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OBJECTIVES/BACKGROUND: Disease-related malnutrition is common in patients with chronic diseases and has detrimental effects, therefore, skills in nutrition care are essential core competencies for paediatric digestive medicine. The aim of this survey, conducted as part of a global survey of paediatric gastroenterology, hepatology and nutrition (PGHN) training in Europe, was to assess nutrition care-related infrastructure, staff, and patient volumes in European PGHN training centres. METHODS: Standardized questionnaires related to clinical nutrition (CN) care were completed by representatives of European PGHN training centres between June 2016 and December 2019. RESULTS: One hundred training centres from 17 European countries, Turkey, and Israel participated in the survey. Dedicated CN clinics exist in 66% of the centres, with fulltime and part-time CN specialists in 66% and 42%, respectively. Home tube feeding (HTF) and home parenteral nutrition (HPN) programmes are in place in 95% and 77% of centres, respectively. Twenty-four percent of centres do not have a dedicated dietitian and 55% do not have a dedicated pharmacist attached to the training centre. Even the largest centres with >5000 outpatients reported that 25% and 50%, respectively do not have a dedicated dietitian or pharmacist. Low patient numbers on HTF and HPN of

Purpose To assess the current attitude and the status quo towards the use of microbiome analysis and fecal microbiota transfer (FMT) in pediatric patients in German-speaking pediatric gastroenterology centers. Methods A structured online survey among all certified facilities of the German-speaking society of pediatric gastroenterology and nutrition (GPGE) was conducted from November 01, 2020, until March 30, 2021. Results A total of 71 centers were included in the analysis. Twenty-two centers (31.0%) use diagnostic microbiome analysis, but only a few perform analysis frequently (2; 2.8%) or regularly (1; 1.4%). Eleven centers (15.5%) have performed FMT as a therapeutic approach. Most of these centers use individual in-house donor screening programs (61.5%). One-third (33.8%) of centers rate the therapeutic impact of FMT as high or moderate. More than two-thirds (69.0%) of all participants are willing to participate in studies assessing the therapeutic effect of FMT. Conclusions Guidelines for microbiome analyses and FMT in pediatric patients and clinical studies investigating their benefits are absolutely necessary to improve the patient-centered care in pediatric gastroenterology. The long-term and successful establishment of pediatric FMT centers with standardized procedures for patient selection, donor screening, application route, volume, and frequency of use is highly required to obtain a safe therapy.

Introduction We aimed to compare the efficacy of cognitive-behavioral therapy (CBT) among children with functional abdominal pain with an attention control (AC), hypothesizing the superiority of CBT group intervention regarding pain intensity (primary outcome), pain duration and frequency (further primary outcomes), functional disability, and quality of life and coping strategies (key secondary outcomes). Methods We conducted a prospective, multicenter, randomized controlled efficacy trial (RCT) with 4 time points (before intervention, after intervention, 3-month follow-up, and 12-month follow-up). One hundred twenty-seven children aged 7-12 years were randomized to either the CBT (n = 63; 55.6% girls) or the AC (n = 64; 57.8% girls). Results Primary endpoint analysis of the logarithmized area under the pain intensity curve showed no significant difference between groups (mean reduction = 49.04%, 95% confidence interval [CI] -19.98%-78.36%). Treatment success rates were comparable (adjusted odds ratio = 0.53, 95% CI 0.21-1.34, number needed to treat = 16). However, time trend analyses over the course of 1 year revealed a significantly greater reduction in pain intensity (40.9%, 95% CI 2.7%-64.1%) and pain duration (43.6%, 95% CI 6.2%-66.1%) in the CBT compared with the AC, but not in pain frequency per day (1.2, 95% CI -2.7 to 5.2). In the long term, children in the CBT benefitted slightly more than those in the AC with respect to functional disability, quality of life, and coping strategies. Discussion Both interventions were effective, which underlines the role of time and attention for treatment efficacy. However, in the longer term, CBT yielded more favorable results.

Position paper of the Federal Association of German Hospital Pharmacists, the nutrition committees of the German and Austrian Societies of Pediatrics and Adolescent Medicine and the working group on intestinal failure of the Society of Pediatric Gastroenterology and Nutrition. In 2019 the German Federal Institute for Drugs and Medical Devices (Bundesinstitut fur Arzneimittel und Medizinprodukte, BfArM) launched a “doctors letter” (Rote-Hand-Brief) recommending light protection of all parenteral nutrition (PN) solutions during administration for preterm infants, term infants and children less than 2 years of age. The aim of the present paper is to review the available evidence and provide evidence-based recommendations for hospital and home PN light protection in children. The Federal Association of German Hospital Pharmacists, the nutrition committees of the German and Austrian Societies of Pediatrics and Adolescent Medicine and the working group on intestinal failure of the Society of Pediatric Gastroenterology and Nutrition recommend in accordance with the recommendations of the ESPGHAN, ESPEN, ESPR and CESPEN guidelines on pediatric parenteral nutrition: 1. Lipid emulsions and/or vitamins containing PN solutions should be protected from light during administration (bags and tubing) to prevent the generation of oxidants. 2. There is no conclusive evidence for recommending light protection for PN solutions without lipid emulsions and without vitamins during administration (solutions containing, e.g. amino acids, glucose, electrolytes, or trace elements). In addition, in home PN non-light-protected spiral tubing may be used because validated light-protected spiral tubing is currently not available, given that spiral tubing improves the range of motion and safety in infants and young children.

ZusammenfassungEpidemiologische und klinische Beobachtungen sowie Tiermodelle weisen auf die Ernährung als Risikofaktor für die Entwicklung einer chronisch entzündlichen Darmerkrankung (CED) hin. Die exklusive enterale Ernährungstherapie (EET) ist das Musterbeispiel einer effektiven Entzündungskontrolle durch eine rein diätetische Intervention. Ausgehend davon haben Patienten, Familien und betreuende Fachkräfte des Gesundheitswesens ein großes Interesse, andere Ernährungsmodifikationen in der Behandlung von CED-Patienten einzusetzen, zum Beispiel eine partielle Ernährungstherapie (PET) mit spezifischer Diät wie die Crohnʼs Disease Exclusion Diet. Die folgende Stellungnahme fasst die aktuelle Datenlage zusammen und gibt Orientierung für Praxis und weitere Forschung.

Background and aims Immunosuppressed patients are at risk of severe infections with vaccination preventable diseases. We evaluated vaccination rate and immunity of children and adolescents with inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH). Methods Immunization rate of 329 children with IBD (n = 300) and AIH (n = 29) was assessed in seven German centres using vaccination certificates, history of chicken pox and by determining anti-varicella zoster virus (VZV) and anti-measles IgG antibodies. Results Of the total cohort 86% received long-term immunosuppression. Four doses of a hexavalent vaccine were documented in 89%, at least one dose of measles, mumps, and rubella (MMR) vaccination was documented in 325 (99%), with 300 (92%) receiving two doses. Anti-measles IgG concentrations were insufficient in 11% of the immunized patients. VZV vaccination was officially recommended in Germany since 2004, and implemented in 88% born from 2005 onwards. In patients born earlier VZV catch up vaccination only reached 25% (n = 67). Of 118 patients with documented VZV vaccination 25 (21%) did not display sufficient anti-VZV IgG. Of 198 patients with a history of chicken pox, six had undetectable anti-VZV IgG. Of 29 patients having neither had chicken pox nor VZV vaccination, 20 were found to have sufficient anti-VZV IgG. Conclusions In our cohort vaccination coverage for hexavalent and MMR vaccinations was good, but insufficient for VZV vaccination in patients born before 2005. Neither the vaccination certificate nor the history of chicken pox is reliable to predict VZV immunity indicating a need for serologic investigations and if needed vaccination before initiating immunosuppressive therapy.

Context Daily growth hormone (GH) injections can be burdensome for patients and carers. Somapacitan is a long-acting, reversible albumin-binding GH derivative in development for once-weekly administration in patients with growth hormone deficiency (GHD). Objective The objective of this study is to evaluate the efficacy, safety, and tolerability of once-weekly somapacitan vs once-daily GH. Design REAL 3 is a multicenter, randomized, controlled, double-blind (somapacitan doses), phase 2 study with a 26-week main and 26-week extension phase (NCT02616562). Setting This study took place at 29 sites in 11 countries. Patients Fifty-nine GH treatment-naive prepubertal children with GHD were randomly assigned; 58 completed the trial. Interventions Interventions comprised 3 somapacitan doses (0.04 [n = 16], 0.08 [n = 15], or 0.16 mg/kg/wk [n = 14]) and daily GH (0.034 mg/kg/d [n = 14]), administered subcutaneously. Main Outcome Measures The primary end point was height velocity (HV) at week 26. Secondary efficacy end points included HV SD score (SDS) and insulin-like growth factor-I (IGF-I) SDS. Results At week 26, mean (SD) annualized HV for the somapacitan groups was 8.0 (2.0), 10.9 (1.9), and 12.9 (3.5) cm/year, respectively, vs 11.4 (3.3) cm/year for daily GH; estimated treatment difference (somapacitan 0.16 mg/kg/week—daily GH): 1.7 [95% CI –0.2 to 3.6] cm/year. HV was sustained at week 52, and significantly greater with somapacitan 0.16 mg/kg/week vs daily GH. Mean (SD) change from baseline in HV SDS at week 52 was 4.72 (2.79), 6.14 (3.36), and 8.60 (3.15) for the somapacitan groups, respectively, vs 7.41 (4.08) for daily GH. Model-derived mean (SD) IGF-I SDS for the somapacitan groups was −1.62 (0.86), −1.09 (0.78), and 0.31 (1.06), respectively, vs −0.40 (1.50) observed for daily GH. Safety and tolerability were consistent with the profile of daily GH. Conclusions In children with GHD, once-weekly somapacitan 0.16 mg/kg/week provided the closest efficacy match with similar safety and tolerability to daily GH after 26 and 52 weeks of treatment. A short visual summary of our work is available (1).

Children and adolescents with chronic gastrointestinal, pancreatic and liver diseases need age-appropriate and qualified treatment. A representative survey is used to analyse the structural and personnel-related outpatient and inpatient care of children with chronic gastrointestinal, pancreatic and liver diseases in Germany.319 paediatric and adolescent medicine clinics and 50 paediatric gastroenterology practices in Germany were invited to participate in the anonymous online survey via EFS Survey. The structure of the facilities, further training authorisations, cooperations, treatment and care data and an assessment of the need for care were systematically recorded and descriptively evaluated.81 clinics and 10 practices participated in the survey. Almost two thirds of the clinics (n=52) provide outpatient paediatric gastroenterology services. Mostly up to 10 (25.4%) or 20 hours/week (33.8%). A quarter of the clinics do not offer consultation hours. Outpatient care needs cannot be met by two-thirds of the institutions. Half of all clinics stated that inpatient paediatric gastroenterology care needs can be met. However, one third cannot cover this and only rarely are there unused capacities. 35 clinics (43.2%) have a further training authorisation according to the state medical association (n=33) and/or are a further training centre of the Society for Paediatric Gastroenterology and Nutrition (GPGE) (n=18).There is a deficit in both outpatient and inpatient care in paediatric and adolescent gastroenterology. This results, among other things, from the economic framework conditions and a lack of personnel. Well-trained specialists with specialisation in paediatric and adolescent gastroenterology are still needed to provide qualified care throughout the country. Future studies should also include the need for paediatric gastroenterological care from the perspective of other groups, such as affected patients, internal gastroenterologists and paediatricians in private practice.Kinder und Jugendliche mit chronischen Magen-, Darm-, Pankreas-, und Lebererkrankungen benötigen eine altersgerechte und qualifizierte Behandlung. Anhand einer repräsentativen Umfrage wird die strukturelle und personelle ambulante und stationäre Versorgung von Kindern mit chronischen Magen-, Darm-, Pankreas- und Lebererkrankungen in Deutschland analysiert.319 Kliniken für Kinder- und Jugendmedizin sowie 50 kindergastroenterologische Praxen in Deutschland wurden eingeladen, an der anonymen Online-Umfrage über EFS Survey teilzunehmen. Es wurden die Struktur der Einrichtungen, Weiterbildungsbefugnisse, Kooperationen, Behandlungs- bzw. Betreuungsdaten und eine Einschätzung des Versorgungsbedarfs systematisch erfasst und deskriptiv ausgewertet.An der Umfrage haben 81 Kliniken und 10 Praxen teilgenommen. Fast zwei Drittel der Kliniken (n=52) erbringen ambulante kindergastroenterologische Leistungen. Meist bis zu 10 (25,4%) oder 20 Stunden/Woche (33,8%). Ein Viertel der Kliniken bietet keine Sprechstunden an. Der ambulante Versorgungsbedarf kann von zwei Dritteln der Institutionen nicht gedeckt werden. Die Hälfte aller Kliniken gab an, dass der stationäre kindergastroenterologische Versorgungsbedarf gedeckt werden kann. Ein Drittel kann diesen jedoch nicht abdecken und nur selten gibt es ungenutzte Kapazitäten. 35 Kliniken (43,2%) verfügen über eine Weiterbildungsbefugnis gemäß Landesärztekammer (n=33) und/oder sind Weiterbildungszentrum der Gesellschaft für pädiatrische Gastroenterologie und Ernährung (GPGE) (n=18).Es besteht sowohl ein ambulantes als auch stationäres Versorgungsdefizit in der Kinder- und Jugendgastroenterologie. Dieses resultiert unter anderem aus den ökonomischen Rahmenbedingungen und Personalmangel. Gut ausgebildete Fachärzt*innen mit Spezialisierung in Kinder- und Jugendgastroenterologie werden für eine flächendeckende qualifizierte Versorgung weiterhin benötigt. Zukünftige Studien sollten auch den kindergastroenterologischen Versorgungsbedarf aus Sicht anderer Gruppen einbeziehen, wie betroffener Patienten*innen, internistischer Gastroenterolog*innen und niedergelassener Kinder- und Jugendärzt*innen.

Although negative selection of developing B cells in the periphery is well described, yet poorly understood, evidence of naive B cell positive selection remains elusive. Using 2 humanized mouse models, we demonstrate that there was strong skewing of the expressed immunoglobulin repertoire upon transit into the peripheral naive B cell pool. This positive selection of expanded naive B cells in humanized mice resembled that observed in healthy human donors and was independent of autologous thymic tissue. In contrast, negative selection of autoreactive B cells required thymus-derived Tregs and MHC class II–restricted self-antigen presentation by B cells. Indeed, both defective MHC class II expression on B cells of patients with rare bare lymphocyte syndrome and prevention of self-antigen presentation via HLA-DM inhibition in humanized mice resulted in the production of autoreactive naive B cells. These latter observations suggest that Tregs repressed autoreactive naive B cells continuously produced by the bone marrow. Thus, a model emerged, in which both positive and negative selection shaped the human naive B cell repertoire and that each process was mediated by fundamentally different molecular and cellular mechanisms.

Myosin Vb (MYO5B) is a motor protein that facilitates protein trafficking and recycling in polarized cells by RAB11- and RAB8-dependent mechanisms. Biallelic MYO5B mutations are identified in the majority of patients with microvillus inclusion disease (MVID). MVID is an intractable diarrhea of infantile onset with characteristic histopathologic findings that requires life-long parenteral nutrition or intestinal transplantation. A large number of such patients eventually develop cholestatic liver disease. Bi-allelic MYO5B mutations are also identified in a subset of patients with predominant early-onset cholestatic liver disease. We present here the compilation of 114 patients with disease-causing MYO5B genotypes, including 44 novel patients as well as 35 novel MYO5B mutations, and an analysis of MYO5B mutations with regard to functional consequences. Our data support the concept that (1) a complete lack of MYO5B protein or early MYO5B truncation causes predominant intestinal disease (MYO5B-MVID), (2) the expression of full-length mutant MYO5B proteins with residual function causes predominant cholestatic liver disease (MYO5B-PFIC), and (3) the expression of mutant MYO5B proteins without residual function causes both intestinal and hepatic disease (MYO5B-MIXED). Genotype-phenotype data are deposited in the existing open MYO5B database in order to improve disease diagnosis, prognosis, and genetic counseling., publishedVersion

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Epidemiological an clinical observations as well as results from animal studies indicate that nutrition can play a role in the development of inflammatory bowel disease (IBD). Exclusive enteral nutrition therapy represents an example for modulating inflammatory responses solely through diet modification. Therefore, caretakers, patients, families, doctors and nutritionists seek for more dietary options to control IBD. These options include partial enteral nutrition therapy as for example the socalled Crohn's disease exclusion diet. The following statement summarizes existing data and provides recommendations for the current management of enteral nutrition therapy in pediatric Crohn's disease.Epidemiologische und klinische Beobachtungen sowie Tiermodelle weisen auf die Ernährung als Risikofaktor für die Entwicklung einer chronisch entzündlichen Darmerkrankung (CED) hin. Die exklusive enterale Ernährungstherapie (EET) ist das Musterbeispiel einer effektiven Entzündungskontrolle durch eine rein diätetische Intervention. Ausgehend davon haben Patienten, Familien und betreuende Fachkräfte des Gesundheitswesens ein großes Interesse, andere Ernährungsmodifikationen in der Behandlung von CED-Patienten einzusetzen, zum Beispiel eine partielle Ernährungstherapie (PET) mit spezifischer Diät wie die Crohnʼs Disease Exclusion Diet. Die folgende Stellungnahme fasst die aktuelle Datenlage zusammen und gibt Orientierung für Praxis und weitere Forschung.

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.

Background Children with a history of caustic or foreign body ingestions (FBI) are frequently presented at the emergency department. An uncertain case history, the different objects and diverse clinical presentation may complicate or delay a proper management and cause serious complications. Methods A structured retrospective data analysis of patients presented in between January 2005 and December 2017 at the University Medical Centre Ulm was performed. All patients up to 17 years of age with food impaction, foreign body or harmful substance ingestion were included by selection of the corresponding International Statistical Classification of Diseases and Related Health Problems (ICD10-GM) codes. Descriptive statistics, parametric or non-parametric tests, and linear regression analysis were performed. Result In total, 1199 cases were analysed; mean age 3.3 years (SD 3.12; range 7 days to 16 years), male to female ratio 1.15:1, thereof 194 (16.2%) were hospitalized. The majority (n = 619) had no symptoms, 244 out of 580 symptomatic patients complained retching or vomiting. The annually recorded cases increased from 66 in 2005 to 119 in 2017 with a rise of the percentage of all emergency cases by 0.52% since 2010 to 1.34% in 2017. Most frequently, coins were ingested (18,8%). Radiopaque objects accounted for 47.6%, and sharp objects for 10.5% of the FBI, which were significantly more often ingested by girls (p

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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The gut is the largest immune organ of the human body with an enormous mucosal interface. By acting as a physical barrier and by hosting many of the body's immune cells and tissues, the gut is the first line of defense against potentially harmful substances. Therefore, diseases leading to impaired immune response or disruption of the epithelial barrier result in autoimmune, infectious, or inflammatory bowel disease, frequently associated with diarrhea, malabsorption, melena, and growth failure. The differential diagnosis represents an interdisciplinary challenge in this group of rare diseases. The diseases are characterized by clinical, immunological, and histopathological features caused by mutations in single genes. In the following, we will focus on histological findings within the various entities of immunodeficiencies.

Background: Vedolizumab, an anti-integrin antibody, has proven to be effective in adults with inflammatory bowel disease [IBD], but the data in paediatrics are limited. We describe the short-term effectiveness and safety of vedolizumab in a European multi-centre paediatric IBD cohort. Method: Retrospective review of children [aged 2–18 years] treated with vedolizumab from 19 centres affiliated with the Paediatric IBD Porto group of ESPGHAN. Primary outcome was Week 14 corticosteroid-free remission [CFR]. Results: In all, 64 children were included (32 [50%] male, mean age 14.5 ± 2.8 years, with a median follow-up 24 weeks [interquartile range 14–38; range 6–116]); 41 [64%] cases of ulcerative colitis/inflammatory bowel disease unclassified [UC/IBD-U] and 23 [36%] Crohn’s disease [CD]. All were previously treated with anti-tumour necrosis factor [TNF] [28% primary failure, 53% secondary failure]. Week 14 CFR was 37% in UC, and 14% in CD [P = 0.06]. CFR by last follow-up was 39% in UC and 24% in CD [p = 0.24]. Ten [17%] children required surgery, six of whom had colectomy for UC. Concomitant immunomodulatory drugs did not affect remission rate [42% vs 35%; p = 0.35 at Week 22]. There were three minor drug-related adverse events. Only 3 of 16 children who underwent endoscopic evaluation had mucosal healing after treatment (19%). Conclusions: Vedolizumab was safe and effective in this cohort of paediatric refractory IBD. These data support previous findings of slow induction rate of vedolizumab in CD and a trend to be less effective compared with patients with UC.

Major histocompatibility complex class II (MHC II) is essential for adaptive immune response. We recently reported on disturbed adaptive mucosal immunity due to MHC II deficiency and prolonged enteropathy. Here, we share medical history, flow cytometric analysis of blood lymphocytes, immunohistopathology, and fecal analysis of seven genetically confirmed patients with MHC II deficiency suffering from enteropathy. Data on flow cytometric analysis of HLA-DR expression on monocytes and B cells before hematopoietic stem cell transplantation (HSCT) and after in-vitro stimulation is shown. The course of immune reconstitution after HSCT of MHC II deficient patients in comparison to severe combined immunodeficiency (SCID) patients is described. In addition, immunohistopathology illustrating CD4 and CD8 T cell infiltration, absence of B lymphocytes and plasma cells, and disturbed immunoglobulin expression in the gut as well as absent HLA-DR expression in the liver is shown. Furthermore, data from fecal analysis such as stool fat, nitrogen, and water fraction as well as faecal markers such as alpha-1-antitrypsin, pancreas specific elastase 1, eosinophilic protein X (EPX), and beta defensin 2 are presented. Altogether this data demonstrates the complex phenotype of MHC II deficiency. The data can be valuable for researchers interested in mucosal immunity. For further interpretation of the data presented in this article, please see the research article “Persisting enteropathy and disturbed adaptive mucosal immunity due to MHC class II deficiency” (Posovszky et al., 2019). Keywords: MHC class II deficiency, Adaptive immunity, Mucosal immunity, Intestinal epithelial cells, Enteropathy, HLA-DR, Invariant chain, Hematopoietic stem cell transplantation

Background and study aims Use of carbon dioxide (CO2) instead of room air (RA) during colonoscopy in adults revealed significantly less flatulence and abdominal pain in several studies. The objectives of this study were to investigate the effects of CO2 usage on post-interventional pain, abdominal discomfort, abdominal girth, pCO2 levels, and narcotic requirement in deeply sedated pediatric patients. Patients and methods A total of 97 children and adolescents aged 4 years to 17 years undergoing colonoscopy were randomized to RA or CO2 in a prospective, randomized, controlled trial. Age-appropriate pain scales assessed abdominal pain as primary outcome. In addition, abdominal girth, abdominal bloating, transcutaneous pCO2, narcotic requirement to achieve deeply sedation, and post-procedural analgesic demand was analyzed in 73 patients. Results Overall, significantly fewer patients reported bloating in the CO2 group (P = 0.0012). However, we observed only a trend to lower post-interventional pain (P = 0.15) and a lower pain score. There was no significant difference in transcutaneous pCO2 level and no adverse events occurred. Although there was no difference in the dosage of propofol and midazolam, we observed a significant increased necessity for use of synthetic opioids in the RA group to achieve optimal examination conditions (P = 0.023). Conclusions The benefits using CO2 in colonoscopy of deeply sedated children predominate. In particular, CO2 insufflation may allow a less painful post-interventional time and it significantly reduces abdominal bloating. Moreover, with CO2, significantly less additional opioids were used. Thus, CO2 insufflation can be considered as safe in deeply sedated patients as there was no relevant pulmonary CO2 retention observed. (DRKS00013914)

Congenital diarrhoeal disorders are a heterogeneous group of inherited malabsorptive or secretory diseases typically appearing in the first weeks of life, which may be triggered by the introduction of distinct nutrients. However, they may also be unrecognised for a while and triggered by exogenous factors later on. In principle, they can be clinically classified as osmotic, secretory or inflammatory diarrhoea. In recent years the disease-causing molecular defects of these congenital disorders have been identified. According to the underlying pathophysiology they can be classified into four main groups: 1) Defects of digestion, absorption and transport of nutrients or electrolytes 2) Defects of absorptive enterocyte differentiation or polarisation 3) Defects of the enteroendocrine cells 4) Defects of the immune system affecting the intestine. Here, we describe the clinical presentation of congenital intestinal diarrhoeal diseases, the diagnostic work-up and specific treatment aspects.

Objectives: Concomitant injuries play an important role when it comes to clinical management of traumatic brain injury (TBI). We examined the incidence of concomitant injuries and their relevance with respect to hospitalization. Methods: Children aged between 0 - 18 years hospitalized for treatment of TBI (ICD 10; S06.0 - 9) during 2010-2011 were included. The data relating to concomitant injuries and the course of treatment were evaluated. Statistical analysis included multivariate regressions at a level of significance of p ≤ 0.05. Results: 794 children were treated for head injury in our hospital. Head injury with other associated injuries had been sustained by 158 (19.9%) children. The face and the extremities were the areas of the body most often affected (p = 0.001). Boys represent the majority within the cohort of multiple injured children (p = 0.0001). The older the child, the higher the percentage of children with concomitant injuries (r = 0.27; p = 0.034). There was a significant correlation between the severity of the head injury and the occurrence of concomitant injuries (r = 0.19; p = 0.046). Children with concomitant injuries were found to suffer significantly more falls (N = 82; 51.9%) than road traffic accidents (N = 68; 43%) (p = 0.0001). A comparison of different variables revealed that age (7 to 10 years), severity of head injury (mild TBI), and trauma mechanism (fall) were most influential (KB = ?1.55; p = 0.023) for concomitant injuries. Children with concomitant injuries have a significant longer stay in hospital than those without: mean stay 2.5 to 4.5 days (p = 0.0001). Conclusion: Concomitant injuries are hints for more severe head injuries and children should be examined with special care.

Intestinal epithelial cells (IECs) form a fundamental mucosal barrier and actively participate in tolerance and immunity against intestinal contents. Major histocompatibility complex class II (MHC II) and invariant chain (Ii) molecules are essential for adaptive immune response. MHC II deficiency often presents with gastrointestinal disorders. Intestinal biopsy samples revealed an absence of HLA-DR, Ii, and local immunoglobulins in both hematopoietic immune cells and IECs accompanied by a lack of faecal sIgA. After successful hematopoietic stem cell transplantation (HSCT) absent HLA-DR and Ii expression persisted in IECs and faecal stool analysis indicated inflammation and high microbial activity. We describe multifaceted disturbance of adaptive mucosal immunity in MHC II deficient patients suffering from enteropathy. HLA-DR and Ii expression on enterocytes is not restored by HSCT. This may account for increased susceptibility to enteric infections and intestinal inflammation leading to prolonged enteropathy reported in MHC II deficient patients.

In the original article, author Carsten Posovszky's surname was incorrectly spelt. This has now been corrected.

Background Children with inflammatory bowel disease (IBD) or autoimmune hepatitis (AIH) are at risk for severe infections. This is partially a result of their chronic disease condition but, moreover, a side effect of their immunosuppressive therapy. Currently, vaccinations with live vaccines are regarded as contraindicated under immunosuppressive therapy, mainly because of concerns about side effects and a lack of data showing an adequate immune reaction. As there is no systematic study on the individual immunoreactivity under immunosuppressive therapy in this patient group, we analyzed the lymphocyte subgroups and immunoreactivity of lymphocytes in children with IBD or AIH with and without immunosuppressive therapy in vitro. Methods We collected whole blood samples from 17 children with IBD or AIH on high-level immunosuppression (IS) (group 1) and 8 on low-level IS (group 2) in comparison with 6 patients without systemic IS (group 3). After Ficoll separation of peripheral mononuclear cells, the samples were analyzed by flow cytometry to determine the lymphocyte subgroups. Furthermore, we stimulated the isolated lymphocytes with phytohemagglutinin (PHA), tetanus antigen, and adenovirus antigen and measured their proliferation by incorporation of H3-thymidine detected in a beta counter. The statistical evaluation was performed by Kruskal-Wallis test and Mann-Whitney U test using a bilateral level of significance of α = 5%. Results Patients with low- or high-level IS showed no significant difference in the number of lymphocytes or T cells. Interestingly, IS did not influence the lymphocyte proliferation assay significantly regarding median reaction to PHA, tetanus antigen, or adenovirus antigen between the three groups. However, comparing all immunosuppressed patients to the patients without IS, there was a significant difference towards stimulation with tetanus antigen. Conclusions Contrary to expectations of a strong influence of IS therapy on the immunoreactivity, this study showed only minor differences between the groups with high-level, low-level, and no IS. Particularly, the in vitro reactivity to adenovirus antigen was nearly the same in all three groups. We assume that—provided a normal distribution and count of lymphocyte subgroups—patients with moderate immunosuppression might be capable of raising an effective immune response to inactivated and live vaccines. Electronic supplementary material The online version of this article (10.1186/s40348-018-0079-0) contains supplementary material, which is available to authorized users.