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

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.

The novel biomarkers for assessing clinical benefits of continuous renal replacement therapy in pediatric sepsis: a pilot study

“…Considering the novelty of LYZ as an indicator of sepsis recovery and clinical benefits of CRRT, the underlying mechanisms of LYZ involved in roles of CRRT in pediatric sepsis is worth of more attention in the future. In addition, several studies have shown that SELL [15] and SERPINA3 [30] are also associated with sepsis, but it was not confirmed in our present study.…”

“…Our previous multicenter study indicated that the level of IL-6 was decreased in the CRRT group compared with the non-CRRT group, and CRRT decreases hospital mortality rate in pediatric severe sepsis, especially in patients with acute respiratory distress syndrome (ARDS) [14]. Consistently, a recent study showed that levels of C-reactive protein (CRP), TNF-α, and IL-6 decreased significantly after CRRT in patients with sepsis-induced acute kidney injury (AKI) [15]. CRRT as an extracorporeal life support could disturb homeostasis and affect the process of sepsis.…”

Prospective flow cytometry analysis of leucocyte subsets in critically ill patients who develop sepsis: a pilot study

“…However, association with subsequent sepsis occurrence was not an endpoint in the latter study. In a more recent study aiming at guiding the optimal timing of non-lifesaving orthopedic surgery for trauma, authors hypothesized that neutrophils and monocytes express activation markers prior to sepsis development [49]. They found that in the perioperative period, elevated monocyte L-selectin (AUC 0.76 [95%CI 0.63-0.89] was a signi cant predictor of sepsis, thereby precluding urgent surgery.…”

Innate immunity and immunotherapy for hemorrhagic shock

“…Neutrophils are the first innate immune cells against pathogens due to their array of microbicidal activities ( 60 , 61 ). Clinically, the drop in circulating neutrophils is positively correlated with the occurrence of MOF ( 62 , 63 ). FS-MSCs have an immunomodulatory action through paracrine activity by secreting anti-inflammatory cytokines and growth factors ( 64 ).…”