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Intestinal fibrosis is a significant complication of Crohn's disease (CD). Gut microbiota reactive Th17 cells are crucial in the pathogenesis of CD; however, how Th17 cells induce intestinal fibrosis is still not completely understood.In this study, T-cell transfer model with wild-type (WT) and AregAlthough Th1 and Th17 cells induced intestinal inflammation at similar levels when transferred into TcrβxδThese findings reveal that Th17-derived AREG promotes intestinal fibrotic responses in experimental colitis and human patients with CD. Thereby, AREG might serve as a potential therapeutic target for fibrosis in CD.

Sustained, transmural inflammation of the bowel wall may result in the development of a fistula in Crohn's disease (CD). Fistula formation is a recognized complication and cause of morbidity, occurring in 40% of patients with CD. Despite advanced treatment, one-third of patients experience recurrent fistulae. Development of targeting treatment for fistulae will be dependent on a more in depth understanding of its pathogenesis. Presently, pathogenesis of CD-associated fistulae remains poorly defined, in part due to the lack of accepted in vitro tissue models recapitulating the pathogenic cellular lesions linked to fistulae and limited in vivo models. This review provides a synthesis of the existing knowledge of the histopathological, immune, cellular, genetic, and microbial contributions to the pathogenesis of CD-associated fistulae including the widely accredited contribution of epithelial-to-mesenchymal transition, upregulation of matrix metalloproteinases, and overexpression of invasive molecules, resulting in tissue remodeling and subsequent fistula formation. We conclude by exploring how we might utilize advancing technologies to verify and broaden our current understanding while exploring novel causal pathways to provide further inroads to future therapeutic targets.

International audience; BACKGROUND: Use of a combination of targeted therapies (COMBIO) in patients with refractory/overlapping immune-mediated inflammatory diseases (IMIDs) has increased, but reported data remain scarce. We aimed to assess effectiveness and safety of COMBIO in patients with IMIDs. METHODS: We conducted a French ambispective multicenter cohort study from September 2020 to May 2021, including adults' patients with 1 or 2 IMIDs and treated at least 3-month with COMBIO. RESULTS: Overall, 143 patients were included. The most common IMIDs were Crohn's disease (63.6%), axial spondyloarthritis (37.7%), and ulcerative colitis (14%). Half of patients had only one IMID, of which 60% were Crohn's disease. Mean duration of COMBIO was 274.5±59.3 weeks, and COMBIO persistence at 104 weeks was estimated at 64.1%. The most frequent COMBIOs combined anti-TNF agents with vedolizumab (30%) or ustekinumab (28.7%). Overall, 50% of patients achieved significant and 27% mild-to-moderate improvement in patient-reported outcomes. Extended duration of COMBIO (aOR=1.09; 95% CI: 1.03-1.14; p=0.002) and diagnoses of two IMIDs (aOR=3.46; 95%CI: 1.29-9.26; p=0.013) were associated with significant improvement in patient-reported outcomes. Incidence of serious infection during COMBIO was 4.51 per 100 person-years (95% CI 2.20-8.27) and 5 COMBIOs were discontinued due to adverse events. CONCLUSIONS: COMBIO can be effective and safe in patients with refractory/overlapping IMIDs.

Strictures are among the most frequent complications in patients with Crohn's disease (CD), usually requiring a combined medical, surgical, and/or endoscopic approach to treatment. Currently, endoscopic balloon dilation (EBD) is the endoscopic treatment of choice, but its effectiveness is not universal, especially in the long term, and it is not free of complications. The technological evolution of stents in recent years has allowed their use in benign diseases of any origin and location, including inflammatory bowel disease (IBD). The current scientific evidence regarding the use of stents in strictures in IBD is limited and it should not be considered the first option in endoscopic treatment. Self-expandable metal stents (SEMS), but no biodegradable stents (BS), can work in cases that are refractory to anterior endoscopic treatment with EBD, in cases in which EBD is not possible, and in cases with strictures of greater length.

Gastrointestinal endoscopy provides detailed information for diagnosis, differential diagnosis, and disease monitoring and delivers therapy for inflammatory bowel disease. Inflammatory bowel diseases are associated with complications such as strictures, gastrointestinal hemorrhage, fistula, perforation, and abscesses. Endoscopic intervention is a valid therapeutic modality for intestinal strictures and other morbidities. The multisegmental involvement of Crohn's disease, surgically altered bowel anatomy, and the postoperative extensive adhesions have made conventional diagnostic and therapeutic enteroscopy difficult. Intraoperative enteroscopy offers a feasible option for diagnosis and therapy. We report intraoperative enteroscopy in the management of small intestinal strictures and other intestinal morbidities.

Stricture is one of the main complications of Crohn's disease (CD). Among the main conservative therapeutic alternatives, endoscopic balloon dilation (EBD) of the strictures stands out, which can improve the symptoms and delay or even avoid the need for more surgeries. The main aim of this study was to evaluate the efficacy of the EBD in CD patients with post-surgical anastomotic strictures from a previous surgery.An observational study of a cohort of 32 patients with CD who underwent EBD due to uncomplicated strictures at a tertiary hospital, since 2009. Demographic, clinical and disease variables, medical treatments and previous surgeries and types, analytical variables at the time of dilation, number of dilations, complications and need for subsequent surgery were collected by searching data in clinical records.Thirty-two patients were included, performing a total of 63 endoscopic dilations. A technical success of 63.5%, a therapeutic success by dilation of 58.75% and a therapeutic success per patient of 62.5% were achieved. Regarding complications, the percentage of post-dilation adverse events was 3.2% and post-dilation incidents were 4.8%. Thirty EBD did not need any medical treatment modification, 9 EBD remained untreated and 12 EBD required further surgery. The length of the strictures, but not the ongoing treatment, was the only statistically significant factor of therapeutic success by dilation and per patient.EBD seems a safe technique in short post-surgical strictures, can avoid the need for new surgery and prevents unnecessary immunosuppression in patients with CD anastomotic strictures.

Crohn disease (CD) patients can develop fistula or abscess from persistent active disease or postsurgical complications. Penetrating CD is traditionally treated with medication and surgery. The role of medication alone in the treatment of fistula is limited, except perianal fistulas or enterocutaneous fistula. Surgery is the standard treatment in those with hollow-organ to hollow-organ fistula, like ileovesicular fistula. Surgery is invasive with a higher risk of postoperative complications. Endoscopic therapy has evolved as a valid option. Fistulotomy, surgical or endoscopic, should be considered first-line therapy when feasible. Incision and drainage of perianal abscesses with an endoscopic device may be attempted.

Background Intestinal fibrosis and subsequent stricture formation represent frequent complications of Crohn’s disease (CD). In many organs, fibrosis develops as a result of epithelial to mesenchymal transition (EMT). Recent studies suggested that EMT could be involved in intestinal fibrosis as a result of chronic inflammation. Here, we investigated whether EMT might be involved in stricture formation in CD patients. Methods Human colonic tissue specimens from fibrotic areas of 18 CD and 10 non-IBD control patients were studied. Immunohistochemical staining of CD68 (marker for monocytes/macrophages), transforming growth factor-β1 (TGFβ1), β-catenin, SLUG, E-.cadherin, α-smooth muscle actin and fibroblast activation protein (FAP) were performed using standard techniques. Results In fibrotic areas in the intestine of CD patients, a large number of CD68-positive mononuclear cells was detectable suggesting an inflammatory character of the fibrosis. We found stronger expression of TGFβ1, the most powerful driving force for EMT, in and around the fibrotic lesions of CD patients than in non-IBD control patients. In CD patients membrane staining of β-catenin was generally weaker than in control patients and more cells featured nuclear staining indicating transcriptionally active β-catenin, in fibrotic areas. In these regions we also detected nuclear localisation of the transcription factor, SLUG, which has also been implicated in EMT pathogenesis. Adjacent to the fibrotic tissue regions, we observed high levels of FAP, a marker of reactive fibroblasts. Conclusions We demonstrate the presence of EMT-associated molecules in fibrotic lesions of CD patients. These findings support the hypothesis that EMT might play a role for the development of CD-associated intestinal fibrosis. Electronic supplementary material The online version of this article (doi:10.1186/s40169-015-0046-5) contains supplementary material, which is available to authorized users.

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.

Case-control studies have shown that patients with Crohn's disease (CD) have a microbial composition different from healthy individuals. Although the causes of CD are unknown, epidemiologic studies suggest that diet is an important contributor to CD risk, potentially via modulation of bacterial composition and gut inflammation. We hypothesized that long-term dietary clusters (DCs) are associated with gut microbiome compositions and gut inflammation. Our objectives were to identify dietary patterns and assess whether they are associated with alterations in specific gut microbial compositions and subclinical levels of gut inflammation in a cohort of healthy first-degree relatives (FDRs) of patients with CD.As part of the Genetic, Environmental, Microbial (GEM) Project, we recruited a cohort of 2289 healthy FDRs of patients with CD. Individuals provided stool samples and answered a validated food frequency questionnaire reflecting their habitual diet during the year before sample collection. Unsupervised analysis identified 3 dietary and 3 microbial composition clusters.DC3, resembling the Mediterranean diet, was strongly associated with a defined microbial composition, with an increased abundance of fiber-degrading bacteria, such as Ruminococcus, as well as taxa such as Faecalibacterium. The DC3 diet was also significantly associated with lower levels of subclinical gut inflammation, defined by fecal calprotectin, compared with other dietary patterns. No significant associations were found between individual food items and fecal calprotectin, suggesting that long-term dietary patterns rather than individual food items contribute to subclinical gut inflammation. Additionally, mediation analysis demonstrated that DC3 had a direct effect on subclinical inflammation that was partially mediated by the microbiota.Overall, these results indicated that Mediterranean-like dietary patterns are associated with microbiome and lower intestinal inflammation. This study will help guide future dietary strategies that affect microbial composition and host gut inflammation to prevent diseases.

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.

Minimally invasive ileocolic resection for complicated Crohn disease, defined as penetrating Crohn disease associated with intra-abdominal fistula, abscess, or phlegmon, is challenging. In addition, the impact of the minimally invasive approach on postoperative outcomes is still debated. This study aimed to compare the intraoperative and postoperative outcomes of minimally invasive ileocolic resection for complicated versus uncomplicated Crohn disease.A retrospective analysis of all consecutive adult patients with Crohn disease undergoing minimally invasive ileocolic resection from 2014 to 2021 was performed. Perioperative outcomes were compared between patients with complicated Crohn disease (complicated group) and patients without these lesions (uncomplicated group).Among the 274 patients undergoing minimally invasive ileocolic resection for Crohn disease, 101 (36.9%) had a robotic approach, and 84 (30.7%) had complicated Crohn disease. Complicated patients were more frequently malnourished (32.1% vs 16.1%, P = .004) and had more frequent previous bowel resections for Crohn disease (22.1% vs 9.5%, P = .002). There were no differences between both groups regarding intraoperative complications (1.1% uncomplicated group vs 2.4% complicated group, P = .463), conversion rate (2.6% uncomplicated group vs 4.8% complicated group, P = .463), postoperative morbidity (27.4% uncomplicated group vs 34.5% complicated group, P = .231), intra-abdominal septic complications (4.2% uncomplicated group vs 7.1% complicated group, P = .309), and length of stay (3.8 ± 2.0 days uncomplicated group vs 4.2 ± 3.0 complicated group, P = .188).Minimally invasive ileocolic resection for complicated Crohn disease is safe and feasible. Future prospective studies are needed to confirm these results.

Patients with postoperative Crohn's disease are difficult to manage because of their risk of experiencing a more severe course, multiple symptom confounders, and poor sensitivity of symptomatic remission to rule out intestinal inflammation. In this group, data are lacking on biologic therapeutic efficacy, and recommendations are lacking for those with multiple medication failures. Novel noninvasive testing can simultaneously exclude alternate causes of symptoms (serum C4, fecal fat, small intestinal bowel overgrowth breath testing) and assess intestinal inflammation (fecal calprotectin, endoscopic healing index). In addition, endoscopy-based disease activity assessment and management are required. Endoscopy should be performed within 6 months of surgery, and aggressive disease activity monitoring can be considered with colonoscopy every 1-2 years subsequently to ensure late recurrence is detected. Patients with multiple resections should be screened for short bowel syndrome. Predictive biomarkers are needed to guide medication selection in this high-risk population. Postoperative prophylactic biologic therapy is prudent for patients with preoperative biologic failure. However, there are no high-quality data to guide which agent should be selected. Selecting biologics with an alternative mechanism of action in those who had failed a biologic with adequate drug concentrations and selection of different agents in those with previous intolerance are reasonable. Significantly more study is required to assess the efficacy of therapies in this setting.

Whether preoperative treatment of inflammatory bowel disease (IBD) with tumor necrosis factor inhibitors (TNFis) increases the risk of postoperative infectious complications remains controversial. The primary aim of this study was to determine whether preoperative exposure to TNFis is an independent risk factor for postoperative infectious complications within 30 days of surgery.We conducted a multicenter prospective observational study of patients with IBD undergoing intra-abdominal surgery across 17 sites from the Crohn'sColitis Foundation Clinical Research Alliance. Infectious complications were categorized as surgical site infections (SSIs) or non-SSIs. Current TNFi exposure was defined as use within 12 weeks of surgery, and serum was collected for drug-level analyses. Multivariable models for occurrence of the primary outcome, any infection, or SSI were adjusted by predefined covariates (age, sex, preoperative steroid use, and disease type), baseline variables significantly associated (P.05) with any infection or SSI separately, and TNFi exposure status. Exploratory models used TNFi exposure based on serum drug concentration.A total of 947 patients were enrolled from September 2014 through June 2017. Current TNFi exposure was reported by 382 patients. Any infection (18.1% vs 20.2%, P = .469) and SSI (12.0% vs 12.6%, P = .889) rates were similar in patients currently exposed to TNFis and those unexposed. In multivariable analysis, current TNFi exposure was not associated with any infection (odds ratio, 1.050; 95% confidence interval, 0.716-1.535) or SSI (odds ratio, 1.249; 95% confidence interval, 0.793-1.960). Detectable TNFi drug concentration was not associated with any infection or SSI.Preoperative TNFi exposure was not associated with postoperative infectious complications in a large prospective multicenter cohort.

Over the past 2 decades, there have been incredible advances in the pharmacotherapeutic options for the treatment of patients with moderately to severely active Crohn's disease. Despite the leaps and strides in safety, efficacy, and mechanistic specificity of treatment targets, a significant portion (up to ∼20-50%) of patients have refractory Crohn's disease ± concomitant rheumatologic disease/extraintestinal manifestations for which existing biologic and small molecule therapies are ineffective. In this review, we will explore the available evidence for the use of dual advanced therapies (combination of biologic and/or small molecule therapies) and novel pharmacotherapies in phase 2 to 3 clinical trials.

Exclusive enteral nutrition (EEN) is the first line management to induce remission of active Crohn's disease (CD). EEN is well established but there continues to be significant variation in practice especially in relation to what first line formula is used, length of time on EEN, and food reintroduction. The survey aimed to establish dietetic practices in implementing EEN in the management of active CD across specialist paediatric inflammatory bowel disease (IBD) centres.An online, cross-sectional survey was developed, piloted, and distributed to dietitians working at tertiary paediatric IBD centres. Centres were identified through a member of the British Society of Paediatric Gastroenterology, Hepatology, and Nutrition (BSPGHAN) working group. All 20 specialist IBD centres within the United Kingdom were approached and invited to complete the survey.Eighty-five percent (17/20) of the specialist IBD centres in the UK responded. 100% of centres used polymeric feeds as their first line and 70% (12/17) of centres recommended EEN for 6 weeks. Dietetic monitoring whilst on EEN over the 6-8 weeks varied significantly, ranging from 30% (5/17) of centres monitored weekly compared with 30% of centres (5/17) only if clinical need indicated. There was a wide range in practices regarding which foods and drinks were permitted whilst on EEN. Forty three percent (7/17) introduced solid foods over five to seven days, 19% (3/17) introduced food over seven to 14 days and 38% (6/17) introduced food over a minimum of 14 days. Eighteen percent (3/17) of centres were offering the Crohn's disease exclusion diet as a treatment for IBD.Despite available evidenced based guidelines there is still considerable variation in the management of EEN to induce remission in active CD especially in relation to frequency of dietetic review and foods permitted during and after EEN. Further research is required to understand the impact this may have on achieving and maintaining remission in CD.

Reactive therapeutic drug monitoring (TDM) is considered the standard of care for optimizing biologics in inflammatory bowel disease (IBD) including Crohn's disease (CD). Preliminary data show that proactive TDM is associated with positive outcomes in IBD and can be also used to efficiently guide therapeutic decisions in specific clinical scenarios. Higher biological drug concentrations are associated with favorable therapeutic outcomes in specific IBD populations or phenotypes including pediatric CD, perianal fistulizing CD, small bowel CD, and following an ileocolonic resection for CD. Future perspectives of TDM include the use of rapid testing, pharmacogenomics, and pharmacokinetic dashboards toward individualized therapy.

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.

Treatment of Crohn's disease (CD) focuses on providing acceptable quality of life for the affected individual by optimizing medical therapy, endoscopic procedures, and surgical intervention. Biologics have changed the medical management of moderate to severe CD. However, despite their introduction, the need for surgical resection in CD has not drastically changed, with two-thirds of the patients still requiring an intestinal resection. Patient outcomes are optimized by focusing on preoperative management and intraoperative technical aspects to maximize bowel preservation. This article reviews some of the important principles of Crohn's surgery to help guide surgeons when approaching this challenging patient population.

Crohn's disease is a chronic inflammatory disease that can affect any portion of the gastrointestinal tract. Associated symptoms can vary based on the severity of disease, extent of involvement, presence of extraintestinal manifestations, and development of complications. Diagnosis is based on a constellation of findings. Many diseases can mimic Crohn's disease and lead to diagnostic conundrums. These include entities associated with the gastrointestinal luminal tract, vascular disease, autoimmune processes, various infections, malignancies and complications, drug- or treatment-induced conditions, and genetic diseases. Careful consideration of possible causes is necessary to establish the correct diagnosis.

Pediatric Crohn's disease is often more severe, requires higher levels of immunosuppression, and is associated with greater morbidity compared with adult Crohn's disease. Unique considerations in pediatric Crohn's disease include growth impairment, pubertal delay, bone disease, longevity of disease burden, and psychosocial impact. Treatment options are limited, requiring off-label use of therapy in this challenging patient population. Understanding the medications available, the existing evidence supporting their use, and side effects is important. There is tremendous potential for growth and improvement in this field and it is essential that all gastroenterologists have an understanding of this complex and unique patient population.

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.

Mucosal healing, the result of endoscopic remission, is associated with prolonged clinical remission and delayed deterioration of Crohn's disease, which is significant and accompanied by reduced hospitalizations and surgeries. Currently, the relationship between ultrasonic parameters and mucosal healing remains controversial. To establish an ultrasonic regression model to evaluate mucosal healing, we conducted this preliminary study using multiple parameters from B-mode ultrasonography, colour Doppler flow imaging and shear wave elastography systematically.This study consisted of two single-centre investigations based on development and validation populations who received endoscopies (as the gold standard) and ultrasound. The involved bowel segments were divided into mucosal healing (MH) and nonmucosal healing (NMH) groups according to endoscopic results. Eight ultrasonic parameters were observed, including bowel wall thickness (BWT), mesenteric fat thickness (MFT), median modulus of elasticity (Emean), average shear wave velocity (SWV), Limberg scoring (LG), bowel wall stratification (BWS), ascites (AS) and lymph node enlargement (LN). We developed an ultrasonic regression model in the development phase to evaluate segmental mucosal healing and undertook prospective validation of this model.A total of 124 patients with 380 involved bowel segments from the development and validation cohorts were evaluated. Eight ultrasonic parameters were significantly different between the two groups (P0.05) in the development phase. Four significant parameters with better AUC performance were selected to establish an ultrasonic regression model to predict mucosal healing. The AUCs of this ultrasonic model were 0.975 and 0.942 in the development and validation cohorts, respectively.The multimodal ultrasonic model has the potential to evaluate segmental mucosal healing in Crohn's disease.

Most patients with Crohn disease (CD), a chronic inflammatory gastrointestinal disease, experience recurrence despite treatment, including surgical resection. However, methods for predicting recurrence remain unclear. This study aimed to predict postoperative recurrence of CD by computational analysis of histopathologic images and to extract histologic characteristics associated with recurrence. A total of 68 patients who underwent surgical resection of the intestine were included in this study and were categorized into two groups according to the presence or absence of postoperative disease recurrence within 2 years after surgery. Recurrence was defined using the CD Activity Index and the Rutgeerts score. Whole-slide images of surgical specimens were analyzed using deep learning model EfficientNet-b5, which achieved a highly accurate prediction of recurrence (area under the curve, 0.995). Moreover, subserosal tissue images with adipose cells enabled highly accurate prediction. Adipose cell morphology showed significant between-group differences in adipose cell size, cell-to-cell distance, and cell flattening values. These findings suggest that adipocyte shrinkage is an important histologic characteristic associated with recurrence. Moreover, there was a significant between-group difference in the degree of mast cell infiltration in the subserosa. These findings show the importance of mesenteric adipose tissue in patient prognosis and CD pathophysiology. These findings also suggest that deep learning-based artificial intelligence enables the extraction of meaningful histologic features.

The role of Vedolizumab (VDZ) as therapeutic option for the postoperative recurrence of Crohn's disease (CD) following ileocolonic resection is unknown.To assess the effectiveness of VDZ in this setting.All consecutive CD patients with a baseline colonoscopy at 6-12 months from the ileocolonic resection showing postoperative recurrence (Rutgeerts score ≥i2) and treated with VDZ after the baseline colonoscopy were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, assessed at the first colonoscopy following initiation of VDZ and defined as reduction of at least one point of Rutgeerts score. The secondary outcome was clinical failure, assessed at one year and at the end of follow-up.Fifty-eight patients were included (mean follow-up: 24.8 ± 13.1 months). Endoscopic success was reported in 47.6% of patients. Clinical failure was reported in 19.0% of patients at one year, and in 32.8% of patients at the end of follow-up. A new resection was required in 7 patients (12.1%).VDZ may be an effective option for the treatment of postoperative recurrence of CD.

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.

Biologic treatment options for Crohn's disease (CD) are increasing and providers will need enhanced support in integrating these therapies into routine practice. Using phase 3 clinical trial programs in CD, we have previously built and validated clinical decision support tools for achieving clinical remission (CREM) with vedolizumab and ustekinumab in CD.1-4 We now aim to develop a clinical decision support tool for infliximab in CD.

Background Mesentery thickening and enlarged lymphnodes are typical findings of Crohn's disease (CD), but their role is unknown. Aim of the present study was to evaluate their prevalence and significance on postoperative complications and long-term surgical recurrence after CD surgery. Methods 1272 consecutive, unselected patients were retrospectively reviewed, divided into 4 groups based on the presence or absence of a thickened mesentery and enlarged lymphnodes, and stratified for primary or recurrent surgical procedure. In all patients but those treated with strictureplasty the mesentery and lymphnodes were removed. Patients’ characteristics, peri-operative findings, and long-term recurrence were compared by univariate and multivariate analysis. Results Thickened mesentery and enlarged lymphnodes were not present in all cases, were typical of ileal location and penetrating behaviour, had a constant decrease over recurrences, were independent of either pre-operative medical therapy or surgical approach, did not increase the duration of surgery and complications, presented similar 20-years recurrence rate to normal mesentery and lymphnodes. Lymphopathy was associated to a worst nutritional status during disease recurrences. At multivariate analysis, age, location, and behaviour, but not mesenteric characteristics, were related to an increased risk of surgical recurrence. Conclusions This study provides new information on mesentery and lymphnodes in CD patients. Further studies are needed to clarify the appropriate surgical approach.

Endoscopic balloon dilation (EBD) is the established endoscopic treatment for short strictures in Crohn's disease. Fully covered self-expandable metal stents (FCSEMS) have been used for endoscopic treatment of patients for whom EBD was unsuccessful. We aimed to determine the efficacy and safety of the two endoscopic treatments in patients with Crohn's disease with stenosis and compare the mean cost of both treatments.This multicentre, open-label, randomised trial was done in 19 tertiary and secondary hospitals in Spain. Patients with Crohn's disease with obstructive symptoms and predominantly fibrotic strictures of less than 10 cm in length were eligible for inclusion. We excluded patients with stenosis treated with SEMS or EBD in the previous year and stenosis not accessible to a colonoscope. Patients were randomly assigned (1:1) to receive either EBD (EBD group) or FCSEMS (FCSEMS group) using a digital en-block randomisation system (block size of four). In the EBD group, dilation was done with a CRE Boston Scientific (Marlborough, MA, USA) pneumatic balloon with the diameter set at the discretion of the endoscopist; a maximum of two sessions of dilation were allowed with a minimum interval of 15-30 days between them. In the FCSEMS group, a 20 mm diameter Taewoong (Gimpo-si, South Korea) fully covered metal stent was placed; stent length was set at the discretion of the endoscopist. The primary outcome was to assess the efficacy of the endoscopic treatment, defined by the proportion of patients free of a new therapeutic intervention (EBD, FCSEMS, or surgery) due to symptomatic recurrence at 1 year of follow-up. Patients were analysed according to the intention-to-treat principle. Adverse events were recorded for all the patients; events were considered associated to be with the procedure when a causal association was possible, probable, or definite. This trial is registered with ClinicalTrials.gov, NCT02395354.From Aug 28, 2013, to Oct 9, 2017, we assessed the eligibility of 99 patients, of whom 19 (19%) patients were excluded. Thus, 80 (81%) patients were randomly assigned to treatment: 39 (49%) patients to the FCSEMS group and 41 (51%) patients to the EBD group. 33 (80%) of 41 patients in the EBD group and 20 (51%) of 39 patients in the FCSEMS group were free of a new therapeutic intervention at 1 year (odds ratio [OR] 3·9 [95% CI 1·4-10·6]; p=0·0061). Two (3%) of 80 patients had severe adverse events (one [2%] patient in the EBD group and one [3%] patient in the FCSEMS group); both patients had perforations.EBD is more effective than FCSEMS for Crohn's disease strictures, with a good safety profile for both treatments.Spanish National Institute of Health, Foundation of Spanish Society of Digestive Endoscopy, Catalan Society of Gastroenterology, and Taweoong.

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.

The spleen, one of the major organs of the reticuloendothelial system, frequently enlarges in a variety of inflammatory states. We propose measurement of splenic volume as an additional marker for inflammatory bowel disease activity.This is a retrospective study of patients with Crohn's disease who had computed tomography (CT) exams. Demographic data of the patients was recorded. To determine activity of the disease we analyzed clinical records, lab results and findings on CT scan. Splenic size and volume was calculated on each exam.The study cohort includes 90 patients with Crohn's disease who underwent 188 [R1.4] CT exams over 6 years. Splenic volume was found to be significantly larger in patients with CD compared to published values for a healthy population. However, the mean splenic volume was 324 cm ± 130.3 did not show significant difference between the group of active 339.2 ± 118.4, and non-active disease 304.2 ± 144.2 (p 0.21 for splenic volume). Interestingly, when splenic volume/BMI index (SV/BMI) was calculated, it was found to be significantly larger in patients with active diseases, 15.26 ± 4.86 compared to non-active phase, 11.69 ± 5.19 (p 0.004).Splenic size is enlarged in patients with Crohn's disease compared to standard published literature of normal individuals. While there is no statistically significant difference in our study between splenic volume in Crohn's disease patients with active versus nonactive disease, indexed splenic volume, as an additional marker, may add value to the assessment of patient with CD and monitoring of the disease activity.

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 We conducted a systematic review and meta-analysis to summarize emerging data on the safety and effectiveness of dual biologic therapy in combination or with tofacitinib in patients with refractory inflammatory bowel disease (IBD). Methods Through a systematic search of multiple electronic databases through November 9, 2020, we identified cohort studies or case series (>10 patients) reporting the safety and effectiveness of simultaneous use of biologic agents in combination or with tofacitinib in patients with IBD. Rates of adverse events, clinical remission, and endoscopic remission were synthesized using pooled data, and we identified factors associated with successful dual therapy. Results We identified 30 studies reporting 288 trials of dual biologic or small molecule therapy in 279 patients (76% Crohn’s disease; median duration of treatment 24 weeks (IQR25-IQR75 1332)). The main indications for dual therapy included medically refractory IBD (81%) and concurrent extra-intestinal manifestations or rheumatologic disease (12%). The most common combinations of dual therapy included tumor necrosis factor-α antagonists & anti-integrins (48%), ustekinumab & anti-integrins (19%); 61% of patients had previously failed at least one of the two therapies used in combination. Over a median follow-up of 32 weeks (IQR25-IQR75 24-52), pooled rates of adverse and serious adverse events were 31% (95% CI, 13%-54%) and 6.5% (95% CI, 2.1%-13.1%); pooled rates of clinical and endoscopic remission were 59% (95% CI, 42%-74%), and 34% (95% CI, 23%-46%), respectively. 12% (95% CI, 4%-24%) of patients required surgery. Rates of success were higher in patients on dual therapy due to EIM. Heterogeneity was not significant for endoscopic response (P = .88, I2 = 0%), endoscopic remission (P = .44, I2 = 0%), and malignancy (P = .87, I2 = 0%). However, significant heterogeneity existed for other outcomes. Conclusions Dual biologic or small molecule therapy may be a possible option in highly selected, refractory IBD patients at specialized centers. Higher quality combination of therapies with a significant improvement in the quality of data is required prior to more widespread use.

No studies evaluating the rapidity of response to biological therapies are available for Crohn's disease (CD). The aim of this study was to evaluate rapidity of onset of clinical response and impact on quality of life (QoL) of adalimumab therapy in adult anti-TNF-naïve patients with moderately-to-severely active CD.RAPIDA was an open-label, single-arm, prospective, multicenter clinical trial. Adult patients with moderately-to-severely active luminal CD, anti-TNF-naïve, and unresponsive to conventional therapy were treated with adalimumab. Clinical disease activity, QoL and inflammatory biomarkers were measured at day 4, and weeks 1, 2, 4, and 12 after treatment initiation.Eighty-six patients were included in the intention-to-treat (ITT) analyses. Clinical disease activity was reduced from a median of 9.0 points to 6.0 points at day 4. Clinical response (≥ 3-point reduction in the Harvey-Bradshaw Index, HBI) was achieved by 61.6% (d4) and 75.6% (w1) of patients in the ITT population (median 2.5 days) and with non-responder imputation (NRI), by 55.8% and 53.4%, respectively. The proportion of patients in clinical remission (HBI5) at weeks 2 and 4 in the ITT population was 54.7% and 62.8%, respectively (median 7.0 days), and 38.4% and 45.3% in the NRI population. All QoL scores significantly improved and inflammatory biomarkers significantly decreased from day 4 onwards (p0.0001).Rapid clinical response and remission, improvement in QoL and fatigue, and a reduction of inflammatory biomarkers were achieved with adalimumab as early as day 4 in adult anti-TNF-naïve patients with moderately-to-severely active CD.

The aims of this study were to describe the trends in the behavior of pediatric CD during the last decade and to describe the seasonal variation of disease presentation.Patients under 18 years old and diagnosed between 2009 and 2019 were included. The clinical, endoscopic, histological, and laboratory data were collected from the medical records. We analyzed the trends of these parameters according to the year and season of diagnosis.654 patients were included in the study. The number of incident CD cases increased yearly. Patients diagnosed between 2015 and 2019 were younger at diagnosis (OR 2.53, p = 0.02), had more perianal diseases (OR: 2.30, p 0.0001) and more granulomas (OR: 1.61, p = 0.003), but fewer eosinophils (OR: 0.35, p 0.0001) and less chronic lymphoplasmacytic infiltrate (OR: 0.56, p = 0.008) as compared to the 2009-2014 cohort. There was fewer CD diagnosis during winter. Patients diagnosed in the fall had lower PCDAIs, less failure to thrive and less extensive digestive involvement. Colonic disease was significantly more frequent during summer and fall.The clinical and histological phenotype of CD has changed over time and there are important seasonal trends in the frequency and severity on disease behavior suggesting possible disease triggers.

Crohn's disease is an inflammatory disease of the gut caused by a complex interplay among genetic, microbial, and environmental factors. The intestinal tract is constantly exposed to metals and other trace elements ingested as food. Synchrotron radiation-induced X-ray fluorescence spectroscopy and X-ray absorption fine structure analysis revealed the deposition of nickel particles within Crohn's disease tissue specimens. After nickel particle stimulation, THP-1 cells showed filopodia formation and autophagic vacuoles containing lipid bodies. Nickel particles precipitated colitis in mice bearing mutations of the IBD susceptibility protein A20/TNFAIP3. Nickel particles also exacerbated dextran sulfate sodium-induced colitis in mice harboring myeloid cell-specific Atg5 deficiency. These findings illustrate that nickel particle ingestion may worsen Crohn's disease by perturbing autophagic processes in the intestine, providing new insights into environmental factors in Crohn's disease pathogenesis.

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: Mirikizumab is a humanized monoclonal antibody targeting interleukin 23p19 with demonstrated efficacy in psoriasis and ulcerative colitis. We investigated the safety and efficacy of mirikizumab in patients with moderate-to-severe Crohn's disease (CD). Methods: Patients (N = 191) were randomized (2:1:1:2) to receive placebo (PBO), 200, 600, or 1000 mg mirikizumab, administered intravenously (IV) every 4 weeks. Patients who received mirikizumab and achieved ≥1 point improvement in Simple Endoscopic Score-CD at Week 12 (rerandomized maintenance cohort) were rerandomized to continue their induction IV treatment (combined IV groups [IV-C]) or receive 300 mg mirikizumab subcutaneously (SC) every 4 weeks. Nonrandomized maintenance cohort included endoscopic nonimprovers (1000 mg) and PBO patients (PBO/1000 mg) who received 1000 mg mirikizumab IV from Week 12. The primary objective was to evaluate superiority of mirikizumab to PBO in inducing endoscopic response (50% reduction from baseline in Simple Endoscopic Score-CD) at Week 12. Results: At Week 12, endoscopic response was significantly higher by the predefined 2-sided significance level of 0.1 for all mirikizumab groups compared with PBO (200 mg: 25.8%, 8/31, 95% confidence interval [CI], 10.4–41.2, P = .079; 600 mg: 37.5%, 12/32, 95% CI, 20.7–54.3, P = .003; 1000 mg: 43.8%, 28/64, 95% CI, 31.6–55.9, P < .001; PBO: 10.9 %, 7/64, 95% CI, 3.3–18.6). Endoscopic response at Week 52 was 58.5% (24/41) and 58.7% (27/46) in the IV-C and SC groups, respectively. Frequencies of adverse events (AE) in the mirikizumab groups were similar to PBO. Through Week 52, frequencies of treatment-emergent AEs were similar across all groups. Frequencies of serious AE and discontinuations due to AE were higher in the nonrandomized maintenance cohort. Conclusion: Mirikizumab effectively induced endoscopic response after 12 weeks in patients with moderate-to-severe CD and demonstrated durable efficacy to Week 52. A detailed summary can be found in the Video Abstract. ClinicalTrials.gov, Number: NCT02891226

Immunotherapy is a treatment modality that has a broad and rapidly growing range of applications to treat both chronic and acute diseases, including rheumatoid arthritis, Crohn disease, cancer, and COVID-19. Emergency physicians must be aware of the breadth of applications and be able to consider the effects of immunotherapies when patients on these treatments present to the hospital. This article provides a review of the mechanisms of action, indications for use, and potential complications of immunotherapy treatments that are relevant in the emergency care setting.

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 Yersinia infection affects terminal ileum and lymph nodes and could therefore mimic the symptoms of appendicitis. We aimed to systematically characterise the suspected or confirmed abdominal diseases and/or surgeries associated with Yersinia infection. Materials and methods This systematic review and meta-analysis was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A protocol (CRD42016053252) was uploaded to PROSPERO. The searches were conducted in PubMed and EMBASE on October 2, 2020. Original reports on patients with abdominal surgical diseases were included. The primary outcome was to characterise suspected or confirmed abdominal surgical diseases and/or surgeries associated with Yersinia infection, while the secondary outcomes were the positive rate of Yersinia species for each disease and surgery, and to investigate the rate of Yersinia spp. in different geographic regions. We calculated the weighted mean prevalence of positive tests for Yersinia spp. for the different diseases and surgeries according to the detection method and for subgroups based on geographic region. Results From the search, 33 studies were included in the systematic review and 18 in the meta-analysis. Across geographic regions, the weighted mean prevalence for Yersinia spp. was 51% (95% CI 34%-69%) in mesenteric lymphadenitis, 65% (95% CI 45%-85%) in terminal ileitis, and 8% (95% CI 2%-15%) in normal appendices. Conclusions Around half of the patients with mesenteric lymphadenitis and terminal ileitis were serologically positive for infections with Yersinia spp. Yersinia infection may cause unnecessary surgery for suspected appendicitis due to symptoms from mesenteric lymphadenitis or terminal ileitis.

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.

Summary Pouchitis, Crohn's disease of the pouch, cuffitis, polyps, and extraintestinal manifestations of inflammatory bowel disease are common inflammatory disorders of the ileal pouch. Acute pouchitis is treated with oral antibiotics and chronic pouchitis often requires anti-inflammatory therapy, including the use of biologics. Aetiological factors for secondary pouchitis should be evaluated and managed accordingly. Crohn's disease of the pouch is usually treated with biologics and its stricturing and fistulising complications can be treated with endoscopy or surgery. The underlying cause of cuffitis determines treatment strategies. Endoscopic polypectomy is recommended for large, symptomatic inflammatory polyps and polyps in the cuff. The management principles of extraintestinal manifestations of inflammatory bowel disease in patients with pouches are similar to those in patients without pouches.

Background & Aims Tumor necrosis factor alpha (TNFα) is considered a major tissue damage-promoting effector in Crohn’s disease (CD) pathogenesis. Patient-derived intestinal organoid (enteroid) recapitulates the disease-specific characteristics of the intestinal epithelium. This study aimed to evaluate the intestinal epithelial responses to TNFα in enteroids derived from healthy controls and compare them with those of CD patient-derived enteroids. Methods Human enteroids derived from patients with CD and controls were treated with TNFα (30 ng/mL), and cell viability and gene expression patterns were evaluated. Results TNFα induced MLKL-mediated necroptotic cell death, which was more pronounced in CD patient-derived enteroids than in control enteroids. Immunohistochemistry and RNA sequencing revealed that treatment with TNFα caused expansion of the intestinal stem cell (ISC) populations. However, expanded ISC subpopulations differed in control and CD patient-derived enteroids, with LGR5+ active ISCs in control enteroids and reserve ISCs, such as BMI1+ cells, in CD patient-derived enteroids. In single-cell RNA sequencing, LGR5+ ISC-enriched cell cluster showed strong expression of TNFRSF1B (TNFR2) and cyclooxygenase-prostaglandin E2 (PGE2) activation. In TNFα-treated CD patient-derived enteroids, exogenous PGE2 (10 nmol/L) induced the expansion of the LGR5+ ISC population and improved organoid-forming efficiency, viability, and wound healing. Conclusions TNFα increases necroptosis of differentiated cells and induces the expansion of LGR5+ ISCs. In CD patient-derived enteroids, TNFα causes LGR5+ stem cell dysfunction (expansion failure), and exogenous PGE2 treatment restored the functions of LGR5+ stem cells. Therefore, PGE2 can be used to promote mucosal healing in patients with CD., Graphical abstract

Background Capsule endoscopy (SBCE) has developed a relevant role in patients with established Crohn's Disease (CD). However, evaluation of the impact in clinical management has been scarce. Aims To evaluate therapeutic impact of SBCE in an 11-year real-life cohort of known CD patients. Methods Retrospective single center study including all patients with established CD submitted to SBCE procedure from 01/01/2008 to 31/12/2019. Patency capsule was used in selected patients. Small bowel mucosal inflammation was quantified using Lewis score. Therapeutic impact was defined as a change in CD-related treatment recommended based on SBCE results. Patients were assigned to four groups regarding SBCE indication: staging, flare, post-op and remission. Results From the 432 SBCE performed 87.5% were conclusive. Active disease was present in 63.7 of patients; 41.6% mild inflammation and 21.9% moderate-to-severe activity. A change of management was guided by SBCE in 51.3% of procedures: 199 (46.1%) escalation and 23 (5.3%) de-escalation, with significant changes in all groups. Escalation increased with disease activity: 57.8% in mild and 89.5% in moderate-to-severe disease. De-escalation was conducted in 13.9% procedures with mucosal healing and 1.1% with mild disease. Conclusion SBCE is a useful tool for guiding therapeutic management in CD patients both for treatment escalation and de-escalation.

Summary Background The Crohn's disease exclusion diet (CDED) with partial enteral nutrition is effective for induction of remission in children with mild-to-moderate Crohn's disease. We aimed to assess the CDED in adults with Crohn's disease. Methods We did an open-label, pilot randomised trial at three medical centres in Israel. Eligible patients were biologic naive adults aged 18–55 years with mild-to-moderate Crohn's disease (defined by a Harvey–Bradshaw Index score of 5–14 points), a maximal disease duration of 5 years, with active disease on colonoscopy, or imaging with elevated inflammatory markers (C-reactive protein >5 mg/L or faecal calprotectin concentration >200 μ/g). Patients were randomly assigned (1:1) to CDED plus partial enteral nutrition or CDED alone for 24 weeks. Randomisation was via block randomisation (block sizes of six) using sealed, numbered, and opaque envelopes. Patients and investigators were aware of which group patients were assigned to due to the nature of the different interventions. The primary endpoint was clinical remission, defined as a Harvey–Bradshaw Index score of less than 5 at week 6. The primary endpoint was assessed in the intention-to-treat (ITT) population, which included all patients who used the dietary therapy for at least 48 h. We report results of the final analysis. This trial is registered with ClinicalTrials.gov , NCT02231814 . Findings Between Jan 12, 2017, and May 11, 2020, 91 patients were screened, of whom 44 were randomly assigned to the CDED plus partial enteral nutrition group (n=20) or CDED alone group (n=24). 19 patients in the CDED plus partial enteral nutrition group and 21 patients in the CDED alone group received the allocated intervention for at least 48 h and thus were included in the ITT analysis. At week 6, 13 (68%) of 19 patients in the CDED plus partial enteral nutrition group and 12 (57%) of 21 patients in the CDED group had achieved clinical remission (p=0·4618). Among the 25 patients in remission at week 6, 20 (80%) were in sustained remission at week 24 (12 patients in the CDED plus partial enteral nutrition group and eight in the CDED alone group). 14 (35%) of 40 patients were in endoscopic remission at week 24 (eight patients in the CDED plus partial enteral nutrition group and six in the CDED alone group). No serious adverse events or treatment-related adverse events were reported in either group. Interpretation CDED with or without partial enteral nutrition was effective for induction and maintenance of remission in adults with mild-to-moderate biologic naive Crohn's disease and might lead to endoscopic remission. These data suggest that CDED could be used for mild-to-moderate active Crohn's disease and should be assessed in a powered randomised controlled trial. Funding Azrieli Foundation and Nestle Health Science.