Background: Combination treatment with bevacizumab and paclitaxel has been approved for treating human epidermal growth factor receptor 2(HER2)-negative metastatic breast cancer(MBC) in Japan. Japan has no official economical guideline showing decision criteria for the approvals of new drugs. However, the National Institute for Health and Clinical Excellence(NICE) in UK hardly recommends the combinational use of bevacizumab for HER2-negative MBC, because of its poor cost-effectiveness.　Objective: The evaluation of the cost-effectiveness of additional bevacizumab as primary chemotherapy for HER2-negative MBC in accordance with the clinical practice guideline in JapanMethods: A Markov cohort simulation was used to follow the clinical course of typical patients with MBC. Transition probabilities were estimated from randomized clinical trials. Direct medical costs were assessed from the perspective of the Japanese health-care system. This study used quality-adjusted life year(QALY), and both costs and QALYs were discounted 3% annually. The time horizon was 10 years. Both a univariate and probabilistic sensitivity analyses were conducted. Results: The additional use of bevacizumab to paclitaxel required an additional cost of JPY 9.12 million(USD 114,000) for obtaining a gain of 0.26 QALYs, and the incremental cost effectiveness ratio was JPY 35 million(USD 437,000). Conclusion：By assuming of GBP 20,000-30,000(JPY 2.5-3.75 million and USD 31,000-46,900) to be an index value threshold by NICE, combination treatment with bevacizumab was found to be hardly cost-effective. Based on the fair and adequate distribution of medical resource, economical guidelines reflecting the Japanese health-care system are necessary. (Jpn J Pharmacoepidemiol 2013；18(1)：1-12)

Partial atrio-ventricular canal is usually symptomatic and treated surgically in a childhood. In the literature, only eight cases have been operated on over fifty years of age. We experienced two cases of partial atrio-ventricular canal; one was 63-year-old female and the other was 67-year-old male. The female patient showed rapid increase of the pulmonary pressure during the last three years. The male patient had moderate mitral regurgitation with mild pulmonary hypertention. Although the repair of the mitral valve was successful in the female patient, it was difficult in the male patient because of massive calcification along the edges of the mitral cleft. Blood biochemistry data revealed the liver cirrhosis due to congestion in the male patient. Because of poor tolerance of the viscera in aged patients, it is quite important not to raise the central venous pressure more than 15cmH₂O at the cessation of the cardio-pulmonary bypass. Over-hydration may cause congestive heart failure easily, and take into vicious cycle. Of course early operation is better, these two cases, however, had uneventful course and resumed active life early in their postoperative days. Results of them encouraged us to treat aged patient of partial atrio-ventricular canal surgically.

Surface induced hypothermia was introduced in six cases with low cardiac output syndrome after open heart surgery to reduce oxgen consumption. The patients were consisted of two ACBG, two LV rupture after MVR, MVR with ACBG and AVR with poor LV function. Hemodynamic changes such as heart rate, mean arterial pressure, cardiac index, systemic vascular resistance, pulmonary artery wedge pressure, were measured every 3-4 hours throughout the course of hypothermia. Acid-base balance, mixed venous oxgen saturation and oxygen consumption were also monitored. Hypothermia was induced using a blanket and ice-beutels. Temperature in hypothermia was maintained at about 33°C. We are intended to increase SVO₂ up to the level of 50% and to improve anerobic condition. Hypothermia was continued for 45 hours in the shortest and 148 hours in the longest case with a mean of 78 hours. Arrythmia was not seen. Hemodynamic and acid-base balance were in significantly changed in comparison of the control values. However, SVO₂ and VO₂ changed significantly after introduction of hypothermia. They increased from 47.8±7.5% to 58.7±7.9% and reduced from 231±29.7 to 188±31.3ml O₂/min respectively. Hemodynamic condition was improved and IABP was successfully weaned in all cases. We suggest that the use of hypothermia is one of the effective modality in the management of low cardiac output syndrome after open heart surgery.

A total of 183 patients who underwent surgical repair of secundum type atrial septal defect (ASD), were divided into 5 age groups. Hemodynamic parameters, arrhythmia, and abnormality of the atrio-ventricular valve function were compared among the 5 groups. Although the pulmonary to systemic blood flow ratio was not different, the pulmonary to systemic pressure ratio was higher in the sixth decade than in the third (p<0.05) and fourth (p<0.01). Pulmonary to systemic vascular resistance ratio increased with age, although the difference was not statistically significant. The cardiothoracic ratio, atrial fibrillation and tricuspid regurgitation (TR) also increased with age. These data suggest that ASD progresses with age. There were 41 patients who showed more than grade II TR, 10 patients underwent tricuspid annuloplasty (TAP), 1 underwent tricuspid valve replacement, and the other 30 patients had no treatment of the tricuspid valve. TAP with DeVega's (6 cases) or Carpentier-ring (1) method was effective. In 30 untreated TR patients, 9 patients remained with grade II TR after closure of the defect. Because TAP is an easy and very effective procedure, TAP should have been applied to all patient with TR more severe than grade II. There were 10 patients with mitral regurgitation (MR) of more than grade II. Two patients in whom mitral valve prolapse had been detected on ultrasound cardiography (UCG) before operation underwent mitral valve plasty successfully. Although MR decreased in 6 patients after only ASD closure, two patients remained with grade II MR. We now recommend that the mitral valve should be assessed under direct vision, and intraoperative trans-esophageal echo cardiography, and also that the mitral regurgitation test as well as preoperative UCG should be performed. Because ASD is progressive with age, surgical repair should be performed before age 40.

Although left anterior descending coronary artery (LAD) grafting with a left internal thoracic artery (ITA) on a beating heart via a small left anterior thoracotomy (LAST) has become widely accepted, significant limitations exist due to the limited surgeon experience, smallness of exposure, thus making harvesting of the ITA, visualization of the surgical field and anastomosis quite difficult. Patients often have significant pain and wound complications postoperatively. A lower mini-sternotomy approach in 4 patients was performed from December 1998 through January 1999. Results: The length of mini-sternotomy incision is 7 to 14cm. These operations were accomplished without morbidity or mortality. No patients required intraoperative conversion to conventional bypass. Postoperative angiography showed patency of graft without stenosis of the anastomosis in all 4 patients. The patients did not complain of significant pain and their postoperative hospital stay was 5 to 11 days. The lower mini-sternotomy approach or“xyphoid” approach proposed by Benetti seems to be an excellent novel approach giving the freedom of extension of the incision if needed with satisfactory exposure for left ITA harvest and access to LAD as well as the distal RCA, and causes less postoperative incisional pain.

BACKGROUND AND OBJECTIVES: Reactive oxygen species (ROS) mediate various signaling pathways that underlie vascular inflammation in atherogenesis and cardiovascular diseases. Cardiac rehabilitation (CR) has a variety of multiple beneficial effects, including anti-inflammatory effects. The purpose of the present study was to investigate the effects of CR on ROS in patients with cardiovascular diseases. SUBJECTS AND METHODS: The serum level of derivatives of reactive oxidative metabolites, an index of oxidative stress, was measured in 100 patients with cardiovascular diseases before, and, subsequently, 3 and 6 months after, CR. A biological antioxidant potential (BAP) test was applied to assess the antioxidant power of the serum. RESULTS: The resting reactive oxidative metabolite levels decreased 3-6 months after CR {pre: 351+/-97 Carratelli unit (CARR U), 3 months: 329+/-77 CARR U, 6 months: 325+/-63 CARR U, all p<0.01} with the increase of the percentage of the predicted values of VO2 peak and the percentage of the predicted values of VO2 at the anaerobic threshold (VO2 AT) and the decrease of the B-type natriuretic peptide (BNP). The BAP test and antioxidative/oxidative stress ratio increased 6 months after CR. The % changes of the antioxidative/oxidative stress ratio was positively correlated with the % changes of VO2 AT, and negatively correlated with the % changes of the BNP. CONCLUSION: These results suggest that intensive supervised CR significantly improved exercise capacity, which may be attributable to an adaptive response involving more efficient oxidative metabolites or the increased capacity of endogenous anti-oxidative systems in patients with cardiovascular diseases.
Anaerobic Threshold ; Antioxidants ; Atherosclerosis ; Cardiovascular Diseases ; Exercise Therapy ; Humans ; Inflammation ; Natriuretic Peptide, Brain ; Oxidative Stress ; Oxygen Consumption ; Reactive Oxygen Species