Influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification in patients with atrial fibrillation and/or pulmonary embolism.

BACKGROUND: Vitamin K antagonists (VKA) such as warfarin or phenprocoumon have been the mainstay of therapy for long-term oral anticoagulant therapy (OAT) in patients with atrial fibrillation or with pulmonary embolism. Due to interferences with matrix Gla-protein, an important vitamin K-dependent local calcification inhibitor in cardiovascular structures, VKA antagonists stimulate cardiovascular calcification (CVC). In contrast, rivaroxaban, a nonvitamin K-dependent oral anticoagulant (NOAC), should be neutral in terms of CVC. We seek to investigate these potential differences in CVC development between VKA versus NOACs in a randomized controlled trial (RCT). METHODS: The influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification in patients with atrial fibrillation and/or pulmonary embolism trial (NCT02066662) is a multicenter, prospective RCT with a two-arm, open-label study design. The primary endpoint is the progression of coronary and aortic valve calcification (quantified as calcification volume score) as assessed by cardiac computed tomography (CT) at 24 months in patients either treated by rivaroxaban or VKA. A total of 192 patients were randomized in a 1:1 fashion. The main inclusion criteria were the presence of atrial fibrillation and/or pulmonary embolism with the indication for OAT and pre-existent coronary calcification. The development of CVC will be assessed by follow-up CT at 12 and 24 months. RESULTS: In total 192 patients (median age 70, 72% male) were enrolled over a period of 5 years and followed up for 2 years.

Dissecting CD8+ T cell pathology of severe SARS-CoV-2 infection by single-cell immunoprofiling.

Introduction: SARS-CoV-2 infection results in varying disease severity, ranging from asymptomatic infection to severe illness. A detailed understanding of the immune response to SARS-CoV-2 is critical to unravel the causative factors underlying differences in disease severity and to develop optimal vaccines against new SARS-CoV-2 variants. Methods: We combined single-cell RNA and T cell receptor sequencing with CITE-seq antibodies to characterize the CD8+ T cell response to SARS-CoV-2 infection at high resolution and compared responses between mild and severe COVID-19. Results: We observed increased CD8+ T cell exhaustion in severe SARS-CoV-2 infection and identified a population of NK-like, terminally differentiated CD8+ effector T cells characterized by expression of FCGR3A (encoding CD16). Further characterization of NK-like CD8+ T cells revealed heterogeneity among CD16+ NK-like CD8+ T cells and profound differences in cytotoxicity, exhaustion, and NK-like differentiation between mild and severe disease conditions. Discussion: We propose a model in which differences in the surrounding inflammatory milieu lead to crucial differences in NK-like differentiation of CD8+ effector T cells, ultimately resulting in the appearance of NK-like CD8+ T cell populations of different functionality and pathogenicity. Our in-depth characterization of the CD8+ T cell-mediated response to SARS-CoV-2 infection provides a basis for further investigation of the importance of NK-like CD8+ T cells in COVID-19 severity.

Prognostic impact of renal arterial resistance index upon renal allograft survival: the time point matters.

BACKGROUND: The renal arterial resistance index (RI) is reported to be a significant predictive parameter for renal allograft failure or death. The influence of the time point after renal transplantation on its predictive power has not been sufficiently evaluated. We performed a retrospective analysis of RI and its power to predict renal allograft failure or death with special emphasis on the time point of RI measurement. METHODS: The present analysis is based on ultrasonographically recorded intrarenal arterial RI measurements, routinely obtained in our outpatient department, over a period of 13 years. Altogether, 88 patients with an RI measurement 0-3, 3-6 and 12-18 months after transplantation were included and retrospectively stratified into two groups according to the RI: those with an index >0.75 and those with an index of ≤0.75. RESULTS: Twenty patients (23%) reached the combined end point, i.e. allograft failure with a return to dialysis or death. The RI measured early after transplantation (0-3 and 3-6 months) did not predict the end point, whereas the RI obtained between 12 and 18 months showed a significant predictive value for renal transplant failure or death in a univariate approach [Wald test, P = 0.0013, hazard ratio (HR) 4.787, 95% confidence interval (CI) 1.846-12.411]. At 12-18 months after transplantation, 14% (12 patients) of the study population had an RI >0.75. Seven (58%) of these patients reached the end point versus 13 of 76 patients (17%) with an RI ≤0.75. In a multivariate Cox model, the RI measured between 12 and 18 months after transplantation exhibited the highest hazard ratio (HR 6.191, 95% CI 2.288-16.756, P = 0.0003) for transplant failure or death. CONCLUSION: In our hands, the RI obtained during the first 6 months after transplantation failed to predict renal allograft failure or death, whereas the RI measured 12-18 months after transplantation appeared useful to predict long-term allograft outcomes.