An international survey on anastomotic stricture management after esophageal atresia repair:considerations and advisory statements

BACKGROUND: Endoscopic dilatation is the first-line treatment of stricture formation after esophageal atresia (EA) repair. However, there is no consensus on how to perform these dilatation procedures which may lead to a large variation between centers, countries and doctor’s experience. This is the first cross-sectional study to provide an overview on differences in endoscopic dilatation treatment of pediatric anastomotic strictures worldwide. METHODS: An online questionnaire was sent to members of five pediatric medical networks, experienced in treating anastomotic strictures in children with EA. The main outcome was the difference in endoscopic dilatation procedures in various centers worldwide, including technical details, dilatation approach (routine or only in symptomatic patients), and adjuvant treatment options. Descriptive statistics were performed with SPSS. RESULTS: Responses from 115 centers from 32 countries worldwide were analyzed. The preferred approach was balloon dilatation (68%) with a guidewire (66%), performed by a pediatric gastroenterologist (n = 103) or pediatric surgeon (n = 48) in symptomatic patients (68%). In most centers, hydrostatic pressure was used for balloon dilatation. The insufflation duration was standardized in 59 centers with a median duration of 60 (range 5–300) seconds. The preferred first-line adjunctive treatments in case of recurrent strictures were intralesional steroids and topical mitomycin C, in respectively 47% and 31% of the centers. CONCLUSIONS: We found a large variation in stricture management in children with EA, which confirms the current lack of consensus. International networks for rare diseases are required for harmonizing and comparing the procedures, for which we give several suggestions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00464-020-07844-6) contains supplementary material, which is available to authorized users

The natural history of primary sclerosing cholangitis in 781 children. A multicenter, international collaboration

There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC-inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome. CONCLUSION: PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC-inflammatory bowel disease are more favorable disease phenotypes

The Use of Fecal Calprotectin Testing in Paediatric Disorders : A Position Paper of the European Society for Paediatric Gastroenterology and Nutrition Gastroenterology Committee

Objectives: The aim of the study was to review the evidence regarding the clinical use and value of fecal calprotectin (FC) measurements in different gastrointestinal disorders in children. Methods: A literature search was conducted in the PubMed, MEDLINE, EMBASE, and Cochrane databases until October 31, 2019. Subtopics were identified and each assigned to individual authors. Results: A total of 28 recommendations were voted on using the nominal voting technique. Recommendations are given related to sampling, measurement methods, and results interpretation. The 14 authors anonymously voted on each recommendation using a 9-point scale (1 strongly disagree to 9 fully agree). Consensus was considered achieved if at least 75% of the authors voted 6, 7, 8, or 9. Conclusions: Consensus was reached for all recommendations. Limitations for the use of FC in clinical practice include variability in extraction methodology, performance of test kits as well as the need to establish local reference ranges because of the influence of individual factors, such as age, diet, microbiota, and drugs. The main utility of FC measurement at present is in the diagnosis and monitoring of inflammatory bowel disease (IBD) as well as to differentiate it from functional gastrointestinal disorders (FAPDs). FC, however, has neither utility in the diagnosis of infantile colic nor to differentiate between functional and organic constipation. A rise in FC concentration, may alert to the risk of developing necrotizing enterocolitis and help identifying gastrointestinal involvement in children with Henoch-Schonlein purpura. FC measurement is of little value in Cow's Milk Protein Allergy, coeliac disease (CD), and cystic fibrosis. FC does neither help to distinguish bacterial from viral acute gastroenteritis (AGE), nor to diagnose Helicobacter Pylori infection, small intestinal bacterial overgrowth (SIBO), acute appendicitis (AA), or intestinal polyps.Peer reviewe

Inflammation in metabolically healthy and metabolically abnormal adolescents: The HELENA study

On behalf of the HELENA study group.[Background and aims] Inflammation may influence the cardio-metabolic profile which relates with the risk of chronic diseases. This study aimed to assess the inflammatory status by metabolic health (MH)/body mass index (BMI) category and to assess how inflammatory markers can predict the cardio-metabolic profile in European adolescents, considering BMI. [Methods and results] A total of 659 adolescents (295 boys) from a cross-sectional European study were included. Adolescents were classified by metabolic health based on age- and sex-specific cut-off points for glucose, blood pressure, triglycerides, high density cholesterol and BMI. C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin (IL-6), complement factors (C3, C4) and cell adhesion molecules were assessed. [Results] Metabolically abnormal (MA) adolescents had higher values of C3 (p < 0.001) and C4 (p = 0.032) compared to those metabolically healthy (MHy). C3 concentrations significantly increased with the deterioration of the metabolic health and BMI (p < 0.001). Adolescents with higher values of CRP had higher probability of being in the overweight/obese-MH group than those allocated in other categories. Finally, high C3 and C4 concentrations increased the probability of having an unfavorable metabolic/BMI status. [Conclusions] Metabolic/BMI status and inflammatory biomarkers are associated, being the CRP, C3 and C4 the most related inflammatory markers with this condition. C3 and C4 were associated with the cardio-metabolic health consistently.The HELENA Study was supported by the European Community Sixth RTD Framework Programme (Contract FOOD-CT-2005-007034) and the Stockholm County Council. This analysis was also supported by the Spanish Ministry of Science and Innovation (JCI-2010-07055) and the gs4:European Regional Development Fund (FEDER). CCS is supported by the Spanish Ministry of Economy and Competitiveness (BES-2014-068829). FBO is supported by a grant from the Spanish Ministry of Science and Innovation (RYC-2011-09011). AIR was funded by a Juan de la Cierva-Formación stipend from the Ministry of Economy and Competitiveness of the Spanish Government (FJCI-2014-19795).Peer Reviewe

Associations between macronutrient intake and serum lipid profile depend on body fat in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study

The present study aimed to investigate the relationships between macronutrient intake and serum lipid profile in adolescents from eight European cities participating in the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) cross-sectional study (2006–7), and to assess the role of body fat-related variables in these associations. Weight, height, waist circumference, skinfold thicknesses, total choles- terol, HDL-cholesterol (HDL-C), LDL-cholesterol, TAG, apoB and apoA1 were measured in 454 adolescents (44 % boys) aged 12·5–17·5 years. Macronutrient intake (g/4180 kJ per d (1000 kcal per d)) was assessed using two non-consecutive 24 h dietary recalls. Associations were evaluated by multi-level analysis and adjusted for sex, age, maternal education, centre, sum of four skinfolds, moderate-to-vigorous

Relative validity of the Planetary Health Diet Index by comparison with usual nutrient intakes, plasma food consumption biomarkers, and adherence to the Mediterranean diet among European adolescents: the HELENA study

Purpose The EAT-Lancet Commission proposed an evidence-based global reference diet to improve human health within planetary boundaries. Recently, the Planetary Health Diet Index (PHDI) was developed based on the EAT-Lancet recommendations and validated among Brazilian adults. However, the relative validity of the PHDI in adolescents has yet to be assessed. Thus, we aimed to evaluate the relative validity of the PHDI in European adolescents. Methods We used cross-sectional data from 1804 adolescents (12.5–17.5 years) enrolled in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study. The PHDI (0–150 points) was calculated based on dietary intake data from two non-consecutive 24-h dietary recalls. Associations between the PHDI and usual nutrient intakes, plasma food consumption biomarkers, and adherence to the Mediterranean diet were evaluated using multivariable-adjusted mixed-effects linear regression models. Results Higher PHDI score was associated with greater intakes of nutrients predominantly from plant-source foods, such as vegetable protein, vitamin E, and folate and with lower intake of nutrients predominately from animal-source foods, such as total and saturated fat, cholesterol, and animal protein. Furthermore, a higher PHDI score was also positively associated with plasma β-carotene, vitamin C, vitamin D, folate, and ferritin concentrations, while negatively associated with trans-fatty acids concentration. Moreover, higher PHDI was related to a greater adherence to the Mediterranean dietary pattern. Conclusions The PHDI showed good relative validity among adolescents in the HELENA study. Hence, future research should assess adherence to the PHDI and long-term health outcomes

Association between dietary inflammatory index and inflammatory markers in the HELENA study

Background: Previous research has shown that diet is associated with low-grade systemic inflammation among adults. However, no study has yet been conducted to explore the association between inflammatory potential of diet and low-grade systemic inflammation among adolescents whose dietary behavior may be different from adults. Methods and Results: We examine the predictive ability of 24-h recall-derived dietary inflammatory index (DII) scores on inflammation among 532 European adolescents in the HELENA cross-sectional study. The DII is a literature-derived dietary index developed to predict inflammation. The DII was calculated per 1000 calories and was tested against C-reactive protein, ILs-1,2,4,10, TNF-alpha, ICAM, vascular cell adhesion molecule (VCAM), and IFN-gamma. All inflammatory markers had nonnormal distributions and therefore were log transformed. Analyses were performed using multivariable linear regression, adjusting for age, sex, city, BMI, smoking, and physical activity. Pro-inflammatory diet (higher DII scores) was associated with increased levels of various inflammatory markers: TNF-alpha, IL-1, 2, IFN-gamma, and vascular cell adhesion molecule (b(DIIt3vs1) = 0.13, 95% CI: 0.001, 0.25; 0.13, 95% CI 0.001, 0.25; 0.40, 95% CI: 0.03, 0.77; 0.53, 95% CI: 0.05, 1.01; 0.07, 95% CI: 0.01, 0.13, respectively). Conclusion: These results reinforce the fact that diet, as a whole, plays an important role in modifying inflammation in adolescents

Development of a Genetic Risk Score to predict the risk of overweight and obesity in European adolescents from the HELENA study

Obesity is the result of interactions between genes and environmental factors. Since monogenic etiology is only known in some obesity-related genes, a genetic risk score (GRS) could be useful to determine the genetic predisposition to obesity. Therefore, the aim of our study was to build a GRS able to predict genetic predisposition to overweight and obesity in European adolescents. A total of 1069 adolescents (51.3% female), aged 11–19 years participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study were genotyped. The sample was divided in non-overweight (non-OW) and overweight/obesity (OW/OB). From 611 single nucleotide polymorphisms (SNP) available, a first screening of 104 SNPs univariately associated with obesity (p < 0.20) was established selecting 21 significant SNPs (p < 0.05) in the multivariate model. Unweighted GRS (uGRS) was calculated by summing the number of risk alleles and weighted GRS (wGRS) by multiplying the risk alleles to each estimated coefficient. The area under curve (AUC) was calculated in uGRS (0.723) and wGRS (0.734) using tenfold internal cross-validation. Both uGRS and wGRS were significantly associated with body mass index (BMI) (p < .001). Both GRSs could potentially be considered as useful genetic tools to evaluate individual’s predisposition to overweight/obesity in European adolescents.European Commission FOOD-CT-2005-007034HELENA projectSpanish Ministry of Economy and Competitiveness RYC-2010-05957 RYC2011-09011Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERObn)Iberus Talent Pre-doctoral fellowships under the European Union 801586Instituto de Salud Carlos III CB15/0004