■细菌感染激活中性粒细胞以释放假体周围关节感染(PJIs)的细菌生物膜中的中性粒细胞胞外陷阱(NETs)。这项研究的目的是评估PJI患者血浆中NET激活和释放(NETosis)和止血标志物的增加,为了评估这种血浆是否诱导嗜中性粒细胞的活化,为了确定增加的NETosis是否也是由降低的DNaseI活性介导的,探索体外治疗PJINETosis的新干预措施,并评估这些标记物的潜在诊断用途。
■我们前瞻性招募了107名患者,71例怀疑PJI和36例因非脓毒性适应症而接受关节成形术作为对照,并获得柠檬酸化血浆。PJI在50例患者中得到证实。我们测量了净标记,炎症标志物,DNaseI活性,止血标志物,和凝血酶生成试验(TGT)。我们分析了来自确认的PJI和对照的血浆诱导NETosis和降解体外产生的NETs的能力,并探讨了用重组人DNaseI降解PJI血浆NETs的治疗性恢复。最后,我们评估了这些标志物对PJI诊断的贡献.
■确诊为PJI的患者的NET标志物水平显着增加(cfDNA(p<0.001),钙卫蛋白(p<0.001),和中性粒细胞弹性蛋白酶(p=0.022))和血浆中的炎症标志物(IL-6;p<0.001)。此外,PJI患者的血浆诱导的中性粒细胞活化明显高于对照组(p<0.001),与肿瘤坏死因子α无关.PJI患者血浆中的DNaseI活性也降低(p<0.001),导致NETs降解显著受损(p<0.001)。这可以用重组人DNaseI治疗恢复至对照中的水平。我们开发了一个模型来改善cfDNA对PJI的诊断,钙卫蛋白,TGT的起始尾部作为预测因子,尽管单独的cfDNA实现了良好的预测,并且更易于测量。
■我们证实PJI患者血浆中NETosis水平升高。它们的血浆既诱导NET释放,又具有由降低的DNaseI活性介导的降解NETs的能力。这可以通过批准的Dornasealfa在体外进行治疗恢复,Pulmozyme,这可能允许新的治疗方法。NETs和止血生物标志物的组合可以改善PJI的诊断,尤其是那些诊断不确定的患者。
UNASSIGNED: Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers.
UNASSIGNED: We prospectively recruited 107 patients in the preoperative period of prosthetic surgery, 71 with a suspicion of PJI and 36 who underwent arthroplasty for non-septic indications as controls, and obtained citrated plasma. PJI was confirmed in 50 patients. We measured NET markers, inflammation markers, DNaseI activity, haemostatic markers, and the thrombin generation test (TGT). We analyzed the ability of plasma from confirmed PJI and controls to induce NETosis and to degrade in vitro-generated NETs, and explored the therapeutic restoration of the impairment to degrade NETs of PJI plasma with recombinant human DNaseI. Finally, we assessed the contribution of these markers to the diagnosis of PJI.
UNASSIGNED: Patients with confirmed PJI had significantly increased levels of NET markers (cfDNA (p < 0.001), calprotectin (p < 0.001), and neutrophil elastase (p = 0.022)) and inflammation markers (IL-6; p < 0.001) in plasma. Moreover, the plasma of patients with PJI induced significantly more neutrophil activation than the plasma of the controls (p < 0.001) independently of tumour necrosis factor alpha. Patients with PJI also had a reduced DNaseI activity in plasma (p < 0.001), leading to a significantly impaired degradation of NETs (p < 0.001). This could be therapeutically restored with recombinant human DNaseI to the level in the controls. We developed a model to improve the diagnosis of PJI with cfDNA, calprotectin, and the start tail of TGT as predictors, though cfDNA alone achieved a good prediction and is simpler to measure.
UNASSIGNED: We confirmed that patients with PJI have an increased level of NETosis in plasma. Their plasma both induced NET release and had an impaired ability to degrade NETs mediated by a reduced DNaseI activity. This can be therapeutically restored in vitro with the approved Dornase alfa, Pulmozyme, which may allow novel methods of treatment. A combination of NETs and haemostatic biomarkers could improve the diagnosis of PJI, especially those patients in whom this diagnosis is uncertain.