Epidemiological data on pediatric inflammatory bowel disease (PIBD) have been reported in Asian countries. However, short-term follow-up data, especially in Southeast Asian countries, are limited.

Analyze and compare the baseline and 1-year follow-up (1FU) data for PIBD in Asian children.

The multinational network included patients with PIBD (aged <19 years) in 5 Asian countries (Malaysia, Philippines, Singapore, Sri Lanka, and Thailand). The diagnosis of PIBD requires gastrointestinal endoscopy. The patients' demographics, clinical information, disease- related outcomes, and treatment data at 1FU were collected.

In 1995-2021, 368 patients were enrolled (Crohn disease [CD], 56.8%; ulcerative colitis [UC], 38%; and inflammatory bowel disease [IBD]-unclassified, 5.2%). At 1FU, symptoms including diarrhea, bloody stools, and nausea/vomiting subsided in <3%, while abdominal pain persisted in 10.5% of patients with CD and 7.1% of patients with UC. Assessment endoscopy was performed at 1FU in 38% of CD and 31% of UC cases, of which 21% and 23% showed mucosal healing, respectively. Oral prednisolone was administered to 55.3% of patients at diagnosis and 26.8% at 1FU, while infliximab was administered to 2.5% and 7.2% of patients at diagnosis and 1FU, respectively. Independent factors of 1-year clinical remission for CD were oral prednisolone (odds ratio [OR], 0.20; 95% confidence interval [CI], 0.06-0.68), antibiotic use (OR, 0.09; 95% CI, 0.01-0.54), and immunomodulator use (OR, 5.26; 95% CI, 1.52-18.22). A history of weight loss at diagnosis was the only independent risk factor of an IBD flare by 1FU (OR, 2.01; 95% CI, 1.12-3.63).

The proportion of children with PIBD and abdominal pain at 1FU remained high. The rates of repeat endoscopy and infliximab use were suboptimal with high rates of systemic corticosteroid use. Quality improvement based on the aforementioned predictors may enhance PIBD care in this geographic region or similar settings.

The aim of the present study was to assess prevalence and disease outcomes of arthritis in a nationwide cohort of pediatric patients with inflammatory bowel disease (IBD).

We collected data of pediatric IBD patients experiencing arthritis from the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition IBD registry. We gathered baseline and one-year follow-up data on concomitant IBD and arthritis diagnosis.

150 patients [(99 Crohn's Disease (CD), 51 Ulcerative Colitis (UC) and Unclassified IBD (IBDU)] with arthritis out of 3061 (1301 CD and 1760 UC) patients were identified, with an overall prevalence of 4.9 %. Arthritis was more frequent in CD than in UC (7.6 % vs 2.9 %, p < 0.01). Peripheral arthritis was more frequently diagnosed in patients with active IBD than in those with quiescent disease (94.6 % vs 67.3 %, p < 0.01). At one-year follow-up, clinically active IBD was independently associated with lower peripheral arthritis remission rates, whereas it did not impact axial arthritis remission. The presence of additional EIMs was associated with lower IBD clinical remission rates.

Clinically active IBD impacts peripheral arthritis but not axial one, whose activity appeared to be independent by intestinal disease. The presence of additional EIMs has a negative prognostic impact on IBD course.

Functional constipation (FC) is a common problem in childhood and the first-line therapy is macrogol. The role of FC in the onset of inflammatory bowel disease (IBD) is poorly understood. Our main aim was to investigate the prevalence of FC in children before the diagnosis of IBD.

This is a cross-sectional observational study in pediatric IBD-patients. We collected data on demographics, clinical and endoscopic characteristics at IBD diagnosis, and on the presence of FC and its treatment before IBD diagnosis.

A total of 238 children with IBD, 104 (44%) with Crohn disease (CD), 130 (56%) with ulcerative colitis (UC) and 4 (0.016%) with IBD Unclassified (IBD-U) were enrolled. The mean age was 174 ± 47 months, 56% were male. Forty-seven out of 238 (19.7%) had a FC history before the IBD diagnosis and 31 out of these 47 patients (65%) received macrogol therapy. In the FC group, we found a delay in the diagnosis of IBD compared to the group with no FC [median (interquartile range [IQR]): 5 months (2.5-9.5) and 2 months (0-4), respectively, p ≤ 0.001]. The difference in terms of endoscopic localization was statistically significant in UC patients presenting FC (p = 0.026) with a prevalence of proctitis and left side colitis (30% and 15%, respectively).

In conclusion our study highlighted a prevalence of constipation in pediatric IBD patients at diagnosis of 19.7%, which must be taken into account to avoid diagnostic delay and which is associated with limited extent of disease in UC pediatric patients.

An increasing incidence of pediatric-onset inflammatory bowel disease (PIBD) has been reported in many countries. However, the global burden and distribution of this disease remain less understood. We aimed to examine the global epidemiology and trends of PIBD from 1990 to 2019.

Data from the 2019 Global Burden of Disease Study, covering 204 countries, were analyzed. We assessed key measures like incidence, prevalence, mortality, and disability-adjusted life years (DALYs) using linear regression to calculate annual percentage changes and assess trends.

Between 1990 and 2019, the PIBD incidence rate increased and the DALY rate and mortality rate declined. The incidence rate was notably elevated in the high Socio-demographic Index (SDI) quintile, reaching 6.3 per 100 000 person-years, corresponding to 13 914 new cases in 2019. Incidence and prevalence of PIBD positively correlated with the SDI, while higher death and DALY burdens were observed in lower-SDI countries. In 2019, the top 5 countries with the highest PIBD incidence rates were Canada (19.9 per 100 000 population), Denmark (12.4 per 100 000 population), Hungary (8.5 per 100 000 population), Austria (8.1 per 100 000 population), and the United States (7.4 per 100 000 population). Several countries experienced significant increases in incidence rates from 1990 to 2019, led by Taiwan (annual percent change 4.2%), followed by China (2.8%), Japan (2.1%), Australia (1.8%), and Hungary (1.6%).

PIBD incidence has significantly increased since 1990. High-SDI countries face higher incidence, while lower-SDI countries experience higher mortality and DALY burdens. The study underscores the need for ongoing monitoring and research to address this emerging public health issue.

To identify racial and ethnic disparities in disease phenotype, treatment, and outcome in a diverse cohort of children with pediatric inflammatory bowel disease (IBD).

Patients aged 7 through 18 with IBD diagnosed at a single institution between March 2020 and June 2021 with self- or parent-identified race and ethnicity of non-Hispanic (NH) Black, NH-White, or Hispanic were included. Demographics, Centers for Disease Control/Agency for Toxic Substances and Disease Registry Social Vulnerability Index, Childhood Opportunity Index, disease phenotype, time to diagnosis, treatment, and health care utilization were compared between the racial and ethnic groups.

Ninety-seven patients were included. A total of 18.6% of the cohort self- or parent-identified as NH-Black, 53.6% as NH-White, and 27.8% as Hispanic. Ulcerative colitis was found to be significantly more common in Hispanic patients. Hispanic patients were also significantly more likely to be hospitalized at time of diagnosis and have more emergency department visits within 2 years of diagnosis compared with non-Hispanic White patients.

Race and ethnicity may affect the diagnosis and treatment of pediatric IBD, and these findings should serve as a foundation for establishing equitable care. Larger cohorts are needed to validate these findings.

The aberrant expression of α defensin 5 (DEFA5) protein in colonic inflammatory bowel diseases (IBDs) underlies the distinct pathogenesis of Crohn's colitis (CC). It can serve as a biomarker for differentiating CC from Ulcerative colitis (UC), particularly in Indeterminate colitis (IC) cases into UC and CC. We evaluated the specificity of commercially available anti-DEFA5 antibodies, emphasizing the need to further validate their appropriateness for a given application and highlighting the necessity for novel antibodies.

We established two mice monoclonal DEFA5 antibody clones, 1A8 and 4F5, by immunizing mice with purified recombinant protein. We validated the specificity, sensitivity, and cross-reactivity of these antibodies in recognizing both endogenous and recombinant DEFA5 protein, especially for use in Immunohistochemistry (IHC), Western blot (WB), Immunoprecipitation (IP), and enzyme-linked immunosorbent assay (ELISA).

Clones 1A8 and 4F5 effectively recognized the endogenous DEFA5 in active human colon tissue from patients with diverticulitis (DV), UC, CC, and IC disease samples, as well as in transiently transfected HEK293T cells expressing DEFA5 with minimal non-confounding cross reactivity.

The 1A8 and 4F5 clones are useful for a wide variety of immunoassays, including WB, IHC, IP/WB, and ELISA. Their specificity enhances their potential as valuable tools for research applications in IBD colitis.

Patients with very early-onset inflammatory bowel disease (VEO-IBD), with an age of onset < 6 years, can present with severe manifestations and may require biologic therapy. Infliximab and adalimumab are approved for induction and maintenance in pediatric IBD patients but are licensed only above the age of 6 years. Effectiveness and safety data on adalimumab in this patient population are lacking. We assessed the therapeutic response to help close this gap.

This retrospective study involved 30 sites worldwide. Demographic, clinical, and laboratory data were collected from patients with VEO-IBD who commenced adalimumab therapy before the age of 6 years.

Seventy-eight patients (37 Crohn's disease, 26 ulcerative colitis, and 15 with IBD-unclassified) were included. Median age of IBD onset was 2.6 (1.3-4.1) years, with 30 (38.5%) patients diagnosed at age <2 years. Median age at adalimumab initiation was 4.2 (2.8-5.1) years. Adalimumab was used as second-line biologic therapy in 45 (57.7%) patients after infliximab. The median time to last follow-up was 63 (22-124) weeks. Significant improvement in clinical scores, CRP, fecal calprotectin, and weight Z-score were observed by Week 52. Adalimumab durability rates were 61.9%, 48.1%, and 35.6% after 1, 2, and 3 years, respectively. Drug discontinuation rates were not dependent on IBD type, age, prior anti-TNF exposure, or concomitant immunomodulatory treatment. Four (5.1%) patients developed serious infections, including 1 patient with TTC7A deficiency who died following adenovirus sepsis.

Adalimumab therapy is a viable therapeutic option in patients with VEO-IBD with an acceptable safety profile.

Genetic discovery in very early-onset inflammatory bowel disease (VEO-IBD) can elucidate not only the origins of VEO-IBD, but also later-onset inflammatory bowel disease. We aimed to investigate the polygenic origins of VEO-IBD in a cohort with a high proportion of Hispanic patients.

Patients with VEO-IBD who underwent whole exome sequencing at our center were included. Genes were categorized as genes of interest (GOIs) (129 genes previously described to be associated with VEO-IBD) or non-GOIs. VEO-IBD "susceptibility" single nucleotide variants (SNVs) were identified through enrichment compared with gnomAD (Genome Aggregation Database) and ALFA (Allele Frequency Aggregator) and were scored by Combined Annotation Dependent Depletion for deleteriousness. Gene networks carrying susceptibility SNVs were created. Myosin 5b immunofluorescence was also studied.

Fifty-six patients met inclusion criteria, and 32.1% identified as Hispanic. Monogenic disease was infrequent (8.9%). Significant enrichment of GOI susceptibility SNVs was observed, notably in MYO5B, especially in Hispanics. MEFV, TNFAIP3, SH3TC2, and NCF2 were also central participants in the GOI networks. Myosin 5b immunofluorescence in colonic mucosa was significantly reduced in those with MYO5B susceptibility SNVs compared with control subjects. Seven genes (ESRRA, HLA-DQ1, RETSAT, PABPC1, PARP4, CCDC102A, and SUSD2) were central participants in the non-GOI networks.

Our results support the polygenic nature of VEO-IBD, in which key participants, like MYO5B, were identified through network analytics. Rare variant load within susceptibility genes may be relevant not only for the genetic origins of inflammatory bowel disease, but also for the age of disease onset. Our findings could guide future work in precision medicine.

Inflammatory bowel disease (IBD) is a persistent and complex condition accomplished by inflammation of the gastrointestinal system, encompassing Crohn's disease (CD) and ulcerative colitis (UC). This condition is caused by the combination of genetic predispositions, environmental triggers, and dysregulated immunological responses, which complicates diagnosis and treatment. The latest developments in gastroenterology have revealed the critical significance of the gut microbiota in the pathogenesis of IBD. Extracellular vesicles (EVs) are a type of microbial component that potentially regulate intestinal inflammation. The impact of microbiota-derived bacterial EVs (bEVs) on intestinal inflammation is mediated through several methods. They can intensify inflammation or stimulate defensive responses by delivering immunomodulatory cargo. Improved comprehension could enhance inventive diagnostic and treatment strategies for IBD. This study aimed to explore the relationship between microbiota-derived bEVs and the complex nature of IBD. We performed a thorough analysis of the formation, composition, mechanisms of action, diagnostic possibilities, therapeutic implications, and future prospects of these microbiota-derived bEVs.

As a traditional Chinese medicine formula used in clinical practice for an extended period, Suxin-Hugan-Fang (SXHGF) exhibits excellent anti-inflammatory properties. However, the efficacy of SXHGF in treating ulcerative colitis (UC) and its mechanism of action are still unclear. In this study, the therapeutic effects of SXHGF on UC were evaluated using network pharmacology and experimental validation, while also investigating its mechanism of action. By administering DSS to C57BL/6 mice to construct a mouse model of ulcerative colitis, the therapeutic effect of SXHGF on ulcerative colitis was evaluated based on weight loss percentage, disease activity index, colon length changes, and pathological conditions as indicators. The main chemical components of SXHGF were determined by LC-MS-QTOF method. The potential targets and mechanisms of action of SXHGF in the treatment of UC were inferred using bioinformatics methods, and further validated through ELISA, IHC, and Western blotting assays. The experimental results demonstrate that SXHGF can suppress oxidative stress and oxidative damage in the colon tissue of UC mice, and alleviate DSS-induced ulcerative colitis by inhibiting the JAK2/STAT3 and NFκB pathways.

The incidence of inflammatory bowel disease (IBD) is increasing worldwide. Dietary patterns may be associated with odds of this disease. Although previous reviews have attempted to summarize the evidence in this field, the growing body of investigations prompted us to conduct an updated comprehensive systematic review.

We used the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to evaluate the association between dietary patterns before disease onset and the risk of IBD. PubMed, SCOPUS, and Web of Science were searched using structured keywords up to November 20, 2023.

Twenty-four publications (13 case-control, 1 nested case-control, and 10 cohort studies) were included in this review. The sample size of these studies ranged from 181 to 482 887 subjects. The findings were inconsistent across the included studies, showing inverse, direct, or no association between different dietary patterns and the risk of IBD.

This review provides comprehensive data on the link between dietary patterns prior to IBD diagnosis and risk of this condition. The explicit finding of present review is the extent gap in our knowledge in this field. Therefore, large-scale, high-quality studies are warranted to improve our understanding of the relationship between dietary patterns and IBD risk.

The objectives of this study is to estimate rates and identify factors associated with erythema nodosum (EN) and pyoderma gangrenosum (PG) in pediatric patients with inflammatory bowel disease (IBD).

This cohort study examined longitudinal visits of patients aged ≤ 21 years from the ImproveCareNow (ICN) registry. We evaluated the association of factors at the patient-level (demographics and IBD diagnosis age) and visit-level (IBD severity scores, markers and phenotypes, comorbidities, and treatment) with the presence of EN and PG, using longitudinal logistic regression models adjusted for time and within-patient clustering.

A total of 285,913 visits from 32,497 patients aged ≤ 21 years from the ICN registry were analyzed. The occurrence of EN was 1.57% (95% confidence interval [95% CI]: 1.43%-1.71%) and the occurrence of PG was 0.90% (95% CI: 0.80%-1.00%). Co-occurrence of EN and PG was reported in 0.30% (95% CI: 0.25%-0.37%) patients. Both EN and PG were associated (p < 0.0001) with worse intestinal disease, lower remission, higher inflammatory markers, and extraintestinal manifestations (EIMs) arthritis and uveitis.

EN and PG were associated with increased disease severity and other noncutaneous EIMs (arthritis and uveitis). A small subset of patients had developed both EN and PG.

This study aimed to establish and characterize patient-derived intestinal organoids (PDOs) from children with Crohn's disease (CD).

To generate PDOs, endoscopic biopsy specimens were obtained from non-inflamed duodenal bulbs of normal controls and CD patients. To verify the presence of PDOs, histological staining and quantitative reverse transcription polymerase chain reaction (RT-qPCR) analyses were performed.

PDOs were successfully established in normal controls (n=2) and CD patients (n=2). Hematoxylin and eosin staining of formalin-fixed, paraffin-embedded PDO sections revealed crypt and villus structures, whereas immunofluorescence staining with EpCAM and DAPI confirmed the epithelial-specific architecture of the PDOs. RT-qPCR results revealed a significant increase in Lgr5, Si, and Chga gene expression and a decrease in Olfm4 and Muc2 expression in CD patients compared to normal controls, suggesting altered stem cell activity and mucosal barrier function (p<0.05).

We successfully established and characterized PDOs in children with CD, providing a valuable tool for understanding the pathophysiology of the disease and evaluating potential therapeutic approaches. The differential gene expression of PDOs in CD patients might be caused by the complex interplay between epithelial adaptation and inflammation in the intestinal epithelium.

Biologics are important therapeutic agents for pediatric Crohn's disease. Discontinuation of biologics is known to increase the relapse rate up to 71.4% in these patients; however, their long-term use increases the risk of opportunistic infections and causes economic burden and psychological fatigue. Therefore, taking a drug holiday is meaningful, even if the biologics cannot be completely discontinued. This study aimed to analyze the risk factors affecting relapse after discontinuation of biologics in children with Crohn's disease.

We retrospectively reviewed the data of 435 children with Crohn's disease who visited a single health center between March 2013 and March 2021. Subsequently, we analyzed data from the patients who discontinued biologics after deep remission.

Among the enrolled patients, 388 were followed up for ≥2 years, and of these, 357 were administered biologics. A total of 103 patients discontinued biologics after deep remission, subsequently 31 maintained remission and 72 relapsed. The shorter the duration of biologic treatment (odds ratio of 0.444, P = 0.029), the higher the ESR (odds ratio of 1.294, P = 0.009) and fecal calprotectin (odds ratio of 1.010, P = 0.032), and the less histological remission at the time of discontinuation of biologics (odds ratio of 0.119, P = 0.026), the greater the risk of relapse after discontinuation of biologics.

We identified factors associated with relapse after discontinuation of biologics. The results suggest that biologics can be discontinued in the absence of these factors after deep remission. However, because the relapse rate may increase after the discontinuation of biologics, close monitoring is important, and if necessary, re-administration of biologics should be actively considered.

In children, ulcerative colitis (UC) is often more severe and extensive than in adults and hospitalization for acute exacerbations occurs in around a quarter of subjects. There is a need for effective drugs, which could avoid or reduce the use of corticosteroids which, especially in children, are burdened by a number of severe side effects. The introduction in therapy of monoclonal antibodies has completely changed the therapeutic scenario and the prognosis of the disease.

In this review, the use of the monoclonal antibodies directed against tumor necrosis factor (TNF)α or other inflammatory targets for the treatment of pediatric UC will be discussed. A search of the literature was done using the keywords 'pediatric,' 'ulcerative colitis,' 'inflammatory bowel disease,' 'monoclonal antibodies;' 'infliximab,' 'adalimumab,' 'golimumab,' vedolizumab," 'ustekinumab' and 'risankizumab.'

The use of monoclonal antibodies has greatly increased in recent years in pediatric UC, both in patients who did not respond to conventional therapies, and, more often, as initial therapy. Thanks to therapeutic drug monitoring and to the availability of biologics with different targets, therapy has become more targeted and personalized, with a significant improvement in response, in quality of life, and with a good safety profile.

Compare the proportions of use of biological therapy, surgeries, and hospitalizations between adults and pediatric inflammatory bowel disease (IBD)-Crohn's disease (CD) and ulcerative colitis (UC)-patients.

Observational, retrospective, and multicenter study. Data were collected from all consecutive IBD patients seen as outpatients or admitted to hospital, during 2015-2021, in two IBD tertiary centers in a South Brazilian capital. Patients with unclassified colitis diagnosis were excluded from this study. Patients were classified as having CD or UC and sub-categorized as adult or pediatric according to age. Data were analyzed using frequency, proportion, Fisher's exact test, and Chi-square test.

A total of 829 patients were included: 509 with CD (378 adults/131 pediatric) and 320 with UC (225/95). Among patients with CD, no differences were observed for proportions of use of biological therapy (80.2% in pediatric vs. 73.3% in adults; P=0.129), surgery (46.6% vs. 50.8%; P=0.419), or hospitalization (64.9% vs. 56.9%; P=0.122). In UC, significant differences were observed for biological therapy (40.0% vs. 28.0%; P=0.048) and hospitalization (47.4% vs. 24.0%; P<0.001). No significant difference was observed in surgery rates (17.9% vs. 12.4%; P=0.219).

Biological therapy and incidence of hospitalization were greater among pediatric patients with UC, compared with adults; no difference was observed in the need for abdominal surgery. In CD, no significant difference was observed in the three main outcomes between the age groups.

Structured reporting (SR) replaced narrative (free text) reporting and utilizes templated headings and subheadings with findings typically based on the anatomy included in the examination. Its use has been widely advocated by radiology and non-radiology organizations as the new reporting standard. There are, however, shortcomings to SR, such as templated text not addressing a specific clinical indication. Contextual reporting (CR) fills this gap. CR is a type of SR which is tailored to a narrow clinical indication by including pertinent positive and negative findings for that specific clinical entity.

This study assesses provider preferences for CR as compared to SR in the pediatric practice environment using a survey methodology.

Surveys with examples of SR and CR reports were sent electronically to two groups. One group was focused on neurological diseases and included pediatric specialists in neurosurgery, neurology, ENT, ED, and ophthalmology (190 people), referred to as the pediatric neuroimaging group. The pediatric neuroimaging group survey contained examples of CR and SR reports of an orbital CT for orbital cellulitis and a head CT for stroke. The other group was focused on gastrointestinal diseases, and included pediatric specialists in gastroenterology, general surgery, and the ED (159 people), referred to as the pediatric gastrointestinal (GI) imaging group. The pediatric GI imaging group survey contained example reports of an abdominal CT for appendicitis and an MRI enterography for Crohn's disease. Surveys utilizing a 5-point Likert scale were analyzed via Fischer's exact test with a p-value deemed statistically significant at less than 0.05.

349 individuals were contacted to participate in the survey. There were 81 (23 %, 81/349) survey respondents; 41 (22 %, 41/190) from the neuro group, and 40 (25 %, 40/159) from the GI group. 56 % (45/81) of all respondents preferred CR reports over traditional SR reports, while 29 % (23/81) did not. Most respondents (59 %, 48/81) indicated that CR reports are easier to interpret than traditional SR reports. Respondents from the pediatric neuroimaging group favored CR reports to a lesser degree (44 %, 36/81) compared to respondents from the pediatric GI imaging group (68 %, 55/81).

We learned from this survey that it would be beneficial to be very intentional about selecting clinical indications where CR would be most valued rather than trying to develop CR for any specific clinical indication. The study results indicate it is reasonable to continue further efforts at exploring the utility of contextualized reports.

Genetic and environmental factors influence pathogenesis and rising incidence of paediatric inflammatory bowel disease (PIBD). The aim was to meta-analyse evidence of diet and environmental factors in PIBD.

A systematic search was conducted to identify diet and environmental factors with comparable risk outcome measures and had been reported in two or more PIBD studies for inclusion in meta-analyses. Those with ≥2 PIBD risk estimates were combined to provide pooled risk estimates.

Of 4763 studies identified, 36 studies were included. PIBD was associated with higher risk with exposure to ≥/=4 antibiotic courses (includes prescriptions/purchases/courses), passive smoking, not being breastfed, sugary drink intake, being a non-Caucasian child living in a high-income country and infection history (odds ratio [OR] range: 2-3.8). Paediatric Crohn's disease (CD) was associated with higher risk with exposure to antibiotics during early childhood, ≥/=4 antibiotic courses, high socioeconomic status (SES), maternal smoking, history of atopic conditions and infection history (OR range: 1.6-4.4). A history of infection was also associated with higher risk of paediatric ulcerative colitis (UC) (OR: 3.73). Having a higher number of siblings (≥2) was associated with lower risk of paediatric CD (OR: 0.6) and paediatric UC (OR: 0.7). Pet exposure was associated with lower risk of paediatric UC (OR: 0.5).

Several factors associated with PIBD risk were identified that could potentially be used to develop a disease screening tool. Future research is needed to address risk reduction in PIBD.

Robust evidence suggests that the aberrant expression of α defensin 5 protein (DEFA5) in colon inflammatory bowel diseases (IBDs) underlies the distinct pathogenesis of Crohn's colitis, can be exploited as a reliable diagnostic biomarker to differential diagnosis of Crohn's colitis (CC) from Ulcerative colitis (UC) in otherwise indeterminate colitis (IC). We evaluated the specificity of the commercially available anti-DEFA5 antibodies and showed further validation of their appropriateness for a given application is required.

We established two mouse monoclonal DEFA5 antibody clones 1A8 and 4F5 by immunizing the mice with purified recombinant protein and validated the specificity, selectivity and cross reactivity in recognizing the endogenous and recombinant DEFA5 protein, especially for Immunohistochemistry, Western blot, Immunoprecipitation, or enzyme-linked immunosorbent assay.

Clones 1A8 and 4F5 recognized effectively the endogenous DEFA5 in active human diverticulitis (DV), UC, CC or IC disease samples, including transiently transfected HEK293T cells expressing DEFA5 with high degree of specificity and minimal non-confounding cross reactivity.

1A8 and 4F5 clones are worth studying in larger IBD cohorts to fully address whether DEFA5 expression may be used as a diagnostic biomarker to discrimination of the diagnosis of UC from CC or IC into authentic CC or UC or a colitis with different pathological characteristics.

Most paediatric inflammatory bowel disease [IBD] studies are performed after medications are approved in adults, and the majority of participants in these studies are adolescents. We hypothesised that adolescent-onset IBD is not fundamentally different from adult-onset IBD. If this is correct, the value of delaying access to novel drugs in adolescents becomes questioned.

Data from 11 randomised, double-blind, placebo-controlled, adult Phases 2 and 3 trials of four biologics were analysed. Participants were categorised as having adolescent- or adult-onset disease [diagnosed 12 to <18, or ≥18 years]. Multivariable modelling explored the association between age at diagnosis and response to treatment, after adjustment for disease duration, extent, and severity at baseline. Data from dose arms were pooled to evaluate similarity of therapeutic response between adolescent- and adult-onset IBD within the same trial [not between doses or across trials]. Ratios of odds ratios [ORs] between the two groups were evaluated.

Data from 6283 study participants (2575 with Crohn's disease [CD], 3708 with ulcerative colitis [UC]) were evaluated. Of 2575 study participants with CD, 325 were 12-<18 years old at diagnosis; 836 participants [32.4%] received placebo. Of 3708 participants with UC, 221 were 12-<18 years old at diagnosis; 1212 [33%] were receiving placebo. The majority of the ratios of ORs were within 2-fold, suggesting that responses in adolescent- and adult-onset participants are generally similar.

Data presented lend support for extrapolating efficacy of biologics from adults to adolescents with IBD, which would facilitate earlier labelling and patient access.

Minimally invasive surgery (MIS) provides superior results in the surgical treatment of inflammatory bowel disease (IBD). There exist various minimally invasive procedures, each possessing its own set of benefits and drawbacks. This literature review outlines these methodologies and underscores their importance in enhancing the outcomes of patients with IBD. A grand total of 192 studies were carefully chosen and succinctly summarized. Conventional multiport laparoscopy is the most widely used MIS for IBD, with single-incision laparoscopy showing even better results. Robotic surgery offers comparable results but at higher costs and longer operation times. In the future, there will be widespread acceptance of single-incision laparoscopy and robotic surgery due to improved training and reduced expenses. Further research into the technology's utility in different IBD presentations could increase its usage.

Few studies have reported the prevalence of inflammatory bowel disease unclassified (IBDU) among Korean pediatric IBD (PIBD) population. To address this gap, we used two tertiary centers and nationwide population-based healthcare administrative data to estimate the prevalence of Korean pediatric IBDU at the time of diagnosis.

We identified 136 patients aged 2-17 years with newly diagnosed IBD (94 Crohn's disease [CD] and 42 ulcerative colitis [UC]) from two tertiary centers in Korea between 2005 and 2017. We reclassified these 136 patients using the revised Porto criteria. To estimate the population-based prevalence, we analyzed Korean administrative healthcare data between 2005 and 2016, which revealed 3,650 IBD patients, including 2,538 CD and 1,112 UC. By extrapolating the reclassified results to a population-based dataset, we estimated the prevalence of PIBD subtypes.

Among the 94 CD, the original diagnosis remained unchanged in 93 (98.9%), while the diagnosis of one (1.1%) patient was changed to IBDU. Among the 42 UC, the original diagnosis remained unchanged in 13 (31.0%), while the diagnoses in 11 (26.2%), 17 (40.5%), and one (2.4%) patient changed to atypical UC, IBDU, and CD, respectively. The estimated prevalences of CD, UC, atypical UC, and IBDU in the Korean population were 69.5%, 9.4%, 8.0%, and 13.1%, respectively.

This study is the first in Korea to estimate the prevalence of pediatric IBDU. This prevalence (13.1%) aligns with findings from Western studies. Large-scale prospective multicenter studies on PIBDU are required to examine the clinical features and outcomes of this condition.

Mycobacterium avium ssp. paratuberculosis (MAP) has been implicated in the development of Crohn's disease (CD) for over a century. Similarities have been noted between the (histo)pathological presentation of MAP in ruminants, termed Johne's disease (JD), and appearances in humans with CD. Analyses of disease presentation and pathology suggest a multi-step process occurs that consists of MAP infection, dysbiosis of the gut microbiome, and dietary influences. Each step has a role in the disease development and requires a better understanding to implementing combination therapies, such as antibiotics, vaccination, faecal microbiota transplants (FMT) and dietary plans. To optimise responses, each must be tailored directly to the activity of MAP, otherwise therapies are open to interpretation without microbiological evidence that the organism is present and has been influenced. Microscopy and histopathology enables studies of the mycobacterium in situ and how the associated disease processes manifest in the patient e.g., granulomas, fissuring, etc. The challenge for researchers has been to prove the relationship between MAP and CD with available laboratory tests and methodologies, such as polymerase chain reaction (PCR), MAP-associated DNA sequences and bacteriological culture investigations. These have, so far, been inconclusive in revealing the relationship of MAP in patients with CD. Improved and accurate methods of detection will add to evidence for an infectious aetiology of CD. Specifically, if the bacterial pathogen can be isolated, identified and cultivated, then causal relationships to disease can be confirmed, especially if it is present in human gut tissue. This review discusses how MAP may cause the inflammation seen in CD by relating its known pathogenesis in cattle, and from examples of other mycobacterial infections in humans, and how this would impact upon the difficulties with diagnostic tests for the organism.

Prior studies on the psychological well-being in pediatric inflammatory bowel disease (PIBD) have reported controversial results. Our aim was to compare the psychological well-being and lifestyle factors in patients with PIBD and their controls and to assess the role of contributing disease characteristics.

This cross-sectional study included 60 PIBD patients aged 6-17 years (26 with Crohn's disease [CD], 34 with ulcerative colitis [UC] or unclassified colitis [IBD-U]) from two university hospitals in Finland, and their age- and sex-matched healthy controls. Psychological well-being was assessed with three measures: a questionnaire on overall psychological well-being (PSWB) and for adolescents also Beck Depression Inventory (BDI Ia) and Perceived Stress Scale (PSS). In addition to disease characteristics and pain, we assessed physical activity, sleep, screen time, and social well-being.

Controls were more likely of stressing more (odds ratio [OR] = 3.67, 95% confidence interval [95% CI] 95% CI = 1.02-13.14), but other measures of psychological well-being did not differ statistically significantly between patients and controls. In CD, a clinically more active disease associated with inferior psychological well-being in adolescents (BDI [ρ = 0.63, p = 0.021], PSS [ρ = 0.70, p = 0.008], PSWB [ρ = 0.56, p = 0.049]). Longer time from diagnosis correlated with better psychological well-being on BDI (ρ = -0.39, p = 0.024) and PSS (ρ = -0.38, p = 0.034). Lifestyle was more sedentary in PIBD (less physical activity in children OR = 0.82, 95% CI = 0.68-0.99 and more screen time in adolescents OR = 1.18, 95% CI = 1.00-1.40).

Although the clinical features of PIBD are potentially a burden for psychological well-being, many young patients cope well with their disease. Individual variation in well-being is remarkable, making supportive measures challenging.

Despite the continuously rising rate of pediatric-onset inflammatory bowel diseases (PIBD), there are no consensus transitional guidelines or standardized practices.

We aimed to examine: (1) the determinants of a successful transfer, (2) the effects of the transfer versus transition on the disease course and patient compliance, (3) the unique characteristics of PIBD patients, that need special attention in adult care.

Longitudinal, follow-up, controlled study conducted between 2001 and 2022, with retrospective data collection until 2018, thence prospective.

Three hundred fifty-one PIBD patients enrolled in the study, of whom 152 were moved to adult care, with a mean post-transfer follow-up time of 3 years. Seventy-three patients took part in structured transition, whereas 79 self-transferred to adult care. The main outcome measures were disease activity (defined by PCDAI, PUCAI, CDAI, and Mayo-scores) and course, hospitalizations, surgeries, IBD-related complications, including anthropometry and bone density, patient compliance, medication adherence, and continuation of medical care.

Patients who underwent structured transition spent significantly more time in remission (83.6% ± 28.5% versus 77.5% ± 29.7%, p = 0.0339) and had better adherence to their medications (31.9% versus 16.4% non-adherence rate, p = 0.0455) in adult care, with self-transferred patients having a 1.59-fold increased risk of discontinuing their medical care and a 1.88-fold increased risk of experiencing a relapse. Post-transfer the compliance of patients deteriorated (38.5% versus 29%, p = 0.0002), with the highest lost-to-follow-up rate during the changing period between the healthcare systems (12.7%), in which female gender was a risk factor (p = 0.010). PIBD patients had experienced IBD-related complications (23.4%) and former surgeries (15%) upon arriving at adult care, with high rates of malnutrition, growth impairment, and poor bone health.

Structured transition plays a key role in ensuring the best disease course and lowering the lost-to-follow-up rate among PIBD patients.

Structured transition plays a key role in ensuring the best disease outcome among PIBD patients, as in our study it was associated with lower disease activity, fewer relapses, better medication adherence, and lower lost-to-follow-up rate as opposed to self-transfer.

Surgical management of pediatric Crohn's disease is fundamentally palliative, aiming to treat the sequalae of complicated disease while preserving intestinal length. Multidisciplinary discussion of risk factors and quality of life should take place prior to operative intervention. Though the surgical management of pediatric Crohn's disease is largely based on the adult literature, there are considerations specific to the pediatric population - notably disease and treatment effects on growth and development. Intrabdominal abscess is approached with percutaneous drainage when feasible, reserving surgical intervention for the patient who is unstable or failing medical therapy. Pediatric patients with fibrostenotic disease should be considered for strictureplasty when possible, for maximum preservation of bowel length. Patients with medically refractory Crohn's proctocolitis should be treated initially with fecal diversion without proctocolectomy.

The incidence of ulcerative colitis (UC) among children and adolescents is rising globally, albeit with notable discrepancies across countries. This systematic review and meta-analysis aims to provide a comprehensive overview of the incidence rates of pediatric UC in various countries and explore potential influencing factors. A systematic literature search was conducted in PubMed and EMBASE (via OVID) for studies published between January 1, 1970, and December 31, 2019. Additionally, a manual search was performed to identify relevant systematic reviews. Meta-analyses and meta-regressions were employed to determine the overall incidence rate and examine potential factors that may influence it. A total of 66 studies were included in the qualitative analysis, while 65 studies were included in the meta-analysis and 50 studies were meta-regression. The study reports a rising incidence of pediatric UC in several countries but significant differences across geographic regions, with no discernible global temporal trend. In addition, our meta-regression analysis showed that geographic location and socioeconomic factors significantly influenced the incidence of UC.

Our findings indicate a rising incidence of pediatric UC in numerous countries since 1970, but with significant geographical variation, potentially presenting challenges for respective healthcare systems. We have identified geographic and socioeconomic factors that contribute to the observed heterogeneity in incidence rates. These findings provide a foundation for future research and health policies, aiming to tackle the growing burden of UC among children and adolescents.

• The incidence of ulcerative colitis in childhood and adolescence appears to be increasing worldwide and varies internationally. • Environmental and lifestyle factors are suspected as potential causes.

• Our results highlight that the heterogeneity in incidence rates can be attributed to geographic and socio-economic factors.

The worldwide incidence of Crohn disease (CD) in childhood and adolescence has an increasing trend, with significant differences between different geographic regions and individual countries. This includes an increase in the incidence of CD in countries and geographic regions where CD was not previously prevalent. In response to the increasing incidence, the pediatric care landscape is facing growing challenges.

This systematic review and meta-analysis were undertaken to comprehensively delineate the incidence rates of CD in pediatric populations across different countries and to explore potential influencing factors.

We performed a systematic review of PubMed and Embase (via Ovid) for studies from January 1, 1970, to December 31, 2019. In addition, a manual search was performed in relevant and previously published reviews. The results were evaluated quantitatively. For this purpose, random effects meta-analyses and meta-regressions were performed to investigate the overall incidence rate and possible factors influencing the incidence.

A qualitative synthesis of 74 studies was performed, with 72 studies included in the meta-analyses and 52 in the meta-regressions. The results of our meta-analysis showed significant heterogeneity between the individual studies, which cannot be explained by a sample effect alone. Our findings showed geographical differences in incidence rates, which increased with increasing distance from the equator, although no global temporal trend was apparent. The meta-regression analysis also identified geographic location, UV index, and Human Development Index as significant moderators associated with CD incidence.

Our results suggest that pediatric CD incidence has increased in many countries since 1970 but varies widely with geographic location, which may pose challenges to the respective health care systems. We identified geographic, environmental, and socioeconomic factors that contribute to the observed heterogeneity in incidence rates. These results can serve as a basis for future research. To this end, implementations of internationally standardized and interoperable registries combined with the dissemination of health data through federated networks based on a common data model, such as the Observational Medical Outcomes Partnership, would be beneficial. This would deepen the understanding of CD and promote evidence-based approaches to preventive and interventional strategies as well as inform public health policies aimed at addressing the increasing burden of CD in children and adolescents.

PROSPERO International prospective register of systematic reviews CRD42020168644; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=168644.

RR2-10.1136/bmjopen-2020-037669.

Inflammatory bowel diseases, consisting of Crohn's disease and ulcerative colitis, are chronic bowel relapsing inflammatory disorders. Inflammatory bowel diseases begin rarely in infants. Approximately 25% of patients with inflammatory bowel diseases present before the age of 20 years. Very early-onset inflammatory bowel disease occurs before the age of 6 years; infantile inflammatory bowel diseases occurs before the age of 2 years, and is extremely rare in infants under 1 year of age.

Herein, we report a case series of 7-month-, 11-month-, and 12-month-old Syrian infants that presented with diarrhea, hematochezia, and pale appearance and were finally diagnosed with infantile inflammatory bowel disease and treated.

Early diagnosis and ruling out infantile inflammatory bowel diseases despite its rarity are recommended. Over and above that, new drugs such as vedolizumab, golimumab, and less invasive treatment methods should also be taken into consideration for better response and adequate remission with improved quality of life.

Multispectral optoacoustic tomography (MSOT) allows non-invasive molecular disease activity assessment in adults with inflammatory bowel disease (IBD). In this prospective pilot-study, we investigated, whether increased levels of MSOT haemoglobin parameters corresponded to inflammatory activity in paediatric IBD patients, too. 23 children with suspected IBD underwent MSOT of the terminal ileum and sigmoid colon with standard validation (e.g. endoscopy). In Crohn`s disease (CD) and ulcerative colitis (UC) patients with endoscopically confirmed disease activity, MSOT total haemoglobin (HbT) signals were increased in the terminal ileum of CD (72.1 ± 13.0 a.u. vs. 32.9 ± 15.4 a.u., p = 0.0049) and in the sigmoid colon of UC patients (62.9 ± 13.8 a.u. vs. 35.1 ± 16.3 a.u., p = 0.0311) as compared to controls, respectively. Furthermore, MSOT haemoglobin parameters correlated well with standard disease activity assessment (e.g. SES-CD and MSOT HbT (rs =0.69, p = 0.0075). Summarizing, MSOT is a novel technology for non-invasive molecular disease activity assessment in paediatric patients with inflammatory bowel disease.

Pediatric inflammatory bowel disease (IBD) has been known to be a disease predominant in the west. There is scarcity of data on pediatric IBD (P-IBD) from northern India. The objective of our study was to analyze the clinical spectrum of P-IBD in northern India.

A retrospective analysis of 126 children (<18-year old) diagnosed with IBD from January 1999 to December 2019 was done on a pre-designed proforma. It was systematically entered in a MS Excel spreadsheet and analyzed using Statistical Package for the Social Sciences (SPSS) version 21.0. The descriptive phenotypes of Ulcerative colitis (UC) and Crohn's disease (CD) were revised according to the Paris classification.

Of 126 children, UC was diagnosed in 76 (60.3%), CD in 44 (34.9%) and IBD-unclassified (IBD-U) in six (4.76%) patients. The mean age at diagnosis was 11.3 years; 38.8% were < 10 years with the male: female ratio of 1.6:1. Sixteen children (12.7%) had very early onset IBD (VEOBD). Overall, the median time to diagnosis in IBD was 12 months (interquartile range [IQR]: 3.25-24), which was as high as 52.5 months (IQR: 11-98) in CD. Pancolitis with bleeding per rectum and ileocolonic involvement with pain in abdomen were the commonest presentations in UC and CD, respectively. Stricturing disease was seen in 27% of CD cases. Relapses were seen in 46% (35/76) of U.C and 23% (10/44) of CD kids. Step-up treatment protocol was employed in them with the use of biologicals in 12% of cases. There was a 2.75-fold rise in the IBD cases in the last 10 years (2010-20). There was reduction in time to diagnosis (21 months vs. 90 months; p - 0.012) and empirical anti-tubercular therapy use (90% vs. 5.8%) in CD over two decades.

From our experience in a tertiary care centre in northern India, P-IBD is on the rise. UC is more common than CD. Pancolitis and ileocolonic disease are the commonest disease sites in UC and CD, respectively There is a significant delay in the time to diagnosis in CD. Stricturing disease was seen in a quarter of children with CD.

ATG16L1 plays a fundamental role in the degradative intracellular pathway known as autophagy, being a mediator of inflammation and microbial homeostasis. The variant rs2241880 can diminish these capabilities, potentially contributing to inflammatory bowel disease (IBD) pathogenesis.

To perform an updated meta-analysis on the association between ATG16L1 rs2241880 and IBD susceptibility by exploring the impact of age, ethnicity, and geography. Moreover, to investigate the association between rs2241880 and clinical features.

Literature searches up until September 2022 across 7 electronic public databases were performed for all case-control studies on ATG16L1 rs2241880 and IBD. Pooled odds ratios (ORP ) and 95% CI were calculated under the random effects model.

Our analyses included a total of 30,606 IBD patients, comprising 21,270 Crohn's disease (CD) and 9336 ulcerative colitis (UC) patients, and 33,329 controls. ATG16L1 rs2241880 was significantly associated with CD susceptibility, where the A allele was protective (ORP : 0.74, 95% CI: 0.72-0.77, p-value: <0.001), while the G allele was a risk factor (ORP : 1.23, 95% CI: 1.09-1.39, p-value: 0.001), depending on the minor allele frequencies observed in this multi-ancestry study sample. rs2241880 was predominantly relevant in Caucasians from North America and Europe, and in Latin American populations. Importantly, CD patients harbouring the G allele were significantly more predisposed to perianal disease (ORP : 1.21, 95% CI: 1.07-1.38, p-value: 0.003).

ATG16L1 rs2241880 (G allele) is a consistent risk factor for IBD in Caucasian cohorts and influences clinical outcomes. As its role in non-Caucasian populations remains ambiguous, further studies in under-reported populations are necessary.

Inflammatory bowel disease (IBD) comprises a group of relapsing, chronic diseases of the gastrointestinal tract that, in addition to adults, can affect children and adolescents. To detect relapses of inflammation, these patients require close observation, frequent follow-up, and therapeutic adjustments. While reference standard diagnostics include anamnestic factors, laboratory and stool sample assessment, performing specific imaging in children and adolescents is much more challenging than in adults. Endoscopic and classic cross-sectional imaging modalities may be invasive and often require sedation for younger patients. For this reason, intestinal ultrasound (IUS) is becoming increasingly important for the non-invasive assessment of the intestine and its inflammatory affection. In this review, we would like to shed light on the current state of the art and provide an outlook on developments in this field that could potentially spare these patients more invasive follow-up procedures.

The incidence of inflammatory bowel disease (IBD) in children is on the increase worldwide. Growth disorders are common in pediatric patients with inflammatory bowel disease. The aim of this paper is to investigate anthropometric indicators, including height and weight in children with inflammatory bowel disease in Saxony, one of the German federal states, and to evaluate growth trends in patients by comparing their height and weight with that of healthy children in Germany.

In Saxony, all children and adolescents with IBD were registered in the Saxon Pediatric IBD Registry from 2000 to 2014. The data used are therefore based on a total area-wide survey over 15 years. For this study, 421 datasets of children and adolescents aged 0-14 years with Crohn's disease (CD) (n = 291) or ulcerative colitis (UC) (n = 130) were analyzed. Z-score and percentile calculations were used to compare differences between IBD patients and the general population.

The children with CD or UC (both sexes) had a significant lower weight at diagnosis (the mean weight z-score had negative values) versus the general population. The weight values lay mostly below P50 (the 50th percentile, median), more precisely, mostly between P10 and P50 of the body weight child growth curve for corresponding sexes (KiGGS 2003-2006). The height values of both sexes at diagnosis lay also mostly below P50 (the 50th percentile, median) of the child body growth curve for corresponding sexes (KiGGS 2003-2006), i.e. the mean height z-score was negative. But only the children with CD had a significant lower height, more precisely, mostly between P25 and P50 versus the general population (KIGGS). For children with UC the difference was not significant.

In pediatric patients with IBD the possibility of growth disturbance, mainly in the form of weight retardation, is very probable.