Abstract Background Endoscopy plays an essential role in the diagnosis and management of inflammatory bowel disease (IBD). Although the interval of endoscopy is important to assess the disease status of IBD, there are limited research date on the real-world use of endoscopy in patients with IBD. Therefore we aimed to evaluate the current status of lower gastrointestinal (GI) endoscopy in IBD patients. Methods We conducted a nationwide, retrospective, observational cohort study using the Korean national health insurance claims data. The endoscopy cohort with IBD was defined as an IBD population who underwent at least one colonoscopy or sigmoidoscopy between 2010 and 2019. We evaluated the annual number of lower GI endoscopy use, including colonoscopy and sigmoidoscopy in the IBD prevalent patients. In addition, we analyzed the trend of endoscopy use stratified by year after diagnosis in the patients with newly diagnosed IBD between 2010 and 2017 and the logistic regression modeling was used to estimate odds ratios and 95% confidence intervals for endoscopy, compared with never having had endoscopy, by demographic factor and therapeutic medications used for IBD. Results The analysis included 54,634 IBD patients (34,633 male and 20,001 female), among whom 24,577 (44.94%) underwent lower GI endoscopy. During a mean follow-up of 4 years, endoscopy was performed the most in the first year after diagnosis, and it showed a decreasing trend after that. Multivariate analysis showed that IBD patients with biologics and small molecules received more endoscopy than patients without the medication (hazard ratio [HR] 27.671, 95% confidence interval [CI] 11.296–67.783). In Crohn’s disease, increased number of biologics and small molecules correlated with increased number of endoscopy (HR 1.049, 95% CI 0.981–1.122 for single biologic; HR 2.343, 95% CI 1.726–3.182 for two or more biologics). In ulcerative colitis, however, only the use of biologics and small molecules, not the number of medication, correlated with increased number of endoscopy (HR 23.26, 95% CI 9.489–57.02). IBD patients with steroid (HR 1.562, 95% CI 1.509–1.61) and 5-aminosalicylic acid (HR 1.622, 95% CI 1.537–1.711) were received more endoscopy than patients without the medication. Conclusion Endoscopy was performed more frequently in the first one year after diagnosis with IBD. Also, this study demonstrated significant association between the use of endoscopy and the biologics/small molecules administered for IBD.
Abstract Background Icariin is a natural flavonoid glucoside from plants in Epimedium family, known to have anti-oxidative and anti-inflammatory activities. This study investigated the effects of Icariin on nuclear factor-kappa B (NF-ĸB) signaling pathway in intestinal epithelial cells (IEC) and macrophages, and in acute and chronic murine colitis models. Methods Human IEC line COLO 205 and murine macrophage cell line RAW 264.7 were pretreated with Icariin and then stimulated with tumor necrosis factor-α (TNF-α) and lipopolysaccharide respectively for in vitro studies. The expression of pro- and anti-inflammatory cytokines were evaluated by real-time RT-PCR (TNF- α, IL-6, IL-8, IL-12, and IL-10), and the effect of Icariin on NF-ĸB signaling pathway was examined by immunoblot analysis to detect IĸBα phosphorylation and degradation. Dextran sulfate sodium (DSS)-induced acute colitis in C57BL/6 wild-type mice and chronic colitis in IL-10-/- mice were treated with or without Icariin for in vivo studies. The severity of colitis was evaluated by daily body weight change, colon length, and colonic tissue histopathology. Results Icariin significantly attenuated the production of pro-inflammatory cytokines and degeneration of anti-inflammatory cytokines, and alleviated IĸBα phosphorylation and degradation in both IEC and murine macrophages stimulated by TNF-α and LPS, respectively. Icariin also significantly reduced the severity of colitis in both DSS-induced acute colitis model and chronic colitis in IL-10-/- mice models. Conclusion Icariin inhibits NF-ĸB signaling in both IECs and macrophages, and attenuates experimental murine colitis. These results suggest that Icariin may be a potential novel therapeutic agent for inflammatory bowel disease.
Abstract Background Tofacitinib is a small molecule which inhibits janus kinase and has been shown to be effective for patients with active ulcerative colitis (UC). We investigated the real-life therapeutic effectiveness and safety of tofacitinib treatment for Korean patient with UC. Methods We retrospectively analyzed the data of patients with UC who received tofacitinib treatment at 10 hospitals in Korea. The primary outcome was clinical remission at week 16 which was defined as a partial Mayo score ≤2 with a combined rectal bleeding subscore and stool frequency subscore ≤1. The secondary outcome was endoscopic remission (Mayo endoscopic subscore ≤1) at week 16. Adverse events including herpes zoster and deep vein thrombosis were also evaluated. Results Between January 2018 and November 2020, a total of 123 patients with UC received tofacitinib treatment (Table 1). Clinical effectiveness was evaluated for those who had completed or stopped the tofacitinib therapy by week 16, week 24 and week 52, respectively (Figure 1). Clinical remission and response rates at week 16 were 65.3% and 73.7%, respectively (Figure 2A). Ninety-one out of 123 patients (74.0%) were followed up to week 52. Their clinical remission and response rates at week 52 were 49.5% and 58.2%, respectively (Figure 2A). Among 117 patients with baseline Mayo endoscopic subscore ≥2, endoscopic remission rate at week 16 was 55.6% (Figure 2C). Any adverse events occurred in 15 patients (12.2%) and serious adverse events occurred in 9 patients (7.3%). Herpes zoster occurred in 4 patients (3.3%) and one patient (0.8%) suffered from deep vein thrombosis (Table 2). Conclusion Tofacitinib was effective with an acceptable safety profile for Korean patients with UC in the real world.
course of the disease, affecting mainly articular, ocular, hepatobiliary, haematologic, and dermatologic levels.These EIMs might present before, after, or at the time of IBD diagnosis, even more, they could emerge several years after a proctocolectomy.Some of these EIMs have a negative effect in daily activities with a significant decrease in the quality of life.No previous studies have been performed in patients with UC from Latin America.The aim of this study was to identify the factors associated with the development of EIMs in patients with UC.Methods: In the study, 260 Mexican patients with diagnosis of UC confirmed by histology were included.These patients were recruited from the Inflammatory Bowel Diseases Clinic at the National Institute of Medical Sciences and Nutrition in Mexico City during the period between January 2007 and December 2014.Demographic, clinical, endoscopic, and histologic data were gathered from medical records and direct interviews.The variables evaluated included sex, current age, age at diagnosis, family history of IBD, disease duration, extent of disease, medical and surgical treatment, clinical course, histologic activity, high-sensitive C-reactive protein (hs-CRP), p-ANCA, history of appendectomy, current or past history of smoking, and concomitant autoimmune disease.Uni-and multivariate analysis was performed for the identification of factors associated with the development of EIMs.The statistical SPSS programme version 20 was used for the analysis.Results: In total, 260 patients with UC were included in the study: 125 females (48.1%) and 135 males (51.9%), with a mean age at diagnosis of 31.6 years (range 6 to 65).The development of EIM was present in 145 UC patients (55.8%) with the following distribution: peripheral arthropathies 30%, primary sclerosing cholangitis 9.2%, pyoderma gangrenosum 3.9%, uveitis 3.8%, sacroiliitis 1.9%, ankylosing spondylitis 1.9%, and erythema nodosum 0.4%.The factors associated with the development of EIM were pancolitis (p = 0.003, OR 2.44, 95% CI 1.34-4.56)and previous colectomy (p = 0.02, OR 7.54, 95% CI 1.20-60.44).A clinical course of initial activity and then long-term remission more than 5 years was found to be a protective factor for the development of EIMs (p = 0.002, OR 0.31, 95% CI 0.14-0.67). Conclusions:The frequency of EIMs was 55.8% in our population, and the factors associated with its development were pancolitis and the presence of colectomy.
Abstract Background Blautia is a genus of anaerobic bacteria known as having probiotic properties in several studies. The aim of this study was to investigate the role of Blautia obeum in inflammatory bowel disease which has not yet been elucidated. Methods To assess the role of B. obeum, 7 weeks-old C57BL/6 mice were treated with 3% dextran sulfate sodium (DSS) for 5 days with or without oral administration of B. obeum simultaneously in the first experiment. Comparing with negative (only phosphate buffered saline) and positive (without intake of microbiome) controls, prior daily administration of B. obeum (day 0 to 7) and subsequent administration of DSS (day 7 to 15) were done in the second experiment. Body weight was evaluated daily in those acute colitis models. Macroscopic analysis and histological evaluation for inflammatory activity were evaluated after sacrifice. Moreover, inflammatory cytokines such as interleukin (IL), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) in the colonic lamina propria mononuclear cells were measured by quantitative real-time polymerase chain reaction. Fecal samples were collected from all subjects during experiments, and the influences on gut microbiota were analyzed by 16S rRNA gene-pyrosequencing. Results B. obeum aggravated colitis assessed by body weight loss. Histologic severity was higher in mice treated with B. obeum than in controls. IL-17, IFN-γ, and TNF-α were increased in mice treated with B. obeum, compared with controls. A significantly lower richness (P<0.05) and difference in community composition (P=0.009) of metagenomic species was seen in mice treated by B. obeum, compared with controls. To confirm the direct role of B. obeum in a murine colitis, we treated antibiotics for 7 days before the administration of B. obeum. In this experiment. B. obeum aggravated colitis assessed by body weight reduction and colon shortening as well as histologic severity. Conclusion B. obeum aggravates colitis in mice. B. obeum can be an organism that is associated with the pathogenesis in inflammatory bowel disease.
patients according to findings on white light endoscopy. Targeted biopsies were taken and assigned a histological grade using the Harpaz score (0 = normal or inactive chronic colitis, 1 = mildly active chronic colitis, 2 = moderately active chronic colitis, 3 = severe chronic active colitis). The pathologist was blinded to the endoscopy findings. Mucosal pattern on iSCAN was graded as 1 = normal, 2 = mosaic pattern, 3 = roundish rosette, 4 = tubular-gyrus, 5 = nodular roundish rosette. The vascular pattern was graded as 1 = normal, 2 = drop-out vessels, 3 = spiral isolated vessels, 4 = crowded tortuous vessels, 5 = honeycomb irregular crowded vessels. iSCAN appearance was correlated with endoscopic Mayo subscore (0 3) and histologic Harpaz score by using Spearman correlation coefficient. Results: There was a high degree of correlation between the I-SCAN scores and histological grading and the Mayo endoscopy subscore. I-SCAN mucosal pattern was significantly correlated with Harpaz score (rs = 0.759; p < 0.00001). Similarly, iSCAN vascular pattern was significantly correlated with Harpaz score (rs = 0.520; p = 0.0002). The overall iSCAN score was also significantly correlated with Harpaz score (rs = 0.6702; p < 0.00001). Finally, endoscopic Mayo subscore was also significantly correlated with overall iSCAN score (rs = 0.802; p < 0.00001). However in patients with a Mayo subscore of 0 (9 patients), seven patients had abnormal vascular pattern and 6 patients had abnormal mucosal pattern and 3 patients had abnormal histology according to Harpaz score. Conclusions: A high degree of correlation was demonstrated between iSCAN mucosal and vascular pattern scores and the Mayo subscore and Harpaz grading. However, patients with endoscopic Mayo subscore 0 demonstrated high proportion of abnormal vascular pattern and mucosal pattern on iSCAN colonoscopy. The significance of this needs to be further explored.
Abstract Background There are a few studies about the relationship between inflammatory bowel disease (IBD) and atopic dermatitis (AD). It implicates that both diseases have common pathophysiologic mechanism and are able to affect each other. However, little information is available for the effect of AD on the clinical course of patients with IBD. Methods This is a retrospective, observational case-control study. Patients with concurrent IBD and AD were defined as case group and those with IBD only as control group. Diagnosis of AD was defined as chronic eczematoid dermatosis diagnosed by dermatologists. Age-, gender-, and IBD subtype-matched patients with a confirmed diagnosis of IBD were included as control group. The ratio of the case and control group was set as, 1:2. Trend in the duration from diagnosis of IBD to first use of biologics, first IBD-related operation and first IBD-related bowel resection were estimated with Cox regression analysis. Results The numbers of patients in the case and control group were, 31 and, 62, respectively. Compared with the control group, the case group showed an earlier disease onset (unit: years, 22.13 ±, 10.66 vs., 17.68 ±, 8.07, p = 0.043) and longer disease duration of IBD (unit: months, 98.37 ±, 69.24 vs., 150.77 ±, 83.45, p = 0.002). In addition, the proportion of biologics use (35% vs., 61%, p = 0.018) and the total numbers of biologics usages (0.48 ±, 0.76 vs., 1.06 ±, 1.12, p = 0.013) were higher in patients in the case group than those in the control group. In the Cox-regression analysis, there was a significant decrease of the duration for the biologics free survival in the case group compared with the control one after the adjustment with age, IBD subtype, onset age and disease duration (p < 0.001). Conclusion Patients having concurrent IBD and AD exhibited different characteristics compared with those having IBD only, particularly in terms of disease onset and severity. Furthermore, AD showed an significant effect on the time for the initiation of biologics. Further research is required to elucidate the common pathogenesis and the role of AD on the clinical course of IBD.
Abstract Background The prevalence of Crohn’s disease (CD) is gradually increasing in South Korea, leading to various complications and negatively impacting quality of life, highlighting the need for early and non-invasive diagnosis. In 2015, the International Organization for Inflammatory Bowel Disease (IO-IBD) developed the Red Flags index for early detection of CD, but it requires validation or improvement for the Korean population. The aim of this study is to develop a Red Flags index tailored to the Korean population. Methods A total of 126 CD patients receiving treatment at Seoul National University Hospital were recruited for the study. These patients were compared with two control groups: Group A (111), consisting of individuals with non-CD conditions, such as irritable bowel syndrome, and Group B (60), comprising high-risk individuals who had not yet been diagnosed with CD but were either first- degree relatives of IBD patients, ASCA-positive or had spondyloarthritis. Patients answered 15 questions selected from the IO-IBD study. Chi-square test and multiple logistic regression were used consecutively to select items for the Red Flags index. To evaluate the diagnostic value of the Red flags index as a tool, ROC analysis was performed. Additionally, fecal calprotectin levels were measured in the study participants and diagnostic accuracy of combining fecal calprotectin with the Red flag index was analyzed. Results The Red flags index was developed for non-CD subjects and high-risk subjects, respectively. When comparing the area under the curve (AUC), the index constructed from high-risk subjects (Control Group B) showed a larger AUC of 0.909. Notably, the AUC increased when the Red Flag index was used in combination with fecal calprotectin, indicating improved diagnostic accuracy with the combined approach. Conclusion We developed the Red Flags index for the Korean population, designed to predict the diagnosis of CD in patients presenting with gastrointestinal symptoms. This index offers a simple, effective tool for the early CD detection. References 1.Allocca M, Fiorino G, Bonifacio C, et al. Validation of the Red Flags Index for Early Diagnosis of Crohn’s Disease: A Prospective Observational IG-IBD Study Among General Practitioners. J Crohns Colitis. 2020;14(4):512-518. 2.Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Development of Red Flags Index for Early Referral of Adults with Symptoms and Signs Suggestive of Crohn’s Disease: An IOIBD Initiative. J Crohns Colitis. 2015;9(8):601-606. 3.Furfaro F, Biamonte E, Vero V, et al. The Earlier You Find, the Better You Treat: Red Flags for Early Diagnosis of Inflammatory Bowel Disease. Diagnostics (Basel). 2023;13(20):3183. 4.Kim JW, Cho YE, Kim JH, et al. Clinical significance of anti-Saccharomyces cerevisiae antibody (ASCA) in Korean patients with Crohn’s disease and its relationship to the disease clinical course. Dig Liver Dis. 2007;39(7):610-616.
Abstract Background Toll-like receptor 3 (TLR3) signalling regulates innate and adaptive immune systems by the recognition of dsRNA. Activation of TLR3 signalling by poly(I:C) attenuates dextran sodium sulphate (DSS)-induced murine colitis. However, little information is available on the role of TLR3 signalling in the development of colitis-associated colon tumourigenesis. Methods Wild-type (WT) and TLR3-deficient (TLR3−/−) mice were intraperitoneally injected azoxymethane (AOM) 12.5 mg/kg on day 0 followed by three cycles of 2% DSS for 5 days and 2 weeks of free water consumption. Clinical indices such as weight change, colon length, the number of tumours, and the histologic severity of colitis were evaluated in each experiment. Immunohistochemical or immunofluorescence analyses for phospho-IκB kinase (IKK) and β-catenin were performed in colon tissues. To elucidate the antitumourigenic mechanism by colon inflammation, poly(I:C) or PBS was intraperitoneally injected in the AOM/DSS-induced tumourigenesis model in WT mice. To evaluate direct antitumor effect on tumourigenesis, as first experimental model, both WT and TLR3−/− mice were intraperitoneally injected AOM weekly for 12 weeks without DSS treatment. As the second experimental model, WT and TLR3−/− mice were received 2% DSS mixed with drinking water three times for 5 days every 2 weeks after one intraperitoneal AOM injection. Results TLR3−/− mice exhibited a higher tumour burden compared with wild-type mice. Body weight loss was greater in TLR3−/− mice than in WT mice. However, here was no significant difference in colon length and the severity of colitis between the two groups. Immunoreactivity for β-catenin was markedly increased in TLR3−/− mice. However, there was no difference in IKK expression. Activation of TLR3 by poly(I:C) was not associated with the reduced tumour development in WT mice. However, repeated AOM injections without DSS resulted in greater body weight loss in TLR3−/− mice than in WT mice, which was associated with the increased tumour development in TLR3−/−mice. Conclusion TLR3 signalling attenuated colitis-associated colon cancer development. Based on our experiments, TLR3 signalling inhibits colon tumourigenesis by direct antitumor activity rather than anti-inflammatory effect of colitis.
Abstract Background Intestinal ultrasound (IUS) has emerged as an important monitoring tool in the clinical course of ulcerative colitis (UC). Previously known factors about UC have been considered in terms of the associations with IUS. However, a few studies reported about the associations between the findings of IUS and clinical factors. Methods We performed a multi-center, cross-sectional study of patients with UC who received IUS and clinical exams including endoscopy simultaneously. The primary endpoint was the association between endoscopic disease activity as Mayo endoscopic score (MES) and IUS finding as Milan ultrasound criteria (MUC). The secondary endpoint comprised the various clinical factors associated with MUC. Patients with MUC<6.2 were defined as low MUC group and others as high MUC group. Results A total of 35 patients were enrolled in this study. The numbers of Low- and high-MUC groups were 23 and 12, respectively. The median age in each group was 41 and 53 years old. The portion of male sex in each group was 57% and 75%. There were no significant differences in terms of body mass index, onset age, disease duration, current medication such as 5-aminosalicylic acid, steroid, immunomodulator, and biologics and small molecules between both groups. Compared with low and high MUC groups, endoscopic remission was more significantly associated with the low MUC group than the high MUC group (35% vs. 0, p = 0.032). In addition, the rate of disease activity ranged from remission to mild, as tolerable clinical activity, was also significantly higher in the low MUC group than the high MUC group (91% vs. 58%, p = 0.033). Other outcomes such as symptomatic remission, histologic remission, and biochemical response revealed similar rates between the two groups. Conclusion Low MUC of IUS in the patients with UC showed significant clinical association such as endoscopic remission and tolerable clinical activity. This study is now ongoing prospective research and further investigation into the relationship between IUS and clinical outcomes of UC will elicit robust results.
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