Evidence map›Paper›PMID 42108508›Full record

ReviewArthroplasty (London, England)2026

Diagnostic accuracy of serum and synovial biomarker thresholds for diagnosing periprosthetic joint infection: a QUADAS-C-guided systematic review and meta-analysis.

Maria Sartori, Silvia Brogini, Deyanira Contartese, Francesco Rosa, Mirco Lo Presti, Maria Pia Neri, Matteo Romagnoli, Dante Dallari, Angelo Toscano, Stefano Zaffagnini and 2 more

Abstract readReview
In one paragraph

Review in Arthroplasty (London, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Maria SartoriSurgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, Via Di Barbiano 1/10, 40136, Bologna, Italy.
Silvia BroginiSurgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, Via Di Barbiano 1/10, 40136, Bologna, Italy.
Deyanira ContarteseSurgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, Via Di Barbiano 1/10, 40136, Bologna, Italy. deyanira.contartese@ior.it.
Francesco RosaSurgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, Via Di Barbiano 1/10, 40136, Bologna, Italy.
Mirco Lo PrestiII Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, Via G.C. Pupilli 1, 40136, Bologna, Italy.
Maria Pia NeriII Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, Via G.C. Pupilli 1, 40136, Bologna, Italy.
Matteo RomagnoliOrthopaedics and Traumatology, Istituto Ortopedico Rizzoli, Via Nazionale Ponente 5, 44011, Argenta, FE, Italy.
Dante DallariReconstructive Orthopaedic Surgery and Innovative Techniques-Musculoskeletal Tissue Bank, IRCCS Istituto Ortopedico Rizzoli, Via G.C. Pupilli 1, 40136, Bologna, Italy.
Angelo ToscanoGeneral Orthopaedics, IRCCS Istituto Ortopedico Rizzoli, Via G.C. Pupilli 1, 40136, Bologna, Italy.
Stefano ZaffagniniII Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, Via G.C. Pupilli 1, 40136, Bologna, Italy.
Milena FiniScientific Direction, IRCCS Istituto Ortopedico Rizzoli, Via Di Barbiano 1/10, 40136, Bologna, Italy.
Gianluca GiavaresiSurgical Sciences and Technologies, IRCCS Istituto Ortopedico Rizzoli, Via Di Barbiano 1/10, 40136, Bologna, Italy.

Funding

Italian Ministry of Health Ricerca Finalizzata grant RF-2019-12370058
6 · The paper itself

Abstract

backgroundPeriprosthetic joint infection (PJI) remains one of the most serious complications after joint arthroplasty, and accurate diagnosis continues to pose significant challenges. A reliable distinction between septic and aseptic failure is essential for appropriate surgical and antibiotic management. This systematic review and meta-analysis evaluate the most recent clinical evidence on the diagnostic accuracy, methodological quality, and standardization potential of established "classical" and emerging serum and synovial biomarkers for PJI diagnosis.

methodsThis systematic review and meta-analysis were conducted in accordance with PRISMA-DTA guidelines, with PRISMA used as a general reporting framework. Selected items from the STARD checklist were used solely to inform data extraction and were not applied as a reporting guideline. Clinical studies published between January 1, 2020, and October 31, 2025, were identified through PubMed, Scopus, and Web of Science. Eligible studies reported sensitivity, specificity, and/or diagnostic thresholds for serum or synovial biomarkers based on MSIS, ICM, or EBJIS criteria for PJI definition. Study quality was assessed using the QUADAS-C tool, and a meta-analysis of chronic PJI cohorts was performed.

resultsTwenty-six studies were included (8 serum, 18 synovial). Among serum biomarkers, C-reactive protein and erythrocyte sedimentation rate showed moderate diagnostic accuracy (Area Under the ROC curve [AUC] 0.82-0.90), while fibrinogen demonstrated comparable performance in selected cohorts. D-dimer and other coagulation indices showed variable results. Synovial biomarkers demonstrated superior diagnostic performance. α-defensin, D-lactate, calprotectin (CP), and neutrophil gelatinase-associated lipocalin achieved excellent accuracy (AUC > 0.90; sensitivity and specificity > 90%). Synovial white blood cell count (WBC) and polymorphonuclear percentage (PMN%) remained reliable and cost-effective. Meta-analysis confirmed high pooled diagnostic performance for WBC (0.88/0.97) and PMN% (0.84/0.97).

conclusionsTraditional serum biomarkers remain useful first-line diagnostic tools, whereas synovial biomarkers-particularly α-defensin, D-lactate, CP, and WBC indices-demonstrate superior diagnostic accuracy and may be especially valuable in culture-negative PJI. However, substantial heterogeneity and risk of bias identified by QUADAS-C-particularly in patient selection, reference standards, and threshold derivation-suggest that pooled estimates may represent optimistic upper-bound performance, limiting generalizability. Future diagnostic strategies should integrate multimodal biomarker panels with molecular diagnostics and artificial intelligence-based approaches to improve diagnostic precision and clinical applicability.

Indexed as

BiomarkersCalprotectinC-reactive proteinD-dimerDiagnostic accuracyPeriprosthetic joint infectionSynovial fluidα-defensin

Identifiers

PMID42108508
PMCPMC13159356

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.