coordinate system may facilitate operative planning and functional mapping, and may help standardize outcome assessment across patients and institutions. SIGNIFICANCE STATEMENT The insular cortex represents an increasingly important surgical target for therapeutic interventions, yet substantial person-to-person anatomical variability hampers standardized targeting and outcome comparison. The insula is simultaneously the subject of expanding scientific inquiry — into interoception, pain, autonomic regulation, salience processing, and sensorimotor representation — much of it now pursued through intracranial recording and stimulation in humans, where cohorts are small, electrode sampling is idiosyncratic, and progress therefore depends on pooling data across patients in a frame that respects insular gyral architecture. We present “ Insulotaxy ,” a stereotactic coordinate system built from consistent, easily identifiable local anatomical landmarks that accounts for the insula’s unique rotational relationship to standard brain coordinates. An open-source MATLAB tool transforms imaging into insular-specific coordinates, facilitating surgical planning for ablation and electrode placement while enabling standardized outcome reporting across institutions. By providing locally anchored, anatomically aligned coordinates rather than relying on whole-brain registration, this framework addresses a practical gap in functional neurosurgery and lays a foundation for pooling clinical and electrophysiological data as insular interventions become more prevalent.

Background TP53 mutational status ( TP53 ms) is prognostically important in myeloid neoplasms. Immunohistochemistry (IHC) of p53 has been used as a surrogate for TP53 mutations, with faster results than next-generation sequencing (NGS) and cytogenetic analysis. Given the challenges posed by heterogeneous p53 IHC expression, this study aims to evaluate the interobserver interpretation of p53 stain as a surrogate marker for TP53m . Methods Fifty-three bone marrow (BM) specimens previously diagnosed as myeloid neoplasms or nonneoplastic BM specimens with available concurrent TP53ms were evaluated. p53 IHC staining was performed on all 53 core biopsy or clot sections. TP53 mutation was found in 24 cases ( TP53 m). Twenty-nine specimens were TP53 wild-type and served as the control group. Six hematopathologists (HPs) blinded to the diagnosis and TP53 m independently scored the p53 staining pattern of the biopsies/clot sections for overall staining percentage (OSP) and staining intensity (dark staining percentage as a percentage of total cells (DCP)). Results The intraclass correlation was excellent for OSP (0.927) and good for DCP (0.848). For OSP, a cutoff of 30% resulted in sensitivity of 83.3%, specificity of 89.7%, PPV of 87.0%, and NPV of 86.7%. For DCP, a cutoff of 10% achieved sensitivity of 87.5%, specificity of 96.6%, PPV of 95.4%, and NPV of 90.3%. Additionally, DCP significantly correlated with the VAF of TP53 m (R = 0.469, p = 0.028). Conclusion High inter-rater reliability for OSP and DCP supports integrating p53 IHC into bone marrow evaluations for rapid TP53 m assessment. With superior specificity and predictive values, DCP proves to be a more reliable diagnostic marker for TP53 mutations. While this approach shows promise for myeloid neoplasms, further validation is needed to overcome challenges and expand its clinical utility for tailored treatment strategies.

Platelets are central to hemostasis and thrombosis. Excessive platelet activation contributes to arterial thrombotic events, including myocardial infarction, ischemic stroke, and complications of peripheral artery disease, whereas excessive platelet inhibition increases bleeding risk. Antiplatelet therapy remains a cornerstone of secondary prevention in atherosclerotic and thrombotic cardiovascular diseases, yet current treatment paradigms do not fully account for biological heterogeneity in platelet function, including differences related to sex, age, hormonal status, and disease context. This state-of-the-art review examines current antiplatelet strategies, fundamental mechanisms of signal transduction, clinical indications, and limitations of preclinical and clinical studies, with a focus on sex-specific considerations and opportunities for personalized antiplatelet therapy. Aspirin and P2Y 12 receptor antagonists are widely used for secondary prevention. However, women have been underrepresented in many pivotal clinical trials, limiting the precision of sex-specific estimates of efficacy and bleeding risk. In parallel, commonly used preclinical models often fail to recapitulate the physiological conditions in which platelets interact with the vasculature, leukocytes, and soluble factors. Emerging therapeutic approaches seek to refine platelet inhibition by targeting pathways that reduce thrombotic risk while preserving hemostasis. Advancing antiplatelet therapy will require integration of mechanistic platelet biology with diverse clinical trial populations, standardized platelet phenotyping, and disease-specific approaches that account for how platelet function is altered across health and vascular disease.

PURPOSE Age ≥40 years is regarded as a high-risk feature and an indication for adjuvant chemoradiotherapy for patients with lower-grade glioma in clinical practice guidelines. It is unclear whether age remains a relevant prognostic factor for contemporary definitions of lower-grade gliomas in the molecular era. METHODS The Prospective Gliomas Research (PROGRES) database contains individual patient-level data from 11 prospective clinical trials or observational registries of histologically defined lower-grade 2-3 oligodendroglioma or astrocytoma. We determined the association of age (18-39 years v ≥40 years) with progression-free survival (PFS) stratified by isocitrate dehydrogenase 1 or 2 ( IDH1/2 ) status, using log-rank tests and Cox regression models. We validated our findings in a separate multi-institutional retrospective cohort (Retrospective Glioma Research [REGRES] database). RESULTS We identified 1,619 and 1,292 eligible patients in the PROGRES and REGRES cohorts, respectively. IDH -wildtype tumors were more common in patients 40 years and older (38% v 5%, odds ratio: 11.3 [95% CI, 6.5 to 19.7]). Age was associated with PFS in IDH -wildtype (5-year PFS for ≥40 v 18-39 years: 6% v 24%, hazard ratio [HR], 1.74 [95% CI, 1.21 to 2.50]) but not in IDH -mutant glioma (60% v 59%, HR, 0.89 [95% CI, 0.76 to 1.05], P interaction < .001). In IDH -wildtype tumors, older age predicted aggressive molecular features, including TERT promoter mutation (65% v 28%), EGFR amplification (41% v 15%), and chromosome +7/–10 alteration (57% v 25%). In a pooled analysis of four clinical trials, age was not predictive of a benefit from chemoradiotherapy versus radiotherapy alone for IDH -mutant glioma. CONCLUSION In the absence of additional clinical or molecular risk factors, age alone should not be considered an indication for administration or deferral of adjuvant treatment. Practice guidelines should be revised to reflect contemporary prognostic factors in the molecular era.