[Which indications and access routes for transcatheter aortic valve implantation? Health technology assessment from HAS]. / Quelles indications et quelles voies d'abord pour l'implantation des valves aortiques percutanées ? Évaluation technologique menée par la Haute Autorité de santé (HAS).

The transcatheter aortic valve implantation should be restricted to patients with severe symptomatic aortic stenosis with a contraindication for a surgical replacement (taking into account surgical risk scores, comorbidities, anatomical conditions, life expectancy and frailty). Patient eligibility should be performed by a heart team with the involvement of a cardiac surgeon, an interventional cardiologist, a clinical cardiologist and an anaesthetist/resuscitation specialist. The advice of a geriatrician is strongly recommended. The long-term efficacy remains unknown. The French National Authority for Health (Haute Autorité de santé [HAS]) reminds that contraindications in the CE mark should be strictly respected (i.e.instructions for use). Extension of current indications should be conditional to the presentation of clinical evidence. Thus, implantation in patients at lower surgical risk or the use of direct transaortic route are not eligible for reimbursement given the current state of knowledge.

Drug-eluting stents in patients at high risk of restenosis: assessment for France.

BACKGROUND: In unselected patients, the incidence of restenosis is lower after placement of drug-eluting stents (DES) than bare-metal stents (BMS) without difference in safety at a time horizon of 4 years. However, DES appears less effective in "off label" patients. OBJECTIVES: The aim of the study was to assess available evidence of DES efficacy and safety by patient category to establish when DES placement may be recommended for reimbursement by the French national health insurance. METHODS: Based on a systematic review by patient category (January 2002 to August 2009), two health technology assessment (HTA) reports and thirty-eight clinical studies not covered by the HTA reports (eleven meta-analysis including ours, eleven randomized trials and sixteen cohort studies) were selected. After assessment of the methodological quality, the studies mostly comparing DES with BMS were reviewed by a panel of health professionals who defined a priori the most relevant end points of safety and efficacy. RESULTS: Seven to fourteen patients treated with DES were needed to avoid one target lesion revascularization (TLR) in patients with lesions >15 mm long, vessel diameter <3 mm, or diabetes, and with some complex lesions (total coronary occlusion, BMS in-stent restenosis multivessel disease, unprotected left main stenosis). DES appeared as safe as other alternatives over a follow-up of up to 4 years when dual antiplatelet therapy was continued for at least 1 year, but statistical power remains limited to conclude for some clinical features. CONCLUSIONS: For reimbursement, DES use should be limited to certain categories of patients. Treatment of particular cases requires a multidisciplinary approach.

Characterization of biomaterials polar interactions in physiological conditions using liquid-liquid contact angle measurements: relation to fibronectin adsorption.

Wettability of biomaterials surfaces and protein-coated substrates is generally characterized with the sessile drop technique using polar and apolar liquids. This procedure is often performed in air, which does not reflect the physiological conditions. In this study, liquid/liquid contact angle measurements were carried out to be closer to cell culture conditions. This technique allowed us to evaluate the polar contribution to the work of adhesion between an aqueous medium and four selected biomaterials widely used in tissue culture applications: bacteriological grade polystyrene (PS), tissue culture polystyrene (tPS), poly(2-hydroxyethyl methacrylate) film (PolyHEMA), and hydroxypropylmethylcellulose-carboxymethylcellulose bi-layered Petri dish (CEL). The contributions of polar interactions were also estimated on the same biomaterials after fibronectin (Fn) adsorption. The quantity of Fn adsorbed on PS, tPS, PolyHEMA and CEL surfaces was evaluated by using the fluorescein-labeled protein. PolyHEMA and CEL were found to be hydrophilic, tPS was moderately hydrophilic and PS was highly hydrophobic. After Fn adsorption on PS and tPS, a significant increase of the surface polar interaction was observed. On PolyHEMA and CEL, no significant adsorption of Fn was detected and the polar interactions remained unchanged. Finally, an inverse correlation between the polarity of the surfaces and the quantity of adsorbed Fn was established.

Do microspheres with narrow or standard size distributions localize differently in vasculature? An experimental study in sheep kidney and uterus.

PURPOSE: To compare standard embolization microspheres (SMS) with microspheres of very narrow size distribution in terms of physical properties and relative distribution within sheep kidney and uterine artery models of embolization. MATERIALS AND METHODS: Standard microspheres (SMS; 500-700 mum and 700-900 mum) were compared with narrow microspheres (NMS) of the same material made with a microfluidic method that produced a much narrower size distribution (600 mum and 800 mum). Characterization of both microspheres was performed in vitro (ie, bead size, water content, and compressive modulus). In the sheep model of kidney and uterus embolization, histopathologic analysis was performed to determine the average vessel size occluded, the number of microspheres per vessel, and the deformation in vivo, with a focus on the localization of the products within the different vascular zones of the organ tissues. RESULTS: In vitro testing showed the physical properties of NMS to be similar to those of SMS. SMS and NMS also possessed the same degree of deformation in vivo. In both embolization models, there were no major differences in the localization of SMS compared with NMS of equivalent mean bead diameters. CONCLUSIONS: Compared with SMS with a normal distribution in size range, NMS with a narrow size distribution did not exhibit a very different distribution within the vasculature of the sheep kidney or uterus.

Probing fibronectin-surface interactions: a multitechnique approach.

The development of adhesive as well as antiadhesive surfaces is essential in various biomaterial applications. In this study, we have used a multidisciplinary approach that combines biological and physicochemical methods to progress in our understanding of cell-surface interactions. Four model surfaces have been used to investigate fibronectin (Fn) adsorption and the subsequent morphology and adhesion of preosteoblasts. Such experimental conditions lead us to distinguish between anti- and proadhesive substrata. Our results indicate that Fn is not able to induce cell adhesion on antiadhesive materials. On adhesive substrata, Fn did not increase the number of adherent cells but favored their spreading. This work also examined Fn-surface interactions using ELISA immunoassays, fluorescent labeling of Fn, and force spectroscopy with Fn-modified tips. The results provided clear evidence of the advantages and limitations of each technique. All of the techniques confirmed the important adsorption of Fn on proadhesive surfaces for cells. By contrast, antiadhesive substrata for cells avoided Fn adsorption. Furthermore, ELISA experiments enabled us to verify the accessibility of cell binding sites to adsorbed Fn molecules.

Enzymatically-tailored pectins differentially influence the morphology, adhesion, cell cycle progression and survival of fibroblasts.

Improved biocompatibility and performance of biomedical devices can be achieved through the incorporation of bioactive molecules on device surfaces. Five structurally distinct pectic polysaccharides (modified hairy regions (MHRs)) were obtained by enzymatic liquefaction of apple (MHR-B, MHR-A and MHR-alpha), carrot (MHR-C) and potato (MHR-P) cells. Polystyrene (PS) Petri dishes, aminated by a plasma deposition process, were surface modified by the covalent linking of the MHRs. Results clearly demonstrate that MHR-B induces cell adhesion, proliferation and survival, in contrast to the other MHRs. Moreover, MHR-alpha causes cells to aggregate, decrease proliferation and enter into apoptosis. Cells cultured in standard conditions with 1% soluble MHR-B or MHR-alpha show the opposite behaviour to the one observed on MHR-B and -alpha-grafted PS. Fibronectin was similarly adsorbed onto MHR-B and tissue culture polystyrene (TCPS) control, but poorly on MHR-alpha. The Fn cell binding site (RGD sequence) was more accessible on MHR-B than on TCPS control, but poorly on MHR-alpha. The disintegrin echistatin inhibited fibroblast adhesion and spreading on MHR-B-grafted PS, which suggests that MHRs control fibroblast behaviour via serum-adhesive proteins. This study provides a basis for the design of intelligently-tailored biomaterial coatings able to induce specific cell functions.

Anti-inflammatory effect of ibuprofen-loaded embolization beads in sheep uterus.

Embolization of blood vessels may result in a variety of side effects which can include pain and inflammation. The objective of this study was to assess the release and effect of ibuprofen (IBU) from Bead Block microspheres (BB) loaded with IBU (IBU-BB) on the foreign body inflammatory reaction in a sheep uterine artery model. Both uterine arteries of 12 hormonally cycled ewes were embolized with 0.5 mL of 500-700 microm BB (n = 6) or IBU-BB (n = 6). Animals were sacrificed at 1 week (1W) or 3 weeks (3W) (n = 3 each group). The gross examination of the organs was performed and distribution of the beads in the tissue was assessed. Inflammation was estimated histologically by quantitative and semiquantitative classification of inflammatory cells on HES and MGG stains and use of videoanalysis after immunohistolabeling with CD-antibodies to a variety of inflammatory cells. At 1W, a significant decrease of inflammatory response was observed for IBU-BB relative to BB in terms of number of lymphocytes and of immunohistochemical staining for CD172a, MHC-II, CD3, and CD4. At 3W, the inflammatory response for IBU-BB was similar to that for BB at 1W in terms of cell populations and moderate intensity. There was no or low amounts of staining for CD8 and CD45RA and none for CD21 in all four groups. Immunohistochemical detection of IBU showed that some drug was still present in the beads at 1W but none was detectable at 3W suggesting it had all eluted. These results signify that the inflammatory response is dampened by the action of IBU eluted from the beads and that IBU-BB can delay postembolization inflammatory reaction.

Modulating in vitro bone cell and macrophage behavior by immobilized enzymatically tailored pectins.

Previous work has reported the results of a multidisciplinary effort producing a proof-of-concept on the use of pectic polysaccharides in the surface modification of medical devices. This study was designed to learn more about the capability of engineered rhamnogalacturonan-I (RG-I) fractions of apple pectin to control bone cell and macrophage behavior. Thermanox or polystyrene Petri dishes were surface modified with two different modified hairy regions (MHRs) obtained by different enzymatic liquefaction processes of apples differing in relative amounts and lengths of their neutral side chains: (long-haired) MHR-alpha and (short-haired) MHR-B. Bone explants from 14-day-old chick embryos were cultured for 14 days on both pectic substrata. MHR-B promoted cell migration and differentiation, MHR-alpha did not. On MHR-alpha, J774.2 macrophages grew well, their percentage in G1 phase was decreased and in S phase increased, and they did not secrete either proinflammatory-cytokines or nitrites. Contrasting results were gained from macrophages on MHR-B, except for nitrite secretion. Thus, we conclude that coatings from tailored pectins show different biological activities in vitro and are potential innovative candidates for improving the biocompatibility of medical devices in various applications.