Two-dimension Tailor-made Therapy: A New Salvage Therapy After Multiple Eradication Failures for Helicobacter pylori Infection.

Background and Aims: Vonoprazan-based eradication therapies have a higher eradication rate than usual proton pump inhibitor (PPI)-based therapies in treating Helicobacter pylori infection. Should we use vonoprazan to treat patients who failed multiple eradication therapies? Because the drug is not available in most countries, we propose 2-dimension tailor-made therapy (2dTMT) without using vonoprazan. Methods: Patients who failed twice or more PPI-based triple therapies were recruited. Patients underwent CYP2C19 genotype and antibiotic susceptibility tests (ASTs). PPI doses per day were decided as per the CYP2C19 genotype: twice for poor and 4 times for extensive metabolizers (dimension 1). Two antibiotics were selected as per the results of the AST in each patient (dimension 2). Regimens of 2dTMT included 2 susceptible antibiotics and a PPI. For those who could not have enough information with the AST, tailor-made PPI dosing was indicated with empirically selected 2 antibiotics (one-dimension tailor-made therapy [1dTMT]). Results: Of 51 candidates with multiple eradication failures, 37 patients underwent the genotype test and AST, and 24 succeeded to obtain sufficient information to select 2 susceptible antibiotics. Of them, 22 patients accepted to receive 14-day 2dTMT. Of the residual patients, 12 accepted to receive 14-day 1dTMT. The mean eradication rate of 2dTMT was 86.4% (95% confidence interval [CI]: 65.1%-98.8%) in intention-to-treat and 90.5% (95% CI: 69.6%-98.8%) in per-protocol analyses, whereas that of 1dTMT was 75.0% (95% CI: 42.8%-94.5%) in intention-to-treat and 90.0% (95% CI: 55.5%-99.7%) in per-protocol analyses. Conclusion: Without vonoprazan, 14-day 2dTMT could be one of the salvage therapies for patients with multiple eradication failures. In cases of insufficient information with the AST, 14-day 1dTMT could be an alternative therapy. Clinical Trials Registry number, UMIN000022154 (https://www.umin.ac.jp/icdr/index.html).

Sources of atmospheric black carbon and related carbonaceous components at Rishiri Island, Japan: The roles of Siberian wildfires and of crop residue burning in China.

A field study was conducted to clarify sources of atmospheric black carbon and related carbonaceous components at Rishiri Island, Japan. We quantified equivalent black carbon (eBC) particle mass and the absorption Ångström exponent (AAE), atmospheric CO and CH4, in addition to levoglucosan in total suspended particles, a typical tracer of biomass burning. Sixteen high eBC events were identified attributable to either anthropogenic sources or biomass burning in Siberia/China. These events were often accompanied by increases of co-emitted gases such as CH4 and CO. Specifically, we observed pollution events with elevated eBC, AAE, levoglucosan, and CH4CO slope in late July 2014, which were attributed to forest fires in Siberia by reference to the FLEXPART model footprint and fire hotspots. In autumn, drastic increases of eBC, AAE, and levoglucosan were observed, accompanied by an eBC-CO slope of >15 ng m-3/ppb, resulting from long-range transport of emissions from extensive burning of crop residue on the Northeast China Plain. Other than the sources of fossil fuel combustion in China and forest fires in Siberia, we report for the first time that pollution events in northern Japan are caused by crop residue burning in China. This study elucidated valuable information that will improve understanding of the effects of biomass burning in East Asia on atmospheric carbonaceous components.

Seven years of observational atmospheric CO2 at a maritime site in northernmost Japan and its implications.

Surface atmospheric CO2 mixing ratio reflects both natural fluctuation of the carbon cycle and the effect of anthropogenic activities. Long-term observation of atmospheric CO2 forms the basis for model simulations of the carbon cycle both in the straightforward and the inversion ways. Atmospheric CO2 has been measured on Rishiri Island (45.1°N, 141.2°E) in the western North Pacific since May 2006. We report the first 7-year temporal CO2 variations from diurnal to inter-annual scales and the implications on the vegetation phenology. Diurnally, an obvious cycle appeared as a minimum in the afternoon and maximum at midnight in the summer months, caused by local vegetation. Seasonally, the maximum CO2 concentration appeared around the beginning of April, while the minimum appeared around the middle of August. This seasonal variation implied the natural cycle of terrestrial biological activities of the boreal forest, mostly in the east Eurasia. A mean growing season length of ~126 days was estimated. In the period from 2007 to 2012, the peak-to-peak amplitude increased until 2009 and decreased thereafter, with a mean value of 19.7 ppm. Inter-annually, atmospheric CO2 is increasing by a mean growth rate of 2.1 ppm year(-1). The study provides invaluable dataset and useful information to better understand the carbon cycle and its interaction with climate change.

Multiple-antibiotic-resistant Helicobacter pylori infection eradicated with a tailor-made quadruple therapy.

In 2008, a 44-year-old woman with mild epigastralgia diagnosed as having Helicobacter pylori-positive chronic gastritis without peptic ulcer underwent eradication therapy with lansoprazole (LPZ), amoxicillin (AMPC) and clarithromycin (CAM) for 7 days, but it failed, so treatment with rabeprazole, AMPC, and metronidazole (MNZ) for another 7 days was given, but it also failed. She was then prescribed a modified, 14-day sequential therapy of LPZ and AMPC with an increased dose of CAM followed by MNZ supplement, but the infection was still not eradicated. The H. pylori was cultured and examined for antibiotic susceptibility with the agar dilution method and was found to be resistant to CAM, MNZ, and levofloxacin, and non-sensitive to AMPC, namely multiple-antibiotic-resistant, although sensitive to minocycline. The CYP2C19 genotype of the patient was an extensive metabolizer (G681A: G/A, G636A: G/G). In 2010, she gave informed consent for a 14-day, tailor-made, modified classical (or modified high-dose PPI + AMPC) quadruple therapy comprising 30 mg LPZ, 500 mg AMPC and 500 mg bismuth subnitrate, qid, and 100 mg minocycline, bid. Two months later, her urea breath test was negative. Histology and bacterial culture were still negative 1 year after the therapy. She did not have any adverse events during or after the novel therapy, nor did she feel any further epigastralgia.

Hepatocellular carcinoma treated by percutaneous hot saline injection.

Percutaneous ethanol injection therapy (PEI) is one of the local methods widely used for hepatocellular carcinoma (HCC) ablation. However, this method is limited by the toxicity of ethanol and severe pain derived from irritation of the peritoneum of the liver capsule. Therefore, we have focused on the heat coagulation necrosis effect of boiled hot saline and devised percutaneous hot water injection therapy (PHoT) as a new local treatment method. PHoT was performed in 17 patients with HCC (total 24 nodules: 11 nodules <2 cm in diameter, 10 nodules from 2-4 cm, and 3 nodules >4 cm). Changes in the AFP values, and both CT and ultrasonography (US) findings before and after treatment were investigated. All 24 tumors received 1 or more treatments (average, 3.3 treat-ments) of PHoT. The injection volume ranged from 3-26 ml (average, 11.2 ml). The total volume of the injection per tumor ranged from 10-37.2 ml (average, 37.2 ml). The AFP values decreased in all patients who initially showed high values. On CT scanning, all lesions receiving PHoT became hypodense. The disappearance of the tumor was also confirmed by contrast-enhanced CT. No severe complications, excluding mild abdominal pain and skin burning, were observed during the procedure. In conclusion, PHoT shows good anti-tumor effects despite a small number of punctures and holds promise as a curative local treatment method for small HCCs.