In patients with intermediate-risk pulmonary embolism, fibrinolytic therapy prevented hemodynamic decompensation but increased the risk of major hemorrhage and stroke. (Funded by the Programme Hospitalier de Recherche Clinique in France and others; PEITHO EudraCT number, 2006-005328-18; ClinicalTrials.gov number, NCT00639743.).

SummaryAlthoughplasminogen activator inhibitor 1(PAI-1) is one of the primaryregulators of thefibrinolytic system,italsohas dramatic effects on cell adhesion,detachment and migration.P AI-1 also differsfromotherserine proteaseinhibitors(serpins) in that it is atrace proteininplasma,ithas ashorthalf-life in vivo,its synthesis is highly regulated, and it binds to theadhesiveglycoprotein vitronectin (VN) with high affinity and specificity.These Keywords PAI-1, vascular disease,fibrosis,obesity,cancer unique and diverse properties of PAI-1 probablyaccount forthe manyobservations in the literaturethat correlate abnormalities in PAI-1 gene expression with av ariety of pathological conditions. In this review, we discuss thed iscovery,origin,propertiesand regulation of PAI-1, and then speculate about its potential role in vascular disease,fibrosis,obesity andt he metabolic syndrome,and cancer.

Background-The new, high-sensitivity troponin T (hsTnT) assay may improve risk stratification of normotensive patients with acute pulmonary embolism (PE). We externally validated the prognostic value of hsTnT, and of the simplified Pulmonary Embolism Severity Index (sPESI), in a large multicenter cohort. Methods and Results-We prospectively examined 526 normotensive patients with acute PE; of those, 31 (5.9%) had an adverse 30-day outcome. The predefined hsTnT cutoff value of 14 pg/mL was associated with a high prognostic sensitivity and negative predictive value, comparable to those of the sPESI. were identified as low risk by a sPESI of 0 and hsTnT Ͻ14 pg/mL; none of them had an adverse 30-day outcome. During 6-month follow-up, 52 patients (9.9%) died. Kaplan-Meier analysis illustrated that patients with hsTnT Ն14 pg/mL (Pϭ0.001) and those with sPESI Ն1 (PϽ0.001) had a decreased probability of 6-month survival. Patients with sPESI of 0 and hsTnT Ͻ14 pg/mL at baseline had a 42% reduction in the risk of dying (hazard ratio, 0.58 [0.01-0.42]; Pϭ0.005). Conclusions-The hsTnT assay and the sPESI improve risk stratification of acute PE. Combination of both modalities may yield additive prognostic information and particularly identify possible candidates for out-of-hospital treatment.