Melanie Cole, MS (Host): Welcome to UF Health MedEd Cast with UF Health Shands Hospital. I'm Melanie Cole. And we have a panel for you today with two physicians from UF Health to highlight BLOCK-SAH, a multi-site research study involving patients with subarachnoid hemorrhage, typically due to ruptured aneurysm or trauma, that's evaluating the use of specialized nerve blocks to reduce the need for narcotic pain medications, as well as other investigator-initiated research by the Guardians of the Neuroaxis, leading neurocritical care research in partnership.

I would also like to mention that we're pleased to point out that the 2025 Blue Ridge Rankings for NIH funding has recognized that the UF Departments of Neurosurgery, Neurology, and Neuroscience Research ranked number two nationally in NIH funding. Joining me in this panel is Dr. Katharina Busl. She's a neurologist in the Division of Neurocritical Care in the Department of Neurology and the Chief in the Division of Neurocritical Care in the Department of Neurology; and Dr. Carolina Maciel, she's a neurologist in the Division of Neurocritical Care in the Department of Neurology and the Director of Research in the Division of Neurocritical Care in the Department of Neurology

Doctors, thank you so much for joining us today. And Dr. Busl, I'd like to start with you. Can you give us a sense of the vision behind what your team calls the Guardians of the Neuroaxis, how that philosophy shapes the neurocritical care program at UF Health, and how that idea shapes the culture of neurocritical care at UF Health?

Dr. Katharina Busl: I'd be happy to. I also will say that the whole spirit of what I'm going to say is really meant to be in partnership, and Carolina is actually the Director of the NeuroGuardians of our NeuroGuardians Lab.

So, in essence, what we are noticing is that in an intensive care unit where stakes are high, intensity is high, acuity is high, and the model is provision in shift work rather than longitudinal continuity of care for the reason that we are a high acuity, high intensity intensive care unit, is that all of us when in the same boat, and here literally a good boat, which is the boat of being able to provide research-guided treatments, research-guided care ideas, and improvements in care paradigms, that when we do this together as a whole group—and that's why we called us the Guardians—the outcome is going to be more cohesive, more palpable perhaps for our patients and more satisfying to us because it is not a single individual.

I think research oftentimes is investigator-driven very much based on whoever has an idea and does their thing in their isolated little research world. Our approach, again, seeks to approach this very differently through the paradigm of provision of care is always a team sport, and we wanted to translate that concept directly back to how we run our research enterprise.

Dr. Carolina Maciel: And that's right. I want to add to what Katharina is saying is that from the inception of the Division of Neurocritical Care at UF, we all came from different institutions, and we experienced really state-of-art research, state-of-art clinical care. And being trained by leaders of the field and seeing how those very successful careers, but with parallel, not necessarily really intertwined across the group in a cohesive way to address all the pillars really of what makes a program really, really strong—a clinical program, that it is really coupled. Those things cannot be really run in parallel: the clinical aspect, the research aspect, or the scientific progress, and the education mission. So, all those are really together, particularly in neurocritical care.

Melanie, I wanted to invite you to think that in the day-to-day of our professional careers, when we are interfacing with patients, it is a specialty that for us, it's another day at work. But that individual or that family member, it is experiencing a potential emotional turmoil. It is either a tragedy or a very serious operation that is required to restore function or to improve something or prevent a deficit from happening. And the advances of the scientific progress in this field are still lagging behind from other areas of medicine. So then, being able to actually push the frontiers of knowledge further and add answers to the therapeutic arsenal for our patients clinically, this sentiment of hope that you can actually achieve something together and make things better, it is something that transforms really the atmosphere of the unit from a nursing perspective, from a trainee perspective, from a clinician perspective. It really doesn't matter which professional that it is over there. And without actually bringing together the education piece and then put this forward that we are doing this together. And one clinical hand does not move forward without the research hand, without the education hand.

So, that is why it is not the Maciel Lab, the Busl Lab. It is really the Guardians of Neuroaxis, because everyone in the division plays am important role in the cohesive definition of the priorities of everything that we are going to pursue. And the scientific pursuit is aligned with the clinical and educational pursuit.

Melanie Cole, MS: That is so interesting. And I hear you when you say that research, it was in a silo. Now, there's so much information sharing and so many ways to get that information and multidisciplinary colleague approach to share with other institutions. It really is amazing.

Now, Dr. Maciel, sticking with you for a minute. For clinicians who may not be as familiar with the field of neurocritical care and how it's evolved in recent years from primarily supportive ICU care, as you were saying, some of the most serious cases, to a space where major investigator-initiated research is really happening. From your perspective, where are we today in terms of translating bedside observations into meaningful research questions?

Dr. Carolina Maciel: Something that we are very passionate about, we know nothing about the brain. And we will only start learning more about the brain when we are really paying attention to what the brain wants in that particular setting. So, when you were saying the clinical observations that really resonate, because it is by really keenly observing, intentionally so, trying to pick it up the signals. And the brain is trying to talk, is trying to really express what it is that it is required from the critical care. So, it is not provision of supportive care. It is actually provisioning, like providing the supportive care to target the demands of the brain, meaning adjusting the ventilator support, the hemodynamic support, the nutritional support, and then picking it up those very—like, sometimes we call it the brain whispers, the whispering of the brain, that it is demanding more attention towards matching what it is the energetic level that the brain needs, that the neurons need to recover, and then to prevent from further damage from happening.

What we know from our field is that we have no control of the primary insult, the primary injury. And then, we will just support through hoping that the person recovers. Now, we know that while we are supporting, a lot of secondary injury may happen, and we need to be better at picking it up, those signs of when it is happening, and then doing a careful conduction of this orchestra of every single player in the unit, in the transdisciplinary care of that patient. So, we actually play together the symphony that the brain really wants to be able to heal. Does that make sense?

Melanie Cole, MS: Well, it certainly does. So then, along those lines, Dr. Busl, as neurocritical care sits at the intersection of neurology, neurosurgery, critical care, and research, as Dr. Maciel was just saying, how has UF Health positioned itself as an academic neurocritical care unit that integrates all of these pieces? I'd like for you to speak about building that care research program and investigator-initiated clinical trials, the BLOCK-SAH that I mentioned in the intro. Tell us about that.

Dr. Katharina Busl: I think the main piece to understand or stress out that it is taking a lot of different pieces and expertise to really provide that cutting-edge piece of provision of care and being able to drive the field further through research. And that does not happen in small pockets of healthcare, right?

I think the big piece is obviously our main hospital in Gainesville, which is an amazing collection of experts in the various fields that you mentioned, neurologists, and specifically our neurology-trained neurocritical care group, our colleagues from emergency medicine, neurology critical care, our colleagues from anesthesiology that have specialized in neuroanesthesiology and pain medicine and then, of course, our neurosurgery colleagues with various sub-specializations. And among our neurology group, then the more longitudinal colleagues that see people when they have healed from the acute stage.

So in essence, I think for a puzzle to be complete, you need many pieces of that puzzle. And for complex puzzles, these pieces are more so than for more simpler pictures. And the UF system has its flagship hospital that is the main centerpiece of a larger puzzle, if that infographical reflection at all resonates.

Melanie Cole, MS: Yeah, it certainly does. So, switching gears just a little bit, Dr. Maciel, let's talk about subarachnoid hemorrhage. And despite advances in aneurysm treatment and ICU management, why does this condition remain such a challenge? Many people focus on the acute phase, obviously. But survivorship after this can be complex. Speak about some of the long-term issues patients face that have motivated these new research efforts.

Dr. Carolina Maciel: Yeah. A lot of the cornerstone for research and scientific progress in subarachnoid hemorrhage has been in understanding how to better treat the culprit, what causes the bleeding in the brain to happen, and then advancing how to treat those aneurysms. Oftentimes they are related to aneurysms. And, honestly, we are really fortunate to have state-of-the-art treatment at University of Florida with every possible new treatment to secure that.

And then, a lot of the effort also is focused on preventing additional brain injury, as we discussed, right? A secondary brain injury. Throughout the process, the survivorship, and actually it starts even in the ICU when the patient is still suffering from the discomfort that this condition causes with this worst headache of life. And then, after they recover enough to be discharged from the hospital, there are several different challenges that they may face in coming back to society. As a matter of fact, this is a condition that affect for the most part middle-age adults. And they are our workforce. Oftentimes, those challenges prevent them from really being integrated again in the society and actually be back to their functional life and be back to work. And those challenges really manifest in sometimes some thinking problems like the cognitive aspect, being able to really think clearly and execute the thought process appropriately. And also, some pain, mood disorder, the subarachnoid hemorrhage, despite all the bleeding be reabsorbed and the brain healing in as much as it can. You can still have chronic symptoms from it, such as ongoing headaches, difficulty thinking, difficulty speaking, difficulty with mobility, tremulousness. So, longitudinal follow-up is important.

And also, neuropsychiatric symptoms, right, with anxiety, depression. It is a traumatic event that oftentimes patients and co-survivors also feel afraid of return to the activity that they were doing at the onset of the bleeding. So, being able to follow those patients and continue to expand the breadth of research to address not only what physicians and clinicians target as priority, but hearing from patients and survivors and co-survivors what additional areas of research are important should be addressed.

And that is really what motivated us on BLOCK-SUB-ARACH when we have all those advances in the management of subarachnoid hemorrhage, but we remained really, left with a very scant therapeutic arsenal for addressing the headache that it is so prevalent. So, we need to continue to partner with patients and survivors to hear from them what are the topics of priority for research, so we leave really no brain behind. We leave really no patient behind in their needs.

Melanie Cole, MS: Yeah, that's so interesting. What an important need that you are both meeting. And Dr. Busl, as we're talking about the clinical problem that the BLOCK-SAH study is designed to address, and we know multi-center trials are complex undertakings, how did you build the collaboration and infrastructure necessary to launch a national investigator-initiated study? If it's described as a patient-centered trial. How does the study design reflect those needs and the experiences of patients that are recovering from subarachnoid hemorrhage?

Dr. Katharina Busl: There's a lot in that one question, and it's probably many questions. So to answer your first question, how did we build the infrastructure? I think the biggest part here was that both Carolina and I—and this comes back to the philosophy of our Guardians of the Neuroaxis Research Lab—is that we are profoundly collaboratively spirited people. And we had built relationships for the longest of our careers. Looking back really from the beginning, one builds, and we come both from different institutions, so the network grew kind of exponentially with us leaving those institutions, training in other institutions. And in each of those, not leaving everything behind, but having left with a network of people.

So when we had the research question flushed out and we had the trial in a state that we were invited by the National Institutes of Health to submit for a funding proposal, we could look back on that network that we had formed and fairly rapidly establish a consortium of sites based on our knowledge and integration within the professional societies, with our own collaborations that we had established and, again, maintained over the years. And while that still is a huge entertaining, it really also rested on personal relationships and knowing of like-minded colleagues that were interested in the topic and likewise wanted to move a field forward in a very niche aspect that is so much more important for the patient.

And that leads me to the next part of your question is, when asking patients what is important to them during the hospital stay, oftentimes pain comes to mind and is one of the very important things that patients and families are emotionally really challenged with, because seeing a loved one in pain and being miserable is awful and, of course, going through it as the patient is awful so the patient-centeredness starts right there with this observation.

While there is this big discrepancy that what Carolina mentioned earlier, the research that have been conducted and has been conducted in that field has, by and large, focused on different aspects, very important aspects on how do we acknowledge, diagnose, predict that secondary brain injury. But in the acute phase, it also has, for the longest of times, left out what is important to patients and what are patients and families bothered by more palpably and directly. So, the patient-centeredness starts right there.

The second piece is that we did really pay attention to what it is known—although a much smaller fraction than many of the numerical values of how this disease evolves over time—but paid attention to what it is known about the outcomes and the challenges that our survivors face in the realm of cognitive and mood dysfunction, depression, anxiety, how to adjust living with this, having gone through a very critical and in many times, potentially near-deadly event. So, we pulled off of those.

We also aligned with what is known as the National Institutes of Health Common Data Elements to align with other researchers that delve into this so that we can have results that are as best as possible comparable. And then, of course, we honed in on the aspect that we are studying first and foremost, which is the pain aspect, and borrowed a lot of elements from pain research, translating them into our neurocritical care context, which is a novelty in itself.

Melanie Cole, MS: Yeah, this is such a fascinating topic. And so Dr. Maciel, one of the themes, a recurring theme that I'm noticing as we're talking here today in your program is that concept of team science and shared leadership. What does that collaboration look like across neurology, neurosurgery, critical care research teams? Tell us about the power of team science and how it works within UF Health.

Dr. Carolina Maciel: The first thing that I want to point out is that resourcefulness is what comes to mind. It is being attuned to what do we have available to us in terms of expertise, in terms of really brain power to make things happen and to innovatively address frustrating questions based on the frontiers of knowledge, right?

So then, what that looks like is that as you could see, if you look at our scientific portfolio, you can see all different themes of research. It is outcome prediction. It is neuromonitoring, so we can actually understand the whispers of the brain. It is novel approaches to refractory seizures. It is novel approaches to pain as the example of BLOCK-SAH. And it is novel approaches to traumatic spinal cord injury. So, whatever it is that we face on the day-to-day, as a frustration from this is all the knowledge that there is available. This is the state-of-the-art, and we have access to everything that it is known to benefit, and that is still not enough because the challenge that we are facing in our field is that we need to push. We need to move the needle further. We need to move forward. It is really a sentiment of looking around, picking in each other's brains with humility, with understanding that there is so much more to get discovered. There is so much more to be learned about the brain and then about the recovery. And then, looking around and see who is the best person that we can partner with for that specific expertise, and we assemble the team. And that's why BLOCK-SAH has this partnership of us in neurocritical care, anesthesia, and neurosurgery with SPICO, which is another clinical trial that we developed together, arising from University of Florida.

It is a partnership across colleges, not only across department in the College of Medicine, but across college with experts in the biomarkers, biochemistry, and understanding neuroplasticity and recovery, including the neurorehabilitation aspect. And the partnership with the expertise here in machine learning that our division also has with bioinformatics and the critical care artificial intelligence group.

And this is what it is about. It is about acknowledging, staying attuned to all the breadth of resources that we have available, and that is the shared leadership. Because this is about making progress, scientific progress, that translates into meaningful impact in the field, to push it forward so then we are better clinicians. And we continue to train leaders of the field. And we cannot do that without sharing the goals and then sharing the accolades, sharing the accomplishments and sharing the resources. And there is no way of doing complex research without team science. It truly is an orchestra with many different instruments, and they all serve a specific purpose. And they are much more simpler and less impactful on their own, but so much more rich and impactful together.

Melanie Cole, MS: Oh, that was beautifully said. And really, what an exciting time in your field and what exciting work you're doing. I'd love to give you each a chance for a final thought here. So Dr. Busl, another major goal that we've talked about a little bit is cultivating that next generation of clinical scientists and physician scientists. So, how are trainees and early career investigators involved in these projects beyond BLOCK-SAH? Tell us a little bit about how these investigator-initiated projects or research directions are emerging from this program and how you're involving these early career investigators in them.

Dr. Katharina Busl: We have built our research enterprise on involving learners of all levels, and we see ourselves, of course, as lifelong learners too. So, that means we have really all stages, both in the clinical as well as purely research-oriented scholars as we have named our team members.

And that starts from undergraduate students, and there is no one that cannot contribute in one way or the other. I think that is our philosophy as long as there is a will and there is the opportunity to join our team. And our scholars, again, that spans from undergrad to graduate to postgraduate students and even graduated physicians that are laying the foundation to become physician in training through residencies and are seeking to acquire research-minded skills before they embark on the clinical training side. We have included them really in all steps and in all layers in our research programs to expose not only them to opportunities to learn in each of those states, but then also when they go on to become clinicians and to train in the clinical field, to think back and integrate those items from the very beginning.

And I think not wanting to necessarily speak for Carolina too, although I think in aspects we probably share a similarity that for us during our training, that was an aspect we had a desire to do, and it was moved to the back burner for a variety of reasons, and then we unfolded it later on. So, we made a real effort to offer this training before the clinical training starts to allow the opportunity to integrate from the very beginning.

Dr. Carolina Maciel: That's right. And then, to add to what Katharina is saying is that we are really mindful that success looks like in a different way to different people. And we really are about being trailblazers in all aspects. And innovation comes from these potentially unexplored pathways. And the more comprehensive and diverse group that we have from different backgrounds, including in level of training and also experiences in life prior to really joining and coming at UF, our strength comes from having these complementary angles and vantage points that allows us to have the complementary skills and growth.

And then, having this shared growth mindset and the complementary skill set, this is what allows us to really propel forward, despite what many will say unconventional pathways, right? Like, as researchers, our trajectory was different than different institutions, right? Like, if you think about the Neurocritical Care Division is actually completing ten years this year, right? As Katharina came to really found the division and create this division. So, we are only ten years old, which is really nothing if you think about the field of neurocritical care and the tradition of institutions.

We are able to actually have such momentum for really pushing the needle and moving the field forward because of this creative and all-encompassing approach to let's explore all the pathways together. Let's really stay attuned to all the resources that we have. And it is truly about legacy, So, by training the next generation of impactful academic neurologists and neuroscientists, it's how we are best positioned to truly make an impact on the field, beyond our own discoveries during our lifetime.

So, it is planting the seed of that dissatisfaction with the status quo, that the progress that we are experiencing right now, it's excellent, but it can be better. And there are many questions left unanswered. And for as long as our patients, their families and our team poses or ponders with a clinical challenging question, the job is not done. And then, the more that we can actually plant that seed, that we need more guardians of the neuroaxis everywhere, not only at University of Florida. We are best positioned for the true mission, that the patient is really the center of everything that we do.

That is really the purpose. That is why we wake up so early in the morning. That is why in the middle of the shower, there is that thought process of like, "Hmm, I wonder what was happening with that patient how could I have done something different? How could our team have done something different?" It is that unsettledness that really propels us to explore further, go deeper, and challenge the status quo.

Melanie Cole, MS: Wow. Thank you so much, both of you, for joining us today. That was an incredible episode, and what a great discussion. Thank you both for all the great work that you're doing and for joining us today and sharing your incredible expertise for other providers.

To learn more about this and other healthcare topics at UF Health Shands Hospital, please visit innovation.ufhealth.org. And to listen to more podcasts from our experts, please visit ufhealth.org/medmatters. That concludes today's episode of UF Health MedEd Cast with UF Health Shands Hospital. I'm Melanie Cole.