• Gabriela K Fragiadakis, Brice Gaudillière, Edward A Ganio, Nima Aghaeepour, Martha Tingle, Garry P Nolan, and Martin S Angst.
• From the Baxter Laboratory in Stem Cell Biology, Stanford University, Stanford, California (G.K.F., B.G., N.A., G.P.N.); Department of Microbiology and Immunology, Stanford University, Stanford, California (G.K.F., G.P.N.); and Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University School of Medicine, Stanford, California (B.G., E.A.G., M.T., M.S.A.).
• Anesthesiology. 2015 Dec 1; 123 (6): 1241-55.

BackgroundRecovery after surgery is highly variable. Risk-stratifying patients based on their predicted recovery profile will afford individualized perioperative management strategies. Recently, application of mass cytometry in patients undergoing hip arthroplasty revealed strong immune correlates of surgical recovery in blood samples collected shortly after surgery. However, the ability to interrogate a patient's immune state before surgery and predict recovery is highly desirable in perioperative medicine.MethodsTo evaluate a patient's presurgical immune state, cell-type-specific intracellular signaling responses to ex vivo ligands (lipopolysaccharide, interleukin [IL]-6, IL-10, and IL-2/granulocyte macrophage colony-stimulating factor) were quantified by mass cytometry in presurgical blood samples. Selected ligands modulate signaling processes perturbed by surgery. Twenty-three cell surface and 11 intracellular markers were used for the phenotypic and functional characterization of major immune cell subsets. Evoked immune responses were regressed against patient-centered outcomes, contributing to protracted recovery including functional impairment, postoperative pain, and fatigue.ResultsEvoked signaling responses varied significantly and defined patient-specific presurgical immune states. Eighteen signaling responses correlated significantly with surgical recovery parameters (|R| = 0.37 to 0.70; false discovery rate < 0.01). Signaling responses downstream of the toll-like receptor 4 in cluster of differentiation (CD) 14 monocytes were particularly strong correlates, accounting for 50% of observed variance. Immune correlates identified in presurgical blood samples mirrored correlates identified in postsurgical blood samples.ConclusionsConvergent findings in pre- and postsurgical analyses provide validation of reported immune correlates and suggest a critical role of the toll-like receptor 4 signaling pathway in monocytes for the clinical recovery process. The comprehensive assessment of patients' preoperative immune state is promising for predicting important recovery parameters and may lead to clinical tests using standard flow cytometry.

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