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

Acute hemorrhagic leukoencephalopathy: pathological features and cerebrospinal fluid cytokine profiles

Acute hemorrhagic leukoencephalopathy is a rare encephalopathy of unknown etiology, causing fulminant, hemorrhagic central nervous system demyelination with high mortality. It is unclear whether acute hemorrhagic leukoencephalopathy is an entirely distinct entity from acute disseminated encephalomyelitis.We report two patients with rapidly progressive neurological illness resulting in raised intracranial pressure and coma, with biopsy-proven acute hemorrhagic leukoencephalopathy (perivascular hemorrhages and demyelination, predominantly neutrophil infiltrates).Acute cerebrospinal fluid showed pronounced T cell-associated cytokine elevation (interleukins 6, 8, and 17A) and CCL2 or CCL3, higher than in patients with acute disseminated encephalomyelitis, but no B cell-associated cytokine elevation.Improved understanding of the immune process may provide rationale for use of anticytokine biologic agents

CANDELS: The Contribution of the Observed Galaxy Population to Cosmic Reionization

We present measurements of the specific ultraviolet luminosity density from a sample of 483 galaxies at 6 . z . 8. These galaxies were selected from new deep near-infrared Hubble Space Telescope imaging from the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey, Hubble UltraDeep Field 2009 and WFC3 Early Release Science programs. In contrast to the majority of previous analyses, which assume that the distribution of galaxy ultraviolet (UV) luminosities follows a Schechter distribution, and that the distribution continues to luminosities far below our observable limit, we investigate the contribution to reionization from galaxies which we can observe, free from these assumptions. Due to our larger survey volume, wider wavelength coverage, and updated assumptions about the clumping of gas in the intergalactic medium (IGM), we find that the observable population of galaxies can sustain a fully reionized IGMat z = 6, if the average ionizing photon escape fraction (fesc) is ∼30%. A number of previous studies have measured UV luminosity densities at these redshifts that vary by a factor of 5, with many concluding that galaxies could not complete reionization by z = 6 unless a large population of galaxies fainter than the detection limit were invoked, or extremely high values of fesc were present. The observed UV luminosity density from our observed galaxy samples at z = 7 and 8 is not sufficient to maintain a fully reionized IGM unless fesc \u3e 50%. We examine the contribution from galaxies in different luminosity ranges, and find that the sub-L∗ galaxies we detect are stronger contributors to the ionizing photon budget than the L \u3e L∗ population, unless fesc is luminosity dependent. Combining our observationswith constraints on the emission rate of ionizing photons from Lyα forest observations at z = 6, we find that we can constrain fesc \u3c 34% (2σ) if the observed galaxies are the only contributors to reionization, or \u3c 13% (2σ) if the luminosity function extends to a limiting magnitude of MUV = -13. These escape fractions are sufficient to complete reionization by z = 6. Current constraints on the high-redshift galaxy population imply that the volume ionized fraction of the IGM, while consistent with unity at z ≤ 6, appears to drop at redshifts not much higher than 7, consistent with a number of complementary reionization probes. If faint galaxies dominated the ionizing photon budget at z = 6–7, future extremely deep observations with the James Webb Space Telescope will probe deep enough to see them, providing an indirect constraint on the global ionizing photon escape fraction