Citations

Chest CTs done for unrelated reasons have the potential to reveal unsuspected abnormalities and provide complementary information to help direct appropriate management. By thoroughly understanding the diagnostic role and limitations of CT in assessing ventricular size and morphology as well as myocardial attenuation, enhancement, and thickness, radiologists will be better equipped to differentiate between normal and abnormal findings and provide precise, clinically appropriate recommendations.

Abstract Background Cardiovascular disease (CVD) is the leading cause of death globally for both men and women, yet women remain historically underrepresented in cardiovascular clinical trials (CV trials), despite facing a disproportionately high burden of morbidity and mortality in many forms of CVD. Purpose We aim to determine the representation of women across a broad range of CV trials. Methods The participation of women in CV trials registered on ClinicalTrials.gov from 2017 to 2023 was systematically determined through the extraction of publicly available information. Data was extracted to identify the country of study, disease type, trial size, clinical intervention and age of the participants. We calculated the proportion of women and the ratio of number of females to male participants (F:M ratio) for each trial. The female participation to prevalence ratio (PPR) was estimated for each trial based on the relative prevalence of the disease by sex in the specified region. Results We identified 1,079 registered CV trials, which included 1,396,104 participants, of whom 571,641 (41.0%) were women. The median F:M ratio was significantly lower for studies on arrhythmia (0.5), coronary heart disease (CHD) (0.39), acute coronary syndrome (ACS) (0.32) and heart failure (HF) (0.51), but was higher for obesity (1.44) and pulmonary hypertension (PH) (2.86) CV trials. F:M ratio was higher for trials on lifestyle intervention (1.51) than for drug trials. PPRs were low for clinical trials on CHD (0.66), ACS (0.79), and stroke (0.74). There was a trend to increasing PPR from 2017 to 2023, p=0.056. Conclusion Representation of women in CV trials varies by disease state, region, intervention, and sponsor type. Better understanding of reasons for these differences may enable more tailored interventions to improve representation of women globally and across therapeutic areas.Figure 1 Figure 2

Abstract Background Alcohol consumption and its relationship with cardiovascular disease (CVD) remains controversial. Observational studies have reported J-shaped associations suggesting cardioprotective effects of moderate drinking, while other observational and Mendelian Randomization studies have found dose-response harm. Biases such as abstainer misclassification, sick quitter effects, and residual confounding may obscure true associations. This study aimed to reassess alcohol’s impact on CVD using novel methods to minimize bias. Purpose We evaluated the relationship between alcohol and subclinical (coronary artery calcium [CAC]) and clinical (myocardial infarction [MI], stroke, cardiovascular death, major adverse cardiovascular events [MACE], and heart failure) outcomes in the Multi-Ethnic Study of Atherosclerosis (MESA). We compared conventional models with those using (1) occasional drinkers as the reference group instead of lifetime abstainers and (2) intention-to-treat (ITT) reallocation of former drinkers based on past drinking patterns. Methods MESA is a prospective cohort study of 6,814 participants aged 45-84 years without baseline CVD. Alcohol use was classified as lifetime abstainer, former drinker, or current drinker (occasional [≤1 drink/week], light [2-7 drinks/week], moderate [8-14 drinks/week], heavy [>14 drinks/week]). We used multinomial logistic regression for CAC and Cox proportional hazards models for clinical outcomes across four models: (1) non-drinker reference, (2) lifetime abstainer reference, (3) occasional drinker reference, and (4) occasional drinker reference with ITT reallocation of former drinkers to their previous drinking levels. Results Increasing alcohol consumption correlated with a dose-response increase in CAC. Heavy drinking was consistently associated with severe CAC (>300). In fully adjusted models, light (OR: 1.23, 95% CI: 1.02-1.48), moderate (OR: 1.27, 95% CI: 1.04-1.55), and heavy drinking (OR: 1.42, 95% CI: 1.12-1.78) were associated with higher CAC scores compared to occasional drinkers. Traditional models replicated protective effects of moderate drinking for MI and cardiovascular mortality. However, these associations attenuated in adjusted models. Moderate drinking showed an attenuated, non-significant benefit for MI (HR: 0.64, 95% CI: 0.38-1.06) and cardiovascular mortality (HR: 0.81, 95% CI: 0.53-1.25) in fully adjusted models. Light drinking shifted from null to increased risk for MI (HR: 1.46, 95% CI: 1.11-1.92), stroke (HR: 1.54, 95% CI: 1.17-2.03), MACE (HR: 1.33, 95% CI: 1.12-1.57), and heart failure (HR: 1.42, 95% CI: 1.10-1.84). Conclusion Adjusting for abstainer and sick quitter biases altered the observed relationship between alcohol and CVD, showing increased harm with light drinking, attenuated protective effects of moderate drinking, and a dose-response relationship for CAC in bias-adjusted models. These findings illustrate the importance of methodology in alcohol-CVD relationships.

Abstract The Association for Diagnostics & Laboratory Medicine (ADLM) aims to improve health by providing education to laboratory scientists worldwide. Different regions of the world face unique challenges shaped by their national and regional contexts. However, the needs of clinical laboratories worldwide remain largely understudied. To address this gap, we conducted a comprehensive needs assessment survey among laboratory professionals in the Latin American region. The survey was distributed to over 2708 individuals across Latin American countries and yielded 148 responses. Most respondents were from urban areas (74%) and worked in private hospital laboratories (45%), with microbiology (25%) and chemistry (23%) identified as the most common specialties. Key findings include continuing education as the top challenge, identified by 59% of respondents, with a predominant preference for virtual learning formats (83%), though not exclusively; 50% also identified a preference for in-person learning. Other challenges, such as staff shortages, lack of equipment and funding, were selected by 30% to 36% of respondents, whereas regulatory oversight and quality management were less frequently identified as priorities. To contextualize the survey findings, we conducted interviews with laboratory professionals in the region. Common themes included resource and technology constraints, uneven implementation of quality standards, and the need for collaboration between government and professional organizations to bridge gaps in practice. This assessment highlights the need for targeted educational interventions to address the distinct challenges faced by Latin American laboratories. Addressing these gaps in continued education, fostering collaboration, and engaging stakeholders in the region offer a roadmap to strengthening laboratory services and health outcomes.

Abstract Background Identification of the microorganisms causing infection in children with central nervous system infection is important. Conventional cerebrospinal fluid (CSF) tests may provide limited pathogen detection. CSF metagenomic next-generation sequencing (mNGS) may provide broader pathogen detection in a single assay. Methods Results of CSF mNGS testing performed at Mayo Clinic on patients and nonpatients between January 2024 and June 2025 were retrospectively analyzed. The subcohort of children treated at Mayo Clinic was analyzed to assess test performance as compared with conventional CSF diagnostics and potential clinical impact. Results In total 134 patients (138 CSF mNGS tests) from 22 US states and 2 international sites were included. Overall positivity was 16% with viruses representing most (59%) detections. In the Mayo Clinic subcohort (n = 15), test positivity was 27%: organisms included single detections of Streptococcus mitis group and HIV type 1, as well as 2 detections of Epstein-Barr virus, all confirmed by conventional tests. Positive results were associated with CSF pleocytosis (P = .026). Higher yield was observed in participants whose care was overseen by pediatric infectious diseases (PID) specialists (P = .026) and when a specimen hold strategy was applied (P = .033). Most results (87%) did not alter antimicrobial therapy, with 2 negative results contributing to antimicrobial de-escalation. Conclusions CSF mNGS demonstrated higher diagnostic yield in patients whose specimens showed CSF pleocytosis and in those who had PID consultation. Diagnostic stewardship strategies were applied, including specimen hold approaches and PID consultation.

Importance As gender-affirming care expands, hysterectomies for gender dysphoria are increasing, but data comparing outcomes to benign hysterectomies remain limited. Objectives The objectives of this study were to compare perioperative characteristics and 30-day outcomes between transgender and gender diverse individuals (TGDI) undergoing gender-affirming hysterectomy (GAH) and patients undergoing hysterectomy for benign indications, by surgical approach. Study Design This was a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program data (October 2015–December 2022). TGDI undergoing GAH were identified by gender dysphoria diagnosis and hysterectomy Current Procedural Terminology codes. Approaches included abdominal hysterectomy (AH), laparoscopic/robotic hysterectomy (L/RH), laparoscopically assisted vaginal hysterectomy (LAVH), and vaginal hysterectomy (VH). A matched cohort was created based on demographics and comorbidities. Primary outcomes were operative time, length of stay (LOS), and 30-day complications. Results A total of 975 TGDI undergoing GAH were included; 82% of GAHs were minimally invasive, mostly L/RH. GAH represented 0.7% of all benign hysterectomies, increasing over time ( P <0.001). TGDI (970) were matched to controls. In L/RH, TGDI had longer operative times (113 vs 97 min, P <0.001) but shorter LOS (0 vs 1 d, P <0.001). Similar patterns were seen in VH: longer operative times (103 vs 62 min, P <0.001) and shorter LOS (0 vs 1 d, P =0.018). In AH, TGDI had shorter LOS (1 vs 2 d, P =0.006) with similar operative times. No significant differences were found in LAVH or complications across groups. Conclusion GAH is safe with perioperative outcomes comparable to benign hysterectomy. TGDI experience shorter hospital stays and low complication rates. Promoting minimally invasive and vaginal approaches can enhance equitable, high-quality care for TGDI.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHIs), characterized by tau tangles around small blood vessels at the depths of the sulci. Currently, CTE can be diagnosed only postmortem , but can present with an array of cognitive, behavioral, mood, and motor symptoms. However, traumatic brain injury is also associated with increased risk of Alzheimer’s disease (AD) and may lead to comorbid neuropathology. Characterization of the in vivo biomarkers of CTE is a necessary next step to facilitate accurate diagnoses. We examined the profile of cerebrospinal fluid (CSF) biomarkers of amyloid-β, total tau (tTau), and phospho-tau (pTau) in a cohort of former professional (PRO, n = 100) and college (COL, n = 40) football players at high risk of CTE compared to asymptomatic unexposed controls (UE, n = 43). CSF was collected under controlled conditions using collection, processing, and cryostorage kits provided by the DIAGNOSE CTE Research Project Biomarker Core, and concentrations of Aβ 40 , Aβ 42 , tTau, and pTau (pTau 181 , pTau 217 , pTau 231 ) were measured at the University of Gothenburg, Sweden, using immunoassays. Associations between CSF biomarker levels with football history, and diagnosis of traumatic encephalopathy syndrome (TES) were examined using linear regression, and corrected for age, education, APOE -ε4 allele status, race, and body mass index. Our analysis revealed that football exposure affected both CSF Aβ 40 ( p = 0.039) and Aβ 42 ( p = 0.038), particularly among those under 60 years of age in the PRO compared to the UE exposure group. Among former football players, estimates of RHI exposure were not generally associated with CSF Aβ, tTau, and pTau biomarker levels. CSF Aβ 40 ( p = 0.0041) and Aβ 42 ( p = 0.011) were lower in former football players with TES diagnosis compared to unexposed participants, although CSF Aβ, tTau, and pTau biomarker levels did not differ between former players with and without a TES diagnosis. Among former football players, reduced CSF Aβ 40 ( p = 0.011) and Aβ 42 (p = 6e-04) were observed in those with cognitive impairment compared to those with neurobehavioral dysregulation. The findings of significant associations of reduced CSF Aβ levels with RHI in elite football players are in line with recent postmortem studies; however, the lack of relationship with CSF tTau and pTau species observed to be altered in the setting of AD suggests that the pathological features of CTE reflected in fluid biomarkers are complex and require further study. The overlapping comorbid age-dependent features of neurodegeneration that occur in those at risk for CTE suggest that tau pathology in CTE is not reliably reflected by currently available fluid biomarkers and that the use of multiple biomarkers related to the compound characteristics of CTE may be required for early detection.

Objective Age of symptom onset is highly variable in familial frontotemporal lobar degeneration (f‐FTLD). Accurate prediction of onset would inform clinical management and trial enrollment. Prior studies indicate that individualized maps of brain atrophy can predict conversion to dementia in f‐FTLD. We used a Bayesian linear mixed‐effect (BLME) prediction method for identifying accelerated brain volume loss to predict conversion to dementia. Methods Participants included 234 asymptomatic or prodromal carriers of C9orf72 , GRN , or MAPT mutations (including 21 dementia converters) with ≥3 longitudinal magnetic resonance imaging (MRI) T1‐weighted scans. The BLME models established individual voxel‐wise gray matter trajectories using the first 2 scans. Person‐specific clusters of accelerated volume loss were estimated in subsequent scans and tested as predictors of dementia conversion compared with other approaches in time‐varying Cox proportional hazard models covarying for age. Receiver‐operating characteristic (ROC) curves estimated utility of cluster volume in discriminating which participants converted to dementia within 24 months. Results The BLME cluster volume predicted conversion to dementia in f‐FTLD mutation carriers overall and separately in C9orf72 , GRN , and MAPT , with comparable hazard ratios observed for atrophy W‐maps and regional volumes. Within a 24‐month timeframe, BLME cluster volume discriminated dementia converters from non‐converters with larger areas under the curve (AUCs) than other approaches. Interpretation Bayesian‐modeled individualized atrophy scores predict dementia progression among asymptomatic f‐FTLD mutation carriers and may have increased utility compared with other structural imaging methods when studying individuals over shorter timeframes that align with clinical trial design. ANN NEUROL 20269999:n/a–n/a

Objective: Epidemiological data have suggested that late-life depression (LLD) occurs as a consequence of cerebrovascular and neurodegenerative disorders, but there is also some evidence suggesting that the relationship may occur in the other direction, namely that LLD may be a risk factor for cerebrovascular and neurodegenerative disorders. However, the neurobiological basis of these associations remain unclear. This study investigated the associations of LLD with markers of cerebrovascular pathology, brain volumes, and cortical thickness from 3-Tesla brain magnetic resonance imaging (MRI). Methods: Participants from the Atherosclerosis Risk in Communities Study received brain MRI scans in late-life (ages 67-90). The following neuroimaging outcomes were assessed: cortical infarcts, lacunar infarcts, any microhemorrhages, lobar microhemorrhages, subcortical microhemorrhages, white matter hyperintensity volume, total and regional brain volumes (z-scores), and total average and regional cortical thickness (z-scores). At the same visit, LLD was evaluated with the 11-item Center for Epidemiological Studies Depression Scale (CES-D) and defined as CES-D score≥9. Associations between LLD and neuroimaging outcomes were examined using logistic and linear regression models, and were adjusted for age, race-center, sex, education level, vascular risk factors, stroke, cognitive status, APOE e4 carrier status, and total intracranial volume when assessing volumes. Results: Among 1,857 participants, the median age was 76 years, 59.5% were female, 28.3% were Black, and 6.8% had LLD. LLD was not associated with infarcts or microhemorrhages. There was no evidence of an association between LLD and total white matter hyperintensity volume or total average cortical thickness. However, LLD was independently associated with smaller volume (SD) of the rostral anterior cingulate (b 1 : -0.18; 95% CI: -0.33, -0.04) and greater cortical thickness (SD) in the medial orbitofrontal cortex (b 1 : 0.19; 95% CI: 0.01, 0.38), though effect sizes were small and did not survive correction for multiple comparisons. Conclusion: Findings from this study suggest LLD is not cross-sectionally associated with neuroimaging markers of cerebrovascular disease. While LLD may be linked to subtle volume and cortical thickness changes in specific regions of interest, future longitudinal research is warranted to validate and clarify these associations and explore their potentially bidirectional relationship.