Effect of intravenous vitamin C on adult septic patients: a systematic review and meta-analysis.

Background: An increasing number of studies indicate that vitamin C (VC) reduces the mortality of adult septic patients, while some articles suggest otherwise. We performed this systematic review and meta-analysis to resolve the discrepancies in reported results concerning the efficacy of VC in septic patients. Methods: We comprehensively searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled trials for randomized controlled trials (RCTs) evaluating the efficacy of intravenous VC (IVVC) on adult septic patients published from inception to November 28, 2022. The quality of outcomes for eligible studies was assessed using the Recommendations Assessment, Development, and Evaluation methodology. The results were analyzed using the pooled mean difference (MD) or risk ratio (RR) and 95% confidence intervals (CIs). Results: Twenty-two studies (3,570 adult septic patients) were included. IVVC treatment did not improve 28-day mortality compared to the control group (RR, 0.92; 95% CI, 0.81-1.04; I2 = 26%; evidence risk, moderate). IVVC monotherapy decreased mortality (RR, 0.69; 95% CI, 0.52-0.93; I2 = 57%), whereas combination therapy did not affect mortality (RR, 1.03; 95% CI, 0.90-1.17; I2 =0%). IVVC had a trend to decrease the mortality of septic patients (RR, 0.83; 95% CI, 0.69-1.00; I2 = 33%) but did not affect septic shock patients (RR, 1.01; 95% CI, 0.85-1.21; I2 = 18%). IVVC reduced the duration of vasopressor use (MD, -8.45; 95% CI, -15.43 to -1.47; evidence risk, very low) but did not influence the incidence of AKI, ICU length of stay, duration of mechanical ventilation. Conclusions: IVVC treatment did not improve the 28-day mortality in septic patients. Subgroup analysis indicated that VC had a trend to decrease the 28-day mortality in patients with sepsis but not septic shock. IVVC monotherapy, rather than combination therapy, decreased the 28-day mortality in septic patients. The findings imply that Hydrocortisone, Ascorbic acid, Thiamine (HAT) combination therapy is not superior to IVVC monotherapy for septic patients. These findings warrant further confirmation in future studies, which should also investigate the mechanisms underlying the enhanced efficacy of IVVC monotherapy in septic patients. Systematic review registration: https://inplasy.com/.

Effects of Gabexate Mesylate on the Gut Microbiota and Metabolomics in Rats with Sepsis.

Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. However, there is still no single drug that could reduce septic mortality. Previous studies have reported gabexate mesylate (GM) significantly reduced serum inflammatory factors, alleviated sepsis-induced lung injury and improved clinical outcomes. This study aimed to combine with microbiome sequencing and metabolomics analysis to explore the effects of GM administration in septic rats. Methods: Sixty SD rats were randomly divided into the sham control (SC), cecal ligation and puncture (CLP), and GM injection (GM) groups. The mortality was measured and colonic feces were collected to examine the gut microbiota and metabolism 24 h after the procedure. The lung tissues were collected for hematoxylin-eosin staining. Results: We observed the relative abundance of Pygmaiobacter, which contributed to short-chain fatty acids (SCFAs) promotion, Lactobacillus and Erysipelotrichaceae UCG-003 increased in the GM-treated rats, while Escherichia-Shigella and Akkermansia decreased compared to the sepsis-induced lung injury group. Furthermore, these 3 metabolites including Palmitoylethanolamide, Deoxycholic acid and Chenodeoxycholic acid correlated significantly to CLP- and GM-rich genus (P < 0.05). Besides, the lung tissues of CLP group showed more severe inflammatory infiltration and edema, and the mortality rate in the CLP group (10/20) was significantly higher than in the SC group (0/20) (P < 0.001) and GM group (4/20) (P < 0.05). Conclusion: Our findings showed that GM attenuated sepsis-induced lung injury rats and regulated metabolites related to gut microbiota, which may provide an effective treatment for sepsis patients.

Metformin Improves the Prognosis of Adult Mice with Sepsis-Associated Encephalopathy Better than That of Aged Mice.

Sepsis-associated encephalopathy (SAE) is often associated with increased ICU occupancy and hospital mortality and poor long-term outcomes, with currently no specific treatment. Pathophysiological mechanisms of SAE are complex and may involve activation of microglia, multiple intracranial inflammatory factors, and inflammatory pathways. We hypothesized that metformin may have an effect on microglia, which affects the prognosis of SAE. In this study, metformin treatment of mice with SAE induced by lipopolysaccharide (LPS) reduced the expression of microglia protein and related inflammatory factors. Poor prognosis of SAE is related to increased expression of tumor necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1ß) in brain tissues. Levels of inflammatory cytokines produced by LPS-induced SAE mouse microglia were significantly increased compared with those in the sham group. In addition, ionized calcium-binding adapter molecule 1 (Iba-1) was significantly reduced in metformin-treated SAE mice compared with untreated SAE mice, suggesting that metformin can reduce microgliosis and inhibit central nervous system inflammation, thereby improving patient outcomes. In conclusion, our results stipulate that metformin inhibits inflammation through the adenosine 5'-monophosphate (AMP-) activated protein kinase pathway by inhibiting nuclear factor kappa beta (NF-κB). Metformin can partially reverse the severe prognosis caused by sepsis by blocking microglial proliferation and inhibiting the production of inflammatory factors.

Identification of metabolomics-based prognostic prediction models for ICU septic patients.

Sepsis-related global mortality remains unacceptably high in intensive care units. Identifying the various molecular processes between survival and death in septic patients may assist in better treatment. Accurate prognostic evaluation of sepsis is an essentially unmet need. This study analyzed the metabolite changes in plasma between healthy controls and septic patients, as well as between survival and dead septic patients using liquid chromatography/mass spectrometry. Univariate and multivariate analyses were applied to identify differential metabolites. The differential metabolites and clinical indicators within 24 h after sepsis diagnosis were run through multivariate logistic regression models to determine the 28-day, hospital, and 90-day septic mortality prediction models. The results suggested markedly changed amino acids metabolism in septic patients compared to healthy controls; 10, 4, and 22 primary differential metabolites related to amino acid and fatty acid metabolisms were identified in the survival and death groups at 28-day, hospital, and 90-day, respectively. Further, we found that model 1 (indoleacetic acid, 3-methylene-indolenine, heart rate, respiratory support, and application of pressure drugs), model 2 (lymphocyte count, alkaline phosphatase, SOFA, and L-alpha-amino-1H-pyrrole-1-hexanoic acid), and model 3 (dopamine, delta-12-prostaglandin J2, heart rate, respiratory support, and application of pressure drugs) could predict 28-day, hospital, and 90-day mortality of sepsis with a sensitivity of 75.51%, 73.58%, and 83.33%, specificity of 78.72%, 72.09%, and 78.57%, and the area under the receiver operating characteristic curve of 0.881, 0.830, 0.886, respectively. Thus, this research presents three multiple-biomarker-based prognostic models for 28-day, hospital, and 90-day mortality septic patients and could be used to guide sepsis treatment.

Positive Effects of Neutrophil Elastase Inhibitor (Sivelestat) on Gut Microbiome and Metabolite Profiles of Septic Rats.

Background: Neutrophil elastase (NE) is associated with sepsis occurrence and progression. We hypothesized that the NE inhibitor Sivelestat might modulate abnormal gut microbiota and metabolites during sepsis. Methods: Sixty Sprague-Dawley (SD) rats were randomly divided into sham control (SC), sepsis (CLP), and sepsis+Sivelestat (Sive) groups. The rats' survival status was monitored for 24 hours postoperatively, and feces were collected for microbiome and non-targeted metabolomics analyses. Results: Sivelestat administration significantly improved the survival of septic rats (80% vs 50%, P = 0.047). Microbiome analysis showed that the microbiota composition of rats in the CLP group was significantly disturbed, as potential pathogens such as Escherichia-Shigella and Gammaproteobacteria became dominant, and the beneficial microbiota represented by Lactobacillus decreased. These changes were reversed in Sive group, and the overall microbial status was restored to a similar composition to SC group. Differential analysis identified 36 differential operational taxonomic units and 11 metabolites between the Sive and CLP groups, such as 6-Aminopenicillanic acid, gamma-Glutamyl-leucine, and cortisone (variable importance in projection>1and P<0.05). These discriminatory metabolites were highly correlated with each other and mainly involved in the phenylalanine, tyrosine, and tryptophan biosynthesis pathways. Integrated microbiome and metabolome analyses found that almost all Sivelestat-modulated microbes were associated with differential metabolites (P < 0.05), such as Lactobacillus and some amino acids, suggesting that the Sivelestat-induced metabolic profile differences were in part due to its influence on the gut microbiome. Conclusion: Sivelestat administration in septic rats improved survival, gut microbiota composition and associated metabolites, which could provide new options for sepsis treatment.

[Analysis of the changes in intestinal microecology in the early stage of sepsis rat based on 16S rDNA sequencing].

OBJECTIVE: To investigate the changes of intestinal microecology in the early stage of sepsis rat model by 16S rDNA sequencing. METHODS: Sixty male Sprague-Dawley (SD) rats were randomly divided into cecal ligation and puncture (CLP) group and sham operation group (Sham group), with 30 rats in each group. In the CLP group, sepsis rat model was reproduced by CLP method; the rats in the Sham group only underwent laparotomy without CLP. At 24 hours after the operation, the intestinal feces and serum samples of 8 rats in each group were collected. The survival rate of the rest rats was observed until the 7th day. The level of serum tumor necrosis factor-α (TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA). Intestinal feces were sequenced by 16S rDNA sequencing technology. The operational taxonomic unit (OTU) data obtained after sequence comparison and clustering was used for α diversity and ß diversity analysis, principal coordinate analysis and linear discriminant analysis effect size analysis (LEfSe) to observe the changes of intestinal microecology in early sepsis rats and excavate the marker flora. RESULTS: At 24 hours after the reproduction of the model, the rats in the CLP group showed shortness of breath, scattered hair and other manifestations, and the level of serum TNF-α increased significantly as compared with that in the Sham group (ng/L: 43.95±9.05 vs. 11.08±3.27, P < 0.01). On the 7th day after modeling, the cumulative survival rate of the Sham group was 100%, while that of the CLP group was 31.82%. Diversity analysis showed that there was no significant difference in α diversity parameter between the Sham group and the CLP group (number of species: 520.00±52.15 vs. 492.25±86.61, Chao1 richness estimator: 707.25±65.69 vs. 668.93±96.50, Shannon index: 5.74±0.42 vs. 5.79±0.91, Simpson index: 0.93±0.03 vs. 0.94±0.05, all P > 0.05). However, the ß diversity analysis showed that the difference between groups was greater than that within groups whether weighted according to OTU or not (abundance weighted matrix: R = 0.23, P = 0.04; abundance unweighted matrix: R = 0.32, P = 0.01). At the phylum level, the abundance of Proteobacteria and Candidatus_sacchari in the CLP group increased significantly as compared with the Sham group [18.100% (15.271%, 26.665%) vs. 6.974% (2.854%, 9.764%), 0.125% (0.027%, 0.159%)% vs. 0.018% (0.008%, 0.021%), both P < 0.05]. At the genus level, the abundance of opportunistic pathogen including Helicobacter, Ruthenium, Streptococcus, Clostridium XVIII in the CLP group was significantly higher than that in the Sham group [5.090% (1.812%, 6.598%) vs. 0.083% (0.034%, 0.198%), 0.244% (0.116%, 0.330%) vs. 0.016% (0.008%, 0.029%), 0.006% (0.003%, 0.010%) vs. 0.001% (0%, 0.003%), 0.094% (0.035%, 0.430%) vs. 0.007% (0.003%, 0.030%), all P < 0.05], and the abundance of probiotics such as Alloprevotella and Romboustia was significantly lower than that in the Sham group [7.345% (3.662%, 11.546%) vs. 22.504% (14.403%, 26.928%), 0.113% (0.047%, 0.196%) vs. 1.229% (0.809%, 2.29%), both P < 0.01]. LEfSe analysis showed that the probiotics belonging to Firmicutes were significantly enriched in the Sham group, and Romboustia was the most significantly enriched species. Opportunistic pathogens such as Helicobacter, Streptococcus and Clostridium XVIII were significantly enriched in the CLP group, Helicobacter_NGSU_ 2015 was the most significantly enriched species. CONCLUSIONS: In the early stage of sepsis, the intestinal microbiota structure of rats is significantly changed, which mainly shows that the abundance of Alloprevotella and other probiotics is significantly reduced, while that of Helicobacter and other opportunistic pathogens is significantly increased.

Metformin attenuated sepsis-associated liver injury and inflammatory response in aged mice.

Sepsis-associated liver injury is with poor survival in intensive care units. Metformin is well known for its therapeutic effects; however, its impact on treating liver injury due to sepsis remains poorly understood. This study investigated the therapeutic effects of metformin on aged mice suffering from sepsis-associated liver injury. Male C57BL/6 J mice aged (18-19 months) were divided into 3 groups: 1) intraperitoneal injection of sterile normal saline (C group), 12.5 mg/kg lipopolysaccharide (LPS) to induce sepsis-associated liver injury (LPS group), and 25 mg/kg metformin (MET) at 1 h after LPS injection (MET group). After 24 h, blood samples and liver tissue were collected for biochemical analysis. Histological assays revealed significantly elevated inflammatory infiltration and apoptosis in the liver, while metformin was found to relieve these aberrant features. The percentage of apoptotic cells decreased after metformin treatment (P < 0.05). Additionally, MET group had significantly reduced plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared to the LPS group (P < 0.05). Furthermore, in the MET group, the mRNA levels of chemokines and inflammatory factors, TNF-α, IL-6, caspase-1, decreased markedly (P < 0.05). Metformin notably reversed the decreased phosphorylated AMP-activated protein kinase (p-AMPK) and PGC-1α expressions in the liver of septic rats. Metformin also inhibited PDK1, HIF-1α expression, including downstream inflammatory mediators, HMGB1 and TNF-α. Metformin attenuated inflammation and liver injury in septic aged mice. Most importantly, we report the effect of metformin on liver injury via the AMPK-PGC1α axis in septic aged mice for the first time.

Metformin attenuated sepsis-related liver injury by modulating gut microbiota.

Increased evidence shows that gut microbiota acts as the primary regulator of the liver; however, its role in sepsis-related liver injury (SLI) in the elderly is unclear. This study assessed whether metformin could attenuate SLI by modulating gut microbiota in septic-aged rats. Cecal ligation and puncture (CLP) was used to induce SLI in aged rats. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in these pathologies. The composition of gut microbiota was analysed by 16S rRNA sequencing. Moreover, the liver and colon tissues were analysed by histopathology, immunofluorescence, immunohistochemistry, and reverse transcription polymerase chain reaction (RT-PCR). Metformin improved liver damage, colon barrier dysfunction in aged SLI rats. Moreover, metformin improved sepsis-induced liver inflammation and damage under gut microbiota. Importantly, FMT assay showed that rats gavaged with faeces from metformin-treated SLI rats displayed less severe liver damage and colon barrier dysfunctions than those gavaged with faeces from SLI rats. The gut microbiota composition among the sham-operated, CLP-operated and metformin-treated SLI rats was different. In particular, the proportion of Klebsiella and Escherichia_Shigella was higher in SLI rats than sham-operated and metformin-treated SLI rats; while metformin could increase the proportion of Bifidobacterium, Muribaculaceae, Parabacteroides_distasonis and Alloprevitella in aged SLI rats. Additionally, Klebsiella and Escherichia_Shigella correlated positively with the inflammatory factors in the liver. Our findings suggest that metformin may improve liver injury by regulating the gut microbiota and alleviating colon barrier dysfunction in septic-aged rats, which may be an effective therapy for SLI.

Association between intake of sweetened beverages with all-cause and cause-specific mortality: a systematic review and meta-analysis.

BACKGROUND: Conclusions remain controversial between the consumption of sugar and artificially sweetened beverages (SSBs and ASBs) and mortality. METHODS: We systematically searched the PubMed, Embase, Cochrane Library and Web of Science databases from their inception date to 1st January 2020, prospective cohort studies researching the mortality risk and SSBs or ASBs consumption were included. Random effects meta-analyses and dose-response analyses were performed to measure the association. Subgroup analyses and sensitivity analyses were further performed to explore the source of heterogeneity. Publication bias was assessed by Funnel plots and Egger's regression test. RESULTS: Across all 15 cohorts, 1211 470 participants were included. High SSB consumption was associated with a higher risk of all-cause mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.06-1.19, P < 0.001; and cardiovascular disease [CVD] mortality [HR 1.20, 95% CI, 1.05-1.38, P < 0.001]), and high ASBs consumption showed similar result (HR 1.12, 95% CI, 1.04-1.21, P = 0.001 for all-cause mortality and HR 1.23, 95% CI, 1.00-1.50, P = 0.049 for CVD mortality), both showed a linear dose-response relationship. CONCLUSIONS: High consumption of both ASBs and SSBs showed significant associations with a higher risk of CVD mortality and all-cause mortality. This information may provide ideas for decreasing the global burden of diseases by reducing sweetened beverage intake.

Corrigendum: Corticosteroids for Treating Sepsis in Adult Patients: A Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.3389/fimmu.2021.709155.].

Safety of mechanical and manual chest compressions in cardiac arrest patients: A systematic review and meta-analysis.

AIM: Summarise the evidence regarding the safety of mechanical and manual chest compressions for cardiac arrest patients. METHODS: Two investigators separately screened the articles of EMBASE, PubMed, and Cochrane Central databases. Cohort studies and randomized clinical trials (RCTs) that evaluated the safety of mechanical (LUCAS or AutoPulse) and manual chest compressions in cardiac arrest patients were included. A meta-analysis was performed using a random effects model to calculate the pooled odds ratios (ORs) and their 95% confidence intervals (CIs). The primary outcome was the rate of overall compression-induced injuries. The secondary outcomes included the incidence of life-threatening injuries, skeletal fractures, visceral injuries, and other soft tissue injuries. RESULTS: The meta-analysis included 11 trials involving 2,818 patients. A significantly higher rate of overall compression-induced injuries was found for mechanical compressions than manual compressions (OR, 1.29; 95% CI, 1.19-1.41), while there was no significant difference between the two groups in respect of the rate of life-threatening injuries. Furthermore, both modalities shared similar incidences of sternal fractures, vertebral fractures, lung, spleen, and kidney injuries. However, compared to mechanical compressions, manual compressions were shown to present a reduced risk of posterior rib fractures, and heart and liver lesions. CONCLUSIONS: The findings suggested that manual compressions could decrease the risk of compression-induced injuries compared to mechanical compressions in cardiac arrest patients. Interestingly, mechanical compressions have not increased the risk of life-threatening injuries, whereas additional high-quality RCTs are needed to further verify the safety of mechanical chest devices. TRIAL REGISTRY: INPLASY; Registration number: INPLASY2020110111; URL: https://inplasy.com/.

Corticosteroids for Treating Sepsis in Adult Patients: A Systematic Review and Meta-Analysis.

Objective: Corticosteroids are a common option used in sepsis treatment. However, the efficacy and potential risk of corticosteroids in septic patients have not been well assessed. This review was performed to assess the efficacy and safety of corticosteroids in patients with sepsis. Methods: PubMed, Embase, and Cochrane library databases were searched from inception to March 2021. Randomized controlled trials (RCTs) that evaluated the effect of corticosteroids on patients with sepsis were included. The quality of outcomes in the included articles was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation methodology. The data were pooled by using risk ratio (RR) and mean difference (MD). The random-effects model was used to evaluate the pooled MD or RR and 95% confidence intervals (CIs). Results: Fifty RCTs that included 12,304 patients with sepsis were identified. Corticosteroids were not associated with the mortality in 28-day (RR, 0.94; 95% CI, 0.87-1.02; evidence rank, moderate) and long-term mortality (>60 days) (RR, 0.96; 95% CI, 0.88-1.05) in patients with sepsis (evidence rank, low). However, corticosteroids may exert a significant effect on the mortality in the intensive care unit (ICU) (RR, 0.9; 95% CI, 0.83-0.97), in-hospital (RR, 0.9; 95% CI, 0.82-0.99; evidence rank, moderate) in patients with sepsis or septic shock (evidence rank, low). Furthermore, corticosteroids probably achieved a tiny reduction in the length of hospital stay and ICU. Corticosteroids were associated with a higher risk of hypernatremia and hyperglycemia; furthermore, they appear to have no significant effect on superinfection and gastroduodenal bleeding. Conclusions: Corticosteroids had no significant effect on the 28-day and long-term mortality; however, they decreased the ICU and hospital mortality. The findings suggest that the clinical corticosteroids may be an effective therapy for patients with sepsis during the short time. Systematic Review Registration: https://inplasy.com/wp-content/uploads/2021/05/INPLASY-Protocol-1074-4.pdf.

Efficacy and Safety of Corticosteroid Use in Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis.

INTRODUCTION: We conducted a comprehensive literature review to synthesize evidence for the relationship between corticosteroid use and mortality in patients with COVID-19. METHODS: The PUBMED, EMBASE, and Cochrane Library were searched from inception to March 13, 2021. We searched and analyzed randomized controlled trials (RCTs) and observational studies (OSs) that examined corticosteroid use in patients with COVID-19. The primary outcome was in-hospital mortality, while the secondary outcome was the need for mechanical ventilation (MV) and serious adverse events. RESULTS: A total of 11 RCTs and 44 OSs involving 7893 and 41,164 patients with COVID-19 were included in the study. Corticosteroid use was associated with lower COVID-19 mortality in RCTs, but was not statistically significant (OR 0.91, 95% CI 0.77-1.07; I2 = 63.4%). The subgroup analysis of pulse dose corticosteroid showed survival benefit statistically (OR 0.29, 95% CI 0.15-0.56). Moreover, the corticosteroid use may reduce the need for MV (OR 0.67, 95% CI 0.51-0.90; I2 = 7.5%) with no significant increase in serious adverse reactions (OR 0.84, 95% CI 0.30-2.37; I2 = 33.3%). In addition, the included OSs showed that the pulse dose (OR 0.66, 95% CI 0.45-0.95; I2 = 30.8%) might lower the mortality in patients with COVID-19. The pulse dose of methylprednisolone (OR 0.60, 95% CI 0.45-0.80; I2 = 0%) had a beneficial effect on survival. It was especially significant when the duration of pulse methylprednisolone use was less than 7 days (OR 0.59, 95% CI 0.43-0.80; I2 = 0%). CONCLUSIONS: This meta-analysis indicated that corticosteroid use might cause a slight reduction in COVID-19 mortality. However, it could significantly reduce the MV requirement in patients with COVID-19 and restrict serious adverse events. Additionally, the pulse dose of methylprednisolone for less than 7 days may be a good treatment choice for patients with COVID-19.

Efficacy and safety of low-dose corticosteroids for acute respiratory distress syndrome: A systematic review and meta-analysis.

BACKGROUND: There are conflicting results regarding whether corticosteroids have better efficacy than placebo in acute respiratory distress syndrome (ARDS) patients. Therefore, we aim to further evaluate the efficacy and safety of corticosteroids in adult ARDS patients. METHODS: The databases, including Medline, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, were searched from their inception to May 2, 2020. Randomized controlled trials (RCTs) and observational cohort studies were selected to assess the use of corticosteroids in adult ARDS patients. The quality of the results was judged by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The inverse-variance method with random or fixed effects modeling was used to compute pooled odds ratio (OR), standardized mean difference (SMD), and their 95% confidence interval (CI). RESULTS: Eight eligible RCTs and six cohort studies were included. The use of corticosteroids was associated with reduced mortality (OR 0.57, 95% CI 0.43-0.76, I2=35.1%, P=0.148) in ARDS patients, and the result was confirmed in the included cohort studies (OR 0.51, 95% CI 0.27-0.95, I2=66.7%, P=0.010). The subgroup analysis stratified by the initiation time and duration of corticosteroid use showed that early ARDS and prolonged corticosteroid use had significant survival benefits in the RCTs. The low-dose corticosteroid use was also associated with significantly more ventilator-free days and a reduced rate of new infections in ARDS patients. CONCLUSIONS: The low-dose corticosteroid therapy may be safe and reduce mortality, especially in patients with prolonged treatment and early ARDS.

Association Between Prior Calcium Channel Blocker Use and Mortality in Septic Patients: A Meta-Analysis of Cohort Studies.

Background: The aim of this study was to comprehensively review the literature and synthesize the evidence concerning the relationship between prior calcium channel blocker (CCB) use and mortality in patients with sepsis. Methods: The Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Cochrane CENTRAL, and Web of Science databases were searched from their inception to April 9, 2020. Cohort studies related to prior calcium channel blocker use in patients with sepsis were analyzed. Pairs of reviewers independently screened the studies, extracted the data, and assessed the risk of bias. The primary outcome of 90-days mortality or secondary outcome of short-term mortality, including 30-days, Intensive Care Unit (ICU), and in-hospital mortality, were analyzed. Heterogeneity among studies was assessed using the I 2 statistic and was considered moderate if I 2 was 50-75% and high if I 2 was ≥75%. Random-effects models were used to calculate the pooled odds ratios (ORs) and 95% confidence intervals (CIs). The quality of the studies was evaluated with the Newcastle-Ottawa Scale (NOS). Sensitivity analyses were performed to examine the robustness of the results. Results: In total, 639 potentially relevant studies were identified, and the full texts of 25 articles were reviewed. Ultimately, five cohort studies involving 280,982 patients were confirmed to have a low risk of bias and were included. Prior CCB use was associated with a significantly lower 90-days mortality in sepsis patients [OR, 0.90 (0.85-0.95); I 2 = 31.9%]. Moreover, prior CCB use was associated with a significantly reduced short-term mortality rate in septic shock patients [OR, 0.61 (0.38-0.97); I 2 = 62.4%] but not in sepsis patients [OR, 0.83 (0.66-1.04); I 2 = 95.4%]. Conclusion: This meta-analysis suggests that prior CCB use is significantly associated with improved 90-days mortality in sepsis patients and short-term mortality in septic shock patients. This study provides preliminary evidence of an association between prior CCB use and mortality in sepsis patients.

Corrigendum: Association Between Prior Aspirin Use and Acute Respiratory Distress Syndrome Incidence in At-Risk Patients: A Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.3389/fphar.2020.00738.].