Synovial fluid NMR-based metabolomics in septic and aseptic revision total knee arthroplasty: Implications on diagnosis and treatment.

Periprosthetic joint infection (PJI) is one of the most challenging complications following total knee arthroplasty. Despite its importance, there is a paucity of reports in the literature regarding its pathogenesis. Recently, cellular metabolic reprogramming has been shown to play an important role in the progression and outcome of infectious diseases. Therefore, the aim of this study was to evaluate the metabolites composition of the synovial fluid from patients with PJI or aseptic failure of total knee arthroplasties. The synovial fluids from 21 patients scheduled for revision total knee arthroplasty (11 with the diagnosis of PJI and 10 with aseptic failures) were analyzed using 1D 1H NMR spectroscopy. Univariate and multivariate statistical analyzes were used to identify metabolites that were differentially abundant between those groups. A total of 28 metabolites were identified and five of them found to be differentially abundant between infected and non-infected synovial fluids. Lactate, acetate and 3-hydroxybutyrate were found to be in a higher concentration, and glucose and creatine were found reduced in the synovial fluid from PJI patients. Synovial fluid from patients with PJI exhibit a distinct metabolic profile, possibly reflecting metabolic adaptation that occurs in the infected periprosthetic microenvironment. Further research and studies are warranted to gain a broader insight into the metabolic pathways engaged by both pathogen and immune cells in the context of a PJI.