Symptomatic and Asymptomatic Neurological Complications of Infective Endocarditis: Impact on Surgical Management and Prognosis

International audienceObjectives:Symptomatic neurological complications (NC) are a major cause of mortality in infective endocarditis (IE) but the impact of asymptomatic complications is unknown. We aimed to assess the impact of asymptomatic NC (AsNC) on the management and prognosis of IE.Methods: From the database of cases collected for a population-based study on IE, we selected 283 patients with definite left-sided IE who had undergone at least one neuroimaging procedure (cerebral CT scan and/or MRI) performed as part of initial evaluation.Results Among those 283 patients, 100 had symptomatic neurological complications (SNC) prior to the investigation, 35 had an asymptomatic neurological complications (AsNC), and 148 had a normal cerebral imaging (NoNC). The rate of valve surgery was 43% in the 100 patients with SNC, 77% in the 35 with AsNC, and 54% in the 148 with NoNC (p<0.001). In-hospital mortality was 42% in patients with SNC, 8.6% in patients with AsNC, and 16.9% in patients with NoNC (p<0.001). Among the 135 patients with NC, 95 had an indication for valve surgery (71%), which was performed in 70 of them (mortality 20%) and not performed in 25 (mortality 68%). In a multivariate adjusted analysis of the 135 patients with NC, age, renal failure, septic shock, and IE caused by S. aureus were independently associated with in-hospital and 1-year mortality. In addition SNC was an independent predictor of 1-year mortality.Conclusions The presence of NC was associated with a poorer prognosis when symptomatic. Patients with AsNC had the highest rate of valve surgery and the lowest mortality rate, which suggests a protective role of surgery guided by systematic neuroimaging results

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel NaV1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on NaV1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings

Yaëlle Amsellem-Mainguy, Les filles du coin. Vivre et grandir en milieu rural

Que signifie vivre et grandir en milieu rural pour un·e jeune, aujourd’hui, en France ? La jeunesse rurale est souvent décrite par la négative, en opposition à la jeunesse urbaine. La vie loin des grandes villes possède pourtant de nombreuses spécificités. C’est d’ailleurs pour mieux en rendre compte que la sociologue Yaëlle Amsellem-Mainguy, chargée de recherche à l’Institut national de la jeunesse et de l’éducation populaire (Injep) a décidé de mener l’enquête au centre de cet ouvrage. Elle..

Daniel Mercure, Jan Spurk (dir.), Les théories du travail. Les classiques

Le sens du « travail » est aujourd’hui au cœur des débats. C’est en vue de souligner la pluralité de ses acceptions que Daniel Mercure et Jan Spurk ont décidé de diriger cet ouvrage collectif. Plus précisément, leur thèse est la suivante : selon les cultures et les époques, le travail n’a pas toujours eu le même sens (p. 1). Aussi proposent-ils aux lecteurs une approche diachronique de la signification du travail. L’objectif est double. Il s’agit d’abord d’inviter le lecteur à prendre de la d..

Sondage vésical évacuateur (audit de pratiques et mise en place d un kit de sondage clos au CHU de Grenoble)

Les infections urinaires représentent encore 40% des infections nosocomiales et sont souvent dues aux sondages. Un sondage évacuateur pratiqué dans de bonnes conditions d asepsie et en système clos permet de limiter ce risque. Les services de maternité sont particulièrement concernés au vu du nombre de patientes sondées par année. L objectif de notre travail était, dans un 1er temps, de réaliser une étude observationnelle des pratiques de sondage dans les services de maternité du CHUG. Dans un 2nd temps, un kit de sondage urinaire clos a été mis en place, et une autre étude de pratiques a été réalisée. Nous avons recueilli les données de 25 sondages avec les pratiques courantes, et de 13 après la mise en place du kit de sondage clos. L analyse des résultats montre que les pratiques actuelles ne sont pas conformes aux recommandations de la Société Française d Hygiène Hospitalière, puisque le système de sondage utilisé n est pas clos. La comparaison des 2 groupes ne montre aucune différence significative sauf sur un item, celui de la contamination des soignants par l urine. Ainsi le kit de sondage clos est significativement plus sûr que les pratiques de sondage actuelles par sonde jet. Cependant une augmentation du temps de préparation du matériel et du sondage a été observée avec le kit. En conclusion, le kit répond aux recommandations et permet un geste plus sûr. Le suivi post partum des patientes à domicile concernant le développement d une éventuelle infection urinaire après leur sortie permettrait d évaluer plus précisément l impact de l utilisation d un système de sondage évacuateur clos sur l incidence des infections urinaires nosocomiales en maternité.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Infrequent Genetic Exchange and Recombination in the Mitochondrial Genome of Candida albicans

Previous analyses of diploid nuclear genotypes have concluded that recombination has occurred in populations of the yeast Candida albicans. To address the possibilities of clonality and recombination in an effectively haploid genome, we sequenced seven regions of mitochondrial DNA (mtDNA) in 45 strains of C. albicans from human immunodeficiency virus-positive patients in Toronto, Canada, and 3 standard reference isolates of C. albicans, CA, CAI4, and WO-1. Among a total of 2,553 nucleotides in the seven regions, 62 polymorphic nucleotide sites and seven indels defined nine distinct mtDNA haplotypes among the 48 strains. Five of these haplotypes occurred in more than one strain, indicating clonal proliferation of mtDNA. Phylogenetic analysis of mtDNA haplotypes resulted in one most-parsimonious tree. Most of the nucleotide sites undergoing parallel change in this tree were clustered in blocks that corresponded to sequenced regions. Because of the existence of these blocks, the apparent homoplasy can be attributed to infrequent, past genetic exchange and recombination between individuals and cannot be attributed to parallel mutation. Among strains sharing the same mtDNA haplotypes, multilocus nuclear genotypes were more similar than expected from a random comparison of nuclear DNA genotypes, suggesting that clonal proliferation of the mitochondrial genome was accompanied by clonal proliferation of the nuclear genome

Symptomatic and Asymptomatic Neurological Complications of Infective Endocarditis: Impact on Surgical Management and Prognosis - Fig 3

<p>One-year survival curves of A) all patients with neuroimaging procedures (n = 283), B) operated patients (n = 150), C) non operated patients (n = 133) according to the presence and the type of neurological complications.</p

Comparison of surgical therapy among patients according to the absence or the presence of neurological complications (NC) either asymptomatic or symptomatic.

<p>Comparison of surgical therapy among patients according to the absence or the presence of neurological complications (NC) either asymptomatic or symptomatic.</p

Relationship between neurological complications and mortality among 283 patients with neuroimaging procedure: multivariate analysis adjusted for surgery.

<p>Relationship between neurological complications and mortality among 283 patients with neuroimaging procedure: multivariate analysis adjusted for surgery.</p