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

Contains fulltext : 218568.pdf (publisher's version ) (Open Access)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, NCT02010073

Clinical characteristics and outcomes of critically ill patients with COVID-19 admitted to an intensive care unit in London: A prospective observational cohort study

Background Cohorts of severely ill patients with COVID-19 have been described in several countries around the globe, but to date there have been few published reports from the United Kingdom (UK). Understanding the characteristics of the affected population admitted to intensive care units (ICUs) in the UK is crucial to inform clinical decision making, research and planning for future waves of infection. Methods We conducted a prospective observational cohort study of all patients with COVID-19 admitted to a large UK ICU from March to May 2020 with follow-up to June 2020. Data were collected from health records using a standardised template. We used multivariable logistic regression to analyse the factors associated with ICU survival. Results Of the 156 patients included, 112 (72%) were male, 89 (57%) were overweight or obese, 68 (44%) were from ethnic minorities, and 89 (57%) were aged over 60 years of age. 136 (87%) received mechanical ventilation, 77 (57% of those intubated) were placed in the prone position and 95 (70% of those intubated) received neuromuscular blockade. 154 (99%) patients required cardiovascular support and 44 (28%) required renal replacement therapy. Of the 130 patients with completed ICU episodes, 38 (29%) died and 92 (71%) were discharged alive from ICU. In multivariable models, age (OR 1.13 [95% CI 1.07–1.21]), obesity (OR 3.06 [95% CI 1.16–8.74]), lowest P/F ratio on the first day of admission (OR 0.82 [95% CI 0.67–0.98]) and PaCO2 (OR 1.52 [95% CI 1.01–2.39]) were independently associated with ICU death. Conclusions Age, obesity and severity of respiratory failure were key determinants of survival in this cohort. Multiorgan failure was prevalent. These findings are important for guiding future research and should be taken into consideration during future healthcare planning in the UK. </jats:sec

Sex-specific microhabitat use is associated with sex-biased thermal physiology in <i>Anolis</i> lizards

If fitness optima for a given trait differ between males and females in a population, sexual dimorphism may evolve. Sex-biased trait variation may affect patterns of habitat use, and if the microhabitats used by each sex have dissimilar microclimates, this can drive sex-specific selection on thermal physiology. Nevertheless, tests of differences between the sexes in thermal physiology are uncommon, and studies linking these differences to microhabitat use or behavior are even rarer. We examined microhabitat use and thermal physiology in two ectothermic congeners that are ecologically similar but differ in their degree of sexual size dimorphism. Brown anoles (Anolis sagrei) exhibit male-biased sexual size dimorphism and live in thermally heterogeneous habitats, whereas slender anoles (Anolis apletophallus) are sexually monomorphic in body size and live in thermally homogeneous habitats. We hypothesized that differences in habitat use between the sexes would drive sexual divergence in thermal physiology in brown anoles, but not slender anoles, because male and female brown anoles may be exposed to divergent microclimates. We found that male and female brown anoles, but not slender anoles, used perches with different thermal characteristics and were sexually dimorphic in thermal tolerance traits. However, field-active body temperatures and behavior in a laboratory thermal arena did not differ between females and males in either species. Our results suggest that sexual dimorphism in thermal physiology can arise from phenotypic plasticity or sex-specific selection on traits that are linked to thermal tolerance, rather than from direct effects of thermal environments experienced by males and females.</jats:p

Transcriptomic profiling and machine learning uncover gene signatures of psoriasis endotypes and disease severity

BACKGROUND: Despite increased understanding of psoriasis pathogenesis, molecular classification of clinical phenotypes and disease severity is poorly defined. Knowledge gaps include whether molecular endotypes of psoriasis underlie distinct clinical phenotypes and the positive and negative molecular regulators of disease severity across tissue compartments.METHODS: We performed comprehensive RNA sequencing of skin and blood (n = 718) from prospectively-recruited, deeply-phenotyped discovery and replication cohorts of 146 subjects with moderate-to-severe chronic plaque psoriasis initiating TNF-inhibitor (adalimumab) or IL-12/23-inhibitor (ustekinumab) therapy.RESULTS: Here we show, using two complementary dimensionality reduction methods, that co-expressed gene modules and factors within skin and blood are significantly associated with psoriasis phenotypes and disease severity. We identify a 14-gene signature negatively associated with BMI in nonlesional skin and with disease severity in lesional skin. Genotype integration reveals that HLA-DQA1*01 and HLA-DRB1*15 genotypes are positively associated with baseline psoriasis severity. Using explainable machine learning models, we define two disease severity-associated gene modules in lesional skin - one positive, one negatively-associated - and a 9-gene signature in lesional skin predictive of disease severity. Disease severity signatures in blood are only seen following adalimumab exposure, suggesting greater systemic impact of adalimumab compared to ustekinumab, in line with its side effect profile. In contrast, a gene signature in blood linked to HLA-C*06:02 status is independent of disease severity or drug.CONCLUSIONS: These findings delineate gene-environmental and genetic effects on the psoriasis transcriptome linked to disease severity.</p

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