The Future of Antitrust: New Challenges to the Consumer Welfare Paradigm and Legislative Proposals

On November 14, 2019, the Federalist Society\u27s Corporations, Securities, & Antitrust Practice Group hosted a panel for the 2019 National Lawyers Convention at the Mayflower Hotel in Washington, DC. The panel discussed The Future of Antitrust: New Challenges to the Consumer Welfare Paradigm and Legislative Proposals”

Vessel Size and Outcome After Coronary Drug-Eluting Stent Placement Results From a Large Cohort of Patients Treated With Sirolimus- or Paclitaxel-Eluting Stents

ObjectivesThis study sought to investigate the influence of vessel size on the outcomes of patients after drug-eluting stent (DES) implantation.BackgroundThere are no dedicated studies on the influence of vessel size on the outcomes of patients treated with different DES.MethodsThe study population was composed of 2,058 consecutive patients who received sirolimus-eluting stents (SES) or paclitaxel-eluting stents (PES). Patients were grouped into tertiles according to vessel size (<2.41 mm in the lower tertile, 2.41 to 2.84 mm in the middle tertile, and >2.84 mm in the upper tertile). The primary end point was target lesion revascularization (TLR). Secondary end points were binary angiographic restenosis and the composite of death or myocardial infarction.ResultsVessel size did not influence the composite end point of death and myocardial infarction. The TLR rates were higher among patients in the lower tertile (12.1%) as compared with the middle (8.4%) and upper (8.0%) tertiles (p = 0.02). In a multivariate analysis, vessel size emerged an independent predictor of TLR (p = 0.009). The model showed also a significant interaction between DES type and vessel size regarding TLR (p = 0.008). There was a significant difference in TLR rates among patients treated with SESs (8.6%) and PESs (16.4%) in the lower tertile (p = 0.002), but not in the middle and upper tertiles.ConclusionsThe influence of vessel size on restenosis is related to the specific DES used, with SESs providing better outcomes than PESs in small but not in large coronary vessels

Sirolimus inhibits key events of restenosis in vitro/ex vivo: evaluation of the clinical relevance of the data by SI/MPL- and SI/DES-ratio's

<p>Abstract</p> <p>Background</p> <p>Sirolimus (SRL, Rapamycin) has been used successfully to inhibit restenosis both in drug eluting stents (DES) and after systemic application. The current study reports on the effects of SRL in various human in vitro/ex vivo models and evaluates the theoretical clinical relevance of the data by SI/MPL- and SI/DES-ratio's.</p> <p>Methods</p> <p>Definition of the SI/MPL-ratio: relation between <b>s</b>ignificant <b>i</b>nhibitory effects in vitro/ex vivo and the <b>m</b>aximal <b>p</b>lasma <b>l</b>evel after systemic administration in vivo (6.4 ng/ml for SRL). Definition of the SI/DES-ratio: relation between <b>s</b>ignificant <b>i</b>nhibitory effects in vitro/ex vivo and the drug concentration in <b>DES </b>(7.5 mg/ml in the ISAR drug-eluting stent platform). Part I of the study investigated in cytoflow studies the effect of SRL (0.01–1000 ng/ml) on TNF-α induced expression of intercellular adhesion molecule 1 (ICAM-1) in human coronary endothelial cells (HCAEC) and human coronary smooth muscle cells (HCMSMC). Part II of the study analysed the effect of SRL (0.01–1000 ng/ml) on cell migration of HCMSMC. In part III, IV, and V of the study ex vivo angioplasty (9 bar) was carried out in a human organ culture model (HOC-model). SRL (50 ng/ml) was added for a period of 21 days, after 21 and 56 days cell proliferation, apoptosis, and neointimal hyperplasia was studied.</p> <p>Results</p> <p>Expression of ICAM-1 was significantly inhibited both in HCAEC (SRL ≥ 0.01 ng/ml) and HCMSMC (SRL ≥ 10 ng/ml). SRL in concentrations ≥ 0.1 ng/ml significantly inhibited migration of HCMSMC. Cell proliferation and neointimal hyperplasia was inhibited at day 21 and day 56, significance (p < 0.01) was achieved for the inhibitory effect on cell proliferation in the media at day 21. The number of apoptotic cells was always below 1%.</p> <p>Conclusion</p> <p>SI/MPL-ratio's ≤ 1 (ICAM-1 expression, cell migration) characterize inhibitory effects of SRL that can be theoretically expected both after systemic and local high dose administration, a SI/MPL-ratio of 7.81 (cell proliferation) represents an effect that was achieved with drug concentrations 7.81-times the MPL. SI/DES-ratio's between 10^-6and 10^-8indicate that the described inhibitory effects of SRL have been detected with micro to nano parts of the SRL concentration in the ISAR drug-eluting stent platform. Drug concentrations in DES will be a central issue in the future.</p

Limus is not limus--a proposal to adjust terminology in the context of drug-eluting stents

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In-stent restenosis: Molecular mechanisms and therapeutic principles

Publicación digital.-- Documento en word.Peer reviewe

Stent restenosis

3 páginas.Peer reviewe