Objectives This study sought to evaluate the safety and efficacy of the CoreValve transcatheter heart valve (THV) for the treatment of severe aortic stenosis in patients at extreme risk for surgery. ...Background Untreated severe aortic stenosis is a progressive disease with a poor prognosis. Transcatheter aortic valve replacement (TAVR) with a self-expanding bioprosthesis is a potentially effective therapy. Methods We performed a prospective, multicenter, nonrandomized investigation evaluating the safety and efficacy of self-expanding TAVR in patients with symptomatic severe aortic stenosis with prohibitive risks for surgery. The primary endpoint was a composite of all-cause mortality or major stroke at 12 months, which was compared with a pre-specified objective performance goal (OPG). Results A total of 41 sites in the United States recruited 506 patients, of whom 489 underwent attempted treatment with the CoreValve THV. The rate of all-cause mortality or major stroke at 12 months was 26.0% (upper 2-sided 95% confidence bound: 29.9%) versus 43.0% with the OPG (p < 0.0001). Individual 30-day and 12-month events included all-cause mortality (8.4% and 24.3%, respectively) and major stroke (2.3% and 4.3%, respectively). Procedural events at 30 days included life-threatening/disabling bleeding (12.7%), major vascular complications (8.2%), and need for permanent pacemaker placement (21.6%). The frequency of moderate or severe paravalvular aortic regurgitation was lower 12 months after self-expanding TAVR (4.2%) than at discharge (10.7%; p = 0.004 for paired analysis). Conclusions TAVR with a self-expanding bioprosthesis was safe and effective in patients with symptomatic severe aortic stenosis at prohibitive risk for surgical valve replacement. (Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement; NCT01240902 )
Familial chylomicronemia syndrome is a rare genetic disorder that is caused by loss of lipoprotein lipase activity and characterized by chylomicronemia and recurrent episodes of pancreatitis. There ...are no effective therapies. In an open-label study of three patients with this syndrome, antisense-mediated inhibition of hepatic
mRNA with volanesorsen led to decreased plasma apolipoprotein C-III and triglyceride levels.
We conducted a phase 3, double-blind, randomized 52-week trial to evaluate the safety and effectiveness of volanesorsen in 66 patients with familial chylomicronemia syndrome. Patients were randomly assigned, in a 1:1 ratio, to receive volanesorsen or placebo. The primary end point was the percentage change in fasting triglyceride levels from baseline to 3 months.
Patients receiving volanesorsen had a decrease in mean plasma apolipoprotein C-III levels from baseline of 25.7 mg per deciliter, corresponding to an 84% decrease at 3 months, whereas patients receiving placebo had an increase in mean plasma apolipoprotein C-III levels from baseline of 1.9 mg per deciliter, corresponding to a 6.1% increase (P<0.001). Patients receiving volanesorsen had a 77% decrease in mean triglyceride levels, corresponding to a mean decrease of 1712 mg per deciliter (19.3 mmol per liter) (95% confidence interval CI, 1330 to 2094 mg per deciliter 15.0 to 23.6 mmol per liter), whereas patients receiving placebo had an 18% increase in mean triglyceride levels, corresponding to an increase of 92.0 mg per deciliter (1.0 mmol per liter) (95% CI, -301.0 to 486 mg per deciliter -3.4 to 5.5 mmol per liter) (P<0.001). At 3 months, 77% of the patients in the volanesorsen group, as compared with 10% of patients in the placebo group, had triglyceride levels of less than 750 mg per deciliter (8.5 mmol per liter). A total of 20 of 33 patients who received volanesorsen had injection-site reactions, whereas none of the patients who received placebo had such reactions. No patients in the placebo group had platelet counts below 100,000 per microliter, whereas 15 of 33 patients in the volanesorsen group had such levels, including 2 who had levels below 25,000 per microliter. No patient had platelet counts below 50,000 per microliter after enhanced platelet-monitoring began.
Volanesorsen lowered triglyceride levels to less than 750 mg per deciliter in 77% of patients with familial chylomicronemia syndrome. Thrombocytopenia and injection-site reactions were common adverse events. (Funded by Ionis Pharmaceuticals and Akcea Therapeutics; APPROACH Clinical Trials.gov number, NCT02211209.).
There is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in CSF are being used in clinical practice. One of ...the most critical factors in CSF biomarker research is the inadequate powering of studies because of the lack of sufficient samples that can be obtained in single-center studies. Therefore, collaboration between investigators is needed to establish large biobanks of well-defined samples. Standardized protocols for biobanking are a prerequisite to ensure that the statistical power gained by increasing the numbers of CSF samples is not compromised by preanalytical factors. Here, a consensus report on recommendations for CSF collection and biobanking is presented, formed by the BioMS-eu network for CSF biomarker research in multiple sclerosis. We focus on CSF collection procedures, preanalytical factors, and high-quality clinical and paraclinical information. The biobanking protocols are applicable for CSF biobanks for research targeting any neurologic disease.
PDF
