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BACKGROUND: This study aimed to evaluate the prevalence of pathogenic/likely pathogenic cardiomyopathy variant carriers in a multiancestry US population and examine the risk of adverse clinical outcomes. METHODS: This retrospective cohort study included multiancestry US adults aged ≥18 years with sequencing data from the All of Us Research Program. Pathogenic/likely pathogenic variants in cardiomyopathy genes were identified using the ClinVar database. The primary outcome was heart failure. Secondary outcomes included cardiomyopathy and arrhythmia. Outcomes were identified from electronic health records. Interval-censored Cox models, taking age on the timescale, were used to assess the risk of outcomes in pathogenic/likely pathogenic variant carriers with noncarriers as the reference group. RESULTS: Among 167 435 individuals (median age, 55.2 [39.5–66.3] years; 61.7% female; 40.7% non-European ancestry) included, the prevalence of pathogenic/likely pathogenic cardiomyopathy variant carriers was 0.7% in the overall population and 0.8%, 0.8%, 0.5%, and 1.2% among European, African, East Asian, and South Asian ancestry individuals, respectively. Over their lifetime, there were 12 867 heart failure events (205 in carriers and 12 662 in noncarriers), with an incidence rate of 3.05 (95% CI, 2.66–3.49) per 1000 person-years in carriers and 1.37 (95% CI, 1.35–1.40) in noncarriers (adjusted hazard ratio, 2.30 [95% CI, 2.04–2.60]). Cardiomyopathy occurred in 5164 (161 in carriers and 5003 in noncarriers), with an incidence rate of 2.38 (95% CI, 2.04–2.78) per 1000 person-years among carriers and 0.54 (95% CI, 0.53–0.56) in noncarriers (adjusted hazard ratio, 4.31 [95% CI, 3.73–4.97]). There were 19 405 arrhythmia events (263 in carriers and 19 142 in noncarriers), with an incidence rate of 3.93 (95% CI, 3.48–4.44) per 1000 person-years among carriers and 2.09 (95% CI, 2.06–2.12) in noncarriers (adjusted hazard ratio, 2.12 [95% CI, 1.78–2.53]). CONCLUSIONS: Pathogenic/likely pathogenic cardiomyopathy variant carriers have an increased risk of heart failure, cardiomyopathy, and arrhythmias. Despite the modest overall prevalence, the associated risks suggest potential benefits of targeted genetic screening for early detection and management.

ABSTRACTBackgroundWe aimed to determine the performance of postoperative computed tomography (CT) and upper gastrointestinal series (UGI) in patients who underwent surgery for a perforated peptic ulcer and to assess the yield of routine postoperative studies.MethodsRetrospective, single‐institution, chart‐review study of patients who underwent a repair of a perforated gastric or duodenal ulcer between August 2004 and September 2021 at Mayo Clinic, Rochester, Minnesota.ResultsWe identified a total of 240 patients, 28 (12%) were found to have leaks. When any of the four findings (extraluminal gas or fluid collection adjacent to the repair, worsening pneumoperitoneum, or enteral contrast extravasation) was present on postoperative CT scan (n = 116) it had sensitivity of 76% (95% CI 53%–90%), with a specificity of 90% (95% CI 84%–91%). Upper gastrointestinal series (UGI, n = 150) showed a sensitivity of 57% (95% CI 25%–84%) and a specificity of 99% (95% CI 96%–100%). UGI demonstrated higher specificity compared to CT (p < 0.01); there was no significant difference in sensitivity (p = 0.34). The findings from CT scans led to changes in management for a significantly greater number of patients compared to UGI (20% vs. 4%, p < 0.01). The diagnostic yield for leak identification was 3% for routine postoperative CT (n = 63) and 2% for routine UGI studies (n = 141).ConclusionsPostoperative CT is more likely to change management in patients who underwent repair of a perforated peptic ulcer compared to postoperative upper gastrointestinal series. The yield of routine postoperative studies is low, and their benefit is uncertain.

Cardiovascular disease is the global #1 cause of mortality and morbidity. The majority of cardiovascular diseases is caused by atherosclerosis, a lipid-driven, inflammatory disease of the middle- and large-sized arteries. The disease is characterized by the formation of atherosclerotic plaques throughout the arterial tree. Over the years, insights into the pathogenesis of atherosclerosis have shifted from a ‘lipid-driven’ model to a ‘response-to-injury’ perspective, and more recently to a ‘lipid-driven inflammatory disease’ viewpoint. We are now aware that a network of multiple immune cell-types and -subsets of the innate and adaptive immune system inhabit our arteries. Intricate interactions between these immune cellsubsets, non-immune cells, and local environmental substances such as lipids, cell debris and calcium cause a fluidic balance of pro-inflammatory and regulatory responses. A dysregulation of this balance towards a pro-inflammatory milieu drives atherosclerotic disease progression. Although we have acknowledged that atherosclerosis is an inflammatory disease, state-of-theart treatments are still based on lipid lowering, anti-hypertensive and lifestyle-changing strategies. In the past decade, clinical phase I, II and III trials targeting the immune system revealed that patients tolerate immunotherapy, show decreased inflammation and/or had a reduction in cardiovascular endpoints. However, the search for novel immunotherapeutic targets and treatment regimens as well as stratification of patients who would benefit from such treatments to combat atherosclerotic cardiovascular disease is only just beginning. In this review article, we will highlight the newest insights on the different cell subsets and components of the immune system in atherosclerosis and elaborate on current and future immunotherapeutics to treat atherosclerotic cardiovascular disease.

Background: Major League Baseball (MLB) recently instituted a combine for their prospective players. Purpose/Hypothesis: The purpose of this study was to report initial epidemiological findings for both physical examination and imaging findings for the MLB Combine. It was hypothesized that most players would have no significant abnormal physical examination findings, but most would have abnormal findings on their shoulder and elbow magnetic resonance imaging (MRI) scans. Study Design: Descriptive epidemiology study. Methods: All players who attended the 2023 MLB Combine were included. History was taken and physical examination was performed by an MLB team physician, and MRI of the shoulder, elbow, cervical spine, and lumbar spine was performed on all players and read by 1 of 2 musculoskeletal radiologists. Physical examination notes and imaging reports were reviewed by the authors and recorded. Data were analyzed separately for pitchers and position players. Results: Overall, 219 players (112 pitchers [51%], 107 position players [49%]) were included. The mean age was 20.4 ± 1.5 years. The majority of players (95%) had no current pain or limitations; 54 players (25%) had a history of previous surgery. For pitchers, 18% underwent previous elbow surgery. With regard to MRI, >80% of pitchers had some abnormality within their ulnar collateral ligament (UCL), the majority of which was UCL scarring/remodeling. 70% of pitchers and 60% of position players had evidence of an olecranon osteophyte. Increased signal within the ulnar nerve was common in pitchers (40%) but rare in position players (4%). For the shoulder, 95% of pitchers and 93% of position players had some rotator cuff abnormality (often tendinosis within the supraspinatus and infraspinatus muscles). Also, 75% of pitchers had MRI evidence of a superior labrum anterior to posterior (SLAP) tear, while 24% of position players demonstrated this. Lumbar spine MRI showed that 47% of position players had a disk protrusion and 46% had a previous pars fracture. Conclusion: Most baseball players who participated in the 2023 MLB Combine had MRI evidence of rotator cuff abnormalities, and many showed evidence of an olecranon osteophyte. Eighteen percent of pitchers had a previous history of elbow surgery. The majority of pitchers had some abnormality within their UCL and evidence of a SLAP tear on MRI scans.

In 2007, the Bárány Society embarked on a project to establish definitions of vestibular syndromes and disorders based on best available evidence, referred to as the International Classification of Vestibular Disorders (ICVD). Since then, numerous publications providing consensus-driven diagnostic criteria for vestibular symptoms, syndromes, and disorders have been published. Here, we reflect on the rationale for developing the ICVD as well as its subsequent achievements, challenges, and outlook. In this summary of the work of the ICVD to date, the authors will focus on practical aspects to help improve the utility and applicability of these diagnostic criteria moving forward.

ABSTRACT In 2005, the Paediatric Radiation Oncology Society (PROS), a multi‐professional association to promote radiotherapy for children and young people, was created. Its mission has been to educate those involved in this field, and to improve the standards of radiation oncology care for children, adolescents, and young adults across the globe, not least in less privileged settings where the majority of the world's children, and most with cancer, live. Through regular congresses, and joint meetings with the International Society of Paediatric Oncology (SIOP), PROS has facilitated a focus on this treatment modality, and advocated on behalf of those who might benefit from it.

Abstract INTRODUCTION Biomarkers play a crucial role in understanding Alzheimer's disease (AD) pathogenesis and treatment effects. However, comparing biomarker measures without standardization and appreciating their magnitude relative to the disease can be challenging. METHODS To address this issue, we propose the CentiMarker approach, similar to Centiloid, which provides a standardized scale between normal (0) and nearly maximum abnormal AD (100) ranges. We applied this scale to cerebrospinal fluid (CSF) biomarkers in dominantly inherited AD and sporadic AD cohorts. RESULTS CentiMarkers facilitated the interpretation of disease abnormality, demonstrating comparable changes and distributions of AD biomarkers across disease stages. CentiMarkers make the treatment effect more comparable than their original scales across various biomarkers. DISCUSSION The versatility of CentiMarkers makes it a valuable tool for standardized biomarker comparison in AD research, enabling informed cross‐study comparisons and contributing to accelerated therapeutic development. Adoption of the CentiMarker scale could enhance biomarker reporting and advance our understanding of AD. Highlights Comparing fluid biomarkers without appreciating their magnitude relative to the disease can be challenging. We propose a CentiMarker metric to standardize biomarker measures from normal (0) and nearly maximum abnormal AD (100) ranges. CentiMarkers make the treatment effect more comparable across various biomarkers than when using the original scales.