Citations

Abstract Introduction Combat casualty care requires standardized proficiency criteria to ensure readiness in austere environments, yet gaps persist in defining performance thresholds for critical trauma skills. The Combat Medical Skills Sustainment Consortium (CMSSC), a novel military-civilian collaboration, aimed to validate competency thresholds for 21 Department of Defense-identified trauma skills. Materials and Methods A prospective cohort study (2022-2025) enrolled 1,495 military and civilian personnel across five academic centers, stratified by experience (novice, intermediate, expert). Skills, including cricothyroidotomy, whole blood transfusion, and ultrasound-guided vascular access, were assessed using validated checklists in Role 2-congruent simulations. Statistical analysis compared checklist performance against participant experience with a priori checklist scores estimated at 40% (novices) and 90% (experts). Results Competency thresholds were established, ranging from 77% (mechanical ventilation) to 100% (handoff). Experts achieved 85%-98% proficiency across most skills, with novices at 34%-97%. A ceiling effect was observed for less complex skills consistent with the power law of practice. Conclusion The Combat Medical Skills Sustainment Consortium validated standardized assessment tools, with potential to address readiness gaps through military-civilian synergy. Findings support consortium-guided curriculum development and highlight the need for longitudinal skill decay studies. Impact This study sets a benchmark for trauma care skills assessment, facilitating rapid adoption across military and civilian settings.

PURPOSE The continuous development of new imaging approaches, molecular phenotyping, genetic subtypes, prognosis assessments, and effective therapies across a range of disease states has created a need to redefine terminology and best practices for clinical trial conduct in patients with advanced prostate cancer. Methods We convened an international expert committee of diverse working groups, the Prostate Cancer Working Group 4 (PCWG4), between 2016 and 2025. Our objective was to formulate updated criteria based on emerging evidence and clinical trial data in a biomarker context to provide guidance for clinical trial design, eligibility, and end point assessments for patients with advanced prostate cancer. RESULTS PCWG4 redefines terminology around the disease state and previous therapies in a patient-centric context and terminology focused on androgen pathway modulation. We consider imaging, with a particular focus on positron emission tomography (PET)–defined disease. New recommendations are provided for disease state terminology, defining eligibility criteria, response and delay/prevent end points, intervals for reassessments including imaging, and patient-reported outcome determination. We provide recommendations in a biomarker-based context of use for the intended indication, reflective of patient benefit for specific interventions. We emphasize the need for development of validated PET imaging and molecular and phenotypic criteria as well as trial designs to appropriately risk stratify patients, predict and assess benefit, and measure post-treatment outcomes reliably in a trial framework. CONCLUSION PCWG4 updates recommendations on patient and tumor characterization, therapy development, and imaging criteria and extends guidance into earlier androgen pathway modulator–naïve/sensitive disease states to reflect an evolving, heterogeneous, and diverse patient population to optimize treatment benefits for all patients.

Importance There is a need for greater recognition of clinical psychopharmacology endpoints, including instances where specific psychotropic medications may become unnecessary, redundant, contradictory, or otherwise inappropriate and therefore merit deprescribing. Objective To address circumstances warranting psychotropic medication deprescribing. Evidence Review The American Society of Clinical Psychopharmacology convened a panel of 45 international psychopharmacology experts who developed and completed a multiround Delphi survey and conducted a focused literature review between January and May of 2025, in order to identify areas of consensus or disagreement on key aspects of the deprescribing of psychotropic medications. These included collaborative risk-benefit assessments with patients; pharmacokinetic and pharmacodynamic factors; pharmacogenomics; distinguishing redundant or conflictual from complementary mechanisms of action; managing adverse effects; assuring medication adherence; drug tolerance or tachyphylaxis; medication misuse; and the psychological context and ramifications of deprescribing. Findings Consensus was achieved on 44 of 50 final Delphi statements (88%). Panelists unanimously agreed that components of a pharmacotherapy regimen should undergo periodic review to ensure that treatments target relevant symptoms and have favorable risk-benefit ratios. Key points of consensus were that deprescribing: (1) should not occur without first assessing medication adherence; (2) merits consideration if less than partial therapeutic response is apparent, or if treatment goals have been reached and relapse prevention is not a long-term objective; (3) involves psychological ramifications that warrant attention; (4) should be followed by close clinical monitoring; and (5) risk-benefit decisions should ideally involve active patient participation within a shared decision-making model. Conclusions and Relevance Through this Consensus Statement, the Task Force identified circumstances in which the selective elimination of certain psychotropic medications may be clinically indicated. Empirical trials are needed to assess the implementation of deprescribing protocols and gauge their safe, effective, and acceptable outcomes.

Abstract Objective: Subjective cognitive complaints (SCC) can precede cognitive decline and are associated with demographic, exposure, lifestyle, and psychological factors. Prevalences of SCC and their correlates in individuals with repetitive head impacts (RHI) are poorly understood. This study characterized SCC in former elite American football players by frequency, mood and behavioral correlates, concordance with informant reports, and associations with neuropsychological test performance, cerebrospinal fluid (CSF), and magnetic resonance imaging (MRI) markers of neurodegeneration. Method: Former American football players ( n = 180) completed measures of global and domain-specific SCC, neuropsychiatric symptom questionnaires, neuropsychological testing, lumbar puncture, and MRI. Elastic net regression evaluated the relative importance of potential SCC correlates. Intraclass correlation coefficients measured concordance between self and informant reports. Multiple linear regressions tested associations between SCC and verbal memory and executive functioning scores. CSF Aβ 1-42 , p-tau 181 , t-tau, neurofilament light (NfL), hippocampal volume, and regional cortical thickness were examined for their potential associations with SCC. Results: Rates of SCC ranged from 43 to 77% depending on the domain. Symptoms of depression, impulsivity, and anxiety were strongly associated with SCC. Self- and informant-reported SCC showed moderate inter-rater agreement. Adjusting for age, race, education, APOE ϵ4 carrier status, and depressive symptoms, SCC were associated with lower objective verbal memory and executive functioning performance. SCC were associated with lower parahippocampal cortical thickness but not with hippocampal volume or any of the measured CSF tests. Conclusions: SCC are strongly associated with neuropsychiatric factors in former American football players. SCC may also be a marker of cognitive decline and neurodegeneration.

ABSTRACT Meningiomas are the most common primary brain tumors and, despite their benign reputation, often behave aggressively. Meningiomas are morphologically heterogeneous, yet the full significance of their histologic diversity is unclear. This is in large part because many features are not readily quantifiable by traditional observer-based light microscopy. Molecular testing improves prognostic stratification, but is not universally accessible. We therefore sought to determine whether an artificial intelligence (AI)-trained program could predict specific genomic and epigenomic patterns in meningiomas, and whether it could extract more prognostic information out of standard hematoxylin and eosin (H&E) histopathology than the current WHO classification. To do this, we developed Morphologic Set Enrichment (MSE), an interpretable computational pathology framework that quantifies statistical enrichment of morphologic patterns, cells, and tissue architecture from H&E whole-slide images. The MSE meningioma histology program was able to accurately predict DNA methylation subtypes and concurrent chromosome 1p/22q losses, in the process identifying specific morphologic patterns associated with key genomic and epigenomic alterations. It also added prognostic value independent of standard clinical and pathological variables. These results demonstrate that AI-based quantitative morphologic profiling can capture clinically and biologically relevant information that redefines risk stratification for meningiomas, incorporating histological information not included in existing grading schemes.

Abstract Patients with multiple myeloma have an elevated risk of severe complications from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) infection. To demonstrate proof of concept for a pandemic preparedness and response network, the American Society of Hematology Research Collaborative Multiple Myeloma Program developed a prospective, decentralized study within a site-based provider network. In the COVID-19 outcomes in myeloma and the impact of vaccines (COSMIC) study, patients provided consent, permitted electronic health record data collection, completed patient-reported outcomes at baseline, day 30, and day 180 through an electronic study portal, and were compensated for participation. Clinicians at participating sites facilitated study recruitment and shared best practices monthly to accelerate study execution. The COSMIC study rapidly consented 201 patients from 8 participating sites over 4 months (22 January 2024 through 17 May 2024). Consented participants were 30 to 93 years old, with a median age of 67; 46% were female, 69% were non-Hispanic White, 17% were non-Hispanic Black, and 8% were Hispanic/Latino. Patient-reported data completion was 97% at baseline, 81% at 1 month, and 79% at 6 months. At baseline, 55% of patients reported a history of COVID-19 infection and had received a median of 4 SARS-CoV-2 vaccines. For all patients, there were an additional 18 COVID-19 infections and 57 vaccines received during the 6-month observation period. There were no significant differences in health-related quality of life over time or by history of COVID-19 infection. COSMIC demonstrates the feasibility of an innovative evidence generation strategy to drive rapid accrual of patients to address an evolving area of need. This trial was registered at www.clinicaltrials.gov as #NCT05831787.

Abstract Context Evidence on the etiology and function of adrenal masses in younger adults is scarce. Objective This work aimed to characterize the clinical, imaging, and biochemical presentation of adrenal masses in 18- to 40-year-olds. Methods A retrospective cohort study was conducted January 2016 to December 2021 at a tertiary academic medical center. Participants included young adults (age 18-40 years) with adrenal masses identified through radiologic registry. Exclusion criteria included preexisting adrenal masses before 2016, hyperplasia, or masses smaller than 1 cm. Outcomes included adrenal mass diagnosis, as determined by reference standard of histopathology, radiologic surveillance, and biochemical evaluation. Results A total of 255 patients (women 142 [56%]; White 156 [61%]; median age 35 years [interquartile range 30-39 years]) were included. Comorbidities included genetic predisposition syndromes (16, 6.3%), preexisting malignancy (70, 27%), obesity (100, 48%), hypertension (89, 35%), and diabetes (25, 10%). The majority of adrenal masses were incidentally found (184, 72%) and median size was 1.9 cm (IQR 1.4-2.7 cm) on detection. Among adrenal masses in young adults, prevalence of malignancy and pheochromocytoma was 16% and 4%, respectively; among adrenal incidentalomas, 5% were malignant. Factors associated with malignancy or pheochromocytoma in multivariable analysis included nonincidental mechanism of discovery (odds ratio [OR] 15.5; 95% CI, 7.2-35.7; P < .001), and larger size (OR 1.5; 95% CI, 1.2-2.0; P < .001). Hormonal evaluation was performed in only 57 (22%) patients and was positive for hormone hypersecretion in 16 (28%) of tested individuals. Conclusion We demonstrated a high prevalence of malignancy and pheochromocytoma in our cohort of young adults with adrenal masses. Completion of appropriate hormonal work-up was infrequent, potentially missing patients with functioning adrenal adenomas.