Knee Synovial Fluid Biomarker Type and Concentration With Long-Term Outcomes After ACL Reconstruction With...

Area of Science:

• Orthopedic Surgery
• Biomarker Discovery
• Inflammation Research

Background:

• Anterior cruciate ligament (ACL) rupture often co-occurs with meniscal injury, altering the joint's inflammatory environment.
• Meniscal injury may exacerbate ACL injury-induced inflammation, potentially contributing to joint degeneration.
• The impact of combined injuries on synovial fluid inflammation and long-term outcomes remains unclear.

Purpose of the Study:

• To define synovial fluid inflammatory phenotypes in patients undergoing ACL reconstruction for combined ACL and meniscal injuries.
• To investigate the association between these phenotypes and patient-reported outcome measures (PROMs) and clinically meaningful improvement.
• To test the hypothesis that distinct phenotypes exist, correlate with symptom severity and recovery, and influence biomarker effects on outcomes.

Main Methods:

• Prospective enrollment of 97 patients undergoing ACL reconstruction with meniscal injury.
• Quantification of 10 synovial fluid biomarkers via unsupervised k-means clustering to identify high- and low-inflammation phenotypes.
• Assessment of PROMs preoperatively and long-term, with regression analyses for biomarker associations and phenotype interactions.

Main Results:

• Two inflammatory phenotypes were identified: high-inflammation (n=66) and low-inflammation (n=31).
• The high-inflammation group exhibited worse baseline pain and function but showed significantly greater improvements in pain and function scores at long-term follow-up.
• Monocyte chemoattractant protein-1 (MCP-1) showed phenotype-dependent associations with PROMs, with high-inflammation patients more likely to achieve minimal clinically important difference for pain.

Conclusions:

• Synovial fluid inflammation profiles at ACL reconstruction identify distinct phenotypes linked to baseline severity and differential recovery.
• While long-term PROMs were similar, phenotype-specific biomarker effects, especially MCP-1, highlight varying biological contexts for recovery.
• These findings suggest that inflammatory status influences the recovery trajectory after combined ACL and meniscal injuries.