Water pipe smoking and stroke: A systematic review and meta-analysis.

OBJECTIVE: Despite the damaging effects of water pipe on physical health, there is little information about the potential harmful effects of this tobacco on stroke. This study aims to investigate the relationship between water pipe smoking and stroke. METHOD: A systematic review was conducted including Ovid SP, Embase, Pubmed, Web of Science, Scopus, and Google Scholar databases with focus on cohort, case-control, and cross-sectional studies. We reviewed all studies reporting on water pipe smoking and stroke. The funnel plot and the Egger regression test were used to assess publication bias. RESULTS: In the four eligible studies, there were a total of 2759 participants that 555 patients had at least once experienced stroke. Meta-analysis revealed positive association between water pipe smoking and stroke with pooled adjusted OR 2.79 (95% CI: 1.74-3.84; I 2 = 0 , p = . 741 ${I^2}\; = \;\;0,{\mathrm{\;}}p\;\; = {\mathrm{\;\;}}.741$ ) and the funnel plot shows asymmetry publication bias. CONCLUSIONS: We found a higher effect of water pipe smoking on stroke compared to cigarette smoking and concluded that water pipe increases the risk of stroke by 2.79. Hence, because most of the water pipe consumer society is young, especially women, policies and decisions need to be taken to control the supply of this tobacco to the market and more provide education on the health problem of water pipe smoking. IMPLICATIONS: This study provides a higher effect of water pipe smoking on stroke. Physicians and researchers who intend to study in the field of stroke should better examine the effects of water pipe (including time of use, dose-response, long-term effects, and risk factors) on stroke.

Zero-Inflated Count Regression Models in Solving Challenges Posed by Outlier-Prone Data; an Application to Length of Hospital Stay.

Introduction: Ignoring outliers in data may lead to misleading results. Length of stay (LOS) is often considered a count variable with a high frequency of outliers. This study exemplifies the potential of robust methodologies in enhancing the accuracy and reliability of analyses conducted on skewed and outlier-prone count data of LOS. Methods: The application of Zero-Inflated Poisson (ZIP) and robust Zero-Inflated Poisson (RZIP) models in solving challenges posed by outlier LOS data were evaluated. The ZIP model incorporates two components, tackling excess zeros with a zero-inflation component and modeling positive counts with a Poisson component. The RZIP model introduces the Robust Expectation-Solution (RES) algorithm to enhance parameter estimation and address the impact of outliers on the model's performance. Results: Data from 254 intensive care unit patients were analyzed (62.2% male). Patients aged 65 or older accounted for 58.3% of the sample. Notably, 38.6% of patients exhibited zero LOS. The overall mean LOS was 5.89 (± 9.81) days, and 9.45% of cases displayed outliers. Our analysis using the RZIP model revealed significant predictors of LOS, including age, underlying comorbidities (p<0.001), and insurance status (p=0.013). Model comparison demonstrated the RZIP model's superiority over ZIP, as evidenced by lower Akaike information criteria (AIC) and Bayesians information criteria (BIC) values. Conclusions: The application of the RZIP model allowed us to uncover meaningful insights into the factors influencing LOS, paving the way for more informed decision-making in hospital management.

Clinico-Pathological and Prognostic Significance of a Combination of Tumor Biomarkers in Iranian Patients With Breast Cancer.

PURPOSE: Breast cancer is one of the most common cancers in the world. It is a multifaceted malignancy with different histopathological and biological features. Molecular biomarkers play an essential role in accurate diagnosis, classification, prognosis, prediction of treatment response, and cancer surveillance. This study investigated the clinico-pathological and prognostic significance of HER3 and ROR1 in breast cancer samples. METHODS: Tissue microarrays (TMA) were constructed using tissue blocks of 444 Iranian breast cancer patients diagnosed with breast cancer. Overall survival (OS) and disease-free survival (DFS) were assessed after 5 years follow-up. TMA slides were stained with monoclonal antibodies against ROR1, HER3, ER, PR, Ki67, P53, HER2 and CK5/6 using IHC and correlation between the investigated tumor markers and the clinico-pathological parameters of patients were analyzed. RESULTS: Our results showed a significant correlation between ROR1 and ER, PR, HER3, and CK5/6 expression. Additionally, there was a significant correlation between HER3 and ER, PR, HER2, and Ki67 expression. Ki67 was also correlated with HER2 and P53 expression. HER3 expression was significantly correlated with tumor stage, lymph node metastasis, perineural invasion, and multifocal tumors. Furthermore, ROR1 expression was significantly associated with tumor metastasis, lympho-vascular invasion, and perineural invasion. While HER2-HER3 coexpression was significantly associated with poor OS, HER3-ROR1 coexpression was associated with lymph node invasion, lymph node metastasis, and distant metastasis. CONCLUSION: ROR1 and HER3 displayed significant association with different clinic-pathological features and in addition to the other tumor biomarkers could be considered as diagnostic and prognostic biomarkers in breast cancer patients.

COVID-19 Vaccination Among Diverse Population Groups in the Northern Governorates of Iraq.

Objectives: The present study was carried out to investigate COVID-19 vaccination coverage among populations of internally displaced persons (IDPs), refugees, and host communities in northern Iraq and the related underlying factors. Methods: Through a cross-sectional study conducted in five governorates in April-May 2022, 4,564 individuals were surveyed. Data were collected through an adapted questionnaire designed to gather data on participants. Results: 4,564 subjects were included (59.55% were 19-45 years old; 54.51% male). 50.48% of the participants (51.49% of host communities, 48.83% of IDPs, and 45.87% of refugees) had been vaccinated with at least one dose of COVID-19 vaccine. 40.84% of participants (42.28% of host communities, 35.75% of IDPs, and 36.14% of refugees) had been vaccinated by two doses, and 1.56% (1.65% of host communities, 0.93% of IDPs, and 1.46% of refugees) were vaccinated with three doses. Conclusion: Sociodemographic factors including age, gender, education, occupation, and nationality could affect vaccination coverage. Moreover, higher acceptance rate of vaccination is associated with belief in vaccine safety and effectiveness and trust in the ability of the vaccine to prevent complications.

The Role of Exercise in the Alleviation of Neuropathic Pain Following Traumatic Spinal Cord Injuries: A Systematic Review and Meta-analysis.

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.

Clinical decision rules in predicting computed tomography scan findings and need for neurosurgical intervention in mild traumatic brain injury: a prospective observational study.

PURPOSE: In this study, we will compare the diagnostic values of head CT decision rules in predicting the findings of CT scans in a prospective multicenter study in university emergency departments in Iran. METHODS: The primary outcome was any traumatic lesion findings in brain CT scans, and the secondary outcomes were death, the need for mechanical ventilation, and neurosurgical intervention. Decision rules including the Canadian CT Head Rule (CCHR), New Orleans Criteria (NOC), National Institute for Health and Clinical Excellence (NICE), National Emergency X-Radiography Utilization Study (NEXUS), and Neurotraumatology Committee of the World Federation of Neurosurgical Societies (NCWFNS) were compared for the main outcomes. RESULTS: In total, 434 mild TBI patients were enrolled in the study. The NCWFNS had the highest sensitivity (91.14%) and the lowest specificity (39.42%) for predicting abnormal finding in CT scan compared to other models. While the NICE obtained the lowest sensitivity (79.75%), it was associated with the highest specificity (66.67%). All model performances were improved when administered to predict neurosurgical intervention among patients with GCS 13-15. NEXUS (AUC 0.862, 95% CI 0.799-0.924) and NCWFNS (AUC 0.813, 95% CI 0.723-0.903) had the best performance among all evaluated models. CONCLUSION: The NCWFNS and the NEXUS decision rules performed better than the CCHR and NICE guidelines for predicting any lesion in the CT imaging and neurosurgical intervention among patients with mTBI with GCS 13-15. For a subset of mTBI patients with GCS 15, the NOC criteria have higher sensitivity for abnormal CT imaging, but lower specificity and more requested CTs.

In-hospital mortality rate in subaxial cervical spinal cord injury patients: a systematic review and meta-analysis.

PURPOSE: To determine existing trends concerning in-hospital mortality in patients with traumatic subaxial cervical spinal cord injury (SCI) over the last four decades. METHODS: We searched MEDLINE and EMBASE to assess the role of the following factors on in-hospital mortality over the last four decades: neurological deficit, age, surgical decompression, use of computed tomography (CT) and magnetic resonance imaging (MRI), use of methylprednisolone in the acute post-injury period, and study location (developing versus developed countries). RESULTS: Among 3333 papers after deduplication, 21 studies met the eligibility criteria. The mortality rate was 17.88% [95% confidence interval (CI): 12.9-22.87%]. No significant trend in mortality rate was observed over the 42-year period (meta-regression coefficient = 0.317; p = 0.372). Subgroup analysis revealed no significant association between acute subaxial cervical SCI-related mortality when stratified by use of surgery, administration of methylprednisolone, use of MRI and CT imaging, study design (prospective versus retrospective study), and study location. The mortality rate was significantly higher in complete SCI (20.66%, p = 0.002) and American Spinal Injury Association impairment scale (AIS) A (20.57%) and B (9.28%) (p = 0.028). CONCLUSION: A very low level of evidence showed that in-hospital mortality in patients with traumatic subaxial cervical SCI did not decrease over the last four decades despite diagnostic and therapeutic advancements. The overall acute mortality rate following subaxial cervical SCI is 17.88%. We recommend reporting a stratified mortality rate according to key factors such as treatment paradigms, age, and severity of injury in future studies.

Effects of Epothilone Administration on Locomotion Recovery after Spinal Cord Injury: A Systematic Review of Animal Studies.

This is a systematic review and meta-analysis of existing evidence regarding the possible effects of epothilones on spinal cord injury (SCI). This study aimed to investigate the possible effects of epothilone administration on locomotion recovery in animal models of SCI. Despite increasing rates of SCI and its burden on populations, no consensus has been reached about the possible treatment modality for SCI. Meanwhile, low-dose epothilones have been reported to have positive effects on SCI outcomes. Electronic databases of Web of Science, Scopus, Embase, and Medline were searched using keywords related to epothilones and SCI until the end of 2020. Two researchers screened the articles, and extracted data were analyzed using STATA ver. 14.0. Final results are reported as a standardized mean difference (SMD) with a 95% confidence interval (CI). After the screening, five studies were included in the analysis. Rats were used in all the studies. Two types of epothilones were used via intraperitoneal injection and were shown to have positive effects on the motor outcomes of samples with SCI (SMD, 0.87; 95% CI, 0.51 to 1.23; p =0.71). Although a slightly better effect was observed when using epothilone B, the difference was not significant (coefficient, -0.50; 95% CI, -1.52 to 0.52; p =0.246). The results of this study suggest that epothilones have positive effects on the improvement of motor function in rats, when administered intraperitoneally until a maximum of 1 day after SCI. However, current evidence regarding the matter is still scarce.

Prevalence of Hypertension among Children Based on the New American Academy of Pediatrics Clinical Practice Guidelines.

Background: In 2017, the American Academy of Pediatrics (AAP) updated clinical practice guidelines for the diagnosis and management of hypertension in children. The present study aimed to assess the prevalence of hypertension in Iranian children based on the latest guidelines. Methods: Data on 7301 student participants (3589 boys and 3712 girls) aged between 7-12 yr were assessed. The data were extracted from the fifth Childhood and Adolescence Surveillance and Prevention of Adult Non-communicable Disease (CASPIAN V) school-based study conducted in the 30 provinces of Iran in 2015. Blood pressure (BP) was classified as normal, elevated BP, and stage 1 and 2 hypertension using weighted analysis and the 2017 AAP guidelines. All analyses were performed in STATA 14.0 statistical software, with findings presented in terms of prevalence. Results: The overall prevalence of high BP in Iranian children was 14.7%. In addition, 15.1% of boys had high BP, with 9.4% and 1.7% of them with stage 1 and 2 hypertension, respectively. Moreover, 14.3% of girls had high BP, of which 10% had stage 1 and 1.3% with stage 2 hypertension. For elevated hypertension, it was observed in 4% of boys and 3% of girls. Conclusion: Using the 2017 AAP guidelines demonstrated a higher prevalence of hypertension in children (14.7%) in Iran. The prevalence of hypertension in boys was slightly higher compared to girls.

Can metformin use reduce the risk of stroke in diabetic patients? A systematic review and meta-analysis.

BACKGROUND AND AIM: Stroke and cardiovascular diseases are major causes of death and disability, especially among diabetic patients. Some studies have shown that metformin has been effective in preventing cardiovascular diseases. In this study, we aim to evaluate the effect of metformin on stroke in type 2 diabetic patients. METHODS: A comprehensive search was conducted in Medline, Embase, Scopus, and Web of Science databases from their inception till 1st July 2022. Randomized clinical trials (RCT) and cohort studies were included. Two independent researchers screened the records, extracted the data, and assessed the risk of bias and certainty of evidence. Findings were reported as risk ratio (RR) and 95% confidence interval (CI). All statistical analyses were performed using the STATA 17.0 software package. RESULTS: Analysis of 21 included studies with 1,392,809 patients demonstrated that metformin monotherapy was effective in reducing stroke risk in both RCTs (RR = 0.66, 95% CI: 0.50, 0.87 p = 0.004) and cohort studies (RR = 0.67, 95% CI: 0.55, 0.81, p < 0.0001). However, combined administration of metformin with other antihyperglycemic agents had no significant effect on stroke risk reduction in either the RCTs (RR = 0.92, 95% CI: 0.69, 1.22 p = 0.558) or the cohort studies (RR = 0.79, 95% CI: 0.59, 1.06, p = 0.122). CONCLUSION: Low to moderate level of evidence in RCTs showed that metformin monotherapy could reduce stroke risk in type 2 diabetic patients. However, the preventive effect of metformin in stroke was not observed in patients who received a combination of metformin plus other hypoglycemic agents.

The Role of Intraspinal Administration of Self-Assembled Peptide on Locomotion Recovery After Spinal Cord Injury: A Systematic Review and Meta-Analysis Study.

BACKGROUND: Spinal cord injury (SCI) treatment is still a challenge and new treatments that help these patients are being considered. Recent studies showed that the use of self-assembled peptide (SAP) can be useful in SCI treatment. MATERIALS AND METHODS: In this meta-analysis, we investigated the effect of SAP administration on locomotion recovery after SCI. Records were obtained from a comprehensive search of data bases. Articles were scrutinized for inclusion and exclusion criteria. Data were analyzed and results were reported as standardized mean difference (SMD) with 95% CI. Subgroup analysis was also performed. RESULTS: A total of 14 studies and 17 separate experiments were included in the final analysis. Treatment with SAP structures after SCI resulted in a significant improvement in animal motor function (SMD = 1.13; 95% CI: 0.68-1.58; p < 0.0001). SAP treatment facilitated axon sprouting (SMD = 0.76; 95% CI: 0.33-1.18; p < 0.0001) and reduction of glial scar (SMD = -1.02; 95% CI: -1.94 to -0.09; p = 0.03). The difference in SAP type, its concentration, follow-up time, and SCI model had no effect on SAP effectiveness. In addition, SAP administration had a similar effect on improving locomotion in all three immediate, acute, and subacute phases which gives the good news of using this treatment for patients who are in the chronic phase. CONCLUSION: SAP treatment can be considered as a potential treatment to help the motor recovery of SCI and axon regeneration.

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.

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.

Changes in Body Composition, Basal Metabolic Rate, and Blood Albumin during the First Year following Laparoscopic Mini-Gastric Bypass.

Bariatric surgery is currently the only method that can significantly and continuously reduce weight and improve obesity-related comorbidities in morbidly obese patients. Significant weight loss through bariatric surgery can lead to changes in body composition. This study shows the changes in body composition, basal metabolic rate (BMR), and serum albumin in obese people following bariatric surgery. The study included 880 patients who underwent laparoscopic mini-gastric bypass surgery (LMGBP) between 2016 and 2020. The body mass index (BMI), bioelectrical impedance analysis (BIA), age, gender, blood albumin, WC (waist circumference), HC (hip circumference), BMR, and blood albumin were recorded at 0, 3, 6, and 12 months, postoperatively. The reduction in serum albumin concentration was not consistent with weight loss. Bariatric surgery promotes the breakdown of both fat and lean mass on the arms, torso, and thighs. This size reduction usually aggravates the concomitant skin redundancy in these areas which is a challenge for the plastic surgery team. Interestingly, the rate of lean mass reduction of the arms is faster than that of the torso and thighs. Excessive loss of lean body mass will also lower BMR and lead to subsequent weight gain. Despite the faster loss of proteins and lean mass in somatic areas, internal organs and viscera lose fats faster than proteins. According to this study, visceral proteins are the latest proteins to be affected by weight loss. This finding shows a different metabolic response of viscera comparing to somatic areas.

Evaluating Mannuronic Acid Effect on Gene Expression Profile of Inflammatory Mediators in Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA) is a multisystem disorder. Various studies have shown the important role of inflammatory factors tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-22, MYD88, and toll-like receptor 2 (TLR2) in this disease. In this study, we investigated the anti-inflammatory effects of B-D-Mannuronic acid (M2000), as a new immunosuppressive drug, on the expression of these inflammatory markers in peripheral blood mononuclear cells (PBMCs) of RA patients. The blood samples of active RA patients and healthy volunteers were used for PBMCsl separation. The cells were cultured with LPS (1 µg/mL), low (5 µg/mL), moderate (25 µg/mL), and high (50 µg/mL) doses of M2000 and a single dose of diclofenac (1 µg/mL) to evaluate TNF-α, IL-6, IL-22, MYD88, and TLR2 genes expression by quantitative real-time (qRT-PCR). Cell surface expression and MFI of TLR2 were assessed; using flow cytometry. Our findings exhibited a significant reduction of TNF-α, IL-6, and MYD88 gene expressions after treatment with three doses of M2000 and an optimum dose of diclofenac. TLR2 gene expression was significantly diminished by moderate and high doses of M2000 and a single dose of diclofenac. Moreoversurface expression of TLR2 was significantly downregulated by moderate and high doses of M2000, while MFI of this receptor was significantly reduced by three doses of M2000. The results of this research showed that M2000 was able to significantly reduce the gene expression of inflammatory molecules  TNF-α, IL-6, MYD88, and TLR2 in patients PBMCs. factor-alpha; Rheumatoid arthritis. These data revealed a part of the molecular mechanisms of M2000 in the treatment process.

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.

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.

A controlled, randomized phase II clinical trial for efficacy and safety evaluation of mannuronic acid in secondary progressive form of multiple sclerosis.

BACKGROUND: The ß-D-Mannuronic acid (M2000) as a novel immunosuppressive drug, patented (PCT/EP2017/067920), has shown positive effects in experimental model of multiple sclerosis (MS). In this study, our aim was to assess efficacy and safety outcomes in MS treated patients with mannuronic acid compared to the conventional drug. METHODS: In a 6-month, randomized controlled, phase II trial, we enrolled patients who had secondary progressive multiple sclerosis (SPMS), were 21-54 years of age, with a score of 1-7 on the Expanded Disability Status Scale (EDSS), and who had at least one relapse in the previous 6 months. Patients were administered orally 1000 mg/day (two 500 mg/capsule daily) of M2000. Endpoints included changes in brain magnetic resonance imaging (MRI) measures and the EDSS score, as compared to the conventional drug (interferon beta-1a, interferon beta-1b). RESULTS: A total of 25 (92.5%) of the M2000 treated patients and 25 conventionally treated patients completed the study. M2000 had better performance compared to the conventional drug regarding to MRI-related measurements, however, the differences between groups were not statistically significant. M2000 decreased the disability progression over the 6-month period. The EDSS score was decreased in the M2000 treated group in the sixth month versus the conventional drug (p < 0.009). Furthermore, we did not observe any short-term side effects. CONCLUSIONS: As compared with the conventional drug, mannuronic acid (M2000) improved the rate of disability progression. This clinical trial demonstrated the efficacy and safety of mannuronic acid in patients with SPMS. (Registered Clinical Trials number, IRCT2016111313739N6).

Prevalence and Mortality of Post-traumatic Acute Kidney Injury in Children; a Systematic Review and Meta-analysis.

Introduction: Numerous studies on acute kidney injury (AKI) following trauma have been performed, and acceptable findings have been reported in the adult population. The present meta-analysis summarizes the studies performed on the pediatric population to evaluate the prevalence of AKI following trauma in this population. Method: The Medline, Embase, Scopus and Web of Sciences databases were searched for articles published until the July, 31, 2021. Two independent reviewers screened observational studies performed on children with physical trauma and AKI related to it. The interested outcomes were the prevalence and mortality of trauma-related AKI in traumatized children. Results: Data of 9 articles were included in the present meta-analysis. The prevalence of trauma-related AKI varied between 0% and 30.30% among included studies. Pooled analysis showed that the prevalence of trauma-related AKI was 9.86% (95% CI: 8.02 to 11.84%). The prevalence of AKI after exertional rhabdomyolysis, direct physical trauma, and earthquake related injuries was 0%, 12.64% and 24.60%, respectively. There was a significant relationship between the prevalence of AKI and trauma etiology (p = 0.038). Moreover, the occurrence of AKI in children with trauma was associated with an increased risk of mortality (OR = 5.55; 95% CI: 2.14 to 13.93). Conclusion: The findings of the present study showed that 9.86% of children develop AKI following trauma, which may increase their risk of death by about 5.5 times. Nevertheless, since none of the studies had adjusted their analyzes for potential confounders, caution should be exercised in interpreting the relationship between trauma-related AKI and mortality.