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Inflammatory bowel disease (IBD) constitutes a substantial risk factor for colorectal cancer. Connexin 43 (Cx43) is a protein that forms gap junction (GJ) complexes involved in intercellular communication, and its expression is altered under pathological conditions, such as IBD and cancer. Recent studies have implicated epigenetic processes modulating DNA methylation in the pathogenesis of diverse inflammatory and malignant diseases. The ten-eleven translocation-2 (TET-2) enzyme catalyzes the demethylation, hence, regulating the activity of various cancer-promoting and tumor-suppressor genes.To investigate Cx43 and TET-2 expression levels and presence of 5-hydroxymethylcytosine (5-hmC) marks under inflammatory conditions bothTET-2 expression was evaluated in parental HT-29 cells and in HT-29 cells expressing low or high levels of Cx43, a putative tumor-suppressor gene whose expression varies in IBD and colorectal cancer, and which has been implicated in the inflammatory process and in tumor onset. The dextran sulfate sodium-induced colitis model was reproduced in BALB/c mice to evaluate the expression of TET-2 and Cx43 under inflammatory conditionsUnder inflammatory conditions, Cx43 and TET-2 expression levels increased compared to non-inflammatory conditions. TET-2 upregulation was more pronounced in Cx43-deficient cells. Moreover, colon tissue sections from normal, ulcerative colitis, and sporadic colon adenocarcinoma patients corroborated that Cx43 expression increased in IBD and decreased in adenocarcinoma, compared to tissues from non-IBD subjects. However, TET-2 expression and 5-hmC mark levels decreased in samples from patients with ulcerative colitis or cancer. Cx43 and TET-2 expression levels were also investigated in an experimental colitis mouse model. Interestingly, mice exposed to carbenoxolone (CBX), a GJ inhibitor, had upregulated TET-2 levels. Collectively, these results show that TET-2 levels and activity increased under inflammatory conditions, in cells downregulating gap junctional protein Cx43, and in colon tissues from mice exposed to CBX.These results suggest that TET-2 expression levels, as well as Cx43 expression levels, are modulated in models of intestinal inflammation. We hypothesize that TET-2 may demethylate genes involved in inflammation and tumorigenesis, such as Cx43, potentially contributing to intestinal inflammation and associated carcinogenesis.

Advances in diagnostics of inflammatory bowel diseases (IBD) and improved treatment strategies allowed the establishment of new therapeutic endpoints. Currently, it is desirable not only to cease clinical symptoms, but mainly to achieve endoscopic remission, a macroscopic normalization of the bowel mucosa. However, up to one-third of IBD patients in remission exhibit persisting microscopic activity of the disease. The evidence suggests a better predictive value of histology for the development of clinical complications such as clinical relapse, surgical intervention, need for therapy escalation, or development of colorectal cancer. The proper assessment of microscopic inflammatory activity thus became an important part of the overall histopathological evaluation of colonic biopsies and many histopathological scoring indices have been established. Nonetheless, a majority of them have not been validated and no scoring index became a part of the routine bioptic practice. This review summarizes a predictive value of microscopic disease activity assessment for the subsequent clinical course of IBD, describes the most commonly used scoring indices for Crohn's disease and ulcerative colitis, and comments on current limitations and unresolved issues.

In this comprehensive evidence-based analysis of ulcerative colitis (UC), a causal role is identified for colonic epithelial hydrogen peroxide (H

This is the first study on the epidemiology of inflammatory bowel diseases (IBDs) in Rio Grande do Sul (RS), the southernmost state of Brazil with the country's fifth largest population. Crohn's disease (CD) and ulcerative colitis (UC) are collectively termed IBDs. They have high incidence and prevalence rates in high-income countries, although in recent years there has been a change in the classic geographical distribution of IBDs, with growing rates in traditionally low-incidence regions.To estimate the incidence and prevalence of IBDs in the RS state, Brazil, between 2014 and 2019.This is a cross-sectional descriptive observational study. Patients with IBD who had initiated treatment and met the inclusion criteria of the RS state free drug distribution program were included. Data were obtained from registration or renewal records of the RS state specialty pharmacy. The male, female, and total populations were estimated according to mid-year data from the Brazilian Institute of Geography and Statistics, which served as a reference for calculating the incidence and prevalence rates of IBDs during the study period. Results were described using mean, standard deviation, and range.We included 1082 patients with IBD, of whom 57.5% were female and 42.5% were male. Patients with CD accounted for 72.45% of the sample, and those with UC accounted for 27.54%. IBD prevalence during the study period was 9.51 per 100000 population, of which 6.89 corresponded to people with CD and 2.62, to people with UC. Incidence rates per 100000 population/year were 2.54 in 2014, 2.61 in 2015, 1.91 in 2016, 0.80 in 2017, 0.83 in 2018, and 0.96 in 2019. The mean IBD incidence rate per 100000 population was 1.61, of which 1.17 corresponded to CD and 0.44, to UC. The mean age was 41 years, and patients were mostly aged 30-40 years. Prevalence by region was higher in the state capital metropolitan area: 12.69 per 100000 population.Our results demonstrated an IBD prevalence of 9.51% and incidence of 1.61 per 100000 population. The patients were predominantly female, and CD was more prevalent than UC.

The mechanisms underlying gastrointestinal (GI) dysmotility with ulcerative colitis (UC) have not been fully elucidated. The enteric nervous system (ENS) plays an essential role in the GI motility. As a vital neurotransmitter in the ENS, the gas neurotransmitter nitric oxide (NO) may impact the colonic motility. In this study, dextran sulfate sodium (DSS)-induced UC rat model was used for investigating the effects of NO by examining the effects of rate-limiting enzyme nitric oxide synthase (NOS) changes on the colonic motility as well as the role of the ENS in the colonic motility during UC.To reveal the relationship between the effects of NOS expression changes in NOS-containing nitrergic neurons and the colonic motility in a rat UC model.Male rats (The proportion of NOS-positive neurons within the colonic myenteric plexus (MP), the relative expression of NOS, and the NOS concentration in serum and colonic tissues were significantly elevated in EG1, EG2, and EG3 compared with CG rats. In UC rats, stimulation with agonists and inhibitors led to variable degrees of increase or decrease for each indicator in the EG2 and EG3. When the rats in EGs developed UC, the mean contraction tension of the colonic smooth muscle detectedIn UC rats, an increased number of nitrergic neurons in the colonic MP leads to the attenuation of colonic motor function. To intervene NOS activity might modulate the function of nitrergic neurons in the colonic MP and prevent colonic motor dysfunction. These results might provide clues for a novel approach to alleviate diarrhea symptoms of UC patients.

Ulcerative colitis (UC) is a chronic, nonspecific intestinal inflammatory disease. Acupuncture and moxibustion is proved effective in treating UC, but the mechanism has not been clarified. Proteomic technology has revealed a variety of biological markers related to immunity and inflammation in UC, which provide new insights and directions for the study of mechanism of acupuncture and moxibustion treatment of UC.To investigate the mechanism of electroacupuncture (EA) and herb-partitioned moxibustion (HM) on UC rats by using proteomics technology.Male Sprague-Dawley rats were randomly divided into the normal (N) group, the dextran sulfate sodium (DSS)-induced UC model (M) group, the HM group, and the EA group. UC rat model was prepared with 3% DSS, and HM and EA interventions at the bilateral Tianshu and Qihai acupoints were performed in HM or EA group. Haematoxylin and eosin staining was used for morphological evaluation of colon tissues. Isotope-labeled relative and absolute quantification (iTRAQ) and liquid chromatography-tandem mass spectrometry were performed for proteome analysis of the colon tissues, followed by bioinformatics analysis and protein-protein interaction networks establishment of differentially expressed proteins (DEPs) between groups. Then western blot was used for verification of selected DEPs.The macroscopic colon injury scores and histopathology scores in the HM and EA groups were significantly decreased compared to the rats in the M group (EA and HM could regulate the expression of ATP5L, Atp5f1, Cox4i1 that associated with oxidative phosphorylation, then might regulate immune-related pathways of intestinal immune network for IgA production, FcγR-mediated phagocytosis, thereby alleviating colonic inflammation of DSS-induced UC rats.

A two- to three-fold increased risk of venous thrombotic events (VTE) has been demonstrated in patients with inflammatory bowel disease (IBD) compared to the general population, but less is known about the risk of VTE in child- and pediatric-onset IBD. In recent years, several studies have reported the rising incidence rate of VTE in juvenile patients with IBD, and the related risk factors have been explored.To evaluate the risk of VTE in children and adolescents with IBD.Articles published up to April 2021 were retrieved from PubMed, Embase, Cochrane Library, Web of Science, SinoMed, CNKI, and WANFANG. Data from observational studies and clinical work were extracted. The outcome was the occurrence of VTE according to the type of IBD. The available odds ratio (OR) and the corresponding 95% confidence interval (CI) were extracted to compare the outcomes. Effect size (P), odds ratio (OR), and 95%CI were used to assess the association between VTE risk and IBD disease. Subgroup analyses stratified by subtypes of VTE and IBD were performed.Twelve studies (7450272 IBD patients) were included in the meta-analysis. Child and adolescent IBD patients showed increased VTE risk (The current meta-analysis showed that the incidence and risk of VTE are significantly increased in pediatric and adolescent IBD patients. Thus, IBD might be a risk factor for VTE in children and young adults. High-quality prospective cohort studies are necessary to confirm these findings.

It is unclear whether the Japan Narrow-Band Imaging Expert Team (JNET) classification and pit pattern classification are applicable for diagnosing neoplastic lesions in patients with ulcerative colitis (UC).To clarify the diagnostic performance of these classifications for neoplastic lesions in patients with UC.This study was conducted as a single-center, retrospective case-control study. Twenty-one lesions in 19 patients with UC-associated neoplasms (UCAN) and 23 lesions in 22 UC patients with sporadic neoplasms (SN), evaluated by magnifying image-enhanced endoscopy, were retrospectively and separately assessed by six endoscopists (three experts, three non-experts), using the JNET and pit pattern classifications. The results were compared with the pathological diagnoses to evaluate the diagnostic performance. Inter- and intra-observer agreements were calculated.In this study, JNET type 2A and pit pattern type III/IV were used as indicators of low-grade dysplasia, JNET type 2B and pit pattern type VThe accuracy of endoscopic diagnosis using both classifications was lower for UCAN than for SN. Endoscopic diagnosis of UCAN tended to be underestimated compared with the pathological results.

Inflammatory bowel disease (IBD) is a chronic disease that requires chronic treatment throughout the evolution of the disease, with a complex physiopathology that entails great challenges for the development of new and specific treatments for ulcerative colitis and Crohn´s disease. The anti-tumor necrosis factor alpha therapy has impacted the clinical course of IBD in those patients who do not respond to conventional treatment, so there is a need to develop new therapies and markers of treatment response. Various pathways involved in the development of the disease are known and the new therapies have focused on blocking the inflammatory process at the gastrointestinal level by oral, intravenous, subcutaneous, and topical route. All these new therapies can lead to more personalized treatments with higher success rates and fewer relapses. These treatments have not only focused on clinical remission, but also on achieving macroscopic changes at the endoscopic level and microscopic changes by achieving mucosal healing. These treatments are mainly based on modifying signaling pathways, by blocking receptors or ligands, reducing cell migration and maintaining the integrity of the epithelial barrier. Therefore, this review presents the efficacy and safety of the new treatments that are currently under study and the advances that have been made in this area in recent years.

BACKGROUND Chromofungin (CHR: chromogranin-A 47-66) is a chromogranin-A derived peptide with anti-inflammatory and anti-microbial properties. Ulcerative colitis (UC) is characterized by a colonic decrease of CHR and a dysregulation of dendritic CD11c+ cells. AIM To investigate the association between CHR treatment and dendritic cells (DCs)-related markers in different immune compartments in colitis. METHODS A model of acute UC-like colitis using dextran sulphate sodium (DSS) was used in addition to biopsies collected from UC patients. RESULTS Intrarectal CHR treatment reduced the severity of DSS-induced colitis and was associated with a significant decrease in the expression of CD11c, CD40, CD80, CD86 and interleukin (IL)-12p40 in the inflamed colonic mucosa and CD11c, CD80, CD86 IL-6 and IL-12p40 within the mesenteric lymph nodes and the spleen. Furthermore, CHR treatment decreased CD80 and CD86 expression markers of splenic CD11c+ cells and decreased NF-κB expression in the colon and of splenic CD11c+ cells. In vitro, CHR decreased CD40, CD80, CD86 IL-6 and IL-12p40 expression in naïve bone marrow-derived CD11c+ DCs stimulated with lipopolysaccharide. Pharmacological studies demonstrated an impact of CHR on the NF-κB pathway. In patients with active UC, CHR level was reduced and showed a negative linear relationship with CD11c and CD86. CONCLUSION CHR has protective properties against intestinal inflammation via the regulation of DC-related markers and CD11c+ cells. CHR could be a potential therapy of UC.

The enteric nervous system (ENS) consists of thousands of small ganglia arranged in the submucosal and myenteric plexuses, which can be negatively affected by Crohn’s disease and ulcerative colitis - inflammatory bowel diseases (IBDs). IBDs are complex and multifactorial disorders characterized by chronic and recurrent inflammation of the intestine, and the symptoms of IBDs may include abdominal pain, diarrhea, rectal bleeding, and weight loss. The P2X7 receptor has become a promising therapeutic target for IBDs, especially owing to its wide expression and, in the case of other purinergic receptors, in both human and model animal enteric cells. However, little is known about the actual involvement between the activation of the P2X7 receptor and the cascade of subsequent events and how all these activities associated with chemical signals interfere with the functionality of the affected or treated intestine. In this review, an integrated view is provided, correlating the structural organization of the ENS and the effects of IBDs, focusing on cellular constituents and how therapeutic approaches through the P2X7 receptor can assist in both protection from damage and tissue preservation.

Background: Patients with inflammatory bowel disease (IBD) are associated with increased cardiovascular risk and have increased overall cardiovascular burden. On the other hand, urotensin II (UII) is one of the most potent vascular constrictors with immunomodulatory effect that is connected with a number of different cardiometabolic disorders as well. Furthermore, patients with ulcerative colitis have shown increased expression of urotensin II receptor in comparison to healthy controls. Since the features of IBD includes chronic inflammation and endothelial dysfunction as well, it is plausible to assume that there is connection between increased cardiac risk in IBD and UII. Aim: To determine serum UII levels in patients with IBD and to compare them to control subjects, as well as investigate possible associations with relevant clinical and biochemical parameters. Methods: This cross sectional study consecutively enrolled 50 adult IBD patients (26 with Crohn's disease and 24 with ulcerative colitis) and 50 age and gender matched controls. Clinical assessment was performed by the same experienced gastroenterologist according to the latest guidelines. Ulcerative Colitis Endoscopic Index of Severity and Simple Endoscopic Score for Crohn's Disease were used for endoscopic evaluation. Serum levels of UII were determined using the enzyme immunoassay kit for human UII, according to the manufacturer's instructions. Results: IBD patients have significantly higher concentrations of UII when compared to control subjects (7.57 ± 1.41 vs 1.98 ± 0.69 ng/mL, P < 0.001), while there were no significant differences between Crohn's disease and ulcerative colitis patients (7.49 ± 1.42 vs 7.65 ± 1.41 ng/mL, P = 0.689). There was a significant positive correlation between serum UII levels and high sensitivity C reactive peptide levels (r = 0.491, P < 0.001) and a significant negative correlation between serum UII levels and total proteins (r = -0.306, P = 0.032). Additionally, there was a significant positive correlation between serum UII levels with both systolic (r = 0.387, P = 0.005) and diastolic (r = 0.352, P = 0.012) blood pressure. Moreover, serum UII levels had a significant positive correlation with Ulcerative Colitis Endoscopic Index of Severity (r = 0.425, P = 0.048) and Simple Endoscopic Score for Crohn's Disease (r = 0.466, P = 0.028) scores. Multiple linear regression analysis showed that serum UII levels retained significant association with high sensitivity C reactive peptide (β ± standard error, 0.262 ± 0.076, P < 0.001) and systolic blood pressure (0.040 ± 0.017, P = 0.030). Conclusion: It is possible that UII is involved in the complex pathophysiology of cardiovascular complications in IBD patients, and its purpose should be investigated in further studies.

BACKGROUND Disease knowledge is associated with increased treatment compliance and improvement of symptoms in inflammatory bowel disease (IBD). IBD-knowledge inventory device (IBD-KID) was developed and validated specifically as a tool to measure disease-related knowledge in children with IBD and their parents. AIM To prospectively assess the determinants of disease-related knowledge regarding paediatric IBD patients and their parents, using the IBD-KID. METHODS A questionnaire-based survey was carried out in paediatric patients and their parents. The determinants of patients' and parents' IBD-KID scores were assessed according to hierarchical linear regression models. RESULTS The study group consisted of 269 IBD patients and 298 parents. The patients' mean (standard deviation, SD) IBD-KID score was 10.87 (± 3.97), while the parents' was 11.95 (± 3.97). Both groups exhibited poor knowledge of the side effects of steroid therapy, the role of surgical treatment in IBD, dietary restrictions and the risks associated with the use of herbal medicines. The patients' IBD-KID scores were statistically associated with patient sex [B coefficient (standard error, SE) = 1.03 (0.44), P = 0.021] and patient age [B (SE) = 0.03 (0.01), P < 0.001]. The parents' IBD-KID scores were significantly related to patient age [B (SE) = 0.02 (0.01), P = 0.003], and treatment with immunosuppressive agent [B (SE) = 1.85 (0.48), P < 0.001]. The final models explained 26.9% of the variance of patients' IBD-KID scores and 18.5% of the variance of parents' scores. CONCLUSION The variables originating from parents' knowledge were significantly associated with patients' IBD-KID scores. The study results indicate the need to implement better education programmes for patients and parents.

BACKGROUND Dysbacteriosis may be a crucial environmental factor for ulcerative colitis (UC). Further study is required on microbiota alterations in the gastrointestinal tract of patients with UC for better clinical management and treatment. AIM To analyze the relationship between different clinical features and the intestinal microbiota, including bacteria and fungi, in Chinese patients with UC. METHODS Eligible inpatients were enrolled from January 1, 2018 to June 30, 2019, and stool and mucosa samples were collected. UC was diagnosed by endoscopy, pathology, Mayo Score, and Montreal classification. Gene amplicon sequencing of 16S rRNA gene and fungal internal transcribed spacer gene was used to detect the intestinal microbiota composition. Alpha diversity, principal component analysis, similarity analysis, and Metastats analysis were employed to evaluate differences among groups. RESULTS A total of 89 patients with UC and 33 non-inflammatory bowel disease (IBD) controls were enrolled. For bacterial analysis, 72 stool and 48 mucosa samples were obtained from patients with UC and 21 stool and 12 mucosa samples were obtained from the controls. For fungal analysis, stool samples were obtained from 43 patients with UC and 15 controls. A significant difference existed between the fecal and mucosal bacteria of patients with UC. The α-diversity of intestinal bacteria and the relative abundance of some families, such as Lachnospiraceae and Ruminococcaceae, decreased with the increasing severity of bowel inflammation, while Escherichia-Shigella showed the opposite trend. More intermicrobial correlations in UC in remission than in active patients were observed. The bacteria-fungi correlations became single and uneven in patients with UC. CONCLUSION The intestinal bacteria flora of patients with UC differs significantly in terms of various sample types and disease activities. The intermicrobial correlations change in patients with UC compared with non-IBD controls.

BACKGROUND Gut microbiota and its metabolites may be involved in the pathogenesis of inflammatory bowel disease. Several clinical studies have recently shown that patients with ulcerative colitis (UC) have altered profiles of fecal bile acids (BAs). It was observed that BA receptors Takeda G-protein-coupled receptor 5 (TGR5) and vitamin D receptor (VDR) participate in intestinal inflammatory responses by regulating NF-ĸB signaling. We hypothesized that altered profiles of fecal BAs might be correlated with gut microbiota and inflammatory responses in patients with UC. AIM To investigate the changes in fecal BAs and analyze the relationship of BAs with gut microbiota and inflammation in patients with UC. METHODS The present study used 16S rDNA sequencing technology to detect the differences in the intestinal flora between UC patients and healthy controls (HCs). Fecal BAs were measured by targeted metabolomics approaches. Mucosal TGR5 and VDR expression was analyzed using immunohistochemistry, and serum inflammatory cytokine levels were detected by ELISA. RESULTS Thirty-two UC patients and twenty-three HCs were enrolled in this study. It was found that the diversity of gut microbiota in UC patients was reduced compared with that in HCs. Firmicutes, Clostridium IV, Butyricicoccus, Clostridium XlVa, Faecalibacterium, and Roseburia were significantly decreased in patients with UC (P = 3.75E-05, P = 8.28E-07, P = 0.0002, P = 0.003, P = 0.0003, and P = 0.0004, respectively). Proteobacteria, Escherichia, Enterococcus, Klebsiella, and Streptococcus were significantly enriched in the UC group (P = 2.99E-09, P = 3.63E-05, P = 8.59E-05, P = 0.003, and P = 0.016, respectively). The concentrations of fecal secondary BAs, such as lithocholic acid, deoxycholic acid, glycodeoxycholic acid, glycolithocholic acid, and taurolithocholate, in UC patients were significantly lower than those in HCs (P = 8.1E-08, P = 1.2E-07, P = 3.5E-04, P = 1.9E-03, and P = 1.8E-02, respectively) and were positively correlated with Butyricicoccus, Roseburia, Clostridium IV, Faecalibacterium, and Clostridium XlVb (P < 0.01). The concentrations of primary BAs, such as taurocholic acid, cholic acid, taurochenodeoxycholate, and glycochenodeoxycholate, in UC patients were significantly higher than those in HCs (P = 5.3E-03, P = 4E-02, P = 0.042, and P = 0.045, respectively) and were positively related to Enterococcus, Klebsiella, Streptococcus, Lactobacillus, and pro-inflammatory cytokines (P < 0.01). The expression of TGR5 was significantly elevated in UC patients (0.019 ± 0.013 vs 0.006 ± 0.003, P = 0.0003). VDR expression in colonic mucosal specimens was significantly decreased in UC patients (0.011 ± 0.007 vs 0.016 ± 0.004, P = 0.033). CONCLUSION Fecal BA profiles are closely related to the gut microbiota and serum inflammatory cytokines. Dysregulation of the gut microbiota and altered constitution of fecal BAs may participate in regulating inflammatory responses via the BA receptors TGR5 and VDR.

Ulcerative colitis (UC) is a chronic, nonspecific, relapsing inflammatory bowel disease. The colorectum is considered the chief target organ of UC, whereas upper gastrointestinal (UGI) tract manifestations are infrequent. Recently, emerging evidence has suggested that UC presents complications in esophageal, stomachic, and duodenal mucosal injuries. However, UC-related UGI tract manifestations are varied and frequently silenced or concealed. Moreover, the endoscopic and microscopic characteristics of UGI tract complicated with UC are nonspecific. Therefore, UGI involvement may be ignored by many clinicians. In addition, no standard criteria have been established for patients with UC who should undergo fibrogastroduodenoscopy. Furthermore, specific treatment recommendations may be needed for patients with UC-associated UGI lesions. Herein, we review the esophageal, gastric, and duodenal mucosal lesions of the UC-associated UGI tract, as well as the potential pathogenesis and therapy.

Background Oral tacrolimus is a therapeutic agent for moderate to severe steroid-dependent or resistant ulcerative colitis (UC), but remission induction is difficult, and it is necessary to treat the patient while considering the next treatment. Aim To examine serum albumin (Alb) level as a prognostic factor for the therapeutic effect of tacrolimus in clinical practice. Methods Forty-seven patients with UC treated with tacrolimus at our institution were divided into remission and failure groups (colectomy or switch to biologics), and the biological data at the start of observation and at weeks 1 and 2 were retrospectively examined. Kaplan-Meier and multivariate analyses were performed using Alb as a prognostic factor in UC treatment. Results During the three months observed, 17 (36.2%) patients failed treatment with tacrolimus. A comparison between the failure and remission groups showed a significant difference only in Alb in week 2, and in the week 2/week 0 Alb ratio, which showed the rate of change in Alb. The cut-off value of the week 2/week 0 Alb ratio that predicted failure was 1, and its area under the curve was 0.751 (95%CI: 0.604-0.898). In the Kaplan-Meier analysis, a week 2/week 0 Alb ratio ≤ 1 had a significantly higher failure rate than that of > 1; Cox proportional hazard regression analysis also showed that a week 2/week 0 Alb ratio ≤ 1 was an independent prognostic factor for failure within 3 mo after the start of tacrolimus treatment. Conclusion A week 2/week 0 Alb ratio ≤ 1 predicts failure within 3 mo of tacrolimus administration for UC. High failure risk exists with week 2 Alb values ≤ 1 on admission.

Background Emerging evidence has demonstrated that fecal microbiota transplantation (FMT) has a promising therapeutic effect on mice with experimental colitis and patients with ulcerative colitis (UC), although the mechanism of FMT is unclear. Aim To evaluate the protective effect of FMT on UC and clarify its potential dependence on the gut microbiota, through association analysis of gut microbiota with colon transcriptome in mice. Methods Dextran sodium sulfate (DSS)-induced experimental colitis was established and fecal microbiota was transplanted by gavage. Severity of colon inflammation was measured by body weight, disease activity index, colon length and histological score. Gut microbiota alteration was analyzed through 16S ribosomal ribonucleic acid sequencing. The differentially expressed genes (DEGs) in the colon were obtained by transcriptome sequencing. The activation status of colonic T lymphocytes in the lamina propria was evaluated by flow cytometry. Results Compared with the DSS group, the weight loss, colon length shortening and inflammation were significantly alleviated in the FMT group. The scores of disease activity index and colon histology decreased obviously after FMT. FMT restored the balance of gut microbiota, especially by upregulating the relative abundance of Lactobacillus and downregulating the relative abundance of Clostridium_sensu_stricto_1 and Turicibacter. In the transcriptomic analysis, 128 DEGs intersected after DSS treatment and FMT. Functional annotation analysis suggested that these DEGs were mainly involved in T-lymphocyte activation. In the DSS group, there was an increase in colonic T helper CD4+ and T cytotoxic CD8+ cells by flow cytometry. FMT selectively downregulated the ratio of colonic CD4+ and CD8+ T cells to maintain intestinal homeostasis. Furthermore, Clostri dium_sensu_stricto_1 was significantly related to inflammation-related genes including REG3G, CCL8 and IDO1. Conclusion FMT ameliorated DSS-induced colitis in mice via regulating the gut microbiota and T-cell modulation.

Made available in DSpace on 2021-06-25T11:14:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-03-28 BACKGROUND Coronavirus disease 2019 (COVID-19) pandemic is still evolving globally, and Brazil is currently one of the most affected countries. It is still debated whether patients with inflammatory bowel disease (IBD) are at a higher risk for developing COVID-19 or its complications. AIM To assess geographical distribution of IBD patients at the highest risk and correlate these data with COVID-19 mortality rates in Brazil. METHODS The Brazilian IBD Study Group (Grupo de Estudos da Doença Inflamatória Intestinal do Brasil) developed a web-based survey adapted from the British Society of Gastroenterology guidelines. The included categories were demographic data and inquiries related to risk factors for complications from COVID-19. Patients were categorized as highest, moderate or lowest individual risk. The Spearman correlation test was used to identify any association between highest risk and mortality rates for each state of the country. RESULTS A total of 3568 patients (65.3% females) were included. Most participants were from the southeastern and southern regions of Brazil, and 84.1% were using immunomodulators and/or biologics. Most patients (55.1%) were at moderate risk, 23.4% were at highest risk and 21.5% were at lowest risk of COVID-19 complications. No association between the proportion of IBD patients at highest risk for COVID-19 complications and higher mortality rates was identified in different Brazilian states (r = 0.146, P = 0.467). CONCLUSION This study indicates a distinct geographical distribution of IBD patients at highest risk for COVID-19 complications in different states of the country, which may reflect contrasting socioeconomic, educational and healthcare aspects. No association between high risk of IBD and COVID-related mortality rates was identified. Department of Gastroenterology University of São Paulo School of Medicine IBD Unit Gastroenterology Department Gastrosaúde Clinic School of Medicine Federal University of Bahia IBD Outpatient Clinics Universidade Federal de Juiz de Fora Health Sciences Postgraduate Program Pontifícia Universidade Católica do Paraná (PUCPR) Departamento de Ciências da Saúde Universidade do Oeste de Santa Catarina (UNOESC) Botucatu Medical School Paulista State University (UNESP) IBD Outpatient Clinics Pontificia Universidade Católica do Paraná (PUCPR) Botucatu Medical School Paulista State University (UNESP)

BACKGROUND 1,3-beta-D-glucan (BG) is a ubiquitous cell wall component of gut micro-organisms. We hypothesized that the serum levels of BG could reflect active intestinal inflammation in patients with inflammatory bowel disease. AIM To determine whether the serum BG concentrations correlate with intestinal inflammation. METHODS A prospective observational study was performed in a tertiary referral center, from 2016 to 2019, in which serum BG was determined in 115 patients with Crohn’s disease (CD), 51 with ulcerative colitis (UC), and 82 controls using a photometric detection kit. Inflammatory activity was determined by ileocolonoscopy, histopathology, magnetic resonance enterography, and biomarkers, including fecal calprotectin (FC), C-reactive protein, and a panel of cytokines. The ability of BG to detect active vs inactive disease was assessed using the area under the receiver operating characteristic curve. In subgroup analysis, serial BG was used to assess the response to therapeutic interventions. RESULTS The serum BG levels were higher in CD patients than in controls (P = 0.0001). The BG levels paralleled the endoscopic activity in CD patients and histologic activity and combined endoscopic and histologic activity in both CD and UC patients. The area under the curve (AUC) in receiver operating characteristic analysis to predict endoscopic activity was 0.694 [95% confidence interval (CI): 0.60-0.79; P = 0.001] in CD, and 0.662 (95%CI: 0.51-0.81; P = 0.066) in UC patients. The AUC in receiver operating characteristic analysis to predict histologic activity was 0.860 (95%CI: 0.77-0.95; P < 0.001) in CD, and 0.786 (95%CI: 0.57-0.99; P = 0.015) in UC patients. The cut-off values of BG for both endoscopic and histologic activity were 60 µg/mL in CD, and 40 µg/mL in UC patients. Performance analysis showed that the results based on BG of 40 and 60 µg/mL were more specific for predicting endoscopic activity (71.8% and 87.2% for CD; and 87.5% and 87.5% for UC, respectively) than FC (53.3% and 66.7% for CD; and 20% and 80% for UC, respectively); and also histologic activity (60.5% and 76.3% for CD; and 90.0% and 95.0% for UC, respectively) than FC (41.7% and 50.0% for CD; and 25% and 50% for UC, respectively). Regarding the clinical, endoscopic, and histologic activities, the BG levels were reduced following therapeutic intervention in patients with CD (P < 0.0001) and UC (P = 0.003). Compared with endoscopic (AUC: 0.693; P = 0.002) and histologic (AUC: 0.868; P < 0.001) activity, no significant correlation was found between serum BG and transmural healing based on magnetic resonance enterography (AUC: 0.576; P = 0.192). Positive correlations were detected between BG and IL-17 in the CD (r: 0.737; P = 0.001) and the UC group (r: 0.574; P = 0.005), and between BG and interferon-gamma in the CD group (r: 0.597; P = 0.015). CONCLUSION Serum BG may represent an important novel noninvasive approach for detecting mucosal inflammation and therapeutically monitoring inflammatory bowel diseases, particularly in CD.

BACKGROUND It is a crucial issue for patients with refractory ulcerative colitis (UC), including steroid-dependent and steroid-refractory patients, to achieve and maintain steroid-free remission. However, clinical studies focused on the achievement of steroid-free remission in refractory UC patients are insufficient. Cytapheresis (CAP) is a non-pharmacological extracorporeal therapy that is effective for active UC with fewer adverse effects. This study comprised UC patients treated with CAP and suggested the efficacy of CAP for refractory UC patients. AIM To clarify the efficacy of CAP in achieving steroid-free remission in refractory UC patients. METHODS We retrospectively reviewed the collected data from 55 patients with refractory UC treated with CAP. We analyzed the following points: (1) Efficacy of the first course of CAP; (2) Efficacy of the second, third, and fourth courses of CAP in patients who experienced relapses during the observation period; (3) Efficacy of CAP in colonic mucosa; and (4) Long-term efficacy of CAP. Clinical efficacy was evaluated using Lichtiger's clinical activity index or Sutherland index (disease activity index). Mucosal healing was evaluated using Mayo endoscopic subscore. The primary and secondary endpoints were the rate of achievement of steroid-free remission and the rate of sustained steroid-free remission, respectively. Statistical analysis was performed using the paired t-test and chi-squared test. RESULTS The rates of clinical remission, steroid-free remission, and poor effectiveness after CAP were 69.1%, 45.5%, and 30.9%, respectively. There were no significant differences in rate of steroid-free remission between patients with steroid-dependent and steroid-refractory UC. The mean disease activity index and Lichtiger's clinical activity index scores were significantly decreased after CAP (P < 0.0001). The rates of steroid-free remission after the second, third, and fourth courses of CAP in patients who achieved steroid-free remission after the first course of CAP were 83.3%, 83.3%, and 60%, respectively. Mucosal healing was observed in all patients who achieved steroid-free remission after the first course of CAP. The rates of sustained steroid-free remission were 68.0%, 60.0%, and 56.0% at 12, 24, and 36 mo after the CAP. Nine patients (36%) had maintained steroid-free remission throughout the observation period. CONCLUSION Our results suggest that CAP effectively induces and maintains steroid-free remission in refractory UC and re-induces steroid-free remission in patients achieving steroid-free remission after the first course of CAP.

Half of the patients with ulcerative colitis require at least one course of systemic corticosteroids in their lifetime. Approximately 75% of these patients will also require immunosuppressive drugs (i.e., thiopurines or biological agents) in the mid-term to avoid colectomy. Immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer, particularly in elderly and co-morbid patients, underlining the unmet need for safer alternative therapies. Granulocyte/monocytapheresis (GMA), a CE-marked, non-pharmacological procedure for the treatment of ulcerative colitis (among other immune-mediated diseases), remains the only therapy targeting neutrophils, the hallmark of pathology in ulcerative colitis. GMA has proven its efficacy in different clinical scenarios and shows an excellent and unique safety profile. In spite of being a first line therapy in Japan, GMA use is still limited to a small number of centres and countries in Europe. In this article, we aim to give an overview from a European perspective of the mechanism of action, recent clinical data on efficacy and practical aspects for the use of GMA in ulcerative colitis.

BACKGROUND Inflammatory bowel disease (IBD) is a chronic, relapsing inflammation of the digestive tract. Although fecal and serum biomarkers have been extremely important and supportive for monitoring of IBD, their low sensitivity and high variability characteristics limit clinical efficacy. Thus, the establishment of better biomarkers is expected. Fucosylation is one of the most important glycosylation modifications of proteins. Fucosylated haptoglobin (Fuc-Hpt) is used as a biomarker for several cancers and inflammation-related diseases. We recently established a novel glycan monoclonal antibody (mAb), designated 10-7G, which recognizes Fuc-Hpt. We developed an enzyme-linked immunosorbent assay (ELISA) to measure serum levels of Fuc-Hpt (10-7G values). AIM To investigate the usefulness of the serum 10-7G values as a potential biomarker for monitoring disease activity in IBD. METHODS This was a case control study. Intestinal tissues of IBD patients (n = 10) were examined immunohistochemically using the 10-7G mAb. We determined 10-7G values using serum from patients with ulcerative colitis (UC, n = 110), Crohn’s disease (n = 45), acute enteritis (AE, n = 11), and healthy volunteers (HVs) who exhibited normal (n = 20) or high (n = 79) C-reactive protein (CRP) levels at medical check-up. We investigated the correlation between the 10-7G value and various clinical parameters of IBD patients by correlation analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the usefulness of the 10-7G values as a biomarker for clinical and endoscopic remission of UC compared to conventional serum biomarkers. RESULTS In the immunohistochemical analysis, positive 10-7G mAb staining was observed in lymphocytes infiltrating into inflammatory sites of the mucosal layer and lymphoid follicles. The 10-7G values were significantly higher in patients with IBD (P < 0.001) and AE (P < 0.05) compared with HVs. In addition, 10-7G values were correlated with clinical examination parameters related to inflammation in patients with UC, particularly the CRP level (rs = 0.525, P = 0.003) and clinical activity index score (rs = 0.435, P = 0.038). However, there was no correlation between 10-7G values and CRP in HVs with high CRP levels, suggesting that the 10-7G values is not the same as a general inflammation biomarker. ROC curve analysis showed that area under the curve (AUC) value of 10-7G values for the diagnosis of endoscopic remission was higher than other biomarkers (AUC value = 0.699). CONCLUSION The serum 10-7G value is a novel biomarker for evaluating intestinal inflammation and endoscopic mucosal healing in UC.

BACKGROUND The expression of jumonji domain-containing 3 (Jmjd3) and trimethylated H3 lysine 27 (H3K27me3) in active ulcerative colitis (UC) and the correlation between vitamin D receptor (VDR) and the Jmjd3 pathway are unknown. AIM To study the relationship between VDR, Jmjd3 and H3K27me3 in patients with active UC. METHODS One hundred patients with active UC and 56 healthy controls were enrolled in this study. The patients with active UC were divided into groups according to mild (n = 29), moderate (n = 32) and severe (n = 29) disease activity based on the modified Mayo score. Vitamin D levels were measured by radioimmunoassay. Colonic mucosal tissues from UC patients and controls were collected by colonoscopy. The expression of VDR, Jmjd3 and H3K27me3 in the intestinal mucosa was determined by immunohistochemistry staining. RESULTS Patients with active UC had lower levels of serum vitamin D (13.7 ± 2.8 ng/mL, P < 0.001) than the controls (16.2 ± 2.5 ng/mL). In the UC cohort, serum vitamin D level was negatively correlated with disease activity (r = -0.323, P = 0.001). VDR expression in the mucosa of UC patients was reduced compared to that in normal tissues (P < 0.001) and negatively correlated with disease activity (r = -0.868, P < 0.001). Similar results for VDR expression were noted in the most serious lesion (defined as UC diseased) and 20 cm proximal to the anus (defined as UC normal) (P < 0.05). Simultaneously, Jmjd3 expression significantly increased in UC patients (P < 0.001), but no difference was found between the different sites in UC patients. H3K27me3 expression in UC patients was significantly down-regulated when compared with normal tissues (P < 0.001), but up-regulated in the mild disease activity group in comparison with the moderate disease activity group of UC patients (P < 0.05). Jmjd3 Level was negatively correlated with the level of VDR (r = -0.342, P = 0.002) and H3K27me3 (r = -0.341, P = 0.002), while VDR level was positively correlated with H3K27me3 (r = 0.473, P < 0.001). CONCLUSION Serum vitamin D and VDR were inversely correlated with disease activity in active UC. Jmjd3 expression increased in the colonic mucosa of active UC patients and was negatively associated with VDR and H3K27me3 level.

Ulcerative colitis (UC) is a chronic relapsed intestinal disease with an increasing incidence around the world. The pathophysiology of UC remains unclear. However, the role of the interaction between the enteric nervous system and the immune system in the pathogenesis of UC has been the focus of attention and has become a research hotspot. Vasoactive intestinal peptide (VIP) is a kind of endogenous neuropeptide with regulatory activity on intestinal immunity. It has been shown to regulate immune disorders in animal and human experiments and has become an effective anti-inflammatory and immune modulator that affects the innate immune system and adaptive immune system. Regulatory B cells (Bregs) are a new group of B cells that negatively regulate the immunity and have received extensive attention in immune circles. Bregs can regulate immune tolerance by producing interleukin (IL)-10, IL-35, and transforming growth factor-β, suppressing autoimmune diseases or excessive inflammatory responses. The secretion of IL-10 by Bregs induces the development of T helper (Th) 0 and Th2 cells. It also induces Th2 cytokines and inhibits Th1 cytokines, thereby inhibiting Th1 cells and the Th1/Th2 balance. With further clarity on the mechanism of the regulation of IL-10 expression by VIP in Bregs in colitis patients, we believe that Bregs can provide a novel strategy for the clinical treatment of UC. Thus, we aim to review the current literature on this evolving topic.

For the optimal management of refractory ulcerative colitis (UC), secondary loss of response (LOR) and primary non-response to biologics is a critical issue. This article aimed to summarize the current literature on the use of cytapheresis (CAP) in patients with UC showing a poor response or LOR to biologics and discuss its advantages and limitations. Further, we summarized the efficacy of CAP in patients with UC showing insufficient response to thiopurines or immunomodulators (IM). Eight studies evaluated the efficacy of CAP in patients with UC with inadequate responses to thiopurines or IM. There were no significant differences in the rate of remission and steroid-free remission between patients exposed or not exposed to thiopurines or IM. Three studies evaluated the efficacy of CAP in patients with UC showing an insufficient response to biologic therapies. Mean remission rates of biologics exposed or unexposed patients were 29.4 % and 44.2%, respectively. Fourteen studies evaluated the efficacy of CAP in combination with biologics in patients with inflammatory bowel disease showing a poor response or LOR to biologics. The rates of remission/response and steroid-free remission in patients with UC ranged 32%-69% (mean: 48.0%, median: 42.9%) and 9%-75% (mean: 40.7%, median: 38%), respectively. CAP had the same effectiveness for remission induction with or without prior failure on thiopurines or IM but showed little benefit in patients with UC refractory to biologics. Although heterogeneity existed in the efficacy of the combination therapy with CAP and biologics, these combination therapies induced clinical remission/response and steroid-free remission in more than 40% of patients with UC refractory to biologics on average. Given the excellent safety profile of CAP, this combination therapy can be an alternative therapeutic strategy for UC refractory to biologics. Extensive prospective studies are needed to understand the efficacy of combination therapy with CAP and biologics.

Medications for inflammatory bowel disease (IBD) have changed dramatically over time. However, no study on long-term medication profiles has been conducted in the Chinese population.To evaluate temporal changes in medication use and treatment patterns for Chinese patients with IBD.A multicenter retrospective cohort study was conducted among Chinese patients newly diagnosed with Crohn's disease (CD) and ulcerative colitis (UC) between January 1999 and December 2019. Baseline characteristics and drug prescriptions were collected. Trends in medication use and therapeutic patterns were analyzed.In total, 3610 patients were analyzed. During follow-up, 5-aminosalicylates (5-ASA) and corticosteroids (CS) prescriptions gradually decreased, accompanied by a notable increase in immunosuppressants (IMS) and infliximab (IFX) prescriptions in patients with CD. Prescription rates of 5-ASA and CS were stable, whereas IMS and IFX slightly increased since 2007 in patients with UC. Subgroup (Long-term treatment strategies analyses has provided unique insight into the switch from conventional drugs to IFX in Chinese patients with CD.

The healthcare burden of inflammatory bowel disease (IBD) is rising globally and there are limited non-invasive biomarkers for accurate and early diagnosis.To understand the important role that intestinal microbiota play in IBD pathogenesis and identify anti-microbial antibody signatures that benefit clinical management of IBD patients.We performed serological profiling of 100 Crohn's disease (CD) patients, 100 ulcerative colitis (UC) patients and 100 healthy controls against 1173 bacterial and 397 viral proteins from 50 bacteria and 33 viruses on protein microarrays. The study subjects were randomly divided into discovery (Anti-bacterial antibody responses showed greater differential prevalence among the three subject groups than anti-viral antibody responses. We identified novel antibodies against the antigens ofWe have identified antibody signatures for CD and UC using a comprehensive analysis of anti-microbial antibody response in IBD. These antibodies and the source microorganisms of their target antigens improve our understanding of the role of specific microorganisms in IBD pathogenesis and, after future validation, should aid early and accurate diagnosis of IBD.

A gap remains in documenting the impact of anti-tumor necrosis factor therapy on disease burden in ulcerative colitis (UC) patients treated in a real-world setting. The use of patient-reported outcomes (PROs) has been discussed as a primary endpoint in the context of the FDA PRO Guidance, for labelling purposes. Specifically, the efficacy and safety of adalimumab have been demonstrated in pivotal trials; however, data are needed to understand how clinical results translate into improvements in key aspects of the daily lives of UC patients, such as symptoms, health-related quality of life (HRQoL), and disability.To assess real-world effectiveness of adalimumab on PRO measures in patients with moderate-to-severe UC.UCanADA was a single arm, prospective, 1-year multicenter Canadian post-marketing observational study in which multiple PRO questionnaires were completed-with psychologic distress/depression symptoms as the primary endpoint-by patients with moderate-to-severe UC. Assessments were performed during patients' routine care visit schedule, which was at the initiation of adalimumab (baseline), after induction (approximately 8 wk), and 52 wk after baseline. Additional optional assessments between weeks 8 and 52 were collected at least once but no more than two times during this period. Serious safety events and per-protocol adverse events were collected.From 23 Canadian centres, 100 patients were enrolled and 48 completed the study. Measured with the Patient Health Questionnaire-9 items at week 52, 61.5% (40/65) [95% confidence interval (CI): 49.7%-73.4%] of the patients improved in psychologic distress/depression symptoms, which was slightly higher in completers [65.9% (29/44); 95%CI: 51.9%-79.9%)]. At week 52, clinical response and clinical remission were achieved respectively by 65.7% (44/73) and 47.8% (32/73) of the patients. The odds of improving depressive symptoms for those achieving a clinical remission at week 52 was 7.94 higher compared with those not achieving a clinical remission (CI: 1.42, 44.41;At week 52, over 60% of the UCanADA patients had depressive symptoms significantly reduced, as well as HRQoL, fatigue symptoms, and work impairment improved. No new safety signals were detected.

Patients with inflammatory bowel disease (IBD) are prone to several nutritional deficiencies. However, data are lacking on vitamin C deficiency in Crohn's disease (CD) and ulcerative colitis (UC) patients, as well as the impact of clinical, biomarker and endoscopic disease severity on the development of vitamin C deficiency.To determine proportions and factors associated with vitamin C deficiency in CD and UC patients.In this retrospective study, we obtained clinical, laboratory and endoscopic data from CD and UC patients presenting to the IBD clinic at a single tertiary care center from 2014 to 2019. All patients had an available plasma vitamin C level. Of 353 subjects who met initial search criteria using a cohort discovery tool, 301 ultimately met criteria for inclusion in the study. The primary aim described vitamin C deficiency (≤ 11.4 μmol/L) rates in IBD. Secondary analyses compared proportions with deficiency between active and inactive IBD. Multivariate logistic regression analysis evaluated factors associated with deficiency.Of 301 IBD patients, 21.6% had deficiency, including 24.4% of CD patients and 16.0% of UC patients. Patients with elevated C-reactive protein (CRP) (39.1%Vitamin C deficiency was common in IBD. Patients with elevated inflammatory markers and penetrating disease had higher rates of vitamin C deficiency.

Detection of prevalence and development of osteopenia or osteoporosis in patients with inflammatory bowel disease using only bone mineral density could be inappropriate to detect all individuals at risk for osteoporosis. Numerous patients could remain undetected by using only bone mineral density as a screening method, especially in patients with ulcerative colitis. Therefore, trabecular bone score should be used as a complementary method.

Ulcerative colitis and Crohn's disease are the main entities of inflammatory bowel disease characterized by chronic remittent inflammation of the gastrointestinal tract. The incidence and prevalence are on the rise worldwide, and the heterogeneity between patients and within individuals over time is striking. The progressive advance in our understanding of the etiopathogenesis coupled with an unprecedented increase in therapeutic options have changed the management towards evidence-based interventions by clinicians with patients. This guideline was stimulated and supported by the Emirates Gastroenterology and Hepatology Society following a systematic review and a Delphi consensus process that provided evidence- and expert opinion-based recommendations. Comprehensive up-to-date guidance is provided regarding diagnosis, evaluation of disease severity, appropriate and timely use of different investigations, choice of appropriate therapy for induction and remission phase according to disease severity, and management of main complications.

Background Single port laparoscopic surgery allows total colectomy and end ileostomy for medically uncontrolled ulcerative colitis solely via the stoma site incision. While intuitively appealing, there is sparse evidence for its use beyond feasibility. Aim To examine the usefulness of single access laparoscopy (SAL) in a general series experience of patients sick with ulcerative colitis. Methods All patients presenting electively, urgently or emergently over a three-year period under a colorectal specialist team were studied. SAL was performed via the stoma site on a near-consecutive basis by one surgical team using a "surgical glove port" allowing group-comparative and case-control analysis with a contemporary cohort undergoing conventional multiport surgery. Standard, straight rigid laparoscopic instrumentation were used without additional resource. Results Of 46 consecutive patients requiring surgery, 39 (85%) had their procedure begun laparoscopically. 27 (69%) of these were commenced by single port access with an 89% completion rate thereafter (three were concluded by multi-trocar laparoscopy). SAL proved effective in comparison to multiport access regardless of disease severity providing significantly reduced operative access costs (> 100€case) and postoperative hospital stay (median 5 d vs 7.5 d, P = 0.045) without increasing operative time. It proved especially efficient in those with preoperative albumin > 30 g/dL (n = 20). Its comparative advantages were further confirmed in ten pairs case-matched for gender, body mass index and preoperative albumin. SAL outcomes proved durable in the intermediate term (median follow-up = 20 mo). Conclusion Single port total colectomy proved useful in planned and acute settings for patients with medically refractory colitis. Assumptions regarding duration and cost should not be barriers to its implementation.

BACKGROUND: Colonic transendoscopic enteral tubing (TET) requires double cecal intubation, raising a common concern of how to save cecal intubation time and make the tube stable. We hypothesized that cap-assisted colonoscopy (CC) might reduce the second cecal intubation time and bring potential benefits during the TET procedure. AIM: To investigate if CC can decrease the second cecal intubation time compared with regular colonoscopy (RC). METHODS: This prospective multicenter, randomized controlled trial was performed at four centers. Subjects ≥ 7 years needing colonic TET were recruited from August 2018 to January 2020. All subjects were randomly assigned to two groups. The primary outcome was the second cecal intubation time. Secondary outcomes included success rate, insertion pain score, single clip fixation time, purpose and retention time of TET tube, length of TET tube inserted into the colon, and all procedure-related (serious) adverse events. RESULTS: A total of 331 subjects were randomized to the RC (n = 165) or CC (n = 166) group. The median time of the second cecal intubation was significantly shorter for CC than RC (2.2 min vs 2.8 min, P < 0.001). In patients with constipation, the median time of second cecal intubation in the CC group (n = 50) was shorter than that in the RC group (n = 43) (2.6 min vs 3.8 min, P = 0.004). However, no difference was observed in the CC (n = 42) and RC (n = 46) groups of ulcerative colitis patients (2.0 min vs 2.5 min, P = 0.152). The insertion pain score during the procedure in CC (n = 14) was lower than that in RC (n = 19) in unsedated colonoscopy (3.8 ± 1.7 vs 5.4 ± 1.9; P = 0.015). Multivariate analysis revealed that only CC (odds ratio [OR]: 2.250, 95% confidence interval [CI]: 1.161-4.360; P = 0.016) was an independent factor affecting the second cecal intubation time in difficult colonoscopy. CC did not affect the colonic TET tube’s retention time and length of the tube inserted into the colon. Moreover, multivariate analysis found that only endoscopic clip number (OR: 2.201, 95%CI: 1.541-3.143; P < 0.001) was an independent factor affecting the retention time. Multiple regression analysis showed that height (OR: 1.144, 95%CI: 1.027-1.275; P = 0.014) was the only independent factor influencing the length of TET tube inserted into the colon in adults. CONCLUSION: CC for colonic TET procedure is a safe and less painful technique, which can reduce cecal intubation time.

Background Ulcerative colitis (UC) is an inflammatory bowel disease that is difficult to diagnose and treat. To date, the degree of inflammation in patients with UC has mainly been determined by measuring the levels of nonspecific indicators, such as C-reactive protein and the erythrocyte sedimentation rate, but these indicators have an unsatisfactory specificity. In this study, we performed bioinformatics analysis using data from the National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) databases and verified the selected core genes in a mouse model of dextran sulfate sodium (DSS)-induced colitis. Aim To identify UC-related differentially expressed genes (DEGs) using a bioinformatics analysis and verify them in vivo and to identify novel biomarkers and the underlying mechanisms of UC. Methods Two microarray datasets from the NCBI-GEO database were used, and DEGs between patients with UC and healthy controls were analyzed using GEO2R and Venn diagrams. We annotated these genes based on their functions and signaling pathways, and then protein-protein interactions (PPIs) were identified using the Search Tool for the Retrieval of Interacting Genes. The data were further analyzed with Cytoscape software and the Molecular Complex Detection (MCODE) app. The core genes were selected and a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed. Finally, colitis model mice were established by administering DSS, and the top three core genes were verified in colitis mice using real-time polymerase chain reaction (PCR). Results One hundred and seventy-seven DEGs, 118 upregulated and 59 downregulated, were initially identified from the GEO2R analysis and predominantly participated in inflammation-related pathways. Seven clusters with close interactions in UC formed: Seventeen core genes were upregulated [C-X-C motif chemokine ligand 13 (CXCL13), C-X-C motif chemokine receptor 2 (CXCR2), CXCL9, CXCL5, C-C motif chemokine ligand 18, interleukin 1 beta, matrix metallopeptidase 9, CXCL3, formyl peptide receptor 1, complement component 3, CXCL8, CXCL1, CXCL10, CXCL2, CXCL6, CXCL11 and hydroxycarboxylic acid receptor 3] and one was downregulated [neuropeptide Y receptor Y1 (NYP1R)] in the top cluster according to the PPI and MCODE analyses. These genes were substantially enriched in the cytokine-cytokine receptor interaction and chemokine signaling pathways. The top three core genes (CXCL13, NYP1R, and CXCR2) were selected and verified in a mouse model of colitis using real-time PCR Increased expression was observed compared with the control mice, but only CXCR2 expression was significantly different. Conclusion Core DEGs identified in UC are related to inflammation and immunity inflammation, indicating that these reactions are core features of the pathogenesis of UC. CXCR2 may reflect the degree of inflammation in patients with UC.

Inflammatory bowel disease (IBD) incidence has been increasing steadily, most dramatically in the Western developed countries. Treatment often includes lifelong immunosuppressive therapy and surgery. There is a critical need to reduce the burden of IBD and to discover medical therapies with better efficacy and fewer potential side-effects. Repurposing of treatments originally studied in other diseases with similar pathogenesis is less costly and time intensive than de novo drug discovery. This study used a treatment repurposing methodology, the literature-related discovery and innovation (LRDI) text mining system, to identify potential treatments (developed for non-IBD diseases) with sufficient promise for extrapolation to treatment of IBD. By searching for desirable patterns of twenty key biomarkers relevant to IBD (e.g., inflammation, reactive oxygen species, autophagy, barrier function), the LRDI-based query retrieved approximately 9500 records from Medline. The most recent 350 records were further analyzed for proof-of-concept. Approximately 18% (64/350) met the criteria for discovery (not previously studied in IBD human or animal models) and relevance for application to IBD treatment. Many of the treatments were compounds derived from herbal remedies, and the majority of treatments were being studied in cancer, diabetes, and central nervous system disease, such as depression and dementia. As further validation of the search strategy, the query identified ten treatments that have just recently begun testing in IBD models in the last three years. Literature-related discovery and innovation text mining contains a unique search strategy with tremendous potential to identify treatments for repurposing. A more comprehensive query with additional key biomarkers would have retrieved many thousands more records, further increasing the yield of IBD treatment repurposing discovery.

BACKGROUND Vedolizumab (VDZ), a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis (UC) patients. AIM To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving remission. METHODS A retrospective review of Australian and Oxford, United Kingdom data for UC patients. Clinical response at 3 mo, endoscopic remission at 6 mo and clinical remission at 3, 6 and 12 mo were assessed. Cox regression models and Kaplan Meier curves were performed to assess the time to remission, time to failure and the covariates influencing them. Safety outcomes were recorded. RESULTS Three hundred and three UC patients from 14 centres in Australia and United Kingdom, [60% n = 182, anti-TNF naïve] were included. The clinical response was 79% at 3 mo with more Australian patients achieving clinical response compared to Oxford (83% vs 70% P = 0.01). Clinical remission for all patients was 56%, 62% and 60% at 3, 6 and 12 mo respectively. Anti-TNF naive patients were more likely to achieve remission than exposed patients at all the time points (3 mo 66% vs 40% P < 0.001, 6 mo 73% vs 46% P < 0.001, 12 mo 66% vs 51% P = 0.03). More Australian patients achieved endoscopic remission at 6 mo compared to Oxford (69% vs 43% P = 0.01). On multi-variate analysis, anti-TNF naïve patients were 1.8 (95%CI: 1.3-2.3) times more likely to achieve remission than anti-TNF exposed (P < 0.001). 32 patients (11%) had colectomy by 12 mo. CONCLUSION VDZ was safe and effective with 60% of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome.

Background Smoking has detrimental effects on Crohn's disease (CD) activity while data on ulcerative colitis (UC) are conflicting. Little is known about the use and impact of alternative smoking products in inflammatory bowel diseases (IBD). Aim To understand the patients' perceptions of the impact of smoking on their IBD and to assess differences between CD and UC patients. Methods The questionnaire was developed by Philip Morris Products SA in cooperation with European Federation of Crohn's and Ulcerative Colitis Associations. The final survey questionnaire consisted of 41 questions divided in 8 categories: (1) Subject screener; (2) Smoking history; (3) Background information; (4) IBD disease background; (5) Current disease status; (6) Current therapeutics and medications; and (7) Current nicotine/cigarettes use and awareness of the impacts of smoking on IBD. The questionnaire was submitted online from 4th November 2019 to 11th March 2020 through the European Federation of Crohn's and Ulcerative Colitis Associations website to IBD patients who were current smokers or had a history of smoking. Results In total 1050 IBD patients speaking nine languages participated to the survey. Among them, 807 (76.9%) patients declared to have ever smoked or consumed an alternative smoking product, with a higher proportion of current cigarette smokers among CD patients (CD: 63.1% vs UC: 54.1%, P = 0.012). About two-thirds of the participants declared to have ever stopped cigarette smoking and restarted (67.0%), with a significantly higher proportion among UC patients compared to CD patients (73.1% vs 62.0%, P = 0.001). We also found significant differences between CD and UC patients in the awareness of the health consequences of smoking in their disease and in the perceived impact of smoking on disease activity, for both cigarettes and alternative smoking products. Conclusion This survey found significant differences between CD and UC patients in both awareness and perception of the impact of smoking on their disease. Further efforts should be done to encourage smoking cessation for all IBD patients, including UC patients.

In 2018, the pan-Janus kinase (JAK) inhibitor tofacitinib was launched for the treatment of ulcerative colitis (UC). Although tofacitinib has proven efficacious in patients with active UC, it failed in patients with Crohn's disease (CD). This finding strongly hints at a different contribution of JAK signaling in both entities. Here, we review the current knowledge on the interplay between the JAK/signal transducer and activator of transcription (STAT) pathway and inflammatory bowel diseases (IBD). In particular, we provide a detailed overview of the differences and similarities of JAK/STAT-signaling in UC and CD, highlight the impact of the JAK/STAT pathway in experimental colitis models and summarize the published evidence on JAK/STAT-signaling in immune cells of IBD as well as the genetic association between the JAK/STAT pathway and IBD. Finally, we describe novel treatment strategies targeting JAK/STAT inhibition in UC and CD and comment on the limitations and challenges of the new drug class.

Background Primary sclerosing cholangitis (PSC) associated inflammatory bowel disease (IBD) is a unique form of IBD (PSC-IBD) with distinct clinical and histologic features from ulcerative colitis (UC) and Crohn disease (CD). In patients with PSC and IBD, the severity of the two disease processes may depend on each other. Aim To study the histologic and clinical features of PSC patients with and without IBD. Methods We assessed specimens from patients with UC (n = 28), CD (n = 10), PSC and UC (PSC-UC; n = 26); PSC and CD (PSC-CD; n = 6); and PSC and no IBD (PSC-no IBD; n = 4) between years 1999-2013. PSC-IBD patients were matched to IBD patients without PSC by age and colitis duration. Clinical data including age, gender, age at IBD and PSC diagnoses, IBD duration, treatment, follow-up, orthotopic liver transplantation (OLT) were noted. Results PSC-UC patients had more isolated right-sided disease (P = 0.03), and less active inflammation in left colon, rectum (P = 0.03 and P = 0.0006), and overall (P = 0.0005) compared to UC. They required less steroids (P = 0.01) and fewer colectomies (P = 0.03) than UC patients. The PSC-CD patients had more ileitis and less rectal involvement compared to PSC-UC and CD. No PSC-CD patients required OLT compared to 38% of PSC-UC (P = 0.1). PSC-IBD (PSC-UC and PSC-CD) patients with OLT had severe disease in the left colon and rectum (P = 0.04). Conclusion PSC-UC represents a distinct form of IBD. The different disease phenotype in PSC-IBD patients with OLT may support liver-gut axis interaction, however warrants clinical attention and further research.

BACKGROUND The etiology of inflammatory bowel disease (IBD) is unknown, but it is believed to be multifactorial. The hygiene hypothesis proposes that better hygiene conditions would lead to less infectious disease during childhood and favor the development of immune-mediated diseases. AIM To test the hygiene hypothesis in IBD by assessing the environmental risk factors associated with IBD development in different regions of Brazil with diverse socioeconomic development indices. METHODS A multicenter case-control study was carried out with 548 Crohn’s disease (CD) and 492 ulcerative colitis (UC) outpatients and 416 healthy controls, from six IBD centers within different Brazilian states at diverse socioeconomic development stages. A semi-structured questionnaire with 87 socioeconomic and environmental questions was applied. Logistic regression model was created to assess the odds ratio (OR) with P value and 95% confidence intervals (CI). RESULTS Predictive variables for both diseases (CD and UC) were women [odd ratios (OR) = 1.31; OR = 1.69], low monthly family income (OR = 1.78; OR = 1.57), lower number of cohabitants (OR = 1.70; OR = 1.60), absence of vaccination (OR = 3.11; OR = 2.51), previous history of bowel infections (OR = 1.78; OR = 1.49), and family history of IBD (OR = 5.26; OR = 3.33). Associated risk factors for CD were age (18-39 years) (OR = 1.73), higher educational level (OR = 2.22), absence of infectious childhood diseases (OR = 1.99). The UC predictive variables were living in an urban area (OR = 1.62), inadequate living conditions (OR = 1.48) and former smokers (OR = 3.36). Appendectomy was a risk factor for CD (OR = 1.58) with inverse association with UC (OR = 4.79). Consumption of treated and untreated water was associated with risk of CD (OR = 1.38) and UC (OR = 1.53), respectively. CONCLUSION This is the first examining environmental exposures as risk factors for inflammatory bowel disease in Brazil. Most of the variables associated with disease risk support the role of the hygiene hypothesis in IBD development.

Inflammatory bowel disease (IBD) is an inflammatory disorder of the gastrointestinal tract that affects millions of patients worldwide. It has a complex and multifactorial etiology leading to excessive exposure of intestinal epithelium to microbial antigens, inappropriate activation of the immune system and ultimately to the damage of intestinal tissues. Although numerous efforts have been made to improve the disease management, IBD remains persistently recurring and beyond cure. This is due largely to the gaps in our understanding of the pathogenesis of IBD that hamper the development of timely diagnoses and effective treatment. However, some recent discoveries, including the beneficial effects of interleukin-22 (IL-22) on the inflamed intestine, have shed light on a self-protective mechanism in IBD. Regenerating islet-derived (REG/Reg) proteins are small secretory proteins which function as IL-22's downstream effectors. Mounting studies have demonstrated that IBD patients have significantly increased REG expressions in the injured intestine, but with undefined mechanisms and roles. The reported functions of REG/Reg proteins in intestinal homeostasis, such as those of antibacterial, anti-inflammatory and tissue repair, lead us to discuss their potential mechanisms and clinical relevance in IBD in order to advance IBD research and management.

Inflammatory bowel diseases (IBD) are chronic and relapsing inflammatory conditions of the gut that include Crohn's disease and ulcerative colitis. The pathogenesis of IBD is not completely unraveled, IBD are multi-factorial diseases with reported alterations in the gut microbiota, activation of different immune cell types, changes in the vascular endothelium, and alterations in the tight junctions' structure of the colonic epithelial cells. Proteomics represents a useful tool to enhance our biological understanding and to discover biomarkers in blood and intestinal specimens. It is expected to provide reproducible and quantitative data that can support clinical assessments and help clinicians in the diagnosis and treatment of IBD. Sometimes a differential diagnosis of Crohn's disease and ulcerative colitis and the prediction of treatment response can be deducted by finding meaningful biomarkers. Although some non-invasive biomarkers have been described, none can be considered as the "gold standard" for IBD diagnosis, disease activity and therapy outcome. For these reason new studies have proposed an "IBD signature", which consists in a panel of biomarkers used to assess IBD. The above described approach characterizes "omics" and in this review we will focus on proteomics.

BACKGROUND Emergency situations in inflammatory bowel diseases (IBD) put significant burden on both the patient and the healthcare system. AIM To prospectively measure Quality-of-Care indicators and resource utilization after the implementation of the new rapid access clinic service (RAC) at a tertiary IBD center. METHODS Patient access, resource utilization and outcome parameters were collected from consecutive patients contacting the RAC between July 2017 and March 2019 in this observational study. For comparing resource utilization and healthcare costs, emergency department (ED) visits of IBD patients with no access to RAC services were evaluated between January 2018 and January 2019. Time to appointment, diagnostic methods, change in medical therapy, unplanned ED visits, hospitalizations and surgical admissions were calculated and compared. RESULTS 488 patients (Crohn’s disease: 68.4%/ulcerative colitis: 31.6%) contacted the RAC with a valid medical reason. Median time to visit with an IBD specialist following the index contact was 2 d. Patients had objective clinical and laboratory assessment (C-reactive protein and fecal calprotectin in 91% and 73%). Fast-track colonoscopy/sigmoidoscopy was performed in 24.6% of the patients, while computed tomography/magnetic resonance imaging in only 8.1%. Medical therapy was changed in 54.4%. ED visits within 30 d following the RAC visit occurred in 8.8% (unplanned ED visit rate: 5.9%). Diagnostic procedures and resource utilization at the ED (n = 135 patients) were substantially different compared to RAC users: Abdominal computed tomography was more frequent (65.7%, P < 0.001), coupled with multiple specialist consults, more frequent hospital admission (P < 0.001), higher steroid initiation (P < 0.001). Average medical cost estimates of diagnostic procedures and services per patient was $403 CAD vs $1885 CAD comparing all RAC and ED visits. CONCLUSION Implementation of a RAC improved patient care by facilitating easier access to IBD specific medical care, optimized resource utilization and helped avoiding ED visits and subsequent hospitalizations.

BACKGROUND Incidence and severity variations of inflammatory bowel disease (IBD) have been reported from Western populations between continents and regions of the same countries. However, no data were available from other countries. AIM To investigate the regional differences in the IBD profiles of pediatric patients from the Kingdom of Saudi Arabia. METHODS Data from a national multicenter IBD study were used. The incidence, time trend, and clinical presentation of Crohn’s disease (CD) and ulcerative colitis (UC) in the Central region (CR), Western region (WR), and Eastern region (ER) were analyzed and compared. Statistical analysis included Poisson regression analysis for incidence variation and Chi-square test for demographic and clinical parameters. A P < 0.05 was considered significant. RESULTS The prevalence of positive family history was lower in children with CD from the ER than the CR or the WR. Consanguinity rate was higher in children with CD and UC from the CR and the ER, respectively. The incidences and time trends of CD and UC were not significantly different between regions. In the ER, a significantly higher percentage of children with CD presented with abdominal pain (P < 0.001), blood in stools (P = 0.048), stricturing or penetrating disease (P = 0.029), higher erythrocyte sedimentation rate (P < 0.001), higher C-reactive protein (P < 0.001), higher anemia (P = 0.017), and lower albumin level (P = 0.014). For children with UC from the ER, a significantly higher percentage presented with anemia (P = 0.006) and a lower percentage with pancolitis (P < 0.001). CONCLUSION The most important finding is the identification of significantly more severe presentation of CD in the ER of the Kingdom of Saudi Arabia. Prospective studies are needed to explain such variations.

There remains a dearth of Asian epidemiological literature for paediatric inflammatory bowel disease (PIBD).To describe the presenting features of PIBD from 7 Asia-Pacific pediatric gastroenterology centersClinical, endoscopic and radiologic data at diagnosis from the registry were extracted between 1There was a distinct rise in new PIBD cases: Nearly half (48.6%) of the cohort was diagnosed in the most recent 5 years (2015-2019). The ratio of Crohn's disease (CD):Ulcerative colitis (UC):IBD-Unclassified was 55.9%:38.3%:5.8%. The mean age was 9.07 years with a high proportion of very early onset IBD (VEO-IBD) (29.3%) and EO-IBD (52.7%). An over-representation of the Indian/South Asian ethnic group was observed which accounted for 37.0% of the overall Singapore/Malaysia subcohort (6.8%-9.0% Indians in census). Indian/South Asian CD patients were also most likely to present with symptomatic perianal disease (We observed a high incidence of VEO-IBD and an over-representation of the Indian ethnicity. South Asian CD patients were more likely to have symptomatic perianal disease.

Therapeutic drug monitoring (TDM) was one of most sought-after objective tools to determine therapeutic efficiency of different biologics and its role in the management of patients with inflammatory bowel disease (IBD) was regarded with great anticipation. But implementation of the TDM in clinical practice was challenged by several factors including uncertainty of the optimal cut-off values, assay variable sensitivity in detecting drug levels and antibodies and, most importantly, individual pharmacokinetics. While reactive TDM was embraced in clinical practice as a useful tool in assessing lack of response to therapy, the utility of proactive TDM in managing IBD therapy is still challenged by the lack of consistency between evidence. Described here, there are four groups of IBD patients for whom proactive TDM has the potential to greatly impact their therapeutic outcomes: Patients with perianal Crohn's disease, patients with severe ulcerative colitis, pregnant women with IBD and children. As the future of IBD management moves towards personalizing treatment, TDM will be an important decision node in a machine learning based algorithm predicting the best strategy to maximize treatment results while minimizing the loss of response to therapy.