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Wright JR, Chen See JR, Ly TT, Tokarev V, Pellegrino J, Peachey L, Anderson SLC, Walls CY, Hosler M, Shope AJ, Gulati S, Toler KO, Lamendella R. Application of a metatranscriptomics technology, CSI-Dx, for the detection of pathogens associated with prosthetic joint infections. Sci Rep 2024; 14:25100. [PMID: 39443495 PMCID: PMC11500344 DOI: 10.1038/s41598-024-74375-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 09/25/2024] [Indexed: 10/25/2024] Open
Abstract
Preoperative identification of causal organism(s) is crucial for effective prosthetic joint infection treatment. Herein, we explore the clinical application of a novel metatranscriptomic (MT) workflow, CSI-Dx, to detect pathogens associated with prosthetic joint infection. MT provides insight into transcriptionally active microbes, overcoming limitations of culture-based and available molecular methods. This study included 340 human synovial fluid specimens subjected to CSI-Dx and traditional culture-based methods. Exploratory analyses were conducted to determine sensitivity and specificity of CSI-Dx for detecting clinically-relevant taxa. Our findings provide insights into the active microbial community composition of synovial fluid from arthroplasty patients and demonstrate the potential clinical utility of CSI-Dx for aiding prosthetic joint infection diagnosis. This approach offers potential for improved sensitivity and acceptable specificity compared to synovial fluid culture, enabling detection of culturable and non-culturable microorganisms. Furthermore, CSI-Dx provides valuable information on antimicrobial resistance gene expression. While further optimization is needed, integrating metatranscriptomic technologies like CSI-Dx into routine clinical practice can revolutionize prosthetic joint infection diagnosis by offering a comprehensive and active snapshot of associated pathogens.
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Affiliation(s)
- Justin R Wright
- Contamination Source Identification, 419 14th St., Huntingdon, PA, 16652, USA
| | - Jeremy R Chen See
- Contamination Source Identification, 419 14th St., Huntingdon, PA, 16652, USA
| | - Truc T Ly
- Contamination Source Identification, 419 14th St., Huntingdon, PA, 16652, USA
| | - Vasily Tokarev
- Contamination Source Identification, 419 14th St., Huntingdon, PA, 16652, USA
| | - Jordan Pellegrino
- Contamination Source Identification, 419 14th St., Huntingdon, PA, 16652, USA
| | - Logan Peachey
- Contamination Source Identification, 419 14th St., Huntingdon, PA, 16652, USA
| | | | - Christine Y Walls
- Contamination Source Identification, 419 14th St., Huntingdon, PA, 16652, USA
| | - Maxwell Hosler
- Contamination Source Identification, 419 14th St., Huntingdon, PA, 16652, USA
| | - Alexander J Shope
- Contamination Source Identification, 419 14th St., Huntingdon, PA, 16652, USA
| | - Simmi Gulati
- CD Laboratories, Zimmer Biomet, Towson, MD, 21286, USA
| | - Krista O Toler
- Department of Diagnostics Research and Development, Zimmer Biomet, Claymont, DE, 19703, USA
| | - Regina Lamendella
- Contamination Source Identification, 419 14th St., Huntingdon, PA, 16652, USA.
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Davis JS, Dewar D, Manning L. Prosthetic joint infection diagnosis in an age of changing clinical patterns of infection and new technologies. Med J Aust 2024; 220:225-228. [PMID: 38351733 DOI: 10.5694/mja2.52228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 01/31/2024] [Indexed: 03/18/2024]
Affiliation(s)
- Joshua S Davis
- University of Newcastle, Newcastle, NSW
- Hunter Medical Research Institute, Newcastle, NSW
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Heckmann ND, Wang JC, Liu KC, Won P, Chung BC, Mayer LW, Longjohn DB, Oakes DA, Christ AB, Lieberman JR. Refining the Role of Routine Synovial Alpha-Defensin in Periprosthetic Joint Infection Following Total Knee Arthroplasty: An Analysis of Limitations. J Arthroplasty 2023; 38:2691-2697. [PMID: 37295619 DOI: 10.1016/j.arth.2023.05.095] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 05/29/2023] [Accepted: 05/31/2023] [Indexed: 06/12/2023] Open
Abstract
BACKGROUND The utility of the synovial alpha-defensin test in diagnosing periprosthetic joint infections (PJIs) remains controversial. This study aimed to examine the diagnostic utility of this test. METHODS A retrospective review was conducted to identify adults evaluated for PJI following total knee arthroplasty at a single institution. Patient demographics, laboratory results, and operative details were recorded. Using the 2018 Musculoskeletal Infection Society (MSIS) criteria, cases were categorized as definitive, inconclusive, or negative for PJI. The sensitivity, specificity, positive predictive value, and negative predictive value of each MSIS criterion was determined. The number of patients whose PJI diagnosis was contingent on alpha-defensin positivity was calculated. RESULTS Overall, 172 total knee arthroplasty patients were included, who had an average age of 70.4 years (range, 39 to 95). Of the 21 patients who met major criteria, 20 (95.2%) were alpha-defensin positive. Of the remaining 151 patients, 85 did not meet minor criteria, all of whom were alpha-defensin negative. Among the 30 patients who met minor criteria, 28 (93.3%) were alpha-defensin positive and 2 (6.7%) were negative. The remaining 36 patients were deemed inconclusive preoperatively. In total, alpha-defensin testing changed the diagnosis in only 9 of 172 patients (5.2%). The sensitivity, specificity, positive predictive value, and negative predictive value of alpha-defensin in this cohort were 94.1, 100, 100, and 97.6, respectively. CONCLUSION Alpha-defensin may assist in the diagnosis of PJI when a preoperative workup is inconclusive. However, this test is often unnecessary when the diagnosis of PJI can be made using the 2018 MSIS criteria.
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Affiliation(s)
- Nathanael D Heckmann
- Department of Orthopaedic Surgery, Keck Medical Center of the University of Southern California, Los Angeles, California
| | - Jennifer C Wang
- Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Kevin C Liu
- Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Paul Won
- Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Brian C Chung
- Department of Orthopaedic Surgery, Keck Medical Center of the University of Southern California, Los Angeles, California
| | - Lucas W Mayer
- Department of Orthopaedic Surgery, Keck Medical Center of the University of Southern California, Los Angeles, California
| | - Donald B Longjohn
- Department of Orthopaedic Surgery, Keck Medical Center of the University of Southern California, Los Angeles, California
| | - Daniel A Oakes
- Department of Orthopaedic Surgery, Keck Medical Center of the University of Southern California, Los Angeles, California
| | - Alexander B Christ
- Department of Orthopaedic Surgery, Keck Medical Center of the University of Southern California, Los Angeles, California
| | - Jay R Lieberman
- Department of Orthopaedic Surgery, Keck Medical Center of the University of Southern California, Los Angeles, California
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Grzelecki D, Grajek A, Otworowski M, Paskal W, Fulin P, Kowalczewski J. The Diagnostic Utility of Fast Tests for Detecting C-Reactive Protein in Synovial Fluid in Periprosthetic Joint Infections. J Bone Joint Surg Am 2023; 105:1759-1767. [PMID: 37733911 DOI: 10.2106/jbjs.23.00252] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/23/2023]
Abstract
BACKGROUND Despite the fact that many synovial fluid biomarkers have found application in the routine diagnosis of periprosthetic joint infection (PJI), this process still remains a challenge for orthopaedic surgeons. To simplify this process, fast point-of-care (POC) tests can be used during ambulatory visits and in operating room conditions. However, before such tests can be routinely used in clinical practice, they require validation. The purpose of the present study was to evaluate the diagnostic accuracy of different fast POC tests for detecting C-reactive protein (CRP) in synovial fluid for the diagnosis of PJI. METHODS Synovial fluid samples were collected from 120 consecutive patients who underwent revision total joint arthroplasty (TJA). The patients were divided into 2 groups. The first group included 76 patients who underwent revision for reasons other than infection (the aseptic revision TJA [arTJA] group), and the second group included 44 patients who underwent revision because of periprosthetic joint infection (PJI). The diagnosis of infection was made according to the International Consensus Meeting (ICM) 2018 criteria. All patients were operatively treated at a single orthopaedic center from January 2022 to February 2023. Four fast CRP tests with different cutoff values (1 and 3 mg/L, ≥8 mg/L, ≥10 mg/L [cassette], ≥10 mg/L [strip]) were used off-label for synovial fluid testing. Tests were performed on the same synovial fluid samples, and the results of these tests were compared with those obtained with the laboratory method. RESULTS The cassette test with a minimum cutoff value of ≥8 mg/L demonstrated the best accuracy for the diagnosis of chronic PJI, with a sensitivity and specificity of 90.9% and 90.8%, respectively. For the cassette test with a cutoff value of >3 mg/L, the sensitivity and specificity were 68.2% and 77.6%, respectively. For the tests with a minimum cutoff value of ≥10 mg/L, the sensitivity and specificity were 77.3% and 94.7%, respectively, for the cassette test and 77.3% and 96.1%, respectively, for the strip test. The laboratory method with the statistically calculated threshold (2.7 mg/L) revealed the highest AUC (area under the receiver operating characteristic curve) value (0.95), with 90.9% sensitivity and 94.7% specificity. CONCLUSIONS The cassette POC test with the minimum cutoff value of ≥8 mg/L had very good accuracy for the diagnosis of chronic PJI. This test had comparable sensitivity and slightly lower specificity in comparison with the laboratory method with the calculated threshold of 2.7 mg/L. LEVEL OF EVIDENCE Diagnostic Level III . See Instructions for Authors for a complete description of levels of evidence.
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Affiliation(s)
- Dariusz Grzelecki
- Department of Orthopedics and Rheumoorthopedics, Centre of Postgraduate Medical Education, Prof. Adam Gruca Orthopedic and Trauma Teaching Hospital, Otwock, Poland
| | - Aleksandra Grajek
- Central Laboratory, Prof. Adam Gruca Orthopedic and Trauma Teaching Hospital, Otwock, Poland
| | - Maciej Otworowski
- Department of Orthopaedic Surgery and Traumatology, Southern Hospital, Warsaw, Poland
| | - Wiktor Paskal
- Department of Methodology, Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland
| | - Petr Fulin
- 1st Department of Orthopaedics, First Faculty of Medicine of Charles University and Motol University Hospital, Prague, Czech Republic
| | - Jacek Kowalczewski
- Department of Orthopedics and Rheumoorthopedics, Centre of Postgraduate Medical Education, Prof. Adam Gruca Orthopedic and Trauma Teaching Hospital, Otwock, Poland
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Yilmaz MK, Abbaszadeh A, Tarabichi S, Azboy I, Parvizi J. Diagnosis of Periprosthetic Joint Infection: The Utility of Biomarkers in 2023. Antibiotics (Basel) 2023; 12:1054. [PMID: 37370373 DOI: 10.3390/antibiotics12061054] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 06/11/2023] [Accepted: 06/12/2023] [Indexed: 06/29/2023] Open
Abstract
Periprosthetic joint infection (PJI) is a rare yet devastating complication following total joint arthroplasty (TJA). Early and accurate diagnosis of PJI is paramount in order to maximize the chances of successful treatment. However, we are yet to identify a single "gold standard" test for the diagnosis of PJI. As a result, the diagnosis of PJI is often challenging. Currently, the 2018 ICM definition of PJI is the only validated diagnostic criteria available. This article will review the importance of serum and synovial biomarkers in the diagnosis of PJI. In addition, it will provide a brief overview of the emerging modalities for the identification of infections in this setting.
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Affiliation(s)
- Mehmet Kursat Yilmaz
- Rothman Orthopaedic Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA
- Department of Orthopaedics and Traumatology, School of Medicine, Istanbul Medipol University, Istanbul 34810, Turkey
| | - Ahmad Abbaszadeh
- Rothman Orthopaedic Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Saad Tarabichi
- Rothman Orthopaedic Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA
| | - Ibrahim Azboy
- Department of Orthopaedics and Traumatology, School of Medicine, Istanbul Medipol University, Istanbul 34810, Turkey
| | - Javad Parvizi
- Rothman Orthopaedic Institute, Thomas Jefferson University, Philadelphia, PA 19107, USA
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Alrayes MM, Sukeik MT. Emerging Technologies in Diagnosing Periprosthetic Joint Infections. Indian J Orthop 2023; 57:643-652. [PMID: 37128562 PMCID: PMC10147868 DOI: 10.1007/s43465-023-00891-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 04/04/2023] [Indexed: 05/03/2023]
Abstract
Periprosthetic joint infection (PJI) is a well-known serious complication following joint replacement surgeries and is responsible for high failure rates of implanted devices. Any delay in the diagnosis can compromise treatment success, putting a huge burden on the patients' wellness and healthcare systems. Diagnosing PJIs is quite complex as there is still no gold standard test to reach the definitive diagnosis in a timely manner. A number of laboratory tests and radiological imaging inventions have evolved in the past few years, requiring consistent updates of the available guidelines to keep up with the latest advances in the field. This article highlights the recent advances in diagnosing PJIs and discusses their validity for use in clinical practice.
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Affiliation(s)
- Majd M. Alrayes
- Department of Trauma & Orthopedics, Dammam Medical Complex, Dammam, 32210 Saudi Arabia
| | - Mohamed T. Sukeik
- Department of Trauma & Orthopaedics, Dr. Sulaiman Al-Habib Hospital–Al Khobar, Al Khobar, 34423 Saudi Arabia
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Jandl NM, Kleiss S, Mussawy H, Beil FT, Hubert J, Rolvien T. Absolute synovial polymorphonuclear neutrophil cell count as a biomarker of periprosthetic joint infection. Bone Joint J 2023; 105-B:373-381. [PMID: 36924172 DOI: 10.1302/0301-620x.105b4.bjj-2022-0628.r1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Abstract
The aim of this study was to evaluate the diagnostic accuracy of the absolute synovial polymorphonuclear neutrophil cell (PMN) count for the diagnosis or exclusion of periprosthetic joint infection (PJI) after total hip (THA) or knee arthroplasty (TKA). In this retrospective cohort study, 147 consecutive patients with acute or chronic complaints following THA and TKA were included. Diagnosis of PJI was established based on the 2018 International Consensus Meeting criteria. A total of 39 patients diagnosed with PJI (32 chronic and seven acute) and 108 patients with aseptic complications were surgically revised. Using receiver operating characteristic curves and calculating the area under the curve (AUC), an optimal synovial cut-off value of 2,000 PMN/µl was determined (AUC 0.978 (95% confidence interval (CI) 0.946 to 1)). Using this cut-off, sensitivity and specificity of absolute synovial PMN count for PJI were 97.4% (95% CI 91.2 to 100) and 93.5% (95% CI 88.9 to 98.1), respectively. Positive and negative predictive value were 84.4% (95% CI 72.7 to 93.9) and 99.0% (95% CI 96.7 to 100), respectively. Exclusion of 20 patients with acute complications improved specificity to 97.9% (95% CI 94.6 to 100). Different cut-off values for THA (< 3,600 PMN/µl) and TKA (< 2,000 PMN/µl) were identified. Absolute synovial PMN count correlated strongly with synovial alpha-defensin (AD) (r = 0.759; p < 0.001). With a positive AD result, no additional PJI could be identified in any case. Absolute synovial PMN count is a widely available, rapid, cost-effective, and accurate marker in PJI diagnostics, whereas synovial AD appears to be a surrogate parameter of absolute synovial PMN count. Despite limitations in the early postoperative phase, wear, and rheumatic diseases in confirming PJI, an absolute synovial PMN count below 2,000/µl is highly suitable for ruling out PJI, with specific cut-off values for THA and TKA.
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Affiliation(s)
- Nico M Jandl
- Department of Trauma and Orthopaedic Surgery, Division of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sebastian Kleiss
- Department of Trauma and Orthopaedic Surgery, Division of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Haider Mussawy
- Department of Trauma and Orthopaedic Surgery, Division of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Frank T Beil
- Department of Trauma and Orthopaedic Surgery, Division of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Jan Hubert
- Department of Trauma and Orthopaedic Surgery, Division of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Tim Rolvien
- Department of Trauma and Orthopaedic Surgery, Division of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Fisher CR, Patel R. Profiling the Immune Response to Periprosthetic Joint Infection and Non-Infectious Arthroplasty Failure. Antibiotics (Basel) 2023; 12:296. [PMID: 36830206 PMCID: PMC9951934 DOI: 10.3390/antibiotics12020296] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/20/2023] [Accepted: 01/29/2023] [Indexed: 02/04/2023] Open
Abstract
Arthroplasty failure is a major complication of joint replacement surgery. It can be caused by periprosthetic joint infection (PJI) or non-infectious etiologies, and often requires surgical intervention and (in select scenarios) resection and reimplantation of implanted devices. Fast and accurate diagnosis of PJI and non-infectious arthroplasty failure (NIAF) is critical to direct medical and surgical treatment; differentiation of PJI from NIAF may, however, be unclear in some cases. Traditional culture, nucleic acid amplification tests, metagenomic, and metatranscriptomic techniques for microbial detection have had success in differentiating the two entities, although microbiologically negative apparent PJI remains a challenge. Single host biomarkers or, alternatively, more advanced immune response profiling-based approaches may be applied to differentiate PJI from NIAF, overcoming limitations of microbial-based detection methods and possibly, especially with newer approaches, augmenting them. In this review, current approaches to arthroplasty failure diagnosis are briefly overviewed, followed by a review of host-based approaches for differentiation of PJI from NIAF, including exciting futuristic combinational multi-omics methodologies that may both detect pathogens and assess biological responses, illuminating causes of arthroplasty failure.
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Affiliation(s)
- Cody R. Fisher
- Mayo Clinic Graduate School of Biomedical Sciences, Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA
- Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA
| | - Robin Patel
- Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA
- Division of Public Health, Infectious Diseases, and Occupational Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA
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Grzelecki D, Grajek A, Walczak P, Kowalczewski J. What is the Accuracy of a Rapid Strip Test That Detects D-lactic Acid in Synovial Fluid for the Diagnosis of Periprosthetic Joint Infections? Clin Orthop Relat Res 2023; 481:120-129. [PMID: 35944072 PMCID: PMC9750661 DOI: 10.1097/corr.0000000000002328] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 06/28/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND D-lactic acid is a specific marker produced almost exclusively by bacterial species; thus, the appearance of this marker in synovial fluid may indicate periprosthetic joint infection (PJI). Recently, studies have investigated the accuracy of enzyme-linked laboratory tests that detect D-lactic acid in synovial fluid to diagnose PJI. However, to our knowledge, no studies have determined the usefulness of rapid strip tests that detect D-lactic acid in synovial fluid in the diagnosis of PJI. QUESTIONS/PURPOSES (1) What is the best cutoff value for the rapid D-lactic acid strip test for diagnosing PJI? (2) What are the diagnostic accuracies (sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) of the rapid D-lactic acid strip test and two different rapid leukocyte esterase (LE) strip tests? METHODS This prospective study enrolled 157 patients who underwent revision THA or TKA from May 2021 to February 2022 at a single orthopaedic center. Seventy percent (110 of 157) were eligible for analysis; 10% of these patients (15 of 157) were excluded based on the exclusion criteria (causes of revisions and additional comorbidities that may interfere with the results), and 20% (32 of 157) of the synovial fluid samples could not be tested (dry taps and blood-contaminated samples that could not be centrifuged). We performed the following off-label diagnostic tests on synovial fluid samples collected from all patients: the D-lactic acid strip test (QuantiQuick TM , BioAssay System), two different LE strip tests (10 EA from ARKRAY and BM 10 from BioMaxima). Differently colored strips were marked with symbols (from [-] to [++++] for D-lactic acid and from [-] to [+++] for LE tests) according to the manufacturers' instructions. For the LE tests, results were different for (++), which corresponds to a minimal value of 250 leu/mL for 10 EA and 125 leu/mL for BM 10 tests. The diagnostic standard for the presence or absence of PJI in this study was the International Consensus Meeting (ICM) 2018 criteria; based on these criteria (without the application of an LE test as a minor criterion), all patients were assessed and divided into two groups. Patients who did not meet the criteria for PJI and underwent revision for aseptic loosening, implant malposition, instability, or implant damage were included in the aseptic revision total joint arthroplasty group (68 patients). Patients with a fistula penetrating the joint, those with two positive culture results of the same pathogen, or those with ≥ 6 points according to ICM 2018 minor criteria were enrolled in the PJI group (42 patients). To ascertain the best cutoff value for the rapid D-lactic acid and both LE strip tests for diagnosing PJI, we used collected results, generated a receiver operating characteristic curve, and calculated the Youden index. To determine the accuracies of the diagnostic tests, we calculated their sensitivities, specificities, PPVs, and NPVs against the diagnostic standard (the ICM 2018 criteria). RESULTS The best cutoff value for D-lactic acid was 22.5 mg/L, which corresponded to a reading of (+) on the test strip. For D-lactic acid, in the diagnosis of PJI, the sensitivity was 83% (95% confidence interval [CI] 68% to 92%) and specificity was 100% (95% CI 93% to 100%). For both LE strip tests, the best cutoff value was the same as that proposed in the ICM 2018 criteria. For LE (10 EA), the sensitivity was 81% (95% CI 66% to 91%) and specificity was 99% (95% CI 91% to 100%); for LE (BM 10), sensitivity was 81% (95% CI 65% to 91%) and specificity was 97% (95% CI 89% to 100%). CONCLUSION A rapid off-label D-lactic acid strip test is valuable for diagnosing PJI. The results of this study indicate very good accuracy with comparable sensitivity and specificity for both LE strip tests. The usefulness of the test in a group of patients with chronic inflammatory diseases and the reproducibility of the reading by different researchers were not analyzed in this study and require further investigations. Before a rapid D-lactic strip test is routinely used for diagnosing PJI, multicenter studies on a larger group of patients should be conducted.Level of Evidence Level II, diagnostic study.
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Affiliation(s)
- Dariusz Grzelecki
- Department of Orthopedics and Rheumoorthopedics, Centre of Postgraduate Medical Education, Prof. Adam Gruca Orthopedic and Trauma Teaching Hospital, Otwock, Poland
| | - Aleksandra Grajek
- Central Laboratory of Prof. Adam Gruca Orthopedic and Trauma Teaching Hospital, Otwock, Poland
| | - Piotr Walczak
- Department of Orthopedics, Centre of Postgraduate Medical Education, Prof. Adam Gruca Orthopedic and Trauma Teaching Hospital, Otwock, Poland
| | - Jacek Kowalczewski
- Department of Orthopedics and Rheumoorthopedics, Centre of Postgraduate Medical Education, Prof. Adam Gruca Orthopedic and Trauma Teaching Hospital, Otwock, Poland
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10
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Owens JM, Dennis DA, Abila PM, Johnson RM, Jennings JM. Alpha-Defensin Offers Limited Utility in Work-Up Prior to Reimplantation in Chronic Periprosthetic Joint Infection in Total Joint Arthroplasty Patients. J Arthroplasty 2022; 37:2431-2436. [PMID: 35803520 DOI: 10.1016/j.arth.2022.06.024] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 06/27/2022] [Accepted: 06/29/2022] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Alpha-defensin (AD) is a synovial biomarker included in the 2018 consensus criteria for diagnosing periprosthetic joint infection (PJI). Its value in assessing eradication of infection prior to second stage reimplantation is unclear. The purpose of this study was to evaluate the impact of AD on eligibility for reimplantation following resection for chronic PJI. METHODS This study included patients who previously underwent resection arthroplasty for PJI. Synovial fluid aspirated from 87 patients was retrospectively reviewed. All patients completed a 6-week course of intravenous antibiotics and an appropriate drug holiday. Synovial white blood cell count, percentage neutrophils, and culture from the AD immunoassay laboratory were reviewed with serum erythrocyte sedimentation rate and C-reactive protein values from our institution. A modified version of the 2018 consensus criteria was used, including white blood cell count, percentage neutrophils, erythrocyte sedimentation rate, and C-reactive protein. AD was then added to determine if it changed diagnosis or clinical management. RESULTS Four patients were categorized as "infected" (score >6), none exhibited a positive AD or positive culture. Sixty eight patients were diagnosed as "possibly infected" (score 2 to 5), none had a positive AD, and one had a positive culture (Cutibacterium acnes). AD did not change the diagnosis from "possibly infected" to "infected" in any case or alter treatment plans. Fifteen patients had a score of <2 (not infected) and none had a positive AD. CONCLUSION The routine use of AD in the work-up prior to a second-stage arthroplasty procedure for PJI may not be warranted.
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Affiliation(s)
| | - Douglas A Dennis
- Colorado Joint Replacement, Denver, Colorado; Department of Mechanical and Materials Engineering, University of Denver, Denver, Colorado; Department of Orthopaedics, University of Colorado School of Medicine, Denver, Colorado; Department of Biomedical Engineering, University of Tennessee, Knoxville, Tennessee
| | | | | | - Jason M Jennings
- Colorado Joint Replacement, Denver, Colorado; Department of Mechanical and Materials Engineering, University of Denver, Denver, Colorado
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11
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Rajput V, Meek RMD, Haddad FS. Periprosthetic joint infection: what next? Bone Joint J 2022; 104-B:1193-1195. [DOI: 10.1302/0301-620x.104b11.bjj-2022-0944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Periprosthetic joint infection (PJI) remains an extremely challenging complication. We have focused on this issue more over the last decade than previously, but there are still many unanswered questions. We now have a workable definition that everyone should align to, but we need to continue to focus on identifying the organisms involved. Surgical strategies are evolving and care is becoming more patient-centred. There are some good studies under way. There are, however, still numerous problems to resolve, and the challenge of PJI remains a major one for the orthopaedic community. This annotation provides some up-to-date thoughts about where we are, and the way forward. There is still scope for plenty of research in this area. Cite this article: Bone Joint J 2022;104-B(11):1193–1195.
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Affiliation(s)
- Vishal Rajput
- University College London Hospital, London, UK
- The Mid Yorkshire Hospitals NHS Trust, Wakefield, UK
| | | | - Fares S. Haddad
- University College London Hospital, London, UK
- The Bone & Joint Journal, London, UK
- The Princess Grace Hospital, London, UK
- The NIHR Biomedical Research Centre, University College London Hospitals, London, UK
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Synovial fluid calprotectin in diagnosing periprosthetic joint infection: A meta-analysis. INTERNATIONAL ORTHOPAEDICS 2022; 46:971-981. [PMID: 35233711 PMCID: PMC9001224 DOI: 10.1007/s00264-022-05357-6] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 02/22/2022] [Indexed: 11/08/2022]
Abstract
Purpose Periprosthetic joint infection (PJI) is one of the most debilitating complications following joint replacement surgery. Synovial biomarkers, such as Calprotectin, have become valuable in the diagnosis of PJI. This meta-analysis aimed to investigate the role of synovial Calprotectin as a diagnostic test in PJI. Methods This meta-analysis was conducted with adherence to PRISMA guidelines. PubMed, Cochrane, Web of Science, and Google Scholar were searched until February 2022. Inclusion criteria were as follows: all studies in which the patients with joint replacements were evaluated for PJI; synovial Calprotectin was the biomarker of choice to diagnose PJI; standardized guidelines were used as the gold standard for the diagnosis; and a comparison between the guidelines and Calprotectin results was made. Diagnostic parameters such as sensitivity, specificity, diagnostic odds ratio (DOR), positive predictive value, negative predictive value, and area under the curve (AUC) were calculated for the included studies to evaluate synovial Calprotectin for PJI diagnosis. Results The total number of the included patients was 618 from eight studies. The pooled sensitivity, specificity, and diagnostic odds ratio of Calprotectin test were 92% (95%CI: 84%-98%), 93% (95%CI: 84%-99%), and 187.61 (95%CI: 20.21–1741.18), respectively. The results showed that the negative and positive likelihood ratios of the Calprotectin test were 0.07 (95%CI: 0.02–0.22) and 9.91 (95%CI: 4.11–23.93), respectively. The SROC showed that the area under the curve for Calprotectin test was 0.935. Conclusion Synovial Calprotectin is a valuable biomarker as it provides a reliable and rapid diagnosis of PJI. It has the potential to be used in clinical practice due to its high sensitivity and specificity that are comparable to the other utilized biomarkers. Another advantage is its low cost relative to other biomarkers.
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Xing J, Li J, Yan Z, Li Y, Liu X, He L, Xu T, Wang C, Zhao L, Jie K. Diagnostic accuracy of calprotectin in periprosthetic joint infection: a diagnostic meta-analysis. J Orthop Surg Res 2022; 17:11. [PMID: 34991666 PMCID: PMC8739654 DOI: 10.1186/s13018-021-02895-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Accepted: 12/30/2021] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Periprosthetic joint infection (PJI) is considered to be one of the most challenging complications of joint replacement, which remains unpredictable. As a simple and emerging biomarker, calprotectin (CLP) has been considered to be useful in ruling out PJI in recent years. The purpose of this study was to investigate the accuracy and sensitivity of CLP in the diagnosis of PJI. METHODS We searched and screened the publications from PubMed, Web of Science, EMBASE, and Cochrane Library from database establishment to June 2021. Subsequently, Stata version 16.0 software was used to combine the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), operating characteristic curve, and area under the curve (AUC). Heterogeneity across articles was evaluated by the I2 statistics. Finally, sources of heterogeneity were detected by subgroup analysis based on study design, detection method, sample size, and cutoff values. RESULTS A total of 7 studies were included in our study, comprising 525 patients. The pooled sensitivity, specificity, PLR, and NLR of CLP for PJI diagnosis were 0.94(95% CI 0.87-0.98), 0.93(95% CI 0.87-0.96), 13.65(95% CI 6.89-27.08), and 0.06(95% CI 0.02-0.15), respectively, while the DOR and AUC were 222.33(95% CI 52.52-941.11) and 0.98 (95% CI 0.96-0.99), respectively. CONCLUSION Synovial CLP is a reliable biomarker and can be used as a diagnostic criterion for PJI in the future. However, the uncertainty resulting from the poor study numbers and sample sizes limit our ability to definitely draw conclusions on the basis of our study.
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Affiliation(s)
- Jisi Xing
- Foshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine, Foshan Hospital of Traditional Chinese Medicine, Foshan, 528000, Guangdong Province, China
| | - Jiahao Li
- The First Clinical Medical School, Guangzhou University of Chinese Medicine, Jichang Road 12#, District Baiyun, Guangzhou, Guangdong, China
| | - Zijian Yan
- The First Clinical Medical School, Guangzhou University of Chinese Medicine, Jichang Road 12#, District Baiyun, Guangzhou, Guangdong, China
| | - Yijin Li
- The First Clinical Medical School, Guangzhou University of Chinese Medicine, Jichang Road 12#, District Baiyun, Guangzhou, Guangdong, China
| | - Xiaofang Liu
- Foshan Hospital of Traditional Chinese Medicine, Foshan, 528000, Guangdong Province, China
| | - Lilei He
- Foshan Hospital of Traditional Chinese Medicine, Foshan, 528000, Guangdong Province, China
| | - Ting Xu
- Foshan Hospital of Traditional Chinese Medicine, Foshan, 528000, Guangdong Province, China
| | - Changbing Wang
- Foshan Hospital of Traditional Chinese Medicine, Foshan, 528000, Guangdong Province, China
| | - Lilian Zhao
- Foshan Hospital of Traditional Chinese Medicine, Foshan, 528000, Guangdong Province, China.
| | - Ke Jie
- Foshan Hospital of Traditional Chinese Medicine, Foshan, 528000, Guangdong Province, China.
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Iorio R, Viglietta E, Mazza D, Petrucca A, Borro M, Iolanda S, Simmaco M, Ferretti A. Accuracy and Cost-Effectivenss of a Novel Method for Alpha Defensins Measurement in the Diagnosis of Periprosthetic Joint Infections. J Arthroplasty 2021; 36:3275-3281. [PMID: 34088569 DOI: 10.1016/j.arth.2021.05.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 04/29/2021] [Accepted: 05/10/2021] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Two methods for detecting synovial fluids alpha defensins are available: the enzyme-linked immunosorbent assay and the lateral flow test. For both, the proper role and accuracy remain uncertain. The purpose of this study was to assess the accuracy of the matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) for alpha defensin detection in synovial fluids of patients with total knee arthroplasty/total hip arthroplasty failures. The hypothesis was that the alpha defensin measurement through MALDI-TOF MS assay could be a high sensitive and specific test for periprosthetic joint infections (PJI) diagnosis as compared with Musculoskeletal Infection Society (MSIS) criteria. METHODS The study included 138 patients. The 2018 MSIS criteria were used to diagnose PJIs. Synovial fluids were assessed for routinely synovial fluid tests and alpha defensin measurement through MALDI-TOF MS. Sensitivity, specificity, overall diagnostic accuracy, positive and negative predictive values, receiver operator curves, and area under the curve were calculated. RESULTS As per the 2018 MSIS criteria, 59 PJIs (43%) and 79 aseptic failures (57%) were diagnosed. The MALDI-TOF MS assay showed an overall accuracy of 94.9%. The sensitivity was 93%, the specificity was 96%, the positive predictive value was 95%, and the negative predictive value was 95%. Receiver operator curves analysis demonstrates an area under the curve of 0.95 (P < .001). CONCLUSION The MALDI-TOF MS assay showed high sensitivity and specificity for alpha defensin detection in case of total knee arthroplasty/total hip arthroplasty failures. The advantages of the technology, such as the few milliliters of sample needed, the rapidity of obtaining results, and the cost-effectiveness of the procedure could make the MALDI-TOF MS alpha defensin assay a useful and widespread test in clinical practice.
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Affiliation(s)
- Raffaele Iorio
- Sant'Andrea Hospital - Sapienza University of Rome, Rome, Italy; Sant'Andrea Hospital - Orthopaedic Unit and Kirk Kilgour Sports Injury Centre, Rome, Italy
| | - Edoardo Viglietta
- Sant'Andrea Hospital - Sapienza University of Rome, Rome, Italy; Sant'Andrea Hospital - Orthopaedic Unit and Kirk Kilgour Sports Injury Centre, Rome, Italy
| | - Daniele Mazza
- Sant'Andrea Hospital - Orthopaedic Unit and Kirk Kilgour Sports Injury Centre, Rome, Italy
| | | | - Marina Borro
- Sant'Andrea Hospital - Sapienza University of Rome, Rome, Italy; Sant'Andrea Hospital - Department of Molecular and Clinical Medicine, Sapienza University of Rome, Rome, Italy
| | - Santino Iolanda
- Sant'Andrea Hospital - Sapienza University of Rome, Rome, Italy; Sant'Andrea Hospital - Microbiology Unit, Rome, Italy
| | - Maurizio Simmaco
- Sant'Andrea Hospital - Sapienza University of Rome, Rome, Italy; Sant'Andrea Hospital - Department of Molecular and Clinical Medicine, Sapienza University of Rome, Rome, Italy; Sant'Andrea Hospital - Microbiology Unit, Rome, Italy
| | - Andrea Ferretti
- Sant'Andrea Hospital - Sapienza University of Rome, Rome, Italy; Sant'Andrea Hospital - Orthopaedic Unit and Kirk Kilgour Sports Injury Centre, Rome, Italy
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15
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Abdo RCT, Gobbi RG, Leite CBG, Pasoto SG, Leon EP, Lima ALLM, Bonfa E, Pécora JR, Demange MK. Performance of alpha-defensin lateral flow test after synovial fluid centrifugation for diagnosis of periprosthetic knee infection. World J Orthop 2021; 12:565-574. [PMID: 34485103 PMCID: PMC8384616 DOI: 10.5312/wjo.v12.i8.565] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Revised: 06/14/2021] [Accepted: 07/09/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The quantitative alpha-defensin enzyme-linked immunosorbent assay (ELISA) demands a prior synovial fluid centrifugation, whereas this processing is not routinely required prior to the alpha-defensin lateral flow test.
AIM To evaluate whether a prior synovial fluid centrifugation could lead the lateral flow performance to achieve comparable results to ELISA during periprosthetic joint infection (PJI) diagnosis.
METHODS Fifty-three cases were included in this study: 22 classified as PJI and 31 classified as aseptic cases, according to Musculoskeletal Infection Society 2013 criteria. Synovial fluid samples were submitted to centrifugation, and the supernatant was evaluated by ELISA and lateral flow tests. The sensitivity (SE), specificity (SP) and accuracy of each method were calculated as well as the agreement between those two methods.
RESULTS In all of the 31 samples from aseptic patients, alpha-defensin ELISA and lateral flow tests showed negative results for infection. Regarding the 22 infected patients, the lateral flow test was positive in 19 cases (86.4%) and the ELISA was positive in 21 (95.5%). Sensibility, SP and accuracy were, respectively, 86.4% (95%CI: 65.1%-97.1%), 100% (95%CI: 88.8%-100%) and 93.2% (95%CI: 82.8%-98.3%) for the lateral flow test and 95.5% (95%CI: 77.2%-99.9%), 100% (95%CI: 88.8%-100%) and 98.1% (95%CI: 89.9%-100%) for ELISA. An agreement of 96.2% between those methods were observed. No statistical difference was found between them (P = 0.48).
CONCLUSION Alpha-defensin lateral flow test showed high SE, SP and accuracy after a prior synovial fluid centrifugation, achieving comparable results to ELISA. Considering the lower complexity of the lateral flow and its equivalent performance obtained in this condition, a prior centrifugation might be added as a valuable step to enhance the PJI diagnosis.
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Affiliation(s)
- Rodrigo Calil Teles Abdo
- Instituto de Ortopedia e Traumatologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Sao Paulo 05403-010, Brazil
| | - Riccardo Gomes Gobbi
- Instituto de Ortopedia e Traumatologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Sao Paulo 05403-010, Brazil
| | - Chilan Bou Ghosson Leite
- Instituto de Ortopedia e Traumatologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Sao Paulo 05403-010, Brazil
| | - Sandra Gofinet Pasoto
- Division of Rheumatology, Faculdade de Medicina da Universidade de São Paulo, Sao Paulo 01246-903, Brazil
| | - Elaine Pires Leon
- Division of Rheumatology, Faculdade de Medicina da Universidade de São Paulo, Sao Paulo 01246-903, Brazil
| | - Ana Lucia Lei Munhoz Lima
- Instituto de Ortopedia e Traumatologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Sao Paulo 05403-010, Brazil
| | - Eloisa Bonfa
- Division of Rheumatology, Faculdade de Medicina da Universidade de São Paulo, Sao Paulo 01246-903, Brazil
| | - José Ricardo Pécora
- Instituto de Ortopedia e Traumatologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Sao Paulo 05403-010, Brazil
| | - Marco Kawamura Demange
- Instituto de Ortopedia e Traumatologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Sao Paulo 05403-010, Brazil
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16
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Gramlich Y, Kremer M, Brüning C, Breuer J, Hofmann L, Klug A, Hoffmann R. Implementation of a standardized clinical test kit for diagnostics of periprosthetic infections in the clinical routine. Unfallchirurg 2021; 124:247-254. [PMID: 34338839 DOI: 10.1007/s00113-021-01016-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/22/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND The number of primary arthroplasties is increasing and the proportion of revision arthroplasties is becoming increasingly more important. The need for standardized and guideline-based diagnostics for the safe detection of a periprosthetic joint infection (PJI) is becoming apparent. In the past 10 years various organizations have published definitions and diagnostic guidelines. The implementation of an inhouse standard test kit could help to simplify the process and could improve the diagnostic quality. METHOD In 2016 a test kit was compiled in a monocentric prospective study, taking the International Consensus Meeting (ICM) criteria 2014 and the Infectious Diseases Society of America (IDSA) criteria into account, which also fulfils the definitions of the ICM criteria 2018 and criteria of the European Bone and Joint Infection Society 2021. The test kit was implemented in the clinical setting of a special department for aseptic and septic revision arthroplasty. The usability and accuracy of the test kit were examined. RESULTS The test kit was implemented using blood samples (leukocyte count; C‑reactive protein, CRP), samples for examining the synovial fluid (white blood cell count, PMN cell differentiation, microbiological culture for incubation over 14 days, alpha-defensin enzyme-linked immunosorbent assay, ELISA, leukocyte esterase test strips) together with information and request forms. Between April 2016 and February 2020 a total of 405 patients were investigated. Within 3 calendar years, the use of the test kit increased from 59% initially to 86%, and finally to 96% of cases in the third calendar year. The leukocyte esterase test strip was reliable in only 72%, due to undifferentiated readability or blood contamination. The costs increased by the only commercially available alpha-defensin ELISA test by approx. 52€ per puncture. The best individual test showed a sensitivity/specificity of 92.8%/95.2% with alpha-defensin. It was calculated which combinations showed a similar test quality and different combinations, such as CRP+ cell count+ microbiology showed a sensitivity/specificity both of around 90%. Metallosis is a challenge for preoperative PJI diagnostics. DISCUSSION In a prospective study it was shown, that the implementation of the standardized test kit lead to a guideline based PJI diagnostic in all cases and thus to a significantly increase of the diagnostic quality. There is currently no single test that reliably excludes or proves an infection. The alpha-defensin laboratory ELISA test showed the best test accuracy, whereby the consideration of test combinations is obligatory and at the same time safe.
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Affiliation(s)
- Y Gramlich
- Department of Trauma and Orthopedic Surgery, Berufsgenossenschaftliche Unfallklinik Frankfurt am Main, Friedberger Landstr. 430, 60389, Frankfurt am Main, Germany.
| | - M Kremer
- Department of Trauma and Orthopedic Surgery, Berufsgenossenschaftliche Unfallklinik Frankfurt am Main, Friedberger Landstr. 430, 60389, Frankfurt am Main, Germany
| | - C Brüning
- Department of Trauma and Orthopedic Surgery, Berufsgenossenschaftliche Unfallklinik Frankfurt am Main, Friedberger Landstr. 430, 60389, Frankfurt am Main, Germany
| | - J Breuer
- Department of Trauma and Orthopedic Surgery, Berufsgenossenschaftliche Unfallklinik Frankfurt am Main, Friedberger Landstr. 430, 60389, Frankfurt am Main, Germany
| | - L Hofmann
- Department of Trauma and Orthopedic Surgery, Berufsgenossenschaftliche Unfallklinik Frankfurt am Main, Friedberger Landstr. 430, 60389, Frankfurt am Main, Germany
| | - A Klug
- Department of Trauma and Orthopedic Surgery, Berufsgenossenschaftliche Unfallklinik Frankfurt am Main, Friedberger Landstr. 430, 60389, Frankfurt am Main, Germany
| | - R Hoffmann
- Department of Trauma and Orthopedic Surgery, Berufsgenossenschaftliche Unfallklinik Frankfurt am Main, Friedberger Landstr. 430, 60389, Frankfurt am Main, Germany
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17
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Gramlich Y, Kremer M, Brüning C, Breuer J, Hofmann L, Klug A, Hoffmann R. [Implementation of a standardized clinical test kit for diagnostics of periprosthetic infections in the clinical routine. German version]. Unfallchirurg 2021; 125:381-388. [PMID: 34189589 DOI: 10.1007/s00113-021-01017-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/22/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND The number of primary arthroplasties is increasing and the proportion of revision arthroplasties is becoming increasingly more important. The need for standardized and guideline-based diagnostics for the safe detection of a periprosthetic joint infection (PJI) is becoming apparent. In the past 10 years various organizations have published definitions and diagnostic guidelines. The implementation of an inhouse standard test kit could help to simplify the process and could improve the diagnostic quality. METHOD In 2016 a test kit was compiled in a monocentric prospective study, taking the International Consensus Meeting (ICM) criteria 2014 and the Infectious Diseases Society of America (IDSA) criteria into account, which also fulfils the definitions of the ICM criteria 2018 and criteria of the European Bone and Joint Infection Society 2021. The test kit was implemented in the clinical setting of a special department for aseptic and septic revision arthroplasty. The usability and accuracy of the test kit were examined. RESULTS The test kit was implemented using blood samples (leukocyte count; C‑reactive protein, CRP), samples for examining the synovial fluid (white blood cell count, PMN cell differentiation, microbiological culture for incubation over 14 days, alpha-defensin enzyme-linked immunosorbent assay, ELISA, leukocyte esterase test strips) together with information and request forms. Between April 2016 and February 2020 a total of 405 patients were investigated. Within 3 calendar years, the use of the test kit increased from 59% initially to 86%, and finally to 96% of cases in the third calendar year. The leukocyte esterase test strip was reliable in only 72%, due to undifferentiated readability or blood contamination. The costs increased by the only commercially available alpha-defensin ELISA test by approx. 52€ per puncture. The best individual test showed a sensitivity/specificity of 92.8%/95.2% with alpha-defensin. It was calculated which combinations showed a similar test quality and different combinations, such as CRP+ cell count+ microbiology showed a sensitivity/specificity both of around 90%. Metallosis is a challenge for preoperative PJI diagnostics. DISCUSSION In a prospective study it was shown, that the implementation of the standardized test kit lead to a guideline based PJI diagnostic in all cases and thus to a significantly increase of the diagnostic quality. There is currently no single test that reliably excludes or proves an infection. The alpha-defensin laboratory ELISA test showed the best test accuracy, whereby the consideration of test combinations is obligatory and at the same time safe.
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Affiliation(s)
- Y Gramlich
- Abteilung für Orthopädie und Unfallchirurgie, Berufsgenossenschaftliche Unfallklinik Frankfurt am Main, Friedberger Landstr. 430, 60389, Frankfurt am Main, Deutschland.
| | - M Kremer
- Abteilung für Orthopädie und Unfallchirurgie, Berufsgenossenschaftliche Unfallklinik Frankfurt am Main, Friedberger Landstr. 430, 60389, Frankfurt am Main, Deutschland
| | - Chr Brüning
- Abteilung für Orthopädie und Unfallchirurgie, Berufsgenossenschaftliche Unfallklinik Frankfurt am Main, Friedberger Landstr. 430, 60389, Frankfurt am Main, Deutschland
| | - J Breuer
- Abteilung für Orthopädie und Unfallchirurgie, Berufsgenossenschaftliche Unfallklinik Frankfurt am Main, Friedberger Landstr. 430, 60389, Frankfurt am Main, Deutschland
| | - L Hofmann
- Abteilung für Orthopädie und Unfallchirurgie, Berufsgenossenschaftliche Unfallklinik Frankfurt am Main, Friedberger Landstr. 430, 60389, Frankfurt am Main, Deutschland
| | - A Klug
- Abteilung für Orthopädie und Unfallchirurgie, Berufsgenossenschaftliche Unfallklinik Frankfurt am Main, Friedberger Landstr. 430, 60389, Frankfurt am Main, Deutschland
| | - R Hoffmann
- Abteilung für Orthopädie und Unfallchirurgie, Berufsgenossenschaftliche Unfallklinik Frankfurt am Main, Friedberger Landstr. 430, 60389, Frankfurt am Main, Deutschland
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18
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Ivy MI, Sharma K, Greenwood-Quaintance KE, Tande AJ, Osmon DR, Berbari EF, Mandrekar J, Beauchamp CP, Hanssen AD, Abdel MP, Lewallen DG, Perry K, Block DR, Snyder MR, Patel R. Synovial fluid α defensin has comparable accuracy to synovial fluid white blood cell count and polymorphonuclear percentage for periprosthetic joint infection diagnosis. Bone Joint J 2021; 103-B:1119-1126. [PMID: 34058872 DOI: 10.1302/0301-620x.103b6.bjj-2020-1741.r1] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
AIMS The aim of this study was to determine the diagnostic accuracy of α defensin (AD) lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) tests for periprosthetic joint infection (PJI) in comparison to conventional synovial white blood cell (WBC) count and polymorphonuclear neutrophil percentage (PMN%) analysis. METHODS Patients undergoing joint aspiration for evaluation of pain after total knee arthroplasty (TKA) or total hip arthroplasty (THA) were considered for inclusion. Synovial fluids from 99 patients (25 THA and 74 TKA) were analyzed by WBC count and PMN% analysis, AD LFA, and AD ELISA. WBC and PMN% cutoffs of ≥ 1,700 cells/mm3 and ≥ 65% for TKA and ≥ 3,000 cells/mm3 and ≥ 80% for THA were used, respectively. A panel of three physicians, all with expertise in orthopaedic infections and who were blinded to the results of AD tests, independently reviewed patient data to diagnose subjects as with or without PJI. Consensus PJI classification was used as the reference standard to evaluate test performances. Results were compared using McNemar's test and area under the receiver operating characteristic curve (AUC) analysis. RESULTS Expert consensus classified 18 arthroplasies as having failed due to PJI and 81 due to aseptic failure. Using these classifications, the calculated sensitivity and specificity of AD LFA was 83.3% (95% confidence interval (CI) 58.6 to 96.4) and 93.8% (95% CI 86.2 to 98.0), respectively. Sensitivity and specificity of AD ELISA was 83.3% (95% CI 58.6 to 96.4) and 96.3% (95% CI 89.6 to 99.2), respectively. There was no statistically significant difference between sensitivity (p = 1.000) or specificity (p = 0.157) of the two AD assays. AUC for AD LFA was 0.891. In comparison, AUC for synovial WBC count, PMN%, and the combination of the two values was 0.821 (sensitivity p = 1.000, specificity p < 0.001), 0.886 (sensitivity p = 0.317, specificity p = 0.011), and 0.926 (sensitivity p = 0.317, specificity p = 0.317), respectively. CONCLUSION The diagnostic accuracy of synovial AD for PJI diagnosis is comparable and not statistically superior to that of synovial WBC count plus PMN% combined. Cite this article: Bone Joint J 2021;103-B(6):1119-1126.
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19
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Warren J, Anis HK, Bowers K, Pannu T, Villa J, Klika AK, Colon-Franco J, Piuzzi NS, Higuera CA. Diagnostic Utility of a Novel Point-of-Care Test of Calprotectin for Periprosthetic Joint Infection After Total Knee Arthroplasty: A Prospective Cohort Study. J Bone Joint Surg Am 2021; 103:1009-1015. [PMID: 34038396 DOI: 10.2106/jbjs.20.01089] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Despite several synovial fluid biomarkers for the diagnosis of periprosthetic joint infection (PJI) having been investigated, point-of-care (POC) tests using these biomarkers are not widely available. Synovial calprotectin has recently been reported to effectively exclude the diagnosis of PJI. Thus, the objective of this study was to test the value of a calprotectin POC test for PJI diagnosis in patients undergoing total knee arthroplasty (TKA) using the 2013 Musculoskeletal Infection Society (MSIS) PJI diagnosis criteria as the gold standard. METHODS Synovial fluid samples were prospectively collected from 123 patients who underwent revision TKA at 2 institutions within the same health-care system from October 2018 to January 2020. The study was conducted under institutional review board approval. Data collection comprised demographic, clinical, and laboratory data in compliance with the MSIS criteria. Synovial fluid samples were analyzed by calprotectin POC tests in accordance with the manufacturer's instructions. Revisions were categorized as septic or aseptic using MSIS criteria by 2 independent reviewers blinded to the calprotectin results. Calprotectin test performance characteristics with sensitivities, specificities, positive predictive values, negative predictive values, and areas under the receiver operating characteristic curve (AUC) were calculated for 2 different PJI diagnosis scenarios: (1) a threshold of ≥50 mg/L, and (2) a threshold of ≥14 mg/L. RESULTS According to the MSIS criteria, 53 revision TKAs were septic and 70 revision TKAs were aseptic. In the ≥50-mg/mL threshold scenario, the calprotectin POC performance showed a sensitivity of 98.1%, a specificity of 95.7%, a positive predictive value of 94.5%, a negative predictive value of 98.5%, and an AUC of 0.969. In the ≥14-mg/mL threshold scenario, the sensitivity was 98.1%, the specificity was 87.1%, the positive predictive value was 85.2%, the negative predictive value was 98.4%, and the AUC was 0.926. CONCLUSIONS The calprotectin POC test has excellent PJI diagnostic characteristics, including high sensitivity and specificity in patients undergoing revision TKA. This test could be effectively implemented as a rule-out test. However, further investigations with larger cohorts are necessary to validate these results. LEVEL OF EVIDENCE Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.
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Affiliation(s)
- Jared Warren
- Department of Orthopedic Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Hiba K Anis
- Department of Orthopedic Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Kathleen Bowers
- Department of Orthopedic Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Tejbir Pannu
- Department of Orthopedic Surgery, Cleveland Clinic Florida, Weston, Florida
| | - Jesus Villa
- Department of Orthopedic Surgery, Cleveland Clinic Florida, Weston, Florida
| | - Alison K Klika
- Department of Orthopedic Surgery, Cleveland Clinic, Cleveland, Ohio
| | | | - Nicolas S Piuzzi
- Department of Orthopedic Surgery, Cleveland Clinic, Cleveland, Ohio
| | - Carlos A Higuera
- Department of Orthopedic Surgery, Cleveland Clinic Florida, Weston, Florida
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20
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Weber M, Meyer M, Grifka J. [Infected endoprosthesis in patients with rheumatism]. Z Rheumatol 2021; 80:339-347. [PMID: 33885947 DOI: 10.1007/s00393-021-00995-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/18/2021] [Indexed: 11/26/2022]
Abstract
Infections are a severe complication after an artificial joint replacement. The clinical symptoms are highly variable, particularly in patients with inflammatory rheumatic diseases, which often makes the diagnosis difficult. In addition to clinical and laboratory findings, joint puncture is an essential component of the diagnostics and enables the identification of pathogens. Treatment of periprosthetic infections in patients with rheumatism should be an interdisciplinary cooperation between surgeons, rheumatologists and specialists for infectious diseases. The two essential pillars of treatment are surgical intervention and antibiotics. For acute joint infections an attempt at preservation of the artificial joint can be carried out, whereas for chronic infection situations only replacement of the prosthesis is possible as a curative treatment. In order to reduce the probability of occurrence of a joint infection, modifiable risk factors should be preoperatively identified and specifically treated.
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Affiliation(s)
- Markus Weber
- Klinik und Poliklinik für Orthopädie, Asklepios Klinikum Bad Abbach, Universität Regensburg, Kaiser Karl V. Allee 3, 93077, Bad Abbach, Deutschland.
| | - M Meyer
- Klinik und Poliklinik für Orthopädie, Asklepios Klinikum Bad Abbach, Universität Regensburg, Kaiser Karl V. Allee 3, 93077, Bad Abbach, Deutschland
| | - J Grifka
- Klinik und Poliklinik für Orthopädie, Asklepios Klinikum Bad Abbach, Universität Regensburg, Kaiser Karl V. Allee 3, 93077, Bad Abbach, Deutschland
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21
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Grzelecki D, Walczak P, Szostek M, Grajek A, Rak S, Kowalczewski J. Blood and synovial fluid calprotectin as biomarkers to diagnose chronic hip and knee periprosthetic joint infections. Bone Joint J 2021; 103-B:46-55. [PMID: 33380202 DOI: 10.1302/0301-620x.103b1.bjj-2020-0953.r1] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
AIMS Calprotectin (CLP) is produced in neutrophils and monocytes and released into body fluids as a result of inflammation or infection. The aim of this study was to evaluate the utility of blood and synovial CLP in the diagnosis of chronic periprosthetic joint infection (PJI). METHODS Blood and synovial fluid samples were collected prospectively from 195 patients undergoing primary or revision hip and knee arthroplasty. Patients were divided into five groups: 1) primary total hip and knee arthroplasty performed due to idiopathic osteoarthritis (OA; n = 60); 2) revision hip and knee arthroplasty performed due to aseptic failure of the implant (AR-TJR; n = 40); 3) patients with a confirmed diagnosis of chronic PJI awaiting surgery (n = 45); 4) patients who have finished the first stage of the PJI treatment with the use of cemented spacer and were qualified for replantation procedure (SR-TJR; n = 25), and 5) patients with rheumatoid arthritis undergoing primary total hip and knee arthroplasty (RA; n = 25). CLP concentrations were measured quantitatively in the blood and synovial fluid using an immunoturbidimetric assay. Additionally, blood and synovial CRP, blood interleukin-6 (IL-6), and ESR were measured, and a leucocyte esterase (LE) strip test was performed. RESULTS Patients with PJI had higher CLP concentrations than those undergoing aseptic revision in blood (median PJI 2.14 mg/l (interquartile range (IQR) 1.37 to 3.56) vs AR-TJR 0.66 mg/l (IQR 0.3 to 0.83); p < 0.001) and synovial fluid samples (median PJI 20.46 mg/l (IQR 14.3 to 22.36) vs AR-TJR 0.7 mg/l (IQR 0.41 to 0.95); p < 0.001). With a cut-off value of 1.0 mg/l, blood CLP showed a sensitivity, specificity, positive predictive value, and negative predictive value of 93.3%, 87.5%, 89.4%, and 92.1%, respectively. For synovial fluid with a cut-off value of 1.5 mg/l, these were 95.6%, 95%, 95.5%, and 95%, respectively. CONCLUSION This small study suggests that synovial and blood CLP are useful markers in chronic PJI diagnosis with similar or higher sensitivity and specificity than routinely used markers such as CRP, ESR, IL-6, and LE. CLP was not useful to differentiate patients with PJI from those with rheumatoid arthritis. Cite this article: Bone Joint J 2021;103-B(1):46-55.
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Affiliation(s)
- Dariusz Grzelecki
- Department of Orthopedics and Rheumoorthopedics, Centre of Postgraduate Medical Education, Otwock, Poland
| | - Piotr Walczak
- Department of Orthopedics, Centre of Postgraduate Medical Education, Otwock, Poland
| | - Marta Szostek
- Central Laboratory, Professor Adam Gruca Hospital, Otwock, Poland
| | | | - Stanisław Rak
- Department of Orthopedics, Centre of Postgraduate Medical Education, Otwock, Poland
| | - Jacek Kowalczewski
- Department of Orthopedics and Rheumoorthopedics, Centre of Postgraduate Medical Education, Otwock, Poland
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22
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Deirmengian C, Madigan J, Kallur Mallikarjuna S, Conway J, Higuera C, Patel R. Validation of the Alpha Defensin Lateral Flow Test for Periprosthetic Joint Infection. J Bone Joint Surg Am 2021; 103:115-122. [PMID: 33165130 DOI: 10.2106/jbjs.20.00749] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The synovial fluid test for alpha defensin has been reported to have an excellent performance in diagnosing periprosthetic joint infection (PJI). The purpose of this study was to evaluate the performance of the lateral flow test for synovial fluid alpha defensin by using the methods of a formal diagnostic accuracy study and to compare its performance with that of the laboratory-based alpha defensin test for PJI. METHODS We conducted a diagnostic accuracy study of the index lateral flow immunoassay for synovial fluid alpha defensin relative to the reference 2013 Musculoskeletal Infection Society (MSIS) multicriteria definition of PJI. The study included a prospective multicenter cohort of outpatients with a failed hip or knee arthroplasty and a supplemental control cohort of fresh synovial fluid specimens submitted by physicians for diagnostic PJI testing. RESULTS Among 57 patients with PJI and 248 patients without PJI in the overall prospective patient cohort, the sensitivity and specificity of the alpha defensin lateral flow test were 89.5% (95% confidence interval [CI]: 78.5% to 96.0%) and 94.8% (95% CI: 91.2% to 97.2%), respectively. The sensitivity increased to 94.3% (95% CI: 84.3% to 98.8%) after exclusion of 17 patients with grossly bloody aspirates (>1 million red blood cells/µL). Among the supplemental control cohort of fresh synovial fluid samples, including 65 samples from patients with PJI and 397 from patients without PJI, the sensitivity and specificity of the alpha defensin lateral flow test were 98.5% (95% CI: 91.7% to 100.0%) and 98.2% (95% CI: 96.4% to 99.3%), respectively. A comparison of the sensitivity and specificity of the alpha defensin lateral flow test with those of the alpha defensin enzyme-linked immunosorbent assay (ELISA) in the combined cohort did not demonstrate a significant difference in sensitivity (94.3% [95% CI: 88.5% to 97.7%] compared with 93.0% [95% CI: 87.1% to 96.7%]) or specificity (96.9% [95% CI: 95.3% to 98.1%] compared with 97.8% [95% CI: 96.4% to 98.8%]) (both p > 0.05). CONCLUSIONS The results of this study demonstrate the solid diagnostic performance of the alpha defensin test and have resulted in the U.S. Food and Drug Administration (FDA) authorization of the lateral-flow test with an intended use as an aid in the clinical diagnosis of PJI. LEVEL OF EVIDENCE Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.
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Affiliation(s)
- Carl Deirmengian
- Department of Orthopaedic Surgery, Rothman Orthopaedic Institute, Lankenau Institute for Medical Research, Wynnewood, Pennsylvania.,CD Diagnostics, Zimmer Biomet, Claymont, Delaware
| | - John Madigan
- CD Diagnostics, Zimmer Biomet, Claymont, Delaware
| | | | - Janet Conway
- Rubin Institute for Advanced Orthopedics, Sinai Hospital of Baltimore, Baltimore, Maryland
| | - Carlos Higuera
- Levitetz Department of Orthopaedic Surgery, Cleveland Clinic Florida, Weston, Florida
| | - Robin Patel
- Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, and Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota
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23
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Akhbari P, Jaggard MK, Boulangé CL, Vaghela U, Graça G, Bhattacharya R, Lindon JC, Williams HRT, Gupte CM. Differences between infected and noninfected synovial fluid. Bone Joint Res 2021; 10:85-95. [PMID: 33502243 PMCID: PMC7845460 DOI: 10.1302/2046-3758.101.bjr-2020-0285.r1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
AIMS The diagnosis of joint infections is an inexact science using combinations of blood inflammatory markers and microscopy, culture, and sensitivity of synovial fluid (SF). There is potential for small molecule metabolites in infected SF to act as infection markers that could improve accuracy and speed of detection. The objective of this study was to use nuclear magnetic resonance (NMR) spectroscopy to identify small molecule differences between infected and noninfected human SF. METHODS In all, 16 SF samples (eight infected native and prosthetic joints plus eight noninfected joints requiring arthroplasty for end-stage osteoarthritis) were collected from patients. NMR spectroscopy was used to analyze the metabolites present in each sample. Principal component analysis and univariate statistical analysis were undertaken to investigate metabolic differences between the two groups. RESULTS A total of 16 metabolites were found in significantly different concentrations between the groups. Three were in higher relative concentrations (lipids, cholesterol, and N-acetylated molecules) and 13 in lower relative concentrations in the infected group (citrate, glycine, glycosaminoglycans, creatinine, histidine, lysine, formate, glucose, proline, valine, dimethylsulfone, mannose, and glutamine). CONCLUSION Metabolites found in significantly greater concentrations in the infected cohort are markers of inflammation and infection. They play a role in lipid metabolism and the inflammatory response. Those found in significantly reduced concentrations were involved in carbohydrate metabolism, nucleoside metabolism, the glutamate metabolic pathway, increased oxidative stress in the diseased state, and reduced articular cartilage breakdown. This is the first study to demonstrate differences in the metabolic profile of infected and noninfected human SF, using a noninfected matched cohort, and may represent putative biomarkers that form the basis of new diagnostic tests for infected SF. Cite this article: Bone Joint Res 2021;10(1):85-95.
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Affiliation(s)
- Pouya Akhbari
- Department of Trauma and Orthopaedics, Imperial College Healthcare NHS Trust, London, UK
| | - Matthew K Jaggard
- Department of Trauma and Orthopaedics, Imperial College Healthcare NHS Trust, London, UK
| | - Claire L Boulangé
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Uddhav Vaghela
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Gonçalo Graça
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Rajarshi Bhattacharya
- Department of Trauma and Orthopaedics, Imperial College Healthcare NHS Trust, London, UK
| | - John C Lindon
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | | | - Chinmay M Gupte
- Department of Trauma and Orthopaedics, Imperial College Healthcare NHS Trust, London, UK.,Department of Surgery and Cancer, Imperial College London, London, UK
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24
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Li Z, Zhang Q, Shi L, Gao F, Sun W, Li Z. Alpha-Defensin versus Leukocyte Esterase in Periprosthetic Joint Infection: An Updated Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2020; 2020:3704285. [PMID: 33294439 PMCID: PMC7688361 DOI: 10.1155/2020/3704285] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 09/22/2020] [Accepted: 10/26/2020] [Indexed: 12/21/2022]
Abstract
Periprosthetic joint infection (PJI) is a devastating complication after arthroplasty. Prompt establishment of an infection diagnosis is critical but can be very challenging at present. In order to evaluate the diagnostic accuracy of alpha-defensin or leukocyte esterase for PJI, we performed systematic research in PubMed, Embase, and Cochrane Library to retrieve relevant studies. Data extraction and quality assessment were performed by two reviewers independently. A total of thirty-one eligible studies were finally included in the quantitative analysis. The pooled sensitivity and specificity of alpha-defensin (21 studies) for the diagnosis of PJI were 0.89 (95% confidence interval (CI), 0.83 to 0.93) and 0.96 (95% CI, 0.95 to 0.97), respectively. The value of the pooled diagnostic odds ratios (DOR) of alpha-defensin for PJI was 209.14 (95% CI, 97.31 to 449.50), and the area under the curve (AUC) was 0.98 (95% CI, 0.96 to 0.99). The pooled sensitivity and specificity of leukocyte esterase (17 studies) for the diagnosis of PJI were 0.90 (95% CI, 0.84 to 0.95) and 0.96 (95% CI, 0.93 to 0.97), respectively. The value of the DOR of leukocyte esterase for PJI was 203.23 (95% CI, 96.14 to 429.61), and the AUC was 0.98 (95% CI, 0.96 to 0.99). Based on the results of our meta-analysis, we can conclude that alpha-defensin and leukocyte esterase are valuable synovial fluid markers for identifying PJI with comparable high diagnostic accuracy.
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Affiliation(s)
- Zhizhuo Li
- Department of Orthopedics, Peking University China-Japan Friendship School of Clinical Medicine, 2 Yinghuadong Road, Chaoyang District, Beijing 100029, China
| | - Qingyu Zhang
- Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong University, No. 324, Road Jing Wu Wei Qi, Jinan, 250021 Shandong, China
| | - Lijun Shi
- Department of Orthopedics, Graduate School of Peking Union Medical College, China-Japan Friendship Institute of Clinical Medicine, 2 Yinghuadong Road, Chaoyang District, Beijing 100029, China
| | - Fuqiang Gao
- Beijing Key Laboratory of Immune Inflammatory Disease, China-Japan Friendship Hospital, 2 Yinghuadong Road, Chaoyang District, Beijing 100029, China
| | - Wei Sun
- Beijing Key Laboratory of Immune Inflammatory Disease, China-Japan Friendship Hospital, 2 Yinghuadong Road, Chaoyang District, Beijing 100029, China
| | - Zirong Li
- Beijing Key Laboratory of Immune Inflammatory Disease, China-Japan Friendship Hospital, 2 Yinghuadong Road, Chaoyang District, Beijing 100029, China
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25
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Senneville E, Robineau O, Loiez C, de Saint Vincent B, Dartus J, Migaud H. A profile on the Synovasure alpha defensin test for the detection of periprosthetic infections. Expert Rev Mol Diagn 2020; 20:895-904. [PMID: 32662687 DOI: 10.1080/14737159.2020.1792780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
INTRODUCTION Clinicians have waited a long time for a 'universal' marker that may help them distinguish infected from non-infected total joint arthroplasties when doubts persist after using classical clinical and biological signs of infection. In recent years, synovial fluid biomarkers including leukocyte esterase, alpha-defensins, and CRP have shown promising results for the diagnosis of periprosthetic joint infections (PJIs). AREAS COVERED This review provides an overview of the rational and the use of the Synovasure® alpha-defensin tests in patients with a suspicion of PJI. Using a systematic investigation by keywords, we looked for all citations (and the citations to these citations) of the selected papers. EXPERT OPINION The Synovasure® alpha-defensin tests demonstrate high potential for the diagnosis of PJIs. However, the data currently available also show that the universal marker of infection in the settings of PJIs is still to be discovered.
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Affiliation(s)
- Eric Senneville
- Rererent Center for Complex Bone and Joint Infections , Gustave Dron Hospital , Tourcoing, France.,Rererent Center for Complex Bone and Joint Infections, Roger Salengro Hospital , Lille, France.,Faculty of Medecine Henri Warembourg, Lille University , France
| | - Olivier Robineau
- Rererent Center for Complex Bone and Joint Infections , Gustave Dron Hospital , Tourcoing, France.,Rererent Center for Complex Bone and Joint Infections, Roger Salengro Hospital , Lille, France.,Faculty of Medecine Henri Warembourg, Lille University , France
| | - Caroline Loiez
- Rererent Center for Complex Bone and Joint Infections, Roger Salengro Hospital , Lille, France
| | - Benoit de Saint Vincent
- Rererent Center for Complex Bone and Joint Infections, Roger Salengro Hospital , Lille, France
| | - Julien Dartus
- Rererent Center for Complex Bone and Joint Infections, Roger Salengro Hospital , Lille, France
| | - Henri Migaud
- Rererent Center for Complex Bone and Joint Infections, Roger Salengro Hospital , Lille, France.,Faculty of Medecine Henri Warembourg, Lille University , France
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26
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Li C, Ojeda-Thies C, Xu C, Trampuz A. Meta-analysis in periprosthetic joint infection: a global bibliometric analysis. J Orthop Surg Res 2020; 15:251. [PMID: 32650802 PMCID: PMC7350679 DOI: 10.1186/s13018-020-01757-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 06/16/2020] [Indexed: 02/07/2023] Open
Abstract
Background Periprosthetic joint infection (PJI) is the most serious complication of joint replacement surgery. Further comorbidities include bedsore, deep vein thrombosis, reinfection, or even death. An increasing number of researchers are focusing on this challenging complication. The aim of the present study was to estimate global PJI research based on bibliometrics from meta-analysis studies. Methods A database search was performed in PubMed, Scopus, and Web of Science. Relevant studies were assessed using the bibliometric analysis. Results A total of 117 articles were included. The most relevant literature on PJI was found on Scopus. China made the highest contributions to global research, followed by the USA and the UK. The institution with the most contributions was the University of Bristol. The journal with the highest number of publications was The Journal of Arthroplasty, whereas the Journal of Clinical Medicine had the shortest acceptance time. Furthermore, the top three frequently used databases were Embase, MEDLINE, and Cochrane. The most frequent number of authors in meta-analysis studies was four. Most studies focused on the periprosthetic hip and knee. The alpha-defensin diagnostic test, preventive measures on antibiotics use, and risk factors of intra-articular steroid injections were the most popular topic in recent years. Conclusion Based on the results of the present study, we found that there was no single database that covered all relevant articles; the optimal method for bibliometric analysis is a combination of databases. The most popular research topics on PJI focused on alpha-defensin, antibiotic use, risk factors of intra-articular steroid injections, and the location of prosthetic hip and knee infection.
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Affiliation(s)
- Cheng Li
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Musculoskeletal Surgery (CMSC), Charitéplatz 1, D-10117, Berlin, Germany
| | | | - Chi Xu
- Department of Orthopaedic Surgery, General Hospital of People's Liberation Army, Beijing, People's Republic of China
| | - Andrej Trampuz
- Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Musculoskeletal Surgery (CMSC), Charitéplatz 1, D-10117, Berlin, Germany.
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27
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Kuiper JWP, Verberne SJ, Vos SJ, van Egmond PW. Does the Alpha Defensin ELISA Test Perform Better Than the Alpha Defensin Lateral Flow Test for PJI Diagnosis? A Systematic Review and Meta-analysis of Prospective Studies. Clin Orthop Relat Res 2020; 478:1333-1344. [PMID: 32324670 PMCID: PMC7319381 DOI: 10.1097/corr.0000000000001225] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Accepted: 02/28/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND Periprosthetic joint infection (PJI) following total joint arthroplasty is a serious complication that causes severe morbidity and adds a major financial burden to the healthcare system. Although there is plenty of research on the alpha-defensin (AD) test, a meta-analysis consisting of only prospective studies investigating AD's diagnostic efficacy has not been performed. Additionally, some important subgroups such as THA and TKA have not been separately analyzed, particularly regarding two commonly used versions of the AD test, the laboratory-based (ELISA) and lateral-flow (LF). QUESTIONS/PURPOSES (1) Does the AD ELISA test perform better in the detection of PJI than the AD LF test, in terms of pooled sensitivity and specificity, when including prospective studies only? (2) Are there differences in sensitivity or specificity when using AD ELISA and AD LF tests for PJI diagnosis of THA or TKA PJI separately? METHODS Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, we included prospective studies describing the use of either AD test in the workup of pain after total joint arthroplasty (primary or revision, but not after resection arthroplasty). Fifteen studies (AD ELISA: 4; AD LF: 11) were included, with 1592 procedures. Subgroup data on THA and TKA could be retrieved for 1163 procedures (ELISA THA: 123; LF THA: 257; ELISA TKA: 228; LF TKA: 555). Studies not describing THA or TKA, those not using Musculoskeletal Infection Society (MSIS) criteria as the standard for determining the presence or absence of PJI, those not clearly reporting data for the AD test for the total cohort, and those describing data published in another study were excluded. Studies were not excluded based on follow-up duration; the MSIS criteria could be used within a few weeks, when test results were available. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 criteria. Study quality was generally good. The most frequent sources of bias were related to patient selection (such as unclear inclusion and exclusion criteria) and flow and timing (uncertainty in place and time of aspiration, for example). Heterogeneity was moderate to high; a bivariate random-effects model therefore was used. To answer both research questions, sensitivity and specificity were calculated for AD ELISA and LF test groups and THA and TKA subgroups, and were compared using z-test statistics and meta-regression analysis. RESULTS No differences were found between the AD ELISA and the AD LF for PJI diagnosis in the pooled cohorts (THA and TKA combined), in terms of sensitivity (90% versus 86%; p = 0.43) and specificity (97% versus 96%; p = 0.39). Differences in sensitivity for PJI diagnosis were found between the THA and TKA groups for the AD ELISA test (70% versus 94%; p = 0.008); pooled AD LF test sensitivity did not differ between THA and TKA (80% versus 87%; p = 0.20). No differences in specificity were found in either subgroup. CONCLUSIONS Both the AD ELISA and AD LF test can be used in clinical practice because both have high sensitivity and very high specificity for PJI diagnosis. The lower sensitivity found for diagnosis of PJI in THA for the AD ELISA test must be carefully interpreted because the pooled data were heterogenous and only two studies for this group were included. Future research should analyze TKAs and THAs separately to confirm or disprove this finding. LEVEL OF EVIDENCE Level II diagnostic study.
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Affiliation(s)
- Jesse W P Kuiper
- J. W. P. Kuiper, S. J. Verberne, S. J. Vos, Department of Orthopaedics and Centre for Orthopaedic Research Alkmaar (CORAL) Noordwest Ziekenhuisgroep Alkmaar, Alkmaar, the Netherlands
| | - Steven J Verberne
- J. W. P. Kuiper, S. J. Verberne, S. J. Vos, Department of Orthopaedics and Centre for Orthopaedic Research Alkmaar (CORAL) Noordwest Ziekenhuisgroep Alkmaar, Alkmaar, the Netherlands
| | - Stan J Vos
- J. W. P. Kuiper, S. J. Verberne, S. J. Vos, Department of Orthopaedics and Centre for Orthopaedic Research Alkmaar (CORAL) Noordwest Ziekenhuisgroep Alkmaar, Alkmaar, the Netherlands
| | - Pim W van Egmond
- P. W. van Egmond, Department of Orthopaedics, Elisabeth-TweeSteden Ziekenhuis, Tilburg, the Netherlands
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Trotter AJ, Dean R, Whitehouse CE, Mikalsen J, Hill C, Brunton-Sim R, Kay GL, Shakokani M, Durst AZE, Wain J, McNamara I, O'Grady J. Preliminary evaluation of a rapid lateral flow calprotectin test for the diagnosis of prosthetic joint infection. Bone Joint Res 2020; 9:202-210. [PMID: 32566141 PMCID: PMC7284294 DOI: 10.1302/2046-3758.95.bjr-2019-0213.r1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
AIMS This pilot study tested the performance of a rapid assay for diagnosing prosthetic joint infection (PJI), which measures synovial fluid calprotectin from total hip and knee revision patients. METHODS A convenience series of 69 synovial fluid samples from revision patients at the Norfolk and Norwich University Hospital were collected intraoperatively (52 hips, 17 knees) and frozen. Synovial fluid calprotectin was measured retrospectively using a new commercially available lateral flow assay for PJI diagnosis (Lyfstone AS) and compared to International Consensus Meeting (ICM) 2018 criteria and clinical case review (ICM-CR) gold standards. RESULTS According to ICM, 24 patients were defined as PJI positive and the remaining 45 were negative. The overall accuracy of the lateral flow test compared to ICM was 75.36% (52/69, 95% CI 63.51% to 84.95%), sensitivity and specificity were 75.00% (18/24, 95% CI 53.29% to 90.23%) and 75.56% (34/45, 95% CI 60.46% to 87.12%), respectively, positive predictive value (PPV) was 62.07% (18/29, 95% CI 48.23% to 74.19%) and negative predictive value (NPV) was 85.00% (34/40, 95% CI 73.54% to 92.04%), and area under the receiver operating characteristic (ROC) curve (AUC) was 0.78 (95% CI 0.66 to 0.87). Patient data from discordant cases were reviewed by the clinical team to develop the ICM-CR gold standard. The lateral flow test performance improved significantly when compared to ICM-CR, with accuracy increasing to 82.61% (57/69, 95% CI 71.59% to 90.68%), sensitivity increasing to 94.74% (18/19, 95% CI 73.97% to 99.87%), NPV increasing to 97.50% (39/40, 95% CI 85.20% to 99.62%), and AUC increasing to 0.91 (95% CI 0.81 to 0.96). Test performance was better in knees (100.00% accurate (17/17, 95% CI 80.49% to 100.00%)) compared to hips (76.92% accurate (40/52, 95% CI 63.16% to 87.47%)). CONCLUSION This study demonstrates that the calprotectin lateral flow assay could be an effective diagnostic test for PJI, however additional prospective studies testing fresh samples are required.Cite this article: Bone Joint Res. 2020;9(5):202-210.
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Affiliation(s)
- Alexander J Trotter
- University of East Anglia, Norwich, UK, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Rachael Dean
- University of East Anglia, Norwich, UK, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | | | | | - Claire Hill
- Quadram Institute Bioscience, Norwich Research Park, Norwich, UK, Norfolk and Norwich University Hospitals Foundation Trust, Norwich, UK
| | | | - Gemma L Kay
- Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | | | - Alexander Z E Durst
- University of East Anglia, Norwich, UK, Norfolk and Norwich University Hospitals Foundation Trust, Norwich, UK
| | - John Wain
- University of East Anglia, Norwich, UK, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Iain McNamara
- University of East Anglia, Norwich, UK, Norfolk and Norwich University Hospitals Foundation Trust, Norwich, UK
| | - Justin O'Grady
- University of East Anglia, Norwich, UK, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
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29
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Amanatullah DF, Cheng RZ, Huddleston III JI, Maloney WJ, Finlay AK, Kappagoda S, Suh GA, Goodman SB. The routine use of synovial alpha-defensin is not necessary. Bone Joint J 2020; 102-B:593-599. [DOI: 10.1302/0301-620x.102b5.bjj-2019-0473.r3] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Aims To establish the utility of adding the laboratory-based synovial alpha-defensin immunoassay to the traditional diagnostic work-up of a prosthetic joint infection (PJI). Methods A group of four physicians evaluated 158 consecutive patients who were worked up for PJI, of which 94 underwent revision arthroplasty. Each physician reviewed the diagnostic data and decided on the presence of PJI according to the 2014 Musculoskeletal Infection Society (MSIS) criteria (yes, no, or undetermined). Their initial randomized review of the available data before or after surgery was blinded to each alpha-defensin result and a subsequent randomized review was conducted with each result. Multilevel logistic regression analysis assessed the effect of having the alpha-defensin result on the ability to diagnose PJI. Alpha-defensin was correlated to the number of synovial white blood cells (WBCs) and percentage of polymorphonuclear cells (%PMN). Results Intraobserver reliability and interobserver agreement did not change when the alpha-defensin result was available. Positive alpha-defensin results had greater synovial WBCs (mean 31,854 cells/μL, SD 32,594) and %PMN (mean 93.0%, SD 5.5%) than negative alpha-defensin results (mean 974 cells/μL, SD 3,988; p < 0.001 and mean 39.4% SD 28.6%; p < 0.001). Adding the alpha-defensin result did not alter the diagnosis of a PJI using preoperative (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.14 to 1.88; p = 0.315) or operative (OR 0.52, CI 0.18 to 1.55; p = 0.242) data when clinicians already decided that PJI was present or absent with traditionally available testing. However, when undetermined with traditional preoperative testing, alpha-defensin helped diagnose (OR 0.44, CI 0.30 to 0.64; p < 0.001) or rule out (OR 0.41, CI 0.17 to 0.98; p = 0.044) PJI. Of the 27 undecided cases with traditional testing, 24 (89%) benefited from the addition of alpha-defensin testing. Conclusion The laboratory-based synovial alpha-defensin immunoassay did not help diagnose or rule out a PJI when added to routine serologies and synovial fluid analyses except in cases where the diagnosis of PJI was unclear. We recommend against the routine use of alpha-defensin and suggest using it only when traditional testing is indeterminate. Cite this article: Bone Joint J 2020;102-B(5):593–599.
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Affiliation(s)
- Derek F. Amanatullah
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Redwood City, California, USA
| | - Robin Z. Cheng
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Redwood City, California, USA
| | - James I. Huddleston III
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Redwood City, California, USA
| | - William J. Maloney
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Redwood City, California, USA
| | - Andrea K. Finlay
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Redwood City, California, USA
| | - Shanthi Kappagoda
- Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
| | - Gina A. Suh
- Department of Medicine, Stanford University School of Medicine, Stanford, California, USA
| | - Stuart B. Goodman
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Redwood City, California, USA
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Ahmed SS, Yaghmour KM, Haddad FS. The Changing Face of Infection, Diagnosis, and Management in the United Kingdom. Orthop Clin North Am 2020; 51:141-146. [PMID: 32138852 DOI: 10.1016/j.ocl.2019.12.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Prosthetic joint infection is still a rare but devastating complication following total hip and knee arthroplasty. The incidence of prosthetic joint infection ranges from 2% to 4% in primary procedures as opposed to nearly 20% in revisions. The challenges that arise here include mainly diagnostic uncertainty, management in immunocompromised patients, recurrent infection, infection around a well-fixed implant, and substantial bone loss, and require careful preoperative assessment and well-defined management plans. This article summarizes recent developments in the diagnosis and management of this increasingly prevalent issue specifically focusing on outcomes following debridement, antibiotics, and implants retention and one-stage revision procedures.
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Affiliation(s)
- Syed S Ahmed
- Lower Limb Arthroplasty, University College London Hospital, 250 Euston Road, Bloomsbury, London NW1 2BU, UK.
| | - Khaled M Yaghmour
- University College London Hospital, 250 Euston Road, Bloomsbury, London NW1 2BU, UK
| | - Fares S Haddad
- University College London Hospital, 250 Euston Road, Bloomsbury, London NW1 2BU, UK
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31
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Bémer P, Bourigault C, Jolivet-Gougeon A, Plouzeau-Jayle C, Lemarie C, Chenouard R, Valentin AS, Bourdon S, Leroy AG, Corvec S. Assessment of a Multiplex Serological Test for the Diagnosis of Prosthetic Joint Infection: a Prospective Multicentre Study. J Bone Jt Infect 2020; 5:89-95. [PMID: 32455099 PMCID: PMC7242409 DOI: 10.7150/jbji.42076] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 02/25/2020] [Indexed: 01/05/2023] Open
Abstract
Introduction: The diagnosis of prosthetic joint infections (PJIs) can be difficult in the chronic stage and is based on clinical and paraclinical evidence. A minimally invasive serological test against the main pathogens encountered during PJI would distinguish PJI from mechanical loosening. Methods: We performed a prospective, multicentre, cross-sectional study to assess the contribution of serology in the diagnosis of PJI. Over a 2-year period, all patients undergoing prosthesis revision were included in the study. A C-reactive protein assay and a serological test specifically designed against 5 bacterial species (Staphylococcus aureus, S. epidermidis, S. lugdunensis, Streptococcus agalactiae, Cutibacterium acnes) were performed preoperatively. Five samples per patient were taken intraoperatively during surgery. The diagnosis of PJI was based on clinical and bacteriological criteria according to guidelines. Results: Between November 2015 and November 2017, 115 patients were included, 49 for a chronic PJI and 66 for a mechanical problem. Among patients with PJI, a sinus tract was observed in 32.6% and a C-reactive protein level ≥10 mg/L in 74.5%. The PJI was monomicrobial in 43 cases (targeted staphylococci, 24; S. agalactiae, 1; C. acnes, 2; others, 16), and polymicrobial in 6 cases (12.2%). Sensitivity, specificity, positive predictive value and negative predictive value were 75.0%, 82.1%, 58.3% and 90.8%, respectively, for targeted staphylococci. Specificity/negative predictive value was 97.3%/100% for S. agalactiae and 83.8% /96.9% for C. acnes. Conclusions: The serological tests are insufficient to affirm the diagnosis of PJI for the targeted bacteria. Nevertheless, the excellent NPV may help clinicians to exclude PJI.
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Affiliation(s)
- Pascale Bémer
- Bacteriology Department, CHU Nantes, Nantes Université, Nantes, France
| | - Céline Bourigault
- Bacteriology and Infection Control Department, CHU Nantes, Nantes Université, Nantes, France
| | | | | | - Carole Lemarie
- Bacteriology Department, CHU Angers, Angers Université, Angers, France
| | - Rachel Chenouard
- Bacteriology Department, CHU Angers, Angers Université, Angers, France
| | | | - Sandra Bourdon
- Bacteriology Department, CH La Roche/Yon, La Roche/Yon, France
| | - Anne-Gaëlle Leroy
- Bacteriology Department, CHU Nantes, Nantes Université, Nantes, France
| | - Stéphane Corvec
- Bacteriology Department, CHU Nantes, Nantes Université, Nantes, France
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Ding BT, Tan KG, Kau CY, Chan HYH, Mohd Fadil MFB. Accuracy of the α-defensin lateral flow assay for diagnosing periprosthetic joint infection in Asians. J Orthop Surg (Hong Kong) 2020; 27:2309499019828459. [PMID: 30744473 DOI: 10.1177/2309499019828459] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE This study aimed to test the accuracy of the Synovasure®, α-defensin lateral flow test kit, in diagnosing periprosthetic joint infections (PJIs) in a predominantly Asian population and to evaluate whether other patient or disease factors may affect its results. METHODS 61 Asian patients comprising 70 hip or knee prosthetic joints, performed between November 2015 and November 2018, were retrospectively evaluated. Cases were categorized as infected or not infected using Musculoskeletal Infection Society (MSIS) Criteria. Synovial fluid was tested for α-defensin using a commercially available kit. . RESULTS The Synovasure test had a sensitivity of 73.7% (95% confidence interval (CI): 48.8-90.9%) and specificity of 92.2% (95% CI: 81.1-97.8%) in an Asian population, which was slightly lower compared to previously reported studies in a predominantly Caucasian population. The positive predictive value was 77.8% (95% CI: 56.8-90.3%) and the negative predictive value was 90.4% (95% CI: 81.5-95.2%). The test had an area under curve (AUC) of the receiver operating characteristic (ROC) graph of 0.938, which represents an accuracy that is similar to synovial white blood cells (WBCs) and almost equivalent to that of synovial polymorphonuclear cells (PMNs). The presence of diabetes ( p = 0.26), systemic inflammatory joint disease ( p = 0.33), other metallic implants ( p = 0.53), immunosuppression ( p = 0.13), prior antibiotic usage ( p = 0.99), and chronicity of symptoms ( p = 0.34) was not significantly associated with a positive test in patients with PJI. CONCLUSION The α-defensin lateral flow test kit is highly accurate in the diagnosis of PJI but with slightly lower sensitivity and specificity in an Asian population when compared with previous studies. The test should be used in conjunction with other MSIS criteria to provide clinically relevant and meaningful results for the diagnosis of PJI.
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Affiliation(s)
- Benjamin Tk Ding
- Department of Orthopaedic Surgery, Tan Tock Seng Hospital, Singapore
| | | | - Chung Yuan Kau
- Department of Orthopaedic Surgery, Tan Tock Seng Hospital, Singapore
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Wahl EP, Garrigues GE. Diagnosis of Shoulder Arthroplasty Infection: New Tests on the Horizon. Orthopedics 2020; 43:76-82. [PMID: 31841608 DOI: 10.3928/01477447-20191212-01] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Accepted: 12/27/2018] [Indexed: 02/03/2023]
Abstract
Periprosthetic shoulder infection (PSI), although less common than prosthetic hip and knee infections, continues to be a devastating complication of shoulder arthroplasty. Unlike its counterparts in the hip and knee, infection with nonsuppurative bacteria is more common than infection with more virulent bacteria in periprosthetic shoulder infection. The diagnosis of PSI can be challenging because the traditional clinical and laboratory findings are not always present. The authors present a narrative review of the current methods used in the diagnosis of PSI, as well as recently developed tests that may hold promise for the diagnosis of PSI. [Orthopedics. 2020; 43(2):76-82.].
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Balato G, de Matteo V, Ascione T, Di Donato SL, De Franco C, Smeraglia F, Baldini A, Mariconda M. Laboratory-based versus qualitative assessment of α-defensin in periprosthetic hip and knee infections: a systematic review and meta-analysis. Arch Orthop Trauma Surg 2020; 140:293-301. [PMID: 31300864 DOI: 10.1007/s00402-019-03232-5] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2018] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Two methods are currently available for the assay of α-defensin: the enzyme-linked immunosorbent assay (ELISA) and the lateral flow test. We aimed to assess the diagnostic accuracy of synovial fluid α-defensin and to compare the accuracy of the laboratory-based test and the qualitative assessment for the diagnosis of hip and knee prosthetic infection. MATERIALS AND METHODS We searched (from inception to May 2018) MEDLINE, Scopus, EMBASE, Web of Science, and Cochrane for studies on α-defensin in the diagnosis of periprosthetic joint infection (PJI). Sensitivity, specificity, positive and negative likelihood ratio (LR), and diagnostic odds ratio were analyzed using the bivariate diagnostic random-effects model. The receiver-operating curve for each method was calculated. RESULTS We included 13 articles in our meta-analysis, including 1170 patients who underwent total hip and knee arthroplasties revision; 368 (31%) had a joint infection according to MSIS and MSIS-modified criteria. Considering the false-positive result rate of 8% and false-negative result rate of 3%, pooled sensitivity and specificity were 0.90 (95% CI 0.83-0.94) and 0.95 (0.92-0.96), respectively. The area under the curve (AUC) was 0.94 (0.92-0.94). No statistical differences in terms of sensitivity and specificity were found between the laboratory-based and qualitative test. The pooled sensitivity and specificity of the two alpha-defensin assessment methods were: laboratory-based test 0.97 (95% CI 0.93-0.99) and 0.96 (95% CI 0.94-0.98), respectively; qualitative test 0.83 (95% CI 0.73-0.91) and 0.94 (95% CI 0.89-0.97), respectively. The diagnostic odds ratio of the α-defensin laboratory based was superior to that of the qualitative test (1126.085, 95% CI 352.172-3600.702 versus 100.9, 95% CI 30.1-338.41; p < 0.001). The AUC for immunoassay and qualitative tests was 0.97 (0.95-0.99) and 0.91 (0.88-0.99), respectively. CONCLUSION Detection of α-defensin is an accurate test for diagnosis of hip and knee prosthetic infections. The diagnostic accuracy of the two alpha-defensin assessment methods is comparable. The lateral flow assay is a valid, rapid, and more available diagnostic tool, particularly to rule out PJI.
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Affiliation(s)
- Giovanni Balato
- Section of Orthopaedic Surgery, Department of Public Health, School of Medicine, Federico II University, Via S. Pansini 5, 80131, Naples, Italy.
| | - Vincenzo de Matteo
- Section of Orthopaedic Surgery, Department of Public Health, School of Medicine, Federico II University, Via S. Pansini 5, 80131, Naples, Italy
| | - Tiziana Ascione
- Department of Infectious Diseases, D. Cotugno Hospital, AORN Dei Colli, Naples, Italy
| | - Sigismondo Luca Di Donato
- Section of Orthopaedic Surgery, Department of Public Health, School of Medicine, Federico II University, Via S. Pansini 5, 80131, Naples, Italy
| | - Cristiano De Franco
- Section of Orthopaedic Surgery, Department of Public Health, School of Medicine, Federico II University, Via S. Pansini 5, 80131, Naples, Italy
| | - Francesco Smeraglia
- Section of Orthopaedic Surgery, Department of Public Health, School of Medicine, Federico II University, Via S. Pansini 5, 80131, Naples, Italy
| | | | - Massimo Mariconda
- Section of Orthopaedic Surgery, Department of Public Health, School of Medicine, Federico II University, Via S. Pansini 5, 80131, Naples, Italy
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Haddad FS. A tumultuous decade. Bone Joint J 2019; 101-B:1465. [PMID: 31786994 DOI: 10.1302/0301-620x.101b12.bjj-2019-1379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Affiliation(s)
- Fares S Haddad
- The Bone & Joint Journal, Professor of Orthopaedic Surgery, University College London Hospitals, The Princess Grace Hospital, and The NIHR Biomedical Research Centre at UCLH, London, UK
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36
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Affiliation(s)
- S S Ahmed
- University College London Hospitals NHS Foundation Trust, The Princess Grace Hospital, London, UK
| | - F S Haddad
- University College London Hospitals NHS Foundation Trust, The Princess Grace Hospital, and the NIHR Biomedical Research Centre at UCLH, London, UK
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Ahmed SS, Begum F, Kayani B, Haddad FS. Risk factors, diagnosis and management of prosthetic joint infection after total hip arthroplasty. Expert Rev Med Devices 2019; 16:1063-1070. [PMID: 31752561 DOI: 10.1080/17434440.2019.1696673] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Introduction: Although a relatively rare complication, the incidence and prevalence of prosthetic joint infection (PJI) is certainly rising. This is mainly due to the number of arthroplasties performed each year and our ability to capture more cases. There is currently no consensus in the optimal diagnosis and management of the infected total hip arthroplasty. Various management techniques have been described in literature.Areas covered: We discuss and summarize the literature in diagnosing prosthetic joint infection (PJI) including next-generation sequencing. An in-depth critical analysis of the biomarkers and the novel tests available in the market is reviewed including the evolving nature of the diagnostic criteria for PJI. The key issues in managing infected THA are identified.Expert commentary: The senior authors' expert opinion on diagnostic criteria is discussed. We also stress the importance of tissue/fluid analysis of microbiology and histology being key to diagnosis of PJI. The indications of one-stage versus two-stage revision arthroplasty is examined, including techniques for successful one-stage revision.
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Affiliation(s)
- Syed S Ahmed
- Trauma & Orthopaedics, University College Hospital, London, UK.,Trauma & Orthopaedics, Princess Grace Hospital, London, UK
| | - Fahima Begum
- Trauma & Orthopaedics, University College Hospital, London, UK.,Trauma & Orthopaedics, Princess Grace Hospital, London, UK
| | - Babar Kayani
- Trauma & Orthopaedics, University College Hospital, London, UK.,Trauma & Orthopaedics, Princess Grace Hospital, London, UK
| | - Fares S Haddad
- Trauma & Orthopaedics, University College Hospital, London, UK.,Trauma & Orthopaedics, Princess Grace Hospital, London, UK
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Abstract
Culture-negative periprosthetic joint infections (CN-PJI) pose a significant challenge in terms of diagnosis and management. The reported incidence of CN-PJI is reported to be between 7% and 15%. Fungi and mycobacterium are thought to be responsible for over 85% of such cases with more fastidious bacteria accounting for the rest. With the advent of polymerase chain reaction, mass spectrometry and next generation sequencing, identifying the causative organism(s) may become easier but such techniques are not readily available and are very costly. There are a number of more straightforward and relatively low-cost methods to help surgeons maximize the chances of diagnosing a PJI and identify the organisms responsible. This review article summarizes the main diagnostic tests currently available as well as providing a simple diagnostic clinical algorithm for CN-PJI. Cite this article: EFORT Open Rev 2019;4:585-594. DOI: 10.1302/2058-5241.4.180067
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Affiliation(s)
- Jeya Palan
- Leeds Teaching Hospitals NHS Trust, Chapel Allerton Hospital, Leeds, UK
| | - Ciaran Nolan
- Leeds Teaching Hospitals NHS Trust, Chapel Allerton Hospital, Leeds, UK
| | - Kostas Sarantos
- Leeds Teaching Hospitals NHS Trust, Chapel Allerton Hospital, Leeds, UK
| | - Richard Westerman
- Leeds Teaching Hospitals NHS Trust, Chapel Allerton Hospital, Leeds, UK
| | - Richard King
- Leeds Teaching Hospitals NHS Trust, Chapel Allerton Hospital, Leeds, UK
| | - Pedro Foguet
- Leeds Teaching Hospitals NHS Trust, Chapel Allerton Hospital, Leeds, UK
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Han X, Xie K, Jiang X, Wang L, Wu H, Qu X, Yan M. Synovial fluid α-defensin in the diagnosis of periprosthetic joint infection: the lateral flow test is an effective intraoperative detection method. J Orthop Surg Res 2019; 14:274. [PMID: 31455372 PMCID: PMC6712677 DOI: 10.1186/s13018-019-1320-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Accepted: 08/16/2019] [Indexed: 12/29/2022] Open
Abstract
Background Synovial fluid α-defensin is a valuable biomarker for periprosthetic joint infection (PJI). Its diagnostic value for PJI has been widely evaluated recently, but results are inconsistent, especially for different test methods. The objective of this study was to evaluate the diagnostic value of laboratory-based immunoassay and lateral flow testing for the detection of α-defensin against hip and knee PJI. Methods We systematically searched MEDLINE and EMBASE for articles on the diagnostic accuracy of α-defensin for PJI published up to September 2018. The pooled sensitivity, specificity, area under the curve (AUC), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated for the evaluation of the diagnostic value of α-defensin for PJI. Results Nineteen studies were included. Eleven evaluated laboratory-based immunoassay, and 10 evaluated the lateral flow test results. The pooled sensitivity, specificity, AUC, PLR, NLR, and DOR of laboratory-based immunoassays were 0.96 (95% confidence interval [CI] 0.90–0.98), 0.97 (95% CI 0.95–0.99), 0.99 (95% CI 0.98–1.00), 35.0 (95% CI 18.5–66.2), 0.04 (95% CI 0.02–0.11), and 811 (95% CI 220–2990), respectively. The pooled sensitivity, specificity, AUC, PLR, NLR, and DOR of the lateral flow test were 0.86 (95% CI 0.81–0.91), 0.96 (95% CI 0.93–0.98), 0.95 (95% CI 0.93–0.97), 21.2 (95% CI 11.7–38.5), 0.14 (95% CI 0.10–0.21), and 148 (95% CI 64–343), respectively. Conclusions Laboratory-based immunoassay of α-defensin is highly accurate for the diagnosis of hip and knee PJI. The lateral flow test is less sensitive but still a useful intraoperative detection tool for PJI.
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Affiliation(s)
- Xuequan Han
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, China
| | - Kai Xie
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, China
| | - Xu Jiang
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, China
| | - Liao Wang
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, China
| | - Haishan Wu
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, China
| | - Xinhua Qu
- Department of Bone and Joint Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University School of Medicine, 145 Middle Shandong Road, Shanghai, China
| | - Mengning Yan
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, China.
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Kleiss S, Jandl NM, Novo de Oliveira A, Rüther W, Niemeier A. Diagnostic accuracy of alpha-defensin enzyme-linked immunosorbent assay in the clinical evaluation of painful hip and knee arthroplasty with possible prosthetic joint infection. Bone Joint J 2019; 101-B:970-977. [DOI: 10.1302/0301-620x.101b8.bjj-2018-1390.r2] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Aims The aim of this study was to evaluate the diagnostic accuracy of the synovial alpha-defensin enzyme-linked immunosorbent assay (ELISA) for the diagnosis of prosthetic joint infection (PJI) in the work-up prior to revision of total hip (THA) and knee arthroplasty (TKA). Patients and Methods Inclusion criteria for this prospective cohort study were acute or chronic symptoms of the index joint without specific exclusion criteria. Synovial fluid aspirates of 202 patients were analyzed and semiquantitative laboratory alpha-defensin ELISA was performed. Final diagnosis of PJI was established by examination of samples obtained during revision surgery. Results Sensitivity and specificity of the alpha-defensin ELISA for PJI were 78.2% (95% confidence interval (CI) 66.7 to 88.5) and 96.6% (95% CI 93.0 to 99.3). Positive and negative predictive values were 89.6% (95% CI 80.6 to 97.8) and 92.2% (95% CI 87.5 to 96.1). The test remained false-negative in 22% of septic revisions, most of which were due to coagulase-negative staphylococci all occurring in either late-chronic or early-postoperative PJI. Conclusion The routine use of synovial fluid alpha-defensin laboratory ELISA in the preoperative evaluation of symptomatic THAs and TKAs is insufficient to accurately diagnose PJI. Particularly in cases involving low-virulence organisms, such as coagulase-negative staphylococci, there remains a need for tests with a higher sensitivity. Cite this article: Bone Joint J 2019;101-B:970–977.
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Affiliation(s)
- S. Kleiss
- Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - N. M. Jandl
- Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - A. Novo de Oliveira
- Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - W. Rüther
- Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - A. Niemeier
- Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Proceedings from the 2018 International Consensus Meeting on Orthopedic Infections: evaluation of periprosthetic shoulder infection. J Shoulder Elbow Surg 2019; 28:S32-S66. [PMID: 31196514 DOI: 10.1016/j.jse.2019.04.016] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 04/20/2019] [Indexed: 02/01/2023]
Abstract
The Second International Consensus Meeting on Orthopedic Infections was held in Philadelphia, Pennsylvania, in July 2018. More than 800 experts from all 9 subspecialties of orthopedic surgery and allied fields of infectious disease, microbiology, and epidemiology were assembled to form the International Consensus Group. The shoulder workgroup reached consensus on 27 questions related to culture techniques, inflammatory markers, and diagnostic criteria used to evaluate patients for periprosthetic shoulder infection. This document contains the group's recommendations and rationale for each question related to evaluating periprosthetic shoulder infection.
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The W.A.I.O.T. Definition of High-Grade and Low-Grade Peri-Prosthetic Joint Infection. J Clin Med 2019; 8:jcm8050650. [PMID: 31083439 PMCID: PMC6571975 DOI: 10.3390/jcm8050650] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Revised: 05/06/2019] [Accepted: 05/09/2019] [Indexed: 12/27/2022] Open
Abstract
The definition of peri-prosthetic joint infection (PJI) has a strong impact on the diagnostic pathway and on treatment decisions. In the last decade, at least five different definitions of peri-prosthetic joint infection (PJI) have been proposed, each one with intrinsic limitations. In order to move a step forward, the World Association against Infection in Orthopedics and Trauma (W.A.I.O.T.) has studied a possible alternative solution, based on three parameters: 1. the relative ability of each diagnostic test or procedure to Rule OUT and/or to Rule IN a PJI; 2. the clinical presentation; 3. the distinction between pre/intra-operative findings and post-operative confirmation. According to the WAIOT definition, any positive Rule IN test (a test with a specificity > 90%) scores +1, while a negative Rule OUT test (a test with a sensitivity > 90%) scores −1. When a minimum of two Rule IN and two Rule OUT tests are performed in a given patient, the balance between positive and negative tests, interpreted in the light of the clinical presentation and of the post-operative findings, allows to identify five different conditions: High-Grade PJI (score ≥ 1), Low-Grade PJI (≥0), Biofilm-related implant malfunction, Contamination and No infection (all scoring < 0). The proposed definition leaves the physician free to choose among different tests with similar sensitivity or specificity, on the basis of medical, logistical and economic considerations, while novel tests or diagnostic procedures can be implemented in the definition at any time, provided that they meet the required sensitivity and/or specificity thresholds. Key procedures to confirm or to exclude the diagnosis of PJI remain post-operative histological and microbiological analysis; in this regard, given the biofilm-related nature of PJI, microbiological investigations should be conducted with proper sampling, closed transport systems, antibiofilm processing of tissue samples and explanted biomaterials, and prolonged cultures. The proposed WAIOT definition is the result of an international, multidisciplinary effort. Next step will be a large scale, multicenter clinical validation trial.
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Chen MF, Chang CH, Yang LY, Hsieh PH, Shih HN, Ueng SWN, Chang Y. Synovial fluid interleukin-16, interleukin-18, and CRELD2 as novel biomarkers of prosthetic joint infections. Bone Joint Res 2019; 8:179-188. [PMID: 31069072 PMCID: PMC6498892 DOI: 10.1302/2046-3758.84.bjr-2018-0291.r1] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Objectives Prosthetic joint infection (PJI) diagnosis is a major challenge in orthopaedics, and no reliable parameters have been established for accurate, preoperative predictions in the differential diagnosis of aseptic loosening or PJI. This study surveyed factors in synovial fluid (SF) for improving PJI diagnosis. Methods We enrolled 48 patients (including 39 PJI and nine aseptic loosening cases) who required knee/hip revision surgery between January 2016 and December 2017. The PJI diagnosis was established according to the Musculoskeletal Infection Society (MSIS) criteria. SF was used to survey factors by protein array and enzyme-linked immunosorbent assay to compare protein expression patterns in SF among three groups (aseptic loosening and first- and second-stage surgery). We compared routine clinical test data, such as C-reactive protein level and leucocyte number, with potential biomarker data to assess the diagnostic ability for PJI within the same patient groups. Results Cut-off values of 1473 pg/ml, 359 pg/ml, and 8.45 pg/ml were established for interleukin (IL)-16, IL-18, and cysteine-rich with EGF-like domains 2 (CRELD2), respectively. Receiver operating characteristic curve analysis showed that these factors exhibited an accuracy of 1 as predictors of PJI. These factors represent potential biomarkers for decisions associated with prosthesis reimplantation based on their ability to return to baseline values following the completion of debridement. Conclusion IL-16, IL-18, and CRELD2 were found to be potential biomarkers for PJI diagnosis, with SF tests outperforming blood tests in accuracy. These factors could be useful for assessing successful debridement based on their ability to return to baseline values following the completion of debridement.Cite this article: M-F. Chen, C-H. Chang, L-Y. Yang, P-H. Hsieh, H-N. Shih, S. W. N. Ueng, Y. Chang. Synovial fluid interleukin-16, interleukin-18, and CRELD2 as novel biomarkers of prosthetic joint infections. Bone Joint Res 2019;8:179-188. DOI: 10.1302/2046-3758.84.BJR-2018-0291.R1.
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Affiliation(s)
- M-F Chen
- Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - C-H Chang
- Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - L-Y Yang
- Biostatistics Unit, Clinical Trial Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - P-H Hsieh
- Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - H-N Shih
- Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - S W N Ueng
- Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Y Chang
- Bone and Joint Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
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Affiliation(s)
- F S Haddad
- The Bone & Joint Journal, Professor of Orthopaedic Surgery, University College London Hospitals, The Princess Grace Hospital, and The NIHR Biomedical Research Centre at UCLH, London, UK
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Carli AV, Abdelbary H, Ahmadzai N, Cheng W, Shea B, Hutton B, Sniderman J, Philip Sanders BS, Esmaeilisaraji L, Skidmore B, Gauthier-Kwan OY, Bunting AC, Gauthier P, Crnic A, Logishetty K, Moher D, Fergusson D, Beaulé PE. Diagnostic Accuracy of Serum, Synovial, and Tissue Testing for Chronic Periprosthetic Joint Infection After Hip and Knee Replacements: A Systematic Review. J Bone Joint Surg Am 2019; 101:635-649. [PMID: 30946198 DOI: 10.2106/jbjs.18.00632] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Chronic periprosthetic joint infection (PJI) is a devastating complication that can occur following total joint replacement. Patients with chronic PJI report a substantially lower quality of life and face a higher risk of short-term mortality. Establishing a diagnosis of chronic PJI is challenging because of conflicting guidelines, numerous tests, and limited evidence. Delays in diagnosing PJI are associated with poorer outcomes and morbid revision surgery. The purpose of this systematic review was to compare the diagnostic accuracy of serum, synovial, and tissue-based tests for chronic PJI. METHODS This review adheres to the Cochrane Collaboration's diagnostic test accuracy methods for evidence searching and syntheses. A detailed search of MEDLINE, Embase, the Cochrane Library, and the grey literature was performed to identify studies involving the diagnosis of chronic PJI in patients with hip or knee replacement. Eligible studies were assessed for quality and bias using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Meta-analyses were performed on tests with sufficient data points. Summary estimates and hierarchical summary receiver operating characteristic (HSROC) curves were obtained using a bivariate model. RESULTS A total of 12,616 citations were identified, and 203 studies met the inclusion criteria. Of these 203 studies, 170 had a high risk of bias. Eighty-three unique PJI diagnostic tests were identified, and 17 underwent meta-analyses. Laboratory-based synovial alpha-defensin tests and leukocyte esterase reagent (LER) strips (2+) had the best performance, followed by white blood-cell (WBC) count, measurement of synovial C-reactive protein (CRP) level, measurement of the polymorphonuclear neutrophil percentage (PMN%), and the alpha-defensin lateral flow test kit (Youden index ranging from 0.78 to 0.94). Tissue-based tests and 3 serum tests (measurement of interleukin-6 [IL-6] level, CRP level, and erythrocyte sedimentation rate [ESR]) had a Youden index between 0.61 to 0.75 but exhibited poorer performance compared with the synovial tests mentioned above. CONCLUSIONS The quality of the literature pertaining to chronic PJI diagnostic tests is heterogeneous, and the studies are at a high risk for bias. We believe that greater transparency and more complete reporting in studies of diagnostic test results should be mandated by peer-reviewed journals. The available literature suggests that several synovial fluid-based tests perform well for diagnosing chronic PJI and their use is recommended in the work-up of any suspected case of chronic PJI. LEVEL OF EVIDENCE Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
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Affiliation(s)
- Alberto V Carli
- Division of Orthopaedic Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Hesham Abdelbary
- Division of Orthopaedic Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Nadera Ahmadzai
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Wei Cheng
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Beverley Shea
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.,School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Brian Hutton
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.,School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Jhase Sniderman
- Division of Orthopaedic Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada
| | | | - Leila Esmaeilisaraji
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Becky Skidmore
- Independent Information Specialist, Ottawa, Ontario, Canada
| | | | | | - Paul Gauthier
- Division of Orthopaedic Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Agnes Crnic
- Division of Orthopaedic Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada
| | | | - David Moher
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Dean Fergusson
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Paul E Beaulé
- Division of Orthopaedic Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada
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Peel TN. Studying Biofilm and Clinical Issues in Orthopedics. Front Microbiol 2019; 10:359. [PMID: 30863390 PMCID: PMC6399144 DOI: 10.3389/fmicb.2019.00359] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Accepted: 02/12/2019] [Indexed: 12/12/2022] Open
Abstract
The association between biofilm-forming microorganisms and prosthetic joint infection influences all aspect of management including approaches to diagnosis, management and prevention. This article will provide an overview of new anti-biofilm strategies for management of prosthetic joint infection.
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Affiliation(s)
- Trisha N Peel
- Department of Infectious Diseases, Monash University, Melbourne, VIC, Australia.,Alfred Health, Melbourne, VIC, Australia
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Aalirezaie A, Bauer TW, Fayaz H, Griffin W, Higuera CA, Krenn V, Krenn V, Molano M, Moojen DJ, Restrepo C, Shahi A, Shubnyakov I, Sporer S, Tanavalee A, Teloken M, Velázquez Moreno JD. Hip and Knee Section, Diagnosis, Reimplantation: Proceedings of International Consensus on Orthopedic Infections. J Arthroplasty 2019; 34:S369-S379. [PMID: 30343965 DOI: 10.1016/j.arth.2018.09.021] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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General Assembly, Treatment, Multidisciplinary Issues: Proceedings of International Consensus on Orthopedic Infections. J Arthroplasty 2019; 34:S239-S243. [PMID: 30348547 DOI: 10.1016/j.arth.2018.09.075] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
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Bauer TW, Bedair H, Creech JD, Deirmengian C, Eriksson H, Fillingham Y, Grigoryan G, Hickok N, Krenn V, Krenn V, Lazarinis S, Lidgren L, Lonner J, Odum S, Shah J, Shahi A, Shohat N, Tarabichi M, W-Dahl A, Wongworawat MD. Hip and Knee Section, Diagnosis, Laboratory Tests: Proceedings of International Consensus on Orthopedic Infections. J Arthroplasty 2019; 34:S351-S359. [PMID: 30343973 DOI: 10.1016/j.arth.2018.09.019] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
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Abdel Karim M, Andrawis J, Bengoa F, Bracho C, Compagnoni R, Cross M, Danoff J, Della Valle CJ, Foguet P, Fraguas T, Gehrke T, Goswami K, Guerra E, Ha YC, Klaber I, Komnos G, Lachiewicz P, Lausmann C, Levine B, Leyton-Mange A, McArthur BA, Mihalič R, Neyt J, Nuñez J, Nunziato C, Parvizi J, Perka C, Reisener MJ, Rocha CH, Schweitzer D, Shivji F, Shohat N, Sierra RJ, Suleiman L, Tan TL, Vasquez J, Ward D, Wolf M, Zahar A. Hip and Knee Section, Diagnosis, Algorithm: Proceedings of International Consensus on Orthopedic Infections. J Arthroplasty 2019; 34:S339-S350. [PMID: 30348566 DOI: 10.1016/j.arth.2018.09.018] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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