Increased Prevalence of Celiac Disease in Patients with Cystic Fibrosis: A Systematic Review and Meta-Analysis

Objectives: Immune regulation seems to be altered in cystic fibrosis (CF), thus potentially predisposing patients to developing autoimmune diseases (AID). In this meta-analysis, we aimed to evaluate the prevalence of celiac disease (CeD) among CF patients as by far the most commonly reported autoimmune disease in this population and, secondly, to review the observations on other, less frequently studied autoimmune diseases. Methods: We conducted a systematic literature search for studies that discussed AIDs among CF patients. Following standard selection and data collection, we calculated pooled raw prevalence with 95% confidence intervals (CI) for biopsy-verified CeD and seropositivity. Results: Out of the 21 eligible studies, 15 reported on CeD. Pooled prevalence of biopsy-verified CeD was 1.8% (CI 1.1–2.7%) according to a homogeneous dataset from six prospective, consecutive screening studies, while it proved to be 2.3% (CI 1.1–4.7%) according to a heterogeneous dataset from the other studies. Tissue transglutaminase IgA positivity was detected in 4.5% of CF cases (CI 2.8–6.9%), while tissue transglutaminase IgA–endomysial antibody IgA double positivity was found in 2.4% of them (CI 1.5–3.9%). Findings on other AIDs were strongly limited. Conclusions: The pooled prevalence of CeD in CF seemed to be more than twice as high compared to the global prevalence; therefore, routine screening of CeD could be considered in CF

The risk of postoperative respiratory complications following adenotonsillar surgery in children with or without obstructive sleep apnea: A systematic review and meta-analysis

Obstructive sleep apnoea (OSA) appears in 2-5% of children, with first-line treatment being adenotonsillar (AT) surgery. Our aim was to examine the risk of postoperative respiratory complications (PoRCs) in non-OSA and the different OSA severity (mild, moderate, severe) groups.We conducted a systematic review and meta-analysis of studies comparing PoRCs following AT surgery in children with and without OSA.19 observational studies were identified with the same search key used in MEDLINE, Embase and CENTRAL. The connection between PoRCs, the presence and severity of OSA, and additional comorbidities were examined. Odds ratios (OR) were calculated with 95% confidence intervals (CI).We found that PoRCs appeared more frequently in moderate (p=0.048, OR: 1.79, CI (1.004, 3.194)) and severe OSA (p=0.002, OR: 4.06, CI (1.68, 9.81)) compared to non-OSA patients. No significant difference was detected in the appearance of major complications (p=0.200, OR: 2.14, CI (0.67, 6.86)) comparing OSA and non-OSA populations. No significant difference was observed in comorbidities (p=0.669, OR: 1.29, CI (0.40, 4.14)) or in the distribution of PoRCs (p=0.904, OR: 0.94, CI (0.36, 2.45)) between the two groups.Uniform guidelines and a revision of postoperative monitoring are called for, since children with moderate and severe OSA are more likely to develop PoRCs following AT surgery based on our results, but no significant difference was found in mild OSA. Furthermore, the presence of OSA only is not associated with an increased risk of developing major complications. This article is protected by copyright. All rights reserved

Utility of Direct Pancreatic Function Testing in Children

OBJECTIVES: Exocrine pancreatic insufficiency (EPI) can have a significant impact on a child's growth and nutrition. Our aim was to evaluate the utility of direct endoscopic pancreatic function testing (ePFT) in pediatrics. METHODS: A single-center retrospective chart review was performed of children who underwent ePFT from December 2007 through February 2015. Endoscopic pancreatic function testings were performed by 1 of 2 methods: (1) intravenous cholecystokinin, followed by the collection of a single duodenal aspirate at 10 minutes, or (2) intravenous cholecystokinin or secretin, followed by the collection of 3 duodenal aspirates at a 5, 10, and 15 minutes. Samples were tested for pH and enzyme activities. RESULTS: A total of 508 ePFTs were performed (481 single-sample tests, 27 multiple-sample tests). Based on the multiple-sample group, enzyme levels for chymotrypsin, amylase, and lipase peaked at 5 minutes, followed by a decrease in activity over time. Exocrine pancreatic sufficiency was identified in 373 (73.4%) and EPI in 93 (18.3%). Exocrine pancreatic sufficiency analysis found all pancreatic enzyme activities significantly increase with age: trypsin, chymotrypsin, amylase, and lipase, (P < 0.05). CONCLUSIONS: Endoscopic pancreatic function testing can be used in the evaluation of EPI in children. Normative data suggest that pancreatic enzyme activities mature with age

Genetic polymorphisms involved in mitochondrial metabolism and pancreatic cancer risk

The mitochondrial metabolism has been associated with pancreatic ductal adenocarcinoma (PDAC) risk. Recent evidence also suggests the involvement of the genetic variability of the mitochondrial function in several traits involved in PDAC aetiology. However, a systematic investigation of the genetic variability of mitochondrial genome (mtSNPs) and of all the nuclear genes involved in its functioning (n-mtSNPs) has never been reported.We conducted a two-phase association study of mtSNPs and n-mtSNPs to assess their effect on PDAC risk. We analysed 35,297 n-mtSNPs and 101 mtSNPs in up to 55,870 individuals (12,884 PDAC cases and 42,986 controls). In addition, we also conducted a gene-based analysis on 1,588 genes involved in mitochondrial metabolism using MAGMA software.In the discovery phase we identified 49 n-mtSNPs and no mtSNPs associated with PDAC risk (P <0.05). In the second phase none of the findings were replicated. In the gene-level analysiswe observed that three genes (TERT, SUGCT and SURF1) involved in the mitochondrial metabolismshowed an association below the Bonferroni-corrected threshold of statistical significance (P=0.05/1588=3.1 x10-5).Even though the mitochondrial metabolism might be involved in PDAC aetiology, our results, obtained in a study with one of the largest sample sizes to date, show that neither n-mtSNPs nor mtSNPs are associated with PDAC risk.This large case-control study does not support a role of the genetic variability of the mitochondrial function in PDAC risk

Meta-Analysis of Early Nutrition: The Benefits of Enteral Feeding Compared to a Nil Per Os Diet Not Only in Severe, but Also in Mild and Moderate Acute Pancreatitis.

The recently published guidelines for acute pancreatitis (AP) suggest that enteral nutrition (EN) should be the primary therapy in patients suffering from severe acute pancreatitis (SAP); however, none of the guidelines have recommendations on mild and moderate AP (MAP). A meta-analysis was performed using the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P). The following PICO (problem, intervention, comparison, outcome) was applied: P: nutrition in AP; I: enteral nutrition (EN); C: nil per os diet (NPO); and O: outcome. There were 717 articles found in Embase, 831 in PubMed, and 10 in the Cochrane database. Altogether, seven SAP and six MAP articles were suitable for analyses. In SAP, forest plots were used to illustrate three primary endpoints (mortality, multiorgan failure, and intervention). In MAP, 14 additional secondary endpoints were analyzed (such as CRP (C-reactive protein), WCC (white cell count), complications, etc.). After pooling the data, the Mann-Whitney U test was used to detect significant differences. Funnel plots were created for testing heterogeneity. All of the primary endpoints investigated showed that EN is beneficial vs. NPO in SAP. In MAP, all of the six articles found merit in EN. Analyses of the primary endpoints did not show significant differences between the groups; however, analyzing the 17 endpoints together showed a significant difference in favor of EN vs. NPO. EN is beneficial compared to a nil per os diet not only in severe, but also in mild and moderate AP

Restoration of energy level in the early phase of acute pediatric pancreatitis

Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellular events in the early phase of AP. Moreover, it has been revealed that restoration of intracellular ATP level restores cellular functions and defends the cells from death. We have recently shown in a systematic review and meta-analysis that early enteral feeding is beneficial in adults; however, no reviews are available concerning the effect of early enteral feeding in pediatric AP. In this minireview, our aim was to systematically analyse the literature on the treatment of acute pediatric pancreatitis. The preferred reporting items for systematic review (PRISMA-P) were followed, and the question was drafted based on participants, intervention, comparison and outcomes: P: patients under the age of twenty-one suffering from acute pancreatitis; I: early enteral nutrition (per os and nasogastric- or nasojejunal tube started within 48 h); C: nil per os therapy; O: length of hospitalization, need for treatment at an intensive care unit, development of severe AP, lung injury (including lung oedema and pleural effusion), white blood cell count and pain score on admission. Altogether, 632 articles (PubMed: 131; EMBASE: 501) were found. After detailed screening of eligible papers, five of them met inclusion criteria. Only retrospective clinical trials were available. Due to insufficient information from the authors, it was only possible to address length of hospitalization as an outcome of the study. Our mini-meta-analysis showed that early enteral nutrition significantly (SD = 0.806, P = 0.034) decreases length of hospitalization compared with nil per os diet in acute pediatric pancreatitis. In this minireview, we clearly show that early enteral nutrition, started within 24-48 h, is beneficial in acute pediatric pancreatitis. Prospective studies and better presentation of research are crucially needed to achieve a higher level of evidence

Common variants in the CLDN2-MORC4 and PRSS1-PRSS2 loci confer susceptibility to acute pancreatitis

BACKGROUND/OBJECTIVES: Acute pancreatitis (AP) is one of the most common gastrointestinal disorders often requiring hospitalization. Frequent aetiologies are gallstones and alcohol abuse. In contrast to chronic pancreatitis (CP) few robust genetic associations have been described. Here we analysed whether common variants in the CLDN2-MORC4 and the PRSS1-PRSS2 locus that increase recurrent AP and CP risk associate with AP. METHODS: We screened 1462 AP patients and 3999 controls with melting curve analysis for SNPs rs10273639 (PRSS1-PRSS2), rs7057398 (RIPPLY), and rs12688220 (MORC4). Calculations were performed for the overall group, aetiology, and gender sub-groups. To examine genotype-phenotype relationships we performed several meta-analyses. RESULTS: Meta-analyses of all AP patients depicted significant (p-value<0.05) associations for rs10273639 (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.81-0.97, p-value 0.01), rs7057398 (OR 1.27, 95% CI 1.07-1.5, p-value 0.005), and rs12688220 (OR 1.32, 95% CI 1.12-1.56, p-value 0.001). For the different aetiology groups a significant association was shown for rs10273639 (OR 0.76, 95% CI 0.63-0.92, p-value 0.005), rs7057398 (OR 1.43, 95% CI 1.07-1.92, p-value 0.02), and rs12688220 (OR 1.44, 95% CI 1.07-1.93, p-value 0.02) in the alcoholic sub-group only. CONCLUSIONS: The association of CP risk variants with different AP aetiologies, which is strongest in the alcoholic AP group, might implicate common pathomechanisms most likely between alcoholic AP and CP