Intensive care unit-acquired Stenotrophomonas maltophilia: incidence, risk factors, and outcome

INTRODUCTION: The aim of this study was to determine incidence, risk factors, and impact on outcome of intensive care unit (ICU)-acquired Stenotrophomonas maltophilia. METHODS: This prospective observational case-control study, which was a part of a cohort study, was conducted in a 30-bed ICU during a three year period. All immunocompetent patients hospitalised >48 hours were eligible. Patients with non-fermenting Gram-negative bacilli (NF-GNB) at ICU admission were excluded. Patients without ICU-acquired S. maltophilia who developed an ICU-acquired NF-GNB other than S. maltophilia were also excluded. Screening (tracheal aspirate and skin, anal, and nasal swabs) for NF-GNB was performed in all patients at ICU admission and weekly. Univariate and multivariate analyses were performed to determine risk factors for ICU-acquired S. maltophilia and for ICU mortality. RESULTS: Thirty-eight (2%) patients developed an S. maltophilia ICU-acquired colonisation and/or infection and were all successfully matched with 76 controls. Chronic obstructive pulmonary disease (COPD) and duration of antibiotic treatment (odds ratio [OR] [95% confidence interval (CI)] = 9.4 [3 to 29], p < 0.001, and 1.4 [1 to 2.3], p = 0.001, respectively) were independently associated with ICU-acquired S. maltophilia. Mortality rate (60% versus 40%, OR [95% CI] = 1.3 [1 to 1.7, p = 0.037]), duration of mechanical ventilation (23 ± 16 versus 7 ± 11 days, p < 0.001), and duration of ICU stay (29 ± 21 versus 15 ± 17 days, p < 0.001) were significantly higher in cases than in controls. In addition, ICU-acquired infection related to S. maltophilia was independently associated with ICU mortality (OR [95% CI] = 2.8 [1 to 7.7], p = 0.044). CONCLUSION: COPD and duration of antibiotic treatment are independent risk factors for ICU-acquired S. maltophilia. ICU-acquired S. maltophilia is associated with increased morbidity and mortality rates. ICU-acquired infection related to S. maltophilia is an independent risk factor for ICU mortality

EMT Inducers Catalyze Malignant Transformation of Mammary Epithelial Cells and Drive Tumorigenesis towards Claudin-Low Tumors in Transgenic Mice

The epithelial-mesenchymal transition (EMT) is an embryonic transdifferentiation process consisting of conversion of polarized epithelial cells to motile mesenchymal ones. EMT–inducing transcription factors are aberrantly expressed in multiple tumor types and are known to favor the metastatic dissemination process. Supporting oncogenic activity within primary lesions, the TWIST and ZEB proteins can prevent cells from undergoing oncogene-induced senescence and apoptosis by abolishing both p53- and RB-dependent pathways. Here we show that they also downregulate PP2A phosphatase activity and efficiently cooperate with an oncogenic version of H-RAS in malignant transformation of human mammary epithelial cells. Thus, by down-regulating crucial tumor suppressor functions, EMT inducers make cells particularly prone to malignant conversion. Importantly, by analyzing transformed cells generated in vitro and by characterizing novel transgenic mouse models, we further demonstrate that cooperation between an EMT inducer and an active form of RAS is sufficient to trigger transformation of mammary epithelial cells into malignant cells exhibiting all the characteristic features of claudin-low tumors, including low expression of tight and adherens junction genes, EMT traits, and stem cell–like characteristics. Claudin-low tumors are believed to be the most primitive breast malignancies, having arisen through transformation of an early epithelial precursor with inherent stemness properties and metaplastic features. Challenging this prevailing view, we propose that these aggressive tumors arise from cells committed to luminal differentiation, through a process driven by EMT inducers and combining malignant transformation and transdifferentiation

Coût de la qualité, stratégie et changement

International audienc

Coût de la qualité, stratégie et changement

International audienc

The local properties of bold signal fluctuations at rest monitor inhibitory control training in adolescents

International audienc

Complex and subtle structural changes in prefrontal cortex induced by inhibitory control training from childhood to adolescence

International audienc

Ultrafast and whole-body cooling with total liquid ventilation induces favorable neurological and cardiac outcomes after cardiac arrest in rabbits.: Liquid ventilation, hypothermia and cardiac arrest

International audienceBackground- In animal models of cardiac arrest, the benefit afforded by hypothermia is closely linked to the rapidity of the decrease in body temperature after resuscitation. Because total liquid ventilation (TLV) with temperature-controlled perfluorocarbons induces a very rapid and generalized cooling, we aimed to determine whether this could limit the post-cardiac arrest syndrome in a rabbit model. We especially focused on neurological, cardiac, pulmonary, liver and kidney dysfunctions. Methods and Results- Anesthetized rabbits were submitted to either 5 or 10 minutes of untreated ventricular fibrillation. After cardiopulmonary resuscitation and resumption of a spontaneous circulation, the animals underwent either normothermic life support (control) or therapeutic hypothermia induced by TLV. The latter procedure decreased esophageal and tympanic temperatures to 32°C to 33°C within only 10 minutes. After rewarming, the animals submitted to TLV exhibited an attenuated neurological dysfunction and decreased mortality 7 days later compared with control. The neuroprotective effect of TLV was confirmed by a significant reduction in brain histological damages. We also observed limitation of myocardial necrosis, along with a decrease in troponin I release and a reduced myocardial caspase 3 activity, with TLV. The beneficial effects of TLV were directly related to the rapidity of hypothermia induction because neither conventional cooling (cold saline infusion plus external cooling) nor normothermic TLV elicited a similar protection. Conclusions- Ultrafast cooling instituted by TLV exerts potent neurological and cardiac protection in an experimental model of cardiac arrest in rabbits. This could be a relevant approach to provide a global and protective hypothermia against the post-cardiac arrest syndrome

: Conséquences en santé et sécurité au travail dans les petites entreprises en France

rapport édité par l'INVS - co produit par les experts1er scénario : Un engagement fort et fructueux de l’État et des entreprises : un développement massifLes expert se placent en 2030 en imaginant que les années 2020 ont été marquées par une succession d’innovations scientifiques et techniques majeures dans différents domaines. Au cours de cette période, les investissements publics et privés alloués à des technologies nouvelles et prometteuses se sont ainsi très fortement accrus.Conséquences : On dispose à la fois des outils et de l’argent pour innover, produire et prévenir les risques. Les nouveaux produits sont correctement catégorisés ce qui permet la mise en place de moyens de prévention des risques professionnels adaptés.2ème scénario : Un rejet éclairé de la part de la société : un développement dans quelques rares filières stratégiquesConséquences : Dans un contexte d’opacité, les systèmes publics de prévention des risques professionnels ne sont pas les bienvenus dans les entreprises. Pour ces dernières, les interventions de l’Etat, à travers une application sans nuance du principe de précaution, peuvent peser gravement. 3ème scénario : Une mainmise industrielle : un développement dans des secteurs porteursConséquences : Le contrat individuel entre l’entreprise et le travailleur est devenu la règle. La prévention est strictement du ressort des entreprises et s’exprime majoritairement en termes de réparation et non pas en termes de prévention primaire. 4ème scénario : Une volonté régionale soutenue : un développement en fonction des compétences localesConséquences : La protection de la santé des travailleurs répond à des exigences très générales définies au niveau européen, mais elle est pilotée par les instances régionales