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Importance Limited granular data exist on breast cancer in transgender, nonbinary, and/or gender-diverse (TGD) individuals. Objective To describe patient demographic and tumor clinicopathological variables, clinically relevant risk factors, method of breast cancer detection, treatment characteristics, and locoregional outcomes and to estimate a 5-year breast cancer–specific survival (BCSS). Design, Setting, and Participants This cohort study obtained data on patients treated from 1990 to 2023 from 22 US academic medical centers using institutional databases, electronic medical records, and tumor registries. Included participants were TGD individuals 18 years or older with stage 0 to IV breast cancer. A comparative breast cancer cohort was selected from the 2016 to 2021 Surveillance, Epidemiology, and End Results Program (SEER) breast cancer dataset. Data were analyzed from January to October 2025. Exposure Breast cancer. Main Outcomes and Measures Estimated 5-year BCSS and locoregional recurrence rates. Wilcoxon rank sum and χ 2 tests were used to compare continuous and categorical variables. Kaplan-Meier analysis was used to estimate 5-year BCSS. Results A total of 112 TGD persons (median [IQR] age at diagnosis, 42.5 [36.5-51.0] years; 104 individuals [92.9%] were assigned female at birth) with breast cancer and 1 with bilateral disease were included in the analysis. Forty-three patients (38.4%) used gender-affirming hormone therapy before diagnosis. Among the entire cohort, 58 patients (51.8%) detected their own breast cancer, 68 (60.7%) had a familial breast cancer history, and 16 (14.3%) had a pathogenic germline variant. Tumors were predominantly hormone receptor positive (96 [85.7%]) and early stage (29 [25.7%] ductal carcinoma in situ [DCIS]; 51 [45.1%] stage I). The TGD cohort, compared with patients with breast cancer in the SEER dataset (N = 480 915), was younger (median [IQR] age, 42.5 [36.5-51.0] years vs 62.0 [52.0-72.0] years), had a higher proportion of persons assigned male at birth (8 [7.1%] vs 3522 [0.7%]), more often had progesterone receptor–positive disease (89 [79.5%] vs 335 491 [69.8%]), and presented with earlier-stage disease (eg, DCIS: 29 [25.9%] vs 79 604 [16.6%]). With a median (IQR) follow-up time for the TGD cohort of 38 (24-74) months, 5-year BCSS was favorable at 96.2% (95% CI, 85.3%-99.0%). Conclusions and Relevance This cohort study of TGD patients with breast cancer found that this population was young and often detected their own tumors via self-examination, suggesting opportunities to improve early detection through screening for individuals at elevated risk. Although short-term BCSS appeared favorable, prospective research is essential to define evidence-based guidelines and elucidate long-term outcomes.

Background: Prior studies have reported higher rates of periprosthetic fracture, superficial infection, and neurologic deficit with the direct anterior approach (DAA), and higher rates of dislocation with the posterior approach (PA) for total hip arthroplasty (THA). Despite these differences, the overall clinical burden of complications between approaches remains unclear. The purpose of this study was to compare the profiles, severity, impact, and resolution of 5 clinically important complications between DAA and PA THA. Methods: A retrospective review was conducted of 11,783 consecutive primary THAs performed between 2010 and 2021 across 3 centers within a single healthcare system, using either the DAA (n = 4,451) or the PA (n = 7,332). Complications assessed included dislocation, infection, periprosthetic fracture (PPFx), aseptic loosening, and neurologic deficit. Severity was graded using the Clavien-Dindo classification (I = minor, V = death). Impact was defined by reoperation burden, and outcomes were categorized as resolved or persistent. Kaplan-Meier survivorship and propensity-weighted Cox proportional hazards models were used to compare complication risk. Results: The overall 1-year risk of surgical complications did not differ between DAA and PA (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.75-1.06; p = 0.208). Dislocation occurred more frequently with PA THA than DAA THA (1.9% vs. 0.4%; HR, 5.20; 95% CI, 3.04-8.90; p < 0.001). Superficial infections were more frequent with the DAA (1.6% vs. 0.8%; HR, 2.43; 95% CI, 1.68-3.53; p < 0.001). The risk of deep infection, PPFx, aseptic loosening, and neurologic deficit did not differ significantly between approaches. Among patients with complications, the proportion classified as severe (Clavien-Dindo III–V) was similar, and adjusted analyses showed no difference in the odds of severe complications (adjusted odds ratio 1.34 for PA vs DAA; 95% CI, 0.95-1.91; p = 0.099). Complication impact and resolution were likewise comparable. Conclusion: Although the profile of complications differed between DAA and PA THA, the severity, early clinical impact, and resolution of complications appeared similar. Notably, DAA was associated with a lower risk of dislocation and a higher risk of superficial infection compared with PA THA. Level of Evidence: Level III , Retrospective Comparative Study. See Instructions for Authors for a complete description of levels of evidence.

Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e/sQTL) analyses in six tissues and cell types, including whole blood ( n = 6454) and lung ( n = 1291). We detected tens of thousands of secondary cis-e/sQTLs, showing that secondary cis-e/sQTL discovery remains unsaturated. We fine-mapped UK Biobank–derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTL colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTLs. Our results suggest that even larger e/sQTL analyses will uncover additional secondary e/sQTLs, further benefiting GWAS interpretation.

Introduction: COVID-19, in addition to its direct detrimental respiratory infection, is associated with multiple systemic complications involving different organs, including the liver. COVID-19 has been associated with liver injury through multiple mechanisms, including direct viral effects on liver cells, immune-mediated injury, cytokine-driven inflammation, ischemic hepatitis, microvascular thrombosis, and sepsis-related multiorgan dysfunction. Acute liver failure (ALF) is the acute form of liver damage, which has a high mortality, and recovery is dependent on various factors. We studied the effect of COVID-19 on clinical outcomes such as mortality, length of stay, and need for non-invasive and invasive ventilation in patients with acute liver failure. Methods: We performed a retrospective cohort analysis using the Nationwide Inpatient Sample (NIS) database from 2020 to 2022. Adult patients admitted to the hospital with acute liver failure were divided into 2 groups based on their COVID-19 infection status. We analyzed differences in mortality, length of stay, need for non-invasive and invasive ventilation, acute kidney injury, need for renal replacement therapy, and total charges to evaluate the effects on outcomes, and the results were then adjusted for demographic and hospital factors. Results: Of 633,155 patients with acute liver failure, 66,785 had concurrent COVID-19 infection, while 566,370 did not. Patients with concurrent COVID-19 infection had significantly higher in-hospital mortality (63.9% vs. 36.0%) and greater utilization of noninvasive ventilation (14.9% vs. 6.4%), invasive mechanical ventilation (68.9% vs. 41.7%), higher incidence of acute kidney injury (81.4% vs. 70.3%) and higher need for renal replacement therapy (26.8% vs. 16.9%). They also experienced longer hospital stays (17.1 vs. 10.7 days) and higher total charges ($345,072 vs. $221,268). The findings were statistically significant after adjusting for demographics and clinical factors. Conclusions: Patients hospitalized with acute liver failure and concurrent COVID-19 infection experienced worse clinical outcomes, including higher in-hospital mortality, greater need for ventilatory support and renal replacement therapy, and higher hospital resource utilization. Notably, COVID-19 was independently associated with worse outcomes even among patients with fewer baseline comorbidities. These findings underscore the importance of early recognition of COVID-19 in patients presenting with acute liver failure, as well as prompt, multidisciplinary management to optimize clinical outcomes.

Abstract Cardiovascular disease is the leading cause of morbidity and mortality globally, imposing a substantial patient burden. Digital biomarkers derived from digital health technologies enable quantifiable, near-continuous, real-world capture of pathophysiological signals and are increasingly used across cardiovascular medicine. Their growth is often supported by big data analytics, artificial intelligence and connected sensors within the Internet of Things. This scientific statement systematically reviews digital biomarkers, their clinical utility across the cardiovascular care continuum, and summarizes major methodological and implementation challenges. We searched PubMed/MEDLINE, Embase and Scopus for phase III–IV cardiovascular trials published between 1 January 2019 and 1 August 2024 that collected digital biomarkers. We identified 541 records and included 32 trials (40 reports) enrolling 32 246 participants (44.71% women; mean age 66.2 ± 11.0 years). Heart failure was the most frequent target condition (16 trials, 50%), followed by cardiac implantable electronic devices trials (12 trials, 38%). Digital biomarkers included cardiac rhythm and heart rate, blood pressure, body weight, impedance-based measures, haemodynamic pressures, and physical activity and sleep patterns captured using diverse sensor technologies. Methodological quality was good (modal quality score 5; range 3–7), although most trials were unblinded. Current studies suggest potential clinical utility in selected cardiovascular conditions. Implementation remains challenging because of measurement variability, privacy and regulatory requirements, affordability and reimbursement barriers and inequities in access. Robust validation and outcome- and cost-effectiveness evidence are still needed. Registration number: CRD42024573879.

Background: Greater trochanteric (GT) fractures after total hip arthroplasty (THA) are typically managed nonoperatively. However, outcome data for patient counseling remain limited. We evaluated the nonoperative results, focusing on fracture union rates and the presence of persistent limp in relation with fracture location, displacement magnitude, and direction. Methods: We retrospectively reviewed 82 postoperative GT fractures not associated with trochanteric osteolysis following primary THA performed between 1984 and 2020. The mean follow-up was 9 years. Fracture location was classified relative to the contralateral lesser trochanter as tip, waist, or base. Initial displacement, migration, final displacement, and bony union were assessed radiographically. Clinical outcomes included the presence of a persistent limp and Harris Hip Score. Multivariable analyses were performed to identify factors associated with nonunion and limp. Results: Fractures were classified as tip (n = 32), waist (n = 29), or base (n = 21). The mean initial displacement was 8.9 mm, with 43% displaced >10 mm. Initial displacement was significantly lower in base fractures (4.8 mm) compared with tip (10.1 mm) or waist (10.8 mm) fractures (p < 0.05). The mean final displacement was 14.6 mm. 45% of fractures achieved complete bony union, and 38% of patients demonstrated a persistent limp. In multivariable analysis, greater final displacement (>12 mm), and tip and waist fractures were independently associated with nonunion. Posterior fracture displacement was significantly associated with persistent limp. Conclusions: Outcomes following nonoperative management of GT fractures after THA depend on fracture morphology and displacement characteristics. Tip and waist fractures and fractures with final displacement >12 mm have a higher risk of nonunion, whereas posterior and superior displacement is associated with persistent limp. Greater than 20 mm of displacement is associated with both limp and nonunion. These findings may assist surgeons in counseling patients and in identifying fracture patterns at higher risk for adverse outcomes of nonoperative management. Level of Evidence: Level III (Prognostic Study). See Instructions for Authors for a complete description of levels of evidence.

Abstract Objective To describe the development and implementation of an automated platform for genomic risk prediction that integrates multiple data types. Materials and methods Using the REDCap infrastructure, we constructed the R4 (Recruitment, Results, and Risk Reduction) platform to intake data from clinical sites, partner laboratories, participant surveys, and electronic health record (EHR) data across 13 institutions. Results The R4 Portal successfully integrated data to generate genome-informed risk assessments (GIRAs) across 11 conditions for a 23 840 person cohort. Testing phases and quality control led to network-wide protocols ensuring consistency and accuracy. Discussion As the science of estimating disease risk evolves, standardized and high-throughput methods of collecting and manipulating complex data are required. Platforms should be open-source, modular, and reusable, ensuring flexibility, security, and integration across healthcare environments. Conclusion The electronic MEdical Records and GEnomics (eMERGE) network successfully generated and returned comprehensive risk profiles using logic and data specific to 11 conditions in a secure and semi-automated fashion employing a customized REDCap database.

Abstract Background Glioblastoma (GB) exhibits marked tumor microenvironmental heterogeneity, contributing to both therapy resistance and poor survival outcomes. Intercellular adhesion molecule 1 (ICAM1) is an inflammation-associated adhesion molecule implicated in immune-stromal interactions, but its clinical and biological significance in GB remains incompletely defined. Methods We performed ICAM1 immunohistochemistry, bulk RNA sequencing, DNA methylation analysis, single-nucleus RNA sequencing, and preoperative MRI-derived morphologic feature analysis across multi-institutional cohorts of treatment-naïve IDH-wildtype GB. Results High ICAM1 expression at both transcript and protein levels is associated with shorter overall survival, particularly within the mesenchymal transcriptional subtype. ICAM1 expression is inversely associated with promoter methylation. Single-nucleus RNA-sequencing analysis shows that ICAM1-high tumors are enriched for mesenchymal, hypoxia, stress-associated, and immunosuppressive myeloid programs, suggesting that ICAM1 reflects a multicompartment inflammatory tumor ecosystem. ICAM1 expression, tumor surface irregularity, and patient age are independently prognostic and minimally correlated, capturing complementary clinical, imaging, and molecular features of GB biology. When combined, our Clinical-Imaging-Molecular (CIM) framework refines outcome prediction across independent GB cohorts using routinely available clinical data, conventional imaging, and standard immunohistochemistry. Conclusions ICAM1 characterizes an immune-remodeled, stress-adapted GB ecosystem associated with poor clinical outcomes. Integrating patient age, surface irregularity, and ICAM1 expression yields a scalable and clinically accessible prognostic framework for GB, supporting tailored outcome prediction, particularly in low- and middle-resource settings without routine access to advanced molecular profiling.

Moderate traumatic brain injury (TBI) is a prevalent entity with a wide, dynamic, and heterogeneous injury spectrum. It has its own characteristics. However, it does not receive enough attention, as evidenced by the scarce representation in the literature and the absence of specific guidelines. Its changing epidemiological profile allows us to predict an increase in its incidence in the future, especially in the fragile population. Moderate TBI is not adequately categorized, and the risk of neuroworsening is elevated. The mortality of moderate TBI is not negligible and its functional outcomes are poor. Non-invasive neuromonitoring tools may have a key role in the initial evaluation and categorization of moderate TBI. Moderate TBI has cloudy, dark, and sunny aspects. To analyze these aspects and to propose management strategies constitute the main objective of this narrative review.

Abstract Background Poor operating room (OR) ergonomics poses risk of injury to OR staff, worsening patient outcomes and threatening workforce wellness and sustainability. How OR staff navigate ergonomic barriers in the interdisciplinary team environment was examined in this qualitative study. Methods Semi-structured, open-ended interviews of surgeons, anaesthesiologists, and OR nurses were conducted at a single institution using a sociomaterial approach with interview-to-the-double. Transcripts were coded by two independent researchers. Themes in the data were outlined using the System Engineering Initiative for Patient Safety (SEIPS) 2.0 framework. Results Five major themes were identified. First, physical environment issues creating cognitive and physical frictions, such as tripping hazards and poor room layouts. Second, influence of social positionality, with hierarchy by role and experience and social dynamics leading to a differential capacity to adjust. Third, team collaboration, with lack of interdisciplinary work and communication and high staff turnover. Fourth, burden of self-initiated workarounds, outlining conflicts between system/organizational issues and individual solutions. Fifth, institutional support, with lack of leadership engagement. Participants suggested solutions including accommodations to foster a collaborative approach to managing discomfort in the OR and new team communication tools. Conclusion Ergonomic barriers were described within the work system of the SEIPS 2.0 framework. Social positionality and differential levels of agency, as well as lack of team collaboration and misperceptions of others’ roles, were central to ergonomic challenges. Conflicts between problems lying with the system/organization and solutions being left to individuals were also central to challenges to optimal OR ergonomics.