Insulin-like growth factor-1 (IGF-1) levels in multiple sclerosis patients: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Multiple sclerosis (MS) is a chronic progressive autoimmune disorder of the central nervous system (CNS) that can cause inflammation, demyelination, and axon degeneration. Insulin-like growth factor-1 (IGF-1) is a single-chain polypeptide mainly synthesized in the liver and brain. IGF-1 causes neuronal and non-neuronal cell proliferation, survival, and differentiation. Therefore, it can be used in treating neuro-demyelinating diseases such as MS. The current systematic review and meta-analysis aims to compare the levels of IGF-1 in MS patients and healthy controls and also investigates IGF binding proteins (IGF-BP) and growth hormone (GH) levels between MS patients and healthy controls. METHODS: In this study, we systematically searched electronic databases of PubMed, Scopus, Web of Science (WOS), and Google Scholar, up to December 2022. Studies that measured IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and healthy controls in either blood or cerebral spinal fluid (CSF) were identified. We calculated Standardized mean differences (SMD) to compare levels of IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and controls. RESULTS: Finally, we included 11 eligible studies from 1998 to 2018. The sample size of included studies varied from 20 to 200 resulting in a total sample size of 1067 individuals, 531 MS patients, and 536 healthy controls. The mean age of the patient and control groups were 38.96 and 39.38, respectively. The average EDSS among patients was 4.56. We found that blood levels of IGF-1 (SMD = 0.20, 95% CI = -0.20 to 0.59, I2 = 82.4%, K = 8, n = 692), CSF level of IGF-1 (SMD = 0.25, 95% CI = -0.06 to 0.56, I2 = 0.0%, K = 3 n = 164) and blood levels of GH were not significantly higher in MS patients than controls (SMD = 0.08, 95% CI = -0.33 to 0.49, I2 = 77.0% K = 3, n = 421). Moreover, the blood levels of IGFBP-1 (SMD = 0.70, 95% CI = 0.01 to 1.40, I2 = 77%, K = 4, n = 255) were significantly higher in MS cases than in controls. However, the blood levels of IGFBP-2 (SMD = 0.43, 95% CI = -0.34 to 1.21, I2 = 64.2%, K = 3, n = 78) and blood levels of IGFBP-3 (SMD = 1.04, 95% CI = -0.09 to 2.17, I2 = 95.6%, K = 6, n = 443) were not significantly higher in patients than controls. CONCLUSION: Our meta-analysis revealed no significant difference in serum levels of IGF-1, GH, IGFBP-2, and IGFBP-3 between the MS group and healthy controls, except for IGFBP1. However, our systematic review showed that the studies were controversial for IGFBP-3 serum levels. Some studies found an increase in serum level of IGFBP-3 in MS patients compared to the healthy group, while others showed a decrease.

Diagnostic Accuracy of Ultrasonography for Identification of Elbow Fractures in Children; a Systematic Review and Meta-analysis.

Introduction: In spite of the results of previous studies regarding the benefits of ultrasonography for diagnosis of elbow fractures in children, the exact accuracy of this imaging modality is still under debate. Therefore, in this diagnostic systematic review and meta-analysis, we aimed to investigate the accuracy of ultrasonography in this regard. Methods: Two independent reviewers performed systematic search in Web of Science, Embase, PubMed, Cochrane, and Scopus for studies published from inception of these databases to May 2023. Quality assessment of the included studies was performed using Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2). Meta-Disc software version 1.4 and Stata statistical software package version 17.0 were used for statistical analysis. Results: A total of 648 studies with 1000 patients were included in the meta-analysis. The pooled sensitivity and specificity were 0.95 (95% CI: 0.93-0.97) and 0.87 (95% CI: 0.84-0.90), respectively. Pooled positive likelihood ratio (PLR) was 6.71 (95% CI: 3.86-11.67), negative likelihood ratio (NLR) was 0.09 (95% CI: 0.03-0.22), and pooled diagnostic odds ratio (DOR) of ultrasonography in detection of elbow fracture in children was 89.85 (95% CI: 31.56-255.8). The area under the summary receiver operating characteristic (ROC) curve for accuracy of ultrasonography in this regard was 0.93. Egger's and Begg's analyses showed that there is no significant publication bias (P=0.11 and P=0.29, respectively). Conclusion: Our meta-analysis revealed that ultrasonography is a relatively promising diagnostic imaging modality for identification of elbow fractures in children. However, clinicians employing ultrasonography for diagnosis of elbow fractures should be aware that studies included in this meta-analysis had limitations regarding methodological quality and are subject to risk of bias. Future high-quality studies with standardization of ultrasonography examination protocol are required to thoroughly validate ultrasonography for elbow fractures.

Valproic acid-induced hyperammonemia in neuropsychiatric disorders: a 2-year clinical survey.

INTRODUCTION: Valproic acid (VPA)-induced hyperammonemia (HA) is a rare adverse effect reported even at therapeutic VPA levels. The present study aimed to investigate the characteristics of VPA-induced HA and its association with the total dose, duration, and level of VPA. This study also investigated whether the use of VPA in combination with other medications has any effect on elevating serum ammonia levels. METHODS: A total of 316 patients with a history of VPA prescribed for underlying neuropsychiatric disorders were found eligible for the study. Data including demographic information, medical history and diagnosis, VPA dosage, VPA treatment duration, VPA level, and ammonia serum level were extracted and reviewed from our hospital records. The history of other neuropsychiatric medications was also included. RESULTS: Among 316 patients receiving VPA, HA was observed in 54 (17%) patients, and 15 patients were symptomatic among them. There was no significant difference in demographics between symptomatic and asymptomatic HA groups except for the number of co-administrated medications (p = 0.044). Besides, VPA duration and dose did not show a significant difference between the two groups. Additionally, the VPA level was significantly higher in patients who used risperidone in addition to VPA (p = 0.019). Eventually, VPA level showed a significant association with ammonia level (p = 0.025) and symptomatic HA (p = 0.033) after adjusting for possible confounders. CONCLUSION: VPA level showed a significant association with ammonia level and symptomatic HA. Moreover, co-administrated medications such as risperidone might have an impact on the serum level of VPA. Further studies are recommended to confirm these findings.