Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Orthop. Dec 18, 2019; 10(12): 424-433
Published online Dec 18, 2019. doi: 10.5312/wjo.v10.i12.424
Pilot study of a novel serum mRNA gene panel for diagnosis of acute septic arthritis
Blake J Schultz, Timothy Sweeney, Malcolm R DeBaun, Melissa Remmel, Uros Midic, Purvesh Khatri, Michael J Gardner
Blake J Schultz, Malcolm R DeBaun, Michael J Gardner, Department of Orthopedic Surgery, Stanford University, Redwood City, CA 94063, United States
Timothy Sweeney, Melissa Remmel, Uros Midic, Inflammatix, Inc, 863 Mitten Road, Suite 104, Burlingame, CA 94010, United States
Purvesh Khatri, Institute for Immunity, Transplantation and Infections, Center for Biomedical Research, Department of Medicine, Stanford University, Stanford, Redwood City, CA 94305, United States
Author contributions: Sweeney T, Remmel M, Midic U, Khatri P ran the laboratory tests and performed data analysis and interpretation. Schultz BJ, DeBaun MR and Gardner MJ organized and ran the clinical trial. All authors provided critical feedback and helped shape the research, analysis and manuscript. All authors have read and approve of the final submitted manuscript.
Institutional review board statement: All specimens from the patients were obtained after their informed consent and ethical permission was obtained for participation in the study.
Conflict-of-interest statement: The authors report no relevant conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Blake J Schultz, MD, Surgeon, Department of Orthopedic Surgery, Stanford University, 450 Broadway Street Pavilion C, 4th Floor, Redwood City, CA 94063, United States.
Telephone: +1-650-4975281
Received: August 14, 2019
Peer-review started: August 14, 2019
First decision: August 30, 2019
Revised: September 19, 2019
Accepted: October 18, 2019
Article in press: October 18, 2019
Published online: December 18, 2019
Research background

Septic arthritis in native joints is an orthopedic emergency, requiting urgent surgical intervention. It can present similarly to non-septic arthritis such as grout, transient synovitis or inflammatory arthritis. Non-septic arthritis can be managed medically, so accurate diagnosis is important. Currently, diagnosis is based on a combination of clinic exam and serum and synovial biomarkers which do not reliability differentiate infection from non-infective inflammation. The gold standard of diagnosis is intra-articular aspiration cultures, which can take days to result, so decisions about urgent surgery are often made with incomplete information. Novel diagnostics are needed to improve the speed and accuracy of diagnosis.

Research motivation

Novel diagnostics are needed to improve the speed and accuracy of diagnosis of septic arthritis to prevent the irreversible damage to cartilage seen in septic arthritis of native joints and to avoid unnecessary surgery in patients with aseptic arthritis. The ability to quickly and accurately identify and monitor infection through serum biomarkers, instead of invasive aspirations, has many potential applications across orthopedics, including peri-prosthetic infection, pediatric transient synovitis, hardware infection and in the work-up of fracture non-union.

Research objectives

The main objective was to compare the ability of the Sepsis MetaScore (SMS) to diagnosis acute septic arthritis in native joints compared to current diagnostic serum and synovial biomarkers. The SMS proved more accurate than serum white blood cell (WBC), erythrocyte sedimentation rate, C-reactive protein and synovial WBC and polymorphonuclear cells %. With the ability to result in 30 min without an invasive intra-articular aspiration, there is potential for future research across orthopedics for diagnosis and monitoring of infection.

Research methods

We conducted a prospective, observational study of adult patients being worked up for acute septic arthritis of native joints in the emergency department. They proceeded through the standard of care work-up including inflammatory labs and aspiration, with an additional venous lab draw into a PAX gene RNA-stabilizing tube that was used to calculate the SMS. Decisions for surgery were made without consideration of SMS which was calculated at the end of the enrollment period, blinded to clinical results. Patients were retrospectively deemed infected or not based on synovial culture results. The SMS and other inflammatory labs were compared to this diagnosis

Research results

There was no significant difference in any of the standard serum or synovial labs between the septic and aseptic groups, except for the SMS which was significantly higher in septic patient compared to aseptic patient (P = 0.008). This pilot study data is encouraging, but still needs to be validated in a larger study.

Research conclusions

The SMS shows potential as a quicker and more accurate diagnostic tool for acute septic arthritis than current serum and synovial biomarkers. It shows unique potential in complicated patients with histories of gout, inflammatory arthritis or immunocompromise where the current serum biomarkers are known to be less accurate. With development of the 30 min point of care testing, this is a potentially valuable diagnostic aid for decisions about emergency surgery and has potential applications across orthopedics subspecialties for infection diagnosis and monitoring.

Research perspectives

Novel serum biomarkers show potential to increase the accuracy and decrease the time to diagnosis of septic arthritis. Future research in a larger study population is needed to validate these findings, which could then be replicated to investigate other topics in orthopedics such as periprosthetic joint infection, septic arthritis in pediatric patients, fracture non-unions and hardware infection.