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Pilot study of a novel serum mRNA gene panel for diagnosis of acute septic arthritis
Blake J Schultz1, Timothy Sweeney2, Malcolm R DeBaun3
1Department of Orthopedic Surgery, Stanford University, Redwood City, CA 94063, United States. blakeschultzmd@gmail.com.
Background:
Septic arthritis is an orthopedic emergency requiring immediate surgical intervention. Current diagnostic standard of care is an invasive joint aspiration. Aspirations provide information about the inflammatory cells in the sample within a few hours, but there is often ambiguity about whether the source is infectious (e.g. bacterial) or non-infectious (e.g. gout). Cultures can take days to result, so decisions about surgery are often made with incomplete data. Novel diagnostics are thus needed. The "Sepsis MetaScore" (SMS) is an 11-mRNA host immune blood signature that can distinguish between infectious and non-infectious acute inflammation. It has been validated in multiple cohorts across heterogeneous clinical settings.
Aim:
To study whether the SMS holds diagnostic validity in determining the etiology of acute arthritis.
Methods:
We conducted a blinded, prospective, non-interventional clinical study of the SMS. All patients undergoing work-up for a septic primary joint were enrolled. Patients proceeded through the normal standard-of-care pathway, including joint aspiration and inflammatory labs [white blood cell (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)]. Venous blood was also drawn into PAX gene RNA-stabilizing tubes and mRNAs were measured using Nano String nCounter™. SMS was calculated blinded to clinical results.
Results:
A total of 20 samples were included, of which 11 were infected based on aspiration or intra-operative cultures. The SMS had an area under the ROC curve (AUROC) of 0.87 for separating infectious from non-infectious conditions. For comparison, the AUROCs for ESR = 0.58, CRP = 0.6, and WBC = 0.59. At 100% sensitivity for infection, the specificity of the SMS was 40%, meaning nearly half of non-septic patients could have been ruled out for further intervention.
Conclusion:
In this pilot study, SMS showed a high level of diagnostic accuracy in predicting septic joints compared to other diagnostic biomarkers. This quick blood test could be an important tool for early, accurate identification of acute septic joints and need for emergent surgery, improving clinical care and healthcare spending.
Insights
The Sepsis MetaScore (SMS) accurately identifies septic arthritis, outperforming traditional markers like ESR and CRP. This rapid blood test aids in early diagnosis and surgical decision-making for joint infections.
Area of Science:
- Orthopedics
- Infectious Diseases
- Immunology
- Molecular Diagnostics
Background:
- Septic arthritis is an orthopedic emergency requiring prompt surgical intervention.
- Current diagnostics rely on joint aspiration, which can be ambiguous and time-consuming.
- The Sepsis MetaScore (SMS) is an 11-mRNA blood signature differentiating infectious from non-infectious inflammation.
Purpose of the Study:
- To evaluate the diagnostic validity of the SMS in determining the etiology of acute arthritis.
- To compare the diagnostic accuracy of SMS against established inflammatory biomarkers.
Main Methods:
- A blinded, prospective, non-interventional study enrolled patients undergoing septic joint work-up.
- Standard-of-care included joint aspiration and inflammatory labs (WBC, ESR, CRP).
- SMS was calculated from blood mRNA measurements using Nano String nCounter™, blinded to clinical outcomes.
Main Results:
- The SMS demonstrated a high diagnostic accuracy with an Area Under the ROC Curve (AUROC) of 0.87.
- Traditional biomarkers showed lower AUROCs: ESR (0.58), CRP (0.6), and WBC (0.59).
- At 100% sensitivity, SMS specificity was 40%, potentially ruling out nearly half of non-septic patients.
Conclusions:
- The SMS shows significant diagnostic accuracy for predicting septic joints compared to other biomarkers.
- This rapid blood test can aid in the early and accurate identification of septic joints.
- SMS has the potential to improve clinical care and reduce healthcare costs by guiding emergent surgical decisions.
