Clinical outcomes of patients with remitting ulcerative colitis after discontinuation of indigo naturalis.

Indigo naturalis is an effective treatment for ulcerative colitis. However, long-term use of indigo naturalis causes adverse events, such as pulmonary hypertension. The natural history of patients with ulcerative colitis who discontinued indigo naturalis after induction therapy is unknown. Moreover, the clinical features of patients who relapsed within 52 weeks after the discontinuation of indigo naturalis are unclear. This study aimed to assess the clinical outcomes of patients with ulcerative colitis after discontinuation of indigo naturalis and to identify potential markers responsible for relapse. This single-center retrospective study investigated the follow-up of 72 patients who achieved a clinical response 8 weeks after indigo naturalis treatment. We observed relapse in patients with ulcerative colitis after the discontinuation of indigo naturalis. We analyzed the factors predicting long-term outcomes after discontinuation of indigo naturalis. Relapse was observed in 24%, 57%, and 71% of patients at 8, 26, and 52 weeks, respectively. There were no predictive markers in patients who relapsed within 52 weeks after the discontinuation of indigo naturalis. The ulcerative colitis relapse rate after indigo naturalis discontinuation was high. Follow-up treatment is required after the discontinuation of indigo naturalis in patients with ulcerative colitis.

D-amino Acids Ameliorate Experimental Colitis and Cholangitis by Inhibiting Growth of Proteobacteria: Potential Therapeutic Role in Inflammatory Bowel Disease.

BACKGROUND & AIMS: D-amino acids, the chiral counterparts of protein L-amino acids, were primarily produced and utilized by microbes, including those in the human gut. However, little was known about how orally administered or microbe-derived D-amino acids affected the gut microbial community or gut disease progression. METHODS: The ratio of D- to L-amino acids was analyzed in feces and blood from patients with ulcerative colitis (UC) and healthy controls. Also, composition of microbe was analyzed from patients with UC. Mice were treated with D-amino acid in dextran sulfate sodium colitis model and liver cholangitis model. RESULTS: The ratio of D- to L-amino acids was lower in the feces of patients with UC than that of healthy controls. Supplementation of D-amino acids ameliorated UC-related experimental colitis and liver cholangitis by inhibiting growth of Proteobacteria. Addition of D-alanine, a major building block for bacterial cell wall formation, to culture medium inhibited expression of the ftsZ gene required for cell fission in the Proteobacteria Escherichia coli and Klebsiella pneumoniae, thereby inhibiting growth. Overexpression of ftsZ restored growth of E. coli even when D-alanine was present. We found that D-alanine not only inhibited invasion of pathological K. pneumoniae into the host via pore formation in intestinal epithelial cells but also inhibited growth of E. coli and generation of antibiotic-resistant strains. CONCLUSIONS: D-amino acids might have potential for use in novel therapeutic approaches targeting Proteobacteria-associated dysbiosis and antibiotic-resistant bacterial diseases by means of their effects on the intestinal microbiota community.

Prospective feasibility study of indigo naturalis ointment for chemotherapy-induced oral mucositis.

OBJECTIVES: Indigo naturalis, a herbal medicine effective against ulcerative colitis, exhibits anti-inflammatory effects and induces interleukin-22-mediated antimicrobial peptide production. Anti-inflammatory activity and the prevention of secondary infection are essential for the management of chemotherapy-induced oral mucositis (CIOM); therefore, we developed an indigo naturalis ointment to be administered topically for CIOM and evaluated its feasibility. METHODS: We performed a single-centre, open-label, prospective feasibility study from March 2017 to December 2018. The key eligibility criteria for the subjects were as follows: (1) receiving chemotherapy for a malignant tumour; (2) grade 1 or 2 CIOM and (3) receiving continuous oral care. The treatment protocol comprised topical indigo naturalis ointment application three times a day for 7 days. The primary endpoint assessed was feasibility. The secondary endpoints assessed were the changes in oral findings, oral cavity pain and safety. RESULTS: Nineteen patients with CIOM were enrolled. The average feasibility (the proportion of prescribed applications that were carried out) observed in this study was 94.7%±8.9% (95% CI 90.5% to 99.0%), which was higher than the expected feasibility. The revised oral assessment guide scores of the mucous membrane domain and total scores were significantly improved. All patients reported a reduction in oral cavity pain, with a median pain resolution duration of 6 days. No serious adverse events were observed. CONCLUSIONS: The indigo naturalis ointment was feasible, and showed the potential for efficacy and safety. Larger randomised controlled trials are needed to further assess the efficacy and safety of indigo naturalis compared with a placebo. TRIAL REGISTRATION NUMBER: UMIN000024271.

Hepatic Adenosine Triphosphate Reduction Through the Short-Chain Fatty Acids-Peroxisome Proliferator-Activated Receptor γ-Uncoupling Protein 2 Axis Alleviates Immune-Mediated Acute Hepatitis in Inulin-Supplemented Mice.

How liver tolerance is disrupted in immune-mediated liver injury is currently unclear. There is also insufficient information available regarding susceptibility, precipitation, escalation, and perpetuation of autoimmune hepatitis. To explore how dietary fiber influences hepatic damage, we applied the concanavalin A (ConA)-induced acute immune-mediated liver injury model in mice fed a diet supplemented with 6.8% inulin, a water-soluble fermentable fiber. Twelve hours after ConA administration, inulin-supplemented diet-fed mice demonstrated significantly alleviated hepatic damage histologically and serologically, with down-regulation of hepatic interferon-γ and tumor necrosis factor and reduced myeloperoxidase (MPO)-producing neutrophil infiltration. Preconditioning with an inulin-supplemented diet for 2 weeks significantly reduced hepatic adenosine triphosphate (ATP) content; suramin, a purinergic P2 receptor antagonist, abolished the protective effect. Of note, the portal plasma derived from mice fed the inulin-supplemented diet significantly alleviated ConA-induced immune-mediated liver injury. Mechanistically, increased portal short-chain fatty acid (SCFA) levels, such as those of acetate and butyrate, by inulin supplementation leads to up-regulation of hepatic γ-type peroxisome proliferator-activated receptor (Pparg) and uncoupling protein 2 (Ucp2), which uncouples mitochondrial ATP synthesis downstream of PPARγ. Pparg down-regulating small interfering RNA cancelled the protective effect of inulin supplementation against MPO-producing neutrophil infiltration and the subsequent immune-mediated liver injury, suggesting that the SCFA-PPARγ-UCP2 axis plays a key role in the protective effect by inulin supplementation. Moreover, significant changes in the gut microbiota, including increased operational taxonomic units in genera Akkermansia and Allobaculum, also characterized the protective effect of the inulin-supplemented diet. Conclusion: There is a possible unraveled etiopathophysiological link between the maintenance of liver tolerance and dietary fiber. The SCFA-PPARγ-UCP2 axis may provide therapeutic targets for immune-mediated liver injury in the future.

Rikkunshito as a Therapeautic Agent for Functional Dyspepsia and its Prokinetic and Non-Prokinetic Effects.

Prokinetics is one of the therapeutic agents for functional and motility disorders of the stomach. However, its efficacy is limited. Kampo medicine is a unique medical system that was developed in Japan. In Kampo medicine, herbal medicine is prescribed based on the patient's condition. Therefore, even for functional and motility disorders of the stomach, some herbal medicines are considered as a therapeutic option. Recently, there has been an increase in evidence for the efficacy or the mechanism of herbal medicine for functional and motility disorders of the stomach. Among these, rikkunshito is a well-studied herbal medicine that could be used as an alternative to prokinetics. In this review, we discuss the possibilities of rikkunshito for functional dyspepsia with its prokinetic and non-prokinetic effects and provide an overview of their current use with a focus on their therapeutic mechanism.

Indigo naturalis is effective even in treatment-refractory patients with ulcerative colitis: a post hoc analysis from the INDIGO study.

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.

Development of an Indigo Naturalis Suppository for Topical Induction Therapy in Patients with Ulcerative Colitis.

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.

10-Year Trends in Helicobacter pylori Eradication Rates by Sitafloxacin-Based Third-Line Rescue Therapy.

BACKGROUND/AIMS: Sitafloxacin (STFX)-containing regimens were shown to be useful options for third-line Helicobacter pylori eradication therapy. It is reported that resistance to quinolone is also increasing globally. Therefore, we conducted an analysis of the current efficacy of a 10-day -STFX-containing third-line rescue therapy and the changes of antibiotic resistance to H. pylori compared to 2 historical controls. METHODS: Patients in whom eradication treatment using both first- and second-line triple therapies failed were enrolled from 2014 to 2015. The minimum inhibitory concentrations of STFX, clarithromycin (CLR), amoxicillin (AMX), metronidazole (MTZ) and the gyrA mutation status of the H. pylori strains were determined before treatment. After that, the patients received a 10-day triple therapy containing esomeprazole (20 mg, b.i.d.), AMX (500 mg, q.i.d.) and STFX (100 mg, b.i.d.; 10-day EAS). The eradication rate and the rate of antibiotic resistance to H. pylori were compared with 2 previous reports about STFX-containing third-line rescue therapies in 2009-2011 and 2012-2013. To explore the association between the eradication rates of regimens containing STFX, AMX and proton pump inhibitors and the location of gyrA mutation or AMX resistance, a meta-analysis was attempted. RESULTS: The overall eradication rates, the eradication rate for gyrA mutation negative- and positive- strains were 81.6% (31/38), 94.7% (18/19) and 68.4% (13/19) respectively. These rates were not significantly different from 2 previous reports. The resistant rates to STFX, CLR, AMX, MTZ and the rate of presence of mutation in gyrA were 50.0, 81.6, 36.8, 78.9 and 50.0%, respectively, which was also not significantly different from 2 previous reports. A meta-analysis showed that the relative risk of the eradication failure is significantly lower in gyrA mutation negative strains compared to gyrA mutation positive strains, and that the relative risk of the eradication failure is significantly lower in gyrA mutation at D91 compared to gyrA mutation at N87 (p < 0.001 and p = 0.022, respectively). Moreover, a meta-analysis showed that the relative risk of the eradication failure is significantly lower in AMX-sensitive strains compared to AMX-resistant ones. CONCLUSION: Changes in the rate of antibiotic resistance to H. pylori were not observed from 2009 to 2015. The status of gyrA mutation is a superior marker for predicting successful eradication in STFX/AMX-containing triple regimen as a third-line rescue therapy.

Adverse events in patients with ulcerative colitis treated with indigo naturalis: a Japanese nationwide survey.

BACKGROUND: Although indigo naturalis (IN) is effective for patients with active ulcerative colitis (UC), IN was associated with adverse events (AEs), including pulmonary arterial hypertension (PAH). Our aim was to evaluate the occurrence of IN-associated AEs and to evaluate any IN dose-effect on AEs. METHODS: A nationwide survey, using questionnaires, was conducted by conducted by the research group funded by the Ministry of Health, Labour and Welfare of Japan, between June 2017 and September 2018. A first questionnaire determined the occurrence of AEs associated with the therapeutic use of IN or herbal medicines containing IN in patients with UC. A second survey identified the clinical characteristics of patients who developed IN-associated critical AEs, namely, liver dysfunction, PAH, and intussusception. RESULTS: Across 337 participating institutions, 49,320 patients with UC were identified, with IN used in 877 (1.8%). AEs were reported in 91 patients (107 events), including liver dysfunction (n = 40), gastrointestinal symptoms (n = 21), headache (n = 13), and PAH (n = 11). No dose-effect relationship between IN and AEs was identified. Liver dysfunction tended to be mild and reversible. Ten cases of intussusception were reported, with 40% of these patients requiring surgical resection. IN-induced PAH was recovered in patients who discontinued to use IN. No IN-associated deaths were reported. CONCLUSIONS: IN-associated AEs were identified among patients with UC, with liver dysfunction often being reversible, while surgical resection was required in a high proportion of patients who developed intussusception. Both healthcare workers and patients should adequately recognize the potential for AEs with the use of IN.

Current new challenges in the management of ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory condition of the gastrointestinal tract. Although the cause of UC is postulated to be multifactorial in nature, including genetic predisposition, epithelial barrier defects, dysregulation of immune responses, and environmental factors, the specific pathogenesis of UC is still incompletely understood. In the treatment of UC so far, a method of suppressing immunity and treating it has been mainstream. Immunosuppressant drugs, including thiopurines (azathioprine or 6-mercaptopurine), anti-tumor necrosis factor-α (anti-TNF-α) antibody (infliximab and adalimumab), and calcineurin inhibitor, can be used in treat patients with corticosteroid-dependent and/or corticosteroid-refractory moderateto- severe UC. Recently, in addition to such a conventional therapeutic agent, golimumab, which is the first transgenic human monoclonal anti-TNF-α antibody to be fabricated, anti α-4/ß-7 integrin antibody, and Janus kinase inhibitor have been reported to novel immunosuppressant therapy. Furthermore, other treatments with unique mechanisms different from immunosuppression, have also been suggested, including fecal microbiota transplantation and Indigo naturalis, which is a Chinese herbal medicine. We compared the features and efficacy of these new treatments. In this issue, the features and treatment options for these new treatments is reviewed.

Efficacy of Indigo Naturalis in a Multicenter Randomized Controlled Trial of Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Indigo naturalis (IN) is a traditional Chinese medicine that contains ligands for the aryl hydrocarbon receptor and promotes regeneration of the mucosa by inducing production of interleukin 22. IN might induce mucosal healing in patients with ulcerative colitis (UC). We performed a randomized controlled trial to investigate the safety and efficacy of IN in patients with UC. METHODS: We performed a multicenter, double-blind trial evaluating the safety of 86 patients in Japan with active UC (Mayo scores of 6 or more), enrolled from March 30 through December 27, 2016. Patients were randomly assigned to groups and given a daily dose of 0.5, 1.0, or 2.0 g IN or placebo (1:1:1:1 ratio) for 8 weeks. The primary endpoint was the rate of clinical response at week 8, defined as a 3-point decrease in the Mayo score and a decrease of at least 30% from baseline, with a decrease of at least 1 point for the rectal bleeding subscore or absolute rectal bleeding score of 0-1. The main secondary endpoint was the rate of clinical remission at week 8, defined as a Mayo score or ≤2 and no subscores with a value >1. Mucosal healing was also assessed at week 8. RESULTS: The trial was terminated because of an external reason: a report of pulmonary arterial hypertension in a patient who used self-purchased IN for 6 months. In the intent-to-treat analysis, we observed a significant, dose-dependent linear trend in proportions of patients with clinical responses (13.6% with a clinical response to placebo; 69.6% to 0.5 g IN; 75.0% to 1.0 g IN; and 81.0% to 2.0 g IN) (Cochran-Armitage trend test P < .0001 compared with placebo). Proportions of patients in clinical remission at week 8 were significantly higher in the 1.0 g IN group (55.0%, P = .0004) and the 2.0 g IN group (38.1%, (P = .0093) than in the placebo group (4.5%). Proportions of patients with mucosal healing were 13.6% in the placebo group, 56.5% in the 0.5 g IN group, 60.0% in the 1.0 g IN group, and 47.6% in the 2.0 g IN group (P = .0278 compared with placebo). Although mild liver dysfunction was observed in 10 patients who received IN, no serious adverse events were observed. CONCLUSIONS: In a randomized, placebo-controlled trial, we found 8 weeks of IN (0.5-2.0 g per day) to be effective in inducing a clinical response in patients with UC. However, IN should not yet be used because of the potential for adverse effects, including pulmonary arterial hypertension. Clinical Trials Registry no: UMIN000021439 (http://www.umin.ac.jp/ctr/).

Intestinal Dysbiosis and Biotin Deprivation Induce Alopecia through Overgrowth of Lactobacillus murinus in Mice.

Metabolism by the gut microbiota affects host physiology beyond the gastrointestinal tract. Here, we find that antibiotic-induced dysbiosis, in particular, overgrowth of Lactobacillus murinus (L. murinus), impaired gut metabolic function and led to the development of alopecia. While deprivation of dietary biotin per se did not affect skin physiology, its simultaneous treatment with vancomycin resulted in hair loss in specific pathogen-free (SPF) mice. Vancomycin treatment induced the accumulation of L. murinus in the gut, which consumes residual biotin and depletes available biotin in the gut. Consistently, L. murinus induced alopecia when monocolonized in germ-free mice fed a biotin-deficient diet. Supplementation of biotin can reverse established alopecia symptoms in the SPF condition, indicating that L. murinus plays a central role in the induction of hair loss via a biotin-dependent manner. Collectively, our results indicate that luminal metabolic alterations associated with gut dysbiosis and dietary modifications can compromise skin physiology.

Colonic dysmotility and morphological abnormality frequently detected in Japanese patients with irritable bowel syndrome.

BACKGROUND/AIMS: Colonoscopy and computed tomography (CT) are used primarily to exclude organic diseases in patients with irritable bowel syndrome (IBS), rather than to assess the pathophysiology of IBS. We aimed to evaluate colonic dysmotility and morphology in Japanese patients with IBS. METHODS: One hundred eighty-four patients with IBS and 49 asymptomatic controls who underwent colonoscopy in combination with CT colonography or barium enema were retrospectively reviewed between 2008 and 2012. Water-aided colonoscopy was performed without sedation by a single endoscopist. The duration and pattern of colonic movement and cecal intubation time were recorded. To assess colonic morphology, barium enema or CT colonography were performed immediately after colonoscopy. RESULTS: Colonic dysmotility was more frequent in the IBS group (28.8% vs. 2.0% in controls, P<0.001), especially in cases of IBS with diarrhea (IBS-D) (IBS with constipation [IBS-C] 28.8% vs. IBS-D 60.0% vs. mixed IBS [IBS-M] 5.1%, P<0.001). Colonic morphological abnormality was more frequent in the IBS group than in the control group (77.7% vs. 24.5%, P<0.001), especially in IBS-M and IBS-C groups (IBS-C 77.5% vs. IBS-D 48.9% vs. IBS-M 100%, P<0.001). Most patients with IBS with colonic dysmotility had experienced stress related to their symptoms. Cecal intubation time was significantly longer in the IBS group than in the control group (12.1±6.9 minutes vs. 4.6±1.9 minutes, P<0.001). CONCLUSIONS: Unsedated colonoscopy, combined with radiographic findings, can detect colonic dysmotility and morphological abnormality. Technical difficulties observed during cecal intubation may partially explain the pathophysiology of IBS.

Recent trends and future directions for the medical treatment of ulcerative colitis.

Recently, several medical treatments for ulcerative colitis (UC) have been developed, including 5-aminosalicylic acids (5-ASAs), corticosteroids, thiopurine, calcineurin inhibitors, and anti-tumor necrosis factor (TNF) α treatments. Treatment options including calcineurin inhibitors and anti-TNF treatment for refractory UC are discussed in this article. Furthermore, upcoming treatments are introduced, such as golimumab, vedolizumab, AJM300, tofacitinib. Budesonide foamwill be used as one treatment option in patients with distal colitis. Herbal medicine, such as Qing-Dai is also effective for active UC and may be useful for patients who are refractory to anti-TNFα treatments. In the near future, physicians will able to use many different treatments for UC patients. However, we should not forget 5-ASA and corticosteroids as the fundamental treatments for UC patients.

Indole compounds may be promising medicines for ulcerative colitis.

Indole compounds are extracted from indigo plants and have been used as blue or purple dyes for hundreds of years. In traditional Chinese medicine, herbal agents in combination with Qing-Dai (also known as indigo naturalis) have been used to treat patients with ulcerative colitis (UC) and to remedy inflammatory conditions. Recent studies have noted that indole compounds can be biosynthesized from tryptophan metabolites produced by various enzymes derived from intestinal microbiota. In addition to their action on indole compounds, the intestinal microbiota produce various tryptophan metabolites that mediate critical functions through distinct pathways and enzymes. Furthermore, some indole compounds, such as indigo and indirubin, act as ligands for the aryl hydrocarbon receptor. This signaling pathway stimulates mucosal type 3 innate lymphoid cells to produce interleukin-22, which induces antimicrobial peptide and tight junction molecule production, suggesting a role for indole compounds during the mucosal healing process. Thus, indole compounds may represent a novel treatment strategy for UC patients. In this review, we describe the origin and function of this indole compound-containing Chinese herb, as well as the drug development of indole compounds.

Clinical Efficacy and Safety of Oral Qing-Dai in Patients with Ulcerative Colitis: A Single-Center Open-Label Prospective Study.

BACKGROUND/AIMS: Chinese herbal medicine Qing-Dai (also known as indigo naturalis) has been used to treat various inflammatory conditions. However, not much has been studied about the use of oral Qing-Dai in the treatment for ulcerative colitis (UC) patients. Studies exploring alternative treatments for UC are of considerable interest. In this study, we aimed at prospectively evaluating the safety and efficacy of Qing-Dai for UC patients. METHODS: The open-label, prospective pilot study was conducted at Keio University Hospital. A total of 20 patients with moderate UC activity were enrolled. Oral Qing-Dai in capsule form was taken twice a day (daily dose, 2 g) for 8 weeks. RESULTS: At week 8, the rates of clinical response, clinical remission, and mucosal healing were 72, 33, and 61%, respectively. The clinical and endoscopic scores, CRP levels, and fecal occult blood results were also significantly improved. We observed 2 patients with mild liver dysfunction; 1 patient discontinued due to infectious colitis and 1 patient discontinued due to mild nausea. CONCLUSION: This is the first prospective study indicating that oral Qing-Dai is effective for inducing remission in patients with moderate UC activity and can be tolerated. Thus, Qing-Dai may be considered an alternative treatment for patients, although further investigation is warranted.

Efficacy of 10-day Sitafloxacin-Containing Third-Line Rescue Therapies for Helicobacter pylori Strains Containing the gyrA Mutation.

BACKGROUND AND AIM: Sitafloxacin-containing Helicobacter pylori eradication therapy is a promising third-line therapeutic approach, but there is no previous studies between gyrA mutation status of H. pylori strains and the efficacy of 10-day sitafloxacin-containing regimens. Here, we assessed the efficacy of 2 different 10-day sitafloxacin-containing rescue regimens. METHODS: Patients who failed first- and second-line eradication therapies were enrolled. The minimum inhibitory concentrations (MICs) of sitafloxacin, amoxicillin, and metronidazole and the gyrA mutation status of the H. pylori strains were determined before treatment. The patients were randomized to receive a 10-day triple therapy containing either esomeprazole (20 mg, b.i.d.), amoxicillin (500 mg, q.i.d.), and sitafloxacin (100 mg, b.i.d.) (EAS regimen) or esomeprazole (20 mg, b.i.d.), metronidazole (250 mg, b.i.d.), and sitafloxacin (100 mg, b.i.d.) (EMS regimen). Eradication rates were evaluated by the [13C] urea breath test or the H. pylori stool antigen test. RESULTS: All patients with gyrA mutation-negative strains (24 in EAS and 16 in EMS) showed successful eradication, irrespective of the regimen they received. In patients with gyrA mutation-positive strains, we found eradication rates of 70.3% (26/37) and 66.7% (26/39) in the EAS and EMS groups in per-protocol population, respectively (p = .81). According to logistic regression analyses, the MICs of sitafloxacin, which were strongly associated with gyrA mutation status, were independently associated with successful eradication in both groups. This study was registered in the UMIN Clinical Trials Registry as UMIN000006483. CONCLUSION: There is no significant difference in the eradication rates between EAS and EMS, regardless of the gyrA mutation status of the H. pylori strains. GyrA mutation status was an important factor in predicting successful eradication with sitafloxacin-containing rescue therapies.

Effect of supplementation with rebamipide for Helicobacter pylori eradication therapy: a systematic review and meta-analysis.

BACKGROUND AND AIM: Several studies have reported that the application of rebamipide during the eradication of Helicobacter pylori can improve the eradication rate. However, the efficacy and safety are controversial. The present study systematically evaluated whether rebamipide improves the eradication rate of H. pylori by conducting a meta-analysis based on randomized controlled trials (RCTs). METHODS: Literature searches were conducted in the following database: PubMed, the Cochrane Library, and the Igaku-chuo-zasshi database in Japan. A meta-analysis of all RCTs comparing rebamipide supplementation with non-rebamipide-containing therapy was performed. RESULTS: We identified six randomized trials (611 patients). Pooled H. pylori eradication rates by per-protocol analysis were 73.3% and 61.4% for patients with or without rebamipide, respectively. The odds ratio was 1.74 (95% confidence interval. 1.19-2.53). CONCLUSIONS: Supplementation with rebamipide might be effective in increasing the H. pylori eradication rates of proton-pump inhibitor-amoxicillin dual therapy.

Modified bowel preparation regimen for use in second-generation colon capsule endoscopy in patients with ulcerative colitis.

BACKGROUND AND AIM: We have reported that second-generation colon capsule endoscopy (CCE-2) might be feasible for assessing the severity of mucosal inflammation in ulcerative colitis (UC). However, because of the low rate (69%) of complete evaluation of the colon and owing to inadequate cleansing. We believe that the method of bowel preparation could be improved by reducing volume. In the present study, we attempted to improve the colon-cleansing regimen in order to optimize the usefulness of CCE-2 in the management of UC patients. METHODS: Twenty patients with histologically confirmed UC were enrolled. Patients took a maximum 2.2 L lavage solution (polyethylene glycol solution and magnesium citrate) in two or three divided doses. To assess the effectiveness of the modified bowel preparation regimen, we evaluated the rate of total colonobservation, the effectiveness of bowel cleansing, andinterobserver agreement in assessing UC disease activity. We used a four-point grading scale (poor, fair, good, and excellent) for evaluating the quality of bowel cleansing. Matts' endoscopic score was used to evaluate disease activity. RESULTS: The rate of total colon observation was 85%, and 15 patients (75%) excreted the CCE-2 within 8 h. The proportion of excellent plus good cleansing was approximately 60%. There was a substantial interobserver agreement (κ = 0.777) in assessment of overall cleansing, which was still substantial at the fair cleansing level (κ = 0.700). CONCLUSION: Using CCE-2, the modified bowel preparation regimen, with reduced volume has the potential to succeed in the evaluation of mucosal severity in UC.