title: Neer Award 2015: Analysis of cytokine profiles in the diagnosis of periprosthetic joint infections of the shoulder.
abstract: BACKGROUND
  Periprosthetic joint infection (PJI) after shoulder arthroplasty can present a diagnostic and therapeutic challenge. This study evaluated the diagnostic utility of broader synovial fluid cytokine analysis for identifying PJI in patients undergoing revision shoulder arthroplasty.
  
  
  METHODS
  Synovial fluid levels of 9 cytokines (interleukin [IL] 6, granulocyte-macrophage colony-stimulating factor, IL-1β, IL-12, IL-2, IL-8, interferon-γ, IL-10, and tumor necrosis factor-α) were measured in 75 cases of revision shoulder arthroplasty with a multiplex immunoassay. Cases were classified into infection categories and groups based on objective perioperative findings. Differences in cytokine levels among infection groups were evaluated. Receiver operating characteristic curves were used to assess the diagnostic utility of the individual synovial fluid cytokines and combinations of cytokines in determining infection status.
  
  
  RESULTS
  Synovial IL-6, granulocyte-macrophage colony-stimulating factor, interferon-γ, IL-1β, IL-2, IL-8, and IL-10 were significantly elevated in cases of revision shoulder arthroplasty classified as infected. Individually, IL-6, IL-1β, IL-8, and IL-10 showed the best combination of sensitivity and specificity for predicting infection, and a combined cytokine model consisting of IL-6, tumor necrosis factor-α, and IL-2 showed better diagnostic test characteristics than any cytokine alone, with sensitivity of 0.80, specificity of 0.93,, positive and negative predictive values of 0.87 and 0.89, and positive and negative likelihood ratios of 12.0 and 0.21.
  
  
  CONCLUSIONS
  Individual and combined synovial fluid cytokine analysis were both more effective than routine perioperative testing, such as serum erythrocyte sedimentation rate and C-reactive protein, in the diagnosis of PJI of the shoulder. Once validated, combined synovial fluid cytokine analysis could be used as a predictive tool to determine the probability of PJI in patients undergoing revision shoulder arthroplasty and better guide treatment.
authors.affiliation: Department of Orthopaedic Surgery, Cleveland Clinic, Orthopaedic & Rheumatologic Institute, Cleveland, OH, USA.
authors.forename: Salvatore J
authors.initials: SJ
authors.lastname: Frangiamore
authors.affiliation: Department of Orthopaedic Surgery, Cleveland Clinic, Orthopaedic & Rheumatologic Institute, Cleveland, OH, USA.
authors.forename: Anas
authors.initials: A
authors.lastname: Saleh
authors.affiliation: Department of Orthopaedic Surgery, Columbia University College of Physicians and Surgeons, New York, NY, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Grosso
authors.affiliation: Department of Orthopaedic Surgery, Cleveland Clinic, Orthopaedic & Rheumatologic Institute, Cleveland, OH, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Farias Kovac
authors.affiliation: Department of Laboratory Medicine, Cleveland Clinic, Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland, OH, USA.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, Cleveland Clinic, Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland, OH, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Daly
authors.affiliation: Department of Pathology, Cleveland Clinic, Robert J. Tomsich Pathology & Laboratory Medicine Institute, Cleveland, OH, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Bauer
authors.affiliation: Department of Orthopaedic Surgery, Cleveland Clinic, Orthopaedic & Rheumatologic Institute, Cleveland, OH, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Derwin
authors.affiliation: Department of Orthopaedic Surgery, Cleveland Clinic, Orthopaedic & Rheumatologic Institute, Cleveland, OH, USA.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Iannotti
authors.affiliation: Department of Orthopaedic Surgery, Cleveland Clinic, Orthopaedic & Rheumatologic Institute, Cleveland, OH, USA. Electronic address: ricchee@ccf.org.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Ricchetti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001170:Arthritis, Infectious / Q000175:diagnosis* / Q000378:metabolism; D000072228:Arthroplasty, Replacement, Shoulder / Q000009:adverse effects*; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016459:Prosthesis-Related Infections / Q000175:diagnosis* / Q000378:metabolism; D012086:Reoperation; D012680:Sensitivity and Specificity; D012785:Shoulder Joint; D013582:Synovial Fluid / Q000737:chemistry
chemical_list: D015415:Biomarkers; D016207:Cytokines; D002097:C-Reactive Protein
keywords: Cytokines; P acnes; periprosthetic joint infection; shoulder arthroplasty; shoulder infection; synovial fluid