In this study, we found that the number of viable osteocytes was significantly smaller in MM patients than in healthy controls, and negatively correlated with the number of OCLs. Moreover, the MM patients with bone lesions had a significantly smaller number of viable osteocytes than those without, partly because of increased apoptosis. These findings were further confirmed by ultrastructural in vitro analyses of human preosteocyte cells cocultured with MM cells, this website which showed that MM cells increased preosteocyte death and apoptosis. A micro-array analysis showed that MM cells affect the transcriptional profiles of preosteocytes by upregulating
the production of osteoclastogenic cytokines such as interleukin (IL)-11, and increasing their pro-osteoclastogenic properties. Finally, the osteocyte expression of IL-11 was higher in the MM patients with than in those without bone lesions. Our data suggest that MM patients are characterized by a reduced number of viable osteocytes related to the presence of bone lesions, and that this is involved in MM-induced OCL formation.”
“BACKGROUND
Dabigatran,
which is administered in a fixed dose and does not require laboratory monitoring, may be suitable for extended treatment of venous thromboembolism.
METHODS
In two double-blind, randomized trials, we compared Dabigatran at a dose Cediranib datasheet of 150 mg twice daily with warfarin (active-control study) or with placebo (placebo-control study) in patients with venous thromboembolism who had completed at least 3 initial months of therapy.
RESULTS
In the active-control study, recurrent venous thromboembolism occurred in 26 of 1430 patients in the Dabigatran group (1.8%) and 18 of 1426 patients in the warfarin group (1.3%) (hazard ratio with Dabigatran, 1.44; 95% confidence interval [CI], 0.78 to 2.64; P = 0.01 for noninferiority). Major bleeding occurred in 13 patients in the Dabigatran group (0.9%) and 25 patients in the warfarin group (1.8%) (hazard ratio, 0.52; 95% CI, 0.27 to 1.02). Major or clinically relevant bleeding was less frequent with Dabigatran (hazard ratio, 0.54;
95% CI, 0.41 to 0.71). Acute coronary syndromes occurred in 13 patients in the selleck Dabigatran group (0.9%) and 3 patients in the warfarin group (0.2%) (P = 0.02). In the placebo-control study, recurrent venous thromboembolism occurred in 3 of 681 patients in the Dabigatran group (0.4%) and 37 of 662 patients in the placebo group (5.6%) (hazard ratio, 0.08; 95% CI, 0.02 to 0.25; P<0.001). Major bleeding occurred in 2 patients in the Dabigatran group (0.3%) and 0 patients in the placebo group. Major or clinically relevant bleeding occurred in 36 patients in the Dabigatran group (5.3%) and 12 patients in the placebo group (1.8%) (hazard ratio, 2.92; 95% CI, 1.52 to 5.60). Acute coronary syndromes occurred in 1 patient each in the Dabigatran and placebo groups.