0304: How long should we keep a temporary pace maker after transcatheter aortic valve replacement (TAVR)

A temporary pace-maker (TPM) is often used after TAVR due to the risk of atrioventricular block (AVB) in the following days, related to progressive conduction system injuries. However guidelines are unclear as when to safely remove it. Between 2013 and 2014, 195 patients without previous permanent pacemaker, were prospectively followed after TAVR (69 Edwards Sapiens (ES) and 126 CoreValve (CV)). 47 had preoperative bundle branch block, 23 left (LBBB), 24 right sided (RBBB). Peri-operative high degree AVB was noted in 37 patients (20%). 24 were transient, less than 10mn and; 13 persisted at the end of the procedure and were implanted with a permanent pace-maker. New LBBB was observed in 55 patients (28%). In the post-operative period, 23 patients (13%) developped AVB (20 patients within 5 days, and 3 patients after 7 days) (4 ES and 19 CV). No new AV block had occurred at one month in the remaining population. Risk factors for late AVB were peri-operative transient AVB (40%), post-operative RBBB (30%), or LBBB (20%); preexistent RBBB and Corevalve model. Conversely 41 of the 42 patients without AVB or bundle branch block did not need temporary pacing in the post operative time. The only patient without any perioperative event who developed a late AV block at day 7 had a CV inserted in an old surgical valve. However, sinus dysfunction occurred in 2 patients treated with amiodarone for atrial fibrillation in the post operative period, needing temporary pacing. Conclusion: The use of TPM after TAVR is common for the management of delayed high degree AVB. The main risk factors are peri-operative AVB and post-operative BBB. Most of delayed AVB occur within 5 days. Later AVB preceded by prolonged PR interval and BBB should increase the length of TPM. However, in the absence of these factors TPM could be shortened.Abstract 0304 – Figure: Time occurence of AVB (CV=Corevalve, ES=Sapien

Time course, factors related to, and prognostic impact of venoarterial extracorporeal membrane flow in cardiogenic shock

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is currently one of the most used devices in refractory cardiogenic shock. However, there is a lack of evidence on how to set the 'optimal' flow. We aimed to describe the evolution of VA-ECMO flows in a cardiogenic shock population and determine the risk factors of 'high-ECMO flow'. A 7 year database of patients supported with VA-ECMO was used. Based on the median flow during the first 48 h of the VA-ECMO run, patients were classified as 'high-flow' or 'low-flow', respectively, when median ECMO flow was ≥3.6 or <3.6 L/min. Outcomes included rates of ventilator-associated pneumonia, ECMO-related complications, days on ECMO, days on mechanical ventilation, intensive care unit and hospitalization lengths of stay, and in-hospital and 60 day mortality. Risk factors of high-ECMO flow were assessed using univariate and multivariate cox regression. The study population included 209 patients on VA-ECMO, median age was 51 (40-59) years, and 78% were males. The most frequent aetiology leading to cardiogenic shock was end-stage dilated cardiomyopathy (57%), followed by acute myocardial infarction (23%) and fulminant myocarditis (17%). Among the 209 patients, 105 (50%) were classified as 'high-flow'. This group had a higher rate of ischaemic aetiology (16% vs. 30%, P = 0.023) and was sicker at admission, in terms of worse Simplified Acute Physiology Score II score [40 (26-58) vs. 56 (42-74), P < 0.001], higher lactate [3.6 (2.2-5.8) mmol/L vs. 5.2 (3-9.7) mmol/L, P < 0.001], and higher aspartate aminotransferase [97 (41-375) U/L vs. 309 (85-939) U/L, P < 0.001], among others. The 'low-flow' group had less ventilator-associated pneumonia (40% vs. 59%, P = 0.007) and less days on mechanical ventilation [4 (1.5-7.5) vs. 6 (3-12) days, P = 0.009]. No differences were found in lengths of stay or survival according to the ECMO flow. The multivariate analysis showed that risk factors independently associated with 'high-flow' were mechanical ventilation at cannulation [odds ratio (OR) 3.9, 95% confidence interval (CI) 2.1-7.1] and pre-ECMO lactate (OR 1.1, 95% CI 1.0-1.2). In patients with refractory cardiogenic shock supported with VA-ECMO, sicker patients had higher support since early phases, presenting thereafter higher rates of ventilator-associated pneumonia but similar survival compared with patients with lower flows

Clinical scenarios for use of transvalvular microaxial pumps in acute heart failure and cardiogenic shock – A European experienced users working group opinion

Abstract For patients with myocardial infarct-related cardiogenic shock (CS), urgent percutaneous coronary intervention is the recommended treatment strategy to limit cardiac and systemic ischemia. However, a specific therapeutic intervention is often missing in non-ischemic CS cases. Though drug treatment with inotropes and/or vasopressors may be required to stabilize the patient initially, their ongoing use is associated with excess mortality. Coronary intervention in unstable patients often leads to further hemodynamic compromise either during or shortly after revascularization. Support devices like the intra-aortic balloon pump failed to improve clinical outcomes in infarct-related CS. Currently, more powerful and active hemodynamic support devices unloading the left ventricle such as transvalvular microaxial pumps are available and are being increasingly used. However, as for other devices large randomized trials are not yet available, and device use is based on registry data and expert consensus. In this article, a multidisciplinary group of experienced users of transvalvular microaxial pumps outlines the pathophysiological background on hemodynamic changes in CS, the available mechanical support devices, and current guideline recommendations. Furthermore, different hemodynamic situations in several case-based scenarios are used to illustrate candidate settings and to provide the theoretic and scientific rationale for left-ventricular unloading in these scenarios. Finally, organization of shock networks, monitoring, weaning, and typical complications and their prevention are discussed

Role of the BAHD1 Chromatin-Repressive Complex in Placental Development and Regulation of Steroid Metabolism.

BAHD1 is a vertebrate protein that promotes heterochromatin formation and gene repression in association with several epigenetic regulators. However, its physiological roles remain unknown. Here, we demonstrate that ablation of the Bahd1 gene results in hypocholesterolemia, hypoglycemia and decreased body fat in mice. It also causes placental growth restriction with a drop of trophoblast glycogen cells, a reduction of fetal weight and a high neonatal mortality rate. By intersecting transcriptome data from murine Bahd1 knockout (KO) placentas at stages E16.5 and E18.5 of gestation, Bahd1-KO embryonic fibroblasts, and human cells stably expressing BAHD1, we also show that changes in BAHD1 levels alter expression of steroid/lipid metabolism genes. Biochemical analysis of the BAHD1-associated multiprotein complex identifies MIER proteins as novel partners of BAHD1 and suggests that BAHD1-MIER interaction forms a hub for histone deacetylases and methyltransferases, chromatin readers and transcription factors. We further show that overexpression of BAHD1 leads to an increase of MIER1 enrichment on the inactive X chromosome (Xi). In addition, BAHD1 and MIER1/3 repress expression of the steroid hormone receptor genes ESR1 and PGR, both playing important roles in placental development and energy metabolism. Moreover, modulation of BAHD1 expression in HEK293 cells triggers epigenetic changes at the ESR1 locus. Together, these results identify BAHD1 as a core component of a chromatin-repressive complex regulating placental morphogenesis and body fat storage and suggest that its dysfunction may contribute to several human diseases

Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease

Celiac disease (CD) is an enteropathy resulting from an abnormal immune response to gluten-derived peptides in genetically susceptible individuals. This immune response is initiated by intestinal transport of intact peptide 31-49 (p31-49) and 33-mer gliadin peptides through an unknown mechanism. We show that the transferrin receptor CD71 is responsible for apical to basal retrotranscytosis of gliadin peptides, a process during which p31-49 and 33-mer peptides are protected from degradation. In patients with active CD, CD71 is overexpressed in the intestinal epithelium and colocalizes with immunoglobulin (Ig) A. Intestinal transport of intact p31-49 and 33-mer peptides was blocked by polymeric and secretory IgA (SIgA) and by soluble CD71 receptors, pointing to a role of SIgA–gliadin complexes in this abnormal intestinal transport. This retrotranscytosis of SIgA–gliadin complexes may promote the entry of harmful gliadin peptides into the intestinal mucosa, thereby triggering an immune response and perpetuating intestinal inflammation. Our findings strongly implicate CD71 in the pathogenesis of CD

Stellar Astrophysics and Exoplanet Science with the Maunakea Spectroscopic Explorer (MSE)

The Maunakea Spectroscopic Explorer (MSE) is a planned 11.25-m aperture facility with a 1.5 square degree field of view that will be fully dedicated to multi-object spectroscopy. A rebirth of the 3.6m Canada-France-Hawaii Telescope on Maunakea, MSE will use 4332 fibers operating at three different resolving powers (R ~ 2500, 6000, 40000) across a wavelength range of 0.36-1.8mum, with dynamical fiber positioning that allows fibers to match the exposure times of individual objects. MSE will enable spectroscopic surveys with unprecedented scale and sensitivity by collecting millions of spectra per year down to limiting magnitudes of g ~ 20-24 mag, with a nominal velocity precision of ~100 m/s in high-resolution mode. This white paper describes science cases for stellar astrophysics and exoplanet science using MSE, including the discovery and atmospheric characterization of exoplanets and substellar objects, stellar physics with star clusters, asteroseismology of solar-like oscillators and opacity-driven pulsators, studies of stellar rotation, activity, and multiplicity, as well as the chemical characterization of AGB and extremely metal-poor stars.Comment: 31 pages, 11 figures; To appear as a chapter for the Detailed Science Case of the Maunakea Spectroscopic Explore

T84-intestinal epithelial exosomes bear MHC class II/peptide complexes potentiating antigen presentation by dendritic cells: Function of intestinal epithelial exosomes

International audienceBackground and aims: Intestinal epithelial cells release antigen presenting vesicles (exosomes) bearing MHC class II/peptide complexes stimulating specific immune responses in vivo. To further characterize the role of human epithelial exosomes in antigen presentation, their capacity to load antigenic peptides, to bind immune target cells and to induce T cell activation was analyzed in vitro. Methods: The capacity of exosomes derived from the HLA-DR4 expressing, intestinal epithelial cell line T84, to load the HLA-DR4-specific peptide 3H-HSA 64-76 and to activate a HLA-DR4-restricted T cell hybridoma, was tested in the presence or absence of human monocyte-derived dendritic cells (DCs). Interaction of FITC-labeled exosomes with T cells and DCs was analyzed by flow cytometry and confocal microscopy. Results: T84-derived exosomes, enriched in CD9, CD81, CD82 and A33 antigen, were capable of binding specifically HSA 64-76 peptide on HLA-DR4 molecules and of interacting preferentially with DCs. HSA-loaded exosomes were unable to activate the T cell hybridoma directly, but induced a productive T cell activation through DCs. When HSA peptide was bound to exosomal HLA-DR4 molecules instead of in a soluble form, the threshold of peptide presentation by DCs was markedly decreased (x10-3). Conclusions: Exosomes released by intestinal epithelial cells bear exogenous peptides complexed to MHC class II molecules and interact preferentially with DCs, strongly potentiating peptide presentation to T cells. Epithelial exosomes constitute a powerful link between luminal antigens and local immune cells by mediating the transfer of tiny amounts of luminal antigenic information and facilitating immune surveillance at mucosal surfaces

Contextualizing students' alcohol use perceptions and practices within French culture: an analysis of gender and drinking among sport-science college students

Although research has examined alcohol consumption and sport in a variety of contexts, there is a paucity of research on gender and gender dynamics among French college students. The present study addresses this gap in the literature by examining alcohol use practices by men and women among a non-probability sample of French sport science students from five different universities in Northern France. We utilized both survey data (N = 534) and in-depth qualitative interviews (n = 16) to provide empirical and theoretical insight into a relatively ubiquitous health concern: the culture of intoxication. Qualitative data were based on students’ perceptions of their own alcohol use; analysis were framed by theoretical conceptions of gender. Survey results indicate gender differences in alcohol consumption wherein men reported a substantially higher frequency and quantity of alcohol use compared to their female peers. Qualitative findings confirm that male privilege and women’s concern for safety, masculine embodiment via alcohol use, gendering of alcohol type, and gender conformity pressures shape gender disparities in alcohol use behavior. Our findings also suggest that health education policy and educational programs focused on alcohol-related health risks need to be designed to take into account gender category and gender orientation