Forsberg Jonathan Agner, Elster Eric A, Andersen Romney C, Nylen Eric, Brown Trevor S, Rose Matthew W, Stojadinovic Alexander, Becker Kenneth L, McGuigan Francis Xavier
Department of Orthopaedic Surgery, National Naval Medical Center, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA.
J Bone Joint Surg Am. 2008 Mar;90(3):580-8. doi: 10.2106/JBJS.G.00265.
Despite technological advances in the treatment of severe extremity trauma, the timing of wound closure remains the subjective clinical decision of the treating surgeon. Traditional serum markers are poor predictors of wound-healing. The objective of this study was to evaluate the cytokine and chemokine profiles of severe extremity wounds prior to closure to determine if wound effluent markers can be used to predict healing.
Serum and effluent (exudate) samples were collected prospectively from adult volunteers with multiple high-energy penetrating extremity wounds sustained during military combat. Samples were collected prior to definitive wound closure or flap coverage. Wounds were followed clinically for six weeks. The primary clinical outcome measures were wound-healing and dehiscence. Control serum samples were collected from normal age and sex-matched adult volunteers. All samples were analyzed for the following cytokines and chemokines: procalcitonin; eotaxin; granulocyte macrophage colony stimulating factor; interferon (IFN)-gamma; interleukin (IL)-1 through 8, 10, 12, 13, and 15; IFN-gamma inducible protein-10; monocyte chemotactic protein-1; macrophage inflammatory protein-1alpha; the protein regulated on activation, normal T expressed and secreted (RANTES); and tumor necrosis factor (TNF)-alpha.
Fifty wounds were analyzed in twenty patients. Four of the fifty wounds dehisced. An increased rate of wound dehiscence was observed in patients with a concomitant closed head injury as well as in those with an associated arterial injury of the affected limb (p < 0.05). Among the serum chemokines and cytokines, only serum procalcitonin levels correlated with wound dehiscence (p < 0.05). Effluent analysis showed that, compared with wounds that healed, wounds that dehisced were associated with elevated procalcitonin, decreased RANTES protein, and decreased IL-13 concentrations (p < 0.05). No wound with an effluent procalcitonin concentration of <220 pg/mL, an IL-13 concentration of >12 pg/mL, or a RANTES protein concentration of >1000 pg/mL failed to heal.
Effluent procalcitonin, IL-13, and RANTES protein levels as well as serum procalcitonin levels correlate with wound dehiscence following closure of severe open extremity wounds. These preliminary results indicate that effluent biomarker analysis may be an objective means of determining the timing of traumatic wound closure.
尽管在严重肢体创伤治疗方面取得了技术进步,但伤口闭合的时机仍是主刀医生的主观临床决策。传统血清标志物对伤口愈合的预测能力较差。本研究的目的是评估严重肢体伤口闭合前的细胞因子和趋化因子谱,以确定伤口渗出液标志物是否可用于预测愈合情况。
前瞻性收集成年志愿者的血清和渗出液(分泌物)样本,这些志愿者在军事战斗中遭受多处高能穿透性肢体伤口。在进行确定性伤口闭合或皮瓣覆盖之前采集样本。对伤口进行为期六周的临床随访。主要临床结局指标为伤口愈合和裂开。对照血清样本取自年龄和性别匹配的正常成年志愿者。对所有样本进行以下细胞因子和趋化因子分析:降钙素原;嗜酸性粒细胞趋化因子;粒细胞巨噬细胞集落刺激因子;干扰素(IFN)-γ;白细胞介素(IL)-1至8、10、12、13和15;IFN-γ诱导蛋白-10;单核细胞趋化蛋白-1;巨噬细胞炎性蛋白-1α;激活调节正常T细胞表达和分泌蛋白(RANTES);以及肿瘤坏死因子(TNF)-α。
对20例患者的50处伤口进行了分析。50处伤口中有4处裂开。伴有闭合性颅脑损伤的患者以及患肢伴有动脉损伤的患者伤口裂开率增加(p < 0.05)。在血清趋化因子和细胞因子中,只有血清降钙素原水平与伤口裂开相关(p < 0.05)。渗出液分析表明,与愈合的伤口相比,裂开的伤口降钙素原升高、RANTES蛋白降低以及IL-13浓度降低(p < 0.05)。渗出液降钙素原浓度<220 pg/mL、IL-13浓度>12 pg/mL或RANTES蛋白浓度>1000 pg/mL的伤口均未愈合。
严重开放性肢体伤口闭合后,渗出液降钙素原、IL-13和RANTES蛋白水平以及血清降钙素原水平与伤口裂开相关。这些初步结果表明,渗出液生物标志物分析可能是确定创伤性伤口闭合时机的一种客观方法。