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Find video protocols related to scientific articles indexed in Pubmed.
Use of Proton Pump Inhibitors Is Associated With Anemia in Cardiovascular Outpatients.
Circ. J.
PUBLISHED: 11-14-2014
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Background:Proton pump inhibitors (PPI) are frequently prescribed in combination with aspirin for preventing peptic ulcer in patients with atherosclerotic diseases. In contrast, long-term use of PPI has been suggested to be associated with iron or vitamin B12deficiency. The effect of PPI on hemoglobin (Hb) concentration, however, has not been clarified in cardiovascular outpatients.Methods?and?Results:We retrospectively investigated the clinical characteristics of 278 continuous outpatients who received blood test including complete blood count and serum creatinine concentration (mean age, 69.9±10.8 years; male, 68.7%). The frequency of anemia was 51% in patients receiving PPI and 19% in those not receiving PPI (chi-squared test, P<0.001). On multivariate analysis female sex (P<0.001), peripheral artery disease (P=0.003), PPI (P=0.003), low white blood cell count (P=0.004), old age (P=0.007), and low estimated glomerular filtration rate (P=0.010) were independently associated with low Hb. Among these patients, we investigated the change in Hb after the initiation of PPI in 36 patients for whom data on Hb level within 1 year before and within 1 year after the initiation of PPI were available. Mean decrease in Hb after the initiation of PPI was 0.38±0.87 g/dl (95% confidence interval: -0.67 to -0.09 g/dl).Conclusions:Use of PPI was associated with anemia in Japanese cardiovascular outpatients.
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MicroRNA-451 Exacerbates Lipotoxicity in Cardiac Myocytes and High-Fat Diet-Induced Cardiac Hypertrophy in Mice through Suppression of the LKB1/AMPK Pathway.
Circ. Res.
PUBLISHED: 11-02-2014
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Rationale: In some type 2 diabetes patients without hypertension, cardiac hypertrophy and attenuated cardiac function are observed, and this insult is termed "diabetic cardiomyopathy." To date, microRNA functions in diabetic cardiomyopathy remain to be elucidated. Objective: To clarify the functions of microRNAs involved in diabetic cardiomyopathy caused by type 2 diabetes. Methods and Results: C57BL/6 mice were fed a high-fat diet (HFD) for 20 weeks, which induced obesity and type 2 diabetes. MicroRNA microarray analyses and real-time PCR revealed that miR-451 levels were significantly increased in the type 2 diabetes mouse hearts. Because excess supply of saturated fatty acids is a cause of diabetic cardiomyopathy, we stimulated neonatal rat cardiac myocytes (NRCMs) with palmitic acid and confirmed that miR-451 expression was increased in a dose- and time-dependent manner. Loss of miR-451 function ameliorated palmitate-induced lipotoxicity in NRCMs. Calcium-binding protein 39 (Cab39) is a scaffold protein of liver kinase B1 (LKB1), an upstream kinase of AMP-activated protein kinase (AMPK). Cab39 was a direct target of miR-451 in NRCMs and Cab39 overexpression rescued the lipotoxicity. To clarify miR-451 functions in vivo, we generated cardiomyocyte-specific miR-451 knockout (miR-451 cKO) mice. HFD-induced cardiac hypertrophy and contractile reserves were ameliorated in miR-451 cKO mice compared with control mice. Protein levels of Cab39 and phosphorylated AMPK were increased and phosphorylated mammalian target of rapamycin (mTOR) was reduced in miR-451 cKO mouse hearts compared with control mouse hearts. Conclusions: Our results demonstrate that miR-451 is involved in diabetic cardiomyopathy through suppression of the LKB1/AMPK pathway.
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Serofendic Acid Protects Against Myocardial Ischemia-Reperfusion Injury in Rats.
J. Pharmacol. Sci.
PUBLISHED: 11-01-2014
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We previously reported that serofendic acid, a lipophilic extract of fetal calf serum, protects against oxidative stress in primary culture of neonatal rat cardiomyocytes. However, the effect of serofendic acid on myocardial ischemia-reperfusion injury in vivo is yet to be determined. In the present study, we investigated the effect of intravenous administration of serofendic acid on ischemia-reperfusion injury induced by transient occlusion of the left coronary artery in rats. The rat heart was subjected to 25-min ischemia followed by 2-h reperfusion. Bolus intravenous administration of serofendic acid (1 - 10 mg/kg) given twice reduced the infarct volume in a dose-dependent manner. The protective effect of serofendic acid was abolished by pretreatment with 5-hydroxydecanoate, a blocker of mitochondrial ATP-sensitive potassium channels. For further testing of the protective effect of serofendic acid at the subcellular level, we monitored mitochondrial membrane potential (MMP) in individual cells using real-time two-photon imaging of Langendorff-perfused rat heart. A 25-min no-flow ischemia, followed by reperfusion caused progressive MMP loss. Serofendic acid significantly reduced the number of cells undergoing MMP loss. These results suggest that serofendic acid protected cardiac myocytes against myocardial ischemia-reperfusion injury by preserving the functional integrity of mitochondria.
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Outcomes of everolimus-eluting stent incomplete stent apposition: a serial optical coherence tomography analysis.
Eur Heart J Cardiovasc Imaging
PUBLISHED: 10-25-2014
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The aim of the present study was to evaluate the natural course of acute incomplete stent apposition (ISA) after second-generation everolimus-eluting stent (EES) when compared with first-generation sirolimus-eluting stent (SES) by using optical coherence tomography (OCT).
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Prasugrel, a Third-Generation P2Y12 Receptor Antagonist, in Patients With Coronary Artery Disease Undergoing Elective Percutaneous Coronary Intervention.
Circ. J.
PUBLISHED: 10-25-2014
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Background:Prasugrel is being developed in Japan as an antiplatelet therapy for use during percutaneous coronary intervention (PCI). Up to 70% of Japanese patients with coronary artery disease undergo elective PCI. The PRASugrel For Japanese PatIenTs with Coronary Artery Diseases Undergoing Elective PCI (PRASFIT-Elective) study investigated the efficacy and safety of different prasugrel dosing regimens in Japanese patients undergoing elective PCI.Methods?and?Results:A total of 742 patients scheduled for elective coronary artery stenting were enrolled. Patients were randomized to receive either prasugrel (20/3.75 mg, loading/maintenance dose) or clopidogrel (300/75 mg) in a double-blind manner. Endpoints, including cardiovascular events and bleeding, were assessed at weeks 24-48. The incidence rate of major cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal ischemic stroke) up to week 24 was 4.1% (15/370) and 6.7% (25/372) in the prasugrel and clopidogrel groups, respectively. Other incidence rates were: non-coronary artery bypass graft-related major bleeding, 0% and 2.2%; major/minor bleeding, 1.6% and 3.0%; and all bleeding events, 38.1% and 34.4% in the prasugrel and clopidogrel groups, respectively. The incidence rate of bleeding-related adverse events was similar in both groups, being 40.8% and 35.8% in the prasugrel and clopidogrel groups, respectively.Conclusions:These results support the risk-benefit profile of an adjusted dosing regimen of prasugrel in Japanese patients undergoing PCI. Larger studies are required to confirm these findings.
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Two-Year Analysis of the Japanese Cohort From the Zilver PTX Randomized Controlled Trial Supports the Validity of Multinational Clinical Trials.
J. Endovasc. Ther.
PUBLISHED: 10-08-2014
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Purpose : To report a subgroup analysis comparing safety and effectiveness outcomes in Japanese and non-Japanese patients as part of a prospective, multinational, randomized controlled trial (ClinicalTrials.gov identifier NCT00120406) evaluating a paclitaxel-coated drug-eluting stent (DES) compared to percutaneous transluminal angioplasty (PTA) for treating peripheral artery disease. Methods : Patients were randomly assigned to primary DES or PTA. In the Japanese cohort, 27 patients (21 men; mean age 71.2±9.6 years) were randomized to PTA and 25 patients (19 men; mean age 69.8±10.2 years) to primary DES. In the non-Japanese cohort, 211 patients (131 men; mean age 67.3±10.6 years) were randomized to PTA and 211 patients (136 men; mean age 67.6±9.5 years) to primary DES. Outcome measures included event-free survival (EFS), freedom from target lesion revascularization (TLR), patency, stent fracture, and sustained clinical benefit through 2 years. Results : Safety and effectiveness outcomes were similar in the Japanese and non-Japanese cohorts, although the outcomes in the Japanese cohort treated with primary DES were numerically better. In the DES group, the 2-year EFS was 92.0% vs. 85.0% (p=0.61), freedom from TLR was 96.0% vs. 85.5% (p=0.55), primary patency was 80.0% vs. 74.3% (p=0.61), and clinical benefit was sustained in 88.5% vs. 80.5% of patients (p=0.31) in the Japanese and non-Japanese cohorts, respectively. Stent fractures were seen in 4 of 457 stents at 12 months: 3 in the Japanese cohort and 1 in the non-Japanese cohort. Conclusion : The subgroup analysis comparing Japanese and non-Japanese patients supports the safety and effectiveness of the paclitaxel-coated DES in Japanese patients with stenotic lesions in the femoropopliteal arteries. The lack of major differences associated with ethnicity in these 2-year outcomes supports the validity and value of multinational clinical trials.
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Inhibition of N-type Ca2+ channels ameliorates an imbalance in cardiac autonomic nerve activity and prevents lethal arrhythmias in mice with heart failure.
Cardiovasc. Res.
PUBLISHED: 08-05-2014
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Dysregulation of autonomic nervous system activity can trigger ventricular arrhythmias and sudden death in patients with heart failure. N-type Ca(2+) channels (NCCs) play an important role in sympathetic nervous system activation by regulating the calcium entry that triggers release of neurotransmitters from peripheral sympathetic nerve terminals. We have investigated the ability of NCC blockade to prevent lethal arrhythmias associated with heart failure.
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Effect of preinfarction angina pectoris on long-term survival in patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention.
Am. J. Cardiol.
PUBLISHED: 07-29-2014
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The influence of preinfarction angina pectoris (AP) on long-term clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) remains controversial. In 5,429 patients with acute myocardial infarction (AMI) enrolled in the Coronary Revascularization Demonstrating Outcome Study in Kyoto AMI Registry, the present study population consisted of 3,476 patients with STEMI who underwent primary PCI within 24 hours of symptom onset and in whom the data on preinfarction AP were available. Preinfarction AP defined as AP occurring within 48 hours of hospital arrival was present in 675 patients (19.4%). Patients with preinfarction AP was younger and more often had anterior AMI and longer total ischemic time, whereas they less often had history of heart failure, atrial fibrillation, and shock presentation. The infarct size estimated by peak creatinine phosphokinase was significantly smaller in patients with than in patients without preinfarction AP (median [interquartile range] 2,141 [965 to 3,867] IU/L vs 2,462 [1,257 to 4,495] IU/L, p <0.001). The cumulative 5-year incidence of death was significantly lower in patients with preinfarction AP (12.4% vs 20.7%, p <0.001) with median follow-up interval of 1,845 days. After adjusting for confounders, preinfarction AP was independently associated with a lower risk for death (hazard ratio 0.69, 95% confidence interval 0.54 to 0.86, p = 0.001). The lower risk for 5-year mortality in patients with preinfarction AP was consistently observed across subgroups stratified by total ischemic time, initial Thrombolysis In Myocardial Infarction flow grade, hemodynamic status, infarct location, and diabetes mellitus. In conclusion, preinfarction AP was independently associated with lower 5-year mortality in patients with STEMI who underwent primary PCI.
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Comparison of five-year outcomes of coronary artery bypass grafting versus percutaneous coronary intervention in patients with left ventricular ejection fractions?50% versus >50% (from the CREDO-Kyoto PCI/CABG Registry Cohort-2).
Am. J. Cardiol.
PUBLISHED: 07-16-2014
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Coronary heart disease is a major risk factor for left ventricular (LV) systolic dysfunction. However, limited data are available regarding long-term benefits of percutaneous coronary intervention (PCI) in the era of drug-eluting stent or coronary artery bypass grafting (CABG) in patients with LV systolic dysfunction with severe coronary artery disease. We identified 3,584 patients with 3-vessel and/or left main disease of 15,939 patients undergoing first myocardial revascularization enrolled in the CREDO-Kyoto PCI/CABG Registry Cohort-2. Of them, 2,676 patients had preserved LV systolic function, defined as an LV ejection fraction (LVEF) of >50% and 908 had impaired LV systolic function (LVEF?50%). In patients with preserved LV function, 5-year outcomes were not different between PCI and CABG regarding propensity score-adjusted risk of all-cause and cardiac deaths. In contrast, in patients with impaired LV systolic function, the risks of all-cause and cardiac deaths after PCI were significantly greater than those after CABG (hazard ratio 1.49, 95% confidence interval 1.04 to 2.14, p=0.03 and hazard ratio 2.39, 95% confidence interval 1.43 to 3.98, p<0.01). In both patients with moderate (35%
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Predictive Performance of SYNTAX Score II in Patients With Left Main and Multivessel Coronary Artery Disease-analysis of CREDO-Kyoto registry.
Circ. J.
PUBLISHED: 07-07-2014
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SYNTAX score II (SSII) provides individualized estimates of 4-year mortality after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in order to facilitate decision-making between these revascularization methods. The purpose of the present study was to assess SSII in a real-world multicenter registry with distinct regional and epidemiological characteristics.
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Differences in coronary risk factors, procedural characteristics, mortality and stent thrombosis between two all-comers percutaneous coronary intervention registries from Europe and Japan: a patient-level data analysis of the Bern-Rotterdam and j-Cypher registries.
EuroIntervention
PUBLISHED: 07-01-2014
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Aims: The reported rate of stent thrombosis (ST) after drug-eluting stent (DES) implantation varies among registries. To investigate differences in baseline characteristics and clinical outcome in European and Japanese all-comers registries, we performed a pooled analysis of patient-level data. Methods and results: The j-Cypher registry (JC) is a multicentre observational study conducted in Japan, including 12,824 patients undergoing SES implantation. From the Bern-Rotterdam registry (BR) enrolled at two academic hospitals in Switzerland and the Netherlands, 3,823 patients with SES were included in the current analysis. Patients in BR were younger, more frequently smokers and presented more frequently with ST-elevation myocardial infarction (MI). Conversely, JC patients more frequently had diabetes and hypertension. At five years, the definite ST rate was significantly lower in JC than BR (JC 1.6% vs. BR 3.3%, p<0.001), while the unadjusted mortality tended to be lower in BR than in JC (BR 13.2% vs. JC 14.4%, log-rank p=0.052). After adjustment, the j-Cypher registry was associated with a significantly lower risk of all-cause mortality (HR 0.56, 95% CI: 0.49-0.64) as well as definite stent thrombosis (HR 0.46, 95% CI: 0.35-0.61). Conclusions: The baseline characteristics of the two large registries were different. After statistical adjustment, JC was associated with lower mortality and ST.
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Purification, crystallization and preliminary X-ray crystallographic analysis of human IL-18 and its extracellular complexes.
Acta Crystallogr F Struct Biol Commun
PUBLISHED: 06-10-2014
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Interleukin-18 (IL-18), a pro-inflammatory cytokine belonging to the interleukin-1 (IL-1) family, is involved in the pathogenesis of autoimmune/autoinflammatory and allergic diseases such as juvenile idiopathic arthritis and bronchial asthma. IL-18 forms a signalling complex with the IL-18 receptor ? (IL-18R?) and ? (IL-18R?) chains; however, the detailed activation mechanism remains unclear. Here, the IL-18-IL-18R? binary and IL-18-IL-18R?-IL-18R? ternary complexes were purified and crystallized as well as IL-18 alone. An X-ray diffraction data set for IL-18 was collected to 2.33?Å resolution from a crystal belonging to space group P21, with unit-cell parameters a = 68.15, b = 79.51, c = 73.46?Å, ? = 100.97°. Crystals of both the IL-18 binary and ternary complexes belonging to the orthorhombic space groups P21212 and P212121, respectively, diffracted to 3.10?Å resolution. Unit-cell parameters were determined as a = 135.49, b = 174.81, c = 183.40?Å for the binary complex and a = 72.56, b = 111.56, c = 134.57?Å for the ternary complex.
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Long-term efficacy and safety outcomes after unrestricted use of drug-eluting stents in patients with acute coronary syndrome: mortality and major bleeding in a single-center registry.
Circ. J.
PUBLISHED: 05-14-2014
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Recent randomized clinical trials have reported favorable clinical outcomes after the use of drug-eluting stents (DES) in patients with acute coronary syndrome (ACS). However, the long-term efficacy and safety outcomes, bleeding outcome in particular, after DES implantation in ACS patients have not been thoroughly evaluated in a real-world population.
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Cost analysis of non-invasive fractional flow reserve derived from coronary computed tomographic angiography in Japan.
Cardiovasc Interv Ther
PUBLISHED: 05-12-2014
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Percutaneous coronary intervention (PCI) based on fractional flow reserve (FFRcath) measurement during invasive coronary angiography (CAG) results in improved patient outcome and reduced healthcare costs. FFR can now be computed non-invasively from standard coronary CT angiography (cCTA) scans (FFRCT). The purpose of this study is to determine the potential impact of non-invasive FFRCT on costs and clinical outcomes of patients with suspected coronary artery disease in Japan. Clinical data from 254 patients in the HeartFlowNXT trial, costs of goods and services in Japan, and clinical outcome data from the literature were used to estimate the costs and outcomes of 4 clinical pathways: (1) CAG-visual guided PCI, (2) CAG-FFRcath guided PCI, (3) cCTA followed by CAG-visual guided PCI, (4) cCTA-FFRCT guided PCI. The CAG-visual strategy demonstrated the highest projected cost ($10,360) and highest projected 1-year death/myocardial infarction rate (2.4 %). An assumed price for FFRCT of US $2,000 produced equivalent clinical outcomes (death/MI rate: 1.9 %) and healthcare costs ($7,222) for the cCTA-FFRCT strategy and the CAG-FFRcath guided PCI strategy. Use of the cCTA-FFRCT strategy to select patients for PCI would result in 32 % lower costs and 19 % fewer cardiac events at 1 year compared to the most commonly used CAG-visual strategy. Use of cCTA-FFRCT to select patients for CAG and PCI may reduce costs and improve clinical outcome in patients with suspected coronary artery disease in Japan.
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AMAP1 as a negative-feedback regulator of nuclear factor-?B under inflammatory conditions.
Sci Rep
PUBLISHED: 05-07-2014
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NF-?B is a major transcriptional factor regulating many cellular functions including inflammation; therefore, its appropriate control is of high importance. The detailed mechanism of its activation has been well characterized, but that of negative regulation is poorly understood. In this study, we showed AMAP1, an Arf-GTPase activating protein, as a negative feedback regulator for NF-?B by binding with IKK?, an essential kinase in NF-?B signaling. Proteomics analysis identified AMAP1 as a binding protein with IKK?. Overexpression of AMAP1 suppressed NF-?B activity by interfering the binding of IKK? and NEMO, and deletion of AMAP1 augmented NF-?B activity. The activation of NF-?B induced translocation of AMAP1 to cytoplasm from cell membrane and nucleus, which resulted in augmented interaction of AMAP1 and IKK?. These results demonstrated a novel role of AMAP1 as a negative feedback regulator of NF-?B, and presented it as a possible target for anti-inflammatory treatments.
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Long-term clinical outcomes after everolimus- and sirolimus-eluting coronary stent implantation: final 3-year follow-up of the randomized evaluation of sirolimus-eluting versus everolimus-eluting stent trial.
Circ Cardiovasc Interv
PUBLISHED: 05-06-2014
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Long-term clinical outcomes of everolimus-eluting stent (EES) compared with sirolimus-eluting stent (SES) have not been evaluated fully yet, especially whether EES implantation could positively affect late adverse events reported after SES implantation occurring >1 year.
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Efficacy and safety of adjusted-dose prasugrel compared with clopidogrel in Japanese patients with acute coronary syndrome: the PRASFIT-ACS study.
Circ. J.
PUBLISHED: 04-22-2014
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Prasugrel is an antiplatelet agent that shows more prompt, potent, and consistent platelet inhibition than clopidogrel. The objective of this study was to confirm the efficacy and safety of prasugrel at loading/maintenance doses of 20/3.75 mg.
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Comparison of long-term mortality after acute myocardial infarction treated by percutaneous coronary intervention in patients living alone versus not living alone at the time of hospitalization.
Am. J. Cardiol.
PUBLISHED: 04-16-2014
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Living alone was reported to be associated with increased risk of cardiovascular disease. There are, however, limited data on the relation between living alone and all-cause mortality in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). The Coronary REvascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) AMI registry was a cohort study of patients with AMI enrolled in 26 hospitals in Japan from 2005 through 2007. For the current analysis, we included those patients who underwent PCI within 24 hours of symptom onset, and we assessed their living status to determine if living alone would be an independent prognostic risk factor. Among 4,109 patients eligible for the current analysis of 5,429 patients enrolled in the CREDO-Kyoto AMI registry, 515 patients (12.5%) were living alone at the time of hospital admission. The cumulative 5-year incidence of all-cause death was 18.3% in the living alone group and 20.1% in the not living alone group (log-rank p = 0.77). After adjusting for potential confounders, risk of the living alone group relative to the not living alone group for all-cause death was not significantly different (adjusted hazard ratio 0.82, 95% confidence interval 0.65 to 1.02, p = 0.08). In a subgroup analysis stratified by age, the adjusted risk for all-cause death was also not different between the living alone group and the not living alone group both in the older population (aged ?75 years) and the younger population (aged <75 years). In conclusion, living alone was not associated with higher long-term mortality in patients with AMI who underwent PCI.
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First clinical experience of the looped Inoue balloon technique for antegrade percutaneous balloon aortic valvuloplasty.
Heart Vessels
PUBLISHED: 04-14-2014
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Balloon aortic valvuloplasty (BAV) has played a limited role in the management of patients with severe aortic stenosis. However, BAV is being performed more frequently these days with the emergence of transcatheter aortic valve implantation (TAVI). We previously described a technique named "looped Inoue balloon technique" to simplify the antegrade transvenous BAV by making a loop in the left atrium using two stylets. We present a case in which the looped Inoue balloon technique was successfully applied. The patient was an 83-year-old woman with progressive dyspnea due to severe aortic stenosis. The aortic valve area was 0.39 cm(2) with a mean transvalvular gradient of 46 mmHg. The patient was deemed high risk for surgical aortic valve replacement or TAVI in view of the multiple comorbidities and frailty. Antegrade BAV using the looped Inoue balloon technique was performed. The procedure was successful without any complications. The post procedural aortic valve area increased to 1.15 cm(2) with a mean pressure gradient of 23 mmHg. This is the first report of clinical use of the looped Inoue balloon technique for antegrade BAV.
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4,5-Dicyano-3,6-diethylbenzo-1,2-diselenete, a highly stable 1,2-diselenete: its preparation, structural characterization, calculated molecular orbitals, and complexation with tetrakis(triphenylphosphine)palladium.
Inorg Chem
PUBLISHED: 04-11-2014
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The first isolable benzo-1,2-diselenete, 4,5-dicyano-3,6-diethylbenzo-1,2-diselenete (4), was prepared by the reaction of 4,5-(o-xylylenediseleno)-3,6-diethylphthalonitrile (3) with aluminum chloride in toluene. X-ray crystallographic analysis demonstrated that 4 contains a trapezoidal diselenide ring rather than a benzo-1,2-diselenone structure. In crystal form, 4 undergoes self-assembly and generates structures based on layered molecular sheets since the unit cell contains only one molecule. While the cyclic voltammogram of 4 exhibited only one irreversible peak (Ep = 1.59 V) during oxidation and two quasireversible couples during reduction, three peaks were observed in the differential pulse voltammogram of the reduction couples (E1/2 = -1.19, -0.75, and -0.69 V). Although a THF solution of 4 in the presence of sodium metal was EPR silent, various signals were readily observed in its (1)H, (13)C, and (77)Se NMR spectra. Molecular orbital calculations for 4 demonstrated that the HOMO orbital is primarily localized at the two selenium atoms and four of the benzene carbon atoms while the LUMO orbital is situated solely on the diselenete ring. It appears that the HOMO and LUMO orbitals of 4 receive significant stabilization from the nitrile groups compared to the level of stabilization in the unsubstituted benzo-1,2-diselenete (BDS). The reaction of 4 with tetrakis(triphenylphosphine)palladium in benzene was found to produce a dinuclear palladium complex (8), and the structure of this complex was determined by X-ray crystallographic analysis. The central four membered ring of 8 consists of the Pd1, Se2, Pd2, and Se3 atoms and is not planar but rather adopts a folded arrangement.
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Intractable itch relieved by 4-phenylbutyrate therapy in patients with progressive familial intrahepatic cholestasis type 1.
Orphanet J Rare Dis
PUBLISHED: 03-31-2014
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Progressive familial intrahepatic cholestasis type 1 (PFIC1), an inherited liver disease caused by mutations in ATP8B1, progresses to severe cholestasis with a sustained intractable itch. Currently, no effective therapy has been established for PFIC1. Decreased function of the bile salt export pump (BSEP) in hepatocytes is suggested to be responsible for the severe cholestasis observed in PFIC1. We found a previously unidentified pharmacological effect of 4-phenylbutyrate (4PB) that increases the expression and function of BSEP. Here, we tested 4PB therapy in three patients with PFIC1.
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Three-year outcomes after percutaneous coronary intervention and coronary artery bypass grafting in patients with heart failure: from the CREDO-Kyoto percutaneous coronary intervention/coronary artery bypass graft registry cohort-2.
Eur J Cardiothorac Surg
PUBLISHED: 03-26-2014
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Ischaemic heart disease is a major risk factor for heart failure. However, long-term benefit of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in those patients has not been well elucidated.
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MicroRNA-33b knock-in mice for an intron of sterol regulatory element-binding factor 1 (Srebf1) exhibit reduced HDL-C in vivo.
Sci Rep
PUBLISHED: 03-20-2014
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MicroRNAs (miRs) are small non-protein-coding RNAs that bind to specific mRNAs and inhibit translation or promote mRNA degradation. Recent reports, including ours, indicated that miR-33a located within the intron of sterol regulatory element-binding protein (SREBP) 2 controls cholesterol homeostasis and can be a possible therapeutic target for treating atherosclerosis. Primates, but not rodents, express miR-33b from an intron of SREBF1. Therefore, humanized mice, in which a miR-33b transgene is inserted within a Srebf1 intron, are required to address its function in vivo. We successfully established miR-33b knock-in (KI) mice and found that protein levels of known miR-33a target genes, such as ABCA1, ABCG1, and SREBP-1, were reduced compared with those in wild-type mice. As a consequence, macrophages from the miR-33b KI mice had a reduced cholesterol efflux capacity via apoA-I and HDL-C. Moreover, HDL-C levels were reduced by almost 35% even in miR-33b KI hetero mice compared with the control mice. These results indicate that miR-33b may account for lower HDL-C levels in humans than those in mice and that miR-33b is possibly utilized for a feedback mechanism to regulate its host gene SREBF1. Our mice will also aid in elucidating the roles of miR-33a/b in different genetic disease models.
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Relation of contrast-induced nephropathy to long-term mortality after percutaneous coronary intervention.
Am. J. Cardiol.
PUBLISHED: 02-24-2014
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There is little information on the effect of contrast-induced nephropathy (CIN) on long-term mortality after percutaneous coronary intervention in patients with or without chronic kidney disease (CKD). Of 4,371 patients who had paired serum creatinine (SCr) measurements before and after percutaneous coronary intervention and were discharged alive in the Coronary REvascularization Demonstrating Outcome Study in Kyoto registry, the incidence of CIN (an increase in SCr of ?0.5 mg/dl from the baseline) was 5% in our study cohort. The rate of CIN in patients with CKD was 11%, although it was 2% without CKD (p <0.0001). During a median follow-up of 42.3 months after discharge, 374 patients (8.6%) died. After adjustment for prespecified confounders, CIN was significantly correlated with long-term mortality in the entire cohort (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.62 to 2.29, p <0.0001) and in patients with CKD (HR 2.62, 95% CI 1.91 to 3.57, p <0.0001) but not in patients without CKD (HR 1.23, 95% CI 0.47 to 2.62, p = 0.6). Sensitivity analyses confirmed these results using the criteria defined as elevations of the SCr by ?25% and 0.3 mg/dl from the baseline, respectively. In conclusion, CIN was significantly correlated with long-term mortality in patients with CKD but not in those without CKD.
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Evolution in practice patterns and long-term outcomes of coronary revascularization from bare-metal stent era to drug-eluting stent era in Japan.
Am. J. Cardiol.
PUBLISHED: 02-24-2014
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Treatment of coronary artery disease has significantly changed over the past decade including an introduction of drug-eluting stents and a more stringent adherence to evidence-based medications. However, the impact of these advanced treatment methods on the practice patterns and long-term outcomes in patients undergoing coronary revascularization in the real world has not been yet fully evaluated. The present study population consisted of the 2 groups of patients who underwent their first coronary revascularization in the Coronary REvascularization Demonstrating Outcome Study in Kyoto Registry Cohort-1 (bare-metal stent era: January 2000 to December 2002, n = 8,986) and Cohort-2 (drug-eluting stent era: January 2005 to December 2007, n = 10,339). Compared with Cohort-1, the proportion of patients treated with percutaneous coronary intervention significantly increased in Cohort-2 (73% vs 81%, p <0.001), particularly for 3-vessel disease (50% vs 61%, p <0.001) and left main disease (18% vs 36%, p <0.001). Evidence-based medications were more frequently used in Cohort-2. The cumulative 2-year incidence of and the adjusted risk for all-cause death were not significantly different between Cohort-1 and Cohort-2 (6.2% vs 6.4%, p = 0.69, and hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.81 to 1.03, p = 0.15). Adjusted risks for both myocardial infarction and repeated coronary revascularization were significantly reduced in Cohort-2 compared with Cohort-1 (HR 0.80, 95% CI 0.67 to 0.96, p = 0.02, and HR 0.73, 95% CI 0.69 to 0.77, p <0.001, respectively). In conclusion, despite changes in treatment methods over time, the long-term mortality of patients undergoing coronary revascularization in the real-world clinical practice has not been changed, although there was a significant reduction of myocardial infarction and repeated coronary revascularization.
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Aspirin augments the expression of Adenomatous Polyposis Coli protein by suppression of IKK?.
Biochem. Biophys. Res. Commun.
PUBLISHED: 02-24-2014
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Aspirin has been widely used as analgesic, antipyretic and anti-inflammatory medicine for long. In addition to these traditional effects, clinical studies suggest that aspirin can protect against cancer, but its mechanism has not been explored. To unveil it, we identified the proteins up- or down-regulated after incubation with aspirin by using proteomics analysis with Nano-flow LC/MALDI-TOF system. Interestingly, the analysis identified the protein of Adenomatous Polyposis Coli (APC) as one of the most up-regulated protein. APC regulates cell proliferation or angiogenesis, and is widely known as a tumor-suppressing gene which can cause colorectal cancer when it is mutated. Western blots confirmed this result, and real-time PCR indicated it is transcriptionally regulated. We further tried to elucidate the molecular mechanism with focusing on IKK?. IKK? is the essential kinase in activation of nuclear factor-kappa B (NF-?B), major transcriptional factors that regulate genes responsible for inflammation or immune response. Previous reports indicated that aspirin specifically inhibits IKK? activity, and constitutively active form of IKK? accelerates APC loss. We found that aspirin suppressed the expression of IKK?, and the deletion of IKK? by siRNA increases the expression of APC in HEK294 cells. Finally, we observed similar effects of aspirin in human umbilical vein endothelial cells. Taken together, these results reveal that aspirin up-regulates the expression of APC via the suppression of IKK?. This can be a mechanism how aspirin prevents cancer at least in part, and a novel link between inflammatory NF-?B signaling and cancer.
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Percutaneous coronary intervention versus coronary artery bypass grafting in patients with end-stage renal disease requiring dialysis (5-year outcomes of the CREDO-Kyoto PCI/CABG Registry Cohort-2).
Am. J. Cardiol.
PUBLISHED: 02-20-2014
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Ischemic heart disease is a major risk factor for morbidity and mortality in patients with end-stage renal disease. However, long-term benefits of percutaneous coronary intervention (PCI) relative to coronary artery bypass grafting (CABG) in those patients is still unclear in the drug-eluting stent era. We identified 388 patients with multivessel and/or left main disease with end-stage renal disease requiring dialysis among 15,939 patients undergoing first coronary revascularization enrolled in the Coronary REvascularization Demonstrating Outcome Study in Kyoto PCI/CABG Registry Cohort-2 (PCI: 258 patients and CABG: 130 patients). The CABG group included more patients with 3-vessel (38% vs 57%, p <0.001) and left main disease (10% vs 34%, p <0.001). Preprocedural Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery score in the CABG group was significantly higher than that in the PCI group (23.5 ± 8.7 vs 29.4 ± 11.0, p <0.001). Unadjusted 30-day mortality was 2.7% for PCI and 5.4% for CABG. Cumulative 5-year all-cause mortality was 52.3% for PCI and 49.9% for CABG. Propensity score-adjusted all-cause mortality was not different between PCI and CABG (hazard ratio [HR] 1.33, 95% confidence interval [CI] 0.85 to 2.09, p = 0.219). However, the excess risk of PCI relative to CABG for cardiac death was significant (HR 2.10, 95% CI 1.11 to 3.96, p = 0.02). The risk of sudden death was also higher after PCI (HR 4.83, 95% CI 1.01 to 23.08, p = 0.049). The risk of myocardial infarction after PCI tended to be higher than after CABG (HR 3.30, 95% CI 0.72 to 15.09, p = 0.12). The risk of any coronary revascularization after PCI was markedly higher after CABG (HR 3.78, 95% CI 1.91 to 7.50, p <0.001). Among the 201 patients who died during the follow-up, 94 patients (47%) died from noncardiac morbidities such as stroke, respiratory failure, and renal failure. In patients with multivessel and/or left main disease undergoing dialysis, 5-year outcomes revealed that CABG relative to PCI reduced the risk of cardiac death, sudden death, myocardial infarction, and any revascularization. However, the risk of all-cause death was not different between PCI and CABG.
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Long-term clinical outcomes after sirolimus-eluting stent implantation for unprotected left main coronary artery disease.
Cardiovasc Interv Ther
PUBLISHED: 02-19-2014
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Previous studies reporting long-term (?5 year) clinical outcome in patients with unprotected left main coronary artery (LMCA) disease undergoing drug-eluting stent (DES) implantation are currently limited, although late adverse events beyond 1 year are one of the major concerns of DES. We evaluated long-term clinical outcomes in 134 consecutive patients who underwent sirolimus-eluting stents (SES) for unprotected LMCA lesion in a single center from 2004 to 2009. The median follow-up duration was 3.8 (range: 0.5-7.9) years. Eight patients suffered from serious cardiovascular events potentially related to LMCA lesion (primary outcome measure) (sudden cardiac death: N = 5, emergent coronary revascularization for the LMCA lesion: N = 2, and acute congestive heart failure related to LMCA lesion: N = 1) with the cumulative 5-year incidence of only 4.4 %. The cumulative 5-year incidence of all-cause death, cardiac death, target vessel myocardial infarction, definite stent thrombosis, and target-lesion revascularization was 26.5, 8.1, 0, 0, and 12.9 %, respectively. In a subgroup analysis, the cumulative incidence of the primary outcome measure was significantly higher in patients with 2-stenting (N = 27) than in patients with 1-stenting (N = 107) (14.0 and 2.2 %, P < 0.001). All 8 patients with serious adverse events had a true bifurcation lesion and 5 patients received 2-stenting for the LMCA lesion. SES implantation in patients with unprotected LMCA lesion was associated with a favorable long-term outcome with acceptably low rate of serious adverse event potentially related to LMCA lesion. However, complex LMCA lesions necessitating 2-stenting strategy might be associated with higher risk for serious adverse events.
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Modification of treatment strategy after FFR measurement: CVIT-DEFER registry.
Cardiovasc Interv Ther
PUBLISHED: 02-14-2014
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The impact of the fractional flow reserve (FFR) on clinical decision-making remains unclear in daily practice. The CVIT-DEFER registry is a prospective multicenter registry enrolling consecutive patients with angiographically intermediate coronary stenosis for whom FFR measurement is clinically indicated. The treatment strategy determined from angiographic findings alone and the strategy selected after FFR measurement were compared. Data on the treatment strategy were obtained for 3093 subjects. The average age of these subjects was 69.5 ± 10.2 years and 73.8 % were men. The majority had stable coronary artery disease, including 60.4 % with stable angina pectoris. The treatment strategy based on angiographic findings was medical management in 34.5 %, percutaneous coronary intervention (PCI) in 63.5 %, and coronary artery bypass grafting in 2.1 %. The FFR was ?0.8 in 1566 lesions (42.2 %). After FFR measurement, medical treatment was changed to revascularization in 19.7 %, while PCI was switched to medical treatment in 57.4 % at the lesion level. As a result, reclassification of the treatment strategy at the patient level was done in 39.0 % of the patients. Revascularization was frequently switched to medical treatment after FFR measurement. These findings support the clinical utility of employing FFR data to guide selection of PCI.
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Anticoagulant and antiplatelet therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention.
Am. J. Cardiol.
PUBLISHED: 02-11-2014
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The prevalence, intensity, safety, and efficacy of oral anticoagulation (OAC) in addition to dual antiplatelet therapy (DAPT) in "real-world" patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have not yet been fully evaluated. In the Coronary REvascularization Demonstrating Outcome Study in Kyoto registry cohort-2, a total of 1,057 patients with AF (8.3%) were identified among 12,716 patients undergoing first PCI. Cumulative 5-year incidence of stroke was higher in patients with AF than in no-AF patients (12.8% vs 5.8%, p <0.0001). Although most patients with AF had CHADS2 score ?2 (75.2%), only 506 patients (47.9%) received OAC with warfarin at hospital discharge. Cumulative 5-year incidence of stroke in the OAC group was not different from that in the no-OAC group (13.8% vs 11.8%, p = 0.49). Time in therapeutic range (TTR) was only 52.6% with an international normalized ratio of 1.6 to 2.6, and only 154 of 409 patients (37.7%) with international normalized ratio data had TTR ?65%. Cumulative 5-year incidence of stroke in patients with TTR ?65% was markedly lower than that in patients with TTR <65% (6.9% vs 15.1%, p = 0.01). In a 4-month landmark analysis in the OAC group, there was a trend for higher cumulative incidences of stroke and major bleeding in the on-DAPT (n = 286) than in the off-DAPT (n = 173) groups (15.1% vs 6.7%, p = 0.052 and 14.7% vs 8.7%, p = 0.10, respectively). In conclusion, OAC was underused and its intensity was mostly suboptimal in real-world patients with AF undergoing PCI, which lead to inadequate stroke prevention. Long-term DAPT in patients receiving OAC did not reduce stroke incidence.
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Statin treatment rescues FGFR3 skeletal dysplasia phenotypes.
Nature
PUBLISHED: 02-01-2014
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Gain-of-function mutations in the fibroblast growth factor receptor 3 gene (FGFR3) result in skeletal dysplasias, such as thanatophoric dysplasia and achondroplasia (ACH). The lack of disease models using human cells has hampered the identification of a clinically effective treatment for these diseases. Here we show that statin treatment can rescue patient-specific induced pluripotent stem cell (iPSC) models and a mouse model of FGFR3 skeletal dysplasia. We converted fibroblasts from thanatophoric dysplasia type I (TD1) and ACH patients into iPSCs. The chondrogenic differentiation of TD1 iPSCs and ACH iPSCs resulted in the formation of degraded cartilage. We found that statins could correct the degraded cartilage in both chondrogenically differentiated TD1 and ACH iPSCs. Treatment of ACH model mice with statin led to a significant recovery of bone growth. These results suggest that statins could represent a medical treatment for infants and children with TD1 and ACH.
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High-dose regimen to achieve novel target trough concentration in teicoplanin.
J. Infect. Chemother.
PUBLISHED: 01-28-2014
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In the treatment of severe MRSA infections such as endocarditis, more than 20 mg/L of plasma trough concentration (C(min)) is recommended for teicoplanin; however, in the treatment of common MRSA infections, recommended C(min) remains more than 10 mg/L. In this study, we set C(min) as 15-30 mg/L to obtain a favorable clinical outcome in the treatment of common MRSA infections, and investigated the optimal loading regimen that achieved the target C(min) in patients with normal renal function. Seventy-eight patients received the high-dose regimen A (6 mg/kg every 12-h for initial two days) and 60 patients received the high-dose regimen B (the first five loading doses of 10-12 mg/kg at 12-h intervals for initial three days, followed by 6 mg/kg once daily). The mean C(min) on the 4th day was 13.7 ± 5.3 mg/L in regimen A, and 20.0 ± 6.6 mg/L in regimen B (P < 0.001), and the proportion of patients achieving the 15-30 mg/L was 25.6% and 68.3% (P < 0.001). Clinical response at end-of treatment were 66.7% and 85.0% (P = 0.014). The patients of initial C(min) with ?15 mg/L had tended to be higher clinical response than those with <15 mg/L (80.9% vs 68.6%, P = 0.084). There were no significant differences in the occurrence of adverse effects in regimen A and B (nephrotoxicity; 1.3% vs 3.3%, P = 0.413, hepatotoxicity; 5.1% vs 3.3%, P = 0.608). In conclusion, to obtain C(min) 15-30 mg/L, the first five loading doses of 10-12 mg/kg at 12-h intervals was required in patients with normal renal function.
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Impact of angiographic peri-stent contrast staining (PSS) on late adverse events after sirolimus-eluting stent implantation: an observation from the multicenter j-Cypher registry PSS substudy.
Cardiovasc Interv Ther
PUBLISHED: 01-25-2014
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This study sought to assess clinical significance of angiographic peri-stent contrast staining (PSS) after sirolimus-eluting stent (SES) implantation in a large multicenter study with 5-year follow-up. The j-Cypher PSS substudy is a multicenter study including 5712 patients (7838 lesions) who underwent follow-up angiographic study within 12 months after SES implantation. Late acquired PSS was observed in 184 patients (3.2 %) or 194 lesions (2.5 %). Independent risk factors of PSS were chronic total occlusion and left anterior descending artery lesion, while negative risk factors were in-stent restenosis, diabetes mellitus, ?70 years of age, and left circumflex coronary artery lesion. Cumulative incidence of definite very late stent thrombosis (VLST) at 4 years after the index follow-up angiography in lesions with PSS was significantly higher than that in lesions without PSS (5.3 versus 0.7 %, P < 0.0001). Late target-lesion revascularization (TLR) was also more frequently observed in the PSS group (13 versus 6.9 %, P = 0.01), while late TLR for restenosis excluding those TLR procedures for VLST tended to be higher in the PSS group (9.9 versus 6.3 %; P = 0.15). PSS found in 2.5 % of lesions within 12 months after SES implantation was associated with higher risk for subsequent VLST.
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Fusion of optical coherence tomographic and angiographic data for more accurate evaluation of the endothelial shear stress patterns and neointimal distribution after bioresorbable scaffold implantation: comparison with intravascular ultrasound-derived reconstructions.
Int J Cardiovasc Imaging
PUBLISHED: 01-15-2014
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Intravascular ultrasound (IVUS)-based reconstructions have been traditionally used to examine the effect of endothelial shear stress (ESS) on neointimal formation. The aim of this analysis is to compare the association between ESS and neointimal thickness (NT) in models obtained by the fusion of optical coherence tomography (OCT) and coronary angiography and in the reconstructions derived by the integration of IVUS and coronary angiography. We analyzed data from six patients implanted with an Absorb bioresorbable vascular scaffold that had biplane angiography, IVUS and OCT investigation at baseline and 6 or 12 months follow-up. The IVUS and OCT follow-up data were fused separately with the angiographic data to reconstruct the luminal morphology at baseline and follow-up. Blood flow simulation was performed on the baseline reconstructions and the ESS was related to NT. In the OCT-based reconstructions the ESS were lower compared to the IVUS-based models (1.29 ± 0.66 vs. 1.87 ± 0.66 Pa, P = 0.030). An inverse correlation was noted between the logarithmic transformed ESS and the measured NT in all the OCT-based models which was higher than the correlation reported in five of the six IVUS-derived models (-0.52 ± 0.19 Pa vs. -0.10 ± 0.04, P = 0.028). Fusion of OCT and coronary angiography appears superior to IVUS-based reconstructions; therefore it should be the method of choice for the study of the effect of the ESS on neointimal proliferation.
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Prevalence of visual-functional mismatch regarding coronary artery stenosis in the CVIT-DEFER registry.
Cardiovasc Interv Ther
PUBLISHED: 01-11-2014
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The fractional flow reserve (FFR) is considered to be a reliable index for the assessment of clinically relevant coronary artery stenosis. However, mismatch in assessing the severity of coronary stenosis between coronary angiography and the FFR has been pointed out. The cardiovascular intervention therapeutics (CVIT)-DEFER registry is a prospective multicenter registry study that has enrolled 3,228 consecutive patients among 3,804 patients with angiographically moderate coronary artery lesions in whom FFR analysis was clinically indicated. The demographic and angiographic parameters associated with an FFR ?0.8 were analyzed, and the incidence of discrepancy between the angiographic severity of coronary stenosis and the FFR was assessed. Based on the visual assessment, 1,609 (42.9 %) lesions were categorized as showing 50 % stenosis, 1,882 lesions (50.2 %) as 75 % stenosis, and 257 lesions (6.9 %) as 90 % stenosis. Angiographic-FFR "mismatch," which was defined as visual stenosis ?75 % with FFR >0.80, was found in 43.4 % of lesions, while reverse angiographic mismatch (visual stenosis <75 % with FFR ?0.8) was found in 23.2 %. The independent predictors for "angiographic-FFR mismatch" were the presence of percutaneous coronary intervention (PCI) history, one-vessel disease, non-left anterior descending artery (LAD) location, non-diffuse lesion, non-ostial lesion, and non-tandem lesion. Conversely, "reverse angiographic mismatch" was independently associated with the multivessel disease, LAD location, and diffuse lesion. The FFR is not only influenced by luminal stenosis but also by coronary artery morphology and the amount of jeopardized myocardium. Angiographic-FFR mismatch is frequent in patients with moderate coronary stenosis, which suggests the clinical importance of using physiological assessment to guide PCI.
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Critical roles of nardilysin in the maintenance of body temperature homoeostasis.
Nat Commun
PUBLISHED: 01-09-2014
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Body temperature homoeostasis in mammals is governed centrally through the regulation of shivering and non-shivering thermogenesis and cutaneous vasomotion. Non-shivering thermogenesis in brown adipose tissue (BAT) is mediated by sympathetic activation, followed by PGC-1? induction, which drives UCP1. Here we identify nardilysin (Nrd1 and NRDc) as a critical regulator of body temperature homoeostasis. Nrd1(-/-) mice show increased energy expenditure owing to enhanced BAT thermogenesis and hyperactivity. Despite these findings, Nrd1(-/-) mice show hypothermia and cold intolerance that are attributed to the lowered set point of body temperature, poor insulation and impaired cold-induced thermogenesis. Induction of ?3-adrenergic receptor, PGC-1? and UCP1 in response to cold is severely impaired in the absence of NRDc. At the molecular level, NRDc and PGC-1? interact and co-localize at the UCP1 enhancer, where NRDc represses PGC-1? activity. These findings reveal a novel nuclear function of NRDc and provide important insights into the mechanism of thermoregulation.
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Impact of statin therapy on patients with coronary heart disease and aortic aneurysm or dissection.
J. Vasc. Surg.
PUBLISHED: 01-08-2014
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The impact of statin therapy on cardiovascular outcome in coronary artery disease (CAD) patients with aortic aneurysm or dissection (AD) is still unclear. The aim of this study was to elucidate the effect of statins at discharge to improve outcomes in CAD patients with AD.
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Twisted gastrulation, a BMP antagonist, exacerbates podocyte injury.
PLoS ONE
PUBLISHED: 01-01-2014
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Podocyte injury is the first step in the progression of glomerulosclerosis. Previous studies have demonstrated the beneficial effect of bone morphogenetic protein 7 (Bmp7) in podocyte injury and the existence of native Bmp signaling in podocytes. Local activity of Bmp7 is controlled by cell-type specific Bmp antagonists, which inhibit the binding of Bmp7 to its receptors. Here we show that the product of Twisted gastrulation (Twsg1), a Bmp antagonist, is the central negative regulator of Bmp function in podocytes and that Twsg1 null mice are resistant to podocyte injury. Twsg1 was the most abundant Bmp antagonist in murine cultured podocytes. The administration of Bmp induced podocyte differentiation through Smad signaling, whereas the simultaneous administration of Twsg1 antagonized the effect. The administration of Bmp also inhibited podocyte proliferation, whereas simultaneous administration of Twsg1 antagonized the effect. Twsg1 was expressed in the glomerular parietal cells (PECs) and distal nephron of the healthy kidney, and additionally in damaged glomerular cells in a murine model of podocyte injury. Twsg1 null mice exhibited milder hypoalbuminemia and hyperlipidemia, and milder histological changes while maintaining the expression of podocyte markers during podocyte injury model. Taken together, our results show that Twsg1 plays a critical role in the modulation of protective action of Bmp7 on podocytes, and that inhibition of Twsg1 is a promising means of development of novel treatment for podocyte injury.
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Myocardial Expression Level of Neural Cell Adhesion Molecule Correlates with Reduced Left Ventricular Function in Human Cardiomyopathy.
Circ Heart Fail
PUBLISHED: 12-23-2013
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-We recently screened for cardiac genes induced by metabolic stress and identified neural cell adhesion molecule (NCAM) as a candidate. This study aimed to clarify the expression pattern of neural cell adhesion molecule (NCAM) in human cardiomyopathy.
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In vitro assessment of mathematically-derived fractional flow reserve in coronary lesions with more than two sequential stenoses.
J Invasive Cardiol
PUBLISHED: 12-04-2013
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Myocardial fractional flow reserve (FFR) is a reliable index in coronary intervention. A simple FFR measurement does not predict the true functional severity of an individual stenosis in multiple sequential coronary stenoses because of complex interaction between the stenoses. Application of the theoretical equations to predict the true FFR of individual stenosis is limited in a tandem lesion. Two novel equations applicable to a multiple sequential coronary stenoses are mathematically derived. One predicts the true FFR of each stenosis (equation A), and the other predicts the true FFR after releasing a given stenosis (equation B). The present study aimed to validate the two derived equations in an in vitro model of coronary circulation.
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Microcatheter-facilitated reverse wire technique for side branch wiring in bifurcated vessels: an in vitro evaluation.
EuroIntervention
PUBLISHED: 11-28-2013
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Aims: To assess when and how the microcatheter-facilitated reverse wire technique should be applied to cross the guidewire into side branches in coronary bifurcations. Methods and results: Three interventional cardiologists with different levels of experience performed in vitro bench testing using an originally developed coronary bifurcation simulator which had six coronary bifurcations. The bifurcation angles were 90, 105, 120, 135, 150 and 165 degrees (°). Experiment 1 was conducted to assess in what coronary bifurcation the reverse wire technique is required. Antegrade guidewire advancement was conducted with two different guidewires: the spring coil guidewire SION blue and the polymer-jacket hydrophilic guidewire Fielder FC. Experiment 2 was conducted to determine what the optimal guidewire selection and the optimal guidewire shape for the reverse wire technique would be. Assessment of the guidewire crossability into the highly angulated side branch was performed, and then the balloon crossability was assessed. A total of four guidewire types were compared in experiment 2. In experiment 1, guidewire crossing was impossible by conventional antegrade wiring when the bifurcation angle became 150° or more. In experiment 2, guidewire crossing of more than 150° of bifurcation angle was achievable independent of the guidewire types and shape. Balloon deliverability was best when using a polymer-jacket hydrophilic guidewire with a round shape 3 cm from the guidewire tip. Conclusions: Although the guidewire crossing into the side branch was impossible by conventional antegrade methods when the bifurcation angle became 150° or more, the guidewire crossing into such a highly angulated side branch was easily possible using the reverse wire technique. The optimal guidewire selection for the reverse wire technique is the polymer-jacket hydrophilic guidewire with a round shape 3 cm from the guidewire tip.
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MicroRNAs and Lipoprotein Metabolism.
J. Atheroscler. Thromb.
PUBLISHED: 11-19-2013
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MicroRNAs(miRNAs; miRs) are small, non-protein-coding RNAs that negatively regulate the gene expression. They bind to specific mRNAs and inhibit translation or promote mRNA degradation. Recently, some miRNAs have been shown to be involved in lipid homoeostasis. In particular, miR122 and miR-33 have a significant impact on lipid homeostasis and are potential therapeutic targets for treating lipid disorders and/or atherosclerosis. In this review, we describe the current understanding of the function of miRNAs in lipid homeostasis, with a focus on lipoprotein metabolism.
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Syncope in High-Risk Cardiomyopathy Patients with Implantable Defibrillators: Frequency, Risk Factors, Mechanisms and Association with Mortality: Results from the MADIT-RIT Study.
Circulation
PUBLISHED: 11-07-2013
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There is a relative paucity of studies investigating the mechanisms of syncope among heart failure patients with implantable cardioverter defibrillators (ICD) and it is controversial whether non-arrhythmogenic syncope is associated with increased mortality.
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Repetitive Two-Step Method for o,o,p- and o,p-Oligophenylene Synthesis through Pd-Catalyzed Cross-Coupling of Hydroxyterphenylboronic Acid.
Molecules
PUBLISHED: 10-16-2013
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A repetitive two-step method involving the Pd-catalyzed Suzuki-Miyaura coupling of hydroxyterphenylboronic acid and the subsequent nonaflation of the hydroxy group has been developed for the synthesis of oligophenylenes. This method readily afforded o,o,p- and o,p-oligophenylenes with defined chain lengths. X-ray crystallography was employed to obtain the structure of the o,p-oligophenylene 9-mer.
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Serotonergic modulation of neuronal activity in the nucleus accumbens following repeated methamphetamine administration in rats.
J. Pharmacol. Sci.
PUBLISHED: 10-04-2013
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Electrophysiological studies were performed to determine whether serotonergic modulation in the nucleus accumbens (NAcc) was affected after repeated methamphetamine (MAP) administration. NAcc slices (400 ?m) from Wistar rats administered MAP (5 mg/kg) or saline once daily for 5 days were prepared 1, 5, or 10 days after the final injection. Population spikes (PS) induced by local stimulation of NAcc were recorded. PS inhibition by serotonin was significantly attenuated in the MAP group at 5 days but did not differ at 1 or 10 days. We next analyzed the effects of serotonin receptor subtype (5-HT1A,2,3,4,6,7)-selective agonists of PS. Differences between saline and MAP groups in 5-HT1A,2,3,4,6 receptor agonist-induced changes of PS were small or not significant. Interestingly, 5-HT7 receptor agonists significantly enhanced PS in the MAP group. Changes in the secondary messenger system related to 5-HT7 receptors were also investigated. Adenylate cyclase activator-induced PS enhancements were significantly larger in the MAP group. However, dibutyryl-cAMP-induced PS enhancement was not significantly different. In conclusion, 5-HT-induced inhibition of PS in NAcc was attenuated 5 days after repeated MAP treatment: the change in the effect of 5-HT was probably due to enhancement of the excitatory modulation via the 5-HT7 receptor with adenylate cyclase signal transduction systems.
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Utility of a scoring balloon for a severely calcified lesion: bench test and finite element analysis.
Cardiovasc Interv Ther
PUBLISHED: 10-03-2013
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We aimed to investigate the effectiveness of a scoring balloon catheter in expanding a circumferentially calcified lesion compared to a conventional balloon catheter using an in vitro experiment setting and elucidate the underlying mechanisms of this ability using a finite element analysis. True efficacy of the scoring device and the underlying mechanisms for heavily calcified coronary lesions are unclear. We employed a Scoreflex scoring balloon catheter (OrbusNeich, Hong Kong, China). The ability of Scoreflex to dilate a calcified lesion was compared with a conventional balloon catheter using 3 different sized calcium tubes. The thickness of the calcium tubes were 2.0, 2.25, and 2.5 mm. The primary endpoints were the successful induction of cracks in the calcium tubes and the inflation pressures required for inducing cracks. The inflation pressure required for cracking the calcium tubes were consistently lower with Scoreflex (p < 0.05, Student t test). The finite element analysis revealed that the first principal stress applied to the calcified plaque was higher by at least threefold when applying the balloon catheter with scoring elements. A scoring balloon catheter can expand a calcified lesion with lower pressure than that of a conventional balloon. The finite element analysis revealed that the concentration of the stress observed in the outside of the calcified plaque just opposite to the scoring element is the underlying mechanism of the increased ability of Scoreflex to dilate the calcified lesion.
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Safety and efficacy of drug-eluting stents in women: a patient-level pooled analysis of randomised trials.
Lancet
PUBLISHED: 09-02-2013
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The safety and efficacy of drug-eluting stents (DES) in the treatment of coronary artery disease have been assessed in several randomised trials. However, none of these trials were powered to assess the safety and efficacy of DES in women because only a small proportion of recruited participants were women. We therefore investigated the safety and efficacy of DES in female patients during long-term follow-up.
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Three-year outcome after percutaneous coronary intervention and coronary artery bypass grafting in patients with triple-vessel coronary artery disease: observations from the CREDO-Kyoto PCI/CABG registry cohort-2.
EuroIntervention
PUBLISHED: 08-23-2013
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We sought to investigate medium-term outcome of percutaneous coronary intervention (PCI) compared with coronary artery bypass grafting (CABG) in patients with triple-vessel coronary artery disease (TVD).
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Utility of nicorandil for the measurement of coronary fractional flow reserve.
Cardiovasc Interv Ther
PUBLISHED: 07-19-2013
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Nicorandil, an adenosine triphosphate (ATP)-sensitive potassium channel opener, has been used as an anti-angina drug that causes coronary vasodilation of both epicardial and resistance vessels. We assessed the hyperaemic efficacy of nicorandil for the measurement of coronary fractional flow reserve (FFR). In this prospective, single-centre study, we enrolled 20 consecutive patients (20 lesions) with intermediate coronary artery stenosis. Hyperaemic efficacy of intracoronary bolus injection of nicorandil (2 mg) was compared with that of continuous intravenous infusion of adenosine triphosphate (ATP, 150 ?g/kg/min). The intra-patient difference of FFR value between the two hyperaemic stimuli was evaluated using a non-inferiority design with the margin of 0.03. Among study patients, no serious event occurred with administration of either stimulus. A strong and linear correlation of FFR with ATP and nicorandil was observed (r (2) = 0.98, P < 0.0001). The intra-patient difference of the FFR between nicorandil and ATP was 0.003 (95 % confidence interval -0.004 to 0.011), and the probability for the non-inferiority margin of 0.03 was <0.0001. In conclusion, bolus intracoronary injection of nicorandil was non-inferior to continuous intravenous injection of ATP in achieving maximal hyperaemia. Nicorandil could be considered as an alternative option for achieving maximal coronary and myocardial hyperaemia for the assessment of FFR.
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Solvothermal fabrication of rubidium tungsten bronze for the absorption of near infrared light.
J Nanosci Nanotechnol
PUBLISHED: 07-18-2013
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For fabricating the crystal of Rb(x)WO3, the solvothermal process was performed using a mixed medium of water and ethanol as solvent. It has been found that the morphological evolutions of samples were greatly changed as disordered nanoparticles, bundle of nanorods and microfibers with increasing content of water in the starting solution. Among them, sample synthesized with assistance of 3 ml water consisted of the nanorods with a diameter in the range of 80-150 nm, showing suitable size and morphology as near-infrared shielding material. On the merits of this nanostructure, the thin film of the Rb(x)WO3 nanorods realized excellent shielding of near-infrared light, meanwhile, it selectively transmitted the major part of visible light.
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[Practical approach to infection control and antimicrobial stewardship by medical technologists].
Rinsho Byori
PUBLISHED: 07-17-2013
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Since establishing an antimicrobial management team (AMT) in 2003, we have been promoting both appropriate diagnosis and treatment and improving the prognosis of hospitalized patients with infections. AMT is composed of 4 doctors, 2 nurses, 2 pharmacists and one medical technologist. AMT members meet twice a week and discuss patients with positive blood cultures, with prescribed anti-MRSA drugs and suspected infections. Antimicrobial prescription and clinical laboratory data are obtained from the database of electric medical records and microbiological data from the laboratory database system. The initial step in infection control and antimicrobial stewardship is an accurate diagnosis of infection. Clinical microbiology laboratories play a critical role in infection control and antimicrobial stewardship by reporting accurate and timely results of both bacterial identification and antimicrobial susceptibility tests. Medical technologists are required to develop better competency and proficiency about clinical microbiology in both infection control and antimicrobial stewardship.
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A multicenter randomized comparison of paclitaxel-coated balloon catheter with conventional balloon angioplasty in patients with bare-metal stent restenosis and drug-eluting stent restenosis.
Am. Heart J.
PUBLISHED: 07-01-2013
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The aim of this study was to investigate the efficacy and safety of paclitaxel-coated balloon (PCB) for the treatment of the bare-metal stent restenosis (BMS-ISR) and drug-eluting stent restenosis (DES-ISR).
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Prognostic implications of anemia with or without chronic kidney disease in patients undergoing elective percutaneous coronary intervention.
Int. J. Cardiol.
PUBLISHED: 06-26-2013
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Little is known about the prognostic implications of anemia in patients undergoing elective percutaneous coronary intervention (PCI), especially when they have coexisting chronic kidney disease (CKD).
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Impact of occult renal impairment on early and late outcomes following coronary artery bypass grafting.
Interact Cardiovasc Thorac Surg
PUBLISHED: 06-21-2013
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High serum creatinine is considered an independent risk factor for poor outcomes following coronary artery bypass grafting (CABG). However, the impact of occult renal impairment (ORI), defined as an impaired glomerular filtration rate (GFR) with a normal serum creatinine (SCr) level, remains unclear. Thus, we sought to investigate the impact of ORI on outcomes after CABG.
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MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice.
Nat Commun
PUBLISHED: 04-27-2013
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MicroRNAs (miRs) are small non-protein-coding RNAs that bind to specific mRNAs and inhibit translation or promote mRNA degradation. Recent reports have indicated that miR-33, which is located within the intron of sterol regulatory element-binding protein (SREBP) 2, controls cholesterol homoeostasis and may be a potential therapeutic target for the treatment of atherosclerosis. Here we show that deletion of miR-33 results in marked worsening of high-fat diet-induced obesity and liver steatosis. Using miR-33(-/-)Srebf1(+/-) mice, we demonstrate that SREBP-1 is a target of miR-33 and that the mechanisms leading to obesity and liver steatosis in miR-33(-/-) mice involve enhanced expression of SREBP-1. These results elucidate a novel interaction between SREBP-1 and SREBP-2 mediated by miR-33 in vivo.
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Percutaneous coronary intervention in patients with previous coronary artery bypass grafting (from the j-Cypher Registry).
Am. J. Cardiol.
PUBLISHED: 04-27-2013
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A paucity of data is available from large-scale studies evaluating the long-term outcomes of percutaneous coronary intervention in patients who had previously undergone coronary artery bypass grafting (CABG) in the drug-eluting stent era. Of 12,812 patients who had undergone sirolimus-eluting stent implantation in the j-Cypher registry, 919 (7.2%) had a history of CABG and had significantly higher crude 5-year mortality (19.9% vs 14.0%, p <0.001). After adjusting for confounders, the excess risk of death was no longer significant (hazard ratio 0.99, 95% confidence interval 0.83 to 1.18, p = 0.90), and the adjusted risk of target lesion revascularization was significantly higher in patients with previous CABG than in those without (hazard ratio 1.25, 95% confidence interval 1.06 to 1.47, p = 0.01). Of the patients with previous CABG, those who had undergone ?1 saphenous vein graft intervention had significantly higher adjusted risks of cardiac death (hazard ratio 2.21, 95% confidence interval 1.26 to 3.76, p = 0.01), myocardial infarction (hazard ratio 2.56, 95% confidence interval 1.10 to 5.60, p = 0.03), target lesion revascularization (hazard ratio 2.65, 95% confidence interval 1.82 to 3.81, p <0.001), and definite stent thrombosis (hazard ratio 7.70, 95% confidence interval 1.99 to 29.1, p = 0.004) compared with those who underwent percutaneous coronary intervention only for the native coronary artery. In conclusion, the adjusted mortality was similar between patients with and without previous CABG, despite a significantly different risk of target lesion revascularization. Among the patients with previous CABG, those with saphenous vein graft intervention using a first-generation drug-eluting stent had worse clinical outcomes than those with a native coronary artery target only.
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Significance of non-type 1 anterior early repolarization in patients with inferolateral early repolarization syndrome.
J. Am. Coll. Cardiol.
PUBLISHED: 04-18-2013
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The aim of this study was to investigate the significance of non-type 1 anterior early repolarization (NT1-AER) combined with inferolateral early repolarization syndrome (ERS).
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Impact of polyvascular disease on clinical outcomes in patients undergoing coronary revascularization: an observation from the CREDO-Kyoto Registry Cohort-2.
Atherosclerosis
PUBLISHED: 03-18-2013
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Patients with coronary artery disease (CAD) often have prior stroke or concomitant extra-cardiac vascular disease (EVD) such as cerebral, aortic, or peripheral vascular disease. However, clinical outcomes after coronary revascularization in patients with polyvascular disease have not been fully elucidated.
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Long-term outcomes after percutaneous coronary intervention for chronic total occlusion (from the CREDO-Kyoto registry cohort-2).
Am. J. Cardiol.
PUBLISHED: 03-07-2013
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Despite improving success rate of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) lesions, the clinical benefit of recanalization of CTO is still a matter of debate. Of 13,087 patients who underwent PCI in the CREDO-Kyoto registry cohort-2, 1,524 patients received PCI for CTO (CTO-PCI). Clinical outcomes were compared between 1,192 patients with successful CTO-PCI and 332 patients with failed CTO-PCI. In-hospital death tended to occur less frequently in the successful CTO-PCI group than in the failed CTO-PCI group (1.4% vs 3.0%, p = 0.053). Through 3-year follow-up, the cumulative incidence of all-cause death was not significantly different between the successful and failed CTO-PCI groups (9.0% vs 13.1%, p = 0.18), whereas the cumulative incidence of cardiac death was significantly less in the successful CTO-PCI group than in the failed CTO-PCI group (4.5% vs 8.4%, p = 0.03). However, after adjusting confounders, successful CTO-PCI was associated with lesser risk for neither all-cause death (hazard ratio 0.93, 95% confidence interval 0.64 to 1.37, p = 0.69) nor cardiac death (hazard ratio 0.71, 95% confidence interval 0.44 to 1.16, p = 0.16). The cumulative incidence of coronary artery bypass grafting (CABG) was remarkably less in patients with successful PCI compared with those with failed PCI (1.8% vs 19.6%, p <0.0001). In conclusion, successful CTO-PCI compared with failed PCI was not associated with lesser risk for 3-year mortality. However, successful CTO-PCI was associated with significantly less subsequent CABG.
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Comparison of outcomes using the sirolimus-eluting stent in calcified versus non-calcified native coronary lesions in patients on- versus not on-chronic hemodialysis (from the j-Cypher registry).
Am. J. Cardiol.
PUBLISHED: 03-04-2013
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The impact of lesion calcium on long-term outcomes after drug-eluting stent implantation has not been adequately addressed. In 10,595 patients (16,803 lesions) who were exclusively treated with sirolimus-eluting stents in the j-Cypher registry, 5-year outcomes were compared between patients with ?1 lesion with moderate or severe calcification (the calcium group) and those with noncalcified lesions only (the noncalcium group). Analyses were stratified by hemodialysis (HD) status (non-HD stratum [calcium n = 3,191, noncalcium n = 6,824] and HD stratum [calcium n = 415, noncalcium n = 165]). Adjusted risk in the calcium group for death and target lesion revascularization was significant in the non-HD stratum (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.18 to 1.52, p <0.0001, and HR 1.2, 95% CI 1.07 to 1.36, p = 0.003) and the HD stratum (HR 1.4, 95% CI 1.06 to 1.86, p = 0.02, and HR 2.25, 95% CI 1.51 to 3.36, p <0.0001). Risk for definite stent thrombosis tended to be higher in the calcium group in the HD stratum (HR 5.05, 95% CI 0.66 to 38.9, p = 0.12) but not in then non-HD stratum (HR 1.16, 95% CI 0.81 to 1.67, p = 0.41). The use of rotational atherectomy in patients with severe calcification did not have a significant impact on the cumulative incidence of target lesion revascularization in the non-HD stratum (17.7% [n = 268] with vs 18.2% [n = 588] without rotational atherectomy, p = 0.68) and the HD stratum (54.7% [n = 115] with vs 51.9% [n = 118] without rotational atherectomy, p = 0.19). In conclusion, regardless of HD status, patients with calcified lesions have increased long-term risk for death and target lesion revascularization after sirolimus-eluting stent implantation.
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Angiographic findings of everolimus-eluting as compared to sirolimus-eluting stents: angiographic sub-study from the Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial (RESET).
Cardiovasc Interv Ther
PUBLISHED: 02-26-2013
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Several recent randomized trials comparing everolimus-eluting stent (EES) and sirolimus-eluting stent (SES) reported similar clinical outcomes. This study was aimed to clarify the differences in the angiographic findings of EES as compared to SES. Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial is a prospective multicenter randomized open-label trial comparing EES with SES in Japan. From February to July 2010, 3197 patients were randomly assigned to receive either EES or SES. Of these, angiographic sub-study enrolled 571 patients (EES 285 patients, SES 286 patients). Angiograms were assessed qualitatively and quantitatively at procedure and at 8-12 months in the independent core angiographic laboratory. Late loss of the proximal edges tended to be greater in the EES group than that in the SES group (0.12 ± 0.49 vs. 0.04 ± 0.43 mm, P = 0.05), although late loss in the other segments was similar between the 2 groups. Edge restenosis was mainly observed in EES group, whereas body restenosis was demonstrated in half of SES group. Stent fracture was observed only in the SES group (1.5 %), and peri-stent contrast staining (PSS) tended to be more frequently observed in the SES group than in the EES group (3.6 and 1.5 %, P = 0.18). Restenotic response in the proximal edge was more prominent in the EES group as compared to the SES group. Abnormal angiographic findings such as stent fracture and PSS tended to be more frequent in the SES group.
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Biodegradable polymer biolimus-eluting stent versus durable polymer everolimus-eluting stent: a randomized, controlled, noninferiority trial.
J. Am. Coll. Cardiol.
PUBLISHED: 02-19-2013
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NEXT (NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial) was designed for evaluating the noninferiority of a biolimus-eluting stent (BES) relative to an everolimus-eluting stent (EES) in terms of target lesion revascularization (TLR) at 1 year.
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Comparison of 5-year outcomes in patients with and without unprotected left main coronary artery disease after treatment with sirolimus-eluting stents: insights from the j-Cypher registry.
JACC Cardiovasc Interv
PUBLISHED: 01-18-2013
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This study assessed 5-year outcomes after implantation of sirolimus-eluting stents (SES) for unprotected left main coronary artery (ULMCA) disease in comparison with that for non-left main disease.
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Nardilysin prevents amyloid plaque formation by enhancing ?-secretase activity in an Alzheimers disease mouse model.
Neurobiol. Aging
PUBLISHED: 01-17-2013
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Amyloid beta (A?) peptide, the main component of senile plaques in patients with Alzheimers disease (AD), is derived from proteolytic cleavage of amyloid precursor protein (APP) by ?- and ?-secretases. Alpha-cleavage of APP by ?-secretase has a potential to preclude the generation of A? because it occurs within the A? domain. We previously reported that a metalloendopeptidase, nardilysin (N-arginine dibasic convertase; NRDc) enhances ?-cleavage of APP, which results in the decreased generation of A? in vitro. To clarify the in vivo role of NRDc in AD, we intercrossed transgenic mice expressing NRDc in the forebrain with an AD mouse model. Here we demonstrate that the neuron-specific overexpression of NRDc prevents A? deposition in the AD mouse model. The activity of ?-secretase in the mouse brain was enhanced by the overexpression of NRDc, and was reduced by the deletion of NRDc. However, reactive gliosis adjacent to the A? plaques, one of the pathological features of AD, was not affected by the overexpression of NRDc. Taken together, our results indicate that NRDc controls A? formation through the regulation of ?-secretase.
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Bmp7 maintains undifferentiated kidney progenitor population and determines nephron numbers at birth.
PLoS ONE
PUBLISHED: 01-01-2013
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The number of nephrons, the functional units of the kidney, varies among individuals. A low nephron number at birth is associated with a risk of hypertension and the progression of renal insufficiency. The molecular mechanisms determining nephron number during embryogenesis have not yet been clarified. Germline knockout of bone morphogenetic protein 7 (Bmp7) results in massive apoptosis of the kidney progenitor cells and defects in early stages of nephrogenesis. This phenotype has precluded analysis of Bmp7 function in the later stage of nephrogenesis. In this study, utilization of conditional null allele of Bmp7 in combination with systemic inducible Cre deleter mice enabled us to analyze Bmp7 function at desired time points during kidney development, and to discover the novel function of Bmp7 to inhibit the precocious differentiation of the progenitor cells to nephron. Systemic knockout of Bmp7 in vivo after the initiation of kidney development results in the precocious differentiation of the kidney progenitor cells to nephron, in addition to the prominent apoptosis of progenitor cells. We also confirmed that in vitro knockout of Bmp7 in kidney explant culture results in the accelerated differentiation of progenitor population. Finally we utilized colony-forming assays and demonstrated that Bmp7 inhibits epithelialization and differentiation of the kidney progenitor cells. These results indicate that the function of Bmp7 to inhibit the precocious differentiation of the progenitor cells together with its anti-apoptotic effect on progenitor cells coordinately maintains renal progenitor pool in undifferentiated status, and determines the nephron number at birth.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.