“We were studying 23 different proteins and could not settle on the best biomarker,” said Dr. Deirmengian. Despite an order from the top to stop learning and pick a biomarker, Keith and I said, ‘Let’s do another run,’ adding a few more biomarkers, including alpha-defensin.’ That run demonstrated alpha defensin as the best biomarker to diagnose PJI.”
Acquiring a Lab
While equipped with talent and data, the young company was still finding its wings when it came to growth. “We were a small company…and we needed substantial progress to reach the market. The solution was to partner with Zimmer Biomet, who funded us on a milestone basis and obtained a position on our board.”
Carl Deirmengian credits his CEO Dr. Birkmeyer with the genius-level next move. “Rick found a CLIA-approved [Clinical Laboratory Improvement Amendments] clinical lab in Maryland and told the two managers—who were near retirement—‘We want to acquire your lab with company equity alone. In two years if you don’t like what you see then you get your lab back, and we get our equity back.’ Pure genius. Now we could make the test available for clinical use, and widely expand our research abilities.”
Building to 1,000 Samples/Week
“We began receiving 50-80 samples a week as people began to understand what we could offer. The next step was not just to perform an alpha defensin test, but to do a complete panel. We optimized our performance of culture, white blood cell counting, crystal analysis, aspirate quality assessment, and also developed tests to identify pathogen antigen in the fluid. Over time we reached the level of processing 1,000 samples a week.”
Initially, Deirmengian’s lateral flow version of the Alpha-defensin test was somewhat controversial.
“Despite our quite comprehensive internal validation that matched the laboratory version, certain smaller European studies indicated that it may not be as sensitive. But these smaller studies did not truly reflect the accuracy of the test.”
Deirmengian and his team designed a prospective, multi-center, blinded clinical trial to evaluate the performance of their Alpha-defensin Lateral Flow Test for PJI which incorporated a disposable cartridge-type device that hospital laboratories can use to get a result in 10 minutes.
The study showed that Deirmengian’s alpha defensin lateral flow test and the laboratory test were identical in sensitivity for infection. FDA authorization of the lateral flow test came shortly thereafter. It was a first in orthopedics.
15-Year Effort Leading to AAOS’ 2020 Kappa Delta Award
“Like most physicians, I thought research was always done in an academic institution. In our case, being under a business umbrella forced us to demand academic rigor with third party oversight…which added even more quality and credibility to what we were doing.”
The great accomplishment of Dr. Deirmengian’s work is that it vastly improved the ease and accuracy of periprosthetic joint infection diagnosis. While various societies, notably the Musculoskeletal Infection Society (MSIS), International Consensus Meeting (ICM), and others, provide criteria-based scoring systems for infection research, they also require a combination of hospital tests that were not intended to diagnose joint infection. Furthermore, they weren’t specifically designed for the orthopedic community. As a result, lab-reported results often do not match the orthopedic recommendations.
Deirmengian’s Alpha-defensin Test gives the orthopedic community its own standardized test and reported in terms of diagnosing PJI.
Seneca said, “No man is more unhappy than he who never faces adversity. For he is not permitted to prove himself.”
Carl Deirmengian has proven himself and, in his own words, “Hopefully there are more tests made for orthopaedics in the future.” No doubt, Dr. Deirmengian will succeed.
[1] Kurtz SM, Lau E, Watson H, Schmier JK, Parvizi J. Economic burden of periprosthetic joint infection in the United States. The Journal of Arthroplasty 2012;27:61-5 e1.
