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BACKGROUND: The pathogenesis of Crohns disease involves genetic and environmental factors, with the gut microbiome playing a crucial role. The Crohns disease-associated variant rs13107325 in the SLC39A8 gene results in an A391T substitution in the ZIP8 metal ion transporter and has previously been linked to alterations in the colonic microbiome in variant carriers. We hypothesized that the A391T substitution alters metal ion homeostasis in the colonic mucosal-luminal interface, thereby inducing dysbiosis which may promote intestinal inflammation. METHODS: To evaluate this hypothesis, we generated a SLC39A8 A393T mouse model (matching human A391T). We first examined trace element abundance in the colonic mucosal epithelium and lumen of homozygous A393T and wild-type (WT) mice to determine if the variant affected metal distribution. We also performed 16S rRNA gene sequencing on colon samples at 2 months, 3-4 months, and 12 months of age, and conducted histological scoring of colon tissue collected from 5-month and 10-month old mice. RESULTS: Consistent with an effect of the variant on ZIP8 function, homozygous A393T mice exhibited increased cobalt in the colonic mucosa, but reduced iron, zinc, manganese, cobalt, copper, and cadmium in the colonic lumen. 16S rRNA gene sequencing of colon samples revealed variant-linked effects on microbiome beta diversity in 2-month-, 3-4-month-, and 12-month-old mice. Histological scoring showed spontaneous intestinal inflammation in 10-month but not in 5-month-old mice. Lastly, predicted pathway analysis of the microbiome samples revealed differential enrichment of iron-, zinc-, and cobalt-dependent pathways in A393T mice compared to wild-type controls. CONCLUSION: These results suggest that the variant in SLC39A8 primarily restricts metal availability to the microbiota, resulting in compositions that can adapt to the environment and that A393T-linked dysbiosis occurs prior to the onset of inflammation. This study paves the way for future studies investigating risk variants as microbiome-disease modifiers.

Crohn's disease (CD) is a complex and heterogeneous condition with no perfect preclinical model or cure. To address this, we explore adult stem cell-derived organoids that retain their tissue identity and disease-driving traits. We prospectively create a biobank of CD patient-derived organoid cultures (PDOs) from colonic biopsies of 53 subjects across all clinical subtypes and healthy subjects. Gene expression analyses enabled benchmarking of PDOs as tools for modeling the colonic epithelium in active disease and identified two major molecular subtypes: immune-deficient infectious CD (IDICD) and stress and senescence-induced fibrostenotic CD (S2FCD). Each subtype shows internal consistency in the transcriptome, genome, and phenome. The spectrum of morphometric, phenotypic, and functional changes within the "living biobank" reveals distinct differences between the molecular subtypes. Drug screens reverse subtype-specific phenotypes, suggesting phenotyped-genotyped CD PDOs can bridge basic biology and patient trials by enabling preclinical phase "0" human trials for personalized therapeutics.

INTRODUCTION: A large proportion of patients with inflammatory bowel disease (IBD) experience IBD-related inflammatory conditions outside of the gastrointestinal tract, termed extraintestinal manifestations (EIMs) which further decreases quality of life and, in extreme cases, can be life threatening. The pathogenesis of EIMs remains unknown, and although gut microbiota alterations are a well-known characteristic of patients with IBD, its relationship with EIMs remains sparsely investigated. This study aimed to compare the gut microbiota of patients with IBD with and without EIMs. METHODS: A total of 131 Danish patients with IBD were included in the study, of whom 86 had a history of EIMs (IBD-EIM) and 45 did not (IBD-C). Stool samples underwent 16S rRNA sequencing. Amplicon sequence variants (ASVs) were mapped to the Silva database. Diversity indices and distance matrices were compared between IBD-EIM and IBD-C. Differentially abundant ASVs were identified using a custom multiple model statistical analysis approach, and modules of co-associated bacteria were identified using sparse correlations for compositional data (SparCC) and related to patient EIM status. RESULTS: Patients with IBD and EIMs exhibited increased disease activity, body mass index, increased fecal calprotectin levels and circulating monocytes and neutrophils. Microbiologically, IBD-EIM exhibited lower fecal microbial diversity than IBD-C (Mann-Whitneys test, p = .01) and distinct fecal microbiota composition (permutational multivariate analysis of variance; weighted UniFrac, R2 = 0.018, p = .01). A total of 26 ASVs exhibited differential relative abundances between IBD-EIM and IBD-C, including decreased Agathobacter and Blautia and increased Eggerthella lenta in the IBD-EIM group. SparCC analysis identified 27 bacterial co-association modules, three of which were negatively related to EIM (logistic regression, p

Background: Inflammatory bowel disease (IBD) is a chronic, systemic condition affecting the gastrointestinal tract. IBD can be severe and are associated with impairment in growth, school absences, abdominal pain, and fatigue. Physical activity (PA) could have an anti-inflammatory effect in addition to other benefits. It is important to address the possible risks, physiological effects of PA, and potential barriers, and facilitators for PA participation in pediatric IBD. However, potential barriers and facilitators to PA have yet to be adequately described. Methods: We conducted a scoping review to map and describe the current literature on PA in pediatric IBD populations between 1980 and April 2022 using Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines for Scoping reviews. Results: Nineteen articles were identified including 10 descriptive, 6 interventional, and 3 physiological responses to PA studies. Patients and healthy controls demonstrated similar responses to exercise. Barriers to participation were low self-esteem, body image, and active IBD symptoms. Facilitators included personal interest, activity with friends, and support from family. Conclusion: This review highlighted that PA participation may reduce in children with IBD-related symptoms. Short- and medium-term impacts of PA on immune modulation require further study; it is possible that regular PA does not negatively affect biomarkers of disease activity. [ABSTRACT FROM AUTHOR]

Background: Children with inflammatory bowel disease (IBD) experience extraintestinal side effects including altered body composition, impaired muscle strength, and aerobic capacity. Exercise training may remedy these issues. Purpose: To assess the feasibility, safety, participant satisfaction, and efficacy of a training program for youth with IBD. Methods: Children with IBD completed 16 weeks of training (2 supervised + 1 home sessions per week). Feasibility was assessed by tracking recruitment, adherence, and compliance rates. Safety was assessed by tracking symptoms and adverse events. Posttraining interviews gauged satisfaction. Circulating inflammatory markers, body composition, muscle strength, aerobic fitness, and habitual physical activity were measured at baseline, midtraining (8 wk), and posttraining. Results: Eleven youth were recruited and 10 completed the study. Participants adhered to 28 (1) of 32 prescribed supervised sessions and 8 (4) of 16 prescribed home sessions. There were no adverse events, and overall feedback on training was positive. Posttraining, we observed an increase in lean mass (+2.4 [1.1] kg), bone density (+0.0124 [0.015] g·cm−2), aerobic fitness (+2.8 [5.7] mL·kg LM−1· min−1), and vigorous physical activity levels (+13.09 [8.95] min·h−1) but no change in inflammation or muscle strength. Conclusion: Supervised exercise training is feasible, safe, and effective for youth with IBD and should be encouraged. [ABSTRACT FROM AUTHOR]

Purpose: To examine whether patient-level disease diagnoses, drug treatments, and dental clinical factors are correlates of early implant failure. Materials and Methods: This historical, nested case-control study used electronic medical records to retrieve patient-level data on individuals with implant failure occurring up to 6 months after implantation, including demographics, clinical information (number, location, and complicated status of implants), underlying diseases (osteoporosis, diabetes, hypertension, inflammatory bowel disease [IBD], myocardial infarction [MI]), and drug purchases (chemotherapy, bisphosphonates, selective serotonin inhibitors, antihypertensive medications, proton pump inhibitors [PPIs], disease-modifying antirheumatic drugs, corticosteroids, and nonsteroidal anti-inflammatory drugs) among adult members of a large, state-mandated health provider in Israel between 2015 and 2020. Individuals with implant extraction occurring up to 6 months after implantation were matched 1:1 to controls. Univariate and adjusted multivariate conditional logistic regression models were used to examine the odds ratios (ORs) of all dental implant risk factors among the patients. Results: A total of 585 individuals with implant failure (mean age, 53 years [42,62], 51.3% females and 49.7% males) were identified among 29,378 eligible patients. Compared to controls, patients who experienced implant failure (ie, cases) were more likely to have smoked in their lifetime (18% vs 11.5%, P = .009), experienced IBD (1.5% vs 0.02%, P = .059), and consumed PPIs within 6 months of the implant surgery (40.0% vs 32.5%, P = .028). Clinical factors, including the number of implants per person (individuals with two implants, OR = 1.53; individuals with at least four implants, OR = 3.33; P < .01), location of implant (maxilla; OR = 1.59; 95% CI: 1.2-2.04), and smoking (OR = 1.57; 95% CI: 1.09-2.26) were significant correlates of early implant failure among the included cases. Crohn's disease, MI, and osteoporosis were found to be borderline significant correlates of early dental implant failure. Conclusions: Among the factors examined, the number of implants, the location of implants, and smoking history were significant correlates of early implant failure, while Crohn's disease, MI, and osteoporosis were found to not be significant. Larger patient-level studies are needed to examine the individual and combined effects of diseases, medications, and clinical factors on early implant failure. [ABSTRACT FROM AUTHOR]

Determining the structure and phenotypic context of molecules detected in untargeted metabolomics experiments remains challenging. Here we present reverse metabolomics as a discovery strategy, whereby tandem mass spectrometry spectra acquired from newly synthesized compounds are searched for in public metabolomics datasets to uncover phenotypic associations. To demonstrate the concept, we broadly synthesized and explored multiple classes of metabolites in humans, including N-acyl amides, fatty acid esters of hydroxy fatty acids, bile acid esters and conjugated bile acids. Using repository-scale analysis1,2, we discovered that some conjugated bile acids are associated with inflammatory bowel disease (IBD). Validation using four distinct human IBD cohorts showed that cholic acids conjugated to Glu, Ile/Leu, Phe, Thr, Trp or Tyr are increased in Crohn's disease. Several of these compounds and related structures affected pathways associated with IBD, such as interferon-γ production in CD4+ T cells3 and agonism of the pregnane X receptor4. Culture of bacteria belonging to the Bifidobacterium, Clostridium and Enterococcus genera produced these bile amidates. Because searching repositories with tandem mass spectrometry spectra has only recently become possible, this reverse metabolomics approach can now be used as a general strategy to discover other molecules from human and animal ecosystems.

Intestinal transplantation is the definitive treatment for intestinal failure. However, tissue rejection and graft-versus-host disease are relatively common complications, necessitating aggressive immunosuppression that can itself pose further complications. Tracking intraluminal markers in ileal effluent from standard ileostomies may present a noninvasive and sensitive way to detect developing pathology within the intestinal graft. This would be an improvement compared to current assessments, which are limited by poor sensitivity and specificity, contributing to under or over-immunosuppression, respectively, and by the need for invasive biopsies. Herein, we report an approach to reproducibly analyze ileal fluid obtained through stoma sampling for antimicrobial peptide/protein concentrations, reasoning that these molecules may provide an assessment of intestinal homeostasis and levels of intestinal inflammation over time. Concentrations of lysozyme (LYZ), myeloperoxidase (MPO), calprotectin (S100A8/A9) and β-defensin 2 (DEFB2) were assessed using adaptations of commercially available enzyme-linked immunosorbent assays (ELISAs). The concentration of α-defensin 5 (DEFA5) was assessed using a newly developed sandwich ELISA. Our data support that with proper preparation of ileal effluent specimens, precise and replicable determination of antimicrobial peptide/protein concentrations can be achieved for each of these target molecules via ELISA. This approach may prove to be reliable as a clinically useful assessment of intestinal homeostasis over time for patients with ileostomies.

Bile acids (BAs) affect the intestinal environment by ensuring barrier integrity, maintaining microbiota balance, regulating epithelium turnover, and modulating the immune system. As a master regulator of BA homeostasis, farnesoid X receptor (FXR) is severely compromised in patients with inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC). At the front line, gut macrophages react to the microbiota and metabolites that breach the epithelium. We aim to study the role of the BA/FXR axis in macrophages. This study demonstrates that inflammation-induced epithelial abnormalities compromised FXR signaling and altered BAs' profile in a mouse CAC model. Further, gut macrophage-intrinsic FXR sensed aberrant BAs, leading to pro-inflammatory cytokines' secretion, which promoted intestinal stem cell proliferation. Mechanistically, activation of FXR ameliorated intestinal inflammation and inhibited colitis-associated tumor growth, by regulating gut macrophages' recruitment, polarization, and crosstalk with Th17 cells. However, deletion of FXR in bone marrow or gut macrophages escalated the intestinal inflammation. In summary, our study reveals a distinctive regulatory role of FXR in gut macrophages, suggesting its potential as a therapeutic target for addressing IBD and CAC.

BACKGROUND: The comparative safety and effectiveness of available biologics for post-operative prophylaxis in Crohns disease (CD) is uncertain. Drug persistence may serve as a real-world proxy for tolerability and effectiveness. We evaluated the comparative persistence of non-TNF and TNF antagonists for post-operative prophylaxis and their comparative effectiveness for preventing early endoscopic post-operative recurrence (POR). METHODS: We conducted a single-center, retrospective study of surgically naïve CD subjects undergoing ileocecal or small bowel resection between 1/1/2000 and 12/31/2021 and prescribed a biologic for post-operative prophylaxis. We compared the risk of prophylaxis failure (requiring recurrent surgery or discontinuation of therapy due to persistent POR despite optimized drug level or dose escalation, immunogenicity, and/or adverse event) and early endoscopic POR (Rutgeerts score ≥ i2 within 15 months postoperatively) between non-TNF and TNF antagonist prophylaxis using Cox proportional hazard and logistic regression, respectively, adjusting for demographic and disease characteristics. RESULTS: The study included 291 subjects (81% TNF antagonists). After multivariable adjustment, non-TNF antagonist prophylaxis was associated with a significantly lower risk of prophylaxis failure than TNF antagonists (hazard ratio 0.26; 95% confidence interval (CI) [0.13-0.53]). Prophylaxis with non-TNF and TNF antagonists had similar risk of early endoscopic POR (odds ratio 0.66; 95% CI [0.32-1.36]). Stratifying the non-TNF antagonists by anti-integrin and anti-IL12/23 yielded similar results. CONCLUSION: In a cohort of surgically naïve CD subjects prescribed a biologic for post-operative prophylaxis, non-TNF antagonists had greater persistence than TNF antagonists with similar risk for early endoscopic POR. If confirmed by large, prospective studies, these findings can inform post-operative management strategies in CD.

Mesenchymal stem cells (MSCs) are novel therapeutics for the treatment of Crohn's disease. However, their mechanism of action is unclear, especially in disease-relevant chronic models of inflammation. Thus, we used SAMP-1/YitFc (SAMP), a chronic and spontaneous murine model of small intestinal inflammation, to study the therapeutic effects and mechanism of action of human bone marrow-derived MSCs (hMSC). hMSC dose-dependently inhibited naïve T lymphocyte proliferation via prostaglandin E2 (PGE2) secretion and reprogrammed macrophages to an anti-inflammatory phenotype. We found that the hMSCs promoted mucosal healing and immunologic response early after administration in SAMP when live hMSCs are present (until day 9) and resulted in a complete response characterized by mucosal, histological, immunologic, and radiological healing by day 28 when no live hMSCs are present. hMSCs mediate their effect via modulation of T cells and macrophages in the mesentery and mesenteric lymph nodes (mLN). Sc-RNAseq confirmed the anti-inflammatory phenotype of macrophages and identified macrophage efferocytosis of apoptotic hMSCs as a mechanism that explains their long-term efficacy. Taken together, our findings show that hMSCs result in healing and tissue regeneration in a chronic model of small intestinal inflammation and despite being short-lived, exert long-term effects via sustained anti-inflammatory programming of macrophages via efferocytosis.

Background: Inflammatory bowel disease (IBD) is a chronic disease in which macrophages play an important role in its pathogenesis. Platelet-derived growth factor-BB (PDGF-BB) secreted by macrophages is involved in the repair of vascular endothelial injury during inflammatory reactions. Methods: The expression levels of M1 macrophages and PDGF-BB in serum and colonic mucosa of 30 patients with Crohn's disease (CD) and 30 patients with ulcerative colitis (UC) were measured using enzyme-linked immunosorbent assays and immunohistochemistry. Logistic regression was used for univariate and multivariate analyses, and receiver operating characteristic curves were used to evaluate diagnostic value. Associations were evaluated using Spearman correlation analysis. Results: The expression of serum PDGF-BB and M1 macrophages with positive CXCL9 expression in patients with active-stage IBD [206.55(160.41,262.90)and 337.30(217.73,472.28) pg/ml] was higher than that in patients with remission stage [153.42(107.02,219.68)and 218.37(144.49,347.33)pg/ml] and controls [156.19(91.16,216.08)and 191.20(121.42,311.76)pg/ml](P < 0.05). The expression of PDGF-BB, CD86, and CXCL9 in the colon of patients with active-stage IBD [0.380(0.266,0.542) 0.663(0.480,0.591) and 0.564(0.378,0.765) /µm2] was higher than that in the remission stage [0.308(0.214,0.420), 0.376(0.206,0.591) and 0.413(0.275,0.570) /µm2] and controls [0.265(0.185,0.384), 0.416(0.269,0.534) and 0.497(0.415,0.642) /µm2] (P < 0.05). A positive correlation was observed between CD86 and PDGF-BB, and CXCL9 and PDGF-BB levels in patients with IBD (P < 0.05). CD86 and PDGF-BB in the colonic mucosa were independent risk factors for active IBD, and the area under the curve for their combined diagnosis was 0.754 (95%CI: 0.654–0.852, P < 0.05). Conclusions: PDGF-BB was associated with M1 macrophages and has a potential diagnostic value for active IBD. Trial registration: Not applicable. Highlights: A potential correlation was observed between PDGF-BB and M1 macrophages. CD86 and PDGF-BB in colonic mucosa were independent risk factors for active IBD. PDGF-BB and M1 macrophages with positive CXCL9 expression were significantly increased during active IBD. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel diseases (IBD) are chronic inflammation conditions affecting the gastrointestinal tract. Studies point out an association between Helicobacter pylori (H. pylori) infection and IBD. This study aims to visually assess the research trends and hotspots in the field of H. pylori infection and IBD, review mainstream perspectives in this field, and provide a foundation for future research and treatment. Methods: We searched the Web of Science Core Collection Database for literature related to H. pylori and IBD, using VOS viewer to generate visual charts. Results: A total of 246 publications were included, with articles being the predominant type of document. A significant increase in the number of publications was observed after 2011. China contributed the most of researches. Keyword clusters revealed that the researches primarily focused on immune mechanism, gut microbiome, diagnosis and treatment of IBD. Time trend results indicated that current researches centered on gut microbiota and immune mechanisms. Conclusion: H. pylori infection may have a protective effect on IBD. The exact mechanisms remain unclear and may involve immunomodulation and changes of gut microbiota. Further researches are necessary for better understanding this relationship and its implications for clinical practice. Further researches and clinical practice should pay attention to this topic. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusions Predose trough concentrations (Ctrough) of intravenous infliximab (IV‐IFX) during maintenance therapy are associated with therapeutic outcomes in patients with Crohn's disease (CD). A subcutaneous formulation of infliximab (SC‐IFX) has shown high Ctrough values due to its favourable pharmacokinetics.To evaluate the association of Ctrough of SC‐IFX with therapeutic outcomes and the threshold of SC‐IFX Ctrough for achieving mucosal healing (MH) and transmural healing (TH) in patients with CD.We performed this cross‐sectional study in patients with CD who had received SC‐IFX maintenance therapy for ≥ 6 months. We measured SC‐IFX Ctrough immediately before SC‐IFX injection. We performed ileocolonoscopy/single‐balloon enteroscopy and/or magnetic resonance enterography within 3 months of SC‐IFX Ctrough measurement. MH was defined as SES‐CD–ulcerated surface subscore of 0. TH was defined as simplified MaRIA score of 0.We enrolled 124 patients with MH in 77.9% (74/95) and TH in 36.3% (37/102). SC‐IFX Ctrough was significantly higher in patients with MH (24.1 vs.16.9 μg/mL; p = 0.001) and TH (26.0 vs. 20.5 μg/mL; p = 0.007) than in those without. ROC analysis identified that the threshold of SC‐IFX Ctrough for MH and TH were 17.5 and 30.3 μg/mL, respectively. Multivariate logistic regression showed that SC‐IFX Ctrough was significantly associated with MH (OR 1.16; 95% CI 1.05–1.27; p = 0.002) and TH (OR 1.08; 95% CI 1.02–1.14; p = 0.005).SC‐IFX Ctrough was positively associated with MH (≥ 18 μg/mL) and TH (≥ 30 μg/mL) in patients with CD, which may guide treatment decisions to optimise therapeutic response in the era of treat‐to‐target. [ABSTRACT FROM AUTHOR]

Introduction: Although endoscopic balloon dilation (EBD) is a common therapeutic approach for managing strictures associated with Crohn's disease (CD), the clinical application and complication rates of EBD remain unclear. Methods: We collected admission data for patients who underwent EBD using a nationwide database. We compared EBD outcomes between ileal and colonic strictures, CD and ulcerative colitis, and CD and anastomotic strictures arising from cancer‐related surgery. Subsequently, propensity score matching was employed to facilitate comparisons between each group. Results: The median duration of hospital stay was 4 days. Endoscopic hemostasis and urgent surgery rates after EBD for CD‐related strictures were considerably low (0.035% and 0.11%, respectively). Most patients with CD underwent only one EBD procedure during a single admission. Although no significant differences in patient backgrounds and severe complications were observed between ileal and colonic stricture in CD, multiple EBD procedures were more commonly performed for ileal strictures than for colonic stricture. Moreover, EBD for ileal stricture was more frequently conducted in high‐volume centers than in low‐volume centers. Regarding severe complications after EBD, no significant differences were observed between CD‐related strictures and ulcerative colitis or anastomotic strictures related to cancer surgery. Conclusion: Our findings support the safe and effective use of EBD for both ileal and colonic strictures associated with CD. The clinical practice and safety outcomes of EBD for CD‐related strictures were comparable to those for strictures stemming from other etiologies. [ABSTRACT FROM AUTHOR]

This study explored the comorbid mechanisms between Crohn's disease (CD) and chronic obstructive pulmonary disease (COPD) using bioinformatics analysis. From the Gene Expression Omnibus (GEO) microarray dataset, 349 common differentially expressed genes (coDEGs) were identified, and 8 shared hub genes were found: CCL2, CXCL1, TLR2, ICAM1, PTPRC, ITGAX, PTGS2, and MMP9, which were vital for immune function and regulation of inflammatory responses. In addition, the study also analyzed the association between coDEGs and immune cell infiltration using the single-sample gene set enrichment algorithm (ssGSEA). Potential drugs related to these genes were identified using the connectivity map (CMap). These findings provided new perspectives for understanding the interaction between CD and COPD. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions Vascular endothelial growth factor (VEGF) is linked to inflammation and angiogenesis, indicating a possible role in inflammatory bowel disease (IBD) and its main clinical manifestations, Crohn's disease (CD) and ulcerative colitis (UC). This systematic review and meta‐analysis investigated studies assessing circulating VEGF concentrations in IBD patients and healthy controls, considering the effect of IBD type, sample type and geographical location.A systematic search identified 18 studies (28 group comparators) investigating 1741 IBD patients and 1291 controls. Data were extracted and analysed using standardized mean differences (SMD) with 95% confidence intervals (CI).VEGF concentrations were significantly higher in IBD patients (SMD = .71, 95% CI .38 to 1.04; p < .001). UC patients showed higher VEGF concentrations than CD patients. Serum samples indicated significant VEGF elevations, unlike plasma samples. Significant VEGF increases were observed in studies conducted in Western Europe and Asia, but not in Eastern Europe. No significant differences were found between active and inactive disease.VEGF concentrations are elevated in IBD patients, with variations by disease type, sample type and geography. However, VEGF is not a reliable marker of disease activity. Future research should standardize methods and explore regional influences to enhance VEGF's clinical utility as a biomarker of IBD. [ABSTRACT FROM AUTHOR]

A plant-based diet has a wealth of pro-health properties. These have been typically attributed to the beneficial effects associated with fruits, vegetables, juices and spices and the various properties of their phytochemical constituents, such as polyphenols. Inflammatory bowel diseases (IBD) are chronic disorders with an unknown etiology; however, an important component of IBD is colon damage, known to be caused by the inflammatory response, oxidative stress or disturbances of the gut microbiota. This review summarizes the current state of knowledge concerning the effects of polyphenol-rich extracts on IBD and assesses their utility. Most of the presented evidence suggests that polyphenol-rich extracts have various beneficial anti-inflammatory and anti-oxidative effects, enhancing the epithelial barrier and restoring disturbances in the gut microbiota. These effects may result from the modulation of multiple cellular signalling pathways. Based on these findings, new dietary strategies supporting the treatment of IBD may be created. [ABSTRACT FROM AUTHOR]

Summary: Background: There are inconsistencies in the results of the studies investigating the association between inflammatory bowel disease (IBD) and lymphoma. Aims: The aim of this study is to systematically appraise the risk of lymphoma development in patients with IBD. Methods: We searched Embase, PubMed and Scopus from inception to 30 April 2024 to identify population‐based cohort studies that evaluated the risk of lymphoma in patients with IBD in comparison with those without IBD. We carried out random‐effects meta‐analyses and estimated pooled relative risks (RRs) with 95% confidence intervals (CIs). Results: We identified 23 eligible studies reporting 2078 lymphoma events in 656,731 patients with IBD. Patients with IBD had 30% higher odds of lymphoma (RR = 1.30 [95% CI: 1.21–1.40]). The risk of developing both Hodgkin's lymphoma (nine studies, RR = 1.29 [95% CI: 1.06–1.53]) and non‐Hodgkin's lymphoma (16 studies, RR = 1.31 [95% CI: 1.20–1.42]) was increased in patients with IBD (p for interaction = 0.881). The increased risk of lymphoma was observed in both Crohn's disease (17 studies, RR = 1.54 [95% CI: 1.27–1.80]) and ulcerative colitis (20 studies, RR = 1.22 [95% CI: 1.09–1.35]) (p for interaction = 0.026). Meta‐regression demonstrated that mean age of patients, study year, mean study follow‐up duration, and percentages of immunomodulators and biologics use did not influence study outcome. Conclusions: The risk of lymphoma is only modestly increased in patients with IBD, with Crohn's disease having a slightly higher risk than ulcerative colitis. In IBD, there appears to be no difference between the risks of Hodgkin's and non‐Hodgkin's lymphoma. [ABSTRACT FROM AUTHOR]

Summary: Background: Previous studies highlighted a more extensive phenotype for paediatric‐onset than adult‐onset inflammatory bowel disease (IBD). However, most lacked long‐term follow‐up, and some were conducted before the era of biologics. Aims: The aim of this study is to compare disease characteristics and treatment exposures between paediatric‐onset and adult‐onset IBD. Methods: From a registry that periodically and uniformly retrieves demographics, disease characteristics/phenotype, and treatments, we compared the characteristics of paediatric‐onset (diagnosed at ≥6 and <18 years) and adult‐onset IBD, diagnosed during 2000–2022 and with ≥12 months follow‐up. Results: Of the 2837 patients with Crohn's disease and 1332 with ulcerative colitis, 3316 had adult‐onset and 853 paediatric‐onset IBD. The median follow‐up was 6 years. Patients with paediatric‐onset presented with more extensive disease and received more intensified therapies, including biologics and JAK inhibitors than those with adult‐onset IBD. Paediatric‐onset ulcerative colitis showed a higher prevalence of E3 extensive colitis including pancolitis and a greater requirement for systemic steroids, immunomodulators, and biologics than adult‐onset ulcerative colitis. Paediatric‐onset versus adult‐onset Crohn's disease exhibited greater L3 ileocolonic involvement and perianal disease phenotype, and higher exposure to immunomodulators and biologics. Kaplan–Meier curve and Cox proportional hazards analyses showed significantly lower 15‐year biologic‐free survival from diagnosis among those with paediatric‐onset IBD than with adult‐onset IBD (p = <0.001), indicating greater and earlier use of biologics in the former. Conclusions: Paediatric‐onset presents with more extensive disease with higher exposures to immunomodulators and biologic therapies than adult‐onset IBD. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prevalence and risk factors of psychological symptoms and quality of life (QoL) in early patients with inflammatory bowel disease (IBD). Methods: From September 2021 to May 2022, a unified questionnaire was developed to collect clinical data from early patients with IBD from 42 tertiary care hospitals. The influencing factors of psychological symptoms and poor QoL are screened by logistic regression analysis for constructing model in predicting poor QoL. The consistency index, receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance of the model. Results: A total of 939 early patients with IBD were surveyed, Among them, 20.3% exhibited anxiety, 21.7% had depression, 57.3% experienced sleep disturbance, and 41.9% reported poor QoL. The factors influencing psychological symptoms varied between ulcerative colitis (UC) and Crohn's disease (CD) patients. The QoL was primarily affected by disease activity, income level and depression. The AUC value of the model in the training group was 0.781 (95% CI: 0.748–0.814). The calibration diagram of the model closely matched the ideal curve. Compared to other prediction models, our model showed superior predictive capability, with NRI and IDI values of 0.324 (95%CI:0.196–0.4513) and 0.026 (95%CI:0.014–0.038), respectively. DCA indicated that the nomogram model could provide clinical benefits. Conclusion: Early patients with IBD exhibit a high prevalence of psychological symptoms and poor QoL. The nomogram prediction model we constructed demonstrates high accuracy and performance in predicting QoL in early patients with IBD. [ABSTRACT FROM AUTHOR]

Background: Since 2015, an infliximab biosimilar, CT-P13, has been approved for commercial use in many countries, easing the economic burden borne by society and patients. Many clinical trials investigating CT-P13 for the treatment of IBD have been conducted and reported that it may be a substitute for infliximab. However, the differences between the efficacy of CT-P13 and infliximab-originator require further elucidation. Methods: Data on the rates of clinical response, clinical remission, and mucosal healing of IBD were pooled for random-effects model meta-analysis using Stata MP 17. A total of 30 studies were included. Results: The pooled risk of clinical remission rate of patients with Crohn's disease and ulcerative colitis who were naïve to biologics at 08–14 weeks were 0.66 (95% CI, 0.58–0.75) and 0.48 (95% CI, 0.43–0.54), respectively, and at 100–104 weeks were 0.66 (95% CI, 0.49 to 0.84) and 0.71 (95% CI, 0.62 to 0.79) respectively. The pooled risk of clinical remission rate of patients with Crohn's disease and ulcerative colitis who were transitioned from the original agent at 24–32 weeks were 0.84 (95% CI, 0.77–0.92) and 0.78 (95% CI, 0.63–0.93), respectively, and at 48–54 weeks were 0.72 (95% CI, 0.62 to 0.82) and 0.78 (95% CI, 0.71 to 0.86) respectively. The pooled rates for mucosal healing in ulcerative colitis were 0.56 (95% CI: 0.46 to 0.67) at 08–14 weeks, and 0.64 (95% CI: 0.42 to 0.85) at 48–54 weeks. RCT studies showed no significant change in efficacy after switching, whether Crohn's disease or ulcerative colitis. Conclusions: CT-P13 is effective in short and long-term periods. The application of CT-P13 for the management of IBD was promising. [ABSTRACT FROM AUTHOR]

Background: Crohn's disease (CD) is a type of inflammatory bowel disease (IBD) that is prevalent worldwide and associated with reduced quality of life for patients. Multimodal therapy approaches, which emphasize lifestyle modifications such as mindfulness and stress reduction, can be promising in enhancing health-related quality of life for IBD patients. However, research on multimodal therapy approaches for CD remains insufficient. Method: This qualitative interview study is part of a mixed-methods approach that is embedded in a randomized controlled trial. It investigates the impact of a comprehensive 10-week day clinic lifestyle modification program on the health condition and quality of life of CD patients. Telephone interviews (n = 19) were conducted three months after the program to examine individuals' viewpoints on the intervention, including perceived changes and transfer of elements into daily life. Reflexive thematic analysis was performed using MAXQDA software. Results: The results indicate that CD can have very individual and comprehensive impacts (psychological, physical, social), leading to reduced perceived quality of life and well-being. By participating in the program, patients wanted to find self-help options to complement conventional pharmacotherapy and actively manage their disease. Patients expressed high satisfaction with the program, feeling it provided valuable support for daily disease management. They were able to integrate adequate therapy elements into their routines to complement their care. Patients recognized significant improvements in various domains, mainly in the psychological domain, e.g., improved self-efficacy, symptom management, and, also partly physical/symptomatic and social improvements. Conclusion: A multimodal stress reduction and lifestyle modification day clinic appears to be beneficial as a complementary therapy for CD patients. It offers additional options and helps patients to address individual symptoms and needs, improve their understanding of the disease and their quality of life. Although promising, further research is needed to assess its long-term effects. Trial registration: ClinicalTrials.gov, identifier: NCT05182645. [ABSTRACT FROM AUTHOR]

Background: The Saudi Food and Drug Authority (SFDA) has approved the subcutaneous (SC) administration of infliximab, presenting a more convenient alternative with reduced outpatient visits and diminished expenses compared to the intravenous (IV) administration. However, the financial implications of this formulation have not been examined from the perspective of Saudi payers. Methods and materials: A prevalence-based budget impact model was developed to evaluate the financial effects of introducing "environment without" versus "with infliximab SC." The model's time horizon spanned over 2 years (2021–2023), aligning with the biennial national pharmaceutical procurement cycle. The comparison focused on infliximab SC versus all available formulations of infliximab IV in the Saudi market for two inflammatory bowel diseases (IBD): Ulcerative Colitis (UC) and Crohn's Disease (CD). Treatment comparators' comparability and dose escalations were substantiated by published studies, utilizing dosing information from the summary of product characteristics. Drug acquisition costs were derived from SFDA registered prices, with IV formulation administration costs included. Scenario analysis assessed the budget impact of infliximab SC introduction at uptake rates ranging from 0% to 100%. Results: Introducing infliximab SC demonstrated cost-saving potential in the treatment of IBD. At 100% uptake with UC patients for 2 years, infliximab SC resulted in savings of -SAR-31.9 million (-SAR29,145 per patient). Similarly, for CD, introducing infliximab SC at 100% uptake over 2 years yielded savings of -SAR106.2 million (-SAR36,585 per patient). Conclusion: This study reveals that infliximab SC is associated with cost-saving potential when compared to infliximab IV formulations available in Saudi Arabia. Future research should address uncertainties related to real-world comparative effectiveness, the convenience of administration, patient tolerability, and physician acceptance of the SC formulation of infliximab, alongside comparisons with other TNF-alpha inhibitors. [ABSTRACT FROM AUTHOR]

Hyperplasia of mesenteric tissues in Crohn's disease, called creeping fat (CrF), is associated with surgical recurrence. Although microbiota translocation and colonization have been found in CrF, convincing mouse phenotypes and the underlying mechanisms of CrF formation remain unclear. Utilizing single-nucleus RNA (snRNA) sequencing of CrF and different mouse models, we demonstrate that the commensal Achromobacter pulmonis induces mesenteric adipogenesis through macrophage alteration. Targeted metabolome analysis reveals that L-kynurenine is the most enriched metabolite in CrF. Upregulation of indoleamine 2,3-dioxygenase 1 (IDO1) enhances kynurenine metabolism and drives mesenteric adipogenesis. Leveraging single-cell RNA (scRNA) sequencing of mouse mesenteric tissues and macrophage-specific IDO1 knockout mice, we verify the role of macrophage-sourced L-kynurenine in mesenteric adipogenesis. Mechanistically, L-kynurenine-induced adipogenesis is mediated by the aryl hydrocarbon receptors in adipocytes. Administration of an IDO1 inhibitor or bacteria engineered to degrade L-kynurenine alleviates mesenteric adipogenesis in mice. Collectively, our study demonstrates that microbiota-induced modulation of macrophage metabolism potentiates CrF formation. [Display omitted] • The commensal Achromobacter pulmonis induces mesenteric adipogenesis • Macrophage-derived L-kynurenine via IDO1 is responsible for mesenteric adipogenesis • L-kynurenine-induced adipogenesis is mediated by AHR activation in adipocytes • Targeting kynurenine metabolism alleviates the formation of mesenteric adipogenesis Wu et al. reveal that the commensal Achromobacter pulmonis induces mesenteric adipogenesis through macrophages alteration. Mechanistically, macrophage-derived L-kynurenine via indoleamine 2,3-dioxygenase 1 (IDO1) promotes adipogenesis by aryl hydrocarbon receptor (AHR) activation in adipocytes. Targeting kynurenine metabolism with an IDO1 inhibitor or bacteria engineered to degrade L-kynurenine alleviates mesenteric adipogenesis. [ABSTRACT FROM AUTHOR]

Background: Bowel urgency, the sudden and immediate need to have a bowel movement, is common in patients with ulcerative colitis (UC) and Crohn's disease (CD). While its impact in UC is well established, less is known about its importance in CD. Further, what level of bowel urgency control patients with UC or CD would consider to be acceptable or in remission has not been established. This qualitative study aimed to understand perceptions of bowel urgency and remission in these patients. Methods: Semi-structured combined concept elicitation and cognitive interviews were conducted to explore how adults with moderate-to-severe UC or CD and current or recent bowel urgency think about the concept of bowel urgency and its remission. The Urgency Numeric Rating Scale (UNRS) was used to examine different levels of bowel urgency severity and to investigate what level of bowel urgency patients would consider as representing remission. Results: Forty adults (n = 19 UC, n = 21 CD) recruited from six US sites completed the study. Sociodemographic and clinical characteristics were similar in both groups. Both groups reported impacts of bowel urgency on physical, social, professional, and emotional aspects of their lives. Most participants (n = 15 UC, n = 18 CD) reported having experienced one or more incidents of urgency-related fecal incontinence. Most participants considered remission to be a state with a normal or reduced number of bowel movements and no or less frequent bowel urgency, and they noted that remission would increase their ability to engage in daily activities without fear of fecal incontinence. Participants were able to map different levels of severity of bowel urgency to UNRS score ranges (scale: 0–10), and they indicated that a mean UNRS score of 5 (UC) or 4 (CD) would be the highest point on the NRS at which they would still consider their bowel urgency to be in remission. Conclusions: Bowel urgency is an important issue for patients with either moderate-to-severe UC or CD, and its remission would improve their lives. Further, these patients may still consider bowel urgency to be in remission even at UNRS scores as high as 4 or 5. Plain English summary: Bowel urgency is the sudden need to rush to the bathroom to have a bowel movement, which is common in people with ulcerative colitis and Crohn's disease. We interviewed adults with moderate or severe ulcerative colitis or Crohn's disease to better understand their experiences. They said that bowel urgency often made them feel anxious, depressed, or embarrassed and interfered with their social lives, work, and chores. Most felt that they would be in "remission" if the bowel urgency stopped or happened less often. They added that this would help them feel more relaxed and be more active. Interestingly, they would consider even a moderate amount of bowel urgency as being in "remission." This information can help healthcare providers better understand the toll that bowel urgency takes on patients with ulcerative colitis or Crohn's disease and better manage their treatment. [ABSTRACT FROM AUTHOR]

In this pilot study, we assessed the role of autophagy in Crohn's Disease (CD), particularly in patients with a stenosing phenotype. Through the analysis of biopsied specimens from 36 patients, including 11 controls and 25 CD patients, categorized into inflammatory and stenosing groups, we identified a significant reduction in the autophagosomal marker Lc3b-II in patients with active inflammation and stenosis. This was paralleled by an increase in oxidative stress markers, including sNOX2-dp and H2O2, and a decrease in the antioxidant capacity measured by HBA, suggesting an imbalance in autophagy and oxidative stress mechanisms. Additionally, our findings show a correlation between autophagy markers and oxidative stress levels, indicating that autophagy dysfunction may play a pivotal role in CD and in the progression of a stenosing disease phenotype, by failing to eliminate detrimental molecules and pathogenic bacteria, thereby promoting fibrosis. This study is the first to demonstrate in vivo autophagy inhibition in stenosing CD patients and suggests that stimulating autophagic processes could offer a new avenue for the prevention and treatment of intestinal fibrosis in CD. Our results highlight the importance of exploring the interactions between autophagy, the fibrotic process, and the inflammatory cascade, opening avenues for potential therapeutic interventions in CD management. [ABSTRACT FROM AUTHOR]

Summary Reactive oxygen species (ROS) production and inflammasome activation are the key components of the innate immune response to microbial infection and sterile insults. ROS are at the intersection of inflammation and immunity during cancer development. Balanced regulation of ROS production and inflammasome activation serves as the central hub of innate immunity, determining whether a cell will survive or undergo cell death. However, the mechanisms underlying this balanced regulation remain unclear. Mitochondria and NADPH oxidases are the two major sources of ROS production. Recently, NCF4, a component of the NADPH oxidase complex that primarily contributes to ROS generation in phagocytes, was reported to balance ROS production and inflammasome activation in macrophages. The phosphorylation and puncta distribution of NCF4 shifts from the membrane‐bound NADPH complex to the perinuclear region, promoting ASC speck formation and inflammasome activation, which triggers downstream IL‐18‐IFN‐γ signaling to prevent the progression of colorectal cancer (CRC). Here, we review ROS signaling and inflammasome activation studies in colitis‐associated CRC and propose that NCF4 acts as a ROS sensor that balances ROS production and inflammasome activation. In addition, NCF4 is a susceptibility gene for Crohn's disease (CD) and CRC. We discuss the evidence demonstrating NCF4's crucial role in facilitating cell–cell contact between immune cells and intestinal cells, and mediating the paracrine effects of inflammatory cytokines and ROS. This coordination of the signaling network helps create a robust immune microenvironment that effectively prevents epithelial cell mutagenesis and tumorigenesis during the early stage of colitis‐associated CRC. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Despite advancements in therapeutic options for Crohn's disease (CD), strictureplasty is a mainstay bowel‐preserving technique for small bowel CD. We sought to audit international practice across three high‐volume centres since the widespread use of biologic medication.A retrospective audit was performed for all strictureplasties undertaken for small bowel CD, over a 15‐year period (2006–2021), in three high‐volume centres in the United Kingdom and Italy. Primary endpoints were clinical recurrence and reoperation for recurrence.In all, 123 patients were included; 58% were men, 25% smoked and 60% had previous abdominal surgery for CD. Median age was 40 years (interquartile range 30–52 years), mean body mass index 22 (15–31) and median disease duration 138 months (81–255 months). 42% had been treated with biologics preoperatively. In total 338 strictureplasties were performed in 123 patients, with a median of two per patient (interquartile range 1–3). Complications occurred in 35%, with 8% scoring Clavien–Dindo Grade 3. There were no Grade 4/5 complications. Postoperative biologic treatment was administered to 84/123 patients (68.3%). Median follow‐up was 54 months. 41/123 patients (33.3%) developed clinical recurrence. Reoperation for recurrent stricturing was performed in 26/123 patients (21%). Clinical recurrence and reoperation rates were significantly higher in patients who continued to smoke after their index surgery.Strictureplasty remains a safe and effective surgical treatment for small bowel CD. Recurrence and reoperation rates remain high, regardless of postoperative biologic therapy. Smoking significantly increases the risk of recurrence. [ABSTRACT FROM AUTHOR]

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) characterised by endoscopic inflammation, progressive bowel damage and gastrointestinal lesions. Although treatment strategies for CD have traditionally focused on a stepwise pharmacological approach to achieve clinical remission or symptom resolution, these treatment goals correlate poorly with disease activity. Thus, achieving full clinical remission and full endoscopic healing alone may be insufficient, as patients may remain at risk of inflammatory complications. Individualised 'treat-to-target' (T2T) pharmacological and treatment approaches represent a promising strategy for improving endoscopic remission and symptom resolution among patients with CD. The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) and STRIDE-II guidelines, launched in 2013 and later renewed, identified individualised targets for a T2T therapeutic approach for patients with IBD. These guidelines facilitate the individualisation of target treatment goals through evidence-based, long-term (health-related quality of life, absence of disability, endoscopic healing) and intermediate/short-term (abdominal pain, stool frequency, normalisation of biomarker levels) treatment targets, allowing patients and clinicians to consider the risk-to-benefit balance of goals and selected therapeutic strategies. This article aims to summarise the STRIDE-II guidelines and provide intellectual guidance for healthcare professionals to apply the STRIDE-II principles to current clinical practice in the United Kingdom (UK). Management recommendations for primary and secondary first-line non-responders are provided, along with suggestions for utilising the endoscopic outcomes scoring system in UK clinical practice. Declaration of interest: This article was commissioned and funded by Takeda UK Ltd, who suggested the author and topic. Takeda UK Ltd also reviewed and approved the content. Prescribing information and adverse event reporting can be found at the end of the article. Plain language summary: Best practice suggestions for incorporating STRIDE-II into UK clinical practice for the management of patients with Crohn's disease Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) characterised by endoscopic inflammation and damage, estimated to affect approximately 11 individuals per 100,000 annually in the United Kingdom (UK). Traditional treatment strategies for IBD, including CD, focus on symptom resolution and clinical remission. However, as symptom resolution correlates poorly with disease activity, a treatment goal of full clinical remission and full endoscopic healing alone may be insufficient. The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) and STRIDE-II initiative released 'treat-to-target' therapy evidence-based guidelines, detailing individualised clinical treatment targets for patients with IBD. STRIDE-II accommodates treatment individualisation through several long-term (health-related quality of life, absence of disability, endoscopic healing) and intermediate/short-term (abdominal pain, stool frequency, normalisation of biomarker levels) treatment targets, allowing patients and clinicians to consider the risk-to-benefit balance of goals and selected therapeutic strategies. This article provides best practice suggestions for healthcare professionals to apply the STRIDE-II principles to current clinical practice in the UK. Management recommendations for primary and secondary first-line non-responders are provided, along with suggestions for utilising the endoscopic outcomes scoring system in UK clinical practice. [ABSTRACT FROM AUTHOR]

Background/aims: Crohn's disease (CD) and intestinal tuberculosis (ITB) are gastrointestinal (GI) inflammatory disorders with overlapping clinical presentations but diverging etiologies. The study aims to decipher CD and ITB-associated gut dysbiosis signatures and identify disease-associated co-occurring modules to evaluate whether this dysbiosis signature is a disease-specific trait or is a shared feature across diseases of diverging etiologies. Methods: Disease-associated gut microbial modules were identified using statistical machine learning and co-abundance network analysis in controls, CD and ITB patients recruited as part of this study. Module reproducibility was reinvestigated through meta-network analysis encompassing >5400 bacteriomes and ~900 mycobiomes. Subsequently, >1600 Indian gut microbiomes were analyzed to identify a central-core gut microbiome of 46 taxa, whose abundances aided in the formulation of an India-specific Core Gut Microbiome Score (CGMS) to measure the degree of core retention. Results: Both diseases witness similar patterns of alterations in [alpha]-diversity, characterized by a significant reduction in gut bacterial (i.e., bacterial/archaeal) diversity and a concomitant increase in the fungal [alpha]-diversity. Specific bacterial taxa, along with the diverging mycobiome enabled distinction between the diseases. Co-abundance network analysis of these taxa, validated by integrated meta-network analysis, revealed a 'disease-depleted' module, consistent across multiple cohorts, with >75% of this module constituting the central-core Indian gut microbiome. CGMS robustly assessed the core-microbiome loss across different stages of gut inflammatory disorders, in Indian and international cohorts. Conclusions: While the disease-specific gain of detrimental bacteria forms an important component of gut dysbiosis, loss of the core microbiome is a shared phenomenon contributing to various GI disorders. [ABSTRACT FROM AUTHOR]

Background: Homocysteine (Hcy) is a pro-inflammatory molecule that has the potential to induce oxidative damage to cells and stimulate the release of inflammatory mediators. Hcy has been observed to enhance the production of inflammatory agents in vascular endothelial cells. However, the impact of Hcy on intestinal mucosal inflammation remains largely unexplored. Therefore, the objective of this study was to examine the potential of Hcy to stimulate the synthesis of inflammatory mediators and elucidate the underlying mechanisms in the intestinal mucosa. Methods: A total of 99 patients diagnosed with inflammatory bowel disease (IBD) and 10 healthy individuals were included in this study to assess the impact of homocysteine (Hcy) on the levels of leukotriene E4 (LTE4) and prostaglandin E2 (PGE2). The underlying mechanism responsible for the generation of LTE4 and PGE2 induced by Hcy was investigated using colitis rats and Caco-2 cells. 32 Sprague–Dawley rats were categorized into four groups: normal control, TNBS model, normal with Hcy injection, and TNBS model with Hcy injection. The mRNA expressions of 5-LOX, COX-2, and NF-κB were assessed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Caco-2 cells were subjected to treatment with varying concentrations (10, 20, 50, 100 μmol/L) of Hcy and incubated for different durations (1, 3, 6 h). The alterations in NF-κB activity, as well as the levels of Hcy, LTE4, and PGE2, were measured using enzyme-linked immunosorbent assay (ELISA). Results: The excretion of Hcy, LTE4, and PGE2 in urine exhibited significant increases in patients with inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC). In addition, Hcy demonstrated a significant increase in the expression of 5-LOX, COX-2, and NF-κB, as well as elevated levels of LTE4 and PGE2 in rats with colitis. Furthermore, Hcy was found to induce NF-κB activation and nuclear translocation, thereby contributing to the enhanced synthesis of LTE4 and PGE2 in Caco-2 cells. Conclusions: Hcy was found to enhance the expression of 5-LOX and COX-2 by activating NF-κB, thereby augmenting the production of LTE4 and PGE2, which ultimately exacerbates colonic inflammation in individuals with inflammatory bowel disease (IBD). [ABSTRACT FROM AUTHOR]

Background: Crohn's disease is a severe chronic and relapsing inflammatory bowel disease. Although contrast-enhanced computed tomography enterography is commonly used to evaluate crohn's disease, its imaging findings are often nonspecific and can overlap with other bowel diseases. Recent studies have explored the application of radiomics-based machine learning algorithms to aid in the diagnosis of medical images. This study aims to develop a non-invasive method for detecting bowel lesions associated with Crohn's disease using CT enterography radiomics and machine learning algorithms. Methods: A total of 139 patients with pathologically confirmed Crohn's disease were retrospectively enrolled in this study. Radiomics features were extracted from both arterial- and venous-phase CT enterography images, representing both bowel lesions with Crohn's disease and segments of normal bowel. A machine learning classification system was constructed by combining six selected radiomics features with eight classification algorithms. The models were trained using leave-one-out cross-validation and evaluated for accuracy. Results: The classification model demonstrated robust performance and high accuracy, with an area under the curve of 0.938 and 0.961 for the arterial- and venous-phase images, respectively. The model achieved an accuracy of 0.938 for arterial-phase images and 0.961 for venous-phase images. Conclusions: This study successfully identified a radiomics machine learning method that effectively differentiates Crohn's disease bowel lesions from normal bowel segments. Further studies with larger sample sizes and external cohorts are needed to validate these findings. [ABSTRACT FROM AUTHOR]

Objective: This study aims to analyze the causal relationship between autoimmune thyroiditis (AIT) and inflammatory bowel disease (IBD) using bidirectional Mendelian randomization (MR). Methods: Single nucleotide polymorphisms were obtained from FinnGen. Exposure-outcome causality was assessed using inverse variance weighted, MR-Egger, and weighted median. MR-Egger intercept, Cochran's Q, and leave-one-out sensitivity analysis were used to evaluate horizontal pleiotropy, heterogeneity, and robustness, respectively. Results: Forward analysis revealed no significant association between AIT and the risk of ulcerative colitis (UC) (odds ratio [OR] 1.008, 95% confidence interval [CI] 0.986 to 1.03, p = 0.460) or Crohn's disease (CD) (OR 0.972, 95% CI 0.935 to 1.010, p = 0.143). Reverse analysis showed that UC (OR 0.961, 95% CI 0.783 to 1.180, p = 0.707) was not associated with AIT risk, while CD (OR 2.371, 95% CI 1.526 to 3.683, p < 0.001) was linked to an increased risk of AIT. Intercept analysis and Cochran's Q test indicated no horizontal pleiotropy or heterogeneity. Sensitivity analysis confirmed the robustness of the MR results. Conclusion: This MR analysis suggests that CD, but not UC, is a risk factor for AIT, whereas AIT is not associated with the risk of IBD. Proactive prevention and treatment of CD can help mitigate the risk of AIT. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions Differentiating between Crohn's disease (CD) and gastrointestinal tuberculosis (GITB) is challenging. We aimed to evaluate the clinical applicability of an artificial intelligence (AI) model for this purpose.The AI model was developed and assessed using an internal dataset comprising 1,132 colonoscopy images of CD and 1,045 colonoscopy images of GITB at a tertiary referral center. Its stand‐alone performance was further evaluated in an external dataset comprising 67 colonoscopy images of 17 CD patients and 63 colonoscopy images of 14 GITB patients from other institutions. Additionally, a crossover trial involving three expert endoscopists and three trainee endoscopists compared AI‐assisted and unassisted human interpretations.In the internal dataset, the sensitivity, specificity, and accuracy of the AI model in distinguishing between CD and GITB were 95.3%, 100.0%, and 97.7%, respectively, with an area under the ROC curve of 0.997. In the external dataset, the AI model exhibited a sensitivity, specificity, and accuracy of 77.8%, 85.1%, and 81.5%, respectively, with an area under the ROC curve of 0.877. In the human endoscopist trial, AI assistance increased the pooled accuracy of the six endoscopists from 86.2% to 88.8% (P = 0.010). While AI did not significantly enhance diagnostic accuracy for the experts (96.7% with AI vs 95.6% without, P = 0.360), it significantly improved accuracy for the trainees (81.0% vs 76.7%, P = 0.002).This AI model shows potential in aiding the accurate differential diagnosis between CD and GITB, particularly benefiting less experienced endoscopists. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions Only a few studies have reported the long‐term effects of ustekinumab on pediatric Crohn's disease. Therefore, this study aimed to describe the long‐term clinical and endoscopic outcomes of ustekinumab and its safety profile in pediatric‐onset Crohn's disease with anti‐tumor necrosis factor failure.Medical records of patients with pediatric‐onset Crohn's disease in whom anti‐tumor necrosis factor therapy failed and ustekinumab treatment was initiated from 2017 to 2022 at a Japanese tertiary children's hospital were retrospectively reviewed. The primary outcome was the continuation rates at weeks 8, 52, and 106. The secondary outcomes were the steroid‐free remission rates at weeks 8, 52, and 106, changes in the Simple Endoscopic Score for Crohn's Disease, and adverse events during follow‐up.Forty‐three patients were enrolled. The median ages at diagnosis and ustekinumab introduction were 9.7 (interquartile range: 6.7–13.0) years and 13.6 (interquartile range: 8.0–16.0) years. The median follow‐up period was 136 (interquartile range: 102–172) weeks. The continuation rates were 100%, 91%, and 80% at weeks 8, 52, and 106, respectively. The incidence of discontinuation was 6.2% per patient‐year of follow‐up. The steroid‐free remission rates were 44%, 71%, and 80% at weeks 8, 52, and 106, respectively. The Simple Endoscopic Score for Crohn's Disease of patients in clinical remission at the last follow‐up significantly decreased (P < 0.01), and the safety profile was acceptable.Ustekinumab appeared effective in maintaining long‐term clinical remission with endoscopic improvement in pediatric‐onset Crohn's disease with anti‐tumor necrosis factor failure. [ABSTRACT FROM AUTHOR]

Background Objectives Materials and Methods Results Discussion Conclusion Dietary factors and chronic gastrointestinal diseases are frequent determinants of sexual dysfunctions (SD). Whether inflammatory bowel diseases (IBD) are associated with SD is not well known as well as the role of diet and quality of life (QoL).To evaluate the prevalence of SD in a cohort of IBD patients and assess the role of clinical‐demographic variables, adherence to Mediterranean diet (MD) and QoL.This is a cross‐sectional observational study involving 301 patients (134 females and 167 males); 119 had Crohn's Disease and 182 had ulcerative colitis. SD were assessed through the Female Sexual Function Index (FSFI) and the International Index of Erectile Function (IIEF). Adherence to MD was evaluated by the MD Score. QoL was investigated by the 12‐item Short‐Form Health Survey (SF‐12) which yields summary scores of physical (PCS) and mental (MCS) health. Multiple logistic regression was used to identify predictors of SD.Prevalence of SD in females was 61.9%, while 52.1% of males had erectile dysfunction. No differences in the prevalence of SD were found between CD and UC in both males and females. IBD activity, as defined by patient‐reported outcomes, was significantly associated with SD in both sexes. In females, MD adherence score (OR 0.8, 95% CI 0.653–0.974, p = 0.027), PCS (OR = 0.936, CI 95% = 0.891–0.983, p = 0.008), and MCS (OR 0.9, 95% CI 0.906–0.985, p = 0.008) were protective against SD, whereas in males a higher PCS was associated with a lower probability of SD (OR 0.9, 95% CI 0.891–0.978, p = 0.004)IBD patients had a significant prevalence of SD which occurred more frequently in females than in males. Disease activity is associated with a higher likelihood of SD in both sexes, whereas dietary factors are differentially associated with SD in males and females. A better QoL is associated with a lower risk of SD.SD is prevalent among men and women with IBD. Adherence to MD, PCS and MCS in females as well as PCS in males were protective against SD. The assessment of sexual function in IBD patients could be relevant in order to reach an early diagnosis and a timely treatment. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) increases the risk of colorectal cancer, and it has the potential to diminish the quality of life. Clinical and experimental evidence demonstrate protective aspects of parasitic helminth infection against IBD. However, studies on the inhibition of inflammation by helminth infection have overlooked a key determinant of health: the gut microbiota. Although infection with helminths induces alterations in the host microbiota composition, the potential influence and mechanism of helminth infections induced changes in the gut microbiota on the development of IBD has not yet been elucidated. In this study, we analyzed the intersection of helminth Trichinella spiralis and gut bacteria in the regulation of colitis and related mechanisms. Methodology/Principal findings: T. spiralis infected mice were treated with antibiotics or cohoused with wild type mice, then challenged with dextran sodium sulfate (DSS)-colitis and disease severity, immune responses and goblet cells assessed. Gut bacteria composition was assessed by 16S rRNA sequencing and short-chain fatty acids (SCFAs) were measured. We found that protection against disease by infection with T. spiralis was abrogated by antibiotic treatment, and cohousing with T. spiralis- infected mice suppressed DSS-colitis in wild type mice. Bacterial community profiling revealed an increase in the abundance of the bacterial genus Muribaculum and unclassified_Muribaculaceae in mice with T. spiralis infection or mice cohoused with T. spiralis- infected mice. Metabolomic analysis demonstrated significantly increased propionic acid in feces from T. spiralis- infected mice. Data also showed that the gut microbiome modulated by T. spiralis exhibited enhanced goblet cell differentiation and elevated IL-10 levels in mice. Conclusions: These findings identify the gut microbiome as a critical component of the anti- colitic effect of T. spiralis and gives beneficial insights into the processes by which helminth alleviates colitis. Author summary: IBD encompasses Crohn's Disease and Ulcerative Colitis. It affects both children and adults. Reports have highlighted the potential use of helminths or their byproducts as a possible treatment for IBD. Accumulating evidence also suggests that the gut microbiota is a key factor in modulating IBD. In this study, we revealed the protective effect of a prior infection with T. spiralis on DSS- induced colitis in mice. Specifically, T. spiralis infection reshaped the gut microbiome of mice, resulting in an increased abundance of SCFA-producing bacteria Muribaculum and unclassified_Muribaculaceae and thereby producing a larger amount of propionic acid. Furthermore, the gut microbiome modulated by T. spiralis exhibited enhanced goblet cell differentiation and elevated IL-10 levels, ultimately ameliorating experimental colitis. These findings suggest that the modulation of host microbiota during T. spiralis infection plays a crucial role in the suppression of colitis, and any intention-to-treat with helminth therapy should be based on the patient's immunological and microbiological response to the helminth. [ABSTRACT FROM AUTHOR]

Background: To evaluate the correlation between simplified MR index of activity (sMaRIA) score and simple endoscopic score (SES-CD) in Crohn's disease activity assessment. A prospective study was done on established Crohn's disease patients referred to our institution. Magnetic resonance enterography and colonoscopy were performed as an activity assessment protocol searching for activity signs through calculation of sMaRIA score and SES-CD score and correlation between them. One hundred patients were enrolled in the study in period from July 2021 to July 2022. Patients with isolated upper gastrointestinal Crohn's disease (n = 4) or performed surgery before completion of activity assessment protocol (n = 9) or dropout (n = 18) were excluded. Patients with any age group, with ileal or colonic or ileo-colonic Crohn's disease and completed the protocol were eligible for the study (n = 69). Results: Sixty-nine patients with 345 bowel segments (five segments for each patient: ileum, right colon, transverse colon, left colon/sigmoid and rectum) were completely evaluated: 33 males and 36 females with mean age 29.16 ± 11.37 years. sMaRIA and SES-CD scores were calculated for each patient (global), and each bowel segment showed 97.50% sensitivity and 79.31% specificity at the level of global scores as well as significant positive correlation between the two scores at patient level/overall segments (rs = 0.816, p < 0.001), at ileal segments (rs = 0.704, p < 0.001) and colonic segments (right colon rs = 0.661, p ≤ 0.001, transverse colon rs = 0.586, p ≤ 0.001, left colon rs = 0.731, p < 0.001 and rectum rs = 0.786, p < 0.001). There were good inter-rater agreement between the two radiologists for the three parameters (wall thickness > 3 mm, mural edema and fat stranding) and moderate for mucosal ulcer detection with k value 0.666, 0.712, 0.712 and 0.565, respectively. Conclusions: sMaRIA score is considered to be a reliable tool for Crohn's disease activity evaluation as compared to SES-CD. [ABSTRACT FROM AUTHOR]

Introduction: Observational studies have discovered a contradictory phenomenon between Helicobacter pylori (H. pylori) infection and inflammatory bowel disease (IBD). The study aimed to confirm the causal association between H. pylori and IBD, including ulcerative colitis (UC) and Crohn's disease (CD). Methods: We conducted a Mendelian randomization (MR) study with two sample Genome-Wide Association Studies (GWAS) to determine whether there is a causal relationship between H. pylori infection and IBD, as well as the possible pathogenic factors that may be involved. The reliability of the main MR assumptions was examined through a series of sensitivity analyses. Results: Two genetic variants (SNPs) previously identified were employed as instrumental variables (IVs) for H. pylori infection. GWAS data for IBD, UC, and CD were obtained from the recent DF10 release10 of the FinnGen study. Our findings indicated a significant association between H. pylori seropositivity and an increased risk of IBD and UC (IBD: OR: 1.16, 95% CI, 1.03–1.31, P < 0.05; UC: OR: 1.22, 95% CI, 1.08–1.37, P < 0.001) while no causal relationship with CD (P > 0.05). Analysis of the main virulence pathogenic factors revealed a causal relationship between cytotoxin-associated protein A (CagA) and IBD and UC (IBD: OR: 1. 06, 95% CI, 1.001–1.11, P < 0.05; UC: OR: 1.07, 95% CI, 1.004–1.14, P < 0.05), while no correlation was found for vacuolar cytotoxin A (VacA) (P > 0.05). After applying the False Discovery Rate (FDR) correction, the causal relationship between CagA and the risk of IBD or UC was no longer statistically significant. Conclusion: This study suggests a potential causal relationship between H. pylori infection and IBD, particularly UC. The effect may be more pronounced in individuals with previous H. pylori infections. [ABSTRACT FROM AUTHOR]

Introduction: In traditional Japanese Kampo medicine, a profound anamnesis is completed by clinical examination. The resulting clinical image forms the basis of the patient's diagnosis pattern, including the recent mental, physical, and social contexts. Kampo questionnaires support pattern diagnosis and bridge traditional and Western medicine diagnoses. Aims of the study: Traditional Kampo therapy is tailored to a specific body constitution, while Western medicine treatment is tailored to a specific disease. The aims of this study were to analyze whether traditional Kampo diagnosis is applicable to German patients and whether specific symptom patterns are characteristic for defined diseases. Material and methods: This study validates for the first time a Kampo questionnaire adapted for German patients. The analysis focuses on patients with gastrointestinal diseases, the main field for Kampo medicines. Results: In total, we prospectively included 251 participants; of those, 58 were cancer patients (23.1%), 35 had Crohn's disease (13.9%), 18 had ulcerative colitis (7.2%), 17 had irritable bowel syndrome (6.8%), and 103 had other abdominal diseases (41%), as well as 20 German controls (8%). The patient population consisted of 144 female (57.4%) and 107 male (42.6%) participants. The median age was 65 years. The disease duration (average: 211 months) varied from 1 month (cancer patient) to 540 months (patient with Crohn's disease). The scores for questions on the state of mind were significantly higher in patients with inflammatory bowel disease (IBD) as well as irritable bowel syndrome (IBS)—in comparison to the tumor and control groups. This was reflected in questions about abdominal discomfort, appetite, fecal habits, and cold sensation. Accordingly, symptoms of Qi (i.e., vital energy) deficiency were mostly observed in patients with chronic diseases such as Crohn's disease and ulcerative colitis. Defined symptom combinations did not reflect conventional Western diagnosis. Conclusion: Our study results show that symptom patterns are independent of the underlying disease. They rather depict the individual patient within an individual time frame. Traditional Kampo questionnaires were found to be valid for the analysis of a patients' body constitution (sho) and serve as a guide for Kampo treatment. We propose that individual pattern diagnosis should be taken into account to help treatment individualization. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) causes chronic inflammation of the colon and digestive tract, and it can be classified as Crohn's disease (CD) and Ulcerative colitis (UC). IBD is more prevalent in Europe and North America, however, since the beginning of the 21st century it has been increasing in South America, Asia, and Africa, leading to its consideration as a worldwide problem. Optical colonoscopy is one of the crucial tests in diagnosing and assessing the progression and prognosis of IBD, as it allows a real-time optical visualization of the colonic wall and ileum and allows for the collection of tissue samples. The accuracy of colonoscopy procedures depends on the expertise and ability of the endoscopists. Therefore, algorithms based on Deep Learning (DL) and Convolutional Neural Networks (CNN) for colonoscopy images and videos are growing in popularity, especially for the detection and classification of colorectal polyps. The performance of this system is dependent on the quality and quantity of the data used for training. There are several datasets publicly available for endoscopy images and videos, but most of them are solely specialized in polyps. The use of DL algorithms to detect IBD is still in its inception, most studies are based on assessing the severity of UC. As artificial intelligence (AI) grows in popularity there is a growing interest in the use of these algorithms for diagnosing and classifying the IBDs and managing their progression. To tackle this, more annotated colonoscopy images and videos will be required for the training of new and more reliable AI algorithms. This article discusses the current challenges in the early detection of IBD, focusing on the available AI algorithms, and databases, and the challenges ahead to improve the detection rate. [ABSTRACT FROM AUTHOR]

Aim: The rate of surgical recurrence following ileorectal anastomosis (IRA) in patients with Crohn's disease (CD) remains poorly understood. Most studies were conducted before the advent of biologics. Our aim was to assess the fate of IRA in patients with CD during the biologics era and identify risk factors for endoscopic, clinical, and surgical recurrence. Methods: This retrospective multicentre cohort study included patients with CD who underwent IRA between 2006 and 2022. The association of patient characteristics and postoperative measures with each type of postoperative recurrence and need for a definitive stoma was investigated using the chi‐square test or Fisher's exact test. Results: During a median follow‐up period of 60 months, the rates of endoscopic, clinical, and surgical postoperative recurrence were 70%, 59%, and 35%, respectively. The rate of perianal lesions was higher in patients who underwent a definitive stoma (70% vs. 35%, p = 0.007) and with endoscopic (50% vs. 25%, p = 0.038), clinical (54% vs. 24%, p = 0.006), and surgical (63% vs. 34%, p = 0.015) recurrence. The incidence of residual microscopic disease at the rectal margin was higher in patients with endoscopic recurrence (p = 0.047). Biologics were identified as protective factors against the need for a definitive stoma (p = 0.044). Conclusion: IRA is a good treatment option for extensive colitis in patients with CD. However, its consideration should be weighed in the presence of perianal lesions, which have been shown to be a risk factor for delayed proctectomy. [ABSTRACT FROM AUTHOR]

Background: The effective management of inflammatory bowel disease (IBD) requires complex self-management behaviors. Both patient activation (the degree to which patients are willing and able to engage in care) and self-efficacy (one's confidence in performing certain behaviors) are thought to play an important role in chronic disease self-management, but patient activation is a broad concept that can be more difficult to precisely target than self-efficacy. We aimed to describe the relationship between patient activation, self-efficacy, and the burden of IBD on patients' daily lives. Methods: Patients with IBD were recruited from a single center to complete a survey including the Patient Activation Measure (PAM-13®), the IBD Self-Efficacy Scale (IBD-SES), and an IBD-specific patient-reported outcome measure. Using multivariable linear regression, we examined the relationship between IBD burden, self-efficacy, and patient activation, adjusting a priori for age, gender, IBD type, IBD medications, active corticosteroid use, anxiety, and depression. We performed a post-hoc mediation analysis to examine self-efficacy as a potential mediator in the relationship between patient activation and the burden of IBD on patient's daily lives. Results: A total of 132 patients with IBD completed the survey (59% Crohn's disease, 41% ulcerative colitis, 52% female). Higher levels of patient activation and higher levels of self-efficacy were each associated with lower IBD burden (patient activation: ß = − 1.9, p < 0.001, self-efficacy: ß = − 2.6, p < 0.001). Post hoc mediation analysis confirmed that the relationship between patient activation and daily IBD burden was mediated by self-efficacy (Average Causal Mediation Effect = − 1.00, p < 0.001, proportion mediated = 0.62, p < 0.001). Discussion: The relationship between patient activation and IBD burden is highly mediated by self-efficacy, suggesting that self-efficacy could be a more precise target for intervention. Future studies could focus on targeting self-efficacy to build individuals' confidence in IBD self-management and testing of IBD-tailored self-management programs to ultimately improve disease outcomes. [ABSTRACT FROM AUTHOR]

Background: Crohn's disease (CD) have an increased risk of gallstone disease. We aimed to systematically evaluate the prevalence rate and relevant risk factors of gallstones in CD patients. Methods: A comprehensive search of PubMed, Embase, and Web of Science databases from inception to September 10, 2023, identified studies investigating risk factors for gallstone development among CD patients. Gender, age, body mass index, disease duration, disease site, stenosis, prior surgery, hospitalization times, corticosteroids, immunomodulators, and total parenteral nutrition (TPN) were assessed as potential risk factors. Odds ratios (OR) and confidence intervals (CI) were calculated. Result: Among 1184 articles, 11 observational studies (3588 patients) were included. The prevalence of CD patients with gallstones was approximately 14.7%. Factors significantly associated with increased gallstone risk included Age ≥ 40 years old (OR 3.06, 95% CI 2.09- 4.48), disease duration > 15 years (OR 3.01, 95% CI 2.06–4.42), lifetime surgery(OR 2.50, 95% CI 1.99–3.12), disease located in ileocolon (OR 1.38, 95% CI 1.04–1.83) and ileocecal(OR 1.93, 95% CI 1.16–3.21), multiple hospitalizations(OR 4.26, 95% CI 2.43–7.46), corticosteroid treatments(OR 2.65, 95% CI 1.52–4.63), immunomodulator therapy(OR 1.94, 95% CI 1.12–3.38), and TPN use(OR 2.66, 95% CI 1.29–5.51). Sex, stenosis, overweight, or low weight did not significantly increase the risk of gallstone developing. Conclusion: Age, long disease duration, specific disease locations (ileocolon, ileocecal), surgery, number of hospitalizations, corticosteroids, immunomodulator therapy, and TPN were identified as factors that increased the risk of gallstones in CD patients. About 14.7% of CD patients experience gallstones, so raising awareness and implementing prevention are needed. Registration: PROSPERO (CRD42023449299). [ABSTRACT FROM AUTHOR]

Background: Patients with Crohn's disease (CD) experience disease progression over time, including strictures/stenoses, penetrating fistulae, and abscesses. Aims: This retrospective US population-based study aimed to characterize CD progression in newly diagnosed patients. Methods: Patient-level data from the Optum® Market Clarity database from January 1, 2016, to June 30, 2020, were used. The study comprised a 12-month baseline period (pre-diagnosis), an index date (diagnosis date), and a follow-up period. The risk of, and time to, CD progression since CD diagnosis, dispensed treatment changes following CD progression, and healthcare resource utilization before and after CD progression were assessed. Results: Overall, 6804 newly diagnosed patients were included. Of these, 1714 (25.2%) experienced CD progression as follows: 19.3% (1183/6117) in the first 6 months, 21.6% (1188/5503) by 1 year, 24.6% (953/3875) by 2 years, and 26.6% (444/1668) by 3 years. Intestinal obstruction/stenosis was more common than fistula or abscess. Among patients with CD progression, the median (interquartile range) estimated time to progression was 2 (0–140) days; the shortest time to progression was seen with a first intestinal obstruction/stenosis (0 [0–137] days). The frequency of several dispensed treatments increased following CD progression. Among patients who experienced progression, CD-related inpatient hospital admissions/visits increased from 436 of 1714 patients (25.4%) in the month before progression to 965 (56.3%) in the month after progression. Conclusions: Over one quarter of patients with newly diagnosed CD experienced CD progression and complications within 3 years of diagnosis, highlighting the importance of monitoring for progression and early intervention to limit progression. [ABSTRACT FROM AUTHOR]

Background and Aim: Luminal strictures, common in inflammatory bowel disease (IBD), especially Crohn's disease (CD), are typically treated with endoscopic balloon dilatation (EBD). The newer endoscopic stricturotomy (ESt) approach shows promise, but data is limited. This systematic review and meta-analysis assess the effectiveness and safety of ESt in IBD-related strictures. Methods: A comprehensive literature search was conducted until November 2023 for studies assessing ESt efficacy and safety in IBD. Primary outcomes were clinical and technical success, with secondary endpoints covering adverse events, subsequent stricture surgery, additional endoscopic treatments (ESt or EBD), medication escalation, disease-related emergency department visits, and hospitalization post-ESt. Technical success was defined as passing the scope through the stricture, and clinical success was defined as symptom improvement. Single-arm meta-analysis (CMA version 3) calculated the event rate per patient with a 95% confidence interval (CI). Heterogeneity was evaluated using I2. Results: Nine studies were included, involving 640 ESt procedures on 287 IBD patients (169 CD, 118 ulcerative colitis). Of these, 53.3% were men, with a mean age of 43.3 ± 14.3 years and a mean stricture length of 1.68 ± 0.84 cm. The technical success rate was 96.4% (95% CI 92.5–98.3, p-value < 0.0001), and the clinical success rate was 62% (95% CI 52.2–70.9, p-value = 0.017, I2 = 34.670). The bleeding rate was 10.5% per patient, and the perforation rate was 3.5%. After an average follow-up of 0.95 ± 1.1 years, 16.4% required surgery for strictures post-ESt, while 44.2% needed additional endoscopic treatment. The medication escalation rate after ESt was 14.7%. The disease-related emergency department visit rate was 14.7%, and the disease-related hospitalization rate post-procedure was 21.3%. Conclusion: Our analysis shows that ESt is safe and effective for managing IBD-related strictures, making it a valuable addition to the armamentarium of endoscopists. Formal training efforts should focus on ensuring its widespread adoption. [ABSTRACT FROM AUTHOR]