Search

Watch a video of this article. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Apheresis therapy involves the selective removal of leukocytes and is used to induce remission in ulcerative colitis (UC) patients. The aim of this study was to demonstrate the efficacy and safety of apheresis therapy for maintaining UC remission.Methods: We conducted a multicenter, prospective, randomised-control trial of patients with remitting UC induced by granulocyte and monocyte adsorption apheresis or leukocytapheresis. Patients were randomly assigned to the apheresis group (twice per month for 12 months) or the control group (no apheresis treatment) using a 1:1 allocation ratio. The primary endpoint was the rate of cumulative clinical remission (Mayo score ≤ 2) at 12 months. The secondary endpoints were the rates of clinical remission, endoscopic remission, and complete endoscopic remission at 12 months.Results: Between March 2013 and March 2017, 164 patients were enrolled. The cumulative remission rate at 12 months was 46.6% in the apheresis group and 36.4% in the control group (p = 0.1621). The rate of endoscopic remission at 12 months was significantly higher in the apheresis group than in the control group (42.5% vs. 25.9%) p = 0.0480). The rate of clinical remission (47.5% vs.32.1%, p = 0.0540) and complete endoscopic remission (33.8% vs.19.8%, p = 0.0513) tended to be higher in the apheresis than in the control group; however, the difference was not significant. No severe adverse events were observed in either group.Conclusions: Apheresis was well tolerated as maintenance therapy for UC although the cumulative clinical remission rate at 12 months was comparable between the apheresis and control groups. [ABSTRACT FROM AUTHOR]

Background: We recently reported the efficacy of indigo naturalis (IN) in patients with active ulcerative colitis (UC) in a randomized controlled trial (INDIGO study). However, few studies have been conducted to investigate whether IN is effective even in treatment-refractory cases, such as in those with steroid dependency and anti-TNF refractoriness.Methods: In the INDIGO study, 86 patients with active UC were randomly assigned to an IN group (0.5-2.0 g daily) or placebo group. The rate of clinical response (CR), mucosal healing (MH), and change in fecal calprotectin (FCP) levels was compared between refractory [patients with steroid-dependent disease, previous use of anti-TNF-α, and concomitant use of immunomodulators (IM)] and non-refractory patients. We also analyzed factors predicting CR and MH at week 8.Results: The rates of CR of IN group were significantly higher than placebo group, even in patients with steroid-dependent disease (p < 0.001), previous use of anti-TNF-α (p = 0.002), and concomitant use of IM (p = 0.013). The rates of MH in IN group were significantly higher than in placebo group in patients with steroid-dependent disease (p = 0.009). In the IN group, median FCP levels, at week 8, were significantly lower than baseline in patients with steroid-dependent disease and patients with the previous use of anti-TNF-α (p < 0.001, respectively). Multivariate analysis indicated that the previous use of anti-TNF-α was not a predictive factor for CR and MH at week 8.Conclusions: In a sub-analysis of data from a randomized placebo-controlled trial, we found that IN may be useful even in patients with steroid-dependent disease and patients with the previous use of anti-TNF-α. [ABSTRACT FROM AUTHOR]

Background and Aim: Endoscopic stone removal has some complications. Although the life expectancy of elderly patients has increased dramatically worldwide, little information is available on the necessity of complete endoscopic stone removal in extremely elderly patients. This study aimed to evaluate the safety and efficacy of complete endoscopic stone removal in extremely elderly patients. Methods: All extremely elderly patients (>90 years) who underwent endoscopic stone removal for choledocholithiasis at our hospital between January 2012 and January 2017 were retrospectively evaluated. The included patients were divided into complete stone removal and incomplete stone removal groups. Complication rate, overall survival (OS), and disease‐specific survival (DSS) rates were compared between the two groups. Results: Overall, 73 patients were included in this study. The median number of stones was one (range, 0–10) and two (range, 1–12) (P = 0.043), while the median diameter of the largest stones was 9 (range, 0–27) and 14 (range, 5–46) mm (P = 0.001) in the complete and incomplete stone removal groups, respectively. During the follow‐up period, OS was 60% and 39% and DSS was 95% and 97% in the complete and incomplete stone removal groups, respectively. Kaplan–Meier analysis found no significant difference in OS and DSS between the two groups (P = 0.052 and P = 0.646, respectively). Conclusion: Complete stone removal might not always be necessary in extremely elderly patients aged ≥90 years. [ABSTRACT FROM AUTHOR]

Defect closure was performed using the ROLM, a defect closure technique using a line and reopenable clip (SureClip 8 mm, 16 mm; MicroTech, Nanjing, China) [3]. Mucosal defect closure after gastric endoscopic submucosal dissection (ESD) is challenging because of the thick mucosal and muscle layers [1]; it is particularly difficult in the gastric antrum. [Extracted from the article]

A nisin-inducible expression system, DnaK proteins from Lactococcus lactis ([DnaK.sub.Lla]) and Escherichia coli ([DnaK.sub.Eco]) were produced in L. lactis NZ9000 to examine the effects of nisin-induced dnaK expression in L. lactis which is found to improve stress tolerance and lactic acid fermentation efficiency. The heterologous expression of [dnaK.sub.Eco] which enhanced the quality control of proteins and enzymes is observed to result in improved growth and lactic acid fermentation at high temperature.

Background and Aim: A missense variant of the nucleoside diphosphate‐linked moiety X‐type motif 15 (NUDT15) gene (R139C) predisposes Asian patients with inflammatory bowel disease (IBD) to thiopurine‐induced leukopenia. This study evaluates the long‐term effect of NUDT15 R139C heterozygosity on hematological parameters during thiopurine administration. Methods: We enrolled 83 Japanese IBD patients who were on anti‐tumor necrosis factor‐α agents and had used thiopurine. NUDT15 R139C was genotyped by polymerase chain reaction. We retrospectively reviewed patient clinical charts to collect data on white blood cell (WBC) count, mean corpuscular volume (MCV), hemoglobin, and platelet count during the 24 months following thiopurine initiation. Results: The included patients had either Crohn's disease (54; 65.1%) or ulcerative colitis (29; 34.9%). Genotyping of NUDT15 R139C identified 62 patients (74.7%) of genotype C/C and 21 (25.3%) of genotype C/T. The median dose of thiopurine was lower in the C/T group than in the C/C group after starting thiopurine. At 6 months, the mean WBC count of the C/T group became significantly lower than that of the C/C group (P = 0.008) and remained lower through the 24 months. The C/T group developed grade 2–4 leukopenia by 6 months, which persisted through 12–24 months. The mean MCV in the C/T group became higher than that of the C/C group after 3 months. Conclusions: NUDT15 R139C heterozygosity affected the WBC count and MCV for 24 months after thiopurine administration. Our results indicate that careful monitoring of leukopenia and dose adjustment are necessary throughout treatment in IBD patients heterozygous for the NUDT15 R139C. [ABSTRACT FROM AUTHOR]

This paper describes a novel process, 'silicon carbide micro-reaction-sintering,' to reaction-sinter three-dimensional silicon carbide microstructures using micromachined silicon molds. This process consists of micromachining of silicon molds, filling the molds with material powders ([Alpha]-silicon carbide, graphite and phenol resin), bonding of the molds with adhesive, reaction-sintering by hot isostatic pressing (HIP) and release of a reaction-sintered workpiece from the mold by wet etching. Using this process, we have successfully fabricated silicon carbide microrotors with a diameter of 5 and 10 mm for a micromachined gas turbine. The shape of the silicon molds could be well transferred to the reaction-sintered samples within 3% shrinkage of the size. We used scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis to evaluate the reaction-sintered samples. They revealed the generation of [Beta]-silicon carbide by the reaction between silicon and graphite in reaction-sintering process. They also revealed the presence of residual free silicon in the reaction-sintered samples due to low concentration of graphite in the material powders. We measured mechanical properties such as bending strength and Vickers hardness. The reaction-sintered samples had approximately 70% bending strength and 70-80% Vickers hardness compared with those of a commercially-available reaction-sintered silicon carbide. [509] Index Terms--Lost mold method, mechanical properties, micromachined gas turbine, micromachining reaction-sintering, silicon carbide, silicon mold.