On behalf of AOFAS, I want to welcome you back to day two of the advanced foot and ankle course. Thank you for the course, chairs, Dr. Errol Bailey, Dr. Christopher Miller, and Dr. Glenn Sheehy for putting together such a fantastic course. Before we get started, I wanted to share a few housekeeping items. All faculty will share their disclosures during their individual presentations, and you can also find them within the virtual platform under Speakers and then Disclosures. This course offers a total of 11.25 AMA PRA Category 1 credits. Use the tile on the platform landing page to claim your CME and complete the evaluation after the course. The broadcasts are being recorded and will be available under the on-demand recordings on the virtual platform within 24 hours of this broadcast. All on-demand recordings will be available on the PRC for future viewing. To send questions to the faculty, please click on the Q&A tab in your navigation bar. If you're experiencing technical difficulties, please try closing your browser and logging back in the same way you did the first time. Lastly, we want to thank our sponsor of the course, MedlineUnite. You can learn more about this company by visiting the Exhibit Hall icon on the platform landing page. With that, I'd like to turn the program over to Dr. Bailey to get us started tonight. Thank you, Julie, and welcome to day two of the Advanced Virtual Foot and Ankle course. We're happy to have you here. Yesterday, we had a fantastic time with a lot of great talks and participation. I'd like to thank Christopher Miller and Glenn Shee, the co-chairman who helped put this talk together, and of course, Julie, who you just heard from, who has been fantastic in putting this all together. It just cannot happen without her. We realize it's Friday, and you're tired, and so we really appreciate the fact that you're here. If you have to step out and do something with family, we understand, but you can please remember that this is on demand as well, and you can watch this at your leisure. Our talks tonight are about regenerative biologics, and then we have a great session on minimally invasive surgery. This year, we wanted to stay away from the bunion and just talk about other things and other areas where you can use this new technique. Our talk should be at or around 15 minutes, so we'll go a little longer. We won't interrupt unless you go significantly longer, and then your moderator may come in and just say, could you wrap it up? It's not personal. It's just something we're doing to just keep on time. If you look at the bottom of your screen, there'll be an area for question and answers. Last night, we had a great time. You can hit that button and type in your question. We'll either entertain it at the end of the session, or that particular speaker that you're directing it to may type the answer back to you. We want the speakers to be speaker ready. When one talk ends, we'll go right into the next talk. Our first talk is going to be about platelet-risk plasma therapy and does it really work. Let's get it going. Thank you for the introduction, Dr. Bailey. I'm grateful to be part of this distinguished panel, and my task today is to summarize the current evidence regarding platelet-rich plasma and its use in foot and ankle surgery. I have nothing to disclose regarding this topic. Platelet-rich plasma, PRP, is the plasma fraction of autologous blood with platelet concentrations above baseline. PRP contains various growth factors that are involved in biosynthetic pathways of healing. Whole blood is composed of 55% plasma, 45% red blood cells, and 1% white blood cells and platelets. The plasma is a liquid portion of whole blood, and 92% of plasma is water. The remaining 8% contains albumin, globulin, electrolytes, fibrinogen, hormones, vitamins, enzymes, and immunoglobulins. Platelets are non-nucleated cells. There are normally 150,000 to 300,000 platelets per microliter of blood. In alpha granules, platelets contain transforming growth factor beta, platelet-rich growth factor, insulin-like growth factor, fibroblast growth factor, VEGF, vaposclenate growth factor, and epidermal growth factor. These are all factors that are involved in tissue regeneration and repair. Let me take a brief look at functions of each of these factors separately. We may have a better appreciation of their potential in tissue regeneration. For example, they stimulate collagen synthesis, epithelialization, stimulation and proliferation of mesenchymal stem cells, angiogenesis, myocyte regeneration, extracellular matrix growth, and differentiation and growth of fibroblasts, chondrocytes, osteoblasts, and other roles in healing. Rationale for using PRPs to obtain higher concentrations of these autologous growth factors and proteins that may improve healing process. Our goal is to enhance recruitment, proliferation, and differentiation of the cells involved in regeneration of injured tissues. When we prepare a PRP, it's pretty simple. It starts with withdrawal of approximately 40 cc of blood from anticoagulant using 21-gauge or a bit larger needles. This is to minimize sheer stress on platelets, which may prematurely activate them. The blood is drawn into tubes containing anticoagulants such as sodium citrates, which binds to ionized calcium to inhibit platelet activation cascades. After that, a two-step centrifugation process is initiated. The first centrifuge separates the plasma and the buffy coat, which includes the plasma and white blood cells from red blood cells. Plasma and buffy coat is collected and red blood cells are discarded. The second centrifuge further concentrates platelets, producing poor plasma and platelet-rich plasma. Following this stage, the upper two-thirds of the tube is discarded, and the remaining content, which includes PRPs, is resuspended by gently shaking the tube. Here, depending on the protocol, preparation protocol, or the amount of blood drawn, in general, 40 cc of all blood gives approximately 4 mL PRP. This includes a minimum of 1 million platelet cells per microliter, and three to five-fold higher factor concentrations. At this point, platelet activators such as thrombin or calcium gluconate can be added, and PRP is injected to target area. Here, the platelet activation is actually a critical step. As you may notice in this slide, in this figure, binding of thrombin to its receptor results in thrombin activation, which in turn gives rise to release of growth factors from alpha granules. You might have seen or done or heard the variants of platelet-rich plasma, leukocyte-rich versus leukocyte-poor. There's one simple difference in preparation of this PRP variance. It is in the second centrifuge step. If you are preparing leukocyte-poor, only the plasma portion is harvested and centrifuged without the bufficote, but if you want a leukocyte-rich PRP, bufficote and plasma is collected together and put into second centrifuge step. Basic research and animal model studies report some potential differences between the effects of leukocyte-rich and leukocyte-poor PRP. Some authors note that leukocyte-rich PRP may actually promote inflammation and might have catabolic effects. However, we have to keep in mind that these are basic studies and they might have limited applicability to complex human systemic healing response. Actually, there is no clinical studies to date support any potential difference between the clinical effects of leukocyte-rich and leukocyte-poor platelet-rich plasma. PRP has some practicality as an orthobiologic in our practice. First of all, it is non-invasive. It requires a simple or any puncture. It's brief and hustle-free. The whole duration of the process is one hour and it can be performed using a benchtop centrifuge. It's relatively affordable. It is on average $750 per injection and this may range, depending on different factors, between $300 up to $2,500 per injection. Medicare does not cover PRP injections. PRP use in the United States increased substantially during the past few decades with 86,000 athletes receiving PRP injections annually. One of the factors worth mentioning is a reason for increased popularity is the elite athletes, celebrities, who are known to receive PRP therapy for their injuries and reflections of their stories in news media. Here, I would like to pause one second and quote from Darren et al. from the Johannes Group. Internet sites commonly misinterpret published scientific results of PRP for orthopedic treatment. Take home message after viewing many sites, maybe, you can prevent and treat all pain and dysfunction with PRP. Currently, data indicates that PRP therapy is the most frequently performed autologous regenerative medicine procedure in orthopedic surgery. In 2015, $160 million spent on PRP injections as payment to providers. In 2024, we expect this to surpass $451 million. When we take a look at this graph from et al., we see a sharp increase in number of PRP-related publications in foot and ankle surgery during recent years. This alone may indicate the variety of foot and ankle pathologies for which PRP can be considered as an adjunct to conservative and surgical treatment, perhaps. In literature, there are studies, there are various studies from different levels of evidence, but some high-level evidence reports the results of PRP therapy in pathologies such as chronic plantar fasciitis, Achilles pathologies, osteoarthritis of the ankle joint, osteochondral lesions of the tail and slat, ligament injury, and chronic foot ulcers. So, in chronic plantar fasciitis, there is really good quality level 1-2 evidence. It suggests a potential superiority of PRP over corticosteroid injections, and these are relatively more recent studies with good case numbers. On the other hand, some other researchers, they also compared the PRP injections in chronic plantar fasciitis with other treatment modalities such as autologous blood injection or plantar fasciotomy or dextrose prolotherapy. Although these were not as good quality as the ones in the other table I showed you, they still could not find any superiority to PRP injection over these other treatment modalities. So, the exact mechanism of PRP's healing effect in chronic plantar fasciitis is actually not known. As you can see in this slide, the histological sections taken from plantar fascia insertion, there is noticeable degeneration of collagen fibers with mucopolysaccharide accumulation in chronic plantar fasciitis. So, chronic plantar fasciitis is not purely an inflammatory, but also a degenerative pathology with micro tears. So, therefore, we can speculate that regenerative treatments such as PRP injections may address the pathology more effectively compared to anti-inflammatory effects we would get by injecting steroids. PRP use in non-surgical treatment of Achilles rupture has been studied by several authors, and in a level one study with 177 cases in total, Kini et al. did not find any superiority over placebo and their results were supported by other studies such as from Boissin in 2020. Similarly, intraoperative augmentation of surgical Achilles repair with PRP in patients with Achilles rupture did not reveal any superiority over controls. However, these were all level two studies and the case numbers were not that high. And there's no literature support for use of PRP in patients with chronic Achilles tendinosis. In a level one study, Kearney had 121 PRP injected patients and he compared those with 119 control patients, and there was no difference between the two groups, and DeVos supported Kearney's result, because he supported Kearney's result as well. And Terman used PRP in patients who underwent endoscopic debridement of non-surgical Achilles tendinosis, and they did not find any advantages. And Boissin, on the other hand, he found some superiority. He noted some superiority with PRP over Selene in a study comparing high-volume injections with placebo, which is Selene, and PRP injections. But this was not a very high-quality level one study. As you may notice, the case numbers were 19 in each group. Let me take a look at the osteoarthritis of the ankle. The use of PRP injections in ankle osteoarthritis was not shown to be effective in level one studies, and very few case studies, level four studies, suggest improvements in ankle osteoarthritis with PRP injection, but due to limited case numbers and methodological deficiencies, these studies should not impact our clinical practice. And allow me to open up this level one study, because it's a good quality study. It was published in 2021. Pajero reported the results of ultrasound-guided PRP injections into ankle and compared 48 PRP-injected ankles with 52 Selene-injected ankles, and this was a multicenter, randomized, double-blind, placebo-controlled trial, but the authors did not find any difference between the two groups in terms of change in AOFAS scores and mean AOFAS scores, both in six weeks and 26 weeks follow-up. And their results did not find any superiority with PRP injections, and these were the secondary outcomes, and they were still, were not showing any difference at six weeks and 26 weeks time. So, let me take a look at the osteochondral lesions of the talus. Interestingly, it appears to be beneficial if we roughly look at these studies, which are mostly level two and one, level one study. One study, for example, from me, Dan, that we critically assessed this, compared PRP with hyaluronic acid injection, and this study did not have a control group. It was both treatment groups, and other authors compared PRP with hyaluronic acid and saline or no injections in patients who underwent microfracture, but all those studies were relatively low case numbers, and their follow-up times were not standard. For example, the level one study from Vermily, they actually calculated the follow-up time, which in my assessment, I kindly would drop the level of evidence from one to two, just because it was not predetermined in the beginning of the study. So, overall, these were scarce, low-quality level one, two studies, small size, non-open, homogenous study populations, and design flaws. Some tried PRP after lateral ankle sprain with the HOPS-T pro outcomes, and very few level two studies showed actually no difference. One from Rivera showed no difference at 24 weeks, and then at eight weeks, there was no difference, and one study reports a little shorter return to play with less residual pain in patients who had grade three high ankle sprain with AI-TFL tear, and dynamics in the muscle instability, but as you may notice, these are only eight cases in each group, which may strongly bias their results. Well, chronic foot ulcers are a continuing problem for all of us, and some authors expected to improve healing by injecting PRP both underneath and around the chronic foot ulcers. There are two organized level two studies where PRP was injected and compared with conventionally treated wounds. However, measurements of wound size were really subjective in both studies. If I open up with the HASSAM study, for example, the location of the lesions were not homogeneous, both plantar, dorsal, and forefoot, hindfoot, and also midfoot ulcers. Regardless, PRP treatment in this study as well did not show any superior to our standard addressing in terms of surface area of the wounds. In summary, PRP in foot and ankle surgery can be considered as an adjunct in non-surgical treatment of chronic plantar tissue itis. However, current high-level evidence does not justify using osteoarthritis of the ankle, Achilles rupture, tendinosis, OCL, loftalis, ankle sprain, or chronic foot ulcers. Thank you. Thank you very much. That was fantastic. I'm sure we'll get some questions about that, and we'll hold those for the end of the session. We're next up. Are we ready to go with our next talk? Hi. Perfect. Thank you. Thank you, Dr. Belli. Thank you, everyone, for having me today, and thank you to everyone joining in on a Friday at four or five. All right. For myself, one disclosure here, as well as journal review. Okay. So, often, foot and ankle were tasked with thinking outside the box. Dr. Atasek just walked us through platelet-rich plasma, and let me continue us through the toolbox of skills that we have. So, orthobiologics, it encompasses numerous substances that are naturally found in the human body. We just touched on one, which was PRP, but it also includes growth factors that are isolated, as well as cell therapy, theoretically thought to optimize our biologic response to healing. Actually, if you go on the Academy website, there's a biologics initiative and a dashboard that's an online tool that you can access that combines both clinical medicine, as well as FDA guidance, and it's really easily accessible if you're interested. Okay. So, looking at how the FDA regulates biologics. So, the FDA has two branches, section 351 and 361, and there's actually an arm called the HCTPS. It stands for human cells, tissues, and cellular and tissue-based products. So, biologics largely falls under section 361, which is much less tightly regulated than, let's say, a drug, because they're considered low risk. But in order to qualify for section 361, you have to meet very specific criteria. The first of which is that it needs to be minimally manipulated cell tissue. So, going through a centrifuge is fine, but doing anything more to the tissue is not okay with the FDA. It needs to be for homologous use, which means that it needs to be used for something that the body is already familiar with. It has to be autologous, so self. It cannot be combined with a drug or device, and it needs to be point of care. So, you can't go into a lab and incubate it. It basically needs to be same-day service. So, we just started through the cellular treatment hierarchy. I'm going to skip over PRP, because we just covered it. And instead, I'm going to take us through mesenchymal stromal cells, or stem cells, often interchangeably used. I'll refer to them as MSCs to keep it simple. So, these are cells that have the ability to become specialized. They can modulate immune responses. They release trophic cytokines. And for this reason, they're very, very, very attractive substrates for regenerative medicine. You can harvest them from multiple sources, including cord, bone marrow, as well as adipose tissue. So, how does the International Society for Cellular Therapy define what is an MSC? So, to qualify, it has to be plastically adherent. It needs to express very specific CD markers and not express others. And it has to have the ability to differentiate into osteoblasts, adipocytes, and chondroblasts in vitro. So, what's the best source? Studies have shown that all three sources actually express very similar surface markers. So, let's take this into a clinical context. So, we have a 53-year-old patient. They are very healthy, no past medical history. They're an avid runner with significant heel pain, limiting their activities. You see them in clinic. And clinically, as well as MRI, they have Achilles tendinopathy. But they're asking you very specifically for non-surgical measures. And they've already tried physical therapy extensively, heel lifts. And they want to know what other adjuvants that you have for them. So, I did a quick Google search. And if you just Google search stem cell therapy, there's like 348 million hits, platelet-rich plasma, that's 26 million. So, it's very clear that people are interested and want to know more. And that's further supported in the literature. So, Dr. Shown and Dr. Zhang recently published this study looking at clinical trials and biologics for cartilage repair. And actually, what they found was that since 2006, the number of trials registered are actually accelerating at a rate of 16% annually. Mesenchymal stem cells or stromal cells are the most commonly investigated. I'm going to skip through some of these slides here because we just covered PRP so in depth. And instead, I'm going to take us to our next option in our toolbox and start talking about shockwave therapy. So, shockwaves are focused single pressure pulses of microsecond duration. It first started in lithotripsy in the 1980s and since has gained a lot of popularity in orthopedics. The reason being is because studies have shown that it decreases calcification. There are some authors that believe that there is some substance P modulation or pain modulation. There's actually a theory called the gating theory where some believe that it essentially modulates nociception via peripheral stimulation. There's also some studies that shows that it stimulates angiogenesis and neovascularization. So, probably two of the big seminal papers in this area for us with regards to Achilles tendon pathology, the first of which is Kosta study that was published in Core back in 2005. It was a randomized controlled trial. It enrolled about 51 patients, 49 included at the end result. And what they included as far as their patient demographics was insertional and non-insertional Achilles tendinopathy. And what they found at the end of their study was that there was no difference in pain relief among those that received shockwave and those that did not. But if you look at this study a little bit further, you'll see that the study was actually underpowered. And so, in order to achieve 80% power, they would have had to enroll 170 patients. And the authors disclose this as one of their limitations. The other criticism of this initial study was that they used a protocol that had previously been published twice in the literature that was known to be ineffective. So, Romp and his colleagues published this randomized control trial in 2009. What it showed after dividing patients into eccentric strength training alone and eccentric training with shockwave was that patients at four months, if they were in the shockwave group, actually had better visa A improvement and better pain improvement. Now, what's interesting about this study is that if you dig a little bit deeper into the paper, you'll see that at one year, there was no difference. So, no difference at one year between those who got shockwave with eccentric training and those who were in the eccentric training group alone. So, going to Dr. Mansur's study and his group, they published very recently in 2021 in JBJS, single-centered, double-blinded, placebo-controlled, randomized clinical trial. They were looking at the efficacy of shockwave therapy with eccentric exercise training versus eccentric alone and a sham. They looked at those two treatment groups after a course of therapy, and what they found at their 24-week follow-up was that there were no difference among either the shockwave group and those that did not receive shockwave at final follow-up. Though, one thing that they did note was that there was a higher failure rate, but a lower recurrence rate in the shockwave group. So, what they defined as failure is not achieving an improvement on the visa A scores from the initial baseline of at least 15 points. So, that was defined as a failure. What was defined as recurrence was a decrease in the visa A of at least equal to or greater than six if they had initially reached that initial 15-point bump in their visa A scores. Now there are a lot of challenges when it comes to biologic research. Not only is there no standardization in the manufacturing methods, but there's several different kits, different centrifugation protocols, there's no standardized dosing, the concentration varies within the same person, time of day, harvest site, the volume used, and then there's no standardization in the return to exercise guidelines. Critically evaluating the literature, if you look at this study in AJSM, it was a prospective single-blind placebo-controlled child looking at BMAC in knee osteoarthritis. If you look at the cellular characteristics of their harvest, you'll see here in the red box, it's highlighted, their number of MSCs harvested averaged out to be 0.05 percent, which is exceedingly small. The range of which was averaged was either none at all to 0.09, which gives you pause for at least critically evaluating the literature. So what we know is that there's not only variation that exists between subjects within systems, but also with single subjects in the same system. We know that older donors have harvest rates of MSCs that are lower, proliferation capacity that is lower, senescence that is increased, and decreased trophic factor secretion. So there's been a lot of push to regulate the research when it comes to biologics, specifically in the realm of PRP and MSCs, and this recent study published in JBJS actually established and looked for a MIBO, which is a minimum information for studies evaluating biologics, and published this 23 list minimum. So now going back to the patient that we talked about, so we had this 53 year old patient was really interested in non-surgical treatment options, specifically the biologic options. So are MSCs, PRP, are they definitively better than placebo? And what about shockwave therapy? I think even though there's really great promise in this area for biologics, definitive or at least consensus evidence within the current literature is still lacking. So I would ask, and how do we use this in our practice? Well I think the first thing you do is you disclose the risks to the patient and any financial relationships that you may have, and then you follow the literature, but you also critically assess the literature and what's being published, and then if possible contribute to the literature as well. And thank you, and these are my recommendations. Thank you very much, great job. It seemed as though very little works, but we keep trying, which is a good thing. Tim, are you ready to go? Yes, sir. Good afternoon, everybody. My name is Tim Badway, and I first want to thank Dr. Bailey for inviting me to be a member of this panel. The faculty that are part of this three-day course is, it's embarrassing how much talent there is amongst the faculty, and I am humbled to be a part of it. So thank you, Dr. Bailey. So I'm going to talk about the OG biologic, if you will, bone grafting, to harvest or not to harvest. Here are my disclosures. I don't have many. If there's any company representatives that would like to be on this slide, I'd be happy to add you. So I'm going to start out by giving you just a brief history of bone grafting, and we'll talk about the indications, a very brief discussion on mechanism of action, the types of bone graft, some newer products that you may not have heard of, and I've got some cases that illustrate some of those different types of bone graft. Bone grafting, interestingly, goes back a long ways. There have been some discoveries where even the ancient Egyptians have shown some signs that bone grafting was done, but the first case that cropped up in the medical literature was in 1668. A Dutch physician, Van Meerkeren, he did the first bone graft documented in the medical literature. He actually grafted a cranium, or to a soldier's cranium, a piece of a dog skull for a defect. The patient was then excommunicated from the church because of this unchristian-like treatment that was performed. The soldier later came back to the physician and asked to have the bone graft removed, and when the surgeon went in to take it out, it had already healed. The first autograft was done in 1820. Another Dutch physician, Van Walter, he actually took some of the bone fragments which were placed, or which were collected after a trepanation, which is actually, it's basically a cranial burr hole. So they save that bone and then put it back into place, and it healed into place. The first documented allograft was by William McEwen. He reconstructed an infected humerus of a four-year-old with bone grafted pain from a child with rickets. I'm not entirely sure, I haven't been able to find out why that particular donor was used, but apparently it was successful. Today, bone graft, there's almost 2 million bone graft procedures that are done worldwide. A quarter of those are done in the United States. It is the second most common tissue transplant in the US after blood transfusions. It's important to remember that a lot of these bone graft procedures are dentals, not just the orthopedic surgeons that are doing bone grafts. And it's a huge market. The global bone graft and graft substitute market is expected to reach over $3 billion by 2028. So if you're looking for a place to invest for the future, this might be it. The indications are pretty straightforward, at least most of them. You know, we use them for primary arthrodesis procedures, sometimes some primary fractures, when we know that those fractures are going to be hard to heal. Delayed unions of both fractures and fusions and non-unions of fractures and fusions. But we also use them for filling of osseous defects. Oftentimes that is, for example, after curatage of a large bone cyst or bone defect, and reconstruction following tumor resection. And I really think it's these last two indications is why the bone graft market is going to continue to expand. We're seeing a lot of patients who have had primary total joints, and now those patients are requiring reconstructions. And they have a lot of bone defects, and also tumor resection. You know, we are saving a lot of people with modern day surgical techniques and chemotherapeutic agents that we didn't have previously. And part of that bone or part of that resection of the skeleton then requires reconstruction. And that's where the bone graft comes in. Bone graft works, well, there's four different ways that bone graft works. One is osteoconduction, which basically serves as a scaffold for new bone growth. Osteoinduction, that's the ability of that graft to encourage or to recruit mesenchymal cells and then stimulate them to differentiate into chondroblast and osteoblast. And osteogenesis, that's basically where de novo bone formation is potentiated by the cells derived from the graft itself. And then the one that we don't ever talk about, osteogenesis, that's basically when it contributes to new blood vessel formation. But if you think about it, what do we do when we have a really hard time getting something to heal? We'll get a vascularized bone graft, a vascularized femur strut graft, but we just don't talk about the angiogenic portion of that. Another example of that, the induced membrane technique popularized or pioneered by Mascolet in in 1986, again, to increase the local circulation into that area. So we always talk about conduction, induction, and osteogenesis, but angiogenesis is equally important. There's often, or there's a lot of types of bone graft. Autograft includes iliac crest, tibia, calcaneus, and there's a few other sites, proximal tibia and distal tibia. Bone marrow aspirate, which I'm not going to talk a lot about today, but bone marrow aspirate and concentrated bone marrow aspirate just by itself is used sometimes for fracturing on unions. Allograft, both fresh frozen, freeze dried, and DBM. Then we've got the synthetic bone grafts, the ceramics, calcium sulfate, calcium phosphate, tricalphosphate, coralline hydroxyapatite from the coral, and then one that I've been playing around with, the bioactive glass. I did a little research and contacted the hospitals where I work, and just to get a relative cost of what some of these things go for. And I basically took what they cost by the size and did a little simple division. And I was really kind of taken by the relative disparity in some of these. The just freeze dried allograft cubes are roughly $25 a cc at one institution. At another institution I work, they've got the price down to about $17 a cc. And there's sometimes the smaller samples are more cost effective than the larger samples. There you see calcium sulfate, how much? $200 a cc. DBM putty, $208. Bioactive glass, $250 a cc. And you take demineralized bone matrix putty and just add cancellous bone to it, you increase the price by another $100. And again, this is just one hospital that either has a very good or very bad contracts. I don't have any comparison. Even with all these substitutes, autologous bone graft is still considered the gold standard. That's what we use when what we've tried before hasn't worked. Sometimes when autologous bone doesn't work, we try it again. Out of those four properties, the four mechanisms of action, it has them all. It's osteoconductive, inductive, promotes osteogenesis, and it promotes angiogenesis. There are some factors which affect the quality of the bone graft. So location. Location is everything. Iliac crest has some of the best nucleated cells. Then as you get further away from the axial skeleton, the tibia and the calcaneus, even though the ease of harvesting that graft gets a little better, it gets a little easier, the quality of the graft is not quite as good. So the cellularity decreases. There's other factors that affect the quality of bone graft. Advancing age, the bone is not as good in older people as younger people. Female sex, the bone graft is considered not as robust, and there are certain medical comorbidities that can affect the quality of bone graft, autologous bone graft. Even though it's the gold standard, autologous bone does have some disadvantages. Pain at the donor site. There was one study that is cited in my bibliography where some patients reported 50% of the time reported pain up to six months after surgery. Sensory loss, especially if you're working on the iliac crest, you have to be very careful of the lateral femoral cutaneous nerve. Wound problems, wound complications, wound infections from the donor site. You know, there's always bleeding that you can't control, you can't put a tourniquet around the pelvis. And sometimes you get hematoma formation. There is an increase in operative time, especially if you're working by yourself, you have to stop what you're doing down on the foot and go up to the iliac crest. And that can take some time. And there's a limited supply. If you're doing a big reconstruction, you don't have an unlimited supply of cancellous bone or and even less of cortical bone. So that's where some of these other substitutes come in. So what I'm going to do now, I'm just going to go through a few surgical cases. Most of these are mine or my partner's using some of these various bone graft substitutes. This is a case that where I did, it's a subtalar fusion for degenerative arthritis using tricalcium phosphate. And this x-ray right here was taken probably three to four weeks after the surgery. And you can see it looks like a pretty good feel when I'm using and I almost always use something autologous bone or some substitute when I'm doing a fusion. And I explained to my patients that it's basically like putting the grout between the tile in your bathroom, it fills in all the little cracks and crevices and voids. I don't even get into it with them about, you know, osteoconduction, osteoinduction, I just tell them it's just to fill in the in the blanks or fill in the spaces. But here she is at about three weeks after surgery. Here she is at eight weeks after surgery. You can see that with this tricalcium phosphate, there is some, it looks like it's healing, there's some incorporation. Now, this surgery was done many years ago, she actually showed up just a few weeks ago, 10 years out, I don't usually get 10 year follow up on my subtalar fusions. But you can see that through the remodeling process, there's been very nice incorporation. This is a very mature subtalar fusion, she was in for something else. And I asked if I could take an x-ray of this procedure that was done 10 years ago. This is an example using calcium sulfate, which, in my experience, it's not the best bone graft substance or substance, or it, it absorbs very quickly. And that's, it's been criticized for that there, it's been associated with a lot of wound drainage. In this case, I was using it as a carrier for antibiotics. So these are antibiotic impregnated calcium sulfate beads, which is not FDA approved in this country. But this is a gentleman that had rheumatoid arthritis, he had already undergone a triple. He actually kept, he had wound problems, was diagnosed with osteomyelitis. And I went in and did a very aggressive debridement. And then the plastic surgeons put a free flap over the lateral side of his foot. And you can see those little staples from that. Came back after the free flap had healed. And again, we've done the primary debridement, but I just felt like we needed a little bit more, a little bit more substance there. And then there was a concern about this, this chronic osteo. So these are antibiotic impregnated calcium sulfate beads. And then here he is, this is only about, about four months later, you can see the beads are completely resorbed, there's been a little bit of bone deposition that's occurred. So this is a case of my partners, Dr. J.P. Halloran, he and I've been in practice together for about, he's been about 10 years now. This is a case that came into his clinic, this is a patient where they had made several attempts to do a calcaneocuboid fusion and couldn't seem to get it to fuse. So they did a resection arthroplasty of the CEC joint or interpositional arthroplasty, they just stuffed something in there. And there's actually a case report in the literature. So there is some support for that procedure, which I was surprised to find. But she, this patient had a CT scan, and she had some degenerative changes in the subtator joint as well. So we took her to surgery and did a fusion of her subtator joint. But we also made another swing at doing the calcaneocuboid joint. This time, this was with a autograft, autologous tricortical bone graft, because we needed to fill that void. You can see that she's obviously got a very short lateral column, and we wanted to push her back over. And this was done just a few weeks ago, so I'm not gonna have any long term follow up. But here she is, you can see the tricortical graft. And we started out with a very big piece of bone, I did, I was in charge of harvesting on that particular case and handed him about a two and a half centimeter piece of Iliac crest. And we used almost every bit of it as you can see. So we've got these bone graft substitutes for those situations where we need more or we're trying to avoid the donor morbidity. And so I've, as I mentioned, I've been kind of playing around with bioactive glass, which is relatively new. It was was the first bioactive glass compound was invented in Florida in 1969. And then after that, a lot of research in the 90s took place in in Europe, especially in Finland. And then the first in 2004, the first bioactive glass was approved for cranial maxillofacial surgery in Europe. And then two years later, it was approved for orthopedic surgery. And it's been FDA approved in this country since 2019. So I'm going to show a few cases where I've actually used bioactive glass, instead of other some of these other either autologous bone or bone graft substitutes. So this is actually a patient of mine. She's a lady in her mid 60s with rheumatoid arthritis, you can see she's already had a resection arthroplasty of the lesser MTP joints, but had a very painful first MTP joint. On this particular day, I decided to use some cup and cone reamers. I'm typically a flat cut person. But I decided to use these cup and cone reamers, you will notice that there's some periarticular cysts on both sides of the MTP joint. And when I put the concave reamer on the metatarsal head, to say that it exploded would probably be an understatement, at least that's how I remember it. But now I'm looking at this great big void. I haven't talked to this patient about bone graft, I'm not going to be able to go up and take any bone off of her iliac crest. I'm not going to be able to use any allograft bone, we have not discussed that there's no consent there. I did have bioactive glass in the building. And so here she is two weeks later, I use this bioactive glass to fill in the voids and the crevices where after that, and I was able to get a little bit of cortical contact medially, or excuse me laterally, but that's about two, almost two and a half cc's of this bioactive glass. This picture, this x-ray was taken about three weeks after the surgery. And then here she is, about five months later, you can see, I'm going to go back one slide, a lot of people get concerned, if you look on that AP, and just medial to the metatarsal, you'll see some of that in the soft tissues, and everyone's worried what happens with this, quote unquote, glass in the soft tissues. Well, it, the body resorbs it, you have to keep it out of joints, if it gets inside a joint, it will chew up the joint, but if it's in the soft tissues, it will basically dissolve over time. I actually operated on this lady this morning, she had a rheumatoid nodule on the same foot and was having some discomfort from the plate, we took the plate out, so I was actually able to examine her fusion site. This is an ankle fusion that I did using nothing more, but for the graft, for bioactive glass, this is a gentleman in his mid 60s, he's diabetic, he actually works as a security guard at a hospital, he's on his feet all day, he's actually been in a double upright brace for several years, was tired of the brace, he had been counseled about the alternatives, including a total ankle, and he opted for a fusion. And so this is his preoperative x-ray. And here he is, at just probably six weeks after surgery, and you can see the radial density of this, of this substance is bioactive glass. Then here he is at about four months, and you can see how the glass is incorporated, and has been replaced, not replaced, but actually forms bone on the surfaces, usually within a few hours. And I think this is my last case, this is a triple arthrodesis, and I just threw this one in. This is six weeks after a triple arthrodesis. Excuse me, this is three weeks after a triple. Please don't, please don't beat me up about the technique that I used to do triples. But this is what works for me. But you can see the radial density at the tail and the vicular joint and the, well, all three joints. This is at three weeks. And here she is at six weeks. I've been really impressed with how rapidly this incorporates. And again, you don't have any donor site morbidity. You don't, you don't have any issues with drainage from calcium sulfate, it seems to work very well. So in summary, I'm going to make one other comment, bioactive glass, because before I get to that, just, I just thought of this this morning, I work at a hospital which has marketed itself in the past as a, as a blood conservation hospital, which I thought all hospitals were, I mean, we don't paint the walls with blood. But they reach out to the community that we're a blood conservation hospital, which brings in people of certain, certain of certain religious affiliations and with certain cultural affiliations, and they do not accept blood transfusions, but they also don't accept allograft bone. And so I found that in a couple of situations where I needed to use bone in those patients who were not accepting of, of allograft. And depending on how strict their particular religious sect is, they may not accept autograft once it's out if taken outside the body. So this has been another area where another one of these synthetic substitutes that has been useful in that particular situation. Right, so in summary, we do a lot of bone grafting in this country, you know, 25% of the bone grafting done in the in the world is done in the United States, either in orthopedic or dental applications, primarily. Autologous bone still is the gold standard. It's it's osteoconductive, inductive, osteogenic and angiogenic. It's not without its drawbacks. I mean, it's not it's not perfect. It's it's it's the best biologic, but it's not it's not perfect. There's a lot of bone graft substitutes available. Bioactive glass is a newer graft product on the market that I have had some experience with and I've been very happy with it. Thank you for your time. Thank you, Tim. That was very thorough and complete. I learned a ton. Again, as I always do from you, my friend. Allison is next on biologics for how we do this in our office practices. Thank you guys so much for having me here today. We're going to talk, as he said, about a little bit of some logistical items to offer orthobiologics out of the office setting. I have no disclosures. Luckily, I get to skip over some FDA regulations since those have already been spoken about, my least favorite topic. Then we'll talk a little bit about billing coding, the inevitable question of cost and what should we be charging for this materials, and then how we've set it up, at least in our practice, to make this really feasible to do on a day-to-day basis. You'll notice in my procedure, I personally don't like to use the term stem cells. I find that patients really latch onto that and it often gives them some unrealistic expectations. We'll mostly talk today just about PRP, but also be back in adipose as well. We'll skip on over this. This is a great document, I do think, from the FDA and surprisingly being an FDA document, it's only about 26 pages. But if you are thinking about doing this in the clinic setting, this is a great place to go and look for some information on the do's and don'ts. We've all seen the headlines over the last couple of years about the FDA really cracking down on some of these stem cell clinics that do everything from these vampire facials, to injections in your corneas, to injections all over the place. Recently, I've been getting a lot of traffic in my office about patients asking for exosome treatments. That seems to be a big thing out in the media right now, and these are unproven treatments as well, and there's actually a consumer watch out for these. Always good to be aware of those things as patients will come in and ask for them. I think when we're talking about doing orthobiologics out of the office setting, the first question to ask is really, what is your goal? Is it to attract new patients or grow your practice? Is it to stay current on what patients are asking for? As we saw, the Google searches are in the millions of patients wanting to know what these treatments can do for them. Some providers use it as a new stream of revenue, and others such as myself, my big goal is really to be able to offer a service to my existing patients. I think with that, luckily it has ended up growing my practice and attracting new patients. But I think once we know what our goals are, we can figure out how are we going to go about marketing this and incorporating it into our day-to-day practice. Mostly so it doesn't take over the practice, because I do think there's a big want and ask from patients. I'm not going to pretend to be an expert in marketing, but marketing promotion materials are subject to FDA scrutiny. Whether it's a TV or radio or a print ad, I think what you say and how you say it really matters, especially for the information that's getting across to the patient. I'm a big fan of websites that you create, that you can direct your patients to, to get some factual information as opposed to going to Google and just reading what they find out there. But again, you've got to be really careful about what you put on there. I have found personally that this can be a struggle sometimes if you're at a larger institution that has a marketing team. I have a lot of push and shove with ours to try to not oversell this treatment. Verbiage has always been really important for me personally. I think that's something to think about as you're creating your website and your materials. We know how much patients love to go on and look at provider reviews. This is one thing I didn't realize until recently that in your marketing materials, these patient claims, if you're putting them up on your website, are also subject to FDA scrutiny. If you had something up like, I was in horrible pain until Dr. So-and-so injected my ankle with PRP and now I can run a marathon. Well, we all know that's not the typical response that PRP is going to give a patient. That would be a false claim. Moving towards something that is much more generic about how patients just talk about how you offer them really great care is often a much safer way to go, although not as juicy content often. Billing and coding, this is the code for PRP that is nationally recognized. Most insurance carriers do not cover for any sort of PRP, BMAC, adipose-type treatments. There are a couple that will cover for lateral epicondylosis or knee osteoarthritis, so I know I'm not really in y'all's purview. And this does change every year, but most of the time these are fee-for-service procedures that are done. And as far as our views go, there are no associated RVUs nationally with this, like you would have for, say, a medium or a large joint injection. One thing I have found is that's actually been fairly problematic for some of my fellows, say, who are graduating and might want to capture those RVUs due to how their contract is set up. So one thing that I would recommend if you were trying to get an RVU associated with this is to find something that's really comparable. So, for example, a cash pay, like at least at our institution for a joint injection, just Palpation-guided is about 300 bucks. It gets you 0.79 RVUs. So if you're going to charge maybe double that cost, you might be able to get double the RVU, and that can help in negotiating with the institutions on what is a fair RVU. So cost. So in 2019, a study came out in the Journal of Sports Health where they surveyed a whole bunch of practices and they got 1,300 responses back, specifically about who was offering PRP, BMAC, or Adipose for knee injections to kind of keep it standard. And it came back with a whole host of prices, as you'll see here, as low as $300 upwards of $1,200 to $1,400 for a single PRP injection. They found that about 40% of clinics were offering PRP and only about 20% of clinics that responded were offering both PRP and either BMAC or an Adipose, some sort of MSC treatments. And the cost for those, obviously, much higher. I actually found the range to be fairly low for the BMAC and Adipose. I have many patients who have gone to some of these big box stem cell companies and they paid upwards of $8,700 for a PRP plus a BMAC injection. They did find that these numbers seem to be higher, at least for PRP, given population size and median household income of the area. When pricing it out, it's really about your materials and overhead. Most of the time, these are going to be done out of the office just because it's more financially feasible for patients. I think a lot of the academic institutions, at least in the Northeast where I'm practicing, tend to favor more like $400 to $500 per injection. It allows us to be able to teach medical students, residents, and fellows. But this is obviously a variable practice. I know certain groups also, different providers offer different costs depending on who you're seeing for that same procedure, which can get a bit messy. But there is a lot. Talk for another time, but there's a lot, at least in our primary care organizations going on right now, about the equity of these types of procedures and how much they cost in trying to offer services to help patients cover these out-of-pocket costs. So when we're talking materials, a lot of it's the cost of renting the unit or the cost of kits. A lot of times you can just kind of rent the units out and they won't charge you for expecting you to buy the kits and then whatever your other materials are for that procedure. And then we're going to kind of go through just some patient experience, how I think there are some good ways to set up going about this in your clinic. So in my practice, at least, I see patients one of two ways. I'm either seeing my own patients and the talk of PRP or BMAC or adipose comes up pretty naturally when I'm talking about any other sort of corticosteroid injection or extracorporeal shockwave therapy. And then I also receive patients from some of my colleagues to do a consult for PRP. That is really mostly so they don't have to spend, one, the time that it takes to go through it, but we can go through what the day of the procedure is going to look like, realistic expectations following the procedure, and unfortunately kind of talk about the cost of the procedure. I always joke with my fellows that I tend to, I feel like I negate placebo effect of any of these procedures because I think I'm a Debbie Downer when talking to patients, really going over the realistic expectations for them and telling them what exists in the literature. Because as we saw earlier, literature does not necessarily support a lot of these treatments. Now, I'm in the world of sports medicine, so we live in gray zone of patients that want to remain active and have somewhat unrealistic expectations. So sometimes I think it's our job to kind of damper that down for what this is really going to do. And then I think documentation is a huge thing, is outlining to them what this is, even if we're doing a bone, a BMAC or an adipose, that there are a limited number of MSCs in this. And then creating dot phrases for that documentation as these tend to be fairly long visits. Then if the patient decides they want to go through with it, you know, getting them scheduled. On that visit where we're doing a consult, we're really discussing it, I tend to take the time to do the physical therapy prescriptions, any post-procedural instructions, day of information and any DME they may need. And that really allows you to cut down on some of the time it takes during your procedure as the procedure times can really vary. On the procedure day, I would really recommend having them sign an advanced beneficiary notice that helps protect you and your office and the patient on any charges that they're going to incur as these aren't usually billed to insurance. We collect payment and then do consent. I do think also, you know, personally, and I know a lot of people might feel that do this, tend to do written consent for this that we've had drawn up by the lawyers at our institutions, just because it is a hot topic right now and a little different than a corticosteroid injection, which I know most people would just get a verbal consent for. So all things to think about as your nurse or MA are rooming the patients. And then I think the time for the procedure really varies. Personally, I draw my own blood. So it takes a little bit longer, but many practices will have a nurse or phlebotomist in the office who draws the blood and gets it into the machine and spinning. The spin time for most of these units that you'll get from a company versus like the tabletop centrifuge that they talked about earlier is going to be somewhere between five and 20 minutes. So often we'll see a patient, we'll draw their blood, I'll go see a follow-up while it's spinning and then come back in and do the injection, which is usually fairly quick. A little different versus an out-of-the-office BMAC or Adipose, usually at that consult visit, we will prescribe them some Ativan and then we'll have them take it on their own power in the office so we're not dispensing a medication. And these are much more involved. They would take usually around two hours for some providers, an hour. So usually this is more of a blocked clinic time type scenario, but I do think both of these are very feasible to do out of the office once you have the right processes in place. That can just take a while, depending on institutional regulations. And that is all I have, thank you. Thank you. Thank you, Allison. That was perfect. In orthopedic foot and ankle practices, we tend to not think about all of those issues. We just kind of do it. And so that was exactly what we were looking for. So that was very, very helpful. Moving in to our question and answer, I don't have any questions from the audience. I do have a comment from RP, who says that he does mechanical shockwave in his office. He's been doing this for about six years and he's in agreement with some of the literature, but says that he's really had great results, 70 to 80% success with mechanical shockwave for plantar fasciitis. And he's seeing similar results in his insertional Achilles patients as well, and lesser so for lateral epicondylitis. So that's just a comment from one of our listeners. I would like to direct the question to the panel about Achilles tendinosis. Every time I read that data, I'm shocked because I do it for Achilles tendinosis. And I find that it works for me. So I would just like for the panelists to comment on that, what your thoughts are. If you think the literature is actually accurate as it relates to your particular practices. Dr. Bailey, you do PRP injections for tendinosis or shockwave, which one? PRP. To me, since the procedure itself is relatively minimally invasive, I think it is always possible to try. As long as the patient is willing to take this and try, if it is working, I would actually recommend, yeah, yes, going with it. The only thing is how long, for example, after the injection for Achilles tendinosis, how far this effect can last? Do you notice that it's actually solving the problem or it is just temporary solution? The timelines of the effect of PRP in your experience? I put them, I do the procedure, I put them in a tall boot with a heel lift and I keep them there for three weeks. And then after that, I start gentle stretching exercises and put them back in a shoe with the lift at three weeks. And then I see them back at six weeks. And I've been somewhat amazed that I'm able to get mid-substance tendinosis to be better. For insertional tendinosis, the few times I've tried it, I've gotten very little. But for mid-substance with eccentric stretching, I've actually been able to get reasonable results because surgically, we just don't have many options there. So I agree with you, it's worth a try. Correct, yeah, I would agree. I think there's nothing we can lose if we just try PRP before stepping up to surgical treatment. So in between, we can always try it. And if it works, then it's fine. Errol, I would agree with you. I don't do them personally, but we have some interventional physiatrists that do some PRP. And I agree completely for that mid-substance where you've got the MRI and you've got that intratendinous signal aberration, almost looks like a intratendinous cyst or something like that. I have seen cases where those patients do respond to intratendinous PRP. And I think you hit on a very important thing. You have to then immobilize them for a while. You have to lock them down, take the tension off of the tendon. I like to try to get them, if they're not in just horrible pain, I like to try to get them stretched out a little bit before the procedure instead of just waiting till afterwards. But I have seen it work for the intratendinous tendinosis, but not at the insertion. Thank you. I have three more questions. One anonymous attendee is, what is the average success rate for PRP and osteoarthritis of the knee? Would anyone like to comment on that? The only high-level evidence, and it's a very organized, high-quality study, they actually did not find any difference between the control groups, which is placebo injection and PRP group. And it was correct for both six weeks and 26 weeks time period. So I'm not sure if in your personal experience, there are different results, but I did not think that PRP use can be justifiable based on this high-level evidence we currently have. So I'm happy to hear your thoughts about this. There was actually some studies that came out recently of decent level evidence showing efficacy and time point about equal to hyaluronic acid, and then a little longer lasting than hyaluronic acid in some other studies. More for mild to moderate knee osteoarthritis. So I think there's definitely, I think a trend in our field, at least to start to try to move towards PRP and especially away from cortisone injections, because we know the detriment that the cortisone can do. So definitely the thinking of not as good as we would like it to be, but overall much better than some of the options that we have. But I think the literature has gotten stronger over the last two years. There have been about, I think, three studies published in the last two years on it that are pretty decent quality evidence. Question number three by Morali. Is there a documented use of ultrasound to guide injection in the literature that was discussed? I can't remember who's talk that was in about ultrasound guided injections. Yeah, lots of studies I've noticed they actually prefer using ultrasound guidance, especially the ones that they use for Achilles or plantar fasciitis even, but there are also some groups they are using, for example, for plantar fasciitis, they prefer finding the maximum point of tenderness and injecting without ultrasound. However, some injections to ankle joint even they used ultrasound or PRP injections. If it was in my hands, I would rather use ultrasound just to make sure that PRP that I'm injecting is going to the right place. But for ankle osteoarthritis, yes, probably it's okay to inject without ultrasound too. Thank you. We have one more additional question from Dr. Gray. And his question is, is the world literature still adverse to cortisone injection trials? And let's say the retrocalculonial bursa for insertional Achilles tendinopathy or mid-substance nodularity. I can begin answering that question. I've been very reluctant to put cortisone in the retrocalculonial bursa. So I don't do it. But there have been rare instances where I'll have an elderly patient who's having trouble and they've got lateral or more medial inflammation. And I'll put a very low dose, a half a cc of dipromethral or something like that in that area and see if I can get something for them because there's certainly not surgical and they're failing physical therapy and I don't have very many options. But so Dr. Gray, I would say that I would think that the literature is still gonna say, don't do that. But I'd like to hear what the panel has to say. Never done it, Errol. Never mid-substance. And I may have had one retrocalculonial bursa that probably was 25 years old in a 97-year-old gentleman who was a doorman. Still working. I too am extremely hesitant. I've never done it. I would not either. All right, let's see. Do we have any more? I think we're done there. It's 6.15 Eastern time, 5.15 Central. I think we can move on. And since it's Friday and try to wrap this up.

foot and ankle surgery

platelet-rich plasma therapy

chronic plantar fasciitis

Achilles tendonitis

ankle osteoarthritis

mesenchymal stromal cells

regenerative medicine

bone grafting techniques

angiogenesis

vascularized grafts

orthobiologics