Intermediate-high-risk pulmonary embolism (PE) is characterized by right ventricular (RV) dysfunction and elevated circulating cardiac troponin levels despite apparent hemodynamic stability at... Show moreIntermediate-high-risk pulmonary embolism (PE) is characterized by right ventricular (RV) dysfunction and elevated circulating cardiac troponin levels despite apparent hemodynamic stability at presentation. In these patients, full-dose systemic thrombolysis reduced the risk of hemodynamic decompensation or death but increased the risk of life-threatening bleeding. Reduced-dose thrombolysis may be capable of improving safety while maintaining reperfusion efficacy. The Pulmonary Embolism International THrOmbolysis (PEITHO)-3 study (ClinicalTrials.gov Identifier: NCT04430569) is a randomized, placebo-controlled, double-blind, multicenter, multinational trial with long-term follow-up. We will compare the efficacy and safety of a reduced-dose alteplase regimen with standard heparin anticoagulation. Patients with intermediate-high-risk PE will also fulfill at least one clinical criterion of severity: systolic blood pressure <= 110mm Hg, respiratory rate >20 breaths/min, or history of heart failure. The primary efficacy outcome is the composite of all-cause death, hemodynamic decompensation, or PE recurrence within 30 days of randomization. Key secondary outcomes, to be included in hierarchical analysis, are fatal or GUSTO severe or life-threatening bleeding; net clinical benefit (primary efficacy outcome plus severe or life-threatening bleeding); and all-cause death, all within 30 days. All outcomes will be adjudicated by an independent committee. Further outcomes include PE-related death, hemodynamic decompensation, or stroke within 30 days; dyspnea, functional limitation, or RV dysfunction at 6 months and 2 years; and utilization of health care resources within 30 days and 2 years. The study is planned to enroll 650 patients. The results are expected to have a major impact on risk-adjusted treatment of acute PE and inform guideline recommendations. Show less
Mahe, I.; Agnelli, G.; Ay, C.; Bamias, A.; Becattini, C.; Carrier, M.; ... ; Laporte, S. 2021
Cancer-associated thrombosis (CT) is associated with a high risk of recurrent venous thromboembolic (VTE) events that require extended anticoagulation in patients with active cancer, putting them... Show moreCancer-associated thrombosis (CT) is associated with a high risk of recurrent venous thromboembolic (VTE) events that require extended anticoagulation in patients with active cancer, putting them at risk of bleeding. The aim of the API-CAT study (NCT03692065) is to assess whether a reduced-dose regimen of apixaban (2.5mg twice daily [bid]) is noninferior to a full-dose regimen of apixaban (5mg bid) for the prevention of recurrent VTE in patients with active cancer who have completed >= 6 months of anticoagulant therapy for a documented index event of proximal deep-vein thrombosis and/or pulmonary embolism. API-CAT is an international, randomized, parallel-group, double-blind, noninferiority trial with blinded adjudication of outcome events. Consecutive patients are randomized to receive apixaban 2.5 or 5mg bid for 12 months. The primary efficacy outcome is a composite of recurrent symptomatic or incidental VTE during the treatment period. The principal safety endpoint is clinically relevant bleeding, defined as a composite of major bleeding or nonmajor clinically relevant bleeding. Assuming a 12-month incidence of the primary outcome of 4% with apixaban and an upper limit of the two-sided 95% confidence interval of the hazard ratio <2.0, 1,722 patients will be randomized, assuming an up to 10% loss in total patient-years (beta=80%; alpha one-sided=0.025). This trial has the potential to demonstrate that a regimen of extended treatment for patients with CT beyond an initial 6 months, with a reduced apixaban dose, has an acceptable risk of recurrent VTE recurrence and decreases the risk of bleeding. Show less
Context. A complex environment exists in the inner few astronomical units of planet-forming disks. High-angular-resolution observations play a key role in our understanding of the disk structure... Show moreContext. A complex environment exists in the inner few astronomical units of planet-forming disks. High-angular-resolution observations play a key role in our understanding of the disk structure and the dynamical processes at work.Aims: In this study we aim to characterize the mid-infrared brightness distribution of the inner disk of the young intermediate-mass star HD 163296 from early VLTI/MATISSE observations taken in the L- and N-bands. We put special emphasis on the detection of potential disk asymmetries.Methods: We use simple geometric models to fit the interferometric visibilities and closure phases. Our models include a smoothed ring, a flat disk with an inner cavity, and a 2D Gaussian. The models can account for disk inclination and for azimuthal asymmetries as well. We also perform numerical hydrodynamical simulations of the inner edge of the disk.Results: Our modeling reveals a significant brightness asymmetry in the L-band disk emission. The brightness maximum of the asymmetry is located at the NW part of the disk image, nearly at the position angle of the semimajor axis. The surface brightness ratio in the azimuthal variation is 3.5 ± 0.2. Comparing our result on the location of the asymmetry with other interferometric measurements, we confirm that the morphology of the r < 0.3 au disk region is time-variable. We propose that this asymmetric structure, located in or near the inner rim of the dusty disk, orbits the star. To find the physical origin of the asymmetry, we tested a hypothesis where a vortex is created by Rossby wave instability, and we find that a unique large-scale vortex may be compatible with our data. The half-light radius of the L-band-emitting region is 0.33 ±0.01 au, the inclination is 52°(-7°/+5°), and the position angle is 143° ± 3°. Our models predict that a non-negligible fraction of the L-band disk emission originates inside the dust sublimation radius for μm-sized grains. Refractory grains or large (≳10 μm-sized) grains could be the origin of this emission. N-band observations may also support a lack of small silicate grains in the innermost disk (r ≲ 0.6 au), in agreement with our findings from L-band data. Show less
Robert-Ebadi, H.; Mostaguir, K.; Hovens, M.M.; Kare, M.; Verschuren, F.; Girard, P.; ... ; Gal, G. le 2017