After Roneet’s passing, I wanted to channel my grief in ways that I could honor her memory and help contribute to bettering the world. I chose to back incredibly dynamic, bright, passionate, and innovative people with whom I had great respect that I thought Roneet would be proud of as well. And while she never got to know Dr. Yama Akbari, the two of them would have hit it off beautifully. His care and concern for her after she had her accident was something that I will never forget and brought healing and closure for our family. I started the Roneet Carmell Memorial Endowment Fund to help support important work and research that Dr. Akbari is carrying out to help create better outcomes for cardiac arrest and coma patients. In an interesting twist of fate, it turns out that Dr. Akbari’s work also has a great application to COVID-19 patients as well.
Last year on May 23rd we held an inaugural lecture in which he spoke, along with Dr. Jack Lin, about their research. Dr. Lin’s emphasis is on epilepsy, which is something that my son Jacob has contended with for 25 years. Because of COVID-19, we could not have a second lecture at this time. As a workaround, we thought an interview would be the next best option in this Zoom age. Dr. Akbari was gracious enough to let me interview him to discuss how his work can benefit COVID-19 patients and some of the extraordinary research breakthroughs he and his team have made to potentially dramatically improve the outcomes for cardiac arrest and coma patients. He is also working on some incredible devices that can help in these areas as well.
What follows is the video interview as well as the transcript of our conversation. I think you will find it fascinating and if you are so inclined, I would be honored to have you participate in helping to support Dr. Akbari‘s research in Roneet’s memory.
Here’s the video of my interview:
Roneet Carmell Memorial Endowment Update Transcript
May 12, 2020
00:22 – Hello Dr. Akbari. I want to thank you so much for this meeting and update. I know you are extremely busy, particularly in these very interesting times.
The Roneet Carmell Endowment Fund and Memorial Lecture last year brought so much healing to my family, to those who attended the lecture, and for those who contributed to the fund. So, I want to thank you for that.
We discussed you giving the lecture every two years, and in between, you would provide us an update on your activities in the areas of cardiac arrest and coma research. And obviously with the global coronavirus pandemic, so much has changed in all of our lives so unexpectedly, and of course, I’m reminded how quickly life can change.
01:10 – First of all, I just want to thank you and all your friends and family members who’ve supported our research lab. It’s really meant a lot to us and it’s really enabled us to fund a lot of research, critical research, over the past year that I’d be delighted to give an update on.
1:29 – Yeah, that would be great. So, with regard to that, I’ve heard that UCI is doing a lot of research in regard to the fight against COVID-19, and I think you are seeing some of those patients yourself. Would you mind starting with that and what you’re observing and experiencing?
1:45 – First of all, UCI is doing a lot of research, both on the clinical research front, as well as the lab and bench side of things the research does. There are many, many people doing research on this, and it’s very special actually to see so many people coming together to work together to try to fight this pandemic. The research revolves from anything on the spectrum of from diagnostics to treatments to prognostication, and all different various effects of COVID, including the epidemiological aspects, physiological aspects, pathological, and psychological. It’s really something that we in the medical community have never seen before, so it’s really wonderful to see everybody coming together.
2:42 – On the clinical side of things, there are some clinical trials going on, and some kind of ended, including Remdesivir. UCI was one of the host sites for that trial. And there are a lot of observational studies going on as well. So, there’s a lot of research going on. And for me, personally, I’ve had a few patients, COVID patients now that I’ve been able to treat. Luckily, I think California has flattened the curve a lot, but we do have a consistent number of patients at UCI Medical Center, some of whom end up having to be under the care of the Neuro ICU team specifically. So, we have had the honor of treating these patients. And I’ve gotten to see firsthand how devastating it can be for both the patients, as well as the family members. Just being able to communicate with them using video conferencing to let the family members look at their devastated family members on life support. It’s certainly something I’ve never done in the past 10 years of critical care that I provided. But we have to do this.
4:11 – Alongside that, the research that we’ve done over the past several years has been on cardiac arrest and resuscitation research. However, one, caveat to what we have done and what we can do with COVID, is that our research deals with cardiac arrest and resuscitation. The way COVID patients die is actually from ultimately having a cardiac arrest, and usually, it’s from a low level of oxygen, so it’s respiratory failure. We believe this is some type of pneumonia, although more recently, we know it’s not. It’s definitely not typical standard pneumonia, by any means. If anything, it’s more sort of a blood-clotting problem and it shows that the oxygen that they’re inhaling does not get transmitted and diffused into the bloodstream. It’s very different than our standard pneumonia. What we found is that we can adapt a lot of different types of research to this, and our lab is actually very uniquely situated to study this from a cardiac arrest resuscitation perspective. Some of what we’ve started to look into are highly relevant to the research that you’ve been able to fund.
05:44 – Can you go into some detail about some of the research and any discoveries that we should pay close attention to?
5:49 – The research that we’re doing is primarily cardiac arrest resuscitation. Our goal prior to COVID has always been to improve the diagnosis of cardiac arrest, improve treatments for cardiac arrest, and to enable better prognostication to allow family members to make better choices. That’s always been our goal. And to help improve patients to get out of a coma and ultimately recover. With COVID, because ultimately, it’s a respiratory failure-induced cardiac arrest, our goals remain the same and what we’re doing in our lab is fighting this through multiple fronts, actually.
6:35 – So, on the clinical side of things, I’ve been able to join consortiums that focus on neurological aspects of COVID and what we’ve noticed. This includes actually an international group. There are several sites in the United States, and several sites across the world, that have joined together to try to understand the neurological devastation. And the type of things that we’re seeing, and my colleagues are seeing elsewhere, is things that we’re not used to.
I’ll give you an example. One of our patients came in with what looks to be like a regular stroke, but the next thing we realized was that the patient ended up with a subarachnoid hemorrhage on top of the ischemic stroke. And then they ended up with hydrocephalus and then they ended up needing a ventriculostomy. That doesn’t happen from a normal standard stroke. What we’re finding is that with these COVID patients, there were significant neurological problems that we’re not used to seeing. It can be as mild as what everybody’s heard of, which is lack of smell. That’s the mildest of neurological symptoms, but without a doubt, COVID patients can end up with catastrophic strokes and hemorrhages in the brain and severe cognitive issues. The consortium that I’m with is looking at clinical patients that are affected by this so that we can learn better and to try to know what the best ways are that we can: 1) understand or predict what can happen to COVID patients with potential neurological problems, and 2) how we can treat them because they’re difficult to treat. One of our patients ended up with clotting and bleeding at the same time – how we treat that is very challenging.
8:37 – The other thing that we’ve noticed is that even patients who don’t have presumed neurological problems – and say they come in with supposed pneumonia – they end up on a ventilator on life support. Well, the oxygen levels get so low that we have to end up putting them in a deep medically induced coma and essentially paralyzing their whole body so that the ventilator can do 100% of the work. What happens when that occurs is that we lose our neurological exam. The patient is in a coma; we don’t know if the patient is having a stroke or not at all. They could be in a medically induced coma for three weeks. And so, when they wake up, then we might be surprised to find that they may have severe neurological problems: a stroke or something of that sort. And they’re not stable enough to be sent to get a CAT scan or an MRI. They’re on so much life support, their oxygen levels are very low.
So that brings me to the next thing that we’ve been working on, which is a translational device that we’re trying to build in the research lab to take to the ICU. It’s a device that uses optics to try to look at the oxygen levels in the brain. This is unique because the way we’re designing this has never been done. It would check for blood flow and circulation in the brain, as well as the amount of oxygen in the brain. It would be a point-of-care device where people can actually use the device at the bedside. Even a nurse could use it to try to provide us with information on the amount of oxygen in the brain. And the reason that’s important is because the brain is the most sensitive organ in the body. The problem with low oxygen levels is always that the brain or another susceptible organ is suffering damage due to low oxygen levels. When a doctor sees an oxygen level of, let’s say, 75% or 80% on the pulse oximeter, that’s very scary for doctors. So, what we do is increase oxygen levels and if we need to put them on life support, on a ventilator and maximize all the oxygen levels, we’ll have to do that.
10:50 –However, if we increase the ventilator settings too much, it damages the lungs. That’s what we found in these patients in New York and Italy and other hotspots. My colleagues have several colleagues in these places and what they’ve communicated to me is that it’s very challenging to oxygenate these patients. The other thing is that many people have found what’s called “Silent Hypoxia” in these patients, meaning that their oxygen level can be 75%, 80%, but they could be talking on a cell phone. That’s unusual. That’s very unusual. That means that their brain is receiving sufficient oxygen to not make them confused. What we hypothesize is that if that’s the case, then we should not maximize the ventilator settings and destroy the lungs, we should tolerate 80%, 85% as long as we’re confident that it’s not doing irreversible brain damage.
And so, the device that we’re building is actually going to enable bedside testing of the level of oxygen in the brain, as compared to something like the finger, for example. And I think it’s going to be critical. It’s going to enable us not only to minimize the ventilator settings but actually not even put people on the ventilator. In other words, we might just be able to put them on a face mask and not freak out if their oxygen level is, let’s say, 85%. Normally if we see somebody with 85%, we rushed to intubate them, put them on a ventilator. But this device we’re building in the lab, we hope to take it to the clinic. It’ll take a while but we’re trying to work as hard as we can. I think it’s going to make a difference.
12:27 – And then the final thing that we’re doing is, in the lab setting we’re actually using our animal model of cardiac arrest and resuscitation, and we’re working with other groups on campus. They’re actually getting a mouse. There’s a mouse model of COVID, a couple of mouse models, because typically animals, especially mice or rats, don’t get COVID. They don’t get symptoms, of course. In order to circumvent that, some people have made transgenic animals that express a specific gene that makes them susceptible to the coronavirus. By expressing that gene called the ACE2 gene, the virus can attack the animal. And that really enables researchers to now have an animal model where we can test specific things, whether it’s lung treatments, whether it’s vaccine treatments, whether it’s cardiac treatments or brain treatments. We’re working with groups so that we can actually take these mice, put them on a ventilator once they have low oxygen levels, or give them a low oxygen level and then study to see how the low oxygen levels in the lungs transmit the blood to the brain or to the heart – are alive – is uniquely able to do that.
Most labs can’t study everything and if the animals suffer severe low oxygen levels and go into cardiac arrest, we’re ready for it because we are a cardiac arrest and resuscitation lab. We’re very excited to be able to work through all the different levels in the lab – in the translational realm of devices, and in the clinical setting directly on patients – in coordination with these consortiums that we’re working with.
14:13 – Expanding beyond COVID 19 for just a little bit, you’re doing some fascinating research in other areas. Things like – with regard to fasting and measuring – there’s edema issues that come up. And, it’s a separate topic but maybe you could talk about some devices you’re working on, and some of this other research I think could have great application as well.
14:37 –A lot of that research has been ongoing. It took a little bit of a pause with the COVID crisis, but we’re just getting back up and going, and we’re very excited to share a lot of wonderful developments over the past year. Caloric restriction has definitely been one of the areas that we’ve been very interested in. We have a manuscript that’s in process of being published that has essentially shown that short term, ultra-short, caloric restriction – literally12 to 18 hours of caloric restriction – provides immense significant benefit, not only cardiac protection but more importantly neurological protection.
And we were quite surprised by those findings, so we’re trying to look at the mechanisms of how this can happen. It can be that we use this information to not only protect us before having a cardiac arrest but potentially improving patient after suffering a cardiac arrest. It could because it’s a pretty robust finding. But several other discoveries that we’re in the process of publishing, one of the key things that we’re proud of is that within literally 30 seconds after the initiation of CPR, we can tell in our animal model whether an animal is going to recover or not, and how well it’s going to recover or not. That is really critical. Initially, we were able to do it within two to three minutes of CPR, and now we can do within 20 to 30 seconds of CPR.
16:13 – So what that enables us to do is that, by knowing the likelihood of survival and how good the neurological status is going to be, we can actually optimize that as a therapeutic. We can actually improve and manipulate blood levels, the blood flow levels in the brain, in the oxygen level, to try to maximize recovery. So, in real-time, essentially, while we’re doing CPR, we can manipulate those treatments to try to optimize recovery. I think that can be transformational. We’re really excited by that, and we’re going to try to test the same thing in our patients as well, to try to see if we can get the same amount of information.
As far as edema and devices that deal with the edema, we’re working with a company that has invented a device that can detect water through different sorts of wavelengths of light. That is incredible because our patients in the Neuro ICU suffer from edema. The cardiac arrest patients are from brain edema. The stroke patients suffer from brain edema. Brain edema is a killer. Because when the edema significantly worsens, patients end up herniating, brain herniation. Sometimes we have to have our neurosurgeons actually remove the skull completely to allow the brain to come out of the whole head at the end. The problem with edema is, the only way we really detect it is through doing CAT scans. Repetitive CAT scans, sometimes we do it every six to 12 hours for a couple of days, and then we see if the edema is getting worse and worse, and then we end up sending them into surgery for brain surgery to remove the skull.
The device that we have that we’re testing – and we’re the only place in the whole world that’s using this kind of device – it attaches to the forehead and essentially, it’s a continuous bedside monitor, noninvasive. To be able to have a second by second readout of the amount of edema and water content essentially in the brain, that can be transformational as well. That was actually up and going the week before COVID hit. We had to pause it, but now we’re restarting that study. We’re basically applying that device to our patients to try to monitor their edema level. We’re really excited by that because we can treat edema. We can do it by surgery. We can do it by giving strong medications that reduce edema, but we only do that when we have confirmed edema. The problem right now is that our patients are too unstable to get a repetitive CAT scan, so bedside devices that are non-invasive are key. We’re really proud of this focus of research.
19:18 – It’s really fascinating. Every time I talk to you, I get more excited about what you’re working on, and the prospect for really improving the outcomes in areas that are really very challenging to do so. I’m just curious with the COVID-19 pandemic, as well as the ongoing fight for effective treatment and recovery from cardiac arrest and coma, do you think that this crisis might accelerate some of your research and device development?
19:50 – Thanks for asking that question. So, a few things. Number one thing that I’m – as horrible and devastating as this pandemic has been to the whole world – is that it’s really brought the world together. I can’t emphasize enough that the scientific community in the medical community has really come together to fight this thing. None of us has ever seen anything like this. We weren’t taught this in medical school. There’s no textbook that we can open up and look it up. It’s basically learning on the job and I witnessed this myself firsthand. You know, I’m looking at these patient’s charts, seeing, examining the patient, looking at the CAT scans, MRIs. I’m like, what the heck is this? So many different groups of people have shifted their work to try to come together to fight COVID. An example is that I’m part of a global initiative with the Neurocritical Care Society called “The Curing Coma Campaign.” This was a campaign that started last year, way before COVID, to try to help patients in a coma, and that brought hundreds of people together. Now I’m part of a small group of people on the scientific advisory council for that.
21:07 – Since COVID, now we’re discussing multiple projects that we can work together to fight COVID. It’s brought people from different areas of study or discipline to try to fight COVID together. Today, I just got off the phone with my NIH program director, who called me to tell me that they basically love our research. They want to help fund our research through new initiatives because the government is now has a lot of funds. They’re supporting COVID-related research more. More in our research because it’s cardiac arrest and resuscitation research, and it deals with the heart, the brain, the lungs, all of it combined. We’re primed to make a difference in this, and I’m really proud of that.
22:07 – That’s fantastic. Well, I just like to say that the Roneet Carmell Memorial Endowment Fund is so proud to support your vital clinical research activity. I really want to thank you so much for your work on the front lines, as well as national and global levels. I just want to say, it’s really a privilege to be associated with you. I really get a lot of energy by working closely and doing my small part to support really passionate, committed, extremely bright people working on the cutting edge to transform lives in very powerful ways.
I would hope that others will continue to join us and be able to grow this endowment more than it’s been and be able to support your vital research and increase the impact of your work. So, we’re going to have a little screenshot here of how you can participate. There’s a URL that you can click on or you can Google: Roneet Carmell Memorial Endowment Fund or call Nancy Young at UCI: 714-509-2109.
Thank you again, Dr. Akbari. Anything you want to conclude with?
23:32 – I just want to thank you. I want to thank your family and your friends for supporting us. The critical thing about the Roneet Carmell Endowment Fund is that it gives us that edge to do this research that’s not funded. Many of our research projects, actually, over the past year, would not have come about without your fund. So, I just want to honor Roneet’s memory and continue our work to do the little bit that we can, hopefully, to make a big difference in this world.