Summary

Synovial fluid biomarker levels in the contralateral uninjured knee at the time of arthroscopic partial meniscectomy were predictive of long-term PROs for the operative knee, with increased levels of pro-inflammatory biomarkers predicting worse PROs and increased levels of anti-inflammatory cytokines predicting improved pain.

Abstract

Objectives: This study aimed to determine the ability of synovial fluid biomarkers in the contralateral uninjured knee to predict 10-year patient-reported outcomes (PROs) for the operative knee in those undergoing arthroscopic partial meniscectomy. This may capture the effects of an underlying systemic inflammatory response to injury on patient recovery.

Methods

Patients undergoing arthroscopic partial meniscectomy for isolated meniscal injury were prospectively enrolled. Prior to surgical incision, synovial fluid was aspirated from the operative knee for all enrolled patients and optionally from the contralateral, uninjured knee for consenting patients. Concentrations of 10 biomarkers of interest (RANTES, IL-6, MCP-1, MIP-B, VEGF, TIMP-1, TIMP-2,IL-1RA, MMP-3, and bFGF) were measured by immunoassay of both fluid samples. Patients were asked to complete VAS Pain, Lysholm, Tegner, and KOOS-PS surveys for the operative knee at 10-year follow-up. To prevent model overfitting, stepwise linear regression was performed to identify the most significant predictor(s) of each 10-year PRO score. Log-normalized contralateral biomarker concentration, age at surgery, sex, and body mass index were included as possible covariates.

Results

A total of 17 arthroscopic partial meniscectomy patients (41.2% male, mean age 51.7 ± 9.6 years) with contralateral knee biomarker data and complete 10-year follow-up were included. Mean follow-up time was 10.0 ± 1.2 years. Stepwise linear regression analysis identified no more than 2 significant predictors for any given PRO score. Elevated RANTES concentration in the contralateral knee was associated with worse Lysholm (p = 0.018), KOOS-PS (p = 0.016), and Tegner (p = 0.040) scores at 10-year follow up. Increased levels of TIMP-1 were associated with improved VAS Pain (p = 0.047). Both IL-1Ra (p = 0.045) and MMP-3 (p = 0.049) were associated with worse 10-year Tegner scores, and bFGF (p = 0.049) was associated with worse KOOS-PS.

Conclusions

Synovial fluid biomarker levels in the contralateral uninjured knee at the time of arthroscopic partial meniscectomy were predictive of long-term PROs for the operative knee. In particular, increased levels of pro-inflammatory biomarkers RANTES and MMP-3 were predictive of worse PROs, while increased levels of TIMP-1, an anti-inflammatory and chondroprotective cytokine, were predictive of improved VAS pain score. These results imply that there may be an underlying systemic inflammatory component to unilateral joint injury that influences patient recovery and the outcomes of surgical intervention.