Pharmacokinetic analysis after implantation of everolimus-eluting self-expanding stents in the peripheral vasculature

Background: A novel self-expanding drug-eluting stent was designed to release everolimus 225 mu g/cm(2) to prevent restenosis following peripheral arterial intervention. The purpose of this study was to measure the pharmacokinetic profile of everolimus following stent implantation. Methods: One hundred four patients with symptomatic peripheral arterial disease underwent implantation of everolimus-eluting stents in the femoropopliteal arteries. In a prespecified subset of 26 patients, blood samples for assay of everolimus content were collected prior to stent implantation, at 1, 4, and 8 hours postprocedure, prior to discharge, and at 1 month postproccdure. Results: A total of 39 stents, ranging from 28 mm to 100 mm in length, were implanted in 26 patients, resulting in a total delivered everolimus dose range of 3.0 to 7.6 mg. Following the procedure, the maximum observed everolimus blood concentrations (C-max) varied from 1.83 +/- 0.05 ng/mL after implantation of a single 80-mm stent to 4.66 +/- 1.78 ng/mL after implantation of two 100-mm stents. The mean time to peak concentration (T-max) varied from 6.8 hours to 35 hours. The pharmacokinetics of everolimus were dose-proportional in that dose-normalized C-max and area under the curve values were constant over the studied dose range. Conclusions: After implantation of everolimus-eluting self-expanding stents in the femoropopliteal arteries, systemic blood concentrations of everolimus are predictable and considerably lower than blood concentrations observed following safe oral administration of everolimus

First clinical trial of nitinol self-expanding everolimus-eluting stent implantation for peripheral arterial occlusive disease

BackgroundA novel self-expanding drug-eluting stent was designed to slowly release everolimus to prevent restenosis following peripheral arterial intervention. The purpose of the first-in-human Superficial Femoral Artery Treatment with Drug-Eluting Stents (STRIDES) trial was to evaluate the safety and efficacy of this device for the treatment of symptomatic superficial femoral and proximal popliteal arterial occlusive disease.Methods and ResultsOne hundred four patients were enrolled at 11 European investigative centers in a prospective, nonrandomized, single-arm trial. The patients had severe symptomatic vascular disease, including a significant proportion of patients with critical limb ischemia (17%), diabetes (39%), and single-vessel outflow (26%). The mean lesion length was 9.0 ± 4.3 cm. Ninety-nine percent of patients were available for 12-month follow-up, including duplex imaging in 90% and arteriography in 83%. Clinical improvement, defined as a sustained decrease in Rutherford-Becker clinical category, was achieved in 80% of patients. Primary patency (freedom from ≥50% in-stent restenosis) was 94 ± 2.3% and 68 ± 4.6% at 6 and 12 months, respectively. Plain radiographic examination of 122 implanted devices at 12 months revealed no evidence for stent fracture.ConclusionsThe everolimus-eluting self-expanding nitinol stent can be successfully implanted in patients with severe peripheral arterial disease with favorable outcomes and clinical improvements observed in the majority of patients

Opening a new window to other worlds with spectropolarimetry

A high level of diversity has already been observed among the planets of our own Solar System. As such, one expects extrasolar planets to present a wide range of distinctive features, therefore the characterisation of Earth- and super Earth-like planets is becoming of key importance in scientific research. The SEARCH (Spectropolarimetric Exoplanet AtmospheRe CHaracerisation) mission proposal of this paper represents one possible approach to realising these objectives. The mission goals of SEARCH include the detailed characterisation of a wide variety of exoplanets, ranging from terrestrial planets to gas giants. More specifically, SEARCH will determine atmospheric properties such as cloud coverage, surface pressure and atmospheric composition, and may also be capable of identifying basic surface features. To resolve a planet with a semi major axis of down to 1.4AU and 30pc distant SEARCH will have a mirror system consisting of two segments, with elliptical rim, cut out of a parabolic mirror. This will yield an effective diameter of 9 meters along one axis. A phase mask coronagraph along with an integral spectrograph will be used to overcome the contrast ratio of star to planet light. Such a mission would provide invaluable data on the diversity present in extrasolar planetary systems and much more could be learned from the similarities and differences compared to our own Solar System. This would allow our theories of planetary formation, atmospheric accretion and evolution to be tested, and our understanding of regions such as the outer limit of the Habitable Zone to be further improved.Comment: 23 pages, accepted for publication in Experimental Astronom

Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study.

Transcatheter arterial chemoembolization (TACE) offers a survival benefit to patients with intermediate hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge-conventional TACE. Recently, a drug-eluting bead (DC Bead) has been developed to enhance tumor drug delivery and reduce systemic availability. This randomized trial compares conventional TACE (cTACE) with TACE with DC Bead for the treatment of cirrhotic patients with HCC. Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and/or multinodular, unresectable, N0, M0 HCCs were randomized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin. Randomization was stratified according to Child-Pugh status (A/B), performance status (ECOG 0/1), bilobar disease (yes/no), and prior curative treatment (yes/no). The primary endpoint was tumor response (EASL) at 6 months following independent, blinded review of MRI studies. The drug-eluting bead group showed higher rates of complete response, objective response, and disease control compared with the cTACE group (27% vs. 22%, 52% vs. 44%, and 63% vs. 52%, respectively). The hypothesis of superiority was not met (one-sided P = 0.11). However, patients with Child-Pugh B, ECOG 1, bilobar disease, and recurrent disease showed a significant increase in objective response (P = 0.038) compared to cTACE. DC Bead was associated with improved tolerability, with a significant reduction in serious liver toxicity (P < 0.001) and a significantly lower rate of doxorubicin-related side effects (P = 0.0001). TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease

High precision astrometry mission for the detection and characterization of nearby habitable planetary systems with the Nearby Earth Astrometric Telescope (NEAT)

(abridged) A complete census of planetary systems around a volume-limited sample of solar-type stars (FGK dwarfs) in the Solar neighborhood with uniform sensitivity down to Earth-mass planets within their Habitable Zones out to several AUs would be a major milestone in extrasolar planets astrophysics. This fundamental goal can be achieved with a mission concept such as NEAT - the Nearby Earth Astrometric Telescope. NEAT is designed to carry out space-borne extremely-high-precision astrometric measurements sufficient to detect dynamical effects due to orbiting planets of mass even lower than Earth's around the nearest stars. Such a survey mission would provide the actual planetary masses and the full orbital geometry for all the components of the detected planetary systems down to the Earth-mass limit. The NEAT performance limits can be achieved by carrying out differential astrometry between the targets and a set of suitable reference stars in the field. The NEAT instrument design consists of an off-axis parabola single-mirror telescope, a detector with a large field of view made of small movable CCDs located around a fixed central CCD, and an interferometric calibration system originating from metrology fibers located at the primary mirror. The proposed mission architecture relies on the use of two satellites operating at L2 for 5 years, flying in formation and offering a capability of more than 20,000 reconfigurations (alternative option uses deployable boom). The NEAT primary science program will encompass an astrometric survey of our 200 closest F-, G- and K-type stellar neighbors, with an average of 50 visits. The remaining time might be allocated to improve the characterization of the architecture of selected planetary systems around nearby targets of specific interest (low-mass stars, young stars, etc.) discovered by Gaia, ground-based high-precision radial-velocity surveys.Comment: Accepted for publication in Experimental Astronomy. The full member list of the NEAT proposal and the news about the project are available at http://neat.obs.ujf-grenoble.fr. The final publication is available at http://www.springerlink.co

The Comet Interceptor Mission

Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum ΔV capability of 600 ms−1. Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule