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.

Real-world clinical efficacy of tofacitinib in moderate-to-severe ulcerative colitis.

Tofacitinib is an oral small-molecule Janus kinase (JAK) inhibitor that preferentially inhibits JAK1 and JAK3. Its efficacy in inducing and maintaining remission in ulcerative colitis (UC) as well as its safety profile has been demonstrated in multicenter, randomized, double-blind, placebo-controlled trials. Additionally, real-world studies evaluating the effectiveness and adverse effects of tofacitinib have been conducted, affirming its clinical efficacy in moderate-to-severe UC.

Game changer: How Janus kinase inhibitors are reshaping the landscape of ulcerative colitis management.

Recent advancements in the treatment landscape of ulcerative colitis (UC) have ushered in a new era of possibilities, particularly with the introduction of Janus kinase (JAK)-signal transducer and activator of transcription inhibitors. These novel agents offer a paradigm shift in UC management by targeting key signaling pathways involved in inflammatory processes. With approved JAK inhibitors (JAKis), such as tofacitinib, filgotinib, and upadacitinib, clinicians now have powerful tools to modulate immune responses and gene expression, potentially revolutionizing the treatment algorithm for UC. Clinical trials have demonstrated the efficacy of JAKis in inducing and maintaining remission, presenting viable options for patients who have failed conventional therapies. Real-world data support the use of JAKis not only as first-line treatments but also in subsequent lines of therapy, particularly in patients with aggressive disease phenotypes or refractory to biologic agents. The rapid onset of action and potency of JAKis have broadened the possibilities in the management strategies of UC, offering timely relief for patients with active disease and facilitating personalized treatment approaches. Despite safety concerns, including cardiovascular risks and infections, ongoing research and post-marketing surveillance will continue to refine our understanding of the risk-benefit profile of JAKis in UC management.

Delayed diagnosis in inflammatory bowel disease: Time to consider solutions.

In this editorial, we discuss a recently published manuscript by Blüthner et al in the World Journal of Gastroenterology, with a specific focus on the delayed diagnosis of inflammatory bowel disease (IBD). IBD, which includes Crohn's disease and ulcerative colitis, is a chronic intestinal disorder. A time lag may exist between the onset of inflammation and the appearance of signs and symptoms, potentially leading to an incorrect or delayed diagnosis, a situation referred to as the delayed diagnosis of IBD. Early diagnosis is crucial for effective patient treatment and prognosis, yet delayed diagnosis remains common. The reasons for delayed diagnosis of IBD are numerous and not yet fully understood. One key factor is the nonspecific nature of IBD symptoms, which can easily be mistaken for other conditions. Additionally, the lack of specific diagnostic methods for IBD contributes to these delays. Delayed diagnosis of IBD can result in numerous adverse consequences, including increased intestinal damage, fibrosis, a higher risk of colorectal cancer, and a decrease in the quality of life of the patient. Therefore, it is essential to diagnose IBD promptly by raising physician awareness, enhancing patient education, and developing new diagnostic methods.

Phase 2 Trial of Anti-TL1A Monoclonal Antibody Tulisokibart for Ulcerative Colitis.

BACKGROUND: Tulisokibart is a tumor necrosis factor-like cytokine 1A (TL1A) monoclonal antibody in development for the treatment of moderately to severely active ulcerative colitis. A genetic-based diagnostic test was designed to identify patients with an increased likelihood of response. METHODS: We randomly assigned patients with glucocorticoid dependence or failure of conventional or advanced therapies for ulcerative colitis to receive intravenous tulisokibart (1000 mg on day 1 and 500 mg at weeks 2, 6, and 10) or placebo. Cohort 1 included patients regardless of status with respect to the test for likelihood of response. Cohort 2 included only patients with a positive test for likelihood of response. The primary analysis was performed in cohort 1; the primary end point was clinical remission at week 12. Patients with a positive test for likelihood of response from cohorts 1 and 2 were combined in prespecified analyses. RESULTS: In cohort 1, a total of 135 patients underwent randomization. A significantly higher percentage of patients who received tulisokibart had clinical remission than those who received placebo (26% vs. 1%; difference, 25 percentage points; 95% confidence interval [CI], 14 to 37; P<0.001). In cohort 2, a total of 43 patients underwent randomization. A total of 75 patients with a positive test for likelihood of response underwent randomization across both cohorts. Among patients with a positive test for likelihood of response (cohorts 1 and 2 combined), clinical remission occurred in a higher percentage of patients who received tulisokibart than in those who received placebo (32% vs. 11%; difference, 21 percentage points; 95% CI, 2 to 38; P = 0.02). Among all the enrolled patients, the incidence of adverse events was similar in the tulisokibart and placebo groups; most adverse events were mild to moderate in severity. CONCLUSIONS: In this short-term trial, tulisokibart was more effective than placebo in inducing clinical remission in patients with moderately to severely active ulcerative colitis. (Funded by Prometheus Biosciences, a subsidiary of Merck; ARTEMIS-UC ClinicalTrials.gov number, NCT04996797.).

Identification and validation of coagulation and fibrinolytic-related diagnostic biomarkers for ulcerative colitis by bioinformatics analysis.

Abnormalities in coagulation and fibrinolytic status have been demonstrated to be relevant to inflammatory bowel disease. Nevertheless, there is no study to methodically examine the role of the coagulation and fibrinolysis-related genes in the diagnosis of ulcerative colitis (UC). UC-related datasets (GSE169568 and GSE94648) were originated from the Gene Expression Omnibus database. The biomarkers related to coagulation and fibrinolysis were identified through combining differentially expressed analysis and machine learning algorithms. Moreover, Gene Set Enrichment Analysis and immune analysis were carried out. A total of 4 biomarkers (MAP2K1, CREBBP, TAF1, and HP) were identified, and biomarkers were markedly enriched in pathways related to immunity, such as T-cell receptor signaling pathway, primary immunodeficiency, chemokine signaling pathway, etc. In total, the infiltrating abundance of 4 immune cells between UC and control was markedly different, namely eosinophils, macrophage M0, resting mast cells, and regulatory T cells. And all biomarkers were significantly relevant to eosinophils. Our findings detected 4 coagulation and fibrinolysis-related biomarkers (MAP2K1, CREBBP, TAF1, and HP) for UC, which contributed to the advancement of UC for further clinical investigation.

Perception of fecal microbiota transplantation in patients with ulcerative colitis in Korea: a KASID multicenter study.

BACKGROUND/AIMS: Fecal microbiota transplantation (FMT) is a promising therapy for inducing and maintaining remission in patients with ulcerative colitis (UC). However, FMT has not been approved for UC treatment in Korea. Our study aimed to investigate patient perceptions of FMT under the national medical policy. METHODS: This was a prospective, multicenter study. Patients with UC ≥ 19 years of age were included. Patients were surveyed using 22 questions on FMT. Changes in perceptions of FMT before and after education were also compared. RESULTS: A total of 210 patients with UC were enrolled. We found that 51.4% of the patients were unaware that FMT was an alternative treatment option for UC. After reading the educational materials on FMT, more patients were willing to undergo this procedure (27.1% vs. 46.7%; p < 0.001). The preferred fecal donor was the one recommended by a physician (41.0%), and the preferred transplantation method was the oral capsule (30.4%). A large proportion of patients (50.0%) reported that the national medical policy influenced their choice of FMT treatment. When patients felt severe disease activity, their willingness to undergo FMT increased (92.3% vs. 43.1%; p = 0.001). CONCLUSION: Education can increase preference for FMT in patients with UC. When patients have severe disease symptoms or their quality of life decreases their willingness to undergo FMT increases. Moreover, national medical policies may influence patient choices regarding FMT.

Practical management of mild-to-moderate ulcerative colitis: an international expert consensus.

INTRODUCTION: Although there are well-defined guidelines for the management of mild-to-moderate ulcerative colitis (UC), there are still unmet needs. For this reason, we conducted an international expert consensus to standardize the management of patients with mild-to-moderate UC and provide practical guidance to clinicians. AREAS COVERED: Based on Delphi methodology, 15 statements were approved after two rounds of voting, addressing several aspects of disease management from sequencing to treatment duration, from monitoring to optimization techniques and safety profile. EXPERT OPINION: Growing knowledge of mild-to-moderate UC has led to the development of new ambitious outcomes such as histological remission and disease clearance. Furthermore, noninvasive tools for patient monitoring such as fecal calprotectin and intestinal ultrasound are now available. Their implementation in clinical practice will allow clinicians to tightly monitor disease activity and promptly adapt treatment, avoiding complications and disease progression and targeting better disease control.

Association Between Vedolizumab Treatment and Arthritis/Arthralgia in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Vedolizumab is a humanized gut selective drug that targets α4ß7 integrin and has been used successfully in the treatment of inflammatory bowel disease (IBD). Pivotal studies have already demonstrated the drug's safety, but some real-life cohorts have shown an increase in arthralgia and arthritis in patients using vedolizumab. These findings raised the question of whether these joint symptoms are extraintestinal manifestations of IBD (since the drug acts only in the gut) or if they are associated with the use of vedolizumab. This systematic review and meta-analysis aimed to assess the incidence of arthralgia/arthritis in patients receiving vedolizumab and to investigate whether these events are indeed drug related. METHODS: Pubmed, Cochrane, and Scopus were searched for randomized clinical trials reporting the incidence of joint manifestations in patients with Crohn's disease (CD) or ulcerative colitis (UC) who were treated with vedolizumab. The considered outcomes were arthritis and arthralgia. We used RevMan to calculate the pooled incidence of the reported outcomes and their corresponding 95% confidence intervals (95% CI). RESULTS: The search strategy yielded 4,206 articles. After removal of duplicates and screening of results, 6 randomized studies met the inclusion criteria. A total of 3,134 patients with moderately to severe IBD were included. Of those, 2,119 were randomized to receive vedolizumab and 1,015 to placebo. In the intervention group, 210 patients developed arthritis or arthralgia of any kind while 84 patients developed those symptoms in the placebo group (RR=1.09; 95%CI: 0.86-1.38; p=0.49, I2=0%), showing no significant association. Results also showed no significant association between exposure and the studied outcome after comparing CD (RR=1.02; 95%CI: 0.76-1.37, p=0.89, I2=0%) and UC (RR=1.24; 95%CI: 0.81-1.89, p=0.32, I2=43%) separately. CONCLUSIONS: The meta-analysis showed no association of these symptoms to the treatment with vedolizumab. Therefore, the new onset of worsening arthritis and arthralgia may be associated with the course of the disease itself, with the body's response to the drugs or with the exclusion of corticosteroids or anti-TNF from concomitant treatment with vedolizumab. Further studies with larger sample sizes are required, especially randomized clinical trials comparing anti-TNF, corticosteroid and immunomodulators to evaluate the incidence of joint manifestations in patients with IBD and even other rheumatological manifestations that may be associated as well.

The Incidence and Risk Factors of Refeeding Syndrome-like Hypophosphatemia in Inflammatory Bowel Disease: A Preliminary Study.

BACKGROUND AND AIMS: Refeeding syndrome (RFS) is defined by the presence of acute electrolyte disturbances, including hypophosphatemia. Underlying disease(s), malnutrition and hospitalisation are known risk factors for RFS. It can occur in patients with inflammatory bowel disease (IBD). We aimed to determine the frequency of hypophosphatemia and the relationship between hypophosphatemia, disease severity and nutritional status in hospitalized patients with IBD. METHODS: This study was performed prospectively in hospitalized adult patients for the treatment of IBD in a tertiary-care hospital. Disease severity was assessed using Truelove and Witts score for ulcerative colitis (UC) and Crohn's Disease Activity Index for Crohn's disease (CD). Nutritional status was determined using Subjective Global Assessment (SGA). Serum phosphate concentration was recorded for first 7 days after hospitalization, and less than 0.65 mmol/l was defined as hypophosphatemia. RESULTS: Fifty participants (33 with UC and 17 with CD) were included in the study. The mean age of the study sample was 43.4±14.9 years, of which 64% were male. A total of 8.8% of patients with UC and 37.5% of patients with CD had severe (>moderate) disease upon study admission. Seventeen patients (34%) were malnourished. During the 7 study days, 23 participants (46%) had at least one episode of hypophosphatemia. Serum phosphate concentration was significantly and moderately correlated with serum potassium concentration in both the patients and the hypophosphatemia group on study day 3 (p<0.05). Multivariate logistic regression analysis showed that the presence of malnutrition [odds ratio (OR) = 3.64, 95% confidence interval (CI): 1.52-5.58, p=0.008), the administration of parenteral nutrition (OR=2.91, 95%Cl: 1.37-4.63, p=0.015), and severe IBD (OR=1.74, 95%CI: 1.03-3.42, p=0.020) were associated with hypophosphatemia. CONCLUSIONS: Approximately half of the participants exhibited at least one instance of hypophosphatemia during the study period. Hypophosphatemia was found to be associated with malnutrition, parenteral nutrition, and severe disease in patients with IBD requiring hospitalization.

Serum vascular endothelial growth factor has diagnostic and prognostic significance in ulcerative colitis.

Background/aim: In ulcerative colitis (UC), serum vascular endothelial growth factor (sVEGF) concentrations are elevated and there are conflicting results about serum calprotectin (SCP) and sVEGF as biomarkers. We aimed to evaluate the relationship between sVEGF and SCP levels in UC patients and the associations of these molecules with the phenotypes of UC. Materials and methods: This prospective case-control study included 60 UC patients and 30 healthy controls. The Mayo Clinical Score (MCS) was used to evaluate patients' clinical features and the Mayo Endoscopic Score (MES) was used to evaluate endoscopic features of the cases. The method proposed by Truelove and Richards was applied in calculating the histology activity index (HAI). Human sVEGF (Cat.E0080Hu) and human calprotectin (Cat.E4010Hu) kits were used for the enzyme-linked immunosorbent assay (ELISA) measurements of sVEGF and SCP levels. Results: The median sVEGF and SCP levels were higher in the patient group compared to the healthy control group [2139 ng/L (126-5783) vs. 888 ng/L (715-5270), p = 0.002 and 932 ng/L (99-2648) vs. 80 ng/L (56-920), p < 0.001, respectively]. There was a strong correlation between SCP and sVEGF values (rho = 0.819, p < 0.001). The MCS, MES, and HAI values were positively correlated with sVEGF and SCP concentrations. Conclusion: sVEGF and SCP may be valuable auxiliary biomarkers for UC.

Design and Synthesis of an Azo Reductase Responsive Flavonol-Indomethacin Hybrid Used for the Diagnosis and Treatment of Colitis.

Human intestinal bacteria are the primary producers of azo reductase, and the content of azo reductase is closely associated with various intestinal diseases, including ulcerative colitis (UC). The rapid detection of changes in azo reductase levels is crucial for diagnosing and promptly intervening in UC. In this study, a therapeutic agent, FAI, specifically targeting UC, was designed and synthesized. This agent was developed by linking the anti-inflammatory drug indomethacin to flavonols with antioxidant activity via an azo bond (off-on). Breakage of the azo bond breaks results in the release of both fluorophores and drugs, achieving targeted tracing and integrated treatment effects. In vivo and in vitro fluorescence imaging experiments were used to demonstrate the potential of FAI in the diagnosis of UC, together with synergistic therapeutic effects through the release of both fluorophores and anti-inflammatory agents. Therefore, this diagnostic agent shows promise as a potential tool for diagnosing and treating UC.

Inflammatory bowel diseases and spondyloarthritis: a focus on female patients.

OBJECTIVE: Ulcerative colitis and Crohn's disease are chronic inflammatory diseases and represent the two most important types of inflammatory bowel diseases (IBD), while spondyloarthritis (SpA) comprises a heterogeneous group of systemic inflammatory chronic rheumatic diseases, including peripheral SpA and axial SpA. Joint manifestations are the most commonly observed extraintestinal manifestations, and they can precede or not the diagnosis of IBD. Notably, in women, misdiagnoses of IBD as irritable bowel syndrome and SpA as fibromyalgia are common, leading to delayed diagnoses, increased disease burden, and poorer prognoses. This narrative review emphasizes the critical role of diagnostic tools in facilitating early referrals of IBD patients with suspected SpA and vice versa to rheumatologists and gastroenterologists, respectively. Special attention is given to the multidisciplinary approach for more effective management of these conditions, particularly in female patients. METHODS: In this narrative review, we critically evaluated the literature on this topic, focusing on papers written in English that address female issues in IBD and SpA. RESULTS: IBD and SpA are chronic inflammatory disorders often occurring in the same patients. Female patients are often misdiagnosed, and this delay in diagnosis is associated with a higher disease burden and a poorer prognosis. CONCLUSIONS: A multidisciplinary approach is needed to enable early referral between gastroenterologists and rheumatologists, as this means a better prognosis for patients with a reduction in the economic and social burden associated with IBD and SpA.

Efficacy and safety of berberine plus 5-ASA for ulcerative colitis: A systematic review and meta-analysis.

PURPOSE: This study aimed to assess the efficacy and safety of berberine(BBR) plus 5-aminosalicylic acid (5-ASA) for treating ulcerative colitis (UC). METHODS: A comprehensive search was conducted in electronic databases, including Medline/PubMed, Sinomed, Embase, CNKI, Wanfang, and VIP, through January 2024 to identify all randomized controlled trials (RCTs) that administered BBR conjunction in standard therapy(5-ASA) for to support the treatment of UC. The data were synthesized using a meta-analysis approach with RevMan 5.4.1. The primary endpoint was the clinical efficacy rate. In contrast, the secondary endpoints included the Baron score, disease activity index (DAI) score, symptom relief latency, inflammatory markers, immunological indicators, and adverse events. RESULTS: In this analysis, 10 RCTs comprising 952 patients with UC were examined. BBR considerably improved the clinical efficacy rate (RR = 1.22, 95% CI [1.15, 1.30], P < 0.00001), attenuated the Baron score (SMD = -1.72, 95% CI [-2.30, -1.13], P < 0.00001) and reduced the DAI score (SMD = -2.93, 95% CI [-4.42, -1.43], P < 0.00001). Additionally, it ameliorated clinical symptoms (SMD = -2.74, 95% CI [-3.45, 2.02], P < 0.00001), diminished inflammatory responses (SMD = -1.59, 95% CI [-2.14, 1.04], P < 0.00001), and modulated immune reactions (SMD = 1.06,95% CI [0.24,1.87], P <0.00001). Nonetheless, the impact of BBR on reducing adverse reactions was not statistically significant (RR = 0.75, 95% CI [0.42, 1.33], P > 0.05). CONCLUSION: BBR demonstrates substantial efficacy in treating UC without causing severe adverse reactions and may serve as a viable complementary therapy. However, its clinical application warrants confirmation by additional high-quality, low-bias RCTs.

Ulcerative colitis: clinical biomarkers, therapeutic targets, and emerging treatments.

Ulcerative colitis (UC) is one of the two forms of inflammatory bowel disease. It affects 5 million people globally, and is a chronic and recurring inflammation of the gastrointestinal tract with clinical presentation of abdominal pain, chronic diarrhea, rectal bleeding, and weight loss. The cause and the etiology of UC remain poorly understood. There is no cure and no 'gold standard diagnostic' for UC. The existing treatments are ineffective, and UC patients have a lower life expectancy with a risk of colorectal cancer. Recent studies in pathophysiology, clinical presentation, and biomarkers have significantly improved our understanding of UC. In this review we summarize recent advances in identifying novel clinical biomarkers, diagnostics, treatment targets, and emerging therapeutics. These insights are expected to assist in developing effective treatments for UC.

Leishmania donovani infection mimicking ulcerative colitis in an immuno-competent patient.

We share a case of a 54-year-old Caucasian immune-competent male with a suspected long latent visceral leishmaniasis presenting primarily with parasitic colitis, splenomegaly, and pancytopenia. Due to histopathologically and endoscopically mimicking ulcerative colitis, the patient was initially treated for UC, until the parasites were identified and eradicated with liposomal Amphotericin B.

Long Non-Coding RNAs and Their Potential Role as Biomarkers in Inflammatory Bowel Disease.

Inflammatory bowel disease is a chronic inflammatory disease that encompasses entities such as Crohn's disease and ulcerative colitis. Its incidence has risen in newly industrialised countries over time, turning it into a global disease. Lately, studies on inflammatory bowel disease have focused on finding non-invasive and specific biomarkers. Long non-coding RNAs may play a role in the pathophysiology of inflammatory bowel disease and therefore they may be considered as potential biomarkers for this disease. In the present article, we review information in the literature on the relationship between long non-coding RNAs and inflammatory bowel disease. We especially focus on understanding the potential function of these RNAs as non-invasive biomarkers, providing information that may be helpful for future studies in the field.

Identifying polyamine related biomarkers in diagnosis and treatment of ulcerative colitis by integrating bulk and single-cell sequencing data.

Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon, and its pathogenesis remains unclear. Polyamine metabolic enzymes play a crucial role in UC. In this study, we aimed to identify pivotal polyamine-related genes (PRGs) and explore the underlying mechanism between PRGs and the disease status and therapeutic response of UC. We analyzed mRNA-sequencing data and clinical information of UC patients from the GEO database and identified NNMT, PTGS2, TRIM22, TGM2, and PPARG as key PRGs associated with active UC using differential expression analysis and weighted gene co-expression network analysis (WCGNA). Receiver operator characteristic curve (ROC) analysis confirmed the accuracy of these key genes in UC and colitis-associated colon cancer (CAC) diagnosis, and we validated their relationship with therapeutic response in external verification sets. Additionally, single-cell analysis revealed that the key PRGs were specific to certain immune cell types, emphasizing the vital role of intestinal tissue stem cells in active UC. The results were validated in vitro and in vivo experiments, including the colitis mice model and CAC mice model. In conclusion, these key PRGs effectively predict the progression of UC patients and could serve as new pharmacological biomarkers for the therapeutic response of UC.

Gas Chromatography-Sensor System Aids Diagnosis of Inflammatory Bowel Disease, and Separates Crohn's from Ulcerative Colitis, in Children.

The diagnosis of inflammatory bowel disease (IBD) in children and the need to distinguish between subtypes (Crohn's disease (CD) and ulcerative colitis (UC)) requires lengthy investigative and invasive procedures. Non-invasive, rapid, and cost-effective tests to support these diagnoses are needed. Faecal volatile organic compounds (VOCs) are distinctive in IBD. VOC profiles can be rapidly determined using a gas chromatography-sensor device (OdoReader©). In an inception-cohort of children presenting with suspected IBD, we directly compared the diagnostic fidelity of faecal calprotectin (FCP, a non-specific protein marker of intestinal inflammation) with OdoReader© VOC profiles of children subsequently diagnosed with IBD with matched controls diagnosed with other gastrointestinal conditions. The OdoReader© was 82% (95% confidence interval 75-89%) sensitive and 71% (61-80%) specific but did not outperform FCP (sensitivity 93% (77-99%) and specificity 86% (67-96%); 250 µg/g FCP cut off) in the diagnosis of IBD from other gastrointestinal conditions when validated in a separate sample from the same cohort. However, unlike FCP and better than other similar technologies, the OdoReader© could distinguish paediatric CD from UC (up to 88% (82-93%) sensitivity and 80% (71-89%) specificity in the validation set) and justifies further validation in larger studies. A non-invasive test based on VOCs could help streamline and limit invasive investigations in children.