Methods and Results: We retrospectively studied 766 consecutive patients taking warfarin long term who underwent device-related procedures. Patients were grouped by treatment:

discontinued warfarin (-warfarin, n = 243), no interruption of warfarin (+warfarin, n = 324), and discontinued warfarin with heparin bridging (+heparin, n = 199). The study primary endpoint was systemic bleeding or formation of moderate or severe pocket hematoma within 30 days of the procedure. Thirty-one (4%) patients had bleeding events, including pocket hematoma in 29 patients. The bleeding events occurred more often for +heparin (7.0%) than -warfarin (2.1%) or +warfarin (3.7%, P = 0.029). For +warfarin group, INR of 2.0-2.5 at time of procedure did not increase bleeding risk compared with INR less than 1.5 (3.7% vs

3.4%; P = 0.72), but INR greater than 2.5 increased the bleeding Selleckchem KU57788 risk (10.0% vs 3.4%; P = 0.029). Concomitant aspirin use with warfarin significantly increased bleeding risk than warfarin buy PD98059 alone (5.6% vs 1.4%, P = 0.02). Median length of hospitalization was significantly shorter for +warfarin than +heparin (1 vs 6 days; P < 0.001).

Conclusion: Continuation of oral anticoagulation therapy with an INR level of < 2.5 does not impose increased risk of bleeding for device-related procedures, although precaution is necessary to avoid supratherapeutic anticoagulation levels. (PACE 2011; 34: 868-874)”
“The population dynamics theory of B cells in a typical germinal center could play an important role in revealing how affinity maturation is achieved. However, the existing models encountered some conflicts with experiments. To resolve these conflicts, we present a coarse-grained model to calculate the B cell population development in affinity maturation, which allows a comprehensive analysis

of its parameter space to look for Go 6983 optimal values of mutation rate, selection strength, and initial antibody-antigen binding level that maximize the affinity improvement. With these optimized parameters, the model is compatible with the experimental observations such as the similar to 100-fold affinity improvements, the number of mutations, the hypermutation rate, and the “”all or none” phenomenon. Moreover, we study the reasons behind the optimal parameters. The optimal mutation rate, in agreement with the hypermutation rate in vivo, results from a tradeoff between accumulating enough beneficial mutations and avoiding too many deleterious or lethal mutations. The optimal selection strength evolves as a balance between the need for affinity improvement and the requirement to pass the population bottleneck. These findings point to the conclusion that germinal centers have been optimized by evolution to generate strong affinity antibodies effectively and rapidly.