scholarly journals Efficacy of mesenchymal stem cell therapy for sepsis: A meta-analysis of preclinical studies

2020 ◽  
Author(s):  
xueyi sun ◽  
xianfei ding ◽  
huoyan liang ◽  
xiaojuan zhang ◽  
shaohua liu ◽  
...  

Abstract 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 1,266 animals, were identified. None of the studies were 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 × 10 6 cells, OR=0.33, 95% CI 0.20–0.56, P <0.001; 1.0 × 10 6 cells, OR=0.24, 95% CI 0.16–0.35, P <0.001) and injection time (<1 hour, OR=0.24, 95% CI 0.13–0.45, P <0.001; 1 hour, 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.

2020 ◽  
Author(s):  
Xueyi Sun ◽  
Xianfei Ding ◽  
Huoyan Liang ◽  
Xiaojuan Zhang ◽  
Shaohua liu ◽  
...  

Abstract 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 1,266 animals, were identified. None of the studies were 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 hour, OR=0.24, 95% CI 0.13–0.45, P<0.001; 1 hour, 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.


Biology ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 230
Author(s):  
Louis D. V. Johnson ◽  
Mark R. Pickard ◽  
William E. B. Johnson

Animal models have been used in preclinical research to examine potential new treatments for spinal cord injury (SCI), including mesenchymal stem cell (MSC) transplantation. MSC transplants have been studied in early human trials. Whether the animal models represent the human studies is unclear. This systematic review and meta-analysis has examined the effects of MSC transplants in human and animal studies. Following searches of PubMed, Clinical Trials and the Cochrane Library, published papers were screened, and data were extracted and analysed. MSC transplantation was associated with significantly improved motor and sensory function in humans, and significantly increased locomotor function in animals. However, there are discrepancies between the studies of human participants and animal models, including timing of MSC transplant post-injury and source of MSCs. Additionally, difficulty in the comparison of functional outcome measures across species limits the predictive nature of the animal research. These findings have been summarised, and recommendations for further research are discussed to better enable the translation of animal models to MSC-based human clinical therapy.


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Mostafa K Fouad ◽  
Ashraf M Hazem ◽  
Kareem M Elnaghy

Abstract Aim of the Work to provide cumulative data about the efficacy and safety of neuro-muscular electrical stimulation (NMES) combined with usual care (UC) versus usual care alone in ICU patients with Critical Illness Myopathy (CIM). Methodology The current systematic review was done on studies published between 2009 and 2019. The total number of patients in all the included studies was 1259 patients; 652 in NMES group, and 607 in UC group. Our data were divided into two groups: NMES (652 patients), and UC (607 patients). Metaanalysis study was done on 11 studies which described and compared the 2 different techniques for treatment of CIM; with overall number of patients (N = 1259). Results Regarding 1ry outcome measures, we found 8 studies reported critical Critical illness myopathy (CIM), critical illness polyneuropathy (CIP), and the overlap, critical care setting   MRC scale for muscle strength, with total number of patients (N = 968). The random-effects model of the meta-analysis study showed non-significant difference in mean MRC scale in NMES group compared to usual care group (p &gt; 0.05). We also found 11 studies reported ICU stay with total number of patients (N = 1259). The random-effects model of the meta-analysis study showed nonsignificant difference in mean ICU stay in NMES group compared to usual care group (p &gt; 0.05). We also found only 2 studies reported SF-36 scale for quality of life, with total number of patients (N = 270). The fixed-effects model of the metaanalysis study showed highly significant decrease in mean SF-36 scale in NMES group compared to usual care group (p = 0.003). Regarding 2ry outcome measure, we found 3 studies reported CIM incidence with total number of patients (N = 394). The fixed-effects model of the meta-analysis study showed marked decrease in CIM incidence in NMES group compared to usual care group, but not reaching statistical significance (p &gt; 0.05). We also found 9 studies reported mortality rate with total number of patients (N = 1044). The fixed-effects model of the meta-analysis study showed non-significant difference in mortality rate in NMES group compared to usual care. Our systematic review and meta-analysis showed that NMES combined with usual care was not associated with significant differences in global muscle strength, ICU stay, quality of life score, CIM incidence and mortality rate in comparison with usual care alone in critically ill patients. Conclusion NMES is not superior to usual care in management of CIM. Usual care remains the mainstay of management of CIM with significant better outcomes, in addition to preventive measures as early aggressive treatment of sepsis and MOF, blood glucose control, optimizing certain drugs use, early enteral nutrition, maintaining water, electrolyte and acidbase balance.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10859
Author(s):  
Lili Qin ◽  
Yueqi Wang ◽  
Na Yang ◽  
Yangyu Zhang ◽  
Tianye Zhao ◽  
...  

Background Tissue inhibitor of metalloproteinase 1 (TIMP-1) has recently been shown to be dependent on or independent of Matrix metalloproteinases (MMPs) in its roles in tumorigenesis and progression. This appreciation has prompted various studies assessing the prognostic value of TIMP-1 in patients with gastrointestinal cancer, however, the conclusions were still inconsistent. The aim of this study was to assess the prognostic value of TIMP-1-immunohistochemistry (IHC) staining and pretreatment serum/plasma TIMP-1 level in gastrointestinal cancer survival as well as the association between TIMP-1 and clinicopathologic features. Methods The meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO; Registration NO. CRD42020185407) and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. A highly sensitive literature search was performed in electronic databases including PubMed, EMBASE and the Cochrane Library. Heterogeneity analysis was conducted using both chi-square-based Q statistics and the I2 test. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to assess the prognostic value of TIMP-1 using the fixed-effects model. Odds ratios (ORs) with 95% CIs were calculated to evaluate the associations between TIMP-1 and clinicopathological characteristics. The meta-analysis was conducted using STATA 12.0 software. Results A total of 3,958 patients from twenty-two studies were included in the meta-analysis. Elevated TIMP-1 levels were significantly associated with poor survival in gastrointestinal cancer (TIMP-1-IHC staining: HR = 2.04, 95% CI [1.59–2.61], I2 = 35.7%, PQ = 0.156; pretreatment serum/plasma TIMP-1 levels: HR = 2.02, 95% CI [1.80–2.28], I2 = 0%, PQ = 0.630). Moreover, clinicopathological parameter data analysis showed that elevated TIMP-1 levels were significantly associated with lymph node metastasis (N1/N2/N3 vs N0: OR = 2.92, 95% CI [1.95–4.38]) and higher TNM stages (III/IV vs I/II: OR = 2.73, 95% CI [1.23–6.04]). Conclusion Both TIMP-1-positive IHC staining and high serum/plasma TIMP-1 levels are poor prognostic factors for the survival of gastrointestinal cancer. In addition, TIMP-1 overexpression was correlated with more advanced clinicopathological features.


2017 ◽  
Vol 45 (2) ◽  
pp. 399-406 ◽  
Author(s):  
Chengmao Zhou ◽  
Yu Zhu ◽  
Zhen Liu ◽  
Lin Ruan

Objective To investigate the effect of pretreatment with midazolam on myoclonus induced by etomidate injection. Methods A meta-analysis was performed using Review Manager software, version 5.2. Two researchers independently searched PubMed, Cochrane Library, and Embase® databases for randomized controlled trials involving patients who underwent etomidate induced general anaesthesia with or without midazolam pretreatment, published between 1990 and 2016. Outcome measures comprised overall myoclonus incidence rate and incidence rate classified by degree of myoclonus following etomidate injection. Data were assessed using a fixed effects model. Results Five studies, comprising 302 patients, were included for analysis. Overall incidence rate of etomidate injection-induced myoclonus was significantly lower in the pooled midazolam group versus controls (relative risk [RR] 0.34, 95% confidence interval [CI] 0.26, 0.44); Results subgrouped by degree of myoclonus showed significantly lower incidence in midazolam groups versus control groups for mild myoclonus (RR 0.56, 95% CI 0.39, 0.80); moderate myoclonus (RR 0.20, 95% CI 0.10, 0.41); and severe myoclonus (RR 0.12, 95% CI 0.04, 0.39). Conclusion Midazolam can effectively prevent etomidate-induced myoclonus, and alleviate the degree of etomidate-induced myoclonus.


2020 ◽  
Author(s):  
He Wang ◽  
Chunyang Chen ◽  
Weijie Zhang ◽  
Keke Ding ◽  
Jianquan Hou

Abstract Background: A growing number of researches suggests that microRNAs (miRNAs) as oncogene or tumor suppressor genes play a fundamental role in various kinds of cancers. Among them, miR-24-3p, as a star molecule, is widely studied. However, the prognostic value of miR-24-3p is unclear and controversial. We conducted this meta-analysis to evaluate the prognostic value of miR-24-3p in a variety of cancers by integrated existing articles from four databasesMethods: PubMed, Embase, Web of Science, and Cochrane Library (last update in March 2020) were searched for approach literature. Hazard ratios (HRs) and odds ratios (ORs) were used to evaluate the association between miR-24-3p expression levels and prognostic value or clinicopathological characteristics, respectively.Results: A total of 15 studies from 14 literature were finally qualified and concluded in the present meta-analysis. A significantly worse overall survival was observed in higher expression of miR-24-3p cancer group for OS(Overall survival) of log rank tests and cox multivariate regression by fixed effects model. Also, we found a significant correlation between elevated miR-24-3p levels to RFS (Recurrence-free survival) and DFS(Disease free survival). In addition, the pooled odds ratios (ORs) showed that evaluated miR-24-3p was also associated with the larger tumor size (≥5cm) and advanced TNM stage (Ⅲ and Ⅳ).Conclusion: Built on the above findings, elevated expression levels of miR-24-3p may serve as a promising biomarker used to predict the worse prognosis of cancer patients.


2019 ◽  
Vol 121 (8) ◽  
pp. 841-848 ◽  
Author(s):  
Shuo Zhang ◽  
Fengxiao Zhang ◽  
Meng Du ◽  
Kun Huang ◽  
Cheng Wang

AbstractFe therapy can be effective in heart failure patients both with and without anaemia. However, the role of Fe therapy in such patients is still uncertain. In this review, the aim was to evaluate the efficacy and safety of Fe therapy in adult patients with heart failure who have reduced ejection fraction (HFrEF). Multiple databases (PubMed, Medline, EMBASE, the Cochrane Library and Clinical Trials) were searched up to December 2017 and the reference lists of relevant articles obtained from the search were reviewed. Data extracted from randomised control trials (RCT) selected for the review were pooled using a fixed effects model or a random effects model, according to heterogeneity between trials. Nine RCT were included in this meta-analysis which included a total of 789 patients who received Fe therapy and who in turn were compared with 585 controls. There was significant improvement in the 6-min walk test (19·05 m, 95 % CI 10·48, 27·62) and peak VO2/kg (0·93 ml/kg per min, 95 % CI 0·16, 1·69) in the Fe supplementation arm. With Fe therapy, fewer patients were hospitalised for heart failure (OR: 0·42, 95 % CI 0·27, 0·65), but no relationship was found for total re-hospitalisation (OR: 0·70, 95 % CI 0·32, 1·51) or mortality (OR: 0·70, 95 % CI 0·38, 1·28). Fe therapy has the potential to improve exercise tolerance, reduce re-hospitalisations for patients with HFrEF having Fe deficiency. In addition, Fe supplementation was found to be safe, with no increased rate of adverse events.


2021 ◽  
Vol 11 ◽  
Author(s):  
Liwei Lv ◽  
Xuefei Sun ◽  
Yuchen Wu ◽  
Qu Cui ◽  
Yuedan Chen ◽  
...  

BackgroundCentral nervous system lymphoma (CNSL) is an aggressive lymphoma. Studies investigating primary CNSL determined that the Bruton tyrosine kinase (BTK) played an important role in pathogenesis. Ibrutinib, an oral BTK inhibitor, is a new treatment strategy for CNSL. The purpose of this meta-analysis was to clarify the effectiveness and safety of ibrutinib in the treatment of CNSL.MethodsA systematic search of PubMed, Embase, Cochrane library, Wanfang Data Knowledge Service Platform, and China National Knowledge Infrastructure databases was conducted through to 31 October 2019. Studies involving patients with CNSL who received ibrutinib that reported the overall response (OR), complete remission (CR), and partial response (PR) were included. The random-effects or fixed-effects model with double arcsine transformation was used for the pooled rates and 95% confidence intervals (CI) were determined for all outcomes.ResultsEight studies including 162 patients were identified and included in the meta-analysis. The pooled OR rate after treatment with ibrutinib was 69% (95% CI, 61–79%, I2 = 47.57%, p = 0.06), while the pooled CR and PR was 52% (95% CI, 35–68%, I2 = 74.95%, p = 0.00) and 17% (95% CI, 7–30%, I2 = 67.85%, p = 0.00), respectively. Among PCNSL patients, including new diagnoses PCNSL and R/R PCNSL, the pooled OR rate was 72% (95% CI, 63–80%, I2 = 49.20%, p = 0.06) while the pooled CR and PR rates were 53% (95% CI, 33–73%, I2 = 75.04%, p = 0.00) and 22% (95% CI, 14–30%, I2 = 46.30%, p = 0.07), respectively. Common adverse events above grade 3 included cytopenia and infections.ConclusionsThe ibrutinib-containing therapy was well tolerated and offered incremental benefit to patients with CNSL. However, randomized-controlled studies that directly compare efficacy and adverse events of ibrutinib are still needed.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42020218974.


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