Congratulations! Transactions of JSMBE No. 300 KUSUOKA, Hideo
Transactions of Japanese Society for Medical and Biological Engineering,
09/2019, Letnik:
57, Številka:
4-5
Journal Article
Objectives The goal of this study was to conduct a direct head-to-head comparison of different stem cell types in vitro for various assays of potency and in vivo for functional myocardial repair in ...the same mouse model of myocardial infarction. Background Adult stem cells of diverse origins (e.g., bone marrow, fat, heart) and antigenic identity have been studied for repair of the damaged heart, but the relative utility of the various cell types remains unclear. Methods Human cardiosphere-derived cells (CDCs), bone marrow–derived mesenchymal stem cells, adipose tissue–derived mesenchymal stem cells, and bone marrow mononuclear cells were compared. Results CDCs revealed a distinctive phenotype with uniform expression of CD105, partial expression of c-kit and CD90, and negligible expression of hematopoietic markers. In vitro, CDCs showed the greatest myogenic differentiation potency, highest angiogenic potential, and relatively high production of various angiogenic and antiapoptotic-secreted factors. In vivo, injection of CDCs into the infarcted mouse hearts resulted in superior improvement of cardiac function, the highest cell engraftment and myogenic differentiation rates, and the least-abnormal heart morphology 3 weeks after treatment. CDC-treated hearts also exhibited the lowest number of apoptotic cells. The c-kit+ subpopulation purified from CDCs produced lower levels of paracrine factors and inferior functional benefit when compared with unsorted CDCs. To validate the comparison of cells from various human donors, selected results were confirmed in cells of different types derived from individual rats. Conclusions CDCs exhibited a balanced profile of paracrine factor production and, among various comparator cell types/subpopulations, provided the greatest functional benefit in experimental myocardial infarction.
Summary Background The antiplatelet drug cilostazol is efficacious for prevention of stroke recurrence compared with placebo. We designed the second Cilostazol Stroke Prevention Study (CSPS 2) to ...establish non-inferiority of cilostazol versus aspirin for prevention of stroke, and to compare the efficacy and safety of cilostazol and aspirin in patients with non-cardioembolic ischaemic stroke. Methods Patients aged 20–79 years who had had a cerebral infarction within the previous 26 weeks were enrolled at 278 sites in Japan and allocated to receive 100 mg cilostazol twice daily or 81 mg aspirin once daily for 1–5 years. Patients were allocated according to a computer-generated randomisation sequence by means of a dynamic balancing method using patient information obtained at registration. All patients, study personnel, investigators, and the sponsor were masked to treatment allocation. The primary endpoint was the first occurrence of stroke (cerebral infarction, cerebral haemorrhage, or subarachnoid haemorrhage). The predefined margin of non-inferiority was an upper 95% CI limit for the hazard ratio of 1·33. Analyses were by full-analysis set. This trial is registered with ClinicalTrials.gov , number NCT00234065. Findings Between December, 2003, and October, 2006, 2757 patients were enrolled and randomly allocated to receive cilostazol (n=1379) or aspirin (n=1378), of whom 1337 on cilostazol and 1335 on aspirin were included in analyses; mean follow-up was 29 months (SD 16). The primary endpoint occurred at yearly rates of 2·76% (n=82) in the cilostazol group and 3·71% (n=119) in the aspirin group (hazard ratio 0·743, 95% CI 0·564–0·981; p=0·0357). Haemorrhagic events (cerebral haemorrhage, subarachnoid haemorrhage, or haemorrhage requiring hospital admission) occurred in fewer patients on cilostazol (0·77%, n=23) than on aspirin (1·78%, n=57; 0·458, 0·296–0·711; p=0·0004), but headache, diarrhoea, palpitation, dizziness, and tachycardia were more frequent in the cilostazol group than in the aspirin group. Interpretation Cilostazol seems to be non-inferior, and might be superior, to aspirin for prevention of stroke after an ischaemic stroke, and was associated with fewer haemorrhagic events. Therefore, cilostazol could be used for prevention of stroke in patients with non-cardioembolic stroke. Funding Otsuka Pharmaceutical.
Background:Acute decompensated heart failure (ADHF) is generally considered to be a problem of fluid volume overload, therefore accurately quantifying the degree of fluid accumulation is of critical ...importance in assessing whether adequate decongestion has been achieved. The aim of this study was to develop and validate a method to quantify the degree of fluid accumulation in patients with ADHF.Methods and Results:Using multi-frequency bioelectrical impedance analysis (BIA), we measured extracellular water (ECW) volume in 130 ADHF patients on admission and at discharge. We also predicted optimal ECW volume using original equations based on data from 60 control subjects without the signs of HF. Measured/predicted (M/P) ratio of ECW in ADHF patients was observed to decrease from 1.26±0.25 to 1.04±0.17 during hospitalization (P<0.001). The amount of ECW volume reduction was significantly correlated with reduction in body weight (r=0.766, P<0.001). On multivariate analysis, higher M/P ratio of ECW at discharge was associated with increased risk of ADHF readmission or cardiac death within 6 months after discharge.Conclusions:Multi-frequency BIA-measured ECW was found to offer valuable information for analyzing the pathophysiology of ADHF, and may be a useful guide in the management of this disease. (Circ J 2015; 79: 2616–2622)
Background: Cardiac event risk is estimated using quantitative gated myocardial perfusion imaging (MPI) and clinical background in patients with ischemic heart disease. The aim of the present study ...was to calculate major cardiac event risk and tabulate it in the Heart Risk Table for clinical use of risk stratification. Methods and Results: Multivariate logistic regression was performed based on a multicenter prognostic database (Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated Single-photon emission computed tomography J-ACCESS investigation) using MPI (n=2,395). The risk of major cardiac events (cardiac death, non-fatal myocardial infarction and heart failure requiring hospitalization) was estimated using age, ejection fraction (EF), estimated glomerular filtration rate (eGFR) and presence of diabetes mellitus (DM). Age-matched standard eGFR was determined in 77 subjects. Major cardiac event risk was calculated using the equation: risk (%/3 years)=1/(1+Exp(-(-4.699-0.0151×eGFR+0.7998×DM+0.0582×age+0.697×SSS-0.0359×EF))×100, where SSS refers to summed stress scores. Risk was determined without eGFR (the initial version) and using the present formula with eGFR (revised version), with consistent results. DM and chronic kidney disease were major determinants of cardiac events. Conclusions: Cardiac event risk was estimated using MPI defect score and left ventricular EF in conjunction with eGFR and the presence of DM. The risk table might be used for risk evaluation in Japanese patients undergoing MPI. (Circ J 2012; 76: 168-175)
Quantitative gated single-photon emission computed tomography (SPECT) is known to have high accuracy and precision for measurement of the principal cardiac functional parameters. We hypothesised that ...normal values for EF and LV volumes may differ among nationalities, and that optimal threshold values specific to the study population are required.
Among 4,670 consecutively registered patients for a J-ACCESS (Japanese investigation regarding prognosis based on gated SPECT) study from 117 hospitals, a total of 268 (149 women, 119 men) were selected who had no baseline cardiac diseases and had experienced no cardiac events during the preceding 3-year period. A gated SPECT study was performed with 99mTc-tetrofosmin and analysed with Cedars Sinai Medical Center's quantitative gated SPECT (QGS) software. The results in respect of ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV), and EDV, ESV and SV normalised by body surface area (EDVI, ESVI and SVI), were calculated and summarised to obtain normal limits.
EF for women and men was 74 +/- 9% and 63 +/- 7%, respectively (p < 0.0001). EDV, ESV and SV were significantly smaller in women than in men. Based on multiple regressions for linear models, the primary and secondary predictors of EF, EDVI, ESVI were gender and age. By stepwise multiple regression analysis, a statistically significant third predictor for EDV, ESV, SV and SVI was body weight. No colinearity was found between age and body weight. Important factors for the studied Japanese population included a high incidence of small hearts in women and the relatively advanced age of the population (the mean age +/-SD was 64.1 +/- 10.0 years for women and 60.9 +/- 11.7 years for men).
EF and volumes determined by gated SPECT with QGS were significantly affected by gender and age, with body weight as a third predictor for volumes. Moreover, the normal limits were so specific for the population studied that standards appropriate for the study in question should be utilised.
International norms and ethical standards have suggested that compensation for research-related injury should be provided to injured research volunteers. However, statistical data of incidence of ...compensation claims and the rate of awarding them have been rarely reported.
Questionnaire surveys were sent to pharmaceutical companies and medical institutions, focusing on industry-initiated clinical trials aiming at new drug applications (NDAs) on patient volunteers in Japan.
With the answers from pharmaceutical companies, the incidence of compensation was 0.8%, including 0.06% of monetary compensation. Of the cases of compensation claims, 99% were awarded. In turn, with the answers from medical institutions, the incidence of compensation was 0.6%, including 0.4% of serious but not death cases, and 0.04% of death cases. Furthermore, most claims for compensation were initiated by medical institutions, rather than by the patients. On the other hand, with the answers from clinical trial volunteers, 3% of respondents received compensations. These compensated cases were 25% of the injuries which cannot be ruled out from the scope of compensation.
Our study results demonstrated that Japanese pharmaceutical companies have provided a high rate of compensation for clinical trial-related injuries despite the possibility of overestimation. In the era of global clinical development, our study indicates the importance of further surveys to find each country's compensation policy by determining how it is being implemented based on a survey of the actual status of compensation coming from statistical data.
Purpose
Diabetic patients have a high risk for cardiovascular events. The role of myocardial perfusion imaging was investigated in asymptomatic diabetic patients to evaluate short-term prognosis in a ...Japanese population.
Methods
A total of 506 asymptomatic patients ≥50 years of age who had carotid artery maximum intima-media thickness ≥1.1 mm, urinary albumin excretion of ≥30 mg/g creatinine, with additional criteria of abdominal obesity, low HDL cholesterol, high triglyceride level, and hypertension were enrolled and followed up over a 3-year period. Gated SPECT with stress-rest protocol was performed and analyzed by summed defect scores and QGS software. One-year cardiovascular events were analyzed.
Results
Myocardial ischemia was observed in 17% of patients, and abnormal perfusion findings of ischemia and/or scar were observed in 32% of patients. By the end of the 1-year follow-up, 33 (6.5%) cardiovascular events occurred including 6 all-cause deaths. Patients with summed stress score (SSS) >8 had a higher incidence of either death or cardiovascular events. Event-free survival rates for SSS 0–3, 4–8, 9–13, and ≥14 were 0.96, 0.95, 0.82, and 0.76, respectively. Multivariate Cox regression analysis showed that significant variables were SSS, history of cerebrovascular accident, and electrocardiographic abnormality at rest.
Conclusion
The 1-year interim summary showed that cardiovascular events were significantly higher in patients with SPECT abnormality, although hard cardiac event rate was relatively low. Targeted treatment strategy is required for asymptomatic but potentially high-risk diabetic patients.
Abstract Background Predicting fluid volume that needs to be removed in acute heart failure syndromes (AHFS) patients remains challenging. Thoracic admittance (TA), the reciprocal of thoracic ...impedance measured by bioelectrical impedance, reflects the amount of fluid in the thorax. Abdominal organs play an important role in AHFS as systemic fluid reservoirs. We investigated the relationship between abdominal admittance (AA) at the time of admission for AHFS and net fluid loss (NFL) during hospitalization. Methods Sixty-two consecutive patients hospitalized for AHFS age 71 ± 10 years, left ventricular ejection fraction (LVEF) 39 ± 17% were studied. The admittance values, i.e. the reciprocals of the impedance values, were derived using a BioZ® (CardioDynamics, San Diego, CA, USA). The change in weight from admission to discharge was used as a surrogate of amount of NFL. Results At the time of admission, a significant correlation was detected between TA and AA ( r = 0.46, p = 0.0001). TA at admission was significantly correlated with the LV structural variables (end-diastolic dimension and end-systolic dimension), and serum sodium level. AA at admission was significantly correlated with New York Heart Association (NYHA) class and plasma BNP, and also correlated with LVEF and variables related to systemic congestion minimal inferior vena cava (IVC) diameter and tricuspid regurgitation grade. Neither TA nor AA values were significantly correlated with weight at admission. During hospitalization, TA and AA declined from 44 ± 8 kΩ−1 to 36 ± 6 kΩ−1 ( p < 0.0001) and from 74 ± 25 kΩ−1 to 56 ± 17 kΩ−1 ( p < 0.0001), respectively. Weight fell from 60.1 ± 10.8 kg to 54.5 ± 9.4 kg ( p < 0.0001), while NFL was 5.8 kg (range, 0.1–17.5 kg). In univariate analyses, the admission NYHA class, TA, AA, weight, and IVC diameter correlated with NFL. Multivariate analysis demonstrated that only admission weight standardized partial regression coefficient (SPRC) = 0.596, AA (SPRC = 0.529), and NYHA class (SPRC = 0.277) were independent predictors of NFL. Conclusion Abdominal admittance measurement helps to predict the amount of fluid volume to be removed in patients with AHFS.