Long-term Clinical Outcomes Following Elective Stent Implantation for Unprotected Left Main Coronary Artery Disease

Background/PurposePercutaneous coronary intervention (PCI) has been increasingly adopted for unprotected left main coronary artery (LMCA) disease. The aim of this study was to evaluate the predictors of long-term clinical outcomes in patients after elective stent implantation for unprotected LMCA disease.MethodsA total of 122 patients with medically refractory angina who received coronary stenting for unprotected LMCA disease between August 1997 and December 2008 were included.ResultsDuring the follow-up period of 45 ± 35 months (range: 1–137 months), the incidence of repeated PCI and/or coronary artery bypass grafting (CABG), and cardiovascular and total mortality were 28% (34 patients), 20% (24 patients), and 25% (31 patients), respectively. Multivariate analysis revealed that young age [p = 0.02; hazard ratio (HR): 2.19, 95% confidence interval (CI): 1.11–4.30] and bare-metal stent (BMS) use (p = 0.02; HR: 5.35, 95% CI: 1.27–22.57) were the independent predictors of repeated PCI and/or CABG. Only lower left ventricular ejection fraction (LVEF) could predict both cardiovascular mortality (p = 0.003; HR: 4.25, 95% CI: 1.63–11.08) and total mortality (p = 0.002; HR: 3.95, 95% CI: 1.65–9.45). Lower LVEF (p = 0.001; HR: 0.31, 95% CI: 0.16–0.61) and small stent size (p = 0.01; HR: 5.95, 95% CI: 1.43–24.80) could predict the composite endpoint, including target vessel revascularization and total mortality.ConclusionWe showed that young age and BMS implantation could predict repeated PCI and/or CABG after stent implantation for unprotected LMCA disease. Only lower LVEF could predict both cardiovascular and total mortality. Lower LVEF and small stent size but not BMS implantation could predict composite target vessel revascularization/total mortality

Regulatory T Cells: Potential Target in Anticancer Immunotherapy

SummaryThe concept of regulatory T cells was first described in the early 1970s, and regulatory T cells were called suppressive T cells at that time. Studies that followed have demonstrated that these suppressive T cells negatively regulated tumor immunity and contributed to tumor growth in mice. Despite the importance of these studies, there was extensive skepticism about the existence of these cells, and the concept of suppressive T cells left the center stage of immunologic research for decades. Interleukin-2 receptor α-chain, CD25, was first demonstrated in 1995 to serve as a phenotypic marker for CD4+ regulatory cells. Henceforth, research of regulatory T cells boomed. Regulatory T cells are involved in the pathogenesis of cancer, autoimmune disease, transplantation immunology, and immune tolerance in pregnancy. Recent evidence has demonstrated that regulatory T cellmediated immunosuppression is one of the crucial tumor immune evasion mechanisms and the main obstacle of successful cancer immunotherapy. The mechanism and the potential clinical application of regulatory T cells in cancer immunotherapy are discussed

A delta-doped quantum well system with additional modulation doping

A delta-doped quantum well with additional modulation doping may have potential applications. Utilizing such a hybrid system, it is possible to experimentally realize an extremely high two-dimensional electron gas (2DEG) density without suffering inter-electronic-subband scattering. In this article, the authors report on transport measurements on a delta-doped quantum well system with extra modulation doping. We have observed a 0-10 direct insulator-quantum Hall (I-QH) transition where the numbers 0 and 10 correspond to the insulator and Landau level filling factor ν = 10 QH state, respectively. In situ titled-magnetic field measurements reveal that the observed direct I-QH transition depends on the magnetic component perpendicular to the quantum well, and the electron system within this structure is 2D in nature. Furthermore, transport measurements on the 2DEG of this study show that carrier density, resistance and mobility are approximately temperature (T)-independent over a wide range of T. Such results could be an advantage for applications in T-insensitive devices

Smooth muscle cells;

doi:10.1093/cvr/cvm057 The molecular regulation of GADD153 in apoptosis of cultured vascular smooth muscle cells by cyclic mechanical stretc

Human Mesenchymal Stem Cells Improve Myocardial Performance in a Splenectomized Rat Model of Chronic Myocardial Infarction

Cellular therapy has been applied to animal studies and clinical trials for acute or subacute myocardial infarction. Little is known about the effect of cell therapy on chronic myocardial infarction. The goal of this study was to investigate myocardial performance after human bone marrow-derived mesenchymal stem cell (hMSCs) transplantation in rats with chronic myocardial infarction. Methods: The hMSCs were obtained from adult human bone marrow and expanded in vitro. The purity and characteristics of hMSCs were identified by flow cytometry and immunophenotyping. Splenectomy in male rats was performed to prevent immune reaction. One week after splenectomy, ligation of the left anterior descending coronary artery was performed to induce myocardial infarction. Four weeks after ligation of the coronary artery, culture-expanded hMSCs were injected intramyocardially at the left anterior free wall. Left ventricular function measured by echocardiography, infarct size and immunohistochemical stain were performed to evaluate the effect of the therapy. Results: The engrafted hMSCs were positive for the cardiac marker troponin T. Infarct size (35.4 ± 3.4% vs. 53.3 ± 3.0%, p < 0.001) and fibrotic area (2.6 ± 0.1% vs. 5.9 ± 0.2%, p < 0.001) were significantly smaller in the hMSC-treated group than in the control group at 28 days after therapy. hMSC transplantation resulted in smaller left ventricular end-diastolic dimension (6.5 ± 0.1 mm vs. 7.9 ± 0.7 mm, p < 0.001) and better left ventricular ejection fraction (88.7 ± 1.2% vs. 65.8 ± 2.5%, p < 0.001) than in the control group. Capillary density was markedly increased after hMSC transplantation compared with the control group. Conclusion: This study demonstrates that intramyocardial transplantation of hMSCs improves cardiac function after chronic myocardial infarction through enhancement of angiogenesis and myogenesis in the ischemic myocardium. Transplantation of hMSCs for myocardial regeneration may become the future therapy for chronic myocardial infarction

The Lived Experience of Frailty in Patients Aged 60 Years and Older with Heart Failure: A Qualitative Study

s u m m a r y: Purpose: The prevalence of frailty among patients with heart failure is about 45%. Frailty may result in patients' functional decline, falls, disability, and decreased quality of life. Qualitative studies can explore older patients' perceptions of frailty and help patients cope with it. However, a qualitative approach that explores the experience of frailty in older patients living with heart failure is lacking. This study aimed to explore the lived experience of frailty in older patients with heart failure. Methods: This qualitative study applies Giorgi's phenomenological method. Data were collected from October 2019 to August 2020. Thirteen older patients with heart failure aged at least 60 years were recruited using purposive sampling from a medical center in Taiwan. The participants participated in an in-depth interview using a semistructured interview guide. Results: Seven themes were identified: “being reborn at the end of the road but having difficulty recovering”, “living with a disease with an ineffable feeling”, “feeling like being drained: physical weakness and a dysfunctional body”, “struggling with impaired physical mobility and facing unexpected events”, “suffering from mental exhaustion”, “receiving care from loved ones”, and “turning over a new leaf”. Conclusions: Frailty in older patients with heart failure was obscure and difficult to describe. Frailty could be improved by medical intervention, self-management, and social support but was difficult to reverse. Patients with heart failure should be evaluated for frailty using multidimensional assessment tools at first diagnosis and provided frailty-related information so that patients have proper insight into their disease as early as possible

Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1)

Bladder cancer is one of the most frequent cancers among males, and its poor survival rate reflects problems with aggressiveness and chemo-resistance. Recent interest has focused on the use of chemopreventatives (nontoxic natural agents that may suppress cancer progression) to induce targeted apoptosis for cancer therapy. Capsaicin, which has anti-cancer properties, is one such agent. It is known to preferentially inhibit a tumor-associated NADH oxidase (tNOX) that is preferentially expressed in cancer/transformed cells. Here, we set out to elucidate the correlation between tNOX expression and the inhibitory effects of capsaicin in human bladder cancer cells. We showed that capsaicin downregulates tNOX expression and decreases bladder cancer cell growth by enhancing apoptosis. Moreover, capsaicin was found to reduce the expression levels of several proteins involved in cell cycle progression, in association with increases in the cell doubling time and enhanced cell cycle arrest. Capsaicin was also shown to inhibit the activation of ERK, thereby reducing the phosphorylation of paxillin and FAK, which leads to decreased cell migration. Finally, our results indicate that RNA interference-mediated tNOX depletion enhances spontaneous apoptosis, prolongs cell cycle progression, and reduces cell migration and the epithelial-mesenchymal transition. We also observed a downregulation of sirtuin 1 (SIRT1) in these tNOX-knockdown cells, a deacetylase that is important in multiple cellular functions. Taken together, our results indicate that capsaicin inhibits the growth of bladder cancer cells by inhibiting tNOX and SIRT1 and thereby reducing proliferation, attenuating migration, and prolonging cell cycle progression