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.

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.

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.

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.

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.

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.

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.

Differences in the intestinal microbiome of healthy children and patients with newly diagnosed Crohn's disease.

The aetiology of inflammatory bowel diseases (IBD) seems to be strongly connected to changes in the enteral microbiome. The dysbiosis pattern seen in Crohn's disease (CD) differs among published studies depending on patients' age, disease phenotype and microbiome research methods. The aims was to investigate microbiome in treatment-naive paediatric patients to get an insight into its structure at the early stage of the disease in comparison to healthy. Stool samples were obtained from controls and newly diagnosed patients prior to any intervention. Microbiota was analysed by 16SrRNAnext-generation-sequencing (NGS). Differences in the within-sample phylotype richness and evenness (alpha diversity) were detected between controls and patients. Statistically significant dissimilarities between samples were present for all used metrics. We also found a significant increase in the abundance of OTUs of the Enterococcus genus and reduction in, among others, Bifidobacterium (B. adolescentis), Roseburia (R.faecis), Faecalibacterium (F. prausnitzii), Gemmiger (G. formicilis), Ruminococcus (R. bromii) and Veillonellaceae (Dialister). Moreover, differences in alpha and beta diversities in respect to calprotectin and PCDAI were observed: patients with calprotectin <100 µg/g and with PCDAI below 10 points vs those with calprotectin >100 µg/g and mild (10-27.7 points), moderate (27.5-40 points) or severe (>40 points) CD disease activity had higher richness and diversity of gut microbiota. The results of our study highlight reduced diversity and dysbiosis at the earliest stage of the disease. Microbial imbalance and low abundance of butyrate-producing bacteria, including Bifidobacterium adolescentis, may suggest benefits of microbial modification therapy.

Serum trace elements profile in the pediatric inflammatory bowel disease progress evaluation.

INTRODUCTION: Inflammatory bowel disease (IBD), a chronic inflammatory disorder of gastrointestinal tract, arises from complex interaction between genetics, environment, gut microbiota and mucosal immune response. Along with clinical, endoscopic and radiological evaluation various biomarkers are needed as an additional diagnostic tool, as well as to predict disease course and therapeutic outcomes. AIM: The aim of this study was to evaluate clinical value of essential trace elements (ETEs) serum concentration profile in the assessment of pediatric IBD diseases development. MATERIALS AND METHODS: Concentration of five ETEs: iron (Fe), zinc (Zn), copper (Cu), manganese (Mn) and selenium (Se) in serum of 41 children with newly diagnosed IBD (27 CD and 14 UC) and 20 healthy controls were determined by inductively coupled plasma mass spectrometry (ICP-MS) and atomic fluorescence spectrometry (AFS) at the moment of diagnosis and after one year of treatment. RESULTS: The obtained results revealed significant differences in serum concentration profile of studied ETEs' for IBD pediatric patients and healthy controls. Decrease of iron, zinc and selenium and increase of copper and manganese serum concentration were observed in IBD patients at the time of diagnosis. The changes were reversible and after one year of treatment the studied ETEs serum concentration profile resembled much more that observed for healthy controls. Correlations between studied ETEs levels within cases (IBD, CD, UC) were also found to be different from those in healthy controls (HC). CONCLUSION: Although much more studies are required on the subject our results demonstrate a clinical value of ETEs serum concentration profile in pediatric IBD patients regarding disease development.

Dependence of Colonization of the Large Intestine by Candida on the Treatment of Crohn's Disease.

The aim of this study was to determine if there are quantitative differences in Candida fungi between pediatric patients with Crohn's disease (before and after exclusive enteral nutrition (EEN), and the biologic therapy with anti-tumor necrosis factor alpha - (IFX)), and healthy controls. DNA was isolated from fecal samples and PCR was used to determine the number of fungal cells. Both therapeutic interventions resulted in a statistically significant decrease in Pediatric Crohn's Disease Activity Index. The numbers of Candida decreased during both therapeutic intervention but the difference was statistically significant for the IFX intervention only (p = 0.045). Moreover, fungi population in both study groups declined during intervention when compared to the control group but the difference was significant before treatment only in the IFX group (p = 0.013). The total distribution of Candida with both IFX and EEN as well as in the control group differed significantly (p = 0.01) before treatment only. No correlation between the numbers of Candida and disease activity as well as the following biochemical parameters: serum iron concentration, protein or glucose level were found. It cannot be ruled out that, in combination with genetic and immunological disorders, fungi can contribute to the initiation of the disease process and perpetuation of active inflammation.The aim of this study was to determine if there are quantitative differences in Candida fungi between pediatric patients with Crohn's disease (before and after exclusive enteral nutrition (EEN), and the biologic therapy with anti-tumor necrosis factor alpha ­ (IFX)), and healthy controls. DNA was isolated from fecal samples and PCR was used to determine the number of fungal cells. Both therapeutic interventions resulted in a statistically significant decrease in Pediatric Crohn's Disease Activity Index. The numbers of Candida decreased during both therapeutic intervention but the difference was statistically significant for the IFX intervention only (p = 0.045). Moreover, fungi population in both study groups declined during intervention when compared to the control group but the difference was significant before treatment only in the IFX group (p = 0.013). The total distribution of Candida with both IFX and EEN as well as in the control group differed significantly (p = 0.01) before treatment only. No correlation between the numbers of Candida and disease activity as well as the following biochemical parameters: serum iron concentration, protein or glucose level were found. It cannot be ruled out that, in combination with genetic and immunological disorders, fungi can contribute to the initiation of the disease process and perpetuation of active inflammation.

Prognostic value of assessment of stool and serum IL-1ß, IL-1ra and IL-6 concentrations in children with active and inactive ulcerative colitis.

INTRODUCTION: Interleukin-1ß (IL-1ß), interleukin-1 receptor antagonist (IL-1ra) and interleukin-6 (IL-6) contribute to the pathogenesis of ulcerative colitis (UC). The aim of our study was to evaluate the serum and stool IL-1ß, IL-1ra and IL-6 concentrations as potential prognostic factors in children with UC. MATERIAL AND METHODS: Thirty-eight children with UC (20 active, 18 inactive) and 14 healthy controls were prospectively included in the study. IL-1ß, IL-1ra and IL-6 concentrations were measured in serum and stool supernatants at inclusion to the study using ELISA immunoassays. The children were followed up over 5 years, and at each follow-up clinical disease activity, quantity and severity of relapses, nutritional status, endoscopic and histopathologic activity, disease complications and the treatment regimen were evaluated. RESULTS: In children with active and inactive UC who had relapsed during a 5-year follow-up period compared to the non-relapse groups we found significantly increased serum IL-1ß (1.34 vs. 0.98 pg/ml, p < 0.05, and 1.02 vs. 0.68 pg/ml, p < 0.01, respectively,) and IL-1ra (718.0 vs. 453.2 pg/ml, p < 0.05, and 567.4 vs. 365.1 pg/ml, p < 0.01, respectively). Additionally, in children who had experienced complications during a 5-year follow-up period we observed significantly increased serum and stool IL-1ß (p < 0.05) and serum IL-1ra (p < 0.01) compared to the group without complications. CONCLUSIONS: We concluded that serum IL-1ß and IL-1ra and to a lesser extend stool IL-1ß concentrations may be useful prognostic factors in children with active and inactive UC over a short-term follow-up period, which may help to identify children that require more aggressive therapy due to an increased risk of relapse or complications resulting from UC.

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.

Diagnostic Value of Fecal Calprotectin (S100 A8/A9) Test in Children with Chronic Abdominal Pain.

Objectives. The aim of the study was to establish whether fecal calprotectin concentration (FCC) may be useful in children with chronic abdominal pain to differentiate between inflammatory bowel disease (IBD), other inflammatory gastrointestinal disorders, and functional gastrointestinal disorders. Methods. The study included 163 patients (median age 13 years), who were assigned to four study groups: group 0 (control), 22 healthy children; group 1, 33 children with functional gastrointestinal disorders; group 2, 71 children with inflammatory gastrointestinal disorders other than IBD; group 3, 37 children with IBD. FCC was measured using ELISA assay. Results. In group 0 and group 1 FCCs were below 100 µg/g. Low FCCs were found in 91% of patients in group 2. In patients with IBD FCCs were markedly elevated with median value of 1191.5 µg/g. However, in children with inflammatory gastrointestinal disorders other than IBD and in children with IBD mean FCCs were significantly higher compared with the control group. Significant differences in FCCs were also found between group 1 and group 2, between group 1 and group 3, and between group 2 and group 3. Conclusion. FCC is the best parameter allowing for differentiation between IBD, other inflammatory gastrointestinal disorders, and functional gastrointestinal disorders. High FCC is associated with a high probability of IBD and/or other inflammatory gastrointestinal disorders, and it allows excluding functional gastrointestinal disorders.

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.

[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.

Laryngopharyngeal Reflux in Children with Chronic Otitis Media with Effusion.

BACKGROUND/AIMS: To evaluate the characteristic properties of laryngopharyngeal reflux (LPR) and gastroesophageal reflux (GER) in children with otitis media with effusion (OME) using 24-hour multichannel intraluminal impedance combined with dual-probe (pharyngeal and esophageal) pH-metry. METHODS: Children aged 7-10 years of age with OME underwent 24-hour multichannel intraluminal impedance pH-metry. The upper pH sensor was situated 1 cm above the upper esophageal sphincter, and the lower pH sensor was placed 3-5 cm above the lower esophageal sphincter. Parents were asked to complete the gastroesophageal reflux assessment of symptoms in a pediatrics questionnaire. RESULTS: Twenty-eight children were enrolled; LPR was detected in 19 (67.9%) children. The criteria of the LPR diagnosis was the presence of at least one supraesophageal episode with a pH < 5.0 and a change in the pH value measured from the initial level at the upper sensor of > 0.2. In total, 64 episodes were observed. Assessment of all LPR episodes showed the presence of 246 episodes in the entire study. A considerable predominance of weakly acidic episodes (87.8%) was noted; there were 6.5% acidic episodes, and weakly alkaline episodes reached 5.7%. Pathological GER was noted in 10 (35.7%) subjects. Acid GER was detected in 8 children, 2 of whom demonstrated non-acidic reflux. In the LPR-negative patients, no pathological GER was confirmed with the exception of a single case of non-acidic reflux. CONCLUSIONS: LPR was frequently noted in the group of children with OME, and it might be an important risk factor in this common disease.

Randomized clinical trial: pharmacokinetics and safety of multimatrix mesalamine for treatment of pediatric ulcerative colitis.

BACKGROUND: Limited data are available on mesalamine (5-aminosalicylic acid; 5-ASA) use in pediatric ulcerative colitis (UC). AIM: To evaluate pharmacokinetic and safety profiles of 5-ASA and metabolite acetyl-5-ASA (Ac-5-ASA) after once-daily, oral administration of multimatrix mesalamine to children and adolescents with UC. METHODS: Participants (5-17 years of age; 18-82 kg, stratified by weight) with UC received multi-matrix mesalamine 30, 60, or 100 mg/kg/day once daily (to 4,800 mg/day) for 7 days. Blood samples were collected pre-dose on days 5 and 6. On days 7 and 8, blood and urine samples were collected and safety was evaluated. 5-ASA and Ac-5-ASA plasma and urine concentrations were analyzed by non-compartmental methods and used to develop a population pharmacokinetic model. RESULTS: Fifty-two subjects (21 [30 mg/kg]; 22 [60 mg/kg]; 9 [100 mg/kg]) were randomized. On day 7, systemic exposures of 5-ASA and Ac-5-ASA exhibited a dose-proportional increase between 30 and 60 mg/kg/day cohorts. For 30, 60, and 100 mg/kg/day doses, mean percentages of 5-ASA absorbed were 29.4%, 27.0%, and 22.1%, respectively. Simulated steady-state exposures and variabilities for 5-ASA and Ac-5-ASA (coefficient of variation approximately 50% and 40%-45%, respectively) were similar to those observed previously in adults at comparable doses. Treatment-emergent adverse events were reported by ten subjects. Events were similar among different doses and age groups with no new safety signals identified. CONCLUSION: Children and adolescents with UC receiving multimatrix mesalamine demonstrated 5-ASA and Ac-5-ASA pharmacokinetic profiles similar to historical adult data. Multimatrix mesalamine was well tolerated across all dose and age groups. ClinicalTrials.gov Identifier: NCT01130844.