Mild Crigler-Najjar Syndrome with Progressive Liver Disease-A Multicenter Retrospective Cohort Study.

Crigler-Najjar Syndrome (CNS) with residual activity of UDP-glucuronosyltransferase 1A1 (UGT1A1) and no need for daily phototherapy is called mild Crigler-Najjar Syndrome. Most of these patients need medical treatment for enzyme induction (phenobarbital) to lower blood levels of unconjugated bilirubin (UCB). Apart from this, no long-term problems have been described so far. The phenotype of patients with the homozygous pathogenic variant c.115C>G p.(His39Asp) in UGT1A1 is described as variable. Clinical observations of our patients led to the assumption that patients with variant c.115C>G have a mild CNS phenotype while having a high risk of developing progressive liver disease. For mild CNS disease, progressive liver disease has not been described so far. Therefore, we conducted a retrospective multicenter analysis of 14 patients with this particular variant, aiming for better characterization of this variant. We could confirm that patients with variant c.115C>G have a high risk of progressive liver disease (seven of fourteen), which increases with age despite having a very mild CNS phenotype. Earlier predictors and causes for an unfavorable disease course are not detectable, but close follow-up could identify patients with progressive liver disease at the beginning. In conclusion, these patients need close and specialized follow-up. Our study questions whether fibrosis in the CNS is really driven by high amounts of UCB or phototherapy.

[Functional Constipation and Nonretentive Fecal Incontinence in Children and Adolescents: Clinical Guideline for Assessment and Treatment]. / Funktionelle (nicht-organische) Obstipation und Stuhlinkontinenz im Kindes- und Jugendalter: Klinische Leitlinie zur Diagnostik und Therapie.

Functional Constipation and Nonretentive Fecal Incontinence in Children and Adolescents: Clinical Guideline for Assessment and Treatment Abstract. Objective: Constipation and fecal incontinence are common disorders in children and adolescents and are associated with incapacitation and a high rate of comorbid psychological disorders. Functional constipation and nonretentive fecal incontinence can be differentiated according to the current Rome-IV classification systems. This interdisciplinary guideline aims to summarize the current state of knowledge regarding somatic and psychiatric assessment and treatment. It formulates consensus-based, practical recommendations. Methods: The members of the Guideline Commission consisted of 11 professional associations and a parental organization. The guideline was based on current literature searches, several online surveys, and consensus conferences based on standard procedures. Results: Functional constipation is much more common than nonretentive fecal incontinence. Constipation requires a detailed medical assessment to exclude somatic causes, especially in young children. Red flags are useful indicators of organic causes to be considered. Most cases of constipation are functional (approximately 95 %). Counseling, toilet training, disimpaction, and long-term oral laxatives, combined with cognitive-behavioral interventions, are most effective. The assessment and treatment of nonretentive fecal incontinence are similar. The rate of somatic factors is much lower (approximately 1 %). Laxatives can worsen outcomes and should be avoided. Comorbid psychological disorders are common (approximately 30 % to 50 %). They should be assessed and treated additionally according to evidence-based guidelines. Conclusions: The recommendations of this guideline were approved with a high consensus. Interdisciplinary cooperation is especially important, as somatic factors and comorbid psychological disorders and symptoms need to be considered. More research is required, especially regarding nonretentive fecal incontinence.

Constipation in Children and Adolescents.

BACKGROUND: According to a population-based study, approximately 6.8% of children and adolescents in Germany suffer from acute or chronic constipation. It can be of organic or functional origin and may be associated with comorbid disturbances, particularly fecal incontinence. METHODS: We selectively searched the PubMed and Google Scholar databases for articles with the keywords "constipation," "children and adolescents," and "incontinence". Recommendations are based on the AWMF guideline on constipation and fecal incontinence and on international guidelines and reviews. RESULTS: More than 90% of cases of chronic constipation are of functional origin. Organic causes vary with age and call for targeted differential diagnosis. Invasive tests are only rarely necessary. Functional constipation may be associated with fecal and urinary incontinence, and the relative risk of urinary tract infections is 2.2 to 6.5. There may be associated psychological symptoms and mental disorders in 30-50% of cases. The cornerstone of treatment is patient and parent education, along with laxative medication and toilet training. Instructional programs have been found effective in otherwise refractory cases. CONCLUSION: The treatment of constipation in childhood should begin as soon as the differential diagnostic evaluation is completed. The education of parents, follow-up at close intervals, and drug treatment and behavioral therapy that are adapted to the symptoms can improve quality of life.

Significant advantages for first line treatment with TNF-alpha inhibitors in pediatric patients with inflammatory bowel disease - Data from the multicenter CEDATA-GPGE registry study.

Background and aims: In recent years, biological agents, such as anti-TNF-α blockers, have been introduced and have shown efficacy in pediatric patients with inflammatory bowel disease (IBD). Here, the prescription mode differentiated into a first/second line application, and efficacy and side effects are evaluated beginning from 2004 until today. Methods: Statistical analyses of the prospective and ongoing CEDATA multicenter registry data from the Society of Pediatric Gastroenterology and Nutrition (GPGE) were performed for patients receiving a biological agent at least once during the period from June 2004 until November 2020 (n = 487). The analyzed parameters were patient demographics, disease extent and behavior, prior or concurrent therapies, duration and outcome of biological therapy, disease-associated complications, drug-related complications, laboratory parameters and treatment response as determined by the Physician's Global Assessment. Results: Crohn's disease (CD) was present in 71.5% of patients, and 52% were boys. Patients showed high disease activity when receiving a first-line TNF-α blocker. After 2016, patients who failed to respond to anti-TNF-α induction therapy were treated with off-label biologics (vedolizumab 4.3% and ustekinumab 2.1%). Propensity score matching indicated that patients with CD and higher disease activity benefitted significantly more from early anti-TNF-α therapy. This assessment was based on a clinical evaluation and lab parameters related to inflammation compared to delayed second-line treatment. Additionally, first-line treatment resulted in less treatment failure and fewer extraintestinal manifestations during TNF-α blockade. Conclusion: First-line treatment with anti-TNF-α drugs is effective and safe. An earlier start significantly reduces the risk of treatment failure and is associated with fewer extraintestinal manifestations during longitudinal follow-up.

Occurrence of Thromboembolism in Paediatric Patients With Inflammatory Bowel Disease: Data From the CEDATA-GPGE Registry.

Objective: Among patients with inflammatory bowel disease (IBD), the risk of thromboembolism (TE) is increased, representing a relevant cause of morbidity and mortality. In contrast to other extraintestinal IBD manifestations, TE receives much less attention because of its low incidence, estimated at merely 0.4-0.9% in hospitalised children with IBD. Methods: Cases with TE, as documented in the German-Austrian Paediatric IBD registry gesellschaft für pädiatrische gastroenterologie und ernährung - large paediatric patient registry (CEDATA-GPGE), were analyzed retrospectively. For all patients with signs of TE, a questionnaire was filled in by the treating paediatric gastroenterologist. Results: Over 10 years, 4,153 paediatric patients with IBD (0-18 years) were registered in the registry, and 12 of them identified with TE. Eight patients were diagnosed with ulcerative colitis (UC), three with Crohn's disease (CD), and one with IBD-unclassified. The median age at IBD diagnosis was 10 years and at the manifestation of TE 13 years, respectively, with a median latency to TE of 2 years. Prevalence of TE was 0.3%, with a significantly higher risk for patients with UC than CD (OR 5.9, CI 1.56-22.33, p = 0.008). More girls than boys were affected (f:m = 7:5) without reaching significance. Approximately 90% of patients experienced TE during active disease, with relevant cerebral and limb involvement in 6/12 patients. Various risk factors, e.g., hospitalisation, coagulopathy, or anaemia were identified. TE management included intensive care and surgery. Among the 12 patients, 11 recovered fully, in which one patient has focal epilepsy as a sequela. Conclusion: Paediatric patients with IBD have a substantially increased risk for TE. Risk factors, such as those identified should be considered when managing paediatric IBD and preventive measures for those hospitalised taken routinely. Initiating pharmacological thromboprophylaxis is challenging for the lack of published trials on efficacy and safety in paediatric IBD but should be considered carefully in each case.

[Paediatric gastroenterological and hepatological care in Germany: results of a nationwide survey]. / Kindergastroenterologische und hepatologische Versorgung in Deutschland: Ergebnisse einer deutschlandweiten Umfrage.

INTRODUCTION: 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. METHODOLOGY: 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. RESULTS: 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). CONCLUSION: 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.

Mode II Behavior of High-Strength Concrete under Monotonic, Cyclic and Fatigue Loading.

An economically efficient yet safe design of concrete structures under high-cycle fatigue loading is a rather complex task. One of the main reasons is the insufficient understanding of the fatigue damage phenomenology of concrete. A promising hypothesis states that the evolution of fatigue damage in concrete at subcritical load levels is governed by a cumulative measure of shear sliding. To evaluate this hypothesis, an experimental program was developed which systematically investigates the fatigue behavior of high-strength concrete under mode II loading using newly adapted punch through shear tests (PTST). This paper presents the results of monotonic, cyclic, and fatigue shear tests and discusses the effect of shear-compression-interaction and load level with regard to displacement and damage evolution, fracture behavior, and fatigue life. Both, monotonic shear strength and fatigue life under mode II loading strongly depend on the concurrent confinement (compressive) stress in the ligament. However, it appears that the fatigue life is more sensitive to a variation of shear stress range than to a variation of compressive stress in the ligament.

Update of the S2k guideline on the management of IgE-mediated food allergies.

Not available.

Mechanical Properties of Hardened 3D Printed Concretes and Mortars-Development of a Consistent Experimental Characterization Strategy.

Today, it is already foreseeable that additive manufacturing of mortar and concrete has groundbreaking potential and will revolutionize or at least fundamentally change the way we build. In recent years, 3D concrete printing (3DCP) with extrusion-based deposition methods has been pushed forward by a growing research community. Albeit being regarded one of the most promising innovations in construction industry, a consistent characterization methodology for assessing the constitutive behavior of 3D printed, hardened cementitious materials is missing, so far, which hinders its widespread use in engineering practice. The major objective of this paper is to fill this gap by developing a new experimental framework that can thoroughly describe the mechanical properties of 3D printed cementitious materials. Based on both a review of state-of-the-art test setups and a comprehensive experimental campaign, the present paper proposes a set of easy-to-use experimental methods that allow us to assess flexural, tensile, shear and compressive strength as well as fracture energy of 3D printed concretes and mortars in a reliable and reproducible manner. The experimental results revealed anisotropic material behavior for flexural, tensile, shear and compressive loading. Furthermore, they confirm that interval time (time gap between deposition of subsequent layers) has a crucial effect on investigated material properties leading to a severe reduction in strength and fracture energy for longer interval times.

Acute Infectious Gastroenteritis in Infancy and Childhood.

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.

[Crohn's Disease Exclusion Diet - an alternative to exlusive enteral nutritional therapy in children and adolescents with Crohn's disease? Statement of the GPGE working groups CEDATA and Nutrition/Nutrition Medicine]. / Crohnʼs Disease Exclusion Diet (CDED) als Alternative zur exklusiven Ernährungstherapie bei Kindern und Jugendlichen mit Morbus Crohn? Stellungnahme der Arbeitsgemeinschaften CEDATA und Ernährung/Diätetik/Ernährungsmedizin der Gesellschaft für pädiatrische Gastroenterologie und Ernährung e. V.

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.

Fictitious Rough Crack Model (FRCM): A Smeared Crack Modelling Approach to Account for Aggregate Interlock and Mixed Mode Fracture of Plain Concrete.

The intention of this paper is to clarify the mechanisms of mixed mode fracture and shear stress transfer in plain concrete. To capture these scarcely explored phenomena, a new mechanical formulation is proposed called the fictitious rough crack model (FRCM). The FRCM considers mode I deformations to control crack formation and residual tensile stress transfer, while mode II deformations are assumed to induce shear stress transfer along the crack surfaces and compressive normal stresses attributed to aggregate interlock. The fundamental idea of the FRCM is to combine these tension-softening and shear-transfer laws and to superimpose the emerging shear and normal stresses of both mechanisms in the crack. The paper illustrates the analytical development of the FRCM and its numerical implementation. Three well-known experimental benchmark problems (concrete panel test series by Nooru-Mohamed and by Hassanzadeh as well as aggregate interlock test series by Paulay and Loeber) are numerically addressed to test plausibility of FRCM results. The numerical implementation of the FRCM is capable of simulating the transition from mode-I fracture to mixed-mode fracture in the structural response and is also able to predict the crack path with reasonable agreement.

School-related experience and performance with inflammatory bowel disease: results from a cross-sectional survey in 675 children and their parents.

OBJECTIVE: We describe school performance and experience in children with inflammatory bowel disease (IBD) across Germany and Austria. Predictors of compromised performance and satisfaction were evaluated to identify subgroups of increased risk. DESIGN: This cross-sectional analysis was based on a postal survey in children aged 10-15 with Crohn's disease, ulcerative colitis or unclassified IBD and their families. Multivariate regression analysis was used to assess influential factors on parental satisfaction with school, attending advanced secondary education (ASE), having good marks and having to repeat a class. Satisfaction was assessed based on the Child Healthcare-Satisfaction, Utilisation and Needs instrument (possible range 1.00-5.00). RESULTS: Of 1367 families contacted, 675 participated in the study (49.4%). Sixty-eight participants (10.2%) had repeated a year, 312 (46.2%) attended ASE. The median school satisfaction score was 2.67 (IQR 2.00-3.33). High socioeconomic status (SES) and region within Germany were predictive for ASE (OR high SES 8.2, 95% CI 4.7 to 14.2). SES, female sex and region of residence predicted good marks. Grade retention was associated with an active disease course (OR 2.7, 95% CI 1.4 to 5.3) and prolonged periods off school due to IBD (OR 3.9, 95% CI 1.8 to 8.6). CONCLUSIONS: A severe disease course impacted on the risk of grade retention, but not on type of school attended and school marks. Low satisfaction of parents of chronically ill children with the school situation underlines the need for a more interdisciplinary approach in health services and health services research in young people.

Modeling determinants of satisfaction with health care in youth with inflammatory bowel disease: a cross-sectional survey.

PURPOSE: Patient satisfaction is frequently used as a health care quality measure despite methodological challenges. By the example of pediatric inflammatory bowel disease (IBD), we assessed factors associated with low satisfaction and examined differences by type of provider. PATIENTS AND METHODS: In a cross-sectional design, a 32-item questionnaire and global questioning were used to assess satisfaction in patients aged 15-25 years. Determinants of low satisfaction were identified by logistic regression (OR with 95% CI). Separate models were calculated for patient-related variables such as age, socioeconomic status (SES), health status (emotional, somatic, quality of life) or region of residence (step 1), and impact of provider (pediatric specialist, adult specialist, no specialist) (step 2). As secondary analysis, we studied the effect of additional indicators such as waiting time, consultation time, and an IBD Management Quality Index (IMQI) on effect estimates (step 3). RESULTS: A total of 567 cases were available for analysis (response 48.2%). The strongest predictors of low satisfaction were anxiety symptoms (OR 2.49, CI 1.14 to 5.45). In step 2, not being seen by a specialist (1.89, 1.16 to 3.10) and having been with the new provider for less than 12 months (1.71, 1.03 to 2.83) were associated with low satisfaction. Satisfaction with adult care provider was similar to pediatric care if adjusted for anxiety, health status, and time with provider (0.95, 0.59 to 1.51). Presence of other quality indicators (step 3), waiting time >30 minutes, consultation time <15 minutes, and low IMQI were all associated with low satisfaction. Age, SES, and region of residence were not found to affect satisfaction in any of the models. CONCLUSION: Anxiety symptoms were most strongly associated with low patient satisfaction. The relevance of recent provider change and not being seen by a specialist underlines the importance of well-planned transition in this age group.

Current health status and medical therapy of patients with pediatric-onset inflammatory bowel disease: a survey-based analysis on 1280 patients aged 10-25 years focusing on differences by age of onset.

OBJECTIVE: There are inconsistent reports on age-related differences in inflammatory bowel disease (IBD). On the basis of patient information, we describe the clinical presentation and therapy in relation to age at diagnosis in longstanding pediatric IBD. PATIENTS AND METHODS: Two surveys were conducted in children and young adults (age: 10-25 years) by pretested postal questionnaires. The main analyses are descriptive, showing proportions and distributions per grouped age of diagnosis. Exploratory logistic regression was used to identify sociodemographic and disease-related factors associated with prognosis. Recent disease course, use of biological therapy, and resecting surgery were chosen as indicators of disease severity. Patients with a diagnosis in infancy (<2 years of age) are presented as a case series. RESULTS: Information of 1280 cases was available [804 Crohn's disease (CD), 382 ulcerative colitis (UC), 94 IBD not specified] (response: 44.6 and 49.6%). Stable remission during the preceding year was reported by 675 (56.7%) patients; 825 (60.9%) patients reported feeling currenty well. Anti-tumor necrosis factor therapy was reported by 33% of CD patients and 9.3% of UC patients, immunomodulation in 82.1 and 63.2%, and corticosteroids by 78.4 and 76.1%, respectively (ever use). Age at diagnosis was not associated with indicators of severe disease. Diagnosis in infancy was reported by 37 patients. CONCLUSION: Our data do not support age at diagnosis-related differences in prognosis in pediatric-onset IBD.

Strengthening of Existing Bridge Structures for Shear and Bending with Carbon Textile-Reinforced Mortar.

Increasing traffic loads and changes in code provisions lead to deficits in shear and flexural capacity of many existing highway bridges. Therefore, a large number of structures are expected to require refurbishment and strengthening in the future. This projection is based on the current condition of many older road bridges. Different strengthening methods for bridges exist to extend their service life, all having specific advantages and disadvantages. By applying a thin layer of carbon textile-reinforced mortar (CTRM) to bridge deck slabs and the webs of pre-stressed concrete bridges, the fatigue and ultimate strength of these members can be increased significantly. The CTRM layer is a combination of a corrosion resistant carbon fiber reinforced polymer (CFRP) fabric and an efficient mortar. In this paper, the strengthening method and the experimental results obtained at RWTH Aachen University are presented.

Inflammatory Bowel Disease in Childhood and Adolescence.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) in childhood and adolescence is 5-11 cases per 100 000 persons per year, corresponding to a new diagnosis of IBD in 800-1470 patients in Germany each year. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed, including guidelines from Germany and abroad. RESULTS: Children and adolescents with IBD often have extensive involvement and an aggressive course of disease. Nonetheless, infliximab and adalimumab are the only biological agents that have been approved for this group of patients. In Crohn's disease, exclusive enteral nutrition is the treatment of first choice for inducing a remission. Patients with (peri-)anal fistulae are treated primarily with infliximab. Corticosteroids and aminosalicylates should be used with caution. In contrast, children and adolescents with ulcerative colitis are treated with either aminosalicylates or prednisolone to induce a remission. As a rule, maintenance pharmacotherapy with thiopurines in Crohn's disease and severe ulcerative colitis, or with aminosalicylates in mild to moderate ulcerative colitis, is indicated for several years, at least until the end of puberty. Patients with refractory disease courses are treated with methylprednisolone, anti-TNF-α-antibodies, and/or calcineurin inhibitors. The spectrum of surgical interventions is the same as for adults. Specific aspects of the treatment of children and adolescents with IBD include adverse drug effects, the areas of nutrition, growth, and development, and the structured transition to adult medicine. CONCLUSION: Children and adolescents with IBD or suspected IBD should be cared for by pediatric gastroenterologists in a center where such care is provided. Individualized treatment with multidisciplinary, family-oriented longterm care is particularly important. Drug trials in children and adolescents are needed so that the off-label use of drugs to patients in this age group can be reduced.