Large scale analysis of routine dose adjustments of mycophenolate mofetil based on global exposure in renal transplant patients.

International audienceBACKGROUND: : We report a feasibility study based on our large-scale experience with mycophenolate mofetil dose adjustment based on mycophenolic acid interdose area under the curve (AUC) in renal transplant patients. METHODS: : Between 2005 and 2010, 13,930 requests for 7090 different patients (outside any clinical trial) were posted by more than 30 different transplantation centers on a free, secure web site for mycophenolate mofetil dose recommendations using three plasma concentrations and Bayesian estimation. RESULTS: : This retrospective study showed that 1) according to a consensually recommended 30- to 60-mg*h/L target, dose adjustment was needed for approximately 35% of the patients, 25% being underexposed with the highest proportion observed in the first weeks after transplantation; 2) when dose adjustment had been previously proposed, the subsequent AUC was significantly more often in the recommended range if the dose was applied than not at all posttransplantation periods (72-80% vs. 43-54%); and 3) the interindividual AUC variability in the "respected-dose" group was systematically lower than that in the "not respected-dose" group (depending on the posttransplantation periods; coefficient of variation %, 31-41% vs 49-70%, respectively). Further analysis suggested that mycophenolic acid AUC should best be monitored at least every 2 weeks during the first month, every 1 to 3 months between months 1 and 12, whereas in the stable phase, the odds to be still in the 30- to 60-mg*h/L range on the following visit was still 75% up to 1 year after the previous dose adjustment. CONCLUSION: : This study showed that the monitoring of mycophenolate mofetil on the basis of AUC measurements is a clinically feasible approach, apparently acceptable by the patients, the nurses, and the physicians owing to its large use in routine clinics

Food allergy enhances allergic asthma in mice

BackgroundAtopic march refers to the typical transition from a food allergy in early childhood to allergic asthma in older children and adults. However the precise interplay of events involving gut, skin and pulmonary inflammation in this process is not completely understood.ObjectivesTo develop a mouse model of mixed food and respiratory allergy mimicking the atopic march and better understand the impact of food allergies on asthma.MethodsFood allergy to ovalbumin (OVA) was induced through intra-peritoneal sensitization and intra-gastric challenge, and/or a respiratory allergy to house dust mite (HDM) was obtained through percutaneous sensitization and intra-nasal challenges with dermatophagoides farinae (Der f) extract. Digestive, respiratory and systemic parameters were analyzed.ResultsOVA-mediated gut allergy was associated with an increase in jejunum permeability, and a worsening of Der f-induced asthma with stronger airway hyperresponsiveness and pulmonary cell infiltration, notably eosinophils. There was overproduction of the pro-eosinophil chemokine RANTES in broncho-alveolar lavages associated with an enhanced Th2 cytokine secretion and increased total and Der f-specific IgE when the two allergies were present. Both AHR and lung inflammation increased after a second pulmonary challenge.ConclusionGut sensitization to OVA amplifies Der f-induced asthma in mice

Modification de la distribution du volume pulmonaire régional au cours du sevrage de la ventilation mécanique lors du syndrome de détresse respiratoire aiguë de l'adulte

LYON1-BU Santé (693882101) / SudocSudocFranceF

Bucy-le-Long "La Grande Pièce de la Croix Rouge" (Aisne). Découverte d'un ensemble caractéristique du début de La Tène ancienne

Debord Jean, Desenne Sophie. Bucy-le-Long "La Grande Pièce de la Croix Rouge" (Aisne). Découverte d'un ensemble caractéristique du début de La Tène ancienne. In: Revue archéologique de Picardie. Numéro spécial 22, 2005. Hommages à Claudine Pommepuy. pp. 163-174

Le dialogue social dans les entreprises en région Auvergne-Rhône-Alpes : évaluation de l'impact des ordonnances du 22 septembre 2017. [2] Les comités sociaux et économiques dans les PME et ETI de la région Auvergne-Rhône-Alpes : une appropriation difficile : Rapport final

Ce rapport a été cofinancé par France Stratégie dans le cadre d’un appel à projets de recherche réalisé pour le comité d’évaluation des ordonnances. Il s'agit du rapport final du second axe de la recherche Dialaura "Le dialogue social dans les entreprises en région Auvergne-Rhône-Alpes" (dir. C. Giraudet/C. Nicod)"Ce rapport est le fruit d’un travail collectif mené par Sophie Béroud (Université Lyon 2, Triangle UMR 5206),Marion Gilles (ANACT), Florence Debord (Université Lyon 2, CERCRID UMR 5137), Carole Giraudet(Université Lyon 2, CERCRID, Coord.), Dorian Mellot (Université Lyon 2 CERCRID), Jean-François Paulin(Université Lyon 1, CERCRID) et Léna Devenceau (Université Lyon 2) avec l’appui d’Agathe Dodin(CERCRID/ANACT)."Le comité d’évaluation des ordonnances Travail du 22 septembre 2017, piloté par France Stratégie et coprésidé par Marcel Grignard et Jean-François Pilliard, a lancé un appel à projets de recherche en octobre 2019. Mis en place en novembre 2017, le comité d’évaluation, composé de partenaires sociaux, d’experts, de praticiens et d’administrations est chargé d’évaluer l’impact social et économique des ordonnances Travail relatives au dialogue social et aux relations de travail. Pour cela, il mène différents travaux de suivi de la mise en œuvre des ordonnances et d’évaluation de leurs effets. Dans ce cadre, le présent appel à projet (APR) visait à étudier l’impact des ordonnances sur la représentation collective des salariés, le dialogue social et la négociation collective, tant au niveau des entreprises que des branches. Il s’agit de déterminer comment ces dispositions modifient les pratiques des partenaires sociaux, le contenu des négociations collectives ou encore l’organisation et le fonctionnement du dialogue social dans l’entreprise

Proof of concept study of mass cytometry in septic shock patients reveals novel immune alterations

Abstract Innovative single cell technologies such as mass cytometry (CyTOF) widen possibilities to deeply improve characterisation of immune alterations mechanisms in human diseases. So far, CyTOF has not been used in sepsis – a condition characterized by complex immune disorders. Here, we evaluated feasibility of CyTOF analysis in patients with septic shock. We designed a mass cytometry panel of 25 extracellular markers to study mononuclear cells from 5 septic shock patients and 5 healthy donors. We explored single-cell data with global and specific unsupervised approaches such as heatmaps, SPADE and viSNE. We first validated relevance of our CyTOF results by highlighting established immune hallmarks of sepsis, such as decreased monocyte HLA-DR expression and increased expressions of PD1 and PD-L1 on CD4 T cells and monocytes. We then showed that CyTOF analysis reveals novel aspects of sepsis-induced immune alterations, e.g. B cell shift towards plasma cell differentiation and uniform response of several monocyte markers defining an immune signature in septic patients. This proof of concept study demonstrates CyTOF suitability to analyse immune features of septic patients. Mass cytometry could thus represent a powerful tool to identify novel pathophysiological mechanisms and therapeutic targets for immunotherapy in septic shock patients

Le dialogue social dans les entreprises en région Auvergne-Rhône-Alpes : évaluation de l'impact des ordonnances du 22 septembre 2017. [2] Les comités sociaux et économiques dans les PME et ETI de la région Auvergne-Rhône-Alpes : une appropriation difficile : Rapport final

Ce rapport a été cofinancé par France Stratégie dans le cadre d’un appel à projets de recherche réalisé pour le comité d’évaluation des ordonnances. Il s'agit du rapport final du second axe de la recherche Dialaura "Le dialogue social dans les entreprises en région Auvergne-Rhône-Alpes"Le comité d’évaluation des ordonnances Travail du 22 septembre 2017, piloté par France Stratégie et coprésidé par Marcel Grignard et Jean-François Pilliard, a lancé un appel à projets de recherche en octobre 2019. Mis en place en novembre 2017, le comité d’évaluation, composé de partenaires sociaux, d’experts, de praticiens et d’administrations est chargé d’évaluer l’impact social et économique des ordonnances Travail relatives au dialogue social et aux relations de travail. Pour cela, il mène différents travaux de suivi de la mise en œuvre des ordonnances et d’évaluation de leurs effets. Dans ce cadre, le présent appel à projet (APR) visait à étudier l’impact des ordonnances sur la représentation collective des salariés, le dialogue social et la négociation collective, tant au niveau des entreprises que des branches. Il s’agit de déterminer comment ces dispositions modifient les pratiques des partenaires sociaux, le contenu des négociations collectives ou encore l’organisation et le fonctionnement du dialogue social dans l’entreprise

Change in cardiac output during Trendelenburg maneuver is a reliable predictor of fluid responsiveness in patients with acute respiratory distress syndrome in the prone position under protective ventilation

Abstract Background Predicting fluid responsiveness may help to avoid unnecessary fluid administration during acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate the diagnostic performance of the following methods to predict fluid responsiveness in ARDS patients under protective ventilation in the prone position: cardiac index variation during a Trendelenburg maneuver, cardiac index variation during an end-expiratory occlusion test, and both pulse pressure variation and change in pulse pressure variation from baseline during a tidal volume challenge by increasing tidal volume (VT) to 8 ml.kg-1. Methods This study is a prospective single-center study, performed in a medical intensive care unit, on ARDS patients with acute circulatory failure in the prone position. Patients were studied at baseline, during a 1-min shift to the Trendelenburg position, during a 15-s end-expiratory occlusion, during a 1-min increase in VT to 8 ml.kg-1, and after fluid administration. Fluid responsiveness was deemed present if cardiac index assessed by transpulmonary thermodilution increased by at least 15% after fluid administration. Results There were 33 patients included, among whom 14 (42%) exhibited cardiac arrhythmia at baseline and 15 (45%) were deemed fluid-responsive. The area under the receiver operating characteristic (ROC) curve of the pulse contour-derived cardiac index change during the Trendelenburg maneuver and the end-expiratory occlusion test were 0.90 (95% CI, 0.80–1.00) and 0.65 (95% CI, 0.46–0.84), respectively. An increase in cardiac index ≥ 8% during the Trendelenburg maneuver enabled diagnosis of fluid responsiveness with sensitivity of 87% (95% CI, 67–100), and specificity of 89% (95% CI, 72–100). The area under the ROC curve of pulse pressure variation and change in pulse pressure variation during the tidal volume challenge were 0.52 (95% CI, 0.24–0.80) and 0.59 (95% CI, 0.31–0.88), respectively. Conclusions Change in cardiac index during a Trendelenburg maneuver is a reliable test to predict fluid responsiveness in ARDS patients in the prone position, while neither change in cardiac index during end-expiratory occlusion, nor pulse pressure variation during a VT challenge reached acceptable predictive performance to predict fluid responsiveness in this setting. Trial registration ClinicalTrials.gov, NCT01965574 . Registered on 16 October 2013. The trial was registered 6 days after inclusion of the first patient