Thanks, Ben. Thanks Mike and the program committee for this opportunity to talk about PRP and hamstring recovery in athletes. I think this is a nice model to end this session with, as it has some real translational kind of research and kind of clinical applications here. So here's my disclosure, which this company does have a product in this market, so note. So why are we, why do we care about hamstrings? Well, really, for this group, I don't have to tell you that hamstring strains really have a huge burden of disease. It's the most common muscle strain we see in athletes. The reports are about 29% across many papers in various sports of all injuries. Re-injury risk is somewhere between 12 and 31%. NCA series shows about 33% of hamstring tears are recurrent. And these injury rates, despite preventative programs, despite the implementation of the FIFA prevention programs, really have not gotten better. And some reports among soccer players are getting worse, about 4% a year. Recent papers out of our societies, Bob Anderson and the NFL Musculoskeletal Committee reported just recently in AJSM that of all lower extremity injuries in the NFL, hamstring injury is the most common injury. The one season risk to all players is about 9%. And really only second in lost days to ACL injuries, just because of the high burden of lost days with ACLs for all player days lost. This is similar to what's seen in the European Soccer Leagues. This is a recent report out of the English League, where it was a cohort study they followed for one year, 243 players, and found that hamstrings were 16% of the injuries, or 27% of these injuries were recurrent. So a huge burden of disease that we're trying to treat. We all know the conventional treatments, rest, ice, compression, modalities. We're starting to get into some more advanced things, BFR, GPS for progression, a lot of eccentric exercise have been shown to be preventatively helpful, but we really haven't mastered this injury. We know there are certain factors that lead to longer recovery times, certain clinical factors that we've seen across these studies, including the degree of injury and the amount of pain that the player's in, as well as certain MRI factors that lead to longer recovery times, including the degree of involvement of the muscle injury. And some of this has come out of my partner Jim Bradley's work over the years with our radiology team. What we know, though, with these MRI studies is that very frequently these injuries that are re-injuries occur at the same level as the first injury. So this published report out of Qatar, AGSM 2016, showed that 80% of these re-injuries occurred at the same location. These players went back at 19 days, they re-injured 24 days later, and their conclusion was there's some incomplete biologic or functional healing to the first injury. So where does that take us? Well, we should look to the basic science. So we know skeletal muscle has the ability to self-repair. We know this is a complex process of degeneration, regeneration, remodeling over the course of six months, and it may result in scar formation. So there's been an intense interest for the treatment of muscle injuries. Can we activate, modulate, accelerate, ameliorate this tissue healing process at the cellular level? So let's go through a little bit of the early papers, and then we'll get to the clinical papers. So the group out of UConn, Gus Mazzocca, Bob Arciero, and Jim Bradley, really looked at this early on, 2012. They wanted to see what's the effect of PRP on muscle, tendon, bone. They found that, you know, really when you expose these tissues to PRP, you get proliferation at the various cell types, so they kind of were unsure what dose effect and what may be the optimal treatment. Many other groups have looked at this at the basic science level. This paper looked at a rat model injury and showed that PRP-treated muscle led to more neovascularization, slight reduction of fibrosis. Johnny Huard's lab, initially out of Pittsburgh and then at Vail, looked at what happens if we try to modify PRP with TGF-beta-1 antibodies to block TGF-beta-1, which may lead to fibrosis. And they found a very significant study that this customized PRP led to increased muscle regeneration, reduced fibrosis, enhanced angiogenesis, and so these findings were all very promising for the effect of PRP on our clinical patients. This has been then done in a mouse model as well as rat models, and what has been seen is that timing is essential. In this paper out of Brazil, when PRP was done at seven days, that was the only time that they saw increased performance and decreased fibrotic area. This group looked at a rat model, a group out of Spain, and also tried to compare what was the effect of using PRP versus our conventional exercise therapy. And they found that both improved outcomes in the forced recovery, but they did not see any synergistic effect when you combined exercise therapy with PRP in these muscle injury models. So what's been shown with hamstring injuries then at the clinical level? We know that there's some promising basic science data, the effect of PRP on muscle healing. While there have been several really well-done studies, as was alluded to earlier, this is a recent critical meta-analysis of the use of PRP, a second one out of the New York group that looked at best and worst case analysis of PRP, and really the long story short is that there's not convincing data, but there is some non-significant evidence this group pointed out that suggests that PRP reduces time to return to play or re-injury rate. In their paper they said about five days improvement at the bottom there in terms of overall return to sport. So let's go through some of those studies. Jim Bradley, my partner, was one of the first to report this at the NFL Physician Society in 2010. He reported on his experience with 26 players over two years, and showed that they had, with PRP injection, less pain early on, and objectively, earlier improvement in their ability to perform plank testing, range of motion, and strength at the terminal 15 degrees of flexion. Most importantly for our discussions with the coaches, front office owners, was that this therapy led to one game difference in return to play for our players in this group. So we've, and I'll talk a little bit more about our protocol at the end here. This has led to several other studies. Art Redding and the group at Indianapolis then published an OJSM in 2014, 10 players, five and five, whether they were injected or not, they reported no difference in return to sport using Biomed GPS, which is a leukocyte-rich preparation of PRP. First randomized study that really looked at this came out in AJSM in 2014. Group out of Malaysia randomized 28 patients with grade two hamstring injuries to either a single PRP injection or no injection, again, using the leukocyte-rich Biomed GPS application. They found return to sport was 42 days in the control group and 26 days in the PRP group, which was a significant difference, as well as a significant difference in the pain severity scales in the PRP group. This was also followed up by a large study by Hamilton and all that randomized 90 athletes to PRP or platelet-rich plasma, PPP, platelet-poor plasma, or no injection. And really found, the only significant difference was they found that return to sport with PRP was reduced timeframe compared to platelet-poor plasma, but not compared to no injection. There was no difference in re-injury rates. An interesting group of studies came out of the Dutch Hamstring Injection Therapy Study. Initially this was published as a letter to the editor in the New England Journal of Medicine in 2015, 14, and then followed up with the more formal report in British Journal of Sports Medicine 2015, where this group randomized 80 patients to saline or PRP injection within five days of injury. And they reported a 42-day return to sport in both groups with no difference in re-injury rate between the two groups. So putting it all together, we published our group report in OJSM in 2020, looking at our experience with a 10-year outcome with our team, 69 grade two injuries that we used using a leukocyte-poor preparation of platelet-rich plasma with the injection given 24 to 48 hours after the injury. Our primary findings was that we did see a significant one-game overall difference in return to play, although there was no difference in the number of days or number of practices missed, and there was one recurrence in each group. So our current protocol is we do utilize a leukocyte-poor platelet-rich plasma injection with our hamstring injuries 24 to 48 hours, primarily in grade two injuries. The grade ones oftentimes we find don't need it, and we've really focused our energy on the grade two injuries. Oftentimes we'll give a second injection or a third injection, depending on the progression. We've started to utilize more functional progression, including workload monitoring with GPS to assess when the player is ready to get back to play. So in summary, hamstring injuries have a huge burden. It's a common athletic injury. It has a high disease burden with time lost. There's been immense interest in PRP, as has been discussed today, as an adjunct to try to return to sport and decrease re-injury rates. But the outcomes are really mixed, and this may be a result of what we've discussed here today, that the formulations of PRP are variable. Each person makes a different type of PRP on a different day. Should we be using leukocyte-rich? Should we be using leukocyte-poor? It seems to us that the leukocyte-poor PRP in these acute muscle injuries may be more beneficial as they don't create as much of a healing inflammatory response and pain as has been discussed here. So again, these variable outcomes may be due to leukocyte concentration, anticoagulants, platelet-activating agents, local anesthetics, and PRP volume, all of which need further study. Thank you very much.

hamstring strains

athletes

re-injury risk

platelet-rich plasma therapy

muscle healing