Mortality In Acute Respiratory Distress Syndrome Research Articles

The Association Between Etiologies and Mortality in Acute Respiratory Distress Syndrome: A Multicenter Observational Cohort Study.

Background: Lung-protective ventilation (LPV) strategies have been beneficial in patients with acute respiratory distress syndrome (ARDS). As a vital part of LPV, positive end-expiratory pressure (PEEP) can enhance oxygenation. However, randomized clinical trials of different PEEP strategies seem to show no advantages in clinical outcomes in patients with ARDS. A potential reason is that diverse etiologies and phenotypes in patients with ARDS may account for different PEEP responses, resulting in variations in mortality. We consider hospital mortality to be associated with a more specific classification of ARDS, such as sepsis induced or not, and pulmonary or extrapulmonary one. Our study aimed to compare clinical outcomes in various patients with ARDS by etiologies using the China Critical Care Sepsis Trial (CCCST) database. This was a retrospective analysis of a prospective cohort of 2,138 patients with ARDS in the CCCST database. According to ARDS induced by sepsis or not and medical history, patients were stratified into different four groups. Differences among groups were assessed in hospital mortality, ventilation-free days, and other clinical features.Results: A total of 2,138 patients with ARDS were identified in the database, including 647 patients with sepsis-induced pulmonary ARDS (30.3%), 396 patients with sepsis-induced extrapulmonary ARDS (18.5%), 536 patients with non-sepsis pulmonary ARDS (25.1%), and 559 patients with non-sepsis extrapulmonary ARDS (26.1%). The pulmonary ARDS group had higher mortality compared with the extrapulmonary group (45.9 vs. 23.0%, p < 0.01), longer intensive care unit (ICU) and hospital stays (9 vs. 6 days, p < 0.01, 20 vs. 18 days, p = 0.01, respectively), and fewer ventilation-free days (5 vs. 9 days) in the presence of sepsis. However, the mortality in ARDS without sepsis was inverted compared with extrapulmonary ARDS (pulmonary 23.5% vs. extrapulmonary 29.2%, p = 0.04). After adjusting for the Acute Physiology and Chronic Health Evaluation II and sequential organ failure assessment scores and other clinical features, the sepsis-induced pulmonary condition was still a risk factor for death in patients with ARDS (hazard ratio 0.66, 95% CI, 0.54–0.82, p < 0.01) compared with sepsis-induced extrapulmonary ARDS and other subphenotypes.Conclusions: In the presence of sepsis, hospital mortality in pulmonary ARDS is higher compared with extrapulmonary ARDS; however, mortality is inverted in ARDS without sepsis. Sepsis-induced pulmonary ARDS should attract more attention from ICU physicians and be cautiously treated.Trial registration: ChiCTR-ECH-13003934. Registered August 3, 2013, http://www.chictr.org.cn.

Research progress of spontaneous respiration in mechanical ventilation of acute respiratory distress syndrome

Mechanical ventilation is an important supportive treatment for acute respiratory distress syndrome (ARDS). However, improper mechanical ventilation can cause a "second hit" to the lung, that is, ventilator-induced lung injury (VILI), characterized by translocation of pulmonary inflammatory mediators into the bloodstream, aggravating systemic inflammatory response syndrome, and multiple organ failure. Although the current protective mechanical ventilation strategy plays an important role in supporting treatment, the mortality of ARDS with mechanical ventilation is still very high. Therefore, to explore the strategy of pulmonary protective ventilation has always been the key orientation of ARDS and has important clinical significance. This article reviews the application, advantages and disadvantages of assisted and non-assisted spontaneous respiration in ARDS patients undergoing mechanical ventilation, in order to provide a reference for research and development of new strategies for ARDS protective ventilation.

Association between lung compliance phenotypes and mortality in COVID-19 patients with acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) in COVID-19 is associated with a high mortality rate, though outcomes of the different lung compliance phenotypes are unclear. We aimed to measure lung compliance and examine other factors associated with mortality in COVID-19 patients with ARDS. Adult patients with COVID-19 ARDS who required invasive mechanical ventilation at 8 hospitals in Singapore were prospectively enrolled. Factors associated with both mortality and differences between high (<40mL/cm H2O) and low (<40mL/cm H2O) compliance were analysed. A total of 102 patients with COVID-19 who required invasive mechanical ventilation were analysed; 15 (14.7%) did not survive. Non-survivors were older (median 70 years, interquartile range [IQR] 67-75 versus median 61 years, IQR 52-66; P<0.01), and required a longer duration of ventilation (26 days, IQR 12-27 vs 8 days, IQR 5-15; P<0.01) and intensive care unit support (26 days, IQR 11-30 vs 11.5 days, IQR 7-17.3; P=0.01), with a higher incidence of acute kidney injury (15 patients [100%] vs 40 patients [46%]; P<0.01). There were 67 patients who had lung compliance data; 24 (35.8%) were classified as having high compliance and 43 (64.2%) as having low compliance. Mortality was higher in patients with high compliance (33.3% vs 11.6%; P=0.03), and was associated with a drop in compliance at day 7 (-9.3mL/cm H2O (IQR -4.5 to -15.4) vs 0.2mL/cm H2O (4.7 to -5.2) P=0.04). COVID-19 ARDS patients with higher compliance on the day of intubation and a longitudinal decrease over time had a higher risk of death.

Lesson learned by COVID-19 outbreak: multilevel triage strategies in patients admitted to the emergency room in southern Italy

After identifying a novel disease inducing a severe acute respiratory syndrome-related to coronavirus 2 (SARS-CoV-2) for epidemic pneumonia in China, the diffusion of infection is ongoing around the world, and Italy has been the second country in which an epidemic has been demonstrated. Clinical features of this infection may be summarized in viral pneumonia that SARS or acute respiratory distress syndrome (ARDS) may complicate. For this reason, this epidemic has been considerably more aggressive than the previous epidemic of SARS and Middle-East respiratory syndrome. Coronavirus disease 2019 (COVID-19) showed an easy diffusion from human to human and also showed to be more contagious than other viruses. So human contact should be avoided at the emergency room and for inpatients too. The Triage should be adapted to these new features in order to speed up procedures for the care of infected patients at high risk of morbidity and mortality for SARS and ARDS and for traditional access to the emergency room. Based on our experiences, this flow chart has been designed with a multi-level triage in which patients have been divided for admission to the emergency room into patients with fever/respiratory symptoms and patients without fever\respiratory symptoms, to improve medical performances while treating COVID-19. This organized, multilevel triage permitted a good selection of patients admitted to the emergency room during the epidemic of COVID-19 in Southern Italy.

Identification of early and intermediate biomarkers for ARDS mortality by multi-omic approaches

The lack of successful clinical trials in acute respiratory distress syndrome (ARDS) has highlighted the unmet need for biomarkers predicting ARDS mortality and for novel therapeutics to reduce ARDS mortality. We utilized a systems biology multi-“omics” approach to identify predictive biomarkers for ARDS mortality. Integrating analyses were designed to differentiate ARDS non-survivors and survivors (568 subjects, 27% overall 28-day mortality) using datasets derived from multiple ‘omics’ studies in a multi-institution ARDS cohort (54% European descent, 40% African descent). ‘Omics’ data was available for each subject and included genome-wide association studies (GWAS, n = 297), RNA sequencing (n = 93), DNA methylation data (n = 61), and selective proteomic network analysis (n = 240). Integration of available “omic” data identified a 9-gene set (TNPO1, NUP214, HDAC1, HNRNPA1, GATAD2A, FOSB, DDX17, PHF20, CREBBP) that differentiated ARDS survivors/non-survivors, results that were validated utilizing a longitudinal transcription dataset. Pathway analysis identified TP53-, HDAC1-, TGF-β-, and IL-6-signaling pathways to be associated with ARDS mortality. Predictive biomarker discovery identified transcription levels of the 9-gene set (AUC-0.83) and Day 7 angiopoietin 2 protein levels as potential candidate predictors of ARDS mortality (AUC-0.70). These results underscore the value of utilizing integrated “multi-omics” approaches in underpowered datasets from racially diverse ARDS subjects.

Bedside estimates of dead space using end-tidal CO2 are independently associated with mortality in ARDS

PurposeIn acute respiratory distress syndrome (ARDS), dead space fraction has been independently associated with mortality. We hypothesized that early measurement of the difference between arterial and end-tidal CO2 (arterial-ET difference), a surrogate for dead space fraction, would predict mortality in mechanically ventilated patients with ARDS.MethodsWe performed two separate exploratory analyses. We first used publicly available databases from the ALTA, EDEN, and OMEGA ARDS Network trials (N = 124) as a derivation cohort to test our hypothesis. We then performed a separate retrospective analysis of patients with ARDS using University of Chicago patients (N = 302) as a validation cohort.ResultsThe ARDS Network derivation cohort demonstrated arterial-ET difference, vasopressor requirement, age, and APACHE III to be associated with mortality by univariable analysis. By multivariable analysis, only the arterial-ET difference remained significant (P = 0.047). In a separate analysis, the modified Enghoff equation ((PaCO2–PETCO2)/PaCO2) was used in place of the arterial-ET difference and did not alter the results. The University of Chicago cohort found arterial-ET difference, age, ventilator mode, vasopressor requirement, and APACHE II to be associated with mortality in a univariate analysis. By multivariable analysis, the arterial-ET difference continued to be predictive of mortality (P = 0.031). In the validation cohort, substitution of the arterial-ET difference for the modified Enghoff equation showed similar results.ConclusionArterial to end-tidal CO2 (ETCO2) difference is an independent predictor of mortality in patients with ARDS.

P/FP ratio: incorporation of PEEP into the PaO2/FiO2 ratio for prognostication and classification of acute respiratory distress syndrome

BackgroundThe current Berlin definition of acute respiratory distress syndrome (ARDS) uses the PaO2/FiO2 (P/F) ratio to classify severity. However, for the same P/F ratio, a patient on a higher positive end-expiratory pressure (PEEP) may have more severe lung injury than one on a lower PEEP.ObjectivesWe designed a new formula, the P/FP ratio, incorporating PEEP into the P/F ratio and multiplying with a correction factor of 10 [(PaO2*10)/(FiO2*PEEP)], to evaluate if it better predicts hospital mortality compared to the P/F ratio post-intubation and to assess the resultant changes in severity classification of ARDS.MethodsWe categorized patients from a dataset of seven ARDS network trials using the thresholds of ≤ 100 (severe), 101–200 (moderate), and 201–300 (mild) for both P/F (mmHg) and P/FP (mmHg/cmH2O) ratios and evaluated hospital mortality using areas under the receiver operating characteristic curves (AUC).ResultsOut of 3,442 patients, 1,057 (30.7%) died. The AUC for mortality was higher for the P/FP ratio than the P/F ratio for PEEP levels > 5 cmH2O: 0.710 (95% CI 0.691–0.730) versus 0.659 (95% CI 0.637–0.681), P < 0.001. Improved AUC was seen with increasing PEEP levels; for PEEP ≥ 18 cmH2O: 0.963 (95% CI 0.947–0.978) versus 0.828 (95% CI 0.765–0.891), P < 0.001. When the P/FP ratio was used instead of the P/F ratio, 12.5% and 15% of patients with moderate and mild ARDS, respectively, were moved to more severe categories, while 13.9% and 33.6% of patients with severe and moderate ARDS, respectively, were moved to milder categories. The median PEEP and FiO2 were 14 cmH2O and 0.70 for patients reclassified to severe ARDS, and 5 cmH2O and 0.40 for patients reclassified to mild ARDS.ConclusionsThe multifactorial P/FP ratio has a greater predictive validity for hospital mortality in ARDS than the P/F ratio. Changes in severity classification with the P/FP ratio reflect both true illness severity and the applied PEEP strategy.Trial registration: ClinialTrials.gov–NCT03946150.

Evaluation of the Immunomodulatory Effect of Mesenchymal Stem Cells on Sepsis-Induced Acute Respiratory Distress Syndrome: A Systematic Review

Introduction Sepsis and acute respiratory distress syndrome are the most important causes of death. Sepsis accounts for 20% of deaths worldwide and is one of the most common causes of acute respiratory distress syndrome (ARDS) with a prevalence of 23%. Sepsis-induced ARDS occurs among 10% of ICU patients. Today, mesenchymal stem cells (MSCs) therapy has been studied as a new treatment in the management of sepsis and as a promising treatment for ARDS. The aim of the present study was to systematically review studies on the use of MSCs for treatment of sepsis and ARDS.Results The results of the search strategy include eight studies: one meta-analysis, three systematic reviews, one clinical trial, one cohort study, one combined cohort study, and a double-blind clinical trial, and one case report with a sample size of animal models from two meta-analyzes, and one systematic review of 1266 and 1326 animal models and 1,085 patients in human studies. The results of most studies indicated a significant relationship between mesenchymal stem cell (MSCs) therapy and reduced mortality of sepsis syndrome and ARDS. The results of systematic studies also supported the efficacy and health of MSCs in the treatment of sepsis and ARDS. Patients tolerated high doses of intravenous or intrathecal therapy.Conclusion Multi-potency MSCs have an extraordinary ability to respond and manage the immune system and have been studied in animal and human studies as an immune regulatory tool in improving acute disease conditions such as sepsis and respiratory distress syndrome. Results of studies showed that these stem cells can be used clinically, but the need for more extensive studies, especially human studies in the future, is still recommended.

The Controversy About the Effects of Different Doses of Corticosteroid Treatment on Clinical Outcomes for Acute Respiratory Distress Syndrome Patients: An Observational Study.

Background: Corticosteroid usage in acute respiratory distress syndrome (ARDS) remains controversial. We aim to explore the correlation between the different doses of corticosteroid administration and the prognosis of ARDS.Methods: All patients were diagnosed with ARDS on initial hospital admission and received systemic corticosteroid treatment for ARDS. The main outcomes were the effects of corticosteroid treatment on clinical parameters and the mortality of ARDS patients. Secondary outcomes were factors associated with the mortality of ARDS patients.Results: 105 ARDS patients were included in this study. Corticosteroid treatment markedly decreased serum interleukin-18 (IL-18) level (424.0 ± 32.19 vs. 290.2 ± 17.14; p = 0.0003) and improved arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) (174.10 ± 65.28 vs. 255.42 ± 92.49; p < 0.0001). The acute physiology and chronic health evaluation (APACHE II) score (16.15 ± 4.41 vs. 14.88 ± 4.57, p = 0.042) decreased significantly on the seventh day after systemic corticosteroid treatment. Interestingly, the serum IL-18 decreased significantly (304.52 ± 286.00 vs. 85.85 ± 97.22, p < 0.0001), whereas the improvement of PaO2/FiO2 (24.78 ± 35.03 vs. 97.17 ± 44.82, p < 0.001) was inconspicuous after systemic corticosteroid treatment for non-survival patients, compared with survival patients. Furthermore, the receiver operating characteristic (ROC) model revealed, when equivalent methylprednisolone usage was 146.5 mg/d, it had the best sensitivity and specificity to predict the death of ARDS. Survival analysis by Kaplan–Meier curves presented the higher 45-day mortality in high-dose corticosteroid treatment group (logrank test p < 0.0001). Multivariate Cox regression analyses demonstrated that serum IL-18 level, APACHE II score, D-dimer, and high-dose corticosteroid treatment were associated with the death of ARDS.Conclusion: Appropriate dose of corticosteroids may be beneficial for ARDS patients through improving the oxygenation and moderately inhibiting inflammatory response. The benefits and risks should be carefully weighed when using high-dose corticosteroid for ARDS.Trial registration: This work was registered in ClinicalTrials.gov. Name of the registry: Corticosteroid Treatment for Acute Respiratory Distress Syndrome. Trial registration number: NCT02819453. URL of trial registry record: https://register.clinicaltrials.gov.

Risk factors in acute respiratory distress syndrome among children with cancer in Brazilian Amazon: An observational study

This study was undertaken to determine the incidence and potential risk factors associated with Acute Respiratory Distress Syndrome (ARDS) in pediatric oncologic patients undergoing invasive mechanical ventilation and the association between mortality risk factors and ARDS. Retrospective cohort study was conducted using data analysis of patients on admission to the PICU, that were submitted to invasive mechanical ventilation for over 24 hours. Shapiro-Wilk test and bivariate analysis within the group exposed to ARDS and the one not exposed, as well as Fisher's, Wilks G, chi-square tests, and Poisson logistic regression were applied, with significant variables p &lt;0.05 and 95% CI. From que 181 pediatric cancer patients included in the study, 69.06% had ARDS, with 48% leukemia, 58.4% pneumonia, 60.8% febrile neutropenia, and 76.1% were in the maintenance chemotherapy phase; pH expressed higher relation with ARDS outcome and mortality. These data are important as this is one of the first studies carried out on ARDS in the pediatric cancer population in the North of Brazil, but further research is needed to better correlate risk factors and acute respiratory distress syndrome on such population.

Research progress on release mechanism of high mobility group protein B1 in acute respiratory distress syndrome

High mobility group protein B1 (HMGB1), a highly conversed non-histone nucleoproteins with strong pro-inflammatory property, is one of the inflammatory mediator of the acute respiratory distress syndrome (ARDS). Numerous studies have confirmed that HMGB1 regulates ARDS by binding to receptor for advanced glycation end product (RAGE), Toll-like receptor (TLR) and etc. And it can significantly increase the mortality of ARDS. But the mechanism of HMGB1 release is still unclear. This study focuses on the HMGB1 release progress, which connected with Janus kinases/signal transducer and activator of transcription (JAK/STAT), nuclear factor-κB (NF-κB), Notch, inflammasome, tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), reactive oxygen species (ROS), peroxisome proliferator-activated receptor (PPAR) and other signaling or dependent pathways in ARDS.

Increased extravascular lung water index (EVLWI) reflects rapid non-cardiogenic oedema and mortality in COVID-19 associated ARDS

Nearly 5% of patients suffering from COVID-19 develop acute respiratory distress syndrome (ARDS). Extravascular lung water index (EVLWI) is a marker of pulmonary oedema which is associated with mortality in ARDS. In this study, we evaluate whether EVLWI is higher in patients with COVID-19 associated ARDS as compared to COVID-19 negative, ventilated patients with ARDS and whether EVLWI has the potential to monitor disease progression. EVLWI and cardiac function were monitored by transpulmonary thermodilution in 25 patients with COVID-19 ARDS subsequent to intubation and compared to a control group of 49 non-COVID-19 ARDS patients. At intubation, EVLWI was noticeably elevated and significantly higher in COVID-19 patients than in the control group (17 (11–38) vs. 11 (6–26) mL/kg; p < 0.001). High pulmonary vascular permeability index values (2.9 (1.0–5.2) versus 1.9 (1.0–5.2); p = 0.003) suggested a non-cardiogenic pulmonary oedema. By contrast, the cardiac parameters SVI, GEF and GEDVI were comparable in both cohorts. High EVLWI values were associated with viral persistence, prolonged intensive care treatment and in-hospital mortality (23.2 ± 6.7% vs. 30.3 ± 6.0%, p = 0.025). Also, EVLWI showed a significant between-subjects (r = − 0.60; p = 0.001) and within-subjects correlation (r = − 0.27; p = 0.028) to Horowitz index. Compared to non COVID-19 ARDS, COVID-19 results in markedly elevated EVLWI-values in patients with ARDS. High EVLWI reflects a non-cardiogenic pulmonary oedema in COVID-19 ARDS and could serve as parameter to monitor ARDS progression on ICU.

"Obesity Paradox" in Acute Respiratory Distress Syndrome Among Patients Undergoing Cardiac Surgery: A Retrospective Study.

BackgroundThe “obesity paradox” exists in many diseases. It is unclear whether it also exists in acute respiratory distress syndrome (ARDS). The purpose of our study was to clarify the relationship between obesity and the development of and hospital mortality from ARDS among patients who underwent cardiac surgery.Material/MethodsThis retrospective case-control study included 202 patients with ARDS and 808 matching patients without ARDS. We clarified the relationship between obesity and the development of ARDS after adjusting for confounding factors by multiple logistic regression analysis. A total of 202 ARDS patients were divided into survival and mortality groups. After all confounding factors were adjusted by multiple logistic regression analysis, we demonstrated the relationship between obesity and mortality from ARDS.ResultsWe found a significant association between body mass index (BMI) and the development of ARDS; the cutoff point of BMI was 24.78 kg/m2 by adjusting for confounding factors for the development of ARDS. When the BMI was lower than 24.78 kg/m2, the higher BMI was a protective factor (odds ratio [OR] 0.68, P=0.000, 95% confidence interval [CI] 0.55–0.84). When the BMI was higher than 24.78 kg/m2, the higher BMI was a risk factor (OR 1.07, P=0.050, 95% CI 1.00–1.14). However, obesity was found to be associated with decreased ARDS mortality by adjusting for confounding factors (OR 0.91, P=0.039, 95% CI 0.83–1.00).ConclusionsAn “obesity paradox” may exist in ARDS among patients with obesity who undergo cardiac surgery.

Predicting the mortality risk of acute respiratory distress syndrome: radial basis function artificial neural network model versus logistic regression model.

To predict the mortality of acute respiratory distress syndrome (ARDS) by using a radial basis function (RBF) artificial neural network (ANN) model. This study included 217 patients who were admitted between June 2013 and November 2019. The RBF ANN model and logistic regression (LR) model were based on twelve factors related to ARDS. Statistical indexes were used to determine the value of the prediction in the two models. The sensitivity, specificity and accuracy of the RBF ANN model to predict mortality were 83.6%, 88.5% and 82.5%, respectively. Significant differences were found between the RBF ANN and LR models (P < 0.05). When the RBF ANN model was used to identify ARDS, the area under the ROC curve was 0.854 ± 0.029. LDH, organ failure, SP-D and PaO2/FiO2 were the most important independent variables. The RBF ANN model was more likely to predict the mortality of ARDS than the LR model. In addition, it can extract informative risk factors for ARDS.

Mortality prediction for patients with acute respiratory distress syndrome based on machine learning: a population-based study.

BackgroundTraditional scoring systems for patients’ outcome prediction in intensive care units such as Oxygenation Saturation Index (OSI) and Oxygenation Index (OI) may not reliably predict the clinical prognosis of patients with acute respiratory distress syndrome (ARDS). Thus, none of them have been widely accepted for mortality prediction in ARDS. This study aimed to develop and validate a mortality prediction method for patients with ARDS based on machine learning using the Medical Information Mart for Intensive Care (MIMIC-III) and Telehealth Intensive Care Unit (eICU) Collaborative Research Database (eICU-CRD) databases.MethodsPatients with ARDS were selected based on the Berlin definition in MIMIC-III and eICU-CRD databases. The APPS score (using age, PaO2/FiO2, and plateau pressure), Simplified Acute Physiology Score II (SAPS-II), Sepsis-related Organ Failure Assessment (SOFA), OSI, and OI were calculated. With MIMIC-III data, a mortality prediction model was built based on the random forest (RF) algorithm, and the performance was compared to those of existing scoring systems based on logistic regression. The performance of the proposed RF method was also validated with the combined MIMIC-III and eICU-CRD data. The performance of mortality prediction was evaluated by using the area under the receiver operating characteristics curve (AUROC) and performing calibration using the Hosmer-Lemeshow test.ResultsWith the MIMIC-III dataset (308 patients, for comparisons with the existing scoring systems), the RF model predicted the in-hospital mortality, 30-day mortality, and 1-year mortality with an AUROC of 0.891, 0.883, and 0.892, respectively, which were significantly higher than those of the SAPS-II, APPS, OSI, and OI (all P<0.001). In the multi-source validation (the combined dataset of 2,235 patients in MIMIC-III and 331 patients in eICU-CRD), the RF model achieved an AUROC of 0.905 and 0.736 for predicting in-hospital mortality for the MIMIC-III and eICU-CRD datasets, respectively. The calibration plots suggested good fits for our RF model and these scoring systems for predicting mortality. The platelet count and lactate level were the strongest predictive variables for predicting in-hospital mortality.ConclusionsCompared to the existing scoring systems, machine learning significantly improved performance for predicting ARDS mortality. Validation with multi-source datasets showed a relatively robust generalisation ability of our prediction model.

The association between outcomes and body mass index in patients with acute respiratory distress syndrome.

Limited information exists about the relationship between body mass index (BMI) and the outcome of acute respiratory distress syndrome (ARDS). To evaluate the hospital mortality of patients with ARDS in relation to BMI. We conducted a retrospective, multicenter study including patients with ARDS. ARDS was defined according to the Berlin criteria. Body weight and height were obtained to calculate BMI. The primary outcome was in-hospital mortality. Secondary outcomes were intensive care unit (ICU) mortality, invasive positive pressure ventilation (IPPV) free days within 28 days and length of stays in the ICU and hospital. Among 523 patients, 28 (5%) were underweight (BMI <18.5 kg/m2 ), 299 (57%) were normal weight (BMI 18.5-24.9 kg/m2 ), 159 (30%) were overweight (BMI 25-29.9 kg/m2 ) and 37 (7%) were obese (BMI ≥30 kg/m2 ). Increasing BMI was associated with younger age (P=0.017), hypertension (P=0.003) and diabetes (P=0.02). Compared with normal weight, being overweight and obese resulted in lower mortality regardless of whether in the hospital (P=0.019) or ICU (P=0.044). However, after risk adjustment, only obesity was associated with lower hospital mortality (OR 0.393, 95% CI 0.169-0.914, P=0.030). With the increase of BMI, the in-hospital mortality and ICU mortality of ARDS dropped gradually (from 57.1% to 24.3%, P=0.021, and from 53.6% to 24.3%, P=0.035). Obesity is associated with lower mortality in patients with ARDS. With the increase of BMI, the mortality of ARDS drops gradually.

Clinical Course and Outcome of COVID-19 Acute Respiratory Distress Syndrome: Data From a National Repository.

Mortality attributable to coronavirus disease-19 (COVID-19) 2 infection occurs mainly through the development of viral pneumonia-induced acute respiratory distress syndrome (ARDS). The objective of the study is to delineate the clinical profile, predictors of disease progression, and 30-day mortality from ARDS using the Veterans Affairs Corporate Data Warehouse. Analysis of a historical cohort of 7,816 hospitalized patients with confirmed COVID-19 infection between January 1, 2020, and August 1, 2020. Main outcomes were progression to ARDS and 30-day mortality from ARDS, respectively. The cohort was comprised predominantly of men (94.5%) with a median age of 69 years (interquartile range [IQR] 60-74 years). 2,184 (28%) were admitted to the intensive care unit and 643 (29.4%) were diagnosed with ARDS. The median Charlson Index was 3 (IQR 1-5). Independent predictors of progression to ARDS were body mass index (BMI) ≥40 kg/m2, diabetes, lymphocyte counts <700 × 109/L, LDH >450 U/L, ferritin >862 ng/ml, C-reactive protein >11 mg/dL, and D-dimer >1.5 ug/ml. In contrast, the use of an anticoagulant lowered the risk of developing ARDS (OR 0.66 [95% CI 0.49-0.89]. Crude 30-day mortality rate from ARDS was 41% (95% CI 38%-45%). Risk of death from ARDS was significantly higher in those who developed acute renal failure and septic shock. Use of an anticoagulant was associated with 2-fold reduction in mortality. Survival benefit was observed in patients who received corticosteroids and/or remdesivir but there was no advantage of combination therapy over either agent alone. Among those hospitalized for COVID-19, nearly 1 in 10 progressed to ARDS. Septic shock, and acute renal failure are the leading causes of death in these patients. Treatment with either remdesivir and corticosteroids reduced the risk of mortality from ARDS. All hospitalized patients with COVID-19 should be placed at a minimum on prophylactic doses of anticoagulation.

High value of mid-regional proadrenomedullin in COVID-19: A marker of widespread endothelial damage, disease severity, and mortality.

The widespread endothelial damage due to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) may lead to a disruption of the adrenomedullin (ADM) system responsible for vascular leakage, increased inflammatory status, and microvascular alteration with multi‐organs dysfunction. The aim of this study was to evaluate the role of mid‐regional proadrenomedullin (MR‐proADM) as a marker of SARS‐CoV2 related widespread endothelial damage, clinically identified by organs damage, disease severity and mortality. Patients with SARS‐CoV‐2 infection has been prospectively enrolled and demographic characteristic, clinical and laboratory data has been evaluated. In the overall population, 58% developed acute respiratory distress syndrome (ARDS), 23.3% of patients died, 6.5% acute cardiac injury, 1.4% of patients developed acute ischemic stroke, 21.2% acute kidney injury, 11.8% acute liver damage, and 5.4% septic shock. The best MR‐proADM cut‐off values for ARDS development and mortality prediction were 3.04 and 2 nmol/L, respectively. Patients presenting with MR‐proADM values ≥2 nmol/L showed a significantly higher mortality risk. In conclusion, MR‐proADM values ≥2 nmol/L identify those patients with high mortality risk related to a multiorgan dysfunction syndrome. These patients must be carefully evaluated and considered for an intensive therapeutic approach.

Non-specialist therapeutic strategies in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is associated with significant morbidity and mortality. We undertook a meta-analysis of randomized controlled trials (RCTs) to determine the mortality benefit of non-specialist therapeutic interventions for ARDS available to general critical care units. A systematic search of MEDLINE, Embase, and the Cochrane Central Register for RCTs investigating therapeutic interventions in ARDS including corticosteroids, fluid management strategy, high PEEP, low tidal volume ventilation, neuromuscular blockade, prone position ventilation, or recruitment maneuvers. Data was collected on demographic information, treatment strategy, duration and dose of treatment, and primary (28 or 30-day mortality) and secondary (P<inf>a</inf>O<inf>2</inf>:FiO<inf>2</inf> ratio at 24-48 hours) outcomes. No improvement in 28-day mortality could be demonstrated in three RCTs investigating high PEEP (28.0% vs. 30.2% control; risk ratio [confidence interval] 0.93 [0.82-1.06]; eight assessing prone position ventilation (39.3% vs. 44.5%; RR 0.83 [0.68-1.01]; seven investigating neuromuscular blockade (37.8% vs. 42.0%; RR 0.91 [0.81-1.03]); ten investigating recruitment maneuvers (42.4% vs. 42.1%; RR 1.01 [0.91-1.12]); eight investigating steroids (34.8% vs. 41.1%; RR 0.81 [0.59-1.12]); and one investigating conservative fluid strategies (25.4% vs. 28.4%; RR 0.90 [0.73-1.10]). Three studies assessing low tidal volume ventilation (33.1% vs. 41.9%; RR 0.79 (0.68-0.91); P=0.001), and subgroup analyses within studies investigating prone position ventilation greater than 12 hours (33.1% vs. 44.4%; RR 0.75 [0.59-0.95), P=0.02) did reveal outcome benefit. Among non-specialist therapeutic strategies available to general critical care units, low tidal volumes and prone position ventilation for greater than 12 hours improve mortality in ARDS.

Unique inflammatory profile is associated with higher SARS-CoV-2 acute respiratory distress syndrome (ARDS) mortality.

The COVID19 pandemic has caused more than a million of deaths worldwide, primarily due to complications from COVID19-associated acute respiratory distress syndrome (ARDS). Controversy surrounds the circulating cytokine/chemokine profile of COVID19-associated ARDS, with some groups suggesting that it is similar to patients without COVID19 ARDS and others observing substantial differences. Moreover, although a hyperinflammatory phenotype associates with higher mortality in non-COVID19 ARDS, there is little information on the inflammatory landscape's association with mortality in patients with COVID19 ARDS. Even though the circulating leukocytes' transcriptomic signature has been associated with distinct phenotypes and outcomes in critical illness including ARDS, it is unclear whether the mortality-associated inflammatory mediators from patients with COVID19 are transcriptionally regulated in the leukocyte compartment. Here, we conducted a prospective cohort study of 41 mechanically ventilated patients with COVID19 infection using highly calibrated methods to define the levels of plasma cytokines/chemokines and their gene expressions in circulating leukocytes. Plasma IL1RA and IL8 were found positively associated with mortality, whereas RANTES and EGF negatively associated with that outcome. However, the leukocyte gene expression of these proteins had no statistically significant correlation with mortality. These data suggest a unique inflammatory signature associated with severe COVID19.