Baseline adiponectin and leptin levels in predicting an increased risk of disease activity in rheumatoid arthritis: A meta-analysis and systematic review

To determine the pathogenic role of adipokines, such as adiponectin and leptin, in rheumatoid arthritis (RA) by investigating whether serum levels of these adipokines correlated with disease activity in RA patients. Medline, Cochrane, EMBASE and Google Scholar were searched for studies published until 5 November 2015 reporting serum levels of leptin and adiponectin and measures of disease activity including DAS scores and radiographic progression scores (such as total change in SHS scores and number of erosions). Secondary outcomes included pain scores, functional status and health questionnaires. Only randomized controlled trials, cohort studies, or two-armed prospective or retrospective studies were included. A χ²-based test of homogeneity was performed using Cochran’s Q statistic and I². A total of 917 predominantly female participants (average age range, 39–56 years) from six prospective cohort studies were included for assessment. A fixed-effects analysis was applied for leptin levels due to lack of heterogeneity among the studies (Q?=?4.4364; I^2?=^?32.38). A random-effects analysis was applied to serum levels of adiponectin because of significant heterogeneity between studies (Q?=?4.444, I^2?=^?77.50%). Serum leptin levels were higher in RA patients with high disease activity (pooled SMD: 0.53, 95% CI: 0.24–0.82); however, serum adiponectin levels did not correlate with RA disease activity (pooled OR: 1.38, 95% CI: 0.77–2.47). The meta-analysis provides an additional factor to determine high disease activity index in RA, that is, serum leptin levels, which can be of benefit when choosing treatment strategies.     

Quantifying, displaying and accounting for heterogeneity in the meta-analysis of RCTs using standard and generalised Q statistics

Background  

Clinical researchers have often preferred to use a fixed effects model for the primary interpretation of a meta-analysis. Heterogeneity is usually assessed via the well known Q and I ² statistics, along with the random effects estimate they imply. In recent years, alternative methods for quantifying heterogeneity have been proposed, that are based on a 'generalised' Q statistic.     

The PD-1 rs36084323 A > G polymorphism decrease cancer risk in Asian: A meta-analysis

The rs36084323 A?>?G polymorphism in programmed cell death-1(PD-1) gene has been reported to be associated with cancer risk. However, the results of previous studies were inconsistent. Therefore, we performed a meta-analysis to identify the potential association, by searching the PubMed, EMBASE, Cochrane Library, and the Chinese CNKI, WANFANG and CBM databases. Data were extracted and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the strength of the association. A total of 10 relevant studies involving 4445 cancer cases and 5126 controls were recruited. Overall, the results indicated that the PD-1 rs36084323 A?>?G polymorphism was not statistically associated with cancer risk. However, stratified analysis revealed that there was a statistically reduced cancer risk in Asians(G vs. A, OR?=?0.89, 95%CI:0.81–0.97, P?=?0.008, I²?=?48.8%; GG vs. AA, OR?=?0.79, 95% CI:0.66–0.94, P?=?0.008, I²?=?48.7%; GG/AG vs. AA, OR?=?0.87, 95%CI:0.76–0.98, P?=?0.017, I²?=?34.9%; GG vs. AG/AA, OR?=?0.85, 95%CI:0.75–0.97, P?=?0.027, I²?=?40%) and in the patients with EOC(AG vs. AA, OR?=?0.69, 95%CI:0.54–0.90, P?=?0.005, I²?=?0%; GG/AG vs. AA, OR?=?0.67, 95%CI:0.52–0.85, P?=?0.001, I²?=?0). Meta-regression showed that ethnicity (P?=?0.029) but not cancer types (P?=?0.792), source of controls (P?=?0.207) or ample size (P?=?0.585) were the sources of heterogeneity. This meta-analysis demonstrates the PD-1 rs36084323 A?>?G polymorphism is associated with decreased cancer risk in Asian, and suggests it could potentially serve as a biomarker to screen high-risk individuals. Large-scale and well-designed case-control studies are needed to enrich the evidence of this result.     

Diagnostic value of microRNA for pancreatic cancer: a meta-analysis

Introduction

MicroRNAs have been reported to be aberrantly expressed in patients with pancreatic cancer. The aim of the present meta-analysis is to establish the overall diagnostic accuracy of the measurement of microRNA for diagnosing pancreatic cancer.

Material and methods

After a systematic review of English language studies from Medline, Embase, and Cochrane Library, the sensitivity, specificity, and other measures of accuracy of microRNA in the diagnosis of pancreatic cancer were pooled using random-effects models. The methodological quality of each study was assessed by QUADAS (quality assessment for studies of diagnostic accuracy). Statistical analysis was performed by employing Meta-Disc 1.4 software and STATA. Summary receiver operating characteristic curves were used to summarize overall test performance. Deeks’ test was used to test the potential publication bias.

Results

Nine studies from seven publications met our inclusion criteria. The summary estimates for microRNAs in the diagnosis of pancreatic cancer in these studies were pooled sensitivity 0.89 (95% CI: 0.86-0.91), specificity 0.93 (95% CI: 0.90-0.95), positive likelihood ratio 11.62 (95% CI: 5.75-23.50), negative likelihood ratio 0.14 (95% CI: 0.08-0.24), diagnostic odds ratio 115.13 (95% CI: 33.73-351.28), and the area under the curve was 0.97.

Conclusions

MicroRNA assay plays an important role in the diagnosis of pancreatic cancer. The results of microRNA assays should be interpreted in parallel with clinical findings and the results of conventional tests.     

Prospects for adoptive immunotherapy of pancreatic cancer using chimeric antigen receptor-engineered T-cells

Abstract

Adoptive immunotherapy using chimeric antigen receptor (CAR) engineered T-cells is emerging as a powerful new approach to cancer immunotherapy. CARs are fusion molecules that couple the antibody-like binding of a native cell surface target to the delivery of a bespoke T-cell activating signal. Recent studies undertaken by several centers have demonstrated highly compelling efficacy in patients with acute and chronic B-cell malignancies. However, comparable therapeutic activity has not been achieved in solid tumors. Modern management of pancreatic ductal adenocarcinoma (PDAC) remains ineffective, reflected in the virtual equivalence of annual incidence and mortality statistics for this tumor type. Increasing evidence indicates that these tumors are recognized by the immune system, but deploy powerful evasion strategies that limit natural immune surveillance and render efforts at immunotherapy challenging. Here, we review preclinical and clinical studies that have been initiated or completed in an effort to develop CAR-based immunotherapy for PDAC. We also consider the hurdles to the effective clinical development of this exciting new therapeutic modality.     

Smoking and Drinking Adjusted Association between Head and Neck Cancers and Oral Health Status Related to Periodontitis: a Meta-Analysis

BackgroundNot so many reports about the association between head and neck cancer (HNC) and oral health status related to periodontitis (OHS-P) has been published in different countries with different methods. So, there is a need for an extensive meta-analysis with the total articles published until 2020. Hence, this study aimed to estimate the association between HNC and OHS-P through a meta-analysis.MethodsBased on Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines, 22 studies were selected through PubMed and Cochrane Library databases. Meta-analysis using them was performed to evaluate the association. The risk of bias assessment using the Newcastle-Ottawa Scale (NOS) was applied to evaluate the quality of non-randomized studies. Publication bias was evaluated by funnel plot and Egger''s regression test.ResultsSince heterogeneity was significant (I² = 88%, P < 0.001), we adopted the random effect model for 22 studies. Those with bad OHS-P, compared to those with good OHS-P, were more likely to have the risk of HNC by 2.4 times (odds ratio [OR], 2.42; 95% confidence interval [CI], 1.88–3.13) for random effect model. The association included publication bias (Egger''s regression, P value < 0.001). The association among five studies (I² = 39%, P = 0.16) using alveolar bone loss (ABL) or clinical attachment level (CAL) for assessing periodontitis increased to OR of 3.85 (CI, 3.04–4.88) in the fixed effect model without publication bias (Egger''s regression, P = 0.66). Moreover, the association was higher in 10 fair or good NOS studies (OR, 3.08) and in 7 Asian studies (OR, 2.68), which were from the fixed model without publication bias.ConclusionOur meta-analysis showed that bad OHS-P was associated with the risk of HNC. The association was stronger in studies using ABL or CAL for assessing periodontitis.     

Prevalence of depression among women with obstetric fistula in low-income African countries: a systematic review and meta-analysis

Depression is one of mental health consequences that present in women with obstetric fistula. It is estimated that over 264 million people of all ages suffer from depression globally. The objective of this systematic review and meta-analysis was to synthesize the epidemiologic evidence from previous studies on the prevalence of depression among women with obstetric fistula in low-income African countries. We followed the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines to conduct this meta-analysis. The common databases (PubMed, SCOPUS, EMBASE, Psych INFO, Google Scholar, African Index Medicus, and African Journals Online (AJOL)) were searched for the relevant literature. We used a random-effect meta-analysis model to estimate the overall prevalence of depression and the Q -and I² -statistics were used to assess the heterogeneity between the studies included in the meta-analysis. Egger’s test and visual inspection of the symmetry in funnel plots were used to check for the presence of publication bias. The pooled estimated prevalence of depression among women with obstetric fistula in low-income African countries was 56.2% (95% CI 43.1–68.4). The prevalence of depression among women with obstetric fistula was 74.4% in Ethiopia, 72.9% in Kenya, 46.0% in Malawi, 41.0% in Sudan, 34.8% in Nigeria, and 27.7% in Tanzania. Furthermore, the prevalence of depression was higher (97.0%) when it was measured by using Beck’s Depression Inventory (BDI) when compared with Patient Health Questionnaire (PHQ9) (62.7%), General Health Questionnaire (GHQ-28) (36.7%), Hamilton Depression Rating Scale (HDRS) (41.0%), and Center for Epidemiologic Studies Depression Scale (CES-D) (27.7%). Moreover, the pooled estimated prevalence of depression among women with obstetric fistula was ranged from 48.1 to 57.7% in a leave-one-out sensitivity analysis. The prevalence of depression among women with obstetric fistula in low-income African countries was high. Screening and appropriate management of depression among women with obstetric fistula are warranted.

     

Experimental manipulation of affective judgments about physical activity: a systematic review and meta-analysis of adults

The purpose of this meta-analysis was to examine the current effectiveness of physical activity (PA) interventions to change affective judgements (AJ) and subsequent behaviour and explore potential moderators. Eligible studies were published in a peer-reviewed English journal and included an experimental design in the PA domain with a measure of AJ as the dependent variable, among adults (>17 years). Literature searches concluded in July 2017 using 11 common databases, with additional hand searching conducted in February 2018. The search yielded 32 independent studies. Random-effects meta-analysis showed positive changes in AJ favouring intervention over control groups, g?=?0.43 (95% CI?=?0.26–0.60). These changes predicted (β?=?0.64) positive changes in PA, g = 0.38 (95% CI = 0.16–0.60), among a sub-sample (k?=?14) of studies that also provided behavioural data. Moderator analyses showed the effects were inflated by potential publication bias, participant gender, baseline PA and focus of the intervention. AJ may show change from intervention but larger sample studies are required to obtain a more reliable effect size estimate. Further, few studies have employed behaviour change techniques that would align with the theoretical reasons for changes in AJ, so our evidence for practical intervention content is limited.     

Addition of the C-terminus of CD6 to a chimeric antigen receptor enhances cytotoxicity and does not compromise expression

T cells expressing chimeric antigen receptors (CARs) are a promising new cancer immunotherapy that has now reached the clinic. CARs are synthetic receptors that redirect T cells towards a tumour-associated antigen and activate them through various fused signalling regions, for example derived from CD3ζ, 4-1BB or CD28. Analysis of the optimal combination of CAR components including signalling domains is not yet comprehensive and may vary with the particular application. The C-terminus of the T-cell surface receptor CD6 is critical for its co-stimulatory effects and signals through two phospho-tyrosine motifs that bind to the intracellular adaptor proteins GADS and SLP-76. Addition of the C terminus of CD6 did not compromise CAR expression, showing it was a stable moiety that can be used independently of the native receptor. A third-generation CAR containing 4-1BB, CD3ζ and the C terminus of CD6 (4-1BBz-CD6) enhanced interferon-γ release and cytotoxicity when compared with the second-generation 4-1BB CD3ζ (4-1BBz) CAR. The CD6 C terminus is a valuable addition to potential components for modular design of CARs to improve effector function, particularly cytotoxicity.     

Association Between CD24-P226-C/T Polymorphism and Multiple Sclerosis: A Meta-Analysis

Background: Multiple sclerosis (MS) is a progressive inflammatory and neurodegenerative disease of the central nervous system (CNS), the etiology of which is still uncertain. Several case-control studies investigated the association between CD24-P226-C/T polymorphism and MS risk, and these studies have shown inconsistent results.

Objective: To address the association of CD24-P226-C/T polymorphism with MS risk by meta-analysis.

Methods: A comprehensive search was conducted to identify all eligible studies of CD24-P226-C/T polymorphism and MS risk up to July 2013. The odds ratios (ORs) of CD24 allele distributions in MS were analyzed against controls.

Results: In total, seven case-control studies with 949 cases of MS and 1177 controls were included in this meta-analysis. The overall results showed a significant association between CD24-P226-C/T polymorphism and MS susceptibility under homozygote comparison model (OR?=?2.496, 95% CI?=?1.813–3.435, p?<?0.0005), dominant model (OR?=?1.367, 95% CI?=?1.147–1.629, p?<?0.0005), recessive model (OR?=?2.305, 95% CI?=?1.700–3.126, p?<?0.0005) and allelic model (OR?=?1.422, 95% CI?=?1.244–1.625, p?<?0.0005). However, no significant association was observed under heterozygous comparison model (OR?=?1.182, 95% CI?=?0.982–1.423, p?=?0.078).

Conclusions: This meta-analysis indicates that CD24 P266-C/T polymorphism is more associated with the risk of MS than healthy controls. However, due to the small sample size in most of the included studies, additional large-scale and well-designed case-control studies were required for the validation of this association.     

Methylenetetrahydrofolate reductase gene polymorphisms and lung cancer: a meta-analysis

So far, case-control studies on the association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and lung cancer provide controversial or inconclusive results. To clarify the effect of MTHFR polymorphisms on the risk of lung cancer, a meta-analysis of all case-control observational studies was performed. The studies provided 5,111/6,415 cases/controls for C677T and 5,087/6,232 cases/controls for A1298C. The heterogeneity (P = 0.0001, I ² = 76.6%) for C677T among the eight studies was extreme. Cluster analyses based on the frequencies of the C677T genotype of the control group in each study revealed that the studies could not cluster together according to their ethnicity. The random effects (RE) model showed that the 677T allele was not associated with the risk of lung cancer compared with the C allele [OR = 1.12, 95% confidence interval (CI) (0.97–1.28), P = 0.12]. The contrast of homozygotes, recessive model, dominant model produced the same pattern of results as the allele contrast. In regard to the A1298C polymorphism, there was no heterogeneity among the seven studies comparing the C versus the A allele (P = 0.24, I ² = 24.4%), but no significant association was detected by the RE model or the fixed effects model [FE odds ratio (OR) = 0.99 (0.93–1.05) and RE OR = 1.00 (0.92–1.08)]. The effect of MTHFR polymorphisms (C677T, A1298C) on the risk of lung cancer was undetectable, even though analyzed on a relatively good number of subjects (totally 11,526 subjects) by meta-analysis (statistical power = 93.9%). Although MTHFR polymorphisms were associated with the risk of colorectal cancer, leukemia, and gastric cancer supported by other meta-analysis, our pooled data suggest no evidence for a major role of these two variants in carcinogenesis of lung cancer. The results implied that different tumors evolve by different pathological pathways and the roles of MTHFR in cancer is determined by its target genes.     

Circulating Levels of Osteoprotegerin,Osteocalcin and Osteopontin in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis

Objective: Currently published data regarding the potential role of osteoprotegerin (OPG), osteocalcin (OCN) and osteopontin (OPN) for the discrimination between rheumatoid arthritis (RA) and osteoarthritis (OA) are contradictory. To derive a more precise evaluation, a meta-analysis was performed. Methods: Published literatures comparing plasma/serum OPG, OCN and OPN levels between RA group and OA controls were searched in PubMed, Embase and the Cochrane Library. The Newcastle-Ottawa Scale was used to assess the study quality. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I². Results: Nine studies including 438 RA patients and 255 OA patients were finally incorporated in the meta-analysis after examining title, type, abstracts and full text. The results showed that RA patients had higher plasma/serum OPN (pooled SMD = ?2.57, 95% CI = ?4.72 to ?0.41) levels when compared to OA patients. No significant difference in plasma/serum OPG (pooled SMD = ?0.29, 95% CI = ?1.07?0.49) and OCN (pooled SMD = ?0.09, 95% CI = ?0.48?0.31) levels were found between RA patients and OA patients. Subgroup analysis indicated that plasma/serum OPG levels had no significant differences between RA patients and OA patients in Europe and Asian. Conclusions: Overall, there is no significant difference in circulating OPG and OCN levels between RA patients and OA patients. However, plasma/serum OPN level is significantly higher in RA patients compared with OA patients.     

The effectiveness of visceral osteopathy in pain,disability, and physical function in patients with low-back pain. A systematic review and meta-analysis

Background and purposeSystematic review and meta-analysis to assess the effectiveness of visceral osteopathy in improving pain intensity, disability and physical function in patients with low-back pain (LBP).Materials and methodsMEDLINE (Pubmed), PEDro, SCOPUS, Cochrane Library and Web of Science databases were searched from inception to February 2022. PICO search strategy was used to identify randomized controlled trials applying visceral techniques in patients with LBP. Eligible studies and data extraction were conducted independently by two reviewers. Quality of the studies was assessed with the Physiotherapy Evidence Database scale, and the risk of bias with Cochrane Collaboration tool. Meta-analyses were conducted using random effects models according to heterogeneity assessed with I² coefficient. Data on outcomes of interest were extracted by a researcher using RevMan 5.4 software.ResultsFive studies were included in the systematic review involving 268 patients with LBP. The methodological quality of the included ranged from high to low and the risk of bias was high. Visceral osteopathy techniques have shown no improvements in pain intensity (Standardized mean difference (SMD) = -0.53; 95% CI; -1.09, 0.03; I²: 78%), disability (SMD = -0.08; 95% CI; -0.44, 0.27; I²: 0%) and physical function (SMD = -0.26; 95% CI; -0.62, 0.10; I²: 0%) in patients with LBP.ConclusionsThis systematic review and meta-analysis showed a lack of high-quality studies showing the effectiveness of visceral osteopathy in pain, disability, and physical function in patients with LBP.     

Association between CARD8 rs2043211 Polymorphism and Inflammatory Bowel Disease: A Meta-Analysis

Objective: The aim of this study was to determine whether caspase recruitment domain-containing protein 8 (CARD8) rs2043211 polymorphism was associated with susceptibility to inflammatory bowel disease (IBD).

Methods: Relevant studies were searched using PubMed and Embase up to February 2014. A meta-analysis was conducted on the association between rs2043211 polymorphism and IBD using: (1) allele contrast, (2) the dominant model, (3) the recessive model, and (4) homozygote contrast. The pooled estimated of risk was obtained by random-effects model or fixed-effects model. Publication bias was assessed by Egger’s test.

Results: Eight relevant articles with a total of 10?534 IBD patients [6785 Crohn’s disease (CD), 3713 ulcerative colitis (UC) and 36 indeterminate colitis (IC)] and 6755 healthy controls were included in the meta-analysis, which consisted of 12 studies, 12 for CD, 10 for UC, 2 for IC. There was no significant association between rs2043211 polymorphism and IBD, CD, and IC in overall population. However, stratified meta-analysis by ethnicity showed significant association between rs2043211 polymorphism and CD in the European population under the dominant model [odds ratio (OR)?=?1.210, 95% confidence interval (CI)?=?1.013–1.445, p?=?0.036] and homozygote contrast (OR?=?1.212, 95% CI?=?1.005–1.461, p?=?0.044).

Conclusions: Our meta-analysis results indicated significant association between rs2043211 polymorphism and the susceptibility to CD under the dominant model and homozygote contrast in the European population.     

Meta-Analysis of Associations Between Interleukin-10 Polymorphisms and Susceptibility to Vasculitis

Objective: This study determined whether interleukin-10 (IL-10) polymorphisms are associated with susceptibility to vasculitis.

Methods: A meta-analysis was conducted of the associations between the IL-10 -1082 G/A, -819 C/T, and -592 C/A polymorphisms and the haplotype of the IL-10-1082 G/A, -819 C/T, -592 C/A polymorphisms and vasculitis.

Results: A total of 21 comparative studies involving 4121 patients and 5504 controls were considered in the meta-analysis. Meta-analysis revealed no association between the IL-10-1082 G allele and vasculitis in all study subjects (OR?=?0.927, 95% CI?=?0.780–1.102, p?=?0.389). However, disease-specific meta-analysis showed an association between Wegener’s granulomatosis (WG) and the IL-10-1082 G allele (OR?=?0.729, 95% CI?=?0.547–0.971, p?=?0.031). Meta-analysis revealed an association between vasculitis and the IL-10-819 C allele (OR?=?0.804, 95% CI?=?0.706–0.916, p?=?0.001) in all study subjects and Behcet’s disease (BD) (OR?=?0.724, 95% CI?=?0.679–0.781, p?<?1.0?×?10^?9). Meta-analysis of the IL-10-592 C allele showed an association with vasculitis in all study subjects (OR?=?0.805, 95% CI?=?0.619–0.938, p?=?0.005) and BD (OR?=?0.718, 95% CI?=?0.661–0.781, p?<?1.0?×?10^?9). Meta-analysis of the IL-10 haplotype revealed an association between the GCC haplotype and vasculitis in Europeans (OR?=?1.239, 95% CI?=?1.105–1.513, p?=?0.035).

Conclusions: This meta-analysis showed that IL-10 polymorphisms are associated with vasculitis susceptibility, especially in WG and BD.     

Comparison of survival outcomes between primary and secondary muscle-invasive bladder cancer: An updated meta-analysis

Objective: Studies have showed that different follow-up starting points might potentially impact the comparison between primary (PMIBC) and secondary muscle-invasive bladder cancer (SMIBC), but the only previous meta-analysis did not differentiate the follow-up starting points of included studies. With more trials published, we aim to update the meta-analysis comparing PMIBC and SMIBC.Methods: PubMed, Embase, Cochrane Library and ClinicalTrial.gov. systematically searched. Literatures comparing the survival outcomes of PMIBC and SMIBC were selected. Outcomes of cancer-specific mortality (CSM), overall mortality (OM) and recurrence-free survival (RFS) were pooled and grouped based on the starting point of follow-up (after initial diagnosis or radical cystectomy (RC)). Newcastle-Ottawa Scale (NOS) and funnel plot were employed to assess the study quality and publication bias, respectively.Results: A total of 17 high-quality studies were selected, with 5558 patients aged from 59.8 to 72.7 (mean value) involved. The male-to-female ratio was roughly 4:1 (4390/1124). SMIBC had lower risk of CSM after initial diagnosis (HR 0.81, 95%CI 0.67-0.98, P=0.03, I²=70%), but higher risk of CSM after RC (HR 1.45, 95%CI 1.27-1.65, P<0.00001, I²=64%). In terms of OM and recurrence, outcomes were pooled only after RC, which both turned out to be higher for SMIBC (OM: HR 1.50, 95%CI 1.30-1.73, P<0.00001, I²=0%; Recurrence: HR 1.66, 95%CI 1.36-2.02, P<0.00001, I²=48%). No obvious publication bias was observed from funnel plot.Conclusion: The current study suggested SMIBC had higher risk of CSM, OM and recurrence after RC, but lower risk of CSM after initial diagnosis.     

Association of 12 polymorphic variants conferring genetic risk to lung cancer in Indian population: An extensive meta‐analysis

Candidate gene as well as genome‐wide association studies identified several polymorphic variants to be associated with lung cancer worldwide including in India. However, contradictory results have failed to estimate the overall effect of the polymorphic variants on the disease. Textmining was conducted on PubMed following specific search strings to gather all the publications related to genetic association with lung cancer in India. Out of 211 PubMed hits only 30 studies were selected for meta‐analysis following specific inclusion criteria. Heterogeneity between studies was calculated by Cochran's Q‐test (P < 0.05) and heterogeneity index (I²). Publication bias was visualized by funnel plots and Egger's regression test. For each variant, following a fixed‐effect model, summary odds ratio (OR) along with 95% confidence interval (CI) was estimated. The meta‐analysis revealed three polymorphic variants viz. ‘deletion polymorphism (del1) (OR = 1.39, 95% CI = 1.03–1.87, P = 0.027) in GSTT1’, ‘deletion polymorphism (del2) (OR = 1.30, 95% CI = 1.01–1.67, P = 0.038) in GSTM1’ and ‘rs1048943 (OR = 1.98, 95% CI = 1.27–3.10, P = 0.002) in CYP1A1’ to be associated with lung cancer. However, after multiple testing correction, only rs1048943 was found to be significantly associated (P value = 0.0321) with lung cancer. None of the polymorphic variants showed any evidence of heterogeneity between studies or of publication bias. Our meta‐analysis revealed strong association of rs1048943 in CYP1A1, but a suggestive association of deletion polymorphisms in GSTT1 and GSTM1 with lung cancer, which provides a comprehensive insight on the overall effect of the polymorphic variants, reported in various case–control studies on Indian population, on the risk of lung cancer development. Environ. Mol. Mutagen. 58:688–700, 2017. © 2017 Wiley Periodicals, Inc.     

Preclinical relevance of probiotics in type 2 diabetes: A systematic review

Type 2 diabetes (T2DM) is among the most prevalent metabolic diseases in the world and may result in several long‐term complications. The crosstalk between gut microbiota and host metabolism is closely related to T2DM. Currently, fragmented data hamper defining the relationship between probiotics and T2DM. This systematic review aimed at investigating the effects of probiotics on T2DM in animal models. We systematically reviewed preclinical evidences using PubMed/MEDLINE and Scopus databases, recovering 24 original articles published until September 27th, 2019. This systematic review was performed according to PRISMA guidelines. We included experimental studies with animal models reporting the effects of probiotics on T2DM. Studies were sorted by characteristics of publications, animal models, performed analyses, probiotic used and interventions. Bias analysis and methodological quality assessments were examined through the SYRCLE's Risk of Bias tool. Probiotics improved T2DM in 96% of the studies. Most studies (96%) used Lactobacillus strains, and all of them led to improved glycaemia. All studies used rodents as models, and male animals were preferred over females. Results suggest that probiotics have a beneficial effect in T2DM animals and could be used as a supporting alternative in the disease treatment. Considering a detailed evaluation of the reporting and methodological quality, the current preclinical evidence is at high risk of bias. We hope that our critical analysis will be useful in mitigating the sources of bias in further studies.     

The Polymorphisms K469E and G261R of Intercellular Adhesion Molecule-1 and Susceptibility to Inflammatory Bowel Disease: A Meta-Analysis

Objective: The aim of this study was to explore whether polymorphisms of intercellular adhesion molecule-1 (ICAM-1) are associated with susceptibility to Crohn’s disease (CD) and ulcerative colitis (UC).

Methods: The authors conducted a meta-analysis on the associations between the polymorphisms K469E and G241R of ICAM-1 and susceptibility to CD and UC.

Results: A total of 8 studies with 801 patients with CD, 672 patients with UC, and 1,828 controls were included in the meta-analysis. The meta-analysis revealed no association between CD and the ICAM-1 469E allele among the subjects (OR?=?1.175, 95% CI?=?0.901–1.533, p?=?0.233). However, stratification by ethnicity indicated an association between the ICAM-1 469E allele and CD in Europeans (OR?=?1.425, 95% CI?=?1.013–2.002, p?=?0.042). Meta-analysis using the homozygosity also showed an association with CD in Europeans (OR?=?2.054, 95% CI?=?1.036–4.073, p?=?0.039). The meta-analysis revealed no association between UC and the ICAM-1 K469E polymorphism. No association between CD or UC and the ICAM-1 G241R polymorphism was observed.

Conclusions: This meta-analysis demonstrates that the ICAM-1 K469E polymorphism may be associated with susceptibility to CD in Europeans, but no association was found between ICAM-1 K469E and UC. In contrast, the G241R polymorphism was not found to be associated with susceptibility to either CD or UC.     

The possible association between the presence of an MPO −463 G > A (rs2333227) polymorphism and cervical cancer risk

Purpose

The association between myeloperoxidase (MPO) polymorphism and the risk of cervical cancer is inconclusive. We performed a meta-analysis to clarify if a correlation exists between MPO polymorphism and the risk for developing cervical cancer.