Effect of Extended Prone Positioning in Intubated COVID-19 Patients with Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.

INPLASY REGISTRATION NUMBER: INPLASY202390072.

The systemic immune-inflammation index is significantly associated with the severity of silicosis: a 9-year retrospective study in Beijing.

Background: Silicosis shows an increasing trend with the development of new industries. However, the potential biomarkers for predicting the disease severity are lacking. A novel inflammatory marker, the systemic immune-inflammation Index (SII), has not been studied in silicosis. Methods: In this retrospective study, we used data from a big database platform of a tertiary general hospital in Beijing, which was established based on the electronic medical records of the hospital. The clinical data of adult patients diagnosed with silicosis at the Department of Occupational Medicine and Toxicology from 2013 to 2022 were collected. The data extracted from the database were in de-identified form. Only patients with a first diagnosis of silicosis and without conditions that might affect the parameters of routine blood tests were included in the analysis. Analyses were performed to assess the relationship between SII and the advanced stage of silicosis. Results: A total of 246 participants were included in the study. Most of the patients were exposed to silica particles during excavation and digging (n = 149, 60.6%). SII level was significantly higher in patients with advanced stages of silicosis. A multivariate logistic regression analysis revealed that a higher SII level was associated with the advanced stage of silicosis [odds ratio (OR) = 1.002; 95% confidence interval (CI): 1.000-1.003, p < 0.001] after adjusting for all covariates. The best cutoff value of SII was 444.1. The results of the subgroup analysis also showed a significant correlation between SII level over 444.1 and the advanced stage of silicosis in groups stratified by gender, history of smoking, and duration of silica exposure. Moreover, our results showed a significant but weak negative correlation between the level of SII and some lung function parameters in silicosis. Conclusion: Higher SII is associated with the advanced stage of silicosis and impaired lung function. More long-term, large-scale studies are needed to confirm these findings.

Metabolomic Profiling of Lungs from Mice Reveals the Variability of Metabolites in Pneumocystis Infection and the Metabolic Abnormalities in BAFF-R-Deficient Mice.

Purpose: The incidence of Pneumocystis pneumonia (PCP) in patients without human immunodeficiency virus (HIV) has been increasing. In this study, we aimed to investigate the metabolic changes in Pneumocystis infection and the metabolic abnormalities in B-cell-activating factor receptor (BAFF-R)-deficient mice with Pneumocystis infection. Methods: The important function of B cells during Pneumocystis infection is increasingly recognized. In this study, a Pneumocystis-infected mouse model was constructed in BAFF-R-/- mice and wild-type (WT) mice. Lungs of uninfected WT C57BL/6, WT Pneumocystis-infected, and BAFF-R-/- Pneumocystis-infected mice were used for metabolomic analyses to compare the metabolomic profiles among the groups, with the aim of exploring the metabolic influence of Pneumocystis infection and the influence of mature B-cell deficiency during infection. Results: The results indicated that many metabolites, mainly lipids and lipid-like molecules, were dysregulated in Pneumocystis-infected WT mice compared with uninfected WT C57BL/6 mice. The data also demonstrated significant changes in tryptophan metabolism, and the expression levels of key enzymes of tryptophan metabolism, such as indoleamine 2,3-dioxygenase 1 (IDO1), were significantly upregulated. In addition, B-cell development and function might be associated with lipid metabolism. We found a lower level of alitretinoin and the abnormalities of fatty acid metabolism in BAFF-R-/- Pneumocystis-infected mice. The mRNA levels of enzymes associated with fatty acid metabolism in the lung were upregulated in BAFF-R-/- Pneumocystis-infected mice and positively correlated with the level of IL17A, thus suggesting that the abnormalities of fatty acid metabolism may be associated with greater inflammatory cell infiltration in the lung tissue of BAFF-R-/- Pneumocystis-infected mice compared with the WT Pneumocystis-infected mice. Conclusion: Our data revealed the variability of metabolites in Pneumocystis-infected mice, suggesting that the metabolism plays a vital role in the immune response to Pneumocystis infection.

The efficiency of convalescent plasma in COVID-19 patients: A systematic review and meta-analysis of randomized controlled clinical trials.

The objective of this study was to assess whether convalescent plasma therapy could offer survival advantages for patients with novel coronavirus disease 2019 (COVID-19). An electronic search of Pubmed, Web of Science, Embase, Cochrane library and MedRxiv was performed from January 1st, 2020 to April 1st, 2022. We included studies containing patients with COVID-19 and treated with CCP. Data were independently extracted by two reviewers and synthesized with a random-effect analysis model. The primary outcome was 28-d mortality. Secondary outcomes included length of hospital stay, ventilation-free days, 14-d mortality, improvements of symptoms, progression of diseases and requirements of mechanical ventilation. Safety outcomes included the incidence of all adverse events (AEs) and serious adverse events (SAEs). The Cochrane risk-of-bias assessment tool 2.0 was used to assess the potential risk of bias in eligible studies. The heterogeneity of results was assessed by I^2 test and Q statistic test. The possibility of publication bias was assessed by conducting Begg and Egger test. GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used for quality of evidence. This study had been registered on PROSPERO, CRD42021273608. 32 RCTs comprising 21478 patients with Covid-19 were included. Compared to the control group, COVID-19 patients receiving CCP were not associated with significantly reduced 28-d mortality (CCP 20.0% vs control 20.8%; risk ratio 0.94; 95% CI 0.87-1.02; p = 0.16; I² = 8%). For all secondary outcomes, there were no significant differences between CCP group and control group. The incidence of AEs (26.9% vs 19.4%,; risk ratio 1.14; 95% CI 0.99-01.31; p = 0.06; I² = 38%) and SAEs (16.3% vs 13.5%; risk ratio 1.03; 95% CI 0.87-1.20; p = 0.76; I² = 42%) tended to be higher in the CCP group compared to the control group, while the differences did not reach statistical significance. In all, CCP therapy was not related to significantly improved 28-d mortality or symptoms recovery, and should not be viewed as a routine treatment for COVID-19 patients. Trial registration number: CRD42021273608. Registration on February 28, 2022. Systematic review registration: https://www.crd.york.ac.uk/prospero/, Identifier CRD42022313265.

Effect of Awake Prone Positioning in non-Intubated COVID-19 Patients with Acute Hypoxemic Respiratory Failure: A Systematic Review and Meta-Analysis.

BACKGROUND: Awake prone positioning (APP) has been considered as a feasible treatment for patients with acute hypoxemic respiratory failure in non-intubated coronavirus disease 2019 (COVID-19). However, the efficacy and safety of APP remain uncertain. This meta-analysis aims to assess the effect of APP on intubation rate and mortality in COVID-19 patients with acute respiratory failure. METHODS: Relevant studies published from January 1, 2020, to June 17, 2022, were systematically searched. The primary outcomes were the intubation rate and mortality; the secondary outcome was the incidence of adverse events. RESULTS: Of 5746 identified publications, 22 were eligible for inclusion in the meta-analysis (N = 5146 patients). In comparison to the non-APP group, APP could decrease the intubation rates (OR 0.64; 95% CI 0.48-0.83; P = .001), particularly in the subgroup of the daily median duration of APP > 8 h and in the subgroup of receiving high flow nasal cannula (HFNC) or non-invasive ventilation (NIV). Patients treated with APP were associated with lower mortality rates (OR 0.61; 95% CI 0.45-0.81; P = .0008), but no mortality benefit was found in the APP group in the subgroup of randomized controlled trials (RCTs). No significant difference was found in the incidence of adverse events between the groups (OR 1.13; 95% CI 0.75-1.71; P = .56). CONCLUSION: Our results demonstrated that APP could be an effective strategy to avoid intubation without detrimental effects in non-intubated patients with COVID-19, especially for patients requiring HFNC or NIV, and the daily APP duration with the target of minimally eight hours was suggested. In the subgroup of RCTs, the pooled results did not demonstrate any benefit of APP on mortality. Given the limited number of RCTs, further high-quality RCTs are needed to confirm the results. INPLASY REGISTRATION NUMBER: INPLASY2021110037.

Prognostic impact of pleural effusion in patients with malignancy: A systematic review and meta-analysis.

The exact role of pleural effusion in the prognosis of cancer patients remains unclear. We aimed to systematically review the prognostic value of pleural effusion in patients with cancer. We performed a systematic review and meta-analysis with a systematic literature search. All cohort studies with available overall survival (OS) and progression-free survival (PFS) results for patients with cancer with or without pleural effusion were included. The Mantel-Haenszel method was used to calculate the pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Heterogeneity and publication bias were examined. Subgroup analysis and sensitivity analysis were performed. A total of 47 studies with 146,117 patients were included in the analysis. For OS, pleural effusion was a prognostic factor associated with a poor prognosis for patients with cancer (HR, 1.58, 95% CI, 1.43-1.75; I2 94.8%). In the subgroup analysis, pleural effusion was a prognostic factor associated with poor survival for patients with lung cancer (HR, 1.44, 95% CI, 1.35-1.54; I2 60.8%), hematological cancer (HR, 2.79, 95% CI, 1.63-4.77; I2 29.4%) and other types of cancer (HR, 2.08, 95% CI, 1.43-3.01; I2 55.1%). For PFS, pleural effusion was a prognostic factor associated with a poor prognosis for patients with cancer (HR, 1.61, 95% CI, 1.28-2.03; I2 42.9%). We also observed that massive pleural effusion was a prognostic factor associated with a poorer prognosis compared to minimal pleural effusion. Pleural effusion had prognostic value in both OS and PFS of patients with cancer, except for patients with malignant pleural mesothelioma, regardless of whether the malignant effusion was confirmed histologically or cytologically. However, future evidence of other pleural effusion characteristics is still needed.

Delayed Initiation of ECMO Is Associated With Poor Outcomes in Patients With Severe COVID-19: A Multicenter Retrospective Cohort Study.

Background: Extracorporeal membrane oxygenation (ECMO) is a rapidly evolving therapy for acute lung and/or heart failure. However, the information on the application of ECMO in severe coronavirus disease 2019 (COVID-19) is limited, such as the initiation time. Especially in the period and regions of ECMO instrument shortage, not all the listed patients could be treated with ECMO in time. This study aimed to investigate and clarify the timing of ECMO initiation related to the outcomes of severe patients with COVID-19. The results show that ECMO should be initiated within 24 h after the criteria are met. Methods: In this retrospective, multicenter cohort study, we enrolled all ECMO patients with confirmed COVID-19 at the three hospitals between December 29, 2019 and April 5, 2020. Data on the demographics, clinical presentation, laboratory profile, clinical course, treatments, complications, and outcomes were collected. The primary outcomes were successful ECMO weaning rate and 60-day mortality after ECMO. Successful weaning from ECMO means that the condition of patients improved with adequate oxygenation and gas exchange, as shown by the vital signs, blood gases, and chest X-ray, and the patient was weaned from ECMO for at least 48 h. Results: A total of 31 patients were included in the analysis. The 60-day mortality rate after ECMO was 71%, and the ECMO weaning rate was 26%. Patients were divided into a delayed ECMO group [3 (interquartile range (IQR), 2-5) days] and an early ECMO group [0.5 (IQR, 0-1) days] based on the time between meeting the ECMO criteria and ECMO initiation. In this study, 14 and 17 patients were included in the early and delayed treatment groups, respectively. Early initiation of ECMO was associated with decreased 60-day mortality after ECMO (50 vs. 88%, P = 0.044) and an increased ECMO weaning rate (50 vs. 6%, P = 0.011). Conclusions: In ECMO-supported patients with COVID-19, delayed initiation of ECMO is a risk factor associated with a poorer outcome. Trial Registration: Clinical trial submission: March 19, 2020. Registry name: A medical records-based study for the clinical application of extracorporeal membrane oxygenation in the treatment of severe respiratory failure patients with novel coronavirus pneumonia (COVID-19). Chinese Clinical Trial Registry: https://www.chictr.org.cn/showproj.aspx?proj=51267,identifier:~ChiCTR2000030947.

Effect of different levels of PEEP on mortality in ICU patients without acute respiratory distress syndrome: systematic review and meta-analysis with trial sequential analysis.

OBJECTIVE: To determine whether higher positive end- expiratory pressure (PEEP) could provide a survival advantage for patients without acute respiratory distress syndrome (ARDS) compared with lower PEEP. METHODS: Eligible studies were identified through searches of Embase, Cochrane Library, Web of Science, Medline, and Wanfang database from inception up to 1 June 2021. Trial sequential analysis (TSA) was used in this meta-analysis. DATA SYNTHESIS: Twenty-seven randomized controlled trials (RCTs) were identified for further evaluation. Higher and lower PEEP arms included 1330 patients and 1650 patients, respectively. A mean level of 9.6±3.4 cmH2O was applied in the higher PEEP groups and 1.9±2.6 cmH2O was used in the lower PEEP groups. Higher PEEP, compared with lower PEEP, was not associated with reduction of all-cause mortality (RR 1.03; 95% CI 0.91-1.18; P =0.627), and 28-day mortality (RR 1.07 ; 95% CI 0.92-1.24; P =0.365). In terms of risk of ARDS (RR 0.43; 95% CI 0.24-0.78; P =0.005), duration of intensive care unit (MD -1.04; 95%CI-1.36 to -0.73; P < 0.00001), and oxygenation (MD 40.30; 95%CI 0.94 to 79.65; P = 0.045), higher PEEP was superior to lower PEEP. Besides, the pooled analysis showed no significant differences between groups both in the duration of mechanical ventilation (MD 0.00; 95%CI-0.13 to 0.13; P = 0.996) and hospital stay (MD -0.66; 95%CI-1.94 to 0.61; P = 0.309). More importantly, lower PEEP did not increase the risk of pneumonia, atelectasis, barotrauma, hypoxemia, or hypotension among patients compared with higher PEEP. The TSA analysis showed that the results of all-cause mortality and 28-day mortality might be false-negative results. CONCLUSIONS: Our results suggest that a lower PEEP ventilation strategy was non-inferior to a higher PEEP ventilation strategy in ICU patients without ARDS, with no increased risk of all-cause mortality and 28-day mortality. Further high-quality RCTs should be performed to confirm these findings.

Intravenous Immunoglobulin Therapy for Critically Ill COVID-19 Patients With Different Inflammatory Phenotypes: A Multicenter, Retrospective Study.

Background: The benefits of intravenous immunoglobulin administration are controversial for critically ill COVID-19 patients. Methods: We analyzed retrospectively the effects of immunoglobulin administration for critically ill COVID-19 patients. The primary outcome was 28-day mortality. Inverse probability of treatment weighting (IPTW) with propensity score was used to account for baseline confounders. Cluster analysis was used to perform phenotype analysis. Results: Between January 1 and February 29, 2020, 754 patients with complete data from 19 hospitals were enrolled. Death at 28 days occurred for 408 (54.1%) patients. There were 392 (52.0%) patients who received intravenous immunoglobulin, at 11 (interquartile range (IQR) 8, 16) days after illness onset; 30% of these patients received intravenous immunoglobulin prior to intensive care unit (ICU) admission. By unadjusted analysis, no difference was observed for 28-day mortality between the immunoglobulin and non-immunoglobulin groups. Similar results were found by propensity score matching (n = 506) and by IPTW analysis (n = 731). Also, IPTW analysis did not reveal any significant difference between hyperinflammation and hypoinflammation phenotypes. Conclusion: No significant association was observed for use of intravenous immunoglobulin and decreased mortality of severe COVID-19 patients. Phenotype analysis did not show any survival benefit for patients who received immunoglobulin therapy.

Effect of convalescent blood products for patients with severe acute respiratory infections of viral etiology: A systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to determine whether convalescent blood products (CBPs) offer a survival advantage for patients with severe acute respiratory infections of viral etiology. METHODS: Up-to-date trials were identified by the authors through searches of the MEDLINE, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and medRxiv databases from inception up to September 14, 2020. Meta-analyses were performed using a random-effects model. RESULTS: According to the observational studies, patients who received CBPs showed a decline in all-cause mortality compared with patients who did not receive CBPs (odds ratio (OR) 0.36, 95% confidence interval (CI) 0.23-0.56; p < 0.00001). However, the randomized controlled trials (RCTs) showed no difference between the intervention group and the control group regarding all-cause mortality (OR 0.82, 95% CI 0.57-1.19; p = 0.30). The use of CBPs did not increase the risk of adverse events (OR 0.88, 95% CI 0.60-1.29; p = 0.51). Using CBPs earlier compared with using CBPs later was associated with a significant reduction in all-cause mortality (OR 0.18, 95% CI 0.08-0.40; p < 0.0001). CONCLUSIONS: Based on the outcomes of RCTs, CBPs may not decrease all-cause mortality. Furthermore, compared with later initiation of CBP therapy, earlier initiation of this therapy may decrease the rate of mortality.

Clinical characteristics and outcomes of critically ill patients with novel coronavirus infectious disease (COVID-19) in China: a retrospective multicenter study.

PURPOSE: An ongoing outbreak of coronavirus disease 2019 (COVID-19) emerged in Wuhan since December 2019 and spread globally. However, information about critically ill patients with COVID-19 is still limited. We aimed to describe the clinical characteristics and outcomes of critically ill patients with COVID-19 and figure out the risk factors of mortality. METHODS: We extracted data retrospectively regarding 733 critically ill adult patients with laboratory-confirmed COVID-19 from 19 hospitals in China through January 1 to February 29, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were collected. The primary outcome was 28-day mortality. Data were compared between survivors and non-survivors. RESULTS: Of the 733 patients included in the study, the median (IQR) age was 65 (56-73) years and 256 (34.9%) were female. Among these patients, the median (IQR) APACHE II score was 10 (7 to 14) and 28-day mortality was 53.8%. Respiratory failure was the most common organ failure (597 [81.5%]), followed by shock (20%), thrombocytopenia (18.8%), central nervous system (8.6%) and renal dysfunction (8%). Multivariate Cox regression analysis showed that older age, malignancies, high APACHE II score, high D-dimer level, low PaO2/FiO2 level, high creatinine level, high hscTnI level and low albumin level were independent risk factors of 28-day mortality in critically ill patients with COVID-19. CONCLUSION: In this case series of critically ill patients with COVID-19 who were admitted into the ICU, more than half patients died at day 28. The higher percentage of organ failure in these patients indicated a significant demand for critical care resources.

Retest positive for SARS-CoV-2 RNA of "recovered" patients with COVID-19: Persistence, sampling issues, or re-infection?

"Retest Positive" for severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) from "recovered" coronavirus disease-19 (COVID-19) has been reported and raised several important questions for this novel coronavirus and COVID-19 disease. In this commentary, we discussed several questions: (a) Can SARS-CoV-2 re-infect the individuals who recovered from COVID-19? This question is also associated with other questions: whether or not SARS-CoV-2 infection induces protective reaction or neutralized antibody? Will SARS-CoV-2 vaccines work? (b) Why could some recovered patients with COVID-19 be re-tested positive for SARS-CoV-2 RNA? (c) Are some recovered pwith atients COVID-19 with re-testing positive for SARS-CoV-2 RNA infectious? and (d) How should the COVID-19 patients with retest positive for SARS-CoV-2 be managed?

Asymptomatic cases with SARS-CoV-2 infection.

On 31 March 2020, Chinese Health Authorization announced that numbers of asymptomatic cases with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection will be made to the public daily. This was a very important step since different counties have different capacities for the detection of SARS-CoV-2 infection and control strategy for the Coronavirus Disease 2019 outbreak. We summarized the characteristics of asymptomatic SARS-CoV-2 infections and the transmission potential of asymptomatic cases. Then we provided guidelines for the management of asymptomatic cases through quarantine and nucleic acid/serology tests.

Early neuromuscular blocking agents for adults with acute respiratory distress syndrome: a systematic review, meta-analysis and meta-regression.

OBJECTIVE: To determine whether neuromuscular blocking agents (NMBAs) can decrease the mortality of patients with acute respiratory distress syndrome (ARDS) and improve their clinical outcomes. DESIGN: Systematic review, meta-analysis and meta-regression. DATA SOURCES: PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov. METHODS: Randomised controlled trials (RCTs) comparing the treatment effect of NMBAs with that of placebo (or traditional treatment) in patients with ARDS were carefully selected. The primary outcome was 90-day mortality. The secondary outcomes were 21-28 days mortality, NMBA-related complications (barotrauma, pneumothorax and intensive care unit (ICU)-acquired muscle weakness), days free of ventilation and days not in the ICU by day 28, Medical Research Council score, Acute Physiology and Chronic Health Evaluation II score and arterial oxygen tension (PaO2)/fractional inspired oxygen (FiO2) (at 48 hours and 72 hours). Random-effects meta-regression was used to explore models involving potential moderators. Trial sequential analysis was performed to estimate the cumulative effect on mortality across RCTs. RESULTS: NMBAs were not associated with reduced 90-day mortality (risk ratio (RR) 0.85; 95% CI 0.66 to 1.09; p=0.20). However, they decreased the 21-28 days mortality (RR 0.71; 95% CI 0.53 to 0.96; p=0.02) and the rates of pneumothorax (RR 0.46; 95% CI 0.28 to 0.77; p=0.003) and barotrauma (RR 0.56; 95% CI 0.37 to 0.86; p=0.008). In addition, NMBAs increased PaO2/FiO2 at 48 hours (mean difference (MD) 18.91; 95% CI 4.29 to 33.53; p=0.01) and 72 hours (MD 12.27; 95% CI 4.65 to 19.89; p=0.002). Meta-regression revealed an association between sample size (p=0.042) and short-term mortality. Publication year (p=0.050), sedation strategy (p=0.047) and sample size (p=0.046) were independently associated with PaO2/FiO2 at 48 hours. CONCLUSIONS: In summary, the results suggested that use of NMBAs might reduce 21-28 days mortality, NMBA-related complications and oxygenation. However, NMBAs did not reduce the 90-day mortality of patients with ARDS, which contradicts a previous meta-analysis. PROSPERO REGISTRATION NUMBER: CRD42019139440.

Effect of High-Flow Nasal Cannula Oxygen Therapy in Immunocompromised Subjects With Acute Respiratory Failure.

BACKGROUND: Various studies have been performed to examine the effect of high-flow nasal cannula (HFNC) in immunocompromised patients with acute respiratory failure (ARF). However, the results were inconsistent. Thus, we conducted a meta-analysis to evaluate the effect of HFNC oxygen therapy in immunocompromised patients with ARF versus conventional oxygen therapy and noninvasive ventilation (NIV). METHODS: Relevant studies published prior to May 11, 2019, were systematically searched. The primary outcome was intubation rate; secondary outcomes were mortality (ICU mortality, in-hospital mortality, and 90-d mortality) and ICU-acquired infections. Data were pooled using the random effects model. RESULTS: Of 832 identified studies, 8 were eligible for inclusion in our analysis (N = 2,167 subjects). HFNC was associated with lower intubation rates compared to conventional oxygen therapy (risk ratio [RR] 0.89, 95% CI 0.79-1.00, P = .040), but we found no significant difference in the rate between HFNC and NIV (RR 0.74, 95% CI 0.46-1.19, P = .22). We also found that HFNC did not increase the risk of ICU-acquired infections (RR 0.86, 95% CI 0.63-1.18, P = .35). However, in comparison to other noninvasive therapies, HFNC exhibited no differences in ICU mortality (RR 0.82, 95% CI 0.58-1.17, P = .28), in-hospital mortality (RR 0.92, 95% CI 0.74-1.15, P = .48), or 90-d mortality (RR 0.98, 95% CI 0.81-1.18, P = .82). CONCLUSIONS: Our results suggest that HFNC may be a feasible alternative to NIV, with lower intubation rates and no increased risk for ICU-acquired infections compared to standard oxygen therapy. However, HFNC did not appear to reduce mortality in immunocompromised subjects with ARF compared with other noninvasive therapies. Further high-quality randomized controlled trials should be performed to confirm these findings.

Recruitment manoeuvres for adults with acute respiratory distress syndrome receiving mechanical ventilation: a systematic review and meta-analysis.

PURPOSE: To determine if recruitment manoeuvres (RMs) would decrease 28-day mortality of patients with acute respiratory distress syndrome (ARDS) compared with standard care. MATERIALS AND METHODS: Relevant randomized controlled trials (RCTs) published prior to April 26, 2018 were systematically searched. The primary outcome was mortality. The secondary outcomes were oxygenation, barotrauma or pneumothorax, the need for rescue therapies. Data were pooled using the random effects model. And the quality of evidence was assessed by the GRADE system. RESULTS: Of 3180 identified studies, 15 were eligibly included in our analysis (N = 2755 participants). In the primary outcome, RMs were not associated with reducing 28-day mortality (RR 0.90; 95% CI 0.74-1.09), ICU mortality (RR 0.92; 95% CI 0.74-1.1), and the in-hospital mortaliy (RR 1.02; 95% CI 0.93-1.12). In the secondary outcomes, RMs could improve oxygenation (MD 37.85; 95% CI 11.08-64.61), the rates of barotrauma (RR 1.42; 95% CI 0.83-2.42) and the need for rescue therapies (RR 0.69; 95% CI 0.42-1.12) did not show any difference in the ARDS patients with RMs. CONCLUSIONS: Earlier meta-analyses found decreased mortality with RMs, in the contrary, our results indicate that RMs could improve oxygenation without detrimental effects, but it does not appear to reduce mortality.