Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Diabetes mellitus: pathophysiological changes and therap

Negative pressure wound treatment with polyvinyl alcohol foam and polyhexanide antiseptic solution instillation in posttraumatic osteomyelitis

In a retrospective, case-control cohort study an assessment was made of the clinical outcome of patients with osteomyelitis treated with a new modality of negative pressure wound therapy, so called negative pressure instillation therapy. In this approach, after surgical debridement, a site of osteomyelitis is treated with negative pressure of at least 300 mmHg applied through polyvinyl alcohol dressing. The polyvinyl alcohol foam is irrigated through the tubes three times a day with a polyhexanide antiseptic solution. In 30 patients (14 males; mean age 52 [range, 26-81]) admitted between 1999 and 2003 with osteomyelitis of the pelvis or lower extremity, we assessed time to wound closure, number of surgical procedures and rate of recurrence of infection as well as need for rehospitalizations. For comparison, a control group of 94 patients (males, 58; mean age 47 [range, 9-85]), matched for site and severity of osteomyelitis, was identified in hospital records between 1982 and 2002. These patients underwent standard surgical debridement, implantation of gentamicin polymethylmethacrylate beads and long-term intravenous antibiotics. In the Instillation group the rate of recurrence of infection was 3/30 (10%), whereas 55/93 (58.5%) of the controls had a recurrence (

Prehospital Endotracheal intubation does not associate with outcome in patients with severe traumatic brain injury

Item does not contain fulltex