Browsing by Author "Malek, Sarah"

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    Proteomic Analyses of Plasma from Patients with Fracture Related Infection Reveals Systemic Activation of the Complement and Coagulation Cascades
    (Wolters Kluwer, 2024) Becker, Kevin; Sharma, Ishani; Slaven, James E.; Mosley, Amber L.; Doud, Emma H.; Malek, Sarah; Natoli, Roman M.; Orthopaedic Surgery, School of Medicine
    Objectives: The objective of this study was to compare plasma proteomes of patients with confirmed fracture-related infections (FRIs) matched to noninfected controls using liquid chromatography-mass spectrometry. Design: This was a prospective case-control study. Setting: The study was conducted at a single, academic, Level 1 trauma center. Patient selection criteria: Patients meeting confirmatory FRI criteria were matched to controls without infection based on fracture region, age, and time after surgery from June 2019 to January 2022. Tandem mass tag liquid chromatography-mass spectrometry analysis of patient plasma samples was performed. Outcome measures and comparisons: Protein abundance ratios in plasma for patients with FRI compared with those for matched controls without infection were calculated. Results: Twenty-seven patients meeting confirmatory FRI criteria were matched to 27 controls. Abundance ratios for more than 1000 proteins were measured in the 54 plasma samples. Seventy-three proteins were found to be increased or decreased in patients with FRI compared with those in matched controls (unadjusted t test P < 0.05). Thirty-two of these proteins were found in all 54 patient samples and underwent subsequent principal component analysis to reduce the dimensionality of the large proteomics dataset. A 3-component principal component analysis accounted for 45.7% of the variation in the dataset and had 88.9% specificity for the diagnosis of FRI. STRING protein-protein interaction network analysis of these 3 PCs revealed activation of the complement and coagulation cascades through the Reactome pathway database (false discovery rates <0.05). Conclusions: Proteomic analyses of plasma from patients with FRI demonstrate systemic activation of the complement and coagulation cascades. Further investigation along these lines may help to better understand the systemic response to FRI and improve diagnostic strategies using proteomics.
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    Utility of Plasma Protein Biomarkers and Mid-Infrared Spectroscopy for Diagnosing Fracture-Related Infections: A Pilot Study
    (Wolters Kluwer, 2022-04) Farooq, Hassan; Wessel, Robert P.; Brown, Krista; Slaven, James E.; Marini, Federico; Malek, Sarah; Natoli, Roman M.; Orthopaedic Surgery, School of MedicinE
    Objectives: To compare a large panel of plasma protein inflammatory biomarkers and mid-infrared (MIR) spectral patterns between patients with confirmed fracture related infections (FRIs) and controls without infection. Design: Prospective case-control. 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 (ELISA) techniques. Fourier transform infrared (FTIR) spectroscopy of dried films was used to obtain MIR spectra of plasma samples. Main Outcome Measurements: Plasma protein levels and MIR spectra of samples. Results: Multivariate analysis-based predictive model developed utilizing ELISA-based biomarkers had sensitivity, specificity, and accuracy of 69.2±0.0%, 99.9±1.0%, and 84.5±0.6%, respectively, with PDGF-AB/BB, CRP, 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 six wavenumbers as explanatory variables (P<0.05). Conclusions: This pilot study demonstrates the feasibility of using a select panel of plasma proteins and FTIR spectroscopy to diagnose FRI. The preliminary data suggest that measurement of these select proteins and MIR spectra may be potential clinical tools to detect FRI. Further investigation of these biomarkers in a larger cohort of patients is warranted.