nearly all regain response upon resuming therapy. Therapy during pregnancy is rarely needed.Background The RESCUE (Randomized Evaluation of Patients with Stable Angina Comparing Utilization of Noninvasive Examinations) trial was a randomized, controlled, multicenter, comparative efficacy outcomes trial designed to assess whether initial testing with coronary computed tomographic angiography (CCTA) is noninferior to single photon emission computed tomography (SPECT) myocardial perfusion imaging in directing patients with stable angina to optimal medical therapy alone or optimal medical therapy with revascularization. Methods and Results The end point was first major adverse cardiovascular event (MACE) (cardiac death or myocardial infarction), or revascularization. Noninferiority margin for CCTA was set a priori as a hazard ratio (HR) of 1.3 (95% CI=0, 1.605). One thousand fifty participants from 44 sites were randomized to CCTA (n=518) or SPECT (n=532). Mean follow-up time was 16.2 (SD 7.9) months. There were no cardiac-related deaths. In patients with a negative CCTA there was 1 acute myocardial infgov/. Identifier NCT01262625.Background Peripheral artery disease (PAD) is a known risk factor for adverse outcomes in patients undergoing percutaneous coronary intervention. However, in some studies PAD is not an independent risk factor. We sought to examine the independent impact of PAD on a large prospective percutaneous coronary intervention registry. Methods and Results From our single-center prospective percutaneous coronary intervention registry, we have retrospectively analyzed 25 690 patients (years 2004-2018). We examined the influence of PAD on short- and long-term outcomes using both regression and propensity-matched analyses. Patients with documented PAD (n=1610, 6.3% of total) were older (66.7±10.8 versus 65.4±12.1, P less then 0.01), had higher rates of diabetes mellitus (69.3% versus 46.3%, P less then 0.01), hypertension (92.1% versus 76.1%, P less then 0.01) and renal failure (38.3% versus 18.2%, P less then 0.01). There were no differences in the rates of stable versus acute presentations, but less were treated with Prasugrel and Ticagrelor (3.3% versus 8.0% and 7.9% versus 11.9%, respectively, P less then 0.001 for both). Both 30-day and 3-year rates of all-cause death and major adverse cardiac events were higher for patients with PAD versus control (4.9% versus 2.1% and 7.3% versus 3.3% death and major adverse cardiac events at 30 days, respectively; 43.4% versus 29.0% and 55.0% versus 37.8%, respectively at 3 years, P less then 0.001 for all). Following multivariate analysis, the presence of PAD was associated with a higher risk of both death (hazard ratio [HR], 1.66; CI 1.52-1.83; P less then 0.001) and major adverse cardiac events (HR, 1.51; CI, 1.40-1.64; P less then 0.001). Conclusions PAD constitutes an independent risk factor for adverse outcomes in patients undergoing percutaneous coronary intervention. Further studies are needed to ascertain which effective therapies may mitigate this risk.Background Hypergravity may promote human hemostasis thereby increasing thrombotic risk. Future touristic suborbital spaceflight will expose older individuals with chronic medical conditions, who are at much higher thromboembolic risk compared with professional astronauts, to hypergravity. Therefore, we tested the impact of hypergravity on hemostasis in healthy volunteers undergoing centrifugation. Methods and Results We studied 20 healthy seated men before and after 15 minutes under 3 Gz hypergravity on a long-arm centrifuge. We obtained blood samples for hemostasis testing before, immediately after, and 30 minutes after centrifugation. Tests included viscoelastic thromboelastometry, platelet impedance aggregometry, endothelial activation markers, blood rheology testing, microparticle analyses, and clotting factor analysis. Exposure to hypergravity reduced plasma volume by 12.5% (P=0.002) and increased the red blood cell aggregation index (P less then 0.05). With hypergravity, thrombelastographic clotting tiibitors release. Hemoconcentration may contribute to the response.Background tPA (tissue-type plasminogen activator) remains the only approved drug for acute ischemic stroke, with a potentially serious adverse effect hemorrhagic transformation. The effects of antithrombotic agents on tPA-induced hemorrhagic transformation after ischemic stroke are not clearly defined. We performed a systematic review and meta-analysis in preclinical studies aiming to evaluate the efficacy of antithrombotic agents on tPA-induced hemorrhagic transformation after ischemic stroke. Methods and Results We conducted a systematic review and meta-analysis of studies testing antithrombotic agents in animal models of tPA-induced hemorrhagic transformation. The pooled effects were calculated using random-effects models, and heterogeneity was explored through meta-regression and subgroup analyses. Publication bias was assessed using trim and fill method and the Egger test. The efficacy of 18 distinct interventions was described in 22 publications. The pooled data showed a significant improvement in cerebral hemorrhage, infarct size, and neurobehavioral outcome in treated compared with control animals (standardized mean difference, 0.45 [95% CI, 0.11-0.78]; standardized mean difference, 1.18 [95% CI, 0.73-1.64]; and standardized mean difference, 0.91 [95% CI, 0.49-1.32], respectively). Subgroup analysis indicated that quality score, random allocation, control of temperature, anesthetic used, stroke model used, route of drug delivery, time of drug administration, and time of assessment were significant factors that influenced the effects of interventions. Conclusions Administration with antiplatelet agents revealed statistically significant improvement in all the outcomes.  https://www.selleckchem.com/products/iso-1.html  Anticoagulant agents showed significant effects in infarct size and neurobehavioral score, but fibrinolytic agents did not show any significant improvement in all the outcomes. The conclusions should be interpreted cautiously given the heterogeneity and publication bias identified in this analysis.