Effect of Vonoprazan on Delayed Bleeding after Endoscopic Submucosal Dissection for Gastric Neoplasia among Antithrombotic Drug Users: A Single-Center, Single-Arm Prospective Observational Case Control Study

Antithrombotic therapy is a major risk factor for delayed bleeding after endoscopic submucosal dissection (ESD) for gastric neoplasia. A potassium-competitive acid blocker, vonoprazan, is expected to prevent delayed bleeding better than conventional proton pomp inhibitors (PPIs), but the evidence is controversial. We sought to clarify the efficacy of vonoprazan for prevention of delayed bleeding after gastric ESD in patients under antithrombotic therapy. We prospectively registered 50 patients who underwent gastric ESD while receiving antithrombotic therapy and vonoprazan in our institution between October 2017 and September 2018. The incidence of delayed bleeding was compared with that in a historical control group of 116 patients treated with conventional PPI. We also evaluated risk factors associated with delayed bleeding. Delayed bleeding was observed in 8 of 50 patients (16.0%), which was not dissimilar from the incidence in the historical control group (12.1%) (p=0.49). In the univariate analysis, age (> 70 years) (p=0.034), multiple antithrombotic drug use (p 200 min) (p=0.038) and tumor size (> 40 mm) (p<0.01) were associated with delayed bleeding after gastric ESD, but vonoprazan was not (p=0.49). Vonoprazan may not be more effective than conventional PPIs in preventing delayed bleeding after gastric ESD in patients receiving antithrombotic therapy

Endoscopic evaluation by the Kyoto classification of gastritis combined with serum anti-Helicobacter pylori antibody testing reliably risk-stratifies subjects in a population-based gastric cancer screening program

Background　We previously demonstrated that the Kyoto classification of gastritis was useful for judging the status of Helicobacter pylori infection in a population-based screening program, and that adding H. pylori antibody test improved its accuracy (UMIN000028629). Here, we tested whether our endoscopic diagnosis of H. pylori infection status reliably estimated gastric cancer risk in the program. Methods　Data were collected from1345 subjects who underwent endoscopic follow-up 4 years after the end of the registration. We analyzed the association of three diagnostic methods of H. pylori infection with gastric cancer detection: (1) endoscopic diagnosis based on the Kyoto classification of gastritis; (2) serum diagnosis according to the ABC method (H. pylori antibody and pepsinogen I and II); and (3) endoscopic diagnosis together with H. pylori antibody test. Results　During the follow-up, 19 cases of gastric cancer were detected. By Kaplan–Meier analysis, the detection rates of cancer were significantly higher in the past or current H. pylori infection groups than in the never-infected group with all 3 methods. By the Cox proportional hazards model, the hazard ratio for cancer detection was highest in evaluation with the combined endoscopic diagnosis and the antibody test (method 3; hazard ratio 22.6, 95% confidence interval 2.99–171) among the three methods (the endoscopic diagnosis (method 1); 11.3, 2.58–49.8, and the ABC method (method 2); 7.52, 2.49–22.7). Conclusions　Endoscopic evaluation of H. pylori status with the Kyoto classification of gastritis, especially combined with serum anti-Helicobacter pylori antibody testing, reliably risk-stratified subjects in a population-based gastric cancer screening program

Magnetic structure and Kondo lattice behavior in CeVGe3_3: an NMR and neutron scattering study

We present nuclear magnetic resonance (NMR), neutron diffraction, magnetization, and transport measurements on a single crystal and powder of CeVGe$_3$. This material exhibits heavy fermion behavior at low temperature, accompanied by antiferromagnetic (AFM) order below 5.8 K. We find that the magnetic structure is incommensurate with AFM helical structure, characterized by a magnetic modulated propagation vector of $(0, 0, 0.49)$ with in-plane moments rotating around the $c$-axis. The NMR Knight shift and spin-lattice relaxation rate reveal a coherence temperature $T^*\sim 15$ K, and the presence of significant antiferromagnetic fluctuations reminiscent of the archetypical heavy fermion compound CeRhIn$_5$. We further identify a metamagnetic transition above $H_m\sim 2.5$ T for magnetic fields perpendicular to $c$. We speculate that the magnetic structure in this field-induced phase consists of a superposition with both ferromagnetic and antiferromagnetic components, which is consistent with the NMR spectrum in this region of the phase diagram. Our results thus indicate that CeVGe$_3$ is a hexagonal structure analog to tetragonal CeRhIn$_5$.Comment: 13 pages, 11 figure

Exacerbation of Bloody Diarrhea as a Side Effect of Mesalamine Treatment of Active Ulcerative Colitis

Mesalamine has been used as the first-line therapy for the treatment of ulcerative colitis (UC) because of its efficacy and fewer side effects. However, earlier study showed that mesalamine occasionally causes diarrhea. We are presenting a patient with active UC in whom bloody diarrhea accompanied by abdominal pain and fever occurred and the symptoms were aggravated after administration of mesalamine. In order to clarify the reason of symptoms aggravation, drug lymphocyte stimulation test and rechallenge trial with mesalamine were performed. The results indicated the possibility that aggravation was related to allergic reaction and was dose-dependent. Furthermore, we examined colonoscopic views but there was no remarkable change in before and after rechallenge trial. Based on the above result, the patient was diagnosed with mesalamine intolerance. In order to differentiate whether the exacerbation of bloody diarrhea is due to the side effects of the mesalamine or a true relapse of UC, taking careful history before and after increasing mesalamine dosage as well as being aware of side effects of mesalamine are required. Clinicians should be aware of diarrhea as a side effect of mesalamine particularly after onset of mesalamine formulation, change in mesalamine formulation, or change in mesalamine dose

A mechanistic multi-centre, parallel group, randomised placebo controlled trial of Mesalazine for treatment of irritable bowel syndrome with diarrhoea (IBS-D)

Introduction: Immune activation has been reported in the mucosa of irritable bowel syndrome patients with diarrhoea (IBS-D) and some small studies have suggested that Mesalazine may reduce symptoms. We performed a double blind, randomised placebo controlled trial of 2g Mesalazine twice daily versus placebo for 3 months in Rome III criteria IBS-D patients. Primary outcome was daily average stool frequency during weeks 11-12; secondary outcomes were abdominal pain, stool consistency, urgency and satisfactory relief of IBS symptoms. Methods: Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of “satisfactory relief of IBS symptoms”. Results: 136 patients with IBS-D (82 F, 54 M) were randomised, 10 patients withdrew from each group. Analysis by intention to treat showed the daily average stool frequency during weeks 11 and 12 were mean (SD), 2.8 (1.2) in Mesalazine and 2.7 (1.9) in placebo group with no significant group difference (95% confidence interval) 0.1 (-0.33,0.53); p=0.66. Mesalazine did not improve abdominal pain, stool consistency nor percentage with satisfactory relief compared to placebo during the last 2 weeks follow up. Conclusion: This study does not support any clinically meaningful benefit or harm of Mesalazine compared with placebo in unselected IBS with diarrhoea. More precise subtyping based on underlying disease mechanisms is needed to allow more effective targeting of treatment in IBS. (ClinicalTrials.gov number NCT01316718

Efficacy and mode of action of mesalazine in the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D): a multicentre, parallel-group, randomised placebo-controlled trial

BackgroundDiarrhoea-predominant irritable bowel syndrome (IBS-D) is a common outcome after inflammation due to bacterial gastroenteritis. Several studies have shown ongoing immune activation in the mucosa of patients with IBS-D and a number of studies have suggested that mesalazine slow-release granule formulation (2?g; PENTASA®, Ferring Pharmaceuticals Ltd) may provide benefit including a reduction in stool frequency.ObjectivesOur primary aim was to compare the effect of mesalazine with placebo on stool frequency. Our secondary aims were to assess the effect of mesalazine on abdominal pain, stool consistency, urgency and satisfactory relief of irritable bowel syndrome (IBS) symptoms.Design/participants/interventionWe performed a double-blind, randomised placebo-controlled trial of 2?g mesalazine twice daily compared with placebo for 3 months in Rome III criteria patients with IBS-D.SettingsParticipants were recruited from the primary care research network and secondary care hospitals. Participants were randomised after a 2-week baseline stool diary. All participants completed a 12-week stool diary and at the end of each week recorded the presence of ‘satisfactory relief of IBS symptoms’. Those recruited in Nottingham had sigmoid biopsies and/or magnetic resonance imaging of the abdomen at the start and end of the trial.ResultsA total of 136 patients with IBS-D (82 female, 54 male) were randomised; 10 patients withdrew from each group. Analysis by intention to treat showed that the mean daily average stool frequency during weeks 11 and 12 was 2.8 [standard deviation (SD) 1.2] in the mesalazine group and 2.7 (SD 1.9) in the placebo group, with a group difference of 0.1 (95% confidence interval –0.33 to 0.53); p?=?0.66.ConclusionsMesalazine did not improve abdominal pain, stool consistency or percentage with satisfactory relief compared with placebo during the last 2 weeks’ follow-up. A post hoc analysis in 13 postinfectious patients with IBS appeared to show benefit but this needs confirmation in a larger group. More precise subtyping based on underlying disease mechanisms may allow more effective targeting of treatment in IBS.Trial registrationCurrent Controlled Trials ISRCTN76612274.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership.<br/

A nationwide, multi-center, retrospective study of symptomatic small bowel stricture in patients with Crohn\u27s disease.

BACKGROUND:Small bowel stricture is one of the most common complications in patients with Crohn\u27s disease (CD). Endoscopic balloon dilatation (EBD) is a minimally invasive treatment intended to avoid surgery; however, whether EBD prevents subsequent surgery remains unclear. We aimed to reveal the factors contributing to surgery in patients with small bowel stricture and the factors associated with subsequent surgery after initial EBD.METHODS:Data were retrospectively collected from surgically untreated CD patients who developed symptomatic small bowel stricture after 2008 when the use of balloon-assisted enteroscopy and maintenance therapy with anti-tumor necrosis factor (TNF) became available.RESULTS:A total of 305 cases from 32 tertiary referral centers were enrolled. Cumulative surgery-free survival was 74.0% at 1 year, 54.4% at 5 years, and 44.3% at 10 years. The factors associated with avoiding surgery were non-stricturing, non-penetrating disease at onset, mild severity of symptoms, successful EBD, stricture length < 2 cm, and immunomodulator or anti-TNF added after onset of obstructive symptoms. In 95 cases with successful initial EBD, longer EBD interval was associated with lower risk of surgery. Receiver operating characteristic analysis revealed that an EBD interval of ≤ 446 days predicted subsequent surgery, and the proportion of smokers was significantly high in patients who required frequent dilatation.CONCLUSIONS:In CD patients with symptomatic small bowel stricture, addition of immunomodulator or anti-TNF and smoking cessation may improve the outcome of symptomatic small bowel stricture, by avoiding frequent EBD and subsequent surgery after initial EBD