Corticotherapy for traumatic brain-injured Patients - The Corti-TC trial: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Traumatic brain injury (TBI) is a main cause of severe prolonged disability of young patients. Hospital acquired pneumonia (HAP) add to the morbidity and mortality of traumatic brain-injured patients. In one study, hydrocortisone for treatment of traumatic-induced corticosteroid insufficiency (CI) in multiple injured patients has prevented HAP, particularly in the sub-group of patients with severe TBI. Fludrocortisone is recommended in severe brain-injured patients suffering from acute subarachnoid hemorrhage. Whether an association of hydrocortisone with fludrocortisone protects from HAP and improves neurological recovery is uncertain. The aim of the current study is to compare corticotherapy to placebo for TBI patients with CI.</p> <p>Methods</p> <p>The CORTI-TC (Corticotherapy in traumatic brain-injured patients) trial is a multicenter, randomized, placebo controlled, double-blind, two-arms study. Three hundred and seventy six patients hospitalized in Intensive Care Unit with a severe traumatic brain injury (Glasgow Coma Scale ≤ 8) are randomized in the first 24 hours following trauma to hydrocortisone (200 mg.day^-1for 7 days, 100 mg on days 8-9 and 50 mg on day-10) with fludrocortisone (50 μg for 10 days) or double placebo. The treatment is stopped if patients have an appropriate adrenal response. The primary endpoint is HAP on day-28. The endpoint of the ancillary study is the neurological status on 6 and 12 months.</p> <p>Discussion</p> <p>The CORTI-TC trial is the first randomized controlled trial powered to investigate whether hydrocortisone with fludrocortisone in TBI patients with CI prevent HAP and improve long term recovery.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01093261">NCT01093261</a></p

CpG-ODN and MPLA Prevent Mortality in a Murine Model of Post-Hemorrhage-Staphyloccocus aureus Pneumonia

Infections are the most frequent cause of complications in trauma patients. Post-traumatic immune suppression (IS) exposes patients to pneumonia (PN). The main pathogen involved in PN is Methicillin Susceptible Staphylococcus aureus (MSSA). Dendritic cells () may be centrally involved in the IS. We assessed the consequences of hemorrhage on pneumonia outcomes and investigated its consequences on DCs functions. A murine model of hemorrhagic shock with a subsequent MSSA pneumonia was used. Hemorrhage decreased the survival rate of infected mice, increased systemic dissemination of sepsis and worsened inflammatory lung lesions. The mRNA expression of Tumor Necrosis Factor-alpha (TNF-α), Interferon-beta (IFN-β) and Interleukin (IL)-12p40 were mitigated for hemorrhaged-mice. The effects of hemorrhage on subsequent PN were apparent on the pDCs phenotype (reduced MHC class II, CD80, and CD86 molecule membrane expression). In addition, hemorrhage dramatically decreased CD8+ cDCs- and CD8- cDCs-induced allogeneic T-cell proliferation during PN compared with mice that did not undergo hemorrhage. In conclusion, hemorrhage increased morbidity and mortality associated with PN; induced severe phenotypic disturbances of the pDCs subset and functional alterations of the cDCs subset. After hemorrhage, a preventive treatment with CpG-ODN or Monophosphoryl Lipid A increased transcriptional activity in DCs (TNF-α, IFN-β and IL-12p40) and decreased mortality of post-hemorrhage MSSA pneumonia

Répertoire des lymphocytes T et biomarqueurs (approches statistiques)

En transplantation rénale, la recherche de marqueurs biologiques liés au devenir à long terme du greffon s oriente vers la prévention du rejet chronique et vers l identification de patients susceptibles de développer une tolérance spontanée de leur greffon, en l absence ou sous faible doses d immunosuppresseurs. L analyse globale du répertoire des lymphocytes T, basée sur l étude des distributions de longueurs des boucles CDR3 de la chaine beta du récepteur des lymphocytes T et sur les quantités de transcrits codant pour cette région, est un indicateur puissant de l état du système immunitaire des patients transplantés. Le développement de méthodes statistiques spécialement dédiées à l analyse des distributions de longueurs CDR3 constitue la majeure partie de ce travail et a permis de mettre en évidence les différences existant entre patients en rejet chronique et patient opérationnellement tolérant. Ces nouvelles méthodes ont aussi permis de révéler la grande hétérogénéité d une cohorte de deux cent patients stables depuis au moins cinq ans et sous immunosuppression. De nombreuses pistes restent encore à explorer, concernant l analyse des distributions de longueurs CDR3 et la validation des signatures du répertoire T, pour une prédiction efficace du devenir à long terme du greffon.In renal transplantation, biomarkers that predict long-term allograft outcome are dedicated towards prevention of chronic rejection or the identification of patients that could potentially develop a spontaneous tolerance versus their graft, without on low doses of immunosupressors. Global T cell repertoire analysis, based on the study of the length distributions of the T cell receptor CDR3 beta chain and of the quantities of transcripts coding for this region, is a powerful indicator of the state of the immune system of transplanted patients. The implementation of statistical methods specially dedicated to the analysis of CDR3 length distributions constitutes the major part of this work and allows putting in evidence the differences existing between patients with chronic rejection and operationally tolerant patients. These new methods also allowed showing the high heterogeneity of a cohort of two hundred patients with a stable graft function for at least five years and under immunosupression. Perspectives are given to this work in term of improving the statistical methods developed for the analysis of the CDR3 length distribution and for the validation of the T cell repertoire signatures in order to efficiently predict long-term allograft outcome.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

Corrigendum to Multi-decadal projections of the surface and interior pathways of the Fukushima Cesium-137 radioactive plume

The authors of Rossi et al. (2013) regret that an incorrect parameter value in their numerical simulations led to an over-estimation of all Cesium-137 concentrations reported in the original manuscript by a factor 10. We would like to acknowledge Professor Michio Aoyama of Fukushima University, Japan, for drawing our attention to this error. Since the Lagrangian approach is linearly scalable, all reported Cs-137 concentrations (i.e. in the abstract, the main text as well as in the original figures 1, 2, 4 and 5) have to be reduced by a factor of 10 to obtain the correct concentrations. While the numerical values have changed, our conclusions remain unchanged.V.R. acknowledges support from MICINN and FEDER through the ESCOLA project (CTM2012-39025-C02-01) while finishing this paper. The OFES simulation was conducted on the Earth Simulator under the support of JAMSTEC. E.V.S. and M.H.E. are supported by the Australian Research Council (ARC), including the ARC Centre of Excellence for Climate System Science.Peer Reviewe

Baclofen to Prevent Agitation in Alcohol-Addicted Patients in the ICU: Study Protocol for a Randomised Controlled Trial

International audienceBACKGROUND: Alcohol is the leading psychoactive substance consumed in France, with about 15 million regular consumers. The National institute on Alcohol Abuse and Alcoholism (NIAAA) considers alcohol abuse to be more than 14 units of alcohol a week for men and 7 units for women. The specific complication of alcoholism is the alcohol withdrawal syndrome. Its incidence reaches up to 30~% and its main complications are delirium tremens, restlessness, extended hospital stay, higher morbidity, and psychiatric and cognitive impairment. Without appropriate treatment, delirium tremens can lead to death in up to 50~% of patients. METHODS/DESIGN: This prospective, double-blind, randomised controlled study versus placebo will be conducted in twelve French intensive care units (ICU). Patients with an alcohol intake level higher than the NIAAA threshold, who are under mechanical ventilation, will be included. The primary objective is to determine whether baclofen is more efficient than placebo in preventing restlessness-related side effects in the ICU. Secondary outcomes include mechanical ventilation duration, length of ICU stay, and cumulative doses of sedatives and painkillers received within 28~days of ICU admission. Restlessness-related side effects in the ICU are defined as unplanned extubation, medical disposal removal~(such as urinary catheter, venous or arterial line or surgical drain), falling out of bed, ICU runaway~(leaving ICU without physician's approval), immobilisation device removal, self-aggression or aggression towards medical staff. Daily doses of baclofen/placebo will be guided by daily creatinine clearance assessment. DISCUSSION: Restlessness in alcoholic patients is a life-threatening issue in ICUs. BACLOREA is a randomised study assessing the capacity of baclofen to prevent agitation in mechanically ventilated patients. Enrolment of 314 patients will begin in June 2016 and is expected to end in October 2018. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02723383 , registered on 3 March 2016