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AASLD ¼ American Association for the Study of Liver Disease, aPTT ¼ activated partial thromboplastin time, CI ¼ confidence interval, CVC ¼ central venous catheter, DAPT ¼ dual antiplatelet therapy, DOAC ¼ direct oral anticoagulant, DVT ¼ deep vein thrombosis, FFP ¼ fresh frozen plasma, INR ¼ International Normalized Ratio, LMWH ¼ low molecular weight heparin, NVAF ¼ nonvalvular atrial fibrillation, PEG ¼ percutaneous endoscopic gastrostomy, PT ¼ prothrombin time, RCT ¼ randomized controlled trial, VKA ¼ vitamin K antagonist, VTE ¼ venous thromboembolism

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The ability of diverse carotenoid to inhibit methylcholanthrene-induced transformation of 10T1/2 cells has been investigated. When delivered using tetrahydrofuran as a novel solvent, all carotenoids were absorbed by cultured cells. When continuously administered to methylcholanthrene-treated cultures 7 days after removal of the carcinogen, canthaxanthin, beta-carotene, alpha-carotene and lycopene inhibited the production of transformed foci in a dose-dependent manner in the above order of potency. This activity was not associated with drug toxicity or antiproliferative effects. Renierapurpurin and bixin did not inhibit transformation at concentrations less than or equal to 10(-5) M. Lutein was inhibitory at 10(-5) M, but was inactive at lower concentrations. Because of differences in stability in culture medium (alpha-carotene less than beta-carotene less than canthaxanthin less than lycopene less than lutein) and structure, cellular levels of drug differed up to 8-fold after administration of identical concentrations of compounds. Carotenoids with polar groups achieved highest cellular levels, however cellular uptake did not correlate with activity. For example, lutein, the most polar and most stable, reached the highest concentration in cells yet required a concentration of 10(-5) M for activity in the transformation assay, while alpha-carotene, the least stable and least concentrated by cells, was comparably active at 3 X 10(6) M. alpha-Tocopherol, a potent lipid-phase antioxidant, was as active as lycopene in the transformation assay but at a 10-fold higher concentration did not approach the activity of beta-carotene or canthaxanthin. Because the most potent of the carotenoids tested (i.e. beta-carotene, alpha-carotene, canthaxanthin) all have the potential for conversion to retinoids (though this has never been demonstrated in mammals for canthaxanthin), it is suggested that these compounds have two components to their action; one related to their antioxidant properties, the other to their pro-vitamin A activities.

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Fifty North American centers have combined to evaluate the benefit of carotid endarterectomy in randomized patients who have experienced symptoms related to arteriosclerotic stenosis of the carotid artery and who have received either best medical therapy alone or best medical therapy plus carotid endarterectomy. The outcome events are nonfatal and fatal stroke or death. A three-tier system identifies and adjudicates the type, severity, and location of each stroke and the cause of any death. Data about patients submitted to carotid endarterectomy outside the trial are compiled at the Nonrandomized Data Center at the Mayo Clinic. Between December 27, 1987, and October 1, 1990, 1,212 patients were randomized, 596 to medical therapy, 616 to carotid endarterectomy. Cross-over from the medical to the surgical arm has been low (4.2%). Patients eligible for the trial, but not randomized totaled 1,044; their characteristics were similar to those randomized so that, for the type of symptomatic patient in this study, our conclusions about the benefit of carotid endarterectomy can be generalized. Patients excluded by medical criteria totaled 679. Another 1,591 had carotid endarterectomy, but either lacked the disease under study, were asymptomatic, or received inadequate investigation to meet entry criteria. We set sample size at 1,900 patients, with continuing enrollment. The Monitoring Committee reviews at intervals the confidential analyses performed on the groups with moderate (30-69%) and severe (70-99%) stenosis. Stopping rules will be invoked for one or both groups if unequivocal benefit or harm is identified.