Sudden cardiac death (SCD) is the leading cause of death in athletes during sport. Whether obtained for screening or diagnostic purposes, an ECG increases the ability to detect underlying cardiovascular conditions that may increase the risk for SCD. In most countries, there is a shortage of physician expertise in the interpretation of an athlete's ECG. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from abnormal findings suggestive of pathology. On 13-14 February 2012, an international group of experts in sports cardiology and sports medicine convened in Seattle, Washington, to define contemporary standards for ECG interpretation in athletes. The objective of the meeting was to develop a comprehensive training resource to help physicians distinguish normal ECG alterations in athletes from abnormal ECG findings that require additional evaluation for conditions associated with SCD.
Background Recent evidence suggests that immunotherapy efficacy in melanoma is modulated by gut microbiota. Few studies have examined this phenomenon in humans, and none have incorporated metatranscriptomics, important for determining expression of metagenomic functions in the microbial community. Methods In melanoma patients undergoing immunotherapy, gut microbiome was characterized in pre-treatment stool using 16S rRNA gene and shotgun metagenome sequencing (n = 27). Transcriptional expression of metagenomic pathways was confirmed with metatranscriptome sequencing in a subset of 17. We examined associations of taxa and metagenomic pathways with progression-free survival (PFS) using 500 × 10-fold cross-validated elastic-net penalized Cox regression. Results Higher microbial community richness was associated with longer PFS in 16S and shotgun data (p < 0.05). Clustering based on overall microbiome composition divided patients into three groups with differing PFS; the low-risk group had 99% lower risk of progression than the high-risk group at any time during follow-up (p = 0.002). Among the species selected in regression, abundance of Bacteroides ovatus, Bacteroides dorei, Bacteroides massiliensis, Ruminococcus gnavus, and Blautia producta were related to shorter PFS, and Faecalibacterium prausnitzii, Coprococcus eutactus, Prevotella stercorea, Streptococcus sanguinis, Streptococcus anginosus, and Lachnospiraceae bacterium 3 1 46FAA to longer PFS. Metagenomic functions related to PFS that had correlated metatranscriptomic expression included risk-associated pathways of l-rhamnose degradation, guanosine nucleotide biosynthesis, and B vitamin biosynthesis. Conclusions This work adds to the growing evidence that gut microbiota are related to immunotherapy outcomes, and identifies, for the first time, transcriptionally expressed metagenomic pathways related to PFS. Further research is warranted on microbial therapeutic targets to improve immunotherapy outcomes.
This study examined the cardiac structure and function of a unique cohort of documented lifelong, competitive endurance veteran athletes (>50 yr). Twelve lifelong veteran male endurance athletes [mean ± SD (range) age: 56 ± 6 yr (50-67)], 20 age-matched veteran controls [60 ± 5 yr; (52-69)], and 17 younger male endurance athletes [31 ± 5 yr (26-40)] without significant comorbidities underwent cardiac magnetic resonance (CMR) imaging to assess cardiac morphology and function, as well as CMR imaging with late gadolinium enhancement (LGE) to assess myocardial fibrosis. Lifelong veteran athletes had smaller left (LV) and right ventricular (RV) end-diastolic and end-systolic volumes (P < 0.05), but maintained LV and RV systolic function compared with young athletes. However, veteran athletes had a significantly larger absolute and indexed LV and RV end-diastolic and systolic volumes, intraventricular septum thickness during diastole, posterior wall thickness during diastole, and LV and RV stroke volumes (P < 0.05), together with significantly reduced LV and RV ejection fractions (P < 0.05), compared with veteran controls. In six (50%) of the veteran athletes, LGE of CMR indicated the presence of myocardial fibrosis (4 veteran athletes with LGE of nonspecific cause, 1 probable previous myocarditis, and 1 probable previous silent myocardial infarction). There was no LGE in the age-matched veteran controls or young athletes. The prevalence of LGE in veteran athletes was not associated with age, height, weight, or body surface area (P > 0.05), but was significantly associated with the number of years spent training (P < 0.001), number of competitive marathons (P < 0.001), and ultraendurance (>50 miles) marathons (P < 0.007) completed. An unexpectedly high prevalence of myocardial fibrosis (50%) was observed in healthy, asymptomatic, lifelong veteran male athletes, compared with zero cases in age-matched veteran controls and young athletes. These data suggest a link between lifelong endurance exercise and myocardial fibrosis that requires further investigation.
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