MRI and muscle enzymes do not support the diagnosis of local anesthetic myotoxicity: a descriptive case series.

BACKGROUND: The presence of thigh muscle edema as characterized by increased signal intensity on MRI has been used to support the diagnosis of presumed local anesthetic-induced myotoxicity reported after total knee arthroplasty (TKA) with continuous adductor canal block (CACB). However, neither postoperative baseline imaging appearance nor muscle enzyme values have been described in conjunction with this clinical scenario. Thus, the usefulness of MRI or enzymatic biomarkers of muscle injury for supporting the diagnosis of local anesthetic myotoxicity is unknown. METHODS: This descriptive case series documents postoperative MRI appearance of the ipsilateral upper leg, plus preoperative and postoperative creatine phosphokinase and aldolase values in volunteer patients who underwent uncomplicated TKA with CACB. RESULTS: In 27 volunteer patients with no postsurgical evidence of clinically relevant myotoxicity, anterior thigh muscle edema was universally evident on imaging (n=12) and muscle enzyme values (n=19) were normal or only slightly elevated. CONCLUSIONS: The non-specificity of these findings suggests that MRI and near normal muscle enzyme levels are of limited diagnostic value when there is clinical suspicion of local anesthetic myotoxicity in the setting of TKA with CACB. TRIAL REGISTRATION NUMBER: NCT04821245.

Multiparameter Analysis Identifies Heterogeneity in Knee Osteoarthritis Synovial Responses.

OBJECTIVE: Synovial membrane inflammation is common in osteoarthritis (OA) and increases cartilage injury. However, synovial fluid and histology studies suggest that OA inflammatory responses are not homogeneous. Greater understanding of these responses may provide new insights into OA disease mechanisms. We undertook this study to develop a novel multiparameter approach to phenotype synovial responses in knee OA. METHODS: Cell composition and soluble protein production were measured by flow cytometry and multiplex enzyme-linked immunosorbent assay in synovium collected from OA patients undergoing knee replacement surgery (n = 35). RESULTS: Testing disaggregation conditions showed that aggressive digestion improved synovial cell yield and mesenchymal staining by flow cytometry, but it negatively impacted CD4+ T cell and CD56+ natural killer cell staining. Less aggressive digestion preserved these markers and showed highly variable T cell infiltration (range 0-43%; n = 32). Correlation analysis identified mesenchymal subpopulations associated with different nonmesenchymal populations, including macrophages and T cells (CD45+CD11b+HLA-DR+ myeloid cells with PDPN+CD73+CD90-CD34- mesenchymal cells [r = 0.65, P < 0.0001]; and CD45+CD3+ T cells with PDPN+CD73+CD90+CD34+ mesenchymal cells [r = 0.50, P = 0.003]). Interleukin-6 (IL-6) measured by flow cytometry strongly correlated with IL-6 released by ex vivo culture of synovial tissue (r = 0.59, P = 0.0012) and was highest in mesenchymal cells coexpressing CD90 and CD34. IL-6, IL-8, complement factor D, and IL-10 release correlated positively with tissue cellularity (P = 0.0042, P = 0.018, P = 0.0012, and P = 0.038, respectively). Additionally, increased CD8+ T cell numbers correlated with retinol binding protein 4 (P = 0.033). Finally, combining flow cytometry and multiplex data identified patient clusters with different types of inflammatory responses. CONCLUSION: We used a novel approach to analyze OA synovium, identifying patient-specific inflammatory clusters. Our findings indicate that phenotyping synovial inflammation may provide new insights into OA patient heterogeneity and biomarker development.