Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.

Quantitative IVUS indices can be reliably used for identifying significant epicardial coronary artery stenoses.

1) DDFP emulsion, an echo contrast agent, significantly enhances the clot-disrupting effect of low frequency ultrasound in vitro and in an in vivo rabbit iliofemoral occlusion model. 2) This simple combination therapy has potential for clinical application in patients with thrombotic arterial occlusions.

In vivo transcutaneous ultrasound significantly augments lysis of thrombi with streptokinase in rabbit iliofemoral arteries.

The nuclear receptor related-1 (Nurr1) protein plays an important role in both the development of neural precursor cells (NPCs) and cognitive functions. Despite its relevance, the effects of Nurr1 on adult hippocampal neurogenesis have not been thoroughly investigated. Here we used RT-PCR, western blot, and immunocytochemistry to show that adult hippocampal NPCs abundantly express Nurr1. We then examined the effect of Nurr1 activation on adult hippocampal NPCs using amodiaquine (AQ), an anti-malarial drug that was recently discovered to be a Nurr1 agonist. Cell proliferation assay showed that AQ significantly increased cell proliferation. AQ-treated NPCs showed increased levels of phosphorylation of Akt and ERK1/2 whereas AQ-treated Nurr1 siRNA-transfected NPCs showed no changes in those levels. Further immunocytochemical and immunohistochemical analyses confirmed the stimulating effect of Nurr1 agonist on the proliferation and differentiation of adult hippocampal NPCs both in vivo and in vitro. In addition to its effects on proliferation and differentiation of NPCs, AQ-treated mice showed a significant enhancement of both short- and long-term memory in the Y-maze and the novel object recognition test. These data suggest that activation of Nurr1 may enhance cognitive functions by increasing adult hippocampal neurogenesis and also indicate that Nurr1 may be used as a therapeutic target for the treatment of memory disorders and cognitive impairment observed in neurodegenerative diseases.

The results of this study show that although women have a higher in-hospital mortality than men, female gender itself is not an independent risk factor for in-hospital mortality.

Objective-Plaque rupture may be the local expression of a widespread coronary instability. This study aimed to investigate:(1) the prevalence and characteristics of nonculprit plaque rupture; (2) the pancoronary atherosclerotic phenotype in patients with and without nonculprit plaque rupture; and (3)

C oronary plaque rupture with subsequent thrombosis is the most common substrate of acute coronary syndrome and sudden cardiac death. 1-4 Although this phenomenon is often considered to result from a local instability, many of the patho-physiological factors believed to trigger plaque rupture (eg, inflammation or mechanical stress modulated by sympathetic tone) exert a widespread effect within the coronary tree. 5,6 In a seminal coronary angiography study, Goldstein et al 7 found that a substantial proportion of patients (≈40%) presenting with acute myocardial infarction (AMI) harbors multiple complex coronary lesions, which are related to adverse clinical outcomes. Subsequent intravascular ultrasound investigations yielded variable results, with a prevalence of plaque rupture at sites remote from the culprit lesion ranging from 14% to 79% in patients with acute presentations. 8-11 Interestingly, some of these studies suggested that additional plaque ruptures may occur even in stable or asymptomatic patients. 9,10 Using coronary angioscopy, Asakura et al 12 observed the diffuse presence of yellow plaques in patients with recent AMI, although the detection of thrombus distant from the culprit lesion was relatively rare. However, the imaging techniques used in these studies were limited in their spatial resolution and were not the modalities of choice for detecting and characterizing plaque rupture. 13 Therefore, the exact incidence and morphological features of plaque rupture at sites remote from the culprit lesion remain unknown. In addition, the clinical background and pancoronary atherosclerotic phenotype of patients experiencing multiple plaque ruptures have not been fully characterized, and it remains unclear whether multiple plaque ruptures occur simultaneously as the result of a generalized acute plaque destabilization. Optical coherence tomog-raphy (OCT) is a novel intracoronary imaging modality with high spatial resolution (≈10-15 μm), which enables detailed in vivo characterization of atherosclerotic plaques 14 and readily Objective-Plaque rupture may be the local expression of a widespread coronary instability. This study aimed to investigate: (1) the prevalence and characteristics of nonculprit plaque rupture; (2) the pancoronary atherosclerotic phenotype in patients with and without nonculprit plaque rupture; and (3) the prevalence and predictors of multiple plaque ruptures. Approach and Results-Six hundred and seventy-five nonculprit plaques from 261 patients (34 acute myocardial infarction, 73 unstable angina pectoris, and 154 stable angina pectoris) were analyzed by 3-vessel optical coherence tomography. Nonculprit plaque ruptures were identified in 51 patients (20%). Patients with nonculprit plaque ruptures had higher prevalence of thin-cap fibroatheroma (51% versus 13%; P<0.001) in the 3 major epicardial coronary vessels. Multiple plaque ruptures were observed in 20% of patients (38% acute myocardial infarction versus 10% unstable angina pectoris versus 19% stable angina pectoris; P=0.042). Thin...