Surgery for Alzheimer's...Is It Real? (and other questions)

In this Q&A session, Dr. Lily Johnston dives into complex viewer questions regarding cardiovascular health and emerging medical research. She covers the impact of hormone therapies on LP(a), the nuances of managing cholesterol after a heart attack, and how to interpret advanced imaging like CIMT and Calcium Scores.

The episode concludes with a fascinating look at a novel, experimental microsurgical approach for Alzheimer’s disease being studied in China, which aims to improve the brain's waste clearance through lymphatic connections. Dr. Lily breaks down the mechanistic rationale, the early clinical data, and the significant physiological and ethical concerns surrounding this "brain plumbing" surgery.

Timestamps
00:00 – Intro: Meet Dr. Lily Johnston, Vascular Surgeon & Cardiometabolic Specialist.
00:16 – Q&A 1: Can hormone replacement therapy (HRT) or testosterone reduce LP(a)?
02:53 – Q&A 2: Recovery after a STEMI—Statins vs. PCSK9 inhibitors and the role of Colchicine.
06:49 – Q&A 3: How to distinguish between stable and inflamed plaque using CIMT tests.
09:34 – Q&A 4: High Calcium Score (CAC) vs. CIMT results—Is a heart cath or CT angiogram next?
12:39 – Q&A 5: Does starting Menopausal Hormone Therapy (MHT) late increase cardiac risk?
16:48 – Addressing the "Omega minus-3" nomenclature (A quick biochemistry deep dive).
17:53 – Q&A 6: Does taking Phosphatidylcholine improve fish oil absorption?
19:02 – Q&A 7: Krill oil vs. traditional fish oil.
20:47 – Deep Dive: Deep Cervical Lymphovenous Anastomosis—A surgical treatment for Alzheimer's?
25:40 – Reviewing clinical evidence and controversies of Alzheimer's surgery.

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___________________________
🧬 About Dr. Lily Johnston
  
Dr. Johnston is a double board-certified vascular and general surgeon in San Diego, specializing in metabolic and cardiovascular prevention. She’s the founder of CorSight Health and a passionate advocate for reimagining how medicine approaches chronic disease.
  
#MetabolicHealth #CardiovascularPrevention #HeartHealth #Longevity #InsulinResistance #DrLilyJohnston #DrLily #WomenInMedicine #Surgeon #VascularSurgeon #PreventiveMedicine #PADPrevention #HeartAttackRisks #HealthPortfolio #California #SanDiego #Arizona #Virginia #Minnesota

Transcript

SPEAKER_00 0:00

It's time for more QA. Hey guys, Dr. Lily Johnston, board certified vascular surgeon, but I'm also a specialist in cardiometabolic prevention. So hopefully you never need me as a surgeon. Maybe NRI asks, hey doc, what are your thoughts on testosterone or other hormone replacement therapies reducing LP little A? So if you have not yet checked out the series on LP little A, please go check that out. We'll link it for you in the description below. But LP little A is, of course, this little cholesterol molecule that predisposes us to plaque formation and also narrowing of the aortic valve. And your levels are largely genetically determined. Women post-menopause will often see an uptick in their levels of LP little A if they're checking pre and post. And it is one of the times that I do think it's interesting and sometimes helpful to repeat an LP little A level because you might be in kind of the intermediate risk bin, which is you're not below the threshold where you're low, low risk totally, but you're not in the really high risk range either. You're in that middle bucket and post-menopause increases in lipids, which happen across the board, including LDLC, can potentially shift you into the higher risk range. And that might be something you could think about managing differently if you knew that were true. Now, menopausal hormone therapy or HRT is the older term, including estrogens, progestins, can help. And it's specifically, by the way, the estradiol that will help reduce back to baseline that LP lil A. It's not something where I would ever just use estrogen for the LPA reduction. I think estrogen for women postmenopause is really good for a very large number of things, including bone health, including the genito-urinary syndrome syndrome of menopause and lots of other things, joint issues sometimes, but uh you get that nice bonus of bringing your LPA hopefully back to your baseline. You're not really going to drop it below your baseline, and it will depend a little bit on how your estradiol is administered, whether it's oral or transdermal. And I don't think there's any significant role for testosterone here. In fact, for women in postmenopausal therapy, the role of testosterone from an evidence-based standpoint is uh really only for low libido and and sexual dysfunction. But um anecdotally, of course, there are many women who are using it and finding great benefit from it, but uh the evidence base is pretty pretty loose there. Nevertheless, back to LP little A. Um, MHT or menopausal hormone therapy can bring you back to baseline, but it's, I would think of it as a um happy bonus, not necessarily a reason specifically to seek out menopausal hormone therapy. All right, next question is from Spanky Biff. He had a STEMI six or she had a STEMI six weeks ago. They give some numbers, currently on statins, but would be better off on a PCSK9 inhibitor and colchicine. Would that be an option? So, um, spanky, hope you're doing okay. Sorry about your heart attack. The LP little A is uh hope we think the culprit. Your LDLC is 52 milligrams per deciliter. Now, I wonder whether that was something that was checked right at the time of your event in the hospital, because sometimes we see that LDL will drop in the acute phases of uh a process. And so some of the studies that, for example, show that like a huge number of people have a normal or low LDLC at the time of their heart attack. Well, that's a little spurious because the levels were checked when people were in the hospital and sick. And so checking levels when somebody is sick and has already had an event is not actually all that illustrative for us. So I'd be interested to know if your LDL levels were that low going into this event or whether we should be rechecking them after you've stabilized. In general, your LDLC goal is going to be less than 55 milligrams per deciliter. And I would want you on therapies that get you there with the minimal amount of side effects and the minimal amount of metabolic disruption. So if it's taking max dose statin therapy to get you there and you're having muscle pains or your glycemic control is worse, or any other symptoms are coming up for you with that high dose, then I would say uh we should maybe do combination therapy, try statin and azetomibes, see how that goes, or get off the statins and go to PCS canine inhibitors. It's less about the specific agent, we think, at this point, than the actual therapeutic target. Now, because LPA is involved, you will see a decrease in your LPA by 20 to 30 percent, we think-ish with the PCS canine inhibitors. That's not a benefit you'll get with the statins. And in fact, your LPA could go up a bit with statin therapy as opposed to PCSK9s. So, in an ideal world, uh you would get the benefit of the PCSK9 inhibitors to bring both your LDLC and your LP little A down. Unfortunately, that is not a reason for any insurance company to approve a PCS-K9 inhibitor at this point. Um, so you're gonna have to work with your clinical team to figure out how you could get access to that class of medications if, in fact, uh your doctors think that that is worthwhile for you. So I encourage you to talk to your team about that and bring them some of this information, see what they say. As for colchicine, that would depend, in my opinion, on whether you had an excess of inflammation as well. So the use of colchicine is really for elevations in HSCRP, high sensitivity, C reactive protein. And if you do have elevations in HSCRP, then yes, adding colchicine may reduce your risk of future cardiac events. Um, it's not super clear to me that it's going to reduce all cause mortality. So that's the little rub with colchicine. Now, if we can figure out why you might have inflammation and get to the root cause of that, whether that's visceral adiposity or a dental infection or something else, then treating the root cause of your inflammation, I think, is a great idea and will also be helpful. Uh, and back to the first part of your question, statins will reduce your HSCRP somewhat. That was shown in the Jupiter study. PCS canine inhibitors are a little less potent for that, actually. So, again, this is about stepping back, taking the bigger picture beyond just the lipids. What is your metabolic situation? What is your inflammatory situation? How are you feeling on your meds? How is the rehab going? And how do we figure out why you had it? Was there anything above and beyond the LP little A that's contributing? And how do we address all of those risk factors? Okay, hope that helps. All right. Paul Elkins gives us some data from a CIMT test carotid into a medial thickness. We have some videos on that. We'll link for you. And says, what is the best path to verify that the risk is relatively low due to stable plaque from past lifestyle versus potential inflamed plaque? So to a first approximation, we're gonna look at the characterization of the plaque on the test. So this is qualitative. It is just the sonographer and the reading text opinion of what that plaque looks like. And the they're one of three options. We have soft or heterogeneous as the middle, and calcified, dense, echogenic is the sort of oldest, most stable form of that plaque. Vast majority of the plaques that I see on CIMT are in that middle heterogeneous range. I have seen a few that are very, the the very soft, vulnerable plaques. And if you have that, that should be pretty obvious to the tech. But beyond that, it's hard to tell from a CIMT or an ultrasound alone how vulnerable that plaque is. There are some very advanced ultrasound techniques that are being done on the research side that look at plaque characteristics and scoring systems and that kind of thing. They are not prime time in clinical practice. Some of the other imaging modalities like MRA or MRI can potentially help with plaque characterization. That is also not something I ever really use in my day-to-day practice. One or two of the neurologists that I have spoken to in the last five years has mentioned it, but it's not super common. From my personal perspective, I would take a broad look at lab values and lifestyle now and see how things are looking. We can look at things like LPPLA2, which is a vascular-specific marker for inflammation. I very rarely check MMP9 or matrix metalloprotonase 9, but that is another potential thing that can eat away at the fibrous cap overlying the plaques and cause plaque rupture and HSCRP and looking at other markers for inflammation and seeing what's going on in the body, what's the lipid count looking like, and do our best to get a gestalt of how well controlled are we now versus what was going on, you know, uh up until the time of someone's health journey and progress into a better lifestyle. So it's a bit of a guesstimate. There's no um easy way to say for sure that this is like stable plaque that's never going to cause a problem, uh, unless you're, you know, in your 80s and it's all just like rock hard calcium with shadows everywhere and we can't really see anything else. So um that's not a super reassuring answer, but it's the best I have for you at this point. Okay. Bob Everson says, I had a CAC of 2800 three years ago and a CIMT six months ago, showing only mixed and hard plaque. Should I go to the cath lab for the potential stent? I have no symptoms, healthy at age 71. Well, good for you, Bob, for getting all those uh tests done. I don't think that the cath lab would be what I would want next. Personally, I think I would get a CT angiogram. So rather than an invasive angiogram, I would get a CT angiogram. And I would want them to actually try to measure the FFR across any areas that were narrowed, and that's the fractional flow reserve. We actually talked about that in the first Ask Me Anything. And that is a way to estimate how narrowed the vessel is from this plaque. And that I think is helpful to guide decisions about stenting therapy. The other thing that you're gonna get from a CTNGO is the distribution of disease. So in somebody who doesn't have symptoms, especially with exercise, there's really only like one or one and a half scenarios in which somebody like that should get surgery or a stent. And the one first one is if there's a huge blockage or narrowing in your left mane. So the very first part of the left um coronary artery that comes off of the aorta, that is truly the widowmaker. And uh that you know, somebody who has that disease probably does need intervention. There is data that support doing basically prophylactic surgical bypass uh in a patient like that to improve life expectancy. There is an equivalent of left main disease, which is a severe disease in uh stenosis, a severe narrowing in all three branch arteries off of the left coronary. So the, you know, LAD, the circumflex, and the diagonal. If you have uh, or you know, even the RCA, you can have uh three vessel disease that way. Severe three vessel disease would also be considered left man equivalent, and that in a trial has also been revascularized and has some mortality benefit. For patients who have a single area, you know, you have diffuse calcium everywhere, but you have one artery that has a high grade narrowing uh and you're not having any symptoms, and that one artery is not your left mane. It's less clear at all that stenting that is any going to improve anything. Um number of cardiologists have I've had patients who go in for angios, they get stents, um, and somehow we all feel better about it because it's been treated, it's been managed. I also see a number of patients who get complications from stenting procedures, and if you didn't really need it, then is it worth incurring that risk? So if you were, if I were you, um, I would personally probably go for a CT angiogram next based on those data and see what the distribution of disease is and talk about it with my clinical team. All right, Paul Elkins, does starting MHT menopausal hormone therapy after 10 years post-menopause increase the risk of major adverse cardiac events if there is subclinical plaque present? I'm gonna start with this question and then we're gonna get to the second part, which is does transdermal estradiol and micronized progesterone MP ameliorate potential risks compared to WHI data? So the Women's Health Initiative in 2002 was stopped prematurely because of an increased risk of heart attack, stroke, and breast cancer, they said, related to the hormone therapy they had at that time, which was premarin and provera. So premarin is conjugated equine estrogen. It does about 17 different kinds of estrogen, some of which are native to humans, many of which are just only native to horses. And uh the progestin they used was provera, which is madroxy progesterone acetate, which is um a bit pro thrombotic. And the other thing about CEE conjugated equine estrogen is it is uh not only a little prothrombotic, but it also increases MMP9. We mentioned that earlier, matrix metalloprotonase nine, which eats away that fibrous cap overlying our plaques and does cause plaque rupture. So in women in Women's Health Initiative, who were on average 10 years post-menopause, who were started on these two medications, uh, they did have an increased risk of plaque rupture events in the first year of their therapy. But there's not really been an equivalent trial who started MHT late and used estradiol and micronites progesterone instead. What I do know is that estradiol does not increase MMP9 and micronites progesterone is not prothrombotic in the same way that um mandroxy progesterone acetate or provera is. So I think it all depends on what your overall risk is. So, you know, the women in WHI were intentionally high cardiac risk because we were trying to answer the question will MHT prevent heart disease? So we asked for and recruited women who were had high blood pressure, who had elevated lipids. There's a whole cohort of them who were probably undiagnosed heterozygous FH. And so there was a lot of um work in that trial of women who had high risk for cardiovascular disease. And indeed in the first year, they did have an increased risk of at least stroke. Um the Cochrane and I'm sorry, the WHI authors went back later and after uh more time had gone by and they had better outcomes adjudication, the outcomes for heart attack were actually uh not quite significant. So long story short, if you or your loved one or your friend has a reason to start menopausal hormone therapy after 10 years post-menopause for symptoms, I think there are safe ways to do it. Um, and I do think in the presence of cardiac risk factors, using transdermal estradiol and micronitis progesterone is probably the safest option that we have. And for most women, that is very safe. Can I promise you that it won't have some increased risk relative to starting earlier? No. But the question is, why are we doing it? Um, I don't think it offers protection after 10 years. Uh, whereas if we start immediately after menopause, I do think it confers some protection for cardiovascular disease. And it also, you know, if we're post-10 years, we're unlikely to be able to rescue a huge amount of the bone loss that will have happened early in the menopausal transition. But we may be able to ameliorate uh vasomotor symptoms. We may be able to deal with GSM, genital urinary syndrome of menopause. So there are a lot of reasons that you might do it, but um is it possible that there's some increased risk? Yes. Do I think it's way less than WHI if we're gonna use transdermal estradiol and micronized progesterone? Also, definitely yes. And I have patients that I have this conversation with and I have started them on this therapy with this informed shared decision making. All right, working into uh the omega-3 fatty acid video, I have this weird thing where I say omega minus three, and that uh was noticed by several of you. Um, most people just say omega-3 fatty acids. This is a holdover from my biochemistry professor who was pretty neurotic about this nomenclature, and it has to do with where the double bond is relative to the omega group, and it is three spots back from the omega group, and so it's called omega minus three as opposed to the other polyunsaturated fatty acids, which are omega minus six or six double bonds or six bonds, carbons back from the omega group. So this was just something that uh was drilled into me when I was in school, and it always helped me remember like what we were talking about and why it was structurally important. So I have persisted with this um slightly neurotic weird convention of saying omega minus three. It is a real thing, nobody else says it. It's correct, but nobody cares. So thanks for putting up with me. All right, Dove 72. If I take phosphocylcholine along with my fish oil, will it be absorbed better? This goes back to the idea that especially for penetration across the blood-brain barrier, phosphocylcholine conjugated DHA may get across and increase levels in the central nervous system better than an ethylester or a triglyceride or even a monoglyceride form of DHA. Uh, the short answer is no, although there might be some animal studies that would support some effect of having them separate, but truly the impact of this as a delivery system means that they should be covalently bonded together, the DHA molecule and the phosphocylcholine groups. So unless they're coming to get packaged together already, I would not expect that taking them separately, like your regular triglyceride fish oil or krill oil and your phosphoacidylcholine as a separate supplement is actually going to combine magically and covalently bond in your GI tract and then get across the blood-brain barrier. You might get a little bit better absorption, but there's no human evidence to support that. All right. So Hackett asks thoughts on krill oil. So krill are coming from the uh Antarctic Sea. They are the little plankton that whales eat and everything. Um, they have some interesting properties. They actually have a lot more of the phosphatylcholine bound DHA and EPA than the bigger fish, like stardine mackerel fish oil. And so there may be some better absorption and blood-brain barrier penetration. This has not really been studied in clinical trials. So there's not a huge body of literature that says for sure you should take the krill oil or for sure you should take the fish oil. Certainly in the cardiovascular space, like the traditional omega-3 has been fish oil based. Um, the other interesting thing about krill oil is that it has an antioxidant called astaxanthin in it, and that may help provide a little protection against oxidation. Not sure about that, for uh to be honest. It may also provide antioxidant benefits for you if you're taking it. Also unclear to me, but uh there is certainly some interest in it. Some people tend to tolerate it a little better, get less fish burps, and are able to take it. It also seems to have a little less on average GHA and EPA per capsule than fish oil. So you may have to take more of it to get the same dose. And um, I saw some stuff in the comments about the possible ecological impact of krill oil or krill harvesting. I don't know anything about that. I'm curious and interested to learn more about it, so I won't speak to that. But um certainly all fish oil has some uh sorry, all omega-3s that are coming from marine sources are gonna have some ecological impact. All of that is uh something for somebody smarter than me to figure out. Okay, at the beginning, I promised you a little bit of a deeper dive on something that another one of you brought up that I found fascinating because I had never heard of it before. So let's get into it. Terry says there was a paper on uh Alzheimer's disease and deep cervical lymphovenous anastomosis, a possible surgical treatment for Alzheimer's disease. Would love to hear your take on this one of these days. Okay, I had never heard about this. I know what a like lymphovenous anastomosis is. So we have right arteries, we have veins. We also have the lymphatic system. The lymphatic system is like, so arteries are red, right? Veins are blue. Lymphatic channels are usually clear or they're yellow in diagrams, but our lymphatic system is all the other fluid that doesn't really travel in the arteries and the veins, the interstitial fluid, our lymphatic system is hugely important in transporting nutrients from our gut and getting them into the actual circulation in our blood. So the lymphatic system is very interesting and important. If you have ever had lymph nodes removed and you have swelling, consequently, you will understand just how important the flow of lymph is in the body. And the premise of this is that in the natural Neck, there are, of course, many lymph nodes, and there is an opportunity to connect the tiny itty bitty little channels that lymph travels in to the veins in the neck. These will be anastomoses or connections that are so small they have to be done with a surgical microscope. So I, even though I do tiny anastomoses, I think, um, I don't have to have a microscope to do mine. So this is actually something, a connection that's even smaller than the ones I do with my little telescopes in the operating room. And I pulled this paper. They have done this in China in a few pilot studies, and they've had some interesting positive outcomes with improvements in mini mental status exam. But the studies have never been, they've never had a control group. So what I did, of course, was go to open evidence to get a little bit of a deeper review and dive on this because I'd never heard of it. Let's hop over there and I will show you what open evidence has to say. So I pasted that citation here into open evidence and said, What do we think about surgical therapy for Alzheimer's disease? Let's see what open evidence has to say. They call deep cervical lymphovenous anastomosis for Alzheimer's disease a novel, highly experimental microsurgical approach that has generated significant interest and significant controversy. And this is all based on the rationale that brain waste clearance via cervical lymphatic pathways could reduce the amyloid beta and tau accumulation that we see on imaging and on autopsy in patients who have Alzheimer's dementia, right? So we know that amyloid beta is bad, we know that tau is bad, and it accumulates in these plaques and tangles in the brain, and it's supposed to be cleared, and it's supposed to be cleared through these lymphatic channels. We talked in the ApoE4 video about how the ApoE4 lipid transporter is supposed to help traffic some of these proteins back and forth, and it's just really inefficient compared to the other Apo3 isoforms, ApoE isoforms. So the premise here is that by connecting the lymphatics in the neck, which should be draining the head and the brain, we might be offering some other new pathway for these toxins to get out of the brain. So let's go through the mechanistic rationale here really quickly. The procedure is grounded in the discovery of the lymphatic system. That's the extra g on there, which is a separate pathway in the brain, and meningial lymphatic vessels, which facilitate clearance of these neurotoxic proteins from the brain. Okay, and they ultimately drain through these deep cervical, meaning neck lymphatic pathways. Age-related decline in this system is associated with increased amyloid beta and tau accumulation. And this surgical procedure aims to bypass impaired lymphatic drainage by making this connection between our cervical lymphatic channels to adjacent veins, theoretically enhancing the outflow. All right, so this figure is just sort of showing that to you, right? Here's your picture of the brain. And on the left panel, they're, you know, the little yellow dots are the toxins that are accumulating or not. Um, so they're trying to get cleared through this lymphatic system into the vein. But on the right side, this pathway isn't working very well. You can see these uh arrows are interrupted here, and there are more yellow dots. So all of the toxins and byproducts, waste products are accumulating in this brain tissue. So let's review the current clinical evidence. The evidence base is limited to small single arm, uncontrolled studies, and they are all in Chinese centers. So the one that I think Terry sent to me was this paper by Chen, which is 26 patients. MMSE, this is mini mental status exam. This is a cognitive test that is administered and is abnormal in patients who have cognitive impairment. The scores were significantly improved at one month post-surgery with an increase of three to five. And about 60% of the caregivers reported subjective improvement. Mocha and NPI changes did not reach significance. And the biomarker trends, meaning checking amyloid beta levels and tau levels, presumably, were non-significant. Two patients experienced transient difficulty raising arms, so that could be a nerve injury or that could be a lymphatic problem even in the arms causing swelling, not clear. There's another series here of 139 patients, which is the largest cohort to date. Modest improvements from 48 hours to six months post-op, reduction in um impairment scores at six months. And in this cohort, there actually were decreases in amyloid beta-42, 40, and PTAW in the CSF, but plasma levels increased. And this is consistent with enhanced central to peripheral clearance, say the authors. No serious adverse events. And again, one more series in 2025, uh, 28 patients who had advanced dementia and showed some improvement. There was also a critical perspective by Wong et al. in 2026 in Frontiers and Aging that raised several important concerns about this literature. The first, physiological plausibility. The pressure disparity between cervical, lymphatic, and venous systems challenges whether the anastomosis can meaningfully augment flow. So this is the idea that if you're going to make a connection between two systems, what will drive whether stuff flows out of the lymphatic system into the veins is a pressure differential, right? The pressure needs to be higher in the lymphatic system than in the venous system to drive flow from lymphatics into the veins. And they're usually pretty close to the same. So it's unclear that just making this connection in the absence of a significant pressure gradient will drive flow out from the lymphatics into the veins. Now, if the channels were already blocked, maybe you know there's actually some higher pressure in the lymphatic system. It's hard to measure that because they're so small that like lymphatics themselves are so small and fragile. There's not a good way to measure the pressure there. But because they're small and fragile, it's a low pressure system, as is the venous system. So there is this question about are we actually improving drainage? This could be checked using visual markers. So you can inject a dye that will get into the lymphatics, and then you could watch it and see if it gets cleared into the venous system. Uh, I don't know whether that has been done. I didn't actually go check to see. The next criticism or concern that none of these are randomized controlled trials. These are all single-arm studies, which makes it impossible to distinguish a placebo effect from a um any confounding or natural fluctuation. Placebo effect in surgical studies is real. In fact, the more risky the intervention, the stronger placebo effect tends to be. And we've seen this in some, you know, cardiac surgery sham studies and spine surgery, knee surgery sham studies. It's hard uh to do a placebo-controlled surgical trial. Obviously, there's a lot in of, you know, um angst about like actually taking somebody to surgery, putting them to sleep, and not doing the procedure, just doing the a sham type of a procedure. But they have been done and they do, they're a huge testament to the impact of the placebo effect. So it's very important to have randomized controlled trials when they are possible to do. Second, biome, or third, biomarker validation is lacking. So the changes in the mini mental status of one to two points is within the margin of error and doesn't represent clinically meaningful improvement. And in only one of these studies did we really show a big change in the amyloid and tau levels. Anesthesia confounding. Next, generally anesthesia can transiently improve gymphatic clearance. So maybe just the general anesthesia actually improved the clearance and it had nothing to do with the microsurgery part of this. And the last, of course, is the ethical concern about offering an invasive surgical procedure to patients who are cognitively impaired with advanced dementia without any evidence of efficacy. But I would say, you know, we don't have a lot else to offer these patients. And if this is something that is really the result of a long informed consent conversation with the patient and their caretakers, their care team, their powers of attorney, then, you know, I'm not sure it's totally crazy to consider it, but I agree it's a vulnerable patient population. We have ethical concerns here. So the bottom line is that leverages real advances in understanding brain lymphatic biology, but it's very, very early days. I would not be booking a plane ticket to go get this done uh for my dad or anybody I loved just yet, but I think it's a fascinating space. And Terry, thank you so much for bringing this to my attention. I learned something new. This was really interesting to read about, and I hope you guys found it interesting as well. Until next time, take really good care.