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• W2782123557 abstract "Commentary Pain following arthroplasty presents the physician with a challenging diagnostic dilemma, and the diagnosis of periprosthetic joint infection is traumatic for the patient and surgeon alike. There are few diagnoses outside of cancer and dementia that cause more angst. Complicating this already difficult diagnosis are lack of adequate laboratory tests to reliably confirm clinical suspicion of infection, the length of time and the high cost associated with the subsequent treatment (such as multiple surgical procedures, long-term antibiotics, rehabilitation, and lost wages), and the greatly increased risk of reinfection following reimplantation. In the case of reinfection, this can lead to highly unsatisfactory outcomes such as arthrodesis or amputation, both of which are associated with substantial morbidity, resulting in long-term decreases in the patient’s quality of life. The lack of high-sensitivity, high-specificity laboratory tests for periprosthetic joint infection has historically resulted in ambiguous diagnoses for a large percentage of arthroplasty cases with a clinical suspicion of infection. In particular, this has been the case when specimens sent for microbial cultures did not support growth of pathogenic bacteria. This lack of an accurate diagnostic test forced the orthopaedic surgeon to rely largely or wholly on his or her clinical judgement. Thus, any rapid, accurate, molecular diagnostic test or biomarker assay would provide a substantive improvement over the current Musculoskeletal Infection Society (MSIS) guidelines for diagnosing periprosthetic joint infection1, and the development of an accurate point-of-care test would be truly transformative. Recently, an immunoassay for the human alpha defensin protein has been developed as a biomarker for periprosthetic joint infection2, and testing of clinical samples has been performed in clinical laboratories using a moderately complex enzyme-linked immunosorbent assay (ELISA)-based method. Alpha defensin is a human host protein that is secreted by both activated neutrophils and, to a lesser extent, macrophages, as part of the innate immune system that provides a primary response to bacterial infection prior to the development of specific adaptive immune responses. On the basis of structural arguments, it is thought that the defensins form pores in the membranes of the bacteria, leading to loss of integrity; they are broadly effective against both gram-positive and gram-negative pathogens. A meta-analysis of 6 published studies examining the alpha defensin immunoassay using the first-generation ELISA-based method produced findings of near unity3 when compared with the MSIS gold standard, firmly establishing alpha defensin as an excellent biomarker for periprosthetic joint infection. In this article, Gehrke et al. report on a second-generation commercial immunoassay for alpha defensin, the Synovasure Alpha Defensin Test, which utilizes (presumably) the same antibodies that were validated in the first-generation alpha defensin ELISA diagnostic test. In the current case, the Synovasure Alpha Defensin Test has been reformatted into a lateral flow format (analogous to an over-the-counter pregnancy test) that provides practitioners with a point-of-care, low-complexity assay that can provide real-time results while the patient is in the examining room or the operating room. Gehrke et al. demonstrate that this point-of-care assay has excellent sensitivity (92.1%) and superb specificity (100%) for the diagnosis of periprosthetic joint infection when compared with the MSIS gold standard. The adoption of such a test could reduce the number of patient visits as the physician does not need to wait for results to come back from the laboratory to make a diagnosis if the test is performed on aspirated synovial fluid in the clinic. Moreover, the test has the potential to be easily integrated into multiple decision points during treatment, for example, aspiration prior to reimplantation during 2-stage revision or in the operating room during a primary revision surgical procedure. The Synovasure Alpha Defensin Test, although a substantive advance, will not be a panacea, because, prior to its use, metallosis needs to be ruled out via magnetic resonance imaging, as this noninfectious etiology will trigger a false-positive result owing to the leukocyte activation produced in response to the metal particles. Moreover, as it is an indirect test of infection, it therefore cannot be used to discriminate among the many possible microbial pathogens that trigger the innate immune response; nor can it provide information regarding what treatment would most likely be effective. Another limitation of the assay is that it is likely to miss the detection of nonpyogenic, slow-growing, chronic bacterial pathogens such as Propionibacterium acnes4, bacteria that have adopted the biofilm mode of growth5, and other fastidious bacterial species, such as periodontal treponemes6, that have been shown to be associated with failed arthroplasties but that do not produce obvious clinical signs and symptoms of infection. These low-grade pathogens are also likely to be missed using the gold-standard MSIS criteria for periprosthetic joint infection as they culture very poorly, if at all, and have developed strategies to suppress the innate immune response. Thus, there remains a need for the development of rapid, pan-domain, molecular diagnostic tests that could provide specific, actionable information with regard to pathogen and antimicrobial treatment." @default.
• W2782123557 created "2018-01-12" @default.
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• W2782123557 date "2018-01-03" @default.
• W2782123557 modified "2023-09-24" @default.
• W2782123557 title "High-Fidelity Point-of-Care Diagnostic Test for Periprosthetic Joint Infection" @default.
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• W2782123557 doi "https://doi.org/10.2106/jbjs.17.01209" @default.
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