Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Toll-like receptor 3 expressing tumor parenchyma and infiltrating natural killer cells in hepatocellular carcinoma patients

Background Hepatocellular carcinoma (HCC) is a highly aggressive cancer that is linked to chronically dysregulated liver inflammation. However, appropriate immune responses can control HCC progression. Here we investigated the role and underlying mechanism of toll-like receptor 3 (TLR3) in HCC. Methods HCC cell death, and natural killer (NK) cell activation and cytotoxicity were assessed in vitro after treatment with the TLR3 ligand poly(I:C). The effect of TLR3 on the tumor parenchyma and infiltrating immune cells was investigated in a spontaneous liver tumor mouse model and a transplanted tumor mouse model (n = 3-9 mice per group). Immunohistochemistry and quantitative polymerase chain reaction were used to analyze tumor samples from 172 HCC patients. Paired t-tests and analysis of variance tests were used to calculate P-values. The relationship between TLR3 expression and survival was determined by the Kaplan-Meier univariate survival analysis and a log-rank test. All statistical tests were two-sided. Results TLR3 activation increased cell death in the TLR3(+) SNU182 HCC cell line (30.5% vs 8.5%, P = .03) and promoted NK-cell activation (32.6% vs 19.4%, P < .001) and cytotoxicity (relative fourfold increase, P = .03) in vitro. In vivo, poly(I:C) treatment increased intratumoral chemokine expression, NK-cell activation and tumor infiltration, and proliferation of tumor-infiltrating T and NK cells. Proliferation of tumor parenchyma cells was decreased. Also, expression of chemokines or treatment with poly(I:C) decreased tumor growth. TLR3 expression in patient samples correlated with NK-cell activation, NK- and T-cell tumor infiltration, and inversely correlated with tumor parenchyma cell viability. TLR3 expression was also associated with longer survival in HCC patients (hazard ratio of survival = 2.1, 95% confidence interval = 1.3 to 3.4, P = .002). Conclusions TLR3 is an important modulator of HCC progression and is a potential target for novel immunotherapy

Immunocompromised patients with acute respiratory distress syndrome: Secondary analysis of the LUNG SAFE database

Background: The aim of this study was to describe data on epidemiology, ventilatory management, and outcome of acute respiratory distress syndrome (ARDS) in immunocompromised patients. Methods: We performed a post hoc analysis on the cohort of immunocompromised patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study. The LUNG SAFE study was an international, prospective study including hypoxemic patients in 459 ICUs from 50 countries across 5 continents. Results: Of 2813 patients with ARDS, 584 (20.8%) were immunocompromised, 38.9% of whom had an unspecified cause. Pneumonia, nonpulmonary sepsis, and noncardiogenic shock were their most common risk factors for ARDS. Hospital mortality was higher in immunocompromised than in immunocompetent patients (52.4% vs 36.2%; p &lt; 0.0001), despite similar severity of ARDS. Decisions regarding limiting life-sustaining measures were significantly more frequent in immunocompromised patients (27.1% vs 18.6%; p &lt; 0.0001). Use of noninvasive ventilation (NIV) as first-line treatment was higher in immunocompromised patients (20.9% vs 15.9%; p = 0.0048), and immunodeficiency remained independently associated with the use of NIV after adjustment for confounders. Forty-eight percent of the patients treated with NIV were intubated, and their mortality was not different from that of the patients invasively ventilated ab initio. Conclusions: Immunosuppression is frequent in patients with ARDS, and infections are the main risk factors for ARDS in these immunocompromised patients. Their management differs from that of immunocompetent patients, particularly the greater use of NIV as first-line ventilation strategy. Compared with immunocompetent subjects, they have higher mortality regardless of ARDS severity as well as a higher frequency of limitation of life-sustaining measures. Nonetheless, nearly half of these patients survive to hospital discharge. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013

Widespread diversity deficits of coral reef sharks and rays

A global survey of coral reefs reveals that overfishing is driving resident shark species toward extinction, causing diversity deficits in reef elasmobranch (shark and ray) assemblages. Our species-level analysis revealed global declines of 60 to 73% for five common resident reef shark species and that individual shark species were not detected at 34 to 47% of surveyed reefs. As reefs become more shark-depleted, rays begin to dominate assemblages. Shark-dominated assemblages persist in wealthy nations with strong governance and in highly protected areas, whereas poverty, weak governance, and a lack of shark management are associated with depauperate assemblages mainly composed of rays. Without action to address these diversity deficits, loss of ecological function and ecosystem services will increasingly affect human communities

ILC Reference Design Report Volume 1 - Executive Summary

The International Linear Collider (ILC) is a 200-500 GeV center-of-mass high-luminosity linear electron-positron collider, based on 1.3 GHz superconducting radio-frequency (SCRF) accelerating cavities. The ILC has a total footprint of about 31 km and is designed for a peak luminosity of 2x10^34 cm^-2s^-1. This report is the Executive Summary (Volume I) of the four volume Reference Design Report. It gives an overview of the physics at the ILC, the accelerator design and value estimate, the detector concepts, and the next steps towards project realization.The International Linear Collider (ILC) is a 200-500 GeV center-of-mass high-luminosity linear electron-positron collider, based on 1.3 GHz superconducting radio-frequency (SCRF) accelerating cavities. The ILC has a total footprint of about 31 km and is designed for a peak luminosity of 2x10^34 cm^-2s^-1. This report is the Executive Summary (Volume I) of the four volume Reference Design Report. It gives an overview of the physics at the ILC, the accelerator design and value estimate, the detector concepts, and the next steps towards project realization

ILC Reference Design Report Volume 4 - Detectors

This report, Volume IV of the International Linear Collider Reference Design Report, describes the detectors which will record and measure the charged and neutral particles produced in the ILC's high energy e+e- collisions. The physics of the ILC, and the environment of the machine-detector interface, pose new challenges for detector design. Several conceptual designs for the detector promise the needed performance, and ongoing detector R&D is addressing the outstanding technological issues. Two such detectors, operating in push-pull mode, perfectly instrument the ILC interaction region, and access the full potential of ILC physics.This report, Volume IV of the International Linear Collider Reference Design Report, describes the detectors which will record and measure the charged and neutral particles produced in the ILC's high energy e+e- collisions. The physics of the ILC, and the environment of the machine-detector interface, pose new challenges for detector design. Several conceptual designs for the detector promise the needed performance, and ongoing detector R&D is addressing the outstanding technological issues. Two such detectors, operating in push-pull mode, perfectly instrument the ILC interaction region, and access the full potential of ILC physics