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Abstract：
BACKGROUND: The prevalence of diabetes mellitus and its sequelae has been on the rise, and diabetic foot ulcer (DFU) is the leading cause of non-traumatic lower limb amputation globally. The rising occurrence and financial burden associated with DFU necessitate improved clinical assessment and treatment. Diabetes has been found to enhance the formation of neutrophil extracellular traps (NETs) by neutrophils, and excessive NETs have been implicated in tissue damage and impaired wound healing. However, there is as yet insufficient evidence to clarify the value of NETs in assessing and predicting outcomes of DFU.
METHODS: We designed this prospective study with three cohorts formed from type 2 diabetes mellitus (T2DM) patients with DFU (n = 200), newly diagnosed T2DM patients (n = 42), and healthy donors (n = 38). Serum levels of NETs were detected for all groups, and the prognostic value for DFU-related amputation was analyzed.
RESULTS: The results showed that serum NET levels of the DFU group were significantly higher than in the T2DM group (P < 0.05), which also had significantly elevated serum NET levels compared to healthy donors (P < 0.05). Multivariate Cox regression showed that serum NET levels, diabetic foot surgical history, and Wagner grade were the risk factors for amputation (P < 0.05), and these three variables also exhibited the highest coefficient values in additional Lasso Cox regression. For patients with DFU, Kaplan-Meier curves showed that high serum NET levels associated with higher amputation probability (HR = 0.19, P < 0.01) and ROC curve based on NET value showed good validity for amputation (AUC: 0.727, CI 0.651-0.803).
CONCLUSIONS: Elevated serum NET levels serve as an easily accessible serological prognostic marker for assessing the risk of DFU-related amputation, thereby offering evaluation metrics for healthcare providers. Further investigations are necessary to understand the mechanisms driving this relationship.
METHODS: We designed this prospective study with three cohorts formed from type 2 diabetes mellitus (T2DM) patients with DFU (n = 200), newly diagnosed T2DM patients (n = 42), and healthy donors (n = 38). Serum levels of NETs were detected for all groups, and the prognostic value for DFU-related amputation was analyzed.
RESULTS: The results showed that serum NET levels of the DFU group were significantly higher than in the T2DM group (P < 0.05), which also had significantly elevated serum NET levels compared to healthy donors (P < 0.05). Multivariate Cox regression showed that serum NET levels, diabetic foot surgical history, and Wagner grade were the risk factors for amputation (P < 0.05), and these three variables also exhibited the highest coefficient values in additional Lasso Cox regression. For patients with DFU, Kaplan-Meier curves showed that high serum NET levels associated with higher amputation probability (HR = 0.19, P < 0.01) and ROC curve based on NET value showed good validity for amputation (AUC: 0.727, CI 0.651-0.803).
CONCLUSIONS: Elevated serum NET levels serve as an easily accessible serological prognostic marker for assessing the risk of DFU-related amputation, thereby offering evaluation metrics for healthcare providers. Further investigations are necessary to understand the mechanisms driving this relationship.
摘要：
背景：糖尿病及其后遗症的患病率一直在上升，糖尿病足溃疡（DFU）是全球非创伤性下肢截肢的主要原因。与DFU相关的发病率上升和经济负担需要改进临床评估和治疗。已发现糖尿病可增强嗜中性粒细胞形成的嗜中性粒细胞胞外陷阱（NETs），过多的NETs与组织损伤和伤口愈合受损有关。然而,目前还没有足够的证据来阐明NETs在评估和预测DFU结果方面的价值.
方法：我们设计了这项前瞻性研究，研究对象是2型糖尿病（T2DM）合并DFU患者（n=200），新诊断的T2DM患者（n=42），和健康的捐赠者（n=38）。检测各组血清NETs水平,并分析DFU相关截肢的预后价值。
结果：结果显示DFU组血清NET水平明显高于T2DM组（P<0.05），与健康供体相比，血清NET水平也显着升高（P<0.05）。多因素Cox回归显示，血清NET水平，糖尿病足手术史,Wagner分级是截肢的危险因素(P<0.05),这三个变量在其他LassoCox回归中也表现出最高的系数值。对于DFU患者，Kaplan-Meier曲线显示，高血清NET水平与较高的截肢概率相关（HR=0.19，P<0.01），基于NET值的ROC曲线显示出良好的截肢有效性（AUC：0.727，CI0.651-0.803）。
结论：血清NET水平升高可作为评估DFU相关截肢风险的血清学预后指标，从而为医疗保健提供者提供评估指标。有必要进一步调查以了解推动这种关系的机制。
方法：我们设计了这项前瞻性研究，研究对象是2型糖尿病（T2DM）合并DFU患者（n=200），新诊断的T2DM患者（n=42），和健康的捐赠者（n=38）。检测各组血清NETs水平,并分析DFU相关截肢的预后价值。
结果：结果显示DFU组血清NET水平明显高于T2DM组（P<0.05），与健康供体相比，血清NET水平也显着升高（P<0.05）。多因素Cox回归显示，血清NET水平，糖尿病足手术史,Wagner分级是截肢的危险因素(P<0.05),这三个变量在其他LassoCox回归中也表现出最高的系数值。对于DFU患者，Kaplan-Meier曲线显示，高血清NET水平与较高的截肢概率相关（HR=0.19，P<0.01），基于NET值的ROC曲线显示出良好的截肢有效性（AUC：0.727，CI0.651-0.803）。
结论：血清NET水平升高可作为评估DFU相关截肢风险的血清学预后指标，从而为医疗保健提供者提供评估指标。有必要进一步调查以了解推动这种关系的机制。
