title: Circulating biomarkers for discrimination between aseptic joint failure, low-grade infection, and high-grade septic failure.
abstract: BACKGROUND
  Late-onset chronic (low-grade) periprosthetic joint infections are often accompanied by unspecific symptoms, false-negative cultures or nonspecific low values of serum biomarkers. This may lead to the unintended implantation of a revision prosthesis into an infected surgical site with the risk of short-term failure developing again. Conversely, false diagnosis of joint infection may result in multistage revision procedures, which expose the patient to unnecessary surgical procedures and inappropriate antibiotic treatment. Here, we investigated whether circulating biomarkers can preoperatively distinguish between aseptic prosthesis loosening and low-grade joint infection, and which biomarker combinations are most accurate.
  
  
  METHODS
  Inclusion criteria for the study were indication for revision arthroplasty due to aseptic implant failure, acute high-grade infection, or (suspected) low-grade infection. C-reactive protein (CRP), procalcitonin, tumor necrosis factor α, interleukin 6 (IL-6), interleukin 10, and lipopolysaccharide binding protein were assessed preoperatively in the serum of 98 adult patients.
  
  
  RESULTS
  The classification tree method revealed IL-6 and CRP as the most suitable biomarker combination for the discrimination of aseptic loosening vs low-grade joint infection. The combination of IL-6 >5.12 pg/mL and CRP >0.3 mg/dL correctly identified 15 of 16 patients as having low-grade infection (94%) whereas just one patient was aseptic (6%).
  
  
  CONCLUSIONS
  This is the first comprehensive prospective clinical study to our knowledge investigating the significance of a combined biomarker approach in differentiating between aseptic prosthesis loosening and low-grade joint infection. CRP plus IL-6 seems to be the most helpful combination for preoperative discrimination of aseptic loosening vs low-grade joint infection.
authors: Department of Orthopaedic Surgery.
authors: Max
authors: M
authors: Ettinger
authors: Department of Orthopaedic Surgery.
authors: Tilman
authors: T
authors: Calliess
authors: Department of Nephrology and Hypertension.
authors: Jan T
authors: JT
authors: Kielstein
authors: Department of Orthopaedic Surgery.
authors: Jasmin
authors: J
authors: Sibai
authors: Department of Orthopaedic Surgery.
authors: Thomas
authors: T
authors: Brückner
authors: Department of Laboratory Medicine, Hannover Medical School.
authors: Ralf
authors: R
authors: Lichtinghagen
authors: Department of Orthopaedic Surgery.
authors: Henning
authors: H
authors: Windhagen
authors: Department of Nephrology and Hypertension Department of Medicine D, Division of General Internal Medicine, Nephrology, and Rheumatology, University Hospital Münster, Germany.
authors: Alexander
authors: A
authors: Lukasz
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D005260:Female; D006622:Hip Prosthesis / Q000009:adverse effects*; D006801:Humans; D007720:Knee Prosthesis / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011475:Prosthesis Failure; D016459:Prosthesis-Related Infections / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D012372:ROC Curve; D018805:Sepsis / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology
chemical_list: D015415:Biomarkers
keywords: high-grade; joint infection; low-grade; septic joint failure