Division of Research, Department of Surgery, College of Medicine, University of Cincinnati, Cincinnati, Ohio.
Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri.
J Surg Res. 2022 Jun;274:94-101. doi: 10.1016/j.jss.2021.12.037. Epub 2022 Feb 5.
Current surgical guidelines for the treatment of intra-abdominal sepsis recommend interventional source control as the key element of therapy, alongside resuscitation and antibiotic administration. Past trials attempted to predict the success of interventional source control to assess whether further interventional therapy is needed. However, no predictive score could be developed.
We utilized an established murine abdominal sepsis model, the cecal ligation and puncture (CLP), and performed a successful surgical source control intervention after full development of sepsis, the CLP-excision (CLP/E). We then sought to evaluate the success of the source control by characterizing circulating neutrophil phenotype and functionality 24 h postintervention.
We showed a significant relative increase of neutrophils and a significant absolute and relative increase of activated neutrophils in septic mice. Source control with CLP/E restored these numbers back to baseline. Moreover, main neutrophil functions, the acidification of cell compartments, such as lysosomes, and the production of Tumor Necrosis Factor-alpha (TNF-α), were impaired in septic mice but restored after CLP/E intervention.
Neutrophil characterization by phenotyping and evaluating their functionality indicates successful source control in septic mice and can serve as a prognostic tool. These findings provide a rationale for the phenotypic and functional characterization of neutrophils in human patients with infection. Further studies will be needed to determine whether a predictive score for the assessment of successful surgical source control can be established.
目前，针对腹腔内脓毒症的外科治疗指南建议，介入性源头控制是治疗的关键要素，同时还需要进行复苏和抗生素治疗。过去的试验试图预测介入性源头控制的成功，以评估是否需要进一步的介入治疗。然而，目前还没有开发出预测评分。
我们利用已建立的小鼠腹腔脓毒症模型——盲肠结扎穿孔（CLP），在脓毒症完全发展后进行了成功的外科源头控制干预，即 CLP 切除术（CLP/E）。然后，我们试图通过在干预后 24 小时内对循环中性粒细胞表型和功能进行特征分析，来评估源头控制的效果。
我们发现脓毒症小鼠的中性粒细胞相对增加，激活的中性粒细胞绝对数量和相对数量显著增加。CLP/E 控制源头可将这些数量恢复到基线水平。此外，中性粒细胞的主要功能，如溶酶体等细胞区室的酸化和肿瘤坏死因子-α（TNF-α）的产生，在脓毒症小鼠中受损，但在 CLP/E 干预后得到恢复。
通过表型分析和评估中性粒细胞的功能特征，可以对脓毒症小鼠的源头控制效果进行评估，这可以作为一种预后工具。这些发现为感染患者中性粒细胞的表型和功能特征分析提供了依据。需要进一步的研究来确定是否可以建立一种用于评估手术源头控制成功的预测评分。
