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Aim: To elucidate the effectiveness of extracorporeal membrane oxygenation (ECMO) in accidental hypothermia (AH) patients with and without cardiac arrest (CA), including details of complications., Methods: This study was a multicentre, prospective, observational study of AH in Japan. All adult (aged ≥18 years) AH patients with body temperature ≤32 °C who presented to the emergency department between December 2019 and March 2022 were included. Among the patients, those with CA or circulatory instability, defined as severe AH, were selected and divided into the ECMO and non-ECMO groups. We compared 28-day survival and favourable neurological outcomes at discharge between the ECMO and non-ECMO groups by adjusting for the patients' background characteristics using multivariable logistic regression analysis., Results: Among the 499 patients in this study, 242 patients with severe AH were included in the analysis: 41 in the ECMO group and 201 in the non-ECMO group. Multivariable analysis showed that the ECMO group was significantly associated with better 28-day survival and favourable neurological outcomes at discharge in patients with CA compared to the non-ECMO group (odds ratio [OR] 0.17, 95% confidence interval [CI]: 0.05-0.58, and OR 0.22, 95%CI: 0.06-0.81). However, in patients without CA, ECMO not only did not improve 28-day survival and neurological outcomes, but also decreased the number of event-free days (ICU-, ventilator-, and catecholamine administration-free days) and increased the frequency of bleeding complications., Conclusions: ECMO improved survival and neurological outcomes in AH patients with CA, but not in AH patients without CA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The clinical features of heart failure (HF) in patients with hypertrophic cardiomyopathy (HCM) in Japan have not been fully elucidated., Methods and results: In 293 patients with HCM (median age at registration, 65 (57-72) years) in a prospective cardiomyopathy registration network in Kochi Prefecture (Kochi RYOMA study), HF events (HF death or hospitalization for HF) occurred in 35 patients (11.9%) (median age, 76 (69-80) years), including 11 HF deaths during a median follow-up of 6.1 years. The 5-year HF events rate was 9.6%. Atrial fibrillation, low percentage of fractional shortening, and high B-type natriuretic peptide level at registration were predictors of HF events. The combination of these 3 factors had a relatively high positive predictive value (55%) for HF events and none of them had a high negative predictive value (99%). There were 4 types of HF profile: left ventricular (LV) systolic dysfunction (40%), severe LV diastolic dysfunction (34%), LV outflow tract obstruction (LVOTO) (20%), and primary mitral regurgitation (MR) (6%). HF deaths occurred in patients with LV systolic dysfunction or LV diastolic dysfunction, but none of patients with LVOTO or primary MR due to additional invasive therapies., Conclusions: In a Japanese HCM cohort, HF was an important complication, requiring careful follow-up and appropriate treatment.

Background: Accessibility to stroke treatments is a challenge that depends on the place of residence. However, recent advances in medical technology have improved health outcomes. Nevertheless, the geographic heterogeneity of medical resources may increase regional disparities. Therefore, evaluating spatial and temporal influences of the medical system on regional outcomes and advanced treatment of cerebral infarction are important from a health policy perspective. This spatial and temporal study aims to identify factors associated with mortality and to clarify regional disparities in cerebral infarction mortality at municipality level., Methods: This ecological study used public data between 2010 and 2020 from municipalities in Hokkaido, Japan. We applied spatial and temporal condition autoregression analysis in a Bayesian setting, with inference based on the Markov chain Monte Carlo simulation. The response variable was the number of deaths due to cerebral infarction (ICD-10 code: I63). The explanatory variables were healthcare accessibility and socioeconomic status., Results: The large number of emergency hospitals per 10,000 people (relative risk (RR) = 0.906, credible interval (Cr) = 0.861 to 0.954) was associated with low mortality. On the other hand, the large number of general hospitals per 10,000 people (RR = 1.123, Cr = 1.068 to 1.178) and longer distance to primary stroke centers (RR = 1.064, Cr = 1.014 to 1.110) were associated with high mortality. The standardized mortality ratio decreased from 2010 to 2020 in Hokkaido by approximately 44%. Regional disparity in mortality remained at the same level from 2010 to 2015, after which it narrowed by approximately 5% to 2020. After mapping, we identified municipalities with high mortality rates that emerged in Hokkaido's central and northeastern parts., Conclusion: Cerebral infarction mortality rates and the disparity in Hokkaido improved during the study period (2010-2020). This study emphasized that healthcare accessibility through places such as emergency hospitals and primary stroke centers was important in determining cerebral infarction mortality at the municipality level. In addition, this study identified municipalities with high mortality rates that require healthcare policy changes. The impact of socioeconomic factors on stroke is a global challenge, and improving access to healthcare may reduce disparities in outcomes., (© 2022. The Author(s).)

Objectives: This study aimed to evaluate a stroke medical delivery system based on population coverage and the potential crowdedness index (PCI) of mechanical thrombectomy and investigate the relationship between PCI and cerebral infarction mortality in Japan., Materials and Methods: This cross-sectional study defined 662 facilities and 1605 neurointerventionalists as supply, population aged 55 years or older as demand, and set the reachable area for demand as 120 min in driving time. Multiple regression analysis adjusted for spatial autocorrelation was used to examine the relationship between PCI and cerebral infarction mortality., Results: In the 2020 data, 99% of the population aged 55 years or older had access to mechanical thrombectomy (≤120 min), and the PCI ranged from 5876 to 129838, with a median of 30426. From 2020 to 2035, the PCI is estimated to increase (30426 to 32510), decreasing after 2035 (32510 to 29469). The PCI distribution exhibited geographical heterogeneity. High PCI values emerged in eastern Japan. According to regression analysis, the increase in PCI by 1% led to an increase of 0.13% in standardized mortality ratio of cerebral infarction in men. However, PCI did not significantly correlate with cerebral infarction mortality in women., Conclusions: PCI for hospitals based on supply and demand was geographically heterogeneous in Japan. Optimization of PCI contributes equalization of mechanical thrombectomy provision system and may improve cerebral infarction mortality., Competing Interests: Declaration of Competing Interest The authors of this manuscript declare no competing interests in association with this study., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The 4th Asia Partnership Conference of Regenerative Medicine (APACRM) was held online on April 15, 2021, to promote regulatory harmonization of regenerative medicine products throughout Asia. Recognizing domestic regulatory guidelines within each country and region, and their underpinning rationales, is an important initial step toward a convergence of regulations. The 4th APACRM consisted of an open dialog with regulatory agencies regarding nonclinical and quality settings for cell therapy products (CTPs) through industry presentations and panel discussions with regulatory agencies. The latest updates on regenerative medicine fields in each country and region, and specific regulatory schematics in Japan, were also introduced. The objective of this paper is to summarize the proceedings of the 4th APACRM for public dissemination and to foster further discussion in the future., (Copyright © 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

The increasing demand for long-term care (LTC) among the ageing population is a serious problem worldwide, which has greatly increased also in Japan since the introduction of the LTC insurance system there. Since there is a difference between insurers with respect to the proportion of people needing LTC, this study aimed at clarifying the spatial patterns of LTC. Insurer (n=156) LTC data for the period 2012-2019 were obtained from Ministry of Health, Labour, and Welfare and those needing LTC were classified into three classes: total, mild and severe with ageand sex-adjusted proportions needing LTC. Global and local Moran’s I statistics were calculated for each 2-year period to clarify the trends of global and local spatial clusters. From 2012 to 2019, the mean proportion of mild class cases increased (10.6% to 11.6%), whereas that of severe class cases decreased slightly (5.9% to 5.7%). The spatial pattern of the proportion of each class revealed positive spatial autocorrelation. Based on analysis by local Moran’s I, differences in spatial patterns were emphasised between the mild and severe classes. In Hokkaido, High-High clusters of mild cases were identified in the central and southern parts and severe ones in the northern and southern parts. Spatial patterns differed depending on the LTC class. Some insurers had distinctly higher or lower certification rates than those of their neighbourhoods.

Background Aims: Cell-based regenerative medicine is an innovative field that can potentially alter the overall survival and quality of life of patients with devastating diseases. Several cell therapy products (CTPs) have been approved within the last two decades, and more are under development. The establishment of an effective developmental strategy in accordance with the regulatory bodies of each country/region is crucial for fast delivery of each respective CTP. In particular, facilitating investigational new drug (IND) approval is important for accelerating the transition from non-clinical to clinical research/trial phases., Methods: Here the authors compared the non-clinical prerequisites for initiating clinical studies in five Asian countries/regions (India, China, Korea, Taiwan and Japan) from an industry viewpoint. The authors first identified the differences and tried to clarify the perspectives/considerations underpinning the different requirements., Results: The authors' findings revealed that differences in regulations and development experiences, especially with CTPs, have led to clear differences in the non-clinical study package and its corresponding study design., Conclusions: By sharing experiences of the research and development of CTPs among Asian countries/regions and including not only industry but also regulatory authorities, we will be able to expedite cross-border IND approval and eventually contribute to the early delivery of innovative CTPs to many Asian patients., (Copyright © 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the relationship between body mass index (BMI) and early outcomes, and specific types of morbidities associated with low and high BMI, in patients undergoing coronary artery bypass grafting., Methods: This was a retrospective study on isolated coronary artery bypass grafting patients (aged ≥60 years) between 2008 and 2017 in the Japan Cardiovascular Surgery Database. The primary end point was defined as operative mortality. The secondary end point was combined morbidity (ie, operative mortality, reoperation for bleeding, stroke, new onset of hemodialysis, mediastinitis, and prolonged ventilation). Patient characteristics and outcomes were compared among BMI groups. Spline curves were fit between BMI and outcomes. Multivariable logistic regression models with categorized BMI and generalized additive models with spline-transformed BMI were used to estimate and visualize the effect of BMI adjusted for other covariates., Results: A total of 96,058 patients were included in the analysis. Low (<18.5) and high (≥30) BMI were both associated with a higher risk of mortality (low: adjusted odds ratio, 1.34; 95% confidence interval, 1.16-1.54; P < .0001, and high: adjusted odds ratio, 2.10; 95% confidence interval, 1.70-2.59; P < .0001) and combined morbidity (low: adjusted odds ratio, 1.18; 95% confidence interval, 1.08-1.29; P = .0002 and high: adjusted odds ratio, 1.82; 95% confidence interval, 1.63-2.03; P < .0001). Low and high BMI were associated with different types of morbidities. In models using spline transformation, the deviation of BMI from a proximately 21 to 23 was proportionally associated with increased risk., Conclusions: In patients undergoing coronary artery bypass grafting, low and high BMI were risk factors of mortality associated with different types of morbidities, which may warrant tailored preventive approaches., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: There is limited information about the clinical profiles of patients with hypertrophic cardiomyopathy (HCM) and thromboembolic events in a community-based Japanese patient cohort., Methods and results: In 2004, we established a cardiomyopathy registration network in Kochi Prefecture that comprised 9 hospitals, and finally 293 patients with HCM were followed. The mean age at registration was 63±14 years, and 197 patients (67%) were men. At registration, 86 patients (29%) had documented atrial fibrillation (AF). During a mean follow-up period of 6.1±3.2 years, thromboembolic events, including 3 embolic stroke deaths, occurred in 23 patients. The 5-year embolic event rate was 5.5%. During the follow-up period, an additional 31 patients (11%) had documentation of AF and finally a total of 117 patients (40%) developed AF. The 5-year embolic event rate in those 117 patients with AF was 12.3%. Of the 23 patients with embolic events, 12 had AF prior to the embolic complications and another 6 had documented AF after thromboembolism. AF was not detected in the remaining 5 patients. The CHADS 2 score did not correlate with the embolic outcome in HCM patients., Conclusions: In this community-based registry, thromboembolic events were not rare in patients with HCM. All patients with HCM in whom AF develops should be given anticoagulation therapy regardless of their CHADS 2 score.

Background: There have been few studies on the clinical course of hypertrophic cardiomyopathy (HCM) in a community-based patient cohort in Japan.Methods and Results:In 2004, we established a cardiomyopathy registration network in Kochi Prefecture (the Kochi RYOMA study) that consisted of 9 hospitals, and finally, 293 patients with HCM were followed. The ages at registration and at diagnosis were 63±14 and 56±16 years, respectively, and 197 patients (67%) were male. HCM-related deaths occurred in 23 patients during a mean follow-up period of 6.1±3.2 years. The HCM-related 5-year survival rate was 94%. In addition, a total of 77 cardiovascular events that were clinically severe occurred in 70 patients, and the HCM-related 5-year event-free rate was 80%. Multivariate Cox proportional hazards model analysis showed that the presence of NYHA class III at registration was a significant predictor of HCM-related deaths and that the presence of atrial fibrillation, lower fractional shortening and presence of left ventricular outflow tract obstruction in addition to NYHA class III were significant predictors of cardiovascular events., Conclusions: In our unselected registry in an aged Japanese community, HCM mortality was favorable, but one-fifth of the patients commonly suffered from HCM-related adverse cardiovascular events during the 5-year follow-up period. Careful management of HCM patients is needed, particularly for those with the above-mentioned clinical determinants.

Background and Purpose: There have been no large-scale studies on the impact of diabetes mellitus (DM) on outcomes in Japanese patients undergoing coronary artery bypass grafting (CABG)., Methods and Subjects: A multi-institutional retrospective cohort study was conducted in 14 Japanese centers. All adult patients who underwent isolated CABG from 2007 to 2008 were included (n=1522, mean age: 68.5years). The definitions of DM were all patients admitted with diagnosis of DM and preoperative glycated hemoglobin (Hb) A1c≥6.5%. Univariate and multivariate analyses were performed to identify the risk of morbidity and mortality., Results: There were 849 DM and 572 non-DM patients. Preoperative mean HbA1c were 7.1% in the DM group and 5.7% in the non-DM group (p<0.0001). Preoperative, intraoperative, and 3-day average postoperative blood glucose (BG) were 146mg/dl, 172mg/dl, and 168mg/dl in the DM group, and 103mg/dl, 140mg/dl, and 136mg/dl in the non-DM group (all p<0.0001). Although there were no significant differences in postoperative cardiovascular events, the incidence of infection was significantly higher in the DM group than in the non-DM group (9.2% vs 6.1%, p=0.036) on the univariate analysis. The all-cause death was also relatively higher in the DM group than in the non-DM group (2.1% vs 1.1%, p=0.12), and this was likely related to infection., Conclusion: DM patients had worse perioperative BG control, higher incidence of infection, and higher mortality than non-DM patients. These results indicate that perioperative BG control guidelines should be standardized to obtain better surgical outcomes in Japanese DM patients., (Copyright © 2012. Published by Elsevier Ltd.)

Aim: The aim was to determine whether the use of statins prevents the progression of chronic kidney disease (CKD) in hypertensive patients., Methods: We retrospectively reviewed data obtained from hypertensive patients, and subjects with diabetes mellitus and those undergoing hemodialysis were excluded. At total of 227 patients were enrolled (83 men, mean age 73 years) and 90% of the patients were of CKD stage 2 or 3. The patients were divided into two groups: those treated with statins (n = 93) and those not treated with statins (n = 134). Renal function was evaluated by estimated glomerular filtration rate (eGFR)., Results: The statin group and the non-statin group were similar in age, sex, blood pressure, follow-up period and prescriptions of antihypertensive medicines. The eGFR in the statin group increased from 62 +/- 14 to 66 +/- 15 (mL/min per 1.73 m(2)), whereas it decreased in the non-statin group from 69 +/- 16 to 64 +/- 18 (mL/min per 1.73 m(2)). The annual eGFR improved in the statin group (2.5 +/- 6.6 mL/min per 1.73 m(2)/year), but decreased in the non-statin group (-3.3 +/- 6.6 mL/min per 1.73 m(2)/year) (P < 0.001). When the patients were divided into two groups by low-density lipoprotein (LDL) cholesterol levels at the second evaluation, annual eGFR improved in the group of LDL to below 100 mg/dL (n = 99) (0.4 +/- 7.2 mL/min per 1.73 m(2)/year), but decreased in the other group (n = 128) (-1.9 +/- 7.0 mL/min per 1.73 m(2)/year) (P = 0.018)., Conclusion: Lipid-lowering intervention with statins inhibits the progression of CKD in hypertensive patients.

Purpose: To examine the walking ability and survival outcome of patients aged 90 years and older who sustained proximal femoral fractures, and to compare the findings with those of younger patients reported in previous studies., Methods: Between January 1997 and June 2004 inclusive, 56 patients (11 men and 45 women) aged 90 years and older (range, 90-103 years; mean, 93 years) with hip fracture were reviewed. Their walking ability and survival outcome at discharge was investigated. Comparison was made between patients aged 60 to 89 years and those aged 90 years and older with respect to sex, fracture type, and other characteristics., Results: Of 56 patients, 26 injured the right side and 30 the left side. Before injury, 33 (59%) were living at home and 23 (41%) were institutionalised in long-term care facilities or other hospitals. Fracture occurred at the femoral neck in 14 patients and at the trochanter in 42. Ten patients were treated conservatively because of severe dementia, co-morbidity, or refusal of surgery by the patients or their families, whereas 46 underwent surgery. Of the 45 who were previously ambulatory, 22 regained walking ability on discharge from hospital. None of the 10 patients treated conservatively were ambulatory on discharge. During hospitalisation, 4 became bedridden and 5 died (mainly due to pneumonia); among these 9 patients, 5 were deemed physically unfit for surgery., Conclusion: Surgery is the treatment of choice for patients aged 90 years and older with proximal femoral fracture. However, they have a lower rate of regaining pre-injury walking ability and a higher in-hospital death rate than younger patients.

Objective: We evaluated risk factors for mortality and stroke after mechanical mitral valve replacement between May 1977 and December 2001., Methods: Early and late mortality and stroke were assessed. Potential predictors of mortality and stroke were entered into a Cox proportional hazards model. Actuarial survival and freedom from stroke were determined by a log-rank test., Results: Mitral valve replacement was performed in 812 patients. Concomitant procedures included left atrial appendage closure in 493 (61%) patients, tricuspid annuloplasty-replacement in 348 (43%) patients, maze procedure in 185 (23%) patients, plication of the left atrium in 148 (18%) patients, and other procedures in 151 (19%) patients. Five-year actuarial survival was 91.1% +/- 2.3%. Freedom from stroke at 8 years was significantly better in patients with sinus rhythm versus atrial fibrillation (P <.001). Ninety-nine percent of patients with mitral valve replacement combined with a maze procedure were free from stroke, whereas only 89% of patients with mitral valve replacement alone were free from stroke at 8 years after surgical intervention. Seventy-two patients had late stroke; sixty-five patients (90%) were in atrial fibrillation, and 47 (65%) patients had the left atrial appendage closed. Multivariate analysis showed that late atrial fibrillation (odds ratio, 3.39; 95% confidence interval, 1.72-6.67; P =.0001) and omission of the maze procedure (odds ratio, 3.40; 95% confidence interval, 1.14-10.14; P =.003) were the significant risk factors for late stroke., Conclusions: Persistent atrial fibrillation was the most significant risk factor for late stroke after mechanical mitral valve replacement. Restoration of sinus rhythm with a maze procedure nearly eliminated the risk of late stroke, whereas neither closure of the left atrial appendage nor therapeutic anticoagulation prevented this complication.

Objective: We sought to determine whether the Cox maze procedure provides additional benefit to patients with atrial fibrillation undergoing mitral valve operations., Methods: Between May 1992 and August 2000, we performed 258 Cox maze procedures with mitral valve replacement (n = 147) or mitral valve repair (n = 111). We compared the outcomes of these patients with those of 61 control patients with preoperative atrial fibrillation who underwent mitral valve replacement alone during the same interval. The three cohorts were similar in age, sex, and proportion of patients in preoperative New York Heart Association functional class 3 or 4., Results: Although 5-year survivals were similar among the groups (94% for mitral valve replacement alone, 95% for mitral valve replacement plus maze, and 97% for mitral valve repair plus maze), freedoms from atrial fibrillation at 5 years were significantly higher in the mitral valve replacement plus maze group (78%) and the mitral valve repair plus maze group (81%) than in the mitral valve replacement group (6%, P <.0001). Freedoms from stroke at 5 years were 97% for the mitral valve replacement plus maze group, 97% for the mitral valve repair plus maze group, and only 79% for mitral valve replacement group (P <.0001). Multivariable analysis with Cox hazard model revealed that the most significant risk factor for late stroke was the omission of the Cox maze procedure (P =.003)., Conclusions: The addition of the Cox maze procedure to mitral valve repair and replacement was safe and effective for selected patients. Elimination of atrial fibrillation significantly decreased the incidence of late stroke.

Objectives: We sought to assess the impact of diabetic retinopathy on long-term outcome among patients with diabetes and multivessel coronary artery disease (MVD) following coronary artery bypass graft surgery (CABG)., Background: For diabetics, CABG is the preferred revascularization strategy. Diabetic retinopathy is a major microvascular complication of diabetes, and its severity is directly related to total glycemic exposure., Methods: We identified 223 consecutive diabetics with MVD whose retinae were evaluated within one year prior to CABG. The most recent ophthalmologic records up until the time of CABG were used to evaluate the severity of retinopathy. The median follow-up after CABG was 11.6 years., Results: Diabetic retinopathy was a strong independent predictor of overall mortality (relative risk [RR], 4.0), and repeat revascularization (RR, 3.0). In separate analyses of diabetics with retinopathy and without retinopathy, predictors of mortality differed significantly between the two groups. Among diabetics with retinopathy, the presence of either preoperative renal (RR, 2.5) or ventricular (RR, 2.0) dysfunction had unfavorable effects on mortality, but the survival curves did not differ significantly according to the presence or absence of internal thoracic artery (ITA) grafting. In comparison, among diabetics without retinopathy, ITA grafting (RR, 0.34) had a beneficial effect on mortality, and the survival curves varied somewhat according to the presence or absence of renal or ventricular dysfunction., Conclusions: Diabetics with retinopathy had a distinct post-CABG course with a worse long-term prognosis, as compared with diabetics without retinopathy. Retina evaluation is useful for prediction of long-term prognosis and management of diabetics who need CABG.

Major advances have been achieved in surgery during the past century and further dynamic changes are expected along with progress in immunology, tissue and mechanical engineering, etc. in the 21st century. However, fewer medical students will choose the surgical field as their specialty, primarily due to the long training period, and inadequate income as compared to the heavy workload. To recruit the best and the brightest students in surgery, early exposure to the positive aspects of the surgical field is desirable. The training system should be further refined, and a sufficient number of positions with appropriate remuneration must be mode available.

During the past 2 years since new legislation for organ transplantation from brain-dead donors came into effect in Japan, 3 cardiac transplants have been carried out, 2 of which were performed at the National Cardiovascular Center (NCVC). The recipient cases were 46- and 25-year-old male patients who suffered from end-stage dilated cardiomyopathy and had been listed for cardiac transplantation in the Japan Organ Transplantation Network as status I candidates. The first patient was supported by the use of a paracorporeal air-driven left ventricular assist device of the NCVC type, and had a moderate degree of renal and hepatic dysfunction at the time of transplantation. Donor hearts were transported from distant hospitals (Tokyo and Miyagi prefecture) and the transportation time was 1 h 33 min and 2h 4 min, respectively. The operation was performed by the standard technique (Lower-Shumway) in the first patient and by the bicaval anastomosis technique in the second patient. Reperfusion of the transplanted heart was performed retrogradely through the coronary sinus utilizing leukocyte-depleted blood with a gradual increase in temperature. Total ischemic time was 3 h 34 min and 3 h 35 min, respectively. Weaning from the cardiopulmonary bypass was easy and uneventful in each patient. Immunosuppressive therapy was conducted with OKT-3 induction in the first patient because of the coexisting renal dysfunction and with a triple immunosuppressive regimen for both patients. Routine endomyocardial biopsy showed acute rejection of less than grade Ib, and the patients were discharged on the 65th and 46th postoperative day, respectively. At present, both patients are in the NYHA class I state and are ready to return to work. The uneventful recovery seen in these patients shows the advances made in transplant medicine, including the progress and improvement of immunosuppressive therapy, surgical techniques, myocardial protection, and detection and treatment of infection. Further efforts are required to fully establish the cardiac transplantation program in Japan.

Eight patients, 4 males and 4 females ranging in age from 10 to 54 years (mean 27 +/- 13 years) underwent the Ross operation using a cryopreserved pulmonary homograft harvested by and cryopreserved in our institutional "Tissue Bank". Seven patients had a congenital bicuspid aortic valve and 3 patients had had healed infective endocarditis of the aortic valve. Four young female patients wanted to have a baby after operation. The Ross procedure was carried out utilizing aortic root replacement techniques in all patients. All patients survived and are currently in NYHA class 1, but 2 cardiac events occurred in 2 patients during the mean follow-up term of 29 +/- 19 months. The one was the anastomic stenosis between the homograft and distal pulmonary artery treated by balloon dilatation and the other was ventricular tachycardia eventually managed by the insertion of an ICD. Pulmonary autograft valve regurgitation is present in 3 patients, but it is not progressive up to the present time. Pulmonary homograft valves function well in all patients. The Ross operation for adolescents and young adults should become more popular along with more easy availability of homograft valves based upon the establishment of the "Homograft Valve Bank" system in Japan.

Although disturbances of the fibrinolytic system and serum lipid, and the presence of inflammation, may be risk factors for coronary artery disease (CAD), few reports have investigated these relationships in Japanese patients. Data on 106 patients (79 men and 27 women, mean age 62.3 years) with atherosclerotic lesions on the coronary angiogram were evaluated prospectively to identify whether the factors were useful in predicting the risk of coronary events during a follow-up of 50+/-4 months. Of the 106 patients who were followed, 11 patients had coronary events (4 acute myocardial infarction and 7 unstable angina pectoris). In univariate Cox analyses, a high level of tissue-plasminogen activator (t-PA), apolipoprotein CII, C-reactive protein (CRP), and a low level of high-density lipoprotein-cholesterol (HDL-C) was each associated with a significant increase in the risk of future cardiac events. The stepwise model of Cox proportional hazards analysis selected only a high level of t-PA and CRP as predictors of cardiac events. Controlling for any risk factor did not lower the relation between t-PA and the risk of cardiac events, whereas the relative risk of cardiac events in CRP was not significant when controlled for HDL-C. Thus, in prospective data obtained from a cohort of Japanese patients with coronary atherosclerotic lesions, the elevation of t-PA was an independent predictor of subsequent cardiac events. The prognostic role of CRP in cardiac events was related to a low level of HDL-C.

The in vitro activity of DU-6859a, a new fluoroquinolone, was compared with those of other fluoroquinolones against clinical isolates of anaerobic bacteria and Gardnerella vaginalis. DU-6859a was the most active agent; it inhibited 90% of isolates of almost all species tested, including Bacteroides fragilis at < or = 0.39 micrograms/mL. Although the other quinolones tested were active against gram-positive anaerobes, inhibiting their growth at < or = 1.56 micrograms/mL, these agents were less active against the B. fragilis group and Prevotella bivia (90% of which were inhibited at > or = 6.25 micrograms/mL). Mobiluncus species and G. vaginalis, which are well associated with bacterial vaginosis, were inhibited by DU-6859a at 0.1 microgram/mL. These results suggest that DU-6859a is a promising oral agent for the treatment of bacterial infections due to anaerobic bacteria; however, further studies, including determination of vaginal levels of this compound, should be performed to study the role of DU-6859a in the treatment of bacterial vaginosis.