74 research outputs found

    Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

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    RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

    Laboratoire sur puce pour la détection d'événements cellulaires rares

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    National audienceAdipose tissue is a rich source of multipotent stem cells: Adipose Stem Cells (or ASCs). Due to their differentiation capabilities, ASCs became cells of considerable interest for regenerative medicine and are of high interest for type II diabetes diagnosis. Known to migrate and circulate in lymph, the hypothesis of their presence in blood is not excluded but no method exists to prove it. The aim of this study is to develop a lab-on-chip able to isolate ASCs from complex biological samples by using passive and label-free microfluidic sorting methods. These methods involve intrinsic properties of fluids and objects. Yet, ASCs do not have specific physical characteristic. We have demonstrated that their diameter is comprised between 10 and 25 µm: they cannot be distinguished from most of other blood cells. In addition, they do not present specific antigen on their membrane. In order to completely isolate ASCs from other cell types, we propose an original approach combining two complementary steps. The first step aims at pre-treating the sample by removing, via hydrodynamic filtration, all the cells with a diameter below 10 µm. With this device, red blood cells, which represent more than 99% of blood cells, platelets and some leukocytes, have to be removed. This study has demonstrated that the device is able to effectively pre-treat pure blood sample (either from human or from mouse) as it removes more than 99.9% of red blood cells. It has also been demonstrated that filtration does not lead to cell lysis, which is a promising result for cell viability and the reuse of cells after filtration. The obtained sample contains cells of interest and some remaining hematopoietic cells. The second step aims at refining ASCs isolation by separating them from remaining hematopoietic cells. The method used, called immunological exclusion by cell rolling, is based on antigen-antibody specific reaction. As ASCs do not have specific antigen, leukocytes antigens have been involved. The objective is so to deplete the sample of the remaining leukocytes. This study led to the elaboration of an optimised surface functionalization protocol. Moreover, promising results on cell rolling realised on a surface functionalized with anti-CD45 antibodies were obtained.Le tissu adipeux est une source riche en cellules souches multipotentes : les Cellules Souches Adipeuses (ASCs pour Adipose Stem Cells). Ces cellules, qui possèdent la capacité de se différencier en différents types cellulaires, ouvrent de nombreuses perspectives dans le domaine de la médecine régénératrice et dans des applications telles que le diagnostic du diabète de type 2. Connues pour migrer et circuler dans la lymphe, l'hypothèse de leur présence dans le sang n'est pas exclue mais aucune méthode n'existe afin de le prouver. L'objectif de ces travaux de thèse est alors de développer un laboratoire sur puce capable d'isoler les ASCs à partir d'échantillons biologiques complexes en mettant en application des méthodes microfluidiques de tri passives et sans marquage. Ce sont ainsi les propriétés intrinsèques des cellules qui sont exploitées. Or, les ASCs ne présentent aucune caractéristique physique spécifique. En effet, nous avons tout d'abord montré que leur diamètre est compris entre 10 et 25 µm, ce qui ne leur permet pas de se distinguer de la plupart des cellules sanguines. De même, ces cellules ne possèdent pas d'antigène spécifique sur leur membrane. Nous proposons alors un dispositif combinant deux étapes complémentaires afin d'isoler complètement les ASCs des autres types cellulaires. La première étape a pour objectif de prétraiter l'échantillon en retirant, par filtration hydrodynamique, toutes les cellules de diamètre inférieur à 10 µm. Ce dispositif doit ainsi permettre de retirer du milieu les globules rouges qui représentent plus de 99 % des cellules constituant le sang ainsi que les plaquettes et quelques globules blancs. Ces travaux de thèse ont démontré que le dispositif développé est capable de prétraiter efficacement un échantillon sanguin pur (humain ou murin) en éliminant plus de 99,9 % des globules rouges. De plus, il a été démontré que la filtration n'engendre pas de lyse cellulaire, ce qui est encourageant pour des questions de viabilité cellulaire et l'exploitation des cellules après filtration. L'échantillon alors obtenu contient les cellules d'intérêt ainsi que quelques cellules hématopoïétiques restantes. La deuxième étape a pour but de parfaire l'isolement des ASCs en les séparant des cellules hématopoïétiques restantes. Pour ce faire, la méthode employée, l'exclusion immunologique par cell rolling, se base sur la spécificité de la réaction antigène-anticorps. Les ASCs ne possédant pas d'antigène spécifique, ce sont les antigènes spécifiques des leucocytes qui ont été ciblés. L'objectif est ainsi de dépléter l'échantillon des leucocytes restants. Ces travaux ont mené à l'élaboration d'un protocole de fonctionnalisation de surface optimal. De plus, de premiers résultats encourageants sur le cell rolling sur une surface fonctionnalisée avec des anticorps anti-CD45 ont été obtenus

    Lab-on-chip for the detection of rare cell events

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    Le tissu adipeux est une source riche en cellules souches multipotentes : les Cellules Souches Adipeuses (ASCs pour Adipose Stem Cells). Ces cellules, qui possèdent la capacité de se différencier en différents types cellulaires, ouvrent de nombreuses perspectives dans le domaine de la médecine régénératrice et dans des applications telles que le diagnostic du diabète de type 2. Connues pour migrer et circuler dans la lymphe, l'hypothèse de leur présence dans le sang n'est pas exclue mais aucune méthode n'existe afin de le prouver. L'objectif de ces travaux de thèse est alors de développer un laboratoire sur puce capable d'isoler les ASCs à partir d'échantillons biologiques complexes en mettant en application des méthodes microfluidiques de tri passives et sans marquage. Ce sont ainsi les propriétés intrinsèques des cellules qui sont exploitées. Or, les ASCs ne présentent aucune caractéristique physique spécifique. En effet, nous avons tout d'abord montré que leur diamètre est compris entre 10 et 25 µm, ce qui ne leur permet pas de se distinguer de la plupart des cellules sanguines. De même, ces cellules ne possèdent pas d'antigène spécifique sur leur membrane. Nous proposons alors un dispositif combinant deux étapes complémentaires afin d'isoler complètement les ASCs des autres types cellulaires. La première étape a pour objectif de prétraiter l'échantillon en retirant, par filtration hydrodynamique, toutes les cellules de diamètre inférieur à 10 µm. Ce dispositif doit ainsi permettre de retirer du milieu les globules rouges qui représentent plus de 99 % des cellules constituant le sang ainsi que les plaquettes et quelques globules blancs. Ces travaux de thèse ont démontré que le dispositif développé est capable de prétraiter efficacement un échantillon sanguin pur (humain ou murin) en éliminant plus de 99,9 % des globules rouges. De plus, il a été démontré que la filtration n'engendre pas de lyse cellulaire, ce qui est encourageant pour des questions de viabilité cellulaire et l'exploitation des cellules après filtration. L'échantillon alors obtenu contient les cellules d'intérêt ainsi que quelques cellules hématopoïétiques restantes. La deuxième étape a pour but de parfaire l'isolement des ASCs en les séparant des cellules hématopoïétiques restantes. Pour ce faire, la méthode employée, l'exclusion immunologique par cell rolling, se base sur la spécificité de la réaction antigène-anticorps. Les ASCs ne possédant pas d'antigène spécifique, ce sont les antigènes spécifiques des leucocytes qui ont été ciblés. L'objectif est ainsi de dépléter l'échantillon des leucocytes restants. Ces travaux ont mené à l'élaboration d'un protocole de fonctionnalisation de surface optimal. De plus, de premiers résultats encourageants sur le cell rolling sur une surface fonctionnalisée avec des anticorps anti-CD45 ont été obtenus.Adipose tissue is a rich source of multipotent stem cells: Adipose Stem Cells (or ASCs). Due to their differentiation capabilities, ASCs became cells of considerable interest for regenerative medicine and are of high interest for type II diabetes diagnosis. Known to migrate and circulate in lymph, the hypothesis of their presence in blood is not excluded but no method exists to prove it. The aim of this study is to develop a lab-on-chip able to isolate ASCs from complex biological samples by using passive and label-free microfluidic sorting methods. These methods involve intrinsic properties of fluids and objects. Yet, ASCs do not have specific physical characteristic. We have demonstrated that their diameter is comprised between 10 and 25 µm: they cannot be distinguished from most of other blood cells. In addition, they do not present specific antigen on their membrane. In order to completely isolate ASCs from other cell types, we propose an original approach combining two complementary steps. The first step aims at pre-treating the sample by removing, via hydrodynamic filtration, all the cells with a diameter below 10 µm. With this device, red blood cells, which represent more than 99% of blood cells, platelets and some leukocytes, have to be removed. This study has demonstrated that the device is able to effectively pre-treat pure blood sample (either from human or from mouse) as it removes more than 99.9% of red blood cells. It has also been demonstrated that filtration does not lead to cell lysis, which is a promising result for cell viability and the reuse of cells after filtration. The obtained sample contains cells of interest and some remaining hematopoietic cells. The second step aims at refining ASCs isolation by separating them from remaining hematopoietic cells. The method used, called immunological exclusion by cell rolling, is based on antigen-antibody specific reaction. As ASCs do not have specific antigen, leukocytes antigens have been involved. The objective is so to deplete the sample of the remaining leukocytes. This study led to the elaboration of an optimised surface functionalization protocol. Moreover, promising results on cell rolling realised on a surface functionalized with anti-CD45 antibodies were obtained

    Magnésium et effort d'endurance chez le poney

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    International audienc

    X-ray investigation of the small bowel in 2005

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    L'exploration classique de l'intestin grêle repose sur les techniques d'opacification, notamment le transit baryté. Pour l'étude des lésions de surface, les opacifications sont concurrencées par les progrès de l'endoscopie (entéroscopie, vidéo-capsule), mais aussi par les techniques d'imagerie axiale (échographie, scanner, imagerie par résonance magnétique). Celles-ci permettent une exploration précise du contenu encloluminal, des parois jéjuno-iléales, une vision directe des structures mésentériques adjacentes et de l'ensemble de la cavité péritonéale. Ces éléments sont d'un intérêt diagnostique majeur pour les pathologies inflammatoires ou tumorales, et dans le domaine des urgences intestinales et mésentériques. Nous détaillerons à travers cette revue générale actualisée, la place des techniques d'imagerie radiologique moderne pour la prise en charge des lésions aiguës ou chroniques de l'intestin grêle

    Socialisation alimentaire des enfants avec le Syndrome de Prader-Willi : une problématisation interdisciplinaire

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    International audienceEating “disorders” of people with Prader-Willi syndrome are frequently reported in the biomedical literature. The eating behaviors are presented as a syndrome-specific trajectory over the course of a lifetime. Infants initially show anorexic behavior, which then develops into hyperphagia that lasts from childhood to adulthood and is characterized by strong cravings for food and relentless thinking about it. However, the sociocultural determinants of these food practices are not fully understood. In the first section of this article, we carry out a literature review of medical articles published on disordered eating in children with PWS. The second section draws on a social science perspective and offers an interdisciplinary problematization using the concept of food socialization. To conclude, the third section explores the challenges facing research and new questions that emerge from the alternative problematization that is the PWS Food Social Norms Internalization (FSNI) theory

    Coping with social stress: heart rate responses to agonistic interactions in king penguins

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    International audienceIn colonial breeders, agonistic interactions between conspecifics are frequent and may have significant physiological implications. Physiological responses (e.g., increased heart rate) to such social stressors may be determined by the potential costs of agonistic interactions, such as personal injury or risk of breeding failure, and by the motivation of the individuals concerned. The latter may vary according to individuals' reproductive status or willingness to engage in agonistic interactions. In this study, we investigated heart rate responses to aggressive interactions in a breeding colony of king penguins Aptenodytes patagonicus. From heart rate (HR) and behavior recorded in 20 adults at various stages of the breeding season, we investigated how king penguins reacted to aggressive neighbors. A total of 589 agonistic interactions, 223 in which birds were actors and 366 in which birds remained bystanders (i.e., witnesses that were not involved in interactions), were characterized. We found that HR increased during agonistic interactions, both in actors and bystanders. The intensity (threat displays or physical attacks), duration, and rate of aggressive events (number of threats/blows per unit time) of an interaction significantly influenced the HR response in actors. For bystanders, however, only the duration of interactions seemed to matter. Our results also suggest a role for individual motivation, as initiators of agonistic interactions displayed higher HR increases than responders, and as increases were not constant throughout the reproductive season. We conclude that individual risk assessment and motivation modulate physiological responses to social stressors in group-living animal

    Prader-Willi syndrome: A model for understanding the ghrelin system.

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    Subsequent to the discovery of ghrelin as the endogenous ligand of growth hormone secretagogue receptor 1a, this unique gut peptide has been found to exert numerous physiological effects, such as appetite stimulation and lipid accumulation via the central regulating mechanisms in the hypothalamus, stimulation of gastric motility, regulation of glucose metabolism and brown fat thermogenesis, and modulation of stress, anxiety, taste sensation, reward-seeking behaviour and the sleep/wake cycle. Prader-Willi syndrome (PWS) has been described as a unique pathological state characterised by severe obesity and high circulating levels of ghrelin. It was hypothesised that hyperghrelinaemia would explain at least a part of the feeding behaviour and body composition of PWS patients, who are characterised by hyperphagia, an obsession with food and food-seeking, and increased adiposity. Initially, the link between hyperghrelinaemia and growth hormone deficiency, which is observed in 90% of the children with PWS, was not fully understood. Over the years, however, the increasing knowledge on ghrelin, PWS features and the natural history of the disease has led to a more comprehensive description of the abnormal ghrelin system and its role in the pathophysiology of this rare and complex neurodevelopmental genetic disease. In the present study, we (a) present the current view of PWS; (b) explain its natural history, including recent data on the ghrelin system in PWS patients; and (c) discuss the therapeutic approach of modulating the ghrelin system in these patients and the first promising results
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