Doc Talk

There is a misconception that palliative means end of life care.  But that's not how we think about palliative surgery at all. Palliative surgery is when we're looking at not necessarily curing something, but alleviating something. Cook Children’s Palliative epilepsy neurosurgery explains how kids with intractable epilepsy are getting a better quality of life.

Any surgery can be challenging and come with risks. But when that surgery involves children, it comes with a unique set of things the surgery team has to consider that are very different from adults. Dr. Kanika Bowen-Jallow delves into how those differences impact both the surgical team and patient outcomes.

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Dr. Scott Perry, Medical Director of Neurosciences and Dr. Christos Papadelis, Director of Neurosciences Research along with Dianna Grado, Clinical Coordinator for Neurosciences Research, explore how breaking research boundaries creates limitless possibilities, paving the way for world-class research – and results once thought impossible for kids and young adults with neurological disorders.

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Meet Dr. Papadelis
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Transcript

00:00:11

Host:  Hello and welcome to this edition of Doc Talk. We're honored and excited today to be speaking with key researchers at Cook Children's Jane and John Justin Neurosciences Center. We're joined by Dr. Scott Perry, Medical Director of Neurosciences, Dr. Christos Papadelis, Director of Neurosciences Research and Diana Grotto, Clinical Coordinator for Neurosciences Research. Made up of some of the brightest minds in the world, individually and together, this research team has won numerous awards and accolades for their many achievements in neurosciences research. As a result of their work. They've had a major impact on improved outcomes for children and young adults with neurological conditions, not only here in Texas, but nationally and internationally as well. Welcome.

00:01:00

Dr. Perry: Thanks for having us, Jan.

00:01:02

Host: I know you all are very busy. So let's just dive right in. You've done a lot of great research here at Cook Children's. Over the last two years Cook Children's Jane and John Justin Neurosciences Center has significantly expanded the Neurosciences Research Center, which includes extensive research into the causes comorbidities and treatments for children and adults with disorders of the nervous system. What was the motivation behind that? Dr. Perry,

00:01:27

Dr. Perry: Jan, you know, Cook has had a long history of clinical excellence, right. And we've been doing research for a long time, but a lot of people honestly don't know that. We wanted to take research a step further. So we'd always embedded it within our clinical practice on a daily scale. But in order to provide the best care for the patients we take care of, you have to take the next step of "innovate," and bring new treatments and therapies and things of that nature. Given that our practice has always been primarily a clinical practice with, you know, physicians seeing patients every single day, research is kind of hard to squeeze into that. So we said you know, how can we put together a neuroscience team that is dedicated to doing research every single day? And that's really where the idea for the Dodson Neuroscience Research Endowment came from. A generous gift from Pitt Dodson provided us an endowment so that we would have essentially grant money available to hire a full research team, which is where Dr. Papadelis came from, as a neuroscience researcher, to join us and create this team who is embedded into our clinical practice every day, is always there with the docs in clinic, and tries to help us develop research that has near-term benefits to our patients. Like we want to do research that is applicable to the care of the kids we're seeing right now, as well as the kids we might see later on in the future. So you know, we're focused primarily right now on epilepsy and movement disorders. Those are the two biggest areas that we built teams around. And the future holds several other sections of neurosciences that I think we'll talk about as we go through the rest of our conversation today. And then we focused on two types of research, which we'll talk about throughout this conversation today, the first being more kind of industry sponsored research. So things where we're working with industries like the pharmaceutical industry, etc., to develop treatments for patients, and we focus specifically on a lot of rare diseases, but then also investigator initiated research. So those are, those are things that are born and bred at Cook Children's. Ideas that we have, that we want to develop to help, uh, help our patients and to innovate in their care.

00:03:43

Host:  So Dr. Papadelis, let's talk about your team. You have pulled together some of the brightest minds in the research field to collaborate. Can you talk about the qualities of the people you have brought together and the expertise they bring to the department?

00:03:59

Dr. Papadelis: Thanks, Jan. Indeed, we think these two last years, we managed to attract productive scientists from all over the world, formulating a research team of 16 people in total. We had Crystal Cooper, a former assistant professor from UT Southwestern, who joined my team last year, bringing expertise on a new imaging technique called functional magnetic resonance imaging, or functional MRI, for studying the comorbidities of epilepsy, such as depression anxiety. Dr. Georgios Alexandraikis, associate professor at the University of Texas at Arlington also joined our research center, serving as our liaison with UTA and bringing tremendous expertise on optical and neuromodulation techniques. We also hired Dr. Yanlong Song, a former postdoctoral fellow from University of Virginia, who joined the team offering expertise on kinesiology and the study of movement disorders such as cerebral palsy and dystonia. Both of them Dr. Cooper and Dr. Song received research grants within the last two years to support their studies from the Jordan Elizabeth Hollis Foundation, and the American Academy Cerebral Palsy and Developmental Medicine. The group has also several PhD students from Europe and Asia, who joined the team to work on epilepsy projects and managed to excel actually within a short period of time. Two of them are Ludovica Corona and Margherita Matarrese, they actually won the Young Investigator Award from the American Epilepsy Society last week, a prestigious award that indicates the quality of our research. Their studies actually were selected among the best from over 1,300 applications submitted in the annual conference of the society.

00:05:43

Host:  So your team has been a leader at using advanced neuroimaging techniques in the evaluation of conditions such as epilepsy, movement disorders and cerebral palsy. As, as Dr. Perry just mentioned, can you tell us a little about your current projects?

00:05:59

Dr. Papadelis:  Yes, of course, like, our team has established a unique set of advanced neuroimaging techniques, which help us better understand the anatomy and the function of both for healthy and sick brain. My main focus is pediatric epilepsy the most common neurological disorder in children. And with my research, I tried to help children with epilepsy, who are unable to control their seizures with anti-seizure drugs and suffer from what's called drug resistant epilepsy. So approximately one out of three children with epilepsy suffer from this condition. And for these children are the best available treatment is brain surgery. The challenging part of this kind of surgery is that, in many cases, we don't know exactly where are the seizures. They start in the brain, so this means that we don't know which brain area we should resect during surgery in order the child to become seizure free. By using a unique combination of data from new imaging techniques such as magnetoencephalography, or MEG, and high-density, electroencephalography, or high-density EEG, my team develops advanced biomarkers which can help in the precise delineation of the area where the seizures they start. So this kind of research can help children with drug-resistant epilepsy to become seizure free. My team also works with children who suffer from movement disorders and more specifically with cerebral palsy. Cerebral palsy is the most common motor disorder and one of the most common neurological disorders in children. Children with cerebral palsy are often unable to walk and, or they have significant motor deficits. And the underlying cause is a kind of a brain injury that took place either during during birth or before birth in utero. So by using a combination of neuroimaging techniques, my team tries to understand what we call brain plasticity. How the human brain in children with cerebral palsy has been adapted to this injury in order to become more functional and effective. Our system also recently purchased a rehabilitation robotic device for treating children with cerebral palsy and trying to map functional and structural changes in their brain due to rehabilitation.

00:08:14

Host: So correct me if I'm wrong, but I understand that not only do you have investigators on site, but you're also working with researchers all over the world on projects related to epilepsy and movement disorders. What is the impact of that for patients through this research?

00:08:30

Dr. Papadelis:  Um, my thing is indeed, active collaboration with top tier academic institutions around the globe, will have an active collaboration with Boston Children's Hospital, and Massachusetts General Hospital, both affiliated with Harvard Medical School, my previous institution, and the New York University, as well as academic and health institutions in Canada and Europe, such as the Hospital for Sick Children affiliated with the University of Toronto, and the University of Campus Bio-Medico of Rome in Italy. Our collaboration my team believes that our research will benefit children with neurological disorders, such as epilepsy and cerebral palsy by providing access to unique data that can help their epilepsy surgery or access to unique rehabilitation techniques, such as the robotic therapy for improving the motor deficits of the upper and lower extremities.

00:09:22

Host:  Now, Dr. Papadelis and his team are not the only members of Cook Children's Neurosciences involved in investigator initiated research. Dr. Perry, I understand we were the first pediatric epilepsy center in Texas, invited to join the Pediatric Epilepsy Research Consortium, also known as PERC. What is that organization and why does that matter?

00:09:44

Dr. Perry:  Now Jan, the Pediatric Epilepsy Research Consortium was was founded several years ago to create an environment for collegial research between institutions. And the reason that's important, especially in the neurology world and epilepsy in particular, which this organization focuses on, is that many of these conditions are quite rare. And so for any center to gain a lot of expertise in one disease process may be difficult and may take years and years to do it. By taking a team that is willing to work together, and I think that's something that we don't see enough of in the world, frankly, and certainly the United States, is institutions willing to share data together and work together to solve problems. And that's what PERC is all about. I'm honored to be a member of their leadership steering committee. As part of that organization I founded a few years ago, something called the Epilepsy Surgery Database Project, that is a project that currently includes 24 pediatric U.S. epilepsy centers, collecting a number of data points on all children referred for epilepsy surgery. And that's just that's just one example of the power of what we can do. You know, why is that important? Epilepsy surgery may only occur a few times, and some centers may occur, you know, 70 or more times, and other centers, and their experience, their expertise and their processes of how they do it, how they select the patients that have surgery, the outcomes of those patients may be very different depending on where you are in the country. And by putting that all together, we hope to be able to compare the effectiveness of the ways we we evaluate children, and when we do pediatric epilepsy surgery so that we improve the outcomes, we standardize the way it's done across the country. And here in only two years’ worth of existence, we've already enrolled well over 1200 children into that database, which would have taken any one institution, you know, a decade or more to have to gather that. And so a lot of exciting things come out of organizations like that. And then each can then take that data and can ask their own questions. And then, you know, as a team, across the country, we're trying to solve these problems. So it's very important to be a member of things like that.

00:11:59

Host:  So the research team at Cook Children's was instrumental in initiating cannabidiol and fenfluramine research to help treat pediatric patients with rare genetic epilepsies. Now, these are considered approved treatments. Dr. Perry, can we dive a little more into clinical trials we are doing now, as well as the process for participating in one of these trials?

00:12:22

Dr. Perry:  Yeah, absolutely. You know, while investigator initiated research is super important, we can't, we can't underestimate the importance of industry sponsored research, and the development of new drugs. And for us, a lot of the focus, as I said earlier, is on rare rare disease or rare genetic epilepsy in particular, because that's, that's an area of my interest, Dravet syndrome and other channelopathies such as such as that. And oftentimes, these these trials, these are conditions that don't have approved therapies, you know, so people are doing whatever is the consensus best approach to treat them. But fortunately, there's been a lot more interest now in developing therapies for them. And by doing these projects, you open that door to those therapies as this may be the only way to get it until it's FDA approved. So being able to offer that is really important, you know, in the past I had always shied away from industry sponsored research, because most of the trials were drugs that had already been tested and approved in adults, they were available at the pharmacy to be used off label. And you know, doing the trial just really didn't help as much, but now we have trials that are specifically designed for children with very rare conditions. And offering those therapies to them is just instrumental to, you know, great outcomes, which you can see what the outcomes of both those trials, you mentioned. The cannabidiol and the fenfluramine had really meaningful impact on people with Dravet syndrome and Lennox Gastaut syndrome. We've got a lot of exciting stuff coming up. We are, you know, we try our best to offer as many, many studies for rare disorders as as we can. We have some upcoming studies for SCN8A encephalopathy, will be the first drug trial for this condition. We have multiple ongoing trials for Dravet syndrome, some of the disease modifying therapies using antisense oligonucleotide therapy and viral vector therapy, which are really exciting treatments that are aimed at the genetic reason for this condition. So not just treating the symptom of seizures, but trying to correct the genetic abnormality. So that that's exciting. A couple other drug compounds we're looking at for Dravet syndrome and some other rare epilepsies. So I yeah, I think it's an important thing. We try to stay engaged and try to offer as many as we can, so that our patients have, you know, lots of options out there.

00:14:51

Host:  Terrific. So since the beginning of COVID-19, we've learned that not everyone is aware of the phases of drug development and the method of getting treatments through FDA approval to make them available to patients. For families or physicians listening, that may not be as familiar with the phases, can you walk us through the process? Where did these ideas come from? And how does one go from discovery to availability?

00:15:18

Dr. Perry:  What a great question. You know, most of these, most of these compounds begin as, you know, drugs and basic science labs that you know, show that, you know, basic science experiments that they may work towards epilepsy or maybe they work for that specific genetic condition that we're talking about. And once there's some kind of signal there that you might have something that is useful, that could benefit, then it's going to go through multiple stages of clinical trials. The first stage, or what we call phase one, is one that is really just taking the compound and mostly using it in healthy volunteers just to get a feel for its its safety, toxicity, doses, you know, is it is it okay to use in a human basically, now that it's moved from an animal model. A phase two trial. So phase two, and three, and four are things that most people are going to encounter more often. A phase two trial is one in which a group that has the disorder under interest is being studied. But the purpose of the study is really to understand the safety of the drug. So these are going to be smaller trials, we want to make sure it's a safe drug to use in this particular disease process. But we're not going to have maybe enough people in the trial to really understand how effective is it yet? The phase three trial is the one where you're going to assess not only how safe is it, but how effective is it for the problem at hand. Most of these are frequently double blind, placebo controlled trials. So if we break that down, you know, what does that mean? So double blind means that myself as the investigator, and the the caregiver, or the patient do not know what treatment they're on. It's placebo controlled, which means one, some people are going to be on a placebo, meaning not an active substance, and some people are going to be on the drug under investigation. And the reason that's important is because that removes, by double blinding it and using a placebo group, we remove the bias that people may have right? You can imagine if you know you're in a research trial, and you're know you're getting a drug that is supposed to be effective for a condition, some of your symptoms may be better, and they might not be better because they're actually better, but they might be better because you feel like they ought to be better, because you're in a trial specific, you know, to this condition. And so that really helps eliminate that. So you can get a real feel for what is the medicine doing. Same with side effects, right? Because lots of side effects are common. Nausea, vomiting, dizziness, headache, I mean, occurs all the time. So you have to have placebo controlled double blinded studies to understand is headache really more frequent people getting this new treatment under investigation? Or is it really the same amount that happens to people who aren't under the you know, on that medicine? And then a phase four trial is after the drug is out it's approved, it's that post kind of marketing information. And that's important, too, because phase three trials are highly regulated protocols, we got lots of rules to follow. You were you know, on top of doing everything exactly as it's supposed to do. And in reality, that's not real life. So when you leave the trial, and you go off to live real life, and you've got all kinds of maybe different medicines, you're using different activities, and whatever we need to understand, did what happened in the trial hold up in the real world as well and as is still safe and as efficacious as we saw in the original trial.

00:18:52

Host:  Performing clinical trials is a complicated endeavor. And it takes a team of experts in research to do it well. Dr. Perry, you amassed quite the team, making Cook Children's a primary site for many studies, particularly those focused on rare genetic epilepsies. You said many times before, the most important member of the team is the clinical research coordinator, often a nurse that serves as the quarterback for the study, making sure the protocol is followed precisely and working closely with you to ensure the safety of all the patients participating. We're lucky to have Diana Grado join us today. Diana serves as the clinical research coordinator for almost all of Dr. Perry's studies and has extensive experience in clinical trial research. So Diana, how do you determine if someone is eligible for a clinical trial?

00:19:40

Diana Grado:  So Dr. Perry is really great at identifying patients. So whether they come from him or an outside referral, he usually starts with a conversation to determine basic eligibility. Do you have this diagnosis? Do you have enough seizures? And once that is confirmed, then they will all come in and do a screening visit with me. To start the screening visit, we always start with informed consent. Informed consent is super important. It goes over the trial from A to Z, what to expect who we are, how long the trial is, how many patients are going to be on that trial, the known side effects so what to expect it every single visit. And one of the most important things that we let everyone know who does a clinical trial is that it's completely voluntary. So at any point and any time, if you want to stop the trial, then you have that right. Once that's signed, then we start working on eligibility criteria. Every study has inclusion and exclusion criteria, that every patient must meet 100%. And that is to ensure that we have good trial data and that we are keeping everybody safe. And to determine that criteria, patients will typically undergo a bunch of assessments. So whether that be labs, an EKG, an echo, just a whole gamut of things to determine eligibility. And then for epilepsy, one of the main things is epilepsy history. Dr. Perry will do a very thorough review of their current seizures and past seizures and diagnosis. And once that is completed, we send that off to an epilepsy consortium, typically, and they will approve that. And then lastly, because all we do, for the most part is epilepsy studies, we will send patients home with a diary. And so they are to document every seizure they have typically for about 28 days to make sure that they are having enough seizures to qualify. Because to determine if a medicine is working, we need to know that they had enough seizures to start with and that we can see a decrease. And so once all that's done, they go home for 28 days, maybe longer. If they meet all the criteria, then they come back and they start the trial.

00:22:11

Host:  So for parents who are patients out there that might be considering participation in clinical trial research, what might you tell them to expect?

00:22:19

Diana Grado:  I would tell them that they will see us often, and that the visits are quite long. Typically, if like I mentioned before you see a whole bunch of disciplines you come in, you will meet with me for every single visit, you'll meet with Dr. Perry for every single visit. But we will send you to lab and we'll send you to EKG and we'll send you to every discipline needed to follow the protocol that the sponsor has, has written. We ask a lot of questions to make sure that you are safe and we're not putting you at risk while you're on this new medication. It's different than Dr. Perry writing you a prescription for a drug that's already FDA approved. We have to make sure that we can document those side effects. And that we're just being really thorough is the big thing. And I think the important thing for patients and parents to know is that it is a huge commitment on their end. Because it is it's it's a lot. But it's very rewarding when you get a new medication that no one else can get. And it works for your child. It's no guarantee. But that's always our hope to offer something that is going to make a change.

00:23:36

Host:  So are there age restrictions or age limitations?

00:23:39

Diana Grado:  Yeah. Every protocol has age requirements. So I mean, I say typically we we see pediatric patients, but we've also seen older patients, adults, because you know, we offer the study, and if they qualify, then we're gonna see them.

00:23:55

Host:  If there is a physician with a patient that might qualify to participate in one of our clinical trials. How would the physician refer their patient or reach out to you for more information?

00:24:06

Diana Grado:  I think if we have a physician or even a parent who's interested, a good thing to do is go to go to our website, go to Cook Children's dot org, go to the search box, search for research and we will have a list of all available trials, it should be up to date and there should be a link to contact us. You can always call Dr. Perry's office they will get you in touch with me or the main phone number for Cook and ask for the research department or myself. And I think if you don't find what you need on Cook Children's website, go to clinical trials.gov. They have a great search engine. You can type in the diagnosis, they will tell you the you know the what's going on in the study who's doing it and have contact information on there as well.

00:24:56

Host:  Cook Children's has been participating in research for decades. And now that we have the Neuroscience Research Center, we are expanding the capabilities of collaborations with more institutions and other researchers worldwide, creating a hub for research. What do you think the future holds for neuroscience research at Cook Children's, Dr. Perry?

00:25:14

Dr. Perry:  Well, you know, Jan, we talked a lot today about, you know, our own investigator research. And of course, we spent a lot of time talking about clinical trials and really focused on epilepsy. And that's logical, because that's what Diana and I do every day. I think the first thing to know is that I think the clinical trial research will continue to grow well beyond that. And it's already grown well beyond that. We have, we have faculty that do research in demyelinating disorders like multiple sclerosis, neuromuscular disorders, like muscular dystrophies, etc. And so and to add to what we were saying earlier about, how would you find out about trials when you when you go to the website, and you look up the faculty members in their areas of neuroscience interest, oftentimes it includes information about maybe what trials they are participating in, and they have available, so those are always important places to look. I think the future is super bright, other otherwise from Dr. Papadelis and his team, you know. I mean, look at what has occurred in basically two years’ worth of being here. A group of none became a group of 16 as got in the American epilepsy society meeting coming up, but 25 abstracts from you know, our institution, and our partner institutions, which is a huge jump over, you know, two or three, just a couple years earlier. So if that happened in two years, I think you can expect a lot of growth from that. We do hope to build out into the other regions of the neurosciences. One of the purposes of bringing in Dr. Cooper was her interest in mental health. And so not just looking at the mental health, comorbidities of epilepsy with mental health, comorbidities of other disorders of the nervous system, building into research and autism and developmental pediatrics with our partners of the Child Study Center at Cook Children's. So there are really endless opportunities. Cook, Cook Children's Neuroscience Center, the Justin Neurosciences Center is a large is a large group, right with over 30,000 outpatients seen each year. There's a great number of children getting care for a number of conditions here and we have a lot of opportunities to continue to improve on all of that condition all of those conditions, with with research and that's what we intend to do. So it's it's really exciting. And the Dodson endowment has just been a great foundation to really get that started. And, you know, we plan to just continue to grow that, grow the team, and continue to expand on the great work that's being done.

00:27:54

Host:  Really is super, super exciting. So if any of our listeners want more information about neuroscience research at Cook Children's, or clinical trials available, or what other resources are available, where can they go?

00:28:06

Dr. Perry:  The website is going to be your best and easiest place to get linked up to lots of things. So that's www dot Cook Children's dot org backslash neurology that'll take you to the main site and if you just look on the left of the page, there's a tab for research, you can click on that you can find out all all about Dr. Papadelis's program. As well as if you look at the individual faculty members, their their research is listed. And those are probably the greatest places to get the up-to-date stuff from from Cook Children's.

00:28:39

Host:  I really want to thank you all for joining us today. Appreciate your valuable time and the groundbreaking work that you're doing.

00:28:46

Dr. Papadelis:  Thank you

0028:47

Dr. Perry:  It's been a pleasure

00:28:49

Host:  And thank you for listening. If you'd like more information about this program or any program at Cook Children's, please visit us at Cook Children's dot org. Like what you heard, you can subscribe to Cook Children's Doc Talk wherever you get your podcasts. You can also subscribe to our Doc Talk newsletter on our Health Professionals website.

With the growing number of pediatric congenital heart patients growing up thanks to ever improving medical care, Dr. Scott Pilgrim takes us inside one of the few programs in the nation that bridges the gap to adult care without missing a beat.

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Transcript

00:00:02

Host 

Hello and welcome to Cook Children's Doc Talk. Today we're talking with Dr. Scott Pilgrim, who is the medical director of the Adult Congenital Heart Disease program here at Cook Children's. Dr. Pilgrim is board-certified in pediatrics, internal medicine, pediatric cardiology and adult congenital cardiology. Prior to coming to Cook Children's, Dr. Pilgrim founded the adult congenital heart disease program at the Steven and Alexandra Cohen Children's Medical Center in Long Island. Today, under his leadership, the Adult Congenital Heart Disease program at Cook Children's Medical Center has shown tremendous growth with over 500 adult visits every year. Welcome Dr. Pilgrim.

00:00:42

Dr. Pilgrim 

Thank you.

00:00:43

Host 

So growing up with a sister who had heart surgery as a child had a major influence in your life, and ultimately led you to your role here at Cook Children's as medical director of the ACHD program, compared to many other cardiac specialties, adult congenital as a specialty is relatively new, can you give us a little history.

00:01:03

Dr. Pilgrim 

So, as you mentioned, my sister was born with a congenital heart disease. And so growing up with this in my family, it became of interest to me at a very young age. But as a field, congenital heart disease is something that has been around obviously, for several decades, this field of adult congenital heart disease has grown primarily because of the success stories that we've had in pediatric cardiology, namely, the surgical outcomes and the longevity of patients related to improved surgical care, improved surgical technique, you know, recognizing disease, early on fetal diagnosis, and so on and so forth. And so the incidence of congenital heart disease really hasn't changed. But the lifespan of individuals growing up with congenital heart disease has tremendously improved. And so when we think about the growth of adult congenital heart disease in the country, it really has grown out of necessity, because these kids are now growing up and becoming adults. In fact, the number of adults with congenital heart disease now far outweighs the number of children with congenital heart disease in the United States, almost to a 60-40 split. That care gap that has then been created, because of the increase in the number of adults with congenital heart disease has put a lot of strain on adult and pediatric services, namely, because adult providers may not be familiar with the congenital heart disease and pediatric providers may not be familiar with adult onset disease. And when you have adult onset disease in the context of an underlying congenital heart problem, it certainly can lend itself to some unique challenges. And that's where the field has essentially been born out of. Over the last decade or two, there has been a real push for subspecialty care in this field, so that individuals are actually seeking out care with adult congenital cardiologists rather than adult cardiologists or pediatric cardiologists so that we can standardize care, and hopefully even further improve outcomes for these individuals. So the first board exam was actually offered in 2015, for this field. So it's a very new subspecialty that's been offered now every other year for the last six years. So 15, 17 and 19. And so there is a growing body of board-certified adult congenital cardiologists in the country, but it still needs many, many more providers in order to fill the care gap that exists.

00:03:16

Host 

Awesome. So when did you begin the program here at Cook Children's?

00:03:20

Dr. Pilgrim 

I would say that the program really began before I got here. And because there was a think tank moving forward with regards to how we were going to manage the number of individuals growing up with heart disease here in the pediatric facility at Cook Children's, obviously, when I got here, the program began in name, there was a fair amount of infrastructure and discussion with the administration and within our group about how that was going to take place. So I think to answer your question more pointedly 2014, February 2014.

00:03:49

Host 

So how prevalent is congenital heart disease?

00:03:52

Dr. Pilgrim 

That's an excellent question. Congenital heart disease is the most common birth defect in children. And it has been for some time. The incidence, as I stated before, has really not changed over the last 80 or 90 years. We think that that incidence is somewhere around eight in 1,000 live births. Just to make the math easy, we tend to quote a 1% incidence of congenital heart disease. And so that 1%, obviously, is made up of a whole spectrum of different types of disease. And when we break down the complexities, if you will, of congenital heart defects, it really breaks down into about 50% of all defects being simple, another 30 to 35% being moderate complexity, and then the very complex types of congenital heart disease account for about 10 to 15% of the remainder, but the incidence has remained the same but because again, of surgical outcomes and improved lifespan of these individuals, they're now becoming adults.00:04:45

Host

So studies show that there's been an increase in the number of adults diagnosed with congenital heart disease is this totally because of better diagnostics in children and adults, longer lifespans or people getting sicker as well?

00:04:57

Dr. Pilgrim 

I think it's a combination of the three. Certainly we know that diagnostics have improved in pediatric cardiology, and our education in the pediatric population of making sure that individuals are aware that they need lifelong care has improved. That said, there is a fairly lengthy amount of time in our history, where kids who have undergone surgery for their congenital heart disease may not have been told or may not have known that they needed lifelong care. And so they're coming back into care later on, either because they heard about an adult congenital cardiologist, or in some circumstances they'd started to develop complications related to their congenital heart defect. So I think it's actually a combination of improved education in pediatrics, as well as adults who are coming back into care after being lost. I would also add that when we look at transitions, which we may talk about later, the transitions education program has certainly improved locally, our ability to make sure that these kids don't get lost to follow up. But in nationwide when we look at the attrition rate, if you will, of kids, there's a large number of kids over the age of 15, that fall out of care for various reasons. Some of it's because they moved, some of it's because they don't know, they may have limited resources, so on and so forth. But there is a fair attrition rates within the pediatric population that don't know that they're supposed to follow up in adulthood. And so they will also come back into care one way or another in adulthood?

00:06:21

Host 

So what is the significance of having an adult congenital program at a children's hospital?

00:06:26

Dr. Pilgrim 

Well, I think the significance is, is that we're successful at what we do. And I'm actually very proud of that, as a group, we've had very, very good success rates with our kids. It's a testament to the care that's been delivered by my partners and the surgery program here to even be able to talk about dealing with adults who have grown up with congenital heart disease, obviously, you have to start with kids, babies and young people to get to that age group. And so the significance of having an adult congenital program at Cook Children's is important, because I think it really establishes a footprint for the legacy that Cook Children's has created by doing congenital heart care for as many years as they've done it. And it also speaks to the Promise of Cook Children's that we did heart surgery as children, but we haven't neglected the fact that by virtue of us doing surgery as a child, now we have a growing population of adults with congenital heart disease that still need specialized care.

00:07:19

Host 

So are there other children's hospitals that are doing this?

00:07:22

Dr. Pilgrim 

There are. I would say that it's very variable as far as the individual institutions and how they tackle this problem, which again, speaks to the unique nature of the field. There are freestanding children's hospitals that do this, there are freestanding adult hospitals that do this, the majority of the time, it's a combination of the two where there are children's hospitals that may have been built within an adult hospital. And so there's lots of different ways to get the program taken care of it really is an institutional decision as far as how they're going to handle the care of adults.

00:07:54

Host 

So is there going to be at some point in need to develop sort of a structure for care across the nation in terms of how this this care is?

00:08:03

Dr. Pilgrim

Oh, for sure. Yes. There are guidelines for the care of adults with congenital heart disease that came out in 2008. And then revised again through the American Heart Association in 2018, that outline basically the primary care of adults with congenital heart disease and various disease processes. That said, where it gets done is, again, institution specific, but as far as protocols, there is an accreditation process that we will be going through here at Cook Children's, hopefully over the next two to three years, where we will actually have an accredited program and recognized nationally as an ACHA accredited, adult congenital heart disease program. And part of that accreditation process is geared towards making sure that the necessary infrastructure is created and followed on a routine basis. Not to say that everybody is cookie cutter recipe based medicine, but it certainly is protocolized to where we know that this type of disease process should be handled at that institution.

00:08:55

Host 

So an unexpected an important service is the connection between pregnancy and heart disease. How did that come about? What is its significance? And where do you see this going?

00:09:05

Dr. Pilgrim 

So pregnancy and heart disease is an interesting field. If you think about, let's say, 30 years ago, the number of women that were of childbearing age that had heart problems, the majority of the time was related to rheumatic heart disease. So more valvular heart disease, mitral and aortic valve disease, and with the increase in the number of adults with congenital heart disease now growing up and becoming childbearing age, both men and women, the idea of having children obviously, is something that you would expect with a young adult, they'd want to raise their own family and live a normal life. That's the whole goal of taking care of these patients. Obviously, half the population that I take care of are female, and they're certainly birth control and pregnancy considerations that factor in. But now congenital heart disease has become the most common reason for women of childbearing age to have a heart problem, which again, speaks to that care gap and who is going to take care of the woman with congenital heart disease, number one, just at baseline, but now you're Adding the pregnancy physiology, which is a different entity in and of itself on top of their congenital heart disease physiology and the interplay there certainly adds some potential challenges. As far as where it's going. It's getting very busy around here with our pregnant ladies. We actually have a very closely networked affiliation with our obstetrics colleagues and our maternal fetal specialists. We've also triangulated that care with our fetal cardiology program to where moms with congenital heart disease are getting their fetuses screened properly, with good fetal echoes through our program here, and they are also getting specialized Maternal Fetal Medicine care with high risk specialists here at the local adult hospitals. We meet on a monthly basis, we're able to essentially come up with a plan of care for each individual woman based off of their specific heart lesion. What the plan of care as far as their pregnancy is, how the delivery might go, anesthetic considerations, pain management considerations, delivery options, whether it should be a normal, spontaneous delivery, or if this is something that needs to be a planned cesarean section, so on and so forth. So those are each considerations that we give to each woman that presents with regards to pregnancy.

00:11:09

Host 

So when you see an expectant mom, or have a patient with a congenital issue, who's considering getting pregnant, what do you discuss with them in terms of their own health and that of the baby?

00:11:19

Dr. Pilgrim 

So that usually is along conversation ideally done before they're pregnant, so that they're understanding the risks that they're getting themselves into. Obviously, the discussions are different with each woman primarily, and I'll add the dads with congenital heart disease, there is a discussion that goes on there as well. But primarily with the women with congenital heart disease, we discuss what their unique physiology might be, what that looks like. Certainly, we want to deal with any human dynamic issues, valvular dysfunction, ventricular dysfunction, rhythm issues, we want to deal with those things, the best we can and get that situation tidied up so that they are in the best physical condition they can be before they take on the challenges of a pregnancy. That usually goes into a pre-pregnancy visit, which is a comprehensive visit looking at their own heart, looking at their echocardiogram, the structure, their function, a rhythm assessment, sometimes even an exercise stress test to see whether or not they have the aerobic capacity to handle the nine month marathon of pregnancy. We also discuss with them the unique challenges of having children with congenital heart disease. So we mentioned the incidence before 1%, or roughly eight in a 1,000 people in the general population being born with congenital heart defects. We know that men and women both with congenital heart disease carry a much higher risk of having children with defects themselves. So for men, we usually quote them a risk somewhere between three and 5%, which is a three to five times increased risk above the general population, prompting fetal screening for women, that risk is even a little bit higher, some literature has shown 4% to possibly even as high as 10% risk of having a child with congenital heart defect, that risk is assumed with each pregnancy. So that's not just for the first or for the fourth, it's for every intended pregnancy moving forward. Obviously, fetal screening becomes important to make sure that we're not missing something in the fetus. But it also is a challenge as far as the mom is concerned, because in some of our patients, there are longevity issues, we know that some of these patients certainly with complex congenital heart disease may not be expected to have the same lifespan as a normal person. And so there's a large ethical consideration and a discussion that you have to go into with them as well about, you know, your heart is not normal. And you're bringing a new life into the world, and what that might look like and what strain you might be putting on their partner. And so it gets to be a fairly heavy conversation. It takes a lengthy amount of time. And sometimes it's over the course of two or three visits, that we have those discussions. When you add the underlying current of potential genetic defects on top of their congenital heart disease that makes the risk potentially even higher. So some of our patients who have specific genetic problems, chromosomal problems, if you will, on top of their congenital heart disease, the risk of having a baby with a defect is that much higher.

00:14:03

Host 

So I'm glad you mentioned genetics. So what role do genetics play in congenital heart disease? And how does that affect the whole family?

00:14:10

Dr. Pilgrim 

That is a moving target. Genetics and congenital heart disease has been a hot point of discussion among congenital cardiologists for a very long time. Unfortunately, we still don't know a lot about the genetics of specific lesions, we are learning more about specific genetic mutations that may predispose to certain types of heart disease, but unfortunately, we don't have pinpoint details as far as certain mutations that cause all of the defects that we handle. As mentioned just a minute ago, though, if we know that there is a specific genetic condition. For instance, some of our genetically inherited heart diseases like Long QT syndrome or hypertrophic cardiomyopathy, we do know the inheritance pattern of those types of diseases. And that certainly goes into the discussion as far as their risk of having a child those are both autosomal dominant conditions, which means that there's a 50% probability of having a child with that same genetic defect whether or not it manifests as actual disease will be determined as they grow. Because you can have the same defect in a father and a child and they may manifest differently with different severity levels. But genetics certainly does factor in tremendously. Unfortunately, we just don't know a lot about the specific genetic mutations with regard to isolated lesions.

00:15:21

Host 

So when you have, say, a couple that comes in, and they bring their baby, and so you have you, that's the whole family, how do you sort of educate them? So let's say you realize that dad has had a heart issue, or maybe they weren't aware early on, and now they do, how do you educate them moving forward?

00:15:38

Dr. Pilgrim 

With regards to the baby?

00:15:39

Host 

With regards to the baby, or just in general, the family like does it like say a dad doesn't even know that he could pass that along. I think a lot of people aren't aware of that.

00:15:48

Dr. Pilgrim 

Right? That is something that basically is an education issue, training the family to understand, I'm assuming you're talking about an adult with congenital heart disease and their risk of having a child with that same problem. So that goes back into making sure the patient is fully aware and educated with regards to their risks, and understanding what that may look like in the baby certain symptoms that may develop certain ways that babies behave with congenital heart disease, clinically what they may present with or if there's specific things the pediatrician may raise in a routine office visits that may be of concern. Those would all be indications to possibly even come in and visit with a pediatric cardiologist for the baby.

00:16:24

Host 

In addition to educating families on their conditions, risks and long term outlooks, you've been responsible for developing the Transitions Education program, a truly unique and beneficial part of care for preteen and teen patients to help prepare them for transition to adult congenital care. Can you tell us a little about how it works and its benefits?

00:16:45

Dr. Pilgrim 

Sure. So the Transitions Education program is something that's near and dear to me, because I take care of the adults with congenital heart disease. But I have found that really knowledge is power. And if the young person coming to see me for the first time already has an idea of what it is they're dealing with, they know what their heart lesion is, they know what the potential long term outcome might be, potential complications might be, it makes my job that much more rewarding, but it also makes it even a little bit easier. So the Transitions Education program has been created here at Cook Children's for our heart center, in an effort to make sure that our young people ages 12 to 18, are receiving a proper and uniform education about their own heart problem. If you will, when a baby is born with a heart defect, obviously, it's usually the parents that are dealing with the medical care of that infant. As the infant grows into a child, the child may or may not understand varying degrees and varying levels of complexity of their heart lesion. When they get to be an age of understanding in adolescence, let's say, they are given more and more autonomy in other parts of their life and making decisions about going to college, for instance, or whether or not they're going to be involved in a sport. But many times in health care that gets forgotten. And so as a pediatric cardiologist, I am often challenged with giving enough information to the parent to make parental decisions, but also making sure that the adolescent is receiving enough information so that they're aware that when they become an adult, it's going to be their responsibility to make those decisions as well. So in getting back to the Transitions Education program, that is an education program that we've created here at Cook Children's that is specifically designed to introducing them to their anatomy initially, first of all, to give parents the understanding that we've thought about it. With many parents, they get nervous when their kid starts to get into those teenage years, like what's going to happen to my child when he becomes an adult? Who's going to care for him? Certainly with our more complex heart problems, there's some anxiety about transitioning them into an adult medical arena, perhaps with physicians that may or may not understand what they have. And so first of all, just letting them know that we've thought about this as a program, and that over the course of the five or six years of them transitioning into adulthood that we will introduce them to their anatomy, their physiology, potential complications, these are the names of your medicines, these are the doses, this is why you take them, these are the potential complications of these medicines, potential side effects. This is who to call in the case of an emergency. If you're not feeling well, what ER do you go to? You have other medical conditions, this is how those other medical conditions might interplay with your congenital heart disease. Certainly, we've talked before about birth control and pregnancy. Those are all reproductive health issues in both men and women, the likelihood of having a child with congenital heart defect. These are all parts of the Transitions Education program, in order to have that well rounded individual graduating from our pediatric program and ready to face the medical arena on the adult side, namely with me in the adult congenital heart disease program, but potentially even with their primary care provider. And it gives them a sense of empowerment. Let's say they end up in a urgent care center or in an emergency room somewhere where they may not have have adult congenital services they know to say, my heart lesion is XYZ. My doctor's name is let's say, Dr. Pilgrim. Here's his number, if you have concerns about my heart, or how my heart might interplay with what I'm here with, you can call him. And that happens routinely where I'm getting phone calls from all over the place for these patients, so that we can have discussions with providers about the appropriate way to manage whatever they're presenting with. So it really gives the patient a sense of empowerment, when they reach adulthood to be their own advocate, and to know what to look for, to know what to ask for and to know when they don't know. And to call me or the group to answer those questions that they may not know. Again, knowledge is power. That's my mantra for a lot of this for transitions education, that the more you know, the more likely it is you're going to handle it properly, or at least get it into the hands of somebody who can.

00:20:53

Host 

So with all the different medical and support needs of your patients, can you talk a little about the key disciplines that may be involved in what a patient team looks like?

00:21:03

Dr. Pilgrim 

Sure. So for adult congenital heart disease, it looks very much like what they did as children, they come in and they see the cardiologist, they get some of the same testing with EKGs and echocardiograms. They may or may not undergo exercise stress testing. So a lot of the testing from a cardiovascular care standpoint is very much the same as what they're used to growing up. When you're talking about the overall team though, we're looking at some of our patients who may have long term gi issues or liver damage or lung disease. And so then you're adding in adult providers in those sub specialties that may not be familiar with congenital heart disease, but can speak to their individual organ system, and the effects that that physiology may have on it. And so we are in process of developing a lot of networking with adult physicians and subspecialists in the region to be able to care for these individuals from a neurologic standpoint, let's say, in some of our patients with developmental delay, making sure they're getting appropriate services. Having a social worker, which we're very blessed to have here that can help with legal guardianship issues from full blown, Mom and Dad make all the decisions to maybe an assisted decision making capacity for individuals who may be able to make some of their decisions but need assistance in others. So the feeding programs, for instance, some of our adults still grow up and they may still be on feeding tubes or gastrostomies. So we have nutritionists that are involved there. Physical therapy, occupational therapy, certainly noncardiac surgery is a big issue, dental care. Those are all things that you may not think about straight up as far as caring for somebody with a heart lesion. But those are all questions that we get almost every day, Am I safe to have this procedure performed as an outpatient? I've even had cosmetic surgeons call me about some of my patients, whether or not certain types of procedures can be performed in an office setting. And so it really runs the gamut as far as the different ways that these patients come to care and how we interact with the adult medical arena. But as far as our comprehensive care here, all of their congenital heart disease issues, save for some specific complex pulmonary hypertensives, and adult heart failure therapy, so namely transplant, all the rest of it is dealt with here at the Heart Center here at Cook Children's.

00:23:13

Host 

So for a primary care physician, particularly, what do they need to be aware of, and when do they need to know to refer a patient or to work with their adult congenital cardiologists?

00:23:27

Dr. Pilgrim 

Well, my hope would be that by the time they're an adult with congenital heart disease, that the primary care provider is already aware that they have a congenital heart defect. So that would be my ideal to where they're not having to make the decision to refer. Now if it's a new diagnosis, which happens, then to look for specific symptoms that may be a tip off a new murmur on exam symptoms of passing out or rhythm problems or something along those lines that would bring them to care. Usually, those patients if they're already in adulthood, the usual track for that would be through an adult cardiologists office where then the adult cardiologists would see them and then recognize that this is perhaps a congenital issue, and then it would come to me or through the program for further care. But from a primary care standpoint, my hope really would be that we're educating our patients enough in pediatrics. So the primary pediatricians are obviously getting notes and updates from us routinely throughout their childhood, but by the time they are transitioning to an adult provider, that they are already in hand, given a summary of care that this is what we have done to your heart, and so that they're aware and know how to contact us.

00:24:31

Host 

And so for a primary care physician who may have a patient that maybe it's a new patient, and they come to them and they know they have a heart issue already or they suspect. At what point do they talk to them about not just going to a cardiology program, but to transition to let them know or let them know that they'll be there to work with them through that.

00:24:50

Dr. Pilgrim 

So the, the awareness of the adult congenital heart disease program, I think, is perhaps the most important thing that we exist, that we're there to handle this care gap of these individuals who may fall in the cracks between pediatric and adult care. And while they may not completely understand, I hope they do after this conversation, that we exist and that we're able to take care of these patients, at least to know that this is something that requires a specialist, and then usually it follows the normal pattern, they would end up with a congenital heart disease specialist. And those items can be ironed out.

00:25:22

Host 

Great. And similar, then for ob/gyns out there that may have a patient with a heart condition or suspect a fetal heart problem, when should they refer the patient to an adult congenital program? And what's the advantage?

00:25:35

Dr. Pilgrim 

In my opinion, the earlier the better. Like we spoke about previously, my ideal scenario would be that I see the young lady before she's pregnant. So we can go through the full pre pregnancy assessment, actually understand risk profiles, and so on and so forth. Obviously, if they're already pregnant, the physiology of pregnancy changes as you get deeper into a pregnancy, you know, blood levels change, and there's hemodynamics that change throughout the pregnancy. And so the earlier I get my hands on a patient who may be pregnant with congenital heart disease, the more likely it is that we can diagnose problems, we can come up with a scheduled delivery plan, speak to the the high risk doctors, make sure that their baby gets proper screening, and be prepared for that aspect of their care as well. And really dictate whether or not they are safe to deliver in their outside wherever they were planning to deliver. Or if they need to be delivered more locally here for advanced care during and after delivery.

00:26:28

Host 

Let's say that the fetus has a heart condition, mom has never known about having one does she need to be checked just in case or ...

00:26:36

Dr. Pilgrim 

Usually no. So again, with the incidents being 1%, and that doesn't sound like a lot. But when you do the math on that there's a fair number of babies being born with heart problems, the majority of the time mom doesn't have a problem. I have had several instances since I've been here where moms have actually been diagnosed with a congenital heart problem during a pregnancy. That's where it actually manifested symptomatically. And then we've had to manage mom with her newly diagnosed congenital heart problem, screen baby for said heart problem, and manage them both and then tackle mom's problem when she's no longer pregnant, either surgically or interventionally, or perhaps medically, if necessary.

00:27:16

Host 

So after everything that we've talked about, where do you see the future of adult congenital medicine going particularly within the realm of pediatrics overall, and especially here at Cook Children's.

00:27:26

Dr. Pilgrim 

So I think the future of adult congenital heart disease is bright. It is a growing field that is now recognized as a separate subspecialty within cardiology, both from the pediatric and adult cardiology realms. The number of kids growing up with heart problems is not going away, that's going to continue to grow as our surgical techniques and the types of care and the amount of care these kids are getting further improve from where we already are, is just going to further increase the number of adults with congenital heart disease. And I think that the future is very bright with regard to the overall nationwide aspect of adult congenital heart care and the networking that's currently going on, but also locally here, where we are now establishing a very firm footprint in the community in Fort Worth, and the surrounding Metroplex for care with adults with congenital heart disease.

00:28:13

Host 

Dr. Pilgrim, thank you so much for taking time out of what we know is an extremely busy schedule to talk with us today and to share the work that you do here in the adult congenital program.

00:28:23

Dr. Pilgrim 

Thank you so much. It's my honor.

00:28:25

Host 

We're so glad you could join us today. If you'd like to learn more about this program or any program at Cook Children's, please visit us at Cook Children's dot org.

Dr. Holly Pacenta, Pacenta takes us into the future of curing and treating pediatric cancer through the use of the patient's own immune system to target the cancer. At the forefront of the technology is CAR T-cell therapy targeting relapsed and refractory B-ALL cells to eradicate cancer with minimal side effects.

Meet the speaker 

Meet Dr. Pacenta

Related information

Cook Children's Cellular Immunotherapy program

Cook Children’s Leukemia and Lymphoma care

Cook Children's Oncology program

 Cook Children's Hematology and Oncology

Transcript

00:00:02 

Host:  Hello and welcome to Cook Children's Doc Talk. Our guest for this episode is pediatric hematologist oncologist Dr. Holly Pacenta. Dr. Pacenta began her career at Children's Hospital Colorado, where she developed her primary interest in new treatments for children with relapsed leukemia, including immunotherapy, cellular therapy and targeted therapy. She has been heavily involved in research, has published several works and received awards and recognition for her work. Today, Dr. Pacenta oversees the Cellular Immunotherapy program at Cook Children's where she and the oncology team are very excited about providing CAR T-cell therapy to patients with relapsed B-cell acute lymphoblastic leukemia, or ALL. Cellular immunotherapy introduces a new era in the treatment of children and young adults here at Cook Children's. Welcome Dr. Pacenta. We are very excited to have you here to talk about this incredible program and CAR T-cell therapy.

00:01:01 

Dr. Pacenta: Thank you so much for having me.

00:01:03

Host: Can you start by giving us a little background on the cellular immunotherapy program and an overview of immunotherapy and CAR T-cell therapy?

00:01:11 

Dr. Pacenta  Sure. So I think first to give an overview of immunotherapy and CAR T-cell therapy, we think at the forefront of the future of curing and treating pediatric cancer is to use, help use the patient's own immune system to target the cancer. So that's what immunotherapy is. Immuno meaning the immune system in therapy meeting treatments, so using the immune system to help treat your own cancer. And then CAR T-cell is a form, kind of a hybrid, of cellular immunotherapy. So we use one of the cells as part of the immune system, the T cells that typically help fight infection, and those get sent to a lab where they're reprogrammed to target the leukemia. So that's CAR T-cell therapy is. Then, our cellular immunotherapy program is a dedicated group of oncologists and stem cell transplant doctors here at Cook Children's along with some supportive services like pharmacy, dieticians, psychologists, etc., that will help provide these types of therapies to our patients.

00:02:13 

Host:  So KYMRIAH® is the CAR T-cell therapy currently approved for pediatric treatment of children and young adults with refractory or relapsed B-cell ALL, why this particular condition?

00:02:26

Dr. Pacenta:  Immunotherapy and cellular therapy are a big interest in pediatric cancer in general. And there has been a lot of research to try to use this type of treatment for many different cancers. But the only one where it's currently approved is in B-cell ALL, which is the most common cancer we see in children. The reason why it's been successful in B ALL, is because this type of leukemia cells have specific markers that aren't located on many other cells in the body, which is the part about it that's a little bit unique. So it's been successful, because we're able to target this one marker on the leukemia cells and not have as much effect on the rest of the body.

00:03:06 

Host:  Chemotherapy and radiation therapy can be really, really harsh for kids with B-cell ALL, especially for those who have relapsed and can have long term effects. How does KYMRIAH differ from those treatments?

00:03:19 

Dr. Pacenta:  Chemotherapy and radiation therapy are more general and KYMRIAH or CAR T-cells are more focused therapy. So, like I had mentioned the CAR T-cells are really just attacking the leukemia cells themselves, they do have some effect on the healthy B-cells that have that same marker. But other than that they don't tend to affect the other cells in the body. So that means that while it does have some side effects, it has fewer than chemotherapy and radiation which affects all of the cells throughout the body. But one thing to point out is that chemotherapy and radiation therapy have been around for many, many years, and so. the long term side effects are better studied. As far as KYMRIAH, it wasn 't FDA approved until 2017. So while the short-term and long-term side effects seem like they are overall less, there are still a lot that we might not know about the long-term side effects and a treatment that's only been around for a couple of years.

00:04:19

Host:  So we know that around 10 to 15% of patients don't respond to traditional treatment or relapse from traditional treatment methods, can you discuss how candidacy is determined for CAR T-cell therapy recipients and why CAR T-cell therapy is a treatment option?

00:04:36

Dr. Pacenta:  CAR T-cell therapy is a treatment option for children with B-cell ALL who haven't responded the way that we've wanted to meaning that it's either refractory that it hasn't responded to the initial treatment or that it's relapse, meaning that it went away and then came back. So first of all, the patient has to meet that initial criteria of relapsed or refractory B-ALL and then they'll come to have a consultation with our cellular immunotherapy program, which includes me, and some other specialized doctors here at Cook Children's to help review the treatment and the process and determine that the patient and family are interested, and that this would be the best treatment for them.

00:05:15 

Host: How does treatment with KYMRIAH work? Can you walk us through the treatment process?

00:05:20

Dr. Pacenta: So after the initial consultation, we'll have to set up a way for us to get the healthy T-cells from the child that we can use to send off to a lab and make into KYMRIAH or CAR T-cells. That involves setting up what we call leukapheresis, meaning that the patient comes to the hospital for one day, and they get connected through a bigger IV to a machine where its job is to separate the T-cells out from the blood, and then the blood gets circled back into the patient. Then, those T-cells are counted, and they're sent off to the laboratory at the drug company. And over a period of three to four weeks, some scientists will work on retargeting those cells to kill the leukemia. During that time, the child will be followed closely by our cellular immunotherapy team doctors to make sure that their leukemia stays well controlled and that they stay healthy, and that they don't develop any infections. At the end of those four weeks, approximately, when the CAR T-cells are ready, the patient will come back to Cook Children's for a four day short-course of chemotherapy. So they'll come and they'll get chemotherapy a few hours, and then they'll go home. The purpose of that chemotherapy is to help prep their body to accept the CAR T-cells. Then, on the day that we infuse the CAR T-cells, the medicine actually looks like any other medicine that we put through an IV, and we connect it up to the patient's IV and we watch the medicine or the cells drip into the patient. Typically, kids are able to go home after they receive the medicine on that day. And then we'll plan to follow them pretty closely in the clinic about twice a week to see if they develop any side effects.

00:07:07

Host:  So are each patient's cells then somewhat different? Is that why things have to be custom designed for each child?

00:07:14 

Dr. Pacenta:  So they're different in that the cells are from them, but the sort of process they do once they arrive at the lab is the same. So we're hoping that someday when we use it for other cancers, that instead of just targeting the leukemia cells, they'll be able to take it and target other things. But so far, they just target that one.

00:07:35 

Host:  There's hope that the T-cells will not only target current cancer cells, but help the patient's immune system recognize new cancer cells in the future preventing the cancer from returning long after treatment. What do we know so far? And when will we know how long the protection lasts?

00:07:51

Dr. Pacenta:  So every patient is a little bit different. But we know that in some children that this can be a long-term cure, meaning that they don't need to receive any additional treatment. Some research studies have found that the CAR T-cells will persist in a patient's body for as long as three and a half years. But it's likely that the cells will be around for much longer. And we're still kind of waiting and doing research to find out really how long they'll last. I think as time passes, and as we continue to learn more about the cells, we'll have better ways to determine which patients are going to have long-term persistence of the cells and which patients might need additional treatment. But we haven't exactly figured all that out just yet.

00:08:36 

Host:  So are you planning to follow these patients over the long term?

00:08:41

Dr. Pacenta:  Yeah.

00:08:42

Host:  Kind of as a research as well as treating them as patients?

00:08:45 

Dr. Pacenta:  So the treatment that we have here at Cook Children's currently, is just the FDA approved treatment. So there are researchers at other hospitals that are kind of looking into more of the scientifics of how long the cells last. But after the patients receive their CAR T-cells, they'll continue to be followed by the cellular and immunotherapy team indefinitely. So there are some side effects. One of them is that since the CAR T-cells attack the B-cells, they kill the B-cells that are affected by the leukemia, but also the healthy B-cells. So these kids will need to continue to be followed by a specialist to make sure to minimize any risk of infection that they might have. And typically after the first month after they receive the CAR T-cells, they'll really just need to have monthly follow up.

00:09:34

Host:  The great strides being made in treating pediatric ALL are very exciting. That said, there are so many other difficult to treat pediatric cancers Do you foresee a day when cellular therapy will replace chemo, surgery, or radiation therapy?

00:09:50

Dr. Pacenta:  So I think there may be a day in the future when cellular therapy does replace chemo, surgery, and radiation for patients with cancer. But I do think that we're still a little ways off. This therapy has been very successful initially, but we still have a lot of work to do. First of all, it's difficult to tell which patients are going to be the ones that respond and which ones won't. So we're trying to do a little bit more research to try to figure that out to know which are the patients that are going to be cured for CAR T-cells. Then the other thing is that there are some patients that are cured with CAR T-cells, but the cure doesn't last. And so I think in the future, we may be able to develop a new or better CAR T-cell that's going to last forever. So hopefully someday, but we're not there yet.

00:10:35 

Host:  I keep thinking will there be like a cancer immunization?

00:10:39 

Dr. Pacenta: That's that's the hope. Or maybe they're looking at some CAR T-cells that target multiple things. So maybe if they could individualize it more where for one person's cancer, they target three things for someone else's they target two, then it would be sort of more personalized and successful. We'll see.

00:10:57

Host: So for referring physicians which patients should they maybe contact our program to refer?

00:11:01 

Dr. Pacenta:  So any patient with B-cell ALL that's under the age of 25. That's the age group that we are currently trading here. In general, it's better to refer a patient earlier or at least have a conversation. Maybe they're not the best candidate right now. But they might be a better candidate in a few months. So in general, I would say any patient who has relapsed or refractory ALL, it'd be great to reach out, have a conversation. And then we can discuss if the patient's eligible. And if not now, then maybe at some point in the future, we could schedule a follow up.

00:11:39

Host:  So you mentioned the age of 25, as kind of the cap, but what's the youngest that a patient could be potentially referred to us?

00:11:48

Dr. Pacenta:  So I would say that there really is no youngest age that we're using to treat CAR T-cells. Patients are potentially eligible from the age of less than one up to 25. For the youngest kids, there can be a few more difficulties just because the babies are small, and we have to be able to collect a certain number of T-cells from their blood for the medicine to work. So it's really an individualized decision whether or not a smaller baby would be eligible, but it certainly is possible. And it's been done before.

00:12:20

Host:  So what does the future look like then for immunotherapy trials and treatments here at Cook Children's?

00:12:26

Dr. Pacenta:  We're working on fully establishing our program for the FDA approved form of CAR T-cells, which is known as KYMRIAH. But I think the future in our program is to work with other pediatric hospitals to try to open up clinical trials so that we can learn more about some of these things I was just describing. So we have some partnerships with other hospitals that we've worked with for other trials. And so I think within the next few years, we'll be planning to open clinical trials where either we'll be following kids getting the FDA approved KYMRIAH a little bit more closely, or we hope to open clinical trials where we'll be evaluating CAR T-cells for other cancers, or different types of CAR T-cells for B-cell ALL.

00:13:15

Host: This is such an exciting time not only for Cook Children's, but also our patients and their families. Thank you so much Dr. Pacenta for taking the time from your hectic schedule to talk about the cellular immunotherapy program and the important work that you're doing for hematology and oncology patients at Cook Children's as well as all across North Texas and the U.S. We look forward to seeing what's next.

00:13:36

Dr. Pacenta: Thank you so much for having me. So good to be here.

00:13:39

Host:  We're so glad you could join us today. If you'd like to learn more about this program or any program at Cook Children's, please visit us at Cook Children's dot org.

Listen Now

Preventing adult heart attacks in early childhood? Don Wilson, M.D., explains why it's absolutely within REACH. Children with high cholesterol, especially those who have a genetic cause, such as familial hypercholesterolemia, also know as fH, are at a higher risk for developing premature heart disease, such as heart attack or stroke as they become adults. At the forefront of developing guidelines for lowering this risk, Dr. Wilson details how the Risk Evaluation to Achieve Cardiovascular Heath, or REACH, clinic at Cook Children's is putting those guidelines to work and changing the outcomes for these in the future, and saving the lives of parents today.

Meet the speaker

Dr. Don Wilson

Related Information
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A Simple Blood Test Could Save Your Child's Life

The Unique Risks of Being a Woman with Diabetes

Number of Children and Adolescents Who are Obese 10 Times Higher than 40 Years Ago

Transcript:

00:00:03

Host:  Hello, and welcome to Cook Children's Doc Talk. Today we're talking with Dr. Don Wilson about genetic dyslipidemia, and cardiovascular disease. But first, here's just a little about Dr. Wilson. He is board certified in pediatrics, pediatric endocrinology and clinical lipidology. He is the founder and currently the medical director of Cook Children's REACH program, one of the first cardiovascular risk assessment clinics for children and adolescents in the nation. Dr. Wilson is a fellow of the National Lipid Association and an associate editor for The Journal of Clinical Lipidology and a member of the board of directors of the Southwest Lipid Association and the American Board of Clinical Lipidology. Welcome Dr. Wilson.

00:00:48

Dr. Wilson:  Thank you.

00:00:49

Host:  So children with high cholesterol, especially those who have a genetic cause, such as familial hypercholesterolemia, also known as fH are at higher risk for developing premature heart disease, such as a heart attack or stroke, as they become adults. You've been at the forefront of developing guidelines for lowering this risk, launching the REACH clinic at Cook Children's, can you tell us a little bit about the clinic and its goals?

00:01:15

Dr. Wilson:  I'd be delighted to. First of all, it might be helpful to understand that what we're talking about really is blood fats. And the words cholesterol, triglycerides tend to be very intimidating, sometimes very frightening. Even worse yet, the word dyslipidemia, which is just a fancy word for the same thing, so blood fats are normal for all of us to stay healthy. It's only until those levels become extremely high that they become problematic. So cholesterol is one form of blood fat. And people who have familial hypercholesterolemia fH, they genetically can't process that fat. So fat comes from two sources. One is what we eat. Most people are familiar with fatty foods, pizza, some of the Mexican foods, whole variety of things can can be high in fat content. But what people may not realize is that fat is also produced primarily in your body. So the liver actually produces cholesterol, about 80% of it, in response to your need, particularly when you're not eating or like at nighttime, for example. So genetically, when you have fH, your levels are going to be extremely high. For example, most children have a cholesterol level, LDL or bad cholesterol level right around 100. But children who have an L level is twice that, say 200-250 have a very high risk of developing heart disease. Not at this age, not even when they're young adult. But usually by the age of 40 or 50 years of age, these people are at very high risk.

00:02:38

Host:  So I know you're a proponent of screening children early when they have a parent with fH, or a history of premature cardiovascular disease. But there are a lot of adults out there who may not know they have this risk. Would you like to see mandatory screening of all children? And if so, at what age?

00:02:55

Dr. Wilson:  So currently, there are recommendations for mandatory screening, it's just not widely held yet. Those recommendations take quite some time to become standard of practice. But you could say, well, why are pediatricians worried about a disease that's not going to happen until you're 50 years of age, is because we particularly those of us at Cook Children's hospital are very committed to the lifelong health of children and their families. So currently, we actually screen those children at 10 years of age, sometimes sooner if they have an informative family history. So if you come from a family in which many of your family members may have had some kind of heart disease, wind up with a procedure of your heart, may have unfortunately succumbed to heart disease, then those of the kids we want to screen early. You'd be amazed because by two years of age, we pick up a lot of high cholesterol in children. So those, what we call focused screening tests, and so forth, can pick those kids up very early with the idea that we need to start implementing some changes early on in their diet, for example, those kids, we'd actually recommend that small children start on low fat milk, starting at one year of age, for example, and then reduce the fat content in the diet. Long term, that's probably not going to be enough to reduce their cardiovascular risk, they're going to usually require medication to do so, simply because their bodies again can't process that fat. But by doing so we can provide tremendous help to those folks in terms of avoiding heart disease when they become older. Now, let me ask answer another question to ask which is very important. And that is, we not only have a focus on the child, but let's say we pick up a two year old that has familial hypercholesterolemia. So they have high blood cholesterol levels, not because of what they eat, but because of how their body cannot process that fat. Well, we know that it's genetic, which means it's simply transmitted by one or both parents. A two year old has fairly young parents most the time so then we start looking at the family members and we asked them to go get their cholesterol tested. We picked up a number of either fathers, mothers or both who, A, hadn't been tested in the past. B, didn't know that their cholesterol level was high and. C. may to actually be much closer to having an event or a bad outcome than the child would be. So we've actually feel like that we've actually done a great job in terms of looking at the entire family's health and trying to keep everybody healthy.

00:05:12

Host:  Cardiovascular heart disease is the leading cause of death in the US. Add to that the fact that every minute in the U.S. a child is born with fH, why do you think early screening in children hasn't gained priority? And what can be done to change this?

00:05:28

Dr. Wilson:  Let me just repeat what you said. Because it takes a moment to realize that every minute of the day, there's a child born with familial hypercholesterolemia. So do the numbers. Lots of kids around. So it's about one in 200-250 kids. So if you have a school system of 1000, kids, you have four kids already, but most recommendations that are promoted to prove health take on average around 17 years to find their way into clinical practice. Why is that? Well, it's because the practice of medicine is very complicated. We have to get out and inform physicians, they rightfully so need to ask questions, they need to make sure that they're comfortable with that recommendation. And then they need to figure out how they're going to implement that in their practice. I think Cook Children's actually has one of the better systems in the country for doing so because we have automated systems that we can plug in these recommendations. And we can monitor the outcome of that. So we know how many kids in our system should be tested, we can figure out right away whether we're doing a good job or not. So about 10 years ago, I looked at this at Cook Children's, with budget physicians to see how we were doing with our screening program. Nationwide, only 4% of physicians were actually testing children for cholesterol. Our rates were actually 20%. So the question sort of become for us a we're doing a good job, right? The question is, can how can we do a better job? That's the question we like to ask how can we do better, right? So we want to go from 20 to 40, to 60, to 100% of these kids, so that we can adequately assess risk and keep kids from having heart disease when they get older. But physicians are not hesitant to implement recommendations, it just takes a while for that process to mature. The second thing is we have to we take great pride in trying to educate our families about the importance of doing it. So we don't want to do anything to or for a child or a family without them understanding what the benefits are. And partnering with them in terms of them being the parents agreeing to an understanding what to do with that information. So we encourage people to ask questions, it may take a visit or two sometimes for them to understand kind of what we're trying to do and what to do with the information. But it has important ramifications not only for their child, and the future of their child, but also themselves and even their grandchildren. Because again, a child with fH is potentially going to pass that along to their children.

00:07:50

Host:  So can you describe some of the barriers that currently exist in childhood screening? What are the shortcomings in current screening protocols for kids? And why do they fall short in terms of preventing a cardiovascular event in the future?

00:08:04

Dr. Wilson:  So we realized that there would be some potential barriers in terms of cost, for example. If you had another test, that means that X number of children are going to be tested. Well, it turns out that the cost for tests are relatively small, we also looked at the mechanism by which kids are tested in the clinic. So for example, if you say 10, that child may not have any other blood tests that are scheduled for that particular visit. They may or may not. But what we do know is that at two years of age, we usually screen the children for other things. So we've talked several of our clinics into screening the two year olds. And so they just don't have the kids don't have to have an extra blood test, they just simply give us another drop of blood. And we test for cholesterol right there in the office. Cook Children's has also been very generous in terms of providing the test equipment for what we call point-of-care, so that those machines are there in the office, and the cholesterol test can be done on the time the visit. And then the pediatricians can have conversation with the families right then. They don't have to wait for a phone call. They don't have to send them information in the mail. And the importance of that is giving timely information to families, but more importantly, being able to look in their eyes and sort of answer their questions as that conversation is being undertaken.

00:09:15

Host:  So some argue that the cost of screening is too much at this level. But what is the long term cost of not screening?

00:09:23

Dr. Wilson:  Yeah, that's a terrific question. So some of the criticisms, for example, doing anything with children, but in particular, screening is frightening children. We have no intent whatsoever to frighten anybody. This is just an informed conversation. But we and others have actually carefully looked at that impact to ascertain whether we're actually causing any fear or harm about having a genetic condition that's lifelong. Unfortunately, if you've had family members who've had a bad outcome with cardiovascular disease, telling a child that he or she is actually at risk for that could evoke fear. But we've carefully looked at that and we also do a lot of education with the child, making sure that they understand what this is and what it isn't. We make very clear that the child does not have any disease at this time, they clearly have a very strong heart, very normal vasculature blood vessels. And we try to do so in an age appropriate way. What I think we can all take great pride in at Cook Children's is that when those kids come back, if you ask them, you know, why did you come to see us? And what were you telling them? What did you understand? Those kids are terrific, they can give you the answers right away. In fact, we've used many of them to teach other children about cardiovascular disease, and the importance of cholesterol screening. Many of them do so as a school project, for example. So come time for the science fair project, many of the kids will actually do that as a science fair project. So I think there's many benefits to obviously involving kids and the families in this conversation. But if you understand that people who have familial hypercholesterolemia, or fH, approximately 50% of the men and 30% of the women are going to have a heart attack by the age of 50. That's a very early age for people to have problems. We hope that they would never have problems. But those are the statistics. So again, by finding through screening, because the kids otherwise look quite healthy. This is not about being overweight. This is not about sedentary behavior. This is not about eating poorly. This is about a genetic process in which your body can't process cholesterol, or blood fat. And just allowing that fat to accumulate in the bloodstream clogs arteries, most people know that term, right? We call it atherosclerosis, or hardening of the arteries, but the reality is they become plugged up. And when they do so you cannot get blood flow to vital organs, like the heart or the kidneys or the brain. For the heart that's going to translate into having a heart attack. For the brain is going to be a stroke. And I think, unfortunately, most people in America understand the signs and symptoms associated with that, and the outcomes. So we never want to have a screening program where we trigger cardiovascular screening based on symptoms, which is unfortunately what happens in the adult world, right, you don't have insurance, you don't take the time to go to the doctor, they don't do the screening test, then you wind up at 40 or 50 years of age complaining of chest pains when you walk upstairs. That means you have clogged arteries. And yes, there are procedures such as stents, that increased blood flow or some people are familiar with cabbages or coronary artery bypass surgery. But you never want to get there, if you can help it. The key to it, test the kids and offer effective treatments early in life where you can reduce that risk over a lifetime.

00:12:28

Host:  That sounds fantastic. And I hadn't even really thought about the kids teaching other kids particularly like out in the community like that, what a fabulous idea.

00:12:37

Dr. Wilson: Children are great resource. First of all, they're inspirational. They're very bright. They talk to other children, they have a credibility with their peers. So we've learned a long time ago that, particularly teens are a great source of information for their peers, but they need to make sure that they have accurate information.

00:12:54

Host:  So let's talk a little about LDL, what is a normal LDL level in a child and when should a pediatrician be concerned?

00:13:03

Dr. Wilson:  So typically, the LDL, sometimes we talk about l as being lousy, right? Good way to remember it. So the LDL cholesterol level below 130, would be considered normal. Some kids have levels that are 80-90, but typically around 100-110. When those levels exceed 130, we become concerned. If they get to be 160, we look to see if there's other risk factors. So then, are other things going to also contribute to heart disease, such as high blood pressure, diabetes, being overweight, being sedentary... unfortunately, some children start experimenting with smoking, or vaping. Those things all contribute. So we start counting up what we call risk factors. So if you have a couple risk factors plus high cholesterol, 160 and above, then we might suggest that you would benefit from treatment at least until you can reduce those other risk factors. If you have levels of LDL cholesterol, or lousy cholesterol, if I can use that term of 190. and above, then the chances of that coming down simply with diet and exercise are not very good, because that's going to be genetic. And we can prove that we can actually show you the genetic mutation in most of the kids. But that one's going to require medication. Now, nobody likes to think about, physicians or parents either one, lifelong medications or need for medication. But the reality is, if your body does not allow processing that cholesterol it's in your best interest. So do we have a 50 year history of treating kids? No, we have at least 20 years history, but we take the responsibility of safety very seriously. And so we look at every parameter we can, in children, just like adults, it's going to be monitoring things like liver function, kidney function, so forth. Number two, we always want to make sure that the medication is actually doing what we hope it will do, which is reducing the bad cholesterol or LDL cholesterol. And it does it's very effective is simply getting them swallow a pill every day. And the good news is the medication is quite inexpensive. In many people who have insurance, for example, a lot of times they give you the medication at no cost, because the insurance companies have also realized that that's helpful for both parties long term. But in children, we also take very seriously growth and development. We want to make sure that there's nothing there that's going to either slow down or hamper their growth and development. And also remember that we have to be very sensitive about reproductive health for both boys and girls. So those things have been looked at extremely carefully. And you could imagine the process of getting a medication like a statin, for example, FDA approved for children, there are going to be a lot of hurdles, as well, it should be. But I think scientists and clinicians have come through that rigor and then been able to demonstrate to the FDA and more importantly to themselves and to parents that this is safe drug.

00:15:45

Host:  So not all high LDL levels in children are genetic, some are acquired, how do you determine the difference in their diagnosis, and is there a difference in treatment protocols?

00:15:55

Dr. Wilson:  So we and others would never be quick to assume that this is necessarily genetic, unless we've done things that have not been successful in bringing the cholesterol level down. So when we see a child in our office, for example, we at least have one or two measures of the cholesterol level, specifically the LDL cholesterol levels. And we've usually given them specific recommendations with regard to alterations in diet, physical activity, weight loss, etc. Sometimes medications can also increase the LDL cholesterol level. So if there's an opportunity to alter those medications, or eliminate them, not always possible, but we do everything we can to reduce the LDL cholesterol, including by the way use of some dietary supplements. So many people may be familiar with the American Heart Association symbol on various things like margarine, or milk or whatever, that simply means that that preparation has been altered a little bit to reduce the fat and also use what we call plant fats, or plant sterols or stanols. Those are just fancy terms to mean that plants also make cholesterol, if you will, what we're concerned about is animal cholesterol, or animal fat, but the plant based fats actually reduce cholesterol in your body. So using those either in those type of food preparations, or as a dietary supplement can help. So we try all those things for as long as the parent or child would like to. And then I think by partnering with them, we figure out after a visit or two, that that's just not going to be possible to do by those means. If you have something like diabetes, it's important also to try to improve control to the level that you can. So we try to take every step that we can before making the decision together with the child and the parent, that other steps or other medications might be necessary and beneficial, as well as safe to do.

00:17:42

Host:  Certain traditional thinking is that cholesterol levels are the direct result of a poor diet. And we know there is some truth to this, but it can also be inherited. And that's where the importance of screening children at an early age becomes really important, correct?

00:17:57

Dr. Wilson:  That's correct. And that's why we've actually started focusing on two year olds not only because of what I said earlier, that is we can incorporate that into the standard blood tests that they're getting so we don't have to have another blood test for the children. But also, because at that age, very few of the kids have weight related problems or have developed other dietary habits that may actually increase the cholesterol, as children get older, and certainly as they become adults, it gets a little bit more confusing, right? Many people have gained weight, they're sedentary now as an adult, because they have jobs or a whole variety of life related issues. But the discrimination, if you look at the LDL cholesterol levels, for example, is much better at a two year old than it is at a 20 year old. So doing early screening really helps us separate the people who have genetic problems from the ones who have acquired problems. Now, in fairness, that you can have both. So we also do screening for children who have weight related problems or thyroid problems or diabetes, but it's a separate distinct conversation from the ones who have genetic mutations.

00:18:58

Host:  There is also a perception that children at risk are predominantly those from lower income families as well as kids who might be part of the drive thru diet generation, if you will. But this isn't necessarily so. Can you give us a view of what populations are actually at risk?

00:19:15

Dr. Wilson:  Yeah, so thank you for bringing that question because if that perception is out there, it's false. fH or familial hypercholesterolemia, pretty much cuts across every race, ethnicity age group. It's something that children are born with just because that's the way their genetic makeup is. So it has nothing to do with selecting a group of patients. We do know that there are certain populations, for example, in African American children, we would look for more hypertension or high blood pressure. And our Mexican American kids, we know that they're much more likely to have insulin resistance or diabetes. But with fH or high cholesterol, it's pretty much all kids. So the nice thing about uniform or universal screening is that there are no criteria. If you have a 10 year old in your office, as a pediatrician, you should realize that that child needs to be screened. It doesn't matter what their family history it is, it doesn't matter what their personal history is, you just go ahead and screen them. And that's the beauty of it.

00:20:09

Host:  So once a child is diagnosed, what are the treatment options, diet medication, a combination? And if medication is chosen, what are the risks short and long term?

00:20:20

Dr. Wilson:  So we always start with trying to understand the problem, because the best fix for something is always understanding what's broken, right? These kids are suspected of having a genetic mutation, but that may or may not be proven. And as I said, we always start with trying to understand the family's eating habits, understanding your physical activity, taking a critical look at the child, we always eliminate secondary factors. So for example, if a child has a problem with their kidneys, or they have problem with their liver, or they have problem with her thyroid function, like hypothyroidism, or an underactive thyroid, those can also affect the cholesterol levels. We take a careful medication history, not only on prescribed medications, but also over the counter preparations as well as dietary herbal preparations and that sort of thing. So understanding all that we start off with lifestyle modification. What can we do as a family to try to improve everyone's cholesterol, not just this child's cholesterol, and it's important not to single the child out because these are usually family issues, right? And they're family solutions, we want people to be supportive of each other. So whatever period of time that takes, but we usually give it six months to a year to see if we can make any improvements with frequent conversations or additional education is necessary, then we'll sit down and say, Okay, this continues, the high LDL cholesterol has not really significantly changed in the parents usually come to the right conclusion, which is this seems to be part of my child, it may be part of our family. We actually screen the other kids, because high cholesterol levels in other family members sort of suggest again, that it's going to be genetic. And then for many of our families, we actually offer genetic testing, so we can actually pinpoint, it's not absolutely necessary for treatment, some people opt not to for a variety of reasons. Some people really like to know whether their child has a genetic mutation, because then that information can be used to tailor the treatment. It can also be used to pinpoint cholesterol problems in other family members because it cholesterol levels can be high, or maybe in midrange. But it'll definitively tell you whether you have that condition or not. And whether young children, for example, might be at risk of passing that on to their future children. But after all that conversation's over the standard of treatment would be use of some type of cholesterol lowering medication. Typically, we use something like a statin, many people are familiar with these terms. There are a variety of them, there's about 12 different statins that are FDA approved for use in children down to at least at age eight. In Europe, it goes down to age six. So beginning at that age, we would start using medications to lower the cholesterol. The good news is even though in the adult world side effects are usually primarily with muscle aches and pains, I'll tell you right away that adults have a lot of aches and pains so we don't want to add to them. But some people do seem to have difficulties as an adult with taking statin medications. So we always ask about that, because sometimes the family members are already being treated. But in children, we actually don't have to use as potent a medication. And we don't have to use very high doses, because what we're trying to achieve is cholesterol lowering, but over a lifetime. In adults, they may start out with an individual who's 42 years of age and already had a heart attack. So you have to jump in really with both feet there and make sure you get the cholesterol levels down to keep them from having any more problems. But in showing we can actually start with less potent medication, we can start with lesser doses. And as a consequence of that we and others really have not seen very many of any concerns in children. Now we always monitor them, we always look at them, we always talk to them about their school performance, their activities and whatever, but they don't seem to have any changes whatsoever. And then we also look at some screening tests. For example, we may look at liver function studies, we've not seen any changes whatsoever. As a consequence, the national recommendations is not to do any more screening tests. Now we tend to kind of hang on to those for a little bit. But most people will just look at the LDL cholesterol response to treat it. And then titrate the dose. You know, the biggest problem with children in terms of taking a medication like a statin?

00:24:18

Host:  Parents?

00:24:19

Dr. Wilson:  No.  The biggest problem is actually remembering to take it. For parents that shouldn't surprise you, right. So the biggest problem when when when the kids come back and they've been on medication for a short time mom says He never remembers, She never remembers, I have to tell him all the time. I said Mom, that's basically going to be your responsibility until they get old enough. And we take the personal responsibility of making sure that they're educated about why they're taking this medication, why it's important, what the benefits are to them, and if this is going to be a lifelong endeavor.

00:24:51

Host:  Interesting. I'm one of those terrible kids who forgets to take her medication. So when I said parents.

00:24:59

Dr. Wilson:  Well, you know I think it's important, I usually tell families Look, you're not gonna be perfect, your child's not going to be perfect doing this. He or she may be perfect in other ways, but they're not going to be perfect in terms of taking their medication. As long as it's an occasional missed pill is not going to be a big problem. Okay, so we just do the best we can.

00:25:16

Host 

So with some of these kids, we've been doing this here at Cook Children's for about 20 years now, have you followed any of the kids into adulthood to see how their outcomes are thus far?

00:25:26

Dr. Wilson:  So most of our kids are too young to be of an age where you think that they might start having symptoms. The other thing that I can't tell you is that once they leave Cook Children's into the adult world, whether they continue with that or not, hopefully they will, we again, try to provide them enough information. And we even provide documentation for their adult physicians as to why we think that this is important and what's been offered to them to that point, and the results of that. But there was recently an article published in the New England Journal, which is the premier journal for medicine, right? So you have to be pretty good to be able to publish in that journal. Wasn't our publication, but it was a group that actually has been treating children starting in childhood with statins for about 20 years. So it was very interesting, because these kids all had genetic definition of their hypercholesterolemia, so they had mutations, we knew exactly what was wrong with them. So the recommendation was appropriate. And these kids were treated consistently with a statin drug for 20 years, the researchers compare them to two groups. One is their parent who has fH, because it's usually inherited by one parent or the other, called autosomal dominant inheritance, that parent has usually had some sort of event. So they have clogged arteries, and they're either having angina, which is heart pain, or they've had a heart attack, or unfortunately, sometimes they've had a fatal outcome. So if you followed those adult patients out about 40-45 years of age, about 15% of them have had some type of event. If you follow these kids, their children who also have exactly the same disease because they have the mutation, and you've treated them and lowered their cholesterol by the time they get to a comparable age. So these kids are now 40 to 45, right? They have zero, they've experienced zero, this is 200, plus kids, zero events. Equally important, because what cholesterol does is accumulates in the blood vessel wall of arteries, it's kind of like ring on your bathtub, right, it just kind of keeps the, it's a bad analogy, but it's something everybody can relate to, right. So you just kind of get this cholesterol build up and the lumen or the way the blood flows through the blood vessel becomes smaller and smaller until it finally clogs up, right. But when you look at that, you can do it through like ultrasound. If you look at that in these children in this study, and you look at their sibling, their brother or sister who doesn't have fH, by the age of 40, or 45, they all look the same. They have no evidence of build up of cholesterol on their blood vessel. So that's very reassuring for all of us, in terms of what we're doing, I think it's very effective in keeping these kids from having problems when they become adults.

00:27:57

Host:  For children and adults who don't get screened, so they don't know they have this issue, what are their risks? And what are the possible outcomes if left untreated?

00:28:06

Dr. Wilson:  So if you have this condition, which genetically causes your bad cholesterol or LDL cholesterol level to be high, over a lifetime, there is a phenomenal increase in risk of having a heart attack prematurely. What do we mean by that? We mean men are going to have a heart attack by prior to age 55. And women by prior to age 60. Plus, they may actually have ill health or symptoms related to reduced blood flow to the brain or the heart. Now remember, people who are less than 50 or 60 years of age are usually still in a prime, right? They're still working or enjoying their families or whatever they enjoy doing. But most people are very functional at that age, physically and cognitively. So we want to try to maintain their good health so that they can enjoy life, enjoy their families, enjoy long longevity. But unfortunately, we do now see, we still see a number of children brought to us whose parent, sometimes the father, sometimes the mother have had a fatal outcome. So if your spouse has just had a fatal heart attack at 42 years of age, you want to know why. And then the surviving parent then asks the questions, What about my children? Are they susceptible to the same thing? And lo and behold, those circumstances sometimes the kids are tested for a known risk factors like high blood pressure, diabetes, cholesterol, low and behold, they have high cholesterol. So in kind of a reverse way, you figure out that that spouse who died at 42 years of age actually had hypercholesterolemia, or fH, right? Which is tragic, because if we'd known that, like in our screening program at age two, we would have done things to prevent them from having symptoms, much less a fatal outcome. So those parents are usually very keen on getting kids treated. They don't want the same outcome for their child that they experienced with their spouse. And that doesn't have to happen. But we have to get really good about screening all children and giving appropriate advice about those who have lifelong elevations of cholesterol. We're getting better. We're doing reasonably well as an institution at Cook Children's. Nationally, we're not doing so well. So if you looked at everybody in the United States who who has fH, we've only identified 1%. That's tragic, we need to do a much, much better job. But in order to do that clinicians, physicians need to get busy about incorporating that into their screening program. But I think we also need to do a better job in terms of informing family members so that they can also be advocates. We tell families, you know, all the families we meet, if your pediatrician hasn't screened your child, and it's time to do so, bring it up to them. They're not reticent to do it. They just simply need a reminder sometimes, because there's a lot of things on that pediatrician's plate these days, you know, gun safety, avoidance of smoking. a whole variety of things. So don't be hesitant to partner with them in terms of saying, Hey, is it time for my child's cholesterol test to be performed?

00:30:54

Host:  So let's say someone is born with this, and they don't know it, and then they find out because their child has it, and when they go get tested, of course, they they have the issue, can you reverse the damage at all? Or is it like once they start taking medication, or are they just kind of at this point, they may have to have surgeries or other things to help them along.

00:31:14

Dr. Wilson:  So it depends upon how far they are into this process. Okay, but here's an analogy that I try to use with some of the families, let's take a rubber band, you can stretch that rubber band so far and it'll break, okay, so if you don't pick this up, someone could have a fatal outcome from a heart attack or stroke, right. But you can also take that rubber band and stretch it to where when you release it, he won't go back to its elasticity. So if you allow this condition to go on, and don't detect it, say until late 30s, or 40s, you may stabilize that, but the rubber band will never go back to its elasticity. However, there is a period of time below which you can actually reverse the whole process. So for example, there are a lot of studies of kids who are 12 to 18 years of age where you can see a buildup of cholesterol in their arteries, and you start them on a statin and reduce their LDL cholesterol levels, it goes right back to normal, just like the study I quoted from the New England Journal. So that's very reassuring. But that also sort of says we need to be screening people early.

00:32:13

Host:  So in presentations, and in your writings, you talk about cascade screening, what does that mean?

00:32:19

Dr. Wilson:  So cascade screening is just a fancy term that says we need to go find everybody in this family who has this condition, because it's, again, it's an autosomal dominant condition. So it means this is the kind of genetic problem that's passed from one parent, could be both. But it only takes one parent having this condition that passes it down to 50% of their children. So if you think about the math, there's a huge case detection. So when you find a child, you know that half their siblings and one of their parents is also going to be affected. So whether those kids or the parent had been tested, we need to at least suggest to those parents that both the children and the parent, go get tested. We actually offer the testing to the siblings if the parents are willing to do so. So we try to take that responsibility and follow up on it. We don't take care of adults, so we have to encourage them to do so. But we've also identified several places around town where testing can be done at low cost. And they can be given the information to take to their primary care physician, for example. Or, if they have a primary physician, we usually suggest that they bring it up at their next scheduled visit. It also helps us in reverse in terms of understanding the potential gravity of their child's condition.

00:33:27

Host:  So mandatory screening could have a kind of reverse cascade because a parent who may have never been screened, because they might be unaware of their own condition or family history, they could then be referred for screening, ultimately saving lives and certainly lightening the burden on the health care system overall. Correct?

00:33:46

Dr. Wilson:  Correct. And let me go back to what you said at the first of this podcast. cardiovascular disease is the number one health condition that causes people significant morbidity, meaning they're suffering from the condition and death. I mean, we think about other conditions that are more dramatic, perhaps not any less important, but if you just looked at numbers-wise, heart disease is what's going to get most people in the United States into trouble. But with early screening and effective intervention, sometimes requiring medication, not always, but many times for these genetic conditions requiring lifelong lowering of cholesterol levels, that dynamic, at least in the United States can change. So in the future cardiovascular disease as far as an outcome for adults would take a backseat. I mean, it would be we could almost eliminate acquired cardiovascular disease that way. Just think about it, that's phenomena that needs to happen.

00:34:39

Host:  It's huge. So what role should both pediatricians and adult primary care doctors play in screening and prevention for their patients?

00:34:47

Dr. Wilson:  Well, people who are in primary care, first of all, they have my gratitude because they have a difficult job. They see lots and lots of people but they're also the forefront for prevention. They know this very well. What they have to consider is the recommendation and make sure first of all that they agree with it. If they don't ask questions, let's debate it. But I think that conversation has been debated pretty effectively on a national international basis. So all the all the healthcare organizations such as the American Academy of Pediatrics, the American Heart Association, the National Lipid Association, they've all pretty much endorsed routine screening. But how one does that in your office that conversation needs to be had. And then if family physicians or pediatricians need help in terms of how to guide folks, or what to do with that information, that's why we're here. That's why we created the REACH clinic, we want to be a resource to the community. So we do actually see children from all over North Texas and several states outside of Texas. We also do consultation for many countries outside the United States, where that expertise may not be known.

00:35:51

Host:  And that's great. What are some of the new medicines and technologies on the horizon for treating kids with fH.

00:35:58

Dr. Wilson:  So currently, for both adults and children, the first line drug is always going to be a statin. And as I said, there's about 12, or 14 of them now. So people have a variety of medications that they can choose from. So for example, if an adult can't tolerate one drug, they could try another one. But some people can't tolerate any of the statin drugs, adults, we've never seen this in children. But if an adult can we now have several other medications, one's actually an injectable drug that can be taken once or twice a month, that will lower their cholesterol level. Sometimes these are used in combination, sometimes they're used just by themselves. But it's nice that we're developing other medications that will give people alternatives. So if they're having difficulties with one or they can't afford one, then perhaps can afford another one. So there should be no no reason that people couldn't be offered affordable, available help. Which one works best for you? I think in the future, we're actually going to be able to, the term's called precision medicine, where we actually take some genetic information from you, and then look at what would be the most effective and safest drug out there. That's kind of an exciting topic in itself. But that's what's coming in medicine. But for today's discussion, what we typically do is to use a medication that's been around the longest, and also the safest, at least the information that we have, and also affordable. So there's no reason to use a more expensive medication or make it more complicated if we don't need to, because again, we want to make sure that young people, once they graduate high school, enter the military go to work, whatever they're going to do in life can still afford that medication, because it's lifelong.

00:37:31

Host 

So what do you see for the REACH Clinic in the future?

00:37:34

Dr. Wilson 

Well, first of all, I'm very grateful that Cook Children's, not surprised by but very grateful, that Cook Children's sees the wisdom in providing this type of a clinic for children for conditions that are not going to happen on our watch, right? These are things that happen when people become 40, or 50, as I alluded to. But I think the organization and certainly the people who work here are very committed to the lifelong health of children and their families. So I do appreciate the support that we've gotten for the clinic. As in any clinical operations, we had to do a lot of education with our community, with our community physicians, we had to set up some screening programs, we put together some educational materials for families, and so forth. And then quite honestly, our families have partnered with us to become advocates. So many of them work on the national level, some of them work locally, to try to inform other family members, for example, they may go to parent teacher organizations and talk about this cholesterol problem with parents who try to answer questions about their child being treated or screened. So that's tremendously helpful. Because there's another mother there who's concerned about her child and doing something about it, Perhaps as a mother, I need to think about my children, have them screened. So it's been a great experience in terms of a community who sees the wisdom of this, have supported us. And I guess our only problem is that we keep growing. So we've identified probably in our six county region for Cook Children's, about 1,500 kids with fH. Wow. That's the estimated population affected. We've actually identified about 350 of them. So we still got a ways to go. But that keeps growing exponentially.

00:39:05

Host:  And that's the six counties?

00:39:07

Dr. Wilson:  That's just in six counties, right. So that's not the state of Texas. But I think at the end of the day, we want to try to reach every one of those children, and at least have the conversation about what your risk is. I mean, we realize that we give people information and advice all the time, whether they choose to take it or not, is up to them. But it's kind of like education of a child in general, right. The investment that you make today has the potential of making huge impacts in their lives. But it may take a few years for that information to sink in. And it may take a level of maturity before they're able to act on it. So we never think that that's a waste of time. But I'll tell you, after one or two visits, those kids could stand up and give a lecture on cholesterol. They are phenomenal kids. They're just a joy. They are great kids, great families. We're just delighted that they have allowed us to be a part of their families. So the other thing that Cook Children's has done is to allow us to have a variety of people in our REACH Clinic who provide other services. So we have a full time dietitian, for example, we have a social worker, we have clinical psychologists. So we offer all those services to our family members, because sometimes there's issues about what should I be feeding my child at various ages? Is this safe to do? You know, fad diets come and go? Are dietary supplements appropriate? So our dietitian does a great job in terms of answering those questions and being a support. There are also issues with regard to finances, so our social workers are very helpful. And then our clinical therapists where it says, Okay, you've been given all this advice, how do you get the kid to do it? How do you get your kid to understand it? Right. So as parents, I think we know that too well, right. We know our kids should be doing, we've told them, now getting them to do it. understanding why that's beneficial. That's a little bit tricky sometimes. So all those people are extremely important in terms of our effort.

00:40:52

Host:  So I like that sort of like not just the child or just even the whole family that in some senses, even the community that the REACH Clinic literally reaches out to so ...

00: 41:01

Dr. Wilson:  Well this has been said before, but we look at every clinical encounter, particularly new patients, we're starting a journey together, right, so let's kind of get used to each other kind of know each other, develop trust, we, we feel that that is extremely important. Learn to effectively communicate. And then as we grow together, let's talk about how we can help

00:41:19

Host : So for pediatricians or other primary care providers, as well, as specialists who have patients, they think may be candidates for the REACH Clinic at Cook Children's, how should they refer them, at what ages, and how early in their care?

00:41:33

Dr. Wilson:  Well, we encourage primary care physicians to first of all, embrace screening, because if you don't know the problem exists, you can't do anything about it. Then some physicians are actually quite conversant with this. And if they have the resources and time that they want to counsel their own patients they're welcome to do so. Even treat them if they want. At this stage of the game, most physicians are not likely to treat them, but they're welcome to do so. And I'm more than happy to help them if I can. What they are capable of doing, though, is taking the first responsibility of making sure that they've been screened, that those who need the services are provided dietary guidance, that they're encouraged to lose weight if they're overweight, that they increase their level of physical activity, that they avoid smoking, all those things that we know that contribute to high blood pressure, diabetes, cholesterol problems, and ultimately heart attacks and stroke. And at some point, if the numbers are high enough, or they're persistently elevated, and they've done all those sort of things that I'm more than happy to see the kids. If they actually screen the kids, and they have extremely high levels, but let's say an LDL or bad cholesterol level of 190 and above, we probably should see those kids early on, because we're going to do all those things that we talked about. But in the end, that's almost always going to be a genetic problem. And so we need to talk to families about genetic testing, we can interpret that for them and then kind of guide them along that treatment path. But the pediatricians, family physicians, are extremely helpful in the process. They also play an important role when kids come back to their practices. And we've provided them information about the diagnosis and our recommendations. We encourage the family members because they have a very nice relationship with their primary care physicians, talk to your doctor, your child's doctor about this, make sure that he or she agrees, ask them any questions you want, make sure that they are in agreement with our treatment plan. But generally the pediatricians, family physicians, are very supportive, and they can be a very important network for the families.

00:43:26

Host:  Is there anything that we've missed during this conversation that you feel is important for our audience or anything you'd like to add?

00:43:32

Dr. Wilson:  Well, this whole business of cholesterol because you hear a lot of conversations about it, but pro and con is just like any other topic, right? So there's a lot of misinformation there. And so we would certainly encourage people to ask reputable professionals such as their pediatrician, family physician, ourselves. There are some websites that are good information, sound information based on science. For example, the fH has a foundation where they have a website, Cook Children's has a lot of information available on their website. So go to reputable sources. Realize that some people are confused about this and provide misinformation. So we don't want to use scare tactics. We want people to use informed decision. But realize that if you come to see us or if you go to see your primary care physicians, what we're trying to establish as a personal relationship with you and your family, and then we want to try to help together make the best decision about your children and their future. So that's what we're really all about is trying to keep kids and families healthy and happy and enjoying life.

00:44:27

Host:  Dr. Wilson, I know you're super busy. So I really appreciate your taking the time to talk about this fantastic program. Thanks for all you do and for making a difference in the lives of kids not only here at Cook Children's but kids everywhere.

00:44:39

Dr. Wilson:  Thank you for the opportunity. And let me first and foremost thank the families that have invested the care of their children in our clinic. It's an overwhelming responsibility sometimes but when we really enjoy you know love to see the smiles on kids faces as our members improve. This is not the kind of condition where you feel better or feel any different but just the smile on their face when they see their numbers reduced is a joy. So thank all of our families for the opportunity and thank cook shoulders for the support that they give us.

00:45:05

Host:  It's been a pleasure. We're so glad you could join us today. If you'd like to learn more about this program or any program at Cook Children's, please visit us at Cook Children's dot org.

Neurosurgeon, Daniel Hansen, M.D. shines a light on this barrier breaking approach to epilepsy surgery. Using an endoscopic method to disconnect the left and right brain, this minimally invasive procedure has the same chance of seizure freedom post-surgery as traditional callosotomy, while reducing operating time and recovery time.

Meet the speaker

Meet Dr. Hansen

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Transcript

00:00:03

Host:  Hello and welcome to Cook Children's Doc Talk. Our guest for this episode is pediatric neurosurgeon Dr. Daniel Hansen. Dr. Hansen sees and treats children for the whole range of pediatric neurosurgical issues, and has special interest in minimally invasive surgery, endoscopic surgery, tumors and epilepsy. He works closely with the neuro-oncology and epileptology teams to provide cutting edge patient-centered treatment, using the most up to date information and treatment options. Dr. Hansen is the first neurosurgeon at Cook Children's and one of only two in the state of Texas to perform an endoscopic corpus callosotomy and endoscopic surgery on the corpus callosum that separates the right and left sides of the brain for children with certain types of intractable epilepsy or severe seizures. He's also one of the first pediatric surgeons in the nation to perform the endoscopic approach. Welcome, Dr. Hansen.

00:00:58

Dr. Hansen:  Thank you.                                                                                                    

00:00:58

Host:  I want to start off with a little background about you. Initially, your career choice was between becoming an astrophysicist or a surgeon, clearly surgery won out. But why neurosurgery and in particular, pediatric neurosurgery?

00:01:12

Dr. Hansen:  Well, you probably noticed, those are two pretty diverse career choices. But the link between them was a love of the unknown, of the unexplored. And I really can't see any better comparison than deep space, and the human brain, something that we live with every day, but is still vastly unknown to all of us practicing medicine. Going to college, I took some physics classes and very quickly realized that I wasn't going to be interacting, I wasn't going to be involved with people through much of my day. And I really craved that human interaction, that ability to have a meaningful impact in people's lives that I could see, I could tangibly touch. I wouldn't be working on esoteric theories, in a classroom writing out equations on whiteboards. But I'd be at the bedside, I'd be in the office next to people and next to families that were going through difficult times. Looking at the spectrum of adult neurosurgery and pediatric neurosurgery, adult neurosurgery is interesting. But to me, my heart has always been drawn to taking care of children, they are often a segment of our population that doesn't have a voice. They don't have someone who's advocating for them, they don't have someone who is supporting them in times of great struggle. And that really appeals to my heart. And the cognitive side of dealing with specific pediatric problems really appeals to my cognitive side.

00:02:36

Host:  So callosotomies have been performed on adults and children for a while now. But the endoscopic approach is fairly new. Can you give us the background on the surgery, how it was originally done in adults, and why it's just now becoming available for children.

00:02:50

Host:  So the goal of a callosotomy is to disconnect the left and right sides of the brain. For certain types of epilepsy, the electrical signals, going from the left to the right side or right to the left causes people to have a very specific type of seizure, as you might guess, and adults with a larger brain and larger anatomy, things that we do are a little bit easier, just from a space constraint standpoint. So many of the pioneering surgeries that we're doing and kids have actually had a basis in adult surgery for a number of years. So there was discovered several decades ago that disconnecting the right and left side would stop people from having something known as drop attacks, which is a very specific type of seizure where patients tense up or become floppy and fall to the ground causing pretty significant injury depending on when they fall. We also know that for people that have significant damage to either the left or the right side of the brain in a way that is causing abnormal electrical activity, sometimes disconnecting that portion of the brain makes a significant impact on their seizures. This was originally performed in adults and performed so well it was carried over into children. In the last decade or so our technology with very small video cameras, or endoscopes, has improved to a point where we are feeling more comfortable in other areas of the body, and in other areas of the brain performing surgeries guided by those video cameras. In the last couple of years, as more practitioners and more surgeons have gotten more used to endoscopic approaches, we've been pushing the boundaries of using those instruments for surgeries that they typically weren't used for. There were a couple of reports from other institutions from other hospitals in the country, about people using an endoscope to perform a callosotomy on adults or in cadavers. During my training, in residency, my medical training, I practiced using an endoscope quite extensively. And I wanted to put those skills to use and try to do a surgery for children that would otherwise be a very large surgery and turn it into something smaller that they could recover quicker from while still giving them the same outcomes.

00:04:49

Host:  So do children have better outcomes with the surgery than adults?

00:04:53

Dr. Hansen:  In general, children usually do a little bit better after surgery than adults because they heal better and their brain is a little bit more adept at rewiring itself for lack of a better term. We also call it neural plasticity, meaning that their brain is able to adapt to changes a little bit better than adults. From a seizure standpoint, the seizures that adults have and that children have, often have very different onsets are different reasons for occurring in the first place. So their outcomes aren't directly comparable, but children are having excellent results from this type of surgery.

00:05:26

Host:  Fantastic. So when did you first become interested in this particular surgery?

00:05:31

Dr. Hansen:  One of my mentors in fellowship, Dr. Sandy Lam at Texas Children's, used the endoscope very extensively in her surgical practice. Although not initially for epilepsy. After I left fellowship, while I was no longer training there, she published a few case reports meaning single patient experiences on using the endoscope to do some epilepsy surgery. With my background in using the endoscope for other types of neurosurgical procedures. I thought that the corpus callosotomy made perfect sense, given its location in the body, the relative ease of getting at that structure, anatomically. And it's traditionally a surgery that has a very big opening in the skull, it traditionally puts a lot of tissue trauma to the brain. So I thought it was a perfect surgery to try and target something more minimally invasive.

00:06:21

Host:  How many other epilepsy centers offer this type of surgery to children?

00:06:25

Dr. Hansen:  That is a great question. And the simple answer is, I don't know. And the reason for that is that we can only have published reports from institutions to suggest that they're doing it. Otherwise, if they're offering it, they don't necessarily broadcast it or make it known. So I know that the University of Washington or Washington University in St. Louis, one of their epilepsy practitioners is doing this. And there are some small reports from Boston Children's, and also Dr. Lam in Texas Children's. But we're amongst a very, very small handful of places that are offering this sort of cutting edge procedure.

00:06:58

Host:  Why do you think that is?

00:06:59

Dr. Hansen:  It's technically very difficult, the feeling comfortable using an endoscope is not something that comes naturally. It is, uh, staring at a video screen, not looking at your surgical field, not directly staring at what you're operating on, but manipulating it through a screen in front of you. And through a rather small opening is a rather daunting task. And there's a pretty steep learning curve with an endoscope. I think a lot of practitioners don't have the time to invest in learning those techniques. And the traditional approach, although very invasive, works very well. So a lot of people don't see the need to try and make something better or reinvent the wheel.

00:07:36

Host:  So who would be eligible for this surgery?

00:07:39

Dr. Hansen:  Wonderful question. So we typically think of children with intractable epilepsy that have an underlying diagnosis of what's known as Lennox Gastaut syndrome, or children that have had damage extensive damage to specifically just one side of their brain. Those are the patients that we're focusing on currently, although if you ever have a child with epilepsy that has not been evaluated by our epileptology group here at Cook Children's, we would strongly recommend referring them so that they can be evaluated to see if this surgery, or any of the other surgery offerings that we have would be available to them.

00:08:14

Host:  So what are the advantages or benefits for the patients?

00:08:18

Dr. Hansen:  So with this specific procedure, we're taking a surgery that would have traditionally taken probably eight to 10 hours in the operating room, and we're now routinely doing them between five and six hours, so it's a shorter procedure. We're taking an incision that would have been 10 to 12 inches long on most children, and we've reduced it down to an incision, that's usually three or four inches. Instead. We're taking a bone flap or the size of what we call our craniotomy or the amount of bone we have to remove to do surgery. Although we do put it back, it's gone from the size of about your hand down to the size of about an inch by an inch and a half square. That means in the long term, that when kids are recovering from this surgery, they have less pain, they have less bleeding during the surgery, they're in the hospital, usually a fewer number of days just because they don't have ... their body didn't go through so much trauma. Now, the goal of surgery, severing the corpus callosum has some pretty significant neurologic impacts, at least temporarily. Those are not lessened through the surgery, because the goal is to do the same thing to the brain. We're just doing it through a smaller opening.

00:09:20

Host:  If I understand correctly, you've performed this procedure on several patients here at Cook Children's. Can you talk a little about their backgrounds, the types of epilepsy or seizures, the severity of their condition and their ages?

00:09:33

Dr. Hansen:  Absolutely. So in the last year, we've done about five of these procedures. We have children ranging from the age of five up to the age of 17. Two of those children had significant what we call perinatal injuries, meaning shortly after birth or at the time of birth, they had extensive damage to one side of their brain or the other. That damage resulted in debilitating seizures. And most of these children are having seizures every day, if not multiple times a day. Two of our other children have a syndrome called Lennox Gastaut syndrome, which it's not entirely clear what causes this, but it has a very specific epilepsy finding on EEG's or brainwave patterns of electrical activity. And it is notorious for causing drop attacks. Drop attacks are again where the child's muscles tense, and the patient falls to the ground. And, obviously, depending on where they are, when they fall, can have some pretty serious consequences from an injury standpoint. These children also are seizing multiple times a day, usually, even through multiple seizure medications.

00:10:36

Host:  So how are the kids doing now?

00:10:38

Dr. Hansen:  Well, I'm happy to say fantastically, so the very first child that we performed a surgery on has been seizure free now for over a year since the day of surgery. And he was seizing multiple times a day prior to that. The other kids have also had wonderful results, although one other is now seizure free and has had no seizures since about six months ago, the others have had over a 90% reduction in their frequency of seizures, but also, more importantly, the severity of the seizure. So instead of seizures that are lasting for minutes, and causing significant cognitive impairment after the seizure is done, many of these seizures now are brief seconds, and the child goes back to their baseline immediately afterwards.

00:11:20

Host:  One of the things that I would be curious about, I know for kids who have these multiple seizures, that a lot of times it can cause long term developmental and cognitive issues. So does this surgery, help repair or at least reduce those future conditions or long term conditions?

00:11:38

Dr. Hansen:  Yeah, that's a wonderful question. I don't think we have enough evidence yet to know if performing the surgery will reverse some of the effects, that long term anti seizure medications cause or that just long term exposure to repetitive seizures cause but I can tell you, as we have lots of data, that the earlier we can treat children, the earlier we can intervene in them surgically, if appropriate, the quicker we can get them off anti epileptic drugs, and very often reduce their seizure frequency that does have a significant impact on their long term cognitive development.

00:12:11

Host:  Fantastic. So when you disconnect the left and right brain, what impact does this have on brain functionality and or cognition?

00:12:19

Dr. Hansen:  So it's kind of a funny thing, the left and right brain like to talk for some very, very specific instances that we can set up in a lab to show that when we disconnect them, they're no longer doing that. But in day to day life, it's really actually very difficult to know that the left and right side are not talking. And in fact, for many of the children, because they were seizing so frequently, and that has such a significant negative impact on cognition, the children actually appear to be better off after surgery than worse. One of the really funny sort of things that you can test, just as an example of what you get with split brain syndrome, which is one of the names for this is if you place an object in a patient's left visual field, so not in their left eye, but in their left visual field, so the left side, and they aren't allowed to see it with their right visual field. So you have to put up blinders. And this is why it's all very simulated, but the left visual field connects to the right side of the brain, the right side of the brain, for most people is not very responsible for language. So that image on the left side going to the right brain is recognized as an object. But if you ask the patient to describe what it is, they're unable to come up with the word for because of the language or identifying that object comes from the left side of the brain. And because the left and right side aren't talking, the right side knows there's something there, and the left side would know what it is, if it could tell that there was something there. But in day to day life, there's very few things that just show up on the left side of our vision, or just the right side of a vision or just in our left hand. So again, these are very simulated tests to show how the left and the right side of the brain talk, but in practicality rarely come up.

00:14:01

Host:  Fascinating. So how does this compare to loss of cognition or functions without treatment?

00:14:06

Dr. Hansen:  If we didn't think it had enormous benefit, we wouldn't offer it. So, again, we know that children who have repetitive seizures over years of life and are on antiepileptic medications which have significant brain chemistry and neurocognitive developmental side effects, we know that stopping the seizures even when it involves severing the left and right sides of the brain from one another or removing parts of the brain for other types of seizures, surgery, their outcomes, the children's outcomes are significantly improved by stopping the seizures even with loss of brain tissue.

00:14:38

Host:  So as you've mentioned, this procedure is appropriate for treating kids with certain types of epilepsy or seizures. But what surgeries are currently available in pediatric surgery for other types of severe epilepsy or seizures, or for that matter, tumors or any other anomalies that may occur in the brain?

00:14:54

Dr. Hansen:  Well that's a pretty big question, but we'll focus on the seizures. So we have several different seizure surgeries that are available, if after a thorough evaluation with our epilepsy group it's deemed appropriate. So the most common seizure surgery that people may be aware of, is something called an anterior temporal lobectomy. And you may be familiar with that because it's one of the most common surgeries for seizures in adults. So the anterior temporal lobe is an area that is commonly a focus of seizures. And a lobectomy simply means we take that portion of the brain out, we can do that to other areas of the brain as well, if we determine that they are a focus of seizures. That's among the more common surgeries, we also have surgeries that sound super cool. Laser ablations, where we put a small fiber optic cable into the brain into an area where we think seizures are coming from, and we can actually burn that area, or thermally coagulate that area, destroying the tissue that's the origin of the seizures. We also have the ability to implant multiple electrodes into the brain itself. So people may be familiar with with what are known as scalp EEGs, where you see children or adults with all the dots scattered on their heads connected to a bunch of wires connected up to machine with all the squiggly lines. We have the ability to move those electrodes from the scalp where the readings are good, but not very accurate, actually down into the brain tissue itself, where the readings are incredibly accurate, and allows us to more accurately diagnose where seizures are coming from letting us know better whether or not a child is a surgical candidate or not. We have a couple more technologies that we don't use very frequently that are available in really difficult to treat cases. One is known as a vagus nerve stimulator, which is a small device that we place onto the nerve in the neck that sends small electrical impulses back up to the brain, and is thought to help certain types of seizures for certain kids who are otherwise difficult to treat. We also have something very new, that is being not used very much in pediatrics yet, but is being more used in adults called an RNS. And that is a device very much like a vagal nerve stimulator. However, instead of stimulating a nerve in the neck, we're stimulating the surface of the brain directly using a special computer and a special electrical impulses to try and help modulate seizure frequency as well.

00:17:12

Host:  So are there any innovative and minimally invasive surgeries on the horizon for kids with severe forms of epilepsy and what advantages do they bring? Or do we hope they'll bring?

00:17:22

Dr. Hansen:  Yeah, so from myself personally and from the other providers I know throughout the country who are really trying to push the boundaries of endoscopic work, I think we will continue to try and refine our use of the endoscope and apply it to other traditional forms of epilepsy being it lobectomies of the temporal lobe or the frontal lobe or a procedure called a hemispherotomy or hemispherectomy. Things that are again, traditionally done through a very large surgery trying to make them performed through a smaller, less invasive opening. But there's also something that is very new on the horizon is not being used that I know of yet in pediatrics, but something called focused ultrasound. So much like our laser ablation is looking to heat up tissue to destroy an area of seizure focus, that still requires us to put a fiber optic cable into the brain which is invasive, even if minimally so. Focused ultrasound is very much almost like stereotactic radiosurgery, which is radiation. But this is using focused ultrasound beams to try and destroy or heat up a small area of tissue in the brain to get the same effect as we would with using a fiber optic cable. So truly non invasive.

00:18:31

Host:  Absolutely amazing. So overall, what does the future look like for these patients?

00:18:37

Dr. Hansen:  You know, unfortunately for epilepsy, a lot of children, they are not surgical candidates. And so they have a very difficult life. They are treated with usually multiple medications, and they continue to have seizures throughout their life. But that's not everyone. And it's difficult to tell those children from the children who are true surgical candidates, which is why we would always recommend referring any children that you might know that have failed as a seizure medicine so that we can evaluate them more in depth. For those children that are surgical candidates, surgery outcomes vary based on the area of the brain that the seizures originate from. But we can have seizure freedom upwards of 50% in some areas of the brain 70% in some areas of the brain and over 90% in other areas of the brain. So it can be substantial impact on the child's life in a positive way if we can perform surgery on them.

00:19:24

Host:  So for pediatricians or other primary care providers, as well as specialists who have patients they think maybe candidates for this or any of the neurosurgeries at Cook Children's, how would they refer them? At what ages? And how early in their care?

00:19:39

Dr. Hansen:  Sure. So if you think that you have a child with a standard neurosurgical issue, refer them immediately. Call up our clinic. Call up, one of the physicians on call will be happy to chat with you. Cook actually has a direct connect line to be able to connect to a specialist of choice within a very small amount of time if you've got something that you're worried about, and we're always happy to see the children if it's something that you're not comfortable managing or diagnosing. From a surgery standpoint for epilepsy specifically, those children should be referred to our epilepsy group. And that is our neurology colleagues first. They really spearhead the effort to diagnose children with seizures, and to determine whether or not they're surgical candidates. We typically think of children who have failed two seizure medications as being medically intractable epilepsy or medically intractable seizures. Those children no matter what their age are, or no matter how long you've been treating them, would be appropriate candidates to be referred to our program for evaluation.

00:20:37

Host:  So it's been really great talking with you today. Dr. Hansen, thanks for taking the time to share about endoscopic corpus callosotomy and the fantastic work you and your team are doing here at Cook Children's. It's truly amazing and so important to the future of these kiddos.

00:20:51

Dr. Hansen:  It's been my pleasure to be here today. Thank you so much. I'm always happy to talk to anyone in our organization or without about these procedures and how they might be able to impact the children that you're caring for.

00: 21:02

Host:  Fantastic, thank you. We're so glad you could join us today. If you'd like to learn more about this program or any program at Cook Children's, please visit us at Cook Children's dot org

Listen Now
Dr. Steve Muyskens, Medical Director, Cardiac MRI, 3-D aPPROaCH Lab, Cook Children's, takes us into the world of 3D heart printing. It’s a fascinating journey into how this advancing technology can take the guess work out of pediatric heart surgery, helping more young patients can thrive into adulthood.

Dr. Steve Muyskens

Related Information
Cook Children's 3D aPPROaCH Lab
Cardiac Magnetic Resonance Imaging
Cook Children's Cardiothoracic Surgery program
Cook Children's Endowed Chair Program
Cook Children's Heart Center

Transcript

00:00:02 

Host:  Hello and welcome to Cook Children's Doc Talk. Today we welcome Dr. Steve Muyskens, medical director of the Cardiac MRI program here at Cook Children's in Fort Worth, Texas. Dr. Muyskens, is an endowed chair supporting the expansion of our CMRI program and its diagnostic uses. He has since established the three-dimensional lab for the planning and printing of congenital heart disease, which uses advanced technology to support presurgical planning and family education for patients with complex heart conditions. He is our expert on this subject. So thank you for being with us today, Dr. Muyskens/

00:00:36 

Dr. Muyskens: Thank you very much for the invitation.

00:00:38

Host: So what exactly is a 3D model? And what is the process for creating that model?

00:00:44 

Dr. Muyskens  So I think the important part is to kind of start with the patient. There are conditions with varying degrees of complexity that our current diagnostic modalities fall short in some manner. So those patients have long been difficult to manage. We started realizing that we can use technology like 3D printing and virtual 3D animation to help us better understand their condition. So when we identify that patient, whether it be an older patient who has already had some surgeries, or a newborn who has a very complex heart, who we're hoping to do an initial palliation, or surgical repair on, the first thing we decide is, what is the best modality to obtain the information that we would need to then use that technology. The two most commonly used technologies would be MRI, or cardiac CT. You can use rotational angiography in the cath lab, but that's much less commonly used. Once we have that selection made, the data is obtained by us obtaining a typical CT scan or a typical cardiac MRI. But then that data, which is in a raw form called DICOM. DICOM data is then moved to specialized software. And from there, I take that data, and we segment it is the term we use, basically manipulate that data and create a virtual model, essentially, from that information. That model can then be viewed either in the virtual space, so on a typical computer that you would flip around, but then again, you're still only in two dimensions you're looking at in a screen. So then typically, we move on to a 3D printing of that data. So the typical segmentation portion, or manipulation of the data, can vary from anywhere to two to 24 hours of time, depending on the complexity of the model. And then the printing on the actual 3D printer can take anywhere from seven to 15, 16 hours. And then we clean the model and remove kind of some of the support material that's necessary. And we have a replica of the patient's heart.

00:02:48 

Host:  Wow, remarkable. So can you discuss then with us the different 3D programs you're using right now in the lab?

00:02:54

Dr. Muyskens:  Yeah. So our lab is in some ways, like other labs, and in some ways different. When we developed our lab, we started trying to think forward and make sure that,  A, where we are five years from now, and then, B, where we are from a understanding of all the different complexities that come along with different forms of heart disease that we were covering all of our bases. So I think in addition to the 3D printing, which is what most people think about, we also have a virtual software program as well. So kind of backing up the 3D printing, which is what most people think of. There's lots of different types of software. And there's lots of different types of printers, we currently use a software program by Materialise, which is that segmentation, that manipulation of the data, or interpretation's probably a better word, of that data, and then creates the virtual model, because it has to be translated to a different language for the printer has to be translated from a two dimensional language into a three dimensional language. And then we currently have a Stratus, this printer that we use that component in different colors in different materials, depending on what we're trying to achieve with our model. And we print on that. The other option is we have something called True 3D by Eco Pixel. True 3D is a software program and virtual viewing station that allows you to manipulate data in virtual 3D. Essentially, like you're in a 3D movie theater, but you're actually in control of the entire environment. The advantages to this are that not everything can be printed. And when you're talking about performing a surgery or doing something invasive, there's also all the other structures become important. Where are the lungs? Where are the airways in relation to the hearts and the vessels. And so 3D printing, you really can't print an entire chest, you can but it's time consuming. And it would be difficult then to visualize some of the structure. So this kind of bridges that gap and allows us to even do some virtual planning on that software. And then the third component that we've been using a little bit is something called 4D Flow, which is a advanced method by MRI to evaluate blood flow in the heart.

00:04:58 

Host:  So what is the difference then between 3D and 4D?

00:05:02 

Dr. Muyskens:  4D is essentially three dimensions. So you have, you know, length, width height, you have your spatial dimensions, and then you're adding a fourth dimension. The fourth dimension is time, we currently use flow in a two dimensional manner in our everyday use for patients that are being evaluated by cardiac MRI. And what this does is it essentially prescribes a coin through a vessel a size of a nickel or a dime, one little slice. And then by using some really fancy computers, we can essentially evaluate what protons are moving through that dimer through that hula hoop is another, I guess, analogy we could use, you can tell how much at which direction how fast. But it's still only one little tiny slice. So what four dimensional flow does is it actually reconstructs the entire heart, chest, vascular space, whatever you want to assess. And then you can not only measure wherever you want, afterwards, but you also visualize all of the blood flow within those vessels. So it actually allows you to track all the protons, all the red blood cells as they move through whether they're swirling and twirling or however direction and gives you a lot of additional information.

00:06:02

Host:  It's remarkable. So then it just gives you that much more of a picture of what's happening in the heart, and what's working properly and what's working improperly.

00:06:11

Dr. Muyskens:  Exactly. And that's really becoming more and more important, as we've moved from beyond just survival to optimization for our patients and our surgical palliations, right? We're not just trying to get patients to survive, like we were 30, 40 years ago. Now we're trying to have patients that thrive as adults. And so understanding the physiological ramifications of our specific surgical palliations is a kind of a new frontier and 4D Flow allows us to do that.

00:06:45 

Host: Technology is exciting in medicine, it is. So what is the benefit then of using these three specialized technologies, the 4D flow, 3D virtual and your 3D printing?

00:06:56

Dr. Muyskens: Yeah, I think all 3D adds information that is unique and not otherwise available with other modalities. So that kind of allows to have a really fully comprehensive 3D lab, the 40 flow, like we talked about allows us to understand the physiology of the anatomy and those vessels and how they're worked and how they look and the valves and what's been leaking. And what's been worked on. The virtual allows us to rapidly assess the anatomy, without having to go through the whole complexity of a segmentation and manipulating the data and interpreting the data, creating a model cleaning the model, and also allows us to look at the relationship of all the structures in the chest to those vessels or to the heart. And then the 3D allows us to really step forward and have this true comprehension of what the heart feels like, looks like to be able to walk through that space.

00:07:49

Host:  So in regards to patient surgery, how does this 3D technology help to accomplish that?

00:07:54 

Dr. Muyskens:  Yeah, I think in a lot of ways, we're still discovering how this technology will be advantageous for patients. I think our feeling and our hopes for the future are that we are creating a better operative plan and operative outcome. So having a really complex congenital heart lesion that we run into that is very atypical from our more conventional forms, can be diagnostically challenging, because looking at our conventional views, things are not where we're used to trying to recreate that heart in your head by using 2D slices by echo or MRI is very difficult. And a surgical kind of template that a surgeon has in their mind where things are, is very different as well. And so being able to take that information, A, identify landmarks for things that they're going to find when they open the chest, you know, next to this airway, or this structure is where I'm going to find these things by using the virtual. And then the 3D really allows that additional information, I think there's two streams of visual processing that we tend to have. And I'm not a neurologist, but the dual stream hypothesis that exists where we have one stream that allows us to do rapid identification, so pattern recognition. You know, when you look at a picture of a path down the woods, you kind of understand that, you know, that's a forest, and there's a path, you've walked down paths in the past, you kind of have an idea as to what that would be like. But then there's a second, which is really the spatial understanding of that space, right? If I had you close your eyes, if you're looking at a picture and put you blindfolded at the beginning of that path, you probably wouldn't feel very comfortable about where you were going to walk. But if I had you walk up and down that path multiple times, and had you close your eyes, you probably have a pretty good idea about walking that path because you rehearsed it, you now have that additional spatial information, having a surgeon being able to look at the heart, hold the heart and understand that and be able to even rehearse that then when they're there. They already have that spatial understanding. So that improves potentially shortening operative times and improving outcomes, less redo surgeries, which are all positive benefits,

00:09:55 

Host:  Right, because we really don't want to birdbox pediatric surgery, situations. No, exactly, exactly. So are there any specific diagnoses for which these technologies are particularly helpful?

00:10:09

Dr. Muyskens:  You know, I think it's a very wide range. And if you look at the institutions that are currently utilizing this technology in some form, the utilization is very expansive from really rather straightforward conditions to conditions that are very complex. At Cooks, and I think probably the majority of institutions that are really invested in the 3D idea, the more complex lesions are, I think, the most useful for exactly what I described before, like, we often times don't have a great understanding because of the limitations of our current 2D technology to understand where things are in these rearranged complex congenital lesions. So different forms of, or more complex forms of, conventional things like tetralogy of fallot, there's many forms where they have VSDs, in different positions, or the great vessels are differently related. And sometimes that repair can then be difficult based on the relationships and it can be somewhat difficult to understand that definitely complex single ventricle things we call upstairs, downstairs, criss cross ventricles, really complex heterotaxy patients who have a multitude of abnormalities and trying to understand whether we can make those patients into a two ventricular repair versus a single ventricle palliation can be difficult, and we don't want to have to make that decision on the fly. And so having that understanding of those relationships, and what the surgeon is going to be able to do by fully understanding their anatomy is probably the most useful use that we have found so far for the technology.

00:11:38 

Host:  Is there a specific case where this technology was particularly helpful that comes to mind?

00:11:43 

Dr. Muyskens:  Here, we've had several, I think that one that comes to mind, which is in line with what we talked about a little bit, and the last question is tetralogy of fallot with multiple AP collateral. So tetralogy of fallot is a condition where the division of the great vessels during development is abnormal. And this can result in a large variability of the size and the condition of the blood vessels that feed the lungs. It typically does have a large hole between the bottom two chambers, with that kind of hypertrophied right side, and the larger aorta. Some severe forms, the pulmonary valve, essentially, is atretic. It's not there at all. And then embryologically, what happens to compensate for that in certain patients is multiple blood vessels that are originating off of the aorta, instead of originating off of the heart, feed the different segments of the lung. And so the repairs are very complex and are typically staged, the surgeon has to within the first either weeks to a few months of life has to identify all those individual vessels where they're coming off in the chest, which can be in a large number of places very variable from patient to patient, essentially, then pull those vessels down to reconstruct what would be pulmonary arteries, and then reconnect them to the heart. And so localizing these one to three millimeter vessels in the child's heart, that are tucked behind lungs and airways, and all these other structures is very arduous. So we've had a case here when relatively early on when we started our lab where we obtained a CT scan. And that helped us identify all of those little individual vessels, the relationships to the small, native kind of pulmonary arteries that were still there, but not being fed by any or flow from the heart, the surgeon was able to identify all of those landmarks, we are able to create a map, essentially a virtual map of where all these are in relationships to other vessels. So the surgeon knew where to look and where to dissect and behind what structures that were going to find these small vessels. And then we were also able to then take that data and create a 3D model that the surgeon could actually have in the OR with them, as well, as part of that model, we included the trachea and the main airways so that they could see the relationships and how that was going to be a challenge and a few of the collaterals as far as we call uniform, coalescing, pulling them all together

00:14:09 

Host:  So clearly being in the cardiac pediatric field, you guys are highly educated. How has this technology been helpful in taking your education even further?

00:14:19 

Dr. Muyskens:  Yeah, I think education is a big part about 3D technology that doesn't get talked about a lot. I think, as clinicians obviously, we're very focused on outcomes, improving patient outcomes, but part of that is making sure that the families because they're a big part of that care team and the other providers such as the nurses, other ICU doctors, people that are not involved strictly from a cardiology or cardiothoracic surgical standpoint, have a good understanding of the anatomy as well. And so it's been very exciting to see the response that some of the families have when they actually see their child's heart as cardiologists we may have a great understanding in our head. That doesn't mean we're good artists. And trying to draw a complex three dimensional on a two dimensional piece of paper, let alone be an artist and draw it accurately and well is very difficult. So depending on the cardiologist, it's somewhere between a decent picture and some chicken scratches. And so I think the family's, especially without a basis of medical knowledge and anatomy, oftentimes feel very lost as to what exactly is going on. So to be able to essentially then provide their child's heart to them to look at, and to have a discussion about with the surgeon, or the cardiologist really opens their eyes as to Wow, this is what is normal, I can see that. And this is how my child's heart looks. And here's the problems and this is what's going on. And this is the magnitude of the problem. I think also for recently, we've started including the models at the bedside, at the patient's bedside, both preoperatively and postoperatively. And so that allows the staff and everybody else to understand because children with complex congenital heart disease have very different physiologies. You know, they're what their saturations are supposed to be, what high or low pressures or high or low oxygen administration can do to that patient is very different. So having a full understanding, especially these complex patients that don't fall our typical rules all the time, I think is very helpful. And it's been, again, exciting to even see the staff get excited about the models and understanding what's going on and being able to translate

00:16:24

Host:  What is the direct benefit to the patient in using a center with this type of technology?

00:16:30

Dr. Muyskens:  What we talked about a little bit before, I think, you know, we don't know for sure what the ultimate benefit is going to be. But having a better understanding of the patient's anatomy, having better operative plans, being able to rehearse those surgeries, less on the fly decisions, should yield improve outcomes. It also allows us to take on more complex two ventricle repairs and patients that oftentimes other institutions would do a more direct, more straightforward, single ventricle palliation with little bit less risk, but with greater long term risk of complex problems, morbidity, mortality, liver failure, those types of things over the course of their life. I think ultimately, what it really says as a patient or as a parent, is that your institution is really striving to be excellent, you're trying to leave no stone unturned, you're trying to make sure that you have all the information that you're doing the ultimate right surgery, because ultimately, what we do is we want to maximize benefit and minimize risk. And so to do that, for our patients, you have to have everything, you have to have all the information. So having your care at a center that is striving to use this type of new technology or new technologies in general helps you I think feel reassured that that institution's not just trying to do adequate care, but trying to do excellent care.

00:17:45 

Host:  Absolutely. And you as a parent, I love the thought that what you keep saying is that the problem solving and all of that information is being collected, all the problem solving is being done prior to surgery, as opposed to when my child is on the operating table. So how could the outcomes not come out better? It makes perfect sense. Is it your hope that this just becomes normal protocol?

00:18:05 

Dr. Muyskens: Exactly. So the idea is that by having other centers and start to adopt this, because there's a demonstrated benefit, it becomes more of a standard of care instead of the exception.

00:18:15

Host:  So what are your future plans with the 3D lab? What exciting stuff is coming up for us?

00:18:20 

Dr. Muyskens:  As new practitioners of 3D in the last few years, we're really trying to, A, improve on what we're doing. B, expand the availability of the technology to our team. And so one of the first things that we're focusing on is improving the infrastructure by having more places that we can view this 3D technology. Right now, a lot of the virtual 3D especially is very confined to that one monitor ,that one screen. So we're in the process of trying to improve the software and the hardware in our areas where we have conferences in our consult rooms for our patients, and then increasing the number of 3D viewer stations that we have. So that Then, during a regular consultation with a family, we can use all that technology to its fullest versus having to try to move one or two pieces around the hospital continually. And then especially in our joint-cast surgical conferences where we do a lot of our surgical planning discussion, then we'll be able to utilize to the fullest that 3D virtual capability. So actually, everybody in the room can put on a pair of 3D glasses and we can actually have our discussions, break some of our first discussions from top to bottom really in three dimensions versus looking at a bunch of two dimensional slices. Additionally, we have found that just printing a 3D model is not the same as encountering that heart in the chest. And what I mean by that is, when a surgeon goes and does an operative repair, they can't pull the heart out and flip it around and open it however they want and then do the repair and then stick it back in. And so having a 3D model that just floating around, provides a lot of information, provides a lot of understanding, but then as far as actually practicing that procedure, it's probably not the best. So we have started working on a supportive template where these models can then be affixed and repositioned so that it is exactly the same position as a surgeon would encounter. So then they can actually look the model, but then they can actually place it like it would be in the chest, when they open the chest. And they can practice and look through, there are very specific views that they'll be able to see because the hearts still tethered, they create a hole, they look through these valves and that view and what access they can get to sew a patch or a baffle or move something, may be very different than they think it's going to be if they just have the model out and floating around. It's really improving the process. and improving the surgical planning for the surgeons and for the families is a big part of that. Additionally, we've started to do more research with 4D Flow, and are working with Siemens on a research project to kind of see how often we can use this, how easy it is to use this new technology. What are all the potential benefits beyond just specific lesions that we already have started to look at? Really again, making it more of a standard of care.

00:21:03

Host:  Is that your hope that this technology and benefit to our patient families and our staff go beyond just the cardiac unit? Are we hoping that maybe there are other specialties and patients with other types of diagnoses other than cardiac could benefit from this?

00:21:18

Dr. Muyskens:  Definitely. So when I created the 3D Lab, the lab was created for everybody at Cook's to be able to use. Obviously, I'm focused on the cardiac standpoint being a cardiologist, but the utility for other specialties is well established. So orthopedics, neurosurgery, interventional radiology, there are definitely other areas that have a history of benefit. If you look in the medical literature for 3D printing,

00:21:45

Host:  Do you predict more programs and or specialties will begin using this technology?

00:21:49

Dr. Muyskens:  I do. I think this definitely kind of goes back on some of the things that we talked about. But I think from a specialty standpoint, lots of other specialties could benefit from using this technology for the same patient understanding, caregiver understanding, provider understanding, preoperative planning. And I think we're really just in our infancy right now as far as where this technology is in the medical world as a whole. And I think as we understand it better and hone our craft a little bit, I think you'll continue to see more and more specialties and more and more centers continue to adopt the technology.

00:22:21

Host:  So you know, the name of our streaming channel is promise and purpose. How does this technology and how does this work that you do couple, our promise and your purpose in this life? How does it meld your passions together?

00:22:35

Dr. Muyskens: My love is pediatric cardiology. The families, the physiology, the complex anatomy, the fact that every month I see something that I haven't seen before, is exciting and challenging. My interest in noninvasive imaging developed because trying to understand that complex anatomy, trying to help the surgeon understand the anatomy and be able to then execute the best possible surgery for that patient is rewarding. And as a cardiologist, what you you want for your patients, I think the part that drove me to three dimensional imaging was that maybe this goes to the promise that I feel like when you bring your child to me or to any cardiologist, you're promising to do the best you can to take care of that child. That's a big goal and a big aspiration. And too often being the noninvasive cardiologist in the room and providing the information in a conference or to a surgeon in really complex cases and the gap of knowledge between what was reality, what was my understanding, and what was the surgical understanding, left me unsatisfied. I live in a completely virtual world in my head. I'm not a surgeon, I don't hold a child's heart, I look at their heart by imaging. The surgeon, on the other hand, holds their heart and makes the surgical revisions, but they aren't an imager. So their thoughts are tangible. Mine are virtual, essentially in my head. And even just crossing those two bridges on a relatively straightforward imaging can be difficult. But too often I heard, "We'll have to see when I'm in there". Because in really complex heart disease there's no simple plan. There's no ‘everybody does it this way, doesn't work out that way’. And I was very fortunate to work at Cooks, where I have Dr. Tam, who's an amazing surgeon and does amazing things. And so, being able to now use this technology to bridge those gaps and to remove that ambiguity or that lack of complete understanding. I don't want him to ever say I'll have to see when I get in there. And that's kind of what has driven me towards pursuing the 3D Lab.

00:24:40

Host:  Well, we're certainly appreciative of all the work and the passion that you bring here, and to our patient families. So thank you, doctor Muyskens.

00:24:47 

Dr. Muyskens:  Oh, thank you. I'm appreciative of the opportunities that Cook Children's and the Foundation have given me and the support they've given me to pursue my passion.

00:24:55 

Host:  We're so glad you could join us today. If you'd like to learn more about this program or any program at Cook Children's, please visit us at Cook Children's dot org.