for this session, which is the Neurotrauma Session in Critical Care. My co-moderator today is Dr. Jayadhar Prahl, and we're happy to be here, happy to be with you. I have just a very few housekeeping announcements from the AANS. First of all, welcome, you've been welcomed, but welcome again. CME, as you probably know, is self-reporting. You can do it here. If you go down to the Neuro Hub, but you'll also be emailed a link with CME self-reporting instructions. Please provide candid feedback because the AANS Scientific Program really takes these things very seriously when considering future offerings. Download the AANS Meeting App. I've got that on my phone, and it's very helpful. A lot of information there for you. A reminder that audio taping, video taping, or photography is strictly prohibited. Oftentimes, and I know we're trying to share information and so forth, I see folks that are clicking pictures. If you just jot down the name of the speaker, sometimes they'll be kind enough to even send you their slide deck, so you really don't have to do that. Please silence all your cell phones, and we're gonna have a break here, and we encourage you to visit the Exhibit Hall. With that, we'll get our program started. It's my pleasure to introduce my friend and colleague, Dr. Dave Okonkwo, who is Professor of Neurosurgery at University of Pittsburgh, and he will be introducing our Marmorow speaker this year. Thank you. All right, good afternoon. It's an honor to be here. A quick word about Douglas Miller, after whom this lectureship is named. We lost him early, and he was a real thought leader in the field of traumatic brain injury. He was born and educated in Glasgow. Did his neurosurgical training with Graham Teasdale, spent time with Tom Langford, and was a public health service fellow, actually, for the U.S. from 1969 to 1971. Spent six years in Richmond with the giants in the field of neurotrauma at the time at MCV, and then returned to Scotland, but to Edinburgh for his career as Professor of Neurosurgery, and a real, real thought leader, and in fact, many of the things that Douglas Miller said a long time ago, so for instance, in 1970, when he was trying to understand how to drive oxygen delivery to the brain, we are still actually pursuing whether hyperbaric oxygen, and there's a phase three randomized controlled trial on the topic, leveraging things that Douglas Miller was thinking about in the late 1960s. Five years later, he talked about what are the ways to maximize brain tissue oxygenation, and in fact, that is the underpinnings of the BOOST3 trial that are happening now, and he was an early adopter towards the end of his career about predictive analytics, actually, and they had come up with a Glasgow predictive analytics process that would be radically more sophisticated now in the world of artificial intelligence, but that seminal work that he was leading is what led to the impact in the crash calculator. A real thoughtful person whose impact on the field went far and wide, and that concept of impact is why it is spectacular that Shelley Timmons is our J. Douglas Miller lecturer this year. Born and raised in Illinois, educated in Illinois, her training in Memphis started her rapid ascent in the world of organized neurosurgery and inside of the AANS through the neurotrauma section, so it is, again, fitting in our neurotrauma section and forum as the Douglas Miller lecturer. Really catapulted herself through her work on the Washington Committee with an outsized impact, not just inside of neurosurgery, but across medicine, culminating in her presidency of the AANS, and she is rightfully recognized as the first female neurosurgeon to be president of the AANS, but it's interesting because she stood on the shoulders of the giant of Louise Eisenhardt, who was the first female president of the AANS, she just wasn't a neurosurgeon, and Shelley is actually the second youngest double AANS president of all time, which I think is even more remarkable than being the first neurosurgeon female was her capacity to impact neurosurgery so profoundly that at such a young age she was chosen as president of our society. The only one younger, Van Wagenen, who was 34, as the first president of the double AANS in 1932. But above all, Shelley is a leader, an advocate, a mentor, friend, and an amazing physician and surgeon. It has been a genuine honor in my life to know Shelley. Congratulations. Thank you. Thank you very much. I appreciate that very kind introduction, David. I think I'm giving the Marmory lecture, not the Miller lecture, but we're going to hear about both Dr. Miller and Dr. Marmory today because I think that was a great, great review of Dr. Miller's contributions, and I'm honored to even have my name stated in the same breath as his. I can't get this to work. I'm sorry. Give me a second. All over the place. I can't start. Okay. It just couldn't get the mouse to go. Thank you. Thank you so much. Okay. Well, I'm going to talk about a little bit. I'm also giving the WINS keynote address simultaneous, and I want to thank both the section and the trauma section and the WINS section for inviting me to do this. I want to talk about where we are in terms of optimal care for traumatic brain injury and some of the national and global intersections of preparedness, where we've come from in the last four to five decades in traumatic brain injury care, and that preparation really being Traumatic Coma Data Bank, lots of research networks, et cetera, and where we can go. I think there's a big opportunity here for us to pursue additional registry science in this area, and that's what I'll be talking about today. I will learn this, I promise. I don't really have any financial disclosures, but I do have several roles in organized neurosurgery, that touch on some of the concepts I'm discussing today. And I want to really talk about some of the historical significance of brain injury research and multi-institutional data sharing, as well as how we might integrate some of the quality concepts that are currently in use with methods of outcomes assessment and TBI, and really see where we are and what our opportunities are for registry science in neurotrauma. So I'll talk a little bit about Tony. Tony Marmaru was born in Philadelphia. He went to Temple, got his Ph.D. in bioengineering there, and was really a pioneer in research in intracranial pressure, CSF dynamics, hydrocephalus, and in TBI, and he spent much of his career also at MCV at Richmond, which was, as most of you know, birthplace of many prolific TBI researchers. Tony passed away in 2010, and after that, I was honored to start the Honor Your Mentor Fund, which supports the Marmaru Lectureship, as well as has registry science at the heart of one of its funding purposes. I met Tony at this meeting in May of 1997. He just walked up to me and said, hey, who are you? What are you doing here? What are your interests? And invited me to sit at his table, and it turned out that he was the honored guest of the 10-year anniversary of the ICP meeting, and I got to meet his wonderful and warm family, and we became friends and had a very long, warm relationship after that. In terms of traumatic brain injury, we know that it has a major, massive global impact. There are millions of patients around the world impacted by all degrees of TBI. In the United States, it's a problem of epic proportions as well, 4.8 million people evaluated in the ED every year for a TBI. Unfortunately, in our country, only about 13% to 25% of those patients get into rehab, and that limits our ability to maximize their outcome and also to understand what their outcomes really are, because they oftentimes get lost to follow up in terms of longitudinal care in our healthcare system. So we know it's a problem. We know it's an expensive problem. It costs multiple trillions of dollars per year in terms of medical care and lost opportunity costs for patients who are not able to return to the workforce, and it really rivals a lot of other chronic diseases in the United States. If you look at the top chronic diseases in the country, they cost several trillion dollars. TBI also costs several trillion dollars, although much less in direct medical care. So what can we learn about how to maximize longitudinal care of these patients over time? Well, in the Civil War, Abraham Lincoln was actually the first person to develop a protocol and procedures manual for how to triage and transport patients that were soldiers injured in the Civil War. Since that time, obviously, military conflicts have informed a lot of what we do in TBI in terms of research and outcomes, and we still have partnerships with military and civilian trauma centers for training purposes. Fast forward 100 years from the Civil War to 1965, which is actually the year I was born, and there was a group put together to look at accidental death and disability in the United States, and they published a report the following year, which informed many of the safety efforts in the U.S., including measures for promoting seat belt use and road safety, establishing regulatory agencies for safety across the country, et cetera. And numerous other reports were generated from that, culminating last year in the production of the National Academy's Traumatic Brain Injury Roadmap for moving care forward for TBI in the United States, and David and Odette Harris and Jeff Manley were seminal in the creation of that document. Out of that came a TBI forum, which I'm proud to be the AANS representative on that forum, and that just started working activities last year and is really aimed at identifying gaps and forming public partnerships with private entities to move the needle on care. Don Berwick, who many of you will recognize, is chairing that forum. He was the one that was the lead author on the Crossing the Quality Chasm document some 20-plus years ago, which outlined medical errors being responsible for mortality, morbidity in U.S. hospitals. And out of that came quality definitions surrounding safety, timeliness, effectiveness, efficiency, equitability, and patient-centeredness, the STEEP principles, so-called. Also we learned the sort of definitions of quality measures that are structural process and outcomes-oriented, and I would argue that most of our trauma-related quality measures are structural and process-oriented, and not very many are outcomes-related, which is why I think that we need to make the argument that it's time for more registry science in TBI. In terms of safety, we're pretty good at safety and the structural processes. We have policies. We have trauma center systems organized. We have certification processes, but we don't really have as much in the way of registries and risk calculators specific to TBI, because it is such a complex injury. Ernest Codman, years ago in the early part of the 20th century, advocated that every hospital should follow every patient as long as necessary to know what their outcomes were, and if they weren't good, how to do them better. I would make that same argument. Unfortunately, in our current healthcare environment, this is very difficult and very expensive to do, but Dr. Codman's philosophy really underwrote a lot of the quality programs in the American College of Surgeons, including the trauma verification systems and trauma improvement systems that are in place today. The trauma verification requirements, as you guys and many in the audience know who've worked on these, are very stringent, and they really underlie a lot of the quality programs that are in place. Performance improvement and patient safety program under the college also has numerous rules and regulations informed in the optimal resources handbook. Those databases that are used to do the performance improvement are available for researchers and for performance improvement projects through the Trauma Quality Improvement Program. There is risk-adjusted benchmarking, but unfortunately, the detail level on the traumatic brain injury is not as robust as it could be in terms of really doing a benchmarking, and so I think there are significant opportunities there for organized neurosurgery in particular to collaborate with the American College and really form more robust benchmarking processes. Timeliness, in addition to, of course, the golden hour that's important in trauma care, we need coordinated timely long-term services, and we know there's a care gap there. In my opinion, not only could registries inform the right care concept, but we could also inform the coordinated need for long-term care with neuropsych, multiple specialties that we know patients aren't getting. One way to do that is through the use of navigation with nurses, care coordination teams, multidisciplinary clinics, et cetera, but in order to make the arguments for these resources with hospital systems because they cost a lot and they don't necessarily show an immediate financial benefit, we need the data to prove that they actually work and that they are improving care, and we need to move away from thinking about TBI as an event to more of a chronic disease. Just as people who have heart failure after an MI or deficit after a stroke, these are events that happen, but they have chronic problems for which they need chronic healthcare. Equity and equitability and identifying care gaps is another way that registries could help by identifying proof of effectiveness of long-term care as well as cost effectiveness, which is the big issue. We know that many patients are disabled after their brain injury and they don't have access to payer or insurance services and therefore can't get the clinical services that they need. There are numerous issues that we could talk about, about patient-centeredness and what is acceptable disability to patients after they've survived a TBI and how to use that in decision-making early on, and I think registry data could help that effort as well. Efficiency, I'm not going to talk too much about because it's economics and I think most of the quality efforts conceive of it as an economic principle, and unfortunately I think that those definitions can oftentimes conflict with patient-centered care because the way that quality-adjusted life years are calculated sometimes is not necessarily in line with what patients expect or want. This area is ripe for research and ripe for registry data science. And then finally, effectiveness. This is where we really can help. Identifying multiple approaches require, we need accurate prognosticators, which we're still working on, and we need integrated care across a lifetime. You'll see some pictures peppered through my presentation from now on that are just, talk about standing on the shoulders of giants. I mean, there's so many people that have worked on TBI in the past, I just wanted to kind of highlight their contributions and mostly it's neurosurgeons that I've worked with closely and I wanted to acknowledge them. But in terms of evidence basis, we have multiple evidence-based guidelines that have been published. We've got the first neurosurgical evidence-based guideline in existence. They exist for civilian and military trauma, pediatrics, and pediatric concussion. The CDC put together a workgroup that I was honored to be a part of recently to define concussion management for kids. And they also have numerous resources on their heads-up program and website for teachers, clinicians, parents, et cetera, coaches to use. There are military and sports-related concussion guidelines that have been published recently. And I think that the attention on mild traumatic brain injury is one of the things where we could also help in the terms of registry science. So what kind of databases do we have? Registrative databases we all feel are leaving us short. They really have mostly inaccurate or no clinical information, although they're large and easily accessible so people use them a lot. And we're talking about billing databases for the most part. EHRs really were designed for billing platforms. They have, they're proprietary, they're subject to input error and inconsistent terminology. But again, there have been major investments in these areas and they're customizable with a lot of numeric lab data and imaging data so people use them a lot as well. But they're really kind of lacking still in terms of having information about outcomes. One can build their own. I did this and many of you in the room have done this, built your own registration, registries and research databases. They have the advantage of being tailorable to specific purposes, but they cost a lot. There's a lot of resource requirements that go into that and they're not portable. And it's oftentimes not interoperable. So we built a registry in 1997 in Memphis for 13 years, maintained continuous funding and entered about over 10,000 patients in that. And it was fairly robust in terms of containing surgical imaging and socioeconomic and other data. We used it for multiple purposes from education to research to quality improvement and identifying disparities in care. And it was very helpful. When I was at Geisinger, we created some dashboards using the power of the EMR technology and repositories. And we were able to use that to create dashboards for neurotrauma, bucketed by diagnosis, and looked at how to measure resource utilization, length of stay, whether the patients were in the right level of care, how often they were transported through the hospital, etc. And that helped us to reduce variability in care and cost. And then finally, we looked at automated links for procedures and best practices. We put in best practices protocols so that we could get loop closure on some of the PI projects that we were doing, such as ensuring that patients were getting appropriate seizure prophylaxis. Besides local databases, there are several national surgery and trauma databases that do exist. And I'll kind of go through those. They are fairly shallow, unfortunately. And they lack neurosurgical specificity, but they are in a lot of hospital systems. So we need to address them. The NISQIP program started in the VA system in the early 90s and was demonstrated that they were able to reduce morbidity and mortality. It was assumed by the ACS in 2004, and now it's in approximately 700 or more hospitals in the United States. It's in multiple countries. The problem is it's got some limitations for what we do in TBI, because it's very shallow. It's sampling methodology. It's focused on elective surgery, and it's really only looking at 30-day mortality. So it has usefulness, but not so much for TBI. The National Trauma Data Bank I referenced earlier has much deeper data related to trauma. But again, it started in 1997, also, and now has 7.5 million electronic records. Again, not so much specificity for the neurological data points that we would want to help us answer questions of treatment and outcomes. However, I do think there are opportunities through the Division of Research and Optimal Patient Care at the college to participate in their trauma quality programs by collaborating with neurosurgical quality projects and registries. We have several research networks I want to touch on. Those are very well organized. They're hypothesis driven. They're predefined variables and operations, et cetera. But they're also very expensive to maintain, and they have long timelines for outcomes. So they do have some limitations as well. However, we've learned a lot. And that first one that we had in our field was the Traumatic Coma Data Bank. It was started in 1980. Many publications came out of that, and many derivative studies followed. The project was actually conceived in 1979. This is the typewritten, for the young people in the room, the typewritten project outline from 1979. But they were surprisingly on point, and not surprisingly on point, but the principles outlined are very relevant today. They had defined data dictionaries, long-term longitudinal follow-up, and you can see here an example of a couple of the forms that were used in the TCDB. And they actually even outlined the computer network that was to be used, and they talked about online data entry versus batch transmission of data, biostatistical analyses, and computer specifications. And so this was all planned in 79, and implemented in 1980, and went on for another 10 or 12 years, with the idea being that they wanted to have real-world data from diverse institutions, high-quality data though, to guide research patient care guidelines and protocols. And it was very successful. You'll see here many of the topics that were addressed by the TCDB. These were all publications that came out of that group, and many things that we use today for prognostication and research. And research networks continued to be formed in the United States, and this is very US-centric, so I will touch on a couple of others. But the American Brain Entry Consortium was formed in the 80s to about 2010. Dr. Marmaru directed that group. And it was really to pair up research sites that were known to have high-quality, high-volume trauma care with companies or sponsors of research projects. And so that was very active during that time. And European Brain Entry Consortium also arose during that time. Unfortunately, after a number of studies that took place in the 90s and 2000s, there really wasn't any drug identified that could move the needle on outcomes for severe TBI. And there were multiple reasons for that. Inclusion criteria, heterogeneity, variation in the treatment, even though there were standard treatments, there was still a lot of variation in how surgical approaches were done, et cetera. So because of that, the NIH brought together a workshop in 2000. Many luminaries in the field were brought together and discussed lessons learned in drug trials, physiology, preclinical trials, outcomes measure selections, and discussed alternative trial designs. And interestingly, Tony Marmaru actually headed the group on quality assurance of ICU data, with which we still struggle to this day. Dr. Bullock, Ross Bullock, wrote a paper outlining these trials, as I would recommend everybody in the field read this, because it talked about the limitations of each one and why they did not show an effect. After that, there were numerous multicenter TBI consortia, neuroprotection trials, and hypothermia, progesterone surgical trials listed there, with the exception of rescue ICP that also really didn't show effect for a number of reasons. I participated in an NIH-sponsored TBI clinical trials network. Here you see the sites, there were eight sites and one data coordinating center from 2003 to 2010. We also did a neuroprotective agent trial of a fairly multi-targeted drug, citokoline, which didn't show an effect, but interestingly, some recent meta-analysis studies have shown that perhaps there was more effect than we could detect. Multiple additional publications came out of that, some of which were combining our data set, which included biomarkers and imaging with a TRACT-TBI data set. Traumatic Brain Injury Model Systems, which is in the rehab world, has had a very robust long-term network for research since 1987. And then, of course, the tour de force that is TRACT-TBI that David and Jeff and Nancy Timkin and others, Claudia Robertson, have been involved in for a number of years, hugely prolific, more than 100 publications since 2010, multiple millions of dollars of funding and has been just an amazing boon to our field of research. The NCAA DOD funds a CARE Consortium, which is a long-term longitudinal study of concussion athletes and military. Again, very prolific and highly funded, and they look at biomarkers and outcomes in the short, intermediate, and long-term after concussion. Center TBI in Europe, related to the EBIC group, and also a 4,500-member, 4,500-subject prospective registry. So you see there are a lot of efforts around the world. That's not all of them, I've just listed a few. There's one in the UK called the Global Neurotrauma Outcomes Study that has published data on a prospective registry. We also have convened several consensus groups to look at what is the current state of the art, what are people doing, what is the evidence, and those include a consensus group on decompressive craniotomy, led by Peter Hutchison out of Cambridge, and the Seattle International Severe TBI Consensus Conference which is looking at utility of ICP monitoring, brain tissue oxygen monitoring, and methodologies for treating ICP. But where does that leave us in terms of outcome science? We have all this research that we've done. That's the preparedness part. But where do we stand with outcome science and registry utilization in the real world? We have had construction of common data elements that took place in around 2010. So these are the NIH common data elements used for research published in PM&R archives. And then FITBR was developed also in the 2000s which is the Interagency Traumatic Brain Injury Registry for Research Data sponsored by DOD, NIH, and others. So any NIH grants that are coming in related to TBI research are asked and expected to submit their data to FITBR so that is creating a larger and larger clinical database. But in terms of outcomes, where are we? Are the outcomes that we use to measure quality really relevant to neurotrauma patients? I think I would argue that some of them are not. Are they sufficient to really define good quality of care, what patients want, to define good and bad outcome even? We have a hard time even doing that in TBI. Are they captured in EMRs? Not routinely. Are they routinely measured even with the appropriate instruments in clinical care? Not so much. So we have a long way to go to get the outcomes that we want that are functional outcomes for patients into these systems. The gold standard is the GOS. We have got the GOS extended and even the dichotomized which has some, one could even argue that there are some lack of consensus on what upper severe disability. Is that good or bad? And that's been different in different trials including rescue ICP. And then there are multiple other functional outcomes measures that we use routinely in assessing patients that aren't done as a standard and they're not necessarily entered into an EMR. So we really have a long way to go to standardize how we can get these outcomes measures. Now lots of people are getting in this business of outcomes assessment and quality. Amazon, Google, Microsoft are the big three. I've got my timer. There are a number of efforts in this area but in order to really avoid this garbage in, garbage out concept, they really need expertise from us as neurotrauma experts to help design these things. We're talking two digit billion in expenses to get sufficient data granularity for surgical outcome science and that requires some really thoughtful people to be involved and I would argue that's us. There are calls for a national TBI registry that's been supported by this NASEM group and there's now a coalition to support that of public private stakeholders. We at the NeuroPoint Alliance are working with foundation funders and research scientists in Pittsburgh to consider formation of a brain injury and sports concussion outcomes registry for women and girls and our next speaker will talk a little bit more about that in detail. But to really get the TBI specific data and outcomes measures that we need for proper data analysis and collection to really support this public health model of TBI care that informs performance improvement, quality care, prevention even, we need more specific TBI outcomes measures to be routinely gathered. So one effort to obtain this is done in collaboration with the American College of Surgeons and the Coalition for National Trauma Research which has published numerous papers on the National Trauma Research Action Plan and both are advocating for a system of care, a federal system of care in the United States for trauma and emergency preparedness and building on some of the lessons that were learned from COVID. In my opinion, those incentives for doing this are gonna be required because there's not a whole lot of will to do things that cost a lot of money with a very long term end point that is really not clear to a lot of people. And those incentives could be in the form of mandates, they could be in the form of incentivizing HR providers, financial support and really public demand. I think if the public realizes that clinical registries are the gold standard for quality efforts in TBI, there will be more of a hue and cry to support them. So just to wrap up, this is the theme of our meeting, neurosurgeons as advocates and I think there are numerous opportunities for everyone in this audience to advocate for TBI patients and for better longitudinal studies through both clinical involvement, training the next generation and our other colleagues in the public in helping with prevention efforts. From seeing office consults all the way to supporting national research efforts and federal and state legislation, which is on the table for creating a National Trauma Registry for TBI to caring for patients on the front lines to help them achieve happiness, peace and a quality of life that they wish and for and deserve. So I thank you for your attention and I thank all of those people who have supported me in my journey. Thank you. I'm glad we let you run on because otherwise our pictures would have been up there. It's my very great pleasure to award you this plaque as the Marmo speaker this year. Congratulations. Thank you, Dan. I appreciate it. Well deserved. Thank you. Thanks. I'm honored to introduce our next speaker, Mr. Michael Anakin. Mr. Anakin serves as CEO of McGee Women's Research Institute and Foundation, which is the largest research institute in the U.S. focused on women's health and reproductive biology. Under his leadership, the Institute and Foundation has expanded its partnerships with industry, academia, and national and local foundations, and has completed a $100 million campaign, doubling the size of its endowment. Prior to serving in this leadership role, Mr. Anakin was CEO of C-Leveled, which helped provide small business consulting services, and has also served as co-founder and CEO of Flyer City Media, a disruptive interactive media and entertainment provider. He is a graduate of Carnegie Mellon University, where he studied industrial management and economics. Mr. Anakin. Thank you. Just one. Okay. So, Reg Hank called me and asked me to speak for a few minutes about a concussion study we're doing with the Chuck Knoll Foundation, and the good news is that we're doing this study. The bad news is that it hasn't kicked off yet, so I don't have any data. So, there's no slides, there's nothing to show you, but I will talk a little bit about what we're attempting to find out, and how we're going to do that, and the why behind the study. So, as you may or may not know, women's health as a field didn't start until 1993. And so, in the last 30 years, we've been playing catch up, and we've made a lot of progress, but we still have a lot of work to do. We've made progress in understanding the sex differences in many diseases, like cardiovascular disease, where women present differently, and outcomes are different in women. We've got other diseases that we can look at, and say women are more prevalent, like Alzheimer's or dementia, but we haven't made as much progress when it comes to injury, including TBI. And so, when we look at TBI, we need to understand what we do know about the disease, and what we don't know about the disease. And contrary to what you may have heard last night, what we do know about the disease is it does tend to present differently in women. Women are more prone to the disease. We see about a 60-40 split in the clinic. But what we don't know is why. In 2016, Meredith Shook from the University of Pittsburgh, Department of OBGYN, published a paper that showed that women who suffered TBI, or were concussed, actually had disruptions in their menstrual cycles. Some of them were longer, some of them were shorter. And that paper was published in 2016, and it was cited several times. But what we haven't done since 2016, was figure out why that occurred. So we got together with the Chuck Noll Foundation, and the AANS, and we decided it's time to kind of move forward a little bit with that understanding. And to understand the differences that this injury could present amongst the sexes. So we're gonna study the pituitary ovarian access point. We're gonna take analytes from the blood and the urine, and try and create correlation between injury or severity of injury. We're gonna follow those cohorts for six to 12 months out, so we could understand when cycle recovery occurs. What it won't allow us to do is to understand some of the long-term effects of this hormonal disruption. But it will tell us some key things about the injury, and how it impacts the rest of the body. So stay tuned, this is just a little snippet, a little teaser, if you will. One of the things that we will be doing, as Shelly said, was we're looking to bolt on a registry to this study. If we can create a national registry, we can better understand this injury. I still think we have a long way to go. I know we've come a long way, through a lot of the great work that you've done, David, and our team at UPMC. But I think that there's still a lot of misunderstanding about how this injury impacts the body, especially the female athlete. So hopefully, we'll be able to report back on this in years to come. Thank you. I'd like to call our next speaker, who is Mr. Daniel Smerin, and he will be talking on the Association of Traumatic Brain Injury and Seizure Development in the United States during 2016-20, a cross-sectional study. Good afternoon everyone, I'm Daniel Smarin, I'm a neurosurgical resident at the University of Texas Health Science Center in San Antonio, and today I will be presenting on an exciting new project out of our institution titled the Association of Traumatic Brain Injury and Seizure Development in the United States during 2016 to 2020, a cross-sectional study. To provide some background information, it is believed that patients with traumatic brain injury or TBI are at risk of developing seizures during their hospital admission. The aim of our study was to further define or determine the associations between different subtypes of TBI and new-onset seizure, define risk factors, and evaluate outcomes in TBI patients with new-onset seizures compared to those who did not develop seizures during that initial hospital admission. Our study used data from the Health Care Cost and Utilization Project and the National Inpatient Sample, which is a 20% sample of all discharged patients from U.S. community hospitals in a given year. We analyzed patient data from patients whose primary ICD code was TBI and compared demographics, main TBI subtype, comorbidities, and presence or absence of new-onset seizure during that admission. We looked at data from a total of 219,005 TBI patients, which is approximately 20% of the total TBI cases for that given year. In terms of demographics, we found that the majority of TBI patients were male and accounted for more seizures proportionally than female TBI patients. There was a significant difference in age between TBI patients without seizure with an average age of 62 versus TBI patients who did not end up developing a new-onset seizure with an average age of about 60. African-American TBI patients were disproportionately overrepresented in the new-onset seizure group while Hispanic patients were disproportionately underrepresented. To assess the effect of socioeconomic status on the development of seizures after TBI, household income was deduced from a zip code, a tax data related to zip code and then put into quartiles. We found that the patients in the 0 to 25th percent quartile so approximately less than $12,000 a year were overrepresented in the TBI seizure group accounting for 27.47% of total TBI patients but 29.77% of total TBI patients that developed a new-onset seizure. And then we found that patients in the 76 to 100th percentile so patients making over approximately $60,000 a year were underrepresented accounting for 22.2% of total TBI patients but only about 20% of TBI patients who developed a seizure. In terms of urban versus rural TBI patients, the vast majority of TBI patients both with and without new-onset seizure were considered urban patients. We think this is just likely due to EMS services taking most of these patients to accepting facilities which tend to be tertiary urban trauma centers. In terms of hospital variables, the total charge of care per TBI patient with seizure was lower than for a TBI patient without seizure, 97,000 approximately compared to 98,000 but that result was not statistically significant. The length of hospital stay though was significantly longer for TBI patients with seizures, 7.49 days on average versus TBI patients without new-onset seizure with an average hospital stay of 6.86 days. Adverse discharges which were defined as any form of discharge that's not home such as a long-term acute care facility, skilled nursing facility, acute rehab facility were significantly higher in the TBI with seizure group, 46% versus TBI group without seizure, about 44%. And there was no statistical difference in discharge and routine discharges between the two groups. Regarding comorbidities, TBI patients with a history of a cardiac disorder, history of a renal disorder, inpatient chemistry disorder on a BMP, history of a GI disorder, history of a neurological disorder, and then inpatient hyponatremia or hypokalemia were all significantly more likely to develop a new-onset seizure during that admission. However, surprisingly, one of the main findings of this study was the only subtype of TBI that we found to positively predict a new-onset seizure development in TBI patients was traumatic subdural hemorrhage or hematoma with an odds ratio of 1.599 and confidence interval of 1.533 to 1.665. Concussion, diffuse traumatic brain injury, epidural hematoma, and traumatic subarachnoid hemorrhage were actually found to predict a lack of seizure development. And we'll talk about that a little bit more. And then the other primary finding of this study was counterintuitively, the mortality rate was actually lower in TBI patients who developed seizure, with a mortality percentage of 5.97 compared to TBI patients without seizure, with a mortality rate of 8.1%. And then a mortality odds ratio of 0.773, with a confidence interval of 0.711 to 0.84 when comparing TBI patients with seizure to those without seizure. And as can be seen, this graph represents this paradoxical mortality finding with a survival probability on the y-axis and a time in days post-TBI on the x-axis. The blue line represents TBI patients who developed new onset seizure, and the red line represents TBI patients who did not have a new onset seizure. And as can be seen on the graph, then there's a significantly higher survival probability until approximately day 25. And then the graph below is a number at risk chart just indicating the total number of TBI patients on a given day that were at risk for our risk factor, which was death. However, when comparing severe TBI patients, which we defined as any TBI patient that required an external ventriculostomy drain or an ICP monitor, there is no longer statistically significant difference between the two groups in terms of the mortality rate. And when looking at additional data on hospice and day of death post-TBI, we find that TBI patients without seizure had a 7.69% hospice rate, while patients that did not have a seizure had a 7.15% rate, and had a mean day of death post-TBI 5.215 versus 7.134 for TBI patients without seizures versus seizures. This led us to the following hypotheses for this paradoxical mortality, one being that severe TBI patients were sicker upon initial presentation and died too early for seizures to develop or be detected, or potentially that patients who developed seizure received closer care and therefore had a lower mortality rate. Which brings us to our final points. Lower income patients and those with certain comorbidities are more likely to develop new onset seizure during an initial hospitalization for TBI. Traumatic subdural hematoma or hemorrhage was the only subtype of TBI found to have a positive predictor of development of new onset seizure. And then paradoxically, TBI patients who developed seizures in hospital had a lower mortality rate than TBI patients who did not develop seizures, with hypotheses being that TBI patients who did not develop seizures were just had more severe injury, died earlier before a seizure could be detected, or that they received closer care. I'd like to acknowledge Dr. Ali Saifi, Principal Investigator of this project, the Division of Neurocritical Care at the University of Texas Health Science Center in San Antonio, and then the Department of Neurosurgery, with Dr. John Floyd as Chairman and Dr. Justin Massatelli as Program Director. And with that, I thank you for your time and welcome any questions. Thank you. Well done, Dr. Smaran. That was a really terrific paper, and you are well deserving of this award from the Natus, in honor of the Natus Corporation for excellence in resident work. Thank you very much. Thank you. Our next speaker will be Dr. Alwin Gomez, the winner of the Natus Neurocritical Care Resident Abstract Award, speaking on the relationship between CPP, brain tissue oxygen, and cerebrovascular pressure reactivity. All right. Good afternoon, everyone. Thanks for coming. My name's Alwin Gomez. I'm a PhD candidate and neurosurgery resident at the University of Manitoba. And I'm here to talk to you a little bit about some of the work we're doing to find the relationship between cerebral perfusion pressure, brain tissue oxygenation, and cerebrovascular activity. I have no disclosures. So as many of you probably know, neurocritical care management and traumatic brain injury has primarily focused around arterial blood pressure, intracranial pressure, and cerebral perfusion pressure directed therapy. But interest is really shifting now towards more personalized medicine strategies and multimodal monitoring, opening of the door towards that, including particularly brain tissue oxygenation monitoring and a burgeoning method of cerebrovascular reactivity monitoring or cerebral autoregulation monitoring. Now, while this audience is probably pretty familiar with brain tissue oxygenation monitoring, I thought I'd touch a little bit about autoregulation monitoring or cerebrovascular reactivity monitoring. So the pressure reactivity index is a continuous measure of cerebrovascular reactivity or autoregulation and ranges, it's essentially a Pearson correlation coefficient between intracranial pressure and arterial blood pressure. And it ranges from negative one to positive one with higher values indicating a greater degree of disrupted autoregulation. And past work shows that above the threshold of 0.25, that pertains to poor outcomes following traumatic brain injury. Now, while the pressure reactivity index isn't directly modifiable, it is able to guide care in certain ways. So if you plot PRX versus the cerebral perfusion pressure, you get, for individual patients, this parabolic relationship. And if you look at the nadir of this parabola, you can see that there is a cerebral perfusion pressure, which we term the optimal cerebral perfusion pressure, where vascular reactivity is at its best. And if you look below this threshold of 0.25, you can identify a range of cerebral perfusion pressure where vascular reactivity is most intact for that particular patient. So what we really wanted to do is examine the relationship of brain tissue oxygenation and cerebral perfusion pressure, but also look at how that relationship is modified through cerebrovascular reactivity. So we performed a retrospective multi-cohort study and with data from the Canadian High Resolution Traumatic Brain Injury Research Collaborative. We collected data from three academic institutions in Canada from Vancouver, Calgary, and Winnipeg. And we included patients with moderate to severe traumatic brain injury treated in adult ICUs with invasive ICP and arterial blood pressure monitoring and concurrent brain tissue oxygenation monitoring. We collected that high resolution physiologic data and we locked it in time series using the intensive care monitoring software. And we were able to produce arterial blood pressure, ICP, brain tissue oxygenation, and calculated pressure reactivity index, optimal CPP values, lower limit of regulation, upper limit of regulation parameters for patients at a minute to minute level for this cohort. We then used our statistical software to calculate what we termed the Delta CPP Opt, which is essentially the patient's difference between what we calculated to be their optimal cerebral perfusion pressure and what their actual cerebral perfusion pressure was for that minute. And then we actually looked at plots of how brain tissue oxygenation related to cerebral perfusion pressure in general and both when vascular reactivity was disrupted and intact. And we also looked at the relationship between brain tissue oxygenation and Delta CPP Opt. So our cohort included 77 patients with almost 400,000 minutes of physiologic data, about 5,000 minutes for each patient. And we got some pretty interesting results. So our first plot here looks familiar to some of you because it really redemonstrates the Lassen curve where we see instead of cerebral blood flow on the side, we see brain tissue oxygenation. Here we see a plateau region ranging from 60 millimeters mercury to 100 millimeters mercury in this triphasic relationship where at lower levels you see hypoxemia or potentially hypo ischemia and at higher levels, higher CPPs, you see hyperoxemia. Notably, this plateau region also finds itself at PBT02 values between 25 to 30 millimeters mercury which is different than what we've been targeting in the past. And third, this plateau region also has these two characteristic features, these humps that we'll get into a little bit later. So what happens when you break this down to whether or not the patient is auto-regulating or having cerebrovascular reactivity intact during that time period? Well, in the green and the red, we see a similar triphasic distribution. But in the green, that's when auto-regulation or cerebrovascular reactivity as determined by the pressure reactivity index is intact. And what we see is a longer plateau region. And even though we still see this triphasic response. And in the red, when vascular reactivity is disrupted, we see narrowing of that plateau, indicating a more difficult to hit kind of situation where brain tissue oxygenation is going to be stable. Finally, when we look at the relationship between brain tissue oxygenation and Delta CPP-Opt, we note that there's still this triphasic response. And that the optimal CPP as well as the lower limit and upper limit of regulation seem to really be focused around the second feature of the plateau region. So what can we really get from this? Well, it seems like brain tissue oxygenation, like cerebral blood flow, produces a triphasic curve when plotted against CPP-Opt or CPP. And that this plateau region is actually truncated when vascular reactivity is disrupted as described by pressure reactivity index. The plateau region is also associated with a PbTO2 value of 25 to 30, which is different than what has typically been targeted in the literature. And interestingly, we talked about those two features of that plateau region, which actually re-demonstrates some features noted by Klein and colleagues in a porosine model of hypo and hypertension. Here, they noted using fluorescence microscopy that the initial hump is associated with the action of both small and large arterioles, where the second at higher ICPs represents the action of purely large arterioles once smaller arterioles have been maximally dilated. So there are limitations to the study. It's an observational study. There's confounding physiologic measures for sure. And then there's also oxygenation and hemoglobin measurements that weren't able to be collected, obviously, throughout this process. And the data was obviously examined over the entire cohort. But in conclusion, PbTO2 seems to have a triphasic relationship with CPP and CPP-Opt. The plateau region is modified by the state of cerebrovascular reactivity. And that this plateau region seems to be in the 25 to 30 millimeters mercury range and may help guide future PbTO2-based management. Finally, the morphology of this plateau region is concurrent with recent large animal studies and that PbTO2 may really serve as a surrogate for cerebral blood flow in the setting of critically ill traumatic brain injury patients. And that PRX primarily seems to focus on the large arterial activity. We were lucky enough to publish this work if you're interested in it. And I'd like to acknowledge the Winnipeg Acute Traumatic Brain Injury Laboratory and the Canadian High Resolution TBI Research Collaborative. Thank you and I'll be happy to take questions during the question period. Thank you. Thank you. Congratulations. Thank you. Our next speaker is also a winner of the Natus Award. This is for the Spinal Cord Injury Resident Abstract Award. I would call Obada Al-Halabi to the podium. And the title of this is Systemic Application of IL-4 Attenuates Inflammation and Confers Enhanced Functional Recovery After Traumatic Spinal Cord Injury in, looks like rats maybe. You want to use this side? Either side. Your choice. Good afternoon, everyone. Thank you for giving us the chance to present our data. My name is Obada Al-Halabi, and I am a PGY-3 neurosurgical resident at the University Hospital of Heidelberg in Germany. So spinal cord injury is indeed a detrimental event that involves a lot of patients. And this is primarily attributed to neuroinflammation post-injury that entertains cascades of secondary injury and limits regeneration. There have been indeed a lot of descriptive studies about the nature of the systemic inflammation response describing its dynamics, which is why we asked ourselves the question as to whether neuroinflammatory immunomodulatory therapy could indeed enhance a functional outcome after a spinal cord injury in a rat model. So this is the experimental design we use, which is female Wister rats after a laminectomy. At T10, we apply a clip contusion compression. It's an aneurysm clip, basically, that we leave for 60 seconds. And after that, you can appreciate the damage left behind. In our experiment, we included 120 rats that we randomized into three groups, one receiving IL-4 and one, of course, a placebo treatment, and had a sham group that only had received a laminectomy. So this is the workflow. We monitor our rats for up to 28 days after spinal cord injury. And what we really do is do baseline neurotests at different time points. And at the same time, the IL-4 or placebo application takes place intraperitoneally for the course of up to seven days. At different time points, day 1, 3, 7, 14, and 28, we obviously sample serum and tissue for further analysis. I just wanted to put a quick note on serum analysis. So what we used was like a flow cytometry-based bead assay. What you can see here is that we have beads that can detect these cytokines that are listed here. And it really allows us to use flow cytometry to quantify these beads in a sort of a high throughput manner to extract the most we can out of one sample from these rats. So how did these rats fare on a functional level? This is data of the BBB score. Basically, it describes how frequently these rats use their hind limbs. And you can appreciate here is a deterioration after spinal cord injury with a gradual recovery that becomes significant after day 14 of the injury in IL-4 rats showing higher scores. Now, at the same time, because this is a bit subjective, we use the more objective modality, which is the catwalk analysis. It's basically a high-sensitivity camera that analyzes gait and locomotion. And what you can use, what you see here is that the print width and step regularity, among other parameters, were significantly higher in IL-4 rats compared to placebo. So not only do they more frequently use their limbs, but also they use them in a more functional manner. This is indeed demonstrated with further tests like the horizontal ladder test, where you sort of count the erroneous steps of these rats. And we could also show that at day 28, the primary endpoint of the study, the IL-4 rats did indeed show a higher rate of errorless steps after IL-4 application. Now, with this better functional outcome, we aimed at finding possible mechanistic explanations at the local level in our spinal cords, which is why we performed a couple of stainings to have a look at classical parameters like glial scarring, the preservation of oligodendrocytes or neurons. And what we could show is that at 28 days, the cyst size, as recalculated by astrogliosis, is indeed much smaller in our IL-4 group compared to the placebo treatment. This was indeed significant, not only at the epicenter of the lesion, but if you work yourself up and down, you could indeed see these differences. In terms of the preservation of oligodendrocytes, APC-positive cells, we could observe a subtle significant difference that favors the IL-4 group, but there was no difference on the neuron density level. So we know that the scarring is low, the astrogliosis is lower under IL-4, and we know that we can preserve a bit of the oligodendrocytes. And because this is a systemic inhibition, we had a look at our serum samples to see what we can find there. What you can see here is just the sham and the vehicle groups on day 1, day 3, day 7, and day 14. And I think you can appreciate that just globally having a look that at day 1, 3, and 7, that there is an increase in these pro-inflammatory cytokines, which is why we focused on these three time points. The effect is sort of diminished at day 14 and day 28. If you add IL-4 to these graphs, what you can appreciate is that you get a down regulation of these pro-inflammatory cytokines through the course of this experiment at day 1, day 3, and day 7. And you can, of course, perform statistical tests on that and sort of map out these deregulations to possibly sort of decipher dynamic effects that might pinpoint the importance of a certain cytokine at a certain stage compared to another. Now, what is this of any use? I've got two examples for you to just see what the effect of this is. First of all, in terms of immune modulation, we know that there are certain cytokines that are associated with a neuro-inflammatory response after SCI and hence others that we can actively suppress using IL-4 that might be associated with neuropathic pain, for example, after SCI, which might explain the better outcome of our rats, but also others that we didn't really know about that we might want to go into further investigation in the future. Another effect is if we can, for example, as you can see here, have a look at patient serum data. This is TNF-alpha out of many cytokines we had a look at. If we observe that in patients that have a less favoured outcome, TNF-alpha is up-regulated at day 3 and day 7 after SCI, and we can show that we can indeed suppress TNF-alpha or any other cytokine, we can indeed maybe give more meaning to our data and help interpret it and possibly translate this kind of immunomodulatory therapy to clinical use. So in conclusion, we've seen that systemic IL-4 application indeed confers a better functional outcome in these rats after SCI, and this is probably due to a better tissue scarring and a reduced astrogliosis after IL-4 therapy. We also see that using these ceramics, we can describe this pro-inflammatory response after SCI and actively detect its manipulation or modulation using our therapy, and possibly with an outlook in correlating these cytokines and the way we manipulate them with clinical data to sort of pick the best candidates, we wanna have a look at in the future, maybe translate an immunomodulatory therapy to clinical use for SCI patients. That's it, thank you very much, and I'm ready to take questions. Thank you. Halabi, terrific work. I misspoke, this is actually the Charles Tatter Award for Spinal Cord Injury Research. I had the pleasure of meeting Dr. Tatter a little while before our illustrious speaker did, and he would be very proud of this work that you're carrying on. I know that for a fact. So congratulations, there you go. Thank you. If you wait right here, we have a 10 minute question session right now. So I'd like to invite all of our illustrious speakers that could still be with us, Shelly and others. And please, if you could, I think we have microphone on this side. If not, try to speak very loudly when you have questions and direct them to the speaker that you'd like to answer. Go ahead. Thank you all for these fantastic talks. Shelly, I have a question for you. You're talking about the way forward. The challenge is that if we're trying to piggyback things like the National Trauma Database, our trauma colleagues are focused on 30 day outcomes, but we need six and better, 12 and better still 24 month outcomes. So what are the key neurosurgery specific things that need to be added to the trauma databases? And how do we get our trauma colleagues to recognize that the process has to go way past 30 days? I'll answer the first question first. I think that the key things need to be added are the known imaging prognosticators, which are not part of the standard collection. Biomarkers, which you have participated in that research. More granular data about the acute care phase during the ICU. The data that are collected are fairly superficial, so that they don't go far enough to inform what we think patients should be like. So on the prognostic side, imaging, clinical data, biomarkers data, maybe even routine lab data that we constantly collect and treat toward, but aren't part of that database. And then specific outcomes measures that are way more granular than the GOS. I think the GOS is part of some of the discharge information, but it's not, to your point, at three months, six months, 12 months, 24 months. So we have to make the argument that that's worth collecting. And I think now with rescue ICP data and other things that have come out through track, that we can make that argument. We just have to partner up and say, hey, look, we wanna be able to have interoperable databases with NTDB and whatever we formulate for traumatic brain injury. We'll do the part that involves the cerebral physiology and the outcomes measures if we can also utilize the mechanics of the NTDB that already exist. So my shoes are in honor of David. They're fancy. I went and changed. So first of all, I want to congratulate all of you winners and you don't have to stand behind Shelly. She's not intimidating. You can sit. Have a seat. I want to thank you all. Your work is encouraging and inspirational for those of us who have been in the field longer than you guys have been alive. But nonetheless, I wanted to ask Dr. Smeron, I hope I'm not mispronouncing your name, but can you speak to what are the factors you think are responsible for those who are identified as having seizures having shorter stays than those not having seizures? Like that seems counterintuitive. And I just wondered if there was something that we are all missing. Thank you for that question. Yeah, it does seem counterintuitive. We're still looking into the possible rationales for that. And at this point, our hypothesis is still, we're still looking into it. And it's possible that they are discharged to other rehab facilities earlier or explanations such as that. Thank you. Thanks very much for a fantastic session, everybody. Dr. Smeron, again, I sort of get the mortality, but a lot of the other trials have shown that particularly contusional injuries associated with a higher risk of post-traumatic seizures. I think your study is one of the biggest and possibly the best conducted. So I just wondered if you could perhaps expand on perhaps these contusional injuries not being so associated with post-traumatic seizures. I'll take the question. Oh, yeah, thank you, Dr. Smeron. I'll take the question. Oh, yeah, thank you for the question as well. I think that leads, kind of, is related to our hypotheses on the paradoxical mortality. Potentially, patients whose, this is based on ICD code, and we use, we excluded patients with multiple subtypes of TBIs and only used the one ICD code which was the primary subtype of TBI. So if a patient were to have a primary subtype of TBI of contusion, it's possible that they just arrived to the hospital in a more critical state and were unfortunately passed prior to seizures being detected or documented and treated. I'm gonna capitalize on your comment because I think, you know, you highlighted some of the things I was trying to point out which is that in utilizing the administrative databases when you only use the primary code, they may be, it may be that you selected that the subdural patients had craniotomies and that's why the code was the primary code. Because they had surgery, they might be at more risk for seizure. And because you're not capturing the secondary codes, you're missing the contusions. And I bet you that's probably what, but that'd be a great opportunity for the follow-up study. Absolutely, yeah, and we plan to do so. Thank you. I remember from your talk, I believe, is that the length of stay was increased but cost was similar. Was that on one slide which I was surprised to see because those two should be linked. Right, so it was total charge which is how much the hospital billed for those patients. Cost is generally the reimbursement. It tends to be a third of the charge usually on average. And there was a difference but that difference was not statistically significant between the two groups. Thank you. Hello, question for Dr. Al-Ahabi. Did I say that right? That's fine. Okay. My question is regarding your IL-4. What barriers do you see in translating that into humans and how do you envision that technology being used? So I think it's something that we could convince people of doing. I mean, we do immunomodulatory therapies within an STI context. We use methylprednisolone, for example. It might be a bit more dirty of a drug but I think prednisolone is also a dirty drug in that sense. So I think this is something that could be transferable. On the other hand, IL-4 antagonists are being used now, antibodies for the treatment of atopic dermatitis and some asthma-related diseases. So it could be the case that this immunomodulation is a bit too much in that context. The purpose of this study was to really, more or less it was a proof of concept to really see that we can detect this immunomodulation and that it makes sense to work further on this axis in the context of STI. And I think the results we show are very convincing. We observe very similar effects in a TBI model as well from our lab. So maybe IL-4 has some sort of neuroprotective effect that we don't know of. But we're looking to further depth along the lines of reduction of neuropathic pain, for example, which might help these rats walk better. These little nuances that might make a difference at the end of the day for STI patients. This is why we teamed up with a clinical database to really have a look at these parallels between both data sets and sort of compare dynamics in an animal study model and a human context. So we look forward to hopefully, if you see a study in 10 years, you'll remember us. Very exciting, thank you. Not seeing any other questions. I think we have a minute or so, but why don't we break there? Fantastic first part of the session. Thank you to all of our speakers. And we're being asked to break, hopefully spend time in the exhibit hall. And with that, it is my great pleasure to introduce Dr. Reg Haid, whom you all know. And he will be introducing our Chuck Knoll Foundation speaker. Reg? Thank you, thank you, oh gosh, it's such an honor. Thank you so much. Sorry people out there at their break. So it's my honor to introduce Nick Theodore as our Chuck Knoll lecturer this year. So who is Chuck Knoll? So if you're an old guy like me, you know who the Stillers are. So he won the Super Bowl four times and Hall of Fame, just an all-in-all phenomenal human being. Now he was also very bright, went to law school for a year and actually considered medicine. He's passed, but I've talked to his widow about this. So in 86, I was at Allegheny General with Joe Maroon. He developed the impact test and we're taking care of the Stillers. And Bobby Brewster had a concussion and Joe turned to Coach Knoll and said, he's got to sit out for a couple weeks. And coach, winner of four Super Bowls, bright guy said, why that long? Well, it's the science. When can he return? And he quotes it. I don't want guesswork from my players. Give me objective data for return to play. And that's before sports medicine was started. So Joe did the impact test. Joe, are you here? I don't know if he's here. And in 1994, they formed a committee by Paul Tagliabue. Altoon, who I've skied with, was a triple jumper, which was his love, but he retired due to concussions. His son later played at Minnesota where he played and Merrill Hodge, who has donated his brain, he retired due to multiple concussions. So the whole thing of concussions and spinal cord injuries started gaining steam then. And since that time, the rules have changed in football. And so if you look at the number of spinal cord injuries, the number of head injuries, they've diminished remarkably. The number of quadriplegic injuries from spine has diminished completely. Because when I played high school balls, 165 pound cornerback wet, I was told to stick my hat in the guy's chest. Well, we don't do that anymore. And Noel, though I did not know him personally, he's kind of like Coach Wooden, right? He talked about integrity, success. And if you think about this, this kind of applies to our social media today. So the Chuck Noel Foundation, in my disclosure, I'm on that foundation as a volunteer. And what we do is we raise money to study the science of head injury. But it's not just in professional football, it's all injuries. So right now we funded with McGee Women's Research Institute a tune of a million dollars for a study for women's concussion. Because as most of you know, after boys football, women's soccer is number two. Now having five daughters and two granddaughters, I see this weekly. And who among us does not get a call about Johnny or Jane weekly? Can they play sports, right? So with that, the Noel Foundation established the Noel Lectureship. And so Nick is a perfect guy. We've had other people, Shelly and Julian and Joe talked before. So Nick went to Cornell, Georgetown, went to the BNI where I first met Nick years ago. Navy guy, like I'm an Air Force guy. And actually was at San Diego and ran that. Went back to the BNI and ran their spine program as a Volker Sontag Endowed Chair. Later left and went to Hopkins, directed the Spine Center, Donovan Lone Professor of Neurosurgery Ortho and Biomedical Engineering. He was a neurosurgeon for the Cardinals back in Phoenix and the consultant for the Diamondbacks and Coyotes. Nick has, I can't keep up, 200 peer reviewed articles, 30 book chapters, 10 patents. He developed the Globot or the Excelsior, which he later licensed or sold or whatever to Globus. He's won multiple awards, including the Mayfield and Tasker Awards. So he's a phenomenal surgeon, works his butt off, high volume, but also has an R01 grant, DOD grant. Years ago was the chair of the Think First Foundation. Nick is really an interesting guy. I've actually, you may not remember, I've actually whitewatered with you years and years and years ago. And Nick is one of the few guys that actually is a phenomenal surgeon, a phenomenal researcher and develops tools that help us do things. So for Nick, who's currently the chair of the NFL Head, Neck and Spine Committee, a very political committee, right? That's a big deal. And so he reports directly to Alan Sills and Roger Goodale. So to have Nick give this talk is a real honor. So Nick, it's an honor to have you here. We'd like to thank you very much. Thank you. All right, I'm not touching the mouse my hands are away from the mouse at this point. It's yeah, I think so There's I uploaded it. Let's should be on there 333 It was uploaded and we looked at it already here we go far right corner, thank you So it's like like Sudoku here for care for right up Nick Theodore far right corner Moving mouse to the right up up. I'm right there one down right there All right, so for those of you looked at the program I don't want to disappoint you, but I'm not talking about chronic subdurals Who is talking about chronic subdurals a young woman from Harvard she here? Perfect so hopefully she'll show up to give a talk. I got a call saying when are you talking on subdurals? It's gonna be great so really the the the theme of the meeting is advocacy and what I'm going to talk about for the next few minutes is as Neurosurgeons our responsibility role in this room here with really so many long time friends Including Dan Michael who I served with on the board I think first for many years and you know the reality is that we have an opportunity as neurosurgeons to do a whole bunch of different things and we're exposed to things and I Think neuro trauma really is in our blood and and and from that standpoint. I think that You know, there's there's a chance for us to continue to To advocate on many fronts. We'll talk about that And these are my disclosures which are really not relevant You know We look historically obviously and we talk about trauma and traumatic brain injury going back Thousands of years the art of trepanation we look at the Edwin Smith papyrus which really outlined really first codified traumatic injury brain injury and spinal cord injury in a way that We know Observations and these are injuries and they can quoting the Edwin Smith papyrus. These are injuries not to be treated So they back from you know thousands of years ago as we looked at neurotrauma We realized that you know It is something that can affect so many people and it affects people in a very profound way and as neurosurgeons We do are at the forefront of this and have that ability to to make changes And to help people along that continue. Oops. There we go You know, we get we look at Hippocrates he himself talked about traumatic brain injury and in a lot of his codices came out with treatment plans for patients who had Been injured with with mild and moderate traumatic brain injury Galen this gentleman here Jacobus Berglin arius de carpen really was talked about different ways to treat skull fractures actually came up with a Neurosurgical kit and this is back in the in the Renaissance period in the 1400s. So there's a very long history obviously of looking at and treating brain injury Probably my favorite those. This is Ambrose Paré and the French neurosurgeon or French surgeon I should say battlefields field surgeon from the 1500s. I mean, I love that. Look at this book cover here You know the method of curing wounds made by gunshot And of course you he's talked about every single place you get shot I was just talking to Mason Blackler former former Navy SEAL looking at talking about but he got shot this is really a situation here and this has really been the genesis of where we are today and and you look back historically obviously a lot of a lot of work being done to get us to the present a Lot of what we've learned in neurotrauma has also been you know in the in the history of conflict and in the Civil War We learned a lot. We learned a lot about brain injury. We learned about spinal cord injury. We learned a lot about peripheral nerve injury and obviously a devastating Conflict but but from that really came a tremendous amount of knowledge for us as neurosurgeons This is a WW Keene really who you know We talked about Cushing's being the father of neurosurgery and as an organized specially probably was but Keene was a surgeon a battlefield surgeon in the Civil War and Took care of blast injuries head injuries worked with with we're and talked about traumatic nerve injuries as well really again as a field in neurotrauma giving us the basic tools starting with observation and then research and how we How we make things better Fast forward to World War one Harvey Cushing was very interested in this and did volunteer to go over and one of the first waves with the Harvard group To treat our soldiers in in conflict during World War one of course you know being a little bit brash He tried a lot of interesting things one of which was to use an Electromagnetic forceps to try to draw bullet fragments out so at the time again We didn't really have an understanding of should we be going after these fragments should we not and really? Looked from a research perspective about outcomes and the mortality rate dropped significantly with his interventions Of course you know not to be outdone He got into a little bit of trouble, too So he would write all these letters saying how the Brits were not doing a very good job about taking care of trauma patients And they really weren't as good as the Americans and these letters got intercepted in a little known fact He was almost court-martialed for this because they thought they were sending data that the enter the enemy might intercept so again These academic things go go deep, but something just from a historical perspective. Then we look at current conflicts in Iran and Afghanistan, in Iraq and Afghanistan, excuse me. Brain injury and blast injury really has become the signature injury. We're now dealing with the aftereffects with hundreds of thousands of soldiers, airmen, sailors that have been exposed to blast injuries. The number is quite high. The problem is it's very difficult making a diagnosis and following these. Leigh gave a great talk earlier, Shelly Timmons, about registries and how do we follow these patients, but we don't really have a lot. The VA system is trying, but we don't have a lot to offer these patients. And then we look into the modern era. My friend Rocco Armando, Rich Teff, Chris Neal, and others who very recently in the Iraq and Afghanistan, neurosurgeons in theater taking care of our patients overseas. And the reality is that we learned a tremendous amount and we're still learning. So the field of neurotrauma, what's exciting to us is that it's an ever-changing field. We are getting better at what we do. But this most recent conflict taught us a lot of different things, looking at blast injuries, survival rates, how do we deal with some of these more just absolutely horrific injuries. This is Rocco Armando overseas. And again, being able to take newer technology now into the battlefield operating room for the care of our patients. Not just volunteering, and this goes back to the theme of neurosurgeons as advocates, but understanding and being able to collect data and also putting on our hat as researchers, and how do we pull this all together to have an understanding of how we take care of these patients. Not just using advanced technologies, but now going back 100 years and taking care of patients in austere environments overseas. And this continues to this day. Rocco Armando I just spoke with last week is on his way to the Ukraine right now to support a hospital there. And again, as neurosurgeons, we do have a special set of tools, and we do have a special training that allows us to take care of patients that could be in any different settings. And we really have learned a tremendous deal from that. We're gonna switch tacks, and we're gonna, sort of the change between the military and sports. And I think that the sports-related neurotrauma has been something I've been very interested in, and really is a fascinating field. And I think this is a quote from MacArthur, who really talked about the fact that organized sports really gave us a way to train our youth, not just for the military, but for life lessons. When we look at trauma in sports, this is from the Atherston ball game. Okay, this seems like a simple game where the object is to get the ball from one side of the city to the other. It started in 1199, so this has been going on for over 900 years. And for those of you who think football's a violent sport, and it's dangerous, and that, okay, it might very well be. But I will tell you that these guys end up sending probably 60 to 70 people to the hospital at the end of this friendly ball game every year. And you can see the guys wearing the yellow and orange jackets who are the officials. God help them, because they're in the middle of the mix here. But at the end of the day, this is a sport, this was a game, and sports-related trauma has been around for a while. When we look at the numbers, obviously they're sobering. 70% of the deaths from trauma in sports occur from head and neck injuries, of course. Hundreds of thousands of Americans, and now because of awareness, we're seeing a higher number of people talking about this, talking about concussions, et cetera. And again, when we go back to sports, when we look at football, this is a famous painting, which I love, this is Winslow Homer's Holiday in Camp, Soldiers Playing Football. Does it look like a game of football to you, or does it look like the hand-to-hand combat? Again, the reality is that football over 100 years ago was a little bit more complicated and a lot more dangerous than it is today. And this is the Yale team, the national champions from 1876, it looks like a prison chain gang. Okay, no offense to those from Yale, but the reality is this is it, and this is Walter Camp. Walter Camp said, you know what, we're gonna try through doing something a little bit different. We're gonna try different formations, and we'll talk about that in a second. Then right around the turn of the century, this is University of Georgia, and you know the Pop Warner, Glenn Pop Warner was the coach for the Georgia team. And this young man, Richard Von Albaid Gammon, suffered a severe concussion, unconscious, came back to consciousness, they had to transport him to the hospital, and he said, you're okay, aren't you? And he goes, yes, I've got too much of Georgia grit to give up. The interesting thing is, and the unfortunate thing is, he passed away hours after this, and football was going to be abolished in the state of Georgia, imagine that now. Literally, his mother went to the governor and said, boys die every year climbing rocks, they fall off their bikes, and we're not gonna outlaw a sport because of this, but is there a way to make this safer? And this is again, look at this, in 1880, this is Yale, they decide, Harvard says, we're gonna counteract this with the flying wedge, and this is a way of formation. In 1905, 18 college players died playing football, with 137 seriously injured. Think about that for one minute. And Teddy Roosevelt, again, we were on the brink of canceling football, the cancel culture of the 1890s, but the reality is that what happened was that we ended up with the NCAA and a way to think about things of how do we make this safer for people? Interestingly enough, we combed through the archives, going back to Cushing, he was really the first to describe a spinal cord injury from a football game, from a football accident, so a 24-year-old student who came in up from North Carolina, was transferred to Baltimore after becoming quadriplegic, and at the time, in the early 1900s, and Cushing wrote this series, if there was any preserved neurologic function, the treatment was laminectomy, and otherwise, there was nothing to do, and this patient had a complete injury, and fortunately, they put in a bladder drainage tube, and he died about a month later. And it really got people thinking about how do we make this sport safer? And one of the things in football has been the evolution of the helmet, and we've come a very long way in the evolution of the helmet. We first started off thinking that probably it's your nose that needs to be protected more than your head, so we came up with this ridiculous sort of nose guards, and you can see that there's a faint resemblance to the chain mail, but really, it was a number of years before we really had an idea of how to do this, and Richard Schneider, who is the chairman at University of Michigan, really dedicated a significant part of his career at looking at traumatic brain and spinal cord injury in the game of football. And he really did an amazing job of rethinking the helmet, rethinking safety. Again, a neurosurgeon using his tools and his training, taking this to the lab and helping us to define what would make a safer helmet design. And along the way, came up with some very interesting concepts, not just about how we make the helmet safer, because again, this was a large part of his work, but what are the injury mechanisms which we're looking at? One of the things that he really was able to codify was this idea that when the head is in a down position and a player strikes another, that neck inflection is the most dangerous position to be in from axial loading perspective. If your head is up and you've got lordosis, it's a much safer position to be in. So he actually was one of the first describers of central cord syndrome, and this whole idea of biomechanics meets injury, especially in sports, and then how do these things happen? So we look at this, and axial loading really is the, when you look at catastrophic injuries, quadriplegian football and whatnot, you see it's a direct axial load. And again, when that head is straight or flexed, it's a much more dangerous position. And that really led to sort of one of the first ideas of changing the rules of a game to be able to prevent injury, and this is 1976, when the NFL abolished spear tackling. Using the head down position, when you look at that, the reality is that there's a number of injuries that were prevented by this rule, and this is, again, 50 years almost now. So Reg Haid had this slide, and we talked about this, and I think changing tacks about how do we learn from our patients and how do we learn from what we're doing, Reg spoke about this, but truthfully, when Joe Maroon had this question from the coach, Chuck Knoll, was how do we make this safer? How do we understand what we're doing? How do we have a more objective way of looking at this? And with Mark Lovell, Joe Maroon spent some time to put together this, the impact testing, which is now used literally across all sports, organized sports, and that gets down into the high school level and even junior high school level. There's six cognitive tests, basically 25 minutes, and it measures, again, reaction time, visual and verbal memory, multitasking, motor speed. We really never had a way before this, any data. We'd talk to a patient, and if he was up and able to play, in most cases, and unfortunately was sent back to play, we'd just dust yourself off and get back to play. But now we do have an objective way to measure. Is it the best way? Well, the time will tell. I mean, David Aconquo is working on blood biomarkers, we've got saliva biomarkers, we have other things that are being looked at. But the reality is that right now, this clinical examination really is very robust and the best we have, and again, being used throughout the world. When I look at my time in the last few years with the NFL, it's been very eye-opening, and there's obviously a tremendous amount of politics involved. And what I will tell you is that, again, all for the safety, health and safety, Jeff Miller, who's the Vice President for Health and Safety, you heard Roger Goodell yesterday. Obviously, the calling card for us is to make the game safer. What can we do to make the game of football safer? And we heard Reg talk about the mild traumatic brain injury committee formation, and then ultimately, Rich Ellenbogen and Hunt Bacher came up with and were able to start the real concussion protocol to start how we understand and how we treat patients. And that was an adventure that took place in 2011, and it is a part of the collective bargaining agreement between the NFL and the NFL Players Association. And it is a document that changes. So every year, as we meet with the NFL's head, neck and spine committee, the idea is going over that document, which I feel I have memorized, you know, to say what can we change? What can we change in that document? Now, the fun thing is, once you change it, about 700 lawyers have to approve it. So it's never as easy as just saying, hey, we're gonna do this. But, you know, it outlines policy, it outlines process, it outlines personnel. When you talk about personnel, you know, think about how many physicians are in an NFL game at any given time on the sidelines. Anybody wanna take a guess? So there's at least 30 medical personnel at every single NFL game. We've got primary care doctors, unaffiliated neurotrauma consultants, ophthalmologists, and of course, we have to have two chiropractors, right? Just because. But you realize that there's a tremendous amount of people, and this is all sort of managed, you know, through an emergency action plan, and it's all managed through, you know, discussions and coordinations with the team, understanding what we need on the field. And that, by the way, all comes to bear when something horrible happens. In this case, with Damara Hamlin, who suffered a cardiac arrest on the field, I'll never forget this, I was watching the game, my wife, who is the survivor of cardiac arrest herself, says, is he gonna be okay? And I said, honey, there's no better place for anything like this to happen than on the field. And I will tell you that through practice, identified immediately that this was not a head or spinal cord injury, that this young man had a cardiac issue, was able to start CPR, get him intubated, he made a full recovery, and as you heard yesterday, is most likely gonna be returning to play in the NFL. That is unbelievable. That doesn't happen without training. That doesn't happen without having people around that know what they're doing. And I think the NFL has done a great job with the medical aspect. So from a neurosurgical perspective, who's there, who's on the field? So we have three unaffiliated neurotrauma consultants at every game. These are people who are not part of the team, so they're unaffiliated. We've got two on each side of the field and one up in the booth, and they're all received training through the NFL, and they can be neurology, mostly are neurosurgeons, the overwhelming majority, but they can be neurologists, and we have a couple of physiatrists and ER physicians. Two on the field, one up with an athletic trainer spotter up in a booth. It's amazing because I get phone calls every Sunday, did you see that? He had a concussion. I mean, everybody's able to diagnose a concussion when they're sitting at home after two beers. I'm like, I didn't see the replay. Let me see it. But when you're on the field, it's difficult. But what we do have is the ability to call up any single play from 18 different angles and have an understanding of exactly what happened. I think that's where the trainer spotters are unbelievable. And these are trained individuals. So we have a neurosurgeon with them. They're the, trainer spotter's the only person that can actually stop the game because if he sees somebody that looks like something happened, attention always is at the ball. Everybody's looking to see what happened, but oftentimes because of what's happening on the field, somebody else will have sustained a concussion and we're able to actually stop the game and get that person out. And then who basically calls out a concussion? Anybody can. The referee can, the spotters can, the unaffiliated trauma consultants, trainers. Interestingly enough, the players now are very astute. The players are very well educated now in concussion and in the majority of times are calling themselves out. I had this play. I don't feel well. I don't feel right. And they get checked out. And that is a big, that's a sea change from the way things were 20 years ago when a lot of times players were not only urged to go back in, but weren't assessed and they really didn't know. So the one aspect of that role that I've enjoyed is a couple of tickets to the Super Bowl, I will say that. But as neurosurgeons, from an advocacy standpoint, what can we do? Well, we can lend our expertise and for years helped high school sporting events. You're working as an affiliated neurotrauma consultant. There are opportunities for us as neurosurgeons to do this in evaluating sports-related injuries. Again, part of the fabric woven into us as neurosurgeons is the care for trauma patients. We have this big debate about what's gonna happen in sport, in organized sport, that's dangerous. It's not, the one thing we have to take pause and look at is the reality is that there's so many positive aspects to team-related sports, fitness, discipline, leadership, teamwork, lifelong skills. I think that at the end of the day, this, while we strive to make things safer, nothing as in life will be 100% safe. So what else about advocacy? I think organized neurosurgery has done a great job in bringing this together. Shelly, in her talk, gave a really beautiful overview of all the different registries and where we're trying to organize neurosurgery through NREF, through AANS, through CNS, is really emphasizing this team concept with the neurosurgeon as team captain. And I think that's important, less we get lost in the shuffle here. But from an organized perspective, I think our specialty has done a tremendous job. And educating. Educating those of us who do this every day on how to take care of emergencies. How do we know, how do we get updated? Because there is so much information that we're getting bombarded with. Taking a course on emergencies and understanding exactly what protocols and procedures are for various neurosurgical emergencies is critical. And I think as organized neurosurgery, we've done a very good job of that. And then when you look at things like the data about codifying large amounts of data and giving us some inkling, I think Beverly Walters has done an amazing job. Shelley Timmons, Mark Hadley. And putting guidelines together for us to understand how, as a practicing neurosurgeon, how do you deal with these things? And again, once again, the guidelines not being a prescriptive, but giving us information of how we manage these problems. And putting this together, obviously, the one thing that struck me was that we don't have a lot of data to guide us. There are some things that we can take to the bank, but others are certainly, there's room for interpretation. Research, I just want to just at a high level, there are some very significant contributions, obviously too numerous to mention. But when you look at something like, do we need to do ICP monitoring? And you've got Randy Chesnut going down to Bolivia and Peru and doing these studies of understanding how we treat traumatic brain injury patients. Things that we couldn't do in this country, showing that we can actually make an impact in the way we treat these patients. Jeff Manley is a dear friend. Really started off in basic science with aquaporins and how we understand edema. And now is with TRACT-TBI, which is absolutely phenomenal registry of patients who've had traumatic brain injury, helping us understand how to treat these patients. Another form of advocacy is innovation. This is Sam Brad from the University of Washington, who's also a dear friend. And Sam was sitting around one day looking at, you know, a way to make helmets better. And how do we make football helmets better? How do we absorb the forces that are applied when your head hits the ground or strikes another helmet? And he spent a lot of time and patented and started a company called Vysis. And I will tell you that as we test the helmets in the NFL, Vysis has come through at the top of testing in almost every single test and really has become a mainstay in professional football to the point now where we are now finally, you know, looking at position-specific helmets. So this year you will see in the NFL, quarterbacks will have a special helmet. You're not gonna notice a difference sitting at home, but this helmet is designed to absorb the impacts that they have, which are at the back of the head. And the reality is that, again, using the data we now have of how patients and players are impacted based on their position, we can now devise equipment to protect them. Uzma Samdani and iBox, again, looking at eye movements for trauma, again, innovating. Jam Gujar also with ThinkSync, looking at NeuroSync, looking at ways to look at eye movements. These are all sort of really on the cutting edge of brain injury. In my own lab, we've looked at spinal cord injury and trying to understand how we treat spinal cord injury. You know, one of the problems is that we don't have any objective data in spinal cord injury. We can't put a Lycox monitor into your spinal cord, although I've thought about it. But the reality is that we don't have a way of treating patients with spinal cord injury with a knowledge base. So one of the things that my lab has developed, we're looking at a small sensor that we can implant at the time of injury that gives us real-time data on blood flow to the spinal cord so that we can understand when auto-regulation has been returned. And then I think that, you know, we look at education reform, we need to talk about Zachary Lystead. Zachary was 13 years old in 2006 when he suffered a severe concussion, was basically sent back to play twice after the game was over, he collapsed unconscious and was taken to Harborview where Rich Ellenbogen and Randy Chestnut took care of him. He suffered severe traumatic brain injury, craniectomies, month of recovery, and had a devastating neurologic outcome. He's since now can walk and talk, but it's never going to be the same. And, you know, Rich and others took that as an advocacy role to understand how do we prevent this from happening in the future? How do we, as organized neurosurgery, how do we do this? And we did that through legislation and that came up with Lystead Law. When the player's suspected of having a concussion now, this now is in all 50 states, he's removed from play, he has to be cleared by a medical professional before he returns, and that there's mandated concussion education. We looked at this in Phoenix as well, understanding that, you know, there was a big chasm when these kids get injured with concussion, they have problems in school and it becomes a real problem of understanding. So Javier Cardenas and I started BrainBook when we were in Phoenix and that basically was a concussion clinic. Now there are thousands of them across the country that bring all everything together including education and other pieces that will help these kids recover and understanding how that works. I think that these are all examples of how as neurosurgeons we can become advocates in what we do. Let's see here. So I think that finally I want to talk about Think First which really is our signature organization in organized neurosurgery. This is Fletcher Isker and Clark Watts who started Think First in 1986 and now we've got over 140 chapters and thousands of pieces of data that we've collected but also impacted millions of children teaching these classes. We've got VIP people to come in who've had head injuries and spinal cord injuries to talk to these. These are my two boys who don't ever get on a bike without a helmet and if you have any question about whether this impacts our youth, if there's any question at all, the reality is when I first moved to Baltimore I took this picture as a joke. I got on the scooter and I sent it to my son and I said here I am at dinner and I got a meme back about two minutes later and this was it and you know to this day I love this because the boys are like dad you did not have a helmet on. I wasn't even moving. I was just standing there. God help me if I was actually moving on the thing but ultimately you know advocacy starts as a grassroots effort. It starts with each and every one of us to understand our patients, educating our patients, providing patient care, research, innovation and then ultimately involvement in what we do. So I want to thank everybody here. I want to thank the Chuck Noel Foundation. Understand that they're playing a big part in our ability now to raise our awareness of traumatic brain injury with their new brain bank and collaboration University of Pittsburgh and I think there's a lot of a lot of great things coming down the pike so thank you very much. Fantastic presentation Dr. Theodore. The next part of the session we're we're gonna do something a little bit different. We've asked several experts in our field to give us some ideas of some things that we're we're commonly doing in our practices all across the country both kind of what's what's up to date and and some clinical nuances. So first is Dr. Alan Hoffer. All right that's a tough act to follow. I'm gonna be talking a little bit about nuances of neural monitoring and I feel a little bit silly because the authors of some of the papers I'm discussing are sitting here in the audience. So Peter, David, we're gonna have you escorted out. So monitoring has been a little bit challenging lately. The fourth edition of the BTF guidelines for severe traumatic brain injury have come out and because it was a very scientific process and they wanted to remove a lot of the guidelines that had low levels of evidence, they really stripped a lot of the stuff about about monitoring out there and so recommendations from earlier editions weren't carried forward. And then on top of that we we had a little bit of data that that maybe monitoring didn't help at all that that you know a close clinical examination and and radiographic imaging was not inferior to placing an ICP monitor. So that really left us with a lot of questions about what we're doing and why we're doing it. Now ultimately being a lot of us being from scientific backgrounds, we want to see this process. We want to see that that we can kind of trace things back that before we get this overall global organ dysfunction that maybe we can see some tissue dysfunction, the local hypoxia, the edema and really even get down to kind of the the cellular molecular level of things. But but we weren't we weren't doing that with what we had. Well the good news is I feel like there's hope and I feel like we're really on the cusp of making some developments that are gonna help us do this and I think that's because of our increasing understanding of the pathophysiology of brain injuries that's allowed some new well kind of new concepts and technologies to emerge. Now it's been known for a very long time that cerebral hypoxia affects the outcome after traumatic brain injuries and way back in 2005 when I was a resident I went to one of my attendings at our County Hospital James Anderson and I told him about this amazing new study that came out about brain oxygen monitoring and and I begged him I said please you know can we look into getting this Lycox and being somebody who was at a resource-limited facility he said well look if we're gonna if we're going to invest in this and do this I want to see some data that it really affects patient outcome. A little bit silly to me because very frequently in neurosurgery we adopt technologies and things without having a very high level of scientific data like you know how many times have you changed the kind of screw that you put in or inner body cage that you put in there aren't large randomized controlled trials that support those changes and yet we do it. So you know the first when the first data came out in 2005 we were very excited about this that we had our very first evidence that brain oxygen monitoring could influence the outcome of patients and it even came with with the first algorithm for how we can treat this. Well it's almost 20 years later now and of course we have the BOOST 2 trial that that has been completed and we are currently in the process of the BOOST 3 trial which hopefully will give us some answers but in the meantime in the absence of that that rigorous a scientific large-scale outcome data we do still have expert consensus and so I would refer you all to the second of the CBIC papers which does have an algorithm for treatment of ICP and brain oxygen related issues which is very nicely done so if there's any well I guess I really can't call you early adopters because it's been over a decade but if you're a true believer like I am you should please make sure that you're familiar with this and our hope is that when BOOST 3 comes out this will be settled once and for all and I can go back to Dr. Anderson and say I told you so. The second thing that I think is really on the on the cusp is this idea of cerebral auto-regulation and and personalized medicine we had a wonderful talk earlier from Dr. Gomez about pressure reactivity and you know the fourth edition guidelines although they take out a lot of stuff they did recommend CPP values between 60 and 70 and they made the statement that that the optimal CPP threshold is unclear and may be dependent on auto-regulatory status and this is now I guess a somewhat older paper a very interesting paper that I think we should be familiar with where they had two centers one that focused on CPP management and one that focused on ICP management and what was very interesting was that if your auto-regulation was intact you did better at the center with CPP management and worse if if your auto-regulation was not intact the exact opposite was true if you were at the ICP Center and this is really of course highlighting the fact that you know the state of your auto-regulation really influences your brain physiology so if your if your auto-regulation is intact I was a fastest five minutes ever that your brain would distribute that profusion where it needed to be and I think the cogitate trial was I think of it's a very important trial and what is showing us is that there is going to be optimal cerebral profusion pressures for every single patient and not just each single patient but even varying times during their hospital stay this is a really dynamic process and so in the the other CBIC paper I'll jump ahead there is this recommendation for consideration of what we consider a map challenge which is seeing giving a little bit of a presser increasing the oxygen and seeing how this affects the how this affects the intracranial pressure so that we can get an idea and the hope I think is that as technology emerges that this will be something that we can do at the bedside monitor at the bedside with a monitor so with that I mean those two points I will say thank you and pass it on to the next person my pleasure to introduce my friend and colleague dr. Jamie Allman who's going to talk about nuances of decompressive craniotomy James five minutes is always a challenge start okay all right all right we're going to talk about decompressive craniotomy and I'm going to cite literature of the authors of which are sitting in this room as well so really just the main question that we all have about decompressive craniotomy is are we really accomplishing anything in severe traumatic brain injury are we reducing mortality at the expense of increasing the incidence of severe disability and and vegetative state and so in an ideal world if we get everybody back to their normal state of functioning we will have had success in ultimate success in treating patients but we really don't have a magic bullet so what we have left is really just our current armamentarium and we're doing a whole bunch of studies on a lot of things and so far we've had a lot of negative trials but decompressive craniotomy has been in our armamentarium for decades decades ever since the turn of the century and even from millennia you know because even the Incas and the Aztecs were doing it so rescue ICP trial came out in 2016 and included about 408 patients ages up to 65 abnormal CT using ICP of 25 as a threshold for 1 to 12 hours in order to treat them to trigger the decompressive craniotomy if they had that elevated intracranial hypertension on tier 1 and tier 2 therapy and so what we have here is that six months and the primary outcome measure was six months and so what we have here is that there was you know some survivors but there was a huge number of people in vegetative state which is the red and lower severe disability which is in the orange and then if you dichotomize using the extended Glasgow outcome score the upper severe disability patients are those who are independent at home for eight hours so I mean some people consider that actually pretty darn good so that's been included as good outcome versus not a good outcome if you look at this compared to a secondary outcome measure which was 12 months you actually see a statistically significant difference in the number of people that are now in the good outcome range compared to the medical group so what you're seeing is really this shift over towards the left-hand side people are starting once you've gotten the people who have had the mortality now those who are remaining surviving are trending towards doing better so unfortunately when you publish in the New England Journal of Medicine these primary outcome measure is what you see at the conclusion in the abstract now how many people really go and delve dive into the paper you're really just going to do a cursory look at abstracts and you say oh my god I shouldn't be doing decompressive craniectomies anymore on the basis of this because it only gives us more severe you know lower severe and vegetative state patients so built into the study was another secondary outcome measured the 24 month outcome and we were fortunate to have that published last year and pretty much remarkably only 20 patients lost to follow up in that study in the decompressive craniectomy arm 22 lost in the medical arm and what they found was that there was a sustained reduction in mortality in the surgical group and there was higher rates of vegetative severe upper and lower and moderate upper and lower disability but patients were more likely to improve over time there was a higher rate of improvement one Glasgow outcomes score level or more so verse six versus 24 months and what we actually had was the 24 six comparing six months and 24 months had the most significant difference in outcome compared to any other time period analyzed so just as a reiteration here of the 12 month in the middle between 12 and 24 you're not really seeing all that much difference but the starkest comparison is really at 6 and 24 months and so what we have here you know patients in the red boxes the good outcome group where the light blue here with this blue here is really the upper severe category you do see that there is a trend even more and now when you have like the moderate and the good outcome they're getting much better over time and you see that in the medical group there's an increase in the mortality and vegetative states I'm not necessarily vegetative but also the mortality over time so we're actually seeing improvements and this argues that when we're looking at six-month outcomes we are going to call a lot of studies negative because severe traumatic brain injury requires a lot of time to recover and so if we're only looking at six months we're really going to short change the results of any of these major studies this box is showing the the vegetative and the lower severe and what you're seeing is a shrinking of that group at 24 months so now we haven't done it at the expense of having more vegetative and severe lower severe people we actually are seeing some improvements and if you look at it this way I know I'm going over time but when you look at the dichotomization at 24 months of the out of a hundred patients if you have 21 more survivors then a 71 percent of those go on to have a good recovery that is a significant increase so this is really I just go from here we had to update of the guidelines in 2020 so one key here was that we included did not include this 24 month obviously but we then adjusted the guidelines to then say that if we wanted to do decompressive craniotomy for a late refractory it's from it is recommended to improve mortality and favorable outcome and so again this other recommendation here was reiterated from the fourth edition was if you're going to do a decompressive correct the craniotomy go big or go home and we did have literature to back that up of course it's evidence-based so so we want to make sure that we maintain decompressive craniotomy in our armamentarium we still have to counsel patients and families as to what that really means but I can honestly say that we also have to give a time it's a day-by-day process and it's a lengthy process in the recovery thank you very much next up we have dr. Eve side talking about nuances of the Asia examination so I think one of the key things that is kind of trending is that there's all these classification systems and some of them are a little bit lacking so for example the Glasgow outcomes score you know this vegetative non-vegetative it becomes very confusing and very difficult and the Asia exam is one of these that has made spinal cord injury assessments and things like that often very difficult and and potentially even flawed and so I'm gonna go through some of that my disclosures aren't necessarily all that relevant except I do a registry style so Asia is the American Spinal Injury Association it's composed of a lot of physiatrists we have physicians as well as neurologists and some neurosurgeons and they create this other thing called an in ski again another one of these acronyms international standards for neurological classification of spinal cord injury and for some of these some of you a lot of this is actually modified and changed and so I thought I'd go through some of the highlights because we're talking about the nuances of it so similar to the previous ones they talk about a motor score so there's the motor score here on this side and then they've got a sensory score and they do the motor score and sensory score on both the right and the left and then there's like a summary score now if you look at that look at all those data points that's way more than when you do a GCS and there's like you know three categories there's like a bazillion little data points and I can you know I haven't asked everyone in this audience but you know briefly when I talk to people you know I asked him do you do all these and and very rarely do neurosurgeons do all of these assessments especially when you're seeing a patient and you're trying to get them to the OR and so that's one of the problems I want to talk about in the with this assessment is it's primarily like I said based on a lot of physiatrists and again for practicing neurosurgeon especially the orthopedic surgeons who are also doing page taking care of these patients oftentimes a lot of these things aren't aren't fully done which makes it difficult for us to do studies so the some of the other changes that they have they have the motor score which everyone pretty much should know and it's like zero to five which is normal but they've got another little category here which is an asterisk category so not testable there's an NT category which is not testable which means if you don't have an arm or you have an amputation you can't test it or if they're in a splint they're not testable but then they've got this other little category here with a chip which is an asterisk and the asterisk used to mean different things in previous versions in the new version now the asterisk means that there's a non spinal cord injury condition present so if they already had a previous problem and that's why they're weak as opposed to a spinal cord injury then you put a little asterisk on that the motor groups are similar to the ones that we've tested before and for the medical students that I usually do this teaching I usually get them to all stand up because they're usually tired by this time and I tell them to do like the Asia dance which is that you know flex your elbow extend your wrist extend your elbow flex your third finger and abduct your thumb so you know if you're into dancing that's something that you do remember it's a little harder for the lower extremity because you're have to balance on one leg but you know they're all sitting behind a desk and they can usually do that so but the other motor exam that's essential is the assessment of the voluntary anal contraction and deep anal pressure and so this is different in the past from those of you who talk about rectal tone and if you go back to some of your trauma colleagues some of them still may be assessing something called a rectal tone and you know that was a very difficult kind of thing to kind of figure out you know what's what's decreased rectal tone what's increased rectal tone so they've actually changed that now and it's voluntary anal contraction and so you may want to go back and if you're some of your trauma colleagues don't do this, because it is also changed in the trauma guidelines, is that it's not directal tone anymore. Nobody should be measuring metrical tone. It's voluntary anal contraction and deep anal pressure. And you know, one of the things, you know, one of the sayings is that the only reason not to do this kind of examination is if your patient has no rectum or you have no finger. So some, again, some of the nuances. I have, you know, some of the residents, they'll say, oh yeah, you know, they've got a C5, you know, C4-5 subluxation, and yet they're able to move, you know, and so what happens is they'll examine the patient, and if there's any kind of wrist extension, then what happens is the fingers will move, because of the tenodesis of the of the ligaments and the tendons there. So when you want to assess that, you have to stabilize, make sure they don't move their wrist, and then ask them to move their fingers and see if there's anything there. Sensory exam. I love this. If you look at all the little dots here, they tell you exactly where you have to measure, so you don't even have to like pay attention. You have to pull this up and it tells you where to go. And clinical pearl, I tell medical students and residents, you know, you hold your arm up, your middle finger is C7, and then you just divide it up like a snowman's arm, and you can figure out where else to test. And then, I'm out of time, so, but this is the thing. There's all these other things that you have to classify, and because it's so hard, right, and so they have this algorithm. If you type this in, they can, as long as you get the numbers right, the examination right, you punch all those numbers in, and then they'll calculate this for you. So they calculate a summary in terms of the neurological level, they calculate a summary in terms of his own partial preservation, and complete is whether or not there's any sensory and motor function in S4 or S5. And so, you know, all of this is, why is this important? Well, you know, you hear these stories all the time where patients go, oh well, you know, they told me we'd never walk again, but here I'm walking again. And part of that is because if you don't do this full examination, you know, if you really do have an ASIA-A, where it's a full examination and it's really an ASIA-A, like the prognosis is poor in terms of full recovery. But if they do have anything, like even a sensation or motor, you know, up to some quote, even up to 50 percent of them can have significant improvement. So this is important not only because it helps in terms of your prognosis, but it's also important in case, if we ever want to have any improvement in any kind of patients or in trials of these patients, we really need to understand this and have a better exam. And to that end, I think one thing we may want to do as a section, and this is something we can think about, is to improve our ability to do this so that everyone actually does an exam. Because right now, based on the registries and trials, people are not doing it and they're doing it poorly. Thank you. James Wright is going to speak to us about nuances managing the combined TBI-SCI spinal cord injured patient. So again, a little hard to do in five minutes. I'm going to try to make it interactive, but there we go. So heterogeneity of diagnoses, when you think about spinal cord injury and brain injury, there's a huge gamut. This is a hard, hard topic to do in such a short period of time, but site of injury considerations, cervical, thoracic, are not all created equally. Patients who have significant spinal instability or need long segment stabilization is a very different patient than, say, someone who has a stable central cord injury. In terms of TBI, mass lesions may or may not meet operative criteria. Those patients are obviously going to be treated differently in the acute setting. You may have patients who have no mass lesion early, but have signs of elevated intracranial pressure or complicated open craniofacial trauma. Some of the specific nuances are, if a mass lesion doesn't meet operative criteria immediately, is it okay to go ahead and commit to a potentially long spine surgery versus waiting, say for instance, in the setting of an incomplete spinal cord injury, six hours or whatever your protocol is for stable imaging. How many of you typically wait and get stable imaging before going to the OR? Okay, everybody's shy today. ICP and CPP considerations in the prone position. Is there an impact on those things in spine surgery? Avoidance of mannitol in patients who have spinal cord injury and are having issues with hypotension. Low GCS patients that you're considering an intracranial pressure monitor. If you have any need whatsoever in the next day or two for advanced imaging, you want to consider doing that early prior to having to futz around with potentially moving your monitors or taking your monitors out. Timing and order of surgery is always an issue when you have two surgical lesions and then aggressive pre-hospital care and resuscitation is something that's really important. This is from the EPIC TBI study out of Arizona a few years ago that looked at pre-hospital blood pressure and the impact of hypotension. Odds ratio of death just in TBI is 2.5 times that if you have a single blood pressure less than 90. In the setting of a concomitant spine injury, those outcomes are likely even worse. This is an excellent diagram that they had that looked at what is the sweet spot in TBI and the odds of death was actually lowest if your lowest out-of-hospital blood pressure ranged from 135 to about 180. So different ranges compared to where our guidelines recommend. This is a publication that we had a couple years ago in critical care medicine that looked at the question of PbTO2 and ICPs. In the prone position, it turns out CPP changes are relatively minimal. ICP change is very minimal. Single digits can be expected. Again, some of the things and tips that you could do are making sure the abdomen is free, some of those things with positioning. And brain tissue oxygen actually improves in the prone position. I just wanted to take a second and try to go through a couple cases if we can but this is this is one that kind of presents as a conundrum but 28 year old gentleman was cutting a tree. It kicked back and hit him. He had a loss of consciousness. His GCS was around 9. He was moving all extremities. Eve will not like this one with the normal rectal tone but he did have normal rectal tone and anal contraction. He had a Foley that was placed for retention. This was, okay, I'm a simple spine surgeon. This is not a spinal cord. This is a lumbar injury clearly but you can see he's got a multi-compartmental TBI. He's got subdurals bilaterally. He's got three column injury at L3. He's got L5 spondyloptosis that you can see on the 3d recons and then the MRI that just looks absolutely terrible. So he was a little hemodynamically unstable. Anybody want to say what you would consider what you would do in a case like this? When you would go? When you would re-image? Re-image first. Six hours. Abdominal imaging. How would you do it with it? How would you do it with the um with a fracture? Yeah. Yeah. So this is I mean this is this is a case he came in in the evening. These spine cases can be very very long cases. Again he didn't meet criteria for an ICP monitor placement so we waited six hours. Got stable imaging. His imaging was stable. We took him the next morning for an anterior posterior approach with reduction and instrument diffusion and got a pretty good result. But you don't want to jump into something like this with an uncertainty in terms of the intracranial injury unless you do have a monitor or a stable image. This is another one. 40 year old was attacked with a baseball bat. Had an open facial fractures, cranial wounds. Ongoing hemorrhage. He was actually GCS 14. Had only some mild bilateral paresthesias in his upper and lower extremities. He hits the hospital again around 6 p.m. so kind of late in the evening. This was his CT and his MRI of his cervical spine. And so you see him in the trauma bay. I actually saw him in the trauma bay. He was massively hemorrhaging from his face. He had actually a sagittal sinus injury and significant craniofacial trauma. And so that was being held. Someone was holding pressure to keep that from bleeding. And then this is a CT of his cervical spine that showed he had C2 spondyloptosis with pretty significant cord compression. So from a blood pressure standpoint, you know, what do you do in this situation from a rush to the OR for the head, rush to the OR for the neck? Anybody want to? Hoffer? Head first, right? He's bleeding out of his head. He's got brain coming out of his forehead. How would you do it? Yeah, all the orbital fractures, his sinus fractures, all those things. So yeah, so I took him for a bifrontal craniectomy in the hopes that he wouldn't leak CSF. How would you deal with the spine? And how would you position him for surgery for the for the head? Mayfield, leave him in a collar, do it on a horseshoe. Those are the things that in the in the midst of this really slow you down. It's very, very tough to figure some of those things out. But we pinned him, did the bicoronal, fixed his head, ENT, put a TFL graph from below. He didn't leak. I did a craniectomy because I was worried about swelling. He had a big hematoma. And then put him in Gardner-Wells traction after that. Got him reduced, put him in a halo, and took him for a posterior cervical the day after. And he did well. So difficult patients to manage. I think you have to take a practical approach. Try to make sure all of your treatment falls within the recommended guidelines. If it's a spinal cord injury in someone who is really unstable or has something else going on, you just want to do it within 24 hours and be safe about it. Thanks. So next we're going to switch a little bit to a different category we're calling clinical quandaries. And Dr. Parr, Ann Parr, is going to speak to us about management of patients with spinal cord injury. Oh, excuse me. Yeah. Yeah. Sorry. That's right. Welcome. All right. Thank you so much. I think mine is significantly more interactive, so hopefully we get some participation. But I think it's a good corollary to what James was talking about with regard to a difficult patient population to manage. Similarly to those with concomitant traumatic brain injury, those patients I think that present us a complex scenario, or at least one that offers us a significant clinical consideration, are those with concomitant polytrauma. So I think as a field we're moving towards ultra-early or hyper acute intervention in traumatic spinal cord injury. I think that even outside of the spinal cord injury context that we are moving towards earlier intervention. So evidence has shown that optimal timing is definitely within 21 hours. This allows time for resuscitation. However, waiting more than 24 hours, especially more than 36 hours, is accompanied by significant complications. So not only medical sequelae of delay of operative intervention, but also with increased ICU length of stay, as well as costs associated with that. And so with that being said, there are two competing aspects of the management in these patients. The timeliness of intervention, and also the appropriate medical stabilization. So I think the best way to go through this is to discuss some cases and give it up to the audience and see what everyone would do. And so the first patient is a 35 year old patient. Motor vehicle collision presented to us with a T12A4 Asia C. Also associated pelvic fractures, rib fractures, and severe refractory ITP on prednisone, on cyclophosphamide, and other immunologics, ramaplastin. So importantly, the platelets were 5,000 on arrival, got a unit incremented to 6,000, and then with that being said, patient came to us on a Friday, and there were two units of platelets left in the entire hospital for the weekend. And so just some discussion points. I don't know what you all think in terms of the important aspects of this management. Anyone have a way to approach this initially? All right, so with that being said, I think there are a couple things to do. And the way that I approach this was one, first discuss with the patient, as we all do, but specifically with the intraoperative versus post-operative hemorrhagic risk in this setting of severe thrombocytopenia. Obviously this is outside the context of any literature with regard to the risk of hemorrhagic complications, but I think that it's important to discuss this nevertheless. And so importantly, I don't think anyone is going to approach this without hematology on board. And so in this particular case, what we decided to do is patient came to us Friday afternoon-ish. We talked to hematology. Patient was able to get infusion of IVIG, as well as they recommended an intraoperative continuous platelet infusion. So we were able to convince trauma to give us at least one of those units of platelets to use intraoperatively. I think the nuances in this case is the operative plan as well. So I think that you can do a traditional open instrumentation and decompression. I think that in this case that's fraught with a significant amount of hemorrhagic risk. We chose to do a percutaneous fascial incision as well as a mini open decompression. With that being said, we had a frank discussion with the patient, even intraoperatively, with that relatively MIS surgery, quite a bit of blood loss. And the other main question is, do you transfer? I'm at LSU in New Orleans. It's a county hospital. Some points are resource-limited setting, but same time a large referral center for the Gulf South. Is there an option to transfer? Do you transfer this patient? I think these are all important considerations. This next case, similar, 35-year-old, also with a motor vehicle collision, came to us with an L1B2, ASIA-B, so incomplete spinal cord injury. Also with significant solid organ injuries, including splenic lacerations with a questionable blush, grade 4 kidney injuries, bilateral rib fractures leading to a dissociated sternum with a flail chest, as well as a sternoclavicular dissociation with lung herniation as well. And then a fascial dehiscence extending into the retroperitoneum. As you can see here, the labs indicate that this patient is quite sick. Fibrinogen of 130, lactic acid of 12, pH of 6.5, hypotensive in shock. Does anyone have any thoughts on approach, any insight, any expertise to offer? Yeah, clearly this patient needs resuscitation. The blush on the on the CT of the abdomen pelvis is concerning. So the first thing is, as James mentioned, hemodynamic stability. So patient went, presented to us relatively in the evening, underwent an angiogram in the morning or overnight. We were able to have a thorough discussion with the traumatologist as well as the anesthesiologist. Their main concern with the dissociated sternum was ability to achieve any sort of ventilation intraoperatively. So we were lucky enough to have enthusiastic trauma surgeons to plate the sternum immediately after the angiogram and then went prone onto an open Jackson table. And so just one more case. So we talked about the order of operations. In terms of this next case, 27 year old male, motor vehicle collision initially came in with this injury. The patient was taken immediately from the CT scanner to the OR for an exploratory laparotomy by trauma surgery. Ended up with an open abdomen. Pre-operatively, patient was moving lower extremities post-operatively, flaccid. And so naturally we took for an immersion MRI and showing the the progression of dislocation there. So I think the main thing with this particular case is how do we position prone with an open abdomen with the patient head secondary to a bowel injury. So with significant bolstering on an open Jackson table, significant padding as well. And so in the end, I think the realm of literature probably is not very applicable to this patient population. It's quite heterogeneous. It requires a constant evaluation of risk and benefit. And my thought is to operate as soon as medically possible to expedite care and be able to achieve our operative timing within guidelines. Albeit sometimes out of the hyper acute window that we would like to achieve so. Alan, you're back up. And now he's going to talk about management of head injury on a direct oral anticoagulants. I'm back. And I'm very excited because I have twice as long for this talk as I had for my last one. All right. So we're gonna talking a little bit about direct oral anticoagulants. Sort of formally known as novel oral anticoagulants. So we call them DOACs. And this is a typical Ohio case of a 68 year old man who fell off the roof of his barn. We do have a large population of barn related accidents. Falling off the roof. Falling out of the hayloft. But this particular gentleman had atrial fibrillation and was on Xarelto. And you know this is kind of an obvious case about a patient that you would want to reverse. But the fact of the matter is that traumatic brain injuries are very heterogeneous. And we see a lot of different patterns. We see patients with large operative hematomas, small non-operative hematomas, contusions, subarachnoids. And I think when we're talking about the some of the new anticoagulants we really have to take all of these things into consideration. Now of course there are a lot of indications for anticoagulation. And I must admit that when the first DOACs came out I was a little bit bitter toward the cardiologists. Because here they had these wonderful new drugs that they didn't have to monitor any levels. They didn't have to worry about the patient's diet. All of these wonderful things for them. But then we were absolutely horrified that these patients would come in with hematomas. Because we really didn't have any way to address them. But there's a lot of stuff about the pharmacopharmacology and pharmacokinetics that actually make these in some ways better than traditional anticoagulation with Coumadin. So the primary mechanisms of action. Dabigatran is a direct thrombin inhibitor. Some of the other medications are factor Xa inhibitors. And as we said the benefits of them are that there's no need for monitoring levels. They have a shorter half-life of medication itself. And there are actually decreased risks of bleeding complications. And because of these advantages they've really kind of taken over where now more than 50 percent of patients started started on these kind of medications. So again the Dabigatran or Pradaxa is a direct thrombin inhibitor. Xarelto Eliquis work on factor Xa. And so it's a little bit good news that there are fewer hemorrhagic transformations in terms of traumatic intracranial hemorrhage and some of the other things. So it's very just important to know what the differences are. Because it really affects how we how we manage and treat some of these. They have much shorter half-lives. The half-lives tend to be in kind of the 9 to 18 hour range. And what that means is that oftentimes within 48 hours a lot of these are out of your system. Dabigatran is not very well protein bound and has a high renal excretion. And so that can be something that we can turn to our advantage if we have to clear it. The 10a inhibitors tend to be more protein bound with less renal excretion. Now when we were talking about Coumadin or Heparin or some of the other some of the other traditional anticoagulants we have ways of monitoring them with commonly commonly available lab tests. That's a little trickier here because we're not looking at the intrinsic or the extrinsic pathways of coagulation but the final common pathway. And one of the tools that that we have unfortunately it is not globally available is the thromboelastography or TEGS. Which can be helpful because they can give you a little bit of idea about what a patient's overall clotting situation is. And so you can get these TEG maps even if you can't follow the traditional measures the laboratory measures of coagulation for these patients. As we said you can't follow them but the question is do some of our other some of our other medications work. And in looking at some of these laboratory measurements this was a trial that looked at dabigatran and the 10a inhibitors whether or not protein complex concentration can concentrates can help with them. Didn't really affect at all the the effects of the dabigatran. But rivaroxaban did have some improvement, at least of the laboratory values for the effects of that. Well, fortunately, I think our era of anxiety is coming to a close because we do have strategies and some specific reversal agents for these. So dabigatran has a monoclonal antibody, Praxbind, that affects the molecule and is very good at decreasing bleeding. And that is with a subjective amount of bleeding. Reversal of the 10A inhibitors is a little bit trickier because they didn't have FDA approval of the specific inhibitor until 2018. So activated charcoal could be used if it was an acute ingestion. But as we said, PCC was very effective. And in fact, that is still, in our hospital system, that is still the medication that is used if they are not at the tertiary medical center where the specific antidote is available. Of course, the specific antidote is the N-dexanet alpha, which, as we said, was approved in 2018. This is a decoy protein that binds the 10A inhibitors and was shown to significantly decrease 10A activity in the clinical setting. So in terms of the guidelines, I have to keep in mind these guidelines from Neurocritical Care Society came out in 2016, which was before the FDA approval of N-dexanet. But the good clinical practice is to discontinue the medication. And remember, these can have shorter half-lives. So if you have a patient who comes in very late in the day, they haven't had it since the morning, or maybe they hadn't had it since the morning before, you may not need to actively reverse them based on what kind of injury pattern that they have. Reversal should be driven by hemorrhage, not by labs. Again, the lab may not necessarily reflect what is going on. And as we said, acute ingestion can be treated with activated charcoal. For dabigatran, again, we have our specific reversal agent, the PraxBind, that can do that. Now, because dabigatran is mostly renally cleared, these patients can sometimes be candidates for dialysis. Not gonna help you if you need to rush that patient off to the OR, but it can help you if you need that in your back pocket. And because the guidelines came up before 2018, they recommended four-factor PCC, but I'm sure that is something that will be rectified in the next set of guidelines. So it turns out that the DOACs aren't quite as scary as they once seemed. They do have fewer hemorrhagic complications, and reversal agents are widely available. There is the possibility of waiting them out. So for some of those patterns of brain injury, the small contusion, the small subdural, if you can closely monitor those patients and make sure that they do not have worsened bleeding, oftentimes you can just wait it out and you don't need to reverse them. And in somewhat questionable situations, TEG can be very useful in determining how thin their blood is, what are the chances of them having further bleeding. Thank you. Thank you. Thank you very much. Now we'll move on to submitted abstracts. Next will be Deborah De Bonha, speaking about early versus late cranioplasty following DC. Well, I'm following some amazing talks, so thank you guys for the time and opportunity to present some of our work. My name is Debbie Bonha, I'm a medical student at Penn State College of Medicine. The title of my talk today is early versus late cranioplasty following decompressive craniectomy, a propensity-matched post-operative outcome analysis, mentored under Dr. Elias Rizek in the Department of Neurosurgery. I have no disclosures. So as we know, in patients requiring decompressive craniectomy, there is a high risk for post-operative complications following their cranioplasty. And there are a number of factors that can be, that may influence this complication rate. But one aspect that has been extensively studied and hypothesized is that timing of cranioplasty may be implicated. Now, controversy exists regarding whether performing the cranioplasty either closer to or further from the craniectomy is superior. And the timing definitions vary a bit, but the most standard reported in the literature is early cranioplasty being within three months from the decompressive craniectomy, and late cranioplasty being sometime three months after. Now, between early and late cranioplasty, both strategies offer distinct benefits and associated risks. The benefits for early cranioplasty include returning the patient to physiologic CSF and CBF dynamics sooner, sometimes easier discrimination of the tissue layers and the skin flap reflection, and then promoting patients to kind of psychosocial well-being. For late cranioplasty, some of the benefits include sufficient time for clearance of the infection, inflammation, and edema. The previous incision site is more likely to be well-healed and well-vascularized, and patients are more likely to be neurologically stable to undergo a second procedure. So, you know, this question has been widely studied, and unfortunately, the literature remains inconclusive. So our goals for this study were to apply a methodology that maximizes patient cohort sizes and accounting for confounding variables, both of which are limitations in the literature. So this was a retrospective cohort study using data collected from Trinet X, a clinical database collating de-identified patient information from 92 healthcare organizations. We used ICD-10 and procedural codes to identify patients who underwent decompressive craniectomy and subsequent cranioplasty. And then we dichotomized them based on the early or late cranioplasty cohorts based on the standard definitions. And then we propensity score matched them to account for confounding variables, and then compared post-operative outcomes within six months following the cranioplasty. Our primary outcomes were incidents of seizure, intracerebral hemorrhage, hydrocephalus, and infection. And then our secondary outcome was looking at survival at six months. So for the propensity score matching, we matched on over 30 characteristics in the realm of demographics, comorbidities, and anticoagulant use. And then we identified through this analysis, 2,700 patients, 1,100 who were in the early cohort and 1,500 in the late cohort. Patients were aged in their mid 40s on average and were predominantly male. And then baseline characteristics were grossly similar with the exception of some differences in diabetes, which were matched. And then for interestingly, patients in the early cohort were more likely to have other neurological injuries, including subdural hematomas, subarachnoid hemorrhages, coma, and TBI. Patients in the late cohort were more likely to have underwent emergency endotracheal intubation. And then in addition, patients in the late cohort were more likely to be on antiplatelets and anticoagulants, including aspirin, warfarin, and epixpan. So for our postoperative outcomes that we found, in general, the data favored late cranioplasty, whereas there were lower rates of all of our outcomes in the late cranioplasty cohort. The two that were significant were hydrocephalus and intracerebral hemorrhage, favoring the late cranioplasty cohort. And then as far as six months survival, there was increased survival at six months in the late cranioplasty cohort as well, at 97% compared to 94% in the early cohort. So in summary, this data just adds a small contribution to the larger set of data that's already in the literature. We did find that intracerebral hemorrhage and hydrocephalus were, you know, associated, there were lower rates of these in the late cranioplasty cohort. And survival was improved in the late cranioplasty cohort as well. But further work should include a comparison of patients who underwent ultra early cranioplasty, because that has been uptrending and specifically at our own institution. And just to better understand the nuances of the decision-making, incorporating patient goals and perspectives, as well as some financial analyses, will be paramount in order to know which approach is better and when. We have some limitations obviously, but thank you so much for your time. Thank you. Thank you Chairman. Today I'd like to talk about expression of extracellular matrix and angiogenic signaling pathway in chronic cerebral hematoma. So as you know, angiogenesis and inflammation plays an important role in the growth of chronic cerebral hematoma. And osteoporosis is also involved in inflammation and angiogenesis. And osteoporosis is cleaved by thrombin, resulting in N-half osteoporosis, which is more prominent in integrin signaling transduction. So this integrin beta one plays an important role in angiogenesis. So this experiment was performed to clarify these questions. So at first, we measured the concentration of osteoporosis and N-half osteoporosis by ELISA kit in 20 chronic cerebral hematoma fluid and five serum samples. So this shows the result. Both osteoporosis and N-half osteoporosis are significantly higher than serum levels. So next, we obtained eight outer membrane samples from these patients. And using these samples, Western blot analysis was performed using these antibodies, which are involved in integrin signaling pathway. So this is the result. As you can see, positive controls are presented at the right side. And all these proteins are detected in almost all samples. So next, we did a Western blot analysis using these antibodies, and feature involved in CD44 signaling pathways. And this slide shows the result. And also, these CD44 signaling pathway proteins are detected in almost all samples. So next, we did immunohistochemical analysis. So as you can see, all these integrin signaling pathway were detected in endothelial cells of chronic cerebral hematoma outer membrane. And also, these CD44 signaling proteins are also detected in endothelial cells. Next, we did cultured endothelial cells were treated with chronic cerebral hematoma fluid. And we did Western blot analysis. And this slide shows the result. And FAK was significantly phosphorylated after treatment with chronic cerebral hematoma fluid. So this slide shows a summary of the result. So it has been reported that integrin alpha-9 beta-1 binds to the thrombin cleaved N-half osteopongenes. And FAK is well known as a regulator of tumor angiogenesis. And paxilin is also promote angiogenesis. And also, osteopongene is a ligand of CD44. And CD44 and ethylene ladexamoycin L-proteins are associated with cancer progression. So this slide shows the conclusion. And high concentration of osteopongene and N-half osteopongene through the integrin alpha-9 and CD44 receptors activate FAK and L-pathway, which result in angiogenesis in outer membrane. Thank you. Thank you very much. Our next speaker, Dr. Mohamed El Abta, speaking on diffuse axonal injury patterns predicting timing of in-hospital neurologic recovery. Hi everybody. My name is Jordan Pettit. I'm a third year medical student at Case Western Reserve. I'll be applying for the upcoming MASH 2024 cycle. I'm actually signing in today for Mohammed because he's taking step one this week. So yeah, thank you. I'll be presenting Diffuse Axonal Injury Pattern Predicts Timing of In-Hospital Neurological Recovery. So diffuse axonal injury is a form of TBI caused by rapid and sustained acceleration deceleration forces on brain tissue. Generally DAI staging has been based on the 1989 histopathological Adams classification as well as the 1994 Gentry radiographic classification in which grade one is defined as mild white matter lesions involving low bar white matter, the cortex. Grade two is involving focal lesions of the corpus callosum and grade three has severe lesions in the brainstem, specifically in the dorsolateral quadrants of the rostral brainstem. These aren't our images but just kind of showing some examples of what DAI grading based on radiographic findings would be. So grade one with the mild lesions within the cortex involvement of the corpus callosum in grade two and then the brainstem in grade three. Several studies have investigated the association between the presence, location, and grade of DAI and mortality and functional outcomes, however there have been no published reports so far on the in-hospital neurological progression in patients with DAI. Therefore our objective for the study was to better understand the association between DAI injury pattern and the timing of neurological recovery. We performed a single center retrospective review of all TBI patients with radiologically confirmed cases of DAI between the years of 2017-2021 and our collected data included the first CT head that was available for the patients, Rotterdam CT score, and DAI grading was determined by two neuroradiologists and furthermore we included neurological exam findings and GCS as well as ICP and EEG monitoring, Trach and PEG, and outcomes such as length of stay and mortality and withdrawal of care. Nineteen patients were included in our study. There is a similar distribution between grade one and grade three. The average age for our patients was approximately 31 years and 79% of the patients were male. Additionally the most common mechanism of injury was MVC at 79% and the most common TBI subtype was subarachnoid hemorrhage. The average Rotterdam CT score, injury severity score, and admission GCS were also comparable at baseline for each grade. As far as significant variables, so average time in days to follow commands was shorter for those with grade one DAI compared to two or three. Then throughout the hospitalization patients with grade one DAI had higher motor I and total GCS score compared to those with grade two or grade three DAI. Seventeen patients received ICP monitoring or EEG monitoring and notably the rate of ICP monitoring was similar across grades. Three of the seven patients that had ICP monitoring developed intracranial hypertension and no patients had any evidence of seizures or epileptiform activity across all DAI grades. And furthermore length of stay, discharge GCS, mortality, and withdrawal of life-sustaining therapies were similar across grades. So in conclusion patients with grade one DAI demonstrated the fastest short-term neurological recovery although final discharge neurological examination is comparable across the DAI grades. DAI classification may be able to provide some short-term prognostic information regarding in-hospital neurological improvement which would aid neurosurgical and critical care providers to counsel patient families and guide resource intensive medical decision making. I'd like to give a big thank you to Case Western Reserve University as well as Metro Health Medical Center and our Neurotrauma Research Group led by Dr. Michael Kelly for making this research possible and the AANS for putting on such a great conference. This is my contact information if anybody would like to further connect after this meeting and I'm looking forward to the upcoming match cycle this year and to learn from all the great minds in this room. Thank you. Our next speaker is Dr. Kavelin Ramallah who will speak on preoperative frailty and 30-day mortality after surgery for type 2 odontoid fractures, a multicenter analysis of 474 patients. Welcome. You guys actually asked us not to present that, so we're going to skip it. Oh, okay. I'm told that this paper has been withdrawn. Okay, so we'll move on to the next paper. And this is given by Evan Corville. Machine learning algorithms for predicting outcomes of traumatic brain injury, systemic review and meta-analysis. Welcome. Thank you. Thanks for having me. Hi, everyone. My name is Evan from the University of New Mexico. Today I'm going to share our research on machine learning algorithms for the prediction of outcomes in traumatic brain injury. I have no disclosures. So a little bit of background. TBI remains one of the most prevalent causes of death and disability globally, affecting nearly 50 million individuals annually. Several TBI sequelae may require extensive intensive care as well as prolonged rehabilitation. Therefore, outcome-based prediction models has a potential to bolster clinical decision-making, facilitate family counseling, as well as improve the need-based allocation and quality of care. In current practice, there are several machine learning strategies that have been used in clinical practice to predict deleterious events as well as alert the appropriate care teams. So what is machine learning? Machine learning is the iterative process that involves the training of algorithms using the data to recognize patterns and make predictions. This process includes data collection, feature extraction, model selection, evaluation, refinement using testing data, as well as optimization. This then translates to a predictive model that can autonomously adapt to new and unseen data and provide us with real-time accurate predictions. So again, we sought to evaluate the predictive power of these machine learning models for outcomes in TBI. To achieve this, we looked at peer-reviewed prospective and retrospective cohort studies. We found a total of 15 articles, and some of the outcomes that we assessed were mortality, unfavorable outcomes at six months, as well as the prediction of secondary insults. There were nine studies with mortality data for a total of 32,000 patients. The overall mortality rate was around 23%. However, as you can see in this plot to the right, there was a decent degree of heterogeneity with the reported mortality rates. Furthermore, machine learning was able to robustly predict in-hospital, 14-day, and 30-day mortality, with the area under the curve ranging from 72 to 96 percent. There was also a high degree of discrimination for unfavorable outcomes at six months and for the prediction of secondary insults. Machine learning was also able to predict ICP reasonably accurately within the five-minute and two-hour timeframe, providing ample opportunity for the potential intervention if a newer care provider would deem it necessary. In every meta-analysis, it's also important to assess for bias. Even though we did see that high degree of heterogeneity in our mortality data, there was no evidence of overwhelming bias, as you can see in our plots right here, which can be appreciated by the cluster of data around the summary points for these two machine learning algorithms. Some of the limitations of the study include the high degree of heterogeneity from the input variables that were used to go into these machine learning algorithms. This in turn limits the cross-comparison between the studies themselves, as well as there was inconsistent TBI classification, which restricts its generalizability. Therefore, in conclusion, machine learning models effectively predicted outcomes. They were superior to linear regression, and some of the most impactful variables in these algorithms included age, admission GCS, serum lactate, as well as serum glucose. Looking forward, we suggest expanding the scope of data collection to improve the accuracy and generalizability. We advocate for the standardization of input variables to enhance consistency, as well as for the implementation of machine learning in the clinical setting to help identify these patients at high risk for early neurologic deterioration. Thank you. Our next speaker will be Ryan Lauder, talking about Cognitive Dysfunction and Mild TBI, a Proposed Mechanism of Action. Hi, everybody. My name is Ryan. I'm a rising fourth-year medical student at the David Geffen School of Medicine here at UCLA. And I'm going to be giving a talk on Cognitive Dysfunction and Mild TBI, a Proposed Mechanism of Action. And I'd like to thank Dr. Kevin Bickert, who's provided amazing guidance throughout this project. So cognitive dysfunction is pervasive and a debilitating consequence of traumatic brain injury and mild TBI. In mild TBI, up to 15% of people continue to experience cognitive impairment, even years following initial injury. The presence of a diagnosed mood disorder is predictive of the development of cognitive dysfunction in this population and has been associated with insufficient suppression of amygdala activity. The structural and functional relationships between the prefrontal cortex and limbic structures, as well as the susceptibility of these regions to injury, may suggest a mechanism underlying emotional and cognitive impairments in TBI. The interplay between cognitive and emotional processing has been well-delineated, and evidence suggests a role of emotional interference in dysfunctional cognitive processing. Recent studies have identified neural correlates of cognitive control during emotional interference tasks. So here is some imaging from a meta-analysis conducted by Song et al. in 2017 that looked at studies assessing the brain activity of healthy controls using fMRI during an emotional stroop task, which is designed to measure the ability of someone to maintain cognitive control with interfering emotional stimuli. The pattern of brain activity seen here is as expected in a healthy sample of individuals who are completing a cognitive task and are successfully overcoming interference by the emotional stimuli with activations of regions associated with cognitive control, including the dorsolateral prefrontal cortex, the medial and superior frontal gyri, and then the dorsal anterior cingulate cortex, which is known to mediate the relationship between prefrontal areas and limbic regions. So this cognitive control network that suppresses emotional interference may be susceptible to dysfunction due to both amygdala hyperactivity as well as damage to the prefrontal cortex following TBI. So this led to our hypothesis that hyperconnectivity between the dorsal amygdala and cognitive control regions will predict impaired cognitive functioning in TBI but not in healthy controls. Our sample included 20 individuals with subacute mild TBI, three of whom were excluded from analyses for these reasons, and then 20 healthy controls, one of whom was excluded for not meeting imaging quality checks. The design was cross-sectional, and the methods included the ANAM, or the Automated Neuropsychological Assessment Metrics. This is a cognitive battery that was developed by the DoD and includes subtests that measure processing speed, executive function, and memory, and higher scores on the ANAM represent better cognitive function. ROI to ROI correlations were then a bold signal time series, were calculated from resting state functional magnetic resonance imaging. ROIs were generated and centered in the cognitive control regions that were published by the meta-analysis by Song et al., which you just saw, as well as another voxel cluster was placed in the dorsal amygdala, which is associated with a previously published dorsal amygdala network that includes many of the cognitive control regions also identified by Song et al. So, for our results, oh, and these are just images of the networks, of the stimuli here. So, briefly, in our results, we just found that both samples were well-matched in age, sex, and years of education. This was a mild TBI sample with a GCS median of 15, and subjects were about 34 days post-injury of subacute. There were no differences in behavioral outcomes on the cognitive subtests or the total score between groups, and so then we just conducted simple correlations to determine if the functional connectivity between the cognitive control regions and the dorsal amygdala was associated with cognitive performance, and we found that the left medial superior frontal gyrus, greater activity, functional connectivity between the dorsal amygdala and left medial superior frontal gyrus predicted worse performance on cognitive testing, only in TBI, not replicated in healthy controls, and age was also associated with performance on cognitive testing. So we then conducted a hierarchical linear regression to control for age, and we found that this relationship was maintained, and the overall model was significant. So conclusions and future directions, this study, we identified some brain regions within the cognitive control network that, through their hyperactive interaction with the dorsal amygdala, predict cognitive dysfunction. I think the most interesting thing about this study is that we actually replicated these findings in a completely separate sample of mild TBI in the chronic phase of injury. Future research is needed to better characterize these associations, but the left superior frontal gyrus and dorsal amygdala may serve as sites of intervention for cognitive dysfunction following TBI. Thank you. Thank you. Dr. Hayden Hoffman will be presenting comparison of preauricular reverse question mark and retroauricular curved linear incisions for decompressive hemicraniectomy. Thank you. My name is Hayden Hoffman. I'm a neurosurgery resident at SUNY Upstate. I'm going to be discussing our study comparing the retroauricular with the traditional reverse question mark incisions for decompressive hemicraniectomy. The retroauricular incision has theoretical benefits compared to the traditional preauricular reverse question mark incision for hemicraniectomy. The primary benefit is that it spares the superficial temporal artery, which may enhance wound healing. However, it provides less exposure of the inferior temporal region where bony removal is critical to decompress the temporal lobe. There's overall limited data comparing the two incisions. And so the goal of our study was to compare wound healing complications, extent of decompression, and other outcomes between the two incisions for both decompressive hemicraniectomy and subsequent cranioplasty. This was a retrospective cohort of consecutive decompressive hemicraniectomies at a single institution. We only included patients who survived at least 30 days after the craniectomy because the primary outcome of interest was wound complication within 30 days after surgery, requiring return to the OR. The other outcomes included size of the craniectomy, length of stay, discharge disposition, and reduction ICPs. This illustration shows the retroauricular incision as well as the traditional preauricular reverse question mark incision where the incision begins a centimeter anterior to the tragus at the posterior root of zygoma. And we did not routinely attempt to preserve the STA with this incision. There were 110 patients that met the inclusion criteria, 83 patients in the reverse question mark group, and 27 in the retroauricular incision group. Overall the demographics, comorbidities, surgical indications, and preoperative ICPs were similar between the two groups. The surgical characteristics were similar between the two groups except for more use of staples for skin closure in the retroauricular group. And most of the retroauricular incisions were performed by one surgeon. So there was only one 30-day wound complication after decompressive craniectomy which was in the reverse question mark group. And there were three 90-day wound complications, two in the reverse question mark group, one in the retroauricular group. After the cranioplasty there was only one 30-day wound complication which was in the reverse question mark group, and three 90-day wound complications which were all in the reverse question mark group. None of these differences were statistically significant. This figure shows the various sizes of the craniectomies. The anterior-posterior dimension in the axial plane was similar between the two incisions. The superior-inferior dimension in the coronal plane was similar. And the distance from the inferior craniectomy defect edge to the middle fossil floor was similar for both incisions. The overall blood loss for both the craniectomy and the cranioplasty were similar between the two incisions. And the operative time was slightly less for the retroauricular group after the craniectomy. However, after adjusting for the age, GCS, and surgical indications, that difference was no longer statistically significant. And the length of stay, the ICP reduction, and postoperative ICPs were similar as well as the discharge dispositions. So in conclusion, the retroauricular incision is associated with similar rates of wound complications as the traditional reverse question mark incision after hemicraniectomy and cranioplasty. And comparable craniectomy sizes and temporal decompressions can be achieved with both incisions. Thank you. And so we'll finish with our last but not least speaker, Mira Salih, speaking about the effect of long-term anticoagulant therapy on the outcome of chronic subural hematoma, a propensity score matched analysis. Thank you. Good afternoon, everyone. My name is Mira. I brought this study from Boston. Today I'd like to talk about the effect of long-term anticoagulation therapy on the outcome of chronic subdural hematoma management, a propensity score matched analysis. As you all know, chronic subdural hematomas are one of the most common neurosurgical conditions, and they're often seen in elderly populations given their increased risk of falls, and they often have the conditions where they require antithrombotic agents. In such case, it's often very hard for neurosurgeons to co-manage chronic subdural hematoma and the patient's ongoing needs for antithrombotic agents. And data and literature is all over the place, as we know, and they're often inconclusive. While we did the literature review, we noticed that studies have certain limitations. They're often designed to study as case control studies or cross-sectional studies, and they often used univariate analysis or multivariate analysis for their statistical methodology. And as you know, in univariate analysis or multivariate analysis, it's often really hard to control different confounders and to see the interactions between different variables. And a lot of studies did not differentiate pre-procedure anticoagulant use from post-procedure anticoagulant use. And some studies looked at the long-term outcome of the anticoagulant use by including patients who were followed up for over 10 or 15 years. And in summary, they often were lack of control. And in our study, we tried to overcome all these limitations. And we designed our study as a retrospective cohort study. We divided the timeline into two phase. The first timeline is pre-procedure anticoagulant use, and the second timeline is post-procedure anticoagulant use. And in our center, we found 476 patients with intervention for chronic subneural hematomas. And among these patients, 104 patients were on long-term anticoagulants before the procedure. And the rest were not. And after propensity score matching, we obtained 55 patients in each group. And we compared for immediate outcomes during the same admission. And in the second timeline, in our data, only 74 patients were restarted back on anticoagulant, and the rest were not. And after propensity score matching, we got 49 patients in each group for the comparison of long-term outcomes. And for the propensity score matching, we included potential confounders, such as patient demographics and subneural hematoma characteristics. And the selection of these potential confounders were based on literature review and expert opinions. And in our data analysis, we used one-to-one nearest neighbor matching. And for the comparison of the data, we used Pierre's chi-square or Fisher's exact test for categorical variables. Mann-Whitney test and Pierre's sample t-test for continuous variables based on distribution of the data. And in the comparison of unmatched groups, we noticed that there is huge difference in certain variables between these groups. And obviously, in this biased data, we got biased results. Here we saw that the length of stay is significantly longer in the anticoagulant use group compared to non-anticoagulant group. However, the pre-prepared procedure complications or reintervention rates were not significantly different. And after propensity score matching between the pre-procedure anticoagulant and non-anticoagulant group, we obtained 55 patients in each group. As you can see here, these two groups are very well balanced. The p-values are about 0.05. And here, we can confidently say that the results are unbiased. And length of stay between these two groups are not significantly different. We also found that the paired procedure complications and salvage treatment during the same admissions are not significantly different either. And in this second timeline, as I mentioned earlier, we identified 74 patients in the post-procedure anticoagulant group and 402 patients in post-procedure non-anticoagulant group. In the comparison of the baseline characteristics, we noticed that there was only one variable that was different between these two groups. The rest of the variables are pretty similar. You may ask why we just keep it that way without doing propensity score matching. Or just do matching for one variable. When we do propensity score matching for one variable, it can automatically select the other variables and can automatically introduce imbalance into the group. So we still matched for those variables we selected and then obtained balanced cohorts. We obtained 49 patients in each group and then compared results. We did not see any significant difference in recurrence rate and re-intervention rate during the three to five month follow-up window. And if you look at the p-value here for the re-intervention rate, you will notice that the p-value is less than 0.2, which means there's a tendency in one of these groups to have more re-intervention rate. And this tendency is not in the post-procedure anticoagulant group. On the opposite, it is in the post-procedure non-anticoagulant group. This is sort of counterintuitive and it is really hard to explain why the post-procedure non-anticoagulant group has this tendency. And earlier I mentioned the strength of our study and discussed the limitations of literature. But our study still has some limitations. The first one is it's still a retrospective design, although we try to overcome the limitations of other study by designing it as a cohort study. And the other limitation is the dosages and types of anticoagulants were different between patients. As you can see here, types of anticoagulants, and I did not put the dosages here, we noticed that dosages, especially in the warfarin, were pretty different among patients. And in conclusion, being on long-term anticoagulant therapy cannot affect the length of stay or paired procedure complications or re-intervention rate during the same admission. And restarting anticoagulant in 7 to 14 days window cannot increase the re-bleeding risk or re-intervention rate in patients who have chronic subdural hematomas. And we think that the patients with chronic subdural hematoma can be managed in a similar way to those who are not on chronic subdural, who are not on long-term anticoagulants. Thank you.

traumatic brain injury

decompressive craniotomy

ASIA examination

monitoring technologies

brain oxygen monitoring

pressure reactivity

improving outcomes

personalized medicine

auto-regulatory status

Rescue ICP trial

spinal cord injuries

thorough examination

retroauricular incision

decompressive hemicraniectomy

wound healing complications