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Exclusive enteral nutrition (EEN) is a first-line therapy for pediatric Crohn's disease (CD), but protective mechanisms remain unknown. We established a prospective pediatric cohort to characterize the function of fecal microbiota and metabolite changes of treatment-naive CD patients in response to EEN (German Clinical Trials DRKS00013306). Integrated multi-omics analysis identified network clusters from individually variable microbiome profiles, with Lachnospiraceae and medium-chain fatty acids as protective features. Bioorthogonal non-canonical amino acid tagging selectively identified bacterial species in response to medium-chain fatty acids. Metagenomic analysis identified high strain-level dynamics in response to EEN. Functional changes in diet-exposed fecal microbiota were further validated using gut chemostat cultures and microbiota transfer into germ-free Il10 -deficient mice. Dietary model conditions induced individual patient-specific strain signatures to prevent or cause inflammatory bowel disease (IBD)-like inflammation in gnotobiotic mice. Hence, we provide evidence that EEN therapy operates through explicit functional changes of temporally and individually variable microbiome profiles. [Display omitted] • EEN induces remission in patients with pediatric Crohn's disease • EEN creates temporally and individually variable microbiome profiles • Medium-chain fatty acids link EEN to changes in the microbiota of CD patients • Protective microbiota functions are validated in chemostat and gnotobiotic models Häcker et al. showed that exclusive enteral nutrition (EEN) in pediatric Crohn's disease (CD) creates temporally and individually variable microbiome profiles. They showed that medium-chain fatty acids link EEN to changes in the microbiota of CD patients. Finally, protective microbiota functions were validated in transfer model systems. [ABSTRACT FROM AUTHOR]

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ABSTRACT Gut dysbiosis is closely related to dysregulated microRNAs (miRNAs) in the intestinal epithelial cells, which plays an important role in the pathogenesis of Crohn’s disease (CD). We investigated the relationship between fecal gut microbiome (GM) and intestinal tissue miRNAs in different stages of pediatric CD. Metagenomic analysis and miRNA sequencing were conducted to examine the GM and intestinal miRNA profiles of CD patients before and after clinical induction therapy and the controls. Twenty-seven newly diagnosed, therapy-naïve pediatric patients with active CD and 11 non-inflammatory bowel disease (IBD) controls were recruited in this study. Among CD patients, 11 patients completed induction treatment and reached clinical remission. Both GM and miRNA profiles were significantly changed between CD patients and controls. Seven key bacteria were identified at species level including Defluviitalea raffinosedens, Thermotalea metallivorans, Roseburia intestinalis, Dorea sp. AGR2135, Escherichia coli, Shigella sonnei, and Salmonella enterica, the exact proportions of which were further validated by real-time quantitative PCR analysis. Eight key miRNAs were also identified including hsa-miR-215-5p, hsa-miR-194-5p, hsa-miR-12135, hsa-miR-509-3-5p, hsa-miR-212-5p, hsa-miR-4448, hsa-miR-501-3p, and hsa-miR-503-5p. The functional enrichment analysis of differential miRNAs indicated the significantly altered cyclin protein, cyclin-dependent protein, and cell cycle pathway. The close interactions between seven key bacteria and eight key miRNAs were further investigated by miRNA target prediction. The association between specific miRNA expressions and key gut bacteria at different stages of CD supported their important roles as potential molecular biomarkers. Understanding the relationship between them will help us to explore the molecular mechanisms of CD.IMPORTANCESince previous studies have focused on the change of the fecal gut microbiome and intestinal tissue miRNA in pediatric Crohn’s disease (CD), the relationship between them in different stages is still not clear. This is the first study to explore the gut microbiota and miRNA and their correlations with the Pediatric Crohn’s Disease Activity Index (PCDAI). Crohn’s Disease Endoscopic Index of Severity (CDEIS), and calprotectin, by applying two omics approach in three different groups (active CD, CD in remission with exclusive enteral nutrition or infliximab induction therapy, and the healthy controls). Both gut microbiome structure and the miRNA profiles were significantly changed in the different stage of CD. Seven key gut microbiome at species and eight key miRNAs were found, and their close interactions were further fully investigated by miRNA target prediction.

Background: The incidence of pediatric Crohn’s disease (PCD) is increasing worldwide every year. The challenges in early diagnosis and treatment of PCD persist due to its inherent heterogeneity. This study’s objective was to discover novel diagnostic markers and molecular subtypes aimed at enhancing the prognosis for patients suffering from PCD. Methods: Candidate genes were obtained from the GSE117993 dataset and the GSE93624 dataset by weighted gene co-expression network analysis (WGCNA) and differential analysis, followed by intersection with platelet-related genes. Based on this, diagnostic markers were screened by five machine learning algorithms. We constructed predictive models and molecular subtypes based on key markers. The models were evaluated using the GSE101794 dataset as the validation set, combined with receiver operating characteristic curves, decision curve analysis, clinical impact curves, and calibration curves. In addition, we performed pathway enrichment analysis and immune infiltration analysis for different molecular subtypes to assess their differences. Results: Through WGCNA and differential analysis, we successfully identified 44 candidate genes. Following this, employing five machine learning algorithms, we ultimately narrowed it down to five pivotal markers: GNA15, PIK3R3, PLEK, SERPINE1, and STAT1. Using these five key markers as a foundation, we developed a nomogram exhibiting exceptional performance. Furthermore, we distinguished two platelet-related subtypes of PCD through consensus clustering analysis. Subsequent analyses involving pathway enrichment and immune infiltration unveiled notable disparities in gene expression patterns, enrichment pathways, and immune infiltration landscapes between these subtypes. Conclusion: In this study, we have successfully identified five promising diagnostic markers and developed a robust nomogram with high predictive efficacy. Furthermore, the recognition of distinct PCD subtypes enhances our comprehension of potential pathogenic mechanisms and paves the way for future prospects in early diagnosis and personalized treatment. [ABSTRACT FROM AUTHOR]

Background: Pediatric inflammatory bowel disease (PIBD) affects different age groups and its incidence is increasing worldwide. However, there is a lack of research focusing on age subgroups in Asian countries. In this nationwide population‐based study, we investigated the epidemiology of PIBD among different age subgroups in Korea. Methods: We analyzed Korean health administration data from 2005 to 2016. Data were divided by age at diagnosis as follows: group 1, 0–1 years; group 2, 2–5 years; group 3, 6–9 years; group 4, 10–16 years. We analyzed the overall incidence, temporal changes, and regional differences by age subgroups, using Poisson regression analysis. Results: From 2005 to 2016, 2734 inflammatory bowel disease (IBD) cases were diagnosed among patients under 17 years of age. In the overall population, the incidence rate of PIBD over the entire study period was 2.248/105 person‐years (PY), significantly increasing from 1.173/105 PY in 2005–2007 to 3.267/105 PY in 2014–2016. The incidence rates in groups 1 and 2 remained unchanged, whereas those of groups 3 and 4 increased significantly. The same trend was observed when analyzed separately for Crohn's disease (CD) and ulcerative colitis (UC). The incidence rates of CD in groups 3 and 4 showed differences between metropolitan and non‐metropolitan areas, whereas those in groups 1 and 2, and UC of all age subgroups showed no difference. Conclusions: The temporal trend and regional differences of PIBD differed among age subgroups, suggesting that genetic and environmental factors have varying impacts on IBD development across different subgroups. [ABSTRACT FROM AUTHOR]

Background Exclusive enteral nutrition (EEN) therapy effectively induces remission in pediatric Crohn's disease (CD). However, this may depend on the type of enteral formula used. Moreover, data on the efficacy of amino acid-based EEN are limited. Thus, we aimed to prospectively evaluate the efficacy of amino acid-based formulas for EEN in pediatric patients with active CD. Methods Patients with active CD aged between 6 and 17 years were recruited into this prospective study from four hospitals in China between March 2019 and December 2021. Patients received EEN for 8 weeks. Inflammatory and nutrition-associated indices were evaluated at 0, 4, and 8 weeks after treatment. Paired t -tests and Wilcoxon signed-rank tests were used to compare continuous and categorical variables before and after intervention, respectively. Results Twenty-four patients were included in the analysis. After an 8-week intervention period, the CD activity index significantly decreased (26.3 ± 12.2 vs 7.1 ± 8.3, P  <   0.001). Most patients (66.7%) achieved complete clinical remission. Among the 22 patients who had ulcers and erosions diagnosed endoscopically at baseline, 10 (45.5%) achieved complete mucosal healing. The degree of thickening of the intestinal wall was significantly reduced after EEN intervention, with a transmural healing rate of 42.9%. Furthermore, the serum inflammatory markers decreased and there was a significant improvement in the nutrition-related indices (P  <   0.05). There were no severe adverse effects. Conclusions Amino acid-based EEN is effective and safe for treating pediatric-onset CD. Studies with larger sample sizes and mechanistic and follow-up studies are required to further validate these findings. [ABSTRACT FROM AUTHOR]

Objectives: About 24% of children with Crohn's Disease (CD) require surgery. In 2003, Kono et al. described a novel anastomosis reported to decrease the rate of anastomotic CD recurrence. Subsequent studies have reproduced these outcomes, but none has demonstrated its effect in pediatric patients. This study evaluates short-term outcomes of pediatric patients following ileocolic resection and Kono-S anastomosis. Methods: A retrospective review of patients < 18 years old who underwent ileocolic resection followed by Kono-S anastomosis compared with those who underwent a stapled anastomosis. Results: Nine Kono-S patients were matched with nine patients preceding them who received traditional side-to-side and end-to-side anastomoses. All patients underwent minimally invasive surgery. Demographics, pre-operative medication usage, and symptom profiles were not significantly different. Traditional anastomosis (TA) patients had longer lengths of stay (4.6 vs 2.9 days; p = 0.03) but had no statistically significant differences in blood loss, procedure length, and pathologic findings. One Kono-S patient had a superficial surgical site infection, and one TA patient had an anastomotic leak requiring reoperation within 30 days. More TA patients experienced post-operative symptoms at both 30-day and 6-month follow-up (66.7% vs 33.3%; p = 0.16 and 77.8% vs 25%; p = 0.03). Conclusion: The Kono-S anastomosis appears to be safe in pediatric CD when compared to traditional stapled anastomoses. [ABSTRACT FROM AUTHOR]

Background: The combination of antitumor necrosis factor-alpha (TNF-α) agents with immunomodulators (IMMs) is a common treatment for pediatric Crohn's disease (CD). Although methotrexate (MTX) can be a first-line medication as an IMM, most clinicians in real-life practice, especially in South Korea, are more familiar with thiopurines. This study aimed to compare the efficacy and immunogenicity of MTX and azathioprine (AZA) as concurrent therapies for pediatric CD. Methods: In this pilot study, 29 newly diagnosed pediatric patients with moderate-to-severe CD were randomized to receive either MTX (n = 15) (15 mg/body surface area (BSA) per week) or oral AZA (n = 14) (0.5 mg/kg per day) in combination with Infliximab (IFX). The primary outcomes were the proportion of patients in endoscopic, biochemical, and transmural remission after 14 and 54 weeks of IFX therapy. The trough levels (TLs) of IFX and anti-drug antibody (ADA) levels were also compared. Results: Among the 29 patients, there were no significant differences in the biochemical (p = 1.0 at week 14, p = 0.45 at week 54), endoscopic (p = 0.968 at week 14, p = 0.05 at week 54), or transmural (p = 0.103 at week 54) remission rates between the two medications during the concurrent therapy. Additionally, the trends in the IFX trough and ADA levels over time during the treatments were similar for both medications, with no significant differences (p = 0.686, p = 0.389, respectively). Conclusion: The MTX showed comparable efficacy to the AZA in pediatric CD patients with moderate-to-severe disease. This effectively maintained adequate IFX levels and reduced ADA production. Therefore, although additional large-scale clinical trials are needed, this study demonstrated that either MTX or AZA can be selected as IMMs in the concurrent treatment of pediatric CD, depending on individual medical institutions' circumstances. [ABSTRACT FROM AUTHOR]

Objective To screen out differential expressed genes (DEGs) of pediatric Crohn′s disease (PCD) by bioinformatics method, and to explore the pathogenesis of PCD, so as to provide a potential target for the diagnosis and treatment of PCD.Methods The microarray database GSE126124 of colon tissue of healthy controls and children with PCD was obtained from the gene expression omnibus data base (GEO) and DEGs was screened by the gene expression omnibus data base to R (GEO2R) .Then, using the DAVID database, the DEGs of PCD was analyzed by the gene ontology (GO) and the Kyoto encyclopedia of genes and genomes (KEGG) .The protein-protein interaction (PPI) was constructed using STRING database, and the first 24 core genes were identified by Cytoscape 3.9.1 software.Finally, the expression level of core genes was verified in GSE3365 gene chip database.Results A total of 141 DEGs were found in GSE126124 chip database, of which 39 were up-regulated and 102 were down-regulated.These DEGs were involved in immune regulation, intestinal adaptation, intestinal mucosal barrier function and other cellular activities and body regulation.A total of 24 potential core genes were screened from the PPI, and the expression differences were all significant in the validation databases, among which CXCL2 and IL-1β were the most significant.Conclusion Core genes such as CXCL2 and IL-1β are likely to be the the key genes of PCD, and may become potential targets for diagnosis and treatment of PCD. [ABSTRACT FROM AUTHOR]

Pediatric Crohn's disease (CD) presents a distinct phenotype from adult-onset disease. A dysregulated immune response is critical in CD pathogenesis; thus, it is clinically important to describe immune cell alterations and to identify a new molecular classification for pediatric CD. To this end, in this study, a RNA-seq derived dataset GSE101794—which contains the expression profiles of 254 treatment-naïve pediatric CD samples, including CIBERSORTx and weighted gene-co-expression network analysis (WGCNA)—were performed to estimate the ratio of immune cells and to identify modules and genes related to specific immune cell infiltration, respectively. Hub genes derived from WGCNA were further employed to create a molecular classification using unsupervised K-means clustering. In the pediatric CD samples, it was found that M2 macrophages, CD4+ memory resting T cells, CD8+ T cells, and resting mast cells were the most prominent immune cells in intestinal tissues. Then, 985 up-regulated genes and 860 down-regulated genes were identified in samples with high immune cell infiltration. Of these differential genes, 10 hub genes (APOA1, CYB5A, XPNPEP2, SLC1A7, SLC4A6, LIPE, G6PC, AGXT2, SLC13A1, and SOAT2) were associated with CD8+T cell infiltration. Clinically, the higher expression of these 10 hub genes was strongly associated with an earlier age of CD onset and colonic-type CD. Furthermore, based on these key genes, pediatric CD could be classified into three molecular subtypes, displaying a different immune landscape. Altogether, this in silico analysis provides a novel insight into the immune signature of pediatric CD, and a new classification of pediatric CD is presented, which may help us develop more personalized disease management and treatments for pediatric CD. [ABSTRACT FROM AUTHOR]

Introduction: Pediatric Crohn's disease is a chronic inflammatory condition that affects the digestive system in children and adolescents. It is characterized by symptoms such as abdominal pain, diarrhea, weight loss, and malnutrition, and can also cause complications like growth delays and delayed puberty. However, diagnosing pediatric Crohn's disease can be difficult, especially when it comes to non-invasive methods. Methods: In this study, we developed a diagnostic model using RNA-seq to analyze gene expression in ileal biopsy samples from children with Crohn's disease and non-pediatric Crohn's controls. Results: Our results showed that pediatric Crohn's disease is associated with altered expression of genes involved in immune response, inflammation, and tissue repair. We validated our findings using two independent datasets from the Gene Expression Omnibus (GEO) database, as well as through one prospective independent dataset, and found that our model had a high accuracy rate. Discussion: These findings suggest the possibility of non-invasive diagnosis for pediatric Crohn's disease and may inform the development of targeted therapies for this condition. [ABSTRACT FROM AUTHOR]

IntroductionDetermination of pediatric Crohn's disease (CD) remains a major diagnostic challenge. However, the rapidly emerging field of artificial intelligence has demonstrated promise in developing diagnostic models for intractable diseases.MethodsWe propose an artificial neural network model of 8 gene markers identified by 4 classification algorithms based on Gene Expression Omnibus database for diagnostic of pediatric CD.ResultsThe model achieved over 85% accuracy and area under ROC curve value in both training set and testing set for diagnosing pediatric CD. Additionally, immune infiltration analysis was performed to address why these markers can be integrated to develop a diagnostic model.ConclusionThis study supports further clinical facilitation of precise disease diagnosis by integrating genomics and machine learning algorithms in open-access database.

Aim: To evaluate the performance of the multiple imputation (MI) method for estimating clinical effectiveness in pediatric Crohn’s disease in the ImproveCareNow registry; to address the analytical challenge of missing data. Materials & methods: Simulation studies were performed by creating missing datasets based on fully observed data from patients with moderate-to-severe Crohn’s disease treated with non-ustekinumab biologics. MI was used to impute sPCDAI remission statuses in each simulated dataset. Results: The true remission rate (75.1% [95% CI: 72.6%, 77.5%]) was underestimated without imputation (72.6% [71.8%, 73.3%]). With MI, the estimate was 74.8% (74.4%, 75.2%). Conclusion: MI reduced nonresponse bias and improved the validity, reliability, and efficiency of real-world registry data to estimate remission rate in pediatric patients with Crohn’s disease.

Objectives: We aimed to evaluate the frequency of extraintestinal manifestations (EIM) in children with inflammatory bowel disease (IBD) and the correlation of EIM with disease activity index, disease type and disease age. Methods: Records of patients who were under the 18 years of age and followed up with the diagnosis of IBD were included in the study. The demographic characteristics of the patients, the age of the patients, the sex of the patients, the type of disease and the age of the disease were recorded. When patients were enrolled in the study disease activity indexes were calculated by examining the physical examination and laboratory values of the patients in their last visits, by using the Pediatric Ulcerative Colitis Activity Index (PUCAI) in Ulcerative Colitis (UC) and the Pediatric Crohn's Disease Activity Index (PCDAI) in Crohn's Disease (CD). Results: It was conducted with a total of 44 patients, 40.9% (n=18) females and 59.1% (n=26) males diagnosed with IBD. The ages of the patients participating in the study ranged from 8 to 19 and the mean was found to be 14.64±3.19 years. According to the type of disease; 27.3% of the patients were CD and 72.7% were UC. When the disease activity is examined; 37.2% were in remission, 37.2% were mild, 16.3% moderate and 9.3% severe. The incidence of EIM in females is 77.8% and 65.4% in males. The incidence of EIM is 75% in CD and 68.8% in UC. Hepatobiliary involvement was detected in 41.5% (n=17) of the patients, joint involvement in 29.5% (n=13), osteopenia in bone in 16.3% (n=7), osteoporosis in 7% (n=3), ocular involvement (uveitis) in 2.3% (n=1) and skin involvement (erythema nodosum) in 2.3% (n=1). Conclusion: EIM are common in childhood IBD patients. It should be kept in mind that EIM are as common in UC as CD. [ABSTRACT FROM AUTHOR]

Cross-sectional imaging is important in the assessment of transmural inflammation in Crohn's disease (CD). Small bowel involvement is often more extensive in pediatric CD, requiring a panentering measuring tool. We undertook to develop a magnetic resonance enterography (MRE)-based index that would measure inflammation in all segments of the intestine, without rectal contrast. Children with CD underwent ileocolonoscopy and MRE and half were prospectively followed for 18 months when MRE was repeated. Item generation and reduction were performed by a Delphi panel of pediatric radiologists, a systematic literature review, a cross-sectional study of 48 MREs, and a steering committee. Formatting and weighting were performed using multivariate modeling adjusted by a steering committee. MREs were read locally and centrally. Reliability, validity, and responsiveness were determined using several clinimetric and psychometric approaches. Thirty items were initially generated and reduced to 5 using regression analysis on 159 MREs: wall thickness, wall diffusion weighted imaging, ulcerations, mesenteric edema, and comb sign. In the validation cohort of 81 MREs, the weighted global PICMI correlated well with the radiologist global assessment (r = 0.85; P <.001) and with the simple endoscopic score in a subsample with ileocolonic disease (r = 0.63; P <.001). Interobserver and test-retest reliability were high (interclass correlation coefficients, 0.84; 95% confidence interval [CI], 0.79–0.87; and 0.81, 95% CI, 0.65–0.90, respectively; both P <.001). Excellent responsiveness was found at repeated visits (n = 116 MREs; area under the receiver operating characteristic curve 0.96; 95% CI, 0.93–0.99). Transmural healing was defined as PICMI ≤10 and response as a change of >20 points with excellent discriminative validity (area under the receiver operating characteristic curve = 0.96; 95% CI, 0.93–0.99). The PICMI is a valid, reliable, and responsive index for assessing transmural inflammation in pediatric CD. It scores the entire bowel length and does not require intravenous contrast or rectal enema and, therefore, is suitable for use in children. (ClinicalTrials.gov , Number: NCT01881490.) [Display omitted] We have developed a validated score, called the Pediatric Inflammatory Crohn's Magnetic Resonance Enterography Index, which quantifies the degree of inflammation in the bowel of children with Crohn's disease, as measured using magnetic resonance imaging of the bowel. [ABSTRACT FROM AUTHOR]

Abstract Background Few published data describe how joint involvement, the most prevalent extraintestinal manifestation, affects quality of life (QoL) of children with Crohn’s disease (CD). Arthritis and arthralgia rates in pediatric CD patients are reportedly 3–24% and 17–22%, respectively, but studies on pre-emptive and systematic screening of joint involvement with detailed musculoskeletal rheumatological exam are lacking. More detailed data collection on joint involvement improves our understanding of how arthropathy relates to disease activity and QoL measured by the Pediatric CD Activity Index (PCDAI) and IMPACT-III questionnaire. Our study aims were to assess joint involvement in pediatric CD and correlate it with the PCDAI and IMPACT-III. Methods In this cross-sectional, observational study, a pediatric gastroenterologist assessed consecutively-seen pediatric CD patients at a tertiary care center. Patients were screened for prevalence of current and previous arthropathy, including arthritis, enthesitis and arthralgia. A single experienced pediatric rheumatologist evaluated detailed musculoskeletal history, joint status, and modified Juvenile Arthritis Multidimensional Assessment Reports (JAMAR). PCDAI, IMPACT-III, sacroiliac MRI, and HLA-B27 genetic testing were also completed. Results A total of 82 (male:female, 1.2:1; age, 13.7 ± 3.2 years) patients were involved in this study. Mean disease duration at time of study was 21.6 ± 21 months; eight of the patients were newly-diagnosed. Of the 82 patients, 29 (35%) had evidence of arthritis; for 24 of those, this was revealed by physical exam during cross-sectional screening, and by prior documentation for the remaining five patients. Joint examination confirmed active arthritis in 8/24 (33%), active enthesitis in 1/24 (4%), and evidence of previous arthritis in 15/24 (62.5%) patients. Hip (41%) and knee (38%) joints were most commonly affected. Cumulative incidence of arthralgia was 48% (39/82), and 46% (18/39) of those patients had only arthralgia without arthritis, usually affecting the knee. Axial involvement was present in 10/82 (12%) patients. Joint involvement correlated with more severe CD disease activity, specifically higher PCDAI and lower IMPACT-III scores, and increased requirement for infliximab treatment. Sacroiliitis and HLA-B27 positivity were insignificant factors in this cohort. Conclusions When a rheumatologist performed the assessment, joint involvement in pediatric CD was more prevalent than previously reported, in this cross-sectional study. Arthritis was associated with more severe CD disease activity and lower QoL.

Background: The combination of antitumor necrosis factor-alpha (TNF-α) agents with immunomodulators (IMMs) is a common treatment for pediatric Crohn’s disease (CD). Although methotrexate (MTX) can be a first-line medication as an IMM, most clinicians in real-life practice, especially in South Korea, are more familiar with thiopurines. This study aimed to compare the efficacy and immunogenicity of MTX and azathioprine (AZA) as concurrent therapies for pediatric CD. Methods: In this pilot study, 29 newly diagnosed pediatric patients with moderate-to-severe CD were randomized to receive either MTX (n = 15) (15 mg/body surface area (BSA) per week) or oral AZA (n = 14) (0.5 mg/kg per day) in combination with Infliximab (IFX). The primary outcomes were the proportion of patients in endoscopic, biochemical, and transmural remission after 14 and 54 weeks of IFX therapy. The trough levels (TLs) of IFX and anti-drug antibody (ADA) levels were also compared. Results: Among the 29 patients, there were no significant differences in the biochemical (p = 1.0 at week 14, p = 0.45 at week 54), endoscopic (p = 0.968 at week 14, p = 0.05 at week 54), or transmural (p = 0.103 at week 54) remission rates between the two medications during the concurrent therapy. Additionally, the trends in the IFX trough and ADA levels over time during the treatments were similar for both medications, with no significant differences (p = 0.686, p = 0.389, respectively). Conclusion: The MTX showed comparable efficacy to the AZA in pediatric CD patients with moderate-to-severe disease. This effectively maintained adequate IFX levels and reduced ADA production. Therefore, although additional large-scale clinical trials are needed, this study demonstrated that either MTX or AZA can be selected as IMMs in the concurrent treatment of pediatric CD, depending on individual medical institutions’ circumstances.

Anemia is the most common extraintestinal manifestation and complication of inflammatory bowel disease (IBD). The aim of our study was to assess the prevalence of anemia in newly diagnosed pediatric patients with IBD and to analyze its association with disease type, extent, and severity. We retrospectively reviewed the medical records of all patients with IBD treated in our department in the period of November 2011 to November 2020. The final analysis included the records of 80 children with newly diagnosed IBD: 45 with ulcerative colitis (UC) and 35 with Crohn’s disease (CD). The prevalence of anemia was 60.0% in the UC patients and 77.1% in the CD patients. Of the UC patients with anemia, 37.1% had pancolitis, 18.5% extensive disease, 33.3% left-sided colitis and 11.1% ulcerative proctitis. Of the CD patients with anemia, 81.5% had ileocolonic disease, 11.1% colonic disease and 7.4% ileal disease. Anemia was less common in patients with mild disease than in patients with moderate–severe disease (22.2 vs. 77.8%, p < 0.001 in UC and 25.9% vs. 74.1%, p < 0.001 in CD). Our study confirmed anemia as a frequent problem in pediatric patients with IBD. Children with more extensive and more severe disease are at higher risk to develop anemia.

Pediatric-onset inflammatory bowel disease differs from adults in its epidemiological and clinical characteristics and courses. Since it is diagnosed at a young age, the duration of the disease is relatively longer than in adults. Therefore, it is necessary to select drugs in consideration of long-term risks and benefits, and efforts such as therapeutic drug monitoring to maximize the treatment effects and minimize side effects are required. In addition, special considerations for treating pediatric-onset inflammatory bowel disease include attention to the effects of the disease on growth and development, nutrition, and psychosocial problems. In children, more aggressive treatment is needed to avoid missing therapeutic window of opportunity during periods of rapid growth and development. Finally, efforts should be made to ensure that the therapeutic goals of mucosal healing are achieved, the quality of life is restored, and the transition to adult therapy is well carried out.

Objective: Pediatric Crohn's disease (CD) has a more aggressive phenotype and course than in adults. Many patients develop complications that require surgery. The aim of this study was to identify the factors associated with increased risk for surgical intervention in pediatric patients with CD.Subjects and Methods: This study is a retrospective review of medical records. We analyzed the following variables: sex, age at diagnosis, presenting symptoms, duration of symptoms before diagnosis, disease location and severity, the presence of extraintestinal manifestations, and the presence of anti-Saccharomyces cerevisiae antibodies. Univariate analysis using the Mann-Whitney test and Fisher's exact test was performed to detect the factors associated with surgery. Potential risk factors with p < 0.05 were further analyzed using a multivariate binary logistic regression model.Results: Fifty-seven patients (27 girls and 30 boys) were included in the analysis. More than one-fourth of them (28.1%) required surgical management. Female sex (p = 0.043), disease behavior (p = 0.012), and the presence of perianal disease at diagnosis (p < 0.001) were the variables associated with surgical intervention. Stricturing disease (B2) (odds ratio [OR], 24.944; p = 0.016), stricturing and penetrating disease (B2B3) (OR, 28.276; p = 0.011), and the presence of perianal disease at diagnosis (OR, 95.802; p = 0.001) were independent risk factors for surgery. Female sex was associated with surgery without being an independent risk factor.Conclusion: Females with B2 or B2B3 or the presence of perianal disease at diagnosis are at a higher risk for surgery and should be considered for more aggressive medical treatments. [ABSTRACT FROM AUTHOR]

Aim To compare the diagnostic yield of small intestinal contrast ultrasonography (SICUS) with magnetic resonance enterography (MRE) in routine clinical practice in a cohort of pediatric patients investigated for Crohn's disease (CD) attending a UK tertiary center. Methods and Results Patients with suspected or established CD who underwent SICUS were identified retrospectively. SICUS was compared to conventional transabdominal ultrasound (TUS), ileocolonoscopy (IC), and MRE. The accuracy and agreement of SICUS in detecting small bowel lesions and CD‐related complications were assessed using kappa (κ) coefficient statistics. A total of 93 patients (median age 15 years, range 2–17, 49 male) underwent SICUS; 58 had suspected and 35 had established CD. In suspected CD, sensitivity and specificity of SICUS in detecting CD small bowel lesions were 81.8 and 100% and for TUS 85.7 and 87.5%, respectively. In established CD, sensitivity and specificity of SICUS were 98.7 and 100% and TUS 80 and 100%, respectively. Agreement between SICUS and IC was substantial for the presence of lesions (κ = 0.73) but fair in TUS (κ = 0.31). Agreement between SICUS and IC was almost perfect for detecting strictures (κ = 0.84), with a sensitivity of 100% and specificity of 97.6%. When comparing SICUS and TUS with MRE, agreement for the presence of lesions was substantial (κ = 0.63) and moderate (κ = 0.53), respectively. Agreement between SICUS and MRE was substantial for detecting strictures (κ = 0.77) and dilatation (κ = 0.68). Conclusions SICUS offers a radiation‐free alternative for assessing pediatric small bowel CD, with diagnostic accuracy that is comparable to MRE and IC, supporting its wider use in routine practice.

Background: Few published data describe how joint involvement, the most prevalent extraintestinal manifestation, affects quality of life (QoL) of children with Crohn's disease (CD). Arthritis and arthralgia rates in pediatric CD patients are reportedly 3–24% and 17–22%, respectively, but studies on pre-emptive and systematic screening of joint involvement with detailed musculoskeletal rheumatological exam are lacking. More detailed data collection on joint involvement improves our understanding of how arthropathy relates to disease activity and QoL measured by the Pediatric CD Activity Index (PCDAI) and IMPACT-III questionnaire. Our study aims were to assess joint involvement in pediatric CD and correlate it with the PCDAI and IMPACT-III. Methods: In this cross-sectional, observational study, a pediatric gastroenterologist assessed consecutively-seen pediatric CD patients at a tertiary care center. Patients were screened for prevalence of current and previous arthropathy, including arthritis, enthesitis and arthralgia. A single experienced pediatric rheumatologist evaluated detailed musculoskeletal history, joint status, and modified Juvenile Arthritis Multidimensional Assessment Reports (JAMAR). PCDAI, IMPACT-III, sacroiliac MRI, and HLA-B27 genetic testing were also completed. Results: A total of 82 (male:female, 1.2:1; age, 13.7 ± 3.2 years) patients were involved in this study. Mean disease duration at time of study was 21.6 ± 21 months; eight of the patients were newly-diagnosed. Of the 82 patients, 29 (35%) had evidence of arthritis; for 24 of those, this was revealed by physical exam during cross-sectional screening, and by prior documentation for the remaining five patients. Joint examination confirmed active arthritis in 8/24 (33%), active enthesitis in 1/24 (4%), and evidence of previous arthritis in 15/24 (62.5%) patients. Hip (41%) and knee (38%) joints were most commonly affected. Cumulative incidence of arthralgia was 48% (39/82), and 46% (18/39) of those patients had only arthralgia without arthritis, usually affecting the knee. Axial involvement was present in 10/82 (12%) patients. Joint involvement correlated with more severe CD disease activity, specifically higher PCDAI and lower IMPACT-III scores, and increased requirement for infliximab treatment. Sacroiliitis and HLA-B27 positivity were insignificant factors in this cohort. Conclusions: When a rheumatologist performed the assessment, joint involvement in pediatric CD was more prevalent than previously reported, in this cross-sectional study. Arthritis was associated with more severe CD disease activity and lower QoL. [ABSTRACT FROM AUTHOR]

Background and Aims: Intensifying therapy for Paediatric Crohn's Disease (CD) by early use of immunomodulators and biologics has been proposed for cases in which predictors of poor outcome (POPO) were present. We investigated therapy stratifying potential comparing POPO-positive and -negative CD patients from CEDATA-GPGE®, a German-Austrian Registry for Paediatric Inflammatory Bowel disease.Methods: CD patients (1–18 years) registered in CEDATA-GPGE® (2004–2018) within 3 months of diagnosis and at least two follow-up visits were included. Disease course and treatments over time were analysed regarding positivity of POPO criteria and test statistical properties.Results: 709/1084 patients included had at least one POPO criterion (65.4%): 177 patients (16.3%) had persistent disease (POPO2), 581 (53.6%) extensive disease (POPO3), 21 (1.9%) severe growth retardation POPO4, 47 (4.3%) stricturing/penetrating disease (POPO6) and 122 (11.3%) perianal disease (POPO7). Patients with persistent disease differed significantly in lack of sustained remission >1 year (Odd Ratio (OR) 1.49 [1.07–2.07], p = 0.02), patients with initial growth failure in growth failure at end of observation (OR 51.16 [19.89–131.62], p < 0.0001), patients with stricturing and penetrating disease as well as perianal disease in need for surgery (OR 17.76 [9.39–33.58], p < 0.001; OR 2.56 [1.58–4.15], p < 0.001, respectively). Positive Predictive Value for lack of sustained remission was >60% for patients with initial growth failure, persistent or stricturing/penetrating disease.Conclusion: Predictors of poor outcome with complicated courses of disease were common in CEDATA-GPGE®. An early intensified approach for paediatric CD patients with POPO-positivity (POPO2-4, 6-7) should be considered, because they have an increased risk to fare poorly.

Introduction: The incidence of early-onset inflammatory bowel disease is increasing in Japan. Objective: This study aimed to analyze the treatment and progress of early-onset inflammatory bowel disease. Methods: This prospective survey evaluated the data of 43 patients aged <8 years who were diagnosed with inflammatory bowel disease (IBD) from the time of diagnosis to 36 months after registration. Results: A total of 12 patients with Crohn's disease (CD), 21 with ulcerative colitis (UC), and 3 with unclassified IBD were enrolled. The mean disease onset age was 3 years and 7 months. Colon and anal lesions were present in 100 and 50% of patients with CD, respectively. Granulomas were detected in 5 patients (41.7%). Dietary elimination including elemental diet was performed in all patients. Eleven patients (91.7%) were in remission by initial induction therapy, and 72.7% maintained remission for 36 months. Three patients (14.3%) with UC had familial history, 71.4% had pancolitis-type UC, and 66.7% exhibited disease of moderate severity. Colectomy was performed in 4 patients (21.1%). Eighteen patients (85.7%) were in remission by initial induction therapy; however, only 15.8% maintained remission for 36 months. Anal complication was more prevalent in infantile-onset IBD than in childhood-onset IBD (p = 0.014). Conclusions: Among Japanese patients aged <8 years who were diagnosed with IBD, colitis-type disease was more common in CD and pancolitis was more common in UC. As the courses of several patients were severe, identifying primary immunodeficiency appears to be necessary to confirm background disease. [ABSTRACT FROM AUTHOR]

Aim: To compare the diagnostic yield of small intestinal contrast ultrasonography (SICUS) with magnetic resonance enterography (MRE) in routine clinical practice in a cohort of pediatric patients investigated for Crohn's disease (CD) attending a UK tertiary center. Methods and Results: Patients with suspected or established CD who underwent SICUS were identified retrospectively. SICUS was compared to conventional transabdominal ultrasound (TUS), ileocolonoscopy (IC), and MRE. The accuracy and agreement of SICUS in detecting small bowel lesions and CD‐related complications were assessed using kappa (κ) coefficient statistics. A total of 93 patients (median age 15 years, range 2–17, 49 male) underwent SICUS; 58 had suspected and 35 had established CD. In suspected CD, sensitivity and specificity of SICUS in detecting CD small bowel lesions were 81.8 and 100% and for TUS 85.7 and 87.5%, respectively. In established CD, sensitivity and specificity of SICUS were 98.7 and 100% and TUS 80 and 100%, respectively. Agreement between SICUS and IC was substantial for the presence of lesions (κ = 0.73) but fair in TUS (κ = 0.31). Agreement between SICUS and IC was almost perfect for detecting strictures (κ = 0.84), with a sensitivity of 100% and specificity of 97.6%. When comparing SICUS and TUS with MRE, agreement for the presence of lesions was substantial (κ = 0.63) and moderate (κ = 0.53), respectively. Agreement between SICUS and MRE was substantial for detecting strictures (κ = 0.77) and dilatation (κ = 0.68). Conclusions: SICUS offers a radiation‐free alternative for assessing pediatric small bowel CD, with diagnostic accuracy that is comparable to MRE and IC, supporting its wider use in routine practice. [ABSTRACT FROM AUTHOR]

Objective: To study the clinical and nutritional characteristics of early‐onset Crohn's disease (EO‐CD) in China. Methods: Patients were defined as having EO‐CD (age at diagnosis <10 y) or late‐onset Crohn's disease (LO‐CD; age at diagnosis of 10‐17 y). Their characteristics, clinical, and nutritional data were collected at baseline and at each follow‐up visit. Statistical analyses were used to compare differences in both groups. Results: From July 1993 to February 2017, of the 137 children enrolled, 68 (49.6%) had EO‐CD and 69 (50.4%) had LO‐CD. More patients with EO‐CD than those with LO‐CD presented with diarrhea, hematochezia, growth delay, anemia and skin disease, and had higher pediatric Crohn's disease activity index scores at diagnosis (all P < 0.05). Fewer patients with EO‐CD achieved their first remission (42.6% vs 76.8%, P < 0.0001) during follow‐up. Patients with EO‐CD required a longer treatment time to reach remission (P = 0.0049) and had a higher mortality rate (P = 0.0133), as well as lower height and weight percentiles (P = 0.0200 and 0.0288, respectively), hemoglobin (P = 0.0185) and albumin levels (P = 0.0002), zinc (P = 0.0024) and iron (P = 0.0110) concentrations in blood at diagnosis. Conclusion: The EO‐CD group had worse clinical outcomes and nutritional status than the LO‐CD group. [ABSTRACT FROM AUTHOR]

Background: Adalimumab (Ada) treatment is an available option for pediatric Crohn's disease (CD) and the published experience as rescue therapy is limited. Objectives: We investigated Ada efficacy in a retrospective, pediatric CD cohort who had failed previous infliximab treatment, with a minimum follow-up of 6 months. Methods: In this multicenter study, data on demographics, clinical activity, growth, laboratory values (CRP) and adverse events were collected from CD patients during follow-up. Clinical remission (CR) and response were defined with Pediatric CD Activity Index (PCDAI) score ≤10 and a decrease in PCDAI score of ≥12.5 from baseline, respectively. Results: A total of 44 patients were consecutively recruited (mean age 14.8 years): 34 of 44 (77%) had active disease (mean PCDAI score 24.5) at the time of Ada administration, with a mean disease duration of 3.4 (range 0.3–11.2) years. At 6, 12, and 18 months, out of the total of the enrolled population, CR rates were 55%, 78%, and 52%, respectively, with a significant decrease in PCDAI scores (P<0.01) and mean CRP values (mean CRP 5.7 and 2.4 mL/dL, respectively; P<0.01) at the end of follow-up. Steroid-free remission rates, considered as the total number of patients in CR who were not using steroids at the end of this study, were 93%, 95%, and 96% in 44 patients at 6, 12, and 18 months, respectively. No significant differences in growth parameters were detected. In univariate analysis of variables related to Ada efficacy, we found that only a disease duration >2 years was negatively correlated with final PCDAI score (P<0.01). Two serious adverse events were recorded: 1 meningitis and 1 medulloblastoma. Conclusion: Our data confirm Ada efficacy in pediatric patients as second-line biological therapy after infliximab failure. Longer-term prospective data are warranted to define general effectiveness and safety in pediatric CD patients. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Epidemiological studies on pediatric‐onset inflammatory bowel disease (PIBD) are scarce in South–East Asia (SEA). This study aimed to evaluate the incidence trend and clinical characteristics of PIBD in a SEA cohort in Singapore over 22 years (1994–2015). METHODS: Case records of PIBD ≤18 years from the only two tertiary pediatric hospitals in Singapore were reviewed. The mean annual incidence (MAI) of PIBD was calculated based on Singapore's age‐specific population data. RESULTS: Overall MAI of PIBD was 1.26 per 100 000 (95% confidence interval [CI] 0.56–1.96). During the first decade (1994‐2004) MAI was 0.23 per 100 000 (95% CI 0.08–0.39); this rose almost 10‐fold to 2.28 per 100 000 (95% CI 1.15–3.41) during the second decade (2005–2015). Linear regression analysis showed significant increase in MAI over the 22‐year period (r = 0.826, P < 0001). Of the 228 patients, 61.0% had Crohn's disease (CD), 30.3% ulcerative colitis and 8.7% IBD‐unclassified, with a mdian age at diagnosis of 10.47 years and a male predominance (58.3%); 37.7% of them aged <10 years at diagnosis and 17.5% were very early‐onset IBD. In CD, 27.3% had stricturing and/or penetrating disease and 21.6% were with perianal disease. Indians had a disproportionately high representation while positive family history was rare (1.3%). CONCLUSIONS: Although PIBD is uncommon in Singapore, its incidence has risen dramatically over recent decades. A younger age of disease onset and higher proportions of perianal and stricturing/penetrating diseases suggest more aggressive disease than in Western data. [ABSTRACT FROM AUTHOR]

Background Free intestinal perforation in children with Crohn's disease (CD) is a rare, but serious complication that requires urgent surgical management. The incidence, contributing risk factors, diagnostic workup, and management strategies for these complex pediatric patients are not well established. Methods We present a recent case of free intestinal perforation in a patient with CD. In addition, a systematic review of the literature was conducted by searching the PubMed, Embase, Ovid, Scopus and Cochrane databases. Two authors independently extracted data, reviewed the abstracts, and assessed them for inclusion in the review. Results The literature review identified 21 pediatric patients documented in 14 publications; including our case, there are a total of 22 pediatric patients reported. The majority of patients presented with features of peritonitis. Perforation occurred early in the disease course (median 6.5 months), and was most commonly a single perforation in the ileum with active Crohn's disease (82%). Colonic perforation occurred in 18% of patients. All patients underwent urgent surgical management. Surgical approaches included resection of the diseased bowel segment with proximal diversion in eleven patients (50%), resection with primary anastomosis in 9 (41%) or direct suture repair in two (9%). Both patients who underwent simple primary repair developed post-operative complications. Conclusions Free intestinal perforation may occur at any age and stage of Crohn's disease. Three-dimensional imaging may be required to confirm the diagnosis. The management of free intestinal perforation in CD is surgical. This should involve resection of the involved segment with proximal diversion or resection with primary anastomosis in selected cases. Primary suture closure of the perforation is discouraged. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study is to report a systematic review (from 2000 to 2017) of all pediatric cases of vulvar Crohn's disease (VCD) and to highlight the key-points for a correct diagnosis and management of this rare condition.Methods: An electronic search using the Pubmed/Medline, Scopus, EMBASE, Cochrane database and Google Scholar database was performed according to PRISMA guidelines.Results: Twenty pediatric studies and 22 cases of VCD were included for analysis. All the articles reported a single case, except two articles where two cases, respectively, are described. Clinical vulvar examination showed the following main manifestations: vulvar erythema (9/22 cases, 40.9%), vulvar swelling (8/22 cases, 36.4%), vulvar edema (8/22 cases, 36.4%), vulvar ulcers (4/22 cases, 18.2%). Perianal and/or anal involvement (fissures, vegetations, skin tags, erythema, papules, nodules) were recorded in ten cases (45.4%). Steroids per os and/or topical administration were the most prescribed treatment, achieving clinical remission in 11 cases (50%), used alone or in combination with metronidazole or 5-aminosalicylic acid, azathioprine or sulphasalazine/mesalazine.Conclusions: This review shows that pediatric VCD is an uncommon disease, difficult to be diagnosed as either symptoms or clinical lesions are not specific. A multidisciplinary approach is advised to reach a correct diagnosis and plan clinical treatment. [ABSTRACT FROM AUTHOR]

Objective: These studies evaluated the safety and efficacy of enteric-coated budesonide for the induction and maintenance of remission of mild-to-moderate Crohn's disease (CD) in children.Methods: The consecutive, multicenter, open-label, non-comparative studies enrolled patients aged 6-17 years. In the induction study, patients with active CD of the ileum and/or ascending colon received budesonide 9 mg or 6 mg once daily for 8 weeks; in the maintenance study, patients in remission received budesonide 6 mg once daily for 12 weeks. The primary objective was assessment of safety, including glucocorticosteroid-related side effects and serum cortisol levels. Efficacy was assessed using the Pediatric Crohn's Disease Activity Index (PCDAI), and health-related quality of life (HRQoL) using the IMPACT-III questionnaire.Results: In the induction study (n = 108), most adverse events were related to CD, commonly abdominal pain; possible glucocorticosteroid-related effects included acne and increased appetite but without significant weight gain. Subnormal morning cortisol levels were observed in 32 of 103 patients after 8 weeks. Budesonide reduced disease activity from baseline (mean ± standard deviation, 9.1 ± 8.5 vs. 19.1 ± 10.1, p < .001) with 58.1% of patients reaching remission (PCDAI <10); HRQoL improved (p < .001). In the maintenance study (n = 50), mean disease activity worsened (p = .047) with HRQoL unchanged (p = .33).Conclusions: Budesonide treatment was generally well tolerated, although the potential for adrenal suppression was noted. Budesonide was effective for induction of remission in children with mild-to-moderate CD but not for maintaining remission (ClinicalTrials.gov identifiers: NCT01444092, NCT01453946). [ABSTRACT FROM AUTHOR]

Purpose: Vitamin D deficiency is common in Crohn disease (CD). The aim of the study was to examine the prevalence of vitamin D deficiency and evaluate the association between vitamin D status and growth outcome in Korean pediatric CD patients. Methods: In this retrospective study, 17 children younger than 18 years old diagnosed with CD were enrolled and their serum 25-hydroxy vitamin D (25[OH]D) was checked between 2011 and 2015. We categorized the patients into two groups, Group 1 and Group 2. Group 1 included patients with serum 25(OH)D levels below 10 ng/mL, and Group 2 was for patients with a 25(OH)D serum levels between 10 ng/mL and 30 ng/mL. The z-scores for height (Htz), weight (Wtz), and body mass index (BMIz) were measured at baseline, 6 months, and 12 months. Results: The mean serum 25(OH)D levels of the total 65 CD patients and 17 enrolled patients were 15.64±6.9 ng/mL and 13.1±5.1 ng/mL , respectively. There was no correlation at the beginning of the study between vitamin D level and growth parameters (Htz, Wtz, BMIz) or other variables including laboratory data and Pediatric Crohn Disease Activity Index. The Htz, Wtz, and BMIz in Group 1 showed no significant improvement at 6 months and 12 months follow-up. In Group 2, Wtz and BMIz showed significant improvements sustained until 12 months of follow-up. Htz showed no significant improvement at 6 months but there was significant improvement at 12 months. Conclusion: It seems that baseline vitamin D status affects growth outcome in pediatric CD. [ABSTRACT FROM AUTHOR]

Background and aims:Increasing evidence in adults demonstrates efficacy and safety of IV iron in inflammatory Bowel disease (IBD) associated iron deficiency anemia; however, evidence in pediatric patients is yet scarce and no previous study has included a long follow-up. This study aimed to evaluate safety and efficacy of IV iron (primary end point), and the need of re-treatment (secondary end point), in this setting. Methods:Prospective recruitment (40 months); PCDAI determined before and after treatment; anemia defined according to WHO criteria; IV iron treatment included iron sucrose and ferric carboxymaltose. Primary and secondary endpoints included hemoglobin, serum ferritin, transferrin saturation at baseline and 4-6 weeks after treatment; and the need of re-treatment during the median follow-up period (18 months), respectively. Results:Nineteen patients (median age: 15.5 years) with remissive/mild disease were included. At recruitment, the median hemoglobin was 10.5 g/dl, (median s-ferritin: 20.1 ug/l, median transferrin saturation; 6%) and 4-6 weeks after treatment was 12.7 g/dl. Median hemoglobin according to age groups before vs. after treatment: <12 years:11 vs. 12.0 g/dl; females ≥12 years:9.9 vs. 12.6 g/dl; and males ≥12 years:11.1 vs. 13.3 g/dl. Patients with remissive vs. mild disease had median Hb of 10.5 g/dl vs. 10.6 g/dl, and median s-ferritin: 6.8 ug/dl vs. 43.3 ug/dl, respectively). Nine patients were treated with iron sucrose (median dose 672.6 mg/dl) and 10 patients with ferric carboxymaltose (median dose 811.5 mg/dl). No major adverse reactions occurred. Six patients needed re-treatment after a median 15.5 months period. Conclusions:Our prospective study, concerning pediatric IBD anemia patients with remission/mild disease and a significant follow-up, emphasizes efficacy and safety of IV-iron and the importance of long-term follow-up of iron status. Summary:In pediatric IBD iron anemia, the evidence supporting the efficacy and safety of IV-iron is scare. This prospective study aims to evaluate the safety and efficacy (short and long term) of IV-iron in these patients. Nineteen pediatric CD patients were evaluated before and after IV iron treatment (40-month period).The median Hb before and after IV iron was 10.5 and 12.7 g/dl, respectively. No major adverse reactions were documented. Six patients needed re-treatment (median period of 15.5 months). This study further demonstrates the efficacy and safety of IV iron. It reinforces the importance of long-term follow-up of the iron status in pediatric CD patients. [ABSTRACT FROM PUBLISHER]

Gastrointestinal system diseases significantly affect physical and emotional development of child and vary from simple absorbsion disturbance to severe malabsorbsion. Early diagnosis and treatment play important role because direct affect of these diseases on growth development. Many of these diseases damage enterocytes, enteric nerve system cells, smooth muscle cells (myocytes) or interstitial Cajal cells (ICCs). Gastrointestinal system diseases usually have multifactorial and polygenic inheritance except some diseases such as cystic fibrosis and familial polyposis coli. Recent years, new genetic methods, next generation sequencing and exom sequencing, have started to illuminate genetic etiology of polygenic diseases. Inherited diseases related chronical problems in childhood period are important because of many of them require hospitalization. Genetic tests may help to certain diagnosis and prediction of the clinical problems of an inherited disease. Recently, many medical therapy options have been tried according to genetic etiology. In next years, when genetic etiology of gastrointestinal diseases explore, personalised medical therapy might be performed. In this review we aimed to update information about frequently seen pediatric gastrointaestinal diseases and genetics reasons of these diseases which are heterogenous and multifactorial. By this way, some informations were given for planning some gene panels which can be beneficial for diagnosis, and useful notions were emphasized for genetic counselling. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to investigate the efficacy and safety of adalimumab in pediatric-onset Crohn's disease patients who had failed treatment with infliximab. Methods: In this retrospective study, patients included were those who had been diagnosed with Crohn's disease before 18 years old, and had received treatment with adalimumab after infliximab failure. The efficacy of adalimumab treatment was investigated at 1 month and 1 year, and adverse events that had occurred during treatment with adalimumab were explored. Results: Ten patients were included in this study. The median duration from diagnosis to adalimumab treatment was 5.5 years (range: 2.4-7.9 years). At 1 month after adalimumab initiation, 80% (8/10) of patients showed clinical response, and 40% (4/10) achieved clinical remission. At 1 year, 71% (5/7) of patients showed clinical response, and 43% (3/7) were under clinical remission. Among the total included patients, 5 patients (50%) showed clinical response at 1 year. Primary non-response to adalimumab was observed in 2 patients (20%), and secondary failure to adalimumab was observed in 3 patients (30%) during 1 year treatment with adalimumab. No serious adverse event had occurred during adalimumab treatment. Conclusion: Adalimumab was effective for 1 year without serious adverse events in half of pediatric-onset Crohn's disease patients who had failed treatment with infliximab. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases are characterized by a chronic relapsing course, high morbidity and impaired quality of life. Their incidence is rising, and about 25% of cases are diagnosed in pediatric age. Anti-TNF-α antibodies, such as infliximab and adalimumab (ADA), are usually administered in patients refractory to conventional therapies. However, increasing evidence suggests that they can be introduced earlier in the course of the disease, especially in patients with aggressive and extensive disease since diagnosis. ADA is a fully human anti-TNF-α antibody recently approved for pediatric Crohn’s disease not only in patients unresponsive to infliximab, but also as a first-line anti-TNF-α therapy. In this review, we aim to summarize the current knowledge on the use of ADA in pediatric Crohn’s disease and to discuss open issues regarding safety as well as future perspectives. [ABSTRACT FROM AUTHOR]

Background and aims Treatment of complex perianal fistulas associated with Crohn's disease is challenging. In adults, seton drainage combined with infliximab therapy has proven to be more effective than either one alone. Results following such treatment among pediatric patients have not been reported previously. The aim of this study was to describe outcomes after combined seton and infliximab treatment for complex perianal fistulas in adolescents with Crohn's disease. Methods We performed a retrospective medical record review of all consecutive Crohn's disease patients treated for perianal fistulas with seton drainage and infliximab between 2007 and 2013 (n = 13). A follow-up interview was conducted at median of two years. Results Median age at fistula diagnosis was 14 years. Following seton placement in fistula tracks, infliximab induction was administered at weeks 0, 2, and 6 and maintenance therapy at 8-week intervals. Over 90% responded to seton drainage and infliximab induction. Final fistula response was obtained at median of 8 weeks, being complete in 77% and partial in 15%. Setons were kept in place for median of 8 months. Fistulas recurred in 23% over a year after the final response. At last follow-up, 85% still had a response and 70% were free from perianal symptoms. Most were still on anti-TNF-α therapy, but one third had switched to adalimumab. Patients' anorectal function was well preserved and overall satisfaction with the treatment was high. Conclusions The results suggest that combining seton drainage with infliximab therapy improves the perianal fistula response rates in pediatric patients. [ABSTRACT FROM AUTHOR]

In Crohn's disease, mild gastrointestinal bleeding often occurs; however massive gastrointestinal hemorrhage, which can have a dramatic effect on a patient's vital sign, is rare. This could result in potentially life-threatening complications, which can lead to death. Massive hemorrhagic Crohn's disease is not well known and for this reason, they are a diagnostic and therapeutic challenge. Various diagnostic and therapeutic methods are currently being developed and used. The surgical method is often used only as a last measure since this approach has the risk of serious complications that may endanger patients. However, if massive bleeding continues even after all therapeutic methods are used, the surgical method must be implemented. In this case, all therapeutic methods were found to be ineffective; therefore, surgery was used as a last option. Ultimately, the surgical method was found to be successfully used to treat life-threatening hemorrhagic Crohn's disease. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy of early infliximab use and to follow the progress of pediatric cases of Crohn's disease for 3 years. Methods: We reviewed the medical records of 28 pediatric patients who had been treated with infliximab for Crohn's disease. Eighteen patients (the 'top-down' group) received infliximab and azathioprine for induction and maintenance therapy for the first year, and then were treated with azathioprine for 2 additional years. Ten patients who were refractory to conventional therapy were categorized in the 'step-up' group. All patients were followed for at least 36 months. Treatment efficacy was assessed by the relapse rate using the pediatric Crohn's disease activity index (PCDAI) score in each group at 12, 24, and 36 months. Blood samples were available from 10 patients, and were used to assess antibody to infliximab (ATI). Results: The relapse rate in 'top-down' group was lower than that in 'step-up' group at 1, 2, and 3 years. But, just the relapse rate at the 2 years was significantly different. At 3 years, the relapse rate according to different characteristic variables (sex, age at diagnosis, involvement, PCDAI at diagnosis) was not significantly different. Only one patient treated with infliximab had an adverse event, consisting of dyspnea and tachycardia. ATI was not detected in the blood samples from 10 patients. Conclusion: Early induction with infliximab at diagnosis ('top-down' therapy) is effective for reducing the relapse rate compared to conventional therapies in pediatric Crohn's disease possibly for up to 3 years. [ABSTRACT FROM AUTHOR]

Burill Crohn’s convincing description of the disease that now carries his name conceived of the illness as arising exclusively from the terminal ileum, involving other sites only secondarily. As a result, he took the condition to be curable by an adequate operative resection. The current concept is that Crohn’s disease may affect any segment of the gastrointestinal tract. The practical implication of this change in thinking is the need to conserve bowel when weighing medical and surgical options for each child. Operations should be used to treat complications of the disease. Absolute indications for the surgery are uncommon and include perforation, bleeding, and refractory obstruction. The margins of resection need only include a short amount of grossly normal intestine. Strictureplasty to relieve obstruction without resection should be done when applicable. Maintenance medication after an operation to limit recurrence or recrudescence is frequently advocated. [Copyright &y& Elsevier]