Thank you, Ken. So an area that's received less attention is muscle, actually, in this area. And if you take care of athletes, muscle injury is probably one of the more common things we see. So Ashish Bedi from Chicago talked to us about muscle. Thank you, Scott. And thanks, Anna, for the opportunity to present. I have no disclosures related to this presentation. I think one theme that's come out nicely in this panel, and I think it's going to be addressed shortly by Dr. Mandelbaum, is one theme that is very clear is one size does not fit all. And so as we're thinking about the various tissues that have just been presented, we have to think about what's our goal. And of course, my focus is on muscle. But what we would want in a biologic reaction after muscle contusion or strain will be very different than, for example, a ligament strain or a contusion. And in thinking about this, we need to customize our approach. And so as Jason showed nicely earlier, whether it's tendinopathy versus a different injury, we need to think about the target tissue in the existing biology. And certainly, one size fits all in terms of PRP or concentrated BMA will not be the universal solution. So for a quick 101 in thinking and shifting towards muscle, let's just review that this is the structural skeletal muscle. It has this very organized architecture with layers of surrounding tissue from which vascularity arises, including the paramecium, epimuseum, and endomuseum. Just as a brief review, let's remember that within this are different types of muscle fibers. So type I or slow-titch fibers are more responsible for oxidative metabolism in endurance-type activities. Type II and fast-twitch are more for short, higher-energy bursts. And of course, the relative proportion of these fibers can have impact in how that muscle recovers in different individuals and different athletes. Similarly, when we use the word muscle injury, you need to take a slightly deeper dive. And remember, there's different types of injury in our athletes. There's muscle contusion in contact sports that can result in one type of fiber disruption and edema. But it's the more common strain pattern that we're often focusing on with our biologic studies, which are usually eccentric loads that result from recurrent submaximal loads. And of course, the most common location for injury in that setting is the myotendinous junction. It's important to take one step back and realize that one of our problems in this area when we're evaluating biologics is we actually don't classify these strain injuries well. You'll use these historical or often see these historically graded terms of grade I, II, and III, referring to no fiber disruption, some fiber disruption, and a complete tear. But studies now show that actually we grade these relatively poorly and we're very heterogeneous. Scott Rodeo and the group has actually done great work with the NFL, and we've done some work with the NBA to point out that, in fact, a standardized classification needs to be utilized with MR imaging. The most common and universally accepted is the so-called BAMIT grade, which localizes not only the severity of injury, but characterizes it as either myofascial, musculostatendinous, or tendinous by a subgroup of A, B, and C. And so it's critical when we refer to the type of biologic we're using that we also think about the type of injury we're treating by BAMIT grade. In terms of the challenge of skeletal muscle injury, I think we've learned across this panel that each one of these tissues has its unique challenges. With regard to muscle, much like was shown earlier, the decrease in muscle mass that we see is really only the tip of the iceberg. Lindsay Lepley and Ryan Palmieri-Smith, some of my former colleagues, have pointed out this complex issues that occur in the muscle that lie deep to the surface. There is a neuromuscular inhibition that occurs immediately with contusion or strain injury. Immediately there can be an influence of local pro-inflammatory cytokines and activation of satellite cells that may be reduced in some muscles, for example, rotator cuff with fatty atrophy, as opposed to healthy skeletal muscle. In terms of what can we do with muscle injury today, what does the literature tell us? These are the best studies I could identify for my presentation. This is one of the best randomized control trials that's been done by Chalabi, where they looked at inclusion criteria age 18 to 50. They looked at incidence of recurrence, but even followed with MRI grading the influence of platelet-rich plasma, but also platelet-poor plasma. What was the end result of this? What often we're seeing in the literature, no significant difference in time of return to play. When you do a deeper dive in terms of recurrence risk with muscle strain, no significant difference between the groups. And then when they even look at percentage decrease in terms of edema on the MRI, no significant differences. So what's the summary here? They saw no improvement with PRP or PPP in high-level professional athletes and elite athletes, but in their group, PRP did better than PPP, but no better than control. What about this well-done study from Zaffignini in 2021? They also looked in 374 patients using platelet-rich plasma. Essentially, no significant differences were found with regard to pain, muscle strength, muscle function, or imaging, indicating that PRP injection for these strains was at least not the anecdotal evidence of increasing and expediting return to play. This study actually done in a high level of Dutch athletes. This was 80 competitive and recreational athletes. This was a double-blinded randomized control trial. They looked at the recurrence rate as well as the incidence of return to play. No significant difference in the two-month re-injury rate, and no significant difference at a year as well. There are some studies that have reported some expedited return to play. This is one back from 2015. They looked at specifically quote-unquote grade 2 hamstring strains. As I pointed out earlier, this is probably more heterogeneous than we realize. But in their group, they reported a mean return to play that was somewhat faster in the PRP compared to the control groups. Josh Chahal and colleagues also reported this in 2018. This was more of a systematic review putting the literature together. There was a treatment effect with regard to expedited return to play. But as Jason pointed out earlier, you have to look at what that effect was. And it was relatively small, only about five days, probably somewhat arbitrary in terms of the return by the team physician as opposed to maybe a treatment effect. So are there exciting things potentially on the horizon? I hope so. As has been mentioned earlier, lipid-based stem cells, as Professor Randelli pointed out, can be advantageous. Again, he pointed out very nicely, this is likely not engraftment of these cells into the tissue. It's more likely a paracrine effect. And this study pointed out that the cells that were injected, in fact, did not survive, but seemed to have some enhancement in terms of myogenic activity. Some other things to pay attention to, Johnny Huard and others have taught us about some other molecules to think about with muscle. In particular, he studied suramin. This happens to be an antiparasitic medication that's been used for African sleeping sickness. But it's been demonstrated to have some favorable effect in terms of inhibiting myostatin and promoting myoblast differentiation. There's also been some studies looking at losartan. We're all familiar with this as an antihypertensive, an angiotensin receptor blocker. It's now been studied as a antifibrotic agent. And there have been some studies demonstrating that PRP plus losartan may have a favorable effect in muscle in terms of inhibiting muscle fibrosis after injury. Lastly, I'll talk about growth hormone. This is some basic science work that points out that local delivery of growth hormone, actually both in tendinopathy but also muscle injury, may have some favorable effects. So in summary, we need to think about muscle contusion and strain. We have to have standardized ways of grading muscle strain with a BAMIC classification system. PRP remains equivocal in terms of expedited return to play and reduced incidence of recurrence. Future opportunity may lie with adipose-derived stem cells. And we need to look at antifibrotic agents like ARBs and losartan that may have some favorable effect after contusion or strain. Thank you.

muscle injuries

treating muscle injuries

biologic reaction

muscle fibers

MR imaging