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4 th International Conference/Orthopedics & Rheumatology Baltimore, Maryland, USA

Interleukin-6 and other inflammatory markers in diagnosis of periprosthetic joint infection (PJI). 4 th International Conference/Orthopedics & Rheumatology Baltimore, Maryland, USA October 27 th , 2015. Adham Elsharkawi Elgeidi , MD Abdelrahman Elganainy , MD Noha Abou Elkhier , MD

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4 th International Conference/Orthopedics & Rheumatology Baltimore, Maryland, USA

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  1. Interleukin-6 and other inflammatory markers in diagnosisof periprosthetic joint infection (PJI) 4th International Conference/Orthopedics & Rheumatology Baltimore, Maryland, USA October 27th, 2015 AdhamElsharkawiElgeidi, MD AbdelrahmanElganainy, MD Noha Abou Elkhier, MD ShirienRakha, MD Mansoura, EGYPT

  2. No Conflict of interest

  3. Background • Aim of the study • Patients & Methods • - Criteria for definitive diagnosis of PJI • Results • Discussion • - Limitations • Conclusions

  4. Background

  5. Background • PJI is one of most common indications for • revision hip and knee arthroplasties . • In revision arthroplasty, distinction bet • septic and aseptic failure is critical → • Rx of failure secondary to PJI is different.

  6. Background • Several serum inflammatory markers → Dx of • suspected PJI. • IL-6 is a cytokine produced by activated • macrophages, monocytes and T cells in • context of inflammatory response. • IL-6 as a dx marker is still under investigation • & is not used routinely.

  7. Aim of the study Validate usefulness of IL-6 & other inflammatory markers (CRP, ESR, and WCC) in dx of PJI

  8. Patients and methods

  9. Prospective study • 40 hip / knee replacement Patients for • 2-stage revision surgery(2011-2013). • 21 ♂ & 19♀. • Age: 38–72 years (58.4 years ). • No arthroplasty was sonicated.

  10. Exclusion criteria • Chronic inflam. conditions (e.g. RA). • Malignancy. • Antibiotic Rx prior to surgery.

  11. Blood test • Blood samples obtained within 2 hrs before surgery. • Collected into two separate tubes. • One: a serum separator tested for CRP and IL-6. • The other : with sodium citrate for ESR and WCC.

  12. Tissue Samples Intra-op 6 deep tissue samples collected for: Histopathological evaluation (formalin preserved, paraffin embedded sections). 2. Conventional microbiologic culture (sterile surgical container ).

  13. Definitive Diagnosis of PJI (1) Visible purulence surrounding prosthesis. (2) Sinus tract communicating to implant. (3) Growth of bacteria on culture: a- ≥ 2 cultures that yield same organism. b- 1 culture with a virulent microorganism (e.g. Staph aureus). (4) Histopathological Examination: a- acute inflammation (≥ 5 PMN / HPF) b. combined with a positive culture.

  14. Results

  15. Results • 40 patients. • 11 (27.5 %): proved to be infected (PJI). • 29 (72.5 %): aseptic failure of prosthesis.

  16. Results • Isolated bacteria included: • Gram positive cocci: a.staphyaureus (n=5) b.coagulase-negative staph (n=3) c.enterococci (n=1) • Gram negative bacilli: a.escherichia coli (n=1) b.pseudomonas aeuroginosa (n=1)

  17. Table 1: Demographic data for the study population Characteristic Infected (n=11) Aseptic (n=29) Age(years) 59.6±6.1 57.9±7.8 Gender Male 4 (36.4 %) 17 (58.6 %) Female 7 (63.6 %) 12 (41.4 %) Joint type Knee 4 (36.4 %) 10 (34.5 %) Hip 7 (63.6 %) 19 (65.5 %) Variables are expressed as mean ± SD, or numbers (percentage)

  18. Table 2: Analysis of inflammatory markers in patients with infected and aseptic revision arthroplasty Inflammatory marker All procedures (hip+knee) Infected Aseptic P value ESR (mm/hour) Mean 85.9 28.3 0.0001 SD 33.9 20.5 WCC (cell×10 9L) Mean 12.3 7.7 0.0001 SD 2.9 1.7 CRP (mg/L) Mean 80.7 11.7 0.004 SD 61.9 13.1 IL-6 (pg/L) Mean 64.6 5.9 0.0001 SD 34.1 3.1

  19. Table 3: sensitivity, specificity, PPV, NPV, & accuracy of inflammatory markers Test Cut-off Sensit (%) Specif (%) PPV (%) NPV (%) Accuracy (%) ESR (mm/hour) 45.0 81.8 82.8 64.3 92.3 82.5 CRP (mg/L) 18.0 100.0 86.2 68.8 100.0 87.5 WCC (cell/10 9 /L) 9.2 90.9 75.9 58.8 95.6 80.0 IL-6 (pg/mL) 10.4 100.0 90.9 79.0 100.0 92.5 IL-6 + CRP 100.0 99.0 92.0 100.0 97.5

  20. Discussion

  21. Discussion • Dx of PJI remains a real challenge. • Standard lab used as first line tests to determine PJI • ieESR,WCC, and CRP, are not consistently reliable. • Cultures of wound drainage and sinus tracts do not • truly reflect organisms deep in joint, due to • likelihood of contamination by other skin flora. • Joint aspirate is useful for determining deep • infection. Sometimes, it cannot be easily obtained or • enough fluid is aspirated.

  22. Discussion • In this study, we evaluated utility of pre-op ESR, • WCC, serum CRP, and IL-6 as markers for PJI. • ESR has little value in diagnosis of PJI since its • sensitivity (81.8%) and specificity(82.8%) are low. • WCC sensitivity of 90.9 % and specificity of 75.9 % • IL-6 sensitivity (100 %) is similar to CRP, its • specificity (90.9 vs 86.2 %) and accuracy (92.5 vs • 87.5 %) are higher.

  23. Discussion • Advantage of IL-6: exhibits more rapid ↑and quicker ↓ to • normal vs CRP or ESR which are ↑ up to 3 wks post-op. • IL-6 level is a superior indicator of post-op. inflam. response • and to monitor infected patient’s response to Rx (1-3). • 1.Odak S, McNicholas M (2012) Diagnosis and management of infection after total knee arthroplasty. Orthop Trauma 26(2):80–85 • 2.Bottner F, Wegner A, Winkelmann W, Becker K, Erren M, Gotze C (2007) Interleukin-6, procalcitonin, TNF-α markers of periprosthetic infection following total joint replacement. J Bone Joint Surg Br 89-B:94–99 • 3.Wirtz DC, Heller KD, Miltner O, Zilkens KW, Wolff JM (2000) Interleukin-6: a potential inflammatory marker after total joint replacement. IntOrthop 24:194–196

  24. Limitations • Small number of included patients: 40 patients. • Not serially monitor IL-6 & markers post-op. • Intra-op. tissue samples chosen is not infected.

  25. Conclusions

  26. Conclusions • IL-6 is reliable marker for PJI, as it disting. between patients with infection and aseptic failure of prosthesis. • IL-6 >10.4 pg/ml and CRP >18 mg/L → identify all patients with PJI (sensitivity 100 %, NPV 100 %). • CRP + IL-6 is an excellent screening test to rapidly rule out deep infection of the implant.

  27. ﺍﻠﻧﻯﺮﺑﻛﻣﺃﻋﺑﺪﻮﺍﻟﻧﺎﺱﺍﻴﺄﻴﻬﺎﻗﺑﻟﻛﻣﻣﻦﻴﻦﻮﺍﻠﻧﺧﻟﻗﻛﻣﺗﺗﻗﻮﻦﻠﻌﻠﻛﻣ(٢۰ﺍﻟﺑﻗﺮﺓ ) O mankind! Worship your lord (Allah) who created you and those before you so that you may become Al-Muttaqun (the pious and righteous persons who fear Allah much and love Allah much, ( The Noble Qur`an, The Cow,20) بسم الله الرحمن الرحيم In the name of Allah , the Beneficent, the Merciful Thank You Mansoura, EGYPT 2015

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