Serum concentrations of fibrosis markers in children with inflammatory bowel disease.

BACKGROUND AND STUDY AIMS: The aim of the study was to assess the usefulness of serum concentrations of YKL-40/ CHI3L1 (a 40-kilodalton glycoprotein also referred to as chitinase 3 like- 1 - CHI3L1) and PIIINP (N-terminal propeptide of type III procollagen), markers of fibrosis, in the monitoring of inflammatory processes and fibrosis in children with inflammatory bowel disease (IBD). PATIENTS AND METHODS: In 60 patients (41 with Crohn's disease (CD), 19 with ulcerative colitis (UC)) concentrations of investigated parameters were measured at baseline (day 0), after 3 and after 6-8 weeks of pharmacological treatment. RESULTS: PIIINP concentrations were significantly higher in CD patients compared to UC (baseline results: median concentrations 1013.73 vs 78.30 ng/mL; P = 0.06 for the Kruskall-Wallis test; results at 6-8 weeks: 1076.48 vs 53.10 ng/mL, P = 0.01). Fibrosis was clearly present in patients with CD and its severity increased (reflected by both YKL-40/ CHI3L1 and PIIINP concentrations) in 6-8 weeks of follow up, regardless of the treatment used during that time. In patients with UC the levels of YKL-40/CHI3L1 and PIIINP were lower at baseline and further decreased after 6-8 weeks (median concentrations were respectively: 39.5 ng/mL vs 24.7 ng/mL and 78.3 ng/mL vs 53.1 ng/mL). CONCLUSION: Fibrosis was more severe in CD than in UC patients. The marker that more accurately reflected these differences was PIIINP.

Is mean platelet volume a good predictor of sustained response to one year infliximab therapy in pediatric patients with Crohn's disease?

Over the past years, there is a growing number of newly diagnosed pediatric patients with Crohn's disease (CD). Severe course of CD often requires biological treatment with Infliximab (IFX). Loss of response to biological treatment is a major problem. Mean platelet volume (MPV) was reported as a good marker of sustained response to IFX therapy in adults. This study is to determine whether MPV measured prior to IFX therapy and a er its third dose can be used as a predictive marker of sustained response to biological therapy in children with severe course of CD. 43 pediatric patients with CD who underwent IFX therapy were enrolled into this study. The clinical response was evaluated after the third dose and after one year of IFX treatment (sustained response). The MPV values at baseline and week 14 were compared to the patients with good response to IFX to those with loss of the response. During 52-week IFX therapy, 2 out of 43 patients enrolled in the study did not achieve primary response a er the third dose, another 18 children lost their response to the above therapy a er one year. There was no significant association between baseline and 14th week values of MPV between patients with the sustained response to those with loss of response. In opposite to adult patients, MPV cannot be regarded as predictive factor of sustained response to IFX treatment in pediatric patients.

[Metabolic bone disease in children with chronic gastrointestinal tract condition]. / Choroba metaboliczna kosci w przebiegu przewleklych chorób przewodu pokarmowego u dzieci.

In this review issues concerning bone metabolism are presented. The diagnostic criteria of decreased mineral bone density is discussed with the significance of densitometry. The necessity of presence of low-trauma fracture to diagnosed the osteoporosis in children is signified. The paper reviews most common chronic gastrointestinal tract condition associated with the altered bone metabolism. The diagnostic and early treatment of decreased mineral bone density in children, who are before obtaining peak bone mass is crucial to prevent the risk of osteoporosis in adulthood.

Clinical presentations of Wilson disease among Polish children.

INTRODUCTION: Wilson disease (WD) may present from early childhood up to the eighth decade, presenting with variable hepatic and neuropsychiatric symptoms. Establishing the diagnosis is straightforward if the major clinical and laboratory features are present. However, clinical phenotypes are highly varied and early, proper diagnosis can be challenging. AIM: The aim of our study was to analyze clinical presentations and diagnostic tests of Polish pediatric patients with WD. METHODS: We retrospectively analyzed medical history of 156 patients with confirmed diagnosis of WD treated at our Institute from 1996 till March 2016. RESULTS: The mean age at onset of symptoms was 10.15±4.23 years of age. Hepatic presentation was the most common one (94.23%) with either liver failure (16.03%) or more frequently increased transaminases (78.2%). In 90.26% cases ceruloplasmin serum concentration was ≤0,2 g/l, in 51.93% patients basal urinary copper excretion was >100 µg/24 h. Mutation analysis was performed in 155 (99.36%) cases. The most common mutation was p.H1069Q. CONCLUSIONS: Wilson disease can present with only significantly increased transaminases activity and hepatomegaly or liver failure, but neurological symptoms are very rare in children. Diagnostic approach is challenging due to wide spectrum of clinical presentations in a high variable degree of severity. Genetic screening is supportive, ceruloplasmin and urinary copper excretion are valuable tests in the majority of patients but do not allow to exclude WD.

[Retrospective analysis of epidemiological and clinical aspects of acute pancreatitis in children]. / Retrospektywna analiza epidemiologiczna i kliniczna ostrego zapalenia trzustki u dzieci.

UNLABELLED: Acute pancreatitis (AP) is becoming more frequent cause of hospitalization in children. There are no guidelines concerning optimal medical treatment in this condition, up to know. The aim of the study was the epidemiological and clinical assessment of AP in pediatric population. The evaluation of influence of administered pharmacotherapy on symptoms remission and the time of laboratory tests normalization. MATERIAL AND METHODS: There were 54 patients with AP, in the age of 3, 5-18 years, admitted to our hospital between 1994-2011. The investigation was led on the basis of retrospective analysis of medical data. RESULTS: 41 (75%) patients were admitted with the first episode of AP. The oedematous pancreatitis was confirmed in 49 patients (91%) and necrotizing pancreatitis in 5 cases (9%). The cause of the condition was determined in 44 cases. The most common clinical symptoms were epigastric pain (94%) and vomiting (43%). CONCLUSIONS: There was no statistically significant difference in the time of obtaining normal range of serum and urine amylase activity and relief of symptoms according to administered pharmacotherapy and nutritional therapy

[Characteristics of eosinophilic inflammation of the gastrointestinal tract in children--a retrospective analysis of clinical material with review of the literature]. / Charakterystyka eozynofilowych zapalen przewodu pokarmowego u dzieci- -analiza retrospektywna wlasnego materialu klinicznego z przegladem pismiennictwa.

Eosinophilic disorders of the gastrointestinal tract are a heterogeneous group of rare and therefore rarely diagnosed chronic diseases occurring in both pediatric and adults. They represent a diverse clinical presentation, but their common feature is the presence of inflammatory infiltration of the intestinal wall with increased number of eosinophils. The study was a retrospective data analysis of patients hospitalized in the Department of Pediatrics, Gastroenterology and Nutrition, Jagiellonian University Medical College in Krakow, in the last 34 months. Among 11191 hospitalized children with symptoms suggesting gastrointestinal tract disorders, 1918 patients underwent endoscopic examination in which only 23 patients had significantly higher number of eosinophils in biopsies. Two of the four patients with eosinophilia in esophageal biopsy were diagnosed retrospectively as eosinophilic esophagitis. In the remaining 21 patients eosinophilia was secondary to other diseases of the gastrointestinal tract. Based on the medical documentation we performed thorough characterization study population in terms of history, physical examination and carried out laboratory tests. The results were referred to the current review of the literature.

Horizontal distribution of the fecal microbiota in adolescents with inflammatory bowel disease.

BACKGROUND AND AIMS: The commensal microbiota of the gastrointestinal tract plays an important role in the pathogenesis of inflammatory bowel disease. We examined the horizontal structure of the fecal microbiota in the colon in adolescents with Crohn disease or ulcerative colitis and a control group. PATIENTS AND METHODS: Fecal samples were collected in 3 fractions from patients with Crohn disease (n = 22), ulcerative colitis (n = 12), and controls (n = 24) during preparation for colonoscopy. Additionally, biopsies from colon tissue were taken. Samples were examined using a culture technique and a fluorescent in situ hybridization method. The mucin degradation assay was carried out. RESULTS: Quantitative composition of the microbiota was different in the consecutive 3 fecal fractions and in the colon tissue of the study groups, but in patients from the control group, the composition of microbiota in the consecutive fractions was similar. Statistical analyses showed that the total distribution of the studied bacterial taxons in the contents in all 3 fecal fractions and in the colon tissue in the given disease group, and in the control group was characteristic for the studied patient group. Differences in species distribution among the cohorts studied were highly significant (P < 0.0001). Moreover, it was shown that in the fecal fraction I and in the colon tissue samples, there is no significant difference for any of the analyzed bacterial groups, using the culture methods or fluorescent in situ hybridization, but significant results were demonstrated in the II and III fractions for specific bacterial groups. The bacterial flora attached to the mucus layer in the UC group had significantly more degraded mucus in comparison with the control group (P = 0.045). CONCLUSIONS: Distribution of the microbiota in the colon is layered, which can be called horizontal distribution of the fecal flora. Only in the ulcerative colitis group, the bacterial flora attached to the mucous layer exerts action on the mucin.

A review of magnetic resonance enterography based Crohn's disease activity indices in paediatric patients.

Magnetic resonance enterography (MRE) is a commonly used method for non-invasive diagnosing and following of inflammatory bowel disease (IBD). Numerous reviews that compare and discuss MRE-based Crohn's disease (CD) activity indices for adults have been published; however, no reviews of this kind have been published for children. Following a PubMed database literature search (January 2008 - November 2021), out of 316 research papers, 10 original papers about MRE-CD activity indices were included in the analysis. Four MRE-based scoring systems were discussed: Magnetic Resonance Index of Activity (MARIA), the Crohn's Disease Magnetic Resonance Imaging Index (CDMI), the Magnetic Resonance Enterography Global Score (MEGS) and the Visual Analogue Scale (VAS). This review revealed that in the last 13 years, studies have proven that MRE-based CD activity indices correspond with endoscopic findings and clinical scores of CD activity.

Clinical usefulness of the Mucosal Inflammation Noninvasive Index in newly diagnosed paediatric Crohn's disease patients.

Introduction: Mucosal healing (MH) has become a therapeutic goal in Crohn's Disease (CD), but its frequent evaluation in endoscopic examination is fraught with several limitations. There is an increasing demand to replace invasive procedures with noninvasive markers of CD. Aim: To assess the clinical importance of the recently developed Mucosal Inflammation Noninvasive Index (MINI) in newly diagnosed paediatric Crohn's Disease patients. Material and methods: Out of 60 consecutive newly diagnosed paediatric CD patients, 55 were enrolled in the study. The study examined the relationship between Simple Endoscopic Score for CD (SES-CD), Paediatric Crohn's Disease Activity Index (PCDAI), laboratory findings and the newly developed MINI index. Results: Out of the 55 paediatric patients involved in the study, ileocolonoscopy was successful in 42 patients. In this group there was a strong positive correlation between MINI and PCDAI (R = 0.61; p < 0.001) and a moderate positive correlation between MINI and SES-CD (R = 0.39; p = 0.011). MINI score of 17 points or more indicated severe CD (defined as SES-CD ≥ 16 points) with a diagnostic sensitivity of 90% but with a low specificity of 50%. There were 13 (23%) patients in whom ileocecal valve intubation was not achieved, and in this group the correlation between MINI and PCDAI was also strong (R = 0.66; p = 0.014). Conclusions: The newly developed MINI index is a simple and intuitive clinimetric score that can be considered a useful tool in assessing mucosal inflammation among newly diagnosed paediatric CD patients.

Serum concentrations of VEGF and TGF-ß1 during exclusive enteral nutrition in IBD.

BACKGROUND AND AIM: Exclusive enteral nutrition (EEN) is an effective method of treatment in achieving remission in inflammatory bowel disease (IBD); however, its mechanism of action is still poorly understood. The objective of our study was to assess the influence of EEN on serum vascular endothelial growth factor (VEGF) and transforming growth factor-beta 1 (TGF-ß1) in children and adolescents with IBD. PATIENTS AND METHODS: Thirty-nine children and adolescents with IBD (24 with Crohn disease [CD] and 15 with ulcerative colitis [UC]) and 25 healthy controls were enrolled in the study. VEGF and TGF-ß1 were assessed at the baseline and after 2 and 4 weeks of EEN in CD and UC groups and once in controls using enzyme-linked immunosorbent assay immunoassays. RESULTS: At the baseline, we found increased serum VEGF in the CD versus UC group and controls (P < 0.05) and serum TGF-ß1 in the UC versus CD group and controls (P < 0.05). During EEN, VEGF decreased in the UC and CD groups, whereas TGF-ß1 increased in the CD group and decreased in the UC group. The CD group achieved disease remission faster than the UC group, and the weight gain of patients with CD during EEN was higher compared with patients with UC. Additionally, TGF-ß1 concentration correlated with protein and energies daily intake in the CD group (R = 0.95; P < 0.05). CONCLUSIONS: Different effectiveness of EEN in achieving remission in CD and UC may result from a modification of growth factor production. EEN stimulated TGF-ß1 production in CD but not in UC, which possibly resulted in higher effectiveness of EEN in this group of patients.

Peptides from adipose tissue in monitoring energy balance in infants.

BACKGROUND/AIM: Overnutrition as well as undernutrition is a serious problem in hospitalized patients, especially in infants. Routine laboratory tests detecting disturbances in energy balance are not specific or accurate. The aim of this study was to evaluate adiponectin and leptin as markers of short-time energy malnutrition. METHODS: Forty-five infants fed orally and parenterally were included in the study. Plasma glucose, leptin and adiponectin were measured in a fasting state and postprandially (1 h after the meal), after a minimum of 24 h of total parenteral nutrition (TPN) and after a minimum of 8 h of intravenous infusion of glucose and crystalloids. RESULTS: Postprandial glucose levels in children fed orally was similar to that observed in children who received intravenous infusion of glucose. The TPN children had slightly higher glucose concentration in contrast to leptin levels which were significantly lower in this group (1.08 mg/mL +/- 0.43) as compared to the others (p < 0.05 in both cases). The mean postprandial levels of the adiponectin in orally fed children were significantly higher (10.7 microg/mL +/- 2.4) than in children with TPN (5.8 microg/mL +/- 2.4; p < 0.001) and in children hydrated intravenously (3.3 microg/mL +/- 2.3; p < 0.001). The concentration of adiponectin correlated significantly with calorie intake. CONCLUSIONS: Oral meal does not affect the plasma concentrations of leptin and adiponectin in infants. Adiponectin is a good short-time marker of energy malnutrition in infants.

Induction of Remission in Pediatric Crohn's Disease Patients Assessed by the Mucosal Inflammation Noninvasive Index.

Mucosal healing (MH) is the main therapeutic goal of Crohn's disease (CD). The Mucosal Inflammation Noninvasive Index (MINI) appears to be a promising tool for distinguishing MH from its inflammation. This study aims to evaluate MINI in monitoring remissions induced by exclusive enteral nutrition (EEN) in pediatric CD patients. Out of 55 newly diagnosed CD children, 31 who completed 6-8 weeks of EEN were analyzed. Clinical and biochemical data, activity of CD assessed with the Pediatric Crohn's Disease Activity Index (PCDAI) and MINI were compared within seven days pre- and post-EEN. Response to induction therapy was defined as a decrease of PCDAI by >12.5 points. The follow-up was performed up to 12 months after EEN termination. Out of 31 children who completed 6-8 weeks of EEN, eight required corticosteroids in addition to EEN. Twenty-four patients (77%) responded to induction therapy. In responders, MINI decreased from 19 (Q1:17; Q3:22) to 12 (Q1:6; Q3:14), p < 0.001. The diagnostic accuracy of post-EEN MINI and post-EEN fecal calprotectin (FC) for treatment failure were AUC: 0.899 (95%CI: 0.737-1.000) and 0.762 (95%CI: 0.570-0.954), respectively. In the follow-up of 25 patients (80.6%), the post-EEN MINI of ≥13 points predicted CD relapse (87.5% sensitivity; 64.7% specificity), while FC had no prognostic value. MINI allows for monitoring of EEN and is superior in predicting disease relapse to FC.

Plasma elafin, cathelicidin, and α-defensins are increased in paediatric inflammatory Crohn's disease and reflect disease location.

INTRODUCTION: The aim of our study was to assess antimicrobial peptides in children with Crohn's disease (CD). METHODS: Plasma elafin, cathelicidin, and α- and ß-defensins were assessed in 35 children with CD using immunoassays. Phenotype and location of CD were assessed based on the results of endoscopic and radiological studies. RESULTS: We found increased elafin, cathelicidin, and α-defensins in children with inflammatory phenotype as compared to stricturing and penetrating phenotypes of CD. Additionally, we found increased elafin and cathelicidin in colonic location and α-defensins in ileal CD locations. CONCLUSIONS: Assessing antimicrobial peptides may be helpful in estimating of phenotype and location of CD lesions.

[Influence of enteral nutrition therapy on serum angiogenic growth factors concentrations in children]. / Wplyw zywienia enteralnego na stezenia czynników naczyniowzrostowych w surowicy u dzieci.

INTRODUCTION: Effectiveness of enteral nutrition therapy is not only connected with improvement of the nutritional status of the patient, but also with its strong anti-inflammatory activity. Angiogenic growth factors play an important role in the early stage of inflammation. Vascular endothelial growth factor (VEGF) and transforming growth factor beta 1 (TGF-beta 1) stimulate the angiogenesis and healing processes. The objective of our study was to assess the influence of the enteral nutrition therapy on the vascular endothelial growth factor (VEGF) and transforming growth factor beta 1 (TGF-beta 1) concentrations in serum in children with different diseases of gastro-intestinal tract, in which enteral nutrition therapy is effective method of treatment. MATERIAL AND METHODS: Sixty two children (29 boys, 33 girls, mean age: 12.5 yrs, range: 6-18 yrs) and 25 healthy controls were included into the study. The Crohn's disease group (CD) consisted of 25 patients, ulcerative colitis group (UC)-18 patients, acute pancreatitis (AP) group-12 patients and severe malnutrition (N) group-7 patients. Serum VEGF and TGF-beta 1 concentrations were assessed at baseline, before starting and after 2 and 4 weeks of enteral nutrition therapy using ELISA immunoassays (R and D Systems, USA). RESULTS: Before starting enteral nutrition, we found increased VEGF concentration in CD group (Me = 600 pg/ml) compared to UC group (266.9 pg/ml), AP group (552.6 pg/ml), N group (238.5 pg/ml) and controls (172 pg/ml) (p < 0.05). We found decrease of VEGF concentrations during enteral nutrition in CD, UC and N group and increase in AP at the beginning, followed by decrease to the initial values. Assessing TGF-beta 1, we found its concentration increased before starting enteral nutrition in UC group (37.5 ng/ml) compared to CD group (29.7 ng/ ml) and controls (24.8 ng/ml) (p < 0.05). During enteral nutrition we observed decrease of TGF-beta 1 concentration in UC group and increase in CD group (32,7 ng/ml) and AP group (26,6 ng/ml) (p < 0.05) The best improvement of nutritional status was observed in CD patients compared to N and AP patients. CONCLUSIONS: Differentiation of serum VEGF and TGF-beta 1 concentrations, what was observed in various gastro-intestinal diseases, reflects different mechanisms of enteral nutrition therapy acting on the inflammatory process. The most efficient therapeutic effect was seen in CD, where stimulation of TGF-beta 1 production was observed.

[Hemophagocytic syndrome in children with different underlying conditions]. / Zespól hemofagocytarny u dzieci w róznych jednostkach chorobowych.

Hemophagocytic syndrome (HS) is a life-threatening condition of hyperinflammation. Main symptoms are: prolonged fever, cytopenia, hepatosplenomegaly, hemophagocytosis, hyperferritinemia, hypertriglyceridemia and hypofibrinogenemia. Primary genetic form and secondary HS associated with infections, malignancies or autoimmune disorders can be distinguished. Untreated HS in most cases leads to death. We analyzed retrospectively 7 cases of HS in children (3 girls, 4 boys; aged 10 days -14 years) treated in 3 different pediatric centers from 2004 to 2009. In 3 cases HS was associated with infections (EBV, CMV, Bacillus Calmette Guerin - BCG), in 1 child with non-Hodgkin anaplastic large cell lymphoma (ALCL), in 1 patients probably with side effect of antiepileptic drug. In 2 cases cause of HS remained unknown. Fever, hepatomegaly, pan- or bicytopenia and hyperferritinemia were present in all children. In addition, splenomegaly was noted in 6 cases, hemophagocytosis in 6 children, impaired function or decreased number of NK cells in 4 cases, hypofibrino-genemia in 5 and hypotriglyceridemia in 4 patients. Among other symptoms and signs we observed: lymphadenopathy, hepatic failure, oedema, rash, neurological symptoms, increased level of LDH and inflammatory markers. In one child acute pancreatitis occurred. Among others, antibiotics, antiviral and immunosuppressive drugs were used in therapy. HLH-2004 protocol was applied in 4 cases. Patient with ALCL was treated with chemotherapy and allogeneic stem cell transplantation. Four patients are alive, 2 died because of HS, child with ALCL died because of generalized infection in peritrans-plantation period. In case of prolonged fever, splenomegaly and cytopenia diagnosis of HS should be considered. Following tests are recommended: complete blood count, ferritin, triglycerides, fibrinogen, bone marrow aspiration and NK cell assessment. Patients should be also screened for infections and malignancies. Early diagnosis of HS and underlying condition is crucial to start lifesaving therapy.

Infliximab Therapy Could Decrease the Risk of the Development of Thyroid Disorders in Pediatric Patients With Crohn's Disease.

Autoimmune diseases, including autoimmune thyroid diseases (AITDs), may be associated with Crohn's disease (CD). Taking into consideration the role of tumor necrosis factor alpha (TNF-alpha) in the immune-mediated inflammation that underlies both diseases, we evaluated an ultrasound of thyroid gland in pediatric CD patients, naïve, and treated with infliximab (IFX), an anti-TNF-alpha antibody, to assess the risk for AITD and evaluated the usefulness of ultrasonography to diagnose AITD in patients with CD. Sixty-one patients with CD were enrolled in the study, including 36 patients (mean age 14.5 ± 3.5 years) treated with IFX (IFX group) for a mean of 13.9 ± 16.6 months and 25 patients (mean age 14.7 ± 2.3 years) who never received anti-TNF-alpha therapy (control group). An ultrasound examination of the thyroid gland was performed; thyroid function tests and thyroid antibodies were assessed. We found 10-times higher prevalence of decreased thyroid echogenicity in CD and IFX-naive patients compared to IFX-treated group [a significant reduction in thyroid echogenicity in 1/36 (2.8%) patients receiving IFX compared to 7/25 (28%) patients naive to biologic therapy]. The latter showed significantly lower thyroid-stimulating hormone (TSH) levels (p = 0.034) and higher levels of thyroid antibodies (p = 0.042) in comparison to control. Our data suggest the protective role of IFX therapy in the development of thyroid disorders and indicate the usefulness of thyroid ultrasound to identify the risk of probable AITD in pediatric patients with CD.

Changes in the Intestinal Microbiota Are Seen Following Treatment with Infliximab in Children with Crohn's Disease.

The aim of the study was to determine the impact of biological treatment with tumor necrosis factor α antibodies (anti-TNF-α) on the intestinal microbiome of children with severe Crohn's disease (CD) and to evaluate the differences in the intestinal microbiome between patients treated with biological therapy and healthy children. Microbiota composition was analyzed by 16S next-generation sequencing (NGS) and microbial profiles were compared between studied groups. Fifty-four samples (from 18 patients before and after anti-TNF-α induction therapy and 18 healthy children) were used in the sequencing analysis. Shannon's diversity index (p = 0.003, adj. p = 0.010) and observed operational taxonomic units (OTUs) (p = 0.007, adj. p = 0.015) were different between controls and patients with prior therapy for CD. Statistically significant dissimilarities between beta diversity metrics, indicating distinct community composition across groups, were observed in patients with CD before and after therapy. We did not observe any differences between controls and patients with CD after therapy. Core microbiome analysis at species level showed that 32 species were present only in patients with CD but not in controls. The results show that biological treatment is associated with changes in the intestinal microbiome of patients with CD: these changes result in an intestinal microbiome pattern similar to that seen in healthy children. Long-term observation is necessary to determine whether treatment can lead to full restoration of a healthy-like microbiome.

Quantitative changes in selected bacteria in the stool during the treatment of Crohn's disease.

PURPOSE: The aim of this study was to determine quantitative changes in selected species of bacteria (Bacteroides fragilis, Lactobacillus fermentum, Lactobacillus rhamnosus, Serratia marcescens) in the stool of patients with Crohn's disease (CD) in the course of induction treatment with exclusive enteral nutrition (EEN) or anti-tumor necrosis factor alpha (Infliximab, IFX) vs. healthy controls (HC). MATERIALS/METHODS: DNA was isolated from stool samples of CD (n = 122) and HC (n = 17), and quantitative real-time Polymerase Chain Reaction (qPCR) was applied. In both treatment groups, the first stool sample was taken before the start of treatment, and the second 4 weeks after its end: in EEN (n = 48; age (mean; SD) 13.35 ± 3.09 years) and IFX groups (n = 13; age (mean; SD) 13.09 ± 3.76 years). RESULTS: The only species that showed a statistically significant difference between the two groups of patients before any therapeutic intervention was L. fermentum. Moreover, its number increased after completion of EEN and differed significantly when compared with the HC. In the IFX group the number of L. fermentum decreased during the therapy but was significantly higher than in the HC. The number of S. marcescens in the EEN group was significantly lower than in the controls both before and after EEN. CONCLUSION: The implemented treatment (EEN or IFX) modifies the microbiome in CD patients, but does not make it become the same as in HC.

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease.

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10-10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10-10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis.

Epidemiology of inflammatory bowel disease among children in Poland. A prospective, population-based, 2-year study, 2002-2004.

BACKGROUND/AIMS: The incidence of pediatric inflammatory bowel disease (IBD) in Western countries is on the rise. No prospective studies have been conducted on the epidemiology of pediatric IBD in Poland. The aim of the study was to define the characteristics of new pediatric IBD and assess the incidence of new IBD among children in Poland between 2002 and 2004. METHODS: Patient records from 24 pediatric gastroenterology centers servicing the whole population of Poland were collected. IBD diagnosis was based on clinical, radiological, endoscopic and histological features. RESULTS: There were 491 new IBD patients, representing an overall incidence of IBD of 2.7 cases/100,000 children/year. The incidence of Crohn's disease (CD) was 0.6, ulcerative colitis (UC) 1.3, and indeterminate colitis (IC) 0.8. The age-related incidence of IBD was 1.8 in the 0- to 10-year-old age group, rising to 3.7 for the 11- to 18-year age group. CONCLUSIONS: The overall incidence of IBD (as well as CD, UC and IC) in Poland is lower than that in Western countries. The relative contribution of UC and IC to the overall IBD incidence is higher in Poland than in most Western countries. These findings may suggest a tendency towards under- or misdiagnosis.