Molecular Techniques, Novel Biomarkers and Coagulation-Based Methods in the Diagnosis of Periprosthetic Joint Infections

Dear Colleagues,

The diagnosis of periprosthetic joint infection (PJI) is especially challenging, while a multidisciplinary approach consisting of clinical microbiologists, infectious disease specialists, and orthopedic surgeons is necessary. Traditionally, diagnosis of PJI is based on the isolation/identification of the causative organism through the culture of the synovial fluid, while other diagnostic modalities include synovial fluid analysis for white blood cell count/type, histopathologic examination of infected tissues, and plasma-based evaluation of inflammatory biomarkers. The diagnostic algorithm with the greatest impact on the diagnosis of PJI is based on the 2018 International Consensus Meeting (ICM) criteria, while the ideal diagnostic approach is still yet to be identified. The financial burden of PJI on health systems poses a serious problem, and the first step to solve this problem is to improve the currently used diagnostic algorithms through the implementation of modern laboratory techniques. This Special Issue will showcase studies evaluating molecular techniques, various biomarkers, and coagulation-based methods for the diagnosis of PJI.

Polymerase chain reaction (PCR) analysis is an established diagnostic tool for the evaluation of PJI and can be applied to tissue samples, synovial fluid and sonicated prosthetic fluid, while multiplex PCR can be used to identify multiple bacteria in a single analysis. Therefore, multiplex PCR can be especially valuable in cases of culture-negative PJI.  Broad-range PCR targets the bacterial 16s gene, but this type of PCR analysis is susceptible to errors as it has been associated with a high rate of false-positive results. Over the last years, a new molecular modality, next-generation sequencing (NGS), has gained ground in the diagnosis of PJI. Moreover, this molecular technique provides a rapid evaluation of antibiotic resistance through a database, even enabling the identification of fungal infections using 18s rRNA. NGS frees laboratory procedures from a culture-based approach and significantly increases the sensitivity of the diagnosis of PJI, as it has been shown that 16–44% of culture-negative infections can be diagnosed through NGS.

Moreover, this Special Issue will focus on articles evaluating the diagnostic potential of several synovial-fluid- and plasma-based biomarkers for PJI. The most widely used plasma-based biomarkers include C-reactive protein, erythrocyte sedimentation rate, and D-Dimer, while commonly used synovial fluid biomarkers include Alpha-Defensin and leukocyte esterase. Recently, there has been promising evidence regarding the application of other novel biomarkers such as aTNF-R1 and sTNFR2 (soluble tumor necrosis factor receptors 1 and 2), calprotectin, lipocalin-2, soluble pecam 1, and various cytokines (IL-1, IL-2, IL-4,IL-5, IL-6, IL-8, TNFa, INF-γ) for the diagnosis of PJI. Finally, viscoelastic studies such as thromboelastography and rotational thromboleastometry have been investigated regarding their diagnostic accuracy for PJI with promising results. For this Special Issue, articles focused on microbiological aspects rather than clinical aspects of novel diagnostic methods for PJI are welcome for submission.

Dr. Andreas G. Tsantes
Dr. Dimitrios V. Papadopoulos
Dr. Christos Koutserimpas
Prof. Dr. Georgia Vrioni
Guest Editors

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• periprosthetic joint infections
• diagnosis
• molecular techniques
• novel biomarkers
• causative organism