Neutrophil extracellular trap (NET)-related index as an indicator of periprosthetic joint infection

Background: Periprosthetic joint infection (PJI) is a devastating complication of arthroplasty and is difficult to diagnose accurately. This study aims to explore the value of neutrophil extracellular traps in synovial fluid (SF-NETs, web-like structures released by neutrophils as a critical innate immune response) for diagnosing PJI. Methods: A retrospective cohort study was conducted, enrolling post-arthroplasty subjects from January 2018 to December 2023. Three components of SF-NETs (cell-free double-strand DNA, SF-dsDNA; citrullinated histone H3, SF-CitH3; SF-Nucleosome) and SF-NETs₁₊ (positive with one out of the three NET components), SF-NETs₂₊ (positive with two out of the three NET components), white blood cell count (SF-WBC), polymorphonuclear cell percentage (SF-PMN %), neutrophil count in SF (SF-PMN), microbiological examinations (Culture) and infection-related systemic indices were evaluated. Results: A total of 64 of 153 included subjects were diagnosed as PJI. SF-dsDNA and SF-CitH3 had significantly higher levels in the PJI group compared to the non-PJI group ( $P$ $<$ 0.001) and showed positive correlations with SF-WBC, SF-PMN % and SF-PMN (0.4 $<$ $\rho$ $<$ 0.7), while SF-Nucleosome had no significant difference. Sensitivity and specificity of SF-NETs₁₊, SF-NETs₂₊ and Culture were 82.2 % and 78.7 %, 59.4 % and 95.5 %, and 54.1 % and 86.8 %, respectively. The NET related index (NETRI) was defined as 10.529 $\times$ SF-NETs ${}_{1+}+$ 28.114 $\times$ SF-PMN % $+$ 8.210 $\times$ Culture-1.452, with the area under the receiver operating characteristic curve of 0.922, making it a novel indicator. Conclusions: SF-NETs₁₊ and SF-NETs₂₊ may serve respectively in the screening and exclusion of PJI. NETRI represented a new discriminator for PJI diagnosis.