Adipose-derived mesenchymal stem cells ameliorate the inflammatory reaction in CLP-induced septic acute lung injury rats via sTNFR1.

We hypothesized that the adipose-derived mesenchymal stem cells (ADMSCs), which secrete high amounts of soluble molecules, such as soluble tumor necrosis factor receptor 1 (sTNFR1), may ameliorate sepsis-induced acute lung injury (ALI). A total of 120 male adult Sprague-Dawley rats were separated into four groups: the sham control (SC), sepsis induced by cecal ligation and puncture (CLP), CLP-ADMSCs, and CLP-sTNFR1 small interfering RNA (siRNA) groups; CLP groups underwent CLP and then received 1 × 106 ADMSCs with or without knockdown of sTNFR1 intravenously at 1 hr after surgery. Rats were killed at 3, 6, 24, and 48 hr after the SC or CLP procedures. 5-Ethynyl-2'-deoxyuridine-labeled ADMSCs extensively colonized the lungs at 6, 24, and 72 hr after injection. The lung wet/dry (W/D) weight ratios in the CLP group were higher than those in SC group; however, ADMSCs ameliorated the W/D weight ratios following CLP, and this effect was abolished by sTNFR1 siRNA treatment. The levels of serum sTNFR1 and interleukin-10 (IL-10) were higher in the CLP-ADMSCs group and lower in the SC group than in other groups; interestingly, these levels were higher in CLP and CLP-sTNFR1 siRNA groups than in SC group. Tumor necrosis factor-α and IL-6 levels increased significantly after CLP, and ADMSCs could alleviate these changes, but the effect was weakened by sTNFR1 siRNA treatment. The lung cell apoptosis and edema levels were consistent with IL-6 levels among all groups. Therapeutically administered ADMSCs secrete sTNFR1, which most likely protects against ALI in septic rats by ameliorating inflammation and lung edema.

Predictive model for acute respiratory distress syndrome events in ICU patients in China using machine learning algorithms: a secondary analysis of a cohort study.

BACKGROUND: To develop a machine learning model for predicting acute respiratory distress syndrome (ARDS) events through commonly available parameters, including baseline characteristics and clinical and laboratory parameters. METHODS: A secondary analysis of a multi-centre prospective observational cohort study from five hospitals in Beijing, China, was conducted from January 1, 2011, to August 31, 2014. A total of 296 patients at risk for developing ARDS admitted to medical intensive care units (ICUs) were included. We applied a random forest approach to identify the best set of predictors out of 42 variables measured on day 1 of admission. RESULTS: All patients were randomly divided into training (80%) and testing (20%) sets. Additionally, these patients were followed daily and assessed according to the Berlin definition. The model obtained an average area under the receiver operating characteristic (ROC) curve (AUC) of 0.82 and yielded a predictive accuracy of 83%. For the first time, four new biomarkers were included in the model: decreased minimum haematocrit, glucose, and sodium and increased minimum white blood cell (WBC) count. CONCLUSIONS: This newly established machine learning-based model shows good predictive ability in Chinese patients with ARDS. External validation studies are necessary to confirm the generalisability of our approach across populations and treatment practices.

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.

Efficacy of mesenchymal stem cell therapy for sepsis: a meta-analysis of preclinical studies.

BACKGROUND: Multiple studies have reported that mesenchymal stem cell (MSC) therapy has beneficial effects in experimental models of sepsis. However, this finding remains inconclusive. This study was performed to systematically determine the connection between MSC therapy and mortality in sepsis animal models by pooling and analyzing data from newly published studies. METHODS: A detailed search of related studies from 2009 to 2019 was conducted in four databases, including MEDLINE, EMBASE, Cochrane Library, and Web of Science. After browsing and filtering out articles that met the inclusion criteria for statistical analysis, the inverse variance method of the fixed effects model was used to calculate the pooled odds ratios (ORs) and their 95% confidence intervals (CIs). RESULTS: Twenty-nine animal studies, including 1266 animals, were identified. None of the studies was judged to have a low risk of bias. The meta-analysis demonstrated that MSC therapy was related to a significantly lower mortality rate (OR 0.29, 95% CI 0.22-0.38, P < 0.001). Subgroup analyses performed based on the MSC injection dose (< 1.0 × 106 cells, OR = 0.33, 95% CI 0.20-0.56, P < 0.001; 1.0 × 106 cells, OR = 0.24, 95% CI 0.16-0.35, P < 0.001) and injection time (< 1 h, OR = 0.24, 95% CI 0.13-0.45, P < 0.001; 1 h, OR = 0.28, 95% CI 0.17-0.46, P < 0.001) demonstrated that treatment with MSCs significantly reduced the mortality rate of animals with sepsis. CONCLUSION: This up-to-date meta-analysis showed a connection between MSC therapy and lower mortality in sepsis animal models, supporting the potential therapeutic effect of MSC treatment in future clinical trials. The results in this study contradict a previous meta-analysis with regards to the ideal dose of MSC therapy. Thus, further research is required to support these findings.

Effect of low high-density lipoprotein levels on mortality of septic patients: A systematic review and meta-analysis of cohort studies.

BACKGROUND: An increase in high-density lipoprotein (HDL) is well associated with a decreased cardiovascular risk, especially atherosclerosis. Recent studies suggest that lower levels of HDL may also be associated with an increased risk of sepsis and an increased rate of mortality in septic patients. However, this conclusion remains controversial. METHODS: MEDLINE, EMBASE, and CENTRAL databases were searched from inception to September 30, 2019. All studies were conducted to evaluate the correlation of lipoprotein levels and the risk and outcomes of sepsis in adult patients. The primary outcomes were the risk and mortality of sepsis. RESULTS: Seven studies comprising 791 patients were included. Lower levels of HDL had no marked relevance with the risk of sepsis (odds radio [OR] for each 1 mg/dL increase, 0.94; 95% CI 0.86-1.02; P=0.078), whereas lower HDL levels were related to an increased mortality rate in septic patients (OR for below about median HDL levels, 2.00; 95% CI 1.23-3.24; P=0.005). CONCLUSION: This meta-analysis did not reveal a significant association between lower HDL levels and an increase in the risk of sepsis, whereas it showed that lower HDL levels are associated with a higher mortality rate in septic adult patients. These findings suggest that HDL may be considered as a promising factor for the prevention and treatment of sepsis in the future.

Efficacy of stem cell therapy for pulmonary arterial hypertension: a systematic review and meta-analysis of preclinical studies.

BACKGROUND: Despite significant progress in drug treatment, the prognosis of patients with advanced pulmonary arterial hypertension (PAH) remains extremely poor. Many preclinical studies have reported the efficacy of stem cell (SC) therapy for PAH; however, this approach remains controversial. The aim of this systematic review and meta-analysis is to assess the potential efficacy of SC therapy for PAH. METHODS: The Medline, EMBASE, Cochrane Library, and Web of Science databases were searched from inception to August 12, 2018. Preclinical studies that evaluated the use of SC therapy for PAH were included. The primary outcome was pulmonary haemodynamics, as assessed by measurement of the right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), and/or mean right ventricle pressure (mRVP). The secondary outcomes included the weight ratio of the right ventricle to the left ventricle plus septum (RV/LV+S), the right ventricle to body weight ratio (RV/BW), the percentage of pulmonary arteriole area index (WA), and/or the percentage of medial wall thickness of the pulmonary arteriole (WT). The quality of outcomes was evaluated using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) bias risk tool. The inverse-variance method with random-effects modelling was used to calculate pooled weighted mean differences (WMDs) and 95% CIs. Statistical analysis was performed with STATA 14.0. RESULTS: Twenty-eight eligible articles (722 animals) were included. SC therapy reduced the pooled WMDs (95% CIs) of RVSP, mPAP, mRVP, RV/LV+S, RV/BW, WA, and WT for animals with PAH, with values of - 14.12 (- 14.63, - 13.61), - 11.86 (- 12.35, - 11.36), - 17.33 (- 18.10, - 16.56), - 0.10 (- 0.10, - 0.09), 0.23 (0.21, 0.24), - 13.66 (- 15.71, - 11.62), and - 7.96 (- 7.99, - 7.93), respectively. CONCLUSIONS: SC therapy is effective for PAH in preclinical studies. These results may help to standardise preclinical animal studies and provide a theoretical basis for clinical trial design in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ( http://www.crd.york.ac.uk/PROSPERO ).