Synovial Cytokines and the MSIS Criteria Are Not Useful for Determining Infection Resolution After Periprosthetic Joint Infection Explantation

Clinical Orthopaedics and Related Research®, Jan 2016

Salvatore J. Frangiamore, Marcelo B. P. Siqueira, Anas Saleh, Thomas Daly, Carlos A. Higuera, Wael K. Barsoum

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Synovial Cytokines and the MSIS Criteria Are Not Useful for Determining Infection Resolution After Periprosthetic Joint Infection Explantation

Synovial Cytokines and the MSIS Criteria Are Not Useful for Determining Infection Resolution After Periprosthetic Joint Infection Explantation Salvatore J. Frangiamore 0 Marcelo B. P. Siqueira 0 Anas Saleh 0 Thomas Daly 0 Carlos A. Higuera 0 Wael K. Barsoum 0 0 S. J. Frangiamore, M. B. P. Siqueira, A. Saleh, T. Daly, C. A. Higuera (&), W. K. Barsoum Department of Orthopaedic Surgery, Cleveland Clinic , 9500 Euclid Avenue/A41, Cleveland, OH 44195 , USA Background Diagnosing periprosthetic joint infection (PJI) requires a combination of clinical and laboratory parameters, which may be expensive and difficult to - One of the authors certifies that he (CAH), or a member of his immediate family, has or may receive payments or benefits, during the study period, an amount of USD 10,000 to USD 100,000 from Stryker (Kalamazoo, MI, USA), an amount of USD 100,001 to USD 1,000,000 from KCI (San Antonio, TX, USA), an amount of USD 100,001 to USD 1,000,000 from Myoscience (Fresno, CA, USA), and an amount of USD 100,001 to USD 1,000,000 from CD Diagnostics (Claymont, DE, USA). One of the authors certifies that he (WKB), or a member of his immediate family, has or may receive payments or benefits, during the study period, an amount of USD 100,001 to USD 1,000,000 from Stryker, an amount of USD 100,000 to USD 1,000,000 from Exatech (Gainesville, FL, USA), an amount of USD 10,000 to USD 100,000 from Custom Orthopaedic Solutions (Cleveland, OH, USA), and an amount of USD 10,000 to USD 100,000 from KEF Healthcare (Dubai, UAE). All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research1 editors and board members are on file with the publication and can be viewed on request. Clinical Orthopaedics and Related Research1 neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDAapproval status, of any drug or device prior to clinical use. Each author certifies that his or her institution approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained. Electronic supplementary material The online version of this article (doi:10.1007/s11999-016-4710-x) contains supplementary material, which is available to authorized users. interpret. Synovial fluid cytokines have been shown to accurately differentiate septic from aseptic failed total knee (TKA) and hip (THA) arthroplasties. However, after firststage explantation, there is still no reliable test to rule out PJI before a second-stage reimplantation procedure. Questions/purposes (1) Which synovial fluid cytokines have the highest diagnostic accuracy for PJI? (2) Which cytokine shows the greatest decrease associated with the resolution of infection in the same patient between explantation and subsequent reimplantation of an infected arthroplasty? (3) What is the accuracy of synovial fluid cytokines and the Musculoskeletal Infection Society (MSIS) criteria to rule out PJI after first-stage explantation? (4) What are the most studied synovial fluid cytokines for diagnosing PJI as reported in the literature and what are their cumulative diagnostic accuracy? Methods Between May 2013 and March 2014, 104 patients with painful THA and TKA evaluated for possible PJI were included in our study. Of these, 90 (87%) had cytokine levels measured from synovial fluid samples collected as part of this prospective study (n = 33 hips, n = 57 knees). A second group of 35 patients (n = 36 samples) who presented during the same time period with an antibiotic spacer also had synovial cytokines measured before second-stage reimplantation. For the first group of 90 patients, the MSIS definition classified each joint at the time of surgery as infected (n = 31) or not infected (n = 59) and was used as the standard to test the accuracy in diagnosing PJI. Of the 35 patients with synovial marker data before second-stage surgery, 15 patients had cytokine measurements both at explantation and reimplantation and were used to quantify the change between stages. The reimplantation group had a minimum 1-year followup (with four [11%] patients lost to followup) and was classified into successful or failed treatment based on Delphibased consensus data and was used to test the accuracy in detecting infection resolution at reimplantation. Results Interleukin (IL)-1b and interferon-c demonstrated the highest diagnostic utility (area under the curve 0.92, 0.91, respectively); IL-1b and IL-6 had the highest sensitivities (0.90 [95% confidence interval {CI}, 0.74– 0.98] and 0.81 [0.63–0.93]). As a measure of infection resolution, IL-1b had the greatest decrease (12.4-fold; level at explantation: 232.4 [range, 23.1–1545.7]; level at reimplantation: 18.8 (range 1.2–298.9); mean difference: 325.5 [95% CI, 65.0–596.0]; p = 0.0001), and IL-6 had a near (...truncated)


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Salvatore J. Frangiamore, Marcelo B. P. Siqueira, Anas Saleh, Thomas Daly, Carlos A. Higuera, Wael K. Barsoum. Synovial Cytokines and the MSIS Criteria Are Not Useful for Determining Infection Resolution After Periprosthetic Joint Infection Explantation, Clinical Orthopaedics and Related Research®, 2016, pp. 1630-1639, Volume 474, Issue 7, DOI: 10.1007/s11999-016-4710-x