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.

The association between apolipoprotein A-1 plasma level and premature coronary artery disease: A systematic review and meta-analysis.

BACKGROUND: Apolipoprotein A-1 (Apo A-1) is a constituent of high-density lipoprotein (HDL) and emerging evidences put forward a potential association between Apo A-1 plasma levels and premature coronary artery disease (pCAD). The aim of the present study is to gather relative literature and perform a systematic review and meta-analysis regarding the association between serum ApoA-1 levels and pCAD. METHODS: Medline (via PubMed), Scopus, Embase and Web of Science databases were searched from the inception of databases until December 7, 2020. All articles reporting the plasma levels of ApoA-1 in patients with pCAD and the control group were included. A meta-analysis with pooled standardised mean difference (SMD) and 95% confidence interval (95% CI) was reported. Subgroup analyses were done based on the observed heterogeneity in results. RESULTS: Seventeen case-control studies were included. ApoA-1 plasma level was calculated to be lower in pCAD patients compared with the control group (SMD: -0.67; 95% CI: -0.48 to -0.86; P < .001). The subgroup analysis and meta-regression showed that the variation in gender distribution, the development level of the target population's country and quality score of included studies were the main sources of heterogeneity. It was observed that the relationship was only significant in the developed countries (P < .001). Also, the heterogeneity was reduced when the analysis was limited to males (I2 = 57.2%) and females only (I2 = 26.0%). CONCLUSION: In conclusion, there seems to be a significant association between the serum levels of ApoA-1 and pCAD. However, all of the included studies had a case-control design and since there is no good quality and prospective cohort studies included, reliability of the current evidence is debatable. Therefore, further well-designed cohort studies are required to assess the impact of serum ApoA-1 reduction on pCAD onset.

Donepezil attenuates injury following ischaemic stroke by stimulation of neurogenesis, angiogenesis, and inhibition of inflammation and apoptosis.

Donepezil has proven to be an effective drug to reduce neuronal death and subsequently injury in neurodegenerative diseases. The current study evaluated the neuroprotective effects of donepezil in a rat model of ischaemic stroke and explored possible mechanisms which by this drug may reduce cell death. Temporary middle cerebral artery occlusion (tMCAO) was exerted for 45 min to induce ischaemic stroke. The animals were assigned into five groups: sham, control, and three groups treated with different doses of donepezil. Donepezil was intraperitoneally (IP) injected 4 h after reperfusion for 10 consecutive days. Infarct size was determined using TTC staining. The expression of proteins was evaluated using immunohistochemistry assays. Compared with the control group, infarct size was significantly reduced in tMCAO rats treated with different doses of donepezil. Moreover, our results showed significant decreased expression levels of apoptotic markers and pro-inflammatory mediators after treatment with different doses of donepezil for 10 days (P < 0.05). Likewise, significant increase of brain-derived neurotrophic factor (BDNF) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) proteins were found in tMCAO rats treated with donepezil compared with the control group (P < 0.05). Collectively, our findings show the validity of donepezil as a new therapeutic agent for attenuation of injury following ischaemic stroke through attenuation of inflammation and improvement of mitochondrial function, neurogenesis, and angiogenesis.

Non-steroidal anti-inflammatory drugs in management of COVID-19; A systematic review on current evidence.

BACKGROUND: Since there is still no definitive conclusion regarding which non-steroidal anti-inflammatory drugs (NSAIDs) are most effective and safe in viral respiratory infections, we decided to evaluate the efficacy and safety of various NSAIDs in viral respiratory infections so that we can reach a conclusion on which NSAID is best choice for coronavirus disease 2019 (COVID-19). METHODS: A search was performed in Medline (via PubMed), Embase and CENTRAL databases until 23 March 2020. Clinical trials on application of NSAIDs in viral respiratory infections were included. RESULTS: Six clinical trials were included. No clinical trial has been performed on COVID-19, Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome infections. Studies show that ibuprofen and naproxen not only have positive effects in controlling cold symptoms, but also do not cause serious side effects in rhinovirus infections. In addition, it was found that clarithromycin, naproxen and oseltamivir combination leads to decrease in mortality rate and duration of hospitalisation in patients with pneumonia caused by influenza. CONCLUSION: Although based on existing evidence, NSAIDs have been effective in treating respiratory infections caused by influenza and rhinovirus, since there is no clinical trial on COVID-19 and case-reports and clinical experiences are indicative of elongation of treatment duration and exacerbation of the clinical course of patients with COVID-19, it is recommended to use substitutes such as acetaminophen for controlling fever and inflammation and be cautious about using NSAIDs in management of COVID-19 patients until there are enough evidence. Naproxen may be a good choice for future clinical trials.

Efficacy of polyarginine peptides in the treatment of stroke: A systematic review and meta-analysis.

BACKGROUND: Disparities exist regarding an efficient treatment for stroke. Polyarginines have shown promising neuroprotective properties based on available published studies. Thus, the present study aims to systemically review and analyze existing evidence regarding polyarginine's administration efficacy in animal stroke models. METHOD: Medline, Scopus, Embase, and Web of Science were systematically searched, in addition to manual search. Inclusion criteria were administrating polyarginine peptides in stroke animal models. Exclusion criteria were previous polyarginine administration, lacking a control group, review articles, and case reports. Data were collected and analyzed using STATA 17.0; a pooled standardized mean difference (SMD) with a 95% confidence interval (CI), meta-regression, and subgroup analyses were presented. Risk of bias, publication bias, and level of evidence were assessed using SYRCLE's tool, Egger's analysis, and Grading of Recommendations Assessment, Development and Evaluation framework, respectively. RESULTS: From the 468 searched articles, 11 articles were included. Analyses showed that R18 significantly decreases infarct size (SMD = -0.65; 95% CI: -1.01, -0.29) and brain edema (SMD = -1.90; 95% CI: -3.28, -0.51) and improves neurological outcome (SMD = 0.67; 95% CI: 0.44, 0.91) and functional status (SMD = 0.55; 95% CI: 0.26, 0.85) in stroke animal models. Moreover, R18D significantly decreases infarct size (SMD = -0.75; 95% CI: -1.17, -0.33) and improves neurological outcome (SMD = 0.46; 95% CI: 0.06, 0.86) and functional status (SMD = 0.35; 95% CI: 0.16, 0.54) in stroke models. CONCLUSION: Moderate level of evidence demonstrated that both R18 and R18D administration can significantly improve stroke outcomes in animal stroke models. However, considering the limitations, further pre-clinical and clinical studies are warranted to substantiate the neuroprotective efficacy of polyarginines for stroke.

Adipose tissue-derived stem cells as a potential candidate in treatment of Alzheimer's disease: A systematic review on preclinical studies.

In recent years, numerous investigations have evaluated the efficacy of adipose tissue-derived stem cells (ADSCs) and their exosome transplantation in managing Alzheimer's disease (AD) in different animal models. However, there are still many contradictions among the studies that hinder reaching a reliable conclusion. Therefore, we aimed to systematically review the existing evidence regarding the efficacy of ADSCs administration in treatment of AD. The systematic search was conducted in the databases of Medline (via PubMed), Embase, Scopus, and Web of Science, in addition to the manual search in Google and Google scholar, to find articles published until March 13, 2021. Preclinical studies were included and two independent reviewers summarized the eligible papers. Ten articles were included in our review. The treatment strategies varied between isolated ADSC, ADSCs exosomes, ADSCs conditioned medium, and combination therapy (ADSCs plus conditioned medium in one study, and ADSCs plus melatonin in another study). Overview of the included articles showed promising results of ADSCs and its conditioned medium/exosome administration in animal models of AD. These studies showed significant learning and memory improvements through ADSCs and their conditioned medium/exosome administration in animal models of AD. In addition, the application of ADSCs reduced the amyloid-beta plaque deposits in the hippocampus and neocortex of these animals. Based on the aforementioned evidence, studies have suggested potential beneficial effects of ADSCs in the treatment of AD, particularly through decreasing the size of Aß plaques and improvement of cognitive deficits. Further investigations regarding the subject are encouraged to achieve more accurate conclusions.

Ultra-early Spinal Decompression Surgery Can Improve Neurological Outcome of Complete Cervical Spinal Cord Injury; a Systematic Review and Meta-analysis.

Introduction: Early decompression within the first 24 hours after spinal cord injury (SCI) is proposed in current guidelines. However, the possible benefits of earlier decompression are unclear. Thus, the present meta-analysis aims to investigate the existing evidence regarding the efficacy of ultra-early decompression surgery (within 12 hours after SCI) in improving patients' neurological status. Methods: A search was performed in Medline, Embase, Scopus and Web of Science electronic databases, until the end of August 2021. Cohort studies and clinical trials were included in the present study. Exclusion criteria were absence of an early or late surgery group, failure to report neurological status based on the American spinal injury association impairment scale (AIS) grade, failure to perform the surgery within the first 12 hours after SCI, and duplicate reports and review articles. Two independent reviewers performed data collection, and risk of bias and certainty of evidence assessments. The outcome was reported as odds ratio (OR) and 95% confidence interval (CI). Results: Data from 16 articles, which studied 868 patients, were included. Compared to early or late decompression surgery, ultra-early decompression surgery significantly improves patients' neurological status (OR = 2.25; 95% CI: 1.41 to 3.58). However, ultra-early surgery in thoracolumbar injuries is not significantly more effective than early to late surgery. Moreover, ultra-early surgery in patients with a baseline AIS A increases the chance of neurologic resolvent up to 3.86 folds (OR=3.86; 95% CI: 1.50 to 9.91). Contrastingly, ultra-early surgery does not result in significant improvement compared to early to late surgery in patients with AIS B (OR = 1.32; 95% CI: 0.51 to 3.45), AIS C (OR = 1.83; 95% CI: 0.72 to 4.64), and AIS D (OR = 0.99; 95% CI: 0.31 to 3.17). Conclusion: Current guidelines emphasize that spinal decompression should be performed within 24 hours after SCI, regardless of injury severity and location. However, results of the present study demonstrated that certain considerations may be taken into account when performing decompression surgery: 1) in patients with AIS A injury, decompression surgery should be performed as soon as possible, since its efficacy in neurological improvement is 3.86 folds higher in the first 12 hours after injury. 2) ultra-early decompression surgery in patients with cervical injury is more effective than in patients with thoracic or lumbar injuries. 3) postponing decompression surgery to 24 hours in SCI patients with AIS B to D does not significantly affect the neurological outcome.

Premature Coronary Artery Disease and Plasma Levels of Interleukins; a Systematic Scoping Review and Meta-Analysis.

Introduction: Interleukins (ILs) can act as a predictive indicator of Premature Coronary Artery Disease (pCAD) and may be useful in screening of high-risk patients. However, there is no consensus on the relationship of serum levels of ILs and pCAD, yet. As a result, this study has been conducted in order to review the literature on the relationship between serum levels of different ILs and pCAD. Methods: Medline, Scopus, Embase, and Web of Science databases were searched until December 7th 2020. Two reviewers independently screened and summarized eligible articles. A meta-analysis was performed to assess the relationship of ILs and pCAD. Results: 12 case-control articles were included. IL-6 plasma changes do happen in pCAD patients with a standardized mean difference (SMD) of 0.51 (95% CI: 0.12-0.90; p=0.010) compared with the control group. This difference was also observed when evaluating the plasma levels of IL-1 and IL-17, with an SMD of 1.42 (95% CI: 1.11-1.73; p<0.001) and 0.59 (95% CI: 0.14-1.04; p=0.011), respectively. Meanwhile, no significant difference existed in plasma levels of IL-10 (SMD=0.26; 95% CI: -0.17-0.70; p=0.236), and IL-18 (SMD=1.44; 95% CI: -0.19-3.07; p=0.083) between pCAD patients and those in the control group. Conclusion: Low level of evidence showed that there may be a significant relationship between increased plasma levels of ILs and the occurrence of pCAD. As a result, prospective cohort studies with serial assessments of serum ILs during follow up period, focusing on controlling classical risk factors of pCAD and increase in level of ILs, should be conducted.

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.

Chondroitinase ABC Administration in Locomotion Recovery After Spinal Cord Injury: A Systematic Review and Meta-analysis.

Introduction: The present systematic review and meta-analysis aims to conduct a comprehensive and complete search of electronic resources to investigate the role of administrating Chondroitinase ABC (ChABC) in improving complications following Spinal Cord Injuries (SCI). Methods: MEDLINE, Embase, Scopus, and Web of Sciences databases were searched until the end of 2019. Two independent reviewers assessed the studies conducted on rats and mice and summarized the data. Using the STATA 14.0 software, the findings were reported as pooled standardized mean differences (SMD) with 95% confidence intervals (CI). Results: A total of 34 preclinical studies were included. ChABC administration improves locomotion recovery after SCI (SMD=0.90; 95% CI: 0.61 to 1.20; P<0.001). The subgroup analysis showed that the differences in the SCI model (P=0.732), the severity of the injury (P=0.821), the number of ChABC administrations (P=0.092), the blinding status (P=0.294), the use of different locomotor score (P=0.567), and the follow-up duration (P=0.750) have no effect on the efficacy of ChABC treatment. Conclusion: The findings of the present study showed that prescribing ChABC has a moderate effect in improving locomotion after SCI in mice and rats. However, this moderate effect introduces ChABC as adjuvant therapy and not as primary therapy.

Six-Month Follow-up of COVID-19 Patients: Mortality and Related Factors.

BACKGROUND: Currently, there is lack of evidence regarding the long-term follow-up of coronavirus disease 2019 (COVID-19) patients. The aim of this study is to present a 6-month follow-up of COVID-19 patients who were discharged from hospital after their recovery. METHODS: This retrospective cohort study was performed to assess the six-month follow-up of COVID-19 patients who were discharged from the hospital between February 18 and July 20, 2020. The primary outcome was 6-month all-cause mortality. RESULTS: Data related to 614 patients were included to this study. Of these 614 patients, 48 patients died (7.8%). The cause of death in 26 patients (54.2%) was the relapse of COVID-19. Also, 44.2% of deaths happened in the first week after discharge and 74.4% in the first month. Risk factors of all-cause mortality included increase in age (odds ratio [OR]=1.09; P<0.001), increase in neutrophil percentage (OR=1.05; P=0.009) and increase in heart rate (OR=1.06; P=0.002) on the first admission. However, the risk of all-cause death was lower in patients who had higher levels of hematocrit (OR=0.93; P=0.021), oxygen saturation (OR=0.90; P=0.001) and mean arterial pressure (OR=0.93; P=0.001). In addition, increase in age (OR=1.11; P<0.001) was an independent risk factor for COVID-19-related death, while higher levels of lymphocyte percentage (OR=0.96; P=0.048), mean arterial pressure (OR=0.93; P=0.006) and arterial oxygen saturation (OR=0.91; P=0.009) were protective factors against COVID-19-related deaths during the 6-month period after discharge. CONCLUSION: Death is relatively common in COVID-19 patients after their discharge from hospital. In light of our findings, we suggest that elderly patients who experience a decrease in their mean arterial pressure, oxygen saturation and lymphocyte count during their hospitalization, should be discharged cautiously. In addition, we recommend that one-month follow-up of discharged patients should be take place, and urgent return to hospital should be advised when the first signs of COVID-19 relapse are observed.

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.

Risk Factors of Readmission in COVID-19 Patients; a Retrospective 6-Month Cohort Study.

Introduction: The available literature regarding the rate of readmission of COVID-19 patients after discharge is rather scarce. Thus, the aim in the current study was to evaluate the readmission rate of COVID-19 patients and the components affecting it, including clinical symptoms and relevant laboratory findings. Methods: In this retrospective cohort study, COVID-19 patients who were discharged from Imam Hossein hospital, Tehran, Iran, were followed for six months. Data regarding their readmission status were collected through phone calls with COVID-19 patients or their relatives, as well as hospital registry systems. Eventually, the relationship between demographic and clinical characteristics and readmission rate was assessed. Results: 614 patients were entered to the present study (mean age 58.7±27.2 years; 51.5% male). 53 patients were readmitted (8.6%), of which 47 patients (7.6%) had a readmission during the first 30 days after discharge. The reasons for readmission were relapse of COVID-19 symptoms and its pulmonary complications in 40 patients (6.5%), COVID-19 related cardiovascular complications in eight patients (1.3%), and non-COVID-19 related causes in five patients (0.8%). Older age (OR=1.04; 95% CI: 1.01, 1.06; p=0.002) and increased mean arterial pressure during the first admission (OR=1.04; 95% CI: 1.01, 1.08; p=0.022) were found to be independent prognostic factors for the readmission of COVID-19 patients. Conclusion: Readmission is relatively frequent in COVID-19 patients. Lack of adequate hospital space may be the reason behind the early discharge of COVID-19 patients. Hence, to reduce readmission rate, extra care should be directed towards the discharge of older or hypertensive patients.

Prevalence of Posttraumatic Stress Disorder Symptoms Following Traumatic Spinal Cord Injury: A Systematic Review and Meta-analysis.

BACKGROUND: Limited evidence is currently available on the prevalence of posttraumatic stress disorder (PTSD) following traumatic spinal cord injury (SCI). This systematic review and meta-analysis aims to assess the prevalence and geographic distribution of PTSD symptoms after SCI. METHODS: After a search in the MEDLINE, Embase, Scopus, and Web of Science databases, two reviewers independently summarized relevant studies published through 20 October 2021. Observational studies were included. The studies were eligible if they assessed PTSD symptoms using standard self-report or clinician-based instruments. Data and results were reported using the overall prevalence and the odds ratio (OR), with 95% confidence intervals (CIs). RESULTS: 24 articles (5646 patients) met the inclusion criteria. The prevalence of PTSD symptoms ranged from 6.33% (95% CI, 2.73-13.97) to 61.76% (95% CI, 52.07-70.61). Pooled analysis demonstrated that the overall prevalence of PTSD symptoms in SCI patients was significantly higher in developing countries (41.64%; 95% CI, 31.11-52.55) than in developed countries (19.35%; 95% CI, 14.66-24.51) (OR = 1.24; 95% CI, 1.08-1.42; p = .003). The highest prevalence of PTSD symptoms was reported in South Africa (56.25%; 95% CI, 47.01-65.08), followed by Sri Lanka (45.71%; 95% CI, 30.47-61.81), and Greece (43.55%; 95% CI, 31.94-55.91). By contrast, Norway (6.33%; 95% CI, 2.73-13.97), Switzerland/Germany (8.65%; 95% CI, 4.8-13.42), and Denmark (10.71%; 95% CI, 6.89-16.30) were found to have the lowest prevalence of PTSD symptoms after SCI. CONCLUSION: Many traumatic SCI patients suffer from PTSD symptoms, and their prevalence seems to be higher in developing countries than in developed countries. These findings underscore the need to consider the psychological aspects of traumatic SCI.

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.

FoxO1 and Wnt/ß-catenin signaling pathway: Molecular targets of human amniotic mesenchymal stem cells-derived conditioned medium (hAMSC-CM) in protection against cerebral ischemia/reperfusion injury.

Ischemia-reperfusion (I/R) injury has weakened the effects of available treatment options for ischemic stroke. Although conditioned medium obtained from human amniotic mesenchymal stem cells (hAMSC-CM) has been reported to exert protective effect against stroke, detailed knowledge about its possible molecular mechanisms is not still completely available. The present study was designed to investigate whether hAMSC-CM can modulate FoxO1 and Wnt/ß-catenin signaling pathway after ischemic stroke to create neuroprotective effects. Middle cerebral artery occlusion (MCAO) model with male Wistar rats was used to evaluate the effects of hAMSC-CM on activities of FoxO1, Wnt/ß-catenin signaling pathway, and endogenous antioxidant system and apoptotic cell death. The results demonstrated that induction of MCAO significantly reduced activities of FoxO1, Wnt/ß-catenin signaling pathway, and endogenous antioxidant system and enhanced apoptotic cell death (P < 0.05). In addition, treatment by hAMSC-CM immediately after cerebral reperfusion resulted in significantly reduced infarct size and increased activities of FoxO1, Wnt/ß-catenin signaling pathway, and restoring endogenous antioxidant system and suppressing apoptotic cell death (P < 0.05). Likewise, increased activity of Wnt/ß-catenin signaling pathway resulted in suppressing the neuroinflammation by inhibiting the expression of TNF-α and increasing the expression of IL-10. These findings demonstrate that hAMSC-CM can be considered as an excellent candidate in the treatment of acute ischemic stroke in clinical routine.

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.

Cardiac Complications and Pertaining Mortality Rate in COVID-19 Patients; a Systematic Review and Meta-Analysis.

INTRODUCTION: Raising knowledge over cardiac complications and managing them can play a key role in their recovery. In this study, we aim to investigate the evidence regarding the prevalence of cardiac complications and the resulting mortality rate in COVID-19 patients. METHOD: Search was conducted in electronic databases of Medline (using PubMed), Embase, Scopus, and Web of Science, in addition to the manual search in preprint databases, and Google and Google scholar search engines, for articles published from 2019 until April 30th, 2020. Inclusion criterion was reviewing and reporting cardiac complications in patients with confirmed COVID-19. RESULTS: The initial search resulted in 853 records, out of which 40 articles were included. Overall analysis showed that the prevalence of acute cardiac injury, heart failure and cardiac arrest were 19.46% (95% CI: 18.23-20.72), 19.07% (95% CI: 15.38-23.04) and 3.44% (95% CI: 3.08-3.82), respectively. Moreover, abnormal serum troponin level was observed in 22.86% (95% CI: 21.19-24.56) of the COVID-19 patients. Further analysis revealed that the overall odds of mortality is 14.24 (95% CI: 8.67-23.38) times higher when patients develop acute cardiac injury. The pooled odds ratio of mortality when the analysis was limited to abnormal serum troponin level was 19.03 (95% CI: 11.85-30.56). CONCLUSION: Acute cardiac injury and abnormal serum troponin level were the most prevalent cardiac complications/abnormalities in COVID-19 patients. The importance of cardiac complications is emphasized due to the higher mortality rate among patients with these complications. Thus, troponin screenings and cardiac evaluations are recommended to be performed in routine patient assessments.

Electrocardiographic Findings and In-Hospital Mortality of COVID-19 Patients; a Retrospective Cohort Study.

BACKGROUND: Although current evidence points to the possible prognostic value of electrocardiographic (ECG) findings for in-hospital mortality of COVID-19 patients, most of these studies have been performed on a small sample size. In this study, our aim was to investigate the ECG changes as prognostic indicators of in-hospital mortality. METHODS: In a retrospective cohort study, the findings of the first and the second ECGs of COVID-19 patients were extracted and changes in the ECGs were examined. Any abnormal finding in the second ECG that wasn't present in the initial ECG at the time of admission was defined as an ECG change. ECGs were interpreted by a cardiologist and the prognostic value of abnormal ECG findings for in-hospital mortality of COVID-19 patients was evaluated using multivariate analysis and the report of the relative risk (RR). RESULTS: Data of the ECGs recorded at the time of admission were extracted from the files of 893 patients; likewise, the second ECGs could be extracted from the records of 328 patients who had an initial ECG. The presence of sinus tachycardia (RR = 2.342; p <0.001), supraventricular arrhythmia (RR = 1.688; p = 0.001), ventricular arrhythmia (RR = 1.854; p = 0.011), interventricular conduction delays (RR = 1.608; p = 0.009), and abnormal R wave progression (RR = 1.766; p = 0.001) at the time of admission were independent prognostic factors for in-hospital mortality. In the second ECG, sinus tachycardia (RR = 2.222; p <0.001), supraventricular arrhythmia (RR = 1.632; p <0.001), abnormal R wave progression (RR = 2.151; p = 0.009), and abnormal T wave (RR = 1.590; p = 0.001) were also independent prognostic factors of in-hospital mortality. Moreover, by comparing the first and the second ECGs, it was found that the incidence of supraventricular arrhythmia (RR = 1.973; p = 0.005) and ST segment elevation/depression (RR = 2.296; p <0.001) during hospitalization (ECG novel changes) are two independent prognostic factors of in-hospital mortality in COVID-19 patients. CONCLUSION: Due to the fact that using electrocardiographic data is easy and accessible and it is easy to continuously monitor patients with this tool, ECGs can be useful in identifying high-risk COVID-19 patients for mortality.