As the clinical implications of Helicobacter pylori infection in children and adolescents continue to evolve, ESPGHAN and NASPGHAN jointly renewed clinical guidelines using a standardized ...evidence-based approach to develop updated recommendations for children and adolescents in North America and Europe.
An international panel of 11 pediatric gastroenterologists, 2 epidemiologists, 1 microbiologist, and 1 pathologist was selected by societies that developed evidence-based guidelines based on the Delphi process with anonymous voting in a final face-to-face meeting. A systematic literature search was performed on 8 databases of relevance including publications from January 2000 to December 2009. After excluding nonrelevant publications, tables of evidence were constructed for different focus areas according to the Oxford classification. Statements and recommendations were formulated in the following areas: whom to test, how to test, whom to treat, and how to treat. Grades of evidence were assigned to each recommendation based on the GRADE system.
A total of 2290 publications were identified, from which 738 were finally reviewed. A total of 21 recommendations were generated, and an algorithm was proposed by the joint committee providing evidence-based guidelines on the diagnostic workup and treatment of children with H pylori infection.
These clinical practice guidelines represent updated, best-available evidence and are meant for children and adolescents living in Europe and North America, but they may not apply to those living on other continents, particularly in developing countries with a high H pylori infection rate and limited health care resources.
NOD2 polymorphisms may affect sensing of the bacterial muramyl dipeptide (MDP) and trigger perturbed inflammatory responses. Genetic screening of a patient with immunodeficiency and enteropathy ...revealed a rare homozygous missense mutation in the first CARD domain of NOD2 (ENST00000300589; c.160G > A, p.E54K). Biochemical assays confirmed impaired NOD2-dependent signaling and proinflammatory cytokine production in patient's cells and heterologous cellular models with overexpression of the NOD2 mutant. Immunoprecipitation-coupled mass spectrometry unveiled the ATPase valosin-containing protein (VCP) as novel interaction partner of wildtype NOD2, while the binding to the NOD2 variant p.E54K was abrogated. Knockdown of VCP in coloncarcinoma cells led to impaired NF-κB activity and IL8 expression upon MDP stimulation. In contrast, tunicamycin-induced ER stress resulted in increased IL8, CXCL1, and CXCL2 production in cells with knockdown of VCP, while enhanced expression of these proinflammatory molecules was abolished upon knockout of NOD2. Taken together, these data suggest that VCP-mediated inflammatory responses upon ER stress are NOD2-dependent.
The array of tests that can be used for diagnosis of
Helicobacter pylori
infection is large, and it can be confusing to define which test to use particularly in children where results may not be ...comparable to those obtained in adult patients. Using PubMed, we reviewed the English literature from January 1999 to May 2009 to identify articles that determined sensitivity and specificity of
H. pylori
invasive and non-invasive diagnostic tests in children. We excluded articles that presented a review of the literature, abstracts, case reports, or series where children’s results could not be separated from adult populations. Of the tissue based methods, rapid urease tests have better sensitivity than histology to detect presence of
H. pylori
; however, histology can detect the pathology associated with disease including gastritis, intestinal metaplasia, and other conditions that could be the cause of the child’s symptoms. Culture of gastric tissues or stool has 100% specificity but sensitivity is low. Of the serologic tests, immunoblot has the best sensitivity. The urea breath tests have >75% sensitivity for detection of
H. pylori
before and after treatment. Immunoassays in stool using monoclonal antibodies have >95% sensitivity for detection of
H. pylori
before and after treatment. PCR testing can be performed in tissue and stool samples and can detect genes associated to antibiotic resistance. In summary, the current commercial non-invasive tests have adequate sensitivity and specificity for detecting the presence of
H. pylori
; however, endoscopy with histopathology is the only method that can detect
H. pylori
and lesions associated with the infection.
•Associations between air pollutants and pubertal development are unclear.•Link between air pollutants and hormone-assessed pubertal development was analyzed.•Neither PM10, PM2.5, NO2, nor ozone was ...associated with pubertal development.•Air pollutants were not associated with concentrations of estradiol and testosterone.
Air pollution is hypothesized to affect pubertal development. However, the few studies on this topic yielded overall mixed results. These studies did not consider important pollutants like ozone, and none of them involved pubertal development assessed by estradiol and testosterone measurements. We aimed to analyze associations between long-term exposure to four pollutants and pubertal development based on sex hormone concentrations among 10-year-old children.
These cross-sectional analyses were based on the 10-year follow-up medical examinations of 1945 children from the Munich and Wesel centers of the GINIplus and LISA German birth cohorts. Female and male pubertal development was assessed by dichotomizing the concentration of hormones in serum at 18.4 pmol/L and 0.087 nmol/L using the lower limits of quantification for estradiol and testosterone, respectively. Land-use regression models derived annual average concentrations of particulate matter with an aerodynamic diameter < 2.5 and 10 µm (PM2.5 and PM10), as well as spatial models assessed yearly average concentrations of nitrogen dioxide (NO2) and ozone, were calculated at the 10-year residential addresses. To evaluate associations, we utilized logistic regressions adjusted for potential covariates. The analyses were stratified by area and sex.
Around 73% of the 943 females and 25% of the 1002 males had a high level of hormones and had already started puberty at the age of 10. Overall, we found no statistically significant associations between exposure to particles (PM2.5 or PM10) and pubertal development. Results on NO2 and ozone were not significant as well; for instance, per 10 µg/m3 increase in ozone concentration, odds ratios and 95% confidence intervals were 0.900 (0.605, 1.339) and 0.830 (0.573, 1.203) for females and males, respectively. Stratified by area, the aforementioned results did not reveal any associations either.
Our study did not observe the associations between ambient air pollutants and pubertal development determined by estradiol and testosterone levels in children. However, due to the current limited number of studies on this topic, our results should be cautiously interpreted. Future longitudinal studies are needed to assess the association.
Objective To compare the effect of budesonide vs prednisone therapy both in combination with azathioprine in pediatric patients with autoimmune hepatitis (AIH). Study design Forty-six patients with ...AIH (11 males and 35 females) aged 9-17 years were enrolled in a 6-month, prospective, double-blind, randomized, active-controlled, multicenter phase IIb study evaluating budesonide (n = 19; 3 mg twice or 3 times daily) vs prednisone (n = 27; 40 mg/day tapered to 10 mg/day), both with azathioprine (1-2 mg/kg/day), followed by a further 6 months of open-label budesonide therapy. The primary efficacy endpoint was complete biochemical remission (normal serum alanine aminotransferase and aspartate aminotransferase levels) without predefined steroid-specific side effects. Results We observed no statistically significant difference in the percentage of patients who met the primary endpoint between the budesonide (3 of 19; 16%) and prednisone groups (4 of 27; 15%) after 6 months, nor in the percentage of patients who experienced biochemical remission (budesonide, 6 of 19 32%; prednisone, 9 of 27 33%), lack of steroid-specific side effects (budesonide, 10 of 19 53%; prednisone, 10 of 27 37%). The mean weight gain was 1.2 ± 3.5 kg in the budesonide group and 5.1 ± 4.9 kg in the prednisone group ( P = .006). A total of 42 patients received open-label budesonide treatment for another 6 months. After 12 months, 46% of these patients achieved complete remission. Conclusion Oral budesonide with azathioprine can induce and maintain remission in pediatric patients with AIH and may be considered an alternative therapy to prednisone. The treatment causes fewer side effects and does not lead to weight gain; however, it may be less effective than prednisone in inducing remission.
Background The long-term effect of nutritional intervention with hydrolysate infant formulas on allergic manifestations in high-risk children is uncertain. Objective We sought to investigate the ...effect of hydrolysate infant formulas on allergic phenotypes in children with family history of allergies at school age. Methods We analyzed data from participants of the prospective German Infant Nutritional Intervention study after 10 years of follow-up. At birth, children were randomly assigned to receive, for the first 4 months, one of 4 blinded formulas as breast milk substitute, if necessary: partially hydrolyzed whey formula (pHF-W), extensively hydrolyzed whey formula (eHF-W), extensively hydrolyzed casein formula (eHF-C), or standard cow's milk formula. Outcomes were parent-reported, physician-diagnosed allergic diseases. Log-binomial regression models were used for statistical analysis. Results The relative risk for the cumulative incidence of any allergic disease in the intention-to-treat analysis (n = 2252) was 0.87 (95% CI, 0.77-0.99) for pHF-W, 0.94 (95% CI, 0.83-1.07) for eHF-W, and 0.83 (95% CI, 0.72-0.95) for eHF-C compared with standard cow's milk formula. The corresponding figures for atopic eczema/dermatits (AD) were 0.82 (95% CI, 0.68-1.00), 0.91 (95% CI, 0.76-1.10), and 0.72 (95% CI, 0.58-0.88), respectively. In the per-protocol analysis (n = 988) effects were stronger. The period prevalence of AD at 7 to 10 years was significantly reduced with eHF-C in this analysis, but there was no preventive effect on asthma or allergic rhinitis. Conclusion The significant preventive effect on the cumulative incidence of allergic diseases, particularly AD, with pHF-W and eHF-C persisted until 10 years without rebound, whereas eHF-W showed no significant risk reduction. There is insufficient evidence of ongoing preventive activity at 7 to 10 years of age.
In vitro studies, animal experiments, and human exposure studies have shown how ambient air pollution increases the risk of atopic diseases. However, results derived from observational studies are ...inconsistent.
To assess the relationship between individual-based exposure to traffic-related air pollutants and allergic disease outcomes in a prospective birth cohort study during the first 6 years of life.
We studied 2,860 children at the age of 4 years and 3,061 at the age of 6 years to investigate atopic diseases and allergic sensitization. Long-term exposure to particulate matter (PM(2.5)), PM(2.5) absorbance, and long-term exposure to nitrogen dioxide (NO(2)) was assessed at residential addresses using geographic information systems based regression models and air pollution measurements. The distance to the nearest main road was used as a surrogate for traffic-related air pollutants.
Strong positive associations were found between the distance to the nearest main road and asthmatic bronchitis, hay fever, eczema, and sensitization. A distance-dependent relationship could be identified, with the highest odds ratios (ORs) for children living less than 50 m from busy streets. For PM(2.5) absorbance, statistically significant effects were found for asthmatic bronchitis (OR, 1.56; 95% confidence interval CI, 1.03-2.37), hay fever (OR, 1.59; 95% CI, 1.11-2.27), and allergic sensitization to pollen (OR, 1.40; 95% CI, 1.20-1.64). NO(2) exposure was associated with eczema, whereas no association was found for allergic sensitization.
This study provides strong evidence for increased risk of atopic diseases and allergic sensitization when children are exposed to ambient particulate matter.
Cesarean Delivery and Risk of Childhood Obesity Pei, Zhengcun, MSc; Heinrich, Joachim, PhD; Fuertes, Elaine, MSc ...
The Journal of pediatrics,
05/2014, Letnik:
164, Številka:
5
Journal Article
Recenzirano
Objective To investigate whether birth by cesarean delivery rather than vaginal delivery is a risk factor for later childhood obesity. Study design Healthy, full-term infants were recruited. ...Overweight and obesity were defined using measured weight and height according to World Health Organization reference data. Associations between cesarean delivery and being overweight or obese were investigated at age 2, 6, and 10 years (n = 1734, 1244, and 1170, respectively) by multivariate logistic regression models adjusted for socioeconomic status, child characteristics, and maternal prepregnancy characteristics. Results Mothers who gave birth by cesarean delivery (∼17%) had a higher mean prepregnancy body mass index (23.7 kg/m2 vs 22.5 kg/m2 ), greater mean gestational weight gain (15.3 kg vs 14.5 kg), and shorter mean duration of exclusive breastfeeding (3.4 months vs 3.8 months) compared with those who delivered vaginally. The proportion of obese children was greater in the cesarean delivery group compared with the vaginal delivery group at age 2 years (13.6% vs 8.3%), but not at older ages. Regression analyses revealed a greater likelihood of obesity at age 2 years in the cesarean delivery group compared with the vaginal delivery group at age 2 years (aOR, 1.68; 95% CI, 1.10-2.58), but not at age 6 years (aOR, 1.49; 95% CI, 0.55-4.05) or age 10 years (aOR, 1.16; 95% CI, 0.59-2.29). Conclusion Cesarean delivery may increase the risk of obesity in early childhood. Our results do not support the hypothesis that an increasing rate of cesarean delivery contributes to obesity in childhood.
•Infancy air pollution exposure affects lung function growth up to adolescence.•Airway size may be more affected than lung volume restriction.•Maternal age, asthma and breastfeeding duration may ...modify the adverse effects.
Limited evidence exists on how air pollution exposure during infancy, i.e. the first year of life, may affect lung function development into adolescence.
To investigate the association between exposure to air pollution during the first-year of life and lung function development up to the age of 15 in Germany.
We investigated 915 children from the GINIplus and LISA birth cohorts from Munich (n = 181) and Wesel (n = 734), who had at least two spirometric measurements at ages 6, 10 and 15. Z-scores of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were calculated. Annual average concentrations of nitrogen dioxide, particulate matter with diameters <2.5, <10 and 2.5–10 µm (PM2.5/10/coarse), and PM2.5 absorbance at home addresses during the first-year of life, were estimated by land-use regression models. Associations between infancy exposure and lung function changes were fitted using multivariable linear mixed models with adjustment for potential confounders.
For per interquartile range increase in air pollutants during the first-year life, FEV1 z-scores declined annually by −0.012 (95% confidence interval (CI): −0.014, −0.009) for PM2.5 to −0.023 (95%CI: −0.028, −0.018) for PMcoarse. The declines in FVC were lower than FEV1 −0.006 (95%CI: −0.008, −0.003) to −0.011 (95%CI: −0.019, −0.003). In Munich, the attenuations were only significant for FEV1. Effect estimates of infancy exposure for certain air pollutants were higher for groups with asthma, older maternal age, and breastfeeding <12 weeks than their counterparts.
Infancy exposure to higher air pollution may reduce lung function development up to adolescence, with airway size more affected than lung volume restriction. The potential modifying effects of maternal age, asthmatic status of children and breastfeeding warrant further exploration.
The primary objective of the RisCoin study was to investigate the interplay of genetic, metabolic, and lifestyle factors as well as stress levels on influencing the humoral immune response after at ...least two COVID-19 vaccinations, primarily with mRNAs, and the risk of SARS-CoV-2 breakthrough infections during follow-up. Here, we describe the study design, procedures, and study population. RisCoin is a prospective, monocentric, longitudinal, observational cohort study. Between October and December 2021, 4515 participants with at least two COVID-19 vaccinations, primarily BNT162b2 and mRNA-1273, were enrolled at the LMU University Hospital of Munich, thereof > 4000 healthcare workers (HCW), 180 patients with inflammatory bowel disease under immunosuppression, and 119 patients with mental disorders. At enrollment, blood and saliva samples were collected to measure anti-SARS-CoV-2 antibodies, their neutralizing capacity against Omicron-BA.1, stress markers, metabolomics, and genetics. To ensure the confidential handling of sensitive data of study participants, we developed a data protection concept and a mobile application for two-way communication. The application allowed continuous data reporting, including breakthrough infections by the participants, despite irreversible anonymization. Up to 1500 participants attended follow-up visits every two to six months after enrollment. The study gathered comprehensive data and bio-samples of a large representative HCW cohort and two patient groups allowing analyses of complex interactions. Our data protection concept combined with the mobile application proves the feasibility of longitudinal assessment of anonymized participants. Our concept may serve as a blueprint for other studies handling sensitive data on HCW.