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The small bowel is affected in more than half of patients with Crohn's disease (CD) at the time of diagnosis, and small bowel involvement has a negative impact on the long-term outcome. Many patients reportedly have active lesions in the small intestine even in patients in clinical remission. This study was performed to compare findings of magnetic resonance enterography (MRE) and ileocolonoscopy. A single-center retrospective study was conducted in 50 patients (60 imaging series) with CD, for whom MRE was additionally performed during the bowel preparation for subsequent ileocolonoscopy. Endoscopic remission was defined as a Simple Endoscopic Score for CD (SES-CD) of <5. MRE remission was defined as a Magnetic Resonance Index of Activity (MaRIA) score of <50. The time to treatment escalation was assessed by the log-rank test. Importantly, 7 of 29 patients (24.1%) with endoscopic remission had a MaRIA score of ≥50. Both SES-CD and MaRIA correlated with the need for treatment escalation (P = 0.025, P = 0.009, respectively). MRE predicted the need for treatment escalation even in patients with endoscopic remission. Although no correlation was present between SES-CD and MaRIA score in patients with structuring/penetrating disease, or insufficient ileal insertion (<10cm), a high MaRIA score still correlated with the need for treatment escalation in stricturing or penetrating disease (P = 0.0306). The MaRIA score predicts the need for treatment escalation even in patients with endoscopic remission, indicating that addition of MRE to conventional ileocolonoscopy alone can be a useful, noninvasive tool for monitoring CD especially in stricturing or penetrating disease.

Fecal calprotectin (FC) is well accepted as a non-invasive biomarker which objectively reflects colonic inflammation in ulcerative colitis (UC). However, its value as a marker of response during the early phase of remission induction treatment has not been well studied. The aim of this study is to evaluate the significance of FC for predicting the short-term outcomes of remission induction treatment in patients with UC. A prospective observational study was conducted among 31 patients with active UC. FC was monitored with two-item patient-reported outcome (PRO2), partial Mayo score (PMS), and Lichtiger clinical activity index (CAI) during the first 4 weeks of remission induction treatment. Clinical response was defined as a decrease in CAI of 3 or more points below baseline. Mucosal healing (MH) was defined as Mayo endoscopic subscore 0 or 1. Within-day and within-stool variability of FC were assessed during the first week of treatment. In week 4-clinical responders, PRO2, PMS, and CAI significantly decreased from day 3, however, FC did not show significant reduction until week 2. Among all markers, the decrease in PRO2 at week 4 most accurately predicted MH at week 12. Within-day variability of FC was remarkably wide even at the first week in clinical responders. Within-stool variability was extremely small. PRO2 predicted the short-term outcomes of remission induction treatment earlier than FC possibly because of the wide within-day variability of FC in active UC.

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.

Genetic studies have indicated possible involvement of the upregulated calcium-nuclear factor of activated T cells pathway in the pathogenesis of Kawasaki disease. We aimed to assess safety and efficacy of ciclosporin, an immunosuppressant targeting this pathway, for protection of patients with Kawasaki disease against coronary artery abnormalities. We did a randomised, open-label, blinded endpoints trial involving 22 hospitals in Japan between May 29, 2014, and Dec 27, 2016. Eligible patients predicted to be at higher risk for intravenous immunoglobulin (IVIG) resistance were randomly assigned to IVIG plus ciclosporin (5 mg/kg per day for 5 days; study treatment) or IVIG (conventional treatment) groups, stratified by risk score, age, and sex. The primary endpoint was incidence of coronary artery abnormalities using Japanese criteria during the 12-week trial, assessed in participants who received at least one dose of study drug and who visited the study institution at least once during treatment. This trial is registered to Center for Clinical Trials, Japan Medical Association, number JMA-IIA00174. We enrolled 175 participants. One patient withdrew consent after enrolment and was excluded and one patient (in the study treatment group) was excluded from analysis because of lost echocardiography data. Incidence of coronary artery abnormalities was lower in the study treatment group than in the conventional treatment group (12 [14%] of 86 patients vs 27 [31%] of 87 patients; risk ratio 0·46; 95% CI 0·25–0·86; p=0·010). No difference was found in the incidence of adverse events between the groups (9% vs 7%; p=0·78). Combined primary therapy with IVIG and ciclosporin was safe and effective for favourable coronary artery outcomes in Kawasaki disease patients who were predicted to be unresponsive to IVIG. Japan Agency for Medical Research and Development (grant CCT-B-2503).

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Recently, the prognosis of NAFLD/NASH has been reported to be dependent on liver fibrosis degree. Liver biopsy remains the gold standard, but it has several issues that must be addressed, including its invasiveness, cost, and inter-observer diagnosis variability. To solve these issues, a variety of noninvasive tests (NITs) have been in development for the assessment of NAFLD progression, including blood biomarkers and imaging methods, although the use of NITs varies around the world. The aim of the Japan NASH NIT (JANIT) Forum organized in 2020 is to advance the development of various NITs to assess disease severity and/or response to treatment in NAFLD patients from a scientific perspective through multi-stakeholder dialogue with open innovation, including clinicians with expertise in NAFLD/NASH, companies that develop medical devices and biomarkers, and professionals in the pharmaceutical industry. In addition to conventional NITs, artificial intelligence will soon be deployed in many areas of the NAFLD landscape. To discuss the characteristics of each NIT, we conducted a SWOT (strengths, weaknesses, opportunities, and threats) analysis in this study with the 36 JANIT Forum members (16 physicians and 20 company representatives). Based on this SWOT analysis, the JANIT Forum identified currently available NITs able to accurately select NAFLD patients at high risk of NASH for HCC surveillance/therapeutic intervention and evaluate the effectiveness of therapeutic interventions.

Background In Japan, carbapenem-resistant Enterobacterales (CRE) infections were incorporated into the National Epidemiological Surveillance of Infectious Diseases (NESID) in 2014, necessitating mandatory reporting of all CRE infections cases. Subsequently, pathogen surveillance was initiated in 2017, which involved the collection and analysis of CRE isolates from reported cases to assess carbapenemase gene possession. In this surveillance, CRE is defined as (i) minimum inhibitory concentration (MIC) of meropenem ≥2 mg/L (MEPM criteria) or (ii) MIC of imipenem ≥2 mg/L and MIC of cefmetazole ≥64 mg/L (IPM criteria). This study examined whether the current definition of CRE surveillance captures cases with a clinical and public health burden. Methods CRE isolates from reported cases were collected from the public health laboratories of local governments, which are responsible for pathogen surveillance. Antimicrobial susceptibility tests were conducted on these isolates to assess compliance with the NESID CRE definition. The NESID data between April 2017 and March 2018 were obtained and analyzed using antimicrobial susceptibility test results. Results In total, 1681 CRE cases were identified during the study period, and pathogen surveillance data were available for 740 (44.0%) cases. Klebsiella aerogenes and Enterobacter cloacae complex were the dominant species, followed by Klebsiella pneumoniae and Escherichia coli . The rate of carbapenemase gene positivity was 26.5% (196/740), and 93.4% (183/196) of these isolates were of the IMP type. Meanwhile, 315 isolates were subjected to antimicrobial susceptibility testing. Among them, 169 (53.7%) fulfilled only the IPM criteria (IPM criteria-only group) which were susceptible to meropenem, while 146 (46.3%) fulfilled the MEPM criteria (MEPM criteria group). The IPM criteria-only group and MEPM criteria group significantly differed in terms of carbapenemase gene positivity (0% vs. 67.8%), multidrug resistance rates (1.2% vs. 65.8%), and mortality rates (1.8% vs 6.9%). Conclusion The identification of CRE cases based solely on imipenem resistance has had a limited impact on clinical management. Emphasizing resistance to meropenem is crucial in defining CRE, which pose both clinical and public health burden. This emphasis will enable the efficient allocation of limited health and public health resources and preservation of newly developed antimicrobials.