Abstract

Objectives: The relationship between structural abnormalities and inflammatory changes in the synovial fluid following ACL injury has not been well defined. The purpose of this study is to compare MRI findings and concentration of inflammatory biomarkers in the synovial fluid (SF) of acute and chronic anterior cruciate ligament (ACL) injury patients. Methods: Patients undergoing surgery for ACL injury from October 2011 to December 2021 were included in a database of patients who had SF samples collected at the time of surgery. From this cohort, 82 patients with acute ACL injury and 28 patients with chronic ACL injury were identified. All patients underwent a preoperative MRI examination of the knee and SF was aspirated from the operative knee prior to the surgical incision and concentrations of inflammatory biomarkers were quantified. MRI examinations were reviewed by a fellowship-trained musculoskeletal radiologist to assess radiographic features of acute and chronic knee injury using the validated ACLOAS system. Nonparametric tests were used to compare demographic factors, MRI findings, clinical symptoms, and SF inflammatory biomarkers between acute versus chronic ACL injury patients. A generalized linear model was used to assess the relationship of each SF biomarker with the ACLOAs subscores. Results: For acute ACL injury patients, mean time from injury to MRI and injury to surgery was 14 ± 35 days and 49 ± 38 days, respectively. The mean time from injury to MRI and injury to surgery was 3.2 ± 3.7 years and 3.4 ± 3.8 years, respectively, for those with chronic ACL injury. There were no significant demographic differences between groups; age (acute: 31.62 ± 8.02 years, chronic: 33.70 ± 10.60 years, p=0.130), sex (acute: 51.2% males, chronic: 57.1%, p=0.588), or body mass index (acute: 5.5 ± 4.4 kg/mm2, chronic: 25.3 ± 3.6 kg/mm2, p=0.931). Acute ACL injury patients had higher bone marrow edema severity scores (p<0.001), Hoffa’s synovitis score (p=0.002), and effusion severity scores (p<0.001). Chronic ACL injury patients had higher cartilage degeneration severity scores (p<0.001), prevalence of meniscus tears (p=0.003), and meniscus tear severity scores (p<0.001). Acute ACL injury patients had significantly higher synovial fluid levels of IL-6 (p=0.032), VEGF (p=0.002), TIMP1 (p<0.001), IL1-RA (p=0.003), and MMP3 (p<0.001) than chronic ACL injury patients. The generalized linear model revealed that after adjusting for age, sex, BMI, and time from injury to surgery, increased VEGF (p=0.003) and MMP3 (p=0.012) were associated with higher effusion score. MMP-3 was associated with a higher bone marrow edema score (p=0.034), and RANTES was associated with both a higher meniscus severity score (p=0.027) and increased cartilage lesions in the chronic ACL injury cohort. Conclusions: The findings from this study suggest that despite having more severe cartilage degeneration and a higher prevalence of meniscus pathology, chronic ACL injury patients had lower levels of synovial fluid inflammatory biomarkers at time of surgery compared to acute ACL injury patients. Additionally, we found that in chronic injuries, RANTES was associated with worse ACLOAS cartilage scores.

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