53 research outputs found
Dysfonctions lymphocytaires et perturbations immuno-métaboliques au cours des états infectieux sévÚres
Severe infectious states are characterized by the occurrence of immune perturbations responsible for an exacerbation of the susceptibility to secondary infections. The development of a standardized murine model of double sequential infections (a sepsis followed 5 days later by an acquired infection) allowed us to explore the T- cells disturbances showing an increase in apoptosis of these cells as well as a decrease in their capacity to proliferate in vitro. These dysfunctions were associated with the presence of an alteration of mitochondrial respiration. On the other hand, an increase in the concentration of regulatory T cells and MDSCs and a decrease in arginine concentration were observed. The correction of hypoargininemia by citrulline supplementation allowed the correction of all these perturbations as well as a decrease in the severity of secondary infections. In order to complete this experimental approach, we have initiated explorations in patients suffering from COVID-19, allowing us to observe, once again, the presence of lymphopenia correlated to the severity of the patients as well as T-cells dysfunctions associated with the occurrence of hypoargininemia and an increased risk of secondary infections. Finally, the presence of immunosuppressive cell populations was observed in severe patients. All these results underline the key role of arginine metabolism within the immunosuppressive mechanisms occurring during infectious states. The correction of hypoargininemia suggests new therapeutic perspectives to limit the consequences of immunosuppressive phenomena induced by sepsis.Les eÌtats infectieux seÌveÌres sont caracteÌriseÌs par la survenue de perturbations immunitaires responsables dâune exacerbation de la susceptibiliteÌ aux infections secondaires. LâeÌlaboration dâun modeÌle murin standardiseÌ de double infections seÌquentielles (un sepsis suivi 5 jours apreÌs dâune infection acquise) nous a permis dâexplorer les perturbations lymphocytaires T objectivant une majoration de lâapoptose de ces cellules ainsi quâune diminution de leurs capaciteÌs aÌ prolifeÌrer in vitro. Ces dysfonctions eÌtaient associeÌes aÌ la preÌsence dâune alteÌration de la respiration mitochondriale. Dâautre part, ont eÌteÌ observeÌes une augmentation de la concentration de lymphocytes T reÌgulateurs et de MDSC ainsi quâune diminution de la concentration en arginine. La correction de lâhypoarginineÌmie par suppleÌmentation en citrulline a permis la correction de lâensemble de ces perturbations ainsi quâune diminution de la seÌveÌriteÌ des infections acquises. Afin dâapprofondir cette approche expeÌrimentale, nous avons initieÌ des analyses chez les patients atteints de COVID-19 permettant dâobserver, laÌ encore, la preÌsence dâune lymphopeÌnie correÌleÌe aÌ la seÌveÌriteÌ ainsi que des dysfonctions lymphocytaires T associeÌes aÌ la survenue dâune hypoarginineÌmie et aÌ une majoration du risque dâinfections secondaires. Enfin, a pu eÌtre objectiveÌe la preÌsence de populations cellulaires immunosuppressives preÌfeÌrentiellement chez les patients seÌveÌres. Lâensemble de ces reÌsultats souligne le roÌle cleÌ du meÌtabolisme de lâarginine au sein des meÌcanismes immunosupresseurs survenant au cours des eÌtats infectieux. La correction de lâhypoarginineÌmie laisse entrevoir de nouvelles perspectives theÌrapeutiques afin de limiter les conseÌquences des pheÌnomeÌnes immunosuppresseurs induits par le sepsis
Lymphocyte dysfunctions and immuno-metabolic impairment during severe infectious states
Les eÌtats infectieux seÌveÌres sont caracteÌriseÌs par la survenue de perturbations immunitaires responsables dâune exacerbation de la susceptibiliteÌ aux infections secondaires. LâeÌlaboration dâun modeÌle murin standardiseÌ de double infections seÌquentielles (un sepsis suivi 5 jours apreÌs dâune infection acquise) nous a permis dâexplorer les perturbations lymphocytaires T objectivant une majoration de lâapoptose de ces cellules ainsi quâune diminution de leurs capaciteÌs aÌ prolifeÌrer in vitro. Ces dysfonctions eÌtaient associeÌes aÌ la preÌsence dâune alteÌration de la respiration mitochondriale. Dâautre part, ont eÌteÌ observeÌes une augmentation de la concentration de lymphocytes T reÌgulateurs et de MDSC ainsi quâune diminution de la concentration en arginine. La correction de lâhypoarginineÌmie par suppleÌmentation en citrulline a permis la correction de lâensemble de ces perturbations ainsi quâune diminution de la seÌveÌriteÌ des infections acquises. Afin dâapprofondir cette approche expeÌrimentale, nous avons initieÌ des analyses chez les patients atteints de COVID-19 permettant dâobserver, laÌ encore, la preÌsence dâune lymphopeÌnie correÌleÌe aÌ la seÌveÌriteÌ ainsi que des dysfonctions lymphocytaires T associeÌes aÌ la survenue dâune hypoarginineÌmie et aÌ une majoration du risque dâinfections secondaires. Enfin, a pu eÌtre objectiveÌe la preÌsence de populations cellulaires immunosuppressives preÌfeÌrentiellement chez les patients seÌveÌres. Lâensemble de ces reÌsultats souligne le roÌle cleÌ du meÌtabolisme de lâarginine au sein des meÌcanismes immunosupresseurs survenant au cours des eÌtats infectieux. La correction de lâhypoarginineÌmie laisse entrevoir de nouvelles perspectives theÌrapeutiques afin de limiter les conseÌquences des pheÌnomeÌnes immunosuppresseurs induits par le sepsis.Severe infectious states are characterized by the occurrence of immune perturbations responsible for an exacerbation of the susceptibility to secondary infections. The development of a standardized murine model of double sequential infections (a sepsis followed 5 days later by an acquired infection) allowed us to explore the T- cells disturbances showing an increase in apoptosis of these cells as well as a decrease in their capacity to proliferate in vitro. These dysfunctions were associated with the presence of an alteration of mitochondrial respiration. On the other hand, an increase in the concentration of regulatory T cells and MDSCs and a decrease in arginine concentration were observed. The correction of hypoargininemia by citrulline supplementation allowed the correction of all these perturbations as well as a decrease in the severity of secondary infections. In order to complete this experimental approach, we have initiated explorations in patients suffering from COVID-19, allowing us to observe, once again, the presence of lymphopenia correlated to the severity of the patients as well as T-cells dysfunctions associated with the occurrence of hypoargininemia and an increased risk of secondary infections. Finally, the presence of immunosuppressive cell populations was observed in severe patients. All these results underline the key role of arginine metabolism within the immunosuppressive mechanisms occurring during infectious states. The correction of hypoargininemia suggests new therapeutic perspectives to limit the consequences of immunosuppressive phenomena induced by sepsis
Organizing and Sharing Medical Knowledge Among Anesthesiology and Intensive care Residents: Evaluating Existing Practices and the Feasibility of Implementing a Dedicated Multiplatform Application
International audienceTreating patients with up-to-date medical knowledge is an ongoing goal for healthcare workers and implies efficient knowledge management at the point of care. Widely available mobile wireless technologies influence practices but a significant gap remains between technological possibilities and actual usage. The purpose of this study was to analyze residentsâ baseline practices in managing medical knowledge and to evaluate the use and impact of an innovative multiplatform application dedicated to anesthesiology and intensive care residents. This study took place in Rennes Teaching Hospital and comprised two distinct surveys. First, in April 2018, all residents received a ten-items online survey focusing on managing medical knowledge. Then, through a second online survey constituted of ten items, we sought to assess the use of a new multiplatform cloud-based application named "DansMaBlouse", dedicated to sharing and indexing medical knowledge, in anesthesiology and intensive care residents. Among 148 residents that answered the evaluation survey, the most sought out pieces of information in clinical setting were a phone or fax number (74%), drugsâ characteristics (68%) and expert guidelines (57%). The main sources were senior staff (68%), medical databases (60%) and an Internet search engine (59%). Computers and smartphones were more frequently used than bound paper notebooks. After implementation of the multiplatform application DansMaBlouse, fifty-nine (82%) of the 72 residents that answered the evaluation survey reported using the application and 39% used it more than ten times. Among application users, 90% found it easy to use and 92% agreed that it improved point-of-care access to knowledge. Accessing appropriate medical knowledge at the point of care remains an issue for residents and can be improved by a multiplatform application combining personal and shared up-to-date resources
Assessing the entire landscape of antifungal immune response to COVID-19-associated pulmonary aspergillosis
International audienc
Selective digestive decontamination to reduce the high rate of ventilator-associated pneumonia in critical COVID-19
International audienc
Toward the personalized and integrative management of voriconazole dosing during COVID-19-associated pulmonary aspergillosis
International audienc
Herpes simplex virus and cytomegalovirus reactivations among severe COVID-19 patients
International audienc
Platelet-derived sCD40L: specific inflammatory marker for early-stage severe acute respiratory syndrome coronavirus 2 infection
International audienceBACKGROUND: The SARS-CoV-2 virus is the causing agent of the Coronavirus disease 2019 (COVID-19) characterized by a huge pro-inflammatory response and coagulation disorders that may lead to for its severe forms, in organ failure or even death. As major players of thrombo-inflammation, platelets release large amounts of immunomodulatory molecules and regulate leukocyte and endothelial activity, which are both altered in COVID-19. Altogether, this makes platelets a very likely actor of the thrombo-inflammatory complications of COVID-19. Thus, we propose to identify a platelet inflammatory signature of severe COVID-19 specifically modulated throughout the course of the disease. METHODS: Luminex technology and enzyme-linked immunosorbent assay were used to assess plasma levels of platelet inflammatory markers in patients with severe acute respiratory syndrome coronavirus 2 infection on admission and for 14Â days afterwards. RESULTS: In accordance with the observations of other teams, we evidence that the plasma levels of the platelet soluble (s)CD40L is significantly elevated in the early stages of the disease. Interestingly we observe that the plasma level of sCD40L decreases overtime while that of sCD62P increases significantly. CONCLUSIONS: Our data suggest that there is a platelet signature of inflammatory response to SARS-COv-2 infection which varies overtime and could serve as monitoring biomarkers of patient inflammatory state. CLINICAL TRIAL REGISTRATION NUMBER: 2020-A01100-39; title: Human Ab Response and immunoMONItoring of COVID-19 Patients, registration date: 05/25/2020; URL of the registry: https://clinicaltrials.gov/ct2/history/NCT04373200?V_5=View
Herpesviridae systemic reactivations in COVID-19 associated ARDS patients
International audienc
1-hour t-piece spontaneous breathing trial vs 1-hour zero pressure support spontaneous breathing trial and reintubation at day 7: A non-inferiority approach
International audiencePurpose: Physiological data suggest that T-piece and zero pressure support (PS0) ventilation both accurately reflect spontaneous breathing conditions after extubation. These two types of spontaneous breathing trials (SBTs) are used in our Intensive Care Unit to evaluate patients for extubation readiness and success but have rarely been compared in clinical studies. Materials and methods: We performed a prospective observational study to confirm the hypothesis that 1-hour T-piece SBT and 1-h PS0 zero PEEP (ZEEP) SBT are associated with similar rates of reintubation at day 7 after extubation. A non-inferiority approach was used for sample size calculation. Results: The cohort consisted of 529 subjects invasively ventilated for more than 24 h and extubated after successful 1-hour T-piece SBT (n = 303, 57%) or 1-h PS0 ZEEP SBT (n = 226, 43%). The reintubation rate at day 7 was 14.6% with PS0 ZEEP and 17.5% with T-piece (difference - 2.6% [95% confidence interval, -8.3% to 4.3%]; p = 0.40). The reasons for reintubation did not differ significantly when compared between patients with 1-h PS0 ZEEP SBT and patients with 1-hour T-piece SBT. Conclusion: Our results suggest that successful 1-hour T-piece and 1-h PSO ZEEP SBTs are associated with similar reintubation rates at day 7. (c) 2021 Published by Elsevier Inc
- âŠ