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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]

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.

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]

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 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.

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.

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]

Background: The natural history of Crohn's disease (CD) can result in complications requiring surgery. Pediatric data are scarce about major abdominal surgery. The IBD Registry from the Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition has been active since 2008 and collects data from major pediatric IBD centers in Italy. The aim of the present report was to explore the prevalence of major abdominal surgery among children affected by CD in an era when antitumor necrosis factor (anti-TNF-α) agents were already used so that we might appraise the incidence of surgical-related complications and identify the factors associated with postoperative disease recurrence., Methods: We retrospectively analyzed data from patients enrolled in the registry from January 2009 to December 2018. Patients with monogenic IBD and patients undergoing surgery for perianal disease were excluded., Results: In total, 135 of 1245 patients were identified. We report the prevalence of major abdominal surgery of 10.8%. Pediatric surgeons performed the procedure in 54.1% of cases, and a laparoscopic approach was used in 47.4% of surgical procedures. Seventeen patients (12.6%) experienced a total of 21 early postoperative complications, none of which was severe. A laparoscopic approach was the only factor negatively associated with the occurrence of postoperative complications (odds ratio, 0.22; 95% confidence interval, 0.06-0.8; P = .02). Fifty-four (40%) patients experienced postoperative endoscopic recurrence, and 33 (24.4%) of them experienced postoperative clinical recurrence. The postoperative treatment with anti-TNF-α drugs was significantly associated with a reduced risk of endoscopic recurrence (odds ratio, 0.19; 95% confidence interval, 0.05-0.79; P = .02)., Conclusion: In our cohort, the overall prevalence of major abdominal surgery was low, as well as the rate of surgical-related complications. Postoperative anti-TNF-α therapy seems be protective against endoscopic recurrence., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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., Competing Interests: Declaration of interests D. Haller served on the Microbiome Expert Panel from Reckitt Benckiser Health Limited. T.S. received lecture honoraria from Nutricia and MSD and travel support from Abbvie and Ferring outside the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Failure to thrive (FTT) refers to a condition where a child does not gain weight or grow at the expected rate for their age and gender. An accepted definition includes a weight less than the lowest acceptable range on standardized growth charts. FTT is often a diagnostic challenge for providers treating children with mixed etiologies. This report discusses the case of an 11-year-old female with a diagnosis of Crohn's disease and avoidant and restrictive food intake disorder (ARFID). Management by an interprofessional healthcare team has been difficult, given the multifactorial nature of the patient's weight loss. This report suggests that behavioral and psychological aspects, such as aversion to eating and reluctance to experiment with different foods, may align with symptoms of Crohn's disease in children. It also emphasizes the importance of timely diagnosis and appropriate interventions, as they can mitigate psychological and developmental setbacks., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Valencia et al.)

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., Importance: Since 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., Competing Interests: The authors declare no conflict of interest.

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]

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]

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 Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), presents significant challenges, particularly in pediatric patients. Vitamin D deficiency has been associated with IBD, but its role in disease activity and remission remains unclear. This study investigates the relationship between serum vitamin D levels and IBD markers, including Pediatric Crohn's Disease Activity Index (PCDAI), Pediatric Ulcerative Colitis Activity Index (PUCAI), fecal calprotectin levels, and endoscopy findings. It also explores racial and ethnic disparities in these relationships. Methodology A retrospective study was conducted involving 51 pediatric patients with IBD from the Nemours Children's Health EMR system. Inclusion criteria required documented serum vitamin D levels at diagnosis and post-treatment, and at least one post-treatment assessment of PUCAI/PCDAI, calprotectin, or endoscopy. The study employed Spearman and Pearson correlation tests to analyze the associations between vitamin D levels and IBD markers. Ethnicity and race were analyzed using t-tests and chi-square tests. Results No statistically significant correlations were found between changes in serum vitamin D levels and IBD markers (endoscopy results, calprotectin levels, PUCAI/PCDAI scores) for both UC and CD. Analysis of racial and ethnic disparities revealed that Hispanic patients had significantly higher post-treatment calprotectin levels compared to non-Hispanics, although other markers showed no significant differences. Vitamin D levels did not significantly differ between racial or ethnic groups. Conclusions This study found no significant correlation between serum vitamin D levels and IBD activity markers in pediatric patients. Despite initial hypotheses, vitamin D levels do not appear to be useful in assessing IBD remission or disease state. Racial and ethnic disparities in IBD severity were observed, but further research with larger sample sizes and more consistent data collection is needed to draw more definitive conclusions., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Nemours Office of Human Subjects Protection issued approval 1910359. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Centner et al.)

Purpose: Identifying reliable prognostic factors for pediatric-onset Crohn's disease (CD) is important for guiding early treatment. This study aimed to evaluate the validity of various clinical parameters for predicting long-term intestinal complications in pediatric-onset CD patients with CD in Taiwan., Methods: This was a single-center, retrospective study. Patients diagnosed with CD under 18 years of age at our hospital between January 1999 and December 2021 were enrolled. The baseline clinical variables and the Pediatric Crohn's Disease Activity Index (PCDAI) were obtained. Patients were categorized into low-, medium-, or high-risk groups based on the 2020 European Crohn's and Colitis Organization and European Society for Pediatric Gastroenterology Hepatology and Nutrition (ECCO-ESPGHAN) guidelines. The primary endpoint was the occurrence of new intestinal complications., Results: Among 53 enrolled patients (33 males and 20 females), 8 patients (33.96%) developed intestinal complications during the follow-up period (median 6.42 years, 3.17-9.75 years). Patients in the initial ECCO-ESPGHAN medium- or high-risk group had a 4.71-fold higher risk of intestinal complications than those in the low-risk group [hazard ratio = 4.71, p = 0.023] after adjusting for PCDAI in the multivariate Cox proportional hazard analysis. The other clinical variables did not reach statistical significance in predicting intestinal complications. The positive and negative predictive values of the ECCO-ESPGHAN stratification method for intestinal complications were 48.15% and 80.77%, respectively., Conclusions: ECCO-ESPGHAN risk stratification is an effective early predictor of long-term intestinal complications in the Taiwanese population and may be used in clinical practice to guide early advanced therapy., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Ustekinumab is a monoclonal antibody that inhibits interleukins 12 and 23. It is approved for treatment of Crohn’s disease (CD) in adults; however, there is a paucity of data regarding its use in pediatric CD. We describe our experience using ustekinumab in anti-TNF refractory CD pediatric patients. Methods: We performed a retrospective chart review on pediatric patients with CD who were started on ustekinumab from January 2016 to November 2018. We collected patient’s clinical history, previous treatment history, surgeries related to CD, disease severity, as measured by abbrPCDAI, and endoscopic severity as recorded by SES-CD before and after ustekinumab. Results: We identified 10 patients with CD who were started on ustekinumab due to non-response to currently approved agents. Seven patients needed augmented maintenance dosing every 4-6 weeks to achieve clinical response or remission. Six of these seven patients had therapeutic drug monitoring during the course of treatment, with five patients showing subtherapeutic drug levels of 4.5 μg/mL on augmented dosing interval. The remaining three patients were on standard maintenance dosing for the duration of treatment. Conclusion: In this retrospective chart review, 7 out of 10 patients with anti-TNF refractory pediatric-onset CD required augmented maintenance doses of ustekinumab to achieve clinical response or remission. A prospective study is needed to define appropriate ustekinumab dosing and interval in management of pediatric CD.

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.

BackgroundNeutrophil expression of the Fcγ receptor I (CD64) is upregulated in adult patients with clinically active inflammatory bowel disease (IBD). We tested the relationship of CD64 with mucosal inflammation and clinical relapse in pediatric Crohn's disease (CD).MethodsIn a cohort of 208 newly diagnosed CD and 43 non-IBD controls, ileal expression of FcγRI/S100A9 was determined by RNA sequencing from biopsies obtained at ileocolonoscopy. In a second cohort, we tested for the peripheral blood polymorphonuclear neutrophil (PMN) CD64 index from 26 newly diagnosed CD, 30 non-IBD controls, and 83 children with established CD.ResultsIleal FcγRIA mRNA expression was significantly elevated in CD at diagnosis compared with non-IBD controls (P < 0.001), and correlated with ileal S100A9 (calprotectin) expression (r = 0.83, P < 0.001). The median (range) PMN CD64 index for newly diagnosed CD was 2.3 (0.74-9.3) compared with 0.76 (0.39-1.2) for non-IBD controls (P < 0.001) with 96% sensitivity and 90% specificity at the cut point of 1.0. The PMN CD64 index significantly correlated with mucosal injury as measured by the simple endoscopic score for CD (r = 0.62, P < 0.001). Patients with CD in clinical remission receiving maintenance therapy with a PMN CD64 index 1.0 (P < 0.01).ConclusionsAn elevated PMN CD64 index is associated with both mucosal inflammation and an increased risk for clinical relapse in pediatric CD. The PMN CD64 index is a reliable marker for sustained remission in patients with CD receiving maintenance therapy.

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]

Background: Ustekinumab is a monoclonal antibody that inhibits interleukins 12 and 23. It is approved for treatment of Crohn’s disease (CD) in adults; however, there is a paucity of data regarding its use in pediatric CD. We describe our experience using ustekinumab in anti-TNF refractory CD pediatric patients. Methods: We performed a retrospective chart review on pediatric patients with CD who were started on ustekinumab from January 2016 to November 2018. We collected patient’s clinical history, previous treatment history, surgeries related to CD, disease severity, as measured by abbrPCDAI, and endoscopic severity as recorded by SES-CD before and after ustekinumab. Results: We identified 10 patients with CD who were started on ustekinumab due to non-response to currently approved agents. Seven patients needed augmented maintenance dosing every 4-6 weeks to achieve clinical response or remission. Six of these seven patients had therapeutic drug monitoring during the course of treatment, with five patients showing subtherapeutic drug levels of 4.5 μg/mL on augmented dosing interval. The remaining three patients were on standard maintenance dosing for the duration of treatment. Conclusion: In this retrospective chart review, 7 out of 10 patients with anti-TNF refractory pediatric-onset CD required augmented maintenance doses of ustekinumab to achieve clinical response or remission. A prospective study is needed to define appropriate ustekinumab dosing and interval in management of pediatric CD.

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]

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tang, Huang, Che, Yang, Pu, Liu and Li.)

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 2.248/10 5  person-years (PY), significantly increasing from 1.173/10 5  PY in 2005-2007 to 3.267/10 5  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., (© 2024 Japan Pediatric Society.)

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., Competing Interests: Shenzhen Wanhe Pharmaceutical Co., Ltd (Shenzhen, P. R. China) funded this study by providing Elental. No honoraria or payments were made for authorship. All authors had access to the relevant data and participated in the drafting, review, and approval of this submission. The authors declare that there is no other conflict of interest regarding the publication of this paper., (© The Author(s) 2023. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

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]

The increase in incidences of pediatric Crohn’s Disease (CD) worldwide has been strongly linked with dietary shifts towards a Westernized diet, ultimately leading to altered gut microbiota and disturbance in intestinal immunity and the metabolome. Multiple clinical studies in children with CD have demonstrated the high efficacy of nutritional therapy with exclusive enteral nutrition (EEN) to induce remission with an excellent safety profile. However, EEN is poorly tolerated, limiting its compliance and clinical application. This has spiked an interest in the development of alternative and better-tolerated nutritional therapy strategies. Several nutritional therapies have now been designed not only to treat the nutritional deficiencies seen in children with active CD but also to correct dysbiosis and reduce intestinal inflammation. In this review, we report the most recent insights regarding nutritional strategies in children with active CD: EEN, partial enteral nutrition (PEN), Crohn’s disease exclusion diet (CDED), and CD treatment-with-eating diet (CD-TREAT). We describe their setup, efficacy, safety, and (dis)advantages as well as some of their potential mechanisms of action and perspectives. A better understanding of different nutritional therapeutic options and their mechanisms will yield better and safer management strategies for children with CD and may address the barriers and limitations of current strategies in children.

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]