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Pascal A, Lambrey PJ, Valentin B, Migaud H, Putman S, Faure PA, Dartus J, Loiez C, Saint Vincent B, Senneville E. Comparative performance analysis of Synovasure™ and Leukocyte Esterase assays for the diagnosis of periprosthetic infections in complex microbiological situations. Orthop Traumatol Surg Res 2024:104046. [PMID: 39527978 DOI: 10.1016/j.otsr.2024.104046] [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: 06/02/2024] [Revised: 08/20/2024] [Accepted: 09/05/2024] [Indexed: 11/16/2024]
Abstract
INTRODUCTION Osteoarticular infections (OAI) after prosthetic surgery have serious functional and economic consequences. Rapid tests for alpha-defensin (TAD) and leukocyte esterase (TLE) are two intra-articular markers involved in the diagnosis of OAIs. TLE cannot be applied in the presence of blood unless centrifugation is used, but the rate of "non-application" of the test for this reason is unknown in complex microbiological situations (discordant or negative puncture, ongoing antibiotic treatment). We therefore conducted a prospective study to determine: 1) the performance of the TAD and TLE rapid tests in diagnosing complex OAI, 2) the rate of non-application of the TLE due to hemarthrosis, and 3) the concordance between the two tests. ASSUMPTION These two diagnostic tests had a negative predictive value (NPV) ≥ 90% for the diagnosis of complex OAI. MATERIALS AND METHODS A total of 79 suspected OAI patients with complex microbiological diagnoses were included between 2018 and 2023. They were 52 men (66%) for 27 women (34%), with a mean age of 66 ± 13.5 years. The hip (n = 41, 52%) and knee (n = 36, 46%) were the most represented, followed by the elbow (n = 1, 1%) and shoulder (n = 1, 1%). These patients were suspected of having an OAI that required joint puncture, but with a complex microbiological diagnosis due to discordant punctures (n = 21, 27%) or sterile punctures despite strong suspicion of infection (n = 50, 63%), or in case of ongoing antibiotic treatment (n = 8, 10%). All patients underwent joint fluid puncture followed by TAD (Synovasure™, Zimmer, Warsaw, IN, USA) and, when the macroscopic appearance of the sample allowed (clear fluid group), TLE (Multistix 8SG, Siemens Healthcare GmbH, Erlangen, Germany). The results of both tests were compared with Musculoskeletal Infection Society (MSIS) criteria. RESULTS Of the 79 patients included, 27 (34%) were considered infected according to the MSIS. In 30% of cases (n = 24), TLE was not feasible due to the presence of blood in the joint fluid. In the "clear fluid" group, the NPV was equal to 90% for both TAD (sensitivity 87%, specificity 88%) and TLE (sensitivity 87%, specificity 81%). The two parameters showed almost perfect agreement (κ = 0.927). CONCLUSION TAD and TLE are two rapid, reliable tests with near-perfect concordance and high NPV, even in situations of complex microbiological diagnosis. They are particularly useful for deciding on a therapeutic strategy for patients with complex OAI. The TLE cannot be used in 30% of cases due to hemarthrosis, but centrifugation can correct this defect. LEVEL OF EVIDENCE III; Prospective comparative diagnostic accuracy study.
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Affiliation(s)
- Adrien Pascal
- Centre de Référence Pour le Traitement des Infections Ostéo-Articulaires Complexes (CRIOAC), Avenue du Professeur-Emile-Laine, 59037 Lille-Tourcoing, France; Université Lille-Hauts de France, 59000 Lille, France; Service de Chirurgie Orthopédique et Traumatologique, CHU de Lille, 2 Avenue Émile Laine, 59000 Lille, France.
| | - Pierre-Jean Lambrey
- Centre de Référence Pour le Traitement des Infections Ostéo-Articulaires Complexes (CRIOAC), Avenue du Professeur-Emile-Laine, 59037 Lille-Tourcoing, France; Université Lille-Hauts de France, 59000 Lille, France; Service de Chirurgie Orthopédique et Traumatologique, CHU de Lille, 2 Avenue Émile Laine, 59000 Lille, France
| | - Benjamin Valentin
- Centre de Référence Pour le Traitement des Infections Ostéo-Articulaires Complexes (CRIOAC), Avenue du Professeur-Emile-Laine, 59037 Lille-Tourcoing, France; Université Lille-Hauts de France, 59000 Lille, France; Service de Pharmacie Clinique, Pharmacie, CHU de Lille, 59000 Lille, France
| | - Henri Migaud
- Centre de Référence Pour le Traitement des Infections Ostéo-Articulaires Complexes (CRIOAC), Avenue du Professeur-Emile-Laine, 59037 Lille-Tourcoing, France; Université Lille-Hauts de France, 59000 Lille, France; Service de Chirurgie Orthopédique et Traumatologique, CHU de Lille, 2 Avenue Émile Laine, 59000 Lille, France
| | - Sophie Putman
- Centre de Référence Pour le Traitement des Infections Ostéo-Articulaires Complexes (CRIOAC), Avenue du Professeur-Emile-Laine, 59037 Lille-Tourcoing, France; Université Lille-Hauts de France, 59000 Lille, France; Service de Chirurgie Orthopédique et Traumatologique, CHU de Lille, 2 Avenue Émile Laine, 59000 Lille, France
| | - Philippe-Alexandre Faure
- Centre de Référence Pour le Traitement des Infections Ostéo-Articulaires Complexes (CRIOAC), Avenue du Professeur-Emile-Laine, 59037 Lille-Tourcoing, France; Université Lille-Hauts de France, 59000 Lille, France; Service de Chirurgie Orthopédique et Traumatologique, CHU de Lille, 2 Avenue Émile Laine, 59000 Lille, France
| | - Julien Dartus
- Centre de Référence Pour le Traitement des Infections Ostéo-Articulaires Complexes (CRIOAC), Avenue du Professeur-Emile-Laine, 59037 Lille-Tourcoing, France; Université Lille-Hauts de France, 59000 Lille, France; Service de Chirurgie Orthopédique et Traumatologique, CHU de Lille, 2 Avenue Émile Laine, 59000 Lille, France
| | - Caroline Loiez
- Centre de Référence Pour le Traitement des Infections Ostéo-Articulaires Complexes (CRIOAC), Avenue du Professeur-Emile-Laine, 59037 Lille-Tourcoing, France; Université Lille-Hauts de France, 59000 Lille, France; Service de Bactériologie-Hygiène, Centre de Biologie-Pathologie, CHU de Lille, 2 Avenue Émile Laine, 59000 Lille, France
| | - Benoîtde Saint Vincent
- Centre de Référence Pour le Traitement des Infections Ostéo-Articulaires Complexes (CRIOAC), Avenue du Professeur-Emile-Laine, 59037 Lille-Tourcoing, France; Université Lille-Hauts de France, 59000 Lille, France; Service de Chirurgie Orthopédique et Traumatologique, CHU de Lille, 2 Avenue Émile Laine, 59000 Lille, France
| | - Eric Senneville
- Centre de Référence Pour le Traitement des Infections Ostéo-Articulaires Complexes (CRIOAC), Avenue du Professeur-Emile-Laine, 59037 Lille-Tourcoing, France; Université Lille-Hauts de France, 59000 Lille, France; Service Universitaire des Maladies Infectieuses et du Voyageur, Hôpital Dron, 59200, Tourcoing, France
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Fu Y, Li Q, Zhao H, Liu W. Construction and evaluation of a combined diagnostic model for chronic periprosthetic joint infection based on serological tests. J Orthop Surg Res 2024; 19:667. [PMID: 39415257 PMCID: PMC11484210 DOI: 10.1186/s13018-024-05146-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 10/05/2024] [Indexed: 10/18/2024] Open
Abstract
BACKGROUND Early diagnosis of chronic periprosthetic joint infection (CPJI) is crucial for ensuring effective treatment and improving patient outcomes. However, many auxiliary diagnostic tests are challenging to implement on a large scale due to economic and technical constraints, making CPJI diagnosis difficult. This study aims to design and validate a combined diagnostic model based on commonly used serological tests to evaluate its diagnostic value for CPJI and develop a diagnostic nomogram. METHODS A retrospective study from January 2019 to February 2024 involving 170 patients undergoing knee and hip arthroplasty revision for CPJI and aseptic loosening (AL) was conducted across two medical centers. These patients were divided into the training set and validation set. Patients were categorized into CPJI and AL groups based on infection status. Serological tests conducted upon admission were collected, and single-factor and multi-factor logistic regression analyses were used to identify independent diagnostic factors for early infection. These factors were integrated to construct a nomogram model. The model's performance was evaluated using the receiver operating characteristic area under the curve (AUC), Hosmer-Lemeshow test, decision curve analysis (DCA), and calibration curve, with external validation conducted on the validation set. RESULTS Multivariate logistic regression analysis showed that C-reactive protein (CRP), procalcitonin (PCT), and Platelet count/mean platelet volume ratio (PVR) were independent diagnostic factors for CPJI (p < 0.05). The AUCs for diagnosing CPJI using these individual factors were 0.806, 0.616, and 0.700 (p < 0.05), respectively, while their combined detection achieved an AUC of 0.861 (p < 0.05). The DCA clinical impact curve shows the combined model has good clinical utility when the threshold probability of infection presence is between 0.16 and 0.95. Similar results were obtained in the external validation cohort, with the combined detection having an AUC of 0.893. CONCLUSION The combined diagnostic model of CRP, PCT, and PVR significantly improves the The combined diagnostic model of CRP, PCT, and PVR significantly improves the diagnostic performance for CPJI compared to individual serum biomarkers. It exhibits good sensitivity, specificity, and clinical applicability, providing valuable references for CPJI diagnosis.
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Affiliation(s)
- Yingqiang Fu
- Department of Joint Surgery/Sports Medicine, The Second Hospital Of Shandong University, Jinan, 250033, China
| | | | - Heng Zhao
- Department of Joint Surgery/Sports Medicine, The Second Hospital Of Shandong University, Jinan, 250033, China
| | - Wenguang Liu
- Department of Joint Surgery/Sports Medicine, The Second Hospital Of Shandong University, Jinan, 250033, China.
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Altsitzioglou P, Avgerinos K, Karampikas V, Gavriil P, Vlachos A, Soucacou F, Zafiris I, Kontogeorgakos V, Papagelopoulos PJ, Mavrogenis AF. Point of care testing for the diagnosis of periprosthetic joint infections: a review. SICOT J 2024; 10:24. [PMID: 38847648 PMCID: PMC11160401 DOI: 10.1051/sicotj/2024019] [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: 04/27/2024] [Accepted: 05/04/2024] [Indexed: 06/09/2024] Open
Abstract
BACKGROUND Periprosthetic joint infection (PJI) remains a major complication following total joint arthroplasties (TJA), significantly affecting patient outcomes and healthcare costs. Despite advances in diagnostic techniques, challenges persist in accurately diagnosing PJI, underscoring the need for effective point-of-care testing (POCT). METHODS This review examines the current literature and latest developments in POCT for diagnosing PJI, focusing on biomarkers such as alpha-defensin, leukocyte esterase, calprotectin, and C-reactive protein (CRP). Criteria from various societies like the Musculoskeletal Infection Society, Infectious Diseases Society of America, and the International Consensus Meeting were compared to evaluate the effectiveness of these biomarkers in a point-of-care setting. RESULTS POCT provides rapid results essential for the timely management of PJI, with alpha-defensin and leukocyte esterase showing high specificity and sensitivity. Recent advancements have introduced novel biomarkers like calprotectin, which demonstrate high diagnostic accuracy. However, challenges such as the variability in test performance and the need for validation under different clinical scenarios remain. DISCUSSION While POCT for PJI shows promising results, their integration into clinical practice requires standardized protocols and further validation. The evolution of these diagnostic tools offers a potential shift toward more personalized and immediate care, potentially improving outcomes for patients undergoing TJA.
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Affiliation(s)
- Pavlos Altsitzioglou
- From the First Department of Orthopaedics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Konstantinos Avgerinos
- From the First Department of Orthopaedics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Vasileios Karampikas
- From the First Department of Orthopaedics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Panayiotis Gavriil
- From the First Department of Orthopaedics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Apostolos Vlachos
- From the First Department of Orthopaedics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Fotini Soucacou
- From the First Department of Orthopaedics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Ioannis Zafiris
- From the First Department of Orthopaedics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Vasileios Kontogeorgakos
- From the First Department of Orthopaedics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Panayiotis J Papagelopoulos
- From the First Department of Orthopaedics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Andreas F Mavrogenis
- From the First Department of Orthopaedics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
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Quinlan ND, Jennings JM. Joint aspiration for diagnosis of chronic periprosthetic joint infection: when, how, and what tests? ARTHROPLASTY 2023; 5:43. [PMID: 37658416 PMCID: PMC10474645 DOI: 10.1186/s42836-023-00199-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 06/14/2023] [Indexed: 09/03/2023] Open
Abstract
Diagnosing chronic periprosthetic joint infection (PJI) requires clinical suspicion in combination with both serological and synovial fluid tests, the results of which are generally applied to validated scoring systems or consensus definitions for PJI. As no single "gold standard" test exists, the diagnosis becomes challenging, especially in the setting of negative cultures or equivocal test results. This review aims to address the workup of chronic PJI and considerations for clinical evaluation to guide treatment. Following aspiration of the joint in question, a multitude of tests has been developed in an attempt to assist with diagnosis, including cell synovial white blood cell count, gram stain, cultures, leukocyte esterase, alpha-defensin, synovial C-reactive protein, multiplex polymerase chain reaction, next-generation sequencing, and interleukins. Each test has advantages and disadvantages and should be used in conjunction with the overall clinical picture to guide further clinical evaluation and treatment in this complex patient population.
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Affiliation(s)
- Nicole Durig Quinlan
- Colorado Joint Replacement, 2535 S. Downing Street, Ste 100, Denver, CO, 80210, USA
| | - Jason M Jennings
- Colorado Joint Replacement, 2535 S. Downing Street, Ste 100, Denver, CO, 80210, USA.
- Department of Mechanical and Materials Engineering, University of Denver, 2155 E. Wesley Ave, Denver, CO, 80210, USA.
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Schindler M, Walter N, Maderbacher G, Sigmund IK, Alt V, Rupp M. Novel diagnostic markers for periprosthetic joint infection: a systematic review. Front Cell Infect Microbiol 2023; 13:1210345. [PMID: 37529352 PMCID: PMC10388554 DOI: 10.3389/fcimb.2023.1210345] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 06/23/2023] [Indexed: 08/03/2023] Open
Abstract
Background Identifying novel biomarkers that are both specific and sensitive to periprosthetic joint infection (PJI) has the potential to improve diagnostic accuracy and ultimately enhance patient outcomes. Therefore, the aim of this systematic review is to identify and evaluate the effectiveness of novel biomarkers for the diagnosis of PJI. Methods We searched the MEDLINE, EMBASE, PubMed, and Cochrane Library databases from January 1, 2018, to September 30, 2022, using the search terms "periprosthetic joint infection," "prosthetic joint infection," or "periprosthetic infection" as the diagnosis of interest and the target index, combined with the term "marker." We excluded articles that mentioned established biomarkers such as CRP, ESR, Interleukin 6, Alpha defensin, PCT (procalcitonin), and LC (leucocyte cell count). We used the MSIS, ICM, or EBJS criteria for PJI as the reference standard during quality assessment. Results We collected 19 studies that analyzed fourteen different novel biomarkers. Proteins were the most commonly analyzed biomarkers (nine studies), followed by molecules (three studies), exosomes (two studies), DNA (two studies), interleukins (one study), and lysosomes (one study). Calprotectin was a frequently analyzed and promising marker. In the scenario where the threshold was set at ≥50-mg/mL, the calprotectin point-of-care (POC) performance showed a high sensitivity of 98.1% and a specificity of 95.7%. Conclusion None of the analyzed biomarkers demonstrated outstanding performance compared to the established parameters used for standardized treatment based on established PJI definitions. Further studies are needed to determine the benefit and usefulness of implementing new biomarkers in diagnostic PJI settings.
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Affiliation(s)
- Melanie Schindler
- Department of Trauma Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Nike Walter
- Department of Trauma Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Guenther Maderbacher
- Department of Orthopaedic Surgery, University Hospital of Regensburg, Asklepios Klinikum Bad Abbach, Bad Abbach, Germany
| | - Irene K. Sigmund
- Nuffield Orthopaedic Centre, Oxford University Hospitals National Health Service (NHS) Foundation Trust, Oxford, United Kingdom
| | - Volker Alt
- Department of Trauma Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Markus Rupp
- Department of Trauma Surgery, University Hospital Regensburg, Regensburg, Germany
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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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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: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [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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Tang H, Xu J, Yuan W, Wang Y, Yue B, Qu X. Reliable Diagnostic Tests and Thresholds for Preoperative Diagnosis of Non-Inflammatory Arthritis Periprosthetic Joint Infection: A Meta-analysis and Systematic Review. Orthop Surg 2022; 14:2822-2836. [PMID: 36181336 PMCID: PMC9627080 DOI: 10.1111/os.13500] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 08/19/2022] [Accepted: 08/23/2022] [Indexed: 02/06/2023] Open
Abstract
Objective The current diagnostic criteria for periprosthetic joint infection (PJI) are diverse and controversial, leading to delayed diagnosis. This study aimed to evaluate and unify their diagnostic accuracy and the threshold selection of serum and synovial routine tests for PJI at an early stage. Methods We searched the MEDLINE and Embase databases for retrospective or prospective studies which reported preoperative‐available assays (serum, synovial, or culture tests) for the diagnosis of chronic PJI among inflammatory arthritis (IA) or non‐IA populations from January 1, 2000 to June 30, 2022. Threshold effective analysis was performed on synovial polymorphonuclear neutrophils (PMN%), synovial white blood cell (WBC), serum C‐reactive protein (CRP), and erythrocyte sedimentation rate (ESR) to find the relevant cut‐offs. Results Two hundred and sixteen studies and information from 45,316 individuals were included in the final analysis. Synovial laboratory‐based α‐defensin and calprotectin had the best comprehensive sensitivity (0.91 [0.86–0.94], 0.95 [0.88–0.98]) and specificity (0.96 [0.94‐0.97], 0.95 [0.89–0.98]) values. According to the threshold effect analysis, the recommended cut‐offs are 70% (sensitivity 0.89 [0.85–0.92], specificity 0.90 [0.87–0.93]), 4100/μL (sensitivity 0.90 [0.87–0.93], specificity 0.97 [0.93–0.98]), 13.5 mg/L (sensitivity 0.84 [0.78–0.89], specificity 0.83 [0.73–0.89]), and 30 mm/h (sensitivity 0.79 [0.74–0.83], specificity 0.78 [0.72–0.83]) for synovial PMN%, synovial WBC, serum CRP, and ESR, respectively, and tests seem to be more reliable among non‐IA patients. Conclusions The laboratory‐based synovial α‐defensin and synovial calprotectin are the two best independent preoperative diagnostic tests for PJI. A cut off of 70% for synovial PMN% and tighter cut‐offs for synovial WBC and serum CRP could have a better diagnostic accuracy for non‐IA patients with chronic PJI.
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Affiliation(s)
- Haozheng Tang
- Department of Bone and Joint Surgery, Department of Orthopedics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jialian Xu
- Department of Bone and Joint Surgery, Department of Orthopedics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei'en Yuan
- Ministry of Education Engineering Research Center of Cell & Therapeutic Antibody, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China
| | - You Wang
- Department of Bone and Joint Surgery, Department of Orthopedics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bing Yue
- Department of Bone and Joint Surgery, Department of Orthopedics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xinhua Qu
- Department of Bone and Joint Surgery, Department of Orthopedics, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Evaluation of the usefulness of the Synovasure alpha-defensin lateral flow test kit for the diagnosis of periprosthetic joint infection in Japanese patients. J Orthop Sci 2022; 27:935-938. [PMID: 35623991 DOI: 10.1016/j.jos.2022.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 03/27/2022] [Accepted: 05/01/2022] [Indexed: 11/23/2022]
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Goud A, Nützinger D, van der Bij A, Jenniskens K, Groenewold J, de Gast A, Bekkers JEJ. Synovial-Based Tests Outperform Serum Markers to Rule Out Infection in Total Knee Arthroplasty and Total Hip Arthroplasty: A Systematic Review and Meta-Analysis. J Arthroplasty 2022; 37:802-808.e5. [PMID: 34952165 DOI: 10.1016/j.arth.2021.12.020] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 11/22/2021] [Accepted: 12/15/2021] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Total knee arthroplasty (TKA) provides successful results in most patients. Periprosthetic joint infection (PJI) accounts for up to 25% of failed TKAs needing revision. In clinical practice, consensus in diagnostic strategy for excluding or diagnosing PJI is still lacking. In this systematic review and meta-analysis, we aim to provide a simplified data-driven diagnostic strategy for aseptic knee and hip revision surgeons to rule out PJI in the outpatient clinic phase. METHODS A literature search in EMBASE, MEDLINE, PubMed, and Cochrane was conducted. Studies involving the diagnosis of PJI in patients with failed TKAs and total hip arthroplasties needing revision were identified. Only studies using the Musculoskeletal Infection Society criteria were included. Quality was assessed using MINORS criteria. Meta-analysis was performed for each diagnostic test identified in the included studies. Pooled estimates of diagnostic accuracy measures were calculated using a bivariate model and plotted in summary receiver-operator characteristic curves. Positive and negative predictive values were calculated in a hypothetical sample of patients with a given disease prevalence. RESULTS Twenty-four studies met the inclusion criteria, describing a total of 2974 patients. Quality scores ranged from 13 to 19. Meta-analysis could be performed on 7 unique diagnostic tests. Highest pooled sensitivity and specificity were demonstrated for α-defensin with values of 86% and 96.6%, respectively. α-defensin and white blood cell count in synovial fluid demonstrate highest negative predictive value values. CONCLUSIONS We recommend, in a clinical setting with low-intermediate prevalence of PJI, performing arthrocentesis and joint fluid analysis using α-defensin and/or white blood cell count before revision TKA and revision total hip arthroplasty surgery to rule out PJI.
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Affiliation(s)
- Annemarie Goud
- Department of Orthopedic Surgery, Diakonessenhuis Utrecht/Zeist, Utrecht, the Netherlands
| | - Don Nützinger
- Department of Orthopedic Surgery, Diakonessenhuis Utrecht/Zeist, Utrecht, the Netherlands; Clinical Orthopedic Research Center Midden Nederland, Diakonessenhuis Utrecht/Zeist, Zeist, the Netherlands
| | - Akke van der Bij
- Department of Microbiology and Immunology, Diakonessenhuis Utrecht/Zeist, Utrecht, the Netherlands
| | - Kevin Jenniskens
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht (UMCU), University Utrecht, Utrecht, the Netherlands
| | - Joel Groenewold
- University Medical Center Utrecht (UMCU), Utrecht, the Netherlands
| | - Arthur de Gast
- Clinical Orthopedic Research Center Midden Nederland, Diakonessenhuis Utrecht/Zeist, Zeist, the Netherlands
| | - Joris E J Bekkers
- Department of Orthopedic Surgery, Diakonessenhuis Utrecht/Zeist, Utrecht, the Netherlands; Clinical Orthopedic Research Center Midden Nederland, Diakonessenhuis Utrecht/Zeist, Zeist, the Netherlands
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Felstead A, Kundasamy P, Penfold G, Whiting K, Buck J, Sturridge S, Meda M. The combined measurement of synovial markers in the diagnosis of periprosthetic joint infection. Ann R Coll Surg Engl 2021; 104:334-339. [PMID: 34939833 DOI: 10.1308/rcsann.2021.0186] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
INTRODUCTION Currently there is no single test for periprosthetic joint infection (PJI) that demonstrates an acceptable level of sensitivity. The aim of this pilot study was to identify a combination of biomarkers that could exclude periprosthetic infection prior to revision surgery in hip and knee arthroplasty. This would help in equivocal cases of PJI, such as those with low-virulence organisms, chronic low-grade infection or 'aseptic' loosening. Current research has focused on measuring the levels of biomarkers in the patient's synovial fluid, and these can be combined to improve accuracy. METHODS We selected synovial white cell count (SF-WCC) and C-reactive protein (SF-CRP), as they demonstrated an acceptable level of sensitivity and specificity which could be measured using existing equipment. One hundred and sixty-one synovial fluid samples from 134 patients were collected and analysed prospectively using calculated cut-off values of 10mg/l for SF-CRP and 3,000×106/l for SF-WCC. Samples were deemed positive for infection when either of the SF-CRP or SF-WCC values were above the cut-off. RESULTS The combined test demonstrated a sensitivity greater than 98.5% and specificity above 80% in all samples analysed or looked at separately for total hip replacement and total knee replacement infections. All ten aspirates taken from chronically infected joints tested positive. CONCLUSIONS The combination of SF-CRP and SF-WCC measurement has been shown to have high sensitivity of over 99% in detecting both acute and chronic PJI in both hip and knee arthroplasty. This ability of the test to exclude infection with a high degree of certainty will help in preoperative planning of PJIs.
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Affiliation(s)
| | | | - G Penfold
- Frimley Health NHS Foundation Trust, UK
| | - K Whiting
- Frimley Health NHS Foundation Trust, UK
| | - J Buck
- Frimley Health NHS Foundation Trust, UK
| | | | - M Meda
- Frimley Health NHS Foundation Trust, UK
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Walker LC, Clement ND, Hashmi M, Green S, Longstaff L, Deehan DJ. The alpha defensin lateral flow test is effective in predicting eradication of periprosthetic joint infection after surgical debridement. Acta Orthop Belg 2021. [DOI: 10.52628/87.3.25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
The primary aim of this study was to assess the utility of the alpha defensin lateral flow (ADLF) test for predicting the eradication of PJI after surgical debridement. The secondary aim was to describe the reliability of ADLF test in diagnosis of PJI intra- operatively. A prospective observational study was conducted in three independent orthopaedic centres. Twenty-two patients undergoing revision surgery (debridement, antibiotics and implant retention (DAIR), single or two-stage revision) for PJI were recruited, 13 female and 9 male with an average age of 64 years. Samples were collected intra-operatively at the start of the first surgical procedure and then at the completion of debridement or prior to reimplantation depending on the operation performed. These samples were tested using ADLF and then sent for microbiological analysis. The ADLF result was then compared to the corresponding culture result in order to determine the diagnostic predictive accuracy. The reliability of ADLF test to predict eradication of infection after debridement of PJI was excellent for specificity and positive predictive value (PPV) of which both where 100%, but had a poor sensitivity (14.3%) and negative predictive value (NPV) (62.5%). The reliability of ADLF test to predict PJI was poor with only a 50% sensitivity and specificity. The ADLF test has a high specificity and PPV for diagnosing eradication of infection after debridement. In contrast the ADLF testing appears to have poor diagnostic accuracy for PJI when used on intra-operative samples, prior to surgical intervention. No benefits or funds were received in suppo
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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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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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Austin MS, Ashley BS, Bedard NA, Bezwada HP, Hannon CP, Fillingham YA, Kolwadkar YV, Rees HW, Grosso MJ, Zeegen EN. What is the Level of Evidence Substantiating Commercial Payers' Coverage Policies for Total Joint Arthroplasty? J Arthroplasty 2021; 36:2665-2673.e8. [PMID: 33867209 DOI: 10.1016/j.arth.2021.03.036] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 03/08/2021] [Accepted: 03/14/2021] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND The prevalence of total joint arthroplasty (TJA) in the United States has drawn the attention of health care stakeholders. The payers have also used a variety of strategies to regulate the medical necessity of these procedures. The purpose of this study was to examine the level of evidence of the coverage policies being used by commercial payers in the United States. METHODS The references of the coverage policies of four commercial insurance companies were reviewed for type of document, level of evidence, applicability to a TJA population, and success of nonoperative treatment in patients with severe degenerative joint disease. RESULTS 282 documents were reviewed. 45.8% were primary journal articles, 14.2% were level I or II, 41.2% were applicable to patients who were candidates for TJA, and 9.9% discussed the success of nonoperative treatment in patients who would be candidates for TJA. CONCLUSION Most of the references cited by commercial payers are of a lower level of scientific evidence and not applicable to patients considered to be candidates for TJA. This is relatively uniform across the reviewed payers. The dearth of high-quality literature cited by commercial payers reflects the lack of evidence and difficulty in conducting high level studies on the outcomes of nonoperative versus operative treatment for patients with severe, symptomatic osteoarthritis. Patients, surgeons, and payers would all benefit from such studies and we encourage professional societies to strive toward that end through multicenter collaboration.
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Affiliation(s)
- Matthew S Austin
- Department of Orthopaedic Surgery, Rothman Orthopaedic Institute at Thomas Jefferson University, Philadelphia, PA
| | - Blair S Ashley
- Department of Orthopaedic Surgery, Rothman Orthopaedic Institute at Thomas Jefferson University, Philadelphia, PA
| | - Nicholas A Bedard
- Department of Orthopaedic Surgery, University of Iowa Hospitals & Clinics, Iowa City, IA
| | | | - Charles P Hannon
- Department of Orthopaedic Surgery, The Mayo Clinic, Ochester, MN
| | - Yale A Fillingham
- Department of Orthopaedic Surgery, Rothman Orthopaedic Institute at Thomas Jefferson University, Philadelphia, PA
| | - Yogesh V Kolwadkar
- Department of Orthopaedic Surgery, VA Central California Health Care System, Fresno, CA
| | - Harold W Rees
- Department of Orthopaedic Surgery, Loyola University Medical Center, Maywood, IL
| | - Matthew J Grosso
- Department of Orthopaedic Surgery, Rothman Orthopaedic Institute at Thomas Jefferson University, Philadelphia, PA; Connecticut Joint Replacement Institute, Hartford, CT
| | - Erik N Zeegen
- Department of Orthopaedic Surgery, University of California Los Angeles, Santa Monica, CA
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Tian B, Cui L, Jiang W. The diagnostic effect of α-defensin, D-dimer, and IL-6 in periprosthetic joint infection: A systematic review and diagnostic meta-analysis. J Orthop Surg (Hong Kong) 2021; 28:2309499020971861. [PMID: 33225796 DOI: 10.1177/2309499020971861] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Periprosthetic joint infection (PJI) is the most common complication after artificial joint replacement as previously reported. However, the main problem at present is its difficulty in diagnosis. This systematic review and meta-analysis aimed to compare the diagnostic accuracy of α-defensin, D-dimer, and interleukin-6 (IL-6) in clinical practice. METHOD Online databases were systematically searched until June 18th, 2020 with keywords and medical sub-headings terms. Studies mentioned the sensitivity and specificity of biological markers in detecting PJI were included in our study. The sensitivity, specificity, and diagnostic odds ratios (DORs) were obtained after integration. RESULTS A total of 34 studies with 1036 patients diagnosing as PJI were included for comparing α-defensin, D-dimer, and IL-6. The sensitivity and specificity of α-defensin for PJI were 0.88 and 0.96, and the DOR was 189 (95% CI 72-496), respectively. The sensitivity and specificity of D-dimer (0.82 and 0.72) and IL-6 (0.80 and 0.89) were lower than α-defensin. CONCLUSION The detection of α-defensin is a promising biomarker for diagnosing PJI. The optional cut-off needs to be curtained when using other biomarkers.
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Affiliation(s)
- Baozhong Tian
- Bone surgery, Affiliated Hospital of Jilin Medical University, Jilin City, China
| | - Liwen Cui
- Changyi District Center for Disease Control and Prevention, Jilin City, China
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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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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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[Diagnosis of periprosthetic joint infection : Development of an evidence-based algorithm by the work group of implant-associated infection of the AE-(German Society for Arthroplasty)]. DER ORTHOPADE 2021; 50:312-325. [PMID: 32666142 PMCID: PMC7990870 DOI: 10.1007/s00132-020-03940-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Hintergrund Die Behandlung periprothetischer Infektionen (PPI) ist eine der größten Herausforderungen im Bereich der Endoprothetik. Der möglichst sichere Ausschluss oder die Bestätigung einer periprothetischen Infektion ist die Voraussetzung für jede Revisionsoperation und kann für den behandelnden Orthopäden und Unfallchirurgen eine große Herausforderung darstellen. Eine sichere evidenzbasierte präoperative Diagnostik ist im Sinne des Patienten notwendig, um einerseits eine periprothetische Infektion zu erkennen sowie die entsprechende chirurgische und antibiotische Therapie zu planen und andererseits unnötige zweizeitige Wechsel zu vermeiden. Ziel der Arbeit Ziel ist es, ein evidenzbasiertes problem- und prioritätenbasiertes Vorgehen zu entwickeln und dies in einem transparenten und standardisierten Algorithmus zusammenzufassen. Methode Durch systematische Literaturrecherche wurden relevante Arbeiten identifiziert und im Rahmen von Expertenrunden bewertet. Nach Extraktion der Daten erfolgte die Berechnung von Sensitivität, Spezifität, positiver und negativer Likelihood-Ratio sowie positiver und negativer prädiktiver Werte. Im Rahmen von 4 Treffen wurden die entsprechenden Studien der Arbeitsgruppe für implantatassoziierte Infektionen präsentiert und analog zu Standard-Delphi-Runden durch die einzelnen Experten bearbeitet und bewertet. Gemäß der Prioritätenliste der Expertenrunde erfolgte die Entwicklung eines zur ISO (International Organization for Standardisation) konformen Algorithmus. Ergebnisse Der entwickelte Algorithmus ist eine Abfolge von evidenzbasierten Prozessen gemäß der verwendeten ISO-Norm. Gemäß der durch die Expertenrunde priorisierten Haupt- und Nebenkriterien erfolgte die Entwicklung logisch strukturiert und problemorientiert. Schlussfolgerung Der Ausschluss einer periprothetischen Infektion ist von enormer Bedeutung vor einer Revisionsoperation und entscheidet in vielen Fällen über den Erfolg und die Invasivität der Operation. Die Diagnose „periprothetische Infektion“ erfordert eine substanzielle Veränderung der therapeutischen Strategie. Der durch die Arbeitsgruppe entwickelte Algorithmus fasst Positionen aus der aktuellen Literatur und spezielle Expertenmeinungen zusammen, dies ermöglicht einen transparenten diagnostischen Ansatz im Sinne einer Standard Operation Procedure.
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Zeng YQ, Deng S, Zhu XY, Sun XB, Feng WJ, Zeng JC, Zhang HT, Zeng YR. Diagnostic Accuracy of the Synovial Fluid α-Defensin Lateral Flow Test in Periprosthetic Joint Infection: A Meta-analysis. Orthop Surg 2021; 13:708-718. [PMID: 33719221 PMCID: PMC8126937 DOI: 10.1111/os.12966] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 01/15/2021] [Accepted: 01/28/2021] [Indexed: 12/12/2022] Open
Abstract
Objectives There is a controversy on the diagnostic reliability and accuracy of synovial fluid α‐defensin in periprosthetic joint infection (PJI). We performed this meta‐analysis to evaluate the diagnostic accuracy of the α‐defensin lateral flow test in PJI. Methods PubMed, Embase, and the Cochrane library were systematically searched, and articles (up to January 2020) on the diagnosis of hip and knee PJIs using the α‐defensin Synovasure lateral flow test were included. The diagnostic accuracy of the α‐defensin lateral flow test in PJI was evaluated using meta‐analysis. The pooled sensitivity, specificity, accuracy, positive and negative likelihood ratio, diagnostic odds ratio, and post‐test probabilities were calculated. Results Seventeen studies including 1443 cases were included. Meta‐analysis showed the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and a diagnostic odds ratio was 0.83 (95% CI 0.77, 0.88), 0.95 (95% CI 0.93, 0.97), 16.86 (95% CI 11.67, 24.37), 0.17 (95% CI 0.13, 0.24) and 85.30 (95% CI 47.76, 152.35), respectively. The area under the hierarchical summary receiver operating characteristic curve was 0.97 (95% CI 0.95, 0.98). Subgroup analysis also confirmed the high efficiency of α‐defensin Synovasure lateral flow test in diagnosing PJIs, irrespective of ethnicity. Fagan's nomogram analysis there was a high positive post‐test probability of 94% and a low negative post‐test probability of 15%. Conclusions We indicated that the α‐defensin lateral flow test had a high accuracy for diagnosing PJI. Large‐scale studies are needed to validate its significance in PJI diagnosis.
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Affiliation(s)
- Yu-Qing Zeng
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.,Department of Orthopaedics, Tongde Hospital of Zhejiang Province, Hangzhou, China
| | - Shu Deng
- Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Xing-Yang Zhu
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiao-Bo Sun
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Wen-Jun Feng
- Department of Orthopaedics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jian-Chun Zeng
- Department of Orthopaedics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Hai-Tao Zhang
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yi-Rong Zeng
- Department of Orthopaedics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
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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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22
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Sharma K, Ivy M, Block DR, Abdel MP, Hanssen AD, Beauchamp C, Perry KI, Rosemark CL, Greenwood-Quaintance KE, Mandrekar J, Patel R. Comparative analysis of 23 synovial fluid biomarkers for hip and knee periprosthetic joint infection detection. J Orthop Res 2020; 38:2664-2674. [PMID: 32485031 DOI: 10.1002/jor.24766] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 04/30/2020] [Accepted: 05/25/2020] [Indexed: 02/04/2023]
Abstract
There is interest in novel synovial fluid biomarkers for the detection of periprosthetic joint infection (PJI). Here, we assessed the diagnostic accuracy of 23 simple or sophisticated synovial fluid biomarkers for periprosthetic hip or knee infection detection. One hundred seven subjects were studied, 57 of whom had aseptic failure (AF) and 50 PJI. The following synovial fluid biomarkers were tested using spectrophotometric assays, immunoassays, lateral flow tests, or test strips: leukocyte count, monocyte percentage, lymphocyte percentage, neutrophil percentage, C-reactive protein (CRP), glucose, lactate, granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin-1β (IL-1β), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, IL-23, tumor necrosis factor-α, α-defensin, and leukocyte esterase. The best-performing synovial fluid biomarkers to differentiate PJI from AF-that is, those with highest area under the curve compared to all other biomarkers-were leukocyte count, percent neutrophils and percent monocytes, CRP, and α-defensin (P < .0001).
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Affiliation(s)
- Katyayini Sharma
- Division of Clinical Microbiology, Mayo Clinic, Rochester, Minnesota
| | - Morgan Ivy
- Division of Clinical Microbiology, Mayo Clinic, Rochester, Minnesota
| | - Darci R Block
- Clinical Core Laboratory Services, Mayo Clinic, Rochester, Minnesota
| | - Matthew P Abdel
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota
| | - Arlen D Hanssen
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota
| | | | - Kevin I Perry
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota
| | | | | | - Jay Mandrekar
- Division of Clinical Microbiology, Mayo Clinic, Rochester, Minnesota
| | - Robin Patel
- Division of Clinical Microbiology, Mayo Clinic, Rochester, Minnesota.,Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota
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23
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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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24
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Wasterlain AS, Goswami K, Ghasemi SA, Parvizi J. Diagnosis of Periprosthetic Infection: Recent Developments. J Bone Joint Surg Am 2020; 102:1366-1375. [PMID: 32769605 DOI: 10.2106/jbjs.19.00598] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
➤ There is no absolute test for the preoperative diagnosis of periprosthetic joint infection (PJI); thus, clinical practice relies on a combination of supportive tests and criteria.➤ Novel serum and synovial tests have improved our ability to diagnose PJI. The 2018 evidence-based algorithm for PJI diagnosis provides weighted scores for serum markers, as well as synovial markers, to facilitate diagnosis when major criteria such as positive cultures or a sinus tract are not present.➤ Culture-independent technologies such as next-generation sequencing can facilitate pathogen identification, particularly in the setting of culture-negative PJI.➤ Despite recent developments, PJI diagnosis remains challenging and warrants further innovation.
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Affiliation(s)
- Amy S Wasterlain
- Rothman Orthopaedic Institute at Thomas Jefferson University, Philadelphia, Pennsylvania
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25
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Chisari E, Parvizi J. Accuracy of blood-tests and synovial fluid-tests in the diagnosis of periprosthetic joint infections. Expert Rev Anti Infect Ther 2020; 18:1135-1142. [PMID: 32715785 DOI: 10.1080/14787210.2020.1792771] [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: 01/10/2023]
Abstract
INTRODUCTION Periprosthetic joint infection (PJI) is one of the most complex complications following total joint arthroplasty. Despite significant progress in recent years, the use of blood and synovial biomarkers to diagnose PJI remains a challenge. AREAS COVERED A combination of serological, synovial, microbiological, histological, and radiological investigations is suggested by consensus and international guidelines. Novel biomarkers and molecular methods have shown promise in recent years. The purpose of this review is to provide an update about the biomarkers used to diagnose PJI and highlight their sensitivity and specificity. In addition, guidance on the diagnostic steps and clinical workflow will be included. EXPERT OPINION The diagnostic algorithm developed and validated by the international consensus meeting group is still the most valuable resource to approach PJI diagnosis. The current combination of blood and synovial biomarkers yield acceptable results and good performance. However, there is a need for new biomarkers and further research to understand the limitations of current tests better, as well as explore new options such as alpha-defensin, D-dimer, interleukin-6, and leukocyte esterase.
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Affiliation(s)
- Emanuele Chisari
- Rothman Orthopaedic Institute, Thomas Jefferson University , Philadelphia, PA, USA
| | - Javad Parvizi
- Rothman Orthopaedic Institute, Thomas Jefferson University , Philadelphia, PA, USA
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26
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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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27
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Morgenstern C, Renz N, Cabric S, Maiolo E, Perka C, Trampuz A. Thermogenic diagnosis of periprosthetic joint infection by microcalorimetry of synovial fluid. BMC Musculoskelet Disord 2020; 21:345. [PMID: 32493292 PMCID: PMC7271508 DOI: 10.1186/s12891-020-03366-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 05/25/2020] [Indexed: 12/19/2022] Open
Abstract
Background Synovial fluid culture is the standard investigation for the preoperative diagnosis of periprosthetic joint infection (PJI). However, the culture has limited sensitivity and requires several days until result. We evaluated the value of isothermal microcalorimetry for real-time diagnosis of PJI based on heat produced by microbial growth in synovial fluid. Methods Patients undergoing aspiration of prosthetic hip or knee joint before revision surgery were prospectively included between 2014 and 2015. The performance of microcalorimetry was compared to synovial fluid culture using McNemar’s chi-squared test. Pearson’s correlation coefficient was calculated for synovial fluid leukocyte count and microcalorimetric heat. Results Of 107 included patients (58 knee and 49 hip prosthesis), PJI was diagnosed in 46 patients (43%) and aseptic failure in 61 patients (57%) according to institutional criteria. In 26 PJI cases (56%) the pathogen grew in synovial fluid and intra-operative cultures. The sensitivity of synovial fluid culture and microcalorimetry was both 39% and the results were concordant in 98 patients (92%). In patients with PJI, microcalorimetry missed 4 pathogens which grew in synovial fluid culture, whereas culture missed 4 pathogens detected by microcalorimetry. A linear correlation (r = 0.366) was found between leukocyte count and microcalorimetric heat in synovial fluid (p < 0.001). The median time to positivity of microcalorimetry was 9 h (range, 1–64 h) vs. 3 days for cultures (range, 1–14 days). Conclusion Microcalorimetry of synovial fluid allows thermogenic diagnosis of periprosthetic joint infection in synovial fluid. The diagnostic performance of synovial fluid microcalorimetry is comparable to culture and delivers results considerably faster. Trial registration This prospective study was registered on August 21, 2015 with the public clinical trial identification NCT02530229.
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Affiliation(s)
- Christian Morgenstern
- 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.
| | - Nora Renz
- 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
| | - Sabrina Cabric
- 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
| | - Elena Maiolo
- 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
| | - Carsten Perka
- 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
| | - 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.,Berlin Institute of Health Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Berlin, Germany
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28
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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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30
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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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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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Weigelt L, Plate A, Stadler L, Sutter R, Frustaci D, Zbinden R, Zingg PO, Gerber C, Achermann Y. Alpha-defensin lateral flow test does not appear to be useful in predicting shoulder periprosthetic joint infections. INTERNATIONAL ORTHOPAEDICS 2020; 44:1023-1029. [PMID: 32172315 DOI: 10.1007/s00264-020-04532-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 03/04/2020] [Indexed: 01/16/2023]
Abstract
PURPOSE Periprosthetic joint infections (PJIs) remain a challenging complication after shoulder arthroplasty. The antimicrobial peptide α-defensin has been proposed as a new synovial fluid biomarker in diagnosing PJIs. To date, only little data are available on the diagnostic accuracy of α-defensin in shoulder PJIs; thus, we aimed to evaluate its diagnostic value in a cohort of patients with a suspected shoulder PJI. METHODS Between June 2016 and June 2018, we prospectively enrolled patients with a diagnostic shoulder aspiration due to painful shoulder arthroplasty or planned revision surgery. PJI diagnostics were performed according to the Musculoskeletal Infection Society (MSIS) criteria. All patients with an antibiotic therapy within two weeks before enrollment, insufficient amount of synovial aspirate, or bloody aspiration were excluded. α-Defensin was measured in the synovial fluid using the α-defensin lateral flow (ADLF) test (Synovasure®). RESULTS Out of 60 patients, we could include 29 (59% female) patients with a mean age of 70 (range, 50-92) years. A shoulder PJI was detected in five cases (Staphylococcus aureus, n = 2; Staphylococcus epidermidis, n = 2; Cutibacterium acnes, n = 1). The ADLF test was positive in seven out of 29 cases. According to the MSIS criteria, the ADLF test was false-negative in two patients and false-positive in four patients, resulting in sensitivity, specificity, and positive and negative predictive value of 60%, 83%, 43%, and 91%, respectively. The overall accuracy was 79%. CONCLUSION The ALDF test does not appear to be useful in predicting shoulder PJIs but may be used as an additional diagnostic factor in rejecting these infections.
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Affiliation(s)
- Lizzy Weigelt
- Department of Orthopedics Surgery , University Hospital Balgrist, University of Zurich, Forchstrasse 340, 8008, Zurich, Switzerland.
| | - Andreas Plate
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Laura Stadler
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Reto Sutter
- Department of Radiology, University Hospital Balgrist, University of Zurich, Zurich, Switzerland
| | - Dario Frustaci
- Department of Orthopedics Surgery , University Hospital Balgrist, University of Zurich, Forchstrasse 340, 8008, Zurich, Switzerland
| | - Reinhard Zbinden
- Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland
| | - Patrick O Zingg
- Department of Orthopedics Surgery , University Hospital Balgrist, University of Zurich, Forchstrasse 340, 8008, Zurich, Switzerland
| | - Christian Gerber
- Department of Orthopedics Surgery , University Hospital Balgrist, University of Zurich, Forchstrasse 340, 8008, Zurich, Switzerland
| | - Yvonne Achermann
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
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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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Kuiper JWP, Pander P, Vos SJ. Good accuracy of the alpha-defensin lateral flow test for hip periprosthetic joint infection: A pilot study in a retrospective cohort of 52 patients. World J Orthop 2020; 11:36-46. [PMID: 31966968 PMCID: PMC6960303 DOI: 10.5312/wjo.v11.i1.36] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2019] [Revised: 10/18/2019] [Accepted: 11/07/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The alpha-defensin lateral flow (ADLF) test is a new diagnostic tool for periprosthetic joint infection (PJI). Test accuracy for combined cohorts of hip and knee PJI has been reported to be good.
AIM To assess the accuracy of the ADLF test for hip PJI, and to compare three different diagnostic criteria for PJI.
METHODS A cohort of 52 patients was identified, with a painful or poorly functioning total hip- or hemi-arthroplasty, that underwent aspiration and a subsequent ADLF test. PJI was diagnosed with Musculoskeletal Infection Society (MSIS) criteria, and sensitivity, specificity, overall accuracy, positive predictive value and negative predictive value were calculated. Furthermore, test specifics were compared with the European Bone and Joint Infection Society (EBJIS) and 2018 International Consensus Meeting (ICM) criteria for PJI.
RESULTS Using MSIS criteria, sensitivity was 100% (CI: 54%-100%) and specificity was 89% (CI: 76%-96%). Six true positives and 5 false positives were found, including one case of metallosis. Using EBJIS criteria, more PJIs were found (11 vs 6), sensitivity was lower (71%, CI: 42%-92%) and specificity was higher (97%, CI: 86%-100%), with 4 false negatives and one false positive result. Using 2018 ICM criteria, sensitivity was 91% (62%-100%) and specificity 100% (91%-100%). The results in this cohort are comparable to previous studies.
CONCLUSION Overall test accuracy of the ADLF test was good in this cohort, with a sensitivity of 100% and specificity of 89%. Using different PJI definition criteria, sensitivity and specificity changed slightly but overall accuracy remained around 90%. Using the ADLF test in metallosis cases can result in false positive results and should be performed with caution.
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Affiliation(s)
- Jesse WP Kuiper
- Department of Orthopedic Surgery, Noordwest Ziekenhuisgroep, Alkmaar 1815 JD, Netherlands
| | - Pieter Pander
- Centre for Orthopedic Research Alkmaar, Noordwest Ziekenhuisgroep, Alkmaar 1815 JD, Netherlands
| | - Stan J Vos
- Department of Orthopedic Surgery, Noordwest Ziekenhuisgroep, Alkmaar 1815 JD, Netherlands
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High-Performance Liquid Chromatography as a Novel Method for the Determination of α-Defensins in Synovial Fluid for Diagnosis of Orthopedic Infections. Diagnostics (Basel) 2020; 10:diagnostics10010033. [PMID: 31936486 PMCID: PMC7167866 DOI: 10.3390/diagnostics10010033] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Revised: 01/06/2020] [Accepted: 01/07/2020] [Indexed: 11/18/2022] Open
Abstract
The α-defensins (AD) present in synovial fluid have been regarded as constituting the most accurate periprosthetic joint infection (PJI) biomarker. The methods most commonly used for estimating AD as a biomarker are the qualitative Synovasure® PJI tests, based on the technique of lateral flow, and quantitative enzyme-linked immunosorbent assay (ELISA). Here, we propose a novel test based on detecting α-defensins in synovial fluid by high-performance liquid chromatography (HPLC). Synovial fluid was collected from 157 patients diagnosed with PJI, infectious arthritis (IA), arthrosis, reactive arthritis, and rheumatoid arthritis. AD concentrations in the fluid were determined by HPLC, and these same samples were used for additional diagnostic analyses. The results were statistically processed to calculate cutoff concentrations for PJI and IA. HPLC testing showed a sensitivity of 94% and a specificity of 92% for diagnosis of PJI, and a sensitivity of 97% and a specificity of 87% for diagnosis of IA. Using HPLC, we detected in synovial fluid a combination of three α-defensins: human neutrophil peptides HNP1, HNP2, and HNP3. All measured AD concentration values shown in this work refer to the sum of these three individual concentrations. Our study shows that the HPLC method meets the conditions for measuring precise concentrations of the sum of AD and can be recommended as part of a diagnostic array for PJI and IA diagnostics. By this method, we have verified that higher levels of AD in synovial fluid can also be seen in rheumatoid illnesses, crystal arthropathies, and reactive arthritis.
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Chen Y, Kang X, Tao J, Zhang Y, Ying C, Lin W. Reliability of synovial fluid alpha-defensin and leukocyte esterase in diagnosing periprosthetic joint infection (PJI): a systematic review and meta-analysis. J Orthop Surg Res 2019; 14:453. [PMID: 31856885 PMCID: PMC6921602 DOI: 10.1186/s13018-019-1395-3] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 09/25/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Synovial fluid proteins had been applied as diagnostic biomarkers for periprosthetic joint infection (PJI) in recent research papers. Thus, this meta-analysis aimed to estimate the diagnostic efficiency of synovial fluid α-defensin and leukocyte esterase (LE) for PJI. METHODS We conducted our systematic review by searching the keywords in online databases such as PubMed, Embase, Cochrane, Elsevier, Springer, and Web of Science from the time of database inception to October 2018. Inclusion criteria were as follows: patients who have undergone knee, hip, or shoulder joint replacements; α-defensin or leukocyte esterase (LE strip) of synovial fluid was detected as the biomarker for PJI diagnosis; and Musculoskeletal Infection Society (MSIS) or utilizing a combination of clinical data was considered as the gold standard. Diagnostic parameters including sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary of receiver operating characteristics curve (AUSROC) were calculated for the included studies to evaluate the synovial fluid α-defensin and LE for PJI diagnosis. RESULTS After full-text review, 28 studies were qualified for this systematic review, 16 studies used α-defensin and the other 12 were conducted using LE strip. The pooled sensitivity, specificity, and DOR of LE strip were 87% (95% CI 84-90%), 96% (95% CI 95-97%), and 170.09 (95% CI 97.63-296.32), respectively, while the pooled sensitivity, specificity, and DOR of α-defensin were 87% (95% CI 83-90%), 97% (95% CI 96-98%), and 158.18 (95% CI 74.26-336.91), respectively. The AUSROC for LE strip and α-defensin were 0.9818 and 0.9685, respectively. CONCLUSION Both LE strip and α-defensin of synovial fluid provide rapid and convenient diagnosis for PJI. Sensitivity of α-defensin and LE strip are the same, while both these two methods have high specificity in clinical practice.
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Affiliation(s)
- Yisheng Chen
- Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xueran Kang
- Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People' s Hospital, Ear Institute, Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jie Tao
- Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Yunpeng Zhang
- Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chenting Ying
- Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiwei Lin
- Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
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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: 18] [Impact Index Per Article: 3.0] [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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Tsai TT, Huang TH, Ho NYJ, Chen YP, Chen CA, Chen CF. Development of a multiplex and sensitive lateral flow immunoassay for the diagnosis of periprosthetic joint infection. Sci Rep 2019; 9:15679. [PMID: 31666656 PMCID: PMC6821814 DOI: 10.1038/s41598-019-52051-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Accepted: 10/10/2019] [Indexed: 02/07/2023] Open
Abstract
The diagnosis of periprosthetic joint infection (PJI) remains a challenge. However, recent studies showed that synovial fluid biomarkers have demonstrated greater diagnostic accuracy than the currently used PJI diagnostic tests. In many diagnostic tests, combining several biomarkers into panels is critical for improving diagnostic efficiency, enhancing the diagnostic precision for specific diseases, and reducing cost. In this study, we prove that combining alpha-defensin and C-reactive protein (CRP) as biomarkers possesses the potential to provide accurate PJI diagnosis. To further verify the result, we developed a multi-target lateral flow immunoassay strip (msLFIA) with staking pad design to obtain on-site rapid response for clinical diagnosis of PJI. A total of 10 synovial fluid samples were tested using the msLFIA, and the results showed that the combined measurements of synovial fluid alpha-defensin and CRP levels were consistent with those obtained from a commercial enzyme-linked immunosorbent assay kit. In addition, we developed a multi-target lateral flow immunoassay strip (msLFIA) with staking pad design to obtain on-site rapid response for clinical diagnosis of PJI, which the multi-target design is used to increase specificity and the stacking pad design is to enhance detection sensitivity. As a result, the turnaround time of the highly sensitive test can be limited from several hours to 20 min. We expect that the developed msLFIA possesses the potential for routine monitoring of PJI as a convenient, low-cost, rapid and easy to use detection device for PJI.
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Affiliation(s)
- Tsung-Ting Tsai
- Department of Orthopaedic Surgery, Bone and Joint Research Center, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, 333, Taiwan
| | - Tse-Hao Huang
- Department of Orthopaedic Surgery, Bone and Joint Research Center, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, 333, Taiwan
| | - Natalie Yi-Ju Ho
- Department of Orthopaedic Surgery, Bone and Joint Research Center, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, 333, Taiwan
| | - Yu-Pei Chen
- Department of Orthopaedic Surgery, Bone and Joint Research Center, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, 333, Taiwan
| | - Chung-An Chen
- Department of Orthopaedic Surgery, Bone and Joint Research Center, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, 333, Taiwan.,Institute of Applied Mechanics, National Taiwan University, Taipei, 106, Taiwan
| | - Chien-Fu Chen
- Institute of Applied Mechanics, National Taiwan University, Taipei, 106, Taiwan.
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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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Abstract
Periprosthetic joint infection (PJI) is a serious complication occurring in 1% to 2% of primary arthroplasties, which is associated with high morbidity and need for complex interdisciplinary treatment strategies. The challenge in the management of PJI is the persistence of micro-organisms on the implant surface in the form of biofilm. Understanding this ability, the phases of biofilm formation, antimicrobial susceptibility and the limitations of host local immune response allows an individual choice of the most suitable treatment. By using diagnostic methods for biofilm detection such as sonication, the sensitivity for diagnosing PJI is increasing, especially in chronic infections caused by low-virulence pathogens. The use of biofilm-active antibiotics enables eradication of micro-organisms in the presence of a foreign body. The total duration of antibiotic treatment following revision surgery should not exceed 12 weeks. Cite this article: EFORT Open Rev 2019;4:482-494. DOI: 10.1302/2058-5241.4.180092
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Affiliation(s)
| | - Olivier Borens
- Service of Orthopaedics and Traumatology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - Andrej Trampuz
- Charité - Universitätsmedizin Berlin, Corporate Member of Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Center for Musculoskeletal Surgery (CMSC), Berlin, 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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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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Does inflammatory joint diseases affect the accuracy of infection biomarkers in patients with periprosthetic joint infections? A prospective comparative reliability study. J Orthop Sci 2019; 24:286-289. [PMID: 30268355 DOI: 10.1016/j.jos.2018.08.022] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2017] [Revised: 07/23/2018] [Accepted: 08/27/2018] [Indexed: 11/24/2022]
Abstract
BACKGROUND The diagnosis of periprosthetic joint infections (PJI) in patients with inflammatory joint diseases (IJD) could be challenging. Several tests used for diagnosing PJI may be inaccurate due to baseline inflammatory characteristics of such diseases. We aimed to evaluate the accuracy of several infection biomarkers, in a specific subgroup of patients with PJI and IJD. METHODS From January 2014 to August 2017, patients with resisting pain at the relevant site, following total knee arthroplasty were evaluated prospectively. A total of 38 patients were undergone revision arthroplasty. Patients were categorized in terms of MSIS criteria: Patients with PJI (Group 1, n = 17) and patients without PJI (Group 2, n = 21). Serum ESR, CRP, Procalcitonin, synovial cell count, percentage of neutrophils in synovial fluid, synovial CRP, Lactoferrin, ELA-2, Thiol - Disulphide levels, BPI and the Alpha defensin test results were obtained. The results of two groups were compared and the diagnostic accuracy of each variable was evaluated. RESULTS There were 22 women, 16 men with a mean age of 67.8 ± 6.9 years. The differences were significant in all evaluated biomarkers in terms of PJI (p values of all biomarker were <0.001). Alpha defensin, Lactoferrin, ELA-2, BPI, Procalcitonin and synovial CRP were the most accurate tests with area under curve >0.90. CONCLUSIONS Our results demonstrated that IJD may not affect the accuracy of infection biomarkers in patients with PJI. Alpha defensin test, Lactoferrin, ELA-2, BPI, Procalcitonin and synovial CRP can be used in the diagnosis of PJI in patients with IJD.
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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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47
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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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A meta-analysis of synovial biomarkers in periprosthetic joint infection: Synovasure™ is less effective than the ELISA-based alpha-defensin test. Knee Surg Sports Traumatol Arthrosc 2018; 26:3039-3047. [PMID: 29557491 DOI: 10.1007/s00167-018-4904-8] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2017] [Accepted: 03/16/2018] [Indexed: 12/13/2022]
Abstract
PURPOSE (1) To determine the overall accuracy of synovial alpha-defensin, synovial C-reactive protein (sCRP), interleukin-6 (sIL-6), and leukocyte esterase (sLE) as diagnostic markers for periprosthetic joint infection (PJI) and (2) to independantly evaluate the accuracy of both the laboratory-based ELISA alpha-defensin test and the Synovasure™ alpha-defensin test kit. METHODS An EMBASE and MEDLINE (PubMed) database search was performed using a set of professionally set search terms. Two independent reviewers rated eligible articles. Sensitivity and specificity were meta-analysed using a bivariate random-effects model. RESULTS Accuracy values were extracted from 42 articles. Pooled sensitivity and specificity of the represented biomarkers were: alpha-defensin ELISA 0.97 (95% CI 0.91-0.99) and 0.97 (95% CI 0.94-0.98), respectively; Synovasure™ test kit assay 0.80 (95% CI 0.65-0.89) and 0.89 (95% CI 0.76-0.96), respectively; sLE 0.79 (95% CI 0.67-0.87) and 0.92 (95% CI 0.87-0.92), respectively; sIL-6 0.76 (95% CI 0.65-0.84) and 0.91 (95% CI 0.88-0.94), respectively; sCRP 0.86 (95% CI 0.81-0.91) and 0.90 (95% CI 0.86-0.93), respectively. CONCLUSION The labararory-based alpha-defensin ELISA test showed the highest ever reported accuracy for PJI diagnosis. However, this did not apply for the Synovasure™ alpha-defensin test, which was comparable in its overall diagnostic accuracy to sCRP, sIL-6 and sLE. The later biomarkers also did not yield an overall diagnostic accuracy higher than that previously reported for synovial white cell count (sWBC) or culture bacteriology. Based on current evidence, no synovial biomarker should be applied as a standalone diagnostic tool. Furthermore, the use of the laboratory-based alpha-defensin ELISA test should be encouraged, still, the Synovasure™ alpha-defensin test kit should be critically appreciated. LEVER OF EVIDENCE III.
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Goswami K, Parvizi J, Maxwell Courtney P. Current Recommendations for the Diagnosis of Acute and Chronic PJI for Hip and Knee-Cell Counts, Alpha-Defensin, Leukocyte Esterase, Next-generation Sequencing. Curr Rev Musculoskelet Med 2018; 11:428-438. [PMID: 30062484 PMCID: PMC6105482 DOI: 10.1007/s12178-018-9513-0] [Citation(s) in RCA: 113] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE OF REVIEW Despite significant progress in recent years, the diagnosis of periprosthetic joint infection (PJI) remains a challenge and no gold standard test exists. A combination of serological, synovial, microbiological, histological, and radiological investigations is performed that are expensive, often invasive, and imperfect. Novel biomarkers and molecular methods have shown promise in recent years. The purpose of this review is to provide an update about the diagnostic recommendations for PJI and cover a selection of emerging diagnostic tools. RECENT FINDINGS Recent literature highlights a new evidence-based definition for diagnosing hip and knee PJI that shows excellent performance on formal external multi-institutional validation. There is also increasing evidence to support the measurement of selected biomarkers in serum and synovial fluid, such as alpha-defensin, D-dimer, and interleukin-6. Finally, the emerging utility of next-generation sequencing for pathogen identification is discussed. In summary, we describe current recommendations and emerging tests for the diagnosis of PJI. Residual limitations and directions for future research are also discussed.
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Affiliation(s)
- Karan Goswami
- The Rothman Institute at Thomas Jefferson University, 125 S 9th St. Ste 1000, Philadelphia, PA, 19107, USA
| | - Javad Parvizi
- The Rothman Institute at Thomas Jefferson University, 125 S 9th St. Ste 1000, Philadelphia, PA, 19107, USA
| | - P Maxwell Courtney
- The Rothman Institute at Thomas Jefferson University, 125 S 9th St. Ste 1000, Philadelphia, PA, 19107, USA.
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