Identification and multimodal characterization of a specialized epithelial cell type associated with Crohn's disease.

Crohn's disease (CD) is a complex chronic inflammatory disorder with both gastrointestinal and extra-intestinal manifestations associated immune dysregulation. Analyzing 202,359 cells from 170 specimens across 83 patients, we identify a distinct epithelial cell type in both terminal ileum and ascending colon (hereon as 'LND') with high expression of LCN2, NOS2, and DUOX2 and genes related to antimicrobial response and immunoregulation. LND cells, confirmed by in-situ RNA and protein imaging, are rare in non-IBD controls but expand in active CD, and actively interact with immune cells and specifically express IBD/CD susceptibility genes, suggesting a possible function in CD immunopathogenesis. Furthermore, we discover early and late LND subpopulations with different origins and developmental potential. A higher ratio of late-to-early LND cells correlates with better response to anti-TNF treatment. Our findings thus suggest a potential pathogenic role for LND cells in both Crohn's ileitis and colitis.

In vitro neutralization of IL-6 receptor exacerbates damage to intestinal epithelial cells during Mycobacterium avium paratuberculosis infection.

Like TNFα, IL-6 is upregulated in Crohn's disease (CD) especially in patients associated with Mycobacterium avium paratuberculosis (MAP) infection, and both cytokines have been targeted as a therapeutic option for the treatment of the disease despite the accepted partial response in some patients. Limited response to anti-IL-6 receptor-neutralizing antibodies therapy may be related to the homeostatic dual role of IL-6. In this study, we investigated the effects and the signaling mechanism of IL-6 involved in intestinal epithelial integrity and function during MAP infection using an in vitro model that consists of THP-1, HT-29 and Caco-2 cell lines. Clinically, we determined that plasma samples from MAP-infected CD patients have higher IL-6 levels compared to controls (P-value < 0.001). In CD-like macrophages, MAP infection has significantly upregulated the secretion of IL-6 and the shedding of (IL-6R) from THP-1 macrophages, P-value < 0.05. Intestinal cell lines (Caco-2 and HT-29) were treated with the supernatant of MAP-infected THP-1 macrophages with or without a neutralizing anti-IL-6R antibody. Treating intestinal Caco-2 cells with supernatant of MAP-infected macrophages resulted in significant upregulation of intestinal damage markers including claudin-2 and SERPINE1/PAI-1. Interestingly, blocking IL-6 signaling exacerbated that damage and further increased the levels of the damage markers. In HT-29 cells, MAP infection upregulated MUC2 expression, a protective response that was reversed when IL-6R was neutralized. More importantly, blocking IL-6 signaling during MAP infection rescued damaged Caco-2 cells from MAP-induced apoptosis. The data clearly supports a protective role of IL-6 in intestinal epithelia integrity and function especially in CD patients associated with MAP infection. The findings may explain the ineffective response to anti-IL6 based therapy and strongly support a therapeutic option that restores the physiologic level of IL-6 in patient's plasma. A new treatment strategy based on attenuation of IL-6 expression and secretion in inflammatory diseases should be considered.

Decoding polyphenol metabolism in patients with Crohn's disease: Insights from diet, gut microbiota, and metabolites.

Crohn's disease (CD) is a chronic and progressive inflammatory disease that can involve any part of the gastrointestinal tract. The protective role of dietary polyphenols has been documented in preclinical models of CD. Gut microbiota mediates the metabolism of polyphenols and affects their bioactivity and physiological functions. However, it remains elusive the capacity of microbial polyphenol metabolism in CD patients and healthy controls (HCs) along with its correlation with polyphenols intake and polyphenol-derived metabolites. Thus, we aimed to decode polyphenol metabolism in CD patients through aspects of diet, gut microbiota, and metabolites. Dietary intake analysis revealed that CD patients exhibited decreased intake of polyphenols. Using metagenomic data from two independent clinical cohorts (FAH-SYSU and PRISM), we quantified abundance of polyphenol degradation associated bacteria and functional genes in CD and HCs and observed a lower capacity of flavonoids degradation in gut microbiota residing in CD patients. Furthermore, through analysis of serum metabolites and enterotypes in participants of FAH-SYSU cohort, we observed that CD patients exhibited reduced levels of serum hippuric acid (HA), one of polyphenol-derived metabolites. HA level was higher in healthier enterotypes (characterized by dominance of Ruminococcaceae and Prevotellaceae, dominant by HCs) and positively correlated with multiple polyphenols intake and abundance of bacteria engaged in flavonoids degradation as well as short-chain fatty acid production, which could serve as a biomarker for effective polyphenol metabolism by the gut microbiota and a healthier gut microbial community structure. Overall, our findings provide a foundation for future work exploring the polyphenol-based or microbiota-targeted therapeutic strategies in CD.

Microbial assimilatory sulfate reduction-mediated H2S: an overlooked role in Crohn's disease development.

BACKGROUND: H2S imbalances in the intestinal tract trigger Crohn's disease (CD), a chronic inflammatory gastrointestinal disorder characterized by microbiota dysbiosis and barrier dysfunction. However, a comprehensive understanding of H2S generation in the gut, and the contributions of both microbiota and host to systemic H2S levels in CD, remain to be elucidated. This investigation aimed to enhance comprehension regarding the sulfidogenic potential of both the human host and the gut microbiota. RESULTS: Our analysis of a treatment-naive CD cohorts' fecal metagenomic and biopsy metatranscriptomic data revealed reduced expression of host endogenous H2S generation genes alongside increased abundance of microbial exogenous H2S production genes in correlation with CD. While prior studies focused on microbial H2S production via dissimilatory sulfite reductases, our metagenomic analysis suggests the assimilatory sulfate reduction (ASR) pathway is a more significant contributor in the human gut, given its high prevalence and abundance. Subsequently, we validated our hypothesis experimentally by generating ASR-deficient E. coli mutants ∆cysJ and ∆cysM through the deletion of sulfite reductase and L-cysteine synthase genes. This alteration significantly affected bacterial sulfidogenic capacity, colon epithelial cell viability, and colonic mucin sulfation, ultimately leading to colitis in murine model. Further study revealed that gut microbiota degrade sulfopolysaccharides and assimilate sulfate to produce H2S via the ASR pathway, highlighting the role of sulfopolysaccharides in colitis and cautioning against their use as food additives. CONCLUSIONS: Our study significantly advances understanding of microbial sulfur metabolism in the human gut, elucidating the complex interplay between diet, gut microbiota, and host sulfur metabolism. We highlight the microbial ASR pathway as an overlooked endogenous H2S producer and a potential therapeutic target for managing CD. Video Abstract.

From serum metabolites to the gut: revealing metabolic clues to susceptibility to subtypes of Crohn's disease and ulcerative colitis.

Background and aims: Inflammatory bowel disease (IBD) is a common chronic inflammatory bowel disease characterized by diarrhea and abdominal pain. Recently human metabolites have been found to help explain the underlying biological mechanisms of diseases of the intestinal system, so we aimed to assess the causal relationship between human blood metabolites and susceptibility to IBD subtypes. Methods: We selected a genome-wide association study (GWAS) of 275 metabolites as the exposure factor, and the GWAS dataset of 10 IBD subtypes as the outcome, followed by univariate and multivariate analyses using a two-sample Mendelian randomization study (MR) to study the causal relationship between exposure and outcome, respectively. A series of sensitivity analyses were also performed to ensure the robustness of the results. Results: A total of 107 metabolites were found to be causally associated on univariate analysis after correcting for false discovery rate (FDR), and a total of 9 metabolites were found to be significantly causally associated on subsequent multivariate and sensitivity analyses. In addition we found causal associations between 7 metabolite pathways and 6 IBD subtypes. Conclusion: Our study confirms that blood metabolites and certain metabolic pathways are causally associated with the development of IBD subtypes and their parenteral manifestations. The exploration of the mechanisms of novel blood metabolites on IBD may provide new therapeutic ideas for IBD patients.

[Small Molecule Therapy for Inflammatory Bowel Disease: JAK Inhibitors and S1PR Modulators].

Small molecules, including Janus kinase (JAK) inhibitors and sphingosine-1-phosphate receptor modulators (S1PRMs), are promising new treatments for inflammatory bowel disease (IBD). Small molecules exhibit more predictable pharmacokinetics than biologics, are less likely to induce immune responses, and can be administered orally. JAK inhibitors function by blocking the activity of JAK enzymes, which prevents the subsequent phosphorylation and activation of signal transducer and activator of transcription (STAT) proteins. Tofacitinib and filgotinib are approved for treating ulcerative colitis (UC), while upadacitinib is approved for UC and Crohn's disease. Nevertheless, JAK inhibitors can increase the risk of herpes zoster, cancer, major adverse cardiovascular events, and venous thromboembolism. S1PRMs bind to S1PRs, particularly S1PR1, on lymphocytes. This interaction inhibits lymphocytes from exiting the lymph nodes and migrating to the gut, thereby reducing inflammation and the immune response in the intestinal mucosa. Ozanimod and etrasimod are S1PRMs approved for the treatment of UC, but they can cause side effects such as bradycardia, conduction disorder, and macular edema. Overall, JAK inhibitors and S1PRMs offer significant benefits in managing IBD, although their potential side effects require careful monitoring.

[Old and New Biologics and Small Molecules in Inflammatory Bowel Disease: Anti-interleukins].

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic inflammatory disease of the gastrointestinal tract. The introduction of biologics, particularly anti-interleukin (IL) agents, has revolutionized IBD treatment. This review summarizes the role of ILs in IBD pathophysiology and describes the efficacy and positioning of anti-IL therapies. We discuss the functions of key ILs in IBD and their potential as therapeutic targets. The review then discusses anti-IL therapies, focusing primarily on ustekinumab (anti-IL-12/23), risankizumab (anti-IL-23), and mirikizumab (anti-IL-23). Clinical trial data demonstrate their efficacy in inducing and maintaining remission in Crohn's disease and ulcerative colitis. The safety profiles of these agents are generally favorable. However, long-term safety data for newer agents are still limited. The review also briefly discusses emerging therapies such as guselkumab and brazikumab. Network meta-analyses suggest that anti-IL therapies perform well compared to other biological agents. These agents may be considered first- or second-line therapies for many patients, especially those with comorbidities or safety concerns. Anti-IL therapies represent a significant advancement in IBD treatment, offering effective and relatively safe options for patients with moderate to severe disease.

Unravelling the role of beta-CGRP in inflammatory bowel disease and its potential role in gastrointestinal homeostasis.

BACKGROUND: The role of beta calcitonin gene-related peptide (beta-CGRP) in gastrointestinal tract is obscure, but experimental models suggest an effect on the homeostasis of the intestinal mucosa. We measured beta-CGRP circulating levels in a large series of subjects with a recent diagnosis of inflammatory bowel disease (IBD), in order to assess the potential role of this neuropeptide in IBD pathogenesis. METHODS: Morning serum beta-CGRP levels were measured by ELISA (CUSABIO, China) in 96 patients recently diagnosed of IBD and compared with those belonging from 50 matched healthy controls (HC) and 50 chronic migraine (CM) patients. RESULTS: Beta-CGRP levels were lower in patients with IBD (3.1 ± 1.9 pg/mL; 2.9 [2.4-3.4] pg/mL) as compared to HC (4.7 ± 2.6; 4.9 [4.0-5.8] pg/mL; p < 0.001) and to CM patients (4.6 ± 2.6; 4.7 [3.3-6.2] pg/mL; p < 0.001). Beta-CGRP levels in CM were not significantly different to those of HC (p = 0.92). Regarding IBD diagnostic subtypes, beta-CGRP levels for ulcerative colitis (3.0 ± 1.9pg/mL; 2.5 [2.1-3.4] pg/mL) and Crohn's disease (3.3 ± 2.0 pg/mL; 3.2 [2.4-3.9] pg/mL) were significantly lower to those of HC (p < 0.01 and p < 0.05, respectively) and CM (p < 0.01 and p < 0.05, respectively). CONCLUSIONS: We have found a significant reduction in serum beta-CGRP levels in patients with a recent diagnosis of all kinds of IBD as compared to two control groups without active intestinal disease, HC and CM, which may suggest a role for this neuropeptide in the pathophysiology of IBD. Our data indicate a protective role of beta-CGRP in the homeostasis of the alimentary tract.

Diagnostic delay in inflammatory bowel diseases in a German population.

BACKGROUND: Early diagnosis is key to prevent bowel damage in inflammatory bowel disease (IBD). Risk factor analyses linked with delayed diagnosis in European IBD patients are scarce and no data in German IBD patients exists. AIM: To identify risk factors leading to prolonged diagnostic time in a German IBD cohort. METHODS: Between 2012 and 2022, 430 IBD patients from four Berlin hospitals were enrolled in a prospective study and asked to complete a 16-item questionnaire to determine features of the path leading to IBD diagnosis. Total diagnostic time was defined as the time from symptom onset to consulting a physician (patient waiting time) and from first consultation to IBD diagnosis (physician diagnostic time). Univariate and multivariate analyses were performed to identify risk factors for each time period. RESULTS: The total diagnostic time was significantly longer in Crohn's disease (CD) compared to ulcerative colitis (UC) patients (12.0 vs 4.0 mo; P < 0.001), mainly due to increased physician diagnostic time (5.5 vs 1.0 mo; P < 0.001). In a multivariate analysis, the predominant symptoms diarrhea (P = 0.012) and skin lesions (P = 0.028) as well as performed gastroscopy (P = 0.042) were associated with longer physician diagnostic time in CD patients. In UC, fever was correlated (P = 0.020) with shorter physician diagnostic time, while fatigue (P = 0.011) and positive family history (P = 0.046) were correlated with longer physician diagnostic time. CONCLUSION: We demonstrated that CD patients compared to UC are at risk of long diagnostic delay. Future efforts should focus on shortening the diagnostic delay for a better outcome in these patients.

Different imaging techniques' diagnostic efficacy for Crohn's disease activity and external validation and comparison of MDCTAs, SES-CD and IBUSSAS.

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disease of the digestive tract with unknown etiology. It follows a relapse-remission pattern, making disease activity assessment crucial for treatment. Our study aims to evaluate the diagnostic accuracy of various imaging modalities and to validate and compare the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS), the multidetector computed tomography enterography score (MDCTEs), and the simplified endoscopic activity score for Crohn's disease (SES-CD). METHODS: We assessed diagnostic performance using the CD Activity Index (CDAI). We first categorized patients into remission and active groups. For those in the active stage, we further categorized them into mild/moderate and severe activity groups. We used Spearman rank correlation to evaluate the relationships among IBUS-SAS, bowel wall thickness (BWT), Color Doppler imaging signal (CDS), inflammatory fat (i-fat), bowel wall stratification (BWS), and clinical inflammatory indicators. RESULTS: A total of 103 CD patients were evaluated. The IBUS-SAS cut-off for remission and activity was 23.8, with an AUC of 0.923, sensitivity of 91.4%, and specificity of 84.8%. The SES-CD had an AUC of 0.801, sensitivity of 62.9%, and specificity of 84.4% at a cut-off of 4.5. The MDCTEs showed an AUC of 0.855, sensitivity of 77.1%, and specificity of 75.8% for a cut-off of 6.5. The Delong test revealed significant differences in diagnostic efficacy when comparing IBUS-SAS to SES-CD and IBUS-SAS to MDCTEs. In the group of mild or moderate-to-severe active, the IBUS-SAS had an AUC of 0.925, sensitivity of 83.7%, and specificity of 88.9% at a cut-off of 40. The SES-CD exhibited an AUC of 0.850, sensitivity of 90.7%, and specificity of 70.4% at a cut-off of 8.5. MDCTEs showed an AUC of 0.909, sensitivity of 83.7%, and specificity of 85.2% at a cut-off of 8.5. During Delong test, the IBUS-SAS, MDCTEs, and SES-CD showed no significant differences in assessing moderate-to-severe activity. Both IBUS-SAS and ultrasound parameters correlated with certain serum indicators (p < 0.05), although only weakly to moderately (all r < 0.5). CONCLUSION: The IBUS-SAS, MDCTEs and SES-CD can evaluate disease remission/active and mild/moderate-to-severe active in CD, and IBUS-SAS offers the potential to precisely define CD activity.

Temporary diverting loop ileostomy in Crohn's disease surgery; indications and outcome.

INTRODUCTION: Crohn's disease can present with complex surgical pathologies, posing a significant risk of morbidity and mortality for patients. The implementation of a loop ileostomy for selected patients may help minimize associated risks. METHODS: In this retrospective cohort study, we investigated the utilization of temporary fecal diversion through the creation of a loop ileostomy in Crohn's surgery. Closure of all ostomies involved a hand-sewn single-layer technique. We then conducted bivariate analysis on 30-day outcomes for closures, focusing on favorable recovery defined as the restoration of bowel continuity without the occurrence of two challenges in recovery: newly developed organ dysfunction or the necessity for reoperation. RESULTS: In total, 168 patients were included. The median age of the patients was 38 years (IQR 27-51). The most common indication for a loop ostomy was peritonitis (49%). After ileostomy closure, 163 patients (97%) achieved favorable recovery, while five encountered challenges; four (2.4%) underwent abdominal surgery, and one (0.6%) developed acute renal failure requiring dialysis. Two patients (1.2%) had a re-creation of ileostomy. Patients encountering challenges were older (56 [IQR 41-61] vs. 37 [IQR 27-50]; p 0.039) and more often required secondary intention wound healing (40% vs. 6.7%; p 0.049) and postoperative parenteral nutrition following their index surgery (83% vs. 26%; p 0.006). CONCLUSION: Selectively staging the Crohn's disease operations with a loop ileostomy is a reliable practice with low morbidity and high restoration rates of bowel continuity. Our hand-sewn single-layer technique proves effective in achieving successful surgical recovery.

Biological Activity of Hybrid Vaterite-Pectin Microparticles Towards Bacteria E. coli and Human Neutrophils.

Interaction of microbiota with hybrid vaterite-pectin microparticles as an attractive multifunctional vehicle for mucosal delivery should not provoke inflammation. Our purpose was to study the reaction of bacteria E. coli strain Mg1655 and isolate SharL from a patient with Crohn disease on the cultivation with hybrid microparticles and vaterite, and the subsequent activation of neutrophils. Vaterite-pectin microparticles enhanced leakage of ATP from bacteria. For E. coli Mg1655, the concentration of DNA decreased, while intracellular ATP increased. For E. coli SharL, the intracellular ATP decreased with simultaneous growth of DNA. Bacteria and microparticles together did not enhance activation of neutrophils in comparison with the particles per se in the medium without serum and in comparison with bacteria in the medium supplemented with serum; microparticles did not reduce functional activity of neutrophils.

Higher alpha diversity and Lactobacillus blooms are associated with better engraftment after fecal microbiota transplant in inflammatory bowel disease.

Fecal Microbiota Transplant (FMT) has shown some success in treating inflammatory bowel diseases (IBD). There is emerging evidence that host engraftment of donor taxa is a tenet of successful FMT. We undertook a double-blind, randomized, placebo-controlled pilot study to characterize the response to FMT in children and young adults with mild to moderate active Crohn's disease (CD) and ulcerative colitis (UC). Subjects with CD or UC were randomized to receive antibiotics and weekly FMT or placebo in addition to baseline medications. We enrolled 15 subjects aged 14-29 years. Four subjects had CD, and 11 had UC. Subjects exhibited a wide range of microbial diversity and donor engraftment. Specifically, engraftment ranged from 26 to 90% at week 2 and 3-92% at 2 months. Consistent with the current literature, increases over time of both alpha diversity (p < 0.05) and donor engraftment (p < 0.05) correlated with improved clinical response. We discovered that the post-antibiotic but pre-FMT time point was rich in microbial correlates of eventual engraftment. Greater residual alpha diversity after antibiotic treatment was positively correlated with engraftment and subsequent clinical response. Interestingly, a transient rise in the relative abundance of Lactobacillus was also positively correlated with engraftment, a finding that we recapitulated with our analysis of another FMT trial.

Transanal circumferential pouch advancement for treatment of pouch vaginal fistulae.

BACKGROUND: Ileal pouch anal anastomosis (IPAA) circumferential pouch advancement (CPA) involves full-thickness transanal 180-360° dissection of the distal pouch, allowing the advancement of healthy bowel to cover the internal opening of a vaginal fistula. We aimed to describe the long-term outcomes of this rare procedure. METHODS: Patients with IPAA who underwent transanal pouch advancement for any indication between 2009 and 2021 were included. Demographics, operative details, and outcomes were reviewed. An early fistula was defined as occurring within 1 year of IPAA construction. Clinical success was defined as resolution of symptoms necessitating CPA, pouch retention, and no stoma at the time of follow-up. Figures represent the median (interquartile range) or frequency (%). RESULTS: Over a 12-year period, nine patients were identified; the median age at CPA was 41 (36-44) years. Four patients developed early fistula after index IPAA, and five developed late fistulae. The median number of fistula repair procedures prior to CPA was 2 (1-2). All patients were diagnosed with ulcerative colitis at the time of IPAA and all late patients were re-diagnosed with Crohn's disease. Four (44.4%) patients had ileostomies present at the time of surgery, three (33.3%) had one constructed during surgery, and two (22.2%) never had a stoma. The median follow-up time was 11 (6-24) months. Clinical success was achieved in four of the nine (44.4%) patients at the time of the last follow-up. CONCLUSIONS: Transanal circumferential pouch advancement was an effective treatment for refractory pouch vaginal fistulas and may be offered to patients who have had previous attempts at repair.

Co-occurrence of oral pemphigus vulgaris and herpes simplex virus infection in a young patient with Crohn's disease: report of a rare case of oral lesions during anti-TFN alpha and immunomodulator therapy.

BACKGROUND: Pemphigus vulgaris (PV) is a potentially life-threatening mucocutaneous autoimmune disease that affects desmoglein-1 and desmoglein-3, leading to intraepithelial vesiculobullous lesions. In the oral mucosa, PV lesions can mimic other diseases such as mucous membrane pemphigoid, other forms of pemphigus, recurrent aphthous stomatitis, erythema multiforme, Stevens-Johnson syndrome, and virus-induced ulcers like herpes simplex virus (HSV), making diagnosis challenging. The co-occurrence of PV with Crohn's disease is rare and predominantly seen in younger patients. The therapeutic mainstay for both PV and Crohn's disease usually involves systemic corticosteroids combined with immunosuppressants and immunobiological drugs. Literature indicates that the use of these drugs, particularly TNF-alpha inhibitors, for managing autoimmune diseases like Crohn's can potentially induce other autoimmune diseases known as autoimmune-like syndromes, which include episodes of lupus-like syndrome and inflammatory neuropathies. There are few cases in the literature reporting the development of PV in individuals with CD undergoing infliximab therapy. CASE REPORT: A young female with severe Crohn's disease, treated with the TNF-alpha inhibitor infliximab, developed friable pseudomembranous oral ulcerations. Histopathological and immunofluorescence analyses confirmed these as PV. The treatment included clobetasol propionate and low-level photobiomodulation, which resulted in partial improvement. The patient later experienced severe intestinal bleeding, requiring intravenous hydrocortisone therapy, which improved both her systemic condition and oral lesions. Weeks later, new ulcerations caused by herpes virus and candidiasis were identified, leading to treatment with oral acyclovir, a 21-day regimen of oral nystatin rinse, and photodynamic therapy, ultimately healing the oral infections. To manage her condition, the gastroenterologists included methotrexate (25 mg) in her regimen to reduce the immunogenicity of infliximab and minimize corticosteroid use, as the patient was in remission for Crohn's disease, and the oral PV lesions were under control. CONCLUSION: Young patients with Crohn's disease should be referred to an oral medicine specialist for comorbidity investigation, as oral PV and opportunistic infections can arise during immunosuppressive therapy. The use of TNF-alpha inhibitors in patients treated for inflammatory bowel disease, such as Crohn's, should be carefully evaluated for potential side effects, including oral PV.

Epidemiology of pediatric inflammatory bowel disease categorized by age subgroups in Korea.

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

Clinical Characteristics and Etiology of Terminal Ileum Ulcers: A Retrospective Study.

Terminal ileal ulcers can have various etiologies, including Crohn's disease (CD), infections, and medication-related causes. This study aims to investigate the incidence of terminal ileal ulcers detected during colonoscopies, explore their underlying causes, and analyze their clinical, endoscopic, and histopathological characteristics. Additionally, the study aims to identify predictive factors that indicate the need for follow-up. Medical records of all patients who underwent colonoscopies, between 2009 and 2019 were retrospectively reviewed. Patients with terminal ileal ulcers, with or without ileocecal valve involvement, were included in the study. Demographic information, medication usage, symptoms, colonoscopy findings, and histopathological data of these patients were analyzed. A total of 398 patients were included in the study. Histopathological examination revealed that 243 patients (61%) had active ileitis, and 69 patients (17.4%) had chronic active ileitis. The final diagnoses for ulcers were: nonspecific ulcers in 212 patients (53.3%), CD in 66 patients (16.6%), and non-steroidal anti-inflammatory drug-induced ulcers in 58 patients (14.6%). In the multivariate analysis, the parameters predicting CD included the presence of 10 or more ulcers (odds ratio (OR) = 7.305), deep ulcers (OR = 7.431), and edematous surrounding tissue (OR = 5.174), all of which were statistically significant (P < .001). Upon final evaluation, only 66 patients (16.6%) were diagnosed with CD, while 212 patients (53.3%) had nonspecific ulcers. The majority of patients with healed ulcers exhibited pathological findings consistent with active ileitis. Therefore, it can be concluded that not all terminal ileal ulcers are indicative of CD. In those cases with active ileitis, repetitive colonoscopies should be reconsidered.

Prediction of Perianal Fistula in Crohn's Disease by Computed Tomography Enterography.

BACKGROUND/AIMS:  The purpose of this study was to investigate whether computed tomography enterography can be used to predict the presence of perianal fistula in Crohn's disease patients. MATERIALS AND METHODS:  According to the presentation of perianal fistula or not, this study divided retrospectively included Crohn's disease patients into 2 groups. The disease duration, incidence of involved intestinal segments, and scoring of the activity of the lesions in all patients were statistically analyzed to explore significant factors between the 2 groups. The statistically significant findings identified in the univariate analysis were incorporated into the multivariate analysis. Logistic regression models were subsequently constructed to assess the predictive factors associated with the occurrence of perianal fistula in individuals with Crohn's disease.The contribution of each factor to the outcome variable was confirmed by the nomogram. The clinical utility of the nomogram was confirmed by calibration and decision curves. RESULTS:  There were 40 cases with perianal Crohn's disease and 58 without perianal Crohn's disease. After univariate and multivariate analysis, disease duration (early stage of Crohn's disease), ascending colon, and rectum were identified as the independent predictive factors for perianal fistula in Crohn's disease patients. The clinical utility of the nomogram was effective, which implied potential benefits for Crohn's disease patients. CONCLUSION:  Computed tomography enterography can be used to predict the presence of perianal fistula in Crohn's disease patients by analyzing the location and the stage of the disease.