Neutrophil extracellular traps and heparin-induced antibodies contribute to vascular access thrombosis in hemodialysis patients

Background Anti-heparin/platelet factor 4 (PF4) antibodies may trigger severe thrombotic complications in hemodialysis (HD) patients. Tetrameric PF4 has a high affinity for extracellular DNA, which is a key component of neutrophil extracellular traps (NETs); therefore, the interactions between anti-heparin/PF4 antibodies and NETs can contribute to prothrombotic events. Methods Anti-heparin/PF4 antibody levels were measured by enzyme-linked immunosorbent assay and an optical density > 1.8 was regarded as clinically significant. We additionally measured serum nucleosome levels as representative markers of NETs, and the contributions of anti-heparin/PF4 and increased serum nucleosome levels to the primary functional patency loss of vascular access was assessed. Results The frequency of anti-heparin/PF4 antibodies was significantly higher in incident HD patients compared to prevalent HD patients (23.6% vs. 7.7%). Serum nucleosome levels, as well as the white blood cell counts, neutrophil counts, and high- sensitivity C-reactive protein levels, were significantly higher in anti-heparin/PF4 antibody-positive patients compared to the control. Platelet counts tended to be lower in the patients with anti-heparin/PF4 of >1.8 than in the controls. Relative risk calculations showed that the presence of anti-heparin/PF4 antibodies increased the risk of primary functional patency failure by 4.28-fold, and this risk increased further with higher nucleosome levels. Furthermore, in the anti-heparin/PF4 antibody-positive group, the time to first vascular intervention was much shorter, and the risk of repeated intervention was higher, compared to the controls. Conclusion In incident HD patients, the presence of anti-heparin/PF4 antibodies was associated with increased NET formation; this could be a strong predictor of vascular access complication

Organic flexible memristor with reduced operating voltage and high stability by interfacial control of conductive filament growth

This work was supported in part through the BK21 Program funded by Ministry of Education of Korea.Herein, the underlying mechanisms for the growth of conductive filaments (CFs) at a metal–polymer electrolyte interface through ion migration in organic electrochemical metallization (ECM) memristor are presented. It is observed that the free volume of voids (nanopores) in the polymer electrolyte serves as the pathways of metal‐cations whereas the interfacial topography between an active electrode and a polymer electrolyte determines the nucleation sites of the CFs. The growth kinetics of the CFs and the resultant resistive memory are found to vary with the molecular weight of the polymer electrolyte and the metal protrusions at the interface. Our direct observations show that the free volume of voids of the polymer electrolyte, varied with the molecular weight, dictates the ion transport for the growth and the disruption of the CFs. Our organic ECM‐based memristor with a hetero‐electrolyte exhibits high mechanical flexibility, low switching voltages reduced by about three times compared to those of conventional devices, and stable memory retention for longer than 104 s under repeated cycles of bending.PostprintPeer reviewe