Objective To explore the correlation of neutrophil extracellular traps(NETs) markers with clinical outcome of diabetic foot ulcer (DFU) and their predictive value.

Methods A total of 120 patients with DFU treated in Department of Vascular Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine during June 2019 to June 2016 were retrospectively enrolled in this study. Sixty non-ulcerative diabetic patients and 60 healthy people were enrolled in the control group. Patients' basic information, morbidity, laboratory test data, ulcer wound measurement data and 1-year follow-up information were collected and analyzed. NETs markers were detected in the blood of DFU patients and control group, and ulcerative tissues of DFU were collected for detecting the level of elastase. In vitro NETs release experiments were conducted to evaluate whether the microenvironment of DFU patients could promote NETs release. The predictive value of NETs markers with 1-year ulcer healing and amputation rate in DFU patients was also evaluated.

Results Compared with the blood of non-ulcerative diabetic patients, plasma and platelets extracted from blood DFU patients were more likely to stimulate neutrophil to release NETs in vitro (P < 0.05). Compared with patients in control group, serum levels of NETs markers in DFU patients were significantly increased (P < 0.05). The level of elastase in ulcer tissue of non-healing group was significantly higher than that of healing group (P < 0.05), and the level of elastase in ulcer tissue of DFU patients with infection was significantly higher than that of non-infected patients (P < 0.05). The ulcer healing rate of DFU patients with high serum citH3 level and high ulcer elastase level was significantly lower than that of DFU patients with low serum citH3 level and high ulcer elastase level (P < 0.05). Univariate analysis and multivariate logistic regression model analysis showed that serum citH3 levels was an independent risk factors of ulcer healing (OR＝0.05, 95% CI 0.01-1.35, P＝0.005) or amputation (OR＝1.86, 95%CI 0.54-7.91) within 1 year in DFU patients.

Conclusions The local microenvironment of DFU patients can promote the release of NETs from neutrophils and prevent wound healing. Elevated NETs markers were closely associated with delayed wound healing and amputation in DFU patients. Serum citH3 may be an independent marker for predicting the clinical outcome of DFU.