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These results suggest that tolvaptan may provide high response rates when used early in the course of hepatic edema, or when both hepatic and renal functions are still retained, leading to an improved disease prognosis.

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complicated and multifactorial, because there are many confounding factors between UA and AF, such as race, sex, and any other risk factors.Our cross-sectional study in a large number of Japanese subjects undergoing health check-ups identified an independent association between UA and the prevalence of AF. 13 We could not, however, clarify the causal relationship between serum UA and AF, or determine the predictive value of UA for the incidence of AF because of its crosssectional design. Moreover, to our knowledge, research on the Japanese population has not demonstrated a relationship between baseline UA and new-onset AF. We therefore investigated this association by analyzing the stored examination data of a large number of Japanese subjects who underwent annual medical health check-ups.Background: The independent role of uric acid (UA) as a risk factor for atrial fibrillation (AF) has not been fully elucidated. Methods and Results:We studied 111,566 subjects (53,416 men; 58,150 women) who underwent annual health check-ups. We divided them by sex into tertile of baseline UA. To investigate the predictive power of UA for new-onset AF, we performed Cox proportional hazard analysis including UA tertiles, body mass index, creatinine, smoking and drinking status, and presence of hypertension, diabetes, and dyslipidemia. During 4.1 years, 467 men (0.87%) and 180 women (0.31%) had AF (P<0.001). Cut-off points for tertiles of UA were as follows: women, ≤3.9, 4.0-4.8, and ≥4.9 mg/dL; men, ≤5.4, 5.5-6.4, and ≥6.5 mg/dL. Hazard ratio (HR) for third to first tertile was 1.74 (95% CI: 1.15-2.70; P=0.008), whereas there were no differences between tertiles in men. Rate of new-onset AF was significantly higher in the group with initially increased UA (ΔUA ≥0.3 mg/dL) than that with unchanged UA (ΔUA, −0.2 or +0.2 mg/dL) in the third tertile of baseline UA in both sexes. Conclusions:Higher baseline UA was significantly associated with higher AF incidence in women. Initial increase in UA was significantly associated with AF incidence when baseline UA was ≥6.5 mg/dL in men, and ≥4.9 mg/dL in women.

Aim Despite accumulating evidence concerning the efficacy of tolvaptan in the treatment of body fluid retention or hyponatremia, the effect of tolvaptan on the prognosis of patients with hepatic ascites has not been fully investigated. Methods A total of 628 patients with hepatic ascites who were treated with diuretics (furosemide, spironolactone, or tolvaptan) between 2007 and 2017 were enrolled and divided into two groups: those who received tolvaptan (original tolvaptan group, n = 278) and those who did not (original control group, n = 350). The cumulative survival rates between the groups were compared and the factors associated with survival in patients with hepatic ascites were identified using a Cox regression analysis. In addition, propensity score matching was applied in patients who started conventional diuretics for new‐onset hepatic ascites after September 2013 (pre‐matching tolvaptan group, n = 177; pre‐matching control group, n = 63), and the cumulative survival rates were compared between the post‐matching tolvaptan and control groups. Results The survival rate was significantly higher in the tolvaptan group than the control group (P = 0.005), and tolvaptan therapy was identified as an independent factor associated with survival (hazard ratio 0.721 for death relative to control, P < 0.001). The propensity score‐matched comparison also showed a significantly higher survival rate in the tolvaptan group (n = 51) than in the control group (n = 51) (P = 0.009). Conclusions This study suggests that tolvaptan might improve the prognosis of patients with hepatic ascites.

The aim of the current study was to determine the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of a combination of paclitaxel and S-1 in patients with advanced gastric cancer. Fifteen patients were enrolled. The dose for S-1 was set at 80 mg/m2/day (days 1-14), while the dose for paclitaxel increased by 10 mg/m2 for every three patients, with a starting dose of 100 mg/m2 and was given biweekly on day 1 and 15. There was no severe toxicity (grade 4) recorded in patients receiving up to 120 mg/m2 of paclitaxel. Leukopenia/neutrophilia with grade 1 to 3 occurred in six patients up to level 3. At 130 mg/m2 of paclitaxel, grade 4 leukocytopenia and neutropenia events and grade 3 diarrhea developed in one out of three patients. One patient in another group of three patients that were enrolled at level 3, developed grade 4 granulocytopenia with fever (a body temperature higher than 38 degrees C) and grade 3 leukocytopenia. Eight patients, out of a total of 15, showed a partial response, resulting in an objective response rate of 53%. Five patients received gastrectomy. Median survival time was 428 days and the 1 year survival rate was 53%. Biweekly paclitaxel/S-1 combination chemotherapy could be safely used for the treatment of advanced gastric cancer. The recommended doses for a phase II study with paclitaxel and S-1 are 120 mg/m2 and 80 mg/m2, respectively.

A combination regimen of biweekly paclitaxel and oral S-1 was well tolerated and showed promising activity against unresectable and recurrent gastric cancer.