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Anti-inflammatory drugs for ulcerative colitis (UC) treatment should specifically penetrate and accumulate in the colon tissue. Herein, a multi-bioresponsive anti-inflammatory drug (curcumin, CUR)-loaded heterogeneous double-membrane microgels (CUR@microgels) for oral administration was fabricated in this study, in which the inner core was derived from polyvinyl alcohol (PVA) and guar gum (GG) and the outer gel was decoration with alginate and chitosan by polyelectrolyte interactions. The structure and morphology of microgels were characterized. In vitro, the formulation exhibited good bio-responses at different pH conditions and sustained-release properties in simulated colon fluid with a drug-release rate of 84.6 % over 34 h. With the assistance of the outlayer gels, the microgels effectively delayed the premature drug release of CUR in the upper gastrointestinal tract. In vivo studies revealed that CUR@microgels specifically accumulated in the colon tissue for 24 h, which suggest that the interlayer gels were apt to reach colon lesion. As expected, the oral administration of microgels remarkably alleviated the symptoms of UC and protected the colon tissue in DSS-induced UC mice. The above results indicated that these facilely fabricated microgels which exhibited excellent biocompatibility and multi-bioresponsive drug release, had an apparent effect on the treatment of UC, which represents a promising drug delivery strategy for CUR in a clinical application.

Silk sericin (SS) has become a noticeable drug nanocarrier due to its excellent biocompatibility and bioactivity. To further extend the application of SS, a facile one-step process was constructed to fabricate SS-stabilized-drug composites. Various insoluble drugs can be encapsulated into SS with high loading amount, and showed good dispersity in aqueous solution. For example, proanthocyanidins (PAC), a natural polyphenol with initial antioxidant and anti-inflammatory effects, can be loaded on SS to form SS/PAC composites. The SS/PAC can disperse uniformly in aqueous solution with an average particle diameter of ~136 nm, and showed high drug loading amount of 1767 mg/g. The SS/PAC exhibited high antioxidant efficiency and excellent biocompatibility (non-irritant, non-hemolysis, and non-cytotoxicity), could remarkably alleviate the symptoms of dextran sulfate sodium-induced ulcerative colitis by decreasing the disease activity index scores, inhibiting the shortening of colon length, regulating oxidative stress, suppressing inflammation, and reversing the histopathological injuries. This work provides a simple method to fabricate SS-stabilized-drug composites, promises high potential in therapeutic and pharmaceutical applications.

Introduction: Restorative proctocolectomy results in the formation of a pouch that adapts to a more colonic phenotype. The incidence of cancer of the pouch is thought to be low with most societal guide-lines differing on their recommendations for surveillance. Aims: We conducted a systematic review with meta-analysis to report the incidence of cancer in all pouch patients. Methods: The Embase, Embase classic and PubMed databases were searched between June 1979- June 2021. A random effects model was performed to find the pooled incidence of pouch cancer. In addition, we also looked for risk factors for pouch cancers. Results: Forty-six studies were included. In 19,964 patients with Ulcerative Colitis (UC) the pooled inci-dence of pouch cancer was 0.0030 (95% CI: 0.0016-0.0 055). In 3741 patients with Familial Adenomatous Polyposis (FAP) the pooled incidence of pouch cancer was 0.01 (95% CI: 0.01 - 0.02). In UC most pouch cancers were found to occur in the pouch body (0.59 (95% CI: 0.29-0.84)). Conclusions: The findings suggest that the pooled incidence of pouch cancer in UC is similar to that which was previously published, and this is the first meta-analysis to report a pooled incidence for pouch cancer in FAP.

Inflammatory bowel disease (IBD) is generally considered a disease of high-income countries and is regarded as rare in sub-Saharan Africa. However, this assumption is almost certainly an underestimate, and the high burden of communicable diseases makes IBD in sub-Saharan Africa difficult to detect. Furthermore, some gastrointestinal infections can closely mimic IBD, contributing to delays in diagnosis and complicating therapeutic decision making. Constraints in endoscopic capacity alongside a scarcity of qualified diagnostic pathologists add to the difficulties. Implementing evidence-based guidelines recommended by international societies is challenging, mostly due to high costs and unavailability of medication. However, cost-effective approaches can still be implemented to manage IBD in sub-Saharan Africa as the predominant disease phenotype is mild-to-moderate ulcerative colitis, which often responds to treatment with basic medication. In this Series paper, we summarise the current management of IBD in sub-Saharan Africa and propose how it can be tailored to suit the epidemiological and socioeconomic specificities of the region. We also discuss measures required to address existing challenges, such as educating health-care workers about the diagnosis and management of IBD or improving endoscopic capacity.

Key differences exist in pediatric and adult inflammatory bowel disease (IBD), and a multidisciplinary approach focused on meeting these needs should be implemented. In an emergency situation, surgical management of pediatric IBD should focus on patient stabilization with an eye toward future intestinal function.

Ulcerative colitis (UC) poses a challenge to patients' health status and lifestyle. Micronutrient intake has been associated with the risk of UC, but the association has been inconsistent. Therefore, we performed a meta-analysis to clarify the overall association between micronutrient intake, as potentially modifiable risk factors, and the risk of UC.Based on the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) protocols, systematic searches were conducted in PubMed, Scopus, and Web of Science up to September 2021. Studies were considered eligible for inclusion if they met the following criteria: (1) observational studies that compared dietary intake of zinc, calcium, or magnesium between the UC group and the control group and (2) had means and standard deviations or medians and interquartile ranges of outcome variables.A total of 7 studies with 1197 participants were included in the meta-analysis. The random-effects meta-analysis showed that there was no significant association between the intake of calcium (WMD: -66.25 mg/day, 95% CI: -276.7 to 144.21, P = 0.54), magnesium (WMD: -21.47 mg/day, 95% CI: -95.54 to 52.6, P = 0.57), and zinc (WMD: 0.3 mg/day, 95% CI: -1.5 to 2, P = 0.74) and the risk of UC. However, there was high significant heterogeneity between studies in dietary intake of calcium (INo significant association was found between dietary calcium, magnesium, and zinc intake and risk of UC.

The use of biologic agents has become the cornerstone of therapy for moderate to severe IBD. Few studies have investigated the efficacy of vedolizumab (VDZ) induction for ulcerative colitis (UC) in Asian patients in a real practice setting.To evaluate the efficacy and safety of VDZ induction therapy for moderate to severe UC in Taiwan.This was a retrospective and observational study. Selected moderate to severe UC patients received VZD 300 mg i.v. at weeks 0, 2, and 6 as induction therapy. Mayo scores were calculated to evaluate the efficacy.A total of 37 patients with UC who received VDZ and completed the induction therapy at Chang Gung Memorial Hospital (2017/10-2021/5) were included. The mean age was 46.5 year-old and the male to female ratio was 1:1 (19/18). 81.8% of the patients were biologic-naive. At weeks 8-10, a clinical response, clinical remission and endoscopic remission with VDZ induction therapy were achieved in 56.8% (21/37), 32.4% (12/37) and 58.3% (7/12) of the patients, respectively. 54.1% (20/37) were able to taper off at week 8. Overall, only 10.8% (4/37) of the patients were primary non-responders during induction therapy. No obvious VDZ-related severe adverse events were noted. Overall, 58.9% (11/19) of the patients relapsed after stopping VDZ, and the relapse rate after VDZ discontinuation was 42.1% (8/19) within first 6 months and 52.6% (10/19) within the first year.In real-world experience, induction therapy with VDZ showed promising clinical benefits and safety profile for patients with UC.

Introduction Ulcerative colitis (UC) is a chronic recurrent idiopathic disease characterized by damage to the colonic epithelial barrier and disruption of inflammatory homeostasis. At present, there is no curative therapy for UC, and the development of effective and low-cost therapies is strongly advocated. Objectives Multiple lines of evidence support that tannic acid (TA) and berberine (BBR), two active ingredients derived from Chinese herb pair (Rhei radix et rhizome and Coptidis rhizoma), have promising therapeutic effects on colonic inflammation. This study aims to develop a targeted delivery system based on BBR/TA-based self-assemblies for the treatment of UC. Methods TA and BBR self-assemblies were optimized, and hyaluronic acid (HA) was coated to achieve targeted colon delivery via HA-cluster of differentiation 44 (CD44) interactions. The system was systematically characterized and dextran sodium sulfate (DSS)-induced mouse colitis model was further used to investigate the biodistribution behavior, effect and mechanism of the natural system. Results TA and BBR could self-assemble into stable particles (TB) and HA-coated TB (HTB) further increased cellular uptake and accumulation in inflamed colon lesions. Treatment of HTB inhibited pro-inflammatory cytokine levels, restored expression of tight junction-associated proteins and recovered gut microbiome alteration, thereby exerting anti-inflammatory effects against DSS-induced acute colitis. Conclusion Our targeted strategy may provide a convenient and powerful platform for UC and reveal new modes of application of herbal combinations.

The efficacy and safety of vedolizumab in bio-naïve patients with ulcerative colitis (UC) and Crohn's disease (CD) remain unknown.To perform a meta-analysis regarding vedolizumab as first line of biological therapy for UC or CD.A systematic review of Medline, EMBASE, and Cochrane databases per December 2020 was undertaken. Meta-analysis was conducted using random-effects models.This systematic review identified 79 eligible studies with 4,520 and 3,494 bio-naïve patients with UC and CD, respectively, and 8,105 and 11,140 bio-exposed patients. Among bio-naïve patients with UC, a total of 40.0% (95%CI 27.0-54.0, IVedolizumab was found to have a favorable efficacy and safety profile in bio-naïve patients with UC and CD. The findings have implications in the management of IBD.

To clarify the effect of quinoa bran soluble dietary fiber (QBSDF) on gut inflammation and homeostasis, ulcerative colitis (UC) mice induced by dextran sodium sulfate (DSS) were fed QBSDF for four weeks. Histological staining, immunofluorescence, western blot and 16S rRNA sequencing analysis were carried out to investigate the action mechanism of QBSDF. Results showed that QBSDF alleviated DSS-induced colitis symptoms accompanied by significant mitigation of colon shortening and colonic epithelial damage. Moreover, QBSDF supplementation downregulated the mRNA and protein expression level of TNF-α and IL-1β, while elevated the expression of tight junction proteins, and significantly reduced colonic cells apoptosis. In addition, the diversity and abundance of gut microbiota in QBSDF fed mice were significantly increased compared to that of UC mice. Moreover, QBSDF notably increased the abundance of Firmicutes at phylum level, while decreased the abundance of Bacteroidetes and pathogenic Helicobacter. Besides, the levels of short-chain fatty acids, especially acetic acid and butyric acid were significantly increased by QBSDF administration. These findings suggested the promising potential of QBSDF as a functional food ingredient to prevent ulcerative colitis through maintaining intestinal barrier function and modulating gut microbiota.

This study aimed to compare the differences between oral administration and intravenous injection of polygalacturonic acid (PGA) in the regulation of immune and intestinal microflora in ulcerative colitis (UC) mice. PGA was administered orally or intravenously. PGA in the high-dose ig group was the most effective in treating UC by increasing colon length and downregulating disease activity index, histopathological score and proinflammatory cytokine levels. In spleen, the efficacy of PGA on restoring Th17/Treg balance in the high-dose iv group was better than that in the high-dose ig group, the opposite was observed in the lamina propria. The level of colonic IL-17A in the high-dose ig group was lower than that in the high-dose iv group, the opposite was observed for that of colonic IL-10. Western blot and immunohistochemistry analysis revealed that PGA in the high-dose ig group decreased the protein expression of RORγt, and increased that of FOXP3. Furthermore, PGA in the high-dose ig group was more effective than that in the high-dose iv group in improving the intestinal microflora structure. Our results suggest that in immune regulation, oral PGA is more effective in the lamina propria and gut microbiota while intravenous PGA is more effective in the spleen.

Programmed death ligand 1 (PD-L1) dysregulation has been implicated in chronic inflammatory diseases, but its role in regulating intestinal mucosa inflammation is still unclear. The aim of this study was to assess PD-L1 expression in the intestinal mucosa of patients with refractory inflammatory bowel disease (IBD) compared to controls. We evaluated PD-L1 expression by immunohistochemistry in colectomy specimens of patients with ulcerative colitis (UC) and Crohn disease (CD) compared to controls. PD-L1 expression was assessed in colonic epithelium and inflammatory cells, along with the location of the inflammatory cells expressing PD-L1. All cases were stained with CD3, CD4, CD8, FOXP3, CD20, CD68, and CD90 immunostains to determine the types of cells expressing PD-L1. The UC group showed significantly higher PD-L1 expression in the colonic epithelium than both CD and control groups (both P 0.001), and CD was also significantly higher than the control group (P = 0.004). Both UC and CD groups showed similar PD-L1 expression in the inflammatory infiltrate but significantly higher than the control group (both P 0.001). Among both IBD groups, higher IBD activity was associated with higher levels of PD-L1 expression in the colonic epithelium (P 0.05) and inflammatory infiltrate (P 0.001). When comparing PD-L1 expression to lineage-specific markers, CD3+, CD4+ T cells, CD68+ macrophages, and CD90+ colonic stromal cells appeared to be expressing PD-L1. These findings implicate a role for PD-L1 in the dysregulation of the immune response in refractory IBD. Further studies are warranted to better understand the role of the immune regulatory pathways in intestinal mucosa.

This cross-cohort study aimed to (1) determine a network-based molecular signature that predicts the likelihood of inadequate response to the tumor necrosis factor-ɑ inhibitor (TNFi) therapy, infliximab, in ulcerative colitis (UC) patients, and (2) address biomarker irreproducibility across different cohort studies. Whole-transcriptome microarray data were derived from biopsies of affected colon tissue from 2 cohorts of infliximab-treated UC patients (training N = 24 and validation N = 22). Response was defined as endoscopic and histologic healing at 4-6 weeks and 8 weeks, respectively. From the training cohort, genes with RNA expression that significantly correlated with clinical response outcomes were mapped onto the Human Interactome network map of protein-protein interactions to identify a largest connected component (LCC) of proteins indicative of infliximab response status in UC. Expression levels of transcripts within the LCC were fed into a probabilistic neural network model to generate a classifier that predicts inadequate response to infliximab. A classifier predictive of inadequate response to infliximab was generated and tested in a cross-cohort, blinded fashion; the AUC was 0.83 and inadequate response was predicted with a 100% positive predictive value and 64% sensitivity. Genes separately identified from the 2 cohorts that correlated with response to infliximab appeared distinct but mapped onto the same network region of the Human Interactome, reflecting a common underlying biology of response among UC patients. Cross-cohort validation of a classifier predictive of infliximab response status in UC patients indicates that a molecular signature of non-response to TNFi therapies is present in patients' baseline gene expression data. The goal is to develop a diagnostic test that predicts which patients will have an inadequate response to targeted therapies and define new targets and pathways for therapeutic development.

The pathogenesis of ulcerative colitis (UC) is associated with severe inflammation, damaged colonic barriers, increased oxidative stress, and intestinal dysbiosis. The majority of current medications strive to alleviate inflammation but fail to target additional disease pathologies. Addressing multiple symptoms using a single 'magic bullet' remains a challenge. To overcome this, a smart epigallocatechin-3-gallate (EGCG)-loaded silk fibroin-based nanoparticle (NP) with the surface functionalization of antimicrobial peptides (Cathelicidin-BF, CBF) was constructed, which could be internalized by Colon-26 cells and RAW 264.7 macrophages with high efficiencies. The resulting CBF-EGCG-NPs efficiently restored colonic epithelial barriers by relieving oxidative stress and promoting epithelium migration. They also alleviated immune responses through downregulation of pro-inflammatory factors, upregulation of anti-inflammatory factors, M2 macrophage polarization, and lipopolysaccharide (LPS) elimination. Interestingly, oral administration of hydrogel (chitosan/alginate)-embedding CBF-EGCG-NPs could not only retard progression and treat UC, but also modulate intestinal microbiota by increasing their overall diversity and richness and augmenting the abundance of beneficial bacteria (e.g., Firmicutes and Lactobacillaceae). Our work provides a "many birds with one stone" strategy for addressing UC symptoms using a single NP-based oral platform that targets immune microenvironment modulation, LPS clearance, and microbial remodeling.

Crohn's disease is associated with an increased risk of adenocarcinoma of the involved portions of the small bowel and colorectum and has similar risk factors to those described in ulcerative colitis, most significantly, extent of bowel involvement, PSC, and duration of unresected disease. Prevention strategies include risk stratification and secondary prevention with colonoscopic screening and surveillance to identify dysplasia or early-stage cancers, with surgery when needed. There is emerging information to suggest that control of inflammation may provide primary prevention of neoplasia, but further studies are required to test this strategy.

BACKGROUND There is a great unmet need for advanced therapies that provide rapid, robust, and sustained disease control for patients with ulcerative colitis. We assessed the efficacy and safety of upadacitinib, an oral selective Janus kinase 1 inhibitor, as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. METHODS This phase 3, multicentre, randomised, double-blind, placebo-controlled clinical programme consisted of two replicate induction studies (U-ACHIEVE induction [UC1] and U-ACCOMPLISH [UC2]) and a single maintenance study (U-ACHIEVE maintenance [UC3]). The studies were conducted across Europe, North and South America, Australasia, Africa, and the Asia-Pacific region at 199 clinical centres in 39 countries (UC1), 204 clinical centres in 40 countries (UC2), and 195 clinical centres in 35 countries (UC3). Patients aged 16-75 years with moderately to severely active ulcerative colitis (Adapted Mayo score 5-9; endoscopic subscore 2 or 3) for at least 90 days were randomly assigned (2:1) to oral upadacitinib 45 mg once daily or placebo for 8 weeks (induction studies). Patients who achieved clinical response following 8-week upadacitinib induction were re-randomly assigned (1:1:1) to upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 52 weeks (maintenance study). All patients were randomly assigned using web-based interactive response technology. The primary endpoints were clinical remission per Adapted Mayo score at week 8 (induction) and week 52 (maintenance). The efficacy analyses in the two induction studies were based on the intent-to-treat population, which included all randomised patients who received at least one dose of treatment. In the maintenance study, the primary efficacy analyses reported in this manuscript were based on the first 450 (planned) clinical responders to 8-week induction therapy with upadacitinib 45 mg once daily. The safety analysis population in the induction studies consisted of all randomised patients who received at least one dose of treatment; in the maintenance study, this population included all patients who received at least one dose of treatment as part of the primary analysis population. These studies are registered at ClinicalTrials.gov, NCT02819635 (U-ACHIEVE) and NCT03653026 (U-ACCOMPLISH). FINDINGS Between Oct 23, 2018, and Sept 7, 2020, 474 patients were randomly assigned to upadacitinib 45 mg once daily (n=319) or placebo (n=155) in UC1. Between Dec 6, 2018, and Jan 14, 2021, 522 patients were randomly assigned to upadacitinib 45 mg once daily (n=345) or placebo (n=177) in UC2. In UC3, a total of 451 patients (21 from the phase 2b study, 278 from UC1, and 152 from UC2) who achieved a clinical response after 8 weeks of upadacitinib induction treatment were randomly assigned again to upadacitinib 15 mg (n=148), upadacitinib 30 mg (n=154), and placebo (n=149) in the primary analysis population. Statistically significantly more patients achieved clinical remission with upadacitinib 45 mg (83 [26%] of 319 patients in UC1 and 114 [34%] of 341 patients in UC2) than in the placebo group (seven [5%] of 154 patients in UC1 and seven [4%] of 174 patients; p

Background Adolescents and young adults (AYAs) seek increased autonomy and self-efficacy. AYAs must learn to manage their medical care in preparation for transition to adult healthcare. Our team’s research found that AYAs need more information about their disease and treatment Objective To develop and test the usability of a decision tool “iBDecide” to promote shared decision-making among AYAs with ulcerative colitis (UC) who are beginning to manage their treatment and medications Methods Using design thinking, 14 AYAs, 6 healthcare providers, 4 designers, a social worker, and a human factors researcher developed a shared decision-making tool. The System Usability Scale (SUS) assessed usability Results AYAs preferred an application with information on treatment, medication, nutrition, and symptom tracking. A web-based application, ‘iBDecide’, was developed to include these options. SUS results indicated that participants on average “agree” that: ‘they would use iBDecide’ and that ‘it was easy to use and streamlined’. The mean SUS score was 78.25 (+/−12.91), range 70–90 Discussion Including AYAs in tool development helps ensure usability and improves engagement in shared decision-making. Co-designed tools may remove barriers for engagement and skill-building needed for the transition to adult care. Conclusion iBDecide can stimulate AYA engagement in shared decision-making in treating UC.

BACKGROUND & AIMS: SERENE UC (Study of a Novel Approach to Induction and Maintenance Dosing With Adalimumab in Patients With Moderate to Severe Ulcerative Colitis) evaluated the efficacy of higher adalimumab induction and maintenance dose regimens in patients with ulcerative colitis. METHODS: This phase 3, double-blind, randomized trial included induction and maintenance studies, with a main study (ex-Japan) and Japan substudy. Eligible patients (18-75 years, full Mayo score 6-12, centrally read endoscopy subscore 2-3) were randomized 3:2 to higher induction regimen (adalimumab 160 mg at weeks 0, 1, 2, and 3) or standard induction regimen (160 mg at week 0 and 80 mg at week 2); all received 40 mg at weeks 4 and 6. At week 8, all patients were rerandomized 2:2:1 (main study) to 40 mg every week (ew), 40 mg every other week (eow), or exploratory therapeutic drug monitoring; or 1:1 (Japan substudy) to 40 mg ew or 40 mg eow maintenance regimens. RESULTS: In the main study, 13.3% vs 10.9% of patients receiving the higher induction regimen vs standard induction regimen achieved clinical remission (full Mayo score ≤2 with no subscore >1) at week 8 (induction primary end point; P = .265); among week-8 responders, 39.5% vs 29.0% receiving 40 mg ew vs 40 mg eow achieved clinical remission at week 52 (maintenance primary end point; P = .069). In the integrated (main + Japan) population, 41.1% vs 30.1% of week-8 responders receiving 40 mg ew vs 40 mg eow achieved clinical remission at week 52 (nominal P = .045). Safety profiles were comparable between dosing regimens. CONCLUSION: Although primary end points were not met, a >10% absolute difference in clinical remission was demonstrated with higher adalimumab maintenance dosing. Higher dosing regimens were generally well tolerated and consistent with the known safety profile of adalimumab in ulcerative colitis. CLINICALTRIALS: gov, Number: NCT002209456. ispartof: GASTROENTEROLOGY vol:162 issue:7 pages:1891-1910 ispartof: location:United States status: published

Background & Aims The rising incidence of inflammatory bowel disease in regions undergoing Westernization has coincided with the increase in ultra-processed food (UPF) consumption over the past few decades. We aimed to examine the association between consumption of UPFs and the risk of Crohn's disease (CD) and ulcerative colitis (UC). Methods We performed a prospective cohort study of 3 nationwide cohorts of health professionals in the United States—the Nurses' Health Study (1986–2014), the Nurses' Health Study II (1991–2017), and the Health Professionals Follow-up Study (1986–2012). We employed Cox proportional hazards models with adjustment for confounders to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for CD and UC according to self-reported consumption of UPFs. Results The study included 245,112 participants. Over 5,468,444 person-years of follow-up, we documented 369 incident cases of CD and 488 incident cases of UC. The median age at diagnosis was 56 years (range, 29–85 years). Compared with participants in the lowest quartile of simple updated UPF consumption, those in the highest quartile had a significantly increased risk of CD (HR, 1.70; 95% CI, 1.23–2.35; Ptrend = .0008). Among different UPF subgroups, ultra-processed breads and breakfast foods; frozen or shelf-stable ready-to-eat/heat meals; and sauces, cheeses, spreads, and gravies showed the strongest positive associations with CD risk (HR per 1 standard deviation increase in intake, 1.18 [95% CI, 1.07–1.29], 1.11 [95% CI, 1.01–1.22], and 1.14 [95% CI, 1.02–1.27], respectively). There was no consistent association between UPF intake and UC risk. Conclusions Higher UPF intake was associated with an increased risk of incident CD. Further studies are needed to identify specific contributory dietary components.

Endoscopic resection (ER) is feasible for well-circumscribed tumors in patients with ulcerative colitis (UC); however, the specific manner for diagnosis of the tumor border is unclear. We evaluated the efficacy of magnifying endoscopy (ME) for the diagnosis of tumor borders in UC.We analyzed endoscopically or surgically resected tumors in UC patients in whom both chromoendoscopy (CE) and ME were performed, retrospectively. We classified the tumors based on tumor border visibility and evaluated tumor's characteristics and ER outcomes.We examined 100 tumors from 76 UC patients (66 distinct and 34 indistinct on CE). In 22 (65%) indistinct tumors on CE, ME improved the tumor border visibility. Compared with distinct tumors on CE, nonpolypoid and large tumors were more common in indistinct tumors on CE. In indistinct tumors even on ME, flat or depressed morphologies and type V pit were more frequently than in other groups. Sixty-five distinct tumors on CE and 18 distinct tumors on ME alone were treated endoscopically, and their R0 resection rate were 91% and 95% (p 0.99).ME can improve the tumor border visibility in UC, and ER is feasible for tumors whose border can be visualized on ME.

Noninfective drug-related pneumonitis (DRP) is a well-known adverse effect of several drugs: clinical manifestations have mostly an acute/subacute onset and vary from mild to life-threatening. Several DRP cases have been described in patients receiving anti-tumor necrosis factor α, rituximab, and tocilizumab.1,2 To date, only 4 reports of vedolizumab-related pneumonitis have been presented.3-5.

Both tea polysaccharides and selenium have certain remission potential for ulcerative colitis (UC), but few reports focused on natural selenium-containing tea polysaccharides. The purpose of this study was to isolate a selenium-containing tea polysaccharide (ASeTP) and determine its structure and effects on UC. Results showed that ASeTP was primarily composed of three purified, β-pyranoside-linked, protein-binding polysaccharides (SeTP-1, SeTP-2, and SeTP-3) with SeOC, OSeO, and SeO linkages. Specifically, SeTP-1 was a neutral heteropolysaccharide principally composed of mannose, glucose, galactose, xylose, and arabinose, while SeTP-2 and SeTP-3 were acidic heteropolysaccharides due to the existence of glucuronic acid. ASeTP effectively alleviated the symptoms of weight loss, colon shortens, and disease activity index scores increase in dextran sodium sulfate (DSS)-induced colitis mice. ASeTP attenuated the histological damage and maintained the colonic mucosal barrier via up-regulating the expression of occludin, claudin-1, and zona occludens-1 (ZO-1). ASeTP suppressed the levels of pro-inflammatory cytokines and enhanced the antioxidant capacity of colon tissue. Besides, ASeTP beneficially increased the selenium content of the colon. Furthermore, ASeTP remodeled the gut microbiota by accelerating the proliferation of beneficial bacteria and inhibiting pathogenic microorganisms. Thus, ASeTP has the potential to be a functional food against colitis.

The association between ulcerative colitis (UC) and primary sclerosing cholangitis has been described for several years and can be classified as having a distinct disease phenotype from inflammatory bowel diseases (IBD). The simultaneous occurrence of decompensated liver disease requiring liver transplant and active IBD is a management challenge, considering that these patients may be at increased risk of infections, thromboembolic events, bleeding, and drug hepatotoxicity.We describe a case of a 37-year-old patient with UC and sclerosing cholangitis presenting with severe decompensated rectocolitis complicated with thromboembolic phenomena and severe liver dysfunction who underwent liver transplant while using biological therapy to control bowel disease.This case highlights the evolution of sclerosing cholangitis to liver transplant in patients with decompensated UC. Despite the risk of recurrence, primary sclerosing cholangitis has excellent results after liver transplant. Despite the use of immunosuppression after liver transplant, biological therapy may be necessary to control IBD.

Patients with primary sclerosing cholangitis (PSC) commonly undergo ileal pouch-anal anastomosis (IPAA) for medically-refractory ulcerative colitis (UC) or colorectal dysplasia. Pouchitis develops more frequently in patients with PSC, potentially leading to increased morbidity. We aimed to assess clinical characteristics and treatment outcomes for pouchitis in patients with PSC compared to a matched, non-PSC cohort.All patients with PSC who underwent IPAA and were diagnosed with pouchitis (PSC-pouchitis) were identified. A matched cohort composed of non-PSC patients who underwent IPAA for UC and subsequently developed pouchitis (UC-pouchitis) was developed. Relevant demographic, clinical, endoscopic, histologic, and treatment data were collected and compared between groups.Of those with PSC-pouchitis (n=182), 53.9% and 46.1% underwent IPAA for medically-refractory disease and dysplasia, respectively, compared to 88.7% and 11.3% in the UC-pouchitis group (P.001). Patients with PSC-pouchitis were more likely to develop chronic pouchitis (68.1% vs 34.1%; P.001), have moderate-to-severe pouch inflammation (54.9% vs 32.4%; P.001), and prepouch ileitis (34.1% vs 11.5%; P.001) compared to UC-pouchitis. Of those with PSC-pouchitis, 50.6% and 17.6% developed chronic antibiotic-dependent or antibiotic-refractory pouchitis, respectively, compared to 25.8% and 7.7% with UC-pouchitis. There was no difference in treatment response between the two groups with use of thiopurines, anti-tumor necrosis factor agents, and newer biologics.PSC-associated pouchitis presents with a unique clinical phenotype, characterized by increased risk of chronic pouchitis, moderate-to-severe pouch inflammation, prepouch ileitis, and less response to conventional antimicrobial therapy.

The coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, is a new type of acute infectious respiratory syndrome that usually presents with mild flu-like symptoms. However, the disease caused widespread illness and death worldwide, and new sequelae are still being discovered. SARS-CoV-2 RNA was isolated from the fecal samples of some infected patients. Many pathogens, including many viral infections, were linked either to the onset or the exacerbation of inflammatory bowel disease (IBD). With this, we report a series of 2 IBD cases that were diagnosed shortly after recovery from COVID-19. This is the first report that discusses the possibility of developing IBD following COVID-19 infection to the best of our knowledge. This could highlight the importance of thoroughly investigating COVID-19 patients who presented with diarrhea, particularly those with bloody diarrhea, and not consider it a simple manifestation of COVID-19 infection.

50% to 80% Crohn's disease (CD) and 10% to 30% ulcerative colitis (UC) patients require surgery over their lifetime. Biologic therapies may alter this natural history, but data on the effect of biologics on surgery rates in this patient population are mixed. We sought to investigate the influence of biologics on surgery prevalence in CD and UC.We used a commercial database (Explorys Inc, Cleveland, OH), which includes electronic health record data from 26 major integrated US healthcare systems. We identified all patients who were diagnosed with CD or UC that were treated with any biologics between 2015 and 2020. The primary outcome was to examine the association between biologics therapy and the prevalence of bowel resection. Also, we identified the factors associated with surgery in IBD patients on biologics.Of 32,904,480 patients in the database, we identified 140,540 patients with CD and 115,260 patients with UC, of whom 25,840 (18%) and 9,050 (7.8%) patients received biologics, respectively. The prevalence of intestinal resection was significantly lower in biologics-treated CD patients (9.3%) compared to those who did not receive biologics (12.1%) (p.001). Similarly, biologic-treated UC patients were significantly less likely to undergo colectomy (7.3%) compared to UC patients who did not receive biologic therapy (11.0%) (p.001). Tobacco use, Clostridium difficile infection, and perianal disease were associated with intestinal resection in CD. Colon neoplasm and Clostridium difficile infection were associated with colectomy in UC.In this study of a large healthcare administrative database, inflammatory bowel disease (IBD) patients treated with biologics were significantly less likely to undergo bowel resection when compared to those who never received biologics. This data suggests that biologics may impact surgical rates in IBD.

Background and aimsPost-colonoscopy colorectal cancers (PCCRCs) account for up to 50% of colorectal cancers (CRCs) in patients with inflammatory bowel disease (IBD). We investigated characteristics of IBD patients with PCCRC and their survival.MethodsWe identified IBD patients (ulcerative colitis [UC] and Crohn’s Disease [CD]) diagnosed with CRC from 1995 to 2015. We defined PCCRC as diagnosed between 6 and 36 months, and detected CRC (dCRC) as diagnosed within 6 months after colonoscopy. We computed prevalence ratios (PRs) comparing PCCRC vs. dCRC and followed patients from the diagnosis of PCCRC/dCRC until death, emigration, or study end. Mortality was compared using Cox proportional hazards regression models adjusted for sex, age, year of CRC diagnosis, and stage. The main analyses focused on patients with UC.ResultsAmong 23,738 UC patients undergoing colonoscopy, we identified 352 patients with CRC, of whom 103 (29%) had PCCRC. Compared with dCRC, PCCRC was associated with higher prevalence of metastatic cancer (33% vs. 20%; PR: 1.64, 95% confidence interval [CI]: 1.13-2.38), cancers exhibiting mismatch repair deficiency (79% vs. 56%; PR: 1.40, 95% CI: 1.13-1.72), and proximally located cancers (54% vs. 40%; PR: 1.34, 95% CI: 1.06-1.69). The one- and five -year adjusted hazard ratios (HRs) of death for PCCRC vs. dCRC among UC patients were 1.29 (95% CI: 0.77-2.18) and 1.24 [95% CI: 0.86-1.79), respectively.ConclusionThe characteristics of UC-related PCCRC suggest tumor biology as an important factor in the progression to cancer. However, the prognosis of PCCRC appears similar to that of dCRC.

Short- and long-term treatment targets in inflammatory bowel diseases (IBDs) evolved during the last decade, shifting from symptom control to endoscopic healing and patient-centered parameters. The STRIDE-II consensus placed these targets on a timeline from initiating treatment and introduced additional targets, normalization of serum and fecal biomarkers, restoration of quality of life, prevention of disability, and, in children, restoration of growth. Transmural healing in Crohn's disease and histologic healing in ulcerative colitis currently serve as adjunct measures to gauge remission depth. However, whether early treatment according to a treat-to-target paradigm affects the natural course of IBD remains unclear, leading to the need for prospective disease-modification trials. The SPIRIT consensus defined the targets for these trials to assess the long-term impact of early treatment on quality of life, disability, disease complications, risk of neoplastic lesions, and mortality. As further data emerge about the risk-benefit balance of aiming toward deeper healing, the targets in treating IBDs may continue to shift.

Background and Aims Despite increasing interest in histologic remission as a treatment target in ulcerative colitis (UC), the accuracy of histologic findings in left colon in detecting pancolonic histologic remission is unknown. Methods In a retrospective cohort study of patients with endoscopically active pancolitis undergoing treat-to-target interventions, we evaluated the diagnostic accuracy of left-sided (distal to splenic flexure) histologic and endoscopic findings on colonoscopy for detecting histologic and endoscopic healing elsewhere in the colon. Results Of 86 patients with moderate to severely active pancolitis who underwent 2 consecutive colonoscopies during treat-to-target interventions, 38% and 51% achieved histologic and endoscopic remission, respectively. Substantial agreement (kappa, 0.67; 95% confidence interval (CI), 0.51-0.83) was observed in histologic findings between left and right colon on follow-up colonoscopy. Histologic, and endoscopic, findings in left colon showed excellent accuracy in detecting pancolonic histologic remission (area under the curve (AUC), 0.96 [95% CI, 0.93-1.0]; misclassification rate, 5.9%), histologic normalization (AUC, 1.0, 0%), endoscopic improvement (AUC, 0.95 [0.96-1.0], 3.5%) and endoscopic remission (AUC, 0.98 [0.96-1.00], 5.8%), respectively. Conclusions In patients with active pancolitis undergoing treat-to-target interventions, histologic and endoscopic findings in the left colon on colonoscopy have excellent accuracy for detecting pancolonic histologic remission, histologic normalization, endoscopic improvement, and endoscopic remission. Flexible sigmoidoscopy may suffice for monitoring histologic and endoscopic activity in patients with pancolitis.

BACKGROUND: Disability in patients with medically refractory ulcerative colitis (UC) after total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) is not well understood. The aim of this study was to compare disability in patients with IPAA vs medically managed UC, and identify predictors of disability. METHODS: This was a multi-center cross-sectional study performed at five academic institutions in New York City. Patients with medically or surgically treated UC were recruited. Clinical and socioeconomic data were collected and the inflammatory bowel disease disability index (IBD-DI) was administered to eligible patients. Predictors of moderate-severe disability (IBD-DI≥35) were assessed in univariable and multivariable models. RESULTS: A total of 94 patients with IPAA and 128 patients with medically managed UC completed the IBD-DI. Among patients with IPAA and UC, 35 (37.2%) and 30 (23.4%) had moderate-severe disability, respectively. Patients with IPAA had significantly greater IBD-DI scores compared to patients with medically managed UC (29.8 vs 17.9, p

Ulcerative colitis (UC) has been characterized by inflammation limited to the mucosa. Although sustained and durable remission has been associated with mucosal healing, the recurrent phenomenon of persistent clinical disease activity despite mucosal healing has been observed in clinical practice and across pivotal trials. Over time, UC appears to confer an increased risk of progression, defined as changes of disease phenotype; adverse transmural effects on the bowel wall; increased risk of neoplasia development; worsening colorectal function; and increased risk of colectomy, hospitalizations, and other extraintestinal comorbidities. Although the treatment paradigm for Crohn's disease has shifted toward early aggressive intervention to prevent disease progression and irreversible bowel damage, such urgency in efforts to halt disease progression in UC have been largely overlooked. This review summarizes the multiple facets of UC contributing to a modified perception of the disease as a progressive one. We propose further study of the natural history and priorities for further treatment goals that include these considerations.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder of the gastrointestinal tract. Although the pathophysiology of IBD is multifaceted, ubiquitination, a post-translational modification, has been shown to have essential roles in its pathogenesis and development. Ubiquitin-modifying enzymes (UMEs) work in synergy to orchestrate the optimal ubiquitination of target proteins, thereby maintaining intestinal homeostasis. Genome-wide association studies (GWAS) have identified multiple UME genes as IBD susceptibility loci, implying the importance of UMEs in IBD. Furthermore, accumulative evidence demonstrates that UMEs affect intestinal inflammation by regulating various aspects, such as intestinal barrier functions and immune responses. Considering the significant functions of UMEs in IBD, targeting UMEs could become a favorable therapeutic approach for IBD.

Early diagnosis and the optimal control of inflammation, with a continuous cycle of assessment, treatment, monitoring, and adjustment of therapy, is best practice for the management of inflammatory bowel disease. However, patients express frustration with ongoing challenging symptoms, often discordant with inflammation, including abdominal pain, fatigue, depression, anxiety, and emotional wellness; these are often not optimally addressed by inflammatory bowel disease clinicians due to lack of time or resources. This review will highlight the burden of these symptoms and issues, suggest ways of assessing these in clinical practice, highlight the importance of acknowledging and validating the symptoms and issues with patients, reassuring them that they are being heard, and discuss different possible models of service delivery for psychosocial support, from fully integrated gastropsychology models to referral pathways that optimize community support. We suggest the importance of the treat-to-target concept, where the target is not only control of inflammation but also emotional wellness.

Background Pediatric inflammatory bowel disease (IBD) carries significant morbidity and requires extensive medical and often surgical intervention. The aim of this study was to evaluate the impact of a dedicated Multidisciplinary clinic on the outcomes of children with IBD. Methods A retrospective review of a prospective database, established to track quality and outcomes of children undergoing an abdominal operation for IBD, was performed. Children who were managed before (09/2017–03/2019) and after (04/2019–06/2020) establishment of the multidisciplinary clinic were examined. The clinic instituted several care process protocols including early recovery (ERAS) and garnered additional resources for patients (wound ostomy, nutrition, social work, etc.) Primary outcomes were unanticipated return to the operating room, length of stay, ER visits within 30 days of surgery and hospital readmissions within 30 days of surgery. Results We identified 41 children who underwent a total of 80 major abdominal operations; 46.3% of procedures occurred before and 53.7% occurred after instituting our clinic. There were no notable changes in disease distribution (e.g., ulcerative colitis vs. Crohn's), disease severity, medication exposure, or case urgency (elective vs. emergent). ER visits within 30 days of surgery decreased (4 (9.3%) vs. 10 (27%), p = 0.04) as did readmissions within 30 days of surgery (1 (2.3%) vs. 9 (24.3%), p = 0.005). Conclusions Implementation of a dedicated multidisciplinary clinic for IBD and its attendant focus on protocols and appropriate use of adjunctive resources was associated with decreased emergency department visits and hospital readmissions in the post-operative setting. Level of evidence : III

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease that typically affects middle-aged men with ulcerative colitis (UC). However, recent studies point out to epidemiological changes. Our aim was to determine if the epidemiology, clinical course and outcome of patients with PSC followed at a reference hepatology center resemble what is described in the literature.Retrospective search of patients with a diagnosis of PSC treated in our center between 2000 and 2019.Cohort of 55 patients (mean age: 37 years), 44% women. Most were large duct type (79%). Most diagnoses were made after 2011. At time of diagnosis, 63% of patients were asymptomatic. The median time from suspicion to diagnosis was 2 years. After a mean follow-up time of 7 years, one third developed cirrhosis, and 25% required liver transplantation (LT); among these, the disease recurred in almost half. Inflammatory bowel disease (IBD) was present in 45%, especially UC. Although statistical significance was not reached, PSC in women was characterized by higher rate of asymptomatic presentation and more frequent association with UC versus other forms of IBD. Women also had more frequently cirrhosis at diagnosis and required LT more often than men.The epidemiology of PSC is changing. The number of women affected is greater than what was expected from the literature, with a recent increase in incidence. There seems to be differences between sexes in the form of presentation and disease course that should be confirmed in subsequent studies.

Background and aims Inflammatory bowel diseases (IBD) are chronic conditions that may be accompanied by autoimmune liver disease (AILD), most commonly primary sclerosing cholangitis (PSC). The objective of this study was to evaluate the behaviour of patients with IBD associated with AILD and compare a PSC group with a non-PSC group. Methods Medical records of patients with IBD associated with PSC, autoimmune cholangitis, primary biliary cholangitis, small-duct PSC, autoimmune hepatitis (AIH) and overlapping syndromes were assessed. Results Fifty-four patients were included: 48 (88.9%) had ulcerative colitis and six (11.1%) had Crohn's disease; 35 (64.8%) had PSC and 19 (35.2%) did not have PSC. There was no difference in outcomes (surgical treatment for IBD, liver transplantation or death) between the groups. Time since the diagnosis of IBD was associated with surgical treatment of IBD (p = 0.041; OR: 1.139, 95% CI: 1.006–1.255). Time since the diagnosis of AILD (p = 0.003; OR: 1.259, 95% CI: 1.1–1.396), as well as portal hypertension at diagnosis (p = 0.014; OR: 18.22, 95% CI: 1.815–182.96), were associated with liver transplantation. In addition, previous diagnosis of AIH was associated with de novo IBD (p = 0.012; OR: 7.1, 95% CI: 1.215–42.43). Conclusion Both groups had similar disease behaviour. A longer time since the diagnosis of IBD increased the risk for surgical treatment (13.9%/year). A 25.9%/year increase in liver transplantation was observed after the diagnosis of AILD, which was increased 18.22 times by the presence of portal hypertension. In addition, the diagnosis of AIH was associated with an increase in the number of diagnoses of de novo IBD (7.1).

Background We conducted a questionnaire-based study of pouch function, quality of life, sexual function, and fertility among patients who had undergone ileal pouch anal anastomosis (IPAA) in childhood and who are now over 18 years old. Methods A consecutive series of patients were asked to complete the following questionnaires: Pouch Function Score (PFS), Short Form 36 (SF-36), International Index of Erectile Function (IIEF) (males), and Female Sexual Function Index (FSFI) (females). Fertility in females was also assessed. Data are quoted as a median (SD). Results Of 144 patients who had IPAA, 101 were eligible, and 70 responded. Mean age at surgery was 14 years, and mean current age is 26 years. Most patients had either ulcerative colitis or familial adenomatous polyposis. The questionnaire was completed by 38/70 (54%). Median PFS score was 6 (5). SF-36 were lower than previous reports. Median FSFI was 30 (7.6), 84% of possible maximum. Median IIEF was 69, 92% of possible maximum. Successful conception was reported in 5/7 women who had tried. However, there were several miscarriages and two surgical emergencies during pregnancies. Conclusions IPAA can be performed in childhood with similar pouch function to reported adult series. Quality of life appears poorer, but sexual function is maintained. There may be an association with adverse events in pregnancy.

Treatment goals in ulcerative colitis have shifted from clinical remission to mucosal healing, and more recently, to histological remission.1,2 Treating patients with healed mucosae has been shown to be beneficial.3 Clinical, endoscopic, and histological findings do not necessarily correlate with each other.4.

Lymphoproliferative disorder (LPD) can occur in patients with inflammatory bowel disease (IBD) such as ulcerative colitis (UC) and Crohn's disease (CD). On rare occasions, patients with IBD develop myeloid neoplasms; however, the frequency and clinicopathological features of IBD-associated lymphoid and myeloid proliferative disorder (LMPD) in Japanese patients are still unclear. In this study, we reviewed 2474 Japanese patients with IBD and found that LMPD occurred in 12 (0.5%) patients with UC (n = 7) or CD (n = 5). Together with an additional 3 cases, we analyzed a total of 15 cases of LMPD for clinicopathological and histological features. Based on the status of using immunosuppressants such as biologics and immunomodulators, Epstein-Barr virus (EBV) infection, and histopathology, the 15 cases were classified into Group I (high-grade LPD; n = 7), Group II (low-grade LPD; n = 5), and Group III (myeloid neoplasms; n = 3). Most patients in Group I were undergoing strong immunosuppressive therapy, and the LPD lesions corresponded to high-grade B-cell or T cell/natural killer cell lymphoma often with EBV infection. Discontinuation of immunosuppressive drugs alone did not resolve these LPDs; Group I patients required chemotherapy, and eventually 4 of them (57%) died of the tumor. Most cases in Group II were low-grade B-cell lymphoma without EBV infection and had an indolent clinical course with excellent prognosis. All patients in Group III developed acute myeloid leukemia (AML) during the course of CD. Two (67%) of these patients died of AML. Our study suggests that IBD-associated LMPD is very rare but can follow an aggressive clinical course.

Item does not contain fulltext BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment. FINDINGS: Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the etrolizumab group and 43 [22%] in the infliximab group). More patients in the etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment. INTERPRETATION: To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, etrolizumab performed similarly to infliximab from a clinical viewpoint. FUNDING: F Hoffmann-La Roche.

Background and Aims Starting biologic treatment early in the course of inflammatory bowel disease (IBD) may be associated with higher efficacy, especially in Crohn's disease (CD). Methods This was a systematic review and individual-patient data meta-analysis of all placebo-controlled trials of biologics approved for IBD at study inception (October 2015), using Vivli data-sharing platform. The primary outcome was the proportional biologic/placebo treatment effect on induction of remission in patients with short-duration (≤18 months) vs long-duration disease (>18 months) analyzed separately for CD and ulcerative colitis (UC). We used meta-regression to examine the impact of patients' characteristics on the primary outcome. Results We included 25 trials, testing infliximab, adalimumab, certolizumab, golimumab, natalizumab, or vedolizumab (6168 patients with CD and 3227 patients with UC). In CD, remission induction rates were higher in pooled placebo and patients in active arms with short-duration disease of ≤18 months (41.4% [244 of 589]) compared with disease duration of >18 months (29.8% [852 of 2857], meta-analytically estimated odds ratio, 1.33; 95% confidence interval, 1.09–1.64). The primary outcome, proportional biologic/placebo treatment effect on induction of remission, was not different in short-duration disease of ≤18 months (n = 589, odds ratio, 1.47; 95% confidence interval, 1.01–2.15) compared with longer disease duration (n = 2857, odds ratio, 1.43; 95% confidence interval, 1.19–1.72). In UC trials, both the proportional biologic/placebo remission-induction effect and the pooled biologic-placebo effect were stable, regardless of disease duration. Primary outcome results remained unchanged when tested using alternative temporal cutoffs and when modeled for individual patient's covariates, including prior anti–tumor necrosis factor exposure. Conclusions There are higher rates of induction of remission with biologics and with placebo in early CD, resulting in a treatment to placebo effect ratio that is similar across disease durations. No such relationships between disease duration and outcomes was found in UC. PROSPERO registration: CRD42018041961.

Background and Aims We conducted a retrospective cohort study comparing the risk of serious infections between patients treated with tumor necrosis factor-a (TNFa) antagonists vs. vedolizumab in patients with inflammatory bowel diseases (IBD). Methods Using an administrative claims database, we identified patients with IBD who were new-users of either TNFa antagonists or vedolizumab between 2014-2018 and had insurance coverage for at least 1y before and after treatment initiation. We compared the risk of serious infections (infections requiring hospitalization) between patients treated with vedolizumab or TNFa antagonists using marginal structural Cox proportional hazard models adjusted for baseline disease characteristics, healthcare utilization, comorbidities, and time-varying use of corticosteroids, immunomodulators and opiates. Results We included 4881 patients treated with TNFa antagonists (age, 41 ± 15y, 60% with Crohn’s disease [CD]) of whom 434 developed serious infections over 5786 person-year [PY] follow-up, and 1106 patients treated with vedolizumab (age, 44 ± 16y, 39% with CD) of whom 86 developed serious infections over 1040-PY follow-up. Vedolizumab was associated with 46% lower risk of serious infections as compared with TNFa antagonists in patients with ulcerative colitis (HR,0.54 [95% CI,0.35-0.83), but no significant differences were observed in patients with CD (HR,1.30 [0.80-2.11]). Vedolizumab was associated with lower risk of extra-intestinal serious infections in patients with UC, but higher risk of gastrointestinal serious infections in patients with CD. Conclusions In an observational study of patients with IBD, vedolizumab was associated with lower risk of serious infections as compared with TNFa antagonists, in patients with UC, but not in patients with CD.

Background Several observational studies on Tofacitinib (TOFA) in ulcerative colitis (UC) have been published over the last 2 years. Aims To estimate effectiveness and safety of TOFA arising from real-world experience. Methods PubMed Central/Medline and Embase were systematically searched for real-world observational studies on TOFA for the treatment of UC through November 2020. Results Seven studies comprising 759 patients met the inclusion criteria. The pooled estimate rates were 49% for clinical response, 40% for clinical remission, and 34% for corticosteroid-free clinical remission at induction, while the rates of endoscopic response and endoscopic remission were 37% and 19%, respectively. At maintenance, the pooled estimate rates of clinical response, clinical remission, and corticosteroid-free clinical remission were 36%, 35%, and 24%, respectively. The pooled estimate of incidence rate of adverse events was 53.0 per 100 person-years (PY), while the pooled estimate of incidence rate of withdrawal of TOFA due to adverse events was 9.3 per 100 PY, with a pooled rate of infections of 17.6 per 100 PY. Conclusions Cumulative analysis of data from real-world studies confirmed the good efficacy of TOFA in UC shown by randomized controlled trials for both induction and maintenance, while the safety profile was consistent with previous reports.

As a fat-soluble carotenoid, astaxanthin has excellent antioxidant and anti-inflammation biological activities, but its poor biocompatibility and low stability limit application of astaxanthin in the food industry. In this study, cauliflower-like carriers (CCs) were constructed based on caseinate, chitosan-triphenylphosphonium (TPP) and sodium alginate through an electrostatic self-assembly method to improve the biocompatibility, stability and targeting transport properties of astaxanthin. The smart CCs showed pH-response release and mitochondrial targeted characteristics. In vitro studies demonstrated that the CCs could improve the internalization of astaxanthin, and significantly inhibited the excessive production of reactive oxygen species and the depolarization of mitochondrial membrane potential caused by oxidative stress. In vivo studies revealed that the astaxanthin-loaded CCs could effectively relieve the colitis induced by dextran sodium sulfate and protect the integrity of the colon tissue structure. The astaxanthin-loaded CCs could significantly inhibit the expression of inflammation factors such as interleukin-1β, interleukin-6, tumor necrosis factor alpha, cyclooxygenase-2, myeloperoxidase, inducible nitric oxide synthase, and nitric oxide. Moreover, the astaxanthin-loaded CCs could maintain the expression of zonula occludens-1, increase the abundance of Firmicutes and Lactobacillaceae in the intestine. In a word, the constructed astaxanthin delivery system provided a potential application for the oral uptake hydrophobic bio-activator in intervention of ulcerative colitis.

Summary Background There is a growing armamentarium for the treatment of moderate-to-severe ulcerative colitis. We aimed to compare the relative efficacy and safety of biologics and small molecule drugs for the treatment of patients with moderate-to-severe ulcerative colitis. Methods In this systematic review and network meta-analysis, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials without language restrictions for articles published between Jan 1, 1990, and July 1, 2021. Major congresses' databases from Jan 1, 2018, to July 3, 2021, were reviewed manually. Phase 3, placebo-controlled or head-to-head randomised controlled trials (RCTs) assessing the efficacy and safety of biologics or small molecule drugs as induction or maintenance therapies for patients with moderate-to-severe ulcerative colitis were included. Phase 2 RCTs were excluded because of their small sample sizes and inclusion of doses not further explored in phase 3 RCTs. Summary data from intention-to-treat analyses were extracted from included reports by JSL and PAO. The primary outcome was the induction of clinical remission. A network meta-analysis was done under the frequentist framework, obtaining pairwise odds ratios (ORs) and 95% CIs. The surface under the cumulative ranking (SUCRA) was used to rank the included agents for each outcome. Higher SUCRA scores correlate with better efficacy, whereas lower SUCRA scores correlate with better safety. Maintenance data on efficacy for treat-straight-through and randomised responder trials are also presented. This study is registered with PROSPERO, CRD42021225329. Findings Our search yielded 5904 results, from which 29 studies (four being head-to-head RCTs) fulfilled our inclusion criteria and were included. Of these, 23 studies assessed induction therapy with either a biologic or small molecule drug, comprising 10 061 patients with ulcerative colitis. A risk of bias assessment showed a low risk of bias for most of the included studies. Upadacitinib was significantly superior to all other interventions for the induction of clinical remission (infliximab [OR 2·70, 95% CI 1·18–6·20], adalimumab [4·64, 2·47–8·71], golimumab [3·00, 1·32–6·82], vedolizumab [3·56, 1·84–6·91], ustekinumab [2·92, 1·31–6·51], etrolizumab [4·91, 2·59–9·31], tofacitinib [2·84, 1·28–6·31], filgotinib 100 mg [6·15, 2·98–12·72], filgotinib 200 mg [4·49, 2·18–9·24], and ozanimod (2·70, 1·18–6·20), and ranked highest for the induction of clinical remission (SUCRA 0·996). No differences between active interventions were observed when assessing adverse events and serious adverse events. Vedolizumab ranked lowest for both adverse events (SUCRA 0·184) and serious adverse events (0·139), whereas upadacitinib ranked highest for adverse events (0·843) and ozanimod ranked highest for serious adverse events (0·831). Interpretation Upadacitinib was the best performing agent for the induction of clinical remission (the primary outcome) but the worst performing agent in terms of adverse events in patients with moderate-to-severe ulcerative colitis. Vedolizumab was the best performing agent for safety outcomes. With the paucity of direct comparisons in the published literature, our results might help clinicians to position drugs in treatment algorithms. Funding None.

Background Proctocolectomy with ileal pouch-anal anastomosis is the standard surgical procedure for ulcerative colitis refractory to medical treatment. In a few cases, ileal pouch-anal anastomosis cannot be completed due to intraoperative technical problems. The aim of this single-center study was to identify risk factors for a technically failed ileal pouch-anal anastomosis. Methods In total, 391 patients with ulcerative colitis who received ileal pouch-anal anastomosis were identified. Clinical and perioperative data from patients with successful ileal pouch-anal anastomosis (IPAA+) were compared to data from failed ileal pouch-anal anastomosis (IPAA-). Definition of failed ileal pouch-anal anastomosis was intraoperative failure to perform ileal pouch-anal anastomosis. Risk factors for failed ileal pouch-anal anastomosis were assessed by logistic regression. Cut-off values were calculated on the basis of receiver operating characteristic curves and the Youden Index. Results The rate of failed ileal pouch-anal anastomosis was 26 of 391 (6.6%). In 22 of 26 cases (84.6%), there was an insufficient length of the small intestinal mesentery. Patients with failed ileal pouch-anal anastomosis were more often male (80.8% vs 54.5%, P = .009), older (47.1 ± 14.1 vs 39.2 ± 12.8 years, P = .007), had a higher body mass index 27.2 ± 4.5 vs 23.7 ± 4.3 kg/m2, P Conclusion Technical failure of ileal pouch-anal anastomosis is elevated in patients with higher body mass index, with refractory ulcerative colitis, and/or extended immunosuppressive medication. Three-staged ileal pouch-anal anastomosis and optimizing preoperative conditions may help to elevate the rate of successful ileoanal pouch construction in these patients.

The dietary management of active ulcerative colitis (UC) is currently poorly understood. Due to the lack of clinical guidelines for this population, diet choice may be based on the personal judgement of the clinician, and without sound evidence. The aim of this systematic review was to appraise the current literature on the dietary management of individuals with active UC, in both inpatient and outpatient settings, to determine if clinical outcomes differ by diet prescription.PUBMED, CINAHL, EMBASE, Web of Science and SCOPUS were comprehensively searched during March and April 2020. Eligible trials recruited adults with active UC comparing different methods of dietary management, including enteral nutrition (EN), total parenteral nutrition (TPN), elimination diets and standard oral diets, in both the inpatient and outpatient settings.10 studies met inclusion criteria of this qualitative synthesis. No difference was found between EN, TPN and bowel rest in terms of disease activity measures when compared to a standard oral diet. The results of this study also showed promising potential for the use of elimination diets in the outpatient setting with four studies finding a significant difference in disease activity measures between the intervention diet and control.There is no strong evidence to support the use of any specific dietary prescription to improve clinical outcomes for individuals with active UC. A number of low quality studies suggest benefit of following an elimination diet, however, additional high quality studies are required before any more specific recommendations can be made.

Curative surgery for ulcerative colitis can be subdivided into restorative (with pouch and anastomosis) and non-restorative operations. Restorative surgery in older adults is controversial, due to concerns about surgical risk and long-term functional outcome. The goal of this study is to compare 30-day outcomes for restorative and non-restorative surgery in older adults with ulcerative colitis.Data were obtained from the American College of Surgeons National Surgical Quality Initiative Program from 2012-2018. Patients were included if they were65 years old and had ulcerative colitis. Restorative and non-restorative surgeries were defined with procedure codes. Patient characteristics and adverse surgical outcomes were compared between restorative and non-restorative surgeries utilizing chi-square tests and Fisher's exact tests. Multivariate logistic regression models were constructed to evaluate the association of restorative versus non-restorative surgery with adverse surgical outcomes while adjusting for potential confounders.Of 392 total patients, 95 had restorative and 297 had non-restorative surgery. Patients undergoing restorative surgery, compared to non-restorative surgery, were significantly younger (P0.01), had lower incidences of steroid usage (P0.001) and higher rates of readmission (P = 0.02). There were no differences in post-operative complications between the groups in both unadjusted analyses and covariate-adjusted regression analysis (P0.05).In carefully selected older patients with ulcerative colitis, restorative surgery is associated with increased readmission, but otherwise similar rates of morbidity or mortality compared to non-restorative surgery. Data regarding postoperative functional outcome and quality of life are also needed to help select the most appropriate curative option for older adults.