Safety and efficacy of cladribine in multiple sclerosis: a systematic review and meta-analysis.

BACKGROUND: Previously, several studies investigated the effect of cladribine among patients with multiple sclerosis (MS) as a treatment option. Due to the contradictory results of previous studies regarding the efficacy and safety of cladribine in the MS population, we aimed to conduct a systematic review and meta-analysis by including clinical trials and observational studies in terms of having more confirmative results to make a general decision. METHODS: The three databases including PubMed, Scopus, and Web of Science were comprehensively searched in May 2022. We included the studies that investigated the efficacy and safety of cladribine in patients with MS. Eligible studies have to provide sufficient details on MS diagnosis and appropriate follow-up duration. We investigated the efficacy of cladribine with several outcomes including Expanded Disability Status Scale (EDSS) change, progression-free survival (PFS), relapse-free survival (RFS), and MRI-free activity survival (MFAS). RESULTS: After two-step reviewing, 23 studies were included in our qualitative and quantitative synthesis. The pooled SMD for EDSS before and after treatment was - 0.54 (95%CI: - 1.46, 0.39). Our analysis showed that the PFS after cladribine use is 79% (95%CI 71%, 86%). Also, 58% of patients with MS who received cladribine remained relapse-free (95%CI 31%, 83%). Furthermore, the MFAS after treatment was 60% (95%CI 36%, 81%). Our analysis showed that infection is the most common adverse event after cladribine treatment with a pooled prevalence of 10% (95%CI 4%, 18%). Moreover, the pooled prevalence of infusion-related adverse events was 9% (95%CI 4%, 15%). Also, the malignancies after cladribine were present in 0.4% of patients (95%CI 0.25%, 0.75%). CONCLUSION: Our results showed acceptable safety and efficacy for cladribine for the treatment of MS except in terms of reducing EDSS. Combination of our findings with the results of previous studies which compared cladribine to other disease-modifying therapies (DMTs), cladribine seems to be a safe and effective drug in achieving better treatment for relapsing-remitting MS (RRMS) patients.

Psychometric Properties of the Persian Version of the Multiple Sclerosis Work Difficulties Questionnaire (MSWDQ) Questionnaire.

Background: Patients with multiple sclerosis (MS) suffer from a wide range of psychological and physical problems. Employment status is a crucial issue for patients with MS as unemployment while it is not completely evaluated in patients with MS. Objectives: To assess psychometrical properties of the Persian version of the Multiple Sclerosis Work Difficulties Questionnaire (MSWDQ). Methods: One hundred and sixty patients were enrolled. They were asked to fill valid and reliable Persian version of the Fatigue Severity Scale (FSS), social support scale, and Short Form Health Survey (SF-36) and translated version of the MSWDQ questionnaire. Twenty cases filed the questionnaire two weeks later to assess reliability. The intra-class correlation coefficient (ICC), Cronbach's alpha, correlation coefficients were used. Results: Mean age and mean duration of the disease were 36.8 ± 9.1, and 7.5 ± 5.1, respectively. The Cronbach alpha for psychological/cognitive barriers subscale was 0.87, for Physical barriers was 0.83 and for external barriers was 0.86. The Cronbach α for the whole questionnaire was 0.89. There was a significant positive correlation between FSS and MSWDQ score, and a significant correlation with SF-36 and social support. The ICCs of all questions were acceptable. Conclusions: Persian version of MSWDQ questionnaire is a valid and reliable instrument for evaluating work-related problems in patients with MS.

Association of Exposure to Particulate Matters and Multiple Sclerosis: A Systematic Review and Meta-Analysis.

The association between air pollution and multiple sclerosis (MS) is not entirely clear. This meta-analysis was aimed at determining the correlation between particulate matter (PM)2.5, PM10, and MS incidence/relapse. The literature search was performed in EMBASE, Web of Science, PubMed, and the gray literature. Sixteen articles were retrieved, and ten articles were included and evaluated. Three measures of association were used for the meta-analysis: odds ratio (cross-sectional and case-control studies), incidence rate ratio, or hazard ratio (cohort studies). Meta-analysis of those 3 studies on PM2.5 indicated that exposure to PM2.5 was associated with MS relapse and incidence ([95% confidence interval; CI] 1.178 [1.102, 1.279]), p > 0.05. Also, assessment of risk ratio for all studies showed a correlation between PMs (PM10 and PM2.5) and MS incidence and relapse ([95% CI] 1.28, [1.13-1.43]) p < 0.05. Collectively, we found that PM exposure (PM10 and PM2.5) in MS patients associates with the occurrence and relapse of disease.

Early predictors of conversion to secondary progressive multiple sclerosis.

BACKGROUND: We conducted this study to estimated the time of conversion from relapsing-remitting MS (RRMS) to SPMS and its early predictor factors. METHODS: In this retrospective study, demographic, clinical, and imaging data from MS patients at diagnosis were extracted. Cox proportional hazards model was used to assess the association between various baseline characteristics and conversion to SPMS. We also assessed the association brtween escalation and early intensive therapy approaches with transition to progressive phase. RESULTS: Out of 1903 patients with RRMS at baseline, 293 (15.4%) patients progressed to SPMS during follow-up. The estimated number of patients converted to SPMS was 10% at 10-years, 50% at 20-years, and 93% at 30-years. On multivariate Cox regression analysis older age at onset (HR: 1.067, 95%CI: 1.048-1.085, p < 0.001), smoking (HR: 2.120, 95%CI: 1.203-3.736, p = 0.009), higher EDSS at onset (HR: 1.199, 95%CI: 1.109-1.295, p < 0.001), motor dysfunction (HR: 2.470, 95%CI: 1.605-3.800, p < 0.001), cerebellar dysfunction (HR: 3.096, 95%CI: 1.840-5.211, p < 0.001), and presence of lesions in spinal cord (HR: 0.573, 95%CI: 0.297-0.989, p = 0.042) increased the risk of conversion from RRMS to SPMS. No significant difference between escalation and EIT groups in the risk of transition to progressive phase (weighted HR = 1.438; 95% CI: 0.963, 2.147; p = 0.076) was found. CONCLUSION: Our data support previous observations that smoking is a modifiable risk factor for secondary progressive MS and confirms that spinal cord involvement, age, and more severe disease at onset are prognostic factors for converting to secondary progressive MS.

An overview of the role of interleukin-8 in colorectal cancer.

Colorectal Cancer (CRC), a common malignancy, is developing globally among people. Mutagenic insults activate peripheral nucleated cells to secrete chemokines in order to cause an inflammatory state. Despite the presence of multi-retrieving factors, elevated production of minor cytokines may speed-up the sever stages of the baseline inflammation targeting normal compensatory mechanism. IL-8 is a pro-inflammatory cytokine that is believed to be up-regulated in CRC to proceed primary condition into tumor behavior via induction of proliferation, angiogenesis and metastasis. Here, we assess the role of IL-8 in every step of CRC from signaling pathway and formation to invasion and discuss around new perspective therapy that targets IL-8 to manage CRC worldwide incidence and survival rate, more precisely.

Association of helicobacter pylori with multiple sclerosis: Protective or risk factor?

Background: Multiple sclerosis (MS) is a common autoimmune inflammatory disease in the central nervous system (CNS) without exact pathology. Environmental factors such as infections have a causal or protective role in MS. Helicobacter pylori (HP) is one of the infections in digestive diseases and previous studies reported controversial findings of this infection role in MS. So, we conducted this study to assess the frequency of HP infection in patients with MS in comparison to the healthy population. Methods: This cross-sectional study was undertaken between 2015 and 2019. 191 participants including 58 patients with clinically isolated syndrome (CIS), 57 patients with relapsing-remitting MS (RRMS), 39 patients with secondary progressive MS (SPMS), and 39 age- and sex-matched healthy controls (HCs) were tested for the presence of HP immunoglobulin G (IgG) and IgM antibodies (Abs) in their serum sample. Results: The frequency of HP IgG seropositivity in patients with SPMS was significantly higher than patients with CIS [Odds ratio (OR): 6.333, 95% confidence interval (CI): 2.522-15.906, P < 0.001], patients with RRMS (OR: 4.583, 95% CI: 1.842-11.407, P = 0.001), and HCs (OR: 8.485, 95% CI: 3.058-23.540, P < 0.001). We did not find a significant difference among other study groups regarding IgG seropositivity. No significant difference among groups regarding HP IgM seropositivity was evident. On univariate model, Expanded Disability Status Scale (EDSS) score (OR: 1.038, 95% CI: 1.038-1.460, P = 0.017) and SPMS (OR: 4.583, 95% CI: 1.842-11.407, P = 0.001) were predictor for HP IgG seropositivity. On multivariate model, only SPMS had higher risk for HP IgG seropositivity compared to RRMS (OR: 5.554, 95% CI: 1.327-23.253, P = 0.019). We did not find a significant association between clinical and demographic variables with HP IgM seropositivity. Conclusion: Based on our findings, progressive MS and HP infection may have association. Further longitudinal studies with large sample size are needed to determine the role of HP infection in MS.