Hello, everyone. Welcome to our session 1406, new technologies for upper extremity amputation. My name is Joe Webster and I'll be moderating the session today. Just a couple of quick updates before we get started. Just a reminder to pose questions to the faculty. Please type your questions into the chat box on the left hand side of your screen. We are planning on having time at the end of the session to address all questions. Also to claim CME credit for the session, you will have to complete an evaluation. Just a reminder from the academy that it is taking up to 48 hours for those to load in the system. So they are recommending that you go in starting Wednesday of next week to claim your credit for your sessions. If you do have questions about that, you can refer to the member resource center. The feedback that you provide on the evaluations is very important, and the program planning committee is planning on using this for future content development. And with that, we'll go ahead and kind of move into our presentation. As I mentioned, I'm Joe Webster and I'll be moderating the session today. Our first presenter for the session is Dr. Alberto Esquenazi. Dr. Esquenazi is a highly regarded clinician and researcher in the field of amputation rehabilitation. Dr. Esquenazi is the chair of the Department of Physical Medicine and Rehabilitation, as well as the chief medical officer at Moss Rehab in Philadelphia. Dr. Esquenazi also serves as a member of the Einstein Health Care Network's Board of Trustees. Our second presenter today is Dr. Jeffrey Heckman. Dr. Heckman is my colleague in the Department of Veterans Affairs. Dr. Heckman is one of our leaders, again, in the field of amputation rehabilitation in the VA. And Dr. Heckman currently serves as the medical director for the VA's Regional Amputation Center in Tampa, Florida. Our final two presenters for the session today are both from the University of Michigan. Dr. Ann Laidlaw is an assistant professor in the Department of PM&R at the University of Michigan. And Dr. Laidlaw has subspecialty certification in sports medicine, as well as electrodiagnostic medicine. Alicia Davis is a certified prosthetist orthotist with over 30 years of experience in the field. Alicia has served as the residency program director for orthotics and prosthetics at the University of Michigan for over 15 years, and currently is serving as a research prosthetist at the University of Michigan. I'd really like to thank all of our presenters for being on the session today. I think we've got a great lineup for the session. This is just the overview for the session today. We're going to start off with Dr. Esquenazi. He's going to be speaking about advances in upper limb prosthetic technology. This will be followed again by Dr. Heckman, who's going to be speaking on research, evaluating the comparative effectiveness of new technologies. Our final presenters will be Dr. Laidlaw and Alicia Davis, who are going to be speaking on RP&I, a new paradigm shift for phantom pain and prosthetic control. So, again, I want to thank all of our speakers, and I'll go ahead now and turn it over to Dr. Esquenazi. Thank you very much, Joe. It's a delight to be here with such an incredible panel. It is rare that we have an opportunity to get this many people together to talk about prosthetics in upper limb amputation. So my job is today to spend a few minutes just talking about some of the prosthetic advances that have occurred. And I want to start with just showing my disclosures and then move forward to really try to explore advances in upper limb prosthetic rehabilitation. And I'll leave the rest in the notes so you can read through. Due to time constraints, I'm going to certainly go very fast so that we get to see as much of this as possible. We know clearly that there are about 1.6 million people with limb amputation in the U.S., but the great majority are lower limb amputees. And what you see here in this is a smaller group of upper limb amputation. Fortunately, the great majority are in the transradial level, but we do have patients with transhumeral and then with shoulder disarticulation. When you look at age in this group, we see from this data that we gather in our institution that clearly the great majority are in the young group age from between 16 to 55. And the great majority of these patients, unfortunately, tend to have amputations that are related to trauma. So the human hand is a very complex instrument with more than 80 degrees of freedom. And on top of that, it has sensation. And so it's really very difficult to try to replace in a good manner the complexity of the hand. In the VA, they've done some very innovative studies, and they've been able to track down patients. And the great majority of them have used either body-powered and then in some cases passive or myoelectric prostheses, even though these patients have access to all three of them. So body power is still pretty prevalent, and I'm sure we're going to hear today about why that happens. When you look at the use of upper limb prosthetics in ADLs, the great majority of individuals tend to utilize prostheses if they actually have a transhumeral or a transradial amputation. In regards to the upper limb, we know that there are a multitude of prosthetic devices that are in development. But the reality is that the human arm has more than 22 complex movements. And current prostheses really have, in body-powered prostheses, maybe three movements, and in those that have more complex systems, maybe seven. But it's hard, again, to replace that missing number of movements. This is data from, or these are images from the original first upper limb myoelectric pattern recognition prosthesis, which was developed at Moss Rehab in the 1970s. Myoelectric prostheses really permit the use of very simple systems to allow highly complex movements. And in this image, you would have seen this individual actually cutting nails. We know that in myoelectric prostheses, there are essentially two kinds, those that have proportional control, in which, depending on how quickly you move your muscles, you are able to generate a faster or slower pace of movement in your prosthesis. With that, there are now dexterous hands that are being developed. Here you see the Michelangelo hand, the Tasca hand, and the b-bionic hands, just as samples of that. And these devices allow really a variety of movements with just the simple use of muscle action to try to generate the control mechanisms. There are some partial hand active fingers that you can utilize. They are not highly complex in the sense of its structure, but they work quite well using tenodesis movement from the partial fingers. We have seen a significant improvement in socket design, and these are just some examples that have reduced the number of sockets, the number of volume of plastic that we need to cover the socket and to really fasten the arm into the prosthesis. But in increasing number of patients, we've seen the implementation of osseointegration as a possible method of suspension. Now, it's not without its own issues, and the Veterans Administration has been doing very interesting work in this country for lower limb amputees, and we are gradually seeing this evolve from countries like Sweden and Australia for the use in the upper limb as well. There have been major improvements in power supply with newer, more flexible batteries with higher charge that last much longer, and so this would be of great importance as we use these devices. This was a short video that it will not show, but it was intended really to showcase what happens when you have a patient who has bilateral transradial and transhumeral amputations using myoelectric components. I will just briefly mention that there is new techniques such as targeted muscle reinnervation intended to create more sites of control for these very complex prosthetic devices. And certainly what we know is that now there are biomes being implanted. There is a group of subjects in Europe that are being implanted with biomes that will allow direct muscle transference of control to the prosthesis without having to worry about the actual electrode placement. And we are seeing also other methods of implantable electrodes that will serve that purpose. The DARPA arm is an incredible step forward in the implementation of these kinds of new technologies, and although it's still being developed, it is now rolled out and some patients are benefiting from using it. Of great importance is that you can have the best technology, but you really need to have a rehabilitation and training program in place, and so it's of the utmost importance that this occurs. Having devices that patients do not get to be trained and do not derive the full benefits of it can be quite frustrating for them. Now, not everything needs to be the most modern. This is an image from the CYBATHLON from two years ago. It clearly shows two very competing, very different devices competing for the metal, and you can see here that a body power device actually won the metal. Arm transplantation is something we need to touch upon. Just to show you, this patient was going to demonstrate driving after bilateral upper limb arm transplantation, one at the shoulder level and one at the transhumeral level. And I think in the not too far future, we're going to see limb regeneration as part of what we will be able to use as a method of transplantation. Again, important to think that rehabilitation expertise really is equal to great experience and commitment to the rehabilitation of these individuals with complex limb amputations. And when you're dealing with bilateral upper limb amputations, don't forget that driving and toileting are clear needs for these patients, and we need to address them. With that, I'm going to stop here and give the forum back to my co-presenters, and just to thank you for your attention. And what you see here came out from a project that was actually part of the VA in which we did a self-management intervention for amputations in a virtual world. I don't think we had predicted that this was what we were going to find because of a pandemic, but here we are. And that's actually my avatar, which has, as I do, an artificial arm, missing hair, and wears glasses. So with that, I thank you. That was great. Thank you, Dr. Eskenazi and Dr. Webster, for the opportunity to participate in this panel. Really, really excited about the opportunity and appreciate the topic certainly here, comparative effectiveness research of prosthesis technology. So when I heard about this opportunity, I was really excited because this really directly relates to what we do every single day. When we're seeing patients with upper extremity amputation and getting to the decision points on prosthesis prescription and determining the differences between suspension systems, control systems, certainly devices and technology. These are all conversations that we're having with our colleagues and we're having with our patients. And so I think the comparative effectiveness research that we will see and that we'll continue to see in the coming years is going to be very important as we create this shared decision-making model, this informed population to go along with who we're caring for. In addition to the introduction, I just wanted to add that in the VA, we've been very fortunate to have created multiple fellowship opportunities. So anyone out there in the audience today who's interested in specialty training and amputation rehabilitation, the VA through the Office of Academic Affiliations has been able to create fellowship training programs in Seattle, in Richmond, and in Tampa. And so these are great opportunities to achieve that subspecialty training. And I'm fortunate to be the fellowship director down in Tampa. There are two-year clinical and research opportunities and one-year clinical opportunities within the VA. And there's also a new fellowship training program out in Houston through the TIER program with Dr. Melton. So with that, I just wanted to move along here. So my disclaimer, this is my work in no way represents or reflects the views or opinions of the Department of Veterans Affairs or the United States government. So let's start with establishing what does comparative effectiveness research mean. The Institute of Medicine did a fantastic job defining this term and this area of research that is really important to what we do, as I mentioned. Comparative effectiveness research is the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor or improve the delivery of care. The purpose of comparative effectiveness research is to assist consumers, clinicians, purchasers, and policymakers to make informed decisions that will improve health care at both the individual and population level. So many important things that they touched on here in this definition. I think referring to generation, meaning primary research, so seeing the primary research in this area, and synthesis of evidence. So we're talking about systematic reviews where we're bringing together all the information to understand what's going on. You see in there alternative methods. So it's really meaning that we have two options that could both work well. So we want to see two available options and be able to put them up head to head in a format in order to understand those benefits and potential risks. I think the definition of comparative effectiveness research all focuses on making head-to-head comparisons in study populations that are typical of clinical practice. So we want to see this research and this discussion, the literature, to demonstrate what these populations can perform. And we'll see a little bit about that as we move forward here. There is outstanding federal support for this, as you'll see here. And effectiveness was published. The development of this Center for Comparative Effectiveness Information, recognizing the importance here. One of the things that the Institute of Medicine Committee did was put together a comparative effectiveness research top 100 priorities. And so it's interesting to see the correlation to our rehabilitation world, to the rehabilitation topics. So here were three of the top 100 priorities from the Institute of Medicine, focusing on comparing the effectiveness of comprehensive care coordination programs, such as the medical home, and usual care in managing children and adults with severe chronic disease, especially in populations with known health disparities. Comparing the effectiveness of different quality improvement strategies in disease prevention, acute care, chronic disease care, and rehabilitation services for diverse populations of children and adults. And also comparing the effectiveness of different strategies to engage and retain patients in care and to delineate barriers to care, especially for members of populations that experience health disparities. So some important things to focus on as we move forward here. Let's dive into the upper extremity amputation population now. So there's a few areas here we wanted to talk about. Alberto mentioned the transplantation. This is looking at replantation. So following that initial trauma, these groups from the University of Washington, University of Michigan, and Baltimore utilized self-report measures for patients with history of traumatic unilateral upper extremity amputation at that trans-radial level who underwent either successful replantation or revision amputation with prosthetic rehabilitation. So these benefits were then compared using the dash, the disabilities of the arm, shoulder, and hand, and the Michigan hand questionnaire instruments. And so, again, we want to focus on the population at hand. So here we compared nine patients with replantation, 22 patients with amputation who underwent prosthetic rehabilitation. And found that based on the Michigan hand questionnaire scores, the affected extremity was significantly higher for the replantation group compared to the prosthetic rehabilitation group. So those significant domains in the Michigan hand questionnaire were overall function, ADLs, and patient satisfaction all found to be statistically significant. So interesting information there when thinking about that initial trauma and that discussion that we're having with our trauma surgeons, thinking about the functional impact of replantation versus the definitive amputation with prosthetic rehabilitation. The next surgical study that we found here was prosthetic rehabilitation and vascularized composite allotransplantation following upper extremity limb loss. This was, again, performed with the University of Michigan and Johns Hopkins. And I think this article and these authors did a really great job discussing that comparative effectiveness vision. And so some of the things that they talk about here, really focusing that treatment plan, meeting the patient's individual goals. So making sure that we recognize what bring our patients in to that decision-making process and making sure that we're focusing in on their goals. They also report prosthetic rehabilitation and upper extremity transplantation should not be viewed as competing options, but rather as two available treatment modalities with different risk to benefit profiles. So this speaks directly to what we just heard about the comparative effectiveness definition. We want to recognize two options that as clinicians we're considering for care, and we want to be able to compare them with that head-to-head format in order to understand better that risk benefit profile. They mentioned how both of these, transplantation and prosthetic rehabilitation, are expected to improve dramatically over the coming years with biological and technical discoveries in both prosthetic interfaces and immune modulation strategies. So exciting things to come in both of these areas, and we want to use this comparative effectiveness research model in order to really understand that benefit and risk profile. I think they just did a phenomenal job here enabling the comparative effectiveness research vision for an improved informed decision and care. We were also able to find some studies looking at the technology of control. You saw a little bit earlier about how there are these new and innovative methods, but what is currently out there, we certainly have our sensor-driven myoelectric control and now postural control. This study compared utilizing the Southampton hand assessment procedure, two types of sensor-driven myoelectric control and a postural control scheme. One of the things this study wasn't able to do was incorporate it into the patient population as we mentioned in the comparative effectiveness definition, but they were able to look at seven non-disabled subjects and reported that postural control did serve benefits similar to the myoelectric traditional sensor control. So I think this gives us a good platform to then move into the patient population that we're interested in studying in order to continue to understand control. One of the most common complaints we hear from our patients who utilize myoelectric hands are the issues related to gloves. So this study looked at comparing the properties of gloves of these prosthetics hands to see how they impacted timing, how they impacted speed, grip, and then also their durability. One of the most common things that we hear just how gloves just aren't durable enough to deal with kind of everyday use and now you're walking around with ripped gloves and that may make you potentially not want to use that prosthesis or reject the use of that device over other devices. This is a national study of veterans with major upper limb amputation. This was performed with Linda Resnick's group up in Providence along with the University of Massachusetts and really creating a nice model of how to understand the population, understand what patients are using out there. You can see similar to Dr. Eskenazi's slide there we had about a little bit over 60% body powered users versus externally powered terminal device users. But this really sets the framework for being able to now compare these people and in this kind of head-to-head format to understand benefits of these devices and so this leads up to a functional abilities comparison bringing people in and testing their functional abilities with different devices and there is an active comparative effectiveness study with this group. It's a multi-center trial with Department of Defense and VA. I was hoping to be able to report more information on that study here in November. Unfortunately with the pandemic and restrictions on research we had to halt recruitment of that study but that really exciting things to come related to being able to compare these terminal device technologies with relatively large patient populations for our rehab studies. Lastly and I think this is something that I certainly want to leave you with and encourage the use of trials. This was a case study done out of Sweden. It was published in the Journal of Neuroengineering and Rehabilitation and in this study the primary author performed comparison study on himself with on-the-job usage for five years with a dedicated and focused intensive two-week use tests at work for both systems. So he compared his use of his externally powered device with his body powered device, found that the body powered device over this period of time in this setting provided reliable and comfortable effective and powerful service with minimal maintenance. All of these types of things that we educate our patients on when we think about the differences between body power and externally powered. Most notably though they report benefits in grip reliability, grip force regulation, grip performance, center of balance, component wear down, sweat and and skin quality as compared to externally powered. So I think they did a really nice job of categorizing the types of things that can speak directly to the user when you're in clinic and talking about these differences being able to target functional goals, activities and utilize these types of characteristics that I think will really be able to hit home with the patient population, the users of these devices. And so we can think about how this information will really influence our clinical decisions for assisting patients in achieving functional independence and achieving their functional goals. Again I want to thank you for the opportunity today. Here's the James A. Haley Tampa VA Hospital, our polytrauma and rehabilitation center. Look forward to the opportunity to see folks in the future and thanks again for the opportunity today. Thank you Dr. Heckman and good afternoon everyone. Just a little bit of housekeeping, please refrain from imaging our slides as it relates to copyright and intellectual property issues. We have no financial disclosures and the research we're presenting today is made possible by grant support from DARPA and the NIH. With those formalities through there, I just want to say that Alicia and I are very excited to be able to speak to you today on the research in which we're involved with at the University of Michigan under the direction of Dr. Sedona. So without further ado, this first video and unfortunately the videos we uploaded are not available, but this first video you would have seen Luke Skywalker in the 1980 Empire Strikes Back moving his new prosthetic fingers status post hand amputation compliments of his father in the same natural way as a native hand. And so you may wonder well what does 1980s Empire Strike Back have to do with today's lecture? We're 40 years later here via the brainchild of Dr. Sedona's regenerative peripheral nerve interface. We're on the cusp of realizing prosthetic control on par with what was only possible with science fiction special effects. So our team is a multidisciplinary coalition of experts and clinicians in the fields of plastic surgery, physical medicine and rehabilitation, kinesiology and biomedical engineering, none of which would be possible without our patients. So unfortunately we had a video here to share with you of our Dr. Sedona, our principal investigator and Dr. Chestek, one of our PhDs discussing the research, but we'll move on. There has been an explosion of technology available in prosthetic hand restoration. The limiting factor has been a method of transmitting adequate signal to power that potential function. So RPNIs serve as that necessary bioamplifier. At the technical level, the RPNI is formed by suturing a severed nerve ending to a denervated and non-vascularized autologous muscle graft. The muscle graft is then rolled to cover the nerve ending and secured with sutures, think of like a burrito. So the muscle graft then undergoes a process of regeneration and revascularization while axonal sprouting of the implanted nerve occurs and reinnervates that muscle graft. The muscle graft then provides an ideal medium for interfacing with the nervous system. The nerve shown here in the diagram has been dissected into individual fascicles and so that allows us to extract high resolution control signals and capture the loss function of individual nerves. The muscle grafts themselves just naturally amplify the nerve signal into a strong muscle signal. The muscle tissue itself is relatively durable and forgiving with robust stability. We're now at the two-year mark with ongoing human subject trial. This imaging is histologic imaging depicting errant aimless axonal sprouting occurring in a control on the left and the formation of new neuromuscular junctions in the RPNI muscle graft on the right. In what would have been an ultrasound video, it would demonstrate the contraction scene of an RPNI unit innervated by the ulnar nerve as the subject who was a proximal transradial amputee was asked to move his little finger. On the left here is a still ultrasound image of the ulnar RPNIs and unfortunately it doesn't project real well. In our research we use ultrasound to both measure stability of the RPNI, the size of it over time, as well as to ensure accurate temporary electrode placement into the RPNI itself. You may be able to see an electrode needle entering from the upper left. We've been able to record good EMG in two experiments now. The image you're seeing on the right is a recording from an ulnar RPNI as the subject was abducting their little finger reassuringly coming from the ulnar nerve. Impressive. The RPNI has now been tested on 800 animal subjects. Our first human case was done in November 2013 now with over 200 human subjects at the University of Michigan and an additional 100 RPNIs have been done worldwide. All this started as a way to provide stable intuitive control of a prosthetic limb, but interestingly during the animal studies we found that there was a notable absence of neuroma formation. This discovery prompted investigation into the use of RPNI for the treatment and prevention of symptomatic neuromas in human subjects. Before discussing the RPNIs in prosthetic hand control, I will be discussing the use for treatment and prevention of post-amputation pain. We've dubbed that the phantom menace in keeping with our Star Wars introduction there. As Dr. Eskenazi mentioned, there's about 1.6 million people living in the United States with extremity loss of which that greater than 50% develop pain. This leads to decreased quality of life and inability to wear the prosthesis. Pain has been cited as a reason why about 30% of people discontinue using their prosthesis. They have an inability to work and a need for often multiple medications including opioids, neuropathic pain medications, anti-depressants, often with suboptimal pain relief, as well as adverse side effects and the risk for abuse as well as addiction. So the cost of treating phantom limb pain in the United States is estimated at 12 million annually. Post-amputation pain consists of two distinct entities, residual limb pain including neuromas as well as phantom limb pain. The neuromas are an inevitable sequelae of major nerve injury or transection. The rate of developing a symptomatic neuroma pain is 12 to 50 percent while the rate of developing chronic phantom limb pain is 70 to 95 percent. So this is a big problem given that we're due about 185,000 amputations annually in the United States. So although residual limb pain and phantom limb pain have different underlying mechanisms, they are deeply interrelated and can often potentiate one another. And so treatment of residual limb pain such as neuroma can affect central sensitization and central reorganization to then reduce the incidence of phantom limb pain. Conventionally treatment for symptomatic neuromas has been non-surgical and elicited a number of different methods there as well as surgical. The surgical methods have the highest efficacy but even with that there are over 150 different reported techniques none of which float to the top as being superior to another with a reoperation rate as high as 65 percent and even then 20 to 30 percent of cases are refractory to treatment regardless of the type of neuroma surgery. I'll be skipping through a couple slides here in the interest of brevity. So enter RPNI. So in addition to the observed lack of neuroma formation in the animal RPNI studies, fortuitously our patients undergoing RPNI for study in controlling prosthetic devices also reported improved neuroma pain and less phantom limb pain. So in 2016 our group published a pilot study reviewing 16 amputees who were treated for symptomatic neuroma relief with 46 different RPNIs and the result of that we used questions from the PROMIS instrument. The results showed that there was a 71 percent reduction in neuroma pain, those are the orange bars, and a 53 percent reduction in phantom limb pain and that's the green bars. It's pre-operative on the left, post-operative on the right. So then the next question is can we use RPNIs to actually prevent formation of symptomatic neuromas and then also reduce phantom limb pain? So in 2019 we published a study looking at just that. It was a retrospective chart review of 45 patients who had undergone RPNI at the time of their primary amputation and 45 control patients who underwent standard amputation techniques without RPNI and those standards include nerve management of suture ligation, traction nerectomy, the nerve unburied in native muscle, and a combination of techniques and some were unknown. But these results showed that the symptomatic neuroma in the post-operative period was 13 percent in the control patients and zero percent in the RPNI group and then phantom limb pain was reported at 91 percent in the control group versus 51 percent in the RPNI group. And so this study showed that the RPNI group had significantly lower incidence of both symptomatic neuroma and phantom limb pain. Additionally, there's no increase in post-operative complications in the RPNI group compared to the control group. So together these studies demonstrate that RPNIs can treat and prevent post-amputation pain. The effectiveness of the RPNIs in diminishing post-amputation pain has transformative implications for successful prosthetic restoration, decreased reliance on pain medication, and improved quality of life after limb amputation. So at this time, I will turn over center stage to my esteemed colleague, Dr. Alicia Davis, who will control of a prosthetic hand, which was the initial goal of our research. Alicia? Thank you so much. So, Misha Davis, I appreciate you, Dr. Latham. Implanted electrode wires are revolutionizing prosthetic control in our patients. And one of the things that you can, what we'd like to show you in this particular video is that our patient was actually capable of moving his finger and thumb as he desired. But before we discuss the intuitive control strategy, it's important to understand why researchers were looking for better ways to control the upper extremity prostheses. So, there are a multitude of reasons why patients abandoned their upper extremity prostheses. And these are most often cited reasons in the literature, as well as my clinical practice. Most patients who desire myoelectrically controlled prostheses have that same sort of Star Wars idea of how a prosthesis will work. Unfortunately, as I'm sure you know, the internet can make managing patient expectations a bit more challenging. That and the effect, or the fact that most currently available myoelectric prostheses are dual site control, make it difficult to replicate the movements of the natural human hand. The beauty of dual site control scheme is that it is incredibly simple and needs minimal recalibration. The challenges of dual site control are a loss of electrode contact within the socket. So, if the patient changes overall shape and size, the electrode contact with the skin will no longer be there. It's also non-intuitive control, as well as cumbersome in terms of grasp selection. Prosthetists can alternate methods of control of a prosthesis by use of alternate external methods. They include force transducers, linear potentiometers, touch pads, and switches. These methods require non-intuitive movements to access the skin. As well as the linear potentiometer are attached to a harness, and when the patient moves to grasp something, they can't actually go ahead and move the prosthesis as well. The other challenge is that the patient can't move the prosthesis as well. They can't actually go ahead and move the prosthesis as well. Pattern recognition is currently seen as the holy grail, if you will, of control of the prosthesis. However, as with most things, there are some significant limitations. Signals require frequent recalibration, and surface electrodes cannot robustly record the EMG signals from the deep muscles. Switching grasp patterns continues also to be non-intuitive. The quest for more intuitive prosthetic control led Dr. Siderna and this team to develop regenerative peripheral nerve interfaces. The nervous system at some level still carries motor information from the lost muscles. When we tap into this communication pathway using neural interfaces, we can extract and control the signals, interpret or predict what the patient is trying to do, and send a command to the prosthetic limb. This allows individuals to naturally and intuitively control their prosthesis. Implanted electrode study began in 2017 and initially required two surgeries. However, we now have approval to create the RPNI and implant the electrode wires in a single surgery. P2 was initially implanted in March of 2018 and unfortunately had to leave this study due to employment in March of 2019. However, during that entire year, his signals remained completely stable throughout the duration of the implantation. P3 has maintained stable EMG signals from November of 2018 until the present day. It's important to note that there are no complications related to the electrode implantation and no adverse effect reported to this date. In our current study, subject P3 had eight pairs of bipolar electrodes surgically implanted into her RPNIs. These were implanted into her ulnar RPNIs, median RPNI, and We have a good surface signal with our adhesive electrodes placed over the thumb extensor. However, the amplitude we record from our intramuscular para electrode is much higher. As you can see, the SNR on that is 111 versus the surface gel adhesive is 22.7. When we asked her to do a more precise movement, like finger flexion, we see a large amplitude response on the implanted electrode on our index flexor. However, this movement proved much more difficult to capture in surface EMG. A high signal-to-noise ratio is important because our electrodes can pick up individual finger movements with less exertion compared to surface EMG, where our participant would need to work a lot harder for electrodes to detect that signal. This means our control signals are more robust and reliable over time. And by accessing better signals, we can deliver better prosthetic control to our patients. In addition to being high amplitude, the EMG recorded from the intramuscular electrodes is also highly specific. Here we see average EMG envelopes from electrodes in her extrinsic muscles and RPIs in rows and response to individual finger movements in the columns. This is very important for pattern recognition algorithms, which require movements to have a unique EMG signature or, as it is shown in this chart, for the columns to be well distinguished from one another. For example, her median RPNI trace during the thumb flexion starts with a low baseline. Time equals zero marks the beginning of her activation, after which we see this beautiful response. Notice that there is not a significant response for any of the other movements here, meaning that the RPNI is a very reliable indicator of thumb activity to our algorithms. There are some localized coactivations that you'll see, but overall her EMG responses are very pronounced and specific to their functional tasks. This means our pattern recognition algorithms can confidently predict movement intentions. We have developed grasp pattern recognition control strategy that allows our participants to intuitively activate the grips without having to do a trigger. When subject number three wants to pinch an object, she simply performs a pinch with her phantom hand. The EMG response from her implanted electrodes is received and input into the pattern recognition algorithm to achieve the intended grasp. Our current framework allows for her to activate point, full close, open, and if she relaxes her hand, it completely relaxes and opens the hand. Unfortunately we have the problem with the videos right now and I apologize for that, but here you would see the subject who is presented with two objects, a can and a tall bottle. We asked her to use a pinch grasp to grab the bottle and a hand close grasp to grab the can and move the items between a shelf. What you would have seen here is that she literally moves the hand, pinches, moves the object, goes back to grab the second object, grasps it without having any kind of a trigger, and then she actually moves the object back and forth to the left. In this video clip, hopefully we'll be able to upload those for you all, P2 is controlling a virtual limb on the computer on day zero and then on day 300 was able to do the same exact video without having any change in his specificity of being able to open and close the hand. The RPNI signals have been shown to be functionally stable over time, which bodes well for trying to make the RPNIs more clinically available for patients in the future. This last video, again, sorry, the thumb control was translated and what was really fascinating about this was that what we were able to do was he was able to track his thumb and follow a paddle and he was able to do this without any triggers whatsoever. He just thought about it and it actually moved. What's amazing about the RPNI signals is that he is able to just simply think it. This is the first time that someone is able to simply think a thought about moving and the algorithm interprets that and is able to simply move it. The last video that we have here basically shows what this patient is able to do and he's able to actually think about moving his finger back and forth and he's able to move it back and forth on his thumb, just like what I'm doing right here. He's able to do it in such a way that it precisely and accurately moves his finger on the thumb without having to do any kind of trigger at all. So it's pretty impressive. There are multiple advantages of RPNIs with indwelling electrodes and this innovation will revolutionize prosthetic control and allow our patients to live fuller and more engaged lives. Thanks so much. All right, well, thank you to all of our presenters and we do have a couple of questions in the chat box. We'll just go ahead and kind of run through those questions and then we'll see if we have time for anything else as well. So the first question we'll direct to Dr. Laidlaw and Alicia. It's asking regarding the RPNIs and whether or not over time the RPNIs might be prone to denervation, such as seen in a post-polio syndrome. We've not seen it so far, but it showed stability over a two-year period. So what we've seen in the lab is that the RPNI signals not only do not degrade but there's been no degradation in the signal whatsoever. Okay, great. And then another comment or question from Dr. So, who is asking about the study looking at the difference between or looking at the study, looking at those who were treated with RPNI specifically for the phantom limb pain and asking whether those individuals had neuromas as well, or if there's any note in those individuals, whether they had neuromas as part of the study. In the study where we were treating symptomatic neuromas or the study where the RPNIs were done at the time of the primary amputation. Dr. So, it doesn't clarify, so, Noah, if you want to, can you type back in the chat box if there's something specific you want us to address there? The other question is about the videos, and again, we do apologize for the fact that those weren't part of the presentation today. We'll have to check with the Academy to see if we're able to, you know, have those available for individuals. It may not be part of this, the archive for this particular presentation, but we may be able to have them available separately. Thank you. And then a question, which may go back to Dr. Heckman's comparative effectiveness studies and kind of thinking about that for the future. But again, we're looking at, you know, for the future of various different types of control strategies, and we're looking at the RPNI, we're looking at possible, you know, using targeted muscle re-innervation, and someone's asking about, you know, brain-computer interface, you know, and what would be the differences or how would it compare to a brain-computer interface for the future? Yeah, well, I think obviously the ability to perform the head-to-head format comparison for surgical procedures will be complex, and there will need to be some research design there where you can have these larger comparative groups. I know to date, the transplant groups are small. Hopefully we will be seeing more and more RPNI, more and more TMR, so that we can have the appropriate group sizes to be able to do those comparisons. But I think that's one of the exciting reasons about a presentation like this on a national forum where we can talk about these things and really promote them to be able to see more and more of this in the future. Dr. Eskenazi, do you have any comments with that based on your experience? Yeah, thank you for the question, and I think it's two points that I would make here. Brain-computer interface is a very difficult, very different model of connection in which you're essentially bypassing the peripheral nerve to try to achieve that, and it has its own set of risks and potential rewards. The idea of using peripheral nerves simplifies the intent of control because you can, as demonstrated very elegantly today by the presenters, you can have a larger array of switching selectors. It's like having each light bulb in your house connected to a separate switch, but then you can have those switches really control in a very elegant way by just deciding how strong your contraction is, and this is really a very different approach. Computer brain interface, I think, is much more suitable for those that have no peripheral nerve interaction, so those patients who are completely paralyzed and have a limb, that may be an appropriate way to do, or you substitute the limb with a robotic device. So I think this is part of what we heard about the research strategies going forward. If I may, I will take just 30 seconds to point out that neuromas are always the result of any injury to a nerve, so you will always end up with a neuroma, but a neuroma is not indicative of phantom limb pain, so keep that in mind. There are two different processes. Sometimes they overlap, sometimes they don't, and the idea that you can resect a neuroma to correct phantom limb pain is probably a false perception. It does not always work like that, but the idea of innervating a muscle, innervating a muscle with a branch of the nerve so that if it creates a neuroma, it is protected within that muscle and you give a role, a specific function to that nerve, it gives us a clear advantage. And as the researchers have demonstrated, we do that potential call for a phantom limb pain. So you can't just assume, really you need the research work to make this tangible to all of us. Right. I think clinically it's been very interesting as someone who has a career prosthetist and focused on that for the last 20 years of my career, it's been amazing to watch my patients who have gone from having significant neuroma pain to literally having almost no pain whatsoever. Not phantom, but neuroma pain, very different. And so thank you for bringing that up. I appreciate your comments. I think what we found with the RPNI is that that muscle, it gave the nerve a place to grow. The nerve is going to grow and it was growing and reinnervating that muscle graft. And so in doing so, it prevented neuroma formation. So I mean, for someone like me, like I said, who has been doing prosthetics all this time, it's a game changer. And I don't say that lightly. It's been fascinating to watch how our patients have actually been able to engage in ways that they haven't been able to previously. So it's very exciting research and I hope that it continues to go forward. And again, we do really appreciate all the questions. We are at the end of our session now. So again, I'd like to just thank the presenters. I think this was a very informative session. And again, just thank you again. And thanks to the Academy for hosting this session. Thank you.

upper extremity amputation

upper limb prosthetic technology

advances in technology

comparative effectiveness research

phantom pain

prosthetic control

regenerative peripheral nerve interfaces

RPNI

post-amputation pain

prosthetic control methods