Anti-BTK (aa1-175) monoclonal antibody, clone 20E22

Purpose The BIOLUX P-III registry was initiated to further assess the safety and efficacy of the Passeo-18 Lux drug-coated balloon (DCB) in infrainguinal lesions in a real-world environment and in prespecified risk groups. Materials and methods BIOLUX P-III is a prospective, global, all-comers registry with patients treated under real-world conditions. We herein report 24-month results of the prespecified subgroup of 151 patients with 185 below-the-knee (BTK) lesions. The primary safety and efficacy endpoints were freedom from major adverse events (a composite of freedom from device and procedure mortality through 30 days, major target limb amputation and clinically driven target lesion revascularization) at 6 months and freedom from clinically driven target lesion revascularization (FfTLR) at 12 months. Results At baseline, 76.0% of patients had critical limb ischemia and 48.9% of lesions were TASC C or D lesions. Technical success was achieved in 97.8%, and bailout stenting was required in 1.1%. Freedom from major adverse events was 86.2% [95% CI 79.4; 90.8] at 6 months, and FfTLR was 90.9% [95% CI 85.2; 94.4] at 12 months. At 24 months, FfTLR was 90.9% [95% CI 85.2; 94.4], freedom from major amputation was 90.1% [95% CI 83.9, 94.0], and overall survival was 79.2% [70.7, 85.5]. There was a significant clinical improvement (mean Rutherford class improvement of - 2.9 +/- 1.9,p < 0.0001) and an improvement in pain (mean improvement on Wong-Baker Faces Pain Scale of - 2.7 +/- 2.9,p < 0.0001). Conclusions In this real-world DCB registry, 24-month outcomes of Passeo-18 Lux demonstrated safety and efficacy in BTK lesions with high patency rates and sustained clinical improvements at 24 months.

The HIV-1 virulence factor Nef promotes high-titer viral replication, immune escape, and pathogenicity. Nef interacts with interleukin-2?inducible T-cell kinase (Itk) and Bruton's tyrosine kinase (Btk), two Tec-family kinases expressed in HIV-1 target cells (CD4 T cells and macrophages, respectively). Using a cell-based bimolecular fluorescence complementation assay, here we demonstrate that Nef recruits both Itk and Btk to the cell membrane and induces constitutive kinase activation in transfected 293T cells. Nef homodimerization-defective mutants retained their interaction with both kinases but failed to induce activation, supporting a role for Nef homodimer formation in the activation mechanism. HIV-1 infection up-regulates endogenous Itk activity in SupT1 T cells and donor-derived peripheral blood mononuclear cells. However, HIV-1 strains expressing Nef variants with mutations in the dimerization interface replicated poorly and were significantly attenuated in Itk activation. We conclude that direct activation of Itk and Btk by Nef at the membrane in HIV-infected cells may override normal immune receptor control of Tec-family kinase activity to enhance the viral life cycle.