There are limited data from randomized trials evaluating the use of antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease.
In a multicenter, open-label trial ...conducted in Japan, we randomly assigned 2236 patients with atrial fibrillation who had undergone percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) more than 1 year earlier or who had angiographically confirmed coronary artery disease not requiring revascularization to receive monotherapy with rivaroxaban (a non-vitamin K antagonist oral anticoagulant) or combination therapy with rivaroxaban plus a single antiplatelet agent. The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause; this end point was analyzed for noninferiority with a noninferiority margin of 1.46. The primary safety end point was major bleeding, according to the criteria of the International Society on Thrombosis and Hemostasis; this end point was analyzed for superiority.
The trial was stopped early because of increased mortality in the combination-therapy group. Rivaroxaban monotherapy was noninferior to combination therapy for the primary efficacy end point, with event rates of 4.14% and 5.75% per patient-year, respectively (hazard ratio, 0.72; 95% confidence interval CI, 0.55 to 0.95; P<0.001 for noninferiority). Rivaroxaban monotherapy was superior to combination therapy for the primary safety end point, with event rates of 1.62% and 2.76% per patient-year, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P = 0.01 for superiority).
As antithrombotic therapy, rivaroxaban monotherapy was noninferior to combination therapy for efficacy and superior for safety in patients with atrial fibrillation and stable coronary artery disease. (Funded by the Japan Cardiovascular Research Foundation; AFIRE UMIN Clinical Trials Registry number, UMIN000016612; and ClinicalTrials.gov number, NCT02642419.).
A highly active iron–nitrogen‐doped carbon nanotube catalyst for the oxygen reduction reaction (ORR) is produced by employing vertically aligned carbon nanotubes (VA‐CNT) with a high specific surface ...area and iron(II) phthalocyanine (FePc) molecules. Pyrolyzing the composite easily transforms the adsorbed FePc molecules into a large number of iron coordinated nitrogen functionalized nanographene (Fe–N–C) structures, which serve as ORR active sites on the individual VA‐CNT surfaces. The catalyst exhibits a high ORR activity, with onset and half‐wave potentials of 0.97 and 0.79 V, respectively, versus reversible hydrogen electrode, a high selectivity of above 3.92 electron transfer number, and a high electrochemical durability, with a 17 mV negative shift of E
1/2 after 10 000 cycles in an oxygen‐saturated 0.5 m H2SO4 solution. The catalyst demonstrates one of the highest ORR performances in previously reported any‐nanotube‐based catalysts in acid media. The excellent ORR performance can be attributed to the formation of a greater number of catalytically active Fe–N–C centers and their dense immobilization on individual tubes, in addition to more efficient mass transport due to the mesoporous nature of the VA‐CNTs.
Oxygen reduction reaction activities of a Fe–N–C doped vertically aligned carbon nanotubes catalyst are investigated. Electrochemical measurements in oxygen‐saturated 0.5 m H2SO4 solution demonstrate a high oxygen reduction reaction (ORR) activity (half‐wave potentials of 0.79 V vs reversible hydrogen electrode and 3.92 to 3.98 electron transfer number) and long‐term electrochemical stability, which is the best ORR performance yet reported for a carbon‐nanotube‐based catalyst.
Background:Since cardiovascular disease accounts for one-quarter of deaths in the Japanese population, we developed a nationwide database using the administrative case-mix Diagnostic Procedure ...Combination (DPC) system (ie, theJapaneseRegistryOfAll cardiac and vascularDiseases (JROAD)-DPC) to reveal the current status of cardiovascular medicine in Japan.Methods and Results:The JROAD-DPC database included 704,593 health records’ data of 2012 from 610 certificated hospitals of the Japanese Circulation Society. The 35,824 patients with acute myocardial infarction (AMI) and 108,665 patients with heart failure (HF) were admitted to hospitals. Increased hospital case volume was associated with reduced in-hospital mortality rates for both AMI and HF (P for trend <0.001). Although there was little variation among AMI patients in terms of aspirin use at discharge (median prescription rate, 83.0%; interquartile range IQR, 76.9–88.0%), there were wide variations in the proportions of patients prescribed β-blockers (BB) and angiotensin-converting enzyme inhibitors (ACEI)/angiotensin-receptor blockers (ARB) at discharge (BB, 41.4%, IQR 27.6–55.7%; ACEI/ARB, 52.0%, IQR 40.3–62.3%). In patients with HF, there were between-hospital variations in medications at discharge (BB, 38.1%, IQR, 27.8–47.6%; ACEI/ARB, 41.0%, IQR 31.7–49.1%).Conclusions:A nationwide administrative database of patients with cardiovascular diseases (JROAD-DPC) provided useful information that will contribute to improved quality of medical care, especially in the aging society of Japan, where HF has become an important health problem. (Circ J 2016; 80: 2327–2335)
The endothelium plays a pivotal role in the regulation of vascular tone by synthesizing and liberating endothelium-derived relaxing factors inclusive of vasodilator prostaglandins (eg, prostacyclin), ...nitric oxide (NO), and endothelium-dependent hyperpolarization factors in a distinct blood vessel size-dependent manner. Large conduit arteries are predominantly regulated by NO and small resistance arteries by endothelium-dependent hyperpolarization factors. Accumulating evidence over the past few decades has demonstrated that endothelial dysfunction and coronary vasomotion abnormalities play crucial roles in the pathogenesis of various cardiovascular diseases. Structural and functional alterations of the coronary microvasculature have been coined as coronary microvascular dysfunction (CMD), which is highly prevalent and associated with adverse clinical outcomes in many clinical settings. The major mechanisms of coronary vasomotion abnormalities include enhanced coronary vasoconstrictive reactivity at epicardial and microvascular levels, impaired endothelium-dependent and endothelium-independent coronary vasodilator capacities, and elevated coronary microvascular resistance caused by structural factors. Recent experimental and clinical research has highlighted CMD as the systemic small artery disease beyond the heart, emerging modulators of vascular functions, novel insights into the pathogenesis of cardiovascular diseases associated with CMD, and potential therapeutic interventions to CMD with major clinical implications. In this article, we will summarize the current knowledge on the endothelial modulation of vascular tone and the pathogenesis of coronary macrovascular and microvascular diseases from bench to bedside, with a special emphasis placed on the mechanisms and clinical implications of CMD.
Background
Although the prognosis of patients experiencing recurrences after surgery for pancreatic cancer is extremely poor, patients who develop recurrence in the lung have a better prognosis ...compared to other types of recurrence. We performed a histo-immunological analysis of the metastatic specimens to identify specific features of this patient subgroup.
Methods
We performed immunohistochemistry for CD4+, CD8+, CD45RO+, Foxp3, and PD-L1 in the lung (
n
= 22), peritoneal (
n
= 18), and liver (
n
= 6) metastases of pancreatic cancer. As microenvironmental and immunonutritional investigations, the tumor-stroma ratio and prognostic nutritional index (PNI) were utilized in the integrative analysis of immunological features.
Results
We identified significantly increased tumor-infiltrating CD4+, CD8+, and CD45RO+ cells in lung metastasis, compared with peritoneal and liver metastases (lung vs. peritoneum/liver, CD4:
P
< 0.001/
P
= 0.015, CD8:
P
< 0.001/
P
= 0.038, CD45RO:
P
= 0.022/
P
= 0.012). The CD8/Foxp3 ratio was higher in the lung than in the liver (
P
= 0.024). PD-L1 expression was significantly higher in lung metastasis than in peritoneal metastasis (
P
= 0.010). Furthermore, we found that lung metastasis had fewer cancer stroma than peritoneal metastasis (
P
< 0.001). A higher PNI was observed in patients with lung metastasis, and PNI was positively correlated with tumor-infiltrating lymphocytes in metastatic sites.
Conclusion
We identified that lung metastasis revealed an immunologically “hot” tumor with increased TILs and PD-L1 expression. This specific feature suggests that patients with lung metastasis can be candidates for immunotherapy, such as immune checkpoint inhibitors; therefore, our study provides a framework for developing individualized treatment strategies for this patient subgroup.
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