Barbara Iwańczak

Immunogenecity of hepatitis A vaccine in pediatric patients with inflammatory bowel disease.

Background: There are only a few studies on immune response to routine vaccinations in children with inflammatory bowel disease (IBD), despite a strong need for this kind of study. The aim of the study was to evaluate the immunogenicity of an inactivated hepatitis A vaccine (HAV) in IBD pediatric patients compared with healthy controls. Methods: This was an open, prospective, and controlled study on anti‐HAV‐negative children and adolescents age 2‐18 years with IBD. HAV using 720 enzyme‐linked immunosorbent assay (ELISA) units were administered at 0 months and at 6‐12 months. Seroconversion and geometric mean titers were measured after each vaccine dose. The evidence of local and systemic adverse effects for 3 days after the first and second dose of vaccine was registered. Results: A total of 134 subjects (66 patients and 68 controls) completed the whole study course consisting of two doses of vaccine and six serum samples. There was no significant difference in the rate of seroconversion between IBD patients and controls when measured after the second dose of vaccine (97% versus 100%, P = 0.2407), but the rate was significantly lower in the IBD group when measured after the first dose (39% versus 64%, P = 0.00001). The mean geometric titers were statistically significantly lower in the IBD group than in the control group at all of the measured timepoints. There were no serious adverse events related to HAV during the study. Conclusions: HAV is both immunogenic and safe in pediatric patients with IBD. (Inflamm Bowel Dis 2010;)

Frequency and risk factors of gastric and duodenal ulcers or erosions in children: a prospective 1-month European multicenter study

There are no solid figures of the frequency of ulcer disease during childhood in Europe. We assessed its frequency and analyzed known risk factors. Patients and methods Ulcers, erosions, indications, and risk factors were recorded in all children undergoing an upper gastrointestinal endoscopy in a prospective study carried out during 1-month simultaneously in 19 centers among 14 European countries. Results Ulcers and/or erosions were observed in 56 out of 694 children. Children with ulcers/erosions were significantly older than those without lesions (10.3±5.5 vs. 8.1±5.7 years, P=0.002). Helicobacter pylori infection was present in 15 of 56 children (27%) where NSAIDs were used in eight, steroids in five, immune-suppressive drugs in five, antibiotics in six, antacids in one, H2-blockers in six and proton pump inhibitors in eight children (more than one risk factor was detected in 32 of 56 children). No risk factors were observed in 24 of 56 children (43%). The main indications for endoscopy were epigastric or abdominal pain (24%) and suspicion of gastroesophageal reflux disease (15%). Similarly, epigastric tenderness, hematemesis, melena, and weight stagnation were significantly associated with ulcers/erosions, whereas sex, H. pylori infection, socioeconomic and lifestyle factors were equally distributed. Conclusion Although limited by the short-time duration and the heterogeneity of the patients included throughout the 19 centers, our study shows a frequency of 8.1% of ulcers and/or erosions in children, occurring mainly in the second decade of life. H. pylori infection and gastrotoxic medications were less frequently implicated than expected.

Correlation of MMP-3 and MMP-9 with Crohn's disease activity in children.

BackgroundRecently published data indicate that the inflammation in Crohn’s disease (CD) may be accompanied by elevated levels of matrix metalloproteinases. AimsThe goals of the present study were the estimation of MMP-3 and -9 concentrations in sera of children with Crohn’s disease, the examination of correlation between the concentrations of MMP-3 and -9 and clinical activity of the disease in the relation to the control group and the evaluation of the utility of MMP-3 and -9 concentration measurements as markers of disease activity.MethodsSerum concentrations of MMP-3 and -9 were estimated in 82 children (45 CD patients divided into severe, moderate and mild subgroups; 37 controls) and correlated with disease activity estimated by the Pediatric Crohn’s Disease Activity Index (PCDAI), CRP, seromucoid and ESR.ResultsMean MMP-3 concentrations were: 2.49xa0ng/ml (95% CI: 1.76–3.52) for mild, 16.44xa0ng/ml (95% CI: 10.34–26.15) for moderate, 5.25xa0ng/ml (95% CI: 2.73–10.11) for severe CD and 1.95xa0ng/ml (95% CI: 1.53–2.48) for the control group (differences between all three groups were statistically significant; Pxa0<xa00.001). Median MMP-9 concentrations were: 2.14xa0ng/ml (95% CI: 0–8.9) for mild, 14.21xa0ng/ml (95% CI: 4.53–21.48) for moderate, 42.2xa0ng/ml (95% CI: 5.74–61.27) for severe CD and 1.3xa0ng/ml (95% CI: 0.7–2.18) for the control group. MMP-9 concentrations in moderate and severe CD differed from the concentrations in mild CD (Pxa0=xa00.002) and control group (Pxa0=xa00.0001). MMP-3 concentration significantly correlated with MMP-9, PCDAI and ESR, while MMP-9 concentration significantly positively correlated with MMP-3, PCDAI, and CRP. Diagnostic utilities of the tests were: MMP-3 accuracy 75%, positive likelihood ratio (LR+)xa0=xa04.11 and negative likelihood ratio (LR−)xa0=xa00.51, sensitivity 56%, specificity 87%, Youden index 0.43; for MMP-9, accuracy 73%, LR+xa0=xa05.14 and LR−xa0=xa00.50, sensitivity 56%, specificity 89%, Youden index 0.45; and for CRP, accuracy 74%, LR+xa0=xa08.56 and LR−xa0=xa00.54, sensitivity 49%, specificity 94%, Youden index 0.43. ConclusionsMMP-9 serum concentration increasing along with the activity of the disease, exhibiting high specificity and correlating well with the indices of inflammation might be of better usefulness in the prediction of CD activity status in children than MMP-3.

New effective treatment regimen for children infected with a double-resistant Helicobacter pylori strain.

Background: The increasing number of pediatric patients infected with multiresistant Helicobacter pylori strains calls for evaluation of treatment regimens. Second-line antibiotics such as tetracycline or quinolones are not licensed for children. Because in vivo resistance to metronidazole may be overcome in vivo by a high dose and prolonged intake, we evaluated the eradication rate and side effects of a high-dose triple therapy in pediatric patients with culture-proven double resistance. Patients and Methods: In this open multicentre trial, 62 children (<18 years, body weight >15 kg) infected with an H pylori strain resistant to metronidazole and clarithromycin were treated according to body weight classes with amoxicillin (∼75 mg/kg/day), metronidazole (∼25 mg/kg/day) and esomeprazole (∼1.5 mg/kg/day) for 2 weeks. Adherence and adverse events were assessed by a 2-week diary and telephone interviews at days 7 and 14 of treatment. Primary outcome was a negative 13C-urea breath test after 6 weeks. Results: Of 62 patients, 5 were lost to follow-up, 12 were nonadherent, and 45 treated per protocol. Eradication rates were 66% (41/62) [confidence interval 54–78] (intention to treat) and 73% (33/45) [confidence interval 60–86] (per protocol). Success of treatment was not related to dose per kilogram body weight. Mild to moderate adverse events were reported by 21 patients, including nausea (10.8%), diarrhoea (8.9%), vomiting (7.1%), abdominal pain (5.4%), and headache (3.6%), and led to discontinuation in 1 child. Conclusion: High-dose amoxicillin, metronidazole, and esomeprazole for 2 weeks is a good treatment option in children infected with a double resistant H pylori strain.

Genetic architecture differences between pediatric and adult-onset inflammatory bowel diseases in the Polish population.

Most inflammatory bowel diseases (IBDs) are classic complex disorders represented by common alleles. Here we aimed to define the genetic architecture of pediatric and adult-onset IBDs for the Polish population. A total of 1495 patients were recruited, including 761 patients with Crohn’s disease (CD; 424 pediatric), 734 patients with ulcerative colitis (UC; 390 pediatric), and 934 healthy controls. Allelotyping employed a pooled-DNA genome-wide association study (GWAS) and was validated by individual genotyping. Whole exome sequencing (WES) was performed on 44 IBD patients diagnosed before 6 years of age, 45 patients diagnosed after 40 years of age, and 18 healthy controls. Altogether, out of 88 selected SNPs, 31 SNPs were replicated for association with IBD. A novel BRD2 (rs1049526) association reached significance of Pu2009=u20095.2u2009×u200910−11 and odds ratio (OR)u2009=u20092.43. Twenty SNPs were shared between pediatric and adult patients; 1 and 7 were unique to adult-onset and pediatric-onset IBD, respectively. WES identified numerous rare and potentially deleterious variants in IBD-associated or innate immunity-associated genes. Deleterious alleles in both groups were over-represented among rare variants in affected children. Our GWAS revealed differences in the polygenic architecture of pediatric- and adult-onset IBD. A significant accumulation of rare and deleterious variants in affected children suggests a contribution by yet unexplained genetic components.

Helicobacter pylori Infection in European Children with Gastro-duodenal Ulcers and Erosions

Background: To analyze risk factors associated with gastro-duodenal ulcers and erosions in children. Methods: Open, prospective, multicenter, case-control study carried out in 11 European countries in patients with gastric or duodenal ulcers/erosions and 2 age-matched controls each. Possible risk factors were recorded. Logistic regression models were performed with adjustment for centers and age groups. Results: Seven-hundred thirty-two patients (244 cases, 153 with erosions only and 91 with ulcers, and 488 controls) were recruited. Children receiving antimicrobials or acid suppressive drugs before endoscopy were excluded (202 cases/390 controls remained for risk factor analysis). Helicobacter pylori was detected more frequently in cases than controls but only in 32.0% versus 20.1% in controls (P = 0.001). Independent exposure factors for gastric ulcers were male gender (P = 0.001), chronic neurologic disease (P = 0.015), chronic renal disease (P < 0.001) and nonsteroidal anti-inflammatory drug consumption (P = 0.035). Exposure factors for duodenal ulcers were H. pylori infection (P < 0.001) and steroid consumption (P = 0.031). Chronic renal disease was the only independent factor associated with gastric erosions (P = 0.026), those associated with duodenal erosions being H. pylori infection (P = 0.023), active smoking (P = 0.006) and chronic arthritis (P = 0.008). No risk factor was identified in 97/202 (48.0%) cases. Conclusions: H. pylori remains a risk factor for duodenal, but not for gastric lesions in children in countries with low prevalence of infection. No risk factor could be identified in half of the children with gastro-duodenal ulcers/erosions.

High- and Low-Dose Oral Delayed-Release Mesalamine in Children With Mild-to-Moderately Active Ulcerative Colitis

Objective: The aim of the study was to assess the safety and efficacy of high- and low-dose oral, delayed-release mesalamine in a randomized, double-blind, active control study of children with mild-to-moderately active ulcerative colitis. Methods: Patients ages 5 to 17 years, with a Pediatric Ulcerative Colitis Activity Index (PUCAI) score of ≥10 to ⩽55 and a truncated Mayo Score of ≥1 for both rectal bleeding and stool frequency, were enrolled. They received body weight–dependent doses of oral, delayed-release mesalamine for 6 weeks in a low- (27–71 mg · g−1 · day−1) or high-dose group (53–118 mg · g−1 · day−1). The primary endpoint was treatment success, defined as the proportion of patients who achieved remission (PUCAI score <10) or partial response (PUCAI score ≥10 with a decrease from baseline by ≥20 points). Secondary endpoints included truncated Mayo Score and global assessment of change of disease activity. Results: The modified intent-to-treat population included 81 of 83 patients enrolled. Treatment success by PUCAI was achieved by 23 of 41 (56%) and 22 of 40 (55%) patients in the mesalamine low- and high-dose groups, respectively (Pu200a=u200a0.924). Truncated Mayo Score (low-dose 30 [73%] and high-dose 28 [70%] patients) and other efficacy results did not differ between the groups. The type and severity of adverse events were consistent with those reported in previous studies of adults with ulcerative colitis and did not differ between groups. Conclusions: Both low- and high-dose oral, delayed-release mesalamine doses were equally effective as short-term treatment of mild-to-moderately active ulcerative colitis in children, without a specific benefit or risk to using either dose.

A Link between Nutritional and Growth States in Pediatric Patients with Functional Gastrointestinal Disorders

Objective To investigate nutritional status and growth status of pediatric patients with functional gastrointestinal disorders (FGIDs) and to examine the relationship between nutritional status and linear growth in these children. Study design In total, 102 pediatric patients diagnosed with functional constipation (FC), irritable bowel syndrome (IBS), or functional abdominal pain (FAP) in years 2013‐2015 were subjected to anthropometric measurements. Anthropometry comprised body height, leg and trunk lengths, body weight, mid‐upper arm circumference, and 3 skinfold thicknesses. Body fat percentage was obtained with bioelectrical impedance analysis. Indices of the nutritional status and body proportions were calculated and adjusted for age and sex. Results Excessive body weight and excessive fatness were the most common in children with IBS. Being underweight was most common in children with FAP, but fat deficiency was similarly frequent in the FAP and in FC groups. Short stature was the most common in children with FC. Children with IBS were the best nourished and the tallest for age and sex due to increased trunk length. Body height and linear body proportions adjusted for age and sex were positively associated with body weight and body fatness in the total sample. Conclusions Children with FGIDs present various linear growth abnormalities that are associated with body weight and body fatness. Although excessive body weight and body fat are common in children with IBS, pediatricians should be aware of the risk of malnutrition in children with other FGIDs.

Th9 lymphocytes and functions of interleukin 9 with the focus on IBD pathology

The work presents the newest knowledge on a new phenotype of T helper lymphocytes (Th9) and on Interleukin 9 (IL-9). Processes leading to transformation of naïve T lymphocyte into Th9 lymphocytes are presented, including the role of IL-4 and TGFβ signaling. Involvement of transcription factor network in production of IL-9 is described. Other cells capable of expressing IL-9 and secreting IL-9 are portrayed. Diversity of IL-9 effects caused by activation of IL-9 receptors on various types of cells is presented. Principal effects of the activation of IL-9 receptor on T-cells seem to be antiapoptotic and stimulatory which leads to enhanced defense against parasitic infection and cancer development but, from the other side, it perpetuate chronic inflammation in autoimmune diseases and allergic processes. In the last years the role of IL-9 in autoimmune diseases such as rheumatic diseases and inflammatory bowel disease gained importance since the increased expression of this cytokine has been observed in animal models of intestinal inflammation and in groups of patients with ulcerative colitis. It was also noted that neutralization of IL-9 in animal models of ulcerative colitis leads to amelioration of inflammatory process, what could have significance in the treatment of this disease in humans in the future.