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. 2021 May 20;10(10):2207.
doi: 10.3390/jcm10102207.

Biomarkers to Guide the Timing of Surgery: Neutrophil and Monocyte L-Selectin Predict Postoperative Sepsis in Orthopaedic Trauma Patients

Gabrielle Daisy Briggs  1   2 , Karla Lemmert  3 , Natalie Jane Lott  2 , Theo de Malmanche  3 , Zsolt Janos Balogh  1   2
Affiliations

Biomarkers to Guide the Timing of Surgery: Neutrophil and Monocyte L-Selectin Predict Postoperative Sepsis in Orthopaedic Trauma Patients

Gabrielle Daisy Briggs et al. J Clin Med. .

Abstract

Deciding whether to delay non-lifesaving orthopaedic trauma surgery to prevent multiple organ failure (MOF) or sepsis is frequently disputed and largely based on expert opinion. We hypothesise that neutrophils and monocytes differentially express activation markers prior to patients developing these complications. Peripheral blood from 20 healthy controls and 162 patients requiring major orthopaedic intervention was collected perioperatively. Neutrophil and monocyte L-selectin, CD64, CD11, CD18, and CXCR1 expression were measured using flow cytometry. The predictive ability for MOF and sepsis was assessed using the Receiver Operating Characteristic (ROC) comparing to C-reactive protein (CRP). Neutrophil and monocyte L-selectin were significantly higher in patients who developed sepsis. Neutrophil L-selectin (AUC 0.692 [95%CI 0.574-0.810]) and monocyte L-selectin (AUC 0.761 [95%CI 0.632-0.891]) were significant predictors of sepsis and were not significantly different to CRP (AUC 0.772 [95%CI 0.650-0.853]). Monocyte L-selectin was predictive of MOF preoperatively and postoperatively (preop AUC 0.790 [95%CI 0.622-0.958]). CD64 and CRP were predictive of MOF at one-day postop (AUC 0.808 [95%CI 0.643-0.974] and AUC 0.809 [95%CI 0.662-0.956], respectively). In the perioperative period, elevated neutrophil and monocyte L-selectin are predictors of postoperative sepsis. Larger validation studies should focus on these biomarkers for deciding the timing of long bone/pelvic fracture fixation.

Keywords: L-selectin; SIRS; multiple organ failure; sepsis; trauma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Neutrophil (n) and monocyte (m) expression of activation markers over the perioperative period. Peripheral blood was collected preoperatively to 3 days postoperatively from trauma patients and cell surface marker expression analysed using flow cytometry. CD45+ granulocyte and monocyte populations were gated and mean fluorescence intensity values (MFI) for each marker were collected and grouped by outcome along with healthy controls. Cell surface markers analysed included (A) neutrophil L-selectin (nCD62L), (B) monocyte L-selectin (mCD62L), (C) neutrophil CD64, (D) monocyte CD64, (E) neutrophil CD11, (F) neutrophil CD18, (G) monocyte CD11, (H) neutrophil CD181. Plotted values represent fold change over the median healthy control values. Significant differences are shown as * = sepsis vs. non-complicated trauma, + sepsis vs. SIRS, and ^ MOF vs. non-complicated trauma. * = p < 0.05, ** = p < 0.01, *** = p < 0.001. Significant differences between healthy controls and clinical groups and significant effects between timepoint have been omitted from the graph for simplicity and are available in Supplementary Table S1.
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