Does taking endurance into account improve the prediction of weaning outcome in mechanically ventilated children?

INTRODUCTION: We conducted the present study to determine whether a combination of the mechanical ventilation weaning predictors proposed by the collective Task Force of the American College of Chest Physicians (TF) and weaning endurance indices enhance prediction of weaning success. METHOD: Conducted in a tertiary paediatric intensive care unit at a university hospital, this prospective study included 54 children receiving mechanical ventilation (≥6 hours) who underwent 57 episodes of weaning. We calculated the indices proposed by the TF (spontaneous respiratory rate, paediatric rapid shallow breathing, rapid shallow breathing occlusion pressure [ROP] and maximal inspiratory pressure during an occlusion test [Pi(max)]) and weaning endurance indices (pressure-time index, tension-time index obtained from P(0.1 )[TTI(1)] and from airway pressure [TTI(2)]) during spontaneous breathing. Performances of each TF index and combinations of them were calculated, and the best single index and combination were identified. Weaning endurance parameters (TTI(1 )and TTI(2)) were calculated and the best index was determined using a logistic regression model. Regression coefficients were estimated using the maximum likelihood ratio (LR) method. Hosmer–Lemeshow test was used to estimate goodness-of-fit of the model. An equation was constructed to predict weaning success. Finally, we calculated the performances of combinations of best TF indices and best endurance index. RESULTS: The best single TF index was ROP, the best TF combination was represented by the expression (0.66 × ROP) + (0.34 × Pi(max)), and the best endurance index was the TTI(2), although their performance was poor. The best model resulting from the combination of these indices was defined by the following expression: (0.6 × ROP) – (0.1 × Pi(max)) + (0.5 × TTI(2)). This integrated index was a good weaning predictor (P < 0.01), with a LR(+ )of 6.4 and LR(+)/LR(- )ratio of 12.5. However, at a threshold value <1.3 it was only predictive of weaning success (LR(- )= 0.5). CONCLUSION: The proposed combined index, incorporating endurance, was of modest value in predicting weaning outcome. This is the first report of the value of endurance parameters in predicting weaning success in children. Currently, clinical judgement associated with spontaneous breathing trials apparently remain superior

Acute respiratory failure in the elderly: etiology, emergency diagnosis and prognosis

INTRODUCTION: Our objectives were to determine the causes of acute respiratory failure (ARF) in elderly patients and to assess the accuracy of the initial diagnosis by the emergency physician, and that of the prognosis. METHOD: In this prospective observational study, patients were included if they were admitted to our emergency department, aged 65 years or more with dyspnea, and fulfilled at least one of the following criteria of ARF: respiratory rate at least 25 minute(-1); arterial partial pressure of oxygen (PaO(2)) 70 mmHg or less, or peripheral oxygen saturation 92% or less in breathing room air; arterial partial pressure of CO(2 )(PaCO(2)) ≥ 45 mmHg, with pH ≤ 7.35. The final diagnoses were determined by an expert panel from the completed medical chart. RESULTS: A total of 514 patients (aged (mean ± standard deviation) 80 ± 9 years) were included. The main causes of ARF were cardiogenic pulmonary edema (43%), community-acquired pneumonia (35%), acute exacerbation of chronic respiratory disease (32%), pulmonary embolism (18%), and acute asthma (3%); 47% had more than two diagnoses. In-hospital mortality was 16%. A missed diagnosis in the emergency department was noted in 101 (20%) patients. The accuracy of the diagnosis of the emergency physician ranged from 0.76 for cardiogenic pulmonary edema to 0.96 for asthma. An inappropriate treatment occurred in 162 (32%) patients, and lead to a higher mortality (25% versus 11%; p < 0.001). In a multivariate analysis, inappropriate initial treatment (odds ratio 2.83, p < 0.002), hypercapnia > 45 mmHg (odds ratio 2.79, p < 0.004), clearance of creatinine < 50 ml minute(-1 )(odds ratio 2.37, p < 0.013), elevated NT-pro-B-type natriuretic peptide or B-type natriuretic peptide (odds ratio 2.06, p < 0.046), and clinical signs of acute ventilatory failure (odds ratio 1.98, p < 0.047) were predictive of death. CONCLUSION: Inappropriate initial treatment in the emergency room was associated with increased mortality in elderly patients with ARF

Guide de l'inventaire topographique

International audienc

Host-Seeking Activity of Bluetongue Virus Vectors: Endo/Exophagy and Circadian Rhythm of Culicoides in Western Europe

Feeding success of free-living hematophagous insects depends on their ability to be active when hosts are available and to reach places where hosts are accessible. When the hematophagous insect is a vector of pathogens, determining the components of host-seeking behavior is of primary interest for the assessment of transmission risk. Our aim was to describe endo/exophagy and circadian host-seeking activity of Palaearctic Culicoides species, which are major biting pests and arbovirus vectors, using drop traps and suction traps baited with four sheep, as bluetongue virus hosts. Collections were carried out in the field, a largely-open stable and an enclosed stable during six collection periods of 24 hours in April/May, in late June and in September/October 2010 in western France. A total of 986 Culicoides belonging to 13 species, mainly C. brunnicans and C. obsoletus, was collected on animal baits. Culicoides brunnicans was clearly exophagic, whereas C. obsoletus was able to enter stables. Culicoides brunnicans exhibited a bimodal pattern of host-seeking activity with peaks just after sunrise and sunset. Culicoides obsoletus was active before sunset in spring and autumn and after sunset in summer, thus illustrating influence of other parameters than light, especially temperature. Description of host-seeking behaviors allowed us to discuss control strategies for transmission of Culicoides-borne pathogens, such as bluetongue virus. However, practical vector-control recommendations are difficult to provide because of the variation in the degree of endophagy and time of host-seeking activity.This study was funded by CIRAD, by the Ministe`re de l’agriculture, de l’alimentation, de la peˆche, de la ruralite´ et de l’ame´nagement du terroire and by the EU FP7-HEALTH-2010-single-stage grant 261504 EDENext. This paper is catalogued by the EDENext Steering Committee as EDENext032 (http://www.edenext. eu). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study

Differential impact of magnitude, polyfunctional capacity, and specificity of HIV-specific CD8+ T cell responses on HIV set point.

CAPRISA, 2014.Defining the characteristics of HIV-specific CD8(+) T cell responses that lead to viral control is crucial for vaccine development. We evaluated the differential impact of magnitude, polyfunctional capacity, and specificity of the CD8(+) response at approximately 6 months postinfection on the viral set point at 12 months in a cohort of HIV-infected individuals. High frequencies of Gag and Nef responses endowed with four functions were the best predictors of a low viral set point

Convergence of TCR and cytokine signaling leads to FOXO3a phosphorylation and drives the survival of CD4+ central memory T cells

The molecular events involved in the establishment and maintenance of CD4+ central memory and effector memory T cells (TCM and TEM, respectively) are poorly understood. In this study, we demonstrate that ex vivo isolated TCM are more resistant to both spontaneous and Fas-induced apoptosis than TEM and have an increased capacity to proliferate and persist in vitro. Using global gene expression profiling, single cell proteomics, and functional assays, we show that the survival of CD4+ TCM depends, at least in part, on the activation and phosphorylation of signal transducer and activator of transcription 5a (STAT5a) and forkhead box O3a (FOXO3a). TCM showed a significant increase in the levels of phosphorylation of STAT5a compared with TEM in response to both IL-2 (P < 0.04) and IL-7 (P < 0.002); the latter is well known for its capacity to enhance T cell survival. Moreover, ex vivo TCM express higher levels of the transcriptionally inactive phosphorylated forms of FOXO3a and concomitantly lower levels of the proapoptotic FOXO3a target, Bim. Experiments aimed at blocking FOXO3a phosphorylation confirmed the role of this phosphoprotein in protecting TCM from apoptosis. Our results provide, for the first time in humans, an insight into molecular mechanisms that could be responsible for the longevity and persistence of CD4+ TCM

Restoration of CD4+ responses to copathogens in HIV-infected individuals on antiretroviral therapy is dependent on T cell memory phenotype.

CAPRISA, 2015.Abstract available in pdf