Hi, everyone, welcome. Welcome to our advanced MSK clinical session titled Rapid Fire Insights, PRP and VIELD, where we will give multiple 10-minute short presentations in a rapid fire fashion, trying to address the provider's top questions on PRP using the latest evidence. The focus of this advanced clinical session is to go past the basics and to provide those who are counseling or doing PRP with the latest updates to help improve clinical care. Please save all questions for the end and submit it through the app, so we'll have a short 10-minute Q&A at the end. All right, so I want to introduce our amazing powerhouse panel who will be speaking to you all today on this topic. While I could spend, you know, 10 minutes talking about everyone's accomplishments, just for the sake of time, I'm just going to briefly introduce everyone. So my name is Jen Suhu, I'm one of the sports medicine physicians at Weill Cornell Medicine and will be also the moderator for today's session. Next we'll have Dr. Allison Schroeder from MetroHealth, followed by Dr. Bill Berrigan from UCSF, followed by Dr. Robbie Bowers from Emory, fifth we have Dr. Brendan Boettcher from Mayo, and last but not least, we have Dr. Jenny Yuan from Uniformed Services University. Here is the list of the topics that we will be covering today, so first I will be kind of setting the stage and giving a little intro, then Dr. Schroeder will be talking about the latest updates on pre-procedural considerations, Dr. Berrigan will talk about the ideal composition of PRP for joint versus tendon, Dr. Bowers will talk about PRP versus PPP for muscle injury, Dr. Boettcher will talk about how to best deliver PRP, and then Dr. Yuan will end us and talk about the best evidence for PRP in upper and lower extremity, and then hopefully we'll have about 10 minutes at the end for Q&A from the whole panel. All right, so I'll just start off by giving a little brief intro on why we should care about this topic before we do a deeper dive into some of the more technical aspects. I have no financial disclosures. So why do we care about this? So musculoskeletal disorders is one of the most common conditions we treat here as physicians. According to the Global Burden of Disease Study in 2020, there are an estimated 494 million people with other musculoskeletal disorders globally, 123 increased since 1990. So what other musculoskeletal disorders include or exclude, or all musculoskeletal disorders excluding rheumatoid arthritis, osteoarthritis, low back pain, neck pain, and gout. So if you add some of those back in that we treat, you could see it would be a lot higher number. The global prevalence of other musculoskeletal disorders is higher in females and increased with age peaking 60 to 69 years. And the forecast increase of other musculoskeletal disorders is projected to be from 494 million in 2020 to 1060 million in 2050. So as you can see here, there's going to be a huge increase over time and something that we need to stay on top of treatment regimen wise. Tendinopathy is one of the most common causes of musculoskeletal disorders. And the incidence of lower limb tendinopathy alone exceeds the incidence of osteoarthritis. It's most common between 18 to 65 years. And the pathogenesis is multifactorial and complex and usually initiated by repetitive tendon overload leading to structural injury of the microscopic collagen fibrils. And then underlying poor intrinsic healing ability or lack of adequate recovery may lead to gradual accumulation of matrix damage over time. Osteoarthritis is also a very common musculoskeletal disorder that we commonly treat. It's the most prevalent form of arthritis and leading cause of adult chronic pain and long-term disability. In 2016 in the US, $80 billion in healthcare spending was spent on treatment of this alone. Globally 595 million people had arthritis in 2020, an increase of 132.2% since 1990. And then projected increase is significant of osteoarthritis as you can see listed here for all the different joints. And then kind of a one sentence definition of osteoarthritis is it's a disorder involving movable joints characterized by cell stress and extracellular matrix degradation initiated by micro and macro injury that activates maladaptive repair responses including pro-inflammatory pathways of innate immunity. So understanding kind of like the definition of like all these disorders that we treat is helpful as we then talk about PRP. So current standard of care for all of these musculoskeletal disorders that is covered by insurance include activity modification and load management, modifial risk factor modification, prescription of NSAIDs, oral and topical, physical therapy, plus or minus corticosteroid injection, which while can be very helpful for pain is not so helpful for healing and can weaken tendons and increase risk of rupture. And then surgery is usually also covered by insurance but something that a lot of our patients would like to avoid. About 20 to 40% of these patients will not improve with the current conservative standard of care which leads to patients always asking what else is there out there to help with pain and function but also there's been a growing interest of what else can help enhance healing and kind of prevent the degradative process. So this has led to the development of multiple other injection and treatment options aimed at helping with healing, pain, and function. The most popular one which we'll talk about today is PRP which has the most literature behind it. So PRP has rapidly gained traction over the past few decades. PRP first became most popular in the 1990s for oral facial wound management and then further gained traction in the sports medicine and ortho world in the 2010s. And then where it really kind of boosted into mainstream popularity is in the 2010s when multiple well-known pro athletes started using it to treat their tendon and joint injuries and it made lots of headlines as you can see here. So what is PRP really quickly because I know this is a more advanced topic. So PRP is autologous plasma derivative in which the concentration of platelets is above the baseline level. The basic underlying scientific rationale of the mechanism of action is that injection of concentrated platelets may augment the body's natural healing response via the release of many biologically active factors and adhesion proteins that are responsible for initiating the healing process. It is safe with no known adverse effects and no FDA approval is needed as it's derived from one's own blood and is not considered a drug. Just really quickly you can guys can look at this later this is just a partial list of PRP based growth factors and how they're evolved in healing and tissue repair. So specifically looking at the mechanism of action on tendons. So this is just like a very summarized simply in one sentence PRP helps modulate the inflammatory environment associated with degenerative tendinopathies as well as promotes healing through growth factors and cytokines to support effective healing. This figure here also helps demonstrate all the proposed mechanisms of action. And this is the nice one sentence on its mechanism of action in joints it helps modulate critical pro-inflammatory mediators and catabolic enzymes involved in OA as well as maintains joint homeostasis. Again some nice tables that demonstrate this effect. So how is PRP made? So usually step one you collect blood from the patient. The amount of blood is really dependent on what you want your end product to be and depending on the kit that you use. Hopefully that will be talked about a little bit later here. Step two is separation of platelets in a centrifuge either single spin versus double spin the most of us use a double spin procedure. So usually the first spin is to separate the whole blood from the plasma and then second spin will help develop that nice buffy coat layer that you can see in B here which concentrates all of those platelets and growth factors. And then step three you inject the PRP into the affected area. This is just a very simplistic figure of treatment options available and where PRP may lie for tendinopathy. The thing that I just want to emphasize when you treat any musculoskeletal disorder including tendinopathy is that you want to tailor the intervention to the stage of pathology and target the primary driver. So you basically want to individualize the treatment regimen for each patient. Early on you might start with load management and addressing poor function biomechanics. If pain is a huge piece of this you might use other modalities such as NSAID shockwave tendon scraping high volume injection. But then when you want to target the structure itself that's where PRP can be helpful. PRP as a lot of you may know faces some challenges when looking at the research and having strong literature to support its efficacy. Here are some a brief summary of some of those challenges. So there are a large number and variability of commercially available PRP and PRP like systems. There's lack of standardization in PRP prep protocols including collection volumes composition. There's a lack of consensus on injection technique and protocol and some of these things will hopefully be addressed a little bit later in these future talks. There's a low level effect how much that plays a role in some of the research that we do. Cost and accessibility as it is not currently covered by insurance and then insufficient understanding of the mechanism. So although PRP contains a lot of growth factors that may be healing the exact mechanisms by which PRP affects the structure that we are injecting it into is not fully understood which makes it a little bit harder to refine treatments and predict which patients may benefit most. All right. So that's just kind of a really brief setting the stage and then I will turn it over to Dr. Schroeder who will talk about start talking about some of the more technical aspects. Awesome, thank you. So, I'm going to talk about some pre-procedural considerations related to PRP. I don't have any disclosures. We're going to talk about medications, supplements, diet, exercise, and then some chronic conditions. These are a lot of questions that I'll have patients ask me about or conditions that patients have where I'm considering is PRP the best treatment option for them. Before I dive into those, or sorry, we're going to talk about medications listed here, and we'll dive in a little bit deeper. But before we get into the specifics, I want to take a step back to a little bit of the basic science that helps to inform some of my decisions in whether or not we're offering a PRP injection to our patients. So, one thing to keep in mind, platelets turn over roughly every nine days, nine to eleven or so. So, anything that we think blocks platelets shouldn't matter after nine days. So, the maximum amount of time before you're doing a PRP injection that you probably need to stop anything would be nine days if you're being a purist. This clotting cascade after I finished first year of med school, I never, ever wanted to see again. But here it is. As a sports medicine physician, I have to deal with it. I do not want you to, you know, re-memorize the clotting cascade. But if we look all the way back at the beginning, I'm sorry, I don't have a pointer. On the left side, our antiplatelets block the platelet at the beginning before that is even activated to get into the intrinsic pathway. So, when we're talking about corticosteroid and NSAIDs, it's this even step before we get down those pathways of clotting. We think that clotting cascade and platelet activation matters, right? Because with PRP, the platelets need to be activated to release their factors. A lot of PRP kits contain activators that already maybe skip that activation step, even if we have things that are trying to block it. And we'll talk a little bit about that later. So, again, the steps through the corticosteroid and NSAID mechanism of actions where corticosteroids block phospholipase A2, NSAIDs block cyclooxygenase, and then prevent these downstream effects. The one thing downstream I want to point out is thromboxane A2. And only because we measure the metabolite thromboxane B2 in all of these basic science studies, looking at whether or not the medications affect platelet function. So, here's me, and I'm sorry if that QR code is cut off, trying to distill down medications and the studies on them. So, this is a picture that you can take. That QR code has the link to all of the references. If we're kind of walking through this, aspirin irreversibly blocks COX. It decreases platelet aggravation, decreases thromboxane A2, does not change platelet count, and then, in theory, decreases post-procedure inflammation. So, if you're being a purist, it irreversibly blocks COX. You probably need to stop the medication for 10 days if you don't want it to affect the platelet degranulation and function. That being said, there are basic science studies that when you use an activator with your PRP, it can overcome some of the blocking of aspirin. From a non-selective NSAID standpoint, those reversibly blocked COX have the same effects as aspirin, but most of the half-lives of these NSAIDs are less, and I'll talk about this briefly. So, you can stop that based on half-life. Selective NSAIDs, we don't think have as much effect on platelets, and some of that goes back to the cardiology literature. So, do we actually need to stop these selective NSAIDs? Probably not, even though many of us do in clinic. Tylenol, which I often prescribe after PRP injections at high dose, especially when combined with NSAIDs, can have some of the same effects that aspirin does on platelets. Statins, looking at the cardiology literature, may also affect platelets, but probably not to any extent that it's going to affect our PRP. NOACs also do affect platelets, but we put anticoagulant in with our PRP. So, these are something I typically continue just because of the risks of stopping those medications are likely more than continuing them, and we do not have any good data that it affects the efficacy of PRP. And from a steroid standpoint, I'll typically hold steroid injections for a month or wait a month after a steroid injection before performing a PRP injection. This is another slide that is busy that you should take a picture of, and I am not going to read through it like I did the last one, but the important thing to keep in mind here is that most medications are out of the system and pretty low in the bloodstream after five half-lives. And so, that's when we think about how long would we, in theory, need to hold something if you're being a purist and really want to hold these medications, particularly looking at NSAIDs. And being honest, from a practicality standpoint, and we were all just talking, we mostly tell patients wait a week. Don't take NSAIDs for a week before you have a PRP injection. That is a blanket statement that prevents nuanced questions, but I will tell you if I have a patient come in and like, oh no, I took an ibuprofen yesterday, can I still get my PRP injection today? And the answer is probably yes. It's probably not. That one ibuprofen is likely not going to have a large effect on their PRP injection. The other thing, most of the studies related to these medications are basic science studies. We're not looking at the efficacy of PRP injections clinically in patients on NSAID medications or on aspirin. It's hard to study. It's hard to control for any other variables that actually matter. From a supplement standpoint, this is another slide to take a picture of. There are several strong antiplatelet effects with garlic, capsaicin, hawthorn, and alcohol. This is all, again, based on the cardiology literature. There's nothing specifically stating that in a study that these will alter the PRP's efficacy, but it's something to think about. A lot of times patients will ask me, well, what about anything that's anti-inflammatory? So those are the strongest anti-inflammatory effects have an asterisk. Ginseng's another one. Those are things that patients are commonly taking, and I typically tell them we don't really know if it matters, and if you're a purist and you're paying for PRP and you're willing to stop these for a week or so, you probably should. Diet is another question that I get asked about. I'm eating clean. I'm on an anti-inflammatory diet. Can I still get my PRP injection? Is it going to change it? We have no data that an anti-inflammatory diet makes a difference. Lipid-rich foods in the cardiology literature affect platelets, and we have no data that that alters our PRP injections as well. So typically when I'm counseling patients, you know, their standard diet is okay. There have been a few studies looking at exercise prior to the blood draw, particularly the studies that look at high intensity exercise for a short amount of time have shown an increase in platelet count and platelet concentration with various other effects, and Dr. Berrigan is going to talk to you about platelet count. So this might actually matter. From a practicality standpoint, having someone on a stationary bike and immediately drawing their blood in clinic is, you know, a challenge. So I don't know if anyone out there is actually doing this, but maybe something to think about. And the other thing to note is they have also looked at an hour of submaximal exercise that has had no effect, so you can't just tell someone, hey, go for a run before you come and then we'll draw your blood. It doesn't seem to have the same effect. Other patient factors are things to consider. Age is one of them. All of these studies on age are just looking at in vitro. The patient-related studies that break down the efficacy of PRP by age are not as strong as some of these basic science studies, but the study by O'Donnell and Chowdhury both show that when you have PRP or ACP in the case of the Chowdhury study used with chondrocytes in a petri dish from aged patients that they actually are chondro, it's actually chondrotoxic compared to younger patients. And then there was a study by Berger on tendinopathy where it showed that the efficacy in aged patients was likely platelet dose response. So in older patients, if they injected a higher platelet dose, they had better outcomes or had better response to the in vitro study. From a sex standpoint, males have a higher cytokine and growth factor levels with PRP, and that specific study also looked at age, and this sex component was higher than the age component. Age and sex are things that we can't change in our patients. Am I still doing PRP injections in females and older adults? Yes. But I think there's a lot that we don't know, and there are probably many ways that we can optimize the PRP for those specific demographics. From a BMI standpoint, this is clinical data, but we don't think that BMI affects platelets with NeoA in general. And so for some of our patients that we see who have a BMI over 40 and are not surgical candidates, this might be an option. From a disease standpoint, and I'm going to rapid fire through these pretty quickly, these are questions that I get. In rheumatoid arthritis or inflammatory arthritis, probably five years ago, I was saying, you know, we maybe shouldn't do PRP. People are on DMARDs. Those are counteracting what we think PRP does from an inflammation standpoint, but there is now data in the rheumatologic literature that PRP is beneficial in some of these patients. In all of those cases, the patients were on DMARDs. Metabolic conditions from a soft tissue standpoint, they, if you think about a surgical procedure, diabetes, smoking might alter your outcomes. This might alter the outcomes of PRP, but we don't really know for sure. Anything that's affecting platelet concentration from a thrombocytopenia standpoint, I typically try to correct if possible. Otherwise, we're going to hear that platelet count probably matters. It might not be the best thing. Anything affecting platelet function in bleeding disorders, von Willebrand, hemophilia, if you can correct them, you should. From a factor V Leiden standpoint, we don't have any data. We don't really know. This causes clotting, so maybe it's helpful. I just counsel patients that it might not be as efficacious. Same thing with the HIV and AIDS and immunosuppressant medications where things alter immune function might not be as efficacious. From a cancer standpoint, again, not a lot of data, but in theory, if you have cancer cells circulating in the bloodstream, do we want to inject those back into someone else or into another part of their body? No, and I think most of us probably avoid PRP injections unless the cancer has been in remission for five years. Here are my take-home points. Just in the interest of time, I'm not going to read through all of them, but I think the thing to keep in mind is that we don't actually know the best thing for a lot of these factors. Patients often will read the internet and get hung up on of like, oh, you didn't have me stop my ibuprofen for two weeks before I took the medication or took the injection. We don't actually know if this matters, and so I'm not holding PRP for people on medications that they can't stop and things like that, and I think up here, you know, there's, we all were just talking, there's a lot that we still don't know to optimize things moving forward. Thank you. And there's references, the QR codes again if you need them. All right, so I'm going to be talking about the ideal composition of PRP. I have nothing to disclose. So we've already heard the definition of PRP and what constitutes it. Well, the question is, what most matters? And to answer this question, you need to understand PRP. But to understand PRP, there's multiple aspects to consider. So what I'm going to be going over today is platelet dose and also leukocyte rich versus leukocyte poor and how that applies clinically. So I mentioned dose, but what is dosing? Well, we need to start to think beyond concentration. Now we already know that the optimal concentration to meet angiogenesis and cell proliferation is about 1.5 million platelets per microliter. But we as clinicians don't necessarily think about concentration. We think about how much we're delivering to the patient. And to calculate this, you multiply the platelet count of the PRP by the obtained PRP volume. We could then classify this as very high, high, medium, or low dose PRP. And this is important because you need to know how to dissect the literature. There's been multiple randomized clinical trials recently that have come out and show that PRP is ineffective for certain musculoskeletal conditions. But when you look at the actual data and the PRP that are used, it's usually a lower dose PRP. And we published that this did not suffice. We performed systematic review of level one and level two clinical trials for knee osteoarthritis, of which we found 29 studies with 31 PRP treatment arms. 28 out of 31 showed that PRP was a successful treatment option. Of those 28, the average dose was about 5.5 billion. Of the three studies that showed that it was ineffective, they used about 2.3 billion platelets. It's a much higher dose within the positive studies. And we took this another step further in a meta-analysis, a meta-regression analysis, where we also included multiple doses of PRP. We found 42 studies that focused on NeoA, and we included 24 studies in our meta-analysis and meta-regression analysis. And we separated our studies based on less than 5 billion platelets, which is at the top of the forest plot, between 5 and 10 billion platelets, which is in the middle, and more than 10 billion platelets on the bottom. What we found is that greater than 10 billion platelets outperformed the controls. Now we also wanted to see if there was a dose-response relationship, and there was. So if you look at the graph there on the right, you can see that as the platelet dose increases, so does the effect size within the WOMAC. And this held true at 12 months, where greater than 10 billion platelets is, again, outperforming the controls, and there remains a dose-response relationship, albeit less than it was at six months. This may, however, be because there's less studies at 12 months than there were at six. Now there was 17 studies that included the visual analog scale, and again, we see that more than 10 billion platelets outperforms the controls, and there remains a dose-response relationship, but less than that at the WOMAC. The VAS at 12 months, greater than 10 billion platelets is, again, effective, and then we don't see as much of a dose-response relationship for the VAS at 12 months. Now interestingly, the highest relationship that we saw is with the COUS sport. So potentially, a higher platelet dose is necessary to achieve better outcomes for higher activity-level patients. Now PRP also gets a bad reputation for tendinopathy, because some of the other studies that use lower-dose PRP. So we wanted to include this within our analysis. And I'll start by saying there's much less literature out there on this topic. But we did find three studies for lateral epicondylopathy and five studies for rotator cuff tendinopathy. All studies show that PRP was an effective treatment option and was statistically significant. Now the difference comes when you look at it compared to the controls. So for lateral epicondylopathy, all studies outperform the controls. This is even at a dose of 2.4 billion platelets. When you look at the rotator cuff, there's only one study that outperformed the controls. This was a dose of 16 billion platelets. This is derived from a series of four injections. Doses of 3 billion, 5 billion, and 7 billion did not outperform the controls. For gluteal patella and Achilles tendinopathy, we again see that PRP is an effective treatment option and a statistically significant improvement. But when you look compared to the controls, only Fitzpatrick and colleagues had a study that showed that there was a significant difference compared to corticosteroid injection. They used about 6 billion platelets for gluteal tendinopathy. Now if you notice that Thompson also used 6 billion platelets for gluteal tendinopathy. But the difference between these two studies is that Thompson didn't actually use ultrasound guidance. For the patella tendon, Scott used about 3 billion platelets. Ross used 6 billion platelets. But compare that to BMAC, or bone marrow aspirate. And so there's a potential that, you know, that's also another good treatment option for patella tendon. For the Achilles tendon, they compared to SVF and ECSW, again, other treatment options that are effective for tendinopathy. But it could still be that the 3 billion dose was not enough. So you might be asking, well, how do we get to this higher dose? What factors lead to it? Well, a higher amount of blood processed gives you a higher platelet count, so a higher blood draw. A double centrifugation protocol will give you more platelets than a single centrifugation protocol. And an increased centrifugation force can also give you a higher platelet yield. But if you're still unsure, you could use this excellent study that was published in 2020 that analyzed 36 different PRP preparations. They looked at volume of blood collected, platelet increase factor, recovery rate, and theoretical platelet dose delivered. And so you could cross-reference the machine that you use with what was published within this study to see if you're getting a good yield. Transitioning to leukocyte-rich versus leukocyte-poor. So I'm going to break this up into osteoarthritis and tendinopathy, since they're two different disease processes. So for osteoarthritis, classically, a leukocyte-poor PRP has been used. And that's because there was early studies by Filardo and colleagues that showed that a leukocyte-rich product actually produced an increase in inflammatory response compared to a leukocyte-poor product, but there was no difference at 12 months in that study. And this was supported by the basic science literature that showed the leukocytes released these pro-inflammatory and catabolic molecules that could be harmful to the joint. Now it's been thought that this may be more clinical speculation than having actual clinical translation. And this is because more recent studies don't necessarily endorse this, whereas some have shown that inflammatory response is self-limited as early as one week. And others have shown that there's actually more anti-inflammatory, maybe more anti-inflammatory properties within a leukocyte-rich product with increased levels of IL-1 receptor antagonists. Now the good news is we don't have to guess about this. There's been randomized controlled trials that have studied this. So there's one with 192 patients and one with 132 patients. Both these studies showed no difference between a leukocyte-rich and a leukocyte-poor PRP at 2, 6, and 12 months. Now both of these studies use a high-dose PRP, which is delivered in a series of three injections. It should also be noted that in the DiMartino study, there was more mild adverse events in the leukocyte-rich group, mostly related to increased swelling or increased pain after the procedure. For tendinopathy, historically a leukocyte-rich product has been used. That's because you need to create inflammation to lead to this proliferative response and also lead to tendon remodeling. And I still believe this is true, but the basic science literature will kind of move you towards a different direction. And some will show that the leukocytes actually produce multiple matrix-type proteinases that increase IL-1, IL-1 beta, IL-6, TNF-alpha, IL-8. It can decrease PDGF. It can decrease TGF beta. And all this can worsen the tendon microenvironment. This is opposed to leukocyte-poor PRP, which can have more anabolic-related factors. It can increase normal collagen synthesis, decrease the cytokine-associated matrix degradation. It can also create these larger collagen fibers and decrease tissue or increase tissue of inhibitors and matrix-type proteinases. So am I saying to use leukocyte-poor PRP over leukocyte-rich PRP for tendinopathy? No, not necessarily. The studies are mixed, and there's some that show that it depends on the severity of tendinopathy, with more acute phases of tendinopathy benefiting from a leukocyte-rich PRP versus more chronic stages benefiting from leukocyte-poor. And that's because leukocyte-poor and the more chronic stages can lead to excessive catabolism and inflammation, and that's not necessarily beneficial to tendon remodeling and repair. Now there's not a randomized clinical trial to date that I'm aware of that compares the two, but there is systematic reviews that come to a conclusion that leukocyte-rich PRP is better than a leukocyte-poor PRP. But if you look at the studies that show the leukocyte-poor PRP is ineffective, they tend to use a lower-dose PRP, about 1.6x or 361,000 platelets per microliter. So it's a lower dose. So in summary, platelet dose matters, but further studies are needed to elucidate the optimal protocols for both osteoarthritis and tendinopathy. A dosage of 10 billion platelets may yield better clinical outcomes in osteoarthritis. Both leukocyte-rich and a leukocyte-poor PRP product is beneficial for osteoarthritis. And leukocyte-poor PRP may be better for chronic degenerative tendons, but it's still unclear if the basic science and animal studies apply clinically. These are my references. Thank you. All right. Let's see if I can not be an idiot and figure out how this works. Oh, there. Hold on. Let's go back. All right. So thanks, everyone, for coming. My name is Robbie Bowers from Emory in Atlanta. So we're going to talk quickly about platelet-poor plasma versus platelet-rich plasma for the treatment of muscle injury and why platelet-poor plasma may actually be a better option for muscle injury. So I have no disclosures. So all of this information exists in this paper from Current Sports Medicine Reports that we published back earlier this year. So if you're interested in this topic and you want more information that fully dives into it, you can look up this paper, and it'll explain that. So here's a quick outline of what we'll talk about, and I'll skip over some of these slides for the sake of time at the end if we're running a little long. So really, in sports medicine, we have had an issue with decreasing the incidence of muscle injury. We've done a better job across all injuries and across other soft tissue injuries. But muscle injury, if you look at the scatter plot there, it actually looks like it's tracking up a bit. And muscle injury overall, it's the number one injury in all of sports medicine. So it's an injury that we need to be aware of, and we need to do a better job of diagnosing and treating. So what we're talking about with biologics for muscle injury, if you look at the muscle injury pattern here, what we're looking at here is to introduce within the first couple days after muscle injury, introduce a biologic injection to help with repair and remodeling. So we push the tissue into repair, but as we'll talk about in a bit, there's some of these factors. If you look at the far right, it says TGF beta 1. And those are some things that are in PRP that may actually push these muscles to fibrosis and scarring as opposed to muscle healing. So I'll talk about really quickly just the RCTs on PRP for muscle injury. And so there certainly are studies that are in the literature that are positive for PRP for muscle injury, but I'm just going to focus on the RCTs for the sake of time. So this RCT, 90 professional athletes looked at PRP versus no injection, used a good PRP system, and there was no significant difference in re-injury rates or return to play between the two groups. This is more weekend warriors. So average age, I believe, was about 45 in these patients. So we had 71 patients, PRP versus hematoma evacuation alone. And again, in the end, they determined that there was no significant difference in return to activity with PRP versus just hematoma evacuation alone. And this was a double, kind of two-part study. The first one in BJSM, the second one in New—or the first one in New England Journal of Medicine, second one in BJSM, and it's where they looked at 80 athletes. They used Arthrex ACP, which, you know, for muscle injury, the platelet dose may not be as important, but this is a lower platelet dose system. They looked at PRP versus saline, and return to play time in the PRP group and placebo group was about the same. Re-injury rate, there was no significant difference. And then they tracked this out to a year, and at all time points, they didn't really see any significant difference. So all of that is to say that with these high-level RCTs on PRP and muscle injury, this literature hasn't really confirmed that PRP is effective for muscle injury. This is a review from 2018, but still probably the best one on the topic that's out there. So why might PRP be ineffective? And really, the reason for that is PRP preparations I'd mentioned before, in vitro, demonstrates increased myocyte proliferation. What does that mean? That means muscle scarring and muscle fibrosis. So what we want is myocyte differentiation, which is muscle healing, where PRP causes myocyte proliferation. So like I said, potential for fibrosis and scarring. PRP increases this fibrosis, but why doesn't? We think it's some of these factors that are in PRP, namely TGF-beta-1, maybe myostatin, but TGF-beta-1 is the one we focus on at this point. So if you look at the figure over on the right, that is collagen staining in rat tibialis anterior muscles. And if you look at PRP, so increased collagen means increased scarring. So there's the most collagen deposition in these when you treat it with PRP. Then if you take this PRP and treat it with antibodies to remove the TGF-beta-1, then you have much less collagen deposition. So it seems like some factors or some ratio of these growth factors that's in PRP could be pushing the tissue more to fibrosis and scarring as opposed to healing. So why might platelet-poor plasma be better? So in this study, another basic science study that was done by Jason Dragoo and his group out at Colorado, platelet-poor plasma, in comparison to platelet-rich plasma, caused increased cell differentiation, like I mentioned before, and myotubule formation, and that's compared to PRP. So what we see with PRP and from a basic science standpoint is myocyte proliferation, fibrosis and scarring, and with platelet-poor plasma, myocyte differentiation, which pushes everything more towards healing. So this is just a summary table really quickly to show you what we're interested in. So platelet-poor plasma, you could probably put IGF in that as well, and it just tells you what our perceived downstream effects are on muscle tissue that I've mentioned already. So what about platelet-poor plasma clinical data? This is where we're lacking on high-level clinical data for platelet-poor plasma and where we need to go in the future. This is probably the best study in the literature with the highest numbers, and so Ryan Kruse and his team at Iowa put this out in AJPMNR here just back in July. Retrospective analysis, but looked at a high number of athletes. So 100 athletes with acute thigh injuries, so quad and hamstring, we see 51 PRP, 49 PPP. And if you look at that return to play, it's pretty striking. So return to play was 28.29 days for the PPP group and 47.71 for the PRP group. So very striking return to play in a larger number of athletes, and there is no difference in injury recurrence between the two groups. So I think this information, along with our understanding from a basic science standpoint versus the early clinical data for platelet-poor plasma for muscle injuries, you know, there is something to this, and there's something going on here, and why, in my opinion, platelet-poor plasma, based on our understanding at this point, is probably a better option if we're looking at one or the other. So these are just a few in my clinical experience. I'll run through these really quickly. So just some baseball players that I've treated with muscle injuries. And so the grade two lat strain, we used an ultrasound guy to platelet-poor plasma injection just a couple days after the injury, and if we look at the return to play data, so average return to throwing, time of 50 days, return to play at 100 days, and return to play previous level performance of 170 days. So if we just look at previous return or return to previous level performance, so we got this athlete back at 119 days, whereas the average in the literature is 170 days. These are a couple collegiate baseball players with higher grade oblique injuries, and again, instead of going all the way through this, essentially, you know, we got these players back faster than what you typically see in the literature with these oblique injuries in baseball players. And then lastly, this is just a hamstring injury. Same thing here, grade two hamstring injury, collegiate baseball player. We did an ultrasound guy to platelet-poor plasma injection. He returned to hitting 14 days post-injury and full return to play at 21 days post-injury. And if you look at data on grade two hamstrings from MLB, the return to play is 33.5 days. So certainly just cases, but these are some of my personal clinical experience where we've gotten athletes back faster than what you typically see in the literature. These images I'll skip through. It's just showing hamstring muscle healing after platelet-poor plasma injury on MRI. So future directions. So that's Halloween this year, and my son wanted to be Marty McFly, so I was docked with him. So future directions. I just wanted an excuse to put this picture in this talk, so, you know, I just made up something, so. So future directions. Whoa. Okay. All right. So this is, I think Dr. Podesta's here, so this is one of his papers with Peter Everts, and I talked with him about this topic just a couple weeks ago, and he got me thinking about some future directions. And so I had mentioned this previously. It may not necessarily be that PRP in and of itself is bad for muscle healing. There are factors within PRP that would be helpful for muscle healing. So maybe it's the ratio of these growth factors. So maybe a combination of PRP and platelet-poor plasma is actually better. So like I mentioned, there are growth factors in PRP that can still help with muscle healing, but possibly combining the two. So platelet-poor plasma concentrate, and that's where we put the platelet-poor plasma through a filter. I'll show you a picture of that in a second. That can create appropriate ratios of these growth factors that are ideal for muscle healing. And so IGF and HGF and platelet-poor plasma concentrate may counteract the negative fibrotic effects of the TGF beta that's in the PRP, where you can still get those healthy healing factors that are in the PRP while counterbalancing some of the fibrotic and scarring effects. But certainly that is more, you know, those are just thoughts at this point. So we need further data to push us that way. But if we're looking at PRP versus platelet-poor plasma in and of themselves, at the state of the data where we are now, I think platelet-poor plasma, using that by itself is a better option. And so these are just some of the factors that are in. So protein-rich plasma, let me go back. Protein-rich plasma is essentially platelet-poor plasma concentrate, and these are just factors that are in both that can be helpful for healing for soft tissues. And if anyone wondered how we make platelet-poor plasma concentrate, so that's another question. Is platelet-poor plasma concentrate superior to platelet-poor plasma alone? And so that's taking the platelet-poor plasma and putting it through this filtration device. So basically you filter it through. It pulls out the water content and concentrates the growth factors in the platelet-poor plasma. This personally is what I use for my muscle injuries that I treat. I'll put it through the filter. But Ryan Caruso at Iowa, who treats a lot of these, just uses the platelet-poor plasma by itself and has good results as well. So I think this is another question for us to answer in the future. So in conclusion, ideal orthobiologic treatment for muscle injury. It's easily attainable. It augments pain relief and recovery. And what we do find, I will say in my clinical experience with platelet-poor plasma, is doing the platelet-poor plasma injection rapidly decreases their acute symptoms. And so that's another benefit that I've noticed in my patients that we need to look at in the future as well. And it will regenerate healthy contractile muscle tissue with minimal scar formation and fibrosis. And this will reduce the re-injury rate. If we talk to some radiologists, when we have these athletes that re-injury or that re-injure, they'll look at the imaging, and it'll look like they've actually torn scar tissue as opposed to healing muscle tissue. And so I think this scarring effect is something that has some credence to it. Current PRP evidence for muscle injury is not strong. Platelet-poor plasma serves as a potential superior alternative. And just like I mentioned multiple times, that leads to muscle cell differentiation, regeneration, and healing, where platelet-rich plasma leads to muscle cell proliferation, fibrosis, and scarring. So more comparative PPP studies are certainly needed in the future. We're just getting started with a multi-site study, just getting it underway. We're in the process of, between the multiple sites, agreeing on our IRB and submitting it. So we're certainly far away from getting that data, but we're working on it, and we're going to get better prospective data in the future that we're currently working on. And then the question of, is platelet-poor plasma concentrate, platelet-poor plasma, or a combination of PRP and PPP, which of those is superior for muscle healing? And those are things we'll have to determine in the future as well. So special thanks to George. He was the first author on that paper that I mentioned. He's a PGY-4 at UPMC, so just wanted to give him a shout out. That's the whole family on Halloween. We kind of did a mashup between what the kids wanted to dress as. And thanks. All right, good morning, everyone. As I get my slides pulled up, I'll introduce myself. I'm Brendan Boettcher at Mayo Clinic Sports Medicine in Rochester. And I'll go pretty quickly. We're running a few minutes behind here, and I want to make sure we have time at the end for questions, because I think there's going to be a lot of them. And so I'm going to cover a handful of topics here, and I'll get through as many as I can in the time we have allotted. I have no disclosures. Here's what we'll talk about. So one of the first questions I get from patients is, gosh, I read online I should do three injections. Why don't we do one PRP? And why would we choose three versus one? Well, we have a higher overall platelet dose, prolonged contact of growth factors, re-dosing of growth factors as that effect wanes within the joint. Or maybe we have a car payment to make. Why would we choose one? Well, it's more convenient for the patient. It's effective for a lot of patients. We have a ton of RCTs showing a single high-quality PRP injection is effective, lower cost of treatment overall, more accessible for patients. I don't know about you, but my clinic is booked out. If I have to book every PRP patient three PRP slots weekly, it'd be very challenging. Well, what does the literature tell us? There's eight RCTs. There's two systematic reviews and meta-analyses looking at single versus multiple PRP injections. And what do we find? Well, we find that for function, three injections is better than one at six months, but VAS maybe not. And when we look up to a year, three is better than one. So it certainly seems like we have some good efficacy or evidence pointing us towards three injections versus one. When we pull up some of the details of those, we find that for early to moderate osteoarthritis, so KL1 through three, three injections is probably better than one. However, when we get to that KL4 level, one injection and three are equivalent. When we look at a single injection compared to three, compared to a placebo normal saline injection, at 24 months, they're all back to baseline. But before 24 months, three is better than one and is better than a placebo. And then what we found in that last paper on the bottom is that five is not better than three. So three may be the sweet spot if we're looking at multiple doses. From a consideration standpoint, my initial reaction was, well, they're probably doing a low dose single injection, and that's why three is better. But digging into the details, a lot of these RCTs, they actually use a relatively high quality PRP system with total platelet delivered greater than 5 billion in a single injection. And so it doesn't matter if they're all delivered at once or if they're spread out over time. What is the frequency of injections? Is it weekly? Is it monthly? And then what about three ACP injections, which would be less expensive compared to one higher dose? One of the things that Dr. Berrigan had on his slide, I believe it was for the shoulder, was that it was effective at 16 billion platelets. And what he had mentioned was this was delivered over four separate injections. Does three times two equal six? And does one times six equal six? Well, yes. Does three times 2 billion equal one times 6 billion? And I don't think we know the answer to that yet. From my practice standpoint, I'll just share with you what I do. My algorithm is relatively evidence-based with a little bit of nuance in it. And so I essentially deliver a single PRP injection. I target at least 5 billion platelets. I always use guidance with my biologic injections. I assess the response at six weeks. If they have a great response at that point, I tell them to call me when it starts to wear off. If they have a partial response, I'll repeat the injection at that point. If they report that they have an adequate response, they have high pain relief, but short duration, so maybe three months or four months, I'll repeat that PRP with a series of three. And if they have no response, then we'll either consider an alternative injection, a series of three, or surgical options. Other questions we get asked. What about local anesthetics in platelets? How does PRP get affected when we use local anesthetics? And we have a lot of basic science here. And I don't have a pointer, so I'm just going to kind of fly through these. But we can see that anesthetics induce cellular toxicity in the short term, so at 30 minutes, those bottom four, the bottom two rows indicate that. We can see that that cellular toxicity is attenuated by PRP. So when we use these equine tenosites and we add PRP to the local anesthetics, those are the gray columns, we see that that cellular toxicity decreases. We can look at the short-term effect on chondrocytes. Those last two slides were tenosites. So in chondrocytes, we see that in the third column, the lidocaine, in the fifth column, bupivacaine, that viability goes way down when the cells are exposed to those. However, in the fourth column and sixth column, you'll see that the addition of PRP to lidocaine and bupivacaine really attenuates that chondrotoxicity. When we look a little bit longer, so we look out to a day, we see that there's still increased viability when we add PRP, which attenuates that toxicity of lidocaine. But if we go beyond that and we look at five days after exposure, we see that that initial lidocaine and bupivacaine toxicity to the cells in that kind of left blue circle is only moderately attenuated by the addition of PRP. So there's probably some time duration effect of that initial exposure to anesthetic. We do see, however, that tenosite proliferation goes way up when we add PRP to these cells relative to the saline, which is the left two columns. We can see that anesthetics do not attenuate growth factor release, but they do attenuate platelet aggregation. We see that they have various effects on the physiology. So cellular viability is reduced, especially with bupivacaine. Intracellular calcium levels are reduced, especially with exposure to bupivacaine. Reactive oxygen species are increased with exposure to all anesthetics. And cellular apoptosis goes way up with bupivacaine relative to the other anesthetics or a control. With that, the conclusion was that bupivacaine is detrimental to platelets, causes shrinkage, decreased adhesion, calcium dysregulation, apoptosis, but a one-to-three exposure concentration of lidocaine or a one-to-three of ropivacaine seems OK relative. So essentially, we see that anesthetics are bad for cells. However, when we really want to look into this, it's more nuanced. So how many of you have cited this study when you tell patients that PRP is effective for lateral appendylitis? I have. We all have. We see that they mix this with bupivacaine. So even some of our initial PRP literature that was very positive uses the most toxic anesthetic and still shows good clinical response. Just going to add this in here for people to reference. So Dr. Kadavy put together a review on some regional anesthesia techniques for orthopedologic procedures. And that is something I've incorporated into my practice. So what I typically do is no role for anesthetic with intra-articular PRP injections. When we're doing soft tissue injections, we utilize regional anesthesia when is applicable and when is appropriate. And my practice with that is we do the blood draw. We do the nerve block right away. We let the patient sit for at least 15 minutes to let that take good efficacy. If they don't have adequate anesthesia with that, I do peritendinous ropivacaine, let that sit for a little bit. If that is inadequate, then I will do intertendinous ropivacaine. I don't want my patients miserable. I had a patient once tell me that she had a PRP injection with no anesthetic, and it was worse than 100 childbirths, and I never want to do that to a patient. And then, sorry, I didn't mention here, but throat ropivacaine, there's no role for it in our practices. All right, is adding HA to PRP better? This is a great question. There's been a number of RCTs over the year comparing these, number of meta-analyses in the last five years with some conflicting results. And so, some show it's equivalent, some show it's a little bit better. There are several different outcome measures that I looked at with a lot of different heterogeneity, including heterogeneity in the HA formulation, as well as heterogeneity in the PRP formulation. I think that's why it's so hard to do a systematic review on this particular topic. In my practice, if a patient is using HA monotherapy and that has been ineffective, I do not recommend adding HA to my PRP injections. If they have utilized HA monotherapy that has been effective or somewhat effective, I will add that to my PRP injections. And for some patients, I'll alternate HA and PRP. And I do offer combination therapy to pretty much every patient that is getting in particular PRP injections. All right, what about acute injuries? I'll fly through this real quick so we have our time. This is an area we have very limited evidence. So we have a couple of studies as early as 2008 that looked at this, as well as 2015. And the initial short-term response is that PRP is not effective after lateral ankle sprain. However, when we follow patients out longer, we do see that at that eight-week point, patients that had a lateral ankle sprain do better with an acute PRP injection. To me, it's unclear if the return to sport was any different in these two groups based on the paper. But by 24 weeks, they all return to the same baseline. We know that patients with lateral ankle sprains tend to heal pretty well if they're treated appropriately. So we expect that outcome. When we look at acute injection versus acute and subacute injections, so 48 hours versus 48 hours and four weeks versus no injection, we see that PRP injection patients do better at that kind of short-to-midterm outcome, six to eight weeks, than do no treatment. And patients who receive two injections do better than one. So maybe there is some role for that acute PRP injection within the first 48 hours. We all see a lot of elbow injuries, especially UCL injuries. And there's a lot of great data using biologics for UCL injuries. However, there's very little data looking at biologics for acute UCL injuries. This paper by Diehl in 2017 was the only one I could find that really shows that kind of immediate injury injection, as well as a follow-up at two weeks. And 22 of these 23 athletes returned to full pitching at a similar or higher level of pitching. When we look at high ankle sprains, there's actually really good data but very small numbers on reduced return to sport, so 40 days versus 60, with PRP injections performed. The patients I have highlighted on the right were the patients that had a delayed presentation to clinic, and they had the longest return to sport. So maybe there is something to that acute injection of ankle ligamentous injuries. And then when we look at these narrative reviews, it's noted that we may consider using these, and I think that's how I practice. There's insufficient data to routinely treat acute injuries with PRP, and I intentionally left all of the muscle injuries out, knowing that Dr. Bowers was going to cover that. I think there's certainly an option in patients with a timeline or season demand. The cost consideration needs to be taken into account, and if performing PRP, there's some suggestion that earlier is better than later. And I'm going to skip this so we can move on to our next talk. I think this is a pretty quick one. I did ask AI. There's open evidence, medical AI, all of these different questions this morning, and I just briefly put in here what their responses were. They're actually very similar to my response, with the exception of the HA. They were a little bit more strongly in favor of adding HA. And then I have a bunch of references at the end. I'll just pull up here. Let's see. And then we get to end here. Thank you. Well good morning everyone. I'm going to be speaking about the current best evidence for PRP and the management of upper and lower extremity neuromusculoskeletal conditions. And here are my disclaimers and I have no disclosures. So I'm going to highlight the AAPNR's methodology for assessing the quality of evidence that's available which is similar to but not exactly the same as the Oxford levels of evidence that you may be familiar with. So level one in evidence is good quality, patient oriented, and includes systematic reviews and meta-analyses of RCTs with consistent findings as well as high quality individual RCTs. Whereas level two evidence is still patient oriented but of more limited quality. This includes systematic reviews and meta-analyses of lower quality clinical trials or those with inconsistent findings. Level three is all other evidence. I'm going to note that I won't be presenting today on any conditions for which only level three evidence is available. So here's a methodology that I used. So I used Google Scholar. I included systematic reviews and meta-analyses of non-surgical studies only. And ideally I included those publications that have been in publication since 2023 which would theoretically include the most recent clinical trials although in some cases I had to go back to since 2020. And if there were no systematic reviews with meta-analyses that were available since 2020 I reported systematic reviews only or individual RCTs. And we're going to present outcomes timelines any adverse events and the risk of bias when reported in meta-analyses. So this methodology yielded this list of upper and lower extremity conditions I'm going to be covering today across body regions that are presented in ABC order and for the sake of time I'm presenting only one example per condition. So first up is adhesive capsulitis. So this was a systematic review and meta-analysis of 14 RCTs. And the authors concluded that PRP was more durable and safer than corticosteroids and other control groups in the treatment of frozen shoulder. And specifically they reported the most significant effect of PRP in the midterm follow up from four to 24 weeks with improvements in pain function and both active and passive range of motion. And there was a gradual diminishing or even the disappearance of these effects after 24 weeks. They reported no adverse effects other than common complications of injection, which occurred only in one study after both types of injections. And they concluded that there was no significant risk of bias across the RCTs that were included. So for glenohumeral osteoarthritis, there have been no systematic reviews or meta-analyses since 2020. In fact, the only RCT I identified is from 2022. And this was a double-blind RCT that included 70 patients who were randomly assigned to a single injection of HA or loop pore PRP. And they found no differences in pain and functional outcomes at any time points over 12 months, but rather there were significant improvements in both groups starting at one to two months. There were similar side effects and satisfaction rates between groups. So for the non-operative management of rotator cuff tendinopathy, this review of 13 RCTs concluded that PRP injection can be a viable alternative to corticosteroid injection for the conservative management of rotator cuff disease. The authors reported that PRP might provide better improvements in pain and function in the median to the long-term, from two to six months to beyond six months. They also determined that PRP may reduce the rates of subsequent injection or surgery in the 12 months following injection compared to steroid. Now, we should note that one trial reported five frozen shoulders in the PRP group. And as for bias across the assessed domains, it was around 50-50 between low and unclear risk of bias. So moving on to the elbow, a systematic review and meta-analysis included 11 RCTs and concluded that PRP and corticosteroid injections are effective treatments for patients with common extensor tendinopathy. So specifically, steroid provided better short-term improvement in function at less than two months, while PRP provided better long-term functional improvement beyond six months. No adverse events were reported. And regarding bias, while the authors excluded all high-risk clinical studies, they noted that only two of the 11 RCTs were considered low-risk. So I included a systematic review only on partial ulnar collateral ligament tears. The authors included five studies, which included four case series as well as one retrospective cohort study. And they concluded a favorable return to sport, clinical and radiographic outcomes in patients that received PRP for partial UCL tears. And this included 75 percent return to sport. Now, within the limitations of the lower quality studies that were included in the systematic review, the authors did report that PRP significantly improved patient outcomes as well as subjective exams. And in one study, MRI that was performed one month after the PRP showed evidence of complete healing of the UCL, apparently, as well as bridging scar with a residual fluid cleft in one other study. And complications were limited to post-injection swelling. So we're going to move distally now to the wrists and hand. So for carpal tunnel syndrome, there was a systematic review and meta-analysis that included 18 RCTs. The authors concluded that PRP should be used as the first line treatment for carpal tunnel syndrome with dextrose and steroids serving as alternative treatment options. And specifically, they reported PRP was effective in alleviating CTS-related pain and symptoms and improved function over both the short and long term, which was less than three months and beyond three months. The most common adverse effect was injection site pain. And in terms of bias, 17 of the 18 RCTs that were included were deemed good to excellent quality. So for trapezial metacarpal osteoarthritis, better known as first CMC joint OA, this was a systematic review and meta-analysis of 10 RCTs in which the authors concluded that corticosteroids were the favorable option when considering the choice of intra-articular injection for the management of TMCOA. And this was given their affordability, ease administration, and efficacy. They specifically found that there was no significant difference in pain and functional outcomes following intra-articular steroid injections compared to HA or PRP. Adverse events noted in this systematic review included a positive ANA test, post-injection hand pain, swelling, or numbness, as well as skin and nail abnormalities. And the risk of bias was deemed to be heterogeneous. All right, we're gonna move now to the lower extremity, and we're gonna start with the hip and greater trochanteric pain syndrome, or gluteal tenopathy. This was a systematic review and meta-analysis from 2021, which included seven RCTs. The authors concluded that PRP injections are more effective than corticosteroids at approximately two years follow-up. And this was based upon statistically greater Harris hip scores after PRP, although there were no differences in pain between PRP and steroid that they found. No serious adverse events or complications were reported, and the overall assessment was a low risk of bias. For hip OA, this systematic review and meta-analysis included eight studies, of which five were RCTs, and the remaining three were non-randomized. The authors concluded that there was low and moderate quality evidence that suggests that PRP can reduce pain and improve function in patients with hip OA compared to baseline, with the strongest evidence for an effect at one to two-month follow-up. And this assessment was based upon VES, WOMAC function, WHO's ADL, and Harris hip scores. Now adverse events or adverse effects included post-injection pain, mild rash, superficial hematoma, and in terms of bias, three of the five RCTs that were included were deemed to be at high risk of bias, whereas the remaining two had some concerns for bias. So for the knee, this is a recent systematic review only on degenerative meniscal tears of 10 studies, which included two RCTs, three case series, and one cohort study. The authors concluded that PRP appears to be a safe enough case as treatment strategy for degenerative meniscal pathology. However, they also indicated that due to heterogeneity across study designs, that additional trials are needed to provide a greater degree of confidence in PRP's clinical impact on patients with meniscal tears. So specifically, their review combined three different types of injection approaches in their analysis, so intra-articular, intra-meniscal, and combined intra-articular, intra-meniscal. And they found that there was improved pain and functionality by three months that persisted for at least one year after PRP. No adverse reactions or complications were reported outside of injection site pain. So for knee OA, this was a systematic review and meta-analysis of 40 studies, which included RCTs or quasi-RCTs. And the authors reported that studies suggest that PRP may be more effective then, or at least as effective, as other diverse treatments that are available non-surgically. And this could range from corticosteroid, hyaluronic acid, oral pharmacological agents, ozone therapy, or saline placebo. And this is in terms of pain function and adverse events. However, they noted that there were serious limitations and considerable methodological flaws in the current literature. And they ultimately deferred any sort of recommendation for clinical practice regarding PRP for knee OA. Specifically, they did say at six-month follow-up, PRP can be as effective as, and in some studies were actually found to be more effective than other therapies for pain function and stiffness. In terms of adverse events, severe pain was reported by three participants across two trials. And then finally, for the knee, this is a review from 2022 on patellar tendinopathy that included five randomized and three non-randomized studies. The authors found that PRP injection did not provide significantly greater pain relief and functional outcomes than non-PRP injections. So specifically, there were no significant differences in pain, functional outcomes, or quality of life in the short term, which was defined from eight to 12 weeks, the median term at six months, or the long term, which was one year, between PRP and the comparators, which included normal saline, dry needling, autologous expanded bone marrow MSCs, high-volume image-guided injections, and HA. No significant adverse events were reported, only increased local pain. And the risk of bias was assessed as heterogeneous. Finally, we're gonna move on to the foot and ankle, and we're gonna start with a systematic review and meta-analysis on ankle osteoarthritis, which consisted of five studies, which included one RCT, two other prospective studies, and two retrospective studies. The authors concluded that PRP may beneficially improve pain and functional scores for ankle OA in a short-term period of around 12 weeks. However, they did not find any significant differences between PRP and placebo in pain and function at six and 26 weeks. No serious adverse events were reported. They assessed a low risk of bias for the RCT, but serious to critical risk of bias for the four other studies that were included. This review on mid-substance Achilles tendinopathy is from 2021 and included four RCTs. The authors concluded that PRP has no clear additional value in management of chronic mid-substance Achilles tendinopathy. Specifically, they found no difference in clinical outcomes between PRP and placebo groups at three, six, or 12 months. There were no reports of infections, hospitalization, or other serious adverse events, and they assessed low or intermediate risk of bias for all studies, although they did note that studies that seemed to favor PRP also seemed to have a higher risk of bias profile. And finally, this is a systematic review and meta-analysis on plantar fasciopathy that included 21 RCTs. The authors concluded that PRP is more effective than steroid, shockwave, and placebo in reducing BAS and is more effective than CSI and placebo in improving the American orthopedic foot and ankle score. And the mean duration of post-interventional follow-up, or I should say the range, was from three to 18 months. However, they noted that PRP did not demonstrate a consistent advantage across all outcome measures, which include thickness of the plantar fascia as well as the foot function index. Some minor side effects included bleeding, pain, and infection at the injection site, and the studies were assessed overall as having a low risk of bias. So, given all that evidence, I attempted to rank and summarize the best evidence in favor of PRP, starting with the most best. And at the top of the list is plantar fasciopathy. Surprisingly, CTS and adhesive capsulitis came up next in terms of best evidence, and this was followed by knee osteoarthritis, which has been the most frequently studied. This is followed by common extensor tendinopathy, rotator cuff tendinopathy, gluteal tendinopathy, and finally, hip osteoarthritis. And moving on to the best evidence, but not in favor of PRP, the top of my list was first CMC joint OA, followed by patellar tendinopathy and mid-substance Achilles. And finally, more evidence is needed for the conditions that are listed on this slide. Ankle OA, degenerative meniscal teres, partial UCL teres, and glenohumeral OA. So, in closing, here are some of the other upper and lower extremity conditions I searched for when creating this presentation, but not find sufficient higher quality evidence to include. And these include ankle sprains, common flexor tendinopathy, for which there is a systematic review, however, it included only two cohort studies, OA of small or intermediate joints, such as the AC joint, non-operative management of labral teres of the shoulder and hip, although there is evidence available for regarding biologic augmentation for surgical repairs. And finally, post-surgical management of upper and lower extremity conditions. In my clinic, which is at a military facility, we often receive referrals from our orthopedic colleagues for PRP management of post-procedural pain, such as performing shoulder injections after some type of arthroscopic shoulder surgery. So, thank you all for your attention, and I look forward to our panel. Thank you. I think we only have a few minutes left, so I won't be able to get through all the questions that we have through here, but we will try to get through as many as possible. So, first question, which seems to be kind of the most popular, is can you walk through how you estimate and document your platelet dosage in your procedure note? Sure. So, it depends if you're cell counting. So, if you're cell counting, you should put everything that you get within the documented note. So, that includes your platelets, your leukocyte content, and then, I mean, the main thing to calculate your platelet dose is your platelets in terms of how many per microliter, and then you want to also put, you know, how many MLs you're injecting into the joint, because that's how you'll calculate your platelet dose. So, platelets, leukocytes, and the amount that you're injecting. Awesome. How many on the panel have, like, a hematology analyzer that they used before they inject every patient? We use our lab. Use your lab? Yeah. Do you take it off each time? Do you know before you inject? No. Oh. We have, you know, we have, we've been doing quality control analysis since maybe, like, 2012 on all of our PRPs, and so we have a pretty good idea. We've come up with a formula that we can use that's pretty good at predicting how many platelets will come out of a patient based on the system that we use. That's not something that we've, you know, put into an app or anything at this point, but I would say, generally speaking, we have a pretty good idea before we do what we do, and sometimes we'll change how we make it based on patient factors. Awesome. Is there an upper limit of platelet dosage above which there is concern for a corrosive effect? What about concentration? Yeah, so it's a good question. There may be a ceiling effect with all this that we're not seeing yet. I mean, we know that the optimal concentration's about 1.5 million platelets per microliter to achieve cell proliferation. Anything above that, you can see a little bit of decreased cell proliferation, and, you know, potentially there could be these corrosive effects. So the question is, you know, how do we deliver this 1.5 million platelets and then in an effective manner? You know, is that one dose? Is it a few doses? Is that clinically relevant to what we're seeing? So, yeah, we just, there's some numbers that we know. For all the presenters, how soon after an acute injury are you generally turning to PRP for tendons or PPP for muscles? If anyone is using PRP or PPP less than three to six months after an injury, how do you justify utilization while the athlete's body is still likely going through its native healing mechanisms? This one work? Yeah. So I think it's two separate categories. So platelet-poor-plasma for muscle injury, we're trying to augment the healing response and get the athlete back faster. So with platelet-poor-plasma, you're doing it in the acute phase. So within a couple days after the injury, and then you don't, it's not like PRP where we have a rehab protocol afterwards where you pull back their activity. We do the platelet-poor-plasma injection and then they move into rehab as they normally would with an acute muscle injury with the expectation that they'll progress faster through their rehab and get back to return to play faster. And so that, I think the rationale for using platelet-poor-plasma for acute muscle injuries is different than what we're using PRP for for other soft tissue injuries. Does someone want to comment about the how soon after tendon injury? I will. I have a little bit of a unique practice in that about half of my patients, PRP is covered under their insurance plan. So we have a pretty, I would say, low threshold to use PRP when it seems appropriate. After an acute injury, I try and judge if I think this is an injury that's likely to heal quickly on its own or something that's likely to give a prolonged recovery. And if it's something I think is gonna be prolonged, I will maybe lean towards using something like PRP. If it's something like a low-grade ankle sprain, and I have a pretty good indication that this is gonna recover on an appropriate timeline, I don't see a lot of value in adding PRP to that. I think the story of the elite athlete is maybe a little bit of a different discussion when you're talking about change in days of return to play is a big deal for these people versus a high school athlete where maybe missing a game isn't the biggest deal. So I think there's a little bit of nuance in discussion as well. And I think if you are gonna do PRP after an acute injury, right away makes most sense. Acute and chronic injuries like a tendon, like so say someone has lateral epicondylitis and then they have an acute worsening of their symptoms, I don't find that the acuity of adding PRP is a huge deal to that. I think you still treat it like the chronic injury it was. Thank you. Last question, because I think we're gonna be cut off here. Not that anyone knows the answer to this question. Why won't insurance companies cover PRP if we now have more studies demonstrating its efficacy? Any thoughts on how we can change this as the cost is prohibitive for so many patients? Anyone wanna tackle that one? I can't tell you why they won't cover it, but I will say that a lot of people that do PRP frequently probably don't want it to actually be covered by insurance from a payment from the patient. So I imagine if PRP were to be covered by insurance, we're gonna get reimbursed less than the kids cost. And so I think part of it is no one that is doing PRP at a high volume actually wants to lose money doing it. And so no one's really pushing for it to be covered by insurance. That's probably unfortunately the truth. I think one of the first things you said is that PRP is not a drug and therefore it's not regulated. I think that's ultimately what it comes down to is it's not really classified under something that is easily, I guess, insurance reimbursable. And then secondarily, there's such heterogeneity in the systems right now. I think it would be unwise for an insurance company to cover it without having some idea of what patients are getting, some identification of quantification methods, standardization, and I say that acknowledging that our insurance company covers PRP for 50,000 people that live in Rochester, Minnesota and Jacksonville and other sites. And so it is definitely reimbursement is a lot lower when it's covered by insurance. Awesome. Well, thank you guys for all for your attention here and hopefully you all learned something. Thank you.

PRP

platelet-rich plasma

musculoskeletal disorders

sports medicine

clinical care

healing

pain relief

PRP preparation

insurance coverage

PPP

muscle injuries

PRP efficacy