All right, so we're going to get started today. Welcome everyone to the session on advances in treating joint pain. I'm really excited to moderate this discussion on treating joint pain. There's been a significant number of advances in the treatment of joint pain that have occurred over the last five to 10 years, and increasingly what were previously difficult or impossible to treat joint paradigms have now become accessible to physiatrists. I'm really pleased to have a tremendous panel join me from several folks from the West Coast and some from the East Coast. Anchoring the West Coast, we've got Dr. George Chang Jian and Dr. Jacqueline Weissbein, and they're going to be talking about imaging in joint pain and radiofrequency ablation in joint pain, respectively. And then from the East Coast, we've got Dr. Jaspal Singh, who is going to be talking about biologics in joint pain. So this should be a really entertaining and interesting discussion, and we're looking forward to hearing what all the folks have to say. So with that, I'm going to pass it over to Dr. Chang Jian for more of an expanded introduction and for his talk. Thank you. All right, thank you so much, Michal. It's a pleasure to be a part of this meeting. I was really looking forward to going down to San Diego and enjoying some tacos, but obviously that's not going to happen this year. So my talk is, I know we're going to be talking, focusing on joints. What I wanted to take the tangent down was to really discuss a little bit about how we can utilize different types of imaging modalities to sort of optimize how we're performing our imaging, or excuse me, how we're performing our procedures. I know a lot of people who have been performing procedures for a long period of time may be very much in love with their fluoroscopy. And the people who have been trained in ultrasound become very diehard in their ultrasound. And I think there's got to be some middle ground between them and the utilization of the dual modality, I think is going to be really the future. So a little bit about myself, I'm a physiatrist. I have a couple of different hats that I wear. I'm a Director of Pain Management and Director of Physical Medicine Rehabilitation at Ventura County Medical Center. I also have a practice down in Newport Beach in Irvine, California, where we focus mostly on complex musculoskeletal cases and regenerative medicine. So let's move along. So, you know, I hear this all the time and people will say, well, George, why should I learn how to use ultrasound when I already have fluoroscopy? And I think there's a lot of benefits to learning how to use both of these modalities. And the thing is that people who use fluoroscopy, I say that they develop something called x-ray eyes where they end up seeing nothing else besides the bone. And that's really because that's the only thing that you can really visualize well. And you focus only on the bony targets, but there's a whole lot of soft tissue in between there that it becomes very important. And we'll talk a little bit about that. So, you know, why can't you use both of them, right? The caveat to that is that if you're going to use a new modality, whether or not it's an adjunct in addition to your fluoroscopy, you're going to have to use them well. And this image is one of a collection of images that I collect off of Instagram, which I find mildly amusing. And if you look at this, you might notice there's something wrong here, right? So you can tell that the person holding the syringe probably doesn't know I use ultrasound. And the person holding the ultrasound probe isn't focused enough on what the person holding the syringe is doing to correct them. And you can tell that there's a couple of things even wrong with the image itself. It's very shallow and looking at the anterior knee, but you can tell that in the image of the what's going on in real time, they're probably about 12 to 14 inches apart. So, you know, the two of them are looking at two separate, totally different things. So what's the case for dual modality, right? Ultrasound is great for a lot of things. Fluoroscopy is great for a lot of things. There's certainly going to be instances where I think ultrasound is clearly advantageous to fluoroscopy. And certainly other instances where fluoroscopy can also be, is more beneficial or better than ultrasound. So let's take a little bit of dive into that, okay? So there's actually dozens and dozens of interesting examples, and I don't have time to go through them all. But I want them to be up here for you to at least take a look at them so you have an idea of what's out there. And I'm going to talk a little bit about knee joints and shoulders and things like that because this is focused on joints. So here are the really good examples where I think ultrasound is clearly superior to fluoroscopy and where the combination is even better. And I know that's probably a little bit contentious for those folks that don't use a lot of ultrasound. So these are images that I found just Googling, Google searching for shoulder x-ray guided injection or shoulder fluoroscopic guided injection. And you'll notice a few things here. If we focus on this first one in the top middle, you see that, let's just look at all three of them actually. You look at all three of them, you'll notice that these people are using x-ray guidance, they've put contrast into it, and they have the needle tip in various portions along the humeral head. This first and second image on the left-hand side, you see this nice stripy outline where it goes towards the glenohumeral joint, and then it also runs down essentially the shaft of the humerus. And that's likely the biceps tendon sheath, okay, if they haven't injected it already. And so the biceps tendon sheath is certainly one way to get into the anterior glenohumeral joint, but it might not necessarily be the approach that you wanted. And it might not necessarily have been of the actual goal for these practitioners performing these injections. In this image on the right-hand side, you'll notice that someone decided to go directly for the cavity between the joint and the glenoid and the humeral head. The issue with that is that you're likely going to be piercing through the bit of labrum that is there as well. So there's some issues with that, right? And it's a bit of an imprecise technique that utilizes a decent amount of volume to get to where you want it to be. Now let's compare that to an ultrasound-guided glenohumeral joint. Now if you can't see what I'm pointing at, I'm just going to verbalize this now, and this is a posterior image of a glenohumeral joint. And all this stuff is labeled with letters, but it's not explained, there's no legend, so I'm going to explain them to you. If you look at this top right image, what we have is the posterior view of the glenohumeral joint, and what's outlined in a dotted yellow outline is a piece of the shoulder labrum. And you'll notice that there's a thin muscle overlying that, and that's the infraspinatus. We can actually target very specifically the interface at where the cartilage, excuse me, the labrum ends, and as it makes contact with the articular cartilage. And so you can get into the capsule and inject directly into the joint. It's a very precise injection as opposed to sort of eyeballing it and waiting for your contrast to flow into the joint. Now, let's talk about genicular nerve blocks. There have been multiple dissections that have demonstrated that it's actually much more complicated than what people are overall doing. That being said, most people go off of the dissections that resulted in the Choi paper in Pain Medicine, I think it was 2013 or so, 2011. And those guys looked at performing genicular RFA on patients that had already undergone grand total knee arthroplasty. Now that being said, most people agree on where they think they're supposed to put their needle tips, but let's take a look at some of the images that I found on the internet. Now I'm not going to critique them, but for those of you in the audience that perform this on a daily basis, you might find some concern with some of these. Let that soak in for a little bit. Some of these might be a little bit too proximal or possibly even more too distal. And the real question is, where are you supposed to put this? Now I can tell you anecdotally from my fellowship, I remember this patient clear as day where we had a patient that underwent nerve blocks, genicular nerve blocks, fluoroscopically guided and 100% benefit both knees. Under what rate of frequency ablation, two separate occasions, one knee was 100% better, the other knee had zero benefit. And they went back and we looked at the imaging based off of where the needles were placed against the bone and people like to do that because they think that's where the nerve is going to be and it should correlate. Well, there must be a reason why you got a great nerve block and you didn't get a good nerve burn. These are just other images that I found on the internet. You might find that these might be a little bit more along the lines of what are considered the classical locations for where to put these needles. And here's another one. This was, I think, a RCT that I found published out of India where they talked about performing bipolar nerve burning because it's such a difficult thing to identify. The thing is that you can actually see these nerves under ultrasound. But before we get there, and I do this exercise when we run in cadaver labs, we'll pull up a knee and we'll get an x-ray and I'll say, well, where do you think along this AP film of the femur and the proximal tibia, where would you like to place the needle? And most people would probably agree on the upper left-hand side, it'd be somewhere between two to four o'clock or excuse me, the numbers two and four, and on the right-hand side, probably between B and C, maybe even A, and on the bottom, maybe F or G. That being said, everybody's interpretation might be a little bit different. And not only that, the anatomy is certainly going to be different, as well as whether or not you have a true AP or there's a little bit of an obliquity to either direction. So it's important actually for this procedure to also make sure you're actually getting a true AP. That being said, let's look at what this looks like under ultrasound. So what I have here, this is actually my own knee when I made this image. Now you'll see that there is this white arrow and that is pointing at the cross section, short axis cross section to a nerve. And directly adjacent to that is an anechoic structure. That's actually a genicular artery. Now if you're familiar with how radio frequency technology creates a lesion around the distal tip of the cannula, you're aware that essentially it creates an elongated lesion along the shaft. So it doesn't come out like a lollipop and it certainly doesn't shoot out at the front like a laser beam. And so just like most techniques, we try to lay it along parallel to the direction of the nerve. You'll also notice in this image that there is a membrane that overlies the periosteum and it sort of ties this nerve and this artery against that bone. Now it's not always going to be found directly adjacent to the bone, such as what's written in a lot of literature. But let me tell you what happens when you get your needle directly adjacent to that bone and you inject. Because there's this tight periosteum that binds it there, it's not hard to get a false diagnostic positive because if you inject even a half milliliter or a millimeter or more of injectate, local anesthetic, it's actually going to tightly adhere to that periosteum film and move cephalad and caudad. So you could have that needle inches away from where you really need to be, inject two or three milliliters of fluid, and you're still going to get a good diagnostic block. And so you have to be cautious for your positive predictive rate. That being said, I have gone and compared this on occasion when I have time, what it looks like when you have, when you utilize both fluoroscopy and ultrasound. Now this happens to correspond pretty well, but I can guarantee you that you don't always see the nerve directly against the bone. You don't always even see it, and you certainly don't always see the genital artery there as well. So you want to keep that in mind that it's there. And there was a study out of New York where they did a cadaveric study, and I want to say that they only found the genital artery next to the nerve somewhere between 40 to 50% of the time. Okay. What does that mean? Now I know we all go for these three common places, but if you really look at this fantastic publication by Professor Philip Pang out of Toronto, Canada, this was published in Regional Anesthesia Pain Management maybe, I don't know, 12 months or so ago. The innervation is actually quite complex. It's not limited just to these larger nerves that we can identify, okay? You can even actually try to de-innervate the patella for people who have patella femoral pain. So what is the option? You can use ultrasound, or you can also, if you're only going to use fluoroscopy, this is actually what I do now. It takes quite a bit of time, but I use bipolar lesioning with a multi-tined cannula, and actually burn two to three times at each spot. I can say that when I've switched to this modality or this methodology, my outcomes have become really, really good, but it definitely takes a bit of time. Okay. I'm moving along now. I speak very quickly, so I apologize. I want to talk about a common procedure that people perform, and we're going to talk about cervical medial branches, okay? And these are certainly some RFA needles that are placed there, and this is me trying to be, you know, placed in parallel to the edges of parallelograms, sort of like how SIS recommends you do them, okay? Here's the thing. It might take a lot of time to place these needles under fluoroscopy. Maybe not for Jackie or Michal, but sometimes for me to get it nice and perfect, that's what it might take. The reality is, though, is that when I do these procedures under ultrasound, they become very quick, very fast and easy procedures. And it's sort of like telling someone about Santa Claus and the first time actually seeing Santa Claus, because you've always been told that the medial branch is lying in that valley of that parallelogram, but you've never actually seen it until someone shows it to you under ultrasound. This top image on the left is showing essentially the cervical facets, and there's a vertebral artery, and that's telling you that on the left of that, which is cephalad, is essentially the occiput, okay? Now look at these images on the right. Now the top right is an x-ray of the c-spine, and it's just to compare that, because you can see actually within the valleys of those parallelograms, essentially the valleys between the facets, you can actually see this hyper-echoic honeycomb, and that corresponds to the medial branch. I actually perform a lot of these in the office now. You can't necessarily build them as cervical medial branch blocks, but you can perform this quite easily. You can do three, four level MBBs in like two, three minutes, you know, very simple thing to do. And that brings us to other things, because let's say your procedure is not meant to be ablative, right? Let's say you want to do prolotherapy, regenerative medicine, PRP, something like that, and your target actually isn't to get to the nerve, but you actually want to address the facet capsule. Now, this is a patient of mine who that has severe cervical facet arthropathy. It looks like a lobster claw, you'll notice it looks like a lobster claw like that. And what that is, is the facet arthropathy, this was probably, I think it was like four or five, okay? And you can see the facet capsule that surrounds it. And you can see a couple of things here, this is my needle, this is a 25 gauge, one and a half inch needle that's coming in from this ear bone, sorry it's supposed to be stylized. Anyway, these are the things that I've worn on, I've injected the capsule, there's a different video where I'm injecting just only the ligaments that run across the capsule, but you also see that I get very good intra-articular flow into that joint and this, you know, is a very simple thing to do in the office. So let's talk about the pudendal nerve block. And I think this is a great example because if you perform a pudendal nerve block under fluoroscopy, what you're really doing is a field block. And I'll show you what the anatomy of it looks like because that pudendal nerve really isn't, it's not really sitting there on the ischial spine, it's actually floating off in space typically between two ligaments. So when we're performing this procedure under fluoroscopy, most people are taught to get a nice AP image to get the ischial spine nice and crisp and you just take your spinal needle, go down, touch bone, make sure you don't hit anything you don't want, inject a little bit of contrast and do a field block. You know, it might be, you know, three, five, six, I don't know, however much volume you want to do. That being said, there is the chances of hitting the sciatic nerve here and then that's been reported in case reports where people ding the sciatic nerve doing a fluoroscopic guided pudendal nerve block. And the opposite has actually been true as well where people have gone for a sciatic nerve block and dinged the pudendal nerve. That being said, or you also want to make sure you're not in the artery or the vein. That's why you should check a little bit of contrast there. But what else is going on here? So let me show you what this looks like under ultrasound. So here's another image. This is the right hand side here, okay? And what we have is the ischial spine. You see that flat ridge of bone right there, right? It's a flat ridge of bone and it abruptly stops. And then to the left of that or medial to that, you have the SSL, the sacrospinous ligament and then you have the STL. It stands for the sacrotuberous ligament. And they actually run in two different directions, okay? You can imagine it's sort of like an L. Sorry, this is backwards. You can imagine it like this, but except one of them is running cephalic caudate and the other one is running sort of diagonally in the other direction. That being said though, the PN, that's the pudendal nerve that actually runs in between here. Now this is a potential place for you to have entrapment of the actual pudendal nerve. So keep in mind, what is the goal of a peripheral nerve block? Peripheral nerve block might identify the pain generator, but it might not necessarily be able to address it, especially when you're doing a field block from so far away. You can actually hydro dissect between these two ligaments and inject a smaller aliquot of medication and achieve your goal. And potentially, if this is the point of nerve entrapment, you can also treat the problem as well. Okay. I'm going to speed through this because I'm probably taking up all of Jackie's time. Let's quickly talk about stellate ganglion blocks because I think this is really interesting because when you do stellate ganglion blocks under fluoroscopy, most people are taught one approach and it's an anterior approach. And Nilesh Patel wrote up a fantastic paper where they actually came from a foraminal approach view and it probably increased the safety. Now that being said, most people will say, well, George, I've done thousands of these anterior approach and I've never had a problem. I can tell you that there are case reports that happen and they're reported in this likelihood injuries that probably never ever got reported. But that being said, when I think about doing a stellate ganglion block, I actually will use the ultrasound and sometimes I'll use dual modality. But my thought process is much more complicated than that. I actually think of four different approaches when I'm going to do a stellate ganglion block. Now let's talk about this, right? These are the general four approaches that categorically, okay? So there's this anterior approach, it's a transthyroid approach, right? Here's the issues with that. You can pop thyroid cysts, which may or may not be really an issue. There's other thyroid pathology that you probably don't, if you can avoid, you probably want to. There are vascular things that you definitely want to avoid, right? You don't want to hit an AVM, arteriovenous malformation. You don't want to hit the inferior thyroid artery, and that's the big no-no. And Samir Narooz wrote, I think, a case report about that, where someone probably hit that artery and they developed a hematoma that actually was bad enough that it caused airway or potential airway loss. So these are some things that you need to think about. You also have to think about the esophagus, and most people aren't thinking about, you know, well which side is the esophagus mostly on, and can I see it any which way? The other thing that happens is, so what's the other approach? The Koreans reported, I think, the transjugular approach, and you can visualize this. You can compress the jugular. You also need to worry for ascending cervical arteries and cervical nerve roots that may or may not be in this area. There's a louder approach, and then a far louder approach, where you have to watch out for the cervical nerve roots. You're gonna have to bypass the anterior tubercle and the ascending cervical arteries, as well as even avoiding the superficial cervical plexus. The other thing that I will mention that I think is fantastic, though, with ultrasound, therefore, is that instead of just hitting that bone, and then sometimes people will say, well, I pull back an arbitrary distance, you can actually identify where the pre-vertebral fascia is at, on top of the longus coli, and inject, because as we all know, it's a ganglion, and it's not really at one discrete location, and it actually traverses down further inferiorly, even into the high T-spine, okay? So, oops, oops, oops, where'd I go? All right, so this is just an example of that. So what we have here in the midline, or rather on the left-hand side of the image, we have the trachea, we have the thyroid, the CA is the carotid artery, and we have the longus coli lying superficial to the transverse process of C6, and then we have the esophagus there, and you know, these are things I identify when I'm performing this procedure. I have a patient swallow for me, so I can make sure that I see the esophagus, and I can avoid it. Now, you can go through the thyroid, which honestly, with a 25-gauge needle, as long as I don't see anything that I want to avoid, is a very fair and reasonable approach. You can do this in-plane or out-of-plane, and for the most part, you're not going to have any problems. This is an image that shows all the other approaches that you can consider. You notice IJ, that's the jugular, and you can compress that such that it becomes thin, like a pancake, or essentially it becomes obliterated, and you can take your needle and go through that, and or you can go lateral to it, and or even far lateral, and either way, the whole point of this is to try to get your needle anterior this to the longus coli muscle. Keep in mind that there are, if you use this approach, there's a possibility that you can actually hit the cervical nerve roots, but we can see those very well. In fact, it's a great way to do cervical transfer amyrals. So just other images for what you can consider doing. Again, here's just another image that you'll see all the anatomy in the front. Those aqua blue dots are actually arteries and veins, and the red line I'm showing is a path that you can actually choose to. Keep in mind with ultrasound, because it's real-time, you can actually take that needle and come down through a certain layers of the muscle, and then and then change your trajectory flat out, and then going interior, and then and then drop your needle down. So it's just kind of a neat approach that you can do real-time imaging. Contrast that with fluoroscopic guidance, which don't get me wrong, I did a dozens, hundreds of these when I was going through my training, where you just have these fixed locations, drop the needle, inject your contrast, see that flow, which is really typically going to be flow of the longest coli muscle, and then you inject. This is the approach by Nilesh Patel, which I think it should be much safer. You should consider adopting this. Make sure you get a nice true oblique view with squared off vertebral body, so that you're not, there's no parallax or anything like that. You're not shooting for the neuroforamen. Okay, I think that's actually it. That's the end of my talk. Hopefully I didn't take up any too much of your time. If you have other questions or thoughts, you can take a look at my website, and that's it. Okay, thank you. It's super hard to follow my friend George, because George is just amazing at the things that he's able to do with ultrasound, and I trained predominantly in a fluoroscopically guided fellowship, so I have to say every time I watch him discuss these techniques, I'm always myself amazed, and I think that, gosh, maybe I need to go take one of his courses for another time, so I can get better at those. I'm going to talk a little bit about treating joints, peripheral joints, with radiofrequency. My name is Jacqueline Weissbein. I go by Jackie. I'm a physician in Napa, California, in an orthopedic group. I am a physiatrist and also board-certified in pain medicine. I primarily am interventionist and also focus on implantable devices, so I'm really eager to talk to you about the techniques that I think of as adjunctive or intermediary techniques that I incorporate into my practice to help my patients with chronic joint pain. So, just a few relevant disclosures. I'm a consultant for medical device companies, and those are them, and again, if you have any questions, please don't hesitate to contact me. So, the shoulder. Recently, it's become, I think, something that, in the last few years, we've had a lot of work, particularly from Ekman and as CoolLeaf and other technologies have gained momentum. When I trained in my fellowship, gosh, it was a long time ago now, but almost 10 years ago, I remember that they had, I think Eli Lilly had a cooled RF machine, and it didn't really gain traction, but now what we're seeing is that there are these targets that we can utilize for shoulder pain, and one of the most concerning things, I think, that we have to recognize is something that George touched on expressly, which is that a lot of these innervations tend to be both motor and sensory. So, specifically, when we think about the innervation of the shoulder, we have to be really careful because what we know is that the suprascapular nerve, the sensory nerve, are coursing through the notch at the same place where we're seeing these motor branches. So, typically, if you have a patient who you plan on doing this treatment for, you need to be acutely aware that if you're going to be doing an RF therapy, there's a possibility of denervating that muscle, all the muscles that are innervated by the suprascapular nerve, and therefore, the patient might lose actually function of their shoulder. So, what Ekman's study presumed to do was essentially take these cadavers, and there was actually 33 shoulders that they looked at from over 17 cadavers, and what they did was identify the branches of the nerve, and they found that almost a hundred percent of the shoulders, and this was only in 16 of the shoulders, that the suprascapular nerve was innervating the posterior head of the humerus. So, the majority of the innervation is coming from that suprascapular nerve, but what we also know are there branches from the axillary nerve, articular branches, that were also part of innervating the posterior lateral head of the humerus, which is why when we talk about patients who have had suprascapular nerve blocks, many of them report that they had significant reduction in their pain, but not a hundred percent of their pain. So, identifying the axillary nerve innervation, as well as the lateral pectoral nerve innervation, as something that could be efficacious in blocking the pain signals to the shoulder, was something that was very helpful in figuring out the next steps, and the way that we could create a radiofrequency lesion of these patients, and it was pretty much something that could be replicated in almost 80% of all the cadaveric studies that they did in these shoulders. So, John Tran also was trying to demonstrate this, and what they were trying to show is that if we were looking at, particularly what I think George was also referencing too, is that, you know, on x-ray, if we're using fluoro, we do develop these x-ray eyes and get really specific at looking at things, but what we have to understand is that the way the branches kind of innervate are varied from patient to patient, but there are some general areas that we can target, and what you can see in this picture is where the majority of these nerves were lying, and so we can see that the posterior superior quadrant of the glenohumeral joint was all supplied by the suprascapular nerve, whereas the posterior inferior was from a posterior division of the axillary nerve, and the anterior superior by the superior nerve to the subscapular. So, you can see that there was also in the front there some infrequent or less frequent innervation from the lateral pectoral nerve, but still it was there, and identifying both bony and soft tissue landmarks to identify the nerves are important because this is something that we need to extrapolate to be able to create a radiofrequency lesion for these nerves. So, when we're looking at the fluoro, we want to be able to identify the landmark. So, here we're looking at the shoulder joint, and you can see that this is essentially demonstrating where the muscles are also being inserted and coming off the bone so that we can understand that when we denervate these nerves, we are going to also affect the range of motion of the shoulder. Now, in a perfect world, we'd be able to do something like pulse radiofrequency, which may be able to offer patients long-term pain relief, but without the concerns of affecting the motor nerves, but as of right now, unless you're in a practice that you're having patients pay cash for the majority of us that are accepting insurance, that's not really feasible because it's not currently covered. Now, when we look at the next slide here, you can see these are the targets when we're doing radiofrequency ablation of the shoulder, and what we're targeting again is a suprascapular nerve at the notch, the axillary nerve, and typically there's two ablations at both of those sites, and one single site on the anterior target, which is the lateral pectoral nerve. So that means that you can actually perform the first four ablations as the patient is prone on the table, and then either break sterility, flip the patient over, and then obtain imaging again of the same shoulder, reprep and drape, and redo everything, or have the assistants in your practice be able to flip the patient so that you can maintain sterility throughout. However you choose to do it is appropriate, but as long as you're maintaining sterility, that's the most important thing. So one area that I think is really interesting to consider is the hip. I think we all know that, particularly as physiatrists, we see a lot of issues with the hip, not just from degenerative joint disease or avascular necrosis, but we also are able to determine that patients may have something like femoroacetabular impingement, or labral tears, potentially a tumor, but the reality is is that we do see a lot of hip issues, and the fact of the matter is is that although it is an issue in a number of patients, particularly as they get older with degenerative changes, there are a number of women, more so women than men, that do have pain in the hips, and so it's something that we frequently see. Now as someone who performs advanced therapies, when I have patients who have like a total hip, and they're still having pain, I might be considering an implantable device for them, but the reality is is that something that we can do for patients who haven't necessarily had a previous surgery, but still are having pain, is perform a radiofrequency ablation. Now when we think about this, we want to understand the anatomy of the hip, because the reality is there are a number of sites, and I'm going to move forward a couple slides, and then go back, but there are a number of sites that we need to consider, because there are a lot of neurovascular structures that travel together. Now the hip is innervated in the intermedial portion by the articular branches of the obturator nerve, or accessory obturator nerve, and the anterior hip capsule is also innervated by sensory articular branches of the femoral nerve. When we think about the posterior hip, however, we're thinking of articular branches derived from the sciatic nerve. So posterior medial is more branches from nerves that tend to the quadratus femoris muscle, and the posterior lateral articular branches from the superior gluteal nerve. So we need to be cautious, because as we're looking at this, we want to make sure that in this previous slide where I was here, that we're understanding there's a number of different things. Now what we're looking at here are these articular branches of the obturator nerve, where we are using these as a target for radiofrequency, and what we're looking at on the right are these bold lines that demonstrate the boundary of each area. So the dotted lines, as you can see, are the lower boundary, and we want to be careful because this is something, again, that for my next slide, demonstrates that there are a number of vascular structures that go together with the nerve structures. So again, thinking about this, if we were to look at this hip joint and actually see where those yellow structures are, I know you can't see my pointer, but where we're looking at the femoral vein artery there, there are two articular branches of the femoral nerve that are basically like at the like 1130 position, and what those would be are the kind of hypothetical lesioning positions where you would be targeting. Now the obturator nerve is actually a little bit lower. You're going to find that more on the ischium, and typically there's going to be two lesions that are performed there kind of close together to create that lesion on the obturator nerve. Now again, so important to recognize that there's a potential for neurovascular injury, femoral nerve, femoral artery, and vein, so making sure that you are not making a lesion before you're actually testing or ensuring that you're, you know, palpating the femoral bundle so that you don't puncture a large vein or artery, and realistically just kind of making sure that you understand the anatomical considerations before you proceed with this. Now there were some studies that demonstrated the efficacy of this, and what we see is that in Rivera's study with Fabrizio, that basically because there are a number of patients who do have significant hip pain and contraindications to undergoing a total hip arthroplasty, we needed to have some treatments for these patients beyond just injecting them with steroids. So what they did was actually a study where they took about 17-18 patients with chronic hip pain and essentially found that in these patients, if they were able to perform radiofrequency ablation of the sensory branches of the nerves that innervate the hip, these patients were actually able to do well, and again these were patients who were unable to undergo a radio, I'm sorry, total hip arthroplasty because of the fact that they had medical comorbidities and were unable to have the surgery. Now these patients presented with hip pain that included groin, thigh, trochanteric pain, and so no one was really excluded because when we think about patients who have groin and thigh pain, we're thinking about more innervation from the obturator nerve as opposed to patients who have more trochanteric pain where we think about things coming from the sensory branches of the femoral nerve. Again, there was six-month data that was followed with these patients. We saw improvements of their Harris hip scores which is a measure of dysfunction of these patients, and also the VAS scores went from nine down significantly to I think like five or six. The reality is is that majority of these patients, I think actually over 50% of them, were still reporting 50% pain relief at six months. So no side effects and these patients didn't have any negative outcomes. So again, for patients who are not able to undergo an intervention like total hip, this is something that can be very beneficial. Now other studies where they've used only like an N of four, we're talking about patients who four out of four of these patients experienced significant, you know, reduction of pain. Two were able to reduce their pain medicines. Three reported improved function. Some had a little bit of peripheral numbness, but again another small study indicating that there is significant benefits to be had for patients who undergo radiofrequency ablation of the hip. Other studies, a retrospective study with 14 patients measuring only VAS, and VAS is difficult because the reality is a lot of patients have a hard time reporting, you know, their pain relief. But as you can see in this study, patients pain went from about a 6.87 to down to 2.7, and they had significant pain relief for up to 11 months. So again, without any reported benefits, this is some significant improvement in their quality of life. Again, one of the things that we need to be conscientious of is that the majority of these studies that I just presented had small sample sizes, and again, you know, this technique can be difficult, particularly if you are not skilled at ultrasound like George, because obviously unless you're using a finder needle to, you know, test for, you know, prior to lesioning, it might be difficult, and there's always the risk for vascular injury. So, you know, keep that in mind before you just cowboy up and start doing that procedure. Now with regards to the knee, I loved watching George present. I actually love seeing George present cases too on social media. I think he is really talented, and I think something that he pointed out was the variability that we see with regard to placement of the needle when we're doing this under fluoroscopy, because there are branches of various nerves, and in the next slide, which is a repeat of the one that George showed, you can see how variable the innervation is. Now, a couple years ago, I was involved in a product that was a cooled kind of cryoblation of the inferior branch of the saphenous nerve, and it was kind of like you had to measure and mark and just kind of, you know, do your little treatment along this line and hope that you maybe caught it. The biggest problem is exactly what this picture and exactly what some of the pictures that George showed were, is that the anatomic variability is definitely there. So anyway, again, things that we want to be concerned about, too, are sensory innervation. I mean, George talked a lot about the knee, so I don't want to beleaguer the point, but these are typically the main places where we see from Carlo Franco's study that the most common placements of needles for placement for radiofrequency, and I think, you know, there are a number of studies. One that I guess George also referenced was the Choi-Woojong study, where essentially a double-blind randomized control study demonstrating that patients had significant improvement in their knee, especially at 1, 4, and 12 weeks respectively. One of the things that is most important when we think about this is that there are no post-procedure adverse events. And always important when we're considering doing this, this was a study that involved 38 elderly patients with severe knee pain and had a positive response to a diagnostic genicular block. You can see that there are much more studies available for pain with knee. In fact, one of our colleagues, Salman Rohani, who is a physician, a physiatrist down in Southern California as well, posted this one. And essentially, this was cooled RF in a patient with chronic knee pain who continued to have pain relief. I think it was like 11, three months out was that reported. But Tim Davis, also a physiatrist down in Southern California, you know, with additional studies, including this perspective, multi-center randomized study. The reality is this, is again, there are a number of studies that, sorry, I can't go back now, but there are a number of studies supporting the use of radiofrequency ablation of the knee. I think if this conversation didn't help you consider that maybe using a multimodal approach, including the use of ultrasound, that's something that I think we should all be considering so that we can avoid targeting any kind of neurovascular structures that we might cause damage in. But these are, again, technologies that offer your patients long-term relief and benefits can be repeated and with done safely can help patients who are trying to either avoid surgery or are not candidates for surgery or potentially are patients who have had surgery and continue to have negative outcomes that are not looking for an implantable device. Thank you so much. And I'm happy to answer any questions by email if you have them. Thank you again, Mehul, for having me on this. Thank you, Mehul. And it's great to be part of this panel with George and Jackie. You know, it's a topic that we do talk a lot about, especially at the society conferences and even offline. George, Mehul, myself, we've all written papers together on this topic as regenerative medicine is very popular, especially among the trainees. So it's really good to put pen to the paper and show what the evidence is in relation to this topic. So my name is Jaspal Ricky Singh. I am here at Weill Cornell Medicine in New York City. I serve as the Vice Chair for the Department of Rehabilitation Medicine and an Associate Professor and also as the Director of International Spine at our multidisciplinary Weill Cornell Center for Comprehensive Spine Care. Here are my disclosures. I have no conflicts of interest related to this talk, but I thought it'd be necessary just to show those with the group. So the topic of joint pain, you know, George and Jackie have so eloquently talked about imaging and the necessity of guidance when doing some of these interventions, along with newer technologies such as radiofrequency ablation, neurotomy. So my focus is going to be mostly on the intra-articular approaches. And the challenge with treating joint pain, specifically knee arthritis, is that we're kind of limited in what we have to offer. We can prescribe oil medications, we can do physical therapy and bracing, but the long-term benefit of some of these therapies is not great, which is why there is a treatment gap when it comes to treating arthritis, especially of the knee origin. The benefits of intra-articular drug delivery, and I say the word drug as any substance we're putting in the knee, whether it's something simple as saline or lidocaine, which is a drug, to things more complex such as biologics, which we're going to go into in a moment. But the benefit of putting something intra-articular is that we avoid systemic absorption, which is great. Sometimes there's side effects, kidney issues, GI issues, things like that. We increase the local bioavailability of that drug, specifically to the target tissue, which is a joint. Fewer adverse events, in theory, again, related to low systemic absorption and potentially reduced cost. You know, previously, all we had at our disposal was hyaluronic acid and cortisone, but now we're finding an increase in the usage of certain biologics to target the inflammatory process of joint degeneration, and that's where I want to focus our talk. One of the interesting things about the synovium around the joint capsule is that this is where fluid and certain chemicals are absorbed, and it all depends on the size of the molecule. You know, we have patients that come in with recurrent knee effusions, and we're draining their knee and draining, and what we realized is that the drainage system of the synovium is clogged, and sometimes a local administration of a cortisone can be beneficial in the short term, but we don't really have a good way to reduce how inflamed the synovium gets. You know, with ultrasound, you can sometimes see a redundant synovium with floating synovites in the fluid. Albumin, for example, has a slower absorption of 1 to 13 hours. Hyaluronic acid, which is a very large chemical on the order of kilodaltons, takes a little bit longer to absorb, whereas non-steroids such as Toradol or corticosteroids get absorbed within the joint within a few hours, which is interesting when we find data that suggests cortisone steroids in the knee can last for six to eight weeks. So it mustn't be the actual anti-inflammatory working at that level, it must be something else, but the biologics tend to last a little bit longer in the joint milieu. So here's kind of an overall approach of what I discuss with patients, and especially with trainees, on how to approach joint pain and joint arthritis. So if you look at the drug category, you have both biologics and small molecules. Small molecules include things like cortisone, glucocorticoids, and another category that's not listed here we could consider a device is hyaluronic acid. Whether it's a drug or device is kind of up for discussion, but that's also off this chart. In the biologic realm, we have the non-cellular products along with the point-of-care autologous cell therapy. Within non-cellular, we have interleukin blockers, growth factor therapy, TNF inhibitors. These are all biologics working to decrease inflammation, whereas the point-of-care cellular therapies include bone marrow and BMAC, bone marrow aspirate concentration, from blood-dry products, as well as adipose graft tissue, which is a cellular therapy done at the time of treatment. So just looking quickly at cortisone, and most of us who've been injecting cortisone for many, many years know and hope that there's going to be an end to how much steroid we use. We know it's effective in the short term for acute inflammation, but we also know there is deleterious effects in the body from chronic steroid administration, including bone loss, hair loss, weight gain, and then more specifically at a local level, destruction of the joint. So many societies have come out, including the American Academy of Orthopedic Surgeons, the Osteoarthritis Research Society, have said, you know, there's no real great support in using cortisone for the treatment for knee arthritis, and the data kind of suggests that as well. You know, we've seen this data out of Jason Dragoo's lab at Stanford looking at the chondrocyte percent death when administering certain cortisones, and while having a clinical benefit is necessary with a higher dose, we know that you put the patient at risk of cartilage damage and chondrocyte loss. So we all try to limit or avoid cortisone at all costs in treating joint degeneration, and I think the discussion of the other biologics and regenerative treatments comes up quickly. Nowadays, you know, probably five, ten years ago, we went to cortisone and HA and didn't really discuss regeneratives early on in the treatment algorithm, but now I feel many of us are discussing this almost at the first visit. Hyaluronic acid, you know, this has been around a long time. I still use it in my clinic for a couple reasons. One, I know there's not much harm I'm doing to the patient. Two, insurance is still covering it, so it kind of gives me some time to consider other regenerative or biologic options in these patients. You know, there was a point, counterpoint, that we wrote a few years ago in the Purple Journal, the PM&R Journal, looking at hyaluronic acid in the treatment of knee arthritis, and I think some of the conclusions from the American Academy of Orthopedic Surgery that they drew was not on great data. Some of the articles published show there is benefit of hyaluronic acid. I've seen that in my own patients who come in religiously every 8 to 12 months for a repeat series, so this suggests there is some evidence against evidence-based medicine, but some of the data suggests that it's only up to a certain size particle that makes a difference between 1,500 and 6,000 kilodaltons. So listed here are some of the popular ones that we use, including Synvisc, Euflexa, Orthovisc. All these have large size of particles which will last in the synovium, in the joint space, as I mentioned previously. So what about biologics? So what we see with joint degeneration and spine degeneration is that it's an imbalance between catabolic and anabolic factors, and the effects of the biologics predominantly is to create a more anti-inflammatory environment which will allow their cells to do the correct thing. When we talk about the cellular therapies, we're talking about not only the anti-inflammatory environment, but also the potential for the native cells and the native structures to produce either collagen or cartilage or supporting structures to help with joint pain. So interleukin-1, we know it's a key mediator in the inflammatory process. It is part of catabolism. It can lead to joint degeneration and the destruction of tissues. So when Chevalier looked at this in a multi-center randomized double-blind control trial, how effective an interleukin-1 antagonist is, what they found was that it does help decrease symptoms and improve function compared to placebo, but not at a statistically significant level. Another biologic known as tumor necrosis factor or TNF, also a pro-inflammatory cytokine, we know this drug to be used in rheumatologic conditions, infliximab, etanerocept, embryol, and basically what this factor does is promote inflammation in a joint. So when Wang looked at using a TNF inhibitor adalimibab, which is Humira, in 56 patients compared to hyaluronic acid, what they found was a significant decrease in pain and improvement in function. However, this data only was out to four weeks, which is a pretty short follow-up when speaking of any drug introduced into the joint for NeoA. So while there might be some promise in using these, and we talk about these at our journal seminars, looking at new papers coming up using TNF as a treatment for NeoA, I think there's some opportunity. So that brings me to the cell therapies. What excites me in this space is that more and more data keeps coming up, new therapies keep emerging, and it's really important for anyone practicing regenerative medicine to stay up on the data to see what new technologies are coming out. So we've learned a lot about mesenchymal stem cell therapy or mesenchymal stromal cell therapy. At first, many believed that these cells were transported from one part of the body into another, and they turned into cartilage. And while we can do that in vitro with a certain environment and growth factors, we can grow cartilage in the body in vivo, we can't really do that. And what we found is that these stromal cells or cells don't actually turn into anything. What they do is they use a paracrine effect to attract other cells in the body, like macrophages and turn on endothelial cells to function more efficiently, to produce collagen and cartilage in certain areas, and to repair the native structure. We know that there is some immunomodulation when using MSCs, mesenchymal stromal cells. I say the word stromal versus mesenchymal stem cell because stem cell implies that I am treating the patient with a cellular product of stem cells, either they're multipotent or not pluripotent, versus what I'm doing is there are these stem cells that exist within the large collection of cells that I'm using for treatment, especially when it comes to adipose graft. It's very difficult to isolate just the adipocytes or just the pericytes when administering this treatment. Instead, we're taking a collection of cells, a collection of growth factors and tissues and putting that into the joint. So that's why stromal is probably more accurate when describing MSCs versus stem cell. As I mentioned, the activation of resident cells. So basically, we are using growth factors such as VEGF and IGF to stimulate the population of stem cells in the joint, again, to produce a supporting structure such as collagen or cartilage. So the term orthobiologic basically could be any chemical, any product that is used to stimulate restoration or regeneration in a certain tissue. And as I mentioned before, mesenchymal stem cell or stromal cells take advantage of the paracrine effect and homing to bring cells from all over the body into where you're targeting. So PRP, platelet-rich plasma, this has been long studied. It's been out for, you know, 20, 25 years. You know, one of the first papers I read was from Dr. Alan Mishra over at Stanford looking at a lateral epicondylitis. And since then, the number of papers has exploded, especially when treating knee arthritis. The challenge with using PRP and studying it is, number one, there's a lack of well-powered studies. And there's really no standardization on the complexity of how to produce PRP. There's no standardization of protocols. Is it leukocyte-poor, leukocyte-rich, fibrin-poor, fibrin-rich? So all these can have an effect on the outcome. More importantly, there's so many growth factors within PRP, whether it's VEGF or IGF or platelet-drive growth factor. We don't know which one's actually having the causative effect. So studying that from a drug aspect is very, very challenging. Some data has suggested that PRP is more efficacious than hyaluronic acid and cortisone, improving function and pain in patients with knee arthritis. Like I mentioned earlier, I think we discussed PRP early on in our treatment algorithm, even before discussing cortisone for these patients. So PRP has the benefit of being anti-inflammatory. We know that leukocytes can cause pro-inflammation in the joint, and PRP can downregulate some of these catabolic factors, which is helpful in restoring the joint to its normal milieu. When comparing PRP to cortisone and AHA, this was a meta-analysis done with more than 1,400 patients looking at 14 randomized control trials. And they looked at WOMAC pain and WOMAC function at 3, 6, and 12-month follow-up. And again, they found that it can be more efficacious than some of these other treatments that we use to treat patients with knee pain. So what about bone marrow? So bone marrow is also a point-of-care autologous blood-derived therapy. Bone marrow aspirate concentration, it contains many, many different stem cells and growth factors, platelets, lymphocytes, things like that. So there are different ways to process it. Most commonly, bone marrow is aspirated either through the posterior iliac crest, which is an easy place to harve it, or even the tibia, and then centrifuged to isolate the high-quality cellular product and removing as much peripheral blood as possible. So this was a nice study done by Kim out in 2014 that looked at 41 patients. And when they stratified this based on Kellergan-Lawrence scale, they showed that average pain decreased in all groups, most importantly in the mild knee arthritis, Kellergan-Lawrence 1, and also an improvement in the IKDC score when looking at up to 12 months following injection of bone marrow aspirate into the knee. Adipose tissue graft, you know, this has become more and more popular over the past couple years. I started to do this maybe three years ago after one of our society meetings when Dr. Jerry Melanga introduced this to me. I actually went to his clinic in New Jersey and he trained me. And since then, I've had very, very good results. I would say I use bone marrow a little more frequently than adipose tissue graft, just because there's a lot of regulations and what the FDA's opinion was on using adipose. Was it more than minimally manipulated? Were we violating any structure of the tissue? And I think the techniques that we use do not violate them, so it is, I don't want to say FDA approved, but it's okay the way that the lipoaspirate is harvested. But adipose has shown some promise. The beauty of the lipoaspirate is that it contains a high quality number of pericytes and stem cells, along with some of the endothelial cells that are useful in turning on the cells in our knee to, again, produce an anti-inflammatory environment and growth factor therapy. Data suggests that when comparing bone marrow to adipose tissue graft, there's a slightly increased expression of chondrogenic potential, which could lead to a better outcome. And another treatment that we use is amniotic tissue. So amniotic tissue is harvested at the time of delivery when a woman undergoes a cesarean section. So the baby comes out and then the placenta comes out. The company comes in and dehydrates this immune-privileged tissue. It's immune-privileged because the placenta is immune-privileged, so the mother doesn't reject the fetus. And there's a good high quality concentration of growth factors that can be dehydrated, sent to us in a powdered form that we reconstitute and deliver to the patients. So a study that came out last year by Castellanos looked at 20 patients of injecting amniotic tissue into the knee joint and found a decrease in pain, stiffness function. And here at Weill Cornell, we are one of the principal investigators of dehydrated human amniocorion membrane looking at knee arthritis with more than 400 patients. So hoping for those results to be released next summer, but something to keep in mind as a viable option. You know, people question the quality of growth factors and stem cells as we age. So this study looked at the age-related decline of chondroid differentiation of bone marrow derived stromal and stem cells. And while there is a decline in the cell's ability to express or turn into chondrocytes, I still think using one's own cells is better than using an off-the-shelf version such as amniotic product. So I still favor either PRP or bone marrow for these patients. And what about a combined approach? Dr. Chris Centeno looked at this in 2014. If you combine bone marrow concentrate with adipose graft, is there any benefit? And what he found was that it did not provide much benefit in one or the other. You know, he does favor bone marrow aspirate in patients with knee arthritis. But again, more and more data has been coming out since 2014 showing the value of adipose. We actually wrote a really nice point counterpoint on this specific topic, refractory knee arthritis adipose drives stromal cells versus bone marrow aspirate concentrate. It's in the PM&R Journal in 2018, so please get a chance to read that. But I think the takeaway is, you know, we need to discuss orthobiologics earlier in the treatment algorithm. Obviously, we want to limit how much cortisone we use in these patients because of the systemic effects. There is a reasonable reason to question the benefit of hyaluronic acid. Again, I still use it because some of these biologics and regenerative therapies are out-of-pocket expenses to patients. And when HA is covered, and I know it's not doing any harm, I might go to that first. PRP does have a good established track record of research, but it requires more standardization along with bone marrow and adipose graft. The big thing is, we need to collaborate multi-center. You know, George and I have talked about this, and hopefully having a talk like this will generate more discussion, and we can do a multi-center trial looking at these biologics for the treatment of knee pain. So thank you. I am here at Weill Cornell. We did start a podcast looking at regenerative medicine, so if you could listen to that and give us your thoughts, that'd be much appreciated. But again, I thank you for my panel here with George and Jackie and, of course, Dr. Desai in putting this together, and hope everyone's having a really nice Academy, even though it's virtual. But mentally, we are all here in San Diego together. So thank you, everyone.

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