title: Changes in Circulating Monocyte Subsets (CD16 Expression) and Neutrophil-to-Lymphocyte Ratio Observed in Patients Undergoing Cardiac Surgery.
abstract: BACKGROUND
  The characteristics of circulating inflammatory cells (leukocytes) in patients undergoing heart surgery remains poorly understood. Recently, neutrophil-to-lymphocyte ratio (NLR) and specific monocyte subsets (based on CD14/CD16 expression) have been suggested as markers of inflammation and predictors of outcomes. The present study aims to characterize the influence cardiac surgery with cardiopulmonary bypass has on specific circulating leukocytes.
  
  
  METHODS
  All enrolled patients had blood samples taken pre- (0 days), early post- (5 days), and late post- (90 days) surgery. Complete blood counts were performed and whole leukocyte isolations were obtained from blood samples and analyzed with flow cytometry. Fluorophore-linked antibodies (CD45, CD11b, CD14, and CD16) were added to the blood cell isolations and later assessed by flow cytometry.
  
  
  RESULTS
  Seventeen patients were enrolled and samples obtained at 0, 5, and 90 days. We demonstrated a significant increase in NLR (2.2-fold;p= 0.0028) and CD16 mean fluorescence index (MFI-measure fluorescence intensity shift of CD16 in a gated cell population) early at day 5 (2.0-fold;p= 0.0051). Both NLR and CD16 MFI levels generally returned to normal by day 90. There was a significant positive correlation between NLR and CD16 MFI (r2= 0.29;p= 0.0064). Adverse cardiovascular event (AE) was defined as prolonged length of hospitalization or readmission to hospital for cardiac reasons after discharge was seen in 59% of patients (no deaths occurred). In an unadjusted analysis of AE, we identified NLR as a likely predictor of AE, which meant that patients developing AE had a significantly higher baseline NLR (p= 0.0065), something that was not observed with CD16 MFI (p= 0.2541).
  
  
  CONCLUSIONS
  Cardiac surgery is associated with a significant increase in NLR and CD16 MFI (non-classical monocytes) early after surgery corresponding to the early inflammatory phase after surgery. Furthermore, we have, for the first time, identified a significant correlation between NLR and CD16 MFI. While the mechanism for this relationship remains unclear, our findings support the use of a simple test of NLR as a biomarker of inflammation for predicting outcomes in cardiac surgery patients.
authors.affiliation: Department of Pathology, Dalhousie University , Halifax, NS , Canada.
authors.forename: Kareem
authors.initials: K
authors.lastname: Gawdat
authors.affiliation: Department of Microbiology and Immunology, Dalhousie University , Halifax, NS , Canada.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Legere
authors.affiliation: Department of Pathology, Dalhousie University , Halifax, NS , Canada.
authors.forename: Chloe
authors.initials: C
authors.lastname: Wong
authors.affiliation: Department of Pathology, Dalhousie University , Halifax, NS , Canada.
authors.forename: Tanya
authors.initials: T
authors.lastname: Myers
authors.affiliation: Department of Microbiology and Immunology, Dalhousie University , Halifax, NS , Canada.
authors.forename: Jean Sylvia
authors.initials: JS
authors.lastname: Marshall
authors.affiliation: New Brunswick Heart Centre, Saint John, NB, Canada; Dalhousie Medicine New Brunswick, Saint John, NB, Canada.
authors.forename: Ansar
authors.initials: A
authors.lastname: Hassan
authors.affiliation: Dalhousie Medicine New Brunswick , Saint John, NB , Canada.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Brunt
authors.affiliation: Dalhousie Medicine New Brunswick , Saint John, NB , Canada.
authors.forename: Petra C
authors.initials: PC
authors.lastname: Kienesberger
authors.affiliation: Dalhousie Medicine New Brunswick , Saint John, NB , Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pulinilkunnil
authors.affiliation: Department of Pathology, Dalhousie University, Halifax, NS, Canada; New Brunswick Heart Centre, Saint John, NB, Canada; Dalhousie Medicine New Brunswick, Saint John, NB, Canada.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Legare
keywords: CD16 expression; NLR; REACH project; biomarkers of inflammation; cardiac surgery; intermediate monocytes; non-classical monocytes; phenotypic shift