Dataset Information

Potential Blood Biomarkers for Diagnosing Periprosthetic Joint Infection: A Single-Center, Retrospective Study.

ABSTRACT:

Background

Blood biomarkers are first-line tools for identifying periprosthetic joint infection (PJI). C-reactive protein (CRP) is currently recognized as the standard biomarker for PJI diagnosis. Other recently reported novel biomarkers, including plasma fibrinogen, platelet count, monocyte/lymphocyte ratio (MLR), neutrophil/lymphocyte ratio (NLR), and platelet count/lymphocyte ratio (PLR), have also shown promise in diagnosing PJI. This study aimed to evaluate whether these biomarkers were superior to CRP for identifying PJI.

Methods

Patients who underwent revision hip or knee arthroplasty at our hospital from January 2008 to September 2020 were included consecutively and divided into infected and non-infected groups according to the 2013 International Consensus Meeting Criteria. Blood samples were collected preoperatively, and erythrocyte sedimentation rate (ESR), CRP, interleukin-6, fibrinogen, platelet count, MLR, NLR, and PLR were analyzed. The diagnostic values of the tested biomarkers and their combinations were compared with CRP based on the area under the receiver operating characteristic curve (AUC) using the z-test. Classification trees were constructed to explore more accurate combinations of the tested markers for identifying PJI.

Results

A total of 543 patients were included, of whom 245 had PJI. Among the tested biomarkers, CRP with a cutoff of 7.39 mg/L showed the highest AUC, which gave a sensitivity of 79.1% and specificity of 86.0%. The AUCs of pairwise combinations of tested markers including CRP also were inferior to CRP itself, as were combinations derived from classification trees.

Conclusions

Preoperative serum CRP with a low cutoff may be the best reliable blood biomarker for identifying PJI, and those traditional or novel available blood biomarkers could not further improve the diagnostic ability on the basis of CRP.

SUBMITTER: Xu H

PROVIDER: S-EPMC9030667 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Potential Blood Biomarkers for Diagnosing Periprosthetic Joint Infection: A Single-Center, Retrospective Study.

Xu Hong H Xie Jinwei J Zhang Shaoyun S Wang Duan D Huang Zeyu Z Zhou Zongke Z

Antibiotics (Basel, Switzerland) 20220411 4

<h4>Background</h4>Blood biomarkers are first-line tools for identifying periprosthetic joint infection (PJI). C-reactive protein (CRP) is currently recognized as the standard biomarker for PJI diagnosis. Other recently reported novel biomarkers, including plasma fibrinogen, platelet count, monocyte/lymphocyte ratio (MLR), neutrophil/lymphocyte ratio (NLR), and platelet count/lymphocyte ratio (PLR), have also shown promise in diagnosing PJI. This study aimed to evaluate whether these biomarkers ...[more]

PMID: 35453256

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Project description:BackgroundExtracellular vesicles (EVs) are considered as crucial players in a wide variety of biological processes. Although their importance in joint diseases or infections has been shown by numerous studies, much less is known about their function in periprosthetic joint infection (PJI). Our aim was to investigate activated polymorphonuclear (PMN)-derived synovial EVs in patients with PJI.Questions/purposes(1) Is there a difference in the number and size of extracellular vesicles between periprosthetic joint aspirates of patients with PJI and aseptic loosening? (2) Are these vesicles morphologically different in the two groups? (3) Are there activated PMN-derived EVs in septic samples evaluated by flow cytometry after CD177 labelling? (4) Is there a difference in the protein composition carried by septic and aseptic vesicles?MethodsThirty-four patients (n = 34) were enrolled into our investigation, 17 with PJI and 17 with aseptic prosthesis loosening. Periprosthetic joint fluid was aspirated and EVs were separated. Samples were analysed by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) and flow cytometry (after Annexin V and CD177 labelling). The protein content of the EVs was studied by mass spectrometry (MS).ResultsNTA showed particle size distribution in both groups between 150 nm and 450 nm. The concentration of EVs was significantly higher in the septic samples (p = 0.0105) and showed a different size pattern as compared to the aseptic ones. The vesicular nature of the particles was confirmed by TEM and differential detergent lysis. In the septic group, FC analysis showed a significantly increased event number both after single and double labelling with fluorochrome conjugated Annexin V (p = 0.046) and Annexin V and anti-CD177 (p = 0.0105), respectively. MS detected a significant difference in the abundance of lactotransferrin (p = 0.00646), myeloperoxidase (p = 0.01061), lysozyme C (p = 0.04687), annexin A6 (p = 0.03921) and alpha-2-HS-glycoprotein (p = 0.03146) between the studied groups.ConclusionsAn increased number of activated PMN derived EVs were detected in the synovial fluid of PJI patients with a characteristic size distribution and a specific protein composition. The activated PMNs-derived extracellular vesicles can be potential biomarkers of PJI.

Project description:The volume of joint replacement surgery has risen steadily in recent years, because the population is aging and increasingly wishes to reserve a high functional status onward into old age. Infection is among the more common complications of joint replacement surgery, arising in 0.2% to 2% of patients, or as many as 9% in special situations such as the implantation of megaprostheses. The associated morbidity and mortality are high. It is thus very important to minimize risk factors for infection and to optimize the relevant diagnostic and therapeutic strategies.This review is based on pertinent publications retrieved by a selective search in PubMed, including current guidelines and expert recommendations.The crucial diagnostic step is joint biopsy for the identification of the pathogenic organism, which succeeds with over 90% sensitivity and specificity. If the prosthesis is firmly anchored in bone, the pathogen is of a type that responds well to treatment, and symptomatic infection has been present only for a short time, then rapidly initiated treatment can save the prosthesis in 35-90% of cases. The pillars of treatment are thorough surgical care (radical débridement) and targeted antibiotic therapy. On the other hand, if the prosthesis is loose or the pathogen is of a poorly treatable type, the infection can generally only be cured by a change of the prosthesis. This can be performed in either one or two procedures, always in conjunction with systemic antibiotic therapy tailored to the specific sensitivity and resistance pattern of the pathogen.The risk of infection of an artificial joint is low, but the overall prevalence of such infections is significant, as the number of implanted joints is steadily rising. Artificial joint infections should be treated by a standardized algorithm oriented toward the recommendations of current guidelines. Many of these recommendations, however, are based only on expert opinion, as informative studies providing high-grade evidence are lacking. Thus, for any particular clinical situation, there may now be multiple therapeutic approaches with apparently comparable efficacy. Randomized trials are urgently needed.

Project description:Periprosthetic joint infection (PJI), a devastating complication of total joint replacement, is of incompletely understood pathogenesis and may sometimes be challenging to clinically distinguish from other causes of arthroplasty failure. We characterized human gene expression in 93 specimens derived from surfaces of resected arthroplasties, comparing transcriptomes of subjects with infection- versus non-infection-associated arthroplasty failure. Differential gene expression analysis confirmed 28 previously reported potential biomarkers of PJI, including bactericidal/permeability increasing protein (BPI), cathelicidin antimicrobial peptide (CAMP), C-C-motif chemokine ligand 3 (CCL3), 4(CCL4), and C-X-C-motif chemokine ligand 2 (CXCL2), colony stimulating factor 2 receptor beta (CSF2RB), colony stimulating factor 3 (CSF3), alpha-defensin (DEFA4), Fc fragment of IgG receptor 1B (CD64B), intercellular adhesion molecule 1 (ICAM1), interferon gamma (IFNG), interleukin 13 receptor subunit alpha 2 (IL13RA2), interleukin 17D (IL17D), interleukin 1 (IL1A, IL1B, IL1RN), interleukin 2 receptors (IL2RA, IL2RG), interleukin 5 receptor (IL5RA), interleukin 6 (IL6), interleukin 8 (IL8), lipopolysaccharide binding protein (LBP), lipocalin (LCN2), lactate dehydrogenase C (LDHC), lactotransferrin (LTF), matrix metallopeptidase 3 (MMP3), peptidase inhibitor 3 (PI3), and vascular endothelial growth factor A (VEGFA), and identified three novel molecules of potential diagnostic use for detection of PJI, namely C-C-motif chemokine ligand CCL20, coagulation factor VII (F7), and B cell receptor FCRL4. Comparative analysis of infections caused by staphylococci versus bacteria other than staphylococci and Staphylococcus aureus versus Staphylococcus epidermidis showed elevated expression of interleukin 13 (IL13), IL17D, and MMP3 in staphylococcal infections, and of IL1B, IL8, and platelet factor PF4V1 in S. aureus compared to S. epidermidis infections. Pathway analysis of over-represented genes suggested activation of host immune response and cellular maintenance and repair functions in response to invasion of infectious agents. The data presented provides new potential targets for diagnosis of PJI and for differentiation of PJI caused by different infectious agents.

Dataset Information

Potential Blood Biomarkers for Diagnosing Periprosthetic Joint Infection: A Single-Center, Retrospective Study.

Background

Methods

Results

Conclusions

Publications

Potential Blood Biomarkers for Diagnosing Periprosthetic Joint Infection: A Single-Center, Retrospective Study.

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