I'm Jim Standard, I'm presenting for Jimmy Cook, and he was a co-author with me on this. We appreciate the opportunity to present this work. My disclosures are in the database. So you may ask, we know we don't have florid, overt immune responses when we do fresh osteochondral allografts. We've been doing them for 40 or more years with some really good results when they heal. But as was pointed out by Dr. Merkley in the Boston group, the failure rates are a lot higher than any of us likes, and we wanted to look at whether there might be a sub-rejection reaction that is contributing to these failures rather than a fully florid immune response. There are many factors, as was pointed out in the first talk in this series, that can lead to failures, but immune response is one that we feel needs to be looked at for whether looking at these factors can potentially increase our success rates. So the methods of this study were relatively straightforward. We have a large IRB approved database that we maintain, a registry, and we took all of our failures at that point for which we had all of this data, the one data type that we were dependent on somebody else for was the donor blood type we had to get from the tissue bank, and we wanted to have a 2-to-1 ratio of successes to failures, and so we matched them for age, body mass index, and then these were a mixture of hips, ankles, and knees with by far the most common being knees, and we wanted to look at ABO and RH incompatibility as well as both. The failures, we then had recovered tissue from as many of those as we could, so of the 33 failures, we had recovered tissue from 18, and we looked at those with histology and immunohistochemistry. So the results are relatively straightforward. The answer is RH mismatches, ABO mismatches, or both did not impact the success or failure of these graphs. In none of the cases was there anything even close to a statistical significance from either of these, so that's good news. What was a little bit interesting from this is when we looked at the 18 failures that we had data for or full tissue for, 66% of those 18 or 12 had a large cellular immune response when we did the histology and immunohistochemistry. So in the failures, there was something going on in terms of the significant immune response, but when we looked at those 18 and again looked at RH, ABO, and the combination, there still was no significance in either of those factors being mismatched leading to this. So what did we learn and why are we even looking at this? What we learned is that first, ABO and RH donor recipient mismatches are not associated with any higher likelihood of failure, so we don't need to match based on blood type. We also learned that even amongst the failures, the mismatches of these two factors are not associated with failures, but we also learned that in amongst failures, a significant amount do have a significant immune response, leading us to need to consider why. Is it the sex mismatch that was presented in the first case? Is it that and other factors? And that's what I think we need to look at because we are seeing a fairly florid response amongst a large number of the failures. So what do we do next to try and address this? I think we do a lot of techniques to minimize the immune response, like washing bone marrow elements out, maybe soaking the grafted bone marrow aspect concentrate. We do both of those things. And then other factors that we can look at to try and decrease any possible immune response and hopefully take our failure rates to a much lower level. Thanks very much.

fresh osteochondral allografts

immune response

failures

ABO and RH mismatches

graft success