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Zonulin-Dependent Intestinal Permeability in Children Diagnosed with Mental Disorders: A Systematic Review and Meta-Analysis.
Asbjornsdottir, B, Snorradottir, H, Andresdottir, E, Fasano, A, Lauth, B, Gudmundsson, LS, Gottfredsson, M, Halldorsson, TI, Birgisdottir, BE
Nutrients. 2020;(7)
Abstract
Worldwide, up to 20% of children and adolescents experience mental disorders, which are the leading cause of disability in young people. Research shows that serum zonulin levels are associated with increased intestinal permeability (IP), affecting neural, hormonal, and immunological pathways. This systematic review and meta-analysis aimed to summarize evidence from observational studies on IP in children diagnosed with mental disorders. The review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of the Cochrane Library, PsycINFO, PubMed, and the Web of Science identified 833 records. Only non-intervention (i.e., observational) studies in children (<18 years) diagnosed with mental disorders, including a relevant marker of intestinal permeability, were included. Five studies were selected, with the risk of bias assessed according to the Newcastle-Ottawa scale (NOS). Four articles were identified as strong and one as moderate, representing altogether 402 participants providing evidence on IP in children diagnosed with attention deficit and hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD). In ADHD, elevated serum zonulin levels were associated with impaired social functioning compared to controls. Children with ASD may be predisposed to impair intestinal barrier function, which may contribute to their symptoms and clinical outcome compared to controls. Children with ASD, who experience gastro-intestinal (GI) symptoms, seem to have an imbalance in their immune response. However, in children with OCD, serum zonulin levels were not significantly different compared to controls, but serum claudin-5, a transmembrane tight-junction protein, was significantly higher. A meta-analysis of mean zonulin plasma levels of patients and control groups revealed a significant difference between groups (p = 0.001), including the four studies evaluating the full spectrum of the zonulin peptide family. Therefore, further studies are required to better understand the complex role of barrier function, i.e., intestinal and blood-brain barrier, and of inflammation, to the pathophysiology in mental and neurodevelopmental disorders. This review was PROSPERO preregistered, (162208).
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Protein induced by vitamin K absence or antagonist-II versus alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: A systematic review with meta-analysis.
Xing, H, Zheng, YJ, Han, J, Zhang, H, Li, ZL, Lau, WY, Shen, F, Yang, T
Hepatobiliary & pancreatic diseases international : HBPD INT. 2018;(6):487-495
Abstract
BACKGROUND As a promising biomarker of hepatocellular carcinoma (HCC), protein induced by vitamin K absence or antagonist-II (PIVKA-II) has been studied extensively. However, its diagnostic capability varies across HCC studies. This study aimed to compare the performance of PIVKA-II with alpha-fetoprotein (AFP) in the diagnosis of HCC. DATA SOURCES A systematic literature search was conducted to identify the studies from MEDLINE, Embase and Cochrane Library Databases, which were published up to December 20, 2017 to compare the diagnostic capability of PIVKA-II and AFP for HCC. The data were pooled using random effects model. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curve (ROC) was employed to evaluate the diagnostic accuracy of each marker. RESULTS Thirty-one studies were included. The pooled sensitivity (95% CI) of PIVKA-II and AFP was 0.66 (0.65-0.68) and 0.66 (0.65-0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity (95% CI) was 0.89 (0.88-0.90) and 0.84 (0.83-0.85), respectively. The area under the ROC curve (AUC) of PIVKA-II and AFP was 0.856 (0.817-0.895) and 0.770 (0.728-0.811), respectively. Subgroup analysis showed that PIVKA-II was superior to AFP in terms of the AUC for both small HCC (< 3 cm) [0.863 (0.825-0.901) vs 0.717 (0.658-0.776)] and large HCC (≥ 3 cm) [0.854 (0.811-0.897) vs 0.729 (0.682-0.776)]; for American [0.926 (0.897-0.955) vs 0.698 (0.594-0.662)], European [0.772 (0.743-0.801) vs 0.628 (0.594-0.662)], Asian [0.838 (0.812-0.864) vs 0.785 (0.764-0.806)] and African [0.812 (0.794-0.840) vs 0.721 (0.675-0.767)] HCC patients; and for HBV-related [0.909 (0.866-0.951) vs 0.714 (0.673-0.755)] and mixed-etiology [0.847 (0.821-0.873) vs 0.794 (0.772-0.816)] HCC. CONCLUSION This meta-analysis indicates that PIVKA-II is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.
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Prognostic value of PIVKA-II in hepatocellular carcinoma patients receiving curative ablation: A systematic review and meta-analysis.
Zhang, D, Liu, Z, Yin, X, Qi, X, Lu, B, Liu, Y, Hou, J
The International journal of biological markers. 2018;(3):266-274
Abstract
BACKGROUND Several studies have been conducted to evaluate the prognostic value of prothrombin induced by vitamin K absence-II (PIVKA-II) overexpression in hepatocellular carcinoma patients treated with curative ablation. However, the results remain controversial. The purpose of this meta-analysis was to explore the correlation between PIVKA-II expression and survival outcomes in these patients. METHODS We performed a systematic literature search in PubMed, EMBASE, Medline, Cochrane Library, and Web of Science to identify the relevant articles investigating the prognostic value of PIVKA-II in patients with hepatocellular carcinoma. Combined hazard ratios (HR) and their 95% confidence intervals (CI) for overall survival and recurrence-free survival were calculated as the analysis endpoints. RESULTS A total of 15 cohorts encompassing 5647 patients were included. The results indicated that elevated PIVKA-II was significantly associated with poorer overall survival (HR 1.59; 95% CI 1.40, 1.82; P < 0.001) and recurrence-free survival (HR 1.76; 95% CI 1.42, 2.17; P < 0.001). Similar results were observed in the subgroup analysis based on sample size, analytical method, treatment modality, and cut-off value. CONCLUSIONS This meta-analysis suggests that elevated PIVKA-II is a predictor of unfavorable overall survival and recurrence-free survival in hepatocellular carcinoma patients receiving curative ablation. More rigorous studies are warranted to confirm the clinical utility of PIVKA-II in determining hepatocellular carcinoma prognosis.
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Performance of protein induced by vitamin K absence or antagonist-II assessed by chemiluminescence enzyme immunoassay for hepatocellular carcinoma detection: a meta-analysis.
Caviglia, GP, Ribaldone, DG, Abate, ML, Ciancio, A, Pellicano, R, Smedile, A, Saracco, GM
Scandinavian journal of gastroenterology. 2018;(6):734-740
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Abstract
OBJECTIVES In the setting of surveillance for hepatocellular carcinoma (HCC) detection, the use of serum biomarkers in addition to ultrasonography (US) is still a matter of debate. Hence, we performed a meta-analysis to evaluate the diagnostic accuracy of protein induced by vitamin K absence or antagonist-II (PIVKA-II) and alpha-fetoprotein (AFP) alone or in combination for HCC detection in patients at risk of tumor development. MATERIALS AND METHODS We performed a systematic search in PubMed and Scopus database for original articles published in English from 2011 to 2017, investigating the accuracy of PIVKA-II alone or in combination with AFP (reported as area under the curve [AUC]) for HCC detection among patients at risk of tumor development. Furthermore, we focused on studies in which serum PIVKA-II was assessed by highly sensitive chemiluminescence immunoassay (CLEIA). RESULTS A total of 11 studies (873 patients with HCC and 1244 patients with advanced liver disease/cirrhosis) were included in the meta-analysis. The weighted summary AUC (sAUC) of PIVKA-II and AFP for the discrimination between patients with HCC and those without was 0.791 (0.746-0.837) and 0.767 (0.732-0.803), respectively. The combination of PIVKA-II + AFP results in a sAUC of 0.859 (0.837-0.882). The performance for HCC detection of PIVKA-II + AFP was significantly superior to each biomarker used alone (ΔsAUC = 0.068, p = .032 and ΔsAUC = 0.092, p < .001, respectively). CONCLUSION In clinical practice, the use of PIVKA-II + AFP in addition to US examination may improve the effectiveness of surveillance among patients at risk for HCC development.
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Prognostic value of procalcitonin in respiratory tract infections across clinical settings.
Kutz, A, Briel, M, Christ-Crain, M, Stolz, D, Bouadma, L, Wolff, M, Kristoffersen, KB, Wei, L, Burkhardt, O, Welte, T, et al
Critical care (London, England). 2015;(1):74
Abstract
INTRODUCTION Whether the inflammatory biomarker procalcitonin provides prognostic information across clinical settings and different acute respiratory tract infections (ARIs) is poorly understood. In the present study, we investigated the prognostic value of admission procalcitonin levels to predict adverse clinical outcome in a large ARI population. METHODS We analysed data from 14 trials and 4,211 ARI patients to study associations of admission procalcitonin levels and setting specific treatment failure and mortality alone at 30 days. We used multivariable hierarchical logistic regression and conducted sensitivity analyses stratified by clinical settings and ARI diagnoses to assess the results' consistency. RESULTS Overall, 864 patients (20.5%) experienced treatment failure and 252 (6.0%) died. The ability of procalcitonin to differentiate patients with from those without treatment failure was highest in the emergency department setting (treatment failure area under the curve (AUC): 0.64 (95% confidence interval (CI): 0.61, 0.67), adjusted odds ratio (OR): 1.85 (95% CI: 1.61, 2.12), P <0.001; and mortality AUC: 0.67 (95% CI: 0.63, 0.71), adjusted OR: 1.82 (95% CI: 1.45, 2.29), P <0.001). In lower respiratory tract infections, procalcitonin was a good predictor of identifying patients at risk for mortality (AUC: 0.71 (95% CI: 0.68, 0.74), adjusted OR: 2.13 (95% CI: 1.82, 2.49), P <0.001). In primary care and intensive care unit patients, no significant association of initial procalcitonin levels and outcome was found. CONCLUSIONS Admission procalcitonin levels are associated with setting specific treatment failure and provide the most prognostic information regarding ARI in the emergency department setting.
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Is M129V of PRNP gene associated with Alzheimer's disease? A case-control study and a meta-analysis.
Del Bo, R, Scarlato, M, Ghezzi, S, Martinelli-Boneschi, F, Fenoglio, C, Galimberti, G, Galbiati, S, Virgilio, R, Galimberti, D, Ferrarese, C, et al
Neurobiology of aging. 2006;(5):770.e1-770.e5
Abstract
The methionine/valine (M/V) polymorphism at codon 129 within the prion protein gene (PRNP) represents a known risk factor for Creutzfeldt-Jakob disease (CJD). Few authors reported also the effects of this polymorphism on the risk of Alzheimer's disease (AD), although with controversial results. To better clarify this issue, we performed a novel case-control study and a meta-analysis of published association studies between PRNP and AD. Our findings argue against PRNP as a susceptibility gene for developing AD in the Italian population but support the hypothesis that the V allele influences cognitive performances. The meta-analysis, revealed that Caucasian subjects homozygous at codon 129 had a 1.3-fold increased risk [95% CI: 1.0-1.6, p = 0.05] of developing AD compared to heterozygous individuals. We also observed that MM genotype and M allele represent a risk factor for AD, independently from the ethnic background, providing a significant but modest association between this polymorphism and AD.