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BackgroundUlcerative colitis (UC) is characterized by chronic intestinal epithelial damage, and previous studies have evaluated the epithelial structure of patients with active UC using electron microscopy.AimsThis study aimed to assess the intestinal epithelial structure using scanning electron microscopy (SEM) and the features of patients with UC who are in remission.MethodsIn total, eight healthy controls and 20 patients with UC were enrolled, and colonic tissue samples from the cecum and rectum were collected. Then, we compared the epithelial surface structure on SEM between patients with UC who are in clinical remission and healthy controls.ResultsIn healthy controls, the colonic surface comprises small lobes (termed units), with one crypt located in the middle of each unit. In patients with UC, we found irregular unit and crypt mouth size, double crypt sign (> 1 crypt per unit), and lower number of small vesicles in the intestinal epithelial cells. Compared with healthy controls, patients with UC often presented with irregular unit size, double crypt sign, and irregular crypt mouth size in the rectum. The small vesicles were observed less frequently in patients with UC than in healthy controls.ConclusionsSEM revealed a unique epithelial structure in patients with UC who are in remission.

BACKGROUND:The therapeutic advancements including anti-TNFα antibody has made dramatically improved the treatment of ulcerative colitis (UC), and the number of cases who can avoid surgery is increasing. However, a certain number of patients remain resistant to treatment. However, few studies have been performed to compare the real-world efficacy and safety of tofacitinib (TOF) and vedolizumab (VDZ) for UC. Here, we assessed the short-term efficacy and safety of TOF and VDZ.METHODS:This was a retrospective single-center observation study in UC patients who initiated TOF (n = 38) and VDZ (n = 28) from May 2018 to May 2019. The primary outcome was short-term efficacy that was evaluated by remission rate and response rate at 2 weeks and 6 weeks after the start of treatment. We defined remission as a partial Mayo score (pMayo) of 1 point or less, and response rate as a pMayo 1 point or less or a decrease of 3 points or more. Furthermore, the clinical background factors contributing to the efficacy at 6 weeks were examined, and the side effects in the mean observation period (TOF group 133.6 days and VDZ group 74.6 days) were evaluated. This study was approved by the ethics committee of Keio University School of Medicine (approval number:20150210).RESULTS:There was no significant difference of clinical background factors between two groups, TOF/VDZ, in terms of clinical duration (10.7 years/7.9 years), relapse-remission type (71.1%/64.3%) and all colitis type (63.2%/60.7%). However, severity of UC was higher in TOF group, average pMAYO 5.7/4.0 (P = 0.002), average endoscopic Mayo score (eMayo) 2.58/1.82 (P = 0.002) and average ulcerative colitis endoscopic index of severity (UCEIS) 4.34/2.71 (P = 0.001), and there were fewer cases of bio-naïve (23.7%/50.0% (P = 0.027)).The remission rate at 2 weeks and 6 weeks were 23.7%/28.5% (P = 0.654) and 39.4%/32.1% (P = 0.611), respectively, and the response rates at 2 weeks and 6 weeks were 50.0%/35.7% (P = 0.248) and 63.2%/35.7% (P = 0.027). The platelet count at the time of introduction and the CRP value at 2 weeks contributed to the efficacy at 6 weeks in TOF group, on the other hand, the ulcer score of eMayo and UCEIS at the time of introduction and pMayo at 2 weeks contributed in the VDZ group. Bio-naïve did not contribute to the clinical efficacy in the both groups. There were no serious side effects and no cases were discontinued due to side effects in the both groups.CONCLUSION(S):In the present study, TOF tended to have higher short-term efficacy regardless of the severity of the disease and the previous usage of biologics. Both groups had no serious side effects within the observation period. In the near future, further head-to-head study is required to extend these findings and determine the appropriate therapeutic options in terms of the mid-to long-term efficacy and safety.

BACKGROUND:In recent years, a number of therapeutic drug for patients with ulcerative colitis (UC) has been developed. Meanwhile, 5-aminosalicylic acid (5-ASA) has few serious adverse events, and remains as the first-line drug in induction therapy and maintenance therapy for UC. However, 5-ASA often cause diarrhea, fever and skin rash, and it is often difficult to maintain remission in these cases. There are few studies about the effect of 5-ASA intolerance on the prognosis of patients with UC. In this study, we aimed to clarify the optimal treatment strategy for patients with 5-ASA intolerance by examining the 5-ASA intolerance using the IBD registry of our hospital.METHODS:A multi-center retrospective cohort study of UC patients, who visited our hospital from January 2015 to June 2018, was performed, and we enrolled 793 UC patients in IBD registry. We collected the detail clinical information of enrolled patients in the prior year, and the primary outcome was hospitalization. Risk factors for hospitalization were assessed by binary logistic regression analysis. This study was approved by the ethics committee of Keio University School of Medicine (approval number: 20160038).RESULTS:We defined 5-ASA intolerance as patients who had at least one in the following symptoms due to 5-ASA administration; headache, gastrointestinal symptoms, cutaneous symptoms, and fever. The rates of 5-ASA intolerance were 28.5% (22/77) in admission group and 5.1% (37/716) in no admission group. Our multivariate analysis showed that the following 3 factors have significant correlations with hospitalization; 5-ASA intolerance (odds ratio (OR) = 5.46, 95% confidence interval (CI) = 2.20–13.5), extent of disease (OR = 9.47, 95% CI = 1.25–71.6), and serum albumin level (OR = 0.122, 95% CI = 0.07–0.20). On the other hand, IM intolerance, age, duration of disease, and 5-ASA non-administration were not significantly correlated with hospitalization. Furthermore, compared with 5-ASA tolerance group, the intolerance group had significantly greater incidences of corticosteroid usage (P < 0.001) and calcineurin inhibitor usage (P < 0.01).CONCLUSION(S):It became clear for the first time that 5-ASA intolerance is the risk factor for hospitalization and worsen the prognosis of patients with UC. Therefore, even when we encounter patients with UC who are intolerant to one of the 5-ASAs, switching to another 5-ASA and continuing 5-ASA administration under strict observation may improve the prognosis of patients with UC.

Background: Indigo naturalis (IN) consists of ligands for the aryl hydrocarbon receptor and exhibits anti-inflammatory effects. Previously, we demonstrated that an 8-week treatment with oral IN is effective in inducing a clinical response in patients with ulcerative colitis (UC). Some UC patients with proctitis are refractory to topical mesalamine or corticosteroids and therefore require an alternative topical treatment. Objectives: We aimed to prospectively evaluate the safety and efficacy of IN suppositories in UC patients. Method: We performed an open-label, single-center, prospective pilot study from February 2018 to October 2018. A total of 10 patients with active UC, who had moderate to severe inflammation from the rectum to the sigmoid colon, were enrolled. The patients received a daily dose of 50 mg IN suppository for 4 weeks. The primary endpoint was safety at week 4. Results: Although 1 patient experienced anal pain, no serious adverse events were observed. At week 4, the rates of clinical remission and mucosal healing were 30 and 40%, respectively. Mayo rectal bleeding subscores significantly improved after treatment (1.80 ± 0.13 vs. 0.90 ± 0.28; p = 0.009). Approximately 80% of the patients with a baseline Mayo endoscopic subscore in the rectum (r-MES) of 2 achieved mucosal healing, but those with a baseline r-MES of 3 did not. Conclusions: We found that 4 weeks of IN suppository can be tolerated by UC patients, but its efficacy was limited by the severity of the disease. Further investigation will be needed in order to confirm the optimum dose of IN suppository for patients with UC.