We estimated the medical expense of treating patients with diabetes mellitus under the health insurance system in Japan. The expense was summed up to 5.07 million yen for a patient who developed NIDDM at the age of 40 and died at the age of 75 without diabetic complications throughout his life. If he had diabetic retinopathy, neuropathy, hypertension and hyperlipidemia, and needed insulin injection, the cost would have increased 2.4 times to 12.32 million yen. It was also estimated at 25.22 million yen for a patient who developed IDDM at the age of 20 and died at the age of 70 without diabetic complications. If the patient had with diabetic retinopathy, neuropathy and hypertension and needed hemodialysis because of nephropathy for 20 years, the figure would have reached a whopping sum of 76.17 million yen. From the viewpoint of medical economy, more effort to prevent diabetic complications should be made.

The patient was a 63-year-old man, who had developed cerebral infarction during treatment for sleep apnea syndrome. He also presented typical features of deep venous thrombosis of the right lower extremity. Transesophageal echocardiography clearly showed the blood flow passing through the patent foramen ovale (PFO) followed by Valsalva maneuver. Paradoxical cerebral embolism caused by a PFO was diagnosed. Several procedures were considered to prevent recurrence of cerebral infarction, he underwent PFO closure by minimally invasive procedure, so-called port-access cardiac surgery. He started walking on the day of surgery, and postoperative echocardiography showed no residual shunt flow. Currently, no catheter-based PFO closure device is allowed in Japan, the PFO closure by the port-access technique should be considered as a feasible alternative.

Background and aims:Lenvatinib(LEN)is a newly developed tyrosine kinase inhibitor,and is approved as a first-line treatment for advanced hepatocellular carcinoma(HCC)in Japan.This retrospective multi-center study investigated the effect of the relative dose intensity(RDI)of LEN on response rate,progression-free survival(PFS),and overall survival(OS). Methods:This retrospective study enrolled 123 patients with advanced HCC who were treated with LEN at six hospitals in Japan between March 2018 and December 2019.These patients were divided into two groups:RDI ≥70％(RDI 70 group,N=70)or RDI＜70％(control group,N=53)in the first 30 days.The following data were compared between groups:patient backgrounds,adverse events,treatment out-comes,PFS,and OS.PFS and OS were analyzed using the Kaplan-Meier method,followed by the log-rank test.To identify significant factors that contributed to response,PFS,and OS,multivariate analysis was performed using factors for which P-values were ＜0.10 in univariate analysis. Results:The proportion of patients with Child-Pugh class 5A was significantly greater in the RDI 70 group than that in the control group(64.3％ vs. 28.3％,P＜0.01).Dose interruption due to adverse events was significantly more common in the control group.The response rate was significantly higher in the RDI 70 group than that in the control group(35.7％ vs. 11.3％,P＜0.01).Median PFS was significantly longer in the RDI 70 group(9.4 vs.4.7 months,P＜0.01).Multivariate analysis showed that RDI ≥70％(hazard ratio(HR)=0.55,P=0.025),hypertension grade ≥2(HR=0.47,P=0.019),and response(HR=0.52,P=0.033)were independently associated with improved PFS.Median OS was also significantly longer in the RDI 70 group(20.0 vs.13.3 months,P=0.045).Multivariate analysis showed that female sex(HR=0.33,P=0.034)and disease control(HR=0.31,P＜0.01)were independently associated with improved OS.RDI ≥70％ was not statistically significant in multivariate analysis. Conclusions:Our study revealed the importance of achieving RDI ≥70％ in the first 30 days of treatment to maximize the effects of LEN.