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

Quantification of microsized fluorescent particles phagocytosis to a better knowledge of toxicity mechanisms

International audienceBackground: The use of micro- or nanometric particles is in full expansion for the development of new technologies. These particles may exhibit variable toxicity levels depending on their physicochemical characteristics. We focused our attention on macrophages (MA), the main target cells of the respiratory system responsible for the phagocytosis of the particles. The quantification of the amount of phagocytosed particles seems to be a major element for a better knowledge of toxicity mechanisms. The aim of this study was to develop a quantitative evaluation of uptake using both flow cytometry (FCM) and confocal microscopy to distinguish entirely engulfed fluorescent microsized particles from those just adherent to the cell membrane and to compare these data to in vitro toxicity assessments. Methods: Fluorescent particles of variable and well-characterised sizes and surface coatings were incubated with MA (RAW 264.7 cell line). Analyses were performed using confocal microscopy and FCM. The biological toxicity of the particles was evaluated [lactate dehydrogenase (LDH) release, tumor necrosis factor (TNF)-α, and reactive oxygen species (ROS) production]. Results and conclusion: Confocal imaging allowed visualization of entirely engulfed beads. The amount of phagocytic cells was greater for carboxylate 2-µm beads (49±11%) than for amine 1-µm beads (18±5%). Similarly, side scatter geometric means, reflecting cellular complexity, were 446±7 and 139±12, respectively. These results confirm that the phagocytosis level highly depends on the size and surface chemical groups of the particles. Only TNF-α and global ROS production varied significantly after 24-h incubation. There was no effect on LDH and H2O2 production

Modèle de quantification de la phagocytose à partir de particules fluorescentes

International audienceLes particules industrielles fines et ultrafines peuvent être inhalées et atteindre les alvéoles pulmonaires où elles interagiront préférentiellement avec des macrophages alvéolaires dotés d'une activité de phagocytose qui leur permet d'internaliser les particules étrangères afin de les éliminer

Standardized Whole-Blood Transcriptional Profiling Enables the Deconvolution of Complex Induced Immune Responses

SummarySystems approaches for the study of immune signaling pathways have been traditionally based on purified cells or cultured lines. However, in vivo responses involve the coordinated action of multiple cell types, which interact to establish an inflammatory microenvironment. We employed standardized whole-blood stimulation systems to test the hypothesis that responses to Toll-like receptor ligands or whole microbes can be defined by the transcriptional signatures of key cytokines. We found 44 genes, identified using Support Vector Machine learning, that captured the diversity of complex innate immune responses with improved segregation between distinct stimuli. Furthermore, we used donor variability to identify shared inter-cellular pathways and trace cytokine loops involved in gene expression. This provides strategies for dimension reduction of large datasets and deconvolution of innate immune responses applicable for characterizing immunomodulatory molecules. Moreover, we provide an interactive R-Shiny application with healthy donor reference values for induced inflammatory genes

Are the GFRUP's recommendations for withholding or withdrawing treatments in critically ill children applicable? Results of a two-year survey.

International audienceOBJECTIVE: To evaluate feasibility of the guidelines of the Groupe Francophone de R?imation et Urgence P?atriques (French-speaking group of paediatric intensive and emergency care; GFRUP) for limitation of treatments in the paediatric intensive care unit (PICU). DESIGN: A 2-year prospective survey. SETTING: A 12-bed PICU at the H?al Jeanne de Flandre, Lille, France. PATIENTS: Were included when limitation of treatments was expected. RESULTS: Of 967 children admitted, 55 were included with a 2-day median delay. They were younger than others (24 v 60 months), had a higher paediatric risk of mortality (PRISM) score (14 v 4), and a higher paediatric overall performance category (POPC) score at admission (2 v 1); all p<0.002. 34 (50% of total deaths) children died. A limitation decision was made without meeting for 7 children who died: 6 received do-not-resuscitate orders (DNROs) and 1 received withholding decision. Decision-making meetings were organised for 31 children, and the following decisions were made: 12 DNROs (6 deaths and 6 survivals), 4 withholding (1 death and 3 survivals), with 14 withdrawing (14 deaths) and 1 continuing treatment (survival). After limitation, 21 (31% of total deaths) children died and 10 survived (POPC score 4). 13 procedures were interrupted because of death and 11 because of clinical improvement (POPC score 4). Parents' opinions were obtained after 4 family conferences (for a total of 110 min), 3 days after inclusion. The first meeting was planned for 6 days after inclusion and held on the 7th day after inclusion; 80% of parents were immediately informed of the decision, which was implemented after half a day. CONCLUSIONS: GFRUPs procedure was applicable in most cases. The main difficulties were anticipating the correct date for the meeting and involving nurses in the procedure. Children for whom the procedure was interrupted because of clinical improvement and who survived in poor condition without a formal decision pointed out the need for medical criteria for questioning, which should systematically lead to a formal decision-making process

In situ heavy ion irradiation in ferritic/martensitic ODS steels at 500°C

International audienceThree different ferritic/martensitic oxide dispersion-strengthened steels (9Cr, 12Cr and 16Cr) were irradiated using dual beam ions (Kr+ and He+), with in situ transmission electron microscope observation. Helium was found to be essential in cavity nucleation and growth. The 9Cr alloy presented the lowest formation of cavities among the three irradiated steels, which is attributed to the presence of significant amounts of martensite. During the irradiation of 16Cr alloy with dual beam ions, cavity segregation to grain boundaries was observed at a relatively low dose ∼1 dpa, whereas it occurred at ∼2 dpa in 9Cr and 12Cr alloys. Nano-sized Y–Ti–O particles were stable during the entire irradiation to ∼8 dpa. The lattice defects were characterised and mainly consist of interstitial loops

Development of innovative methods for phagocytosis quantification of microsized particles.

Inhaled particles exhibit variable toxicity levels which mainly depends on their physicochemical characteristics (size, morphology, surface chemical...). The relationship between the potential toxicity and the amount of phagocytosed particles is rarely investigated. The aim of this study was to develop a quantitative evaluation of phagocytosis using both direct and indirect methods in order to distinguish entirely engulfed microsized particles from those which are adherent to the cell surface. Fluorescent beads with variable and well-characterized sizes and surface coatings were incubated with RAW 264.7 macrophages at different concentrations and incubation times. The direct quantification of phagocytosis was based 1) on the measure of SSC parameter and fluorescence of intracellular beads 2) on the measure of pHrodo fluorescence, a specific sensor of acidic conditions. Indirect quantification of phagocytosed beads was based on cytoskeleton modifications evaluated by fluorescent phalloidin labeling. For all experiences, analysis were performed using both flow cytometry and confocal microscopy. The phagocytic cell percentage was greater for carboxylate 2 µm beads (60%) as compared to amine 1 µm beads (20%). Similarly SSC values were respectively 441 versus 131 for the two types of beads. Confocal imaging based on phalloidin labeling allowed visualization of entirely engulfed beads. Moreover the percentage of phagocytic cells increased with the beads/cell ratio and incubation duration. These results confirm that the phagocytosis level highly depends on physicochemical characteristics of particles