Utility of Plasma Protein Biomarkers and Mid-infrared Spectroscopy for Diagnosing Fracture-related Infections: A Pilot Study

Objectives: To compare a large panel of plasma protein inflammatory biomarkers and mid-infrared (MIR) spectral patterns in patients with confirmed fracture-related infections (FRIs) with those in controls without infection. Design: Prospective case-control study. Setting: Academic, Level 1 trauma center. Patients: Thirteen patients meeting confirmatory FRI criteria were matched to 13 controls based on age, time after surgery, and fracture region. Intervention: Plasma levels of 49 proteins were measured using enzyme-linked immunosorbent assay techniques. Fourier transform infrared spectroscopy of dried films was used to obtain MIR spectra of plasma samples. Main outcome measurements: The main outcome measurements included plasma protein levels and MIR spectra of samples. Results: Multivariate analysis-based predictive model developed using enzyme-linked immunosorbent assay-based biomarkers had sensitivity, specificity, and accuracy of 69.2% ± 0.0%, 99.9% ± 1.0%, and 84.5% ± 0.6%, respectively, with platelet-derived growth factor-AB/BB, C-reactive protein, and MIG selected as the minimum number of variables explaining group differences ( P < 0.05). Sensitivity, specificity, and accuracy of the predictive model based on MIR spectra were 69.9% ± 6.2%, 71.9% ± 5.9%, and 70.9% ± 4.8%, respectively, with 6 wavenumbers as explanatory variables ( P < 0.05). Conclusions: This pilot study demonstrates the feasibility of using a select panel of plasma proteins and Fourier transform infrared spectroscopy to diagnose FRIs. Preliminary data suggest that the measurement of these select proteins and MIR spectra may be potential clinical tools to detect FRIs. Further investigation of these biomarkers in a larger cohort of patients is warranted. Level of evidence: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.