title: Pre-Operative, High-IL-6 Blood Level is a Risk Factor of Post-Operative Delirium Onset in Old Patients.
abstract: BACKGROUND
  Post-operative delirium (POD) is a common complication in elderly patients undergoing surgery, but the underpinning causes are not clear. We hypothesized that inflammaging, the subclinical low and chronic grade inflammation characteristic of old people, can contribute to POD onset. Accordingly, we investigated the association of pre-operative and circulating cytokines in elderly patients (>65 years), admitted for elective and emergency surgery.
  
  
  METHODS
  This is a secondary analysis of a sub-cohort of patients belonging to a previous large case-control study, where 351 patients were clinically and cognitively thoroughly characterized, together with the assessment of POD (47 patients) by confusion assessment method and delirium rating scale. Seventy-four pre-operative plasma samples were selected from a larger bio-bank and they included 37 subjects with POD and 37 without POD. Inflammaging related cytokines, i.e., IL-1β, IL-2, IL-6, IL-8, IL-10, and TNF-α, were assayed by ELISA in pre-operative blood samples; univariate and multivariable analyses have been applied to identify cytokines independently associated to POD. Associations of cytokine levels with functional status, cognitive decline, intra-hospital mortality, and comorbidity were also analyzed independently of POD onset.
  
  
  RESULTS
  High IL-6 and low-IL-2 levels were significantly associated with POD. After adjustment for potential confounders in multivariate analysis, high level of pre-operative IL-6 was confirmed to be significantly associated with risk of POD onset. High level of IL-6 was also associated with several baseline features (including poor functional status, cognitive impairment, emergency admission, and higher comorbidity burden) and intra-hospital mortality.
  
  
  CONCLUSIONS
  Pre-operative, high-plasma level of IL-6 (≥9 pg/mL) was significantly associated with POD onset. We propose IL-6 as an additional risk factor of POD onset together with the previously identified factors. Discovery of all risk factors contributing to POD onset will permit to improve hospitalized patient management and the decrease of healthcare cost.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna , Bologna , Italy ; Interdepartmental Center Galvani, University of Bologna , Bologna , Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Capri
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna , Bologna , Italy ; Interdepartmental Center Galvani, University of Bologna , Bologna , Italy ; Institute for Biomedical Aging Research, University of Innsbruck , Innsbruck , Austria.
authors.forename: Stella Lukas
authors.initials: SL
authors.lastname: Yani
authors.affiliation: Department of Psychology, University of Bologna , Bologna , Italy.
authors.forename: Rabih
authors.initials: R
authors.lastname: Chattat
authors.affiliation: Agency for Health and Social Care of Emilia-Romagna , Bologna , Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Fortuna
authors.affiliation: Interdepartmental Center Galvani, University of Bologna , Bologna , Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Bucci
authors.affiliation: Interdepartmental Center Galvani, University of Bologna , Bologna , Italy.
authors.forename: Catia
authors.initials: C
authors.lastname: Lanzarini
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna , Bologna , Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Morsiani
authors.affiliation: Units of General, Emergency and Transplant Surgery, St. Orsola-Malpighi Hospital , Bologna , Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Catena
authors.affiliation: General Surgery I, Ospedali Riuniti di Bergamo , Bergamo , Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Ansaloni
authors.affiliation: Department of Surgical and Anesthesiological Sciences, St. Orsola-Malpighi Hospital , Bologna , Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Adversi
authors.affiliation: Agency for Health and Social Care of Emilia-Romagna , Bologna , Italy ; Department of Surgical and Anesthesiological Sciences, St. Orsola-Malpighi Hospital , Bologna , Italy.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Melotti
authors.affiliation: Agency for Health and Social Care of Emilia-Romagna , Bologna , Italy ; Department of Surgical and Anesthesiological Sciences, St. Orsola-Malpighi Hospital , Bologna , Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Di Nino
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna , Bologna , Italy ; Interdepartmental Center Galvani, University of Bologna , Bologna , Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
keywords: IL-6; aging; inflammaging; inflammatory cytokines; post-operative delirium