European Association of Cardiothoracic and Vascular Anesthesiology and Intensive Care Fellowship Program: The Graduates' Experience

Objectives: In 2009, the European Association of Cardiothoracic Anesthesiology and Intensive Care (EACTAIC) established a fellowship pro -gram to train highly qualified specialists in the field of cardiac anesthesia. For the further development of the program, a survey among graduates was distributed to get information about the individual motivation and career perspectives of fellows.Design: Online survey among graduates of the EACTAIC cardiothoracic and vascular anesthesia (CTVA) fellowship program.Setting: Twenty-four-item online survey after personal invitation from the EACTAIC officeParticipants: Forty-nine graduates.Interventions: None.Measurements and Main Results: The survey had a response rate of 77%. On average, graduates joined the EACTAIC fellowship program four years after completing their residency program. Participants felt well-prepared by the program regarding their clinical and nonclinical skills. The majority participated in research activities during the fellowship and continued to work in the field of CTVA. Ninety-two percent of the respond-ents found a job opportunity within a reasonable time after completing the training.Conclusions: Among the respondents, the survey showed a high satisfactory rate with the received training and good job opportunities after completing the fellowship. Further research should investigate the question of beneficial effects on research activities after completing the fel-lowship. (c) 2021 Elsevier Inc. All rights reserved

Necroptosis controls NET generation and mediates complement activation, endothelial damage, and autoimmune vasculitis

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes life-threatening autoimmune diseases affecting every organ, including the kidneys, where they cause necrotizing crescentic glomerulonephritis. ANCA activates neutrophils and activated neutrophils damage the endothelium, leading to vascular inflammation and necrosis. Better understanding of neutrophil-mediated AAV disease mechanisms may reveal novel treatment strategies. Here we report that ANCA induces neutrophil extracellular traps (NETs) via receptor-interacting protein kinase (RIPK) 1/3- and mixed-lineage kinase domain-like (MLKL)-dependent necroptosis. NETs from ANCA-stimulated neutrophils caused endothelial cell (EC) damage in vitro. This effect was prevented by (i) pharmacologic inhibition of RIPK1 or (ii) enzymatic NET degradation. The alternative complement pathway (AP) was recently implicated in AAV, and C5a inhibition is currently being tested in clinical studies. We observed that NETs provided a scaffold for AP activation that in turn contributed to EC damage. We further established the in vivo relevance of NETs and the requirement of RIPK1/3/MLKL-dependent necroptosis, specifically in the bone marrow-derived compartment, for disease induction using murine AAV models and in human kidney biopsies. In summary, we identified a mechanistic link between ANCA-induced neutrophil activation, necroptosis, NETs, the AP, and endothelial damage. RIPK1 inhibitors are currently being evaluated in clinical trials and exhibit a novel therapeutic strategy in AAV