Background: Oral mucositis frequently occurs in cancer patients treated with chemotherapy and chemoradiotherapy (CRT). This study examined the safety and efficacy of ibuprofen gargle in healthy volunteers and patients with chemotherapy-and concomitant CRT-induced oral mucositis. Methods: We enrolled healthy volunteers and patients with chemotherapy-and CRT-induced oral mucositis. In cohort I, single and multiple doses of ibuprofen gargle (0.6% or 1.0%) were administered to healthy volunteers on day 1 and days 4-10. In cohort II, multiple doses of ibuprofen gargle (0.6%) were administered to patients with complicated grade 2-3 oral mucositis based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The primary endpoint of cohort I was the treatment-related adverse events (TRAEs) as defined by CTCAE version 4.0. The primary endpoint of cohort II was the change in the visual analogue scale (VAS) pain score from before to 15 min after gargle use on day 3. The incidence and severity of TRAEs were assessed based on the CTCAE version 4.0 and a subjective rating scale completed by healthy volunteers and patients. Results: In cohort I, 9 of 10 healthy volunteers were evaluable for safety. All 9 healthy volunteers reported the TRAE of oral irritation with single or multiple use of the gargle. In cohort II, 10 patients were enrolled and evaluable for safety and 7 of 10 patients were evaluable for efficacy. The mean change in the VAS pain score from before to 15 min after using the gargle on day 3 was − 1.28 (95% confidence interval: − 2.06, − 0.51), and all patients experienced some degree of pain relief (range: − 0.2 to − 2.5). All 10 patients reported the TRAE of oral irritation. No other TRAEs of ibuprofen gargle were observed in the healthy volunteers and patients. Conclusion: Despite oral irritation, the ibuprofen gargle appeared to be safe and effective for the pain related to chemo-or CRT-induced oral mucositis. However, ibuprofen-related oral irritation warrants further formulation improvement. Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000014433).

We have established a collaboration system between community pharmacies and our hospital using the sharing tools of patient information such as tracing reports and continuous training sessions by the team-based learning method. In this study, we evaluated the clinical effectiveness of this collaboration system in patients treated with oral anti-cancer drugs as adjuvant chemotherapy for gastrointestinal cancers. This retrospective study involved outpatients who started adjuvant chemotherapy including tegafur-gimeracil-oteracil potassium or capecitabine during the pre-collaboration period (from January to September 2016) and the post-collaboration period (from August 2018 to April 2019) of 9 months, respectively. Forty-ve and 65 outpatients visited our hospital in the pre-collaboration and post-collaboration periods, respectively. The rate of treatment discontinuation due to side effects within 3 months of the start of treatment was signi cantly lower during the post-collaboration period than the pre-collaboration period (2 patients (3.1％) versus 7 patients (15.6％), P = 0.03). There were no signi cant differences between pre-and post-collaboration periods in the rates of emergency consultation and emergency hospitalization for 3 months after the start of treatment (emergency consultation: 9 patients (20.0％) versus 12 patients (18.5％), P = 1.00; emergency hospitalization: 6 patients (13.3％) versus 4 patients (6.2％), P = 0.31). These results suggest that this collaboration system could contribute to the reduction of treatment discontinuation due to the side effects of adjuvant chemotherapy for gastrointestinal cancers.

Objective High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) is an effective treatment option for relapsed and refractory aggressive malignant lymphoma. However, patients frequently experience treatment-induced gastrointestinal symptoms. Synbiotics, including live microorganisms and nondigestible food ingredients, reportedly ameliorate chemotherapy-induced mucosal damage. In this study, we assessed the efficacy and safety of synbiotics in patients undergoing auto-HSCT. Methods This randomized, double-blinded study included patients with malignant lymphoma eligible for auto-HSCT. The patients were randomly assigned to either a synbiotic group receiving Bifidobacterium longum (BB536) and guar gum or a placebo group receiving a placebo containing dextrin. The supplements were administered twice daily from the start of conditioning chemotherapy up to 28 days after auto-HSCT. The primary endpoint was the duration of total parenteral nutrition (TPN). Results In total, 12 patients were included and randomized. The median duration of TPN was 15 (range, 12-33) days in the synbiotic group and 17.5 (range, 0-32) days in the placebo group. The median duration of grade ! 3 diarrhea was shorter in the synbiotic group than in then placebo group (2.5 vs. 6.5 days), as was the duration of hospital stay (31.5 vs. 43 days). The oral intake and quality of life regarding diarrhea and anorexia improved in the synbiotic group after engraftment. Synbiotic infections, including bacteremia, were not observed. Conclusion Synbiotics may reduce gastrointestinal toxicity, thereby reducing nutritional problems and improving the quality of life of patients undergoing auto-HSCT, without severe adverse events.

An environmental isolate of Salmonella enterica serovar Enteritidis (SE) clone, SE Cl#15-1, loses its culturability during 72-h culture in M9 minimal medium containing 0.8% glucose, a concentration twice higher than that in normal M9 medium, whereas the bacterium retains its culturability in normal M9 medium. Live/dead analysis using the 5-cyano-2,3-di( p-tolyl) tetrazolium chloride (CTC)-reduction assay revealed that SE cells cultured in M9 medium containing 0.8% glucose died with time when in the "viable but nonculturable" (VBNC) state. Assay of the culturability of SE cells in the used supernatant (0.4 spent M9 or 0.8 spent M9) also indicated that 0.8 spent M9 soon showed a lethal effect on intact SE cells. These results suggest that large amounts of glucose metabolites might have been responsible for the toxicity. Analysis of the 0.8 spent M9 revealed that formate rapidly accumulated in the medium. The pH of the medium rapidly dropped to 4.7, leading to conversion of formate to formic acid, which might have damaged the bacterial cell membrane. These results suggest that the excessive amount of glucose in the M9 medium might have injured SE cells in the VBNC state by being metabolized to formic acid and other acidic compounds.Key words viable but non-culturable (VBNC) induction; Salmonella; formate; glucose; prolonged culture Salmonella is one of the most causative of food-borne diseases in the world; and it is detected not only in food but also in natural environments including river water, soil, manure, and air-borne dust.1-5) Among Salmonella spp., Salmonella enterica serovar Enteritidis (SE) is one of the dominant species, and has sometimes caused mass food poisoning in many countries. [6][7][8][9][10] In consideration of the strong infectivity of Salmonella, a better understanding of the characteristics of environmental Salmonella isolates is necessary for the control of spreading and contamination of foods by Salmonella as well as for the risk management for food safety in general.We previously reported that SEp22, [11][12][13][14] which is a novel pathogenicity-related factor of S. Enteritidis, and is identical to Salmonella Dps, 15) plays a very important role in the acquisition of the dry-resistance of S. Enteritidis. 16) In the course of studying the characteristics of SEp22, we happened to find that the prolonged batch culturing of SE cells in M9 minimal medium containing 0.8% glucose (a concentration twice higher than that used in the standard culture) significantly reduced their culturability. Analysis of the resultant culture supernatant revealed that this two-fold higher dose of glucose induced a sudden decrease in pH and the accumulation of large amounts of acetate, formate, and pyruvate. It was also remarkable that pyruvate was produced to a much higher extent in the medium with 0.8% glucose than in that with 0.4% glucose in the same time-course studies.Recent findings revealed that many pathogens could enter a viable but non-culturable (VBNC) state 17,18) after exposure to adverse environm...

Background/Aim: Osimertinib is a key drug for treating epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). Genetic differences may be associated with adverse events (AEs) induced by osimertinib. This retrospective observational multicenter study evaluated the association of genotypes, including STAT3 -1697C>G, CYP3A5 6986A>G, and ABCG2 421C>A, with the incidence of osimertinibinduced AEs in patients with EGFR mutation-positive NSCLC. Materials and Methods: 85 patients treated with osimertinib (Institution A: 33, Institution B: 52) were enrolled in the study.Single nucleotide polymorphisms were determined by real-time PCR, and the incidence of AEs were compared for each genotype. Results: The paronychia incidences were 59% for the CC genotype, 19% for the CG genotype, and 19% for the GG genotype at STAT3 -1697C>G. A genotype-related trend was observed (Cochran-Armitage test, p=0.009).Multivariate analysis showed that the CC genotype at STAT3 -1697C>G and female were significant independent factors associated with paronychia (odds ratio (OR)=6.41, 95% confidence interval (CI)=1. respectively). The incidence of diarrhea was 53% for the CC genotype, 30% for the AC genotype, and 29% for the AA genotype at ABCG2 421C>A, and a genotype-related trend was observed (p=0.048).However, the CC genotype at ABCG2 421C>A was not a significant independent factor associated with diarrhea in the multivariate analysis. No significant associations were detected between other polymorphisms and the incidence of AEs. Conclusion: STAT3 -4 1697C>G may be a novel risk factor for osimertinib-induced paronychia in patients with NSCLC.