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Hello and welcome back to the Neuro transmitters, a podcast about everything related to clinical neurology. I'm your host, Dr Michael Ken Tress and I am joined today by Lloyd Harada who is experienced nurse in the Phoresis or a Pheresis field. Laurie. Tell us a little bit about your background and kind of what led you you into that field of medicine. So I'm a registered nurse, as you said, I've been in nursing for more than 35 years, but I got into a Phoresis by starting the A Pheresis or Collection department at ST Louis University Hospital back in the late eighties. And what a freeze this is, is to separate blood and to remove different components of blood. And so we can do this in many different ways, but it's usually done with a large centrifuge or a device that has a centrifuge in it to separate each blood component out and we separate by specific gravity. But how I got into it was um my, I had lost my brother to cancer and the oncologist wanted to start a transplant program for cancer therapy and to do that, you needed an A Pheresis department and at the time, I was working in the open heart intensive care unit at Saint Louis University Hospital. And I said, sure, why not? Well, I need a change and, and I had no idea what I was getting into, but it led me down a path that I have stayed in for over 35 years in therapeutic a fery sis cancer therapy, stem cell transplant, the whole um variety of things that you can do with a Pheresis. Now, particularly interested it from kind of the the autoimmune urologic perspective, you know, the classic entities. Uh they're going back like myasthenia gravis. And we also see it in the past for things like some cases of Guillain Barre even multiple sclerosis or things in the kind of demyelinating sphere. So, so in your, in your clinical practice over the last several decades, what has been the shift? You know, it is one of those things where it's a lot of times a neurology. Well, we think it's autoimmune, but we're not quite sure we don't necessarily have an antibody to put the name to it. So as a neurologist were like, well, let's let's do some plasmapheresis plasma exchange, what goes into that from the back end, you know, after we like give a call to your department. So when a when a call comes in to say, hey, we have this patient that has a neuromuscular disorder, whether it be any of the ones that you had described and we want to try therapeutic a phoresis TPE is what we call it tpe on this patient. And so the first step is okay. Where is the patient? How cute is the patient, you know, in the situation of Jamboree, which you mentioned, um they can be very debilitated and on a ventilator when we finally get to call because lots of times these neuromuscular diseases are difficult to diagnose. As you said, you don't know if they're autoimmune, you don't know, you know what's going on. And there's been a lot of research in the last 35 years about how to treat these different diseases. And um the American Association, the American Society for a for is, is we call it asthma to has guidelines on all these different diseases. But back to your original question was what happens. What's the next step? Well, first, we have to assess the patient for vascular access because we need to gain access to their bloodstream because that's where we get the blood to separate the plasma off. Right. And in most cases, using a centrifugal a phoresis device, not a membrane separation, but centrifugal you don't need as high of flow rates. So you can do this procedure peripherally if the patient has decent peripheral veins and you need to have access to a vein that would be able to manage at least an 18 gauge needle or IV catheter with that if you if and and the other thing is you need to good veins, one in each arm. So some patient's have this, some patient's don't. That's the really the first step is to assess okay. What kind of vascular access do we have with this patient or do we need to put a central line in of some sort? The other question we ask is, what are the orders? How many plasma volumes do you want to remove? Now, when we think about a plasma volume, we look at the whole blood and to make the math simple, if our hematocrit is 50% that means we have 50% red cells and 50% plasma, one plasma volume would be removing 50% of their total blood volume in plasma. So how much do you want to remove most orders run between one and 1.5 plasma volumes? Which could be anywhere from 3 to 4 leaders of plasma that would be removed. Then the next question is what do you want to replace it with? Because we're doing an exchange. So we're taking the plasma off. And at the same time, we're replacing with some sort of um replacement fluid. And that typically depending on the disease is either albumin or fresh frozen plasma. You mentioned John Beret, Jamboree is typically replaced with fresh frozen plasma, but other disease, um neuro muscular diseases, you can use albumin. So it just depends on what the disease is and going back to that asthma guidelines. I actually happen to have one of the books right here in front of me. And this one just from 2, uh 2016, they published in seven and 19. They come out every three years in 19 and it doubled in size. And then there's another one coming out this year that I can't wait to see because they categorize each disease based on four categories. 123 and 41 is that is the treatment of choice, therapeutic plasma exchange or red blood cell exchange. That's the treatment of choice. And then it goes down from there. When you get to category four, it's when all a spells you for is kind of situation. There's not a lot of, of, of studies that say this is what you need to be doing. We tried it, it worked and uh let's try it again. That's the kind of situation, but it's a great guideline to follow in the neurology world because a lot of neurologists don't underst stand a phoresis. And what the benefit is when we remove that plasma, we remove the disease mediator cause causing that plasma, whether it's IG or I GM or some sort of antibodies that are causing the issues with a one plasma volume exchange, we can remove roughly 63% of those disease mediators that are causing the symptoms. Now TP is not curative, it's an adjunct to therapy. So it's a way to help the patient recover some and get back some of their functionality and then use other chemotherapeutic agents or other medicines to control the disease. So for example, in MS or, or myasthenia gravis, you know, they may come in every two or three weeks and get exchanged as part of their routine for maintenance of their disease. Now anecdotally have, you know, I know, I know uh one of the things that we are seeing a lot in uh in like kind of the neuroimmunology sphere over the last, you know, 5, 10 years as this real explosion, like you said, of chemotherapeutic or immune modulating different medications. Are you seeing any shift in the patient population that is coming in for uh pheresis treatments? So we're seeing a lot more neuromuscular disease is being treated with therapeutic plasma exchange or gene therapy where we take their stem cells out there, manipulated with gene therapy, turned into various um fighting cells and then given back to the patient. So not just plasma exchange, but the whole realm of a Pheresis is growing and expanding uh exponentially over the last 10 years. Now, as far as the stem cell pieces that mostly in the context of like research trials and things like that. Well, the stem cell piece has been around for probably 30 to 40 years in stem cell transplant in treating cancer, especially hematologic disorders like leukemia, lymphoma, myeloma, those um hematologic disorders, stem cell transplant has been really the the curative factor in the last 10 years, there's been a new therapy called chimeric antigen receptor T cell therapy or Car T. And with car T, it's been curative where transplant therapy 30 or 40 years ago would get you into remission. You may have five years, 10 years of remission. And then your cancer was back right now. What we're seeing with car T therapy is they are being cured and that's a big word cured. It's not coming back. And it's exciting because you're seeing these Children that come down with leukemia and they live a normal healthy life and not have to worry about the leukemia coming back because they're cured. So, Carty is a big, big new research area. Also, gene therapy is a big, it's, it's interesting you, you mentioned some of these new uncle logic medications, right? So like the, the car T is the checkpoint inhibitors, things like that. Because one of the thing on the neuro side, I remember seeing this for the first time when I was in residency a few years back now. But because they just started getting a lot of traction more widespread for like Melanoma and things like that, which, you know, like you said, we didn't really have treatments for those sorts of things so that we're very effective. And we are starting to see cases of Guillain beret in the last year. I can recall one case of like a paraneoplastic myasthenia gravis that developed after checkpoint inhibitor therapy. And then even just in the last couple of months, some with paraneoplastic cerebellar degeneration also who had just recently been initiated on, on these uh immune modulating chemotherapy drugs. So it is interesting that we are seeing a, a little bit of a change in some of the presentation of these kind of traditional paraneoplastic entities which you know, we still do. I always think of like 33 primary treatments, you know, steroids, ivig, and uh plasmapheresis, plasma exchange. And as uh you probably know, right, the most common one or I should say the one with probably most data would be like, yeah Emburey where they've done head to head and was like, well, they're about the same and one of the problems you always run into is, you know, it's a lot easier to get Ivig started say, and someone who might be a little bit more of an acute stage just because, you know, vascular access isn't as much of an issue. Some people who have more severe cases of Jamboree where they are developing some autonomic instability with fluctuations in blood pressure, you know, plasmapheresis might be a little dicey. Which that is a question I would like to ask you actually because you did mention like obviously there's different flows and rates and things like that. So let's say we have someone in the ICU, you know, who's on a ventilator who has, has been having lots, lots of tachycardia, uh BP instability. How does that affect the approach? Like, let's say maybe they got clotting disorder. We don't want to give them Ivig or whatever the reason might be. They've had immune reactions to like the first dose we can't keep giving it to them. How do we approach plasmapheresis in, in a patient like this? Well, and we used to call it autonomic hyperreflexia is what you were describing and, and it in Jamboree patient's, it can be very tricky to pick up on this autonomic hyperreflexia, especially if they're on a ventilator and they can't talk to you. So monitoring the patient is so important to be uh in tune to yes, what's happening with your device. But you need to pay attention to your patient and monitor their BP, their respirations there. You know all the basic um physical assessment of what's going on. And then if you see that something is happening, you pause the system, pause it and you stop and let the patient recover from that um autonomic incident. Gotcha in my, in my own again, anecdotal experience most sessions around four hours is that, is that accurate? It could be 2 to 4. It depends on your vascular access, how fat as you can flow. And as I said before, the number of plasma volumes, you're exchanging most of the time you're exchanging 1 to 1.5 plasma volumes, which could be three liters of plasma. Now, it could be that it only takes an hour and a half to do it. It just depends on the patient condition, how fast you can flow many different factors in, in managing the device itself. But it's, it's unless you don't have good flow, I have never seen it go as long as four hours for a plasma exchange. Usually it's somewhere around the 1.5 to 2 hour mark at the most to. So I know you've been talking a little bit more about kind of on the acute side of things. And one of the points you've mentioned earlier, people will be coming in sometimes on a regular basis, every three for even longer, sometimes interval wise, depending on their clinical response. What does that look like on the patient side of things? What kind of vascular access do they have to maintain? What are the considerations they have to keep in mind on the long term side. So, on the on the long term side, on the chronic side versus the acute side, on the chronic side, if they have good peripheral veins and they're coming in say once a month, that's easy enough to access peripherally and you have less risk of systemic infection when you have a central line. I personally, I call it the white tube of death because it's directly into your central vascular system. And if the nurses are not diligent and taking care of that access, then you can easily develop an infection or thrombosis even at the end of that catheter, that in the end causes more damage than just doing the procedure itself. So, back to your original question, what can the patient expect? Well, if it's long term, there are many different, um, long term vascular access options. Sure. There's peripheral, if they've got great veins, as we know those veins wear out, right, some places will put in if it's long term, put in a AV fistula like what is used in dialysis. And you can use an ab fistula for um a therapeutic plasma exchange procedure as well. You can also put ports in. So ports that are just under the skin skin. And the great thing about um the centripetal device that I'm most familiar with, which is the, the spectra apnea. We have single needle options for plasma exchange. So you don't need to have to, you can get away with just one. Therefore, if you only have one good vein in one arm, we can do a single needle exchange versus dual needle, which is great. It saves, it saves on sticking, you know, sticking the patient the time difference. As long as you can maintain good flow in a good vein, the time difference is relatively incidentally longer, it's not significantly longer. Some people will cap there, inlet flow rates and it will double the time when you do a single needle procedure. But if you don't cap that flow rate and let the system run as it is designed, then there's not much difference in a single needle versus a double needle time to. And yeah, that was, that's an excellent point actually cause I'm very familiar more with like, like you said, people with ports, central lines, things like that again. Just because like you said, some of the patient's were treating are on the older side and they don't have good peripheral access. So it does become a bit of a sticking point when we talk about what we're doing sessions every four weeks for 1 to 2 days. And they just don't have the peripheral access to, to sustain that kind of treatment. So this is something I'm not familiar with. Tell me a little bit more about these one versus two site transfusions. The single needle versus dual needle procedure. So in a duel needle procedure, the blood comes out of one arm goes into the centrifuge is separated and we take off the plasma, the replacement fluids added to the red cells and it's given back through the other. So it's this continuous loop in a single needle procedure, we pull the blood off and on our device, there is a reservoir that we fill up and we're still processing the blood in the centrifuge and separating the plasma off getting rid of the plasma, the red cells come back into the reservoir and then the replacement fluid comes into the reservoir. When that reservoir fills up then all the pumps that pull from the patient's stop and our, our one return pump turns and evacuates the reservoir giving it back. So it's this intermittent flow back and forth through the single access. Okay. Okay. That makes sense. Yeah. A little counterintuitive. Not somebody would think about necessarily right out of the gate now, in terms of, so this is something, you know, just in the last few months I've been noticing, you know, the huh hospital I work at, we're constantly getting alerts about shortages of various things and like I I can see you shaking your head. Uh One of the things that comes up almost every week is plasma and other blood products. How have you guys been handling that in your clinical practice? Well, um Michael, I am not in a clinical practice. I work for a medical device company, but what I have seen in our customers in their clinical practice is they're getting very um clever and how they manage these um shortages because right now we're seeing a shortage everywhere. If you go to try to buy a car right now, you have a year to wait if you order one. I mean, it's pretty bad, it's bad. It's the supply chain is in dire straits right now. Anyway, without human, it comes an FFP FFP is the fresh frozen plasma that we get, get from whole blood donations and yes, whole blood donations are down we're trying to get the word out to go and donate blood so that we have the blood supply replenished. Right now. We're running on maybe a one or two day supply. It's, it's very critical across the country and other areas of the US are in worse situations. You know, it just depends on the metropolitan area, but in general, across the United States, there needs to be more blood donors. And what we're seeing is back in World war two, Korea Vietnam, the baby boomers were the big source of blood donations. They were dedicated donors. Now they're aging out, they're not wanting to do that donation any longer. And we're trying to get replenishment of a younger population of donors. I'm going down the donor side and I know that's not where you want it to go. But anyway, it's, it is pertinent because that's where plasma come comes from is the whole blood donation. Albumin. On the other hand, comes from plasma donations at plasma centers and those are paid donors versus volunteer donors. So when you collect plasma from a donor, it's fractionated into all the different components that um we need to treat our patient's. One is albumin, the other is ivig the others factor eight. I mean, there's so many different factors in the plasma that can be um fractionated out. And right now there is a shortage of albumin. Albumin comes in two different strengths. One is 5% which is what's typically used in the plasma exchange as replacement fluid, 5% albumin. The other is 25% albumin. And what a lot of centers are doing when they have a shortage of 5% albumin is they take that 25% albumin and dilute it with normal saline down to 25% and then they have their supply back. Reasonably other centers will use a combination of albumin and saline. Now you have to be careful with using too much saline because we're dealing with a crystalloid versus a colloid colloid is the, you know, the protein portion of the blood, which is albumin and that's what holds everything together in our vascular system. If we take too much colloid out and replace it with saline or crystalloid, then we get these fluid shifts in the vascular system and you can cause more damage than good because then the fluid shifts out, their BP drops, their hematocrit goes up and the patient ends up crashing. Not, not a, you know what I mean when I say crash, right. Yeah. So in shortages and anything plasma derived, there's shortage right now, whether it's albumin or Ivig, there's a shortage and it's being creatives on how we can manage the patient's symptoms and manage the procedure and still use the albumin or a combination of things together to treat the patient with the plasma exchange. Yeah, that's something I always rely on my nephrology colleagues to help manage or probably should say, primarily manage in terms of maintaining those different osmotic gradients to avoid that exact situation you're describing. And to that point, I know you mentioned that your background is a little bit more on the oncological side of things like in your, in your past. Would you work primarily with oncologists or nephrologists or a little mix of the, both, actually a mix of the, both hematologist, oncologist, no nephrologist and neurologists, all four. Because a phoresis can be utilized in any one of those um medical areas. We, we think primarily hematology, they're the ones with the most experience with the blood, right? Hematologists. But as you know, a lot of nephrologists have a combo unit in the hospital that is both renal dialysis and a phoresis together because it's medical device and there's a, there's some similarities to running a dialysis machine versus a, a Pheresis machine, but they do different things. You know, dialysis cleans the blood versus a Pheresis, separates the blood and removes the protein portion or the red cell portion. You know, depending on what we're trying to do. So, it's important to know the distinction and nephrologists if they're trained appropriately can understand the difference is the sticky wicket that we get into with nephrology is they treat it like it's dialysis and it is not like dialysis. It is you're dealing with plasma proteins and not just waste product in the blood. Interesting. I've seen this one might be a little more unusual. I, I have encountered one pathologist who was also in charge of pheresis. Is that fairly common? Is that a little unusual? Um, no, that can be common to. I, I left pathology out because it's interesting that you say that when I started the department at Saint Louis University, I was under a pathologist. Now, I worked with all the other, you know, departments, but I, my boss was the head of pathology and the head of the blood bank. And so, yes, pathology is a common area where a Pheresis will reside. Gosha. Now, I might have missed this earlier. Did you say that you were, were you at Washington University in ST Louis, ST Louis University? Okay. Okay. So there's wash you in ST Louis and then there's Saint Louis University in ST Louis. Gotcha. I was just wondering because I know uh Yes. Yes. Woo. Still as, as it's clo clearly known. All right, I know they're, they're huge into the neuro muscular sphere and I was wondering, I'm sure being in the same town, especially in those early days of the identification of a lot of these auto antibodies, you're probably kind of right at the epicentre for that. Uh Would that be fair to say? Yeah, it was, it was very interesting in the eighties, what, what diseases we were treating and what they were coming up with just to try to relieve the symptoms of the patient. You know, as I said, when I lost fails you for Reese. And it was very interesting and I was so glad to see the American Society for a Pheresis come out with these guidelines on what diseases to treat. Which one is proven to be most effective? Where are there just certain case studies that say it kind of worked. It's really a great guideline for physicians that are not well educated in the a phoresis area to go and look up. Okay. I've got this disease. How do I treat it? And it was funny, I was listening to your podcast about Stiff Person since and in the book in the Bible Stiff Person Syndrome is considered a category three for therapeutic plasma exchange. So there's some studies that show it helps with stiff person syndrome. But it's interesting, it's, it's in the guidelines from ASFA. How about that? From that's, that's the problem with neurology. A lot is that it is a lot of the entities are so rare, but the quality of the data isn't, you know, we're certainly not the level of randomized controlled trials. Um So you kind of have to fall back on your path of physiology and be like, well, there's an antibody, we can theoretically remove antibodies. So theoretically. Uh but yeah, there, there certainly is uh an element of that to a lot of things like I have had a couple different autoimmune and stuff like chronic autoimmune encephalitis. These in the past things like that, that didn't respond to final immunotherapy or that we even do like combination chemotherapy with for is, is like they get the phoresis and then they would within a few days get the chemotherapeutic agent to clear out the antibodies and then kind of bring down the B cell population again, like with riTUXimab or something similar. Well, and that's exactly like in leukemia, you know, when a flu leukemic patient's in crisis, their white blood cell count is sky high and we use a phoresis to separate the blood and remove the white cells, not, you know, not the plasma portion, but the white cells and get it down to a lower level so that you can start them on chemotherapy to control that overproduction of white cells, B cells, T cells, whatever type of leukemia we're talking about, but help control that production in the bone marrow with chemotherapeutic agents. Interesting, I do have, this is more of a historical questions. Are there any disease entities that we, that I should say you back in 2030 years ago in your practice that were frequently a for East and then we over time learned like we definitely shouldn't be doing that. That's a good question. And I'm thinking if there are any diseases, we've added a lot of diseases, but have we removed any that don't respond? I don't know if I know of anything specifically that have been removed. There's been so many more added to. Then it does seem to be the trend where I could keep identifying more well. And as, as I said, the guidelines from Aspe keeps growing and growing and they actually change their categories from year to year. And most of the time they up the category from like a category three to a category two because there's more data because they look at the data, they look at the trials that are run. Are they controlled double blind blah blah blah trials that are the most important trials or are they just case studies that people are publishing as abstracts? So they look at all the data and they evaluate every single disease and they make adjustments every three years to how these diseases are treated. So again, I I refer any physician back to the asthma guidelines because that's, that's really clinical proof of what works and what doesn't gotcha. And I know there's some notable exceptions but our most uh neurologic entities kind of in the like the class three class to family. No uh class one. Well, that, that was one of the exceptions I would say probably that and John very or that in my esteem, er probably like more in the class one family. Exactly. They're more in the class one. I would have to look them up but yes, probably more than neuro muscular are in class too. But it depends on what that neuro muscular diseases because you know, as, as, as I said, John Bray, that's like I, and personally when I was a practicing a Pheresis nurse, I would see treat aguila Emburey patient start their plasma exchange. And by the end of it, they would be talking to me where they couldn't be talking to me before and they would be moving. They would, you would see just by one treatment, the change in their symptoms, which is very rewarding as a nurse to see that. Hey, what I'm doing is helping and that is one of the arguments in favor of Pheresis over Ivig is that it's supposed to have a quicker onset in terms of symptom control. So, although it's never really been fully quantified for a lot of disease states, but can I add one more thing about Ivig versus TPE? Sure cost? Tell me about the cost. Now, I don't have the numbers off the top of my head, but the cost of Ivig is significantly higher than the cost of Teepee. And that's where if you can get it faster and do it perfectly as a single needle and get the results faster than Ivigivig takes a long time to infuse, it's, it takes what, four hours to infuse tolerance. So I can uh as long as they tolerate it. Well, all that, all that and with, with TPE, we're talking less time, we're talking faster um response and you can, you can see it happen right there. I mean. And overall, there have been studies that show overall the cost effectiveness of TPE is less than IVIG and depending on who's doing the TPE, whether it's in hospital department or if it's a service provider, is there a lot of service providers across the country that provide a Pheresis services? And a lot of them are dialysis companies that have an, a phoresis arm to it. They come in with their devices and they perform and then they charge the hospital a set fee for that procedure. And that can vary depending on which um which service provider is writing the service. So, but it is less than $20,000 a treatment. Well, that's fair. And that's always good to know. You know, we do have to live in the real world where things cost money, especially if we're talking about monthly treatments or things like in a chronic condition in a chronic state. So you said that you're more in the medical devices side of things in your career at this stage? Yes. So what does that look like? So, um I left active clinical practice in 1990. So I've been out of the clinical practice for a while. But what I went into was industry and I teach, I started out teaching people how to use these devices and that's where I, I still am today. I manage a team of specialists. We call them specialists at paramo blood and cell technologies. It's our team of specialists that go out and train our customers on how to use our devices and training and learning is my passions in because having someone understand what the benefits of a phoresis is, is really exciting to me because most of the time people, it's, it's hocus pocus, it's, it's, you know, you hook this patient up, you run their blood through. It's like an oil change or something. It's like old school bloodletting. Right. Yeah. It's like old school bloodletting and, and it has come so far in the last 35 40 years. In technology wise, the early devices that I used were open systems. They took a long time to set up. It still accomplished. But today's devices are so much more streamlined and more safe for the patient and more cost effective than some other therapies. Would you say that a lot of people that you're teaching, are they also dialysis nurses or they usually do serve a dual function in their communities? Especially for talking like smaller towns, more referral areas, things like that. Yes. Yes. Especially inr oral areas. You'll see dialysis nurses be co trained or double trained in both a phoresis and dialysis. And that's typically where we see this. Also, there are dedicated a phoresis nurses which really focus on and understand a phoresis. I like those nurses the best because they don't relate it to dialysis. And there is a difference in, in dialysis were cleaning the blood in a phoresis, we're removing proteins and it's, it's different. But if you look in large metro metropolitan areas, university hospitals, you're going to see their own, a phoresis department versus a combo in rule areas, you're going to see them serviced by. So, service providers where a service provider comes in and provides the A for is a service to the local hospital or they ship those patients' to a larger medical university setting where they have those procedures available? That's good to know. What else do you think that position who are working with patient's who might need for racist or patient's who might be under going for recess or having that present to them as a treatment option? What kind of things do you think someone who's not directly involved with the planning and execution of, of the treatment protocol should know that we haven't already hit on? Well, I I think the main thing is vascular access and don't um immediately jumped to a central line without assessing veins and, and in the recent two or three years, ultrasound, guided placement of IV catheters have become more and more popular and readily available. It's a skill set that is specific for placing, you know IV catheters. But if they don't immediately jump to a central line, I think it's better for the patient. We believe in doing no harm. And that's a, that's ASFA, that's my company that's nursing in general, we believe in doing no harm. And to me, a central line is opening up the patient to harm an infection. And if you can take a step back and think, okay. Do we have the capabilities of doing this peripherally? Do we have ultrasound capabilities? Can we place a catheter with an ultrasound versus sticking, you know, the way to Kathrine? Exactly. Exactly. I think that's a thing to keep in mind. Also know that what the costs are between both. Yeah, it can be very expensive. So if people want to find you, are you online anywhere? Should they look you up email? Um I am, I do not, I do not have a website. I am not online but they can reach me through my company. My email mail address is Laurie dot Harada and you'll have my name up there at two room obese et dot com. They can easily email me and reach me that way. Excellent. Well, thank you so much for taking the time to talk with me today. I think I learned a few things about phoresis and uh it's, it's definitely a useful tool to have in the toolkit for a lot of our autoimmune uh neurologic conditions. It is, it's a useful tool. Absolutely. Thank you so much. Thank you, Michel was a pleasure. Thank you again to Lorrie today for teaching us all a little bit more about a phoresis and I will include her email in the show notes for today. If you ever want to reach her for finding some more information about a phoresis. If you enjoy this podcast, please do leave a five star review on at Apple Spotify or wherever you get your podcast. This helps with any show noticed and it just makes me feel nice to hear from you. So please be sure to subscribe for future episodes and you can reach me on Twitter at Doctor Ken Trees. That's Drkentris or by email at the Neuro transmitters podcast at gmail dot com. With any questions or show suggestions. See you next time.