Subscribe to RSS
DOI: 10.1055/a-1303-5105
Diagnostic Accuracy of Synovial Neopterin, TNF-α and Presepsin in Periprosthetic Joint Infection: A Prospective Study
Die Wertigkeit von synovialem Neopterin, TNF-α und Presepsin in der Diagnostik von Periprothetischen Infektionen: Eine prospektive StudieAbstract
Background Due to the lack of specificity of conventional diagnostic tools, the prediction of periprosthetic joint infections (PJI) remains challenging. The purpose of this study was to evaluate the accuracy of synovial fluid neopterin, presepsin, and TNF-α as diagnostic parameters and to compare it to the biomarkers recommended in the 2018 definition of periprosthetic hip and knee infection.
Methods Between August 2018 and July 2019, a prospective cohort study was conducted in 80 patients with painful hip, shoulder, and knee arthroplasty. In addition to medical history, clinical and laboratory data were gathered. PJI was diagnosed based on the 2018 definition of periprosthetic hip and knee infection. Synovial joint fluid was analyzed for biomarker measurement using standard quantitative enzyme immunoassay kits.
Results Fifty-three patients (66%) were classified as the aseptic group and twenty-seven patients (34%) as the PJI group. The mean levels of synovial fluid neopterin were significantly higher (p < 0.01) in the PJI group than those in the aseptic group (aseptic 8.3 ± 6.9 vs. PJI 20.9 ± 21.4 nmol/L). The average values of synovial fluid TNF-α and presepsin were not significantly higher in the PJI group than those in the aseptic group (presepsin: aseptic 0.13 ± 0.19 vs. PJI 0.11 ± 0.32 ng/mL, p = 0.08; TNF-α: aseptic 6.6 ± 7.3 vs. PJI 46.3 ± 123.2 pg/mL, p = 0.17). Synovial fluid neopterin was 59% specific and 74% sensitive with a cut-off value of 7.2 nmol/L. The sensitivity and specificity of synovial fluid TNF-α were 63 and 51% with a cut-off value of 3.9 pg/mL. Synovial fluid presepsin was 51% specific and 29% sensitive with a cut-off value above 0.06 ng/mL.
Conclusion Synovial fluid neopterin appears to a reliable diagnostic marker for detection of PJI. In contrast, synovial fluid TNF-α and presepsin are not suitable to exclude or diagnose PJI.
Zusammenfassung
Hintergrund Aufgrund der Unzuverlässigkeit der aktuell zur Verfügung stehenden diagnostischen Tests bleibt die Diagnosestellung von periprothetischen Infektionen (PPI) eine Herausforderung. Das Ziel dieser Studie war es, die Zuverlässigkeit von Neopterin, Presepsin und TNF-α aus der Synovialflüssigkeit als Parameter in der Diagnostik von PPI zu bewerten und diese mit denen von Biomarkern, die in der 2018er-Definition von PPI des Knie- und Hüftgelenks empfohlen werden, zu vergleichen.
Methoden Zwischen August 2018 und Juli 2019 wurde eine prospektive Kohortenstudie mit 80 Patienten, die über Schmerzen bei einliegender Endoprothese an Knie-, Schulter- und Hüftgelenk klagten, durchgeführt. Neben der Anamnese wurden klinische und laborchemische Daten erhoben. Die Diagnose PPI wurde anhand der Definition von periprothetischen Infektionen aus dem Jahr 2018 gestellt. Neopterin, TNF-alpha und Presepsin wurden mit standartisierten ELISA in der Synovialflüssigkeit gemessen
Ergebnisse 53 (66%) Patienten wurden als aseptisch und 27 (34%) als die PPI-Gruppe klassifiziert. Die mittleren Konzentrationen von Neopterin in der Synovialflüssigkeit waren bei Patienten mit PPI signifikant höher (p < 0,01) als in der aseptischen Gruppe (aseptisch 8,3 ± 6,9 nmol/l vs. PPI 20,9 ± 21,4 nmol/l). Die mittleren Konzentrationen von synovialem TNF-α und Presepsin waren nicht signifikant höher bei Patienten mit PPI als in der aseptischen Gruppe (Presepsin: aseptisch 0,13 ± 0,19 ng/ml vs. PPI 0,11 ± 0,32 ng/ml, p = 0,08; TNF-α: aseptisch 6,6 ± 7,3 pg/ml vs. PPI 46,3 ± 123,2 pg/ml, p = 0,17). Synoviales Neopterin zeigte eine Spezifität von 59% und eine Sensitivität von 74% bei einem Cut-off-Level von 7,2 nmol/l. Die Sensitivität und Spezifität von snyovialem TNF-α lag bei 63% und 51% bei einem Cut-off-Level von 3,9 pg/ml. Synoviales Presepsin wies eine Sepzifität von 51% und eine Sensitivität von 29% bei einem Cut-off-Level über 0,06 ng/ml auf.
Schlussfolgerungen Synoviales Neopterin erwies sich als vielversprechender Biomarker in der Diagnostik von periprothetischen Infektionen. Synoviales TNF-α und Presepsin sind nicht geeignet, um eine periprothetische Infektion auszuschließen.
Publication History
Article published online:
09 December 2020
© 2020. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Clark CR, Heckman JD. Volume versus outcomes in orthopaedic surgery: a proper perspective is paramount. J Bone Joint Surg Am 2001; 83-A: 1619-1621
- 2 Otto-Lambertz C, Yagdiran A, Wallscheid F. et al. Periprosthetic Infection in Joint Replacement. Dtsch Arztebl Int 2017; 114: 347-353 doi:10.3238/arztebl.2017.0347
- 3 Gundtoft PH, Overgaard S, Schonheyder HC. et al. The “true” incidence of surgically treated deep prosthetic joint infection after 32,896 primary total hip arthroplasties. Acta Orthop 2015; 86: 326-334
- 4 Kurtz S, Ong K, Lau E. et al. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am 2007; 89: 780-785
- 5 Tetreault MW, Estrera KA, Kayupov E. et al. Are patients being evaluated for periprosthetic joint infection prior to referral to a tertiary care center?. Arthroplast Today 2017; 4: 216-220 doi:10.1016/j.artd.2017.10.001
- 6 Parvizi J, Jacovides C, Antoci V. et al. Diagnosis of periprosthetic joint infection: the utility of a simple yet unappreciated enzyme. J Bone Joint Surg Am 2011; 93: 2242-2248 doi:10.2106/JBJS.J.01413
- 7 Parvizi J, Tan TL, Goswami K. et al. The 2018 Definition of Periprosthetic Hip and Knee Infection: An Evidence-Based and Validated Criteria. J Arthroplasty 2018; 33: 1309-1314.e2 doi:10.1016/j.arth.2018.02.078
- 8 Bjerke-Kroll BT, Christ AB, McLawhorn AS. et al. Periprosthetic joint infections treated with two-stage revision over 14 years: an evolving microbiology profile. J Arthroplasty 2014; 29: 877-882 doi:10.1016/j.arth.2013.09.053
- 9 Yuan K, Chen HL, Cui ZM. Diagnostic accuracy of C-reactive protein for periprosthetic joint infection: a meta-analysis. Surg Infect (Larchmt) 2014; 15: 548-559 doi:10.1089/sur.2013.066
- 10 Kheir MM, Tan TL, Shohat N. et al. Routine Diagnostic Tests for Periprosthetic Joint Infection Demonstrate a High False-Negative Rate and Are Influenced by the Infecting Organism. J Bone Joint Surg Am 2018; 100: 2057-2065 doi:10.2106/JBJS.17.01429
- 11 Glehr M, Friesenbichler J, Hofmann G. et al. Novel biomarkers to detect infection in revision hip and knee arthroplasties. Clin Orthop Relat Res 2013; 471: 2621-2628 doi:10.1007/s11999-013-2998-3
- 12 Patel R, Alijanipour P, Parvizi J. Advancements in Diagnosing Periprosthetic Joint Infections after Total Hip and Knee Arthroplasty. Open Orthop J 2016; 10: 654-661 doi:10.2174/1874325001610010654
- 13 Bottner F, Wegner A, Winkelmann W. et al. Interleukin-6, procalcitonin and TNF-α: markers of peri-prosthetic infection following total joint replacement. J Bone Joint Surg Br 2007; 89: 94-99
- 14 Marazzi MG, Randelli F, Brioschi M. et al. Presepsin: A potential biomarker of PJI? A comparative analysis with known and new infection biomarkers. Int J Immunopathol Pharmacol 2018; 31: 394632017749356 doi:10.1177/0394632017749356
- 15 Müller N, Heistermann M, Strube C. et al. Age, but not anthelmintic treatment, is associated with urinary neopterin levels in semi-free ranging Barbary macaques. Sci Rep 2017; 7: 41973 doi:10.1038/srep41973
- 16 Cats-Baril W, Gehrke T, Huff K. et al. International consensus on periprosthetic joint infection: description of the consensus process. Clin Orthop Relat Res 2013; 471: 4065-4075 doi:10.1007/s11999-013-3329-4
- 17 Bilgen O, Atici T, Durak K. et al. C-reactive protein values and erythrocyte sedimentation rates after total hip and total knee arthroplasty. J Int Med Res 2001; 29: 7-12 doi:10.1177/147323000102900102
- 18 Larsson S, Thelander U, Friberg S. C-reactive protein (CRP) levels after elective orthopedic surgery. Clin Orthop Relat Res 1992; 275: 237-242
- 19 Ellenrieder M, Lenz R, Haenle M. et al. Two-stage revision of implant-associated infections after total hip and knee arthroplasty. GMS Krankenhhyg Interdiszip 2011; 6: Doc17 doi:10.3205/dgkh000174
- 20 Murr C, Widner B, Wirleitner B. et al. Neopterin as a marker for immune system activation. Curr Drug Metab 2002; 3: 175-187
- 21 Ghanem E, Antoci V, Pulido L. et al. The use of receiver operating characteristics analysis in determining erythrocyte sedimentation rate and C-reactive protein levels in diagnosing periprosthetic infection prior to revision total hip arthroplasty. Int J Infect Dis 2009; 13: e444-e449
- 22 Deirmengian C, Kardos K, Kilmartin P. et al. Combined measurement of synovial fluid α-Defensin and C-reactive protein levels: highly accurate for diagnosing periprosthetic joint infection. J Bone Joint Surg Am 2014; 96: 1439-1445 doi:10.2106/JBJS.M.01316
- 23 Sghiri R, Feinberg J, Thabet F. et al. Gamma interferon is dispensable for neopterin production in vivo. Clin Diagn Lab Immunol 2005; 12: 1437-1441
- 24 Werner-Felmayer G, Werner ER, Fuchs D. et al. Tumour necrosis factor-alpha and lipopolysaccharide enhance interferon-induced tryptophan degradation and pteridine synthesis in human cells. Biol Chem Hoppe Seyler 1989; 370: 1063-1069
- 25 Werner-Felmayer G, Baier-Bitterlich G, Fuchs D. et al. Detection of bacterial pyrogens on the basis of their effects on gamma interferon-mediated formation of neopterin or nitrite in cultured monocyte cell lines. Clin Diagn Lab Immunol 1995; 2: 307-313
- 26 Shaw AC. Serum C-reactive protein and neopterin concentrations in patients with viral or bacterial infection. J Clin Pathol 1991; 44: 596-599
- 27 Yildirim K, Misir A, Kizkapan TB. et al. Neopterin, Interleukin-6, Procalcitonin, C-Reactive Protein And PET-CT Staining As Markers In Infected Total Knee Prosthesis, A Retrospective Analysis. Acta Orthop Belg 2017; 83: 624-630
- 28 Francesconi LP, Ceresér KM, Mascarenhas R. et al. Increased annexin-V and decreased TNF-α serum levels in chronic-medicated patients with schizophrenia. Neurosci Lett 2011; 502: 143-146
- 29 Levi M, Ten Cate H. Disseminated intravascular coagulation. N Engl J Med 1999; 341: 586-592
- 30 Yaegashi Y, Shirakawa K, Sato N. et al. Evaluation of a newly identified soluble CD14 subtype as a marker for sepsis. J Infect Chemother 2005; 11: 234-238
- 31 Hessle CC, Andersson B, Wold AE. Gram-positive and Gram-negative bacteria elicit different patterns of pro-inflammatory cytokines in human monocytes. Cytokine 2005; 30: 311-318
- 32 Erdemli B, Özbek EA, Başarir K. et al. Proinflammatory biomarkersʼ level and functional genetic polymorphisms in periprosthetic joint infection. Acta Orthop Traumatol Turc 2018; 52: 143-147 doi:10.1016/j.aott.2017.11.002
- 33 Sargentini V, Ceccarelli G, DʼAlessandro M. et al. Presepsin as a potential marker for bacterial infection relapse in critical care patients. A preliminary study. Clin Chem Lab Med 2015; 53: 567-573
- 34 Pizzolato E, Ulla M, Galluzzo C. et al. Role of presepsin for the evaluation of sepsis in the emergency department. Clin Chem Lab Med 2014; 52: 1395-1400
- 35 Enguix-Armada A, Escobar-Conesa R, García-De La Torre A. et al. Usefulness of several biomarkers in the management of septic patients: C-reactive protein, procalcitonin, presepsin and mid-regional pro-adrenomedullin. Clin Chem Lab Med 2016; 54: 163-168
- 36 Endo S, Suzuki Y, Takahashi G. et al. Usefulness of presepsin in the diagnosis of sepsis in a multicenter prospective study. J Infect Chemother 2012; 18: 891-897
- 37 Zou Q, Wen W, Zhang XC. Presepsin as a novel sepsis biomarker. World J Emerg Med 2014; 5: 16-19 doi:10.5847/wjem.j.1920-8642.2014.01.002
- 38 Wright SD, Ramos RA, Tobias PS. et al. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 1990; 249: 1431-1433
- 39 Vicenti G, Pesce V, Bizzoca D. et al. Perioperative plasmatic presepsin levels in patients undergoing total hip or knee replacement: a preliminary study. J Biol Regul Homeost Agents 2017; 31: 1081-1086
- 40 Etzerodt A, Rasmussen MR, Svendsen P. et al. Structural basis for inflammation-driven shedding of CD163 ectodomain and tumor necrosis factor-alpha in macrophages. J Biol Chem 2014; 289: 778-788
- 41 Wu CC, Lan HM, Han ST. et al. Comparison of diagnostic accuracy in sepsis between presepsin, procalcitonin, and C-reactive protein: a systematic review and meta-analysis. Ann Intensive Care 2017; 7: 91 doi:10.1186/s13613-017-0316-z
- 42 Scemama C, Anract P, Dumaine V. et al. Does vitamin E-blended polyethylene reduce wear in primary total hip arthroplasty: a blinded randomised clinical trial. Int Orthop 2017; 41: 1113-1118 doi:10.1007/s00264-016-3320-2