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Introduction: Given the lack of data, we aimed to explore which therapeutic endpoints pediatric patients with eosinophilic esophagitis (EoE) and their parents consider to be relevant. Methods: We created an educational brochure on EoE and a questionnaire, both of which were content-validated by pediatric patients and parents. Validated documents were sent to 112 patients and parents. They ranked the importance (5 levels) of short (during next 3 months) and long-term (≥1 year) treatment effect on symptoms, quality of life, endoscopic inflammation, stricture formation, histological inflammation, and fibrosis. Results: A total of 45 parents and 30 pediatric patients ≥11 years completed the questionnaires. Pediatric patients identified improvement in the following domains as most important in the short- and long-term, respectively: symptoms (73% vs. 77%), QoL (53% vs. 57%), histologic inflammation (47% vs. 50%), histologic fibrosis (40% vs. 33%), endoscopic inflammation (47% vs. 40%), and strictures (33% vs. 40%). Parents of children ≥11 years old classified improvement in the following domains as most important in the short- and long-term, respectively: symptoms (70% vs. 83%), QoL (63% vs. 80%), histologic inflammation (67% vs. 77%), histologic fibrosis (47% vs. 63%), endoscopic inflammation (77% vs. 80%), and strictures (40% vs. 53%). Agreement between caregiver and children on the short-term importance of treatment outcomes was as follows: symptoms (77%), QoL (40%), histologic inflammation and fibrosis (47% and 43%), endoscopic inflammation and strictures (50% and 40%). Conclusion: Pediatric patients and parents attributed most importance to improvement in symptoms and QoL. Agreement between parents and patients regarding therapy goals is limited. [ABSTRACT FROM AUTHOR]

Purpose: The Swiss voluntary salt iodisation programme has successfully prevented iodine deficiency for 100 years, but dietary habits are changing and today only one-third of processed foods contain iodised salt. We aimed to monitor the current iodine status in children and pregnant women. Methods: We conducted a nationwide cross-sectional study in children (6–12 years) and pregnant women and measured the urinary iodine concentration (UIC) in spot urine samples. We estimated the iodine intake using UIC and urinary creatinine concentration (UCC) and determined the prevalence of intakes below the average requirement (AR) using the SPADE method. We measured dried blood spot (DBS) thyroglobulin (Tg), TSH and total T4 in pregnant women. Results: The median UIC was 127 μg/L (bootstrapped 95% CI 119, 140, n = 362) in children and 97 μg/L (bootstrapped 95% CI 90, 106, n = 473) in pregnant women. The estimated prevalence of inadequate iodine intake (< 65 μg/day) was 5.4% (bootstrapped 95% CI 0.0, 14.6) in children. Half (47%) of the women consumed iodine-containing multivitamin and mineral supplements (≥ 150 μg/day). Compared to non-users, users had higher median UIC (129 vs. 81 μg/L, P < 0.001), lower prevalence of inadequacy (< 160 μg/day; 0.2 vs. 31%) and lower DBS-Tg (23 vs. 29 μg/L, P < 0.001). All women were euthyroid. Conclusions: The Swiss diet and current salt fortification provides adequate iodine intake in children, but not in all pregnant women. Iodine supplements cover the dietary gap in pregnancy but are not universally consumed. Therefore, improved use of iodised salt in processed foods is desired to ensure adequate iodine intake in all population groups. This trial was registered at clinicaltrials.gov as NCT04524013. [ABSTRACT FROM AUTHOR]

Background: The CF transmembrane conductance regulator (CFTR), whose mutations cause cystic fibrosis (CF), depends on ATP for activation and transport function. Availability of ATP in the cell and even more in specific cellular microcompartments often depends on a functional creatine kinase system, which provides the ‘energy buffer’ phosphocreatine. Creatine supplementation has been shown to increase phosphocreatine levels, thus promoting muscle growth and strength in athletes and having protective effects in neuromuscular disorders. Aim: To test clinically, if creatine supplementation improves maximal isometric muscle strength (MIMS), lung function and CFTR channel activity in patients with CF, and to determine enzymatic activity of creatine kinase in respiratory epithelial cells. Methods: In an open-label pilot study 18 CF patients (8–18-year-old) with pancreatic insufficiency and mild to moderate lung disease received daily creatine supplementation during 12 weeks. Patients were monitored during 24–36 weeks. Enzymatic activity of creatine kinase was measured in primary epithelial cell cultures. Results: After creatine supplementation, there was no change in lung function and sweat electrolyte concentrations, possibly due to the very low creatine kinase activities detected in respiratory epithelia. However, the patients consistently showed signicantly increased MIMS (18.4%; P<0.0001), as well as improved general well-being, as assessed by a standardized questionnaire. Except for one patient with transient muscle pain, no side effects were reported. Conclusions: Our pilot study suggests, that creatine supplementation should be further evaluated as a possible clinically beneficial adjuvant therapy for patients with CF to increase muscle strength, body-weight and well-being [Copyright &y& Elsevier]

: ObjectivesThe aim of this study was to assess the efficacy and safety of a single infusion of infliximab in the treatment of pediatric Crohn’s disease (CD).: MethodsA total of 21 pediatric CD patients were enrolled at seven study centers and randomized to receive a single infusion of infliximab 1 mg/kg (n = 6), 5 mg/kg (n = 7), or 10 mg/kg (n = 8) over at least 2 hrs at week 0 in this multicenter, open-label, dose-blinded trial. Efficacy assessments, including the Pediatric Crohn’s Disease Activity Index (PCDAI), modified CDAI, C-reactive protein concentration (CRP), and erythrocyte sedimentation rate (ESR) determinations, were made at screening and at weeks 1, 2, 4, 8, and 12. Adverse events were assessed throughout study participation.: ResultsImprovements in the PCDAI, modified CDAI, ESR, and CRP were observed with all infliximab doses, beginning at week 1. On average, all treated patients experienced approximately 50% improvement in the PCDAI by week 2. By week 12, the PCDAI remained approximately 30% improved from baseline. During the study, all 21 patients (100%) achieved a clinical response, and 10 patients (48%) achieved clinical remission. There were no infusion reactions in any of the treatment arms.: ConclusionsThe results of this trial suggest that infliximab may be safe and effective as short-term therapy of medically refractory moderate to severe CD in a pediatric population. [Copyright &y& Elsevier]

Thirty HIV-infected children were cross-sectionally examined for morphologic hepatic abnormalities, using ultrasonography or histology. Abdominal ultrasonography was performed in 27 children. The liver structure was normal in four patients, one of whom had moderate symptoms of the HIV infection and three of them severe symptoms. Abnormal liver structure, compatible with hepatic steatosis, was found in 23 (85%) patients. Five of them were in an early stage of the HIV infection (category N or A), three patients were ranked in category B and 15 patients in category C. Histological examination of the liver was performed in 11 children and steatosis was documented in ten (91%). In seven (70%) of these ten children steatosis had been suspected by ultrasonography. In conclusion, steatosis is common in HIV-infected children. It is non-specific and has no impact on disease, diagnostic evaluation or management. Conclusion Ultrasonography is a sensitive, accurate, non-invasive screening tool. It is more reliable than liver function tests. [ABSTRACT FROM AUTHOR]

Both immunological hypersensitivity and vascular abnormalities have been implicated in the pathogenesis of inflammatory bowel disease. In an attempt to link the two hypotheses, we sought evidence of local production of endothelin-1, a potent vasoconstrictor, in patients with Crohn's disease and ulcerative colitis. An immunohistochemical method was used to detect endothelin-1 in tissue samples from sixteen Crohn's disease patients, nine ulcerative colitis patients, and thirteen controls. In the controls, positively staining cells were infrequent in both lamina propria (mean 0-9% of total cells, 95% confidence interval 01-1.7%) and submucosa (2.3%, 0.4-4.1%). The percentage of endothelin-immunoreactive cells was significantly higher in the two disease groups than in the controls. Among the Crohn's disease patients, there were more immunoreactive cells in the submucosa than in the lamina propria (19.1%, 15.2-22.1% vs 12.3%, 8.1-16.5%; p < 0.001), whereas the converse was true for the ulcerative colitis group (8.6%, 1.1-16. 1% vs 24.4%, 14.1-34.6%; p < 0.001). Immunoreactive macrophage aggregates around submucosal blood vessels were common in samples from Crohn's disease patients. Endothelin concentrations, measured by radioimmunoassay, in supernatants of homogenised tissue samples were significantly higher in Crohn's disease and ulcerative colitis than in controls. We suggest that local endothelin production by inflammatory cells may contribute to vasculitis in chronic inflammatory bowel disease by inducing intestinal ischaemia through vasoconstriction. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Iodine intake in the Swiss population 100 years after the introduction of iodised salt: a cross‑sectional national study in children and pregnant women" published in a previous issue of the periodical.

Stress in early life can affect the progeny and increase the risk to develop psychiatric and cardiometabolic diseases across generations. The cross-generational effects of early life stress have been modeled in mice and demonstrated to be associated with epigenetic factors in the germline. While stress is known to affect gut microbial features, whether its effects can persist across life and be passed to the progeny is not well defined. Here we show that early postnatal stress in mice shifts the fecal microbial composition (binary Jaccard index) throughout life, including abundance of eight amplicon sequencing variants (ASVs). Further effects on fecal microbial composition, structure (weighted Jaccard index), and abundance of 16 ASVs are detected in the progeny across two generations. These effects are not accompanied by changes in bacterial metabolites in any generation. These results suggest that changes in the fecal microbial community induced by early life traumatic stress can be perpetuated from exposed parent to the offspring. A study on early life traumatic stress in mice suggest that changes in the fecal microbial community induced by early life stress can be perpetuated from exposed parent to the offspring across two generations. [ABSTRACT FROM AUTHOR]

No abstract available Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: Little is known about disease-specific health-related quality-of-life (HRQoL) changes over time in paediatric patients with inflammatory bowel disease (IBD), and about their associations with baseline medical characteristics.Methods: In this study, 153 paediatric patients with IBD from the multicentre prospective Swiss IBD cohort study were included at baseline. Of these, 90 patients were analysed at a 1-year follow-up. Medical data were extracted from hospital records, while HRQoL data were measured using the standardized, self-report disease-specific IMPACT-III questionnaire.Results: The IBD diagnosis of the included children was made an average of 2.0 years before their baseline assessment. Over the 1-year follow-up period, a significant increase in overall HRQoL and in the HRQoL domain 'physical functioning' was evident. On multivariate analysis, overall HRQoL changes over time were predicted by baseline HRQoL, baseline disease activity, and disease activity changes over time. HRQoL improvements were significantly associated with decreases in physician-assessed disease activity. Children reporting a low baseline HRQoL and children with inactive or mildly-active disease experienced greater improvements.Conclusions: Children with more severe baseline disease activity had the greatest risk for HRQoL deterioration over the 1-year follow-up period. However, among possible factors that might influence HRQoL changes over time, the child's medical characteristics explained only a small proportion of their variability in our sample. We, therefore, recommend that researchers and clinicians focus on factors that are not incorporated within the multidimensional HRQoL concept if they seek to gain better insights into factors that influence HRQoL changes over time in children with IBD. [ABSTRACT FROM AUTHOR]

Reports on the case of a girl with symptoms which included mouth lesions, abdominal pain, and irregular bowel movements. Details of oral irregularities; Diagnosis of Crohn's disease; Treatment with oral prednisone; Outcome.

The colonization of the infant gut is crucial for early life development. Although the composition and diversity of the infant gut microbiota (GM) has been well described at a taxonomic level, functional aspects of this ecosystem remain unexplored. In the infant gut, lactate is produced by a number of bacteria and plays an important role in the trophic chain of the fermentation process. However, little is known about the lactate-utilizing bacteria (LUB) community in infants and their impact on gut health. By combining culture-based and molecular methods, we intensively studied LUB in fecal samples of 40 healthy infants on both taxonomic and functional levels. We demonstrated metabolic cross-feeding of lactate and identified keystone species specified for lactate utilization. The interactions of such species and their metabolic outcome could have direct impacts on infant health, either beneficial (production of short chain fatty acids) or detrimental (accumulation of hydrogen or hydrogen sulfide). We identified mode of delivery as a strong determinant for lactate-producing and -utilizing bacteria levels. These findings present the early establishment of GM with a novel perspective and emphasize the importance of lactate utilization in infancy. [ABSTRACT FROM AUTHOR]

Neonatal gut microbiota establishment represents a crucial stage for gut maturation, metabolic and immunologic programming, and consequently short- and long-term health status. Human milk beneficially influences this process due to its dynamic profile of age-adapted nutrients and bioactive components and by providing commensal maternal bacteria to the neonatal gut. These include Lactobacillus spp., as well as obligate anaerobes such as Bifidobacterium spp., which may originate from the maternal gut via an enteromammary pathway as a novel form of mother-neonate communication. Additionally, human milk harbors a broad range of oligosaccharides that promote the growth and activity of specific bacterial populations, in particular, Bifidobacterium and Bacteroides spp. This review focuses on the diversity and origin of human milk bacteria, as well as on milk oligosaccharides that influence neonatal gut microbiota establishment. This knowledge can be used to develop infant formulae that more closely mimic nature's model and sustain a healthy gut microbiota. [ABSTRACT FROM AUTHOR]

Breast milk has recently been recognized as source of commensal and potential probiotic bacteria. The present study investigated whether viable strains of gut-associated obligate anaerobes are shared between the maternal and neonatal gut ecosystem via breastfeeding. Maternal faeces, breast milk and corresponding neonatal faeces collected from seven mothers-neonate pairs at three neonatal sampling points were analyzed by culture-independent (pyrosequencing) and culture-dependent methods (16 S rRNA gene sequencing, pulsed field gel electrophoresis, random amplified polymorphic DNA and repetitive extragenic palindromic polymerase chain reaction. Pyrosequencing allowed identifying gut-associated obligate anaerobic genera, like Bifidobacterium, Bacteroides, Parabacteroides and members of the Clostridia ( Blautia, Clostridium, Collinsella and Veillonella) shared between maternal faeces, breast milk and neonatal faeces. Using culture, a viable strain of Bifidobacterium breve was shown to be shared between all three ecosystems within one mother-neonate pair. Furthermore, pyrosequencing revealed that several butyrate-producing members of the Clostridia ( Coprococcus, Faecalibacterium, Roseburia and Subdoligranulum) were shared between maternal faeces and breast milk. This study shows that (viable) obligate gut-associated anaerobes may be vertically transferred from mother to neonate via breastfeeding. Thus, our data support the recently suggested hypothesis of a novel way of mother-neonate communication, in which maternal gut bacteria reach breast milk via an entero-mammary pathway to influence neonatal gut colonization and maturation of the immune system. [ABSTRACT FROM AUTHOR]

Scarce research has been performed to assess whether the human maternal gut microbiota undergoes changes during the perinatal period. Therefore, in the present study, gut microbiota composition of seven healthy mothers(to-be) was assessed at different time points during the perinatal period (i.e. weeks 3-7 prepartum and days 3-6, 9-14, and 25-30 postpartum) using quantitative polymerase chain reaction (qPCR) and pyrosequencing, and was complemented by short-chain fatty acids (SCFA) and calprotectin quantification using high-performance liquid chromatography and enzyme-linked immunosorbent assay, respectively. qPCR revealed the predominance of members of the Firmicutes, Bacteroides, and Bifidobacterium without detectable changes over the perinatal period. Pyrosequencing supported these data in terms of microbiota stability for any population at any taxonomic level, although ratios of members of the Actinobacteria and Bacteroidetes differed between the two methods. However, the number of operational taxonomic units observed by pyrosequencing was subjected to fluctuations and the relative abundance of Streptococcus decreased numerically postpartum ( P = 0.11), which may indicate that aberrancies in subdominant populations occur perinatally. Furthermore, total fecal SCFA concentrations, particularly the branched-chain fatty acids isobutyrate and isovalerate, were higher than for non-pregnant subjects throughout the perinatal period. This suggests metabolic changes and increased energy extraction via proteolytic, in addition to saccharolytic fermentation, accompanied by low-grade inflammation based on fecal calprotectin levels. Our data show that the maternal gut microbiota remained stable over the perinatal period despite altered metabolic activity and low-grade inflammation; however, it remains to be confirmed whether changes preceded earlier during pregnancy and succeeded later postpartum. [ABSTRACT FROM AUTHOR]

Oxidative stress and low-grade systemic inflammation may contribute to the pathogenesis of obesity-induced comorbidities, including nonalcoholic fatty liver disease. Increasing intake of dietary antioxidants might be beneficial, but there are few data in obese children. To examine the effect of antioxidant supplementation on biomarkers of oxidative stress, inflammation, and liver function, we randomly assigned overweight or obese children and adolescents (n = 44; mean ± SD age: 12.7 ± 1.5 y) participating in a lifestyle modification program to a 4-mo intervention with daily antioxidants (vitamin E, 400 IU; vitamin C, 500 mg; selenium, 50 μg) or placebo. We measured anthropometrics, antioxidant status, oxidative stress (F2-isoprostanes, F2-isoprostane metabolites), inflammation, liver enzymes, fasting insulin and glucose, and lipid profile at baseline and endpoint. There was a significant treatment effect of antioxidant supplementation on antioxidant status [α-tocopherol, β = 23.2 (95%CI: 18.0, 28.4); ascorbic acid, β = 70.6 (95% CI: 51.7, 89.4); selenium, β = 0.07 (95% CI: 0.01, 0.12)] and oxidative stress [8-iso-prostaglandin F2α, β =-0.11 (95% CI: -0.19, -0.02)] but not on any of the inflammatory markers measured. There was a significant treatment effect on alanine aminotransferase [β = -0.13 (95% CI: -0.23, -0.03)], a trend toward a significant effect on aspartate aminotransferase [β = -0.04 (95% CI: -0.09, 0.01)], and no significant effect on γ-glutamyltransferase [β = -0.03 (95% CI: -0.11, 0.06)]. In summary, antioxidant supplementation for 4mo improved antioxidant--oxidant balance and modestly improved liver function tests; however, it did not reduce markers of systemic inflammation despite significant baseline correlations between oxidative stress and inflammation. The study was registered at clinicaltrials.gov as NCT01316081. [ABSTRACT FROM AUTHOR]

The establishment of a pioneer gut microbiota is increasingly recognized as a crucial stage in neonatal development influencing health throughout life. While current knowledge is mainly based on either culture or molecular analysis of feces, we opted for a comprehensive approach complementing culture with state-of-the-art molecular methods. The bacterial composition in feces from seven healthy vaginally-delivered, breast-fed neonates was analyzed at days 4-6, 9-14 and 25-30 postnatal, using culture, 16S rRNA gene sequencing of isolates, quantitative PCR and pyrosequencing. Anaerobes outnumbered facultative anaerobes in all seven neonates within the first days of life, owing to high levels of Bifidobacterium and unexpectedly also Bacteroides, which were inversely correlated. Four neonates harbored maternal Bacteroides levels, comprising typical adult species, throughout the neonatal period, while in three only subdominant levels were detected. In contrast, the major adult-type butyrate- producing anaerobic populations, Roseburia and Faecalibacterium, remained undetectable during the neonatal period. The presence of Bacteroidetes as pioneer bacteria in the majority of neonates studied demonstrates that adult- type strict anaerobes may reach adult-like population densities within the first week of life. Consequently the switch from facultative to strict anaerobes may occur earlier than previously assumed in breast-fed neonates, and the establishment of the major butyrate-producing populations may be limited by other factors than the absence of anaerobic conditions. The impact of breast milk components on the timing of establishment of anaerobic pioneer bacteria, as well as opportunistic pathogens should be further studied in regard to priming of the gut-associated immune system and consequences on later health. [ABSTRACT FROM AUTHOR]

Background: the addition of oligosaccharides to infant formula has been shown to mimic some of the beneficial effects of human milk. The aim of the study was to assess the tolerance and safety of a formula containing an innovative mixture of oligosaccharides in early infancy. Methodology/Principal Findings: this study was performed as a multi-center, randomized, double-blind, placebocontrolled trial including healthy term infants. Infants were recruited before the age of 8 weeks, either having started with formula feeding or being fully breast-fed (breastfeeding group). Formula-fed infants were randomized to feeding with a regular formula containing a mixture of neutral oligosaccharides and pectin-derived acidic oligosaccharides (prebiotic formula group) or regular formula without oligosaccharides (control formula group). Growth, tolerance and adverse events were assessed at 8, 16, 24 and 52 weeks of age. The prebiotic and control groups showed similar mean weight, length and head circumference, skin fold thicknesses, arm circumference gains and stool frequency at each study point. As far as the anthropometric parameters are concerned, the prebiotic group and the control group did not attain the values shown by the breastfeeding group at any study point. The skin fold thicknesses assessed in the breastfeeding group at 8 weeks were strikingly larger than those in formula fed infants, whereas at 52 weeks were strikingly smaller. The stool consistency in the prebiotic group was softer than in the control group at 8, 16 and 24 weeks (p<0.001) and closer to that of the breastfeeding group. There was no difference in the incidence of adverse events between the two formula groups. Conclusions: our findings demonstrate the tolerability and the long term safety of a formula containing an innovative mixture of oligosaccharides in a large cohort of healthy infants. [ABSTRACT FROM AUTHOR]

A 20-month-old male child died during an episode of acute bronchitis. The autopsy revealed massive hypertrophy and acute dilatation of the right heart which was caused by pulmonary hypertension exhibiting plexogenic arteriopathy and necrotizing arteriitis of small lung vessels. Further examination revealed complete old fibrotic occlusion of the extrahepatic portal vein and a large porto-systemic shunt. Esophageal varices indicating portal hypertension were not present. Histology showed enlarged hepatic arteries within the portal tracts while branches of the portal vein were lacking. The placenta had been examined at the time of birth and multiple chorangiomas reported. Furthermore, multiple old and florid occlusions of fetal vessels had been detected together with focal lymphoplasmocytic inflammation, which may indicate that intrauterine infection and vascular compromise were the cause of the complete closure of the portal vein around birth. The association of pulmonary hypertension with liver disease is well known, and portal hypertension has been considered a key factor in the pathogenesis of pulmonary hypertension. However, this case illustrates that portal hypertension is not a requisite for the development of pulmonary hypertension. It rather suggests that plexogenic arteriopathy of the lungs can be caused by portocaval shunting independent of liver damage and portal hypertension. Toxic metabolites of nutrients or residual activity of pancreatic enzymes reaching the pulmonary vascular bed may be involved in the pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Vitamin D and calcium deficiencies are common worldwide, causing nutritional rickets and osteomalacia, which have a major impact on health, growth, and development of infants, children, and adolescents; the consequences can be lethal or can last into adulthood. The goals of this evidence-based consensus document are to provide health care professionals with guidance for prevention, diagnosis, and management of nutritional rickets and to provide policy makers with a framework to work toward its eradication. Evidence: A systematic literature search examining the definition, diagnosis, treatment, and prevention of nutritional rickets in children was conducted. Evidence-based recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system that describes the strength of the recommendation and the quality of supporting evidence. Process: Thirty-three nominated experts in pediatric endocrinology, pediatrics, nutrition, epidemiology, public health, and health economics evaluated the evidence on specific questions within five working groups. The consensus group, representing 11 international scientific organizations, participated in a multiday conference in May 2014 to reach a global evidence-based consensus. Results: This consensus document defines nutritional rickets and its diagnostic criteria and describes the clinical management of rickets and osteomalacia. Risk factors, particularly in mothers and infants, are ranked, and specific prevention recommendations including food fortification and supplementation are offered for both the clinical and public health contexts. Conclusion: Rickets, osteomalacia, and vitamin D and calcium deficiencies are preventable global public health problems in infants, children, and adolescents. Implementation of international rickets prevention programs, including supplementation and food fortification, is urgently required. © 2016 S. Karger AG, Basel and The Endocrine Society [ABSTRACT FROM AUTHOR]

Background The impact of early treatment with immunomodulators ( IM) and/or TNF antagonists on bowel damage in Crohn's disease ( CD) patients is unknown. Aim To assess whether 'early treatment' with IM and/or TNF antagonists, defined as treatment within a 2-year period from the date of CD diagnosis, was associated with development of lesser number of disease complications when compared to 'late treatment', which was defined as treatment initiation after >2 years from the time of CD diagnosis. Methods Data from the Swiss IBD Cohort Study were analysed. The following outcomes were assessed using Cox proportional hazard modelling: bowel strictures, perianal fistulas, internal fistulas, intestinal surgery, perianal surgery and any of the aforementioned complications. Results The 'early treatment' group of 292 CD patients was compared to the 'late treatment' group of 248 CD patients. We found that 'early treatment' with IM or TNF antagonists alone was associated with reduced risk of bowel strictures [hazard ratio ( HR) 0.496, P = 0.004 for IM; HR 0.276, P = 0.018 for TNF antagonists]. Furthermore, 'early treatment' with IM was associated with reduced risk of undergoing intestinal surgery ( HR 0.322, P = 0.005), and perianal surgery ( HR 0.361, P = 0.042), as well as developing any complication ( HR 0.567, P = 0.006). Conclusions Treatment with immunomodulators or TNF antagonists within the first 2 years of CD diagnosis was associated with reduced risk of developing bowel strictures, when compared to initiating these drugs >2 years after diagnosis. Furthermore, early immunomodulators treatment was associated with reduced risk of intestinal surgery, perianal surgery and any complication. [ABSTRACT FROM AUTHOR]

Background: Pulmonary involvement in adult patients with inflammatory bowel disease (IBD) seems more common than previously appreciated. Its prevalence and development over time in pediatric IBD patients are largely unknown. Objectives: The aim was to study lung function including fraction of exhaled nitric oxide (FeNO) and transfer capacity for carbon monoxide (TLCO) in pediatric IBD patients and to describe the longitudinal development in a subset of patients with lung function abnormalities. Methods: Sixty-six measurements were made in 48 IBD patients (30 patients with Crohn's disease and 18 with ulcerative colitis) and 108 matched controls. Patients with abnormal TLCO or elevated residual volume/total lung capacity (RV/TLC) ratios were invited for a follow-up. Statistical comparisons were made by nonparametric tests and ANOVA. Results: TLCO was decreased in IBD patients [median: 88% predicted (interquartile range, IQR, 22) vs. 99% predicted (IQR 19) in controls]. RV/TLC ratios were mildly elevated in patients with ulcerative colitis [32% (IQR 9) vs. 27% (IQR 8) in controls], and maximum expiratory flows at 50 and 25% of vital capacity were mildly reduced in patients with Crohn's disease. FeNO and disease activity did not correlate with lung function abnormalities. Abnormalities did not consistently persist over a median follow-up period of 34 months. Conclusions: This study supports evidence that variable and fluctuating pulmonary involvement also occurs in pediatric IBD patients. Its clinical significance is unclear. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background Studies that systematically assess change in ulcerative colitis ( UC) extent over time in adult patients are scarce. Aim To assess changes in disease extent over time and to evaluate clinical parameters associated with this change. Methods Data from the Swiss IBD cohort study were analysed. We used logistic regression modelling to identify factors associated with a change in disease extent. Results A total of 918 UC patients (45.3% females) were included. At diagnosis, UC patients presented with the following disease extent: proctitis [199 patients (21.7%)], left-sided colitis [338 patients (36.8%)] and extensive colitis/pancolitis [381 (41.5%)]. During a median disease duration of 9 [4-16] years, progression and regression was documented in 145 patients (15.8%) and 149 patients (16.2%) respectively. In addition, 624 patients (68.0%) had a stable disease extent. The following factors were identified to be associated with disease progression: treatment with systemic glucocorticoids [odds ratio ( OR) 1.704, P = 0.025] and calcineurin inhibitors ( OR: 2.716, P = 0.005). No specific factors were found to be associated with disease regression. Conclusions Over a median disease duration of 9 [4-16] years, about two-thirds of UC patients maintained the initial disease extent; the remaining one-third had experienced either progression or regression of the disease extent. [ABSTRACT FROM AUTHOR]

This is a follow up study of a multicenter randomised placebo-controlled trial in seven centres in five West European countries. The RCT assessed the effect of infant formula supplemented with a mixture of prebiotics (with neutral short-chain and long-chain oligosaccharides and pectin-derived acidic oligosaccharides) during infancy in term-born children (n=1130). In the follow-up study 672 children (60% of the study population) participated: 232 (56%) from the prebiotics group (PG), 243 (58%) from the control group (CG), and 197 (66%) from the non-randomised breast-fed group (BG). The primary outcome was the occurrence of febrile episodes at three to five years of age prospectively documented by the parents: in the PG 1.17 (interquartile range 0.50-2.08) episodes per year versus 1.20 (0.52-2.57) in the CG; and 1.48 (0.65-2.60) in the BG. This specific prebiotics mixture given during infancy in healthy non-atopic subjects does not decrease febrile episodes and therefore seems not to prevent infection between their third and fifth birthday. [ABSTRACT FROM AUTHOR]

Purpose: Gender differences in paediatric patients with inflammatory bowel disease (IBD) are frequently reported as a secondary outcome and the results are divergent. To assess gender differences by analysing data collected within the Swiss IBD cohort study database since 2008, related to children with IBD, using the Montreal classification for a systematic approach. Methods: Data on gender, age, anthropometrics, disease location at diagnosis, disease behaviour, and therapy of 196 patients, 105 with Crohn's disease (CD) and 91 with ulcerative or indeterminate colitis (UC/IC) were retrieved and analysed. Results: The crude gender ratio (male : female) of patients with CD diagnosed at ≥10 years of age was 2.57, the adjusted ratio was 2.42, and in patients with UC/IC it was 0.68 and 0.64 respectively. The non-adjusted gender ratio of patients diagnosed at =10 years was 1.58 for CD and 0.88 for UC/IC. Boys with UC/IC diagnosed <10 years of age had a longer diagnostic delay, and in girls diagnosed with UC/IC >10 years a more important use of azathioprine was observed. No other gender difference was found after analysis of age, disease location and behaviour at diagnosis, duration of disease, familial occurrence of IBD, prevalence of extra-intestinal manifestations, complications, and requirement for surgery. Conclusion: CD in children <10 years affects predominantly boys with a sex ratio of 2.57; the impact of sex-hormones on the development of CD in pre-pubertal male patients should be investigated. [ABSTRACT FROM AUTHOR]

Background: The fatty acid mixture of human milk is ideal for the newborn but little is known about its composition in the first few weeks of lactation. Of special interest are the levels of long-chain PUFAs (LCPUFAs), since these are essential for the newborn's development. Additionally, the LCPUFAs arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are precursors for lipid mediators which regulate inflammation. Methods: We determined the composition of 94 human milk samples from 30 mothers over the first month of lactation for fatty acids using GC-MS and quantified lipid mediators using HPLC-MS/MS. Results: Over the four weeks period, DHA levels decreased, while levels of γC18:3 and αC18:3 steadily increased. Intriguingly, we found high concentrations of lipid mediators and their hydroxy fatty acid precursors in human milk, including pro-inflammatory leukotriene B4 (LTB4) and anti-inflammatory and pro-resolving lipoxin A4 (LXA4), resolvin D1 (RvD1) and resolvin E1 (RvE1). Lipid mediator levels were stable with the exception of two direct precursors. Conclusions: Elevated levels of DHA right after birth might represent higher requirements of the newborn and the high content of anti-inflammatory and pro-resolving lipid mediators and their precursors may indicate their role in neonatal immunity and may be one of the reasons for the advantage of human milk over infant formula. [ABSTRACT FROM AUTHOR]

Objectives: Whether behavioural and emotional maladjustment is more prevalent in children with inflammatory bowel disease (IBD) than in healthy controls remains controversial. The aim of this study was to assess paediatric IBD patients for problems with emotional and behavioural adjustment and to examine associations with clinical and demographic variables. Methods: Data from paediatric patients with IBD enrolled in the Swiss IBD Cohort Study and the results of both the parent-rated Strengths and Difficulties Questionnaire (SDQ) and the self-reported Child Depression Inventory (CDI) were analysed. Of the 148 registered patients, 126 had at least one questionnaire completed and were included. Results: The mean age of 71 patients with Crohn's disease (44 males, 27 females) was 13.4 years, and 12.8 years for the 55 patients with ulcerative or indeterminate colitis. The mean duration of disease was 1.2 and 2.7 years, respectively. The total score of the SDQ was abnormal in 11.4% of cases compared to 10% in the normal population. Abnormal sub-scores were found in 20.2% of subjects for the domain of emotional problems and in 17.1% for problems with peers. The total CDI T score indicated a significantly lower prevalence of clinical depression in IBD patients than in normal youth. No correlation between the total SDQ scores or the CDI T scores and gender, type or duration of IBD, inflammatory markers or disease scores was found. Conclusions: The prevalence of problems with behavioural and emotional adjustment among Swiss paediatric IBD patients is low and comparable to that of the normal population. INSETS: What is already known on this topic;What this study adds. [ABSTRACT FROM AUTHOR]

Aim: To assess in infants the number of illness episodes treated with antibiotics and prescription rates in five European countries. Methods: This study was embedded in a multicenter nutritional intervention study and was conducted in five European countries. Infants were followed until 1 year of age. Illness episodes and prescriptions of systemic antibiotics were recorded by the parents. Results: Illness episodes were caused by upper respiratory tract infections (URTIs) in 55-64% and by otitis media (OM) in 2-6.8%. URTIs were statistically significant and more frequently treated with antibiotics in Italy (18.8%), and less frequently in Switzerland (1.4%). OM was statistically significant and less frequently treated with antibiotics in the Netherlands (55%) when compared to Italy (82%). The antibiotic prescription rate varied between countries, ranging from 0.2 to 1.3 prescriptions per infant per year. Conclusions: As the frequency of illness episodes did not differ between countries, other factors, such as physician's attitude, parental pressure or other socio-economic determinants, most likely play a role in antibiotic prescribing habits in the first year of life. [ABSTRACT FROM AUTHOR]

The Early Nutrition Academy and the Child Health Foundation, in collaboration with the Committee on Nutrition, European Society for Paediatric Gastroenterology, Hepatology and Nutrition, held a workshop in March 2011 to explore guidance on acquiring evidence on the effects of nutritional interventions in infants and young children. The four objectives were to (1) provide guidance on the quality and quantity of evidence needed to justify conclusions on functional and clinical effects of nutrition in infants and young children aged <3 years; (2) agree on a range of outcome measures relevant to nutrition trials in this age group for which agreed criteria are needed; (3) agree on an updated 'core data set' that should generally be recorded in nutrition trials in infants and young children, and (4) provide guidance on the use of surrogate markers in paediatric nutrition research. The participants discussed these objectives and agreed to set up six first working groups under the auspices of the Consensus Group on Outcome Measures Made in Paediatric Enteral Nutrition Clinical Trials (COMMENT). Five groups will aim to identify and define criteria for assessing key outcomes, i.e. growth, acute diarrhoea, atopic dermatitis and cows' milk protein allergy, infections and 'gut comfort'. The sixth group will review and update the 'core data set'. The COMMENT Steering Committee will discuss and decide upon a method for reaching consensus which will be used by all working groups and plan to meet again within 2 years and to report and publish their conclusions. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Objective: : To define the molecular defect that causes analbuminemia in an apparently healthy boy, son of non-consanguineous Swiss parents. Design and methods: : Total DNA, extracted from peripheral blood samples from the proband and from both parents, was PCR-amplified using oligonucleotide primers designed to amplify the 14 exons of the human albumin gene and the flanking intron regions. The products were screened for mutations by single-strand conformation polymorphism (SSCP) and heteroduplex analyses (HA) either directly or after digestion with restriction enzymes. The combination of these methods identified the abnormal fragment, which was then sequenced. Results: : DNA sequence analysis identified in the homozygous proband a C → T transition at nucleotide 4446. The mutation changes the codon CGA for Arg 114 to a stop codon TGA, resulting in premature termination and is therefore responsible for the analbuminemic trait. The same mutation has been previously reported to cause analbuminemia in an American female. The putative protein product would have a length of 113 residues. The parents were found to be heterozygous for the mutation. Conclusions: : Gel-based mutation detection and DNA sequencing confirmed the diagnosis of congenital analbuminemia in the proband. Our results show that the combination of SSCP and HA represents a powerful tool to study the molecular defects causing analbuminemia in humans. [Copyright &y& Elsevier]

Establishment of the infant gut microbiota affects gut maturation and influences long-term health. Cutibacterium (formerly Propionibacterium) have been identified as early colonizers, but little is known about their function. Using a cultivation-dependent and -independent approach, we determined Cutibacterium prevalence, diversity and functional potential. In feces from a Swiss infant cohort (n = 38), prevalence of Propionibacterium/Cutibacterium decreased from 84% at 2 weeks, to 65% at 4 weeks, 47% at 8 weeks and 41% at 12 weeks of age. Abundance varied among individuals, and persistence depended on the colonization levels at 2 weeks. Cutibacterium isolates (n = 87) were obtained from 10 infants from a smaller cohort (n = 12); restriction fragment length polymorphism clustered isolates in four groups, and all identified as Cutibacterium avidum. Colonization potential and metabolic effects of C. avidum addition were tested in an in vitro continuous intestinal fermentation model mimicking infant proximal colon conditions. Cutibacterium avidum spiked daily at 108 or 109 cells mL−1 colonized, decreased formate and persisted during the washout period. Significant correlations were observed between Propionibacterium/Cutibacterium and lactate-producers and protein-degraders in both reactors and infant feces. Our findings highlight the natural presence of C. avidum and its role as a lactate-consumer and propionate-producer in infants younger than 3 months. [ABSTRACT FROM AUTHOR]