Combined application of neural stem/progenitor cells and scaffolds on locomotion recovery following spinal cord injury in rodents: a systematic review and meta-analysis.

BACKGROUND: This present study evaluates the pre-clinical evidence on the efficacy of NS/PC and scaffold (NS/PC + scaffold) transplantation on locomotor recovery after traumatic spinal cord injury (SCI). METHOD: Two independent reviewers screened the records gathered through a systematic search in MEDLINE, Embase, Scopus, and Web of Sciences databases. Studies on rats/mice evaluating the efficacy of simultaneous transplantation of NS/PCs and scaffold in the treatment of SCI were included. The results were reported as standardized mean difference (SMD) and 95% confidence interval (95% CI). RESULTS: Forty-seven articles were retrieved. Analyses showed that NS/PC + scaffold transplantation significantly improved locomotion in animals with SCI compared to that of the non-treatment group (SMD = 2.71, 95% CI: 1.89 to 3.54; I2 = 95.15%, p < 0.0001), scaffold alone (SMD = 2.28; 95% CI: 1.56 to 3.00; I2 = 94.38%; p < 0.0001), and NS/PCs alone (SMD = 1.74, 95% CI: 0.64 to 2.83; I2 = 92.02%, p < 0.0001). Moreover, the effectiveness of the treatment significantly increases when PLGA-based scaffolds and antibiotics are used. In addition, the NS/PC + scaffold transplantation during the first week after injury led to a significant improvement in locomotion, while concomitant transplantation of NS/PC + scaffold did not improve locomotion in cervical lesions. CONCLUSION: The findings showed that using NS/PCs with scaffold not only improves locomotion recovery, but also is superior to NS/PCs alone and scaffold alone. Future experiments and translational clinical studies are recommended to focus on the assessment of the safety and efficacy of the application of NS/PC + scaffold on SCI recovery.

Growth Factor Gene-Modified Cells in Spinal Cord Injury Recovery: A Systematic Review.

BACKGROUND: Numerous preclinical studies have been performed in recent years on the effects of the administration of growth factor gene-modified cells in spinal cord injury (SCI). However, findings of these studies are contradictory. OBJECTIVE: The present study aims to conduct a systematic review and meta-analysis of animal studies evaluating the effects of administration of growth factor gene-modified cells on locomotion recovery after SCI. METHODS: A search of the MEDLINE, Embase, Scopus, and Web of Science databases was conducted, including all animal studies until the end of 2020. Two researchers screened search results, summarized relevant studies and assessed risk of bias, independently. RESULTS: Thirty-three studies were included in the final analysis. Transplantation of growth factor gene-modified cells in the injured spinal cord resulted in a significant improvement in locomotion of animals compared with nontreated animals (standardized mean difference = 1.86; 95% confidence interval, 1.39-2.33; P < 0.0001)] and non-genetically modified cell-treated animals (standardized mean difference = 1.30; 95% confidence interval, 0.80-1.79; P < 0.0001). Transplantation efficacy of these cells failed to achieve significance in moderate lesions (P = 0.091), when using modified neural stem/progenitor cells (P = 0.164), when using synthetic neurotrophins (P = 0.086) and when the number of transplanted cells was less than 1.0 × 105 cells per animal (P = 0.119). CONCLUSIONS: The results showed that transplantation of growth factor gene- modified cells significantly improved locomotion in SCI animal models. However, there is a major concern regarding the safety of transplantation of genetically modified cells, in terms of overexpressing growth factors. Further studies are needed before any effort to perform a translational and clinical study.

Carotid intima-media thickness measurements in patients with multiple sclerosis.

OBJECTIVES: The goal of this study was to evaluate the mean carotid intima-media thickness (CIMT) in patients with Multiple Sclerosis (MS). METHODS: In this cross-sectional study, 100 patients with MS were enrolled. Carotid intima-media thickness was measured by Doppler Ultrasonography. The mean CIMT was then compared between different groups of sex, age, body mass index (BMI), medications, and site of the MS plaques in the brain and cervical MRI. In addition, disease duration, annual relapse rate, and Expanded Disability Status Scale (EDSS) were compared between high and normal CIMT groups. RESULTS: Among 100 patients, Sixty-two percent of the patients were female. The mean age was 35.95 ± 9.32 years. Mean CIMT was 0.38 ± 0.2 mm, and 22% of the patients had abnormal CIMT measures. CIMT was significantly associated with higher age (P = 0.01) and prolonged disease duration (P < 0.001). CIMT was not associated with other disease factors or types of the disease-modifying drug (P > 0.05). CONCLUSION: Multiple Sclerosis might be associated with carotid atherosclerotic vascular disease.

The value of interleukin levels in the diagnosis of febrile urinary tract infections in children and adolescents; a systematic review and meta-analysis.

INTRODUCTION: In recent years, researchers have been looking for tools and biomarkers to identify urinary tract infections (UTI) in children. Since there exists no systematic reviews and meta-analyses on the matter, the present study intends to determine the diagnostic value of serum and urinary levels of interleukins (IL) in the diagnosis of febrile UTI in children and adolescents. METHODS: Medline, Embase, Scopus, and Web of Science were searched until the end of 2020, using keywords related to UTI and serum and urinary ILs. Two independent researchers included relevant studies and summarized the data. Analyzed data were reported as standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS: Data from 23 articles were included in the present study. Analyses showed that IL-6, IL-8, IL 1 beta and IL-1 alpha urinary levels are significantly higher in children with UTI than that of other children. Moreover, serum levels of IL-6 and IL-8 in children with UTI were significantly higher than that of healthy children. However, IL-6 and IL-8 serum levels were not significantly different between children with UTI and non-UTI febrile group. Finally, the area under the curve of urinary IL-6 and IL-8 and serum IL-8 levels in the diagnosis of pediatric UTIs were 0.89 (95% CI: 0.86, 0.92), 0.95 (95% CI: 0.92, 0.96) and 0.80 (95% CI: 0.77, 0.84), respectively. CONCLUSION: The findings of the present study showed that the diagnostic utility of ILs 8 and 6 urinary levels is most desirable in the detection of febrile UTIs from other febrile conditions in children and adolescents, in comparison with the diagnostic utility of other ILs' urinary and serum levels in the detection of febrile UTI. However, even after nearly 3 decades of research on these biomarkers, their optimal cut-off points in diagnosing pediatric UTIs are still to be determined in further studies.

Assessing the value of serum and urinary interleukins for diagnosis of acute kidney injury in children and adolescents: A systematic review and meta-analysis.

INTRODUCTION: Several studies have questioned the diagnostic utility of interleukins (IL) in detecting acute kidney injury (AKI) in pediatric population. Therefore, the present systematic review and meta-analysis aims to assess the diagnostic value of ILs in pediatric AKI patients. METHOD: Two independent researchers screened records acquired through searching in Medline, Embase, Scopus, and Web of Science, until the end of 2020. Articles evaluating serum and urinary levels of ILs in AKI patients were included in this study. Data were extracted and analyzed using STATA software. RESULTS: Twenty-one studies were included. Analyses showed that AUC, sensitivity, specificity and diagnostic odds ratio of urinary IL-18 for diagnosing AKI were 0.77 (95% CI: 0.74, 0.81), 0.64 (95% CI: 0.32, 0.87), 0.75 (95% CI: 0.62, 0.85) and 6 (95% CI: 1, 23), respectively. Those values were 0.79 (95% CI: 0.75, 0.83), 0.58 (95% CI: 0.37, 0.76), 0.87 (95% CI: 0.66, 0.96), and 9 (95% CI: 4, 20) for serum IL-6, and 0.72 (95% CI: 0.68, 0.76), 0.53 (95% CI: 0.34, 0.72), 0.79 (95% CI: 0.60, 0.91) and 4 (95% CI: 2, 8) for serum IL-8, respectively. Urinary levels of ILs 6, 8 and 10 were not significantly different between AKI patients and the non-AKI control group. Serum levels of ILs 10 and 18 were not adequately evaluated in the studies. CONCLUSION: IL-18 urinary levels and IL-6 and IL-8 serum levels are significantly higher in AKI patients compared to the non-AKI group. However, their low sensitivity and specificity in detecting AKI questions their diagnostic value.

Contrast-enhanced voiding urosonography, a possible candidate for the diagnosis of vesicoureteral reflux in children and adolescents; a systematic review and meta-analysis.

INTRODUCTION: The diagnostic value of contrast-enhanced voiding urosonography (ceVUS) in the diagnosis of vesicoureteral reflux (VUR) is still a subject of dispute. OBJECTIVE: Assessing the diagnostic value of ceVUS in VUR, performing a systematic review and meta-analysis. METHODS: An extensive search on Medline, Embase, Scopus and Web of Science databases was conducted by the end of 2020. The inclusion criteria were studies on the diagnostic value of ceVUS for VUR. Two independent researchers summarized the included articles and the findings were reported as area under the curve (AUC), sensitivity and specificity with a 95% confidence interval (95% CI). RESULTS: Finally, the data of 36 articles were included in the present meta-analysis (2768 children). The VUS assessment showed that 1297 of the cases were true positives, 3661 were true negatives, 398 were false positives and 169 were false negatives. The AUC, sensitivity and specificity of ceVUS with the first-generation contrast agent in the diagnosis of VUR in children and adolescents were obtained as 0.97 (95% CI: 0.95, 0.98), 0.92 (95% CI: 0.86, 0.96) and 0.94 (95% CI: 0.95, 0.98), respectively. Moreover, AUC, sensitivity and specificity of ceVUS with the second-generation contrast agent were 0.97 (95% CI: 0.95, 0.98), 0.93 (95% CI: 0.86, 0.97) and 0.91 (95% CI: 0.86, 0.95). CONCLUSION: The findings of the present study showed that diagnostic value of ceVUS with both first-generation and second-generation contrast agents for VUR, is in an excellent range. Although it seems that ceVUS may be applied as a radiation-free alternative to imaging techniques such as VCUG, the presence of 3% of false negatives in this test is a limitation. Since the lack of punctual management of VUR is associated with serious renal complications in children, future studies are recommended to be focused on the evaluation of the Benefit-risk evaluation of ceVUS.

Active and Passive Immunization with Myelin Basic Protein as a Method for Early Treatment of Traumatic Spinal Cord Injury; a Meta-Analysis.

INTRODUCTION: Traumatic spinal cord injury (SCI), as a dangerous central nervous system damage, continues to threaten communities by imposing various disabilities and costs. Early adjustment of the immune system response using Myelin Basic Protein (MBP) immunization may prevent the SCI-related secondary damages. As a result, the current study is designed to review and analyse the evidence on active and passive immunization with MBP for treatment of traumatic SCI. METHODS: Medline, Embase, Scopus, and Web of Science databases were systematically searched until the end of 2020. Criteria for inclusion in the current study included pre-clinical studies, which performed passive (injection of MBP-activated T cells) or active (administration of MBP or MBP-modified peptides) immunization with MBP after traumatic SCI. Exclusion criteria was defined as lack of a non-treated SCI group, lack of evaluation of locomotion, review studies, and combination therapy. Finally, analyses were conducted using STATA software, and a standardized mean difference (SMD) with a 95% confidence interval (CI) were reported. RESULTS: Data from 17 papers were included in the present study. Finally, analysis of these data showed that passive immunization (SMD=0.87; 95%CI: 0.19-1.55; p=0.012) and active immunization (SMD=2.08, 95%CI: 1.42-2.73; p<0.001) for/with MBP both have good efficacy in improving locomotion following traumatic SCI. However, significant heterogeneity was observed in both of them. The most important sources of heterogeneity in active immunization were differences in SCI models, route of administration, time interval between SCI and transplantation, and type of vaccine used. In passive immunization, however, these sources were the model of SCI and the time interval between SCI and transplantation. Although, there was substantial heterogeneity among studies, subgroup analysis showed that active immunization improved locomotion after traumatic SCI in all tested conditions (with differences in injury model, severity of injury, method of administration, different time interval between SCI to vaccination, etc.). CONCLUSION: The results of the present study demonstrated that immunization with MBP, especially in its active form, could significantly improve motor function following SCI in rats and mice. Therefore, it could be considered as a potential treatment in acute settings such as emergency departments. However, the safety of this method is still under debate. Therefore, it is recommended for future research to focus on the investigation of safety of MBP immunization in animal studies, before conducting human clinical trials.

The Value of Physiological Scoring Criteria in Predicting the In-Hospital Mortality of Acute Patients; a Systematic Review and Meta-Analysis.

INTRODUCTION: There is no comprehensive meta-analysis on the value of physiological scoring systems in predicting the mortality of critically ill patients. Therefore, the present study intended to conduct a systematic review and meta-analysis to collect the available clinical evidence on the value of physiological scoring systems in predicting the in-hospital mortality of acute patients. METHOD: An extensive search was performed on Medline, Embase, Scopus, and Web of Science databases until the end of year 2020. Physiological models included Rapid Acute Physiology Score (RAPS), Rapid Emergency Medicine Score (REMS), modified REMS (mREMS), and Worthing Physiological Score (WPS). Finally, the data were summarized and the findings were presented as summary receiver operating characteristics (SROC), sensitivity, specificity and diagnostic odds ratio (DOR). RESULTS: Data from 25 articles were included. The overall analysis showed that the area under the SROC curve of REMS, RAPS, mREMS, and WPS criteria were 0.83 (95% CI: 0.79-0.86), 0.89 (95% CI: 0.86-0.92), 0.64 (95% CI: 0.60-0.68) and 0.86 (95% CI: 0.83-0.89), respectively. DOR for REMS, RAPS, mREMS and WPS models were 11 (95% CI: 8-16), 13 (95% CI: 4-41), 2 (95% CI: 2-4) and 17 (95% CI: 5-59) respectively. When analyses were limited to trauma patients, the DOR of the REMS and RAPS models were 112 and 431, respectively. Due to the lack of sufficient studies, it was not possible to limit the analyses for mREMS and WPS. CONCLUSION: The findings of the present study showed that three models of RAPS, REMS and WPS have a high predictive value for in-hospital mortality. In addition, the value of these models in trauma patients is much higher than other patient settings.

Efficacy of adipose tissue-derived stem cells in locomotion recovery after spinal cord injury: a systematic review and meta-analysis on animal studies.

BACKGROUND: Considerable disparities exist on the use of adipose tissue-derived stem cells (ADSCs) for treatment of spinal cord injury (SCI). Hence, the current systematic review aimed to investigate the efficacy of ADSCs in locomotion recovery following SCI in animal models. METHODS: A search was conducted in electronic databases of MEDLINE, Embase, Scopus, and Web of Science until the end of July 2019. Reference and citation tracking and searching Google and Google Scholar search engines were performed to achieve more studies. Animal studies conducted on rats having SCI which were treated with ADSCs were included in the study. Exclusion criteria were lacking a non-treated control group, not evaluating locomotion, non-rat studies, not reporting the number of transplanted cells, not reporting isolation and preparation methods of stem cells, review articles, combination therapy, use of genetically modified ADSCs, use of induced pluripotent ADSCs, and human trials. Risk of bias was assessed using Hasannejad et al.'s proposed method for quality control of SCI-animal studies. Data were analyzed in STATA 14.0 software, and based on a random effect model, pooled standardized mean difference with a 95% confidence interval was presented. RESULTS: Of 588 non-duplicated papers, data from 18 articles were included. Overall risk of bias was high risk in 8 studies, some concern in 9 studies and low risk in 1 study. Current evidence demonstrated that ADSCs transplantation could improve locomotion following SCI (standardized mean difference = 1.71; 95%CI 1.29-2.13; p < 0.0001). A considerable heterogeneity was observed between the studies (I2 = 72.0%; p < 0.0001). Subgroup analysis and meta-regression revealed that most of the factors like injury model, the severity of SCI, treatment phase, injury location, and number of transplanted cells did not have a significant effect on the efficacy of ADSCs in improving locomotion following SCI (pfor odds ratios > 0.05). CONCLUSION: We conclude that any number of ADSCs by any prescription routes can improve locomotion recovery in an SCI animal model, at any phase of SCI, with any severity. Given the remarkable bias about blinding, clinical translation of the present results is tough, because in addition to the complexity of the nervous system and the involvement of far more complex motor circuits in the human, blinding compliance and motor outcome assessment tests in animal studies and clinical trials are significantly different.

The Efficacy of Ketamine Administration in Prehospital Pain Management of Trauma Patients; a Systematic Review and Meta-Analysis.

INTRODUCTION: Although previous articles and reviews suggest that ketamine might effectively manage pain in trauma patients, these articles have serious limitations. Accordingly, the current meta-analysis aims to investigate the efficacy of ketamine administration in prehospital pain management of trauma patients. METHOD: In the present meta-analysis, controlled human studies were included. An extensive search was conducted in electronic databases including Medline (via PubMed), Embase, Central, Scopus, Web of Science, and ProQuest, gathering data to the end of 2018. The efficacy and side effects of ketamine administration in pre-hospital pain management were compared with those of opioid analgesics based on standard mean difference (SMD) and odds ratio (OR) calculations with 95% confidence interval (95% CI). RESULTS: Data from seven articles were included in the present meta-analysis. Ketamine administration was not more effective than administrating morphine or fentanyl in prehospital pain management of trauma patients (SMD = -0.56, 95% CI: -1.38 to 0.26, p = 0.117). However, co-administration of ketamine+morphine was considerably more effective than ketamine alone, in alleviating pain in prehospital settings (SMD = -0.62, 95% CI: -1.12 to -0.12, p = 0.010). Finally, it was concluded that ketamine alone had less side effects than morphine alone (OR = 0.25, 95% CI: 0.11 to 0.56, p = 0.001). However, co-administration of ketamine+morphine increases the risk of side effects to 3.68 times compared to when morphine is prescribed solely (OR=3.68, 95% CI: 1.99 to 6.82, p<0.001). CONCLUSION: For the first time, findings of the current meta-analysis demonstrated that ketamine, being administered alone, is an effective and safe medication in prehospital pain management in trauma patients, and can be considered as an acceptable alternative to opioid analgesics.