Objectives. To assess efficacy, comparative effectiveness, and harms of ps ychological and pharmacological treatments for adults with posttraumatic stress disorder (PTSD).
BackgroundMajor advances have been made in the treatment of ST‐elevation myocardial infarction (STEMI) in outpatients. In contrast, little is known about outcomes in STEMI that occur in patients hospitalized for a noncardiac condition.Methods and ResultsThis was a retrospective, single‐center study of inpatient STEMIs from January 1, 2007, to July 31, 2011. Forty‐eight cases were confirmed to be inpatient STEMIs of a total of 139 410 adult discharges. These patients were older and more often female and had higher rates of chronic kidney disease and prior cerebrovascular events compared with 227 patients with outpatient STEMIs treated during the same period. Onset of inpatient STEMI was heralded most frequently by a change in clinical status (60%) and less commonly by patient complaints (33%) or changes on telemetry. Coronary angiography and percutaneous coronary intervention were performed in 71% and 56% of patients, respectively. The median time to obtain ECG (41 [10, 600] versus 5 [2, 10] minutes; P<0.001), ECG to angiography time (91 [26, 209] versus 35 [25, 46] minutes; P<0.001) and ECG to first device activation (FDA) (129 [65, 25] versus 60 [47, 76] minutes; P<0.001) were longer for inpatient versus outpatient STEMI. Survival to discharge was lower for inpatient STEMI (60% versus 96%; P<0.001), and this difference persisted after adjusting for potential confounders.ConclusionsPatients who develop a STEMI while hospitalized for a noncardiac condition are older and more often female, have more comorbidities, have longer ECG‐to‐FDA times, and are less likely to survive than patients with an outpatient STEMI.
Myocyte apoptosis is central to myocardial dysfunction following ischemia/reperfusion (I/R) and during the transition from hypertrophy to heart failure. Focal adhesion kinase (FAK), a non-receptor tyrosine kinase regulates adhesion-dependent survival signals and unopposed FAK activation has been linked to tumor development. We previously showed that conditional myocyte-specific deletion of FAK (MFKO) in the adult heart did not affect basal cardiomyocyte survival or cardiac function but led to dilated cardiomyopathy and heart failure following pressure overload. In the present study, we sought to determine if FAK functions to limit stress-induced cardiomyocyte apoptosis. We reasoned that (I/R), which stimulates robust apoptotic cell death, might uncover an important cardioprotective function for FAK. We found that depletion of FAK markedly exacerbates hypoxia/re-oxygenation-induced cardiomyocyte cell death in vitro. Moreover, deletion of FAK in the adult myocardium resulted in significant increases in I/R-induced infarct size and cardiomyocyte apoptosis with a concomitant reduction in left ventricular function. Finally, our results suggest that NF-κB signaling may play a key role in modulating FAK-dependent cardioprotection, since FAK inactivation blunted activation of the NF-κB survival signaling pathway and reduced levels of the NF-κB target genes, Bcl2 and Bcl-xl. Since the toggling between pro-survival and pro-apoptotic signals remains central to preventing irreversible damage to the heart, we conclude that targeted FAK activation may be beneficial for protecting stress-dependent cardiac remodeling.
Objective-The peroxisome proliferator activated receptor-gamma (PPAR␥) protein is a nuclear transcriptional activator with importance in diabetes management as the molecular target for the thiazolidinedione (TZD) family of drugs. Substantial evidence indicates that the TZD family of PPAR␥ agonists may retard the development of atherosclerosis. However, recent clinical data have suggested that at least one TZD may increase the risk of myocardial infarction and death from cardiovascular disease. In this study, we used a genetic approach to disrupt PPAR␥ signaling to probe the protein's role in smooth muscle cell (SMC) responses that are important for atherosclerosis. Key Words: PPAR␥ Ⅲ smooth muscle cell Ⅲ restenosis P PAR␥, a dynamic nuclear transcriptional regulator, has well characterized roles in adipocyte differentiation, 1 lipid metabolism, 2 and insulin sensitivity. 3,4 Clinically, PPAR␥ is the molecular target of the insulin sensitizing thiazolidinedione (TZD) class of drugs that includes rosiglitazone and pioglitazone. 5 TZD 6 and other PPAR␥ agonists 7 effectively increase insulin sensitivity in type 2 diabetic patients. Many preclinical and clinical studies have suggested that PPAR␥ agonists protect against the development of atherosclerosis 8 -11 and reduce the development of intimal hyperplasia. 9,[12][13][14] In the PROACTIVE trial, the PPAR␥ agonist pioglitazone had beneficial effects on the combined secondary end points of myocardial infarction, stroke, and death. 15 However, a recent meta-analysis suggested that the use of the PPAR␥ agonist rosiglitazone for the treatment of diabetes was associated with an increase in risk of myocardial infarction and a trend toward a higher risk of cardiovascular death. 16 Endogenous ligands for PPAR␥ include unsaturated and oxidized fatty acids, eicosanoids, prostaglandins, and possibly lysophospholipids. The putative PPAR␥ agonist lysophosphatidic acid (LPA) accelerates neointimal formation after vessel injury in rodents in a PPAR␥-dependent manner, 17 suggesting that activation of PPAR␥ may promote the development of intimal hyperplasia. However, at present, the role that PPAR␥ plays in regulating vascular responses that underlie atherosclerosis and restenosis remain incompletely understood.Proliferation and migration of vascular smooth muscle cells (SMCs) are key events in the development of intimal hyperplasia that occurs in the context of atherosclerosis and restenosis. 18 PPAR␥ is present in vascular SMCs, 19 and the atheroprotective effects of PPAR␥ ligands have been proposed to relate in part to beneficial effects on SMC biology. Indeed, studies have shown that TZDs inhibit vascular SMC proliferation 12,13 and migration, 12,13,20 while increasing apoptosis. 21 It is not clear whether this is a direct effect of TZDs on PPAR␥ or an "off-target" effect of the drugs, as most studies have inferred a role for PPAR␥ in atherosclerosis on the basis of results with pharmacological interventions. Homozygous deficiency of PPAR␥ is embryonic lethal. 1 Atherosclero...
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