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Objective:To compare the efficacy and safety of sitagliptin (a dipeptidyl peptidase-4 inhibitor) and voglibose (an α-glucosidase inhibitor) monotherapy in Japanese patients with type 2 diabetes who have inadequate glycaemic control (HbA1c ≥6.5% and <10.0%) on diet and exercise. Methods:In a multi-center, randomized, double-blind, parallel-group study, 319 patients were randomized (1:1) to 12-week treatment with sitagliptin 50 mg once daily or voglibose 0.2 mg thrice daily before meals. The primary analysis assessed whether sitagliptin was non-inferior to voglibose in lowering HbA1c.Results: After 12 weeks, sitagliptin was non-inferior to voglibose for HbA1c-lowering efficacy. Furthermore, sitagliptin was superior to voglibose, providing significantly greater reductions in HbA1c from baseline [least squares mean changes in HbA1c [95% confidence intervals (CI)] = −0.7% (−0.8 to −0.6) and −0.3% (−0.4 to −0.2), respectively; between-group difference = −0.4% (−0.5 to −0.3), p < 0.001]. Sitagliptin was also superior to voglibose on other key efficacy endpoints, including change from baseline in 2-h postmeal glucose (−2.8 mmol/l vs. −1.8 mmol/l, p < 0.001) and fasting plasma glucose (−1.1 mmol/l vs. −0.5 mmol/l, p < 0.001). After 12 weeks, the incidences of clinical adverse experiences (AEs), drug-related AEs and gastrointestinal AEs in the sitagliptin group (48.5, 10.4 and 18.4%, respectively) were significantly (p < 0.05) lower than those in the voglibose group (64.7, 26.3 and 34.6%, respectively). The incidences of hypoglycaemia, serious AEs and discontinuations due to AEs were low and similar in both groups. Conclusions:In Japanese patients with type 2 diabetes, once-daily sitagliptin monotherapy showed greater efficacy and better tolerability than thrice-daily voglibose over 12 weeks.

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The Gyro centrifugal pump, PI (permanently implantable) series, is being developed as a totally implantable artificial heart. Our final goal is to establish a "functional TAH," a totally implantable biventricular assist system (BiVAS) with centrifugal pumps. A plastic prototype pump, Gyro PI 601, was evaluated through in vitro and in vivo studies as a single ventricular assist device (VAD). Based upon these results, the pump head material was converted to a titanium alloy, and the actuator was modified. These titanium Gyro pumps, PI 700 series, also were subjected to in vitro and in vivo studies. The Gyro PI 601 and PI 700 series have the same inner dimensions and characteristics, such as the eccentric inlet port, double pivot bearing system, secondary vane, and magnet coupling system; however, the material of the PI 700 is different from the PI 601. The Gyro PI series is driven by the Vienna DC brushless motor actuator. The inlet cannula of the right ventricular assist system (RVAS) specially made for this system consists of 2 parts: a hat-shaped silicone tip biolized with gelatin and an angled wire reinforced tube made of polyvinylchloride. The pump-actuator package was implanted into 8 calves in the preperitoneal space, bypassing from the left ventricle apex to the descending aorta for the left ventricular assist system (LVAS) and bypassing the right ventricle to the main pulmonary artery for the RVAS. According to the PI 601 feasibility protocol, 2 LVAS cases were terminated after 2 weeks, and 1 LVAS case and 1 RVAS were terminated after 1 month. The PI 700 series was implanted into 4 cases: 3 LVAS cases survived for a long term, 2 of them over 200 days (72-283 days), and 1 RVAS case survived for 1 month and was terminated according to the protocol for a short-term antithrombogenic screening and system feasibility study. Regarding power consumption, the plastic pump cases demonstrated from 6.2 to 12.1 W as LVAS and 7.3 W as RVAS, the titanium pump cases showed from 10.4 to 14.2 W as LVAS and 15.8 W as RVAS. All cases exhibited low hemolysis. The renal function and the liver function were maintained normally in all cases throughout these experimental periods. In the 2 RVAS cases, pulmonary function was normally maintained. No calves demonstrated thromboembolic signs or symptoms throughout the experiments except Case 1 with the plastic pump. However, in the plastic pump cases, bilateral renal infarction was suspected in 2 cases during necropsy whereas no abnormal findings were revealed in the titanium pump cases. There were also no blood clots inside the PI 700 series. As for the 601, the explanted pumps demonstrated slight thrombus formations at the top and bottom pivots except in 1 case. The Gyro PI series, especially the PI 700 series, demonstrated superior performance, biocompatibility, antithrombogenicity and low hemolysis. Also, the durability of the actuator was demonstrated. Based on these results, this titanium centrifugal pump is suitable as an implantable LVAS and RVAS. It is likely that the Gyro PI ...

Hemolysis remains one of the most serious problems during cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), and percutaneous cardiopulmonary support (PCPS). However, the hemolytic characteristics associated with oxygenators are not well defined. A specialized hemolysis test protocol for oxygenators was developed. A comparative study was performed following this protocol to determine the hemolytic characteristics of the clinically available oxygenators during CPB; pressure drop measurements in the blood chamber were also performed. Four oxygenators (Medtronic Affinity, Cobe Optima, Terumo Capiox SX25, and Bard Quantum) were evaluated. Fresh blood from healthy Dexter calves anticoagulated with citrate phosphate dextrose adenine solution was used. The blood flow was fixed at 5 L/min, similar to that used in CPB. The Normalized Index of Hemolysis for Oxygenators (NIHO) has been modified according to the American Society of Testing and Materials (ASTM) standards. The NIH value, which was obtained from the circuit without an oxygenator, was subtracted from the primary NIH value, obtained from the circuit with an oxygenator to eliminate the effects of a centrifugal pump or other artifacts. The NIHO value was the lowest in the Affinity (0.0116 +/- 0.0017) and increased from Affinity < Optima (0.0270 +/- 0.0038) < Capiox (0.0335 +/- 0.0028) < Quantum (0.0416 +/- 0.0015 g/100 L). The Optima and Capiox did not demonstrate a significant difference. In addition, this NIHO value has a close relationship to the pressure drop. In conclusion, this new evaluation method is suitable to compare the biocompatibility performance of different types of clinically available oxygenators for CPB usage.