Knee Synovial Fluid Biomarker Type and Concentration With Long-Term Outcomes After ACL Reconstruction With Concomitant Meniscal Injury

Background: Anterior cruciate ligament (ACL) rupture frequently occurs alongside meniscal injury, together altering the intra-articular environment. While ACL injury triggers an inflammatory cascade within synovial fluid, meniscal injury may intensify these responses, contributing to joint degeneration. However, little is known about how combined ACL and meniscal injuries shape the synovial inflammatory milieu or whether these profiles influence long-term outcomes. Purpose/Hypothesis: The purpose was to characterize synovial fluid inflammatory phenotypes at the time of ACL reconstruction with concomitant meniscal injury and assess their association with patient-reported outcome measures (PROMs) and clinically meaningful improvement. It was hypothesized that (1) distinct inflammatory phenotypes would exist, (2) these phenotypes would correlate with symptom severity and recovery, and (3) individual biomarkers’ effects on outcomes would vary by phenotype. Study Design: Cohort study; Level of evidence, 3. Methods: Patients undergoing arthroscopic ACL reconstruction with concomitant meniscal injury were prospectively enrolled between July 2011 and January 2024. Synovial fluid was aspirated before incision, and the concentrations of 10 biomarkers were quantified. Unsupervised k -means clustering identified high- and low-inflammation phenotypes. PROMs were collected preoperatively on the day of surgery (baseline) and at long-term follow-up. Linear regression assessed biomarker associations with PROMs, with interaction models evaluating effect modification by inflammation phenotype. Minimal clinically important difference (MCID) achievement thresholds were calculated using a distribution-based approach (0.5 × baseline SD) and compared between clusters. Results: A total of 97 patients were stratified into high-inflammation (n = 66) and low-inflammation (n = 31) clusters. Patient and surgical characteristics were similar, but the high-inflammation cluster demonstrated significantly worse baseline pain and function (all P ≤ .008). At a mean follow-up of 8.2 ± 2.5 years, postoperative PROMs were similar, but the high-inflammation cluster experienced greater improvements in VAS pain (−13.5 vs 3.1; P = .008) and Lysholm (28.6 vs 8.9; P = .002) scores. Monocyte chemoattractant protein-1 (MCP-1) demonstrated strong, phenotype-dependent associations with PROMs, and patients with high inflammation were more likely to achieve the MCID for VAS pain score (57.6% vs 17.6%; P < .05). Conclusion: Synovial fluid biomarker profiles at the time of ACL reconstruction with concomitant meniscal injury identified distinct inflammatory phenotypes associated with baseline symptom severity and differential patterns of clinical improvement. Although long-term PROMs were similar between groups, phenotype-dependent biomarker associations, particularly involving MCP-1, suggest that the biological context of recovery differs across inflammatory profiles.