Noninvasive ventilation immediately after extubation improves weaning outcome after acute respiratory failure: a randomized controlled trial

Abstract\ud \ud \ud \ud Introduction\ud \ud Noninvasive ventilation (NIV), as a weaning-facilitating strategy in predominantly chronic obstructive pulmonary disease (COPD) mechanically ventilated patients, is associated with reduced ventilator-associated pneumonia, total duration of mechanical ventilation, length of intensive care unit (ICU) and hospital stay, and mortality. However, this benefit after planned extubation in patients with acute respiratory failure of various etiologies remains to be elucidated. The aim of this study was to determine the efficacy of NIV applied immediately after planned extubation in contrast to oxygen mask (OM) in patients with acute respiratory failure (ARF).\ud \ud \ud \ud Methods\ud \ud A randomized, prospective, controlled, unblinded clinical study in a single center of a 24-bed adult general ICU in a university hospital was carried out in a 12-month period. Included patients met extubation criteria with at least 72 hours of mechanical ventilation due to acute respiratory failure, after following the ICU weaning protocol. Patients were randomized immediately before elective extubation, being randomly allocated to one of the study groups: NIV or OM. We compared both groups regarding gas exchange 15 minutes, 2 hours, and 24 hours after extubation, reintubation rate after 48 hours, duration of mechanical ventilation, ICU length of stay, and hospital mortality.\ud \ud \ud \ud Results\ud \ud Forty patients were randomized to receive NIV (20 patients) or OM (20 patients) after the following extubation criteria were met: pressure support (PSV) of 7 cm H2O, positive end-expiratory pressure (PEEP) of 5 cm H2O, oxygen inspiratory fraction (FiO2) ≤ 40%, arterial oxygen saturation (SaO2) ≥ 90%, and ratio of respiratory rate and tidal volume in liters (f/TV) < 105. Comparing the 20 patients (NIV) with the 18 patients (OM) that finished the study 48 hours after extubation, the rate of reintubation in NIV group was 5% and 39% in OM group (P = 0.016). Relative risk for reintubation was 0.13 (CI = 0.017 to 0.946). Absolute risk reduction for reintubation showed a decrease of 33.9%, and analysis of the number needed to treat was three. No difference was found in the length of ICU stay (P = 0.681). Hospital mortality was zero in NIV group and 22.2% in OM group (P = 0.041).\ud \ud \ud \ud Conclusions\ud \ud In this study population, NIV prevented 48 hours reintubation if applied immediately after elective extubation in patients with more than 3 days of ARF when compared with the OM group.\ud \ud \ud \ud Trial Registration number\ud \ud ISRCTN: 41524441.We thank all the physicians, physiotherapists, and nurses that took care of the patients throughout the protocol, the statisticians for the statistical analyses, and Adriana Pardini for revision of the language. This study was supported by Division of Critical Care, Hospital de Base de São José do Rio Preto, Rio Preto, SP, Brazil, and Division of Pulmonary and Critical Care Hospital das Clínicas of São Paulo Medical School, University of São Paulo, São Paulo, Brazil

Brucella beta 1,2 cyclic glucan is an activator of human and mouse dendritic cells

Bacterial cyclic glucans are glucose polymers that concentrate within the periplasm of alpha-proteobacteria. These molecules are necessary to maintain the homeostasis of the cell envelope by contributing to the osmolarity of Gram negative bacteria. Here, we demonstrate that Brucella beta 1,2 cyclic glucans are potent activators of human and mouse dendritic cells. Dendritic cells activation by Brucella beta 1,2 cyclic glucans requires TLR4, MyD88 and TRIF, but not CD14. The Brucella cyclic glucans showed neither toxicity nor immunogenicity compared to LPS and triggered antigen-specific CD8(+) T cell responses in vivo. These cyclic glucans also enhanced antigen-specific CD4(+) and CD8(+) T cell responses including cross-presentation by different human DC subsets. Brucella beta 1,2 cyclic glucans increased the memory CD4(+) T cell responses of blood mononuclear cells exposed to recombinant fusion proteins composed of anti-CD40 antibody and antigens from both hepatitis C virus and Mycobacterium tuberculosis. Thus cyclic glucans represent a new class of adjuvants, which might contribute to the development of effective antimicrobial therapies

Guidelines for studying diverse types of compound weather and climate events

Compound weather and climate events are combinations of climate drivers and/or hazards that contribute to societal or environmental risk. Studying compound events often requires a multidisciplinary approach combining domain knowledge of the underlying processes with, for example, statistical methods and climate model outputs. Recently, to aid the development of research on compound events, four compound event types were introduced, namely (1) preconditioned, (2) multivariate, (3) temporally compounding, and (4) spatially compounding events. However, guidelines on how to study these types of events are still lacking. Here, we consider four case studies, each associated with a specific event type and a research question, to illustrate how the key elements of compound events (e.g., analytical tools and relevant physical effects) can be identified. These case studies show that (1) impacts on crops from hot and dry summers can be exacerbated by preconditioning effects of dry and bright springs. (2) Assessing compound coastal flooding in Perth (Australia) requires considering the dynamics of a non-stationary multivariate process. For instance, future mean sea-level rise will lead to the emergence of concurrent coastal and fluvial extremes, enhancing compound flooding risk. (3) In Portugal, deep-landslides are often caused by temporal clusters of moderate precipitation events. Finally, (4) crop yield failures in France and Germany are strongly correlated, threatening European food security through spatially compounding effects. These analyses allow for identifying general recommendations for studying compound events. Overall, our insights can serve as a blueprint for compound event analysis across disciplines and sectors