Evidence map›Paper›PMID 42221203›Full record

ReviewOrthopaedic journal of sports medicine2026

Synovial Fluid Biomarkers Associated With Anterior Cruciate Ligament Injury and Reconstruction: A Systematic Review.

Daniel C Touhey, Derrick M Knapik, Sina Tartibi, Varun Gopinatth, Tanya Boghosian, Matthew J Matava, Matthew V Smith, Robert H Brophy

Abstract readReview
In one paragraph

Review in Orthopaedic journal of sports medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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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.

Daniel C TouheyDepartment of Orthopaedic Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA.ORCID https://orcid.org/0000-0002-9558-8147
Derrick M KnapikDepartment of Orthopaedic Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA.
Sina TartibiDepartment of Orthopaedic Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA.ORCID https://orcid.org/0009-0005-6092-3776
Varun GopinatthDepartment of Orthopaedic Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA.ORCID https://orcid.org/0000-0002-6127-1221
Tanya BoghosianDepartment of Orthopaedic Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA.
Matthew J MatavaDepartment of Orthopaedic Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA.
Matthew V SmithDepartment of Orthopaedic Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA.
Robert H BrophyDepartment of Orthopaedic Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA.ORCID https://orcid.org/0000-0002-2912-8265

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Synovial fluid biomarkers reflect the inflammatory response after joint injury and surgery. Previous studies have identified synovial fluid biomarker concentrations in the knee after both anterior cruciate ligament (ACL) injury and ACL reconstruction (ACLR). Purpose: To systematically review the literature to summarize reported changes in synovial fluid biomarkers and their concentrations after acute ACL injury/ACLR. Study Design: Systematic review; Level of evidence, 4. Methods: Studies published in the PubMed, EMBASE, and the Cochrane Library databases reporting in English on humans sustaining ACL tears and undergoing ACLR from inception to August 2025 were identified and included if postinjury/preoperative and/or postoperative concentrations of synovial fluid biomarkers were reported. Study quality, risk of bias, and heterogeneity were evaluated. Results: A total of 44 studies were identified, comprising 2428 patients and 4721 synovial fluid profiles. Postinjury (pre-ACLR) biomarker concentrations were reported across 38 studies (N = 2101 patients). Nineteen studies (N = 676 patients) reported mean biomarker concentrations post-ACLR. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-8 (IL-8), interleukin-10 (IL-10), and interleukin-1 receptor antagonist (IL-1Ra) were reported in ≥10 studies (22 studies postinjury; 11 studies post-ACLR). Mean concentrations of all 6 biomarkers were elevated immediately after both injury (pre-ACLR) and surgery (post-ACLR), followed by progressive decrease. Increased mean concentrations for TNF-α and IL-8 were reported from 3 to 6 months after ACL injury (pre-ACLR), with IL-6, TNF-α, and IL-8 remaining elevated over 1 year after injury. Increased mean concentrations of IL-6 and IL-8 were reported from 3 to 6 months after ACLR, with IL-6 and IL-8 remaining elevated over 1 year post-ACLR. Methodological quality was moderate based on Methodological Index for Non-Randomized Studies scores (overall mean, 17.3 [range, 10-23]). Randomized studies demonstrated low to moderate risk of bias according to the Risk of Bias 2 assessment. Considerable heterogeneity in biomarker concentrations was observed. Conclusion: Immediate elevation of synovial fluid levels of proinflammatory biomarkers occurs after ACL injury and ACLR, followed by a progressive, yet variable, decrease over 1 year. These biomarkers reflect the underlying inflammatory and healing responses within the knee. However, their correlation with subjective and objective measures of knee function, as well as with the risk of secondary osteoarthritis, is unknown.

Indexed as

anterior cruciate ligament injuryanterior cruciate ligament reconstructionbiomarkerssynovial fluid

Identifiers

PMID42221203
PMCPMC13221605

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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.