Rationale and design of the Aortic Valve replAcemenT versus conservative treatment in Asymptomatic seveRe aortic stenosis (AVATAR trial): A randomized multicenter controlled event-driven trial.

Aortic valve replacement (AVR) therapy is an obvious choice for symptomatic severe aortic stenosis (AS) patients as it improves symptoms, left ventricular function, and survival. The treatment decisions and indication for AVR in asymptomatic patients with severe AS and normal left ventricular ejection fraction are less well established and the subject of ongoing debate. Many efforts have been made to define the best treatment option in asymptomatic AS patients with normal left ventricular ejection fraction. Retrospective and observational data imply that elective AVR for asymptomatic severe AS may lead to improvement in outcomes in comparison to surgery performed after onset of symptoms. The AVATAR trial will aim to assess outcomes among asymptomatic AS patients randomized to either elective early AVR or medical management with vigilant follow-up. In the latter group, AVR would be delayed until either the onset of symptoms or changes in predefined echocardiographic parameters. To the best of the authors' knowledge, it will be the first large prospective, randomized, controlled, multicenter clinical trial that will evaluate the safety and efficacy of elective AVR in this specific group of patients.

Preliminary clinical experience with the preparation and therapeutic use of autologous osteoblasts and chondrocytes.

Particular results of autologous osteoblasts preparation from patient's bone marrow and autologous chondrocytes from cartilage, both for therapeutic application are given. Osteoblastic cells were cultivated from fresh bone marrow in the presence of dexamethasone in alpha MEM medium containing 10% of patient's and 10% of fetal bovine sera and other necessary additives without any cytokine stimuli. Alkaline phosphatase cell surface activity was used as a marker for quick osteoblastic phenotype confirmation. Autologous chondrocytes were enzymatically separated from fresh knee cartilage. Pieces of cartilage, 2 mm(3) in volume, were sufficient for live cellular graft preparation. Viability of chondrocytes obtained by this approach was more than 90%. In both cases, in osteoblasts as well as in chondrocytes, the amount of cells obtained during the 4 week culture, was sufficient for clinical use.