Features Of Colitis Research Articles

Incident Colorectal Cancer in Inflammatory Bowel Disease.

Simple SummaryThe sequence chronic inflammation-dysplasia-cancer is involved in the development of several gastrointestinal cancers, including colorectal cancer (CRC) in Inflammatory Bowel Disease (IBD). Several risk factors for CRC are recognized in Ulcerative Colitis (UC) and Crohn’s Disease (CD) colitis. The combined role of IBD characteristics and incident CRC, including CRC-related symptoms at onset, in determining the long-term outcome needs further investigation. These issues were addressed in our multicenter study in IBD patients with incident CRC. CRC was more frequently diagnosed by colonoscopy in UC and by imaging in CD. CRC occurred in one fourth of patients at a young age (≤40 years), and a high rate of CRC-related mortality was observed, particularly in patients with CRC diagnosed at an older age. The present findings from incident CRC in IBD support the need to focus the attention on surveillance programs in subgroups of patients at higher risk for CRC and CRC-related death.Colorectal cancer (CRC) risk is increased in Inflammatory Bowel Disease (IBD) and surveillance needs to be tailored according to individual risk. The open issues include the role of the characteristics of IBD and CRC in determining the long-term outcome. These issues were assessed in our multicenter study, including a cohort of 56 IBD patients with incident CRC. The clinical and histopathological features of IBD patients and of CRC were recorded. Incident CRC in IBD occurred at a young age (≤40 years) in 25% of patients (median age 55.5 (22–76)). Mucinous signet-ring carcinoma was detected in 6 out of the 56 (10.7%) patients, including 4 with Ulcerative Colitis (UC) and 2 with Crohn’s disease (CD). CRC was more frequently diagnosed by colonoscopy in UC (85.4% vs. 50%; p = 0.01) and by imaging in Crohn’s Disease CD (5.8% vs. 31.8%; p = 0.02). At onset, CRC-related symptoms occurred in 29 (51.9%) IBD patients. The time interval from the diagnosis of IBD to CRC was shorter in UC and CD patients with >40 years (p = 0.002; p = 0.01). CRC-related death occurred in 10 (29.4%) UC and in 6 (27.2%) CD patients (p = 0.89), with a short time interval from CRC to death (UC vs. CD: 6.5 (1–68) vs. 14.5 (8–40); p = 0.85; IBD: 12 months (1–68)). CRC occurring at a young age, a short time interval from the diagnosis of IBD to CRC-related death in the elderly, CRC-symptoms often mimicking IBD relapse and the observed high mortality rate may support the need of closer surveillance intervals in subgroups of patients.

P189 Perceptions of Cannabis use in women with Inflammatory Bowel Disease of reproductive age: A cross-sectional study

Abstract Background Cannabis use in inflammatory bowel disease (IBD) may lead to improvement in pain and general health perception. However, its use during pregnancy may result in adverse outcomes such as preterm birth and altered fetal brain development. It remains unknown how women with IBD perceive Cannabis use during pregnancy and whether they discuss its use with their health-care providers. We aimed to determine practices in, and perceptions of, cannabis use during pregnancy in women with IBD of reproductive age. Methods Women with IBD (age 18–45) were recruited at Mount Sinai Hospital and via social media platforms. Participants anonymously completed surveys on baseline demographics and IBD characteristics. They also completed a Cannabis questionnaire which asked about current use, perceived risks during pregnancy, and discussions with health-care providers. Categorical variables were reported as frequencies and compared using the chi-square test. Continuous variables were reported as medians and compared using the Mann-Whitney U test. Results Sixty-four women were included, 26 (40.6%) with ulcerative colitis, 37 (57.8%) with Crohn’s disease, and 1 (1.6%) with indeterminate colitis. Nineteen (29.7%) were preconception, 40 (62.5%) were pregnant, and 5 (7.8%) were post-partum. Eleven (18.0%) patients reported current Cannabis use, 4 (6.3%) during pregnancy. Cannabis users were more likely to have discussed its use with a health-care provider compared to non-users (45.5% vs. 5.7%, p<0.001) and had longer IBD duration (12.00 vs. 9.00 years, p=0.05). Twenty-five (42.4%) were unsure of the risks of Cannabis use in pregnancy, of which only two had discussed this with a health-care provider. Reasons for fear of Cannabis use included risk of fetal oxygen restriction (n=13, 20.3%), impact on brain development (n=29, 46.0%), and risk of fetal respiratory issues (n=18, 28.6%). Only eight (12.5%) patients reported having a conversation about Cannabis use during pregnancy with their health-care provider; all of whom felt its consumption was unsafe during pregnancy. Conclusion Many women with IBD report being unsure of risks of Cannabis use during pregnancy. With the legalization of Cannabis in Canada, it is imperative patients and health-care providers discuss the risks and benefits of its use, particularly during vulnerable times such as pregnancy.

Clinical differentiation of inflammatory bowel disease (IBD) in Latin America and the Caribbean.

The aim of the present study was to describe the epidemiological and clinical characteristics of inflammatory bowel disease (IBD), including medical and surgical treatments, in several countries in Latin America and the Caribbean.IBD is recognized as a global health problem because its incidence and prevalence have increased significantly over the last few years.This multicenter retrospective cohort study included 4714 patients with IBD diagnosed from 9 countries in Latin America and the Caribbean: Colombia, Cuba, Dominican Republic, Ecuador, Mexico, Peru, Puerto Rico, Uruguay, and Venezuela.Crohn disease (CD) was more frequent in Puerto Rico (71.9%), the Dominican Republic (61.0%), and Peru (53.1%). Ulcerative colitis was more frequent in Colombia (78.6%), Venezuela (78.2%), Mexico (75.5%), Cuba (69.9%), Ecuador (64.1%), and Uruguay (60.9%). The following clinical characteristics were more frequent in the Caribbean: penetrating behavior in CD, steroid dependence, steroid resistance, intolerance to thiopurines, extraintestinal manifestations, surgeries, hospitalizations due to IBD, and family history of IBD. The factors associated with the use of biological therapy were pancolitis in ulcerative colitis, penetrating behavior in CD, steroid resistance and dependence, presence of extraintestinal manifestations, and the need for surgery.This study from Latin America and the Caribbean demonstrated the different epidemiological and clinical characteristics of IBD.

Expression of Fibrosis-Related Genes in Liver and Kidney Fibrosis in Comparison to Inflammatory Bowel Diseases.

Fibrosis is an important feature of inflammatory bowel diseases (IBD), but its pathogenesis is incompletely understood. Our aim was to identify genes important for fibrosis in IBD by comparison with kidney and liver fibrosis. First, we performed bioinformatics analysis of Gene Expression Omnibus datasets of liver and kidney fibrosis and identified CXCL9, THBS2, MGP, PTPRC, CD52, GZMA, DPT and DCN as potentially important genes with altered expression in fibrosis. We then performed qPCR analysis of the selected genes’ expression on samples of fibrotic kidney, liver, Crohn’s disease (CD) with and without fibrosis and ulcerative colitis (UC), in comparison to corresponding normal tissue. We found significantly altered expression in fibrosis for all selected genes. A significant difference for some genes was observed in CD with fibrosis in comparison to CD without fibrosis and UC. We conclude that similar changes in the expression of selected genes in liver, kidney fibrosis and IBD provide further evidence that fibrosis in IBD might share common mechanisms with other organs, supporting the hypothesis that fibrosis is the common pathway in diseases of various organs. Some genes were already active in IBD with inflammation without fibrosis, suggesting the early activation of profibrotic pathways or overlapping function in fibrosis and inflammation.

Prevalence and Factors Associated with Depression, Anxiety and Stress in IBD Patients Undergoing Intravenous Biological Therapy during the COVID-19 Pandemic-Montenegro Experience

Throughout its duration, the coronavirus disease 2019 (COVID-19) pandemic has been affecting lives worldwide and has had a sizeable impact on mental health, particularly for those who already suffer from a chronic illnesses. Depression, Anxiety and Stress (DAS) are common psychiatric comorbidities in inflammatory bowel disease (IBD) patients. This study aims to determine the prevalence and risk factors for moderate and severe symptoms of DAS in IBD patients have been undergoing intravenous biological therapy (IvBTh) during the COVID-19 pandemic. The study was conducted between September 1st and November 30th, 2020 at the Clinical Center of Montenegro-IBD unit, where all patients from Montenegro received the registered IvBTh. This case control study consists of 94 IBD patients that completed a validated questionnaire Depression, Anxiety and Stress Score-21 (DASS-21). A total of 59 patients received tumor necrosis factor alpha inhibitors (anti-TNF therapy), while 35 received anti-integrin therapy. After we calculated the DASS-21 score, we divided the patients into two groups: those who had moderate and severe symptoms (if they had any of the mentioned DASS-21 subscale score above limit for moderate or more severe symptoms: DASS-21 Depression, higher than 14; DASS-21 Anxiety, higher than 10 and DASS-21 Stress, higher than 19) and those who did not have significant symptoms (DASS-21 subscale score did not exceed the limit). We also examined demographic data, data on IBD characteristics and COVID-19 data and their impact on mental disorders. Standard statistical processing tests were used to identify risk factors for examined mental disorders. Following the DASS-21 criteria, we diagnosed the least moderate depression in 19.1%, anxiety in 14.9% and stress in 20.2% patients. The multivariate analysis indicated there to be a statistically significant relation of being higher at risk of developing depression, anxiety and stress when suffering from an active form of IBD (OR 6.487; 95% Cl 1.220–34.500, P = 0.028). Almost one third (30.9%) of patients have at least one of the examined mental disorders during the COVID-19 pandemic. Particular attention and efforts must be better focused on patients who suffer from an active form of IBD during the ongoing COVID-19 pandemic.

A potential pathogenic association between periodontal disease and Crohn's disease.

Oral conditions are relatively common in patients with inflammatory bowel disease (IBD). However, the contribution of oral maladies to gut inflammation remains unexplored. Here, we investigated the effect of periodontitis on disease phenotypes of patients with IBD. In all, 60 patients with IBD (42 with ulcerative colitis [UC] and 18 with Crohn’s disease [CD]) and 45 healthy controls (HCs) without IBD were recruited for this clinical investigation. The effects of incipient periodontitis on the oral and gut microbiome as well as IBD characteristics were examined. In addition, patients were prospectively monitored for up to 12 months after enrollment. We found that, in both patients with UC and those with CD, the gut microbiome was significantly more similar to the oral microbiome than in HCs, suggesting that ectopic gut colonization by oral bacteria is increased in patients with IBD. Incipient periodontitis did not further enhance gut colonization by oral bacteria. The presence of incipient periodontitis did not significantly affect the clinical outcomes of patients with UC and CD. However, the short CD activity index increased in patients with CD with incipient periodontitis but declined or was unchanged during the study period in patients without periodontitis. Thus, early periodontitis may associate with worse clinically symptoms in some patients with CD.

HLA-DQA1*05 Associates with Extensive Ulcerative Colitis at Diagnosis: An Observational Study in Children.

The human leukocyte antigen (HLA) allele group HLA-DQA1*05 predisposes to ulcerative colitis (UC) and is associated with the development of antibodies against infliximab in patients with inflammatory bowel disease (IBD). Therefore, we hypothesized that the presence of HLA-DQA1*05 correlates with characteristics of pediatric IBD. Within a multi-center cohort in Poland, the phenotype at diagnosis and worst flare was established and HLA-DQA1*05 status was assessed enabling genotype-phenotype analyses. HLA-DQA1*05 was present in 221 (55.1%) out of 401 children with IBD (UC n = 188, Crohn’s disease n = 213). In UC, the presence of HLA-DQA1*05 was moderately associated with a large extent of colonic inflammation at diagnosis (E4 55% more frequent in HLA-DQA1*05-positive patients, p = 0.012). PUCAI at diagnosis (p = 0.078) and the time from UC diagnosis to the first administration of biologic treatment (p = 0.054) did not differ depending on HLA-DQA1*05 status. The number of days of hospitalization for exacerbation was analyzed in 98 patients for whom sufficient follow-up was available and did not differ depending on HLA-DQA1*05 carriership (p = 0.066). HLA-DQA1*05 carriers with CD were less likely to present with both stenosing and penetrating disease (B2B3, p = 0.048) and to have active disease proximal to the ligament of Treitz (L4a) at the worst flare (p = 0.046). Future research focusing on explaining and preventing anti-TNF immunogenicity should take into account that ADA may develop not only as an isolated reaction to anti-TNF exposure but also as a consequence of intrinsic differences in the early course of UC.

Serum inter-alpha-trypsin inhibitor heavy chain 4 in patients with inflammatory bowel disease: correlation with disease risk, inflammation, activity, and its variation after treatment

Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) plays vital roles in inflammatory and auto-immune diseases, but its correlations with disease risk and clinical features in inflammatory bowel disease (IBD) need further investigation. The present study intended to explore the correlation of ITIH4 with disease activity and inflammation, as well as its change after treatment in IBD patients. Totally, 40 active Crohn's disease (A-CD) patients, 40 clinical-remission CD (R-CD) patients, 40 active ulcerative colitis (A-UC) patients, 40 clinical-remission UC (R-UC) patients, and 40 health controls (HCs) were enrolled. ITIH4 in serum was assessed by ELISA. ITIH4 was lower in A-CD, R-CD, A-UC, and R-UC patients than in HCs (P < 0.001). Notably, ITIH4 reduced in A-CD patients than in R-CD patients (P = 0.017), and in A-UC patients compared with R-UC patients (P = 0.010). Besides, in A-CD patients, ITIH4 negatively correlated with tumor necrosis factor-alpha (TNF-α), interleukin (IL)-17A, IL-1β, C-reactive protein (CRP), and clinical disease activity index score (all P < 0.05). In A-UC patients, ITIH4 negatively correlated with TNF-α, IL-17A, IL-1β, IL-6, CRP, and Mayo score (all P < 0.05). However, in R-CD and R-UC patients, these correlations were less obvious than in A-CD and A-UC patients. ITIH4 was increased after treatment (all P < 0.05), and its expression at W12 after treatment was higher in response patients compared with no response patients in A-CD (P = 0.022) and A-UC groups (P = 0.038). ITIH4 correlates with IBD susceptibility, active risk, inflammation level, and its elevation after treatment relates to clinical response in IBD patients.

Evaluation of the Clinical Effects and Frequency of MEFV Gene Mutation in Patients with Inflammatory Bowel Disease.

Background The clinical and pathological features of inflammatory bowel disease (IBD) and Familial Mediterranean Fever (FMF) are similar. Objective Here, the frequency of Mediterranean Fever (MEFV) gene mutation and its effect on the outcome of IBD were evaluated. Methods DNA sequence analysis detected the variants on the MEFV gene in patients with IBD. The relationship between mutations and the need for steroids, immunomodulators, biologics, and surgery was assessed. Results We evaluated 100 patients with IBD (55 with ulcerative colitis (UC) and 45 with Crohn's disease (CD)) and 60 healthy individuals as controls. The frequency of MEFV gene mutation was 26.7% (n = 12) and 14.5% (n = 8) for UC and CD, respectively. No relationship was found between MEFV gene mutation and the need for steroids, immunomodulators, and biologics (p = 0.446; p = 0.708; p > 0.999, resp.); however, in UC, the need for surgery in those with mutation (p = 0.018) and E148Q mutation alone was significant (p = 0.037). Conclusion The rate of MEFV gene mutations was high in patients with UC who required surgery. These patients have frequent and severe attacks, indicating that the mutations are related to disease severity. MEFV mutation as a modifier factor of IBD should be considered.

Histologic Diagnosis of Inflammatory Bowel Diseases.

Inflammatory bowel disease, including ulcerative colitis and Crohn disease, is an idiopathic chronic inflammatory condition of the gastrointestinal tract. Since neither the clinical manifestations nor the morphologic features of inflammatory bowel disease are pathognomonic alone, the differential diagnosis to consider is relatively broad, and it relies on the synthesis of clinical, endoscopic, and microscopic features. Long-held histologic diagnostic principles include recognizing structural and inflammatory features of chronicity, that is, architectural distortion, basal plasmacytosis, and expansion of the lamina propria lymphoplasmacytic infiltrate. In addition, evaluation of the neutrophilic inflammation and related crypt and epithelial destruction is essential to gauge the activity of the disease. Nevertheless, these features can be difficult to confirm in special settings, including at the inception of the disease or in partially treated cases. This review will explore the classic morphologic features of ulcerative colitis and Crohn disease, followed by a detailed discussion of atypical and diagnostically challenging presentations and a brief review of the clinical aspects necessary for the daily practice of pathologists.

Multisystem Autoimmune Inflammatory Disease, Including Colitis, Due to Inborn Error of Immunity

Our understanding of inflammatory bowel disease is changing as we identify genetic variants associated with immune dysregulation. Inflammatory bowel disease undetermined, even when diagnosed in older children and adolescents, in the setting of multiple inflammatory and infectious diseases should raise the suspicion of complex immune dysregulation with a monogenic basis. We report a case of inflammatory bowel disease undetermined triggered by exposure to a nonsteroidal antiinflammatory drug in a 16-year-old girl with a background history of juvenile idiopathic arthritis, cytopenias, recurrent respiratory tract and middle ear infections, and esophageal candidiasis. Immunologic assessment included measurement of immunoglobulin levels, lymphocyte immunophenotyping, B-cell functional tests, and whole-exome sequencing. Laboratory investigation revealed defects of humoral immunity, including mild persistent hypogammaglobulinemia affecting all 3 isotypes and absent isohemagglutinins. Whole exome sequencing revealed a heterozygous TNFRSF13B (Tumor Necrosis Factor Receptor Superfamily Member 13B, or Transmembrane Activator and Calcium-modulating cyclophilin ligand Interactor, TACI) gene variant, which is associated with common variable immunodeficiency and the development of autoimmune diseases. In conclusion, a clinical history of recurrent infections, atypical histologic features of inflammatory bowel disease, additional autoimmune manifestations, and an inadequate response to conventional therapy should prompt the physician to refer to an immunologist with the query of inborn error of immunity. We report how extensive immune evaluation and genetic diagnosis can individualize care and facilitate a multidisciplinary team approach.

The Role of Epigenetic Mechanism in the Pathogenesis of Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic inflammation of the intestine due to interaction between inappropriate immune response and environmental factors. It consists of ulcerative colitis and Crohn’s disease. The incidence of IBD is increasing globally and disrupts patient’s quality of life and causes heavy economic burden. Several risk factors are involved in IBD including genetic, environment, lifestyle, and socioeconomic status. Antigen enters host’s gastrointestinal tract and triggers an immune reaction. In subject with IBD, the immune reaction is hyperactive. Some conditions such as intestinal barrier disintegration, gut microorganism imbalance, molecular mimicry, and abnormal autophagy trigger chronic inflammation and end with IBD. Genetic predisposition plays a central role in IBD. NOD2, IL23R, and ATG16L1 have the most significant association with IBD. With the presence of epigenetic mechanisms, patients with genetic predispositions have higher probability for suffering from IBD. The most common epigenetic mechanisms in the pathogenesis of IBD are DNA methylation and non-coding RNAs. The epigenetic mechanisms lead to changes in T-cell activity, cytokine production, intestinal epithelial integrity, autophagy activity, and innate immunity response. All of those cause chronic inflammation as the main characteristic of IBD. Genetic aspect can be a promising approach in managing IBD. The field of genetic may be applied in diagnosing, treating, and predicting disease outcomes. However, this topic still needs further investigations.

A Seroprevalence Study of Anti-SARS-CoV-2 Antibodies in Patients with Inflammatory Bowel Disease during the Second Wave of the COVID-19 Pandemic in Italy.

Background and Objectives: Studies have shown a lower prevalence of anti-SARS-CoV-2 antibodies in patients with inflammatory bowel disease (IBD), including amongst those receiving biological therapy. Aims were to determine the seroprevalence of anti-SARS-CoV-2 antibodies in IBD patients and to assess any association between seropositivity and IBD characteristics. Materials and Methods: Serum from adult IBD patients was prospectively collected between December 2020 and January 2021 and analyzed for anti-SARS-CoV-2 antibodies. Information about IBD characteristics and SARS-CoV-2 exposure risk factors was collected and analyzed. Serum from non-IBD healthcare workers formed the control group. Results: 311 IBD patients on biologics and 75 on mesalazine were enrolled. Ulcerative colitis (UC) extension (p < 0.001), Crohn’s disease (CD) phenotype (p = 0.009) and use of concomitant corticosteroids (p < 0.001) were significantly different between the two IBD groups. Overall seroprevalence among IBD patients was 10.4%. The control group showed a prevalence of 13.0%, not significantly different to that of IBD patients (p = 0.145). Only a close contact with SARS-CoV-2 positive individuals and the use of non-FFP2 masks were independently associated with a higher likelihood of seropositivity amongst IBD patients. Conclusion: In IBD patients, the prevalence of anti-SARS-CoV-2 antibodies is not determined by their ongoing treatment. Disease-related characteristics are not associated with a greater risk of antibody seropositivity.

Increasing rate of a positive family history of inflammatory bowel disease (IBD) in pediatric IBD patients.

The role of a positive family history in pediatric inflammatory bowel disease (IBD) in the era of biologic therapy has not been elucidated. We retrospectively reviewed the medical records of children with IBD and retrieved demographic and clinical characteristics, including the presence of a positive family history of IBD, IBD phenotype, disease course, and therapy. Overall, 325 children (age range at diagnosis 11-15years) were included, of whom 82 (25.2%) had a positive family history. Children diagnosed during 2016-2020 had a higher frequency of positive family history compared to those diagnosed during 2010-2015 (31.8% versus 20.7%, respectively, p = 0.024). Children with a positive family history had a higher risk for a stricturing phenotype than those with a negative family history (11.3% versus 2.8%, respectively, p = 0.052). They more often received nutritional therapy (53.7% versus 36.6%, p = 0.007) and less often received corticosteroids (36.6% versus 52.7%, p = 0.012). More children with a negative family history needed intensification of biologic therapy (p = 0.041).Conclusion: The rate of a positive family history of IBD in the pediatric IBD population is increasing. A positive family history may have some impact upon IBD phenotype but none on IBD outcome. What is Known: •Familial clustering of inflammatory bowel disease (IBD) has been reported in 5%-15% of IBD patients. •The investigation of the impact of a positive family history upon IBD characteristics and severity revealed conflicting results. What is New: •In this cohort of 325 children with IBD, 25.2% had a positive family history. •The rate of a positive family history of IBD in the pediatric IBD population is increasing. •A positive family history may have some impact upon IBD phenotype but none on IBD outcome.

TNF-\u03b1 synergises with IFN-\u03b3 to induce caspase-8-JAK1/2-STAT1-dependent death of intestinal epithelial cells

Rewiring of host cytokine networks is a key feature of inflammatory bowel diseases (IBD) such as Crohn’s disease (CD). Th1-type cytokines—IFN-γ and TNF-α—occupy critical nodes within these networks and both are associated with disruption of gut epithelial barrier function. This may be due to their ability to synergistically trigger the death of intestinal epithelial cells (IECs) via largely unknown mechanisms. In this study, through unbiased kinome RNAi and drug repurposing screens we identified JAK1/2 kinases as the principal and nonredundant drivers of the synergistic killing of human IECs by IFN-γ/TNF-α. Sensitivity to IFN-γ/TNF-α-mediated synergistic IEC death was retained in primary patient-derived intestinal organoids. Dependence on JAK1/2 was confirmed using genetic loss-of-function studies and JAK inhibitors (JAKinibs). Despite the presence of biochemical features consistent with canonical TNFR1-mediated apoptosis and necroptosis, IFN-γ/TNF-α-induced IEC death was independent of RIPK1/3, ZBP1, MLKL or caspase activity. Instead, it involved sustained activation of JAK1/2-STAT1 signalling, which required a nonenzymatic scaffold function of caspase-8 (CASP8). Further modelling in gut mucosal biopsies revealed an intercorrelated induction of the lethal CASP8-JAK1/2-STAT1 module during ex vivo stimulation of T cells. Functional studies in CD-derived organoids using inhibitors of apoptosis, necroptosis and JAKinibs confirmed the causative role of JAK1/2-STAT1 in cytokine-induced death of primary IECs. Collectively, we demonstrate that TNF-α synergises with IFN-γ to kill IECs via the CASP8-JAK1/2-STAT1 module independently of canonical TNFR1 and cell death signalling. This non-canonical cell death pathway may underpin immunopathology driven by IFN-γ/TNF-α in diverse autoinflammatory diseases such as IBD, and its inhibition may contribute to the therapeutic efficacy of anti-TNFs and JAKinibs.

Features of inflammatory bowel diseases in St. Petersburg and peculiarities of basic therapy in the regional healthcare system: cross-sectional study results

Background. Inflammatory bowel diseases (ulcerative colitis and Crohn’s disease) are serious problem in modern gastroenterology, as these diseases affect the working population, have a progressive chronic course, a high risk of disabling complications and require significant costs for the drug management.Aim. We wanted to assess the inflammatory bowel diseases structure and features of the use of basic drugs in outpatient and inpatient treatment in St. Petersburg, Russia.Materials and methods. A cross-sectional study was performed. Data about drug therapy, disease features and demographic from 42 outpatient institutions and from 6 city hospitals for the period 2018–2020 in St. Petersburg was collected. The analysis included data from 617 patients with ulcerative colitis and 455 patients with Crohn’s disease.Results. The median age of patients with ulcerative colitis was 44 years, which was statistically significant more than with Crohn’s disease (39 years). In ulcerative colitis, the left-sided localization of colon lesions (56%) prevailed over total colitis (23%) and proctitis (21%) In Crohn’s disease, the prevalence of ilecocolitis (36%) was approximately equal to the prevalence of colitis (35%), the frequency of terminal ileitis was significantly less (26%), other variants of gastrointestinal lesions were found in 3% cases. In Crohn’s disease compared to ulcerative colitis, the proportion of patients with mild disease was similar (36.6% and 38.2% respectively), but in in Crohn’s disease the frequency of severe disease there was more than three times compared to ulcerative colitis. There has been a significantly higher incidence of surgery in the past for Crohn’s disease compared to ulcerative colitis (14.8% and 2.6%, respectively). The vast majority of patients (more than 80%) received therapy with oral 5-aminosalycilic acid drugs. Topical formulas of 5-aminosalycilic acid drugs in ulcerative colitis were prescribed in about 50% of cases (it was significantly less than commonly used in Crohn’s disease). Corticosteroids were used in the treatment of 16.6% of ulcerative colitis patients and in 24.4% Crohn’s disease patients. In both diseases in the conditions of inpatient treatment, this group of drugs was used several times more often than in outpatient observation. Immunosuppressants (tyopurines, methotrexate) were administered in 6.9% ulcerative colitis patients with and in 17.0% Crohn’s disease patients.Conclusion. Clinical features of inflammatory bowel diseases in St. Petersburg and the features of basic therapy in comparison with the nationwide indicators in Russia demonstrate similar trends. The key problem points of therapy of inflammatory bowel diseases remains the widespread use of drugs of the group of 5-aminosalycilic acid in Crohn’s disease, insufficient use of rectal forms of 5-aminosalycilic acid in ulcerative colitis, a relatively small frequency of use of immunosupressors to maintain remission in Crohn’s disease. The solution to the problem of optimizing the therapy of patients with inflammatory bowel diseases within the framework of routine practice includes educational activities, as well as the creation of a regional register of patients with inflammatory bowel diseases in St. Petersburg.

Therapeutic Targeting of Nrf2 Signaling by Maggot Extracts Ameliorates Inflammation-Associated Intestinal Fibrosis in Chronic DSS-Induced Colitis.

Intestinal fibrosis is induced by excessive myofibroblast proliferation and collagen deposition, which has been regarded as a general pathological feature in inflammatory bowel disease (IBD). Therefore, identifying clinical markers and targets to treat and prevent intestinal fibrosis is urgently needed. The traditional Chinese medicine maggot, commonly known as “wu gu chong”, has been shown to reduce oxidative stress and alleviate inflammation in chronic colitis. This study investigated the mechanisms underlying the effects of maggot extract (ME) on inflammation-associated intestinal fibrosis in TGF-β1-stimulated human intestinal fibroblasts (CCD-18Co cells) and dextran sodium sulphate (DSS)-induced chronic colitis murine model. To assess the severity of inflammation and fibrosis, histological and macroscopic evaluation were carried out. The results showed that ME was a significant inhibitor of body weight loss and colon length shortening in mice with chronic colitis. In addition, ME suppressed the intestinal fibrosis by downregulating TGF-β1/SMADs pathway via upregulation of Nrf2 expression at both protein and mRNA levels. ME markedly increased the expression of Nrf2, thus resulting in a higher level of HO-1. After treatment with Nrf2 inhibitor (ML385) or siRNA-Nrf2 for deactivating Nrf2 pathway, the protective effects of ME were abolished both in vitro and in vivo. Moreover, the histopathological results for the major organs of DSS mice treated with ME showed no signs of clinically important abnormalities. Treatment with ME had no effect on the viability of CCD-18Co cells, suggesting its low in vitro cytotoxicity. Furthermore, ME could mediate intestine health by keeping the balance of the gut microbes through the enhancement of beneficial microbes and suppression of pathogenic microbes. In conclusion, this is the first ever report demonstrating that ME ameliorates inflammation-associated intestinal fibrosis by suppressing TGF-β1/SMAD pathway via upregulation of Nrf2 expression. Our findings highlight the potential of Nrf2 as an effective therapeutic target for alleviating intestinal fibrosis.

The Clinical Features of Inflammatory Bowel Disease in Patients with Obesity.

Methods We retrospectively reviewed the medical records of IBD patients who visited Asan Medical center. We used a large, well-characterized referral center-based cohort. The clinical features of IBD patients with body mass index (BMI) over 30 and matched controls with BMI under 30 were compared. Results Among the 6,803 IBD patients enrolled in the Asan IBD Registry between June 1989 and December 2016, we identified 16 patients with Crohn's disease (CD) and 27 patients with ulcerative colitis (UC) whose BMI was over 30 at the time of diagnosis. Their clinical characteristics and course were compared with those of 64 and 108 matched patients with CD and UC, respectively. There were no significant differences in the risk of using steroids (hazards ratio (HR) = 0.633 and P=0.254), immunomodulators (HR = 0.831 and P=0.517), and anti-tumor necrosis factor (TNF) therapy (HR = 1.539 and P=0.351) and risk of bowel resections (HR = 1.858 and P=0.231) between CD patients with BMI over 30 and those with BMI under 30; similarly, UC patients did not show significant differences in the risk of using steroids (HR = 0.613 and P=0.145), immunomodulators (HR = 0.492 and P=0.111), anti-TNF therapy (HR = 0.385 and P=0.095), and risk of colectomy (HR = 0.262 and P=0.104). In the subgroup analysis, under-weight UC patients had a higher cumulative probability of needing steroids (HR = 0.2510 and P=0.042), needing immunomodulators (HR = 0.097 and P=0.014), and a higher risk of receiving colectomy (HR = 0.024 and P=0.019) than obese UC patients. Conclusions Obese IBD patients with CD or UC did not show significantly different clinical features from nonobese IBD patients.

Venous Thromboembolism Among Patients With Inflammatory Bowel Diseases is Not Related to Increased Thrombophilia: A Case-Control Study.

The aim was to assess whether thrombophilia significantly contributes to the risk of venous thromboembolic events (VTEs) in patients with inflammatory bowel disease (IBD). Patients with IBD have a high risk of VTE. The underlying mechanism has been only partially defined. A case-control study in adults with IBD and an episode of VTE (IBD-VTE) were matched and compared with non-IBD patients with a VTE (non-IBD-VTE). The study population was comprised of patients seen in 2 tertiary medical centers in Israel between 2000 and 2013. Characteristics of IBD and risk factors for VTE were retrieved from medical charts, and a comprehensive thrombophilia panel was completed in all patients. Forty-four IBD-VTE cases (27 Crohn's disease) were matched with 127 non-IBD-VTE controls. The majority of VTE had a clear etiology and were considered provoked events. Provoked and unprovoked VTE rates were not different between the 2 groups. Likewise, thrombophilia rates were similar among patients with IBD-VTE and controls (40.9% vs. 53.5%, respectively, P=0.14). However, among patients with unprovoked VTE, thrombophilia rates were significantly lower in the IBD-VTE group compared with controls (42.1% vs. 70.7%, respectively, P=0.03). Among patients with IBD-VTE, an unprovoked event, and negative thrombophilia, 77% had active inflammation at the time of VTE. Thrombophilia rates are similar among patients with IBD-VTE and controls but are less common among patients with unprovoked IBD-VTE. This finding suggests that either inflammation or other novel pathways drive VTE in patients with IBD.

Deficits in Geriatric Assessment Associate With Disease Activity and Burden in Older Patients With Inflammatory Bowel Disease

Background & AimsWe aimed to perform geriatric assessment in older patients with inflammatory bowel disease (IBD) to evaluate which IBD characteristics associate with deficits in geriatric assessment and the impact of deficits on disease burden (health-related quality of life). MethodsA prospective multicenter cohort study including 405 consecutive outpatient patients with IBD aged ≥65 years. Somatic domain (comorbidity, polypharmacy, malnutrition), impairments in (instrumental) activities of daily living, physical capacity (handgrip strength, gait speed), and mental (depressive symptoms, cognitive impairment) and social domain (life-partner) were assessed. Deficits in geriatric assessment were defined as ≥2 abnormal domains; 2–3 moderate deficits and 4–5 severe deficits. Clinical (Harvey Bradshaw Index >4/partial Mayo Score ≥2) and biochemical (C-reactive protein ≥10 mg/L and/or fecal calprotectin ≥250 μg/g) disease activity and disease burden (short Inflammatory Bowel Disease Questionnaire) were assessed. ResultsSomatic domain (51.6%) and activities of daily living (43.0%) were most frequently impaired. A total of 160 (39.5%) patients had moderate deficits in their geriatric assessment; 32 (7.9%) severe. Clinical and biochemical disease activity associated with deficits (clinical: adjusted odds ratio, 2.191; 95% confidence interval, 1.284–3.743; P = .004; biochemical: adjusted odds ratio, 3.358; 95% confidence interval, 1.936–5.825; P < .001). Deficits in geriatric assessment independently associate with lower health-related quality of life. ConclusionDeficits in geriatric assessment are highly prevalent in older patients with IBD. Patients with active disease are more prone to deficits, and deficits associate with lower health-related quality of life, indicating higher disease burden. Prospective data validating impact of frailty and geriatric assessment on outcomes are warranted to further improve treatment strategies.