Citations

Abstract Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease linked to repetitive traumatic brain injury, but its prevalence and risk factors in the general population remain poorly defined. We investigated CTE neuropathological changes (CTE-NC) in an admixed, population-based clinicopathological cohort. Neuropathological evaluation was conducted on brain samples from 1151 individuals in the University of São Paulo Biobank for Aging Studies collected from 2004 to 2022. CTE-NC and aging-related tau astrogliopathy (ARTAG) were assessed across 14 963 histological slides using p-tau immunostaining. Clinical, cognitive, and neuropsychiatric data were obtained via informant interviews; information on sports exposure and traumatic brain injury history was limited. Seven cases (0.6%) met criteria for CTE-NC, mean age at death 73.4 ± 12.5 years; 1 was female. Dementia was present in 43% of CTE-NC cases; 57% exhibited neuropsychiatric symptoms. Most common co-pathologies were Alzheimer disease-type changes, ARTAG, and argyrophilic grain disease. Comprehensive exposure histories were unavailable for most cases; 2 had documented soccer involvement. These findings indicate that CTE-NC is rare in this population-based Brazilian cohort and predominantly affects males with frequent coexisting neuropathologies. Findings align with reports from high-income countries and support prioritizing primary prevention by reducing exposure to repetitive head impacts in sport and other settings.

Context.— Optical genome mapping (OGM) represents a promising cytogenomic technology that detects structural variants, including fusions, rearrangements, copy number variants, and loss of heterozygosity, in a single assay. Unlike karyotyping, fluorescence in situ hybridization, or chromosomal microarray, OGM leverages long-molecule imaging to map the whole genome with high resolution. This positions OGM as a novel tool for constitutional and somatic/cancer genomics. However, its current and planned utilization in clinical and research settings remains unknown, necessitating further investigation. Objective.— To investigate the current utilization of OGM in clinical and research laboratories, assess its applications, and evaluate future utilization strategies. Design.— In 2024, a supplemental questionnaire was incorporated into 6 College of American Pathologists proficiency testing programs to evaluate OGM’s utilization. Results.— Of 921 returned questionnaires, 712 were analyzed after duplicates were removed. Sixty-seven (9.4%) currently offered OGM testing: 5.2% (37) for research only, 1.8% (13) for only clinical use, and 2.4% (17) for both. Future adoption plans showed 7.6% (53 of 700 laboratories) and 7.9% (55 of 700 laboratories) aiming to implement OGM clinically within 12 and 24 months, respectively. The most common applications included hematologic malignancies and constitutional/germline postnatal disorders, followed by prenatal testing. International laboratories demonstrated statistically higher utilization rates than domestic laboratories ( P = .001). Conclusions.— This first survey on OGM clinical utilization reveals its status as a niche technology, with 67 laboratories currently using it. Its primary clinical applications are in constitutional/germline analysis and hematologic malignancies. Although international laboratories led in 2024, 108 laboratories (domestic and international) plan clinical adoption within 24 months, signaling OGM’s potential for broader integration.

Importance Accurate classification and reliability in assessment for lesions of hidradenitis suppurativa (HS) by investigators is critical to the determination of responder status and to overall data quality in clinical trials. Objective To establish consensus-based morphological definitions of HS lesions and guidance statements that standardize investigator lesion assessments for implementation in clinical trials. Evidence Review Health professionals (primarily dermatologists) with expertise in the measurement of HS disease activity as well as novice raters completed a preliminary questionnaire in which participants were asked to assess images of HS lesions and provide qualitative feedback on their decision making. Based on this feedback, detailed morphologic definitions for lesions and guidance statements that standardize lesion assessments were formulated and presented for consensus voting in 2 electronic Delphi surveys. A virtual group discussion after round 1 supported participants in round 2 voting. Findings Response rates were 84.7% (50 of 59), 86.0% (43 of 50), and 90.9% (40 of 44) in the preliminary, electronic Delphi round 1, and electronic Delphi round 2 surveys, respectively. Morphological definitions for 11 lesion types achieved the prespecified 70% consensus threshold, with 9 definitions reaching at least 90% agreement. After 2 electronic Delphi rounds, 16 of 18 guidance statements achieved the prespecified consensus threshold, with 13 statements receiving endorsement from more than 80% of participants. Two guidance statements related to assessment of tunneled plaques with multiple openings and assessment of scalp lesions failed to reach consensus. Conclusions and Relevance Common morphologic definitions and guidance that standardize assessment of HS lesions can be implemented in clinical trial protocols and investigator trainings with the goals of improving accuracy and reliability of investigator ratings.

Background Immune‐checkpoint inhibitors (ICI) are associated with adverse cardiac events. Although troponin elevation is a diagnostic criterion for ICI‐related myocarditis (ICIrM) and myocardial infarction, data on other causes of troponin elevation and their outcomes in ICI‐treated patients are limited. Methods All patients treated with ICI who had hs‐TnT (high‐sensitivity troponin T) measured at a multicenter institution from 2011 to 2022 were included. Clinical data, outcomes (cardiac death, heart failure (HF), major adverse cardiovascular events [myocardial infarction, stroke, heart failure]), and cause of hs‐TnT elevation were assessed. Risks of cardiac events were compared across hs‐TnT elevation causes. Results Of 5423 patients treated with ICI, 1669 had post‐ICI hs‐TnT measurement (mean age 68.7±11.3 years, 58.3% male), with 1‐year follow‐up. Hs‐TnT elevation in patients with ICIrM (n=59) was associated with the highest risk for cardiac death (hazard ratio [HR], 52.7 [95% CI, 11.7–238.0], P <0.001), followed by hs‐TnT elevation due to heart failure (HR, 15.9), myocardial infarction/type 2 ischemia (HR, 11.6), and infection/sepsis (HR, 5.7), compared with those with no hs‐TnT elevation. ICIrM also carried highest risk for major adverse cardiovascular events (HR, 8.2, [95% CI, 4.4–15.3], P <0.001), followed by myocardial infarction/type 2 ischemia (HR, 8.1), heart failure (HR, 7.6), pulmonary embolus (HR, 5.1), infection/sepsis (HR, 4.1), and indeterminate cause (HR, 2.4). Among ICIrM, HsTnT value >576 ng/L best predicted risk for cardiac death and >319 ng/L for major adverse cardiovascular events. Conclusions Hs‐TnT elevation after ICI therapy is associated with increased risk of cardiac events, particularly in ICIrM, and a graded prognostic association depending on the cause of hs‐TnT elevation. Identifying the underlying cause and troponin thresholds may guide risk stratification and management.

Abstract Introduction This is the first International Consultation on Sexual Medicine (ICSM) position paper on sexual health in older adults. Physical, cognitive, and psychosocial factors create a unique set of challenges related to sexuality in older adults. Objectives This study explores the impact of the physiological aspects of aging, state of health, psychological, relationship-related, and sociocultural factors, on sexual health in older adults. The goal of this review is to provide recommendations for the comprehensive evaluation and treatment of this population. Methods A narrative review was conducted under the auspices of the ICSM, as part of its ongoing efforts to develop expert, evidence-based guidance in the field of sexual health. A multidisciplinary panel of international experts composed of specialists in urology, gynecology, psychiatry, sexual medicine, social work, and sex therapy was convened. A comprehensive literature review was conducted based on a search of psychological sources (PsycInfo), medical databases (PubMed, Medline), and Google Scholar. All retrieved articles were reviewed and critically assessed. Recommendations were then formulated using a modified Delphi method. Results Although there is extensive literature on the prevalence and risk of sexual challenges of adults over the age of 65, there is limited evidence regarding the quality of treatment modalities. In particular, there is scant data on women in this age group. This population faces specific and multifactorial challenges, which point to the need for a comprehensive approach to their care. Conclusion Any approach to sexual health in older adults needs to take all the factors that affect sexual health into account, while endorsing the full spectrum of sexual expression in a non-judgmental way. Individuals in a relationship should be offered a couple-centered approach. Special attention is needed for individuals in cognitive decline. Healthcare providers must be aware of ageist biases, which may prevent them from providing appropriate care.

ABSTRACT Introduction Cardiac resynchronization therapy (CRT) improves clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, data on its efficacy in patients with sarcoidosis and HFrEF are limited. Methods Using the TriNetX network, we identified patients with sarcoidosis, heart failure with a left ventricular ejection fraction (LVEF) below 35%, and either left bundle branch block (LBBB) or prolonged QRS duration ( > 150 ms) between 2014 and 2019. Patients were categorized into two cohorts: (1) those who received CRT and (2) those who received an ICD‐only implant. Five‐year outcomes included all‐cause mortality, all‐cause hospitalization, heart failure exacerbation, and the proportion of patients with improvement in LVEF to greater than 40% and greater than 50%. Results Out of 245 eligible patients, we identified a cohort of 87 patients (mean age 62.6 ± 9.5 years) who received CRT and 87 patients (mean age 62.1 ± 11.1 years) who received ICD‐only implant, with similar propensity scores, and included them in a comparative analysis. At 5‐year follow‐up, the CRT group demonstrated outcomes comparable to the ICD‐only implant group for all‐cause mortality (14.9% vs. 20.7%; HR 0.63; 95% CI 0.31–1.28; p = 0.19), all‐cause hospitalization (83.9% vs. 77.0%; HR 1.24; 95% CI 0.89–1.73; p = 0.19), and heart failure exacerbation (28.7% vs. 28.7%; HR 0.90; 95% CI 0.52–1.57; p = 0.72). The proportion of patients with improvement in LVEF to greater than 40% and greater than 50% was also similar in both groups (LVEF > 40%, 43.7% vs. 33.3%; HR 1.30; 95% CI 0.80–2.10; p = 0.29; LVEF > 50%, 31.0% vs. 17.2%; HR 1.72; 95% CI 0.92–3.24; p = 0.09). Conclusion CRT implantation had similar long‐term outcomes compared to ICD‐only implantation in patients with sarcoidosis and HFrEF, particularly all‐cause mortality, all‐cause hospitalization, heart failure exacerbation, and the proportion of patients with improvement in LVEF to greater than 40% and greater than 50%.

ABSTRACT Central venous catheters (CVCs) are a cornerstone of hematopoietic stem cell transplantation (HSCT), facilitating the delivery of chemotherapy, parenteral nutrition, medications, and blood products. Despite CVCs’ essential role, prolonged use can lead to complications such as increased risk of infection, thrombosis, mechanical issues, and psychosocial burden. However, the timing of CVC removal remains highly variable across institutions. Additionally, there are no standardized guidelines to balance the benefits of extended access against the risks of prolonged use. This narrative review examines the existing literature on CVC management post‐HSCT, highlighting key factors influencing the removal timing, such as patient characteristics, disease‐specific considerations, and institutional practices. The review emphasizes the urgent need for multi‐institutional research and standardized protocols to improve outcomes, reduce complications, and enhance the quality of care for HSCT patients.