So, all right, guys, we'll get started here. This is our first and hopefully future boards. So, this is our editor-in-chief panel, like I said, first of its kind, and hopefully future conferences will continue to hold this. And so, my name is Ryan D'Souza. I work at Mayo Clinic in Rochester, Minnesota, and I've had the pleasure of working on a lot of these editorial boards. I will say I thought of this idea about five years ago, but I couldn't muster up the energy and courage to ask them. So, what I did is I got to know each one of these guys, and I'm like, you know what, we should just all meet together and have a great discussion, a collegial discussion, because at the end, we're all in here for patients and all have a common goal. Even though we're competing journals, we're here just to take care of patients, so. Yeah, and I'm Nasser Hussain. I'm out of the Ohio State University. We just won the national championship, so go us. But yeah, for Ryan and I, I think this was very important because it's challenging to know what the editors are thinking when they receive manuscripts, what revisions mean, what the covered letters mean. I think having a candid discussion and debate amongst themselves in a collegial way is nice, so without further ado. So, what we'll do is we have a lot of questions ready to go, but we also encourage if there are any questions from the audience, please ask, and we have a mic that we'll pass around here, all right? But we'll get started here. What we'll do is we'll actually introduce the entire editorial board here, so we'll start off with Michael Shatman. We'll go ahead and introduce yourself and go down the line here. Michael Shatman, Javier Spain, NYU Pain Medicine, Journal of Pain Research Editor-in-Chief for 12 years. Good morning. Chris Gilligan, and I'm Editor-in-Chief of Pain Practice. And I'm Robert Levy, and I am and have been for, gee, 15 years now, the Editor-in-Chief of Neuromodulation Technology at the Neural Interface. It's the official INS journal, which includes NANS as well. Good morning, everyone. I'm Rob Hurley. I'm the Editor-in-Chief of Pain Medicine, and I'm a professor of Anesthesiology, Translational Neuroscience, and Public Health at Wake Forest University. Good morning, everyone. Nick Nasevich, I'm Vice Chair for Research and Advocate at Illinois Masonic Medical Center in Chicago, Clinical Professor at the University of Illinois, Section Editor for Pain Practice, Section Editor for Pain Physician, Associate Editor of Anesthesia and Angesia, Interventional Pain Medicine. You name it. Could be my full-time job if I have enough time just to do reviews. Awesome. Thank you all for being here. And like I said, this is for the membership. This is for you. This is a chance to really ask our future, obviously our current and future leaders here, and they're obviously shaping the way the research field is going. We're going to be covering a lot of different topics. We're going to talk about vision for future research, collaboration among societies, amongst journals, preparation of impactful manuscripts and pitfalls. Let's start off with a controversial topic here, guidelines. We all love guidelines. We know there's an abundance of them at times. They're impactful. They get highly cited. What are your thoughts about the guideline arena? Do you think there's a lot of them? Do you think there's potential to consolidate them? Cover things including like collaboration between journals and publishing guidelines. So open question. I want to hear from you all. Well, I take the radical position that we're in the midst of a clinical practice guideline overdose crisis. We're putting out a lot of guidelines. I'm on a ton of guidelines. My journal is the official journal of ASPN. We love guidelines. We're going to have some controversy here. I'm not quite the scientist that some of my colleagues here are. I'm more of a policy guy, and my concern, real succinctly, is that all the guidelines in the world are wonderful for informing practice, yet at the same time, the real crisis is all about payers making decisions and declaring everything we want to do as experimental irrespective of the beautiful evidence bases that we present. And I think we need to shift our efforts to a degree away from guidelines, not ignore them completely, and look more at policy issues as journal editors-in-chief. I think the landscape of guidelines has changed profoundly. In the past, until I think about six years ago, there was a federal agency in the United States that reviewed and accepted or rejected guidelines and kept that registry of good and not so good guidelines so people had a clear direction to go. The government abandoned that policy and closed down that organization. So anyone can put out any kind of guideline without any consistency, without any directions. I think, for example, the PRISMA guidelines for systematic reviews really helped clean up the field of systematic reviews and meta-analyses because people had a gold standard with which to follow. Since we don't have that, guidelines, one, have less integrity. Two, every society, every organization does not want to give up its power, and so they compete rather than collaborate. And then last of all, so many guidelines are not so much evidence-based as they are... I remember when I first submitted a manuscript 20 years ago on a topic like this, the review came back from a very respected Texas academic neurosurgeon, but the review came back and said, this is just a bunch of good old boys sitting around and shooting the shit. And that sort of expert consensus is very low on the totem pole when it comes to evidence-based medicine. And so I believe the best direction to go in the future is to first establish guidelines for guidelines. Require, in order for any of us or any journal editor to review and publish a guideline, it has to follow certain policies like PRISMA is to systematic reviews. And then once we have that, it's better if we put out guidelines that aren't directly in opposition with each other, because that just confuses everyone, including the practitioner, the government, the insurance payers. So we have to decrease our ego a little bit and increase our collaborations to put out things that have national and international bearing. My opinion. Yeah, so I don't know if I'm going to split the difference on this one. So full disclosure, I write several guidelines, so I obviously have a somewhat positive opinion of guideline writing. However, I'll make a broader statement. In my opinion, there's way too many pain societies and way too many spine societies, and there's way too much overlap. That in and of itself poses a problem for the guidelines, because it's very hard to come together when each society has their own interest and board and leadership. And people don't like giving up their autonomy or beliefs in things because it serves their purpose. That's fine, well, and good. That's where we are. We've got, what, 15 to 16 societies, so people are going—it's actually minimum. The most recent guideline that we have written has 27 societies on it, to give you perspective. So I think guidelines can be good as far as the regulation of guidelines. The PRISMA guidelines are fantastic. They have those for scoping reviews. They have those for how to do a literature search. On the Oxford site, it's got basically a guideline for almost every single study you could possibly imagine, meaning study design. In fact, they do have a guideline for guidelines, and it's called AGREE, and there is a revision of that that's called AGREE 2. It involves both a paper but also a checklist that one can follow to perform what is considered sort of the bare minimum of acceptable guidelines. The vast majority of guidelines that have been published in the last, we'll say, five to 10 years usually are single-society based, and most of those wouldn't qualify for AGREE 2 guidelines. So to Michael's point, if we're putting out guidelines that are not of terribly high quality, it's a disservice to all of us. CMS follows these guidelines. Several of the guidelines that I participated in are in the LCDs for a couple of the procedures that a lot of us perform. So our guidelines have impact. So they need to be exceedingly judiciously written and focused. My one argument pro in guidelines is, as Bob said, they have changed over the years. One of the things that has changed is a decrease in collaboration among the societies to produce guidelines. I think multi-society guidelines do provide benefit, and where you clearly publish what each society felt about all the things that are written within the guidelines. As far as publication between journals, many of us are on a sort of consortium of EICs that try and publish things together because we do believe saying things with one voice are going to provide greater benefit. I think when it comes specifically to guidelines, it becomes more difficult because you now have a different business entity being the publisher that may or may not want you to share those guidelines. Although RAPM isn't represented up here, Pain Medicine and RAPM have co-published several guidelines and several future guidelines that are coming out. And that's at least an attempt to speak with similar voices. So my positive would be multi-society guidelines following at least as closely as possible to the agree guidelines for guidelines, as well as co-publishing agreements, I think are exceptionally helpful. One of the best examples of co-publishing agreements was the NIH Low Back Pain Task Force guidelines that were published, at least best of my knowledge, in over 15 journals simultaneously. That was an example of something where people actually came together to try their best to say the same thing. That was very insightful. So I guess, in one word, do you feel that the quality of guidelines has increased or decreased over the past several years? DR. HARTZBERGER. Since I'm super opinionated, decreased. DR. GOLDSTEIN. I would say decreased, but also to the points that the others made, a tremendous amount of heterogeneity. And certainly in interactions with payers about patient access, there is a clear hierarchy of which guidelines carry a lot of weight with them and which guidelines they are relatively quick to dismiss. And that hierarchy may not be perfectly calibrated, but there is some justification to it, I would say. HARTZBERGER. I also think it bears mentioning that industry has managed, and this isn't nefarious, but they've managed to foster key opinion leaders in the field who are very biased toward their approaches or products. And so what happens is that if you tease apart several of these guidelines, what you find are differences that are really based on the members of the panel and their interests with industry. And it used to be, and it still is, the INS gets its COI policy as an augmented policy of the American Society of Medical Specialty Societies. And one of their rules is that industry cannot either financially support, nor can it be involved with the publication of guidelines. And so it's a little naive to think that takes care of the issue, because so often we see people who are legitimate members of a panel to come up with guidelines, but their financial interests with industry affect some of what they recommend. And the process to cleanse that is not so clear. And that's been the case for the last at least 10 to 15 years. I don't remember that being as rampant in the distant past. I guess first, before we ask more questions on our end between Dr. Boussouza and I, are there any questions from the audience? We have about 60 questions, but we're not going to get through those. Good morning. I'm Rogel Simplisson from Brazil. I would like to ask about aims and scope. So all the journals have its aim and scope, but they're pretty much static. And each editorial board decides what would be the future of the interest of the publication the next year, the next two years. So it could be useful or possible to have an open letter for the scientific community each year or every two years saying what's the intention of the journal, which types of publications or which specific areas to publish. I can take a stab at that. So Pain Practice is the official journal of the World Institute of Pain. So I would say we always have a couple of considerations. One is we're especially interested in, as World Institute of Pain, in international articles, articles from researchers around the world and or articles that would have implications for practitioners. And then as the title implies, Pain Practice, our core audience is clinicians. So we're interested in articles that are going to be relevant to somebody in practice. Now, what that could be could be a very broad range, but I would say those are our two areas of focus that are things that have implications to practitioners around the world and things that have, would be of interest and of value to active clinicians. Perfect. As more questions come up, please raise your hand and we can certainly solicit more questions from the audience. One of the things that was mentioned from the panel was conflicts of interest. So let's kind of delve a little bit into that. So a couple of questions related to that. How do you handle submissions with clear industry sponsorship? And also, do you feel like industry sponsorship and bias compromises the perceived credibility of journals? I know it's a very controversial type topic, but I'm a firm believer that our field, there's a very, we need that mutual collaboration with industry to get things done because a lot of times this funding does not come from government sources or NIH or other types of sources. Anyways, I want to hear, I'm really interested to hear your thoughts on it. It is a very interesting topic, particularly because we are talking about neuromodulation, something that is extremely expensive for anyone else to do without any involvement of the industry because someone has to pay for devices and stuff and it's just a federal agency. I'm not going to cover for sure those type of studies. That means from one point, all studies are coming from the industry. The question is now if they're sponsoring a study, which level of involvement is in producing data, analyzing and writing the papers and stuff. That's the key that actually should be as much as possible independent and less conflicted in people who are participating in the manuscripts. However, I guess the majority of the things are, if you recruit more patients, then you're going to get authorship in the paper. This is how it works. Sure, thank you. So, I'd have probably two points. One, the comment that Bob brought up with guidelines applies to conflict of interest, as he said. Outside of the pain world and the spine world, guidelines have different conflict of interest policies than we do within our area. So, I'll give you an example. American Society of Hematology does not allow any person to be on a guideline if within the last three years they have industry COIs or any. It can even extend to federally funded grants that have a particular bent to them because there can be secondary gain associated with those as well. So, that's one approach to decreasing the influence of an individual's personal goals, conscious or otherwise. With regard to COI in general, so pain medicine has probably, I think, one of the more rigid ones on conflict of interest, at least as of recently. And while we're discussing it, we might as well discuss what my conflicts are. So, I declare my NIH grants as conflicts of interest. The reason for that, I'll expound upon in a second. But I also have industry funding for a research trial from Nevro and then three years ago, one from Avanos. So, take my comments as you wish. I would like journals, but also scientists, clinician scientists and otherwise to maybe view conflict of interest a little bit more broadly. So, everyone points to industry funding as, oh my goodness, there's a conflict of interest. Industry funders, for the most part, for their large randomized clinical trials, and I'm putting a very broad general here. There are exceptions, obviously, have been under sort of a microscope from everybody for minimum of 15 years, maybe longer. And so, a lot of the trials that many of us are participating in, possibly many of you, are very regimented. They're double blinded, et cetera, et cetera. They have many of the bells and whistles of an exceedingly rigorous trial. There are groups that are considered accepted from conflict of interest. So, an NIH grant is not supposed to represent a conflict of interest, nor is a PCORI grant, nor is anything else. There is a difference between the industry and the federal grants. The federal grants have never been under any sort of microscope. They've always had an exception to whether there are conflict of interest. One can say that the NIH grants, most of them are something called cooperative grants, meaning NIH people, administrative staff, have just as much of an opinion on your science as you are going to have. So, one could argue that that appears to be a pretty significant conflict of interest. That's obviously my opinion. The point with that is every funder has secondary gain. It may be clear and apparent, like industry, in improving their P&L statement. For an NIH program officer, it's their ability to maintain employment or be promoted. But there is secondary gain, and we should probably just declare anything that could possibly be something that influences a paper. So, what we require is, to the best of a person's ability, which follow the publication standards for COPE and ICJME, just declare everything, and then the EIC has to manage, or the editorial team has to manage, what is considered too much conflict of interest. And that does get subjective, and I'll admit to that. But I think there are maybe pathways, and maybe we should think about them a little bit differently than we have over previous years. And the question, as I heard it, is much more specific, and that is, if you have industry involvement in a paper, how do you handle it? And we are one of those medical specialties that is entirely reliant on industry to provide us with the tools we need to do for research. You can buy a patch clamp system and you can go in your back room and do all the research you want, but you can't do a spinal cord stimulation trial or peripheral nerve stimulation trial without devices, and devices are expensive. So unless you have unlimited financial resources, collaboration with industry, even to a minimal degree, is required in our field. So there are all different levels of industry involvement, from the lowest, just providing devices for free or at a discount, all the way to their people collecting the data, doing the data analysis, writing the manuscript, and then handing it to their authors. We subscribe to the belief that not the only, but a required part of that process, when a manuscript is submitted, is being open and transparent. And we even have someone in the organization who checks, they go to the Sunshine Act page, they contact companies for verification. The companies won't give out raw numbers, but when this person calls them and says, we have a report from the doctor that they received X dollars from you last year, is this about what your numbers reflect? So we do that. We demand transparency and reporting all of the potential conflicts, although we don't believe NIH grants are conflicts, but it's sort of a different process. But also we have all of our authors sign an affidavit, and you may say, well, people lie. Sure they do. But the affidavit is legally binding. And so for many people, if they're university employees or employees of big hospital systems, if they are caught falsifying a legal document, it can cost them their job. And so we have a detailed form that has to be completed and signed before we even accept an article for review. It's not perfect, but I don't think in this field we will ever be perfect. And you would think it would just be clinicians who have this problem. But as many of you know, we have large sections of the journal that have to do with basic science and have to do with bioengineering. And even there, these conflicts arise and need to be dealt with. One of the blessings that we enjoy as editors-in-chief to help safeguard against conflicts of interest is our peer reviewers, who are very, very quick, I find, to call out conflicts of interest. Sometimes too quick. Now, recently I was on a study, and a peer reviewer said Dr. Chapman committed an ethical violation by refusing to, by failure to report that he's the editor-in-chief of the journal. That was a little bit disconcerting. The section editor said, you know, Michael, don't worry about that. But you know, I think peer reviewers are very, very, becoming progressively more in tune to conflicts of interest, and they do us a great service. I know some of you do peer reviews, and we have to collectively all thank you. And I just quickly should mention that we have a process where all of the people that are involved in the society in a leadership role and in the journal, section editors, editors, every year there is a labor-intensive process that sets out to confirm their COI disclosures. And we have on occasion found people whose disclosures were incomplete and needed to address those. Last of all, the American Society of Medical Specialty Societies, which we base our COI policy on, although ours is much more detailed, they require in any guideline document that at least 50% of the people involved in the manuscript are documented to be without any relation to industry. And they also state that the first author must be unconflicted. Now, that's obviously only a partway measure, but at least it's an attempt to ensure a significant proportion of the people involved in creating the document are truly non-conflicted. We have about 15 minutes remaining. So, if there are definitely questions from the audience, just please raise your hand and we'll give you the mic. But otherwise, Dr. Hussain. All right, well, we've addressed kind of the abundance of guidelines. We've addressed this conflict of interest concept. You all are reputable journals. But if I'm an author and I'm creating a manuscript and I've gotten rejected by all you journals, how do you address the concept of open access? What do you guide an author about that and in this concept of predatory journals? There's an abundance of pain journals that are popping up now as well. I maybe see a new journal every month and it's a fee for access or fee for submission, essentially is accepted. What do you do about that? How do you guide an author? I can address that because the Journal of Pain Research was, you know, going back to 2008. It was a pay-for-play journal, but publication fees were not associated with any society. Now, we are the official journal of ASPN and soon ISPN. But, you know, I have a lot of concern about the journals that you mentioned that are just starting to pop up that will publish things that we reject that never even get the peer review in our journal. And then you see them being published in the journals. You know, the question is, should everything be published? I think not. You know, all of our journals have relatively low percentages of accepted papers. Probably, you know, 20% something in that range. And some things that are just fair science maybe should be published, but some terrible science is being published in the pain space. And that's a concern because these publications allegedly are going to guide practice and science is bad, and practice will be bad as well. So, Pain Medicine is a hybrid journal. So, we do open access and sort of the traditional model. It's really hard to balance that. And open access or article processing charges that are theoretically how much it costs to put a paper in a certain journal. I think the reality of APC charges is they are all rated. They pretty much correlate very well to the impact factor of the journal. So, it clearly is not really the APC reflecting the cost to actually produce the article. But that sort of cynicism aside, there is value to open access. So, for example, our journal publishes a very large number of international papers. To our questioner from Brazil, Brazil contributes the third highest number after U.S. and Canada for our journal. And many, and I know you're not a European country, but let's expand to a European countries, there are mandates that they have to publish in open access formats. So, a lot of journals, ours included, and I suspect probably everybody's, have different rates that are available based on certain conditions. The NIH has also mandated that any of the studies funded by the public need to be published in an open access model. I'll tell you, almost everyone ignores that, but that is a policy that does exist. So, I think there is a necessity that we have that open access model. Unfortunately, it has also opened up the opportunity for predatory journals. And there's lots of them, and I suspect we all know which ones they are. But I think Michael has pointed out one problem is the plethora of legitimate journals that have sort of exploded onto the field recently. So, I think probably all of us look to see where the articles that we rejected, where they ended up. And some of us, like myself, that love to go down rabbit holes, read the paper and see if it was changed at all based on the peer review that ours did. And rarely is there a single word that is changed despite very rigorous peer review that pointed out problems that led to a reject. So, I think, again, that is a bit of a problem of there's a lot of less than ideal science going in. But that also relates to why are people publishing at such an astounding rate compared to what they used to be publishing? I started 25 years ago publishing, and a couple of papers a year was what was considered sufficient. Now it seems to be 10, so. And we also have people who are publishing one a week and doing it in good journals as well, including yours, mine, everyone's. So, there are some of the young publishing machines, Ryan. And one of the things that we do, a number of journals do, they have other, their publishers have developed cascading relationships. So, ours is with the Canadian Journal of Pain, which is also part of the Taylor and Francis family. And about half our papers are rejected before they even get the peer review. And if they're rejected by peer review, but there's some good qualities to them, then we're great with sending them off to the Canadian Journal of Pain now. Do you have a cascading? We do, but I've got a comment about it. Are you done? Yeah. Oh, okay. I have a problem with that. And I've gone back and forth with our publisher Elsevier many times because they want an automatic process. So, if we reject a manuscript, it goes into the cascade of their journals. But there are many articles that shouldn't be published, as you mentioned. And I feel a responsibility to our community to say, this is a bad paper. It shouldn't be published, and you shouldn't be able to shop it around to 20 journals and find some crap journal to publish it. So, we have opted in only for manuscripts that I select as being potentially of value. But if I don't do that, they're required not to submit it to another one of their journals. We have the same thing for the Wiley journals. We have, if we are rejecting a paper, we can reject it and refer it to some of the other Wiley journals, or we can reject it and, like Rob said, opt not to refer it, depending on the quality. And we do the same thing. You know, the action editor who's the section head, it's her or his decision as to whether it's going to go to another journal. But again, there's so many, you know, we're talking about, you know, great papers, good papers, mediocre papers, and papers that just never, ever should see the light of day. And there's not, I don't think there's a lot that we as editors of better journals can do about that. Yeah, for Pain Medicine, we don't have a cascade journal that was done on purpose, just because I could think I'm a stalwart and not thinking that you guys have a process for it. I'm having a feeling it's very labor intensive. It's not that I didn't just want to take that on. I felt that there's already too many journals out there to begin with. And I think one thing the audience needs to understand is three years ago, the company that really does science citation index and does the indexing of all of our journals changed its policy, as did PubMed. So now anything can be indexed. They do not have a quality barrier for what is indexed, which is why you'll see a journal that started three years ago is already in PubMed. My point with this is it becomes more up to you as the reader to decide what is a quality paper from what is maybe not terribly well done. There aren't those barriers anymore, and those journals that are all now out there have copycat names to several of the ones that are up here. So again, it's a problem of quality, but that's where you all have to come in and be able to judge for yourself. We have a little under seven minutes remaining. Let's kind of go a little bit into that quality piece. So we're living in a generation where artificial intelligence is changing the field. I'm very bullish on AI. I think there's a lot of potential if safely done and safely vetted and guarded. But there's also potential cons with it. I've known that one of the things that a lot of journals are struggling with is there's AI-generated manuscripts that have completely falsified data, and that makes it incredibly hard for editor-in-chiefs and section editors and reviewers to really, you know, look into that. So is that an issue that your journals have been undergoing, and what guardrails and what processes do you have in place to prevent that from happening? It is becoming increasingly a problem. And while I'd like to say it's only from non-English-speaking countries, that's no longer the case. It's almost impossible, especially when the major publishers will not allow a blanket statement that we don't accept AI. And so, you know, we have to work with our publishers to negotiate something that protects us and protects them. So we have a document which originally was created by our publisher and then modified, which basically requires, again, it's an affidavit. So that if you...everybody who submits a paper has to say whether or not they used AI. Two, they must guarantee that they themselves have read the entire content, and that they, after having reading it, are responsible for all of the content that's in there, whether it was written by them or AI. Right now, I think that's the best we can do. But I have seen those kind of egregious errors where papers are just created, or a paper is cited that has nothing to do with what the article says it does. And in the old days, it may not have been the case, but it gets to the point where we have to sometimes run comparison programs to make sure that the paper hasn't been published in large extent somewhere else, that their claims are correct, and even to review an AI-generated article ourselves and read it. And, you know, if you have hundreds and hundreds of submissions like we all do, I'm sure, you know, that's a lot of midnight oil that we, in addition to our section editors, but we as editors-in-chief, are sitting there reading manuscripts to look for those kind of problems as well as their quality. Pain in the ass. Pardon my French. Yeah, because we do have a program. You know, I authenticate you have the program to find similarity, but I assume we need the program to determine whether they use the AI or not. I've seen some few presentations, and I know some students, some European conference, they have a very great presentation that they gave to the AI to write the paper. They did a good job, but they mess up with references because those references actually they couldn't find. They came up with some references, sounded, they looked like perfect reference when you type it, didn't exist. But I guess we need the program to, you know, to detect whether AI was used or not. Yeah, this is something that we're all going to be facing, and AI is a very general term. There's certain levels of it, just like we talked about levels of conflict of interest. One of the things, so, and this is not, I'm not speaking for pain medicine in this because we're currently working on how are we going to deal with this. So some of the thoughts that we're having, so there is a program like Grammarly AI, and it does punctuation, syntax, and grammar, and it's an AI program. Is that bad to use? I would argue that's the same job that a lot of authors hire a medical editor to literally just help them with that. That seems fine to me. Then there are the other extreme, as mentioned, is ones that are fully written by AI. And I'll admit to this, literally this week, I blew this. I got apparently a paper that one of my peer reviewers caught that was written by AI. Now, the description of written by AI, how did they figure this out? It happened to be one of those people in the world that has reported multiple big time scientists from lots of universities that we know that had stuff with AI. So he has computer programs that are able to differentiate when parts of papers or full papers are written by AI. So I've got that software now. The ability to use that software, it's still going to be me putting it in there. And then there's some aspect about AI. It may say this is 100% AI, but how did it figure out that it's really AI? Because it's not really pulling a watermark from chat GPT or Claude. It's saying this is written too well for a human to write it. What happens? No, that's literally what the algorithm is. I happen to have a relation that does AI research. So I understand that. But it becomes a problem of where do we draw the line. So some aspects, I love these policies. And I'm going to have to read your instructions to authors to maybe steal some. But share some. Thank you. I'm happy to share. Because those are great ideas on the trust portion. But where we are now, the author that submitted that paper had submitted 15 papers that week. And when we looked at PubMed, they had done this for like 40 or 50 journals. And they had published like 100 papers in the last month. No human can do that. Maybe. No, we can take this very seriously, but also have fun with it. Last year, I think Y. Ray Oruhuru, who's one of the chairs of this conference, Chris Robbins, and some others, we wrote a paper on AI and academic pain medicine. And Y. Ray decided to slip in chat GTP as a second author when we submitted it. The publisher didn't find it funny. I found it funny, though. We didn't use AI. All right, guys. We are at the end of our editor panel. This could have gone all day. We had 60-something questions. We covered like six questions. I loved the discussion. You guys are amazing. You guys are leaders in the field and shaping our field. I love how you're competing journals. But that's what I love about NAMS. We got them all together to have a very insightful and meaningful and collaborative discussion. So thank you all. And we're going to have more of these sessions in the future. And I hope you guys will continue to participate. So thank you all. We're going to continue next with our abstract speakers next. So our first abstract, and actually for the editor-in-chiefs, you guys are all set. We're going to actually continue with our abstract presenters. So thank you all. All right, for our first abstract presenter, we have Dr. Rocha Flores. He will be presenting on human-sized softening multi-electrode arrays for optimized spinal cord stimulation. So, welcome. Okay. Good morning, everyone. It's a pleasure to be here. I'll be great to have a picture with all the big names that we have here before. So, I'm gonna discuss about spinal cord lead, specifically softening spinal cord lead. This is a device that we developed to increase the compatibility with the body. So, this is based on the fact that so far, all the novelty and all the innovation is happening on the IPG side with artificial intelligence, with closed loop, with novel patterns for stimulations. But in this case, the lead itself, the innovation is not happening on that side. For clarity, I just want to also point out that when I divide this on the lead, which is the portion that is in contact with the spinal cord and the cable lead. So, I'll be focusing on the lead only. One way to improve this, all the limitations, is by design or redesign the lead. And we are doing that by focusing on three aspects, three key aspects. In this case, it's reducing passiveness, which is one of the aspects. The other one is customized treatments. And the third one is optimized stimulation. The way that we are doing this is on three different options. In this case, it's the first one, through technology, new materials, through designs, and also processing. The device that we developed looks like this. This is a very thin device, and very stiff at room temperature, and also it's supple and conformal. The first thing that I would like to talk about is the reduced invasiveness, because the process for implantation is still invasive. So, that's the first thing that we want to tackle. We have a safe for devices in two ways. The first one is a safer device during the implantation procedures, but it's also a safer device once implanted. In this case, during the implantation, and everything is based on the fact of this smart polymer, we can see on the plot that DMA is dynamic mechanical analysis plot, where we have the temperature on the x-axis, and then we have the modulus, the Jones modulus on this part of the storage modulus, and we can see a drop. As we increase the temperature, it will be a drop in the Jones modulus, and this, what it means is that even the device is thin, it will be stiff enough to be inserted, but when it's inside the body at 37 degrees C, and physiological conditions, it will be supple and conformal, and it will be much more flexible. So we have, while implanted, it will be very thin, so less resistance is expected. Once implanted, it could be even 15 times softer than our room temperature. So we have a drop from 3.28 gigapascals to 188 megapascals, so more than 15 times softer. The second part that I want to comment here is increased conformability, and this is because of the same. First, it's very thin. It will conform the spinal cord. The other one is soft. One is inside the spinal cord, so I created a 3D print with a different topographic profile here, so we can see that it will conform the radius of curvature, and this is because of the same softening and the thickness of the device. At some point, this is expected to reduce the energy that we need to stimulate, because the electrode will be closer to the target tissue, so it's expected to use less current to stimulate. It will also minimize the lead migration, which is one of the problems that we still have, and at the same time, we're gonna reduce the impedance fluctuation, which is key for all the trends on the closed loop and artificial intelligence. If we want to get a quality of data with a good quality, we have to eliminate these artifacts, so this is promising technology for that as well. The second part that I would like to talk about is customization for the patient treatment. We have different anatomy in the spinal cord. We have also different pain patterns, so we have to accept that one size fits all is not an optimized solution anymore. Everything has been, we tried to fix that from the IPG software AI closed loop, but if we provide a little bit more help by designing the lead as well, I think we're gonna have very good results. This is because we use a photolithography process. This is a process that is compatible with the semiconductor technology, so we can fabricate devices with any position, any size, separation, and as many channels as we need. So this process is highly compatible with the microfabrication process. Any configuration is possible. The second part of the same claim is that not only the photolithography process, we have also the position, first part is the position of metal, and then we're gonna have the photolithography process, and then we can cut, we are cutting the devices with the oxygen plasma, with this really high precision process. We can see here on the pictures, sorry about that, like this device is really small, but we can have a lot of cables on it, and cuts around it, we can cut on different outline, different shape. We can add some perforation that will increase mechanical biocompatibility. So all this is possible, and everything will be in a single process, single step process, which is the edge. The first part that I mentioned is that we deposit a very thin layer of metal, so that means that it will have an intrinsic MRI compatibility, because it's so thin that the device won't interact with any magnetic field at all. So that is another advantage and another trend, MRI intrinsic compatibility is a plus. The miniaturization of the device to make it more compatible, we can increase the number of channels in case that we need to redefine new paint patterns. All this is possible, and every time that we increase the number of channels, at some point we have to reduce the size of the electrodes. But in this case, we don't have that problem of increasing impedance because reduction of the area, because we are adding also, since it is compatible with the processing on the clear room, titanium nitride as a coating material. And this part of the third last claim, which is the optimized electrode technology. In this case, titanium nitride, you can see that on the picture. This part, we can see the roughness that is generated when we deposit the titanium and nitrogen atmosphere. So this roughness, what is happening is that it is increasing the electrochemical surface area compared with the geometrical surface area, which means is that this is kind of a roughness that at some point the surface will be bigger area compared with the same geometrical area. And titanium nitride has a capacity behavior for capacity mechanism for stimulation. So that means that if we increase the area, we can increase also the charge storage capacity. This is the ability to inject current for stimulation. This is compatible with the process that we have. We compare these with a typical electrode, platinum iridium. We keep the same size on this metal electrode. You can see here a voltage transient plot. And this voltage transient here is just comparing a biphasic pulse that we send through the electrode of titanium nitride and through the electrode of platinum iridium. To calculate the charge injection capacity, we typically take the water window limits and then the polarization in the middle. So you see that the polarization in the case of the titanium nitride is less. The water window on the titanium nitride is 0.9 minus 0.9 volts. So in this case, it's also broader water window. So the charge injection capacity at the end for titanium nitride is almost four times better than platinum iridium. So the capacity to inject current is four times better. And this is because of the roughness and the characteristics of the titanium nitride. We have to also confirm this using electrochemistry. So the part of the electrochemistry, we typically run the cyclic voltammograms, which is cyclic voltammetries to calculate the charge storage capacity. So we can see here the highest charge storage capacity, typical capacity behavior, which is another, at the beginning I mentioned that it's a safer way to stimulate. We are using titanium nitride. So the capacity mechanism of titanium nitride is not generating any new species in where we are stimulated. So that is also another plus compared with the faradic way to stimulate of platinum iridium. We have to also measure the electrochemical impedance spectroscopy. And this part is based on the different frequency that we can stimulate. So we can see here that the stimulation, the high frequency, the electrode is almost invisible. It's not dependent on the frequency. It starts to be dependent on the frequency from here. So that means that it's highly compatible with any stimulation, a high frequency stimulation. And still low frequency stimulation is not that high in impedance. So this is a good way to compare the frequency versus the impedance. Yeah, just as a conclusion, we demonstrate three things here. The first one is that we have a device that is stiff. It could be inserted. When it's inside the body, it could be 15 times softer, which is gonna increase the biocompatibility. The second part is we have a high conformability. We saw that on the pictures, and this is because of the thickness of the device that is very thin, and also because of the softening effect. And at the end, we compare both lead, titanium nitride and platinum iridium. Titanium nitride is almost four times better on shot injection capacity than platinum iridium. With that right finish, and also thanks to my collaborators. Yeah, I will be open to your questions. Thank you. Much for that talk. Next up, we have Dr. Sullivan, who's gonna talk about evoked compound acupuncturals in patients or across spinal cord injury and chronic pain. And we'll have time for questions. We have three abstracts planned today. So we'll have all the abstract presenters come on the panel after this. And please, we want questions from the audience. Thank you. Hello, maybe, okay. Hi, I'm Deesa Sullivan. I'm a graduate student working with Dr. David Darrow at the University of Minnesota. And today, as you can see by my title, I'll be talking about evoked compound action potentials across chronic pain and spinal cord injury. More broadly, what that means is how we can use transdiagnostic approaches to understand spinal cord stimulation therapies better. Maybe, okay. So to begin, most of you probably think of spinal cord stimulation and think of chronic pain, but there's growing interest in using spinal cord stimulation to treat spinal cord injury. I've highlighted papers from both our lab and other researchers in the field. And while there are a lot of exciting findings in this area right now, I will be specifically focusing on motor outcomes in relation to this. So here I have a participant with a chronic flaccid, or with chronic complete spinal cord injury with flaccid paralysis for the past 10 years. And they have a spinal cord stimulator implanted at T12L1, which is below their site of injury. And they've been asked to volitionally engage their leg. And when I play the video, you should see that. And so you can see that they have strong control and engagement and volition when stimulation is turned on. And this is validated with our EMG recordings during the volitional movement task as well. And importantly, this is only occurring when stimulation is turned on and not without stimulation. In chronic pain, we often associate lower stimulation amplitudes to minimize side effects and focus on prolonging battery life. However, clinically it's known that at higher stimulation amplitudes, we can engage motor networks. And this is often a side effect that we're trying to avoid. And so here I have a participant implanted at around T8 with an externalized lead, and they are being stimulated at seven milliamps. And when I start the video, you'll see like this director's clap of one of our collaborators. And that is when stimulation turns on and you should see a reflexive movement in the quadriceps and abduction. So that stimulation is turned on and you can see the movement right now. And then once stimulation turns off, you can see relaxation of these muscles. And it maybe just stopped. And stimulation stopped right then. And so we can see that spinal cord stimulation is obviously engaging these motor networks, but how is this really working? So in the field, there's two main hypotheses on whether this is using motor pools directly or whether inner neurons are involved. And so to better investigate this question, I look at both EMG activity, because how can you really look at motor networks without looking at the muscles themselves? And then also taking a page from the spinal cord stem field for chronic pain and looking at epidural activity and recording from the spinal cord leads themselves. And this is really where the ECAPs come into play. And so evoked compound action potentials are produced in response to stimulation. We've probably heard a lot about them this weekend, but they tend to grow linearly with stimulation amplitude. And they begin to be observed when patients report sensation. And you can see that they grow linearly across stimulation amplitudes. And then people often stop recording once patients reach whether there's comfort threshold, because that is not the outcome or motor outcomes are not the desire or patient comfort is high priority. And so recording stopped, but when we're interested in motor networks, we need to understand what's happening at higher stimulation amplitudes. And so this presents a really interesting opportunity to look at ECAPs across stimulation amplitudes that produce movement. And so maybe to first look at ECAPs when movement is observed, we have to know when movement is produced and which muscles they are being produced. And so here we have, again, that participant implanted at T8 for chronic pain. And you can see that we get not only local engagement of the paraspinal muscles being recruited, but we're also getting right rectus femoris and right gastrocnemius being recruited as well. And interestingly, if you look at the right rectus femoris, you can see engagement about four milliamps versus when the right paraspinal muscle is starting to be activated, that is about seven milliamps. So with this knowledge in mind, we can now look at the ECAPs and try to make sense of how they might change with motor activity. And so when we look at the thoracic ECAP in response to stimulation, we see it grows pretty linearly, but there's some interesting features at the around seven milliamps. And when we correspond the motor activity from what we saw on a previous slide, we can see that when the distal motor pools in the right of the right rectus femoris are recruited, we're not necessarily changing, seeing those are not corresponding to the changes in ECAP morphology. But then when we look at the paraspinal activity and how that correlates, we can see those little bumps on the ECAP correlate quite well. And so when we think about this, we know that thoracic spinal cord stimulation is propagating antidermically through the dorsal column to engage these distal motor pools as thoracic, or not thoracic, as the right rectus femoris is engaging at lower stimulation amplitudes than the local paraspinal muscles. And this supports the dorsal column rather than the CST because of this recruitment order. However, once we're getting down the dorsal column, we don't necessarily know how stimulation is going from the dorsal to the ventral side of the spinal cord to activate these motor pools, whether they're being targeted directly or through inner neurons. And so here is where lumbar stimulation and spinal cord injury really helps shed light on these questions. And so here I have our participant with a spinal cord injury for over 15 years at T4, implanted at L1-T12. And you can see we've got a wide range of motor responses evoked, and I'll be specifically focusing at the right bicep femoris as it is the most strongly activated, suggesting this is in the local target. When we look at the ECAP and the EMG activity across this, we can see that as the ECAP, as stimulation amplitudes increase, we get increasing ECAP responses. And interestingly, we see again that nonlinear change around four milliamps for that green line in the ECAP. However, when we were looking at the right rectus or bicep femoris, excuse me, we again see growing amplitudes with stimulation intensity. However, we get this really interesting dampening effect when the ECAP response is still growing. And so this suggests that we're getting inner neurons mediating this response rather than just the motor pools themselves. And so together, when we look at all these features across growth curves, we can really see these nonlinearities emerge. And so when we're getting motor recruitment around three or four milliamps in the lumbar spinal cord, we can see the nonlinear features emerge in the ECAP. And then when we get local activity engagement in the thoracic EMG around seven and eight milliamps, we again get this nonlinear bump in the thoracic ECAP. And so to summarize, transdiagnostic approaches are really useful in understanding spinal cord stimulation therapies and ECAPs provide mechanistic insight on how this might be working. And we believe that spinal cord stimulation is traveling down the dorsal column and mediating through these inner neuron pathways to produce these effects. Lastly, I'd like to thank my lab and all the participants that we have. Clinical science has truly seen team science and I cannot do the work I do without them. So thank you to them and thank you to you. All right. Our next speaker does not need introduction. It's Jason Pope. He is the chairman of the Pacific Spine and Pain Society, as well as immediate past president. And he's going to be presenting today on SCS trial responders after postoperative, ECAP, and closed-loop programming. So, welcome, Dr. Pope. Thank you. Thank you. Good morning. True believers. Quick question as we get started. How many people in this room perform spinal cord stimulation trials? A handful. How many people perform spinal cord stimulation implants? Same group of people. That's great. In my first session yesterday, we gave an abstract on the ECAP data, which was the first premiere of that data looking at different populations using physiologic closed-loop controlled spinal cord stimulation therapy, which demonstrated sustainable outcomes. Interestingly, when I was serving the audience at that time, the connotation was trials don't work. Spinal cord stimulation trials don't work. One of the speakers at that section said, well, I do trials, but I can never emulate the results when we do the implant. And to take anything away from this presentation as we get started, acknowledging I have seven or eight minutes to talk about this, spinal cord stimulation trials do work with a high fidelity if you are using a physiologic closed-loop controlled spinal cord stimulation therapy, which I think innately makes sense. So, if we measure what we're doing, great presentations earlier in the session, if we measure what we're doing and we respond to it millions of times in a day, you have an opportunity to control the dose where you can actually predict a sustainable outcome. And I'm going to show you some data on that. So, a lot of this is built foundationally on the work that's been done using physiologic closed-loop controlled spinal cord stimulation. That being said, when you survey the literature in our space, what do you see? You see that 80% of people get 80% relief, and we see trial conversions of around 85 to 90%. And that's across all devices that we see that have been presented within NANCE. Interestingly, there's randomized controlled work that also describes that trials don't work. And I would submit to you that the reason they don't work is because we're in this black box of what we're doing to the spinal cord when we use a fixed output system. So, we deliver electricity to the spinal cord not really knowing what we're doing or how we're doing it, not really knowing how much we have to give, placing a lead in an epidural space that we know is dynamic. So, by definition, if you're using a fixed output system, you are going to be overstimulating and understimulating at multiple time points throughout the day. So, wouldn't it make sense to do something different? Because we know the consequences associated with fixed output therapy. I published on this some time ago looking at explants and reasons for explant. What's the number one reason why people get their devices taken out? Doesn't work. Loss of efficacy. And we see that in multiple iterations. So, again, I think one of the innovations that I've seen within NANDS this year is a lot of abstracts on evoked compound action potential, a lot of abstracts on measuring what we're doing to the spinal cord, both in the breakouts and in the plenary session. And so, if you have an opportunity where you can stimulate, you can measure, you can respond, you can auto-adjust with high fidelity, with accuracy to deliver a dose that we know will potentially provide maximal analgesic efficacy, that's the best that we have to determine whether someone is going to be a responder to electrical therapeutic stimulation of the spinal cord or not. And we see that within the evoked study, I think it speaks for itself. So, we did a study, I presented the premiere of this yesterday at the abstract presentation looking at the whole cohort, but we did a sub-analysis looking at what would happen if you, or how early, rather, can we detect signals of success using an evoked compound action potential with a physiologic closed-loop controlled therapy at day zero. And so, we created a validated strategy looking at assessing outcome of spinal cord stimulation trial at day zero, which included measurement of kneecap, controlling the loop, subjective pain relief reported by the patient, minimizing anesthesia and analgesia-related confounders, and the willingness to proceed without any education that they could have had a day zero trial. We compared that to end-of-trial. And what's interesting is that when you look at this data, we have a 98.4% positive predictive value that at day zero, their outcome is like it is at day seven, or end-of-trial. And this is the first chapter in the story of day zero to day seven. We have data that's already been published, presented at NANDS, day seven to three months, and then we also have data at three months to three years. So, I would submit to you that when you do measure activation levels of the spinal cord and dose it appropriately and maintain that dose, you can accurately predict with high fidelity if someone is going to respond to therapeutic electrical stimulation of the spinal cord at day zero to predict an outcome at 36 months. And I'll share with you a little snippet that may not be in this presentation regarding my experience specifically of day zero to 12-month outcome. And how do we do this? Dr. Levy, who was just on the editorial panel here, which I thought was excellent by the way, great job moderating, they described, he described this concept of maximal analgesic efficacy. So, now that we know that we can stimulate the spinal cord, we define that dose based on an ECAP threshold. So, what this describes here, and this dose ratio is something that has been consistent and retrospectively reviewed across the millions of patients that have had an EVOKE system since, I guess, within the last nine years. And what it shows is that this dose ratio is predictable, it is accurate, and it hovers roughly around 1.3 to 1.4. So, what does this do when you inform a spinal cord stimulation trial? What information can you get? This is, I think, one of the biggest value propositions that we have in our space. It's interesting. So, at day zero or day of trial, if you have a dose ratio of 1.4, and they're using their therapy, they're reporting pain relief, the likelihood of that being a true responder, understanding placebo can complicate a lot of this work, but a true responder, it would suggest that this person would be a long-term candidate with sustainable benefit with spinal cord stimulation. If you have someone that has a dose ratio of 1.4, showing that that's the dose where we're achieving the likelihood of profound maximal analgesic efficacy, and they're using their device with a high utilization, and they don't get relief, then I think you've confirmed that that person is not a candidate for electrical stimulation of the spinal cord to develop a therapeutic response. But interestingly, if you have someone that's got a dose ratio of 1.4, and they're not utilizing their device, I would also allow you to say this person may need either re-education to optimize utilization, and they may be a candidate for a retrial. And we have not had that in our space since the time that I've been a part of it. So, when we talk about us being stewards of spinal cord stimulation and the headwinds that we've noticed, and I think we're all aware of what's on in Australia, this gives us an opportunity to select for candidates where actually people can get a sustained therapeutic response with spinal cord stimulation. So, this is the value prop in my opinion. So, in summary, you can detect the signal very quickly. Think about those vulnerable patient populations that you have. Anticoagulant management for a variety of other different reasons. But we have a 98.4% positive predictive value that what you see on day zero is what you get at day seven when all these other check boxes are fulfilled. And I think this is all built on the foundation of some of the best data that we have in our space around biometrically objective individualized patient dosing and utilizing therapy at a dose where people can have profound maximal analgesic efficacy. So, tell your friends, because this is something that will revolutionize our space. Thank you. Well, thank you all to our presenters. This will start our 10-minute panel discussion here for questions. Dr. Hussain also has a mic. He'll be going around. So, please, it looks like we have some questions from the audience. So, just raise your hand and Dr. Hussain will give you the mic. Don't be shy. Don't be shy. Good morning. Thank you for that presentation. To Dr. Pope, forgive me for asking an elemental question. Can you explain the concept of dose ratio? Absolutely. So, when we're using electricity to stimulate the spinal cord, as you ramp up the amplitude, you'll get something that's called an evoke compound action potential. That evoke compound action potential has a threshold. And then when you go above that threshold, you can qualify the dose based on normalizing it to when that person had a evoke compound action potential. Evoke compound action potential. So, the ratio is the dose relative to the ECAP threshold. And we know retrospectively that that dose, where people have a good likelihood of profound benefit based on where you place the leads, and I think Dr. Nyhaus is describing that in one of the best abstract awards at this NAHNS, is around 1.4. So, the ratio is between the ECAP threshold and the dose. And the dose. So, that's how you normalize it. ECAP numerator, dose denominator. Correct. Okay. So, that's a way where you can normalize and create guidances surrounding dosing of the spinal cord. And if I understand correctly, you want to have a dose that responds at, well, you want a lower dose per ECAP threshold, ideally. No, you want a higher dose. Okay, sorry. Well, you want the denominator to be lower. So, you want a more sensitive... Do you want to pull the slide back up? Maybe we can go through this one more time. Sorry, I'm not understanding this correctly. So, the ECAP threshold is lower, right? So, that's your ECAP threshold. And then you're going to raise the amplitude above the ECAP threshold to a dose that achieves maximal analgesic efficacy. So, the dose ratio is the dose that achieves maximal analgesic efficacy divided by the threshold. That's your dose ratio. And so, you've defined a very narrow dose ratio, 1.2 to 1.4, I believe. 1.2 to 1.4. And so, if it's below that or above that, you think it's probably going to be predictive of a bad outcome for implantation. Potentially, right? So, when you implant a lead into the cervical spine, that dose ratio is probably going to be closer to 1.2. But retrospectively, looking at energy requirements to achieve maximal analgesic efficacy with the physiologic closed-loop controlled therapy, interestingly enough, it's between 1.3 and 1.5. So, it's around 1.4. Okay. If I can ask a follow-up. Sorry to — but this is also based on the ability to filter out noise, correct? That's correct. There's more than one company offering closed-loop system. Do you think one is better than the other in that respect? Yes. I know I want to be unbiased here, so I'm not going to ask you elaborate on that. But is there more than one company that actually allows ECAP measuring during the trial, or is there just one company that does that? To my knowledge, what's commercially available is that there's one company that allows for measurement of an ECAP during a trial. Thank you very much. Additional questions from the audience? Looks like we have several there. Hi. This question is for Pedro. Can you give us a little more detail on the materials that you're using for the polymer, and then also some thickness measurements? Sure. So, the material that we are using is based on tile-clay chemistry. So, these tiles, you can modify the ratio between them, so we can control where to start the dropping of the modulus based on temperature. Thickness, we typically do devices on 200 microns, 0.2 millimeters. But in the microfabrication process, we have 50 microns, 100 microns. So, it's 0.1 millimeters. We have 50 microns, 100 microns. So, it's 0.1 millimeters, really thin. And then the metal thickness? Metal is typically 300 nanometers. Yeah, that's for conductors and also for the coating material. That's enough for titanite to create enough roughness and improve the electrochemical surface area. Okay. Thank you. You're welcome. Another couple of questions for Pedro. These are mostly about the titanium nitride coatings. So, do you coat the electrodes prior to fabrication of the array, or are they coated in situ when the array is built? I understood that if I coat the electrodes, but the last part I couldn't hear. Can you repeat? I'm sorry. Is the titanium nitride coating process applied on the electrode array? Electrode array post-fabrication, or are they coated prior to the fabrication of the electrode array? It is part of the process, and it's in the same position in the middle. So, we keep everything on the middle plane to avoid any mechanical problems. So, the titanium nitride is also in the middle plane, or neutral plane. So, we have the position first, and then encapsulation. And do you know the thickness of the titanium nitride coating? Yeah. 260, 300 nanometers. 300 nanometers. Yeah. Because of the conformability of the electrode array, you're not concerned about coating, cracking, or espalation, because titanium nitride is very columnar, and with that amount of bending, I'm wondering if you have any concerns. Right. Yeah, that's a great question. Because we are on the nanometer scale, that's a recipe that we tune specifically for flexibility. So, whereas we increase the thickness of titanium nitride, for example, one micron, that thickness will be risky, and you may create some cracks. But in this case, we keep everything on the nanometer scale, 260, 300, and that's great for flexibility, and if we keep everything on the neutral plane, that's enough to avoid any cracking problem. Okay. You're welcome. So, I wonder. So, this question for Dr. Pope, do you think the parent seizure during testing, or during the trial, is correlated pretty well with the ECAP threshold? No. Okay. So, okay. So, my next question is, so if a patient with existing spinal cord stimuli without the ECAP capability, so there's no point to try to detect the parent seizure threshold and times 40% more just to simulate this, the magic number you got? Yeah, I'll elaborate. I mean, I think that ECAP threshold and paresthesia threshold are two different things. ECAP threshold typically occurs first. When we look at the patient population that we served in the ECAP study, we asked those questions about paresthesia inducement versus not. About 30% of people didn't feel any paresthesia whatsoever. Some people do feel a sensation, kind of like if you wear your watch or a coat or a shirt. So, it's a consistent application of the electricity. So, I used to describe it as being paresthesia independent. Currently, to my knowledge, I'm not aware of a strategy that's commercially available where you can test drive this strategy on someone that has implanted leads already. I think that that innovation is probably coming. But as was described with the filtering, I think that's really critical. So, not every strategy and pulling out and teasing out that ECAP in order to maintain that dose accurately is done as well as others. And so, there's iterations in that filter technology. And recently, there was an FDA approval where there was a press release a couple of days ago, kind of surrounding some of that newer technology. So, I think ultimately, when we look at our space, I think it will become or need to be the Intel inside, just like with continuous glucose monitoring, how that revolutionized the management of diabetes. It's going to be the same thing with electricity in the spinal cord. I have a question for Dr. Sullivan. I loved your talk. I think this is a huge area for kind of moving forward in spinal cord stimulation. Obviously, in SCS, we have a lot of negative trials. And in the pain field, you know, I'm comparing SCS to placebo showing no difference. But I think, you know, with spinal cord injury patients, if they're able to ambulate and do things, there's no placebo in that. That's a real effect. So, I have two questions for you. The first part is, what is it going to take to get this indication out in the market in terms of FDA approval? Because I've looked into the MERS studies. There have been 64 studies that have been published. There was a recent review paper that highlighted that aspect. So, that's my first question. And my second question is, do you see any potential side effects or complications in terms of the type of motor fibers you stimulate? If I want knee extension, is there a possibility that if the leads are moving, I might instead get knee flexion? And could that potentially lead to falls or other complications? So, I appreciate you calling me doctor. I'm not yet a student. I just want to be clear. But as to what this takes to get an indication, when we think about the number of people with chronic pain on a daily basis experiencing that, living with that, it's a much, much larger patient pool than the people living with a chronic spinal cord injury. In the U.S., there's about 300,000 people with a chronic spinal cord injury. And so, that number makes it less appealing to industry to move forward with these indications. I think the more research that comes out about the positive outcomes with spinal cord stimulation for spinal cord injury, the more appealing that becomes as well. And some other work in our group is really interested in thinking about how we think about indications and not just necessarily looking at a single outcome within that. And so, I think both those things can contribute, but we're not necessarily close. Additionally, as far as ambulation and large motor outcomes, I don't think we understand what's going on well enough to have necessarily these really big, huge ambulatory effects either. We're getting motor engagement and we're having better control, but that does not necessarily equate to walking or modulation or movement in that context. Your last question within that on positioning and flexion extension, I'm sure there's some considerations just like when we think about spinal cord stim and sensitivity with pain. I don't know if there's been enough research to indicate whether we get patterns of that, but spatial placement is very important in considering spinal cord stim for spinal cord injury. Thank you. Any additional questions from the audience? Do we have time for one more or no? We're kind of over time, so I'll save it. I'll save my question. All right. I'll save the audience. All right. Thank you all. Appreciate it. Thanks so much to our speakers.

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