ABSTRACT
Introduction: Exosomes function as cell signaling carriers and have drawn much attention to the cell-free treatments of regenerative medicine. This meta-analysis aimed to investigate the efficacy of mesenchymal stem cell-derived (MSC-derived) exosomes in animal models of spinal cord injuries (SCI). Method: A comprehensive search was conducted in Medline, Embase, Scopus, and Web of Science to attain related articles published by January 31, 2023. The eligible keywords were correlated with the spinal cord injury and MSC-derived exosomes. The evaluated outcomes were locomotion, cavity size, cell apoptosis, inflammation, neuro-regeneration, and microglia activation. A standardized mean difference was calculated for each sample and a pooled effect size was reported. Results: 65 papers fully met the inclusion criteria. Treatment with MSC-derived exosomes ultimately improved locomotion and shrunk cavity size (p<0.0001). The administration of MSC-derived exosomes enhanced the expression of beta-tubulin III, NF200, and GAP-43, and increased the number of NeuN-positive and Nissl-positive cells, while reducing the expression of glial fibrillary acidic protein (p<0.0001). The number of apoptotic cells in the treatment group decreased significantly (p<0.0001). Regarding the markers of microglia activation, MSC-derived exosomes increased the number of CD206- and CD68-positive cells (p=0.032 and p<0.0001, respectively). Additionally, MSC-derived exosome administration significantly increased the expression of the anti-inflammatory interleukin (IL)-10 and IL-4 (p<0.001 and p=0.001, respectively) and decreased the expression of the inflammatory IL-1b, IL-6, and TNF-a (p<0.0001). Conclusion: MSC-derived exosome treatment resulted in a significantly improved locomotion of SCI animals through ameliorating neuroinflammation, reducing apoptosis, and inducing neuronal regrowth by facilitating a desirable microenvironment.
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Introduction: Large vessel occlusion (LVO) strokes are associated with worse functional outcomes and higher mortality rates. In the present systematic review and meta-analysis, we evaluated the diagnostic yield of the Cincinnati Prehospital Stroke Scale (CPSS) in detecting LVO. Methods: We performed an extensive systematic search among online databases including Medline, Embase, Web of Science, and Scopus, until July 31st, 2023. We also conducted a manual search on Google and Google scholar, along with citation tracking to supplement the systematic search in retrieving all studies that evaluated the diagnostic accuracy of the CPSS in detecting LVO among patients suspected to stroke. Results: Fourteen studies were included in the present meta-analysis. CPSS showed the sensitivity of 97% (95% CI: 87%-99%) and the specificity of 17% (95% CI: 4%-54%) at the cut-off point of ≥1. The optimal threshold was determined to be ≥2, with a sensitivity of 82% (95% CI: 74%-88%) and specificity of 62% (95% CI: 48%-74%) in detecting LVO. At the highest cut-off point of ≥3, the CPSS had the lowest sensitivity of 60% (95% CI: 51%-69%) and the highest specificity of 81% (95% CI: 71%-88%). Sensitivity analyses showed the robustness of the results regardless of study population, inclusion of hemorrhagic stroke patients, pre-hospital or in-hospital settings, and the definition of LVO. Conclusion: A very low level of evidence demonstrated that CPSS, with a threshold set at ≥2, is a useful tool for identifying LVO stroke and directing patients to CSCs, both in prehospital and in-hospital settings.
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OBJECTIVE: The objective of this systematic review and meta-analysis was to assess the efficacy of exercise in neuropathic pain following traumatic spinal cord injuries. METHODS: The search was conducted in MEDLINE, Embase, Scopus, and Web of Science by the end of 2022. Two independent researchers included the articles based on the inclusion and exclusion criteria. A standardized mean difference was calculated for each data and they were pooled to calculate an overall effect size. To assess the heterogeneity between studies, I2 and chi-square tests were utilized. In the case of heterogeneity, meta-regression was performed to identify the potential source. RESULTS: Fifteen preclinical studies were included. Meta-analysis demonstrated that exercise significantly improves mechanical allodynia (standardized mean difference [SMD], -1.59; 95% confidence interval [CI], -2.16 to -1.02; p < 0.001; I2 = 90.37%), thermal hyperalgesia (SMD, 1.95; 95% CI, 0.96-2.94; p < 0.001), and cold allodynia (SMD, -2.92; 95% CI, -4.4 to -1.43; p < 0.001). The improvement in mechanical allodynia is significantly more in animals with a compression model of SCI (meta-regression coefficient, -1.33; 95% CI, -1.84 to -0.57; p < 0.001) and in mild SCI (p < 0.001). Additionally, the improvement was more prominent if the training was started 7 to 8 days postinjury (coefficient, -2.54; 95% CI, -3.85 to -1.23; p < 0.001) and was continued every day (coefficient, -1.99; 95% CI, -3.07 to -0.9; p < 0.001). Likewise, voluntary exercise demonstrated a significantly more effect size (coefficient, -1.45; 95% CI, -2.67 to -0.23; p = 0.02). CONCLUSION: Exercise is effective in the amelioration of neuropathic pain. This effect in mechanical allodynia is more prominent if voluntary, continuous training is initiated in the subacute phase of mild SCI.
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Background: : Muscimol's quick onset and GABAergic properties make it a promising candidate for the treatment of pain. This systematic review and meta-analysis of preclinical studies aimed at summarizing the evidence regarding the efficacy of muscimol administration in the amelioration of nerve injury-related neuropathic pain. Methods: : Two independent researchers performed the screening process in Medline, Embase, Scopus and Web of Science extracting data were extracted into a checklist designed according to the PRISMA guideline. A standardized mean difference (SMD [95% confidence interval]) was calculated for each. To assess the heterogeneity between studies, I2 and chi-square tests were utilized. In the case of heterogeneity, meta-regression and subgroup analyses were performed to identify the potential source. Results: : Twenty-two articles met the inclusion criteria. Pooled data analysis showed that the administration of muscimol during the peak effect causes a significant reduction in mechanical allodynia (SMD = 1.78 [1.45-2.11]; P < 0.0001; I2 = 72.70%), mechanical hyperalgesia (SMD = 1.62 [1.28-1.96]; P < 0.0001; I2 = 40.66%), and thermal hyperalgesia (SMD = 2.59 [1.79-3.39]; P < 0.0001; I2 = 80.33%). This significant amendment of pain was observed at a declining rate from 15 minutes to at least 180 minutes post-treatment in mechanical allodynia and mechanical hyperalgesia, and up to 30 minutes in thermal hyperalgesia (P < 0 .0001). Conclusions: : Muscimol is effective in the amelioration of mechanical allodynia, mechanical hyperalgesia, and thermal hyperalgesia, exerting its analgesic effects 15 minutes after administration for up to at least 3 hours.
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Introduction: Several scoring systems have been proposed to predict the outcomes of patients with ischemic heart disease. Global Registry of Acute Coronary Events (GRACE) and History, ECG, Age, Risk Factors, and Troponin (HEART) scores are two of the more widely used risk prediction tools in patients with acute coronary syndrome (ACS). The present systematic review and meta-analysis aimed to compare the value of GRACE and HEART scores in the outcome prediction of ACS patient. Method: The online databases of Medline, Embase, Web of Science, and Scopus were search until September 2022 for articles directly comparing GRACE and HEART scores value in prediction of outcome in patients with ACS. GRACE score cut-offs were categorized into two groups of less than and equal to 100 and more than 100, and HEART score cut-offs were categorized into three groups of less than 4, equal to 4, and more than 4. Investigated outcomes were major adverse cardiovascular events (MACE), acute myocardial infraction (AMI) and all-cause mortality. Results: 25 articles were included. The sensitivity and specificity of the GRACE score for prediction of MACE were 0.96 and 0.26 for cut-offs of ≤ 100, and 0.58 and 0.69 for cut-offs of >100, respectively. The sensitivity and specificity of the HEART score for prediction of MACE were 0.99 and 0.16 for cut-offs less than 4, 0.93 and 0.47 for equal to 4, and 0.77 and 0.78 for cut-offs greater than 4. GRACE score was shown to be predictive of AMI with sensitivity and specificity of 0.95 and 0.29, respectively. The analysis for the value of HEART score in the prediction of AMI a sensitivity and specificity of 0.94 and 0.48, respectively. The risk scores were not found to be suitable predictors of all-cause mortality. Conclusion: The results demonstrated the low specificity of GRACE and HEART scores in predicting the MACE, AMI and all-cause mortality, irrespective of the utilized cut-off. Considering the acceptable sensitivity of two scores in predicting the MACE and AMI, these scores were more suitable to be used as a rule-out tool for identification of ACS patients with low risk of developing adverse outcomes.