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Background and aim Helicobacter pylori eradication can disrupt the gut microbiome. Here, we investigated the short-term impact of minimum antibiotic treatment-a 7-day vonoprazan and low-dose amoxicillin regimen (VA-dual therapy)-on gut microbiota and compared it with that of vonoprazan-based triple therapy (VAC-triple therapy). Methods Fifty-nine patients with H. pylori infection were recruited (UMIN000034140) from March to May 2019 and randomly assigned to the VAC-triple therapy or VA-dual therapy groups, according to the first-line H. pylori treatment received. Fecal samples were collected before treatment initiation and 1 and 8 weeks after eradication therapy completion. The composition ratios of the bacterial taxa and the alpha and beta diversities were evaluated in both groups via polymerase chain reaction amplification of the V3-V4 region of the 16S rRNA gene and sequencing using the MiSeq system. Results Nineteen patients were assigned to the VA-dual group and 24 to the VAC-triple group. Compared with baseline, the alpha diversity reduced significantly 1 and 8 weeks after VAC-triple therapy. However, for VA-dual therapy, the alpha diversities at 1 and 8 weeks after the treatment did not change significantly compared with those at baseline. Additionally, the beta diversity differed significantly between baseline and 1 and 8 weeks after VAC-triple therapy. VAC-triple therapy led to significant alteration in the relative abundance of Actinobacteria at the phylum level and Collinsella, Blautia, and Streptococcus at the genus level. Conclusions Compared with VAC-triple therapy, VA-dual therapy induced minimal changes in the diversity and relative abundance of gut microbiota.

Aims This study aims to investigate the prognostic impact of mineralocorticoid receptor antagonists (MRAs) on cardiovascular events in patients hospitalized for acute decompensated heart failure with preserved ejection fraction (HFpEF; defined as left ventricular ejection fraction ≥45%). Methods and results A prospective multicentre cohort study was conducted in Nagano prefecture, Japan, between July 2014 and December 2018 that contained 518 consecutive HFpEF patients hospitalized for acute decompensated heart failure (HF). The primary outcome was a composite of cardiovascular death and HF readmission. We compared the incidence of cardiovascular events between patients who were prescribed with MRAs and those who were not in a propensity score matched cohort using a Cox proportional hazards regression model with a propensity score derived from 23 baseline variables. For sensitivity analysis, we conducted Cox proportional hazards regression models for the primary outcome adjusting for 16 clinically relevant variables in the crude cohort. The median age was 83 years, and 53% were female. The median left ventricular ejection fraction was 61%. During a median follow‐up of 553 days, the primary outcome occurred in 192 (37%) patients. MRAs were used in 255 (49%) patients. After analysis, a matched cohort consisting of 370 patients was created. After propensity score matching, the baseline characteristics were well balanced between the two groups. The incidence of the primary outcome was significantly lower in MRA users than in non‐users [32% (59/185) vs. 49% (90/185); hazard ratio (HR) 0.669, 95% confidence interval (CI) 0.482–0.929, P = 0.016]. The incidence of cardiovascular death was also significantly lower in the MRA users [11% (21/185) vs. 22% (41/185); HR, 0.563; 95% CI, 0.333–0.953; P = 0.032]. The risk of HF readmission tended to be lower in the MRA users [29% (54/185) vs. 41% (75/185); HR, 0.738; 95% CI, 0.520–1.048; P = 0.089]. MRA use was also associated with a lower risk of the primary outcome after Cox proportional hazards analysis adjusting for 16 clinically relevant variables in the crude cohort (HR, 0.710; 95% CI 0.507–0.995; P = 0.047). Conclusions Mineralocorticoid receptor antagonist use was significantly associated with a lower risk of the primary composite outcome of cardiovascular death and HF readmission in patients hospitalized for acute decompensated HFpEF. The incidence of cardiovascular mortality was also significantly lower in these patients.

Background and Aim Minimizing endoscopist exposure to bodily fluids is important for reducing the risk of infection transmission. This study investigated the patient‐endoscopist vertical distance necessary to minimize an endoscopist's facial exposure to a patient's visible droplets during upper gastrointestinal endoscopy and the ability of a new device to prevent droplets from reaching the endoscopist's face. Methods A model was developed to simulate a patient experiencing a forceful cough during an upper gastrointestinal endoscopy with a model endoscopist. Fluorescent dye was expelled from the model patient's mouth towards the model endoscopist during simulated coughs; dye adhesion to the model endoscopist's face was evaluated using ultraviolet light. The simulation was repeated with the model patient positioned 70–100 cm above the floor, with and without a barrier to shield the patient's face. The accuracy of the cough simulation model and the relationship between patient‐endoscopist vertical distance and endoscopist's facial exposure were evaluated. Results The flow dynamics of the cough simulation model were similar to that of an actual human cough. There was a significant inverse correlation between the patient‐endoscopist vertical distance and the model endoscopist's facial exposure, with positive exposures decreasing from 87% at 70 cm to 0% at 100 cm (P

Background and Aim Endoscopic resection for early gastric cancer (EGC) is widely performed. However, there is still a paucity of strong evidence regarding long‐term outcomes after endoscopic submucosal dissection (ESD) for the expanded indication criteria of the Japanese guidelines (ver. 2010). Methods Endoscopic submucosal dissection was performed in patients with EGC that met the expanded indication criteria: (i) cT1a, differentiated‐type EGC of 2 to 5 cm, ulcer negative or (ii) cT1a, differentiated‐type EGC of ≤3 cm, ulcer positive. Patients whose pathological examination fulfilled the curative resection criteria were then enrolled in this cohort study: negative vertical margin, negative lymphovascular invasion, and (i) pT1a, differentiated‐type, and ulcer negative; (ii) pT1a, differentiated‐type, ≤3 cm, and ulcer positive; or (iii) pT1b1 (2 cm in diameter and ulcer‐negative lesions, and 94 (44%) had ≤3 cm and ulcer‐positive lesions. The vital status at 5 years after ESD was confirmed in all (100%) patients. No local or metastatic recurrence was detected; however, 26 metachronous gastric cancers developed, and 1 patient died of metachronous gastric cancer. The 5‐year disease‐specific and overall survival rates were 99.5% (95% confidence interval [CI], 97.2%–100%) and 93.9% (95% CI, 89.8%–96.4%), respectively. Conclusion ESD for EGC that fulfills the expanded criteria is feasible and shows favorable long‐term outcomes.

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OBJECTIVES Colonic spasm can interfere with colonoscopy, but antispasmodic agents can cause complications. This study aimed to assess the inhibitory effect of topical lidocaine compared with a placebo control. METHODS In five tertiary-care hospitals in Japan, 128 patients requiring endoscopic resection of a colorectal lesion were enrolled and randomly and double-blindly allocated to colonoscopy with topical administration of 2% lidocaine solution 20mL (LID, n = 64) or normal saline 20mL (control, n = 64). During colonoscopy, the assigned solution was applied with a spray catheter near the lesion and the area was observed for three minutes. primary endpoint was the inhibitory effect at three time-points (1, 2 and 3 minutes after dispersion), using a three-point scale (excellent, fair, poor). Secondary endpoints were rebound spasm and adverse events. All endpoints were scored in real time. Serum lidocaine levels were measured in 32 patients (LID 16, control 16). RESULTS There were no significant differences between groups in patient demographics. At all time-points, the proportion of patients with "excellent" scores was greater in LID group than control group, with significant differences observed at 2 minutes (p = 0.02) and 3 minutes (p = 0.02). In LID group, the rate of "excellent" scores increased by 12.5% at 2 minutes and was maintained at 3 minutes. Rebound spasm did not occur in LID group, compared with 15.6% of control group (p = 0.001). There were no adverse events in LID group. All serum lidocaine levels were below detectable levels. CONCLUSIONS Topical lidocaine is an effective and safe method for suppressing colorectal spasm during colonoscopy (UMIN000024733).

The optical properties of arrays of hexagonal GaN microdisks, which potentially act as whispering-gallery-mode-type optical microcavities, were investigated. The arrays were fabricated from a GaN film using a top–down process, and the side lengths and height of the hexagonal GaN microdisks were approximately 1.5 and 500 nm, respectively. The microdisk arrays exhibited optically pumped lasing actions. The estimated lasing intensities which were obtained from one microdisk in the arrays were related to the period of the arrays. We discuss the optical properties of the microdisk arrays in view of experimental results and numerical analyses obtained using a two-dimensional finite-difference time-domain method.

Menthol is used widely as a constituent of functional foods and chemical drugs. The present study investigated changes in the pharmacokinetic behavior of intravenously administered midazolam (MDZ), a probe for CYP3A, when rats were treated with menthol. The study also examined which isoforms of CYP3A1 and 3A2 were menthol-inducible and contributed to the altered disposition of midazolam. Menthol was administered intraperitoneally to rats once daily for 3 days at a dose of 10 mg/kg, while the control rats received vehicle alone. The pharmacokinetic examination of i.v. administered midazolam revealed that serum midazolam concentrations at each sampling point were lower in the menthol-treated rats than in the control rats. Regarding the pharmacokinetic parameters of the menthol-treated group, the area under the curve (AUC) was decreased significantly and, correspondingly, the elimination rate constant at terminal phase (ke) was increased significantly without significant changes in the volume of distribution at steady state (Vdss). The metabolic production of the 1'-hydroxylated and 4'-hydroxylated forms of MDZ by hepatic microsomes was significantly greater in the menthol-treated rats than in the control rats. The expression levels of mRNA and protein for hepatic CYP3A2 were more than 2.5-fold higher than the control levels when the rats were treated with menthol, whereas no changes were observed in the expression levels of CYP3A1. These results indicate that menthol enhanced the elimination clearance of midazolam by inducing hepatic CYP3A2 and that careful attention should be paid when menthol is ingested in combination with drugs that act as substrates for CYP3A.

A domino cyclization of α-alkoxyalkyl ortho-alkynylaryl ethers and electron-rich arenes affords benzofurans.

Durch Elektronenbeugung wurde nachgewiesen, das CdBr2 durch Bestrahlung mit Elektronen zu Cd zersetzt wird.