90 research outputs found

    Increased mortality in hematological malignancy patients with acute respiratory failure from undetermined etiology : a Groupe de Recherche en RĂ©animation Respiratoire en Onco-HĂ©matologique (Grrr-OH) study

    Get PDF
    Background: Acute respiratory failure (ARF) is the most frequent complication in patients with hematological malignancies and is associated with high morbidity and mortality. ARF etiologies are numerous, and despite extensive diagnostic workflow, some patients remain with undetermined ARF etiology. Methods: This is a post-hoc study of a prospective multicenter cohort performed on 1011 critically ill hematological patients. Relationship between ARF etiology and hospital mortality was assessed using a multivariable regression model adjusting for confounders. Results: This study included 604 patients with ARF. All patients underwent noninvasive diagnostic tests, and a bronchoscopy and bronchoalveolar lavage (BAL) was performed in 155 (25.6%). Definite diagnoses were classified into four exclusive etiological categories: pneumonia (44.4%), non-infectious diagnoses (32.6%), opportunistic infection (10.1%) and undetermined (12.9%), with corresponding hospital mortality rates of 40, 35, 55 and 59%, respectively. Overall hospital mortality was 42%. By multivariable analysis, factors associated with hospital mortality were invasive pulmonary aspergillosis (OR 7.57 (95% CI 3.06-21.62); p 7 (OR 3.32 (95% CI 2.15-5.15); p < 0.005) and an undetermined ARF etiology (OR 2.92 (95% CI 1.71-5.07); p < 0.005). Conclusions: In patients with hematological malignancies and ARF, up to 13% remain with undetermined ARF etiology despite comprehensive diagnostic workup. Undetermined ARF etiology is independently associated with hospital mortality. Studies to guide second-line diagnostic strategies are warranted

    Estimating the Timing of Mother-to-Child Transmission of the Human Immunodeficiency Virus Type 1 Using a Viral Molecular Evolution Model

    Get PDF
    Background: Mother-to-child transmission (MTCT) is responsible for most pediatric HIV-1 infections worldwide. It can occur during pregnancy, labor, or breastfeeding. Numerous studies have used coalescent and molecular clock methods to understand the epidemic history of HIV-1, but the timing of vertical transmission has not been studied using these methods. Taking advantage of the constant accumulation of HIV genetic variation over time and using longitudinally sampled viral sequences, we used a coalescent approach to investigate the timing of MTCT. Materials and Methods Six-hundred and twenty-two clonal env sequences from the RNA and DNA viral population were longitudinally sampled from nine HIV-1 infected mother-and-child pairs [range: 277–1034 days]. For each transmission pair, timing of MTCT was determined using a coalescent-based model within a Bayesian statistical framework. Results were compared with available estimates of MTCT timing obtained with the classic biomedical approach based on serial HIV DNA detection by PCR assays. Results: Four children were infected during pregnancy, whereas the remaining five children were infected at time of delivery. For eight out of nine pairs, results were consistent with the transmission periods assessed by standard PCR-based assay. The discordance in the remaining case was likely confused by co-infection, with simultaneous introduction of multiple maternal viral variants at the time of delivery. Conclusions: The study provided the opportunity to validate the Bayesian coalescent approach that determines the timing of MTCT of HIV-1. It illustrates the power of population genetics approaches to reliably estimate the timing of transmission events and deepens our knowledge about the dynamics of viral evolution in HIV-infected children, accounting for the complexity of multiple transmission events

    The FOXO1 Transcription Factor Instructs the Germinal Center Dark Zone Program

    Get PDF
    SummaryThe pathways regulating formation of the germinal center (GC) dark zone (DZ) and light zone (LZ) are unknown. In this study we show that FOXO1 transcription factor expression was restricted to the GC DZ and was required for DZ formation, since its absence in mice led to the loss of DZ gene programs and the formation of LZ-only GCs. FOXO1-negative GC B cells displayed normal somatic hypermutation but defective affinity maturation and class switch recombination. The function of FOXO1 in sustaining the DZ program involved the trans-activation of the chemokine receptor CXCR4, and cooperation with the BCL6 transcription factor in the trans-repression of genes involved in immune activation, DNA repair, and plasma cell differentiation. These results also have implications for the role of FOXO1 in lymphomagenesis because they suggest that constitutive FOXO1 activity might be required for the oncogenic activity of deregulated BCL6 expression

    DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

    Get PDF
    We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR&nbsp;=&nbsp;2.05, 95%CI&nbsp;=&nbsp;1.39–3.02, p&nbsp;&lt;&nbsp;0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR&nbsp;=&nbsp;0.42, 95%CI&nbsp;=&nbsp;0.18–0.99, p&nbsp;=&nbsp;0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

    New strategies for the development of ion conducting polymers and networks based 1,2,3-triazolium

    No full text
    Cette thèse propose de nouvelles stratégies de synthèse de poly(liquides ioniques) à base 1,2,3-triazolium (TPILs) impliquant deux réactions successives et orthogonales de cycloaddition azoture-alcyne catalysée par le cuivre(I) et de N-alkylation des intermédiaires 1,2,3-triazole. Cette séquence réactionnelle permet d’élaborer des monomères liquides ioniques d’une vaste diversité de structure et de fonctions polymérisables mais également de modifier chimiquement des polymères de manière quantitative. En tirant parti des avantages de la chimie des 1,2,3-triazoliums, trois nouveaux TPILs ont été développés par des méthodes de synthèse originales. Le premier chapitre propose deux nouvelles classes de TPILs linéaires élaborés selon deux approches distinctes. La première consiste en la polymérisation AA+BB d’un monomère 1,2,3-triazolium diol synthétique avec quatre diisocyantes commerciaux pour obtenir des polyuréthanes. La seconde repose sur la modification chimique post-polymérisation d’un polysiloxane neutre fonctionnalisé thiol par greffage thiol-ène d’un liquide ionique à base 1,2,3-triazolium possédant un groupement vinylique. Ce premier exemple de TPIL à base polysiloxane possède des propriétés de conductivités ioniques remarquables. Le deuxième chapitre présente une littérature exhaustive des différentes voies de synthèses permettant d’élaborer des matériaux poly(liquides ioniques) (PILs) réticulés. Cette étude est divisée en trois parties qui distinguent les réseaux PILs obtenus par polymérisation en chaine, polymérisation par étapes et réticulation post-polymérisation. Ces matériaux sont également différenciés selon leurs microstructure (membranes denses, poreuses, gélifiées et colloïdes) et leurs applications (électrolytes solide, absorption et stockage du CO2, catalyse…). Le troisième chapitre propose une nouvelle voie d’accès à des PILs réticulés. Il traite de la synthèse d’un monomère diépoxy liquide ionique 1,2,3-triazolium puis de son homopolymérisation par ouverture de cycle cationique. Les cinétiques de polymérisation et la détermination des propriétés physicochimiques du réseau sont comparées à un analogue structural ne possédant pas de groupement liquide ionique. Cette nouvelle stratégie permet d’obtenir des matériaux de haute conductivité ionique sans l’usage de co-monomères.This thesis proposes new strategies for synthesis of poly(ionic liquid)s based 1.2,3-triazolium (TPILs) involving two successive and orthogonal reactions of azide-alkyne cycloaddition catalyzed by copper (I) and N-alkylation of 1,2,3-triazole intermediates. This reaction sequence allows the development of ionic liquid monomers of a wide variety of structure and polymerizable functions, but also to chemically modify polymers quantitatively. Taking advantage of the chemistry benefits of 1.2,3-triazoliums, three new TPILs were developed by original synthesis methods. The first chapter proposes two new classes of linear TPILs developed using two distinct approaches. The first one consists of the AA + BB polymerization of a 1.2,3-triazolium synthetic diol monomer with four commercial diisocyants to obtain polyurethanes. The second one is the post-polymerization chemical modification of a neutral polysiloxane functionalized thiol by thiol-ene grafting of a 1.2.3-triazolium-based ionic liquid with a vinyl group. This first example of polysiloxane-based TPIL has remarkable ionic conductivity properties. The second chapter presents an exhaustive literature of the different synthesis pathways for the development of crosslinked poly(ionic liquid)s materials (PILs). This study is divided into three parts that distinguish the PILs networks obtained by chain growth polymerization, step growth polymerization and post-polymerization cross-linking. These materials are also differentiated according to their microstructure (dense, porous, gel membranes and colloid) and their applications (solid electrolytes, CO2 sorption and storage, catalysis, etc.). The third chapter proposes a new pathway to crosslinked PILs. It deals with the synthesis of an ionic liquid monomer diepoxy based 1.2,3-triazolium and then its homopolymerization by cationic ring opening polymerization. Polymerizing kinetics and physical properties of the network are compared to a structural analogue that does not have ionic liquid groups. This new strategy afforded materials with high ionic conductivity without the use of co-monomers

    L'insuffisance cardiaque aiguë (pronostic, stratification des risques dans la prise en charge initiale)

    No full text
    PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

    Séminaire d’initiation à la philosophie politique

    No full text
    info:eu-repo/semantics/nonPublishe

    Enhanced Ionic Conductivity of a 1,2,3-Triazolium-Based Poly(siloxane ionic liquid) Homopolymer

    No full text
    International audienceA 1,2,3-triazolium-based poly(siloxane ionic liquid) (PSIL) is synthesized by UV-triggered thiol-ene ligation between a poly[(mercaptopropyl)methylsiloxane] and a tailor-made vinyl-functionalized triethylene glycol-based 1,2,3-triazolium ionic liquid. The quantitative nature of the thiol-ene coupling is demonstrated by H-1 and C-13 NMR, whereas properties of this new PSIL are discussed based on solubility, size exclusion chromatography, differential scanning calorimetry, thermogravimetric analysis, and broadband dielectric spectroscopy measurements. Besides exhibiting low glass transition temperature (T-g = -62 degrees C) and high thermal stability (T-d10 = 284 degrees C), this new class of poly(1,2,3-triazolium) demonstrates the highest value of bulk anhydrous ionic conductivity reported to date for PILs (sigma(DC) = 7 x 10(-5) s cm(-1) at 30 degrees C)
    • …
    corecore