Citations

Objective: To determine the etiology of sudden cardiac arrest and death (SCA/D) in competitive athletes through a prospective national surveillance program. Design: Sudden cardiac arrest and death cases in middle school, high school, college, and professional athletes were identified from July 2014 to June 2016 through traditional and social media searches, reporting to the National Center for Catastrophic Sports Injury Research, communication with state and national high school associations, review of the Parent Heart Watch database, and search of student-athlete deaths on the NCAA Resolutions List. Autopsy reports and medical records were reviewed by a multidisciplinary panel to determine the underlying cause. Setting and Participants: US competitive athletes with SCA/D. Main Outcome Measures: Etiology of SCA/D. Results: A total of 179 cases of SCA/D were identified (74 arrests with survival, 105 deaths): average age 16.6 years (range 11-29), 149 (83.2%) men, 94 (52.5%) whites, and 54 (30.2%) African American. One hundred seventeen (65.4%) had an adjudicated diagnosis, including 83 deaths and 34 survivors. The most common etiologies included hypertrophic cardiomyopathy (19, 16.2%), coronary artery anomalies (16, 13.7%), idiopathic left ventricular hypertrophy/possible cardiomyopathy (13, 11.1%), autopsy-negative sudden unexplained death (8, 6.8%), Wolff-Parkinson-White (8, 6.8%), and long QT syndrome (7, 6.0%). Hypertrophic cardiomyopathy was more common in male basketball (23.3%), football (25%), and African American athletes (30.3%). An estimated 56.4% of cases would likely demonstrate abnormalities on an electrocardiogram. Conclusions: The etiology of SCA/D in competitive athletes involves a wide range of clinical disorders. More robust reporting mechanisms, standardized autopsy protocols, and accurate etiology data are needed to better inform prevention strategies.

AbstractObjectiveTo evaluate poly(GP), a dipeptide repeat protein, and neurofilament light chain (NfL) as biomarkers in presymptomatic C9orf72 repeat expansion carriers and patients with C9orf72‐associated frontotemporal dementia. Additionally, to investigate the relationship of poly(GP) with indicators of neurodegeneration as measured by NfL and grey matter volume.MethodsWe measured poly(GP) and NfL levels in cerebrospinal fluid (CSF) from 25 presymptomatic C9orf72 expansion carriers, 64 symptomatic expansion carriers with dementia, and 12 noncarriers. We explored associations with grey matter volumes using region of interest and voxel‐wise analyses.ResultsPoly(GP) was present in C9orf72 expansion carriers and absent in noncarriers (specificity 100%, sensitivity 97%). Presymptomatic carriers had lower poly(GP) levels than symptomatic carriers. NfL levels were higher in symptomatic carriers than in presymptomatic carriers and healthy noncarriers. NfL was highest in patients with concomitant motor neuron disease, and correlated with disease severity and survival. Associations between poly(GP) levels and small grey matter regions emerged but did not survive multiple comparison correction, while higher NfL levels were associated with atrophy in frontotemporoparietal cortices and the thalamus.InterpretationThis study of C9orf72 expansion carriers reveals that: (1) poly(GP) levels discriminate presymptomatic and symptomatic expansion carriers from noncarriers, but are not associated with indicators of neurodegeneration; and (2) NfL levels are associated with grey matter atrophy, disease severity, and shorter survival. Together, poly(GP) and NfL show promise as complementary biomarkers for clinical trials for C9orf72‐associated frontotemporal dementia, with poly(GP) as a potential marker for target engagement and NfL as a marker of disease activity and progression.

Introduction. Optimization of outcomes of extra-abdominal STS is not clearly understood. We sought to determine whether hospital surgical volume and adherence to NCCN guidelines, or both, are associated with outcomes in the treatment of extra-abdominal soft tissue sarcoma (STS).Methods. The National Cancer Database (NCDB) was queried for patients undergoing surgery for extra-abdominal STS diagnosed from 2003 to 2007. Mean annual hospital volume for STS surgery was divided into volume terciles (1T ≤3, 2T 4–10, and 3T ≥11 cases/year). Adherence to NCCN guidelines was determined. Primary outcome was overall survival.Results. Our study population consisted of 13,684 patients with a median age of 56 years. 3T hospitals were more likely to adhere to NCCN guidelines for stage III patients (63% versus 47%;p≤0.001) than 1T hospitals. On multivariable analysis, adherence to NCCN guidelines was associated with improved survival (HR = 0.79, CI 0.73–0.87;p<0.001), but hospital volume was not (3T versus 1T: HR = 0.92, CI 0.82–1.02;p=0.12). Five-year overall survival was comparable for compliant groups at 1T, 2T, and 3T hospitals (72%, 72.4%, and 72.6%, resp.). 3T hospitals were not associated with a lower risk of 30-day mortality (OR 0.70, 95% CI 0.44–1.11) compared to 1T hospitals but did have a higher R0 resection rate (OR 1.43, 95% CI 1.32–1.54).Conclusions. Adherence to NCCN guidelines, irrespective of hospital volume, is associated with improved overall survival for patients with extra-abdominal STS. High-volume hospitals more often adhere to guidelines, but low-volume hospitals that follow national guidelines may achieve comparable outcomes.

AbstractEpidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (rg = 0.23, P = 9.3 × 10−3), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10−3) and concordance in effect direction (P = 2.0 × 10−3) between the two diseases. Cross‐disease GWAS meta‐analysis highlighted 13 distinct loci associated at P ≤ 10−5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10−8, OR = 1.11, 95% CI = 1.07–1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross‐disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases.

Abstract Introduction Neuroimaging modalities can measure different aspects of the disease process in Alzheimer's disease, although the relationship between these modalities is unclear. Methods We assessed subject‐level regional correlations between tau on [ 18 F]AV‐1451 positron emission tomography (PET), β amyloid on Pittsburgh compound B PET, hypometabolism on [ 18 F] fluorodeoxyglucose PET, and cortical thickness on magnetic resonance imaging in 96 participants with typical and atypical Alzheimer's disease presentations. We also assessed how correlations between modalities varied according to age, presenting syndrome, tau‐PET severity, and asymmetry. Results [ 18 F]AV‐1451 uptake showed the strongest regional correlation with hypometabolism. Correlations between [ 18 F]AV‐1451 uptake and both hypometabolism and cortical thickness were stronger in participants with greater cortical tau severity. In addition, age, tau asymmetry, and clinical diagnosis influenced the strength of the correlation between [ 18 F]AV‐1451 uptake and cortical thickness. Discussion These findings support a close relationship between tau and hypometabolism in Alzheimer's disease but show that correlations between neuroimaging modalities vary across participants.