Two-year clinical outcome from the Iberian registry patients after left atrial appendage closure

AIMS: The aim of this study was to observe the percentage of thromboembolic and haemorrhagic events over a 2-year follow-up in patients with non-valvular atrial fibrillation (NVAF) undergoing closure of the left atrial appendage (LAA) with an occlusion device. Observed events and CHADS2 (congestive heart failure, hypertension, age, diabetes, stroke history), CHA2DS2-VASc (also adding: vascular disease and sex) and HAS-BLED (hypertension, abnormal liver/renal function, stroke history, bleeding predisposition, labile international normalised ratios, elderly, drugs/alcohol use)-predicted events were compared. METHODS: LAA closure with an occlusion device was performed in 167 NVAF patients contraindicated for oral anticoagulants and recruited from 12 hospitals between 2009 and 2013. At least two transoesophageal echocardiograms were performed in the first 6 months postimplantation. Antithrombotics included clopidogrel and aspirin. Patients were monitored for death, stroke, major and relevant bleeding and hospitalisation for concomitant conditions. Mean age was 74.68±8.58, median follow-up was 24 months, 5.38% had intraoperative complications and implantation was successful in 94.6% of subjects. Mortality during follow-up was 10.8%, mostly (9.5%) non-cardiac related. Bleeding occurred in 10.1% of subjects, 5.7% major and 4.4% minor though relevant, and 4.4% suffered stroke. Major bleeding and stroke/transient ischaemic attack events within 2 years (annual event rates, 290 patients/year) were less frequent than expected from CHADS2 (2.4% vs 9.6%), CHA2DS2-VASc (2.4% vs 8.3%) and HAS-BLED (3.1% vs 6.6%) risk scores (p<0.001, p=0.003, p=0.047, respectively). CONCLUSIONS: LAA closure with an occlusion device in patients contraindicated for oral anticoagulants is a therapeutic option associated with fewer thromboembolic and haemorrhagic events than expected from risk scores, particularly in the second year postimplantation

Two Origins for the Gene Encoding α-Isopropylmalate Synthase in Fungi

BACKGROUND: The biosynthesis of leucine is a biochemical pathway common to prokaryotes, plants and fungi, but absent from humans and animals. The pathway is a proposed target for antimicrobial therapy. METHODOLOGY/PRINCIPAL FINDINGS: Here we identified the leuA gene encoding alpha-isopropylmalate synthase in the zygomycete fungus Phycomyces blakesleeanus using a genetic mapping approach with crosses between wild type and leucine auxotrophic strains. To confirm the function of the gene, Phycomyces leuA was used to complement the auxotrophic phenotype exhibited by mutation of the leu3+ gene of the ascomycete fungus Schizosaccharomyces pombe. Phylogenetic analysis revealed that the leuA gene in Phycomyces, other zygomycetes, and the chytrids is more closely related to homologs in plants and photosynthetic bacteria than ascomycetes or basidiomycetes, and suggests that the Dikarya have acquired the gene more recently. CONCLUSIONS/SIGNIFICANCE: The identification of leuA in Phycomyces adds to the growing body of evidence that some primary metabolic pathways or parts of them have arisen multiple times during the evolution of fungi, probably through horizontal gene transfer events