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Current therapeutic strategies for inflammatory bowel disease (IBD) have reached a plateau in the rates of response and/or remission achieved with a single therapeutic agent. Consequently, the advanced combination therapy (ACT) strategy has emerged as a novel treatment concept for IBD. ACT involves the use of two different targeted therapies, whether biologic or small molecules, with the primary goal of overcoming the therapeutic plateau. Real-world evidence is accumulating among patients undergoing ACT, especially those dealing with concurrent IBD and extraintestinal manifestations or grappling with medically refractory IBD. The recently conducted VEGA study, a randomized clinical trial, has provided crucial insights by demonstrating that the short-term combination of dual biological agents can lead to superior disease control compared to single agents in patients diagnosed with ulcerative colitis (UC). This suggests that ACT holds promise as a therapeutic option to enhance disease control effectively. However, there is still limited evidence of ACT in UC patients who have proven refractory to biologic therapy and patients with Crohn's disease. This review aims to discuss whether ACT represents the optimal approach for overcoming the therapeutic ceiling in IBD. [ABSTRACT FROM AUTHOR]

Objective: Inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), are chronic conditions primarily affecting the intestines. This study aims to identify the nature and frequency of oral symptoms and signs in patients with ulcerative colitis and to explore the connection between these complications and the activity of the disease. Methods: This descriptive-analytical study involved ulcerative colitis patients who visited the gastroenterology clinic at Shahid Sayad Shirazi Hospital in Gorgan, along with an equal number of healthy companions as a control group in 2019. A gastroenterology internist assessed the disease severity through clinical examination and a simple clinical disease activity index for colitis patients. The collected data were then analyzed statistically using SPSS version 19. Results: The average age of patients in the case group was 41.84 ± 11.66 years, while in the control group it was 40.43 ± 12.67 years. There was a significant correlation between difficulty swallowing, burning sensation in the mouth, vomiting, acidic taste, the presence of oral ulcers, and a coated tongue with the severity of disease activity (p < 0.05). However, no significant relationship was found between other variables and the severity of disease activity (p > 0.05). Conclusion: The results of this study confirm that as the severity of ulcerative colitis increases, the occurrence of oral lesions also rises, particularly during severe disease activity. Among oral symptoms, dry mouth had the highest incidence, followed by bad breath and changes in taste. The most common oral lesions observed were a coated tongue, grooved tongue, and oral ulcers, respectively. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) is a chronic, relapsing condition wherein biologics have improved disease prognosis but introduced elevated infection susceptibility. Vedolizumab (VDZ) demonstrates unique safety advantages; however, a comprehensive systematic comparison regarding the risk of Clostridioides difficile infection (CDI) between vedolizumab and alternative medications remains absent. Method: Medline, Embase, Cochrane, and clinicaltrials.gov registry were comprehensively searched. Pooled estimates of CDI proportion, incidence, pooled risk ratio between ulcerative colitis (UC) and Crohn's disease (CD), vedolizumab and other medications were calculated. Data synthesis was completed in R using the package "meta". Results: Of the 338 studies initially identified, 30 met the inclusion/exclusion criteria. For CDI risk, the pooled proportion was 0.013 (95% CI 0.010–0.017), as well as the pooled proportion of serious CDI was 0.004 (95% CI 0.002–0.008). The comparative pooled risk ratios revealed: UC versus CD at 2.25 (95% CI 1.73–2.92), vedolizumab versus anti-TNF agents at 0.15 (95% CI 0.04–0.63) for UC and 1.29 (95% CI 0.41–4.04) for CD. Conclusion: The overall CDI risk in IBD patients exposed to vedolizumab was estimated to be 0.013. An increased risk of CDI was noted in UC patients receiving vedolizumab compared to those with CD. Vedolizumab potentially offers an advantage over anti-TNF agents for UC regarding CDI risk, but not for CD. Trial registration: The study was registered on the PROSPERO registry (CRD42023465986). [ABSTRACT FROM AUTHOR]

Background: Inflammation is characterized by a metabolic switch promoting glycolysis and lactate production. Hexokinases (HK) catalyze the first reaction of glycolysis and inhibition of epithelial HK2 protected from colitis in mice. HK2 expression has been described as elevated in patients with intestinal inflammation; however, there is conflicting data from few cohorts especially with severely inflamed individuals; thus, systematic studies linking disease activity with HK2 levels are needed. Methods: We examined the relationship between HK2 expression and inflammation severity using bulk transcriptome data derived from the mucosa of thoroughly phenotyped inflammatory bowel disease (IBD) patients of two independent cohorts including both subtypes Crohn's disease (CD) and ulcerative colitis (UC). Publicly available single-cell RNA sequencing data were analyzed, and immunofluorescence staining on colonic biopsies of unrelated patients with intestinal inflammation was performed to confirm the RNA-based findings on cellular and protein level. Results: HK2 expression gradually increased from mild to intermediate inflammation, yet strongly declined at high inflammation scores. Expression of epithelial marker genes also declined at high inflammation scores, whereas that of candidate immune marker genes increased, indicating a cellular remodeling of the mucosa during inflammation with an infiltration of HK2-negative immune cells and a loss of terminal differentiated epithelial cells in the apical epithelium—the main site of HK2 expression. Normalizing for the enterocyte loss clearly identified epithelial HK2 expression as gradually increasing with disease activity and remaining elevated at high inflammation scores. HK2 protein expression was mostly restricted to brush border enterocytes, and these cells along with HK2 levels vanished with increasing disease severity. Conclusions: Our findings clearly define dysregulated epithelial HK2 expression as an indicator of disease activity in intestinal inflammation and suggest targeted HK2-inhibition as a potential therapeutic avenue. [ABSTRACT FROM AUTHOR]

Aim Method Results Conclusion To identify patient‐reported complaints affecting quality of life in Crohn's disease patients with a perianal fistula, and to compare differences between subgroups.A questionnaire was distributed to 1667 patients from the Dutch Crohn's and Colitis Patients' organization, those patients with Crohn's disease and perianal fistula were included. Patients were asked to report (using free text) their most important fistula‐related complaints affecting their quality of life. All responses were structurally analyzed and categorized. Data comparisons were made between subgroups: women versus men, patients with versus without current presence of a seton, and patients aged ≤40 versus >40 years.Of 743 respondents (44.6%), 123 patients with Crohn's disease and perianal fistula were included (92 women, median age 41 years [IQR 34–56] and 36 with seton). A total of 776 complaints were allocated to 36 categories, with 19 reported in >10% of patients. Perianal fistula‐related complaints affected nearly all patients (95.9%). Impact on psychological status (71.7% vs. 29.0%; p < 0.0001) and on sexual activities (37.0% vs. 16.1%; p = 0.003) were more common in women than men. Younger patients more often reported insecurity (38.7% vs. 18.0%; p = 0.026), shame (29.0% vs. 11.5%; p = 0.024), and impact on sexual activities (40.3% vs. 23.0%; p = 0.048) than older patients. Patients with a seton more frequently reported self‐experienced malodour (50.0% vs. 23.0%; p = 0.005), physical activity limitations (41.7% vs. 19.5%; p = 0.014), and work/study impact (22.2% vs. 5.7%; p = 0.019).We identified 19 perianal fistula‐related complaints reported by >10% of patients. These complaints may guide improvement of current outcome measures. [ABSTRACT FROM AUTHOR]

Background: Crohn's disease (CD) is a chronic intestinal inflammatory disorder, the etiology of which remains unknown, and is characterized by symptoms such as chronic abdominal pain, diarrhea, obstruction, and perianal lesions. Histopathology is widely regarded as the preferred method for diagnosing CD, although the histological diagnosis may lack specificity. The identification of granulomas is commonly believed to be the most reliable diagnostic indicator for CD, surpassing all other clinical features in significance. Nevertheless, research indicates that the detection rate of granulomas in CD exhibits considerable variability. Furthermore, granulomas can manifest in various specific infections including tuberculosis and Yersinia, as well as in a range of diseases characterized by macrophage reactions such as sarcoidosis and drug-induced enteritis. Granulomas associated with CD typically do not exhibit necrosis. However, the formation of caseous granulomas may occur as a result of secondary infections related to anti-CD drug treatment or perforation of the intestinal wall. Case presentation: In this study, we present a case of a 28-year-old female patient diagnosed with CD exhibiting histologic granulomas, including both caseating and non-caseating forms, which demonstrated a positive response to medical treatment. Conclusion: In clinical practice, various forms of granulomas may indicate diverse underlying diseases, yet lack specificity. It is suggested that the presence of caseous granulomas should not be considered as a definitive exclusion criterion for the diagnosis when clinical, endoscopic, imaging and other histopathological features are consistent with CD. This study is the first report of caseous granulomas in CD without concomitant tuberculosis infection. [ABSTRACT FROM AUTHOR]

Background: Crohn's disease (CD) is characterized by chronic intestinal inflammation. Diet is a key modifiable factor influencing the gut microbiome (GM) and a risk factor for CD. However, the impact of diet modulation on GM function in CD patients is understudied. Herein, we evaluated the effect of a high-fiber, low-fat diet (the Mi-IBD diet) on GM function in CD patients. All participants were instructed to follow the Mi-IBD diet for 8 weeks. One group of CD patients received one-time diet counseling only (Gr1); catered food was supplied for the other three groups, including CD patients (Gr2) and dyads of CD patients and healthy household controls (HHCs) residing within the same household (Gr3-HHC dyads). Stool samples were collected at baseline, week 8, and week 36, and analyzed by liquid chromatography-tandem mass spectrometry. Results: At baseline, the metaproteomic profiles of CD patients and HHCs differed. The Mi-IBD diet significantly increased carbohydrate and iron transport and metabolism. The predicted microbial composition underlying the metaproteomic changes differed between patients with ileal only disease (ICD) or colonic involvement: ICD was characterized by decreased Faecalibacterium abundance. Even on the Mi-IBD diet, the CD patient metaproteome displayed significant underrepresentation of carbohydrate and purine/pyrimidine synthesis pathways compared to that of HHCs. Human immune-related proteins were upregulated in CD patients compared to HHCs. Conclusions: The Mi-IBD diet changed the microbial function of CD patients and enhanced carbohydrate metabolism. Our metaproteomic results highlight functional differences in the microbiome according to disease location. Notably, our dietary intervention yielded the most benefit for CD patients with colonic involvement compared to ileal-only disease. 9orssYZV9GnhTtyZm1JCtC Video Abstract [ABSTRACT FROM AUTHOR]

Long-standing chronic inflammation of the digestive tract leads to Inflammatory Bowel Diseases (IBD), comprising Crohn's Disease (CD) and Ulcerative colitis (UC). The persistent prevalence of these conditions in the gut is a predisposing factor for Colitis-Associated Cancer (CAC), one of the most common sub-types of Colorectal Cancer (CRC), emphasizing the role of inflammation in tumorigenesis. Therefore, targeted intervention of chronic intestinal inflammation is a potential strategy for preclusion and treatment of inflammation-driven malignancies. The association between bile acids (BA) and gut immune homeostasis has been explored in the recent past. However, the exact downstream mechanism by which secondary BA successfully regulating intestinal inflammation and inflammation-dependent CAC is unclear. Our study demonstrated that Ursodeoxycholic acid (UDCA), a secondary bile acid of host gut microbial origin, finetunes the dialogue between activated macrophages and intestinal epithelial cells, modulating inflammation-driven epithelial-mesenchymal transition (EMT), a hallmark of cancer. UDCA treatment and dependency on the TGR5/GPBAR1 receptor significantly upregulated the Suppressor of Cytokine Signaling 1 (SOCS1) expression, contributing to the regulation of pro-inflammatory cytokines in activated macrophages. In this study, we also noticed heightened expression of SOCS1 in UDCA-mitigated CAC in the AOM-DSS mouse model with reduced inflammatory gene expression. Overall, our observations highlight the possible utility of UDCA for inflammation-driven intestinal cancer. [ABSTRACT FROM AUTHOR]

Although observational clinical studies have established an association between Intestinal Diseases (IDS) and Anal Diseases (ADS), the causal relationship is still not fully understood due to the limitations of observational studies. Genome-wide association study (GWAS) statistical data for IDS and ADS were obtained from publicly available databases. To assess the causal effects of IDS on ADS, we conducted Mendelian randomization analysis. The inverse variance weighted method indicated that Inflammatory bowel disease (IBD) had a significant causal relationship with three kinds of ADS: Anorectal abscess (ARB), Haemorrhoidal disease (HEM), and Fissure and fistula of anal and rectal regions (FISSANAL). Crohn's disease (CD) and Ulcerative colitis (UC) also showed significant causal effects with three ADS: ARB, HEM, and FISSANAL. Furthermore, a potential link between CD and BNA(Benign neoplasm of anus and anal canal), Irritable bowel syndrome (IBS) and HEM, Colorectal cancer (CRC) and BNA, and Celiac disease and MNA (Malignant neoplasm of anus and anal canal) was observed. This comprehensive MR analysis highlight the significant and increased risk of common Anal Diseases (ARB, FISSANAL, and HEM) in patients with IBD, CD, and UC. Additionally, potential positive causal associations emerged between IBS and HEM, CRC and BNA, as well as between celiac disease and MNA. [ABSTRACT FROM AUTHOR]

Background Aim Methods Results Conclusion The incidence of Clostridioides difficile infection (CDI) in inflammatory bowel disease (IBD) is rising and associated with adverse outcomes. Optimal treatment for CDI in IBD remains unknown, with various organisations suggesting vancomycin as first‐line therapy.To compare treatment outcomes for metronidazole versus vancomycin in mild to moderate CDI in IBD.A retrospective analysis of IBD patients with CDI between January 2015 and December 2019 was conducted. Laboratory data and clinical outcomes were examined.Forty‐seven discrete episodes of CDI in 34 patients occurred during the study period. Fifty‐three per cent (18) had Crohn's disease, 44% (15) ulcerative colitis and 3% (1) IBD unclassified. Six per cent (3/47) of CDI cases were severe and excluded. In 68% (30/44) of mild to moderate CDI, metronidazole was prescribed, with treatment failure in 20% (6/30), CDI recurrence in 13% (4/30) and 20% (6/30) experiencing a further CDI episode. Comparatively, vancomycin was prescribed in 23% (10/44) without any treatment failures; however, 10% (1/10) had CDI recurrence and 40% (4/10) experienced another CDI episode. No statistically significant difference was noted between metronidazole and vancomycin therapy for treatment failure (P = 0.31), CDI recurrence (P = 1.0) or further CDI episodes (P = 0.23). Proton‐pump inhibitor therapy was the only risk factor associated with a higher rate of the composite outcome and remained significant on multivariate logistic regression (odds ratio 12.99 (95% confidence interval = 1.21–139.97), P = 0.03).Metronidazole compared to vancomycin for treatment of mild to moderate CDI in IBD is effective however may be associated with higher rates of treatment failure. [ABSTRACT FROM AUTHOR]

Background: Crohn's disease (CD) is a complex systemic entity, characterized by the progressive and relapsing inflammatory involvement of any part of the gastrointestinal tract. Its clinical pattern may be categorized as penetrating, stricturing or non-penetrating non-stricturing. Methods: In this paper, we performed a database search (Pubmed, MEDLINE, Mendeley) using combinations of the queries "crohn", "stricture" and "elastography" up to 19 June 2024 to summarize current knowledge regarding the diagnostic utility of ultrasound (US) and magnetic resonance (MR) elastography techniques in the evaluation of stricturing CD by means of an assessment of the transmural intestinal fibrosis. We decided to include papers published since 1 January 2017 for further evaluation (n = 24). Results: Despite growing collective and original data regarding numerous applications of mostly ultrasound elastography (quantification of fibrosis, distinguishing inflammatory from predominantly fibrotic strictures, assessment of treatment response, predicting disease progression) constantly emerging, to date, we are still lacking a uniformization in both cut-off values and principles of measurements, i.e., reference tissue in strain elastography (mesenteric fat, abdominal muscles, unaffected bowel segment), units, not to mention subtle differences in technical background of SWE techniques utilized by different vendors. All these factors imply that ultrasound elastography techniques are hardly translatable throughout different medical centers and practitioners, largely depending on the local experience. Conclusions: Nonetheless, the existing medical evidence is promising, especially in terms of possible longitudinal comparative studies (follow-up) of patients in the course of the disease, which seems to be of particular interest in children (lack of radiation, less invasive contrast media) and terminal ileal disease (easily accessible). [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that sense lipophilic molecules and act as transcription factors to regulate target genes. PPARs have been implicated in the regulation of innate immunity, glucose and lipid metabolism, cell proliferation, wound healing, and fibrotic processes. Some synthetic PPAR ligands are promising molecules for the treatment of inflammatory and fibrotic processes in immune-mediated intestinal diseases. Some of these are currently undergoing or have previously undergone clinical trials. Dietary PPAR ligands and changes in microbiota composition could modulate PPARs' activation to reduce inflammatory responses in these immune-mediated diseases, based on animal models and clinical trials. This narrative review aims to summarize the role of PPARs in immune-mediated bowel diseases and their potential therapeutic use. [ABSTRACT FROM AUTHOR]

Background/Objectives: With the increasing prevalence of Crohn's disease (CD), treatment options for patients who fail conventional and advanced therapy are highly needed. Therefore, we explored the safety and efficacy of extracorporeal photopheresis (ECP) using 5-aminolevulinic acid (ALA) and blue light (405 nm). Methods: Patients with active CD who failed or were intolerant to biological therapy were eligible. Mononuclear cells (90 mL) were collected from each patient using a Spectra Optia® apheresis system and diluted with 100 mL of 0.9% sodium chloride in a collection bag. The cells were incubated with ALA at a concentration of 3 millimolar (mM) for 60 min ex vivo and illumination with an LED blue light (405 nm) source (BLUE-PIT®) before reinfusion to the patient. Recording of vital signs and adverse events were regularly performed. At week 13, we assessed the patients with colonoscopy, the Harvey Bradshaw Index (HBI), the Inflammatory Bowel disease Health Related Quality of Life Questionnaire, and the measurement of serum C-reactive protein and fecal calprotectin (FC) levels. Biopsies of the intestines were taken for immunohistochemistry. Results: Seven patients were included. Four patients completed the treatments, with a total of 24 treatments. Three of the four patients achieved a favorable response, including a lower HBI, lower FC levels, and/or endoscopic improvement. No significant adverse events were observed. The remaining three patients received only one, three, or five treatments due to technical difficulties, medical reasons, or the withdrawal of informed consent. Conclusions: ALA-based ECP appears safe and seems to give some clinical improvement for the patients with active CD who failed to respond to conventional and advanced therapies. [ABSTRACT FROM AUTHOR]

Background/Objectives: Inflammatory bowel diseases primarily encompass Crohn's disease and ulcerative colitis. Insufficient levels of tryptophan cause an imbalance in the gut microbiota, leading to inflammation in the gastrointestinal tract. The main catabolic pathway of tryptophan is the kynurenine pathway. Our study aims to evaluate serum tryptophan, the kynurenine pathway, and oxidative stress parameters, including total oxidant status and total antioxidant capacity, in patients with Crohn's disease and ulcerative colitis. Methods: The study included 80 follow-up patients in remission diagnosed with Crohn's disease and ulcerative colitis who attended the Gastroenterology Outpatient Clinic, as well as 78 healthy controls. Serum tryptophan, kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, and kynurenic acid levels were measured with liquid chromatography and tandem mass spectrometry (LC-MS/MS). All statistical analysis was performed using R version 4.2.1. Statistical Language. Results: Serum tryptophan, 3-hydroxyanthranilic acid, and total antioxidant capacity were lower in patients with ulcerative colitis and Crohn's disease compared to those in the control group. The serum total oxidant status in the control group was significantly lower than in patients with Crohn's disease and ulcerative colitis. Conclusions: The results of our research indicate that tryptophan and kynurenine pathway metabolites could potentially contribute to the pathogenesis of inflammatory bowel diseases. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory condition of the gut affecting both adults and children. Neutrophil extracellular traps (NETs) are structures released by activated neutrophils, potentially contributing to tissue damage in various diseases. This study aimed to explore the presence and role of NETs in pediatric IBD. We compared intestinal biopsies and peripheral blood from 20 pediatric IBD patients (UC and CD) to controls. Biopsy staining and techniques for neutrophil activation were used to assess neutrophil infiltration and NET formation. We also measured the enzymatic activity of key NET proteins and evaluated NET formation in UC patients in remission. Both UC and CD biopsies showed significantly higher levels of neutrophils and NETs compared to controls (p < 0.01), with UC exhibiting the strongest association. Peripheral blood neutrophils from UC patients at diagnosis displayed increased NET formation compared to controls and CD patients. Interestingly, NET formation normalized in UC patients following remission-inducing treatment. This pilot study suggests a potential role for NETs in pediatric IBD, particularly UC. These findings warrant further investigation into the mechanisms of NET involvement and the potential for targeting NET formation as a therapeutic strategy. [ABSTRACT FROM AUTHOR]

SAPHO syndrome, a rare inflammatory disorder of bone, joints, and skin, is named based on the presence of synovitis, acne, pustulosis, hyperostosis, and osteitis. The hallmark of SAPHO syndrome includes osteoarticular and dermatologic manifestations, however, rarer associations with inflammatory bowel disease (particularly Crohn's disease) have been documented. The literature on the relationship between SAPHO syndrome and inflammatory bowel disease (IBD), especially ulcerative colitis (UC), remains limited. We report an unusual case of SAPHO syndrome in a patient with UC. Chest x‐ray and MRI showed enlargement of the right first rib and adjacent sternum. Bone scintigraphy revealed hyperostosis and ankylosis of the costochondral junction, and bone biopsy revealed reactive bone and costal cartilage without findings of infection or malignancy. Complete resolution of symptoms was achieved 4 months after starting zoledronic acid without significant adverse events. The diagnosis of SAPHO syndrome in IBD patients is rare, even more so in UC patients, likely attributable to underdiagnosis given the clinical heterogeneity of SAPHO syndrome and overlap with the extra‐intestinal manifestation of IBD. Our treatment approach provides critical data to the underreported literature on diagnosis and managing SAPHO syndrome in UC. [ABSTRACT FROM AUTHOR]

Background: The gut-brain axis has garnered increasing attention, with observational studies suggesting its involvement in the disease activity and progression of inflammatory bowel disease (IBD), but the precise mechanisms remain unclear. Materials and methods: In this study, we aimed to investigate "novel proteins" underlying IBD in the brain using a comprehensive multi-omics analysis approach. We performed integrated analyses of proteomics and transcriptomics in the human prefrontal cortex (PFC) tissue, coupled with genome-wide association studies (GWAS) of IBD, crohn's disease (CD), and ulcerative colitis (UC). This included performing protein-wide association studies (PWAS), transcriptome-wide association studies (TWAS), Mendelian randomization (MR), and colocalization analysis to identify brain proteins associated with IBD and its subtypes. Results: PWAS analyses identified and confirmation 9, 9, and 6 brain proteins strongly associated with IBD, CD, and UC, respectively. Subsequent MR analyses revealed that increased abundance of GPSM1, AUH, TYK2, SULT1A1, and FDPS, along with corresponding gene expression, led to decreased risk of IBD. For CD, increased abundance of FDPS, SULT1A1, and PDLIM4, along with corresponding gene expression, also decreased CD risk. Regarding UC, only increased abundance of AUH, along with corresponding gene expression, was significantly associated with decreased UC risk. Further TWAS and colocalization analyses at the transcriptome level supported strong associations of SULT1A1 and FDPS proteins with reduced risk of IBD and CD. Conclusion: The two "novel proteins," SULT1A1 and FDPS, are strongly associated with IBD and CD, elucidating their causal relationship in reducing the risk of IBD and CD. This provides new clues for identifying the pathogenesis and potential therapeutic targets for IBD and CD. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusion The rising prevalence of IBD globally has raised concerns about antibiotic exposure. This study's meta‐analysis examines antibiotic exposure, frequency, year before diagnosis, regional differences, and IBD incidence.The literature review used PubMed, Web of Science, Elsevier, ScienceDirect, and Cochrane CENTRAL databases up to June 2024 to explore the link between antibiotic exposure and IBD risk. Stratified analysis was conducted by years of antibiotic exposure before IBD diagnosis, frequency, and region. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were combined using a random effects model.Eighteen case–control studies and five cohort studies were included (n = 99, 104 IBD patients and n = 2 273 336 controls). The findings indicate that antibiotic exposure significantly has a positive association with the risk of developing IBD (OR, 1.66; 95% CI, 1.28–2.16). Antibiotic exposure of ≥3 years (OR, 1.49; 95% CI, 1.12–1.98), 2 years (OR, 1.46; 95% CI, 1.37–1.55), and ≤1 year (OR, 1.55; 95% CI, 1.17–2.04) prior to the diagnosis of IBD is associated with a higher risk of developing IBD. Cumulative exposure of ≥3 dispensations (OR, 2.02; 95% CI, 1.49–2.74) and two dispensations (OR, 1.36; 95% CI, 1.03–1.78) also had a positive association with IBD risk, while one dispensation did not (OR, 0.96; 95% CI, 0.72–1.26). No significant association was found in developing countries (OR, 1.92; 95% CI, 0.71–5.19), but developed countries showed a significant positive association with the risk (OR, 1.58; 95% CI, 1.27–1.96).The meta‐analysis suggests that antibiotic use has a positive association with the risk of IBD, and limiting unnecessary antibiotic use may be one way to reduce the risk of developing IBD. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) is a complex autoimmune disorder, although some medications are available for its treatment. However, the long-term efficacy of these drugs remains unsatisfactory. Therefore, there is a need to develop novel drug targets for IBD treatment. Methods: We conducted two-sample Mendelian randomization (MR) analysis using Genome-Wide Association Study (GWAS) data to assess the causal relationships between plasma proteins and IBD and its subtypes. Subsequently, the presence of shared genetic variants between the identified plasma proteins and traits was explored using Bayesian co-localization. Phenome-wide MR was used to evaluate evaluated adverse effects, and drug target databases were examined for therapeutic potential. Results: Using the Bonferroni correction (P < 3.56e-05), 17 protein-IBD pairs were identified. Notably, the genetic associations of IBD shared a common variant locus (PP.H4 > 0.7) with five proteins (MST1, IL12B, HGFAC, FCGR2A, and IL18R1). As a subtype of IBD, ulcerative colitis shares common variant loci with FCGR2A, IL12B, and MST1. In addition, we found that ANGPTL3, IL18R1, and MST1 share a common variant locus with Crohn's disease. Furthermore, phenome-wide MR analysis revealed that except for ANGPTL3, no other proteins showed potential adverse effects. In the drug database, identified plasma proteins such as FCGR2A and IL18R1 were found to be potential drug targets for the treatment of IBD and its subtypes. Conclusion: Six proteins (FCGR2A, IL18R1, MST1, HGFAC, IL12B, and ANGPTL3) were identified as potential drug targets for the treatment of IBD and its subtypes. [ABSTRACT FROM AUTHOR]

Introduction: Despite advantages for patients with ulcerative colitis, Crohn's disease, and familial adenomatous polyposis, restorative proctocolectomy with ileal pouch-anal anastomosis carries a risk of pouch failure, necessitating pouch excision. The traditional open approach is associated with potential complications. Robotic and laparoscopic techniques are emerging, but comparative outcome data are limited. Methods: We conducted a retrospective study of consecutive adult patients undergoing robotic, laparoscopic, and open ileal pouch excision at Mayo Clinic, Rochester, MN, between January 2015 and December 2023. We analyzed data on patient characteristics, perioperative variables, and postoperative outcomes, focusing on short-term complications. Statistical analysis included appropriate tests. Results: The study included 123 patients: 23 underwent robotic-assisted pouch excision, 12 laparoscopic, and 82 open. The robotic approach had the longest median operative time (334 ± 170 min, p = 0.03). However, it demonstrated significantly lower estimated blood loss than open (150 ± 200 ml vs. 350 ± 300 ml, p = 0.002) and laparoscopic surgery (250 ± 250 ml, p = 0.005). Robotic and laparoscopic groups required fewer preoperative ureteral stents than the open group (p = 0.001). Additionally, the robotic approach utilized fewer pelvic drainages (p < 0.0001) and had a lower rate of lysis of adhesions > 60 min compared to open surgery (p = 0.003). Robotic procedures had significantly lower 30-day postoperative complications than the open approach (30.4% vs. 65.9%, p = 0.002) while also demonstrating fewer 30-day reoperations than the laparoscopic group (p = 0.04). Conclusions: Robotic-assisted pouch excision offered significant benefits, including decreased EBL, reduced need for preoperative ureteral stents, and significantly fewer 30-day postoperative complications compared to open surgery. [ABSTRACT FROM AUTHOR]

Background: The prostaglandin receptor PTGER4 facilitates homeostasis in the gut. Previous reports indicate that goblet cells, marked by SPINK4 expression, might be affected by PTGER4 activity. Current evidence suggests that prostaglandin E2 (PGE2) produced by mesenchymal stromal cells (MSC) stimulates PTGER4 in epithelial cells during inflammatory conditions. Here, we investigate the subcellular mechanisms and mRNA levels downstream of PTGER4 activity in epithelial cells. Methods: Mucosal cells, organoids, and MSC were obtained from patient biopsies harvested by endoscopy. Using independent and co-cultures, we manipulated the activity of PTGER4, the downstream enzymes, and mRNA levels, by using PGE2, in combination with chemical inhibitors, L-161982, H89, LB100, DAPT, LMK-235, or with butyrate. Immunofluorescence, single cell sequencing, RNAscope, ELISA, real time PCR, and Western blotting were used to examine these samples. Results: SPINK4 mRNA levels were increased in organoids by co-culture with MSC or exogenous stimulation with PGE2 that could be blocked by L-161982 or LMK-235, PTGER4 or HDAC4 inhibitors, respectively. Expression of PTGER4 was co-localized with JAM-A in the basolateral surfaces in rectal epithelial cells grown as organoids. PGE2 treatment of rectal organoids decreased HDAC4, 5, and 7 phosphorylation levels that could be blocked by L-161982 treatment. Butyrate treatment, or addition of L-161982, increased the phosphorylated levels of HDAC4, 5, and 7. Conclusions: These findings suggest a mechanism during mucosal injury whereby MSC production of PGE2 increases HDAC4, 5, and 7 activities in epithelial cells by upregulating PTGER4 signaling, ultimately increasing SPINK4 mRNA levels and extracellular release of SPINK4. [ABSTRACT FROM AUTHOR]

Summary: Background: Dietary advanced glycation end products (AGEs) may promote oxidative stress and inflammation in the gastrointestinal tract. Aims: The aim of this study is to investigate the association between dietary AGE intake and the risk of inflammatory bowel disease (IBD). Methods: We included 121,978 participants without IBD at baseline from the UK Biobank. We estimated consumption of three common AGEs (Nε‐(carboxymethyl)‐lysine (CML), Nε‐(1‐carboxyethyl)‐lysine (CEL), and Nδ‐(5‐hydro‐5‐methyl‐4‐imidazolon‐2‐yl)‐ornithine (MG‐H1)) by matching 24‐h dietary questionnaires to a validated dietary AGE database. We used Cox proportional hazards regression models to calculate the hazard ratio (HR) and 95% CI of the association between dietary AGEs and IBD risk. Results: During a median follow‐up of 13.72 years, 671 participants developed IBD (192 with Crohn's disease (CD) and 478 with ulcerative colitis (UC)). Among the assessed dietary AGEs, only CEL was associated with an increased risk of IBD (HR = 1.09, 95% CI: 1.01–1.18, p = 0.020) and CD (HR = 1.18, 95% CI: 1.03–1.36, p = 0.014), particularly for participants who were overweight, physically inactive, and non‐smokers. Among participants at a high genetic risk of CD, HRs (95% CI) of CD were 1.26 (1.00–1.57) for CML, 1.41 (1.12–1.77) for CEL, and 1.28 (1.01–1.62) for MG‐H1 (p < 0.05 for each). However, none of the dietary AGEs was significantly associated with UC risk, irrespective of genetic predisposition. Conclusions: Dietary CEL was associated with an increased risk of IBD and CD, but not UC. Further interventional studies are required to support the potential benefit of AGE restriction, especially for individuals at a high genetic risk of CD. [ABSTRACT FROM AUTHOR]

Summary: Background: Elevated allostatic load (AL) has been associated with the risk and poor prognosis of many chronic diseases. The association between AL and inflammatory bowel disease (IBD) is unknown. Aims: The aim of this study is to investigate the associations between AL and the risk and prognosis of IBD. Methods: We included 326,345 adults and 3767 patients with IBD from the UK Biobank. AL served as the exposure, estimated using the AL biomarker panel, with the primary outcomes including the risk and prognosis of IBD. We used Cox regression models to examine the associations. Results: High AL biomarker panel was associated with a greater risk of IBD (hazard ratio: 1.19, 95% CI: 1.08–1.31), ulcerative colitis (1.17, 95%CI: 1.04–1.32), and Crohn's disease (1.25, 95%CI: 1.05–1.49). Risk of developing IBD increased by 12% in quartile 2, 20% in quartile 3, and 37% in quartile 4 as AL biomarker panel increased. The all‐cause mortality risk in IBD compared with quartile 1 rose by 54% for quartile 2, 72% for quartile 3, and 82% for quartile 4, as AL biomarker panel increased. Similar effects were also observed for ulcerative colitis and Crohn's disease. An increase in AL biomarker panel count was associated with an elevated risk of intestinal resection and colorectal cancer in IBD. Conclusions: Increased AL is associated with IBD risk, as well as the risks of intestinal resection, colorectal cancer and mortality. [ABSTRACT FROM AUTHOR]

Summary: Background: The performance of bowel preparation (BP) in patients with Crohn's disease (CD) is unknown. Aims: To evaluate the operating properties of instruments used to assess BP quality in patients with CD. Methods: We used the Boston Bowel Preparation Scale, modified Boston Bowel Preparation Scale, Harefield Cleansing Scale, Food and Drug Administration Bowel Cleansing Assessment Scale (BCAS), and a 100‐mm visual analogue scale of bowel cleanliness to assess BP quality in 50 videos from 40 patients with CD. We assessed endoscopic activity with the Simple Endoscopic Score for CD (SES‐CD). Assessments were on endoscope insertion and withdrawal. Reliability was quantified using the intraclass correlation coefficient (ICC). We assessed validity by within‐patient correlation between instruments and the visual analogue scale using mixed‐effect models. The correlation between BP quality and SES‐SD scores was assessed using Spearman's rho. Results: Inter‐ and intra‐rater reliability for all BP quality instruments was substantial (ICC ≥0.61) except for the Food and Drug Administration BCAS on insertion (inter‐rater reliability ICC ≥0.41). The visual analogue scale had substantial inter‐ and almost perfect (ICC ≥0.81) intra‐rater reliability. Correlation coefficients for the validity of the instruments exceeded 0.58. BP quality and endoscopic disease activity scores in the colon were negatively correlated. Conclusion: Most existing instruments reliably assess BP quality in patients with CD. These results support the use of these instruments in clinical practice, provide a framework for scoring BP quality in CD clinical trials, and support evaluation of novel BP agents in patients with CD. [ABSTRACT FROM AUTHOR]

Background: Treatments and strategies for inflammatory bowel disease (IBD) have gradually evolved in the 2000s. Objectives: We investigated whether the prescription of corticosteroids (prednisolone and budesonide) in patients with IBD in the first 5 years after diagnosis changed in patients diagnosed between 2006 and 2018. Design: Retrospective observational study. Methods: The cumulative prescribed dosage of corticosteroids for the first 5 years after diagnosis was registered in all patients with IBD (n = 386) at our clinic for those diagnosed between 2006 and 2018. Results: The proportion of patients with IBD who were prescribed at least one prescription of corticosteroids in year 1–5 after diagnosis was 55.3%, 27.9%, 22.7%, 14.1%, and 14.6%, respectively. The proportion of patients who had a cumulative dose of prednisolone >1 g in the first 5 years after diagnosis was 40.1% for ulcerative colitis and 34.9% for Crohn's disease (CD). The cumulative prescribed dosage (within 3 years after diagnosis) of prednisolone had declined (rs = −0.164, p = 001), but had increased for budesonide (rs = 0.202, p < 0.001) between 2006 and 2020. The prescription of any immunomodulator for IBD in the first 5 years from diagnosis was stable between 2006 and 2018 (rs = 0.056, p = 0.257), but there was a minor increase in the prescription of Tumor Necrosis Factor (TNF)-inhibitors (rs = 0.119, p = 0.020). The use of five-acetyl salicylic acid (5-ASA) decreased in patients with CD (rs = −201, p = 0.012). Conclusion: There was a decrease in the prescription of prednisolone and an increase in the prescription of budesonide treatment from 2006 to 2023; however, the cumulative exposure to corticosteroids in patients with IBD remains at a relatively high level. Plain language summary: The use of steroids in patients with inflammatory bowel disease diagnosed between 2006 and 2020 In the 1950s, corticosteroids and immunomodulators were introduced, and in combination with improved surgery, the mortality rates dramatically decreased in patients with inflammatory bowel disease (IBD) Although corticosteroids are effective in the short term they have no proven efficacy in long-term therapy for IBD, and owing to the risk of side effects, their long-term use should be restricted. Based on the evolution of treatments and treatment strategies for IBD in the 2000s, we aimed to study to the extent to which corticosteroids have been used in the first five years after diagnosis for patients with IBD diagnosed at our clinic between 2006 and 2020. To what extent is prednisolone prescribed in the first five years after diagnosis? Has the pattern of corticosteroid prescription changed after the introduction of advanced therapy and biosimilars to TNF inhibitors? We found that the proportion of patients with IBD who were prescribed at least one prescription of corticosteroids in year one to five after diagnosis was 55.3%, 27.9%, 22.7%, 14.1%, and 14.6%, respectively. The proportion of patients who had a cumulative dose of prednisolone >1g in the first five years after diagnosis was 40.1% for ulcerative colitis (UC) and 34.9% for Crohns disease (CD). The cumulative prescribed dosage (within 3 years after diagnosis) of prednisolone had declined but increased for budesonide between 2006-2020. The prescription of any immunomodulator for IBD in the first five years from diagnosis was stable between the years 2006-2018, but there was a minor increase in the prescription of TNF-inhibitors. The use of 5-ASA decreased in patients with CD. We conclude that there was a decrease in the prescription of prednisolone and an increase in the prescription of budesonide treatment from 2006 to 2023; however, the cumulative exposure to corticosteroids in patients with IBD remains on relatively high level. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionsPatients with Crohn’s disease (CD) and subsequent ocular manifestations may have worse outcomes when compared to matched patients with CD without ocular disease.In this retrospective cohort study, an aggregated electronic health records research network, TriNetX (Cambridge, MA, USA), was used to identify patients diagnosed with CD stratified by the presence or absence of ocular involvement with at least 1 year of follow-up. Propensity score matching (PSM) was performed to control for baseline demographics and medical comorbidities.Patients with CD with ocular disease showed a greater risk of undergoing bowel resections (RR: 2.06, 95% CI: 1.48–2.85, p < 0.001), developing other CD-related gastrointestinal complications (RR: 1.31, CI: 1.15–1.49, p < 0.001), or acquiring Clostridioides difficile infections (RR: 2.19, CI: 1.89–2.54, p < 0.001). Further, patients with CD with ocular sequelae had a greater risk of developing NASH (RR: 1.43, CI: 1.31–1.56, p < 0.001), CD-related nutrient deficiencies (RR: 1.38, CI: 1.29–1.49, p < 0.001), iron deficiency anemia (RR: 1.41, CI: 1.33–1.50, p < 0.001), CD-related dermatological disease (RR: 1.84, CI: 1.65–2.05, p < 0.001), osteoporosis (RR: 1.49, CI: 1.37–1.64, p < 0.001) and primary sclerosing cholangitis (RR: 1.63, CI: 1.11–2.38, p = 0.011). Among patients with CD with ocular involvement, there was an elevated risk of MI (RR: 1.36, CI: 1.14–1.63, p < 0.001), stroke (RR: 1.42, CI: 1.18–1.70, p < 0.001), VTE (RR: 1.37, CI: 1.22–1.54, p < 0.001), and sepsis (RR: 1.53, CI: 1.37–1.71, p < 0.001).Patients who have CD and subsequent ocular involvement have an increased risk of local intestinal complications, extraintestinal morbidity, and cardiovascular complications when compared to patients with CD without ocular involvement. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD), comprised of Crohn's disease (CD) and ulcerative colitis (UC), are gut inflammatory diseases that were earlier prevalent in the Western Hemisphere but now are on the rise in the East, with India standing second highest in the incidence rate in the world. Inflammation in IBD is a cause of dysregulated immune response, wherein helper T (Th) cell subsets and their cytokines play a major role in the pathogenesis of IBD. In addition, gut microbiota, environmental factors such as dietary factors and host genetics influence the outcome and severity of IBD. Dysregulation between effector and regulatory T cells drives gut inflammation, as effector T cells like Th1, Th17 and Th9 subsets Th cell lineages were found to be increased in IBD patients. In this review, we attempted to discuss the role of different Th cell subsets together with other T cells like CD8+ T cells, NKT and γδT cells in the outcome of gut inflammation in IBD. We also highlighted the potential therapeutic candidates for IBD. [ABSTRACT FROM AUTHOR]

Background: Vitamin D, through the activation of its receptor (VDR), plays an immunomodulatory role in the gastrointestinal tract. Single-nucleotide polymorphisms (SNPs) in the VDR gene have been associated with Crohn's disease (CD) risk, and patients carrying the TaqI polymorphism in this gene run a higher risk of developing a penetrating behavior. Aims: We analyzed the association of BsmI, ApaI, TaqI, and FokI SNPs in the VDR gene with the clinical characteristics of CD. Methods: Four polymorphisms identified in the VDR gene (BsmI, FokI, ApaI, and TaqI) were genotyped in blood samples from CD patients (n = 115) by using PCR-RFLP. The disease's location and behavior and the presence of perianal fistulas were collected from each patient. Intestinal fibroblasts from ileal resections of CD patients (n = 10) were genotyped, and the expression of fibrotic and inflammatory markers was analyzed by RT-PCR. Results: The data reveal no association between any of the polymorphisms and CD risk. A strong linkage disequilibrium was detected between TaqI and both ApaI and BsmI, which in turn were strongly associated. Homozygosis or heterozygosis for the a allele of the ApaI SNP or b allele of the BsmI SNP was significantly associated with a lower risk of a penetrating behavior, while the aa genotype was associated with a lower risk of perianal fistulas. Fibroblasts carrying the aa genotype expressed lower levels of fibrotic and inflammatory markers. Conclusion: The aa genotype of the ApaI SNP in the VDR gene is associated with a lower risk of perianal fistulas in CD and a reduced expression of fibrotic and inflammatory markers in intestinal fibroblasts. [ABSTRACT FROM AUTHOR]

Loss-of-function mutations in nucleotide-binding oligomerization domain 2 (NOD2) constitute the primary risk factors for Crohn's disease. NOD2 is an intracellular sensor for muramyl dipeptide (MDP), a small molecule derived from the peptidoglycan layer of bacterial cell wall. Although NOD2 is involved in host immune responses, much attention has been paid to the involvement of NOD2 in the maintenance of intestinal homeostasis. Despite the fact that the proinflammatory cytokine and chemokine responses induced by NOD2 activation alone are weaker than those induced by toll-like receptors (TLRs), NOD2 plays a crucial role in host defense against invading pathogens and in the regulation of immune responses. Recent studies have highlighted the importance of negative regulatory functions of NOD2 in TLRs-mediated proinflammatory cytokine responses. MDP-mediated activation of NOD2 induces interferon regulatory factor 4 (IRF4) expression, thereby suppressing nuclear factor-kB-dependent colitogenic cytokine responses through the inhibition of Lys(K)63-linked polyubiquitination on receptor-interacting serine/threonine protein kinase 2. MDP-mediated activation of NOD2 also downregulates TLR9-induced type I IFN responses by inhibiting the K63-linked polyubiquitination of TNF receptor-associated factor 3 via deubiquitinating enzyme A (DUBA) expression. Thus, NOD2 exerts dual negative regulation of TLRs-mediated proinflammatory cytokine and type I IFN responses by inducing the expression of IRF4 and DUBA, respectively. In this review, we summarize the molecular mechanisms whereby NOD2 activation suppresses TLRs-mediated proinflammatory and type I IFN responses. In addition, we discuss the clinical relevance of the NOD2-mediated negative regulation of TLRs in inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Background: Acute pancreatitis (AP) is an extraintestinal manifestation of inflammatory bowel disease (IBD). Numerous observational studies have reported an increased risk of AP in patients diagnosed with IBD. However, the causal association and directionality between IBD or its subtypes and the development of AP remains unclear due to the limitations of observational research. This study aims to explore the relationship between IBD or its subtypes and AP risk using Mendelian Randomization (MR) method. Methods: A two-sample bidirectional MR study was conducted, selecting genetic variants associated with IBD and AP as instrumental variables from the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC) and FinnGen databases, respectively. The inverse-variance weighted (IVW) method used as the primary approach for causal inference. The Cochran Q test was employed for heterogeneity assessment. Sensitivity analyses were performed using the MR Egger intercept test, MR-Presso, and Leave-one-out method. Results: The results revealed that IBD (OR = 1.049, 95% CI = 1.010-1.090, p = 0.013) and ulcerative colitis (UC) (OR = 1.057, 95% CI = 1.013-1.102, p = 0.011) were significantly associated with an increased risk of AP. However, Crohn's disease (CD) (OR = 1.023, 95% CI = 0.993-1.055, p = 0.134) did not show a causal association with the risk of AP. Interestingly, AP was suggestively associated with a decreased risk of CD (OR = 0.797, 95% CI = 0.637-0.997, p = 0.047). Furthermore, there was no causal association between AP and the risk of IBD (OR = 0.886, 95% CI = 0.753-1.042, p = 0.144) or UC (OR = 0.947, 95% CI = 0.773-1.159, p = 0.595). Conclusion: In conclusion, this study provides genetic evidence supporting the causal influence of IBD (specifically UC) on AP, while CD does not appear to have a causal impact on AP. [ABSTRACT FROM AUTHOR]

Intestinal fibrosis is the primary cause of disability in patients with Crohn's disease (CD), yet effective therapeutic strategies are currently lacking. Here, we report a multiomics analysis of gut microbiota and fecal/blood metabolites of 278 CD patients and 28 healthy controls, identifying characteristic alterations in gut microbiota (e.g., Lachnospiraceae, Ruminococcaceae, Muribaculaceae, Saccharimonadales) and metabolites (e.g., L-aspartic acid, glutamine, ethylmethylacetic acid) in moderate-severe intestinal fibrosis. By integrating multiomics data with magnetic resonance enterography features, putative links between microbial metabolites and intestinal fibrosis-associated morphological alterations were established. These potential associations were mediated by specific combinations of amino acids (e.g., L-aspartic acid), primary bile acids, and glutamine. Finally, we provided causal evidence that L-aspartic acid aggravated intestinal fibrosis both in vitro and in vivo. Overall, we offer a biologically plausible explanation for the hypothesis that gut microbiota and its metabolites promote intestinal fibrosis in CD while also identifying potential targets for therapeutic trials. Synopsis: The gut microbiota and its functional metabolites play crucial roles in the development of intestinal fibrosis in patients with Crohn's disease (CD). The severity of intestinal fibrosis was associated with alterations in the gut microbiota (e.g., Lachnospiraceae) and the fecal and blood metabolites (e.g., L-aspartic acid). Specific microbes and their metabolites were associated with fibrosis-related luminal and extraluminal morphological alterations (i.e., stricture, penetration, effusion and comb sign). L-aspartic acid, identified as a potential target, promoted the progression of intestinal fibrosis in vitro and in vivo. A machine learning-based classifier had been developed based on the combination of 11 microbial and metabolic predictors for distinguishing the severity of intestinal fibrosis in patients with CD. The gut microbiota and its functional metabolites play crucial roles in the development of intestinal fibrosis in patients with Crohn's disease (CD). [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the molecular links and mechanisms between Crohn's disease (CD) and colorectal cancer (CRC). Methods: This study used the Gene Expression Omnibus (GEO) database to identify Differentially expressed genes (DEGs) in CD (GSE112366) and CRC (GSE110224), analyzed by 'edgeR' and 'limma'. The Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes explored DEG functions, and the Search Tool for the Retrieval of Interacting Genes (STRING) informed the protein–protein interaction network construction visualized in Cytoscape (version 3.7.2). Cyto-Hubba identified key genes, whose biomarker potential for CD and CRC was evaluated. Results: The study discovered 61 DEGs, with 44 up- and 17 down-regulated, linked to immune responses and signaling pathways. CXCL1, highly expressed in colon cancer, correlated with better prognosis and lower staging. It also showed associations with immune infiltration and checkpoint molecules, suggesting a role in cancer progression and retreat. Conclusion: CXCL1 may play a role in the development of colorectal cancer from inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Fecal samples were collected from 640 individuals in Korea, including 523 patients with IBD (223 with Crohn's disease [CD] and 300 with ulcerative colitis [UC]) and 117 healthy controls. The samples were subjected to cross-sectional gut metagenomic analysis using 16 S rRNA sequencing and bioinformatics analysis. Patients with IBD, particularly those with CD, exhibited significantly lower alpha diversities than the healthy subjects. Differential abundance analysis revealed dysbiotic signatures, characterized by an expansion of the genus Escherichia-Shigella in patients with CD. Functional annotations showed that functional pathways related to bacterial pathogenesis and production of hydrogen sulfide (H2S) were strongly upregulated in patients with CD. A dysbiosis score, calculated based on functional characteristics, highly correlated with disease severity. Markers distinguishing between healthy subjects and patients with IBD showed accurate classification based on a small number of microbial taxa, which may be used to diagnose ambiguous cases. These findings confirm the taxonomic and functional dysbiosis of the gut microbiota in patients with IBD, especially those with CD. Taxa indicative of dysbiosis may have significant implications for future clinical research on the management and diagnosis of IBD. [ABSTRACT FROM AUTHOR]

Background: Crohn's disease (CD) is a chronic inflammatory condition primarily affecting the digestive system. When dealing with complex cases like intestinal blockages or perforations, surgery becomes the primary treatment option. However, surgery doesn't offer a complete cure, and the possibility of recurrence remains. To manage CD recurrence after surgery, various treatment choices are available, including steroids, monoclonal antibodies, immunomodulators, and further surgery. Regrettably, the current body of evidence doesn't definitively establish which of these treatments is the most effective and safe. Thus, our research aims to provide insights into the Validity and security of different treatment approaches for managing CD recurrence after surgery. Methods: Search of EMBASE, PubMed, Web of Science Core Collection and the Cochrane Central Register of Controlled Trials will be conducted to include researches that examine the validity of treatments for recurrent CD after surgery. Our analysis will distinguish between two types of studies: randomized controlled trials (RCTs) and non-randomized studies with at least two different treatments, each evaluated separately. We will employ Bayesian network meta-analyses to systematically compare the effectiveness and safety of these treatments. Additionally, subgroup analyses will be performed according to recurrence status and postoperative prophylactic medication. To clarify the variation of studies, sensitivity analyses will be performed. And we may use meta-regression as an additional approach if relevant data are available. We will also rigorously access the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Discussion: This analysis will provide a comprehensive assessment of the latest evidence on available treatments for patients with postoperative recurrence of CD, which will provide recommendations for clinical practice. Trial registration: Systematic review registration INPLASY2023110021. (DOI: 10.37766/inplasy2023.11.0021). [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusions Given the introduction of new advanced therapies for inflammatory bowel diseases (IBDs), expanded risk mitigation strategies are essential.To create a comprehensive set of statements on assessment procedures and vaccinations before starting monoclonal antibodies, Janus kinase (JAK) inhibitors or sphingosine‐1‐phosphate (S1P) modulators for IBD.We examined literature, guidelines and drug product information regarding vaccination and assessment recommendations for initiating advanced IBD therapies. Using a modified Delphi approach, delegates voted anonymously on the acceptability of these statements prior to and following consensus discussion.We developed eight statements on the domains of infectious diseases screening, vaccinations and assessments prior to commencing JAK inhibitors and S1P modulators. Six statements received agreement. Pre‐advanced therapy screening for infectious diseases was established, and the vaccination protocol was revised. Malignancy, cardiovascular and thromboembolic risk assessments are necessary before initiating JAK inhibitors. Those starting S1P modulators need cardiac and ophthalmic assessments.These consensus statements combine vaccination and assessments on the currently available advanced therapies for IBD as a single comprehensive document that may reduce IBD complications associated with use of advanced therapies. Knowledge gaps identified during the consensus process will provide further research opportunities. [ABSTRACT FROM AUTHOR]

Background: Delayed diagnosis of inflammatory bowel disease (IBD) is common, there is still no effective imaging system to distinguish Crohn's Disease (CD) and Ulcerative Colitis (UC) patients. Methods: This multicenter retrospective study included IBD patients at three centers between January 2012 and May 2022. The intestinal and perianal imaging signs were evaluated. Visceral fat information from CT images was extracted, including the ratio of visceral to subcutaneous fat volume (VSR), fat distribution, and attenuation values. The valuable indicators were screened out in the derivation cohort by binary logistic regression and receiver working curve (ROC) analysis to construct an imaging report and data system for IBD (IBD-RADS), which was tested in the validation cohort. Results: The derivation cohort included 606 patients (365 CD, 241 UC), and the validation cohort included 155 patients (97 CD, 58 UC). Asymmetric enhancement (AE) (OR = 87.75 [28.69, 268.4]; P < 0.001), perianal fistula (OR = 4.968 [1.807, 13.66]; P = 0.002) and VSR (OR = 1.571 [1.087, 2.280]; P = 0.04) were independent predictors of CD. VSR improved the efficiency of imaging signs (AUC: 0.929 vs. 0.901; P < 0.001), with a threshold greater than 0.97 defined as visceral fat predominance (VFP). In IBD-RADS, AE was the major criterion, VFP and perianal fistula were auxiliary criteria, and intestinal fistula, limited small bowel disease, and skip distribution were special favoring items as their 100% specificity. Grade 3 to 5 correctly classified most CD patients (derivation: 96.5% (352/365), validation: 98.0% (95/97)), and 98% of those were eventually diagnosed with CD (derivation: 97.8% (352/360), validation: 98.0% (95/97)). Conclusions: IBD-RADS can help radiologists distinguish between CD and UC in patients with suspected IBD. [ABSTRACT FROM AUTHOR]

The aim was to evaluate predictors of clinical outcomes in infliximab (IFX)-treated Crohn's disease (CD) patients in western China and provide evidence for future treatment optimization. Our retrospective study included CD patients at Chongqing General Hospital from July 2022 to July 2023. Clinical data of CD patients at baseline and the endpoint (the seventh IFX treatment, 38 weeks) were collected. Baseline variables of IFX-treated patients with regard to clinical remission [Crohn's Disease Activity Index (CDAI) < 150] at endpoint were assessed, and the correlation of serum vitamin D (Vit-D) levels before initiating IFX therapy and CDAI at week 38 was analyzed. Sixty patients with IFX-treated CD were included. The Vit-D-deficient rate was 51.7% at baseline, 81.7% of patients achieved clinical remission, and 66.7% achieved endoscopic remission at week 38 of IFX treatment. Vit-D level at baseline was an independent predictors of clinical remission after IFX treatment (P < 0.05). Receiver operating characteristic curve analysis showed that when Vit-D concentration was 15.81 ng/ml, the area under the curve was 0.711 (95% CI 0.523–0.899, P = 0.03). The sensitivity and specificity were 81.6% and 63.6%, respectively. Vit-D level in the normal BMI, non-smoking, immunosuppressant-treated subgroup had independent predictive value for CDAI at endpoint (P < 0.05). Baseline Vit-D level predicted clinical remission in CD patients after IFX treatment, especially in those with normal body mass index, who do not smoke, and who take IFX in combination with immunosuppressants. [ABSTRACT FROM AUTHOR]

Background: The relationship with the treating gastroenterologist has been shown to significantly influence the quality of life of patients with IBD (Inflammatory Bowel Disease). Still, the expectations of patients have not been studied in detail. This study aimed to explore the messages and recommendations of IBD patients towards their gastroenterologists who treat them. Methods: This qualitative study was conducted using the DIPEx method developed by the Health Experiences Research Group at Oxford University. Semi-structured interviews with 36 participants (19 with Crohn's disease and 17 with ulcerative colitis) were analysed using thematic analysis. Results: Three main areas emerged as relevant for patients: doctors' expertise, patient-physician relationships, and the organisation of the healthcare system. Participants underscored the importance of comprehensive information, symptom recognition, exceptional care, and addressing outcome disparities by their treating physicians. Patient-centeredness, including dignified treatment, collaborative management of embarrassment, and trust, was mentioned as crucial for a good patient-physician relationship. The patients stressed the importance of sufficient time for care and the incorporation of mental health interventions. They emphasised professionalism, expertise, and friendly rapport as crucial for building trust in treating the unpredictable nature of IBD. The study also highlights the systemic impact of these interactions on healthcare systems. Conclusions: Patients actively engaged in their treatment bring novel perspectives, underscoring the value of a collaborative, respectful, and patient-physician dynamic. The implementation of this approach requires systemic healthcare shifts. This qualitative study on patient expectations underscores factors for a robust patient-physician bond, including gastroenterologists' expertise, personalised care, and adequate time provision. [ABSTRACT FROM AUTHOR]

Summary: Background: Risankizumab is efficacious and well tolerated in adults with moderately to severely active Crohn's disease (CD). Aim: To evaluate the corticosteroid‐sparing effect of risankizumab in CD. Methods: During the 12‐week induction period, patients maintained stable baseline corticosteroid doses, up to 20 mg/day prednisone or equivalent. At week 0 of maintenance, a mandatory corticosteroid taper was started. This post hoc analysis evaluated corticosteroid‐free clinical and endoscopic outcomes at week 52 of maintenance; safety was also assessed. Results: Of 889 patients randomised to induction with risankizumab 600 mg or placebo, 285 (32.1%) were taking baseline concomitant corticosteroids. Week 12 clinical remission and endoscopic response rates were greater for risankizumab 600 mg versus placebo, regardless of concomitant corticosteroid use. At week 52, 66.7%, 50.0% and 41.2% of patients taking risankizumab 180 mg, risankizumab 360 mg and (withdrawal) placebo, respectively, discontinued corticosteroids. Week 52 corticosteroid‐free clinical remission per stool frequency/abdominal pain score (risankizumab 180 mg [42.7%] or 360 mg [49.8%]; [withdrawal] placebo [39.0%]), corticosteroid‐free clinical remission per Crohn's Disease Activity Index (risankizumab 180 mg [51.0%] or 360 mg [49.5%]; [withdrawal] placebo [40.2%]), and corticosteroid‐free endoscopic response (risankizumab 180 mg [44.6%] or 360 mg [44.7%]; [withdrawal] placebo [20.7%]) rates were greater for risankizumab than placebo. Adverse event rates were generally similar, regardless of baseline corticosteroid use. Conclusions: Efficacy of risankizumab 600 mg induction therapy was independent of concomitant corticosteroid use. Risankizumab 180 and 360 mg maintenance therapy yielded high rates of corticosteroid‐free clinical and endoscopic outcomes at week 52. [ABSTRACT FROM AUTHOR]

Summary: Background: Although dietary emulsifiers are implicated in the pathogenesis of Crohn's disease, their effect has not been studied in humans. Aim: To determine the effects of high‐ and low‐emulsifier diets (HED, LED) on intestinal barrier function in healthy subjects in unstressed and acutely stressed states. Methods: We conducted a single‐blinded, cross‐over, controlled feeding trial in 22 healthy adults. After recording 7 days of their habitual diet, we randomised participants to HED or LED with ≥3‐week washout between diets. On dietary completion, acute stress was induced via intravenous corticotrophin‐releasing hormone. We assessed dietary adherence, effects on 2‐h urinary lactulose: rhamnose ratio (LRR), serum concentrations of lipopolysaccharide‐binding protein, soluble‐CD14 and markers of epithelial injury and inflammation. Results: Dietary adherence was excellent. In an unstressed state, median (interquartile range) LRR during HED was 0.030 (0.018–0.042); on LED, this was 0.042 (0.029–0.078; p = 0.04). LPB concentrations were lower on HED than LED (p = 0.026), but no differences were observed for epithelial injury or inflammation. Under acute stress, LRR increased by 89% (−1% to 486%) on HED (p = 0.004), differing (p = 0.001) from 39% (1%–90%) decrease on LED (p = 0.009). Soluble‐CD14 also increased (p < 0.001). The LED had a prolonged carry‐over effect on suppressing HED‐induced changes during stress. Similar changes in LRR and soluble‐CD14 were observed when HED was used as the first diet (both p < 0.01). Conclusion: High intake of emulsifiers improved barrier function in the unstressed state, but increased intestinal permeability to stress, without evidence of inflammation. A LED was protective of the stress effect. [ABSTRACT FROM AUTHOR]

Objective and Rationale: Inflammatory bowel disease, including Crohn's disease and ulcerative colitis, manifests with chronic intestinal inflammation and frequent sequential fibrosis. Current pharmacological therapies may show harmful side effects and are not useful for prevention or resolution of fibrosis. Thus, the use of alternative therapies is emerging as a novel useful approach. Previous results suggest that Scutellaria baicalensis Georgi (SBG) and Boswellia serrata (BS) display anti‐inflammatory properties. The aim of this study was to investigate in intestinal epithelial cells and fibroblasts the anti‐inflammatory and anti‐fibrotic potential of SBG and BS, alone or in combination. Methods: Human colorectal adenocarcinoma cells (HT29), human intestinal epithelial cells (HIEC6) and human colon fibroblasts (CCD‐18Co) were used. Cells were pretreated with SBG and BS and then exposed to pro‐inflammatory and pro‐fibrotic cytokines. Results: SBG and BS extracts significantly decreased pro‐inflammatory cytokine expression and improved epithelial restitution in HT29 and HIEC6 cells. Besides, fibrotic marker expression, including SNAIL, ACTA2, ZNF281, was strongly reduced. Colon myofibroblasts treated with SBG and BS showed a significant decrease of fibrotic markers as well. Conclusions: SBG and BS extracts significantly reduce inflammation and impair fibrosis in intestinal epithelial cells and colon myofibroblasts. No cooperative effect is observed. [ABSTRACT FROM AUTHOR]

Gastrectomy, a prevalent surgical procedure for gastric cancer, results in substantial alterations to the gastrointestinal tract, including reduced gastric acid production and significant modifications to the gut microbiota. These changes can impair postoperative recovery, influence metabolic functions, and predispose patients to inflammatory bowel disease (IBD). Studies have shown an increased risk of IBD, particularly Crohn's disease (CD) and ulcerative colitis (UC), in patients following gastrectomy and bariatric surgeries such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). For instance, patients undergoing RYGB have a higher hazard ratio for developing CD, while SG patients show an increased risk for UC. The surgical alteration of the gastrointestinal tract promotes dysbiosis, with a significant increase in pathogenic bacteria and a decrease in beneficial microbial populations. This dysbiosis can impair the intestinal mucosal barrier and promote systemic inflammation. Understanding the mechanisms behind these changes and their clinical implications is essential for developing effective postoperative management strategies. Probiotics and enhanced recovery after surgery (ERAS) protocols have shown promise in mitigating these adverse effects, improving gut microbiota balance, and enhancing patient outcomes. Further research is necessary to fully elucidate the long-term impacts of gastrectomy on gastrointestinal health and to refine therapeutic approaches for postoperative care. [ABSTRACT FROM AUTHOR]

Serotonin (5-hydroxytryptamine: 5-HT), a neurotransmitter that regulates mood in the brain and signaling in the gut, has receptors throughout the body that serve various functions, especially in the gut and brain. Selective serotonin reuptake inhibitors (SSRIs) are used to treat depression, but their efficacy is uncertain. Depression is often associated with early gastrointestinal symptoms. Gut disorders such as functional dyspepsia (FD), irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are linked to elevated serotonin levels. In this review, we would like to discuss the approach of using serotonin as a biomarker for gut–brain, and body-wide organ communication may lead to the development of preventive and innovative treatments for gut–brain disorders, offering improved visibility and therapeutic monitoring. It could also be used to gauge stress intensity for self-care and mental health improvement. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) is characterized by persistent inflammation and is often associated with metabolic dysfunction-associated steatotic liver disease (MASLD). IBD patients are at risk of developing MASLD due to shared risk factors such as gut dysbiosis and systemic inflammation. The new MASLD nomenclature emphasizes the link between liver steatosis and cardiometabolic comorbidities. However, the prevalence of MASLD in IBD patients remains poorly explored. The main aim of this cross-sectional study is to assess the prevalence of ultrasound (US) and the clinical features of MASLD in patients with IBDs. Materials and Methods: We conducted a retrospective study enrolling 272 Italian IBD patients attending Renato Dulbecco Teaching Hospital in a period between 1 January 2021 and 31 December 2023. MASLD was diagnosed based on the presence of liver steatosis with cardiometabolic risk factors, using established guidelines. Demographic, clinical, and laboratory data were collected and analyzed. Statistical significance was determined at a p-value < 0.05. Results: Of the 272 IBD patients, 6% had non-alcoholic fatty liver disease (NAFLD), while 18% had MASLD. Patients with IBD-MASLD were significantly older, had higher body mass index, waist circumference, and triglyceride levels, and were more likely to have type 2 diabetes mellitus and hypertension compared to those with IBD-NAFLD. IBD-MASLD patients also showed higher disease activity scores and required more frequent surgical interventions. Bivariate logistic regression revealed triglyceride levels as a significant predictor of MASLD in IBD patients. Conclusions: MASLD is more prevalent in IBD patients, highlighting the importance of early detection of liver steatosis in this at-risk population. The association between MASLD and cardiometabolic risk factors underscores the need for a multidisciplinary approach to manage these patients effectively. Further studies in larger cohorts are necessary to confirm these findings and explore the pathophysiological mechanisms involved. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) includes patients affected by Crohn's disease or ulcerative colitis. IBD is thought to be a chronic immune-mediated disease, but its origin remains elusive, and this limits new therapeutic approaches. Human endogenous retroviruses (HERVs) originate from ancestral infections and represent 8% of the human genome. HERVs are no longer infectious, but some retroviral sequences can be activated, and their aberrant expressions have been implicated in inflammatory and autoimmune disorders. HERV transcription is regulated by TRIM28 and SETDB1, which are also directly involved in epigenetic processes and modulation of the immune response. Using a PCR real-time Taqman amplification assay, we assessed, for the first time, the transcription levels of pol genes of HERV-H, -K, and -W families of env genes of syncytin 1 (SYN1), SYN2, and HERV-W, as well as of TRIM28 and SETDB1 in the whole blood of 48 patients with Crohn's disease (CD), 20 with ulcerative colitis (UC), and in healthy controls (HC) of comparable age. The transcriptional levels of HERV-H-pol (p = 0.0003) and HERV-K-pol (p = 0.001) were significantly higher in IBD patients compared with HC, with no differences between patients with CD and UC. No significant differences were found for the remaining HERVs between IBD patients and HC. The transcript levels of TRIM28 were significantly downregulated in IBD patients (p < 0.001), without differences between CD and UC, while the SETDB1 levels were preserved. The enhanced transcription of HERV-H-pol and HERV-K-pol, as well as the impaired activation of TRIM28, were not influenced by clinical disease activity and type of treatment. The overexpression of HERVs and impaired transcription of TRIM28 in patients affected by CD or UC suggest that they might be the main actors in the pathophysiology of IBD, opening the way to innovative targeted interventions. [ABSTRACT FROM AUTHOR]

The article discusses the history, clinical characteristics, diagnosis, genetic factors, pathophysiology, treatment, and prognosis of Adamantiades‐Behcet's disease (ABD), a chronic inflammatory disorder. ABD primarily affects the Eastern Mediterranean area and Central and East Asia, with a suspected autoimmune etiology. Diagnosis is based on clinical presentation, and treatment varies depending on the severity and organs involved. Biologic agents are increasingly used in managing severe and refractory cases of ABD. The article emphasizes the importance of multidisciplinary care and reference centers for optimal management of ABD. [Extracted from the article]

Background: The pathogenesis of Crohn's disease involves genetic and environmental factors, with the gut microbiome playing a crucial role. The Crohn's 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. [ABSTRACT FROM AUTHOR]

Background and Aims: Upadacitinib is an oral selective Janus kinase (JAK) inhibitor approved in the United States for ulcerative colitis (UC) and Crohn's disease (CD). However, data regarding its use following prior treatment with the JAK inhibitor tofacitinib is sparse. As such, we aimed to evaluate the effectiveness of upadacitinib therapy following tofacitinib exposure. Methods: This is a multicenter retrospective study of patients with confirmed diagnosis of UC or CD who received upadacitinib after prior treatment with tofacitinib. The primary outcome of interest was patient-reported clinical improvement at first follow-up. Secondary outcome included discontinuation of corticosteroids, change in Mayo Endoscopic Score (MES) and change in inflammatory marker levels. Results: A total of 31 patients met the inclusion criteria. Following upadacitinib initiation, 80.6% (25/31) of patients had clinical improvement, including 92.3% (24/26) of those with UC and 20% (1/5) of those with CD. Of the patients initially requiring systemic corticosteroid therapy, 80% (12/15) were able to discontinue corticosteroids. Individual mean change of fecal calprotectin was a decrease of 501.5 mcg/g ± 608.6 (P value = 0.01) while C-reactive protein decreased on average by 14.8 mg/L ± 25.3 (P value = 0.02) compared to when patients were on tofacitinib, with significant changes observed in the UC cohort. In patients with UC, individual MES after initiating upadacitinib decreased compared to prior to tofacitinib discontinuation (P value = 0.04). Conclusion: Our study demonstrates that upadacitinib therapy in patients with prior tofacitinib exposure is associated with clinical improvement and a decrease in objective markers of inflammation in patients with UC. [ABSTRACT FROM AUTHOR]

Background: Inflammatory Bowel Disease (IBD) is an early onset condition that affects individuals of all ages. Approximately 15%–25% of patients present before the age of 20 years, with peak onset occurring during adolescence. Aims: To evaluate transition readiness among adolescents diagnosed with IBD and identify barriers to transition. Methods: We conducted a cross-sectional study of patients with IBD aged 12–21 years. Patients were stratified by age into three groups: A (12–14 years), B (14–17 years), and C (17 + years). Patients were asked to complete a questionnaire which assessed patient knowledge in three areas of transition: 'Taking Charge,' 'My Health,' and 'Using Health Care.' Fisher's Exact and Chi-Square tests were used to evaluate the associations between age and transition readiness. Results: A total of 127 participants (68 males and 59 females) with a mean age of 16.14 years were included. Transition readiness increased with age from 60.7% in Group A to 63.2% and 77.9% in Groups B and C, respectively (p < 0.001). Patient confidence and the importance of transition increased with age, with means of 5.51, 6.17, and 6.94 in Groups A, B, and C (p = 0.02). Patient-reported knowledge of their health condition was > 70%, with no statistical differences between the groups (p = 0.65). Patient knowledge regarding 'Using Health Care' increased from 52% in Group A to 79% in Group C (p < 0.001). The greatest barriers to transitioning were carrying health information for Group A (100%) and obtaining provider referrals for Groups B (75%) and C (51%). Conclusion: This study demonstrated that transition readiness increases with age in adolescents with IBD. [ABSTRACT FROM AUTHOR]