Publications by authors named "Sibylle Koletzko"

266 Publications

A European Survey on Digestive Perianastomotic Ulcerations, a Rare Crohn-Like Disorder Occurring in Children and Young Adults.

J Pediatr Gastroenterol Nutr 2021 Jun 10. Epub 2021 Jun 10.

Department of pediatric surgery, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, Paris, France Children's Hospital, Zagreb University Medical School, Zagreb, Croatia Centre Hospitalier Universitaire de Saint Etienne, Saint Etienne, France Division of Gastroenterology and Hepatology, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Germany Department of Paediatrics, School of Medicine Collegium Medicum University of Warmia and Mazury, Olsztyn, Poland Hôpital Timone Enfants, service de pédiatrie multidisciplinaire, Marseille, France Aix Marseille Univ, INSERM, MMG, Marseille, France Department of pediatric gastroenterology and nutrition, Hopital Robert Debré, Assistance Publique Hopitaux de Paris, Paris, France Université de Paris ; INSERM UMR1149 ; Paris, France Unidade de Gastrenterologia Pediátrica, Centro Hospitalar do Porto, Porto, Portugal Bordeaux University Hospital, Paediatric Gastroenterology Unit, CIC 1401, F-33000, Bordeaux, France Department of pediatric gastroenterology and nutrition, Hôpital Trousseau, Assistance Publique-Hopitaux de Paris, Paris, France Children's Hospital, University of Helsinki, Helsinki, Finland Centre Hospitalier Lyon Sud, Pierre Bénite, France Pediatric gastroenterology Unit, Ospedale Maggiore Carlo Alberto Pizzardi di Bologna, Bologna, Italy Sapienza University - Umberto I Hospital, Rome, Italy Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II", Naples, Italy Department of pediatrics, Hospices Civils de Lyon, Lyon, France. University Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France Department of pediatrics. Centre Hospitalier universitaire de Limoges, Limoges, France Department of pediatrics. Centre Hospitalier Universitaire Clocheville, Tours, France Department of pediatrics. University Normandie, UNICAEN, CHU de Caen Normandie, F-14000 Caen, France INSERM UMR 1073, University Rouen, F-76000 Rouen, France Al Jalila Children's Specialty Hospital, Dubai, United Arab Emirates Shaare Zedek Medical Center, Jerusalem, Jerusalem, Israel.

Objectives: Digestive perianastomotic ulcerations (DPAU) resembling Crohn's disease lesions are long-term complications of intestinal resections, occurring in children and young adults. They are known to be uncommon, severe and difficult to treat.

Methods: In the absence of recommendations, we performed a large European survey among the members of the ESPGHAN working group on inflammatory bowel disease (IBD) in order to collect the experience of expert pediatric gastroenterologists on DPAU.

Results: 51 patients (29 males and 22 females) were identified from 19 centers in 8 countries. Most patients were followed after necrotizing enterocolitis (n = 20) or Hirschsprung's disease (n = 11). The anastomosis was performed at a median age (interquartile range) of 6 (1-23) months, and first symptoms occurred 39 (22-106) months after surgery. Anemia was the most prevalent symptom followed by diarrhea, abdominal pain, bloating and failure to thrive. Hypoalbuminemia, elevated CRP and fecal calprotectin were common. Deep ulcerations were found in 59% of patients usually proximally to the anastomosis (68%). During a median follow-up of 40 (19-67) months, treatments reported to be the most effective included exclusive enteral nutrition (31/35, 88%), redo anastomosis (18/22, 82%) and alternate antibiotic treatment (37/64, 58%).

Conclusions: Unfortunately, persistence of symptoms, failure to thrive and abnormal laboratory tests at last follow-up in most of patients show the burden of DPAU lacking optimal therapy and incomplete understanding of the pathophysiology.
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http://dx.doi.org/10.1097/MPG.0000000000003200DOI Listing
June 2021

Gamma-gliadin specific celiac disease antibodies recognize p31-43 and p57-68 alpha gliadin peptides in deamidation related manner as a result of cross-reaction.

Amino Acids 2021 Jul 31;53(7):1051-1063. Epub 2021 May 31.

Department of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Celiac disease (CeD) is a T-cell-dependent enteropathy with autoimmune features where tissue transglutaminase (TG2)-mediated posttranslational modification of gliadin peptides has a decisive role in the pathomechanism. The humoral immune response is reported to target mainly TG2-deamidated γ-gliadin peptides. However, α-gliadin peptides, like p57-68, playing a crucial role in the T-cell response, and p31-43, a major trigger of innate responses, also contain B-cell gliadin epitopes and γ-gliadin like motifs. We aimed to identify if there are anti-gliadin-specific antibodies in CeD patients targeting the p31-43 and p57-68 peptides and to examine whether deamidation of these peptides could increase their antigenicity. We explored TG2-mediated deamidation of the p31-43 and p57-68 peptides, and investigated serum antibody reactivity toward the native and deamidated α and γ-gliadin peptides in children with confirmed CeD and in prospectively followed infants at increased risk for developing CeD. We affinity-purified antibody populations utilizing different single peptide gliadin antigens and tested their binding preferences for cross-reactivity in real-time interaction assays based on bio-layer interferometry. Our results demonstrate that there is serum reactivity toward p31-43 and p57-68 peptides, which is due to cross-reactive γ-gliadin specific antibodies. These γ-gliadin specific antibodies represent the first appearing antibody population in infancy and they dominate the serum reactivity of CeD patients even later on and without preference for deamidation. However, for the homologous epitope sequences in α-gliadins shorter than the core QPEQPFP heptapeptide, deamidation facilitates antibody recognition. These findings reveal the presence of cross-reactive antibodies in CeD patients recognizing the disease-relevant α-gliadins.
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http://dx.doi.org/10.1007/s00726-021-03006-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241804PMC
July 2021

Associations of breastfeeding with childhood autoimmunity, allergies, and overweight: The Environmental Determinants of Diabetes in the Young (TEDDY) study.

Am J Clin Nutr 2021 Jul;114(1):134-142

Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany; and Forschergruppe Diabetes, Technical University Munich, at Klinikum rechts der Isar, Munich, and Forschergruppe Diabetes eV, Neuherberg, Germany.

Background: Breastfeeding has beneficial effects on numerous health outcomes.

Objectives: We investigated whether breastfeeding duration is associated with the development of early childhood autoimmunity, allergies, or obesity in a multinational prospective birth cohort.

Methods: Infants with genetic susceptibility for type 1 diabetes (n = 8676) were followed for the development of autoantibodies to islet autoantigens or transglutaminase, allergies, and for anthropometric measurements to a median age of 8.3 y (IQR: 2.8-10.2 y). Information on breastfeeding was collected at 3 mo of age and prospectively thereafter. A propensity score for longer breastfeeding was calculated from the variables that were likely to influence any or exclusive breastfeeding. The risks of developing autoimmunity or allergy were assessed using Cox proportional hazards models, and the risk of obesity at 5.5 y of age was assessed using logistic regression with adjustment by the propensity score.

Results: Breastfeeding duration was not associated with a lower risk of either islet or transglutaminase autoimmunity (any breastfeeding >6 mo, adjusted HR: 1.07; 95% CI: 0.96, 1.19; exclusive breastfeeding >3 mo, adjusted HR: 1.03; 95% CI: 0.92, 1.15). Exclusive breastfeeding >3 mo was associated with a decreased risk of seasonal allergic rhinitis (adjusted HR: 0.70; 95% CI: 0.53, 0.92; P < 0.01). Any breastfeeding >6 mo and exclusive breastfeeding >3 mo were associated with decreased risk of obesity (adjusted OR: 0.62; 95% CI: 0.47, 0.81; P < 0.001; and adjusted OR: 0.68; 95% CI: 0.47, 0.95; P < 0.05, respectively).

Conclusions: Longer breastfeeding was not associated with a lower risk of childhood (islet or transglutaminase) autoimmunity in genetically at-risk children but was associated with decreased risk of seasonal allergic rhinitis and obesity at 5.5 y of age.
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http://dx.doi.org/10.1093/ajcn/nqab065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246624PMC
July 2021

Inflammatory bowel disease in patients with congenital chloride diarrhoea.

J Crohns Colitis 2021 03 26. Epub 2021 Mar 26.

Assistance Publique - Hôpitaux de Paris, Hôpital Necker Enfants Malades, Pediatric Gastroenterology Hepatology and Nutrition, Paris, France, Université de Paris, Faculté de Médecine, Paris, France.

Introduction: Congenital chloride diarrhoea (CLD) is a rare autosomal recessive disease caused by mutations in the solute family carrier 26 member 3 (SLC26A3) gene. Patients suffer from life-long watery diarrhea and chloride loss. Inflammatory bowel disease (IBD) has been reported in individual patients with CLD and in scl26a3-deficient mice.

Methods: We performed an international multicentre analysis to build a CLD cohort and to identify cases with IBD. We assessed clinical and genetic characteristics of subjects and studied the cumulative incidence of CLD-associated IBD.

Results: In a cohort of 72 patients with CLD caused by 17 different SLC26A3 mutations, we identified 12 patients (17%) diagnosed with IBD. Nine patients had Crohn's disease, two ulcerative colitis, and one IBD-unclassified (IBD-U). Prevalence of IBD in our cohort of CLD is higher than the highest prevalence of IBD in Europe (p < 0.0001). The age of onset was variable (13.5 years, IQR: 8.5 - 23.5 years). Patients with CLD and IBD had lower z-score for height than those without IBD. 4/12 patients had required surgery (ileostomy formation n=2, ileocaecal resection due to ileocaecal valve stenosis n=1, and colectomy due to stage II transverse colon cancer n=1). At last follow-up, 5/12 were on biologics (adalimumab, infliximab, or vedolizumab), 5/12 on immunosuppressant (azathioprine or mercaptopurine), one on 5-ASA and one off-treatment.

Conclusions: A substantial proportion of patients with CLD develop IBD. This suggests potential involvement of SL26A3-mediated anion transport in IBD pathogenesis. Patients with CLD-associated IBD may require surgery for treatment failure or colon cancer.
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http://dx.doi.org/10.1093/ecco-jcc/jjab056DOI Listing
March 2021

Outdoor air pollution and hormone-assessed pubertal development in children: Results from the GINIplus and LISA birth cohorts.

Environ Int 2021 07 10;152:106476. Epub 2021 Mar 10.

Institute and Clinic for Occupational, Social and Environmental Medicine, LMU University Hospital Munich, Comprehensive Pneumology Center (CPC) Munich, member, German Center for Lung Research (DZL), Munich, Germany; Allergy and Lung Health Unit, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia. Electronic address:

Background: Air pollution is hypothesized to affect pubertal development. However, the few studies on this topic yielded overall mixed results. These studies did not consider important pollutants like ozone, and none of them involved pubertal development assessed by estradiol and testosterone measurements. We aimed to analyze associations between long-term exposure to four pollutants and pubertal development based on sex hormone concentrations among 10-year-old children.

Methods: These cross-sectional analyses were based on the 10-year follow-up medical examinations of 1945 children from the Munich and Wesel centers of the GINIplus and LISA German birth cohorts. Female and male pubertal development was assessed by dichotomizing the concentration of hormones in serum at 18.4 pmol/L and 0.087 nmol/L using the lower limits of quantification for estradiol and testosterone, respectively. Land-use regression models derived annual average concentrations of particulate matter with an aerodynamic diameter < 2.5 and 10 µm (PM and PM), as well as spatial models assessed yearly average concentrations of nitrogen dioxide (NO) and ozone, were calculated at the 10-year residential addresses. To evaluate associations, we utilized logistic regressions adjusted for potential covariates. The analyses were stratified by area and sex.

Results: Around 73% of the 943 females and 25% of the 1002 males had a high level of hormones and had already started puberty at the age of 10. Overall, we found no statistically significant associations between exposure to particles (PM or PM) and pubertal development. Results on NO and ozone were not significant as well; for instance, per 10 µg/m increase in ozone concentration, odds ratios and 95% confidence intervals were 0.900 (0.605, 1.339) and 0.830 (0.573, 1.203) for females and males, respectively. Stratified by area, the aforementioned results did not reveal any associations either.

Conclusions: Our study did not observe the associations between ambient air pollutants and pubertal development determined by estradiol and testosterone levels in children. However, due to the current limited number of studies on this topic, our results should be cautiously interpreted. Future longitudinal studies are needed to assess the association.
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http://dx.doi.org/10.1016/j.envint.2021.106476DOI Listing
July 2021

Long-term Air Pollution Exposure Under European Union Limits and Adolescents' Lung Function: Modifying Effect of Abnormal Weight in the GINIplus and LISA Birth Cohorts.

Chest 2021 Jul 10;160(1):249-258. Epub 2021 Feb 10.

Department of Epidemiology, IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany. Electronic address:

Background: Abnormal weights, eg, obesity, has shown a strong modifying effect on the association between air pollution exposure and lung function impairment in adults.

Research Question: How might weight status modify the effects of long-term air pollution exposure on adolescents' lung function, particularly in areas with pollution levels much lower than the current European Union (EU) air quality standards?

Study Design And Methods: In this observational study, we investigated 2,224 adolescents from the German Infant Study on the Influence of Nutrition Intervention Plus Environmental and Genetic Influences on Allergy Development and the Influence of Life Style Factors on the Development of the Immune System and Allergies in East and West Germany birth cohorts. Lung function was measured at age 15 years. Underweight, normal weight, and overweight or obese were defined using percentiles of BMI. Average concentrations of air pollution were modelled at residential addresses at four exposure windows between 0 and 15 years. Multivariate linear regression models were fitted by weight group on lung function with exposure at each window or cumulative exposure since birth.

Results: The median air pollution concentrations were half to two-thirds of the EU standards. Significant associations were observed only for individuals who were underweight and overweight or obese. For example, per interquartile range increase in nitrogen dioxide at the 15-year exposure window, FEV declined by -2.9% (95% CI, -5.2% to -0.5%) for the underweight group and -3.4% (95% CI, -5.4% to -1.2%) for the overweight or obese group. Similarly, longer exposure to moderate-level air pollution since birth was associated significantly with lung function impairment for groups with abnormal weight.

Interpretation: Exposure to low to moderate levels of air pollution was associated with lung function impairment for adolescents with abnormal weight. Longer exposure aggravated the adverse effect. Whether a critical exposure window since birth exists warrants further exploration.
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http://dx.doi.org/10.1016/j.chest.2021.02.007DOI Listing
July 2021

Early High-Dose Gluten Intake to Prevent Celiac Disease: Data Do Not Allow Conclusions.

JAMA Pediatr 2021 May;175(5):534-535

Department of Paediatrics, Leiden University Medical Center, Leiden, the Netherlands.

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http://dx.doi.org/10.1001/jamapediatrics.2020.6516DOI Listing
May 2021

Identifying Health Economic Considerations to Include in the Research Protocol of a Randomized Controlled Trial (the REDUCE-RISK Trial): Systematic Literature Review and Assessment.

JMIR Form Res 2021 Jan 25;5(1):e13888. Epub 2021 Jan 25.

Pediatric Gastroenterology and Nutrition, Vrije Universiteit Brussel, University Hospital Brussels, Brussels, Belgium.

Background: The REDUCE-RISK trial was set up to compare the effectiveness of weekly subcutaneously administered methotrexate with daily oral azathioprine or 6-mercaptopurine in low-risk Crohn disease (CD) or subcutaneously administered adalimumab (ADA) in high-risk CD in a pediatric population (age 6-17 years).

Objective: The aim of this study is to perform a systematic review to provide input into the research protocol to gather the necessary information to improve the performance of an evidence-based economic evaluation when the trial is finished.

Methods: The Centre for Reviews and Dissemination (CRD) Health Technology Assessment (HTA) database, websites of HTA institutes, CRD's National Health Service Economic Evaluation Database, MEDLINE (OVID), and Embase databases were consulted to retrieve (reviews of) relevant economic evaluations. Studies were eligible if they included a pediatric or adult population with inflammatory bowel diseases (CD and ulcerative colitis [UC]) treated with ADA (Humira). There were no restrictions on the comparator. Only economic evaluations expressing outcomes in life years gained or quality-adjusted life years gained were selected.

Results: A total of 12 primary studies were identified. None of these studies included a pediatric population because of a lack of supporting trials. The economic evaluations identified in our systematic review indicate that ADA is an appropriate intervention for inclusion in such a trial. From a health economic point of view, it is important to make an incremental analysis comparing such an intervention with standard care and not immediately versus another (expensive) biological treatment. Information on the impact of children's school attendance and parents' productivity is currently lacking in economic evaluations, and none of the underlying trials measured quality of life (QoL) using a generic utility instrument.

Conclusions: The review of the economic literature on ADA for the treatment of patients with CD supports the performance of a trial with biologicals in pediatric patients, including making a distinction according to disease severity. Conducting an economic literature review enabled us to decide which variables should be added to the research protocol from an economic point of view. Measurements for children's and parents' QoL (EuroQol 5-Dimension questionnaires), children's school attendance, and parents' productivity (WPAI-CD-CG questionnaire) were added to the research protocol. This will provide support for the calculation of the cost-effectiveness of the interventions evaluated in the REDUCE-RISK trial.

Trial Registration: ClinicalTrials.gov NCT02852694; https://clinicaltrials.gov/ct2/show/NCT02852694.
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http://dx.doi.org/10.2196/13888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870354PMC
January 2021

Sarcopenia is a prognostic outcome marker in children with high-risk hepatoblastoma.

Pediatr Blood Cancer 2021 May 12;68(5):e28862. Epub 2021 Jan 12.

Department of Pediatrics, Division of Gastroenterology and Hepatology, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.

Background: Children with hepatoblastoma (HB) are at risk of sarcopenia due to immobility, chemotherapy, and malnutrition. We hypothesized that children with HB have a low preoperative total psoas muscle area (tPMA), reflecting sarcopenia, which negatively impacts outcome.

Procedure: Retrospective study of children (1-10 years) with hepatoblastoma treated at a large university children's hospital from 2009 to 2018. tPMA was measured as the sum of the right and left psoas muscle area (PMA) at intervertebral disc levels L3-4 and L4-5. z-Scores were calculated using age- and gender-specific reference values and were compared to anthropometric measurements, clinical variables, and outcomes. Sarcopenia was defined as a tPMA z-score below -2.

Results: Thirty-three children were included. Mean tPMA z-score was -2.18 ± 1.08, and 52% were sarcopenic. A poor correlation between tPMA and weight was seen (r = 0.35; confidence interval [CI] 0.01, 0.62; P = .045), and most children had weights within the normal range (mean z-score -0.55 ± 1.39). All children categorized as high risk with relapse (n = 5/12) were sarcopenic before surgery. Relapse was significantly higher in the high-risk sarcopenic group compared to the nonsarcopenic group (P = .008). The change in tPMA z-score 1-4 months after surgery did not improve in patients with relapse, but did improve in 75% of children without relapse.

Conclusions: The majority of children with HB were sarcopenic prior to surgery. Especially in children with high-risk hepatoblastoma, sarcopenia is an additional risk factor for relapse. Large multicenter studies are needed to confirm these preliminary results.
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http://dx.doi.org/10.1002/pbc.28862DOI Listing
May 2021

Management of coeliac disease patients after the confirmation of diagnosis in Central Europe.

Eur J Gastroenterol Hepatol 2021 Jan 6;Publish Ahead of Print. Epub 2021 Jan 6.

Gastroenterology, Hepatology and Nutrition Unit, Department of Paediatrics, University Medical Centre Maribor, Maribor, Slovenia IRCCS Burlo Garofolo Trieste, Institute for Maternal and Child Health, Trieste, Italy Municipality of Maribor, Project Office, Maribor, Slovenia Coeliac Disease Centre, Heim Pál National Paediatric Institute, Budapest, Hungary Stiftung Kindergesundheit (Child Health Foundation) at Dr. von Hauner Children's Hospital Dr. von Hauner Children's Hospital, Clinical Medical Centre, LMU, Munich, Germany Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, Olsztyn, Poland Hungarian Celiac Society, Celiac Society, Budapest, Hungary Faculty of Medicine, Department of Paediatrics, University of Debrecen, Debrecen, Hungary Association of Celiac Patients, Primorsko-Goranska County Department for Gastroenterology, Paediatric Clinic, University Hospital Rijeka, Rijeka, Croatia Department of Life Sciences, University of Trieste, Trieste, Italy Medical Faculty, Department of Paediatrics, University of Maribor, Maribor, Slovenia.

Background: Recently published paediatric guidelines for diagnosing coeliac disease do not include recommendations on the follow-up of coeliac disease patients.

Goal: The aim of this study was to assess the management practices and experience of coeliac disease patients with their follow-up appointments in Central Europe.

Study: Gastroenterologists and coeliac disease patients in five Central European countries were asked to complete the web-based questionnaire focusing on coeliac disease management practices.

Results: Answers from 147 gastroenterologists and 2041 coeliac disease patients were available for the analysis. More than half of the gastroenterologists (58.5%) schedule the first follow-up visit within 3 months after the diagnosis. At follow-up, tissue transglutaminase antibodies are checked in almost all patients (95.9%). Approximately two-thirds (60.7%) of gastroenterologists refer all of their patients to the dietitian at diagnosis. Similarly, 42.8% of coeliac disease patients reported that they had not been appointed to a dietitian. Almost one-third of coeliac disease patients (30.8%) reported that they had no follow-up appointments with gastroenterologist at all.

Conclusions: Follow-up of coeliac disease patients is suboptimal in Central Europe. Many patients are not followed regularly. A lot of patients are not referred to a dietitian. The recommendations on the optimal follow-up of coeliac disease patients are needed in order to improve patient care.
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http://dx.doi.org/10.1097/MEG.0000000000002039DOI Listing
January 2021

The Knowledge About Celiac Disease Among Healthcare Professionals and Patients in Central Europe.

J Pediatr Gastroenterol Nutr 2021 04;72(4):552-557

Department of Pediatrics, Gastroenterology, Hepatology and Nutrition Unit, University Medical Centre Maribor, Maribor, Slovenia.

Objectives: Celiac disease (CD) remains undiagnosed for a long time in many adult and pediatric patients. We assessed the knowledge about CD among healthcare professionals (HCPs) and CD patients in Central Europe (CE).

Methods: HCPs and CD patients from 5 CE countries were asked to complete the web-based questionnaire about CD. The questions were divided into subsections on epidemiology, clinical presentation, diagnostics, treatment, and follow-up. Achieved scores of different specialists managing patients with CD were compared and regional differences in patients' knowledge were analyzed.

Results: Questionnaire was completed by 1381 HCPs and 2262 CD patients or their caregivers from Croatia, Hungary, Germany, Italy, and Slovenia. Mean score achieved by HCPs was 50.9%, and by CD patients 56.4%. Pediatric gastroenterologists scored the highest (69.4%; P < 0.001). There were significant differences in knowledge of patients from different CE regions with German participants scoring the highest (58.3%). Members of CD societies scored higher compared with nonmembers (mean score 58% vs 53.2%; P < 0.001) and patients diagnosed less than 5 years ago scored higher compared with those diagnosed more than 10 years ago (mean score 57.3% vs 54.6%; P < 0.001).

Conclusions: The knowledge about CD among HCPs and CD patients is not satisfactory. Further awareness-raising and learning activities are needed to improve HCPs' knowledge and to minimize the number of unrecognized patients and unnecessary diagnostic delays. Patients should be better informed about their disease to reach higher compliance with the gluten-free diet.
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http://dx.doi.org/10.1097/MPG.0000000000003019DOI Listing
April 2021

Long-term effects of hydrolyzed formulae on atopic diseases in the GINI study.

Allergy 2021 06 24;76(6):1903-1907. Epub 2020 Dec 24.

Institute of Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.

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http://dx.doi.org/10.1111/all.14709DOI Listing
June 2021

Clinical Presentation in Children With Coeliac Disease in Central Europe.

J Pediatr Gastroenterol Nutr 2021 04;72(4):546-551

Department of Paediatrics, Gastroenterology, Hepatology and Nutrition Unit, University Medical Centre Maribor, Maribor, Slovenia.

Objectives: During the past decades, there has been a shift in the clinical presentation of coeliac disease (CD) to nonclassical, oligosymptomatic, and asymptomatic forms. We assessed clinical presentation of CD in children and adolescents in Central Europe.

Methods: Paediatric gastroenterologists in 5 countries retrospectively reported data of their patients diagnosed with CD. Clinical presentation was analyzed and the differences among very young (<3 years) and older children and adolescents were studied.

Results: Data from 653 children and adolescents (median age 7 years 2 months; 63.9% girls) from Croatia, Germany, Hungary, Italy, and Slovenia were available for the analysis. One fifth (N = 134) of all children were asymptomatic. In symptomatic children, the most common leading symptom was abdominal pain (33.3%), followed by growth retardation (13.7%) and diarrhoea (13.3%). The majority of symptomatic children (47.6%; N = 247) were polysymptomatic. Abdominal pain was the most common symptom in polysymptomatic (66.4%) as well as in monosymptomatic children (29.7%). Comparing clinical presentation of CD in very young children (younger than 3 years) with older children (3 years or older), we found that symptoms and signs of malabsorption were significantly more common in younger (P < 0.001), whereas abdominal pain and asymptomatic presentation were more common in older children and adolescents (both P < 0.001).

Conclusion: In children with CD, abdominal pain has become the most common symptom. However, in younger children, symptoms of malabsorption are still seen frequently. This raises a question about the underlying mechanism of observed change in clinical presentation in favour of nonclassical presentation and asymptomatic disease at certain age.
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http://dx.doi.org/10.1097/MPG.0000000000003015DOI Listing
April 2021

Acute Infectious Gastroenteritis in Infancy and Childhood.

Dtsch Arztebl Int 2020 Sep;117(37):615-624

Department of Pediatric and Adolescent Medicine, University Medical Center Ulm; Department of Pediatrics, GFO-Kliniken Bonn, St. Marienhospital Bonn; Department of Pediatric and Adolescent Medicine, Klinikum Links der Weser and Klinikum Bremen-Mitte, Bremen; Practice for Pediatric and Adolescent Medicine, Arnsberg; DKD Helios Klinik Wiesbaden, Betriebsstätte Helios Dr. Horst Schmidt Klinik; Department of Pediatric and Adolescent Medicine, Dr. von Hauner Children's Hospital, LMU Klinikum der Universität München; Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, Olsztyn, Poland.

Background: Despite the introduction of vaccination against rotavirus, and even though it can often be treated on an outpatient basis, acute infectious gastroenteritis is nevertheless the second most common non-traumatic cause of emergency hospitaliza - tion in children aged 1 to 5 years, accounting for approximately 9% of cases (39 410 cases in 2017). The most common path - ogens are viruses (47% rotavirus, 29% norovirus, and 14% adenovirus).

Methods: This review is based on publications retrieved by a selective search in PubMed employing the terms "acute gastro - enteritis children" AND "dehydration" OR "rehydration" OR "prevention," and by manual searching (based, for example, on reference lists and expert knowledge), with subsequent evaluation including consideration of the relevant guidelines.

Results: The degree of dehydration can be judged from weight loss and other clinical findings. In 17 randomized controlled trials conducted on a total of 1811 children with mild or moderate dehydration, oral rehydration with oral rehydration solution was just as effective as intravenous rehydration with respect to weight gain, duration of diarrhea, and fluid administration, and was associated with shorter hospital stays (weighted mean difference, -1.2 days; 95% confidence interval [-2.38; -0.02]). Oral rehydration therapy failed in 4% of patients [1; 7]. In children who are vomiting or who refuse oral rehydration solution, continuous nasogastric application is just as effective as intravenous rehydration and is the treatment of first choice.

Conclusion: In Germany, children with mild or moderate dehydration are often hospitalized for intravenous rehydration therapy, despite the good evidence supporting ambulatory oral rehydration. Obstacles to intersectoral care, the nursing shortage, and inadequate reimbursement must all be overcome in order to reduce unnecessary hospitalizations and thereby lessen the risk of nosocomial infection.
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http://dx.doi.org/10.3238/arztebl.2020.0615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805585PMC
September 2020

Metabolomic Signatures in Pediatric Crohn's Disease Patients with Mild or Quiescent Disease Treated with Partial Enteral Nutrition: A Feasibility Study.

SLAS Technol 2021 Apr 18;26(2):165-177. Epub 2020 Nov 18.

Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.

Little is known about the metabolic response of pediatric Crohn's disease (CD) patients to partial enteral nutrition (PEN) therapy and the impact of disease activity and inflammation. We analyzed plasma samples from a nonrandomized controlled intervention study investigating the effect of partial enteral nutrition (PEN) on bone health and growth throughout one year with untargeted metabolomics using high-performance liquid chromatography (HPLC) coupled with high-resolution mass spectrometry (HRMS). Thirty-four paired samples from two time points (baseline and 12 months) were analyzed. Patients (median age: 13.9 years, range: 7-18.9 years, 44% females) were in remission or had mild disease activity. The intervention group received a casein-based formula for 12 months, providing ~25% of estimated daily energy requirements. Sparse partial least squares discriminant analysis (splsda) was applied for group discrimination and identifying sources of variation to identify the impact of PEN. We also investigated the correlation of metabolites with inflammation markers, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and fecal calprotectin. After 12 months, our results show substantial difference between PEN and non-PEN groups in the metabolome of CD patients in remission or with mild disease activity. Inflammatory markers were associated with individual compounds and chemical classes such as isoprenoids and phospholipids. Identified compounds comprise metabolites produced by human or bacterial metabolism, as well as xenobiotics recognized as flavoring agents and environmental contaminants and their biotransformation products. Further longitudinal studies that also include patients with higher disease activity are warranted to evaluate the suitability of these metabolic biomarkers for predicting disease activity.
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http://dx.doi.org/10.1177/2472630320969147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985853PMC
April 2021

Varicella-zoster-virus vaccination of immunosuppressed children with inflammatory bowel disease or autoimmune hepatitis: A prospective observational study.

Vaccine 2020 11 5;38(50):8024-8031. Epub 2020 Nov 5.

University Medical Center Ulm, Department of Pediatrics and Adolescent Medicine, Ulm, Germany. Electronic address:

Background And Aims: Children with inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH) receiving immunosuppressive treatment are at risk for severe varicella zoster virus (VZV)-induced disease. This study evaluated vaccination of susceptible patients with stable disease and documented immunoreactivity without interruption of their current immunosuppression (IS).

Methods: This prospective multicentre observational study used a prevaccination checklist to select patients with low-intensity and high-intensity IS for VZV vaccination. Tolerability and safety after immunization were assessed by questionnaire. The immune response was measured by the VZV-IgG concentration, relative avidity index (RAI), and specific lymphocyte proliferative response.

Results: A total of 29 VZV vaccinations were performed in 17 seronegative patients aged 3-16 years (IBD n = 15, AIH n = 2). Eight patients received high-intensity immunosuppression, another six low-intensity immunosuppression, and three patients interrupted IS before VZV vaccination. All 29 vaccinations were well tolerated; only minor side effects such as fever and abdominal pain, were reported in two patients. One patient experienced a flare of Crohn's disease the day after vaccination. The VZV-IgG-concentration increased significantly (p = 0.018) after vaccination, and a specific lymphocyte response towards VZV in vitro was detected in all tested patients which correlated with the RAI (r = 0.489; p = 0.078).

Conclusions: VZV vaccination was well tolerated, safe and immunogenic in children receiving ongoing IS due to IBD and AIH. Ensuring immunoreactivity by clinical and laboratory parameters, rather than the type and dosage of IS, is a reasonable approach to decide on live-attenuated virus vaccinations in immunosuppressed children (German clinical trials DRKS00016357).
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http://dx.doi.org/10.1016/j.vaccine.2020.10.028DOI Listing
November 2020

Ulcerative Colitis-Diagnostic and Therapeutic Algorithms.

Dtsch Arztebl Int 2020 Aug;117(33-34):564-574

Department of General Internal Medicine and Gastroenterology, University Teaching Hospital Lüneburg; Dr. von Hauner Children's Hospital, LMU Klinikum, University of Munich; Department of Pediatrics, Gastroenterology and Nutrition, School of Medicine Collegium Medicum University of Warmia and Mazury, Olsztyn, Poland; Department of Pediatric Gastroenterology, LMU Klinikum, University of Munich; Medical Clinic I, Agaplesion Markus Krankenhaus, Frankfurt/Main.

Background: Ulcerative colitis is a chronic inflammatory bowel disease with an estimated 150 000 patients in Germany alone.

Methods: This review is based on publications about current diagnostic and therapeutic strategies for ulcerative colitis that were retrieved by a selective search in PubMed, and on current guidelines.

Results: The primary goal of treatment is endoscopically confirmed healing of the mucosa. Mesalamine, in various forms of administration, remains the standard treatment for uncomplicated ulcerative colitis. Its superiority over placebo has been confirmed in meta-analyses of randomized, controlled trials. Glucocorticoids are highly effective in the acute treatment of ulcerative colitis, but they should only be used over the short term, because of their marked side effects. Further drugs are available to treat patients with a more complicated disease course of ulcerative colitis, including azathioprine, biological agents, JAK inhibitors (among them TNF antibodies, biosimilars, ustekinumab, vedolizumab, and tofacitinib), and calcineurin inhibitors. Proctocolectomy should be considered in refractory cases, or in the presence of high-grade epithelial dysplasia. Ulcerative colitis beginning in childhood or adolescence is often characterized by rapid progression and frequent comorbidities that make its treatment a special challenge.

Conclusion: A wide variety of drugs are now available for the treatment of ulcerative colitis, enabling the individualized choice of the best treatment for each patient. Regular surveillance colonoscopies to rule out colon carcinoma should be scheduled at intervals that depend on risk stratification.
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http://dx.doi.org/10.3238/arztebl.2020.0564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171548PMC
August 2020

Association of early life and acute pollen exposure with lung function and exhaled nitric oxide (FeNO). A prospective study up to adolescence in the GINIplus and LISA cohort.

Sci Total Environ 2021 Apr 20;763:143006. Epub 2020 Oct 20.

Department of Public Health, School of Psychology and Public Health, La Trobe University, Melbourne, Australia; Faculty of Public Health, Universitas Airlangga, Surabaya, Indonesia. Electronic address:

Background: Pollen exposure has both acute and chronic detrimental effects on allergic asthma, but little is known about its wider effects on respiratory health. This is increasingly important knowledge as ambient pollen levels are changing with the changing global climate.

Objective: To assess associations of pollen exposure with lung function and fractional exhaled nitric oxide (FeNO) at age 15 in two prospective German birth cohorts, GINIplus and LISA.

Methods: Background city-specific pollen exposure was measured in infancy (during the first three months of life), and contemporary (on the day of and 7 days prior to lung function measurement). Greenness levels within circular buffers (100-3000 m) around the birth and 15-year home addresses were calculated using the satellite-derived Normalized Difference Vegetation Index. Regression models were used to assess the associations of grass and birch pollen with lung function and FeNO, and the modifying effects of residential greenness were explored.

Results: Cumulative early life exposure to grass pollen was associated with reduced lung function in adolescence (FEV: -4.9 mL 95%CI: -9.2, -0.6 and FVC: -5.2 mL 95%CI: -9.8, -0.5 per doubling of pollen count). Acute grass pollen exposure was associated with increased airway inflammation in all children, with higher FeNO increases in children living in green areas. In contrast acute birch pollen exposure was associated with reduced lung function only in children sensitised to birch allergens.

Conclusion: This study provides suggestive evidence that early pollen exposure has a negative effect on later lung function, which is in turn influenced by acute pollen exposures.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143006DOI Listing
April 2021

Air pollution during infancy and lung function development into adolescence: The GINIplus/LISA birth cohorts study.

Environ Int 2021 01 21;146:106195. Epub 2020 Oct 21.

Department of Epidemiology, IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany. Electronic address:

Background: Limited evidence exists on how air pollution exposure during infancy, i.e. the first year of life, may affect lung function development into adolescence.

Objectives: To investigate the association between exposure to air pollution during the first-year of life and lung function development up to the age of 15 in Germany.

Methods: We investigated 915 children from the GINIplus and LISA birth cohorts from Munich (n = 181) and Wesel (n = 734), who had at least two spirometric measurements at ages 6, 10 and 15. Z-scores of forced expiratory volume in one second (FEV) and forced vital capacity (FVC) were calculated. Annual average concentrations of nitrogen dioxide, particulate matter with diameters <2.5, <10 and 2.5-10 µm (PM), and PM absorbance at home addresses during the first-year of life, were estimated by land-use regression models. Associations between infancy exposure and lung function changes were fitted using multivariable linear mixed models with adjustment for potential confounders.

Results: For per interquartile range increase in air pollutants during the first-year life, FEV z-scores declined annually by -0.012 (95% confidence interval (CI): -0.014, -0.009) for PM to -0.023 (95%CI: -0.028, -0.018) for PM. The declines in FVC were lower than FEV [-0.006 (95%CI: -0.008, -0.003) to -0.011 (95%CI: -0.019, -0.003)]. In Munich, the attenuations were only significant for FEV. Effect estimates of infancy exposure for certain air pollutants were higher for groups with asthma, older maternal age, and breastfeeding <12 weeks than their counterparts.

Discussion: Infancy exposure to higher air pollution may reduce lung function development up to adolescence, with airway size more affected than lung volume restriction. The potential modifying effects of maternal age, asthmatic status of children and breastfeeding warrant further exploration.
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http://dx.doi.org/10.1016/j.envint.2020.106195DOI Listing
January 2021

Addendum to S3-Guidelines Crohn's disease and ulcerative colitis: Management of Patients with Inflammatory Bowel Disease in the COVID-19 Pandemic - open questions and answers.

Z Gastroenterol 2020 Oct 9;58(10):982-1002. Epub 2020 Oct 9.

Klinik für Innere Medizin, Gastroenterologie, Klinikum Lüneburg, Lüneburg.

The COVID-19 pandemic is a global outbreak of new onset infections with the SARS-CoV-2 virus. To date, more than 3.4 million people have been infected throughout the world. In Germany, approximately 450,000 patients suffer from inflammatory bowel disease; these patients generally require continuous expert care and support. Against the background of a rapidly accumulating knowledge base on SARS-CoV-2, 68 expert authors of the current DGVS guidelines for Crohn's disease and ulcerative colitis took part in a virtual meeting to compile up-to-date, practice-orientated recommendations aimed at improving the care of patients with IBD. These recommendations address the risk of infection, including the risk for specific patient groups, the possible course of the disease, and consequences for pharmacological and surgical therapies of the underlying disease, as well as general measures for infection prevention and adjuvant prophylactic and therapeutic options.
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http://dx.doi.org/10.1055/a-1234-8079DOI Listing
October 2020

The Medical Management of Paediatric Crohn's Disease: an ECCO-ESPGHAN Guideline Update.

J Crohns Colitis 2020 Oct 7. Epub 2020 Oct 7.

Assistance Publique- Hôpitaux de Paris, Hôpital Necker Enfants Malades, Pediatric Gastroenterology, Paris, France.

Objective: We aimed to provide an evidence-supported update of the ECCO-ESPGHAN guideline on the medical management of paediatric Crohn's disease [CD].

Methods: We formed 10 working groups and formulated 17 PICO-structured clinical questions [Patients, Intervention, Comparator, and Outcome]. A systematic literature search from January 1, 1991 to March 19, 2019 was conducted by a medical librarian using MEDLINE, EMBASE, and Cochrane Central databases. A shortlist of 30 provisional statements were further refined during a consensus meeting in Barcelona in October 2019 and subjected to a vote. In total 22 statements reached ≥ 80% agreement and were retained.

Results: We established that it was key to identify patients at high risk of a complicated disease course at the earliest opportunity, to reduce bowel damage. Patients with perianal disease, stricturing or penetrating behaviour, or severe growth retardation should be considered for up-front anti-tumour necrosis factor [TNF] agents in combination with an immunomodulator. Therapeutic drug monitoring to guide treatment changes is recommended over empirically escalating anti-TNF dose or switching therapies. Patients with low-risk luminal CD should be induced with exclusive enteral nutrition [EEN], or with corticosteroids when EEN is not an option, and require immunomodulator-based maintenance therapy. Favourable outcomes rely on close monitoring of treatment response, with timely adjustments in therapy when treatment targets are not met. Serial faecal calprotectin measurements or small bowel imaging [ultrasound or magnetic resonance enterography] are more reliable markers of treatment response than clinical scores alone.

Conclusions: We present state-of-the-art guidance on the medical treatment and long-term management of children and adolescents with CD.
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http://dx.doi.org/10.1093/ecco-jcc/jjaa161DOI Listing
October 2020

Breast-Milk Microbiota Linked to Celiac Disease Development in Children: A Pilot Study From the PreventCD Cohort.

Front Microbiol 2020 23;11:1335. Epub 2020 Jun 23.

Microbial Ecology, Nutrition and Health Research Unit, Institute of Agrochemistry and Food Technology, Spanish National Research Council, Valencia, Spain.

Celiac disease (CeD) is an immune-mediated disorder triggered by exposure to dietary gluten proteins in genetically predisposed individuals. In addition to the host genome, the microbiome has recently been linked to CeD risk and pathogenesis. To progress in our understanding of the role of breast milk microbiota profiles in CeD, we have analyzed samples from a sub-set of mothers ( = 49) included in the PreventCD project, whose children did or did not develop CeD. The results of the microbiota data analysis indicated that neither the BMI, HLA-DQ genotype, the CeD condition nor the gluten-free diet of the mothers could explain the human milk microbiota profiles. Nevertheless, we found that origin country, the offspring's birth date and, consequently, the milk sampling date influenced the abundance and prevalence of microbes in human milk, undergoing a transition from an anaerobic to a more aerobic microbiota, including potential pathogenic species. Furthermore, certain microbial species were more abundant in milk samples from mothers whose children went on to develop CeD compared to those that remained healthy. These included increases in facultative methylotrophs such as and as well as in species such as , that consumes fucosylated-oligosaccharides present in human milk, and other breast-abscess associated species. Theoretically, these microbiota components could be vertically transmitted from mothers-to-infants during breastfeeding, thereby influencing CeD risk.
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http://dx.doi.org/10.3389/fmicb.2020.01335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324710PMC
June 2020

Impact of Residential Green Space on Sleep Quality and Sufficiency in Children and Adolescents Residing in Australia and Germany.

Int J Environ Res Public Health 2020 07 7;17(13). Epub 2020 Jul 7.

Population Wellbeing and Environment Research Lab (PowerLab), School of Public Health, Faculty of Social Sciences, University of Wollongong, Wollongong NSW 2522, Australia.

Increasing evidence suggests adults living in greener areas tend to have more favourable sleep-related outcomes, but children and adolescents are under-researched. We hypothesised that children and adolescents living in greener areas would have better quality and more sufficient levels of sleep on average, especially within the context of high traffic noise exposure. These hypotheses were tested using multilevel logistic regressions fitted on samples from the nationally representative Longitudinal Study of Australian Children (10-11 years old, = 3469, and 14-15 years old, = 2814) and the GINIplus and LISA cohorts (10 years old, = 1461, and 15 years old, = 4172) from the Munich, Wesel, and Leipzig areas of Germany. Questionnaire-based binary indicators of sleep sufficiency and sleep quality in each cohort were assessed with respect to objectively measured green space exposures adjusting for age, sex, and maternal education. Models were augmented with proxy measures of traffic noise and two-way interaction terms to test for effect modification. Cross-tabulations illustrated little convincing evidence of association between green space and insufficient sleep or poor sleep quality in either sample, except for insufficient sleep among 10 year old participants in Germany. These null findings were replicated in adjusted models. The proxy for traffic noise was associated with poor quality sleep in 15 year old participants in Germany, but no convincing evidence of modified association with green space was observed.
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http://dx.doi.org/10.3390/ijerph17134894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369701PMC
July 2020

International prospective observational study investigating the disease course and heterogeneity of paediatric-onset inflammatory bowel disease: the protocol of the PIBD-SETQuality inception cohort study.

BMJ Open 2020 07 1;10(7):e035538. Epub 2020 Jul 1.

Department of Paediatric Gastroenterology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands

Introduction: Patients with paediatric-onset inflammatory bowel disease (PIBD) may develop a complicated disease course, including growth failure, bowel resection at young age and treatment-related adverse events, all of which can have significant and lasting effects on the patient's development and quality of life. Unfortunately, we are still not able to fully explain the heterogeneity between patients and their disease course and predict which patients will respond to certain therapies or are most at risk of developing a more complicated disease course. To investigate this, large prospective studies with long-term follow-up are needed. Currently, no such European or Asian international cohorts exist. In this international cohort, we aim to evaluate disease course and which patients are most at risk of therapy non-response or development of complicated disease based on patient and disease characteristics, immune pathology and environmental and socioeconomic factors.

Methods And Analysis: In this international prospective observational study, which is part of the PIBD Network for Safety, Efficacy, Treatment and Quality improvement of care (PIBD-SETQuality), children diagnosed with inflammatory bowel disease <18 years are included at diagnosis. The follow-up schedule is in line with standard PIBD care and is intended to continue up to 20 years. Patient and disease characteristics, as well as results of investigations, are collected at baseline and during follow-up. In addition, environmental factors are being assessed (eg, parent's smoking behaviour, dietary factors and antibiotic use). In specific centres with the ability to perform extensive immunological analyses, blood samples and intestinal biopsies are being collected and analysed (flow cytometry, plasma proteomics, mRNA expression and immunohistochemistry) in therapy-naïve patients and during follow-up.

Ethics And Dissemination: Medical ethical approval has been obtained prior to patient recruitment for all sites. The results will be disseminated through peer-reviewed scientific publications.

Trial Registration Number: NCT03571373.
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http://dx.doi.org/10.1136/bmjopen-2019-035538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332186PMC
July 2020

Protocol for a multinational risk-stratified randomised controlled trial in paediatric Crohn's disease: methotrexate versus azathioprine or adalimumab for maintaining remission in patients at low or high risk for aggressive disease course.

BMJ Open 2020 07 1;10(7):e034892. Epub 2020 Jul 1.

Department of Paediatric Gastroenterology, Royal Hospital for Children Glasgow, Glasgow, UK.

Introduction: Immunomodulators such as thiopurines (azathioprine (AZA)/6-mercaptopurine (6MP)), methotrexate (MTX) and biologics such as adalimumab (ADA) are well established for maintenance of remission within paediatric Crohn's disease (CD). It remains unclear, however, which maintenance medication should be used first line in specific patient groups.

Aims: To compare the efficacy of maintenance therapies in newly diagnosed CD based on stratification into high and low-risk groups for severe CD evolution; MTX versus AZA/6MP in low-risk and MTX versus ADA in high-risk patients. Primary end point: sustained remission at 12 months (weighted paediatric CD activity index ≤12.5 and C reactive protein ≤1.5 fold upper limit) without relapse or ongoing requirement for exclusive enteral nutrition (EEN)/steroids 12 weeks after treatment initiation.

Methods And Analysis: REDUCE-RISK in CD is an international multicentre open-label prospective randomised controlled trial funded by EU within the Horizon2020 framework (grant number 668023). Eligible patients (aged 6-17 years, new-onset disease receiving steroids or EEN for induction of remission for luminal ± perianal CD are stratified into low and high-risk groups based on phenotype and response to induction therapy. Participants are randomised to one of two treatment arms within their risk group: low-risk patients to weekly subcutaneous MTX or daily oral AZA/6MP, and high-risk patients to weekly subcutaneous MTX or fortnightly ADA. Patients are followed up for 12 months at prespecified intervals. Electronic case report forms are completed prospectively. The study aims to recruit 312 participants (176 low risk; 136 high risk).

Ethics And Dissemination: ClinicalTrials.gov Identifier: (NCT02852694), authorisation and approval from local ethics committees have been obtained prior to recruitment. Individual informed consent will be obtained prior to participation in the study. Results will be published in a peer-reviewed journal with open access.

Trial Registration Number: NCT02852694; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2019-034892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332179PMC
July 2020

Association between objectively assessed physical activity and sleep quality in adolescence. Results from the GINIplus and LISA studies.

Sleep Med 2020 08 23;72:65-74. Epub 2020 Mar 23.

Institute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany. Electronic address:

Study Objectives: Population-based studies on the association of objectively assessed physical activity (PA) with sleep among adolescents are rare. We examined this association by applying accelerometry and accounting for the day-by-day variability.

Methods: Accelerometers (Actigraph GT3X) were worn for one week by 1223 participants during the 15-year follow-up of the German birth cohorts (German infant study on the Influence of Nutrition Intervention plus air pollution and genetics on allergy development, GINIplus) and (Influence of Lifestyle factors on the development of the Immune System and Allergies in East and West Germany, LISA) to measure PA and sleep. PA was categorised into sedentary, lifestyle and moderate-to-vigorous physical activity (MVPA) referring to Sasaki and Romanzini. Sleep was analysed according to the algorithm developed by Sadeh. Sleep quality was represented by sleep efficiency (SE), sleep onset latency (SOL) and time awake per hour after sleep onset (TAPH). Sleep and activity were additionally reported by diaries. Linear and generalized mixed-effects-models with logit-link with subject specific random intercepts were used stratified by sex and adjusted for confounding variables.

Results: Physical activity appears to be associated only with sleep quality the following night. Among female participants, SE improved (β = 0.12 [95% CI = (0.05; 0.18)]) per 10 minutes increase of MVPA. SOL decreased (OR = 0.83 [95% CI = (0.69; 0.99)]) among male participants with at least 60 min of MVPA per day. Engaging in leisure sport MVPA was associated with higher SE among female (β = 0.70 [95% CI = (0.22; 1.17)]) and male participants (β = 0.76 [95% CI = (0.18; 1.34)]). Also, TAPH among female (β = -0.37 [95% CI = (-0.65; -0.09)]) and SOL among male subjects (OR = 0.70 [95% CI = (0.57; 0.85)]) decreased. Increasing lifestyle activity was related to longer SOL among female (OR = 1.36 [95% CI = (1.15; 1.62)]) and male subjects (OR = 1.32 [95% CI = (1.10; 1.58)]).

Conclusions: In this large population-based sample of German adolescents MVPA and leisure sport improved short term sleep quality, supporting regular PA in adolescents for their health benefit.
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http://dx.doi.org/10.1016/j.sleep.2020.03.007DOI Listing
August 2020

[Inflammatory bowel diseases-the biopsychosocial reality in childhood and adolescence].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020 Jul;63(7):839-845

Abteilung Pädiatrische Gastroenterologie und Hepatologie, Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, Klinikum der Ludwig-Maximilians-Universität München, München, Deutschland.

The prevalence of inflammatory bowel diseases (IBD) in children is rising. These complex diseases typically take an unpredictable course with disease flares. This review serves to illustrate the psychosocial consequences and risks of inflammatory bowel diseases in children and adolescents against the background of the essential medical aspects.Pediatric gastroenterologists should perform diagnostic procedures and medical care. Central elements of diagnostic workup include upper and lower endoscopy with multiple biopsies and imaging procedures. Therapeutic options comprise immunomodulating and immunosuppressive agents, nutrition therapy and surgical interventions. With its various symptoms, complications, diagnostic procedures, and therapies, including side effect concerns, the disease is challenging for young patients and their families. Quality of life, social life, and education may be impaired. There is also an increased risk for mental-health problems. An interdisciplinary approach with the involvement of various healthcare professions such as medical doctors, psychologists, social workers, dieticians, and nurses is necessary to satisfy the needs of children and adolescents with these complex medical conditions and their families.
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http://dx.doi.org/10.1007/s00103-020-03166-zDOI Listing
July 2020
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