Evidence map›Paper›PMID 42519810›Full record

ReviewJournal of experimental orthopaedics2026

Synovial fluid proteomic biomarkers in periprosthetic joint infection: A systematic review with gene ontology and protein network analyses.

Giorgia Lucia Benedetto, Elvira Immacolata Parrotta, Raffaele Covello, Giovanni Cuda, Giorgio Gasparini, Olimpio Galasso, Umile Giuseppe Longo, Michele Mercurio

Abstract readReview
In one paragraph

Review in Journal of experimental orthopaedics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

8 authors.

Giorgia Lucia BenedettoDepartment of Medical and Surgical Sciences University "Magna Graecia" Catanzaro Italy.ORCID https://orcid.org/0009-0008-8585-2144
Elvira Immacolata ParrottaDepartment of Medical and Surgical Sciences University "Magna Graecia" Catanzaro Italy.ORCID https://orcid.org/0000-0001-8145-3623
Raffaele CovelloDepartment of Experimental and Clinical Medicine University "Magna Graecia" Catanzaro Italy.
Giovanni CudaDepartment of Experimental and Clinical Medicine University "Magna Graecia" Catanzaro Italy.
Giorgio GaspariniDepartment of Orthopaedic and Trauma Surgery "Magna Græcia" University, "Renato Dulbecco" University Hospital Catanzaro Italy.
Olimpio GalassoDepartment of Medicine, Surgery and Dentistry University of Salerno Salerno Italy.
Umile Giuseppe LongoFondazione Policlinico Universitario Campus Bio-Medico Roma Italy.
Michele MercurioDepartment of Orthopaedic and Trauma Surgery "Magna Græcia" University, "Renato Dulbecco" University Hospital Catanzaro Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: Periprosthetic joint infection (PJI) is a severe complication of total joint arthroplasty associated with significant morbidity, implant failure and increased healthcare costs. Diagnosis remains challenging, particularly in low-grade and culture-negative infections, because conventional markers lack specificity. Proteomic analyses may identify more reliable synovial biomarkers and provide insights into the molecular mechanisms underlying PJI. Methods: A systematic review was conducted according to PRISMA guidelines using PubMed and Scopus databases. Studies published within the last 10 years involving adults undergoing revision hip or knee arthroplasty for suspected PJI and assessing synovial fluid biomarkers by proteomic or immunoassay techniques (liquid chromatography-tandem mass spectrometry, matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry, enzyme-linked immunosorbent assay) were included. Functional enrichment analyses (gene ontology [GO], Kyoto encyclopaedia of genes and genomes [KEGG], human phenotype ontology [HPO], DISEASES and protein-protein interaction (PPI) network analyses were performed. Results: Six studies met the inclusion criteria. A focused set of dysregulated synovial proteins was identified, predominantly related to innate immunity and inflammation, including lactoferrin, myeloperoxidase, lysozyme C, PRTN3, defensin alpha 1, defensin alpha 3, calprotectin (S100 calcium-binding proteins A8 and A9), annexin A6, alpha-2-HS-glycoprotein (Fetuin-A), MNDA, GRO-α, interleukin (IL)-8 and IL-5. GO and KEGG analyses demonstrated enrichment of antimicrobial defense and cytokine-mediated inflammatory pathways. PPI analysis identified key hub proteins involved in inflammatory and oxidative stress responses, while HPO and DISEASES analyses further supported their association with immune dysregulation and infectious inflammatory conditions. Conclusions: Synovial proteomic and immuno-inflammatory biomarkers may improve diagnostic accuracy in PJI, particularly in low-grade and culture-negative infections. Biomarker panels including α-defensins and calprotectin (S100A8/A9) represent promising next-generation diagnostic tools. Further multicenter studies are needed to validate these findings and facilitate their integration into standardised diagnostic algorithms. Level of Evidence: Levels II-III.

Indexed as

biomarkerscytokinesinflammationMS/MSPJIPPI networkproteomicssynovial fluid

Identifiers

PMID42519810
PMCPMC13384346

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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.