All right, let's go ahead and get started. I want to welcome everybody back to AAP Virtual Didactics for today. My name is Sterling Herring. I'm a PGY3 at Vanderbilt. Appreciate everybody joining us today. We've already gone through some of these goals for today, but we will recap housekeeping. We're going to keep everybody video and audio muted except our presenter. If you have any questions, if you click on your participant list, you should see my name up near the top. Again, my name is Sterling Herring. If you double click my name, you can send me a message in the chat and I can ask those questions to our presenter at appropriate times. If you have any kind of big questions in terms of the series itself or logistical issues, please feel free to reach out to Candice. Her email is there on the screen or you can find her via the AAP Twitter account. So without further ado, we're excited to have Dr. Asad Siddiqui here with us today from Columbia University up in New York. How are you today? Doing great. Glad to be with everybody. Great. Thank you for joining us. My pleasure. All right. I'm just going to... Can I go ahead and share my screen? Yes, I'm sorry. I should have clarified. Perfect. Thank you. Looks great. OK. All right, great. So first off, thanks to the AAP leadership and everyone involved in putting this didactic series on. And just want to start off with a really big shout out to all of the trainees who are really making us proud and the way that they've helped with the response to everything that's happened. I was a PGY2 in New York when Hurricane Sandy hit. So I can certainly emphasize with how challenging it can be to have your training disrupted and upended in this way. But you guys are doing a great job and really making us proud. And I know us as faculty really are trying to stay engaged in ways that we can help you get back on track as things start to normalize. So along those lines, we're going to be talking today about a bread and butter topic for me as a sports medicine physician. We'll be talking about tendinopathy with an emphasis on mechanisms of tissue injury and healing. So our objectives for today, we're going to be talking about what are the normal and pathologic anatomic and physiologic features of tendons. We're going to talk about the role of load in directing tendon development and maintaining homeostasis via a process called mechanotransduction. We're going to be describing the phases of tissue healing, reviewing acute injury mechanisms, and kind of relating them to the pathophysiology of chronic tendinosis and trying to explain how those interplay with each other. We'll be talking about some common loading paradigms and trying to make sense of how we can actually use load in a way that can be beneficial to our patients without overloading them. And we're going to briefly touch on some therapeutic management options. That won't be the focus of this talk. So we'll kind of breeze through. There's a lot of content in this deck. And I'm happy to make this slide deck available to anyone who's interested. We probably won't hit everything that's in here. But we'll try to highlight the main event. So let's start off with where our tendons come from. So in early development, tendon is derived from the mesoderm, which gives rise to the mesenchyme. And the mesenchyme is made up of these mesenchymal stem cells, which are the source of all connective tissue in our body. These mesenchymal stem cells are able to be preferentially differentiated into specific cell types based off of the signaling factors and the transcription factors that are present. And so between all these different types of tissue, adipose, areola, tendon, ligament, bone, cartilage, et cetera, tendons kind of fall into this realm of dense, regular connective tissue that's right here, this middle component right here. And again, that's a product of the mesenchyme. This process is initiated early in fetal development and typically at about six to eight weeks, you start to see progenitor cells, which express a scleraxis transcription factor, which appear between the muscle and cartilage cell layers. And then load really is responsible for directing the development and maturation of these tissues. So initially, that happens with growth of skeletal elements. And as the progenitor cells, which ultimately develop into muscle and the myotendinous junction continue to develop, then later on in the process, you get active muscle forces, which also provide that load signaling to direct the tendon development. So what does a normal tendon look like? A normal mature tendon is typically predominantly made up of type 1 collagen. 60% to 80% of the dry weight of a tendon is type 1 collagen. With a small portion of type 3 collagen in normal tendons, though what we see in pathologic tendons is that share of type 3 collagen does increase, the collagen really functions to provide tensile strength. Nestled in between these collagen fibrils are tenosites, which are the active metabolic cell of the tendon. And these tenosites are regenerative in the sense that they are the source of synthesizing collagen and extracellular matrix in response to load. We also have elastin, which is responsible for compliance of the tendon, proteoglycans, which function as pulse dampeners and dissipators of force, and then lipids, which reduce shear stress-induced friction between the cells. So when you look at these diagrams, basically these little purple dots are the nucleus of the tenosites, which are nestled in between the collagen fibers. This is cross-sectional view, where you see the endotenon surrounding the fascicles, and again, those little purple nuclei of the tenosites present. So normal tendon is structured in this hierarchical structure with collagen triple helix making up the base of the collagen fibril, which is wrapped in loose connective tissue. And that connective tissue layer functions to provide a check against friction between collagen fibrils to allow the tendon to functionally stretch and move. And it's also a conduit for blood vessels and nerves to the extent that these tendons are vascularized and innervated. And then surrounding the whole thing is the epitenon, which kind of holds the structure together. So you get this bundle of fascicles, which is then bundled with other bundles to create the tendon structure. And that's what gives it its tensile strength. So the question then becomes, how do these tendons respond to loading? And that's where this concept of mechanotransduction comes in. And mechanotransduction is described as a process by which mechanical stimulus is transferred to the tenosites and induces a biochemical cellular response. So it's sort of the conversion of a mechanical stimulus to a cellular response. And in tendons, that happens via direct mechanical deformation of the ECM, which is typically a tension-induced process, but can also be compression-induced. And then there are interstitial fluid shifts within those connective tissue layers, which also create mechanical load on the tenosite and induce a response. So the optimal amount of load is defined as that amount of load which maintains tendon homeostasis. So basically, it's an amount of load where the load matches the rate of repair. In tendon overload, what we typically see is that you get this breakdown of the ECM, which then is not allowed sufficient time to regenerate or restore itself. And as a result, the ECM does a worse job of actually transmitting that load to the tenosites. So the tenosites are actually hypostimulated, even though the actual load on the tendon is maybe greater than it's actually being sent. So you get this load repair mismatch and dysregulation of the tendon, which spirals down into tendinopathy. So when we break out injury of a tendon, we think, broadly speaking, acute versus chronic. And so acute typically involves direct either contusion, laceration, strain, or rupture, direct disruption of the tendon architecture, often in the setting of a super physiologic load placed on a tendon when it's not ready. So that's where you typically see this, in spikes of load for a tendon that's not habituated. Chronic tendinopathy is a much more insidious process and can be the result of repetitive microtrauma without the interval allowance for restoration or regeneration, age-related physiologic change, and then biomechanical degradation over time, either through other issues with the kinetic chain, depending on where the tendon is located, or biomechanical degradation in the setting of occupational activity. So it's a much more insidious and less identifiable etiology, but what we typically see is that these two processes kind of work in parallel, but they also feed each other. So you get this interplay between the acute injury, which can predispose to chronic injury, and then chronic pathophysiologic change can predispose to lower the threshold for an acute on-chronic injury. So that's where these two pathophysiologic paradigms kind of intersect. So what does an acute tendon injury look like? Well, a little squeamish. I apologize. Boom, you can kind of see it right there. That's a very clear demonstration of an acute physiologic injury. This is Kevin Durant. Some of you guys might have seen this a couple of years ago in the playoffs. So it's usually that acute application of a load, which is greater than the tendon's capacity. And immediately after, the injured tissue enters these phases of healing. So the first phase of healing is the hemostasis. So this tendon disruption causes disruption not only of the tendon structure, but of the vasculature and the blood flow that feeds the structure. And so you get immediate vasoconstriction to try and control the bleeding and activation of the coagulation cascade. Platelets are then activated, and you get the initiation of inflammation. And this happens almost immediately. And that leads into, that's sort of the impetus for that inflammatory phase of healing, which basically comprises the first week after an injury and is typically modulated by ecosanoids. Particularly in this case of tendon, TGF beta is a significant growth factor, which is going to play a large role in directing the healing process. At the same time, you have all this cellular debris from the injury site itself. And so you get neutrophil infiltration and proteolytic breakdown of that debris, which is then phagocytized by macrophages. And these macrophages stimulate fibroblasts to congregate in the area of injury. And that leads to the initiation of proliferation. Along with that, VEGF and other growth factors initiate capillary formation, and you get new pathways of vascularity into the area that is injured so that it creates a conduit for a lot of these healing mechanisms and these inflammatory mediators. So that's where you get some swelling and some infiltration into the injured area with these neo vessels. And ultimately, those fibroblasts that have been recruited, they are activated by platelet-derived growth factor and TNS alpha. You get this provisional matrix laid down, which is primarily type III collagen. So if you recall, we said that the majority of normal tendon is type I collagen with a very little proportion of type III. But as tendons are injured and progressively injured over time, that proportion of type III collagen increases. GAGs and fibronectin are also important mediators of the provisional matrix. And then THGS beta directs phenocyte production of the collagen and the ECM. So we've talked about the first week, and that takes us through the inflammatory and proliferative phases. But now, once that provisional matrix is set down, you get the process of maturation occurring, and that can progress for months to years. So that provisional matrix is remodeled. Collagen is then laid down in sort of an organized network, and the collagen matrix matures in response to loading. So again, post-injury loading is a very important feature of the healing. So it's not just what the body is doing. It's how the body responds to the forces that we place on the injured structure after injury. What we do know is that prolonged immobilization immediately after injury is protective and is probably helpful in the immediate setting. But prolonged immobilization in the long term has deleterious effects. The tendon can atrophy. You can get reduced water content and proteoglycan content, which, as you recall, are very important components of the tendon to dampen force and to preserve the collagen. So what we typically see is that after the inflammatory phase, stretching can be appropriate because the stretching is a soft enough load to increase collagen synthesis. It can improve fiber alignment. It can result in higher tensile strength when applied appropriately. And repetitive motion does seem to increase DNA content and protein synthesis in tenosytes. Interestingly enough, there is such a thing as doing too much. In some of the animal studies that have been done, they show that taking the cultures of tendon stem cells or progenitor cells and applying either a 4% or an 8% cyclic stretch in terms of tension, a lower stretch or a less intense stretch actually was better at preferentially inducing tenosyte differentiation, whereas a harder or a more intense stretch, it directed the differentiation of those stem cells into not just tenosytes, but adipocytes, chondrocytes, and osteocytes. And so that's where, in chronic tendinopathy, when you start to see other structures, calcium deposition, that sort of thing, within the tendon structure, it speaks to that overload phenomenon and how the tendon progenitor cells responded to the load after the injury. So how do you then prevent an acute injury from becoming a chronic injury? And this is a question really of training load. So like we described, loading is important and appropriate after the injury, but it has to be within the appropriate bounds. And that's sort of a moving target because there's no way to really quantify that in a way that we have strict guidelines for. We have rules of thumb, but the general concept is that training load is essentially a measure of system stress. And the system of a tendon is not just, it's primarily biomechanical and physiologic, but there's also a behavioral environmental element when you kind of consider how we load in the setting of our lives. And so the name of the game is really capacity. We're trying to increase capacity of the tendon at a rate which is slow enough to allow appropriate recovery in the interval setting, but not so slow that the tendon is not being loaded and is not getting those signals that it needs to direct resources to its repair. So we're trying to optimize the cycle of loading, recovery, and fueling. In sport, this question of load management has become very popular. And we're really speaking about existing all tissues and all people at a macro and micro level, we're existing on this continuum between homeostasis or everything being in line with each other and death, whether that's cell death or athlete death. But essentially any load is gonna take a tissue and move it on this continuum away from homeostasis and towards death, but recovery is what restores it back to homeostasis. So what we're looking to do is we recognize that as we load our bodies and as we load these tissues, there's gonna be a period of reduced capacity, but with appropriate recovery, we hope to not only get back to our baseline, to actually induce the changes in the tissue so that the next time we apply load, we're actually at a higher baseline. And then over time, that results in increased capacity. And that's what good training regimens do. What happens far too often is that you get this period of load and diminished capacity. The recovery is insufficient. And so you load a tissue that is not fully recovered. And so you end up on this negative trajectory. And over time you get worse capacity despite your training regimen. And so that's what we're trying to avoid at all costs. So tendinopathy, particularly in the chronic setting, we're talking about a pathologic state in which tendon function and or architecture, that's gonna be an important caveat we're gonna talk about in a second, function and or architecture is disrupted secondary to injury, overuse, or a pathomechanical process resulting in pain and dysfunction. So again, it seems to be a continuum, and this was described by Joe Cook, who's one of the leaders in tendon research back in 2008 and 2009, where this is exactly what we've been describing so far. There's a tendon, which is loaded and unloaded, and when that's optimized, you induce adaptation, which then strengthens the tendon, and then you can continue to stay in this top part of the continuum. When the load is excessive, you can end up with these structural changes, which are reactive, and if those are not afforded the appropriate time to recover and improve, you end up in these irreversible tendon disrepair and degenerative tendinopathy states. So, that's kind of how we understood tendinopathy in the early setting. This is the time period where we were going away from tendinitis as a term, because we were recognizing that this was more of a biomechanical process than we appreciated, and the role of inflammation was being downplayed. We'll talk about that in a second. But in 2016, they updated this because there was a recognition of the fact that structure, pain, and function are not as closely aligned as we might think. There are plenty of people, and we see this all over the body. We see this in the spine. We see this in joints. There are a lot of people for whom their functional level and their pain level does not match what we see on imaging, and so the recognition of this led these researchers to expand this continuum and account for the fact that structural disrepair does not necessarily mean that you have a tendon or a tissue that is nonfunctional. So how you read this, this right side is basically that initial representation of the schematic we just saw describing the tendon continuum. But then down here we have this other element, this sort of branch, which recognizes that even if the tendon is in a structural state of disrepair, you can still load the tendon in a way that will allow you to be functional and active despite the fact that the tendon is structurally not what it used to be. That's an important thing to recognize because that really informs how we counsel our patients and allows us to give them the confidence to know that just because their MRI says one thing or their ultrasound says one thing, that doesn't dictate their future or their clinical course. So the histopathology of this, when we talk about those structural changes, really what we're talking about is this organized collagen alignment, alteration of the ECM composition with increased collagen type 3, calcium deposition, and the presence of matrix metalloprotein cases really seems to drive a lot of the structural change. And then interestingly enough, tendonopathy, chronic tendonopathy actually seems to be a hypercellular process. So the problem is not that you have insufficient number of tendon progenitor cells or stem cells that could potentially become tenocytes. You actually have those in good numbers and often in increased numbers. But the problem is these cells have less regenerative capacity and that is the problem. So whether that's due to a disruption of the mechanotransduction or just the innate reduced capacity of that cell to produce collagen and ECM, we're not entirely sure. It's probably a combination of the two. So again, when we talk about inflammation, in the early 2000s there was this big move to say that inflammation is not what's happening in chronic tendonopathy, that it's a biomechanical process. Well, it's not so clear-cut. There have been a number of studies over the years which have demonstrated that macrophages, T cells, B cells, and a number of inflammatory mediators are present on histologic studies of chronic tendonopathy. We know that three weeks after an acute injury, inflammatory mediators are still there. The question is, are these inflammatory mediators the primary drivers of pain, of structural degradation, or of healing? Because the implication is different with each of those. And even as recently as February of this year, we see that the literature is very mixed on the presence or absence of inflammatory mediators, with macrophages most often identified as the mediator present, which is sort of a low level of inflammation because that's just a marker of tendon injury. So what we do know is that the inflammatory cascade is a very key signaling mechanism to direct healing, and it does play a role in the healing. The question is, once you get to that chronic state, what does the presence of those mediators mean? Because oftentimes, the inflammatory process directs additional things which can mediate pain. For example, neovessel formation in tendonopathy has been widely recognized as a feature of chronic tendonopathy, where this increased power Doppler signal and ultrasound, which recognizes that, or which alerts us to the fact that these neovessels have been stimulated to enter into the tendon, the healing tendon structure. Now as we described in the phases of healing, there seems to be some element of this which is by design because tendons are relatively avascular and need some degree of a new conduit to get some of these inflammatory mediators into the tendon in the acute phase. However, in the chronic phase, we don't know if these are actually helpful, and they also seem to be accompanied by neural sprouting or neo-innervation, so these little immature nerves which follow along with the neovessels, and then these nerves can then become a mediator of pain, which is not necessarily protective or helpful, and so this is a potential therapeutic target and folks like Alfredson and a number of the leaders in our field have published on tendon scraping and high-volume injections and a number of interventional ways to disrupt these vessels and nerves mechanically in a minimally invasive fashion, which often times does reduce pain dramatically immediately, which is a pretty satisfying procedure when you get to do it. So in imaging, really what we're seeing is the sequelae of the structural changes in the tendon, so like on x-ray if we see calcetic tendinopathy, that reflects the calcium which has been deposited into the tendon substance. In MRI, when we expect, or in ultrasound rather, when we expect to see this very densely packed fibrillar pattern on long axis and in short axis where we expect to see sort of this broom end pattern, I describe it to the patients often at tendon structure as like a bundle of spaghetti, and when we expect to see this, we often see the sequelae of these histopathic changes. So we see hypoechoic signal because the water content or the linear structure is no longer densely packed and there's edema within the tendon. We can see actual fiber disruption represented by this anechoic area right here. So we're seeing the histopathologic manifestations of tendinopathy when we sort of image these tendons. Same thing on MRI. If you compare the quadriceps tendon to the patellar tendon in both T1 and T2 sequences, you see that tendons are normally typically low signal, uniform thickness when they're healthy like these quad tendons, but when you look at the patellar tendon, you get increased signal, you get fusiform thickening, oftentimes you'll have reactive bone marrow edema, and that's just, you're seeing the manifestations of overload. So like I said, we're going to briefly touch on treatment strategies, let me just take a look at our time, looks like we're doing okay, we're going to briefly touch on treatment strategies, but the one I want to highlight is the cornerstone of treatment for tendinopathy is activity modification. And this notion of RICE, which has been around I feel like forever in medicine, we'll talk about sort of how the sports medicine world is moving towards this notion of peace and love, and we're going to talk about what that means. The use of medications, physical therapy, modalities, injections, surgeries, all of these have an impact on the way that the tendon responds to the body's innate healing mechanisms and we'll talk a little bit about that as well. So peace and love, if you're a reader of the British Journal of Sports Medicine, they've proposed this change to the traditional RICE framework after injury, and it really speaks to our understanding of the importance and the sort of central location of load in the management of these injuries, whether they're acute or chronic. So P stands for protection, you should in the initial moments after injury avoid the activities that significantly increase pain in the first few days after injury. Elevation, it made the cut from RICE. You do want to try to improve fluid flow and lymphatic drainage from an area that is swollen. Avoid anti-inflammatories, we'll briefly touch on this because this could be a lecture in and of itself, but it's somewhat of a controversial statement, but the idea is that anti-inflammatory medications slow or impede a process, a natural process by which the body heals itself. And so there's a short-term, long-term trade-off when you use anti-inflammatories. Compression, again, another means of reducing fluid flow or fluid accumulation and promoting lymphatic drainage. Education, empowering the patient to find that sweet spot for themselves to where they can continue to be somewhat active, but not too much. Moving into love, we're talking about loading. Again, central to the management of these injuries. We do want to let pain guide our gradual return to normal activities, and we want to avoid We want to avoid acute spikes in load, and we do that by listening to our body. Optimism, this is an interesting inclusion because it really speaks to the psychological toll that these injuries can have on patients, whether they're acute or chronic, particularly in people who are already active to a certain degree. As clinicians, and as educators, and as coaches, and as the resources for these injured patients and athletes, we want to be a source of optimism for them and empowerment because that's going to be really important to prevent some of the deleterious effects of making this injury a sentinel event that leads towards a sedentary life or takes someone off the course of being an active person. We want to avoid that at all costs. Vascularization, so encouraging cardiovascular fitness and cardiovascular activities to increase blood flow throughout the body as a means of augmenting healing. And then general exercise in a graduated sense of ecological and heterogeneity. We do know that exercise on the whole does seem to increase maximal tensile failure to load, and in animal studies, there's been some evidence that exercise in general does increase load-bearing capability and has some impact on the histologic and morphologic recovery of tendons. We even see that on ultrastructural investigations. But when people hear tendinopathy, they're going to say, okay, so what kind of exercise should I do? And like I said, there's a number of different sort of treatment paradigms or load paradigms which people talk about. In tendinopathy, eccentric exercise probably gets the most or has gotten the most pub over the last decade. But there's a number of other ways to load a structure. So isometric exercise tends to be a load-limited. Same thing with isotonic, so the difference being isometric is a contraction without any shortening or elongation of the structure. Isotonic is maintain a consistent velocity throughout the range of motion. So these tend to be load-limited because you can't really go all out with these. They seem to have, in some studies, a potentially neuromodulatory effect which some people really advocate for these as analgesic exercise, particularly for use within seasons where you can't really shut someone down if you're like you could be off-season. Concentric exercise is where you are loading a tissue while it is shortening. So typically, this results in a steeper slope of force production and greater force development for a given length throughout the contraction. So traditionally, these are thought to be good for strengthening. Eccentric exercise is interesting because this is where you're contracting the tissue while lengthening it. So you can think about the negatives from a heel raise. So once you've gone all the way up on your toes, a lot of people will just drop back down. So you're getting the concentric with the heel raise and bringing the heel all the way up, but you're not actually getting the eccentric component when you don't have a control descent. So the eccentric component has a more consistent distribution of load throughout the range of motion, which can make it an ideal exercise when you're trying to confer higher loads to the tissue. So when you combine, people talk about, well, you should do concentric or you should do eccentric. They're usually talking about maximizing one phase of the motion at the expense of the other. This paradigm of heavy, slow resistance training, where you're sort of doing bidirectional maximization of load, has gained a lot of favor, particularly in the pre-injury setting as a means of really conferring the highest load to a tendon in a way that is not necessarily going to induce spikes. And then once you build up strength and once you've sort of restored normal mechanics to the tendon and the tendon muscle junction, plyometrics is probably the most important. These plyometrics are basically where you are doing quick, rapid stretch and shortening cycle-type exercises, which are proprioceptive. So they have a neurodevelopmental element to them, and they're ballistic. And they're a little less controlled, and so they have a little bit more carryover to sport and may influence performance a little bit more than we might appreciate. So being familiar with all of these tells us that they're connected and they overlap in certain places. But when people ask you, what is the best type of exercise, we don't really have one magic bullet. We just know that progressive gradual loading is the way to go. And so a tendinopathy rehab progression should include all of these. So initially, you're trying to reduce pain and reduce swelling and reduce normal range of motion. Then isometrics are a good way to start activating a structure which may have been deconditioned in the immediate injury setting. And then progression to concentric, where you can add additional load, can help build functional strength. And again, combining concentric and eccentric exercises. And then once you have restored that functional strength, redeveloping that proprioceptive capacity through plyometrics, stretch-shortening cycle type exercises, which is what transitions you back into sport-specific type exercises, which really focus on the goals of sport. So that's one example. We're not going to get too deep into modalities. There are a number of modalities which do claim and have some varying degrees of literature behind them to suggest that they can impact the way that a tendon heals. Integral medication, again, we'll keep this brief. This could be a lecture in and of itself. But NSAIDs are a hot-button topic in tendinopathy, and that kind of goes back to what role you think inflammation actually plays in the progression or the development of tendinopathy. Nociceptive modulation is important because we do want pain. Pain that is not protective, we want to minimize that so that we can allow people to move and they're not deterred from moving and loading. So naproxen is one medicine that is pretty commonly recommended for tendinopathy, not for its anti-inflammatory effects, but really for its nociceptive effects. These NSAIDs, in the way that they're studied, there's not really that much translation capability from the studies to clinical practice, and one of the reasons is that a lot of these studies are transection repair models, in which an animal's tendon is transected and then surgically repaired, and then they dose them with an anti-inflammatory or not, and look to see if that, you know, they then sacrifice the animal and look at the mechanical properties of the tendon. And certainly, you know, the one that's been studied or that I see in a lot of studies is paracoxib, which does seem to have a lower load to failure level in these repaired tendons than controls. Interestingly enough, there's some data going back to the 70s and 80s, which showed that indomethacin, which is a very potent anti-inflammatory, actually increased tensile strength, as well as the proportion of insoluble collagen, and increases fibril cross-linkages. So, you know, the role of the NSAID is debated, and I think there has to be sort of a shared decision-making model when you decide to put somebody on NSAIDs and a lot of education to explain what the goals of giving them that treatment is. The goal is not to cure, so to speak, their tendinopathy or just take away their pain. It's really a means to an end. If other analgesics and topical medications have not been helpful, then this may be an option to help induce some improvement in pain and allow for earlier loading and mobilization. So acetaminophen also is a COX inhibitor, but it primarily acts in the CNS and not peripherally, so it seems that that is sort of what modulates pain experience rather than inhibition of local inflammation, and that's why we tend to be a little bit more okay with people who are maximizing acetaminophen as opposed to the NSAIDs. And topicals, you can get topical NSAIDs and topical analgesics, but also nitroglycerin patches are kind of an interesting off-label medication in which it seems as though the application of nitroglycerin in small doses as a patch over a tendinopathic tendon can induce some nitric oxide-mediated cell signaling pathways, which can assist in pain reduction. So there is a role for medication, but again, it's medication in service of load. Same thing with injections. The adoption of ultrasound and the widespread presence of ultrasound has been certainly helpful in this situation because it's allowing us to inject a number of substances in very precise ways, often in a way that is more tolerable for a patient. So where you can, using image guidance certainly is recommended. And again, we're gonna kind of fly through these injection topics just because the various injections themselves have a lot of nuance to them and kind of beyond the scope of this talk. But corticosteroid has been a longstanding treatment option for tendinopathy, tendinitis, et cetera. There does seem to be some short-term improvement in pain, but long-term, we know that this inhibits the biosynthesis of collagen and can result in progressive thinning and reduction in collagen content, which can increase the risk of rupture. Again, we're injecting the steroid ostensibly for that exact purpose because you think about the traditional thinking behind tendon pain, they thought there was inflammation, steroids shut down all cellular processes and are potent anti-inflammatories. And so for pain, sure, it might be a good idea, but if you're trying to use these injections with load as your guide, you also don't wanna put them at risk for rupture. So the judicious use of steroid, you really wanna have that shared decision-making process with the patient and certainly in lower extremity tendons I think as a matter of practice, we've all gone away from doing steroids in lower extremity tendons at the very least, if not all tendons where we can get away with it. There are a number of other regenerative techniques. Again, I'm happy to make these slides available to you and we can kind of talk about this offline, but I'll kind of fly through these. PRP is probably the one that is the most studied, but a number of sources of mesenchymal stem cells are present. Prolotherapy is another treatment paradigm by which you use, more commonly we use dextrose, which kind of functions as an irritant or a sort of a kickstart for that cell signaling process in either an inflammatory or non-inflammatory way. And that often seems to correlate to the concentration. PRP, again, basically what we're trying to do is concentrate those platelets as sort of the mediator of healing and concentrate that and deliver it exactly to the area that is the most affected by the chronic structural change. MSCs, again, like we talked about before, these are pluripotent and have the potential to differentiate into a number of cell types that inform connective tissue production. So there's certainly a lot of literature out there on these, but I think this is an area where the evidence is still building. What I'm most interested in is, so now you've done whatever injection you've meant to do. How do you then inform your patient after that? And this is another area where rehabilitation post-procedure is largely pretty heterogeneous, because we don't have great data that is guiding us. Ken Mountner out of Emory and a number of the colleagues that he works with in the regenerative space have been really sort of our guiding light so far in how to think about loading after these procedures. So this is an example of a post-procedural loading program where the first two weeks really seem to be somewhat protective and very low load with giving the tissue the time to actually make it through the inflammatory and start the proliferative phase and get to that point where that provisional matrix has been laid down. And now the application of load can be instructive rather than deleterious. So if you look at what that looks like on the timeline, so that phase one is gonna be those first three days where you're non-weight bearing, partial weight bearing, relative rest, gentle active range of motion, and pretty low demand. Once you sort of kickstart that proliferative phase and the inflammation has kind of died down, now you can progress to weight bearing is tolerated and full weight bearing with some gentle prolonged stretch. And you're gonna start to kind of optimize the kinetic chain surrounding the effective structure and try to find ways to exercise the rest of the limb without actually loading the structure itself. After two weeks, now you can increase the loading of the target structure in a more specific way. And again, starting that isometric, concentric, eccentric progression. Isometrics can be helpful in that early loading period just to kind of rehabilitate the muscle and the muscle kind of junction to, if you've been off of exercise for two weeks that has an impact on your conditioning and on your load capacity. And some early soft tissue mobilization can also be helpful. And then in that maturation phase, we're talking about week six to 12, but really week six to a year, you kind of increase through that exercise progression where there's now eccentric loading brought in, there's higher levels of load, there's plyometrics for neural development and the development of appropriate sections and then moving into sport specific motion, but hopefully with the goal of preventing a repeat tended injury down the line. And some of our folks have kind of looked at the literature and tried to kind of see what has been published on this. And largely there isn't all that much agreement in how people are protocoling this after procedures, but there does seem to be some agreement that that two week period is kind of a protective period. And then we don't really expect to see much improvement or much change until six weeks. So that's helpful when you're trying to counsel these patients on what they can expect going forward. And again, there are plenty of gaps in this literature, but it's an area of scientific inquiry that is very exciting and has a lot of potential for us and can be potentially rewarding for folks who wanna get into this space. But really at this point, we're suffering from a lack of standardization of orthobiologic preparation, characterization of what we're actually injecting, a lack of consensus on the administration protocols. There's individual variability on people's injection techniques and how comfortable or facile they are with the ultrasound in making sure that the medication is getting where it needs to get. There's individual variation in healing capacity. So again, we're taking an individual patient and they're mediators of healing. And if they have a baseline impairment in their ability to heal, then that will have an impact on outcomes. And that makes it very difficult to standardize expectations and protocols in a one-size-fits-all fashion. So again, the impact of medical comorbidities and lifestyle factors all affect this literature. Surgery, we're not really gonna talk about, but just briefly, oftentimes this is a direct repair versus reconstruction. In the acute tendon setting, in the chronic tendinopathy setting, you're looking to remove extrinsic compromising factors, restore normal mechanics and anatomy to the extent that you can. And oftentimes direct tendon debridement versus tenotomy can be helpful depending on what the pathomechanics are of the initial injury. And the protocols to load vary based on the reconstruction. So what you hope is that you end up like Kevin Durant a couple of years, 18 months after his Achilles tendon repair, where you can get back to as close to your prior level of function as possible. But again, we're talking, the procedure is only the start of it. And then how you load really depends on what your outcomes will be. So with that, I got some references and happy to take any questions. Thank you so much. This is really a phenomenal kind of review of this particular topic that again is so, it's common enough and yet so specific that I'm not sure, I think we all need a lecture like this and don't often get it. So thank you for that. My pleasure. Would you mind putting that last slide back up with your contact information? Sure, of course. I've had requests, and you mentioned that you may be willing to make these slides available to folks. Yeah, yeah, I'm happy to. I've had requests for exactly that, trying to figure out the logistical side of that. I'm not exactly sure how to do it. The best way may be just to have folks email you directly if that's okay with you. Exactly, yeah, yeah, that's perfectly fine. Okay, so there's his email address right there. If you're interested in getting a copy of these slides, obviously the recording of this lecture will be available on the AAP website. But if you're interested in getting copies of the slide deck itself, if you would email Dr. Siddiqui directly, that is his email address, and he can reply to you and attach these slides. Further, I have a couple of questions, content-related. One is, I'll occasionally hear about nitro patches being used for pain or for healing, localized, increasing blood flow locally, or what have you. How often, in true practice, how often do you actually do that or see that? Sure, so particularly as the field is kind of moving towards going away from our old standard of care, which was kind of like NSAIDs and other analgesics, as our tools are becoming more and more limited, unfortunately, by the science that's being produced, I've started to use these patches more. The literature does seem to suggest that they're probably more helpful for mid-substance tendinopathy rather than insertional tendinopathy, and that's not something that we talked about specifically, but certainly there are different mechanical features and pathophysiologic features. When you're talking about tendinopathy that develops along the course of the tendon versus added insertion in that sort of fibrocartilaginous place at the enthesis. So I typically use them more on mid-substance tendinopathy, and you do have to kind of be mindful of a patient's comorbidities, but let them know that headaches are possible because they do function like nitro patches function, but oftentimes we're taking a very low dose and cutting it in fourths, which I don't recall the dosage off hand, but it's a fourth of a commercially available patch, so it's pretty small. Okay, and the mid-substance tendinopathy is the most common form, is that correct? Yes, yes, that is typically what we see, yeah. So this is something that we might consider, thank you. Another question that came through was, are we correct in interpreting that the peace and love approach is preferable to NSAIDs in general? I know you mentioned this is kind of a hot topic, some of it may still be up for debate, but the question is, are we safe or following best practices to take that peace and love approach? Yeah, yeah, so that approach, if you think about it, it's really not necessarily a radical departure from our current standard of care, it's just recentering early loading within that initial treatment paradigm. So I would not say that the science is at a point where I would say that NSAIDs are contraindicated in tendinopathy or even acute tendon injury, and the pendulum swings on this, I feel like, in all musculoskeletal tissues. I mean, when you talk about fracture healing, when you talk about people who have had ankle sprains and associated ligament tears, there's always this concern that like, are we actually impeding our body's ability to heal the way it's meant to heal? Which is a valid concern, but at the same time, you do have to recognize that people have to be functional, and so basically, I think what peace and love is really doing is saying, let's try to optimize activity modification extra corporeal ways of reducing swelling, reducing, improving lymphatic drainage, really optimizing all of the other mechanisms of healing, and if you're still in a place where you can't function, I mean, you're not going to do long-term damage, it's not malpractice to give someone a leave or naproxen or something like that, it's just trying to reorder how quickly you do that, because I think, oftentimes we see this with primary care doctors and even a number of our musculoskeletal colleagues that like, someone comes in with an injury, I mean, they're in your office because they're in pain, and so the easiest way to get them to not have pain may be to give them a medication or give them a shot, but it's a lot of work to actually educate a patient on the fact that, well, no, I'm not going to give you ibuprofen or give you NSAIDs for these reasons, and oftentimes, our ideal practice style may not match our realistic practice style because you've got patients in the waiting room, and well, prior to COVID, we had patients in the waiting room, and that sort of thing, so yeah, so again, this is all sort of speaking to the broader philosophical approach to soft tissue injury rather than, and how you apply that philosophical approach to your individual patient in front of you, I do feel has to be a, and there needs to be an individualized application of that overarching philosophy. Okay, that makes a lot of sense. I have to say, rice is a lot easier to remember. Peace and love has like a side of it and a Q in it. Yeah, there's a lot, but that said, I'm glad we're kind of taking an evidence-based approach to this. Another question that came through with heavy training, eccentric or concentric, is the goal to change tendon physiology, and I'm assuming structure in there as well, or influence the musculotendinous junction, which then assists with tendinous healing, or both? Yeah, so my understanding is that it's both, because the tendon does not exist in isolation, and we know, particularly in adults, that that myotendinous junction is really the weak link in the chain, and often where those strains occur, whereas in pediatrics, the weak link tends to be the apotheosis and that growth plate. So certainly, we're trying to influence both, and I think in some of my references, there's some papers in here that kind of talk about how load is sensed at the myotendinous junction, so you can kind of peruse that. Okay, thank you very much. We are right up against the end of the hour, so I appreciate you very much for joining us today. If anybody has any further questions, please feel free to reach out to Dr. Siddiqui individually. His Twitter information was also just on the last screen. You can reach out to me or AAP as well. If you need to go back and review some of this, you can reach out to him and get a copy of these slides, if you want to kind of share them with your program there locally, or you can go back and watch this video. Again, the links are at physiatry.org slash webinars. Dr. Siddiqui, thank you so much for joining us. We know you guys are busy. Things have been a little bit crazier for those of you in New York than for the rest of us kind of in the central part of the country. So we appreciate you taking the time to do this. Absolutely, my pleasure, and I'm really happy to be a part of this initiative and certainly happy to engage with folks offline. Thank you so much. For everybody else, thank you for joining us today. We appreciate it, and we look forward to having you tomorrow. Thanks. All right, folks, be well.

tendinopathy

tissue healing

load and tendon development

rehabilitation

medications

physical therapy

injections

peace and love approach

regenerative techniques

comprehensive overview