Potential interventions and interactions of bioactive polyphenols and functional polysaccharides to alleviate inflammatory bowel disease - A review.

Inflammatory bowel disease is a multifaceted condition that is influenced by nutritional, microbial, environmental, genetic, psychological, and immunological factors. Polyphenols and polysaccharides have gained recognition for their therapeutic potential. This review emphasizes the biological effects of polyphenols and polysaccharides, and explores their antioxidant, anti-inflammatory, and microbiome-modulating properties in the management of inflammatory bowel disease (IBD). However, polyphenols encounter challenges, such as low stability and low bioavailability in the colon during IBD treatment. Hence, polysaccharide-based encapsulation is a promising solution to achieve targeted delivery, improved bioavailability, reduced toxicity, and enhanced stability. This review also discusses the significance of covalent and non-covalent interactions, and simple and complex encapsulation between polyphenols and polysaccharides. The administration of these compounds in appropriate quantities has proven beneficial in preventing the development of Crohn's disease and ulcerative colitis, ultimately leading to the management of IBD. The use of polyphenols and polysaccharides has been found to reduce histological scores and colon injury associated with IBD, increase the abundance of beneficial microbes, inhibit the development of colitis-associated cancer, promote the production of microbial end-products, such as short-chain fatty acids (SCFAs), and improve anti-inflammatory properties. Despite the combined effects of polyphenols and polysaccharides observed in both in vitro and in vivo studies, further human clinical trials are needed to comprehend their effectiveness on inflammatory bowel disease.

Colitis in a patient with familial Mediterranean fever: Is it Crohn's disease or ulcerative colitis?

A 24-year-old woman was referred to our hospital with joint pain, fever, abdominal pain, and diarrhea. A colonoscopy revealed longitudinal ulcers with a cobblestone appearance throughout the entire colon, suggestive of Crohn's disease. However, treatment with 5-aminosalicylic acid, azathioprine, and infliximab failed to achieve clinical remission. A colonoscopy 5 months later revealed a diffusely spreading granular mucosa without visible vasculature, compatible with active ulcerative colitis. Based on these serial changes in colonic lesions, we tested the patient for MEFV gene mutations and found variants E148Q and L110P in exon 2. Administration of colchicine resulted in complete clinical remission. Our experience suggests that drastic changes in the features of colonic inflammation may be a clue to the diagnosis of enterocolitis associated with familial Mediterranean fever.

Risk Factors for Recurrence of Crohn's Disease After Ileocecal Resection and Management Strategies.

INTRODUCTION: Pediatric patients with ileocecal Crohn's Disease (CD) refractory to medical management frequently require ileocecectomy. However, risk factors for post-operative ileocecal recurrence and appropriate management strategies are poorly defined in the pediatric literature in the biologic era. METHODS: We queried our institutional database from 1/1/2012-12/31/2022 for patients aged 1-21 who underwent primary ileocecectomy for CD. We analyzed baseline characteristics, operative details, medical management, recurrence patterns, and management patterns. RESULTS: We identified 208 patients who underwent primary ileocecal resection, of which 66 (23%) demonstrated endoscopic recurrence at 2.1 ± 0.5 years and 28 (13%) developed clinical recurrence at 2.5 ± 0.8 years. Recurrence was at the surgical anastomosis in 43 (21%). Before surgery, 138 (66%) were treated with a biologic, of which 25 (18%) were transitioned to a second line biologic pre-operatively. Requiring a separate intervention for perianal or intestinal disease increased the odds of recurrence on multivariable analysis, as did requiring a second line biologic. Of those with endoscopic recurrence, most [62/66 (94%)] were successfully managed with medical optimization alone. Only four (6.7%) required procedural intervention with two being managed with endoscopic balloon dilation and two requiring repeat resection and re-anastomosis. Median follow up was 2.6 years [IQR 1.2-4.5]. CONCLUSION: Requiring separate interventions for perianal or intestinal disease and demonstrating disease difficult to medically control may increase the risk of recurrent post-operative ileocecal CD. Such patients should be closely surveilled for endoscopic recurrence and may warrant more aggressive medical regimens. Recurrence can typically be managed medically with few patients requiring procedural intervention. LEVEL OF EVIDENCE: III.

Crohn's disease and ulcerative colitis share two molecular subtypes with different mechanisms and drug response.

BACKGROUND AND AIMS: Several therapies have been approved to treat crohn's disease (CD) and ulcerative colitis (UC), indicating that both diseases may share the same molecular subtypes. The aim of this study is to identify shared patient subtypes with common molecular drivers of disease. METHODS: Five public datasets with 406 CD and 421 UC samples were integrated to identify molecular subtypes. Then, the patient labels from six independent datasets and eight treatment datasets were predicted for validating subtypes and identifying the relationship with response status of corticosteroids, infliximab, vedolizumab, and ustekimumab. RESULTS: Two molecular subtypes were identified from the training datasets, in which CD and UC patients were relatively evenly represented in each subtype. We found six S1-specific gene modules related to innate/adaptive immune responses and tissue remodeling and nine S1-specific cell types (cycling T, Tregs, cd8+ lamina propria, follicular B, cycling B plasma, inflammatory monocytes, inflammatory fibroblast, and post-capillary venules). Subtype S2 was associated with three modules related to metabolism functions and four cell types (immature enterocytes, transit amplifying, immature goblet and WNT5B+). The subtypes can be replicated in six independent datasets based on a 20-gene classifier. Furthermore, response rates to four treatments in subtype S2 were significantly higher than those in subtype S1. CONCLUSIONS: This study discovered and validated a robust transcriptome-based molecular classification shared by CD and UC and built a 20-gene classifier. Because two subtypes have different molecular mechanisms and drug response, our classification may aid interpretation of heterogeneous molecular and clinical information in IBD patients.

Machine learning as a tool predicting short-term postoperative complications in Crohn's disease patients undergoing intestinal resection: What frontiers?

The recent study, "Predicting short-term major postoperative complications in intestinal resection for Crohn's disease: A machine learning-based study" investigated the predictive efficacy of a machine learning model for major postoperative complications within 30 days of surgery in Crohn's disease (CD) patients. Employing a random forest analysis and Shapley Additive Explanations, the study prioritizes factors such as preoperative nutritional status, operative time, and CD activity index. Despite the retrospective design's limitations, the model's robustness, with area under the curve values surpassing 0.8, highlights its clinical potential. The findings align with literature supporting preoperative nutritional therapy in inflammatory bowel diseases, emphasizing the importance of comprehensive assessment and optimization. While a significant advancement, further research is crucial for refining preoperative strategies in CD patients.

Prediction of Crohn's disease based on deep feature recognition.

BACKGROUND: Crohn's disease is a complex genetic disease that involves chronic gastrointestinal inflammation and results from a complex set of genetic, environmental, and immunological factors. By analyzing data from the human microbiome, genetic information can be used to predict Crohn's disease. Recent advances in deep learning have demonstrated its effectiveness in feature extraction and the use of deep learning to decode genetic information for disease prediction. METHODS: In this paper, we present a deep learning-based model that utilizes a sequential convolutional attention network (SCAN) for feature extraction, incorporates adaptive additive interval losses to enhance these features, and employs support vector machines (SVM) for classification. To address the challenge of unbalanced Crohn's disease samples, we propose a random noise one-hot encoding data augmentation method. RESULTS: Data augmentation with random noise accelerates training convergence, while SCAN-SVM effectively extracts features with adaptive additive interval loss enhancing differentiation. Our approach outperforms benchmark methods, achieving an average accuracy of 0.80 and a kappa value of 0.76, and we validate the effectiveness of feature enhancement. CONCLUSIONS: In summary, we use deep feature recognition to effectively analyze the potential information in genes, which has a good application potential for gene analysis and prediction of Crohn's disease.

Shared Pathophysiology of Inflammatory Bowel Disease and Psoriasis: Unraveling the Connection.

Psoriasis (PS) and inflammatory bowel disease (IBD) are immune-mediated chronic conditions that share pathophysiological processes, including immune system dysfunction, microbiome dysbiosis, and inflammatory pathways. These pathways result in increased turnover of epithelial cells and compromised barrier function. The assessment of the literature suggests that immunopathogenic mechanisms, such as tumor necrosis factor (TNF)-α signaling and IL-23/IL-17 axis dysregulation, are shared by PS and IBD. Clinical characteristics and diagnostic approaches overlap significantly, and advances in biomarker identification benefit both conditions. Current treatments, namely biologics that target TNF-α, IL-17, and IL-23, show promising results in decreasing inflammation and controlling symptoms. Precision medicine approaches are prioritized in prospective therapeutic procedures to tailor pharmaceuticals based on specific biomarkers, perhaps improving outcomes and minimizing side effects. This study thoroughly examines and evaluates the body of research on PS and IBD. Several papers were examined to compile data on clinical features, diagnosis, therapies, pathophysiology, epidemiology, and potential future therapeutic developments. The selection of articles was based on three methodological qualities: relevance and addition to the knowledge of IBD and PS. The retrieved data were combined to provide a coherent summary of the state of the knowledge and to spot new trends. The overview of the latest studies demonstrates that both PS and IBD share pathophysiological foundations and therapeutic approaches. With a spotlight on particular biomarkers, advances in precision medicine provide a promising path toward enhancing therapeutic effectiveness and minimizing side effects.

A complex case of PASH syndrome: pyoderma gangrenosum, acne, suppurative hidradenitis, and Crohn's disease in a 36-year-old smoker.

Introduction and importance: PASH syndrome, is autoinflammatory condition driven by immune system dysfunction, resulting in elevated interleukin 1 levels and subsequent production of proinflammatory cytokines and chemokines. The clinical progression of PASH typically starts with acne conglobate in adolescence, followed by hidradenitis suppurativa, and pyoderma gangrenosum. Diagnosis relies on recognizing these hallmark features, but treatment remains a challenge despite current understanding. Conventional immunosuppressive therapies have shown limited efficacy in managing PASH syndrome. Case presentation: The authors present a 36-year-old man with a complex combination of pyoderma gangrenosum, acne, suppurative hidradenitis, obesity, and Crohn's disease. The patient's symptoms began in adolescence with acne and recurrent furuncles, evolving into painful skin ulcers and fistulas over time. Histological examination confirmed the diagnosis of pyoderma gangrenosum. Despite various treatment modalities, including isotretinoin, cyclosporine, azathioprine, and adalimumab, the patient experienced only partial improvement until receiving Infliximab, which led to remarkable improvement. Discussion: PASH syndrome, a rare neutrophilic dermatosis linked to autoinflammatory conditions like Braun Flaco, is characterized by Pyoderma gangrenosum, acne, and suppurative hidradenitis. This clinical entity presents diagnostic challenges due to its unique features and association with obesity and bowel diseases, such as Crohn's disease. Treatment options, including TNF-α blockers like Infliximab, have shown promising results in controlling cutaneous manifestations. Our case study underscores the complexity of treating PASH syndrome and highlights the importance of personalized therapeutic approaches for optimal outcomes. Conclusion: PASH syndrome presents significant diagnostic and treatment challenges due to its complex symptomatology and associations with conditions like Crohn's disease. The case of a 36-year-old man demonstrates the partial efficacy of conventional therapies and highlights the promising results of infliximab. This underscores the need for personalized treatment strategies and ongoing research to improve outcomes for patients with this rare and intricate syndrome.

Darvadstrocel for complex perianal fistulas in Crohn's disease: A systematic review and meta-analysis.

BACKGROUND: Local injection of darvadstrocel, a suspension of expanded adipose-derived allogenic mesenchymal stem cells, has been used for treatment-refractory perianal fistulas in Crohn's disease (CD). OBJECTIVE: This study aimed to investigate efficacy and safety of darvadstrocel for complex perianal fistulas in CD. METHODS: A systematic search was conducted through April 2024 in relevant databases for observational studies evaluating darvadstrocel. A random-effects meta-analysis model was used to calculate the pooled effect sizes (proportions or incidence rates [IRs]) with 95% confidence intervals (CIs) of effectiveness and safety outcomes. The risk of bias was evaluated using the Joanna Briggs Institute Critical Appraisal Tool. The I2 value assessed heterogeneity. Sensitivity and subgroup analyses were also conducted. RESULTS: Twelve studies were included with 595 patients. The pooled rate of patients achieving clinical remission, defined as fistula healing, was 68.1% at month 6 (95% CI 63.4-72.7) and 77.2% (95% CI 70.1-83.8) at month 12. Combined remission, defined as clinical remission and absence of collections >2 cm confirmed by magnetic resonance imaging, was reported in 60.6% and in 69.7% of patients at months 6 and 12, respectively. The rate of patients with treatment failure, defined as no clinical remission at the last follow-up (mean 18.7 months; SD 9.9), was 34.5%. Failure rate was independent of follow-up time (p = 0.85). For effectiveness outcomes, between-study heterogeneity was negligible. Subgroup analysis indicated that none of the covariates modified the treatment effect. Pooled IRs per 100 patient-years of adverse events (AE), serious AEs, perianal abscesses, and reoperations were 19.6, 3.2, 16.9 and 7.1, respectively. CONCLUSION: Evidence from observational studies supports the efficacy and safety of darvadstrocel for complex perianal fistulas in CD. Studies have reported high fistula healing rates that can be sustained long-term in most patients, with negligible between-study heterogeneity, as well as a favorable safety profile.

Inflammatory bowel disease uncovered in fecal immunochemical test positive patients in a Canadian provincial colon cancer screening program.

Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition that usually affects younger adults but has a second incidence peak in the older population. Although diagnosis of IBD is driven by symptoms, some patients are asymptomatic and incidentally discovered while participating in colon screening program (CSP). We aimed to identify the incidence and outcome of IBD in fecal immunochemical test (FIT) positive patients in the British Columbia CSP. We conducted a retrospective chart review of patients who had colonoscopies for positive FIT and were found to have colitis based on endoscopic and histological assessment. Of 93,994 patients who underwent screening colonoscopy for positive FIT between 2009 and 2017, 608 (0.6%) were found to have colitis. From 11 CSP sites, 191 patients met the inclusion criteria. 58 patients (30.4%) were diagnosed with ulcerative colitis, 109 (57.1%) with Crohn's disease (CD), and 24 (12.6%) with IBD unclassified. 124 patients (64.9%) received treatment, of which 34 (17.8%) received biologics and 4 (2.1%) required surgery. Our study demonstrated a clinically significant incidence of IBD, with novel finding of CD predominance, within a Canadian provincial CSP. Further research is needed to guide management of older patients with varying rates of IBD progression after incidental diagnosis.

Causal Relationship Between Autism Spectrum Disorder and Inflammatory Bowel Disease: A Bidirectional Mendelian Randomization Study.

Patients with autism spectrum disorder (ASD) are often accompanied by inflammatory bowel disease (IBD) in observational research; however, the potential causal link between the two conditions remains unknown. In this study, we used a two-sample bidirectional Mendelian randomization (MR) approach to assess the causal relationship between ASD and IBD and its main subtypes, Crohn's disease (CD), and ulcerative colitis (UC). Independent genetic instruments from a genome-wide association study (GWAS) for IBD (25,042 cases and 34,915 controls) were used to investigate the association of IBD with ASD data obtained from the PGC and the iPSYCH consortia (N = 46,351). The primary analysis employed the random effects inverse variance weighting (IVW) method. Horizontal pleiotropy was detected using the MR Egger regression and the MR-pleiotropy residual sum and outlier (MR-PRESSO) analysis while heterogeneity was detected using Cochran's Q. The IVW method indicated a positive causal relationship of IBD with ASD (odds ratio (OR) = 1.028, 95% confidence interval (CI) = 1.001-1.056, p = 0.042). In subtype analyses, CD was positively related to ASD (OR = 1.036; 95% CI = 1.004-1.069; p = 0.02); however, UC showed no relationship (OR = 1.021; 95% CI = 0.999-1.044; p = 0.065). In contrast, no evidence of a causal relationship between ASD and IBD or its subtypes (p > 0.05) was found. Our findings provided evidence in support of potential causal associations between IBD/CD and ASD.

Granulomas without foreign body giant cells in perianal fistula tissue suggest Crohn's disease.

OBJECTIVES: Histopathological characteristics of granulomas in perianal fistula of patients with Crohn's disease (CD) remain unexplored. We aimed to assess the histopathological features of granulomas in perianal fistula in CD. METHODS: A retrospective analysis was conducted by reviewing the medical and pathological records of 4430 cases who underwent perianal fistulectomy at our hospital between June 2015 and June 2023. The patients were divided into the CD group, tuberculosis (TB), and non-CD group, respectively, based on their final diangosis. The detection rate of granulomas and differential histopathological features were investigated. RESULTS: Among the 4430 patients, granulomas were identified in 41 cases, including 25 had CD, 2 had pulmonary TB, and 14 only exhibiting perianal lesions with no other comorbidities. Additionally, there were altogether 93 CD cases, resulting in a detection rate of granuloma of 26.9%, which was considerably higher than that in the non-CD group (26.9% vs 0.3%, p < 0.001). The majority (85.7%) of the perianal fistula tissues in the non-CD group contained foreign body giant cells, while this was observed in only 1 (4.0%) out of the 25 cases with CD. We proposed that granulomas in the perianal fistula in the non-CD group were mostly foreign body granulomas. Moreover, granulomas in the non-CD group were larger than that of the CD group (1135 µm vs 519 µm, p < 0.001). CONCLUSION: Most CD cases have less granulomas (≤3) and no foreign body giant cells. Ribbon-like granulomas can be seen only in CD cases.

Oral health in patients with inflammatory bowel disease: A cross-sectional survey in Sweden.

OBJECTIVES: The aim of this cross-sectional survey was to assess oral health, including prevalence of periodontitis and rate of tooth loss, in a Swedish cohort of patients with inflammatory bowel disease (IBD). METHODS: A questionnaire on general anamnestic and socio-economic aspects, IBD diagnosis, and various oral health aspects was distributed online. The analyses focused on the comparison between patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) as well as on factors associated with self-reported severe periodontitis and tooth loss. RESULTS: Analyses were based on answers from 786 patients; 415 with UC, 371 with CD, 74% female. In both disease entities, high prevalence of severe periodontitis (i.e., 38.5%) was reported, and about 19% of the population had less than 20 remaining teeth and 6.5% a poor oral health-related quality of life. CD patients tended to be more severely affected than UC patients (p > 0.05 in the adjusted analysis). Almost 90% of CD patients were aware of being entitled to a bi-annual governmental financial support for dental care due to IBD; however, 1 out of 4 UC patients did not. Furthermore, IBD patients largely believe that the interest of their physicians in any oral lesions due to IBD diagnosis is low. CONCLUSIONS: Severe periodontitis and high rate of tooth loss are frequent in Swedish IBD patients. CLINICAL RELEVANCE: Even though IBD patients receive bi-annually some special financial support for dental care, it seems this is still not sufficient and more preventive measures appear necessary.

Pancreatic Heterotopia Presenting as a Mimic of Fistulizing Crohn's Disease: Expanding the Differential Diagnosis of Inflammatory Bowel Disease.

Pancreatic heterotopia (PH) involves pancreatic tissue located outside its typical anatomical position, lacking vascular or ductal communication with the pancreas. Despite frequently having acini with the capacity to produce digestive enzymes, PH is usually asymptomatic. When symptoms do occur, they typically present in middle to late adulthood and include abdominal pain, nausea, and diarrhea. This clinical presentation is similar to that of Crohn's disease, an autoimmune inflammatory bowel disease (IBD). The presentation of symptomatic PH varies depending on the location of the ectopic pancreatic tissue and its microanatomical constituents, including exocrine and endocrine tissue as well as a duct system. We present a case of a patient who came to medical attention with abdominal pain and was found on colonoscopy to have a non-obstructing stricture of the transverse colon without an associated mass. Biopsies of the area revealed chronic active colitis, leading to a diagnosis of Crohn's disease. Her gastroenterological symptoms remained stable for several years while receiving infliximab infusions until she presented to the emergency department with severe abdominal pain, diarrhea, and sepsis, meeting the criteria for systemic inflammatory response syndrome. Imaging studies revealed a fistula between the previous colonic stricture and the jejunum, again attributed to Crohn's disease. She underwent surgery to remove the fistula between the small and large bowels. Unexpectedly, the resection specimen showed a mass insinuated between the loops of the large intestine, which histological review revealed to be ectopic pancreatic tissue. Following the resection of the ectopic pancreatic tissue, her symptoms resolved without the need for further treatment. In retrospect, the ectopic pancreatic tissue, which contained acini with digestive enzymes, ducts, and islets, may have also caused seemingly unrelated pathology in the patient. Symptomatic PH should be recognized as a pathology that can mimic IBD, prompting reconsideration of the diagnosis in cases of refractory disease while on biologics.

Isolated Gastric Crohn's Disease: A Growing Tendency.

Isolated gastric Crohn's disease (IGCD) is a rare manifestation of Crohn's disease confined to the stomach, unlike its more common forms that primarily affect the ileum and colon. We report the case of a 25-year-old female presenting with a one-month history of epigastric discomfort and nausea, with no other significant gastrointestinal or systemic symptoms. Upper endoscopy revealed an aphthous ulceration on the greater curvature of the stomach, with biopsies showing non-caseating granulomas consistent with Crohn's disease. The diagnosis of IGCD was confirmed through a positive ASCA test and negative p-ANCA test, alongside the absence of ileal and colonic involvement. The patient was treated with prednisone for acute symptom management, followed by infliximab for long-term maintenance. Follow-up evaluations showed no significant relapse episodes. This case highlights the diagnostic challenges and management strategies for IGCD, emphasising the need for further research to optimise treatment protocols and improve long-term outcomes. LEARNING POINTS: This case highlights the challenges and complexities of diagnosing and managing isolated gastric Crohn's disease (IGCD), a rare manifestation of Crohn's disease confined to the stomach.Serological tests such as the anti-Saccharomyces cerevisiae antibody (ASCA) test and the perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) test help in distinguishing Crohn's disease from other conditions.This case emphasises the importance of considering IGCD in patients with unexplained gastric symptoms, and the need for individualised treatment plans due to the lack of specific guidelines for IGCD.

The Intestinal Microbiome but not Clinical Aspects of Inflammatory Bowel Disease is Impacted by Lactose Malabsorption Compared to Lactose Digestion in Children.

BACKGROUND: Dietary exclusion of lactose from patients with inflammatory bowel disease persist with speculation that deleterious effects are mediated through intestinal microbes. OBJECTIVE: To compare inflammatory bowel disease characteristics and changes in the intestinal microbiome at diagnosis in children with and without lactose malabsorption. METHODS: A cross-sectional cohort of children (8-17 years of age) diagnosed with Crohn's disease (n=149 [63%]) or ulcerative colitis (n=86) that had undergone lactose breath hydrogen testing was evaluated. The intestinal microbiome of mucosal luminal aspirates was profiled at the time of diagnosis using 16S rRNA gene amplicon sequencing of the V6 hypervariable region. RESULTS: Of the 235 children, 61 (26%) had lactose malabsorption. Microbial characterization yielded differences in bacterial differential abundance between children that could and could not absorb lactose that varied by intestinal site and between sub-types of inflammatory bowel disease. There were no differences in the ages (13.2±3.0 years [mean±SD] versus 12.7±3.4 years; p=0.25), sex (p=0.88), extent of disease involvement or severity of disease at presentation (p=0.74) when comparing those that could or could not absorb lactose nor was there a difference in the need for initiation of biological agents (p=0.43) during two years of follow-up. CONCLUSIONS: Lactose malabsorption does not affect the clinical presentation or outcomes of children with inflammatory bowel disease. However, this study establishes that a single non-absorbed fermentable food product can alter the intestinal microbiome in both a regional and disease specific manner. As we continue to learn more about the pathophysiology of inflammatory bowel disease and the role of the intestinal microbiome in disease onset and progression, it would be of benefit to examine the impact of other potential fermentable nutrients and their products on inflammatory bowel disease outcomes.

Evaluating the predictive effect of vitamin D on clinical outcomes of infliximab-treated Crohn's disease patients in western China.

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.

Defining mucosal healing in randomized controlled trials of inflammatory bowel disease: A systematic review and future perspective.

BACKGROUND: Mucosal healing (MH) is an established treatment goal in inflammatory bowel disease (IBD). However, various definitions of MH exist. We aimed to identify how MH is defined in randomized controlled trials (RCTs) in ulcerative colitis (UC) and Crohn's disease (CD). METHODS: We searched MEDLINE, EMBASE, and the Cochrane library from inception to December 2023 for phase 2 and 3 RCTs of advanced therapies in IBD. RESULTS: One hundred forty-four studies were included, 72 in UC and 72 in CD, published between 1997 and 2023. In UC, 64% (46/72) RCTs reported MH as an endpoint. 12 definitions of MH were found, from endoscopic assessment alone (35/46; 76%) to the more recent combination of histology and endoscopy (10/46; 22%). 96% (44/46) of studies used the Mayo Endoscopic Subscore. In CD, reporting of MH lagged behind UC, with only 12% (9/72) of trials specifically defining MH as an endpoint, 7 as "absence of ulceration," 2 as Simplified Endoscopic Score for CD score ≤2 or 0. Histological assessment was performed in 3 RCTs of CD. Centralized reading of endoscopy was used in 48% (35/72) of RCTs of UC and 22% (16/72) of CD. Only 1 RCT included transmural healing as an endpoint. CONCLUSIONS: A standard definition of MH in IBD is lacking. Definitions have evolved particularly in UC, which now includes the addition of histological evaluation. Transmural healing holds promise as a future target in CD. We support a greater standardization of definitions as we expect endpoints to become increasingly stringent and multimodal with computers automating the assessment.

Oxidative stress-related biomarkers as promising indicators of inflammatory bowel disease activity: A systematic review and meta-analysis.

Oxidative stress is believed to play an important role in the pathogenesis of inflammatory bowel disease (IBD), specifically Crohn's disease (CD) and ulcerative colitis (UC). This meta-analysis aimed to identify and quantify the oxidative stress-related biomarkers in IBD and their associations with disease activity. We systematically searched Ovid MEDLINE, Ovid Embase, and Web of Science databases, identifying 54 studies for inclusion. Comparisons included: (i) active IBD versus healthy controls; (ii) inactive IBD versus healthy controls; (iii) active CD versus inactive CD; and (iv) active UC versus inactive UC. Our analysis revealed a significant accumulation of biomarkers of oxidative damage to biomacromolecules, coupled with reductions in various antioxidants, in both patients with active and inactive IBD compared to healthy controls. Additionally, we identified biomarkers that differentiate between active and inactive CD, including malondialdehyde, Paraoxonase 1, catalase, albumin, transferrin, and total antioxidant capacity. Similarly, levels of Paraoxonase 1, erythrocyte glutathione peroxidase, catalase, albumin, transferrin, and free thiols differed between active and inactive UC. Vitamins and carotenoids also emerged as potential disease activity biomarkers for CD and UC, but their intake should be monitored to obtain meaningful results. These findings emphasize the involvement of oxidative stress in the pathogenesis of IBD and highlight the potential of oxidative stress-related biomarkers as a minimally invasive and additional tool for monitoring the activity of IBD.

Early life exposures and risk of inflammatory bowel disease: A nested case-control study in Quebec, Canada.

BACKGROUND: Early life factors for inflammatory bowel disease are likely to impact the gut microbiota. AIM: We investigated the associations between early exposures and inflammatory bowel disease. METHODS: This case-control study was nested within the CO·MMUNITY cohort. Cases of Crohn's disease (CD) and ulcerative colitis (UC) were identified using validated algorithms. All cases and randomly selected controls were invited to complete a questionnaire including early life exposures. Analyses were conducted by logistic regression and causal mediation (direct/indirect effects for passive/active smoking). RESULTS: Early introduction of solid foods at 3-6 months tended to increase CD risk compared to later introduction (>6 months): OR = 1.23; 95 % CI: 0.96-1.56, but not of UC. Exclusive breastfeeding tended to decrease the risk of CD (OR = 0.77; 95 % CI: 0.55-1.08), less so for UC. Antibiotics tended to decrease CD (OR = 0.89; 95 % CI: 0.74-1.07) and UC (OR = 0.88; 95 % CI: 0.71-1.09). No association was found between pets and CD or UC. Passive smoking increased CD risk (OR = 1.23; 95 % CI: 1.00-1.51), 20 % of which was mediated by active smoking, but not UC. CONCLUSION: Differences were noticed in early risk factors for CD and UC. The impact of passive smoking was largely independent of active smoking, highlighting its importance for prevention.