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The Glasgow Neurosociety
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in association with SI, or Surgical Neurology International, and SI Digital are happy to present
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the abstracts and discussion of the 10th anniversary Glasgow Neurosociety meeting held in November of 2022 in Glasgow, Scotland.
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Hassan Ishmael is president of the Glasgow Neurosociety at that time. He's from the Wolfson School of Medicine at the University of Glasgow in Scotland and the United Kingdom
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Faculty commentators are Likith L. Akhandi, who's the consultant neurosurgeon at the Queen Elizabeth University Hospital in Glasgow
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And Amy Davidson, a neurologist, also at the University of Glasgow, also at the Institute of Infection, Immunity, and Inflammation in Glasgow, Scotland.
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Other Glasgow neural hosts were Alidith Middleton, Vice President of Glasgow neural, and Attica Choudry, another Vice President of Glasgow neural
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Introductory remarks for this meeting will be given by Haassan Ishmael, President of the Glasgow Neuro Society. Hello
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everyone, watching. My name is Haassan and it's with great pleasure that I am this year's President of Glasgow Neuro Society. And I'd like to welcome you to our panel discussion recordings where we
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have invited the authors who presented their research at our 10th anniversary conference to discuss their work in our round table discussion format And before we get onto it, I've really quick bit
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about Glasgow Nuro. Our ethos has always been to raise the bar. And we're very proud that despite being a student society, we are one of the largest neuro-societies in the UK for junior members of
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the medical profession. However, these sessions are not made for us to talk about what we have achieved, but instead aimed at inspiring and accelerating the future generation of clinical academics.
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And we hope that through panel discussions like the one you're about to watch, it gives the opportunity to explore research in a pragmatic, real world fashion and give appreciation for the work with
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an organic round table discussion, giving expert insight and clinical expertise. Before we get going, I'd just like to give a very quick thank you to the committee this year who have ensured that
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events continue to strive and we continue to be as large as we are now. And thanks must, of course, also be given to surgical neurology international and SI digital, with special thanks to
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Professor James Osman, the founder of SI and Emeritus Editor-in-Chief, Professor Nancy Epstein, the current editor-in-chief, and Mr. James Cook, the managing editor. And it's very important for
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us to acknowledge a very quick thing that's very near and dear to me and something that I'm glad we're new to taking a big part of and we'd like to give some attention to SI Digital, which is the new
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initiative by SI aimed to revolutionize the way that we listen to abstracts, taking research from being too dependent paper and encompassing it into an interesting dynamic format through panel
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discussions like the ones you're watching, shading information, open talks like SI and Glasgow Nuro, let's talk, and a whole bunch of other exciting initiatives which are taking shape and aiming
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to change the way that medical research is discussed. And that's just a big thank you to SI Digital. And with that further ado, we'll hand over to this year's, to the panelists we have, where
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we've got Dr. Davidson, Mr. Alacandi and Atika, a fellow of the committee. And so I'll just hand over to themselves to give a very quick introduction. So hi there, I'm Amy Davidson I'm a
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consultant. neurologist based at the Institute of Neurological Sciences at the Queen Elizabeth Hospital in Glasgow. My special areas are based really around peripheral nerve and MS, but I also run
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general clinics. So I've got a broad spectrum of neurology and delighted to be the honorary president and I'm really pleased to see the kind of quality and caliber of abstracts. So very excited to
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be able to dig deep and have some discussions about it tonight
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Hello, I'm look at allocandy. I'm a neurosurgeon based at the Queen Elizabeth Hospital in Glasgow. I'm currently the honorary president along with Dr. Davidson and it's an immense pleasure to be
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part of this fantastic enthusiastic group. They had this new conference in Glasgow the other day and
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the quality of presentations were fantastic. So today I'm looking forward to this discussion of this person and I'm excited about it
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Thank you. Hi everyone, my name is Asuka. I'm the treasurer for the society this year. I'm a medical student currently interclating in clinical neuroscience and yeah I'm really excited to see all
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the speakers and what they're going to present today.
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Hi so I'm Aili, I'm the vice president from this year. I'm a fifth year medical student at Glasgow Uni and yeah really excited to be part of the club now. And it's thanks to this excellent lineup
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of true experts in the field of neurology neurosurgery that we hope through the next recordings and the next videos you'll be able to take on board some of the excellent panel discussions that we have.
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Hi welcome back everyone. So our next up is Andrew Kingley site. We'll be discussing solid damage therapy for glioblastoma focused out in mapping. In-the interrupt mitochondria are always in just
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apoptosis and neurosphere models so they'll pass you over to Andrew.
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Hi so I'm Andrew, I'm one of the medical students at Dundee and I've been doing some work with the Center for Medical Engineering and Technology in Dundee as well. So we're interested in looking at
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sonodynamic therapy as an adjuvant therapy in glioblastoma treatment. So currently glioblastoma, it's an extremely malignant brain cancer, which causes patients to
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often pass away within two years and there's very limited treatment options at the moment. One of the main things is surgery and chemotherapy is a standard of care. And there's quite a big movement
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to try and look for additional therapies that can go along with this. One of them, which is quite new, is trying to look at MRI-guided focused ultrasound. There's a number of ways that this new
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technology can be utilized. At the moment, it's being utilized in essential tremor, using high-frequency focused ultrasound. We are trying to investigate as low frequency, low-intensity focused
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ultrasound to cause apoptosis of tumor cells.
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At the moment in cancer surgery for glioblastoma, some people more often,
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ALA5, a fluorescent chemical can be given orally, two hours prior to surgery. So what that does is it goes through the blood brain barrier and it goes into cells, it's a precursor to heme. And so
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glioblastoma being a very hypoxic tumor, it takes up as much as it can get.
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It's metabolised, not quite to him, but to a substrate of that pathway, which is fluorescent. So in
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surgery, the surgeon can enact can activate a blue light and get a pink fluorescence of the tumor to look at margins. We are looking at trying to induce with focused ultrasound, cavitation of
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basically small particles of dissolved gas within the cell. So when those bubbles collapse back in on themselves, they give off fluorescence which can cause this, the ALA to substrate to fluoresce,
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induced roasts, reactive oxygen species and then go through the normal cell apoptosis channels. There's a number of big problems that still haven't been fully solved with this therapy The Barrow
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Institute in America is trying to do a Phase 1 human trial, Dundee is also looking at doing a Phase 1 human trial. within the next couple of years, the big unanswered questions are, how does it
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work
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and what mechanism does it use to work? And then if you're looking at that, well, over on a trial, okay, what settings do we need to use? How should we actually try to minister this therapy?
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So what this project is aimed to do is to do three things really It's tried to develop a system to test these theories and solve these problems in vitro and in a number of different tumor models.
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We've tried to look at the mechanistic testing using cells and we tried to look at
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the effects of different parameters, so frequency, intensity, duty cycle on both thermal and actual cell death implications that that has Yes So. In terms of building the system, you effectively,
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you have to eliminate air, which is a really difficult thing to do when you're testing cells. So effectively, we have an insert that we put into a 96-well plate. That's also merged. We have a
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transducer in a water bath and the cells sit submerged just into the top of the water bath in media and get ultrasound from underneath What we've done is we have a automated system that we've
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developed which allows the plate to get moved and allows for rapid testing. Our main findings from this have been that we used a number of different fluorescent dyes to look at the production of
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reactive oxygen species. So does it produce ross? And then to look at apoptosis So if it creates Ross, does it cause apoptosis?
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We ran the tests
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using 90 millisecond pulses, a 10 duty cycle and 55 watts, which is roughly what they've used in successful animal models in rats, but there's been no human cell testing of anti-tumor effects. So
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this is a new area, so we're not quite sure what we should be using. So this is our best guess
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So we found that it produces ROS selectively and you have to have both given five ALA to the cells and have exposed them to ultrasound to get any ROS production.
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We then tested it again with apoptosis. We found the same selective induction of apoptosis of GBM cells. So this kills tumor cells in vitro. There was no necrosis, so it's not that it's calling
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the cells to break down,
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and release tumor factors into the extracellular environment, it's causing controlled cell death, which is an important thing to look at. Another thing we looked at is we gave a Ross scavenger and
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then ran this whole thing again. So effectively what a Ross scavenger does is you give it prior to doing any therapy that would cause Ross and it takes it all in.
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We ran the tests and we ran it with him without the scavenger. If you don't, if you scavenge Ross and you take Ross away, you do not get apoptosis. Therefore, it
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is the Ross that causes apoptosis. So we have a better idea of what actually causes the cell death in synodidotic therapy for glute blastoma.
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Going on from this, what we looked at doing is using simulations and we had a number of different field mapping simulations to try and figure out right. If we're trying to improve this system, we
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can always just use a hydrophone, which is effectively like a measuring device that goes into the well and measure and map all the field. We have to be able to find a way to simulate it, which also
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pushes us into more rapid determinations of different setups for more accurate dose determination. 'Cause that's one of the big things is, if we're going to try and translate this to practice, we
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need to know what we're giving in vitro, so we can know what to expect in people.
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We tried neurospheres, so we've looked at both formation and formed assays, and I'll explain what those
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are. Neurospheres are 3D-organoid cultures, so you dissolve, well not dissolve, but you trypsinize and split up a cell culture into single cells that don't aggregate together You plate them in.
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stem cell media because they are stem cells. And they grow their own mini tumors. And so they're extremely good models at looking at GBM. So one of the problems with GBM is it's a very hypoxic
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tumor and it has a hypoxic and necrotic core. In a normal cell culture, you don't actually get that necrotic core, you don't know how that interacts. We will use these mini tumors to actually look
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at how does aerodynamic therapy work with almost a micro tumor environment with
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the actual same structure as a human GBM in situ.
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So we've given the ALA, we've given the FUS, and we are going to do one of two things. We're either going to plate the individual cell, treat them, and wait and see how they grow after three
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weeks. That's a formation assay So in that case, synodemic therapy reduced the diameter of those small tumors. by 83 and that was significant. And that was selective to sonodynamic therapy. So
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that's ALA and focused ultrasound together.
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We then looked at a formed assay. So where you've plated the cells, you let them grow for three weeks, you then treat them and you continue to watch them for another three, that reduced their
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continued growth by 53, so more than half. And that again was significant and selective for sonodynamic therapy.
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What this all tells us is that we have a way to simulate
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sonodynamic therapy quickly. We can change the parameters and run, say 10 different parameters a day, so we can find out more rapidly what parameters we should be using for upcoming human trials.
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We know that Mitochondral Ross So, we looked at confocal microscopy with. fluorescent dyes and we could localise those to mitochondria, which is where this heme metabolism is occurring and where,
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put before nine, the fluorescent substrate is located. That's where the Ross is being produced and that's also where apoptosis
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is being triggered from. We've been able
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to look at why is apoptosis caused and the fact that we've now sort of figured out that it is because of this Ross. We've looked at tumor models. So
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in with the new aquatic cores that we've got, we know that
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GBM cells are susceptible to sonodemic therapy and human stem cells as well. And we tested in a variety of different types. So from everything from borderline cells to necrotic cells to peripheral
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cells, all of them had selective apoptosis.
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Going on to sort of look at, okay, this is all great. How does this actually change anything? We were able to effectively run mock
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examples of different field parameters. So we know that if we give a cell X dose, we get a certain response. We can run effectively almost many trials of different doses to know more quickly what
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we should be giving in humans, rather than having to do a whole year cycle of a specific dose tweak it a whole year cycle tweak that and run it again. We can do it in maybe a week rather than a year.
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And we can do far more in depth assays as well. So we looked at Western plotting, we looked at a variety of things and won't put you with that But.
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we've basically got an effective, rapid way of looking at how sonodynamic therapy can be used. We know it works and we know that it can be an alternative to treat GBM without surgery, without
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chemotherapy or without radiation dose. That's me, thank you.
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Thanks very much Andrew, that was, that was really interesting. Now I'm a neurologist to trade so apologies Mr. Alexander will be much more knowledgeable about this so I'm going to ask probably
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some fairly straightforward questions and you're going to be like you. But so when we're talking about this in the glioblastomas and you talked about it being an adjuvant therapy, so are you talking
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about we would do this beforehand to shrink the tumor down before going into reception or something if we've tried to debug rather than completely resect would they then go in and I guess an
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additional to that. So I obviously have a tiny bit of experience about the essential tremor side with the high frequency, but do you still obviously if you need to see if it's lighting up, still
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needing a clean automated, still going to be a fairly invasive procedure, even if we're using ultrasound? Sorry, that was two questions at once, but take your time Okay, no, no, so effectively
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what there is, is.
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We'd be suggesting this as a treatment that could be used anytime in the patient's journey. However, I think the initial thought is to use it on tumor margins. So it's not possible to achieve
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complete resection of every single cell in
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a resection of a GBM. Also a very long time ago, the biopsied both left and right hemispheres. So the lateral and contralateral hemispheres from a tumor and they found that small seed cells had
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permeated their way through both hemispheres. So it's not necessarily a surgically curable disease alone. So we'd suggest looking at it
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initially after surgery.
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with your second point about comparing it to a central tremor. So that high frequency looks to ablate it. Or we use far, far lower intensities. And we actually have a thermal effect of about 02
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degrees rather than 20 degrees. So it's far less uncomfortable for the patient to actually go through. You mentioned the craniotomy to see if it's
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lighting up. We don't do that. So it would be completely transcranial We wouldn't have any surgery. You'd have to get haloin as with an essential tremor. You'd still have that big fluid cap. So
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you'd still have to have your head shaved. But it's as non-invasive as possible to kill cells. And it would have probably less risk than radiation therapy or chemotherapy, my cytotoxic chemotherapy
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And so I take it, it's minute like. minimally damaging then to normal cells. I mean, there'll be a small uptake of your fluorescence throughout normal cells with, you know, metabolism, but you
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would be aiming to run the ultrasound over a large field. So not just the tumor area, you were trying to reach kind of seeding. So not quite as phallic, but, you know, is it with the AMB that
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you covered more than just the area that you suspected the tumor to be in against this matter? So initially what we'd think is we'd aim for tumor margins So where we thought there might be tumor
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cells. But the thing about sonodynamic therapy is it's almost double selective. So not only can we aim within the millimeter where we want the focused ultrasound to actually be, where we want the
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dose to sort of distribute itself, the ALA is only up taken by the GBM because of two factors. The GBM itself disrupts the blood brain barrier.
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And so that allows it to permeate through. And also it's hypoxic nature helps it actually gives it active uptake through an additional channel, which is a mutation. So we saw effectively just even
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so our controls were actually other tumor cells. So we compared it to, so giving ALA alone to a tumor cell, it makes it a bit unhappy, but it's not gonna kill it. Giving focused on the lung does
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nothing So the focused ultrasound is inert unless they've already been exposed to five ALA. GBM also, it has a enzyme deficiency, which stops it actually clearing proof before in nine. So it's got
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a small natural accumulation that we're basically just bolstering by giving it oral or IV ALA
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prior to practice onodynamic therapy
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Thank you very much, that would be really helpful.
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Okay, can I ask, so
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basically it's a very interesting concept, thanks a
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lot for that. My question, the first I've asked two parts, the first part is more of a practical point of view. As a surgeon that's what we do and that's what you're interested in basically So in
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real life, first of all is this question of biopsy, you wouldn't want to do something with the radiological diagnosis, you need a tissue diagnosis, you need to have a biopsy. So operation, until
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you can get excellent MR spectroscopy to get
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the gene, but the molecular diagnosis, we'll still need some tissue diagnosis Secondly, we know in normal practice 5LAs,
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the uptake of 5LAs in GBM is not uniform. There are some parts of GBM where you actually don't see any expression of 5A and no fluorescence at all and there are some where your intensity of the
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pinkness, you know, it decreases as we go. This is for tumor cells which are infiltrative. So obviously there is a variation in the level of expression of this 5A So from
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your ultrasound point of view, how do we know first of all if the tumor is expressed or is sticking up viral clavs in several tumors which don't have any fluorescence at all. And if it is doing,
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for example, you know, even if the patient is taking it orally, it may not be absorbed or it may have enough time to release the tumor or it may not So how do we know that we need ultrasound, you
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know, like a focus therapy?
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Did you, did you get the question? Sorry. My internet may not be there.
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So
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part one of the question, I'll come back a little bit on to discuss this bit here. Sure, so first you mentioned tissue diagnosis. Initially, any trials would be post-surgery, so we would have a
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tissue diagnosis, and that would, I think, be required for enrollment. In
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terms of the different expressions and different cell lines expressing or having different uptake of 5A late,
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that is true. So we did most of our testing in GBM22, which is a fairly resistant cell line. So we basically gave it almost a steel man-type scenario where we tested our experiments against the
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most resistant cell type. One of the issues we actually ended up running into is that our dose was a bit high for some of the other cell lines, the tumors even not exposed to FUS were a bit unhappy.
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But what we actually think was, this was down to is that weren't able to clear metabolites but in humans with circulation, that wouldn't be the case. So that would be fine.
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There is a difference, you're all right. And that's one of the reasons we use neurospheres because not only do when they become a hypoxic and necrotic does it change how the early circulates through
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the cells, but when cells are able to aggregate together, the share waste products, and they have a way of basically trying to spread the burden of reactive oxygen.
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We think, and because we tested them in the neurosphere models, that that would be fine. And we tested them across a wide in cell lines alone GCE both. across,
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gin and standard GBM cell lines.
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So everything from fairly central cells to quite peripheral.
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I think that's a valid thing in a neurosphere, it's definitely better than cell lines. But when you come to real in vivo, there is going to be a big hurdle because it behaves very differently.
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That's a good thing. The second question is more of the signs behind it Now, the rosus are part of, you know, are required for many cellular functions, not just tumors, isn't it? You know,
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they can be in edema, the edema, there is necrosis, there is some ischemia. So there is various, you know, the ros involvement. So what is the effect of this focus on ultrasound on these kind
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of cells, which are part of a cancer, you know, a tumor? And like you mentioned, the tumor is not a surgical, The garb-bastama is not a surgical disease, it's a disease of the. of the brain,
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so there's nothing to cut out. And what you're proposing is, in fact, as well as you're removing bits of cells, it's not re-conditioning the whole brain. So the question is, you know, the Ross
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is part of a general metabolism. It's not just a tumor thing can happen in ischemia, edema, infarction, et cetera, et cetera. So will that be very specific for this? So it is. So Ross, you're
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right, is a general metabolite It's involved in a number of different pathways. What we looked at is we did actually look at some of these pathways. So we looked at things like cell signaling
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pathways, either 24
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hours before or two hours, sorry, 24 hours after or two hours after treatment. So even in, you're all right that in, if you just give ALA or if you expose it to FUS, there is a slight increase
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in cell signaling terms of self-stress, from changes to Ross metabolism in other cells, sort of other tumor cells who haven't been exposed to both ALA and FUS, either control ALA alone or
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FUS alone. That resolves within 24 hours and there's no sort of actual damage to those cell cultures. The only ones that cause apoptosis, and it causes apoptosis
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alone, it doesn't cause necrosis, and it doesn't actually cause just complete lysing of the cell either. It is selective for apoptosis, and the other cells, though they may have a transient
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disturbance in metabolism, these would only be tumor cells which are actively uptake, and
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the actively uptake in by the LA, unable to clear Put before 9. and are also disrupting the blood brain barrier. So it's all these different factors, select for. Yeah, okay. Well, that's a
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good idea. Yeah, you're selecting it by the method. So yeah, I won't take up much, but this is my area. So one more final question. So have you thought about using it intraoperatively? For
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example, you
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know, you've done a five-elegant resection and I look at the bed and there is a little faint hints of
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pain. Can you think of ultrasound to target these?
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So is there a possibility? There's a great mechanism in what you have proposed is a really good study and I congratulate you and your team on that. So for that sort of scenario, we wouldn't be
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looking at sonodynamic therapy. We'd be looking at photodynamic therapy, where instead of - No, I'm asking specifically about sonodynamic therapy intraoperatively instead of the light So why the
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requires.
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or the current systems which use focused option are MRI-guided unless it
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be very difficult to clear or use intra-operative diagnostic ultrasound to look for tumor residue, put a probe inside the tumor cavity. So it's an idea, but this, you know, a thought process for
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you to have. Anyway, I think that's the end of my question, yeah The current system,
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it's not one probe. I think
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the proposed system for human use is 1200 ultrasound transducers, extremely high power, much more than what we'd be using for diagnostic use. That's why we're having to worry about thermal effect,
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which it's not an issue for us, but it is for higher frequencies, higher intensities than in that system.
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an intraoperative thing would be looking at the same mechanism which also we've looked at in the same models. So we know that, again, look through this research that Ross has produced an apoptosis
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of produced because once you activate protein before nine, we're in a common pathway between sonodynamic and photodynamic therapy. Interoperative photodynamic therapy is a proposed new addition
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which would fit the scenario that you're discussing But that's been tried in the past and it's not been groundbreaking to say the least. Anyway, so yeah, well done. That's a good paper you've done.
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Thank you.
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Thank you very much. And I think on this, there's any other questions any other questions from the panelists?
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Well, and I think that in that case that concludes talk to my Andrew can say.
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This abstract is presented by Erika Major Farias and
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her colleagues from the University College of London. London, the United Kingdom. She's a postdoctoral researcher and others are involved in different departments there.
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On this study, elucidating, which is elucidating the role of regulatory T cells and CD5 expression in human and mouse glioblastoma using single cell RNA sequencing
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I'd like to give you a short summary of the abstract, which you'll see on the screen.
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Glioblastoma, we all know, is a most malignant brain tumor. It's third most common. The first is our metastases to the central nervous system And the second is meningiomas, but those are
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described as being from the meninges. And
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tumors arriving from
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the tumor cells of the central nervous system itself are glioblastoma and astrocytoma, and of those, and others, glioblastoma is the most common, it's the most deadly All after
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treatment of glioblastoma by from radiation or chemotherapy and surgery. It's somewhere between 11 and 15 months. Generally, there's some who will live a little bit longer. So Hylom and Lignon
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Tumor. So these investigators were exploring whether the immune system could be used to attack the nervous system and develop some experiments to prove that.
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We know that the glioblastoma grows up in an environment in the central nervous system. That's an environment that can both inhibit the tumor from growing and also has factors which can accelerate it
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from growing. There are those factors in the cell itself which can do that and also factors in the environment which may do that.
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From the work there, work on others, they found that the immune environment can produce substances Basically. molecular substances which would inhibit the rest of the immune system from attacking
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the brain tumor.
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And they were able to find an agent called RG6292
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that had been used in other studies that prevents the immune system from shutting off the other parts of the immune system that would attack the brain cells.
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And they used this in an experiment using animal models in mice.
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So they had treated mice and untreated mice.
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And what they found is in the treated mice, the survivals were longer. The cells which were these cells suppressing the immune system were found to diminish in numbers and the treatment appeared to
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be very
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They proposed that this would be a model that could be used in humans because essentially the same system of immune suppression and support is carried on up into the human species. And so suggest
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that this is a treatment that could be considered. So by manipulating the immune environment, they were able to increase the death rate of the glioblastoma cells and extend the survival of the
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animals. The discussion of this work will follow. Back everyone. Our next panelist is Erica Meer-Farias, who will be presenting our very exciting work, elucidating the role of regulatory T-cells
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and CD25 expression in human and
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mouse glioblastoma using single cell RNA sequencing without further ado, over to you, Erika. Take the floor. Okay, hi, my name is Erica Mjia. I'm a final year of medical student at King's
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College London. Thank you so much for the opportunity to share some more about the work I did with the UCL Cancer Institute.
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So yeah, as you can read from the title, this project focuses on Guilleblastoma, which is one of which is the deadliest form of brain cancer. And so it's has a very poor prognosis in patients and
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it has a pretty poorly understood tumor micro environment. So you know, sort of what makes up the tumor. However, regulatory T cells, also known as T-Rex, have been found to greatly contribute
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to this environment and likely are causing it to be very immunosuppressive. So to likely preventing the immune system from fighting the TBM as known also, Guilleblastoma.
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And this is found to likely be through CD25 expression. So our lab has done previous experiments targeting CD25 positive T-RAGS, regulatory T-cells, using like a specific anti-CD25 monoclonal
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antibody. And it's done this in mouse studies, in other cancers, so not GBM, and it's had success So this particular project focused on
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mouse GBM models targeted using this monoclonal antibody. And so in the focus of this project was to use single cell RNA sequencing data to analyze the results, see what we find, and compare it to
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human data sets to see if there could be a translation of the effect in the mice into human patients in the clinic And so this project did - so basically, the model integral. I'm Monica Antibody did
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successfully deplete the regulatory T cells in the mice and this resulted in also tumor cell depletion and then increased mouse survival in the treated mice compared to control mice that weren't
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treated with anything.
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And so this was a very positive result
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that was found and so by doing some more digging into the single cell RNA sequencing data that we had, we found that
40:05
there was a regulatory T cell signature. So like the T-Rex had a particular genetic signature and it had several oncogenes and immunosuppressive genes in this signature and this was translated into
40:18
what we found in
40:21
the human data set So it had a very similar signature as well, showing that the strong monoclonal antibody effect we found in the mice does have the potential to translate into humans based on the
40:36
similarities we found between the regulatory T cells in both species.
40:41
Yeah, so this was a very positive result and this monocle antibody known as RG6292 is now currently in phase 1 clinical trials as well. And so, yeah, we hope that by, you know, sort of
40:56
harnessing these positive results we found and,
41:01
you know, the great possibility that there is of these results transing the humans. This could then, you know, provide better outcomes for this patient group with these aggressive cancers who
41:09
don't really have as many treatment options at the moment. So that's, you know, what we found what we're hoping for and yeah, it's all very exciting.
41:20
Thank you. That's really good I still, you know, trying to understand the hypothesis here. Are you trying to suppress the Tregs
41:34
so that the outcome is improved, just from a very basic point of view? Yeah, so the Tregs, Soregatory T cells, they usually down regulate the immune system, just in general. And then what we've
41:49
been found by sort of digging into the GBM tumor microenvironment is that it appears that these Tregs are using up
41:59
IL2, which is usually involved in T cell proliferation. So basically it's taking up all the IL2 and preventing T cell proliferation. And so then by targeting the Tregs and depleting them, so we
42:12
also found that this also resulted in marked T cell clonal expansion. So it does seem like if you target the Tregs, this allows other T cells to then activate, particularly in our study we found
42:25
cytotoxic CD8 T cells. to then activate and actually, you know, be able to work on the tumor, deplete the tumor cells, and then hopefully, and then as we found, increase survival. So that's
42:37
the correlation. So are we talking about T-Rex in blood or T-Rex in the tumor infiltrating T-Rex because they have two different populations? Yeah, so we, I think we focused on tumor infiltrating
42:51
T-Rex. So we were looking at like samples in the like in the brain specifically not necessarily in the like in the vessels if that makes sense. So the next question I'm sure you would have been
43:01
asked before is the role of steroids. You know what do they do to the T-Rex and you know when you're actually treating a
43:10
patient with when you translate this into a clinical trial you have to withhold your steroids otherwise because they have a separate effect in the T-Rex but then steroids are needed for controlling
43:22
the dema. So how do you overcome this problem? That's an Excellent question. So when we looked at the human data sets, we looked at two different data sets. And one of them did look at, we said
43:37
one of them did have dexamethasone treated patients and non-dexamethasone treated patients. And so we were also able to look into that a bit and see what
43:50
was happening, what it was doing to the regulatory T-cells. So we did find that, so I guess, like you said, with the dexamethasone, is it is a bit more complicated because it does cause
44:04
immunosuppression, but it's also needed for
44:07
the cerebral edema.
44:12
So it is sort of, yeah, it's just quite complex, but I mean, I guess what we found just by looking at the data is that there were less - So just for -
44:24
No, no, okay, that's a, you know, thing. But, you know, when you're doing a critical trial, would you have two arms, would you propose it? I know it's a difficult proposition, but are you
44:32
going to propose it two arms, one with steroids and one without dexamethasone? Yeah, I think that could definitely be something we'd look into. I think in the current clinical trial that's
44:42
happening right now, it's just just looking at, it's basically just looking at solid tumors and recurrent tumors just to see if it could do anything there. And, you know, see how tolerable it is,
44:51
how safe it is And I think from then on, we can then look into, you know, more finer details like combination treatments or, you know, we should avoid this treatment with the, with this
44:60
monoclonal antibody and that sort of thing. But it's definitely like a really great consideration. So, for one final question, how do we, how much do we know about the crossing the blood brain
45:11
barrier for the maps?
45:15
Yeah, that's also a great question. So, I found, we found several studies that sort of support the idea that some amount of. monoclonal antibodies can actually cross the blood being brain barrier
45:28
in pathological conditions like as in cancer. But then additionally, there are also new techniques being looked into such as peptide shuttles. So by attaching the monoclonal antibody to a peptide,
45:42
that would hopefully allow it to cross the blood brain barrier and things like that. But yeah, I think as with most neurological conditions, that's one of the biggest issues we have is crossing the
45:52
blood brain barrier But that's definitely something, another thing to look into and to hopefully achieve more results with. And then hopefully by seeing if we get these positive results from the
46:04
phase one clinical trial, seeing if it's horrible and safe, we could pursue that avenue as well to make sure that we can actually safely deliver the drug to patients. Thank you very much, Jacob.
46:15
Good work and great responses, Erica. Thank you very much I had a really quick question if that's okay.
46:24
the opposite of what Mr. Alchandi was saying there. So you're talking about kind of systemically administering a map to target a brain tumor. What's going to be the response of the rest of the body?
46:39
If you give an anti-CD-25
46:47
monoclonal, what do we think it's going to do to the kind of systemic immune system? What kind of side effects are the patients going to see? Yeah, that's a really good question. I think it's one
46:56
of those things that we see with most immunotherapies or systemic therapies. A lot of GI effects are like GI negative side effects or just general sometimes immune over activation. But I think
47:11
because what we've done is tried to
47:15
elucidate a signature that these regulatory T cells have And so I think if we're able to sort of pinpoint like a more specific signature for the T-Rex in the brain and then have a look also at blood
47:26
samples, see what the T-Rex and the other parts of the body look like, how they differ, and see how we can sort of tailor our treatments specifically to the ones in the brain. I feel, I think
47:37
that would be good because, you know, the more it would be better to, you know, like you said, not have all these systemic effects and everything like that. But yeah, it's quite a common
47:45
problem with, you know, most immunotherapy and hopefully by further looking into the signature, we can sort of harness the signature a bit better. And could it ever be something that you think of
47:58
administering more locally? I don't know, interthically or directly during surgeries or, you know, is it always gonna have to be something that's systemically delivered, do you think? Yeah,
48:10
that's a really good question. I'm not entirely sure the answer to that, but I think 'cause like I mentioned, like, you know, different treatment routes are being explored,
48:22
and like blood brain barrier, all these things. I think that would definitely be something to explore as well, especially because in the mice, we do tend to inject it directly, but that doesn't
48:30
necessarily translate into humans. And so yeah, that's definitely something to think
48:38
about. It's not impossible though. It's not impossible. That's probably one of the delivery routes as well. So good. Interesting. Thank you very much. Great. Thank you so much for your time
48:49
Lovely, and Erica, before we let you go, any other comments or anything from your end?
48:58
Not really. Thank you for your time.
49:01
It was very nice to meet you. That question always catches people off. No, no, absolutely. And again, thank you so much for that. And that wraps up this panel recording. Thank you. Mzuki Ueda,
49:11
who's going to be talking to us about a comparison of Alzheimer's disease-indicated drugs on neurons generated from Alzheimer's disease, The patient derived in just pluripotent stem cells. I'll hand
49:22
over to yourself now. Thank you for your introduction. My name is Mizuki Weta, and I'm currently a second year medical student at Newcastle University. So this research was conducted as part of my
49:36
summer research internship at Professor Inoiz Group at Kyoto University. Prior to my internship, Professor Inoiz Group found that Brahma Krypton had an anti-ameloid beta effect on cortical neurons
49:52
generated from familial Alzheimer's disease patients with mutation in the presentoline one gene. Since the mechanism of action of Brahma Krypton was not quite understood, my study aimed to compare
50:05
the effect of Brahma Krypton and for other Alzheimer's indicated drugs on patients. Patient-derived IPSCs using immunofluorous sustaining.
50:18
So what I first did was to culture IPSCs and differentiate them into cortical neurons. Then I introduced five Alzheimer's disease indicated drugs into the neurons. The three drugs, beta-separatease
50:33
inhibitor four, semi-guessative diet and JJ, are already approved Alzheimer's disease drug. I additionally selected erobotamin, which was chosen because it has a similar chemical structure to
50:49
bromocrypton. After the cortical neurons were differentiated, they were stained
50:58
with 14 different primary antibodies, and their images were taken using a fluorescence microscope. These 14 primary antibodies either did not stay in at all, only stained the cell bodies, only
51:12
stained the neurons, or stained both of them.
51:17
There were three primary antibodies that I wanted to focus on, which were APH1A, base one, and personal in one, which showed different staining patterns in neurons treated with the drugs. So the
51:31
key finding here is that all proteins with the different staining patterns are a component of either beta-secretase or gamma-secretase enzyme, which are proteins involved in the cleavage of amyloid
51:46
precursor protein to form amyloid beta. So I concluded that bromocrypton may affect the proteins involved in amyloid beta production similar to some of the already approved drugs. Please let me know
52:01
if you have any questions about this.
52:08
Excellent. Thank you. That was such a great and eloquent summary of what has really brought, you know, you've done a lot of work there, you know, to somewhere that has it. So succinctly and so
52:18
that's a short amount of time, you know, is very clever. And so when you were just, when you were talking about comparing the drugs in the picture, go to me, because it was similar to from Krit
52:30
Team, did you say any trace, you know, with your, or with your theorizing that from Krit Team, could you be involved in the earlier stages? Did Ergotamine have a signal as well, or did it not
52:39
have, you know, did it not feel the same? So in the initial research that was done by Professor Inouye's lab, they tried a lot of drugs. And one of the drugs that also showed a similar effect was
52:58
Ergotamine. And also in my research, it was that Ergotamine and Bromocrypton tend to show a similar. staining pattern. So I think that my choice that they may have a similar structure and then
53:13
what for similar effect may be supported by the research.
53:19
And with what you've learned from this, you know, this is, you know, very good high throughput very much the kind of study at this, how would you take it forward? So as a clinician, I'm always
53:29
interested in the kind of bed bench to bedside approach. So what would be your next step? What would you think about going forward in terms of what I understood from here and how that would apply in
53:42
clinical scenarios. It is that I found that it may be involved in amyloid beta production. And we think in terms of the amyloid beta hypothesis that it's like the production and the buildup that
53:56
leads to the clinical manifestation. So if it is actually that the production is what is being targeted, then it means that we would have to detect Alzheimer's early and start this treatment early
54:09
for it to actually be effective for Alzheimer's disease.
54:15
Do you have any, I don't worry if you don't have an answer to this, but do you have any ways that you, like early detection of Alzheimer's, do you mean like doing kind of PET scans? Or is there a
54:25
kind of a clinical way that you could look for this? Do we have one just now?
54:30
Or is that something we need to think about? How are we going to find these early detections? I don't believe you can answer that question. I don't truly understand all the ways, but I understand
54:43
there are some new ways that they're doing, they're trying to detect it earlier and also find genetic people with dispositions that increases the risk to that might be one way that we could detect
54:59
this early I would like no more about it. really interesting. Yeah, absolutely. Doing a genetic profile, and then you could pick out people at risk using family histories, and then classifying
55:09
them genetically, and then considering drugs like bromachctin.
55:14
And would you have any concerns about bromachctin, the side effects? You know, would you be quite happy to have people on it long-term? Want me to write anything? I think one of the benefits of
55:23
bromachriptin is
55:25
that it's an already approved drug by the FDA, and already used for things like Parkinson's. So there's lots of data that we can use to see who would be more at risk for using districts. I think
55:39
that is a great benefit for trying drug-style already approved. Absolutely. That's great. Thank you very much for talking through your research. Have you did those anything else that you wanted to
55:50
discuss or?
55:54
One thing I would like to and that is that here. Since I wanted to try many different primary antibodies, each of the samples were quite small. So I would like to expand this by just focusing on
56:08
the primary antibodies that show the different staining pattern and increase the sample size and see whether they just happen to be that way in this time or it's actually something that's replicatable.
56:19
Brilliant, that's good. It's always good to have a thought about how you tweak the research and how to move on to it. So that's a really good thing to be able to do Thank you very much. Thank you.
56:30
Thank you, that was fantastic. And I guess I've got a quick question, what's next I guess for yourself? Are you continuing working this? Are you gonna still stay with the lab and try to take it
56:39
forward? Or what are you up to now? Okay, thank you for your question. I really enjoyed this experience. So I
56:48
got more interested in like doing research and what I'm currently thinking of now is that I learned immunofluorone. since doing it, which is a thing that can be used in many ways. But I'm also
57:02
interested in things like Western blotting and things like CRISPR-Cas9. And I'm discussing some summer projects that I can learn some new skills and consider what I would like to do in like masters
57:16
and future research.
57:19
Excellent. Fantastic, thank you so much. And that concludes our first panel discussion Hi everyone, welcome back to our session. Our next speaker is Mary Hunter. We'll be talking us through
57:32
perioperative pain assessment and management in the Institute of Neurological Science and audit. I'll hand over to you, Mary. Hi everybody, I'm Mary. Thank you so much for the opportunity to do
57:45
this today. So I'll just talk to you briefly about my audit. It was a small study conducted in the Institute of Neurosciences of September of this year
57:54
with a prospective audit, including just 13 patients, so it was quite a small population. I did look at sort of analgesic prescriptions of these patients, their PRN breakthrough requirements, the
58:08
levels of anxiety they had pre and post-op they're sort of guideline compliance overall and to do this I looked at the Royal College of Anesthetist guidelines and the NHS, GDC guidelines, so looking
58:23
at their prescriptions and whether they were compliant and also their news charts and how they matched guidelines.
58:34
So overall headline figures where the deadlines were maintained in the vast majority of patients who I spoke to, so two thirds not perfect but they were
58:52
maintained quite quite well and those who did have compliance, it was found that they had reduced levels of postoperative pain so they had reduced average NRS pain scores and they also had a reduced
59:08
PRN requirement. So they had just sort of an average of 24 doses required per day versus four for the non-compliant groups. I forgot to mention but the main non-compliances I find were sort of
59:22
co-prescriptions of opiates, so somebody being on a weak opiate and a strong opiate, which obviously reduces the efficacy and also having sort of errors in their pain scores recorded. So while
59:34
every single patient did regularly have a pain score taken, which is appropriate, sometimes they run up with a zero when the patient was reported severe pain, so things that could be worked on.
59:47
Interestingly, I found that in patients who had chronic pain or more complex pain requirements and guidelines were sort of more often than not followed, so of the five patients who didn't have
1:00:04
guidelines followed in their care, 80 of them were chronic pain patients. I think this is probably to be expected due to their sort of higher complexity and their increased needs, so it was
1:00:18
something that was noted and that it can be worked on and proactive anxiety also seemed to have a bit of a role in sort of more severe pain after surgery. So patients who said they were anxious or
1:00:31
very anxious, pre-operatively had higher NRS pain scores post-operatively on day one and day three.
1:00:39
This was quite consistent actually and I found that if they'd had a discussion about their pain prior, it was sort of useful in reducing anxiety and also pain scores afterwards and really
1:00:55
reassuringly 100 of patients who I spoke to said that their care was either good or excellent, so really overall promising for the INS. The sort of main things that I found for this and the
1:01:12
importance of this study is that up to 40 of surgical patients can have really severe pain after surgery and I'm sure it's well understood that purely controlled post-operative pain is associated with
1:01:27
things like hyperalgesia and higher levels of chronic pain post-op, so it's quite important to know when
1:01:36
pain can be better controlled and some really promising changes were discussed and I think implemented after this audit as well, so the main sort of big thing that's changed is that the anaesthetists
1:01:49
are now giving people leaflets about their pain prior to their surgeries. So, it gives them a chance to ask questions and patients a chance to sort of read about their analgesic options. It can
1:02:04
help increase the quality of their care because they know what to expect both cooperatively and it might help reduce anxiety levels afterwards as well. So, hopefully, increasing
1:02:16
quality of care while sort of reducing errors if possible There was also a discussion on re-education of documentation, so letting ward staff know about the importance of accurate documentation and
1:02:31
while the regular documentation is being done, which is really promising, just making sure that every pain score is actually asked and recorded properly so we can sort of have patients who are
1:02:44
having severe requirements or increasing requirements flagged up quicker. And also, sort of earlier, refers the acute Pain Service was discussed as well. So for patients, especially those with
1:02:57
chronic pain and complex needs getting sort of spoken to earlier by those who are professionals and experts in it, of the three patients of the 13 who referred to the acute pain service, only two of
1:03:10
them had chronic pain. So it's a way to easily help manage these patients' complex requirements and ensuring that they're getting treated properly as well for their level
1:03:23
of pain. So I think that's a pretty good summary of what I did. So thank you so much for listening to me. Go on there.
1:03:36
I mean, thank you for that, that was really great. Can I just ask? So I mean, I know this is kind of perioperative pain stuff, obviously as a neurologist, you know, repeat is something I deal
1:03:49
with a lot
1:03:57
but just to contextualize, so did it matter what they were getting an operation for? Like, was brain surgery different from spinal surgery? Was there a feel, I know that, you know, just 13
1:04:03
patients were involved, but was there a sense that, you know, some operations led to more postoperative pain? Or do you feel that it was more patient driven factors? I think you might be doing it
1:04:14
for too. No, I definitely agree. I think because of the patients that were sort of available to discuss this with most of my patients were neurosurgery patients. And
1:04:28
it was more sort of the longer procedures were definitely associated with more pain, max facts patients. They made up just, I think it's four of my patients were max facts and they had really high
1:04:38
levels of pain. So I think, yeah, there was an element of how
1:04:45
sort of severe the surgery was that contributed but also I think, um, there were patients who sort of had higher levels of pain pre-work, who statistically, not statistically sorry, and they
1:04:59
still had higher levels of pain post-work as well, I'm trying to say. That's, yeah, I'm trying to say that. And so, just think, oh, I'm sorry, I just had another question, I just popped
1:05:11
right in my head there, be making notes, let me go back to it.
1:05:14
Yes, when you talked about the level of anxiety and anxiety, just made me think of it kind of co-morbidities, and was there any kind of pattern? Was it people who had more co-morbidities? Was it
1:05:25
a kind of, we know that mental health can play a role in pain? So was it an anxiety related to their surgery or was it people that perhaps had history of anxiety that had more pain? Was there a way
1:05:38
of teasing that out? I mean, naturally, I guess everyone getting an operation will be a bit anxious, but was it a kind of an unexpected anxiety? Were you struck by the anxiety? level of it like
1:05:49
kind of keep. And that had a role in the pain, or is it just anyone with any anxiety? I think, you know, that's definitely fair enough. I didn't actually look at sort of chronic or sort of
1:06:01
diagnosed anxiety, but it was a sort of sliding scale. So I asked people just sort of generally, how are you feeling? And then sort of if they could say they were not anxious at all, which would
1:06:12
obviously nobody said and quite anxious. And sort of fairly anxious or very anxious and sort of And use that and obviously the patients who said they were very anxious, did have the higher pain
1:06:26
scores afterwards. And I think that was almost to be expected. But the
1:06:32
patients who'd had the discussions about pain. So even if they said they were very anxious and they had a nurse or a doctor speak to them about their sort of pain control options and the things that
1:06:43
were to come. They said it made them feel better afterwards So,
1:06:49
and I'm. You'd mentioned some interventions, so they need to test how we're given leaflets and the nurses who are gonna do some education around
1:07:01
the kind of pain skills and things like that. What do you think we could do for the doctors? How can we help more, you know, like the kind of clinicians on the ward? What can we do to help out of
1:07:12
the pain? So I think the other sort of main thing that was picked up was that there's quite a lot of co-prescription of sort of weak opiates and strong opiates. So just making sure that if you are
1:07:25
prescribing analgesia, making sure that you're doing it in line with the who you pain matter is probably really good. And then also co-prescribing opiates with paracetamol can reduce the dose you
1:07:36
need so it can help sort of minimize symptoms for patients, but also maximize their analgesic control. So I think just making sure people regularly sort of think back as well because I'm I know
1:07:50
personally, I didn't know any of this until I done this project and I find it really useful. So, okay, thank you very much.
1:07:59
My, that's very, very, can I speak over here? That's very good. And I was going to ask the same question about the nature of the procedure, but doing a prospective study is quite difficult, you
1:08:10
know, and to stratify them based on creating a whole new spinal and, you know, max factors will be very much more difficult. Yeah, but the pain requirement, the pain relief requirements for
1:08:23
cranial surgery is very different from a spine surgery. And if you look at the anterior neck, even less than a posterior neck, I think like that. But my question is with regards to what the
1:08:38
doctors can do. Have you considered whether these patients had Pre-emptive in Al Jazeera.
1:08:46
The two things we normally use are one, but the next thing is to give a pain killer even before the patient comes out of an operation. Or as a surgeon, we inject local anesthetic and block the pain
1:08:59
from manifesting and the patient wakes up. So that is known. So what are your thoughts on that? And have you had any of those factors included in this assessment? Yeah, absolutely. So one of the
1:09:13
questions that I sort of checked in the performer was about local anaesthetic use. But there wasn't quite enough patients to sort of look at the effect it had on
1:09:24
pain afterwards. But I would imagine it would reduce it as well. But again, the patients who were having the sort of bigger procedures were the ones who had the local anaesthetic. So I suppose it
1:09:34
goes hand in hand almost. And as far as the
1:09:43
other aspect of sort of having sort of having. immediate control. And I think most patients
1:09:52
actually had IV paracetamol while in recovery. So it was something that it was 90 or something of patients had that done. And I think for those that didn't need it, or for those that didn't get it,
1:10:01
they required to get pure end doses as well. That's sort of why noticed. But it wasn't something I sort of looked at specifically Yeah, so from your in your study, with the law, any patients on
1:10:16
patient control analysis here, and how effective do you think them? Are they are they useful in
1:10:23
the situation? Probably not in cranial patients, but in at least spinal patients.
1:10:29
And I didn't actually see any on PCA. And I've seen, I've seen how effective they are since, especially in patients for like cancer patients, I think quite a lot of that is very valuable. I think
1:10:43
letting the patient choose when get their pain controls is for the best because they know their own body and they know what
1:10:51
they need. And I think it's probably quite useful and it's maybe something that could be used a little bit more. But again, I think most of my patients were cranial patients as well. So thinking
1:11:03
back and how it's probably it would have been better to stratify them Anyway, I think that's all I have. Thank you rooms. Thank you. Just got another. I just remember thinking, I mean, we're
1:11:17
and rightly so and kind of petty occupations might be limited what we can do, but we're thinking a lot about the medications. Can there ever be a role for kind of adjuvant kind of, you know,
1:11:27
things that aren't
1:11:30
tablets or injections? Do you think there'd be a role for other ways of trying to cope with pain? I don't know getting the psychologists involved or any other kind of, you know, tens machines,
1:11:41
anything like that, like we could do anything to reduce the the need for painkillers, so to say. I really think that would be, I think it would be useful, definitely. There's sort of studies
1:11:55
I've seen that, especially the Royal College of Annesa test, they suggest that using the pre-operative and post-operative periods to make sure the patients are, especially the levels of anxiety,
1:12:06
make sure there is low as possible, make sure they're understanding what's going on, and it's been shown that if a patient's well-informed of their sort of control and their options, they're more
1:12:17
likely to have well-managed pains is what I find. So I
1:12:23
think, yeah, having patients be able to talk about it with somebody's probably really useful. And I suppose that's where the sort of introspective
1:12:33
personality's coming a little bit as well. So yeah, it's probably useful.
1:12:39
Thank you very much Was it?
1:12:45
Lovely, and I think in that case, Mary, do you have any final comments or anything on your end? No, I don't think so, thank you so much. I know it's quite small compared to some of the other
1:12:56
ones that pop through, but enjoy doing it. No, absolutely. Any due perspective is really hard to do and you've done well, you know. Thanks.
1:13:07
Lovely, and that concludes our third panel discussion too. We are looking at the effect of Xanthine oxidase inhibitors on post stroke cognitive status, a post-hoc analysis of the
1:13:22
CLO first randomized control trial presented by Sally Wong, Union Wong. Go ahead, Sally, over to you.
1:13:31
Everyone, so I'm Sally Wong, I'm one of four of your medical students from the
1:13:35
University of Glasgow. And today I'm very excited to present my project and as has another story statement title So
1:13:43
just a short background. Like as you know, the
1:13:48
ischemic stroke and transition ischemic attack is a
1:13:53
high risk for collective impairment in the long run. And it has been shown that about 30 will eventually progress to vascular dementia. And unfortunately, we don't have a very good management plan
1:14:06
for vascular dementia compared to Alzheimer's disease. Even the Alzheimer's disease also helps certain vascular components to it So it will be quite interesting to know what's the pattern mechanisms
1:14:19
behind cognitive impairments of the stroke. And so to know if there is any targets we could pharmacologically target to. And so my project is to know whether a alprino, which is a xanphinoxidase
1:14:36
inhibition, is going to reduce the level of the stromary acid level in the body and which eventually may. lead to improvement in the cognitive impairment in the long run. So to understand the aim
1:14:49
of project, we must first understand the data's research done on this. So eventually the serum uric acid level has been found to be recorded in the science of cardiovascular diseases and as well as
1:15:06
the cognitive impairment. And from our research, literature research, we found that many of us have shown a correlation between high level of serum uric acids and an increased risk of cognitive
1:15:23
impairments, but there are different results in different literatures and this creates a very equivocal conclusion to it. For example, some of them found there is a U-shaped relationship where very
1:15:39
low level of serum uric acid has also been found too. contributes to any sort of cardiovascular disorders and so forth and the core in among all this mechanism is the xanthine and oxidase. So
1:15:55
xanthine and oxidase is an enzyme which degrades purine which is the sort of metabolite from any cellular breakdown and it creates purine into serum uric acid, so uric acid level. We measure the
1:16:13
uric acid as an indirect a predictor to the level of xanthine and oxidase inside the body. So xanthine and oxidase releases the free oxygen radicals during the process and this contributes to
1:16:29
oxidative stress and as you all know inflammatory pathways which leads to worsening of ischemia and It's also one of the major components in atherosclerosis and all of which has been shown to cause a
1:16:45
major increase in a vascular dementia. However, the serum drink acid itself has been shown to be protective against Alzheimer's disease and Parkinson's disease. So that's an interesting realm. And
1:17:02
so the use of alprenal as a drug to show if there's unfair oxidized level reduction will improve cognitive is a first trial as far as we know. And we just compared between two groups. So
1:17:21
one group received alprenal and the other group received the control. And both groups they have been, the patients have been selected based on their recent ischemic stroke diagnosis or transient
1:17:34
ischemic stroke.
1:17:37
And the results have been compared, but unfortunately it's found that there is no significant difference between the two groups. Although we also did like a sort of a regression analysis to see if
1:17:50
there is any baseline variables that may be associated with worsening cognition within the populations in the study. And we have found that the high level of white matter hyperintensities and
1:18:04
diabetes have been shown to results in worse than in their cognitive test throughout the two years of study. And this is very interesting because it actually agrees to the previous studies that have
1:18:21
found that white matter hyperintensities, which is a component of a small vessel stroke, is a major risk factor in cognitive impairment And so, this list of conclusions that maybe a new direction
1:18:37
in the future research could lead to looking at the effect of santhine oxidase and sumeric acid specifically in the small vessel stroke and therefore to see if whether this actually improved cognitive
1:18:52
impairment in the long term. Thank you.
1:19:01
Thank you very much for that, that was really great and really interesting and I think you know it's very important that we present you know even if you don't see a positive response I think it's
1:19:14
really important that we present all these trials and I think about it because it's how we move things forward. So you talked about the kind of U-shaped curve and how you know the levels low or high
1:19:26
Do you think that we'd have some relevance on the fact that you didn't see a response? Could you be that you were pushing people too low or you're reaching them at the wrong point or putting them
1:19:36
into the wrong point of the curve I guess? Yeah, that's one of the downside of a project actually because we did not measure the Schumler Creek acid level throughout the entire project. I think we
1:19:49
only measured it at a start as a baseline and as you know the baseline would be high because of recent stroke but whether we should have targeted like each individual's ceramic acid level and a dosage,
1:20:04
it is something which we have thought about. As I've mentioned, the US.
1:20:10
shape relationship has been found that a low serum acid level, actually it's a risk factor within itself. And this has been shown in one of us study by OPTCHF, which has shown that people with low
1:20:26
level of serum regacid do not benefits from the alprenal treatment. And whereas people with high baseline, high
1:20:38
serum regacid level, actually benefits more. So yeah, definitely it is something to be considered in a future project to have a regular measurements of serum regacid level. Excellent. Thank you
1:20:52
for that really thoughtful answer Do you think. timing after the stroke would be important for interventions like this. Are we given this day one, reload them with aspirin and give all appearance
1:21:05
or is it something that we do down the line? Where do you see these therapies fitting in in the, where do you think they have more use, I guess? Yeah.
1:21:19
So I suppose because we don't really have a previous research to compare to with the use of alkranals, it's very hard to decide on the timeline itself. I
1:21:33
suppose we should need to understand
1:21:36
the
1:21:42
petal physiology. The xanthan oxidase is part of the oxidative stress in pathways and within the stroke, it's most likely to be like the head injury, like I said, injury damage to the head, to
1:21:51
the brain. I mean, and
1:21:56
I don't think it should be understood like after we've been like a long duration after the first event of stroke. In our project, the patients received their first dose after one month, but you'll
1:22:14
be interested to see whether giving the drugs at the first instance will make a difference, and whether giving the drugs, let's say at three months give a different result So I suppose with more
1:22:28
projects and more research could be done to see whether the timeline is important in
1:22:36
terms of lowering the urate level in the body.
1:22:39
And so what would be, how would you take this on next? What would be your next move? So personally, I suppose the most important thing here is to acknowledge whether the serum rig acid itself has
1:22:55
a definitive role being played in the cognitive impairment, always there are other factors, because given the multiplicity of cognitive impairment, it is definitely a multifactorial pathology. And
1:23:10
one of the interesting film, field I've been discussing with my colleagues is to look at a bigger population range using the genetic testing and using the biobanks So seeing if whether there are
1:23:28
other factors which we could take into considerations in terms of cognitive impairments in the
1:23:34
stroke population and to see if there are more easy targets to put in a simple ways for management of vascular stroke and vascular dementia. Great, thank you very much.
1:23:50
Thank you very, very interesting, Salisa.
1:23:54
So, my question is, as the study, I've heard up a couple of studies for using alloperable for head injuries. So, the biochemical mechanism is pretty similar in terms. So, as they've been worked
1:24:05
down on head injury outcomes in a similar way. Once
1:24:18
you say, I've got another question after this. So, what is your understanding about this particular aspect in head injury and the cognitive outcome from following head injuries? Head injury has a
1:24:33
very well researched mechanisms. It has a primary and a sedentary brain injuries. First, you mean by the sedentary injuries, there is a wider
1:24:47
inflammatory process going on. So xanthine oxidase itself being the
1:24:53
enzyme which is used to degrade the purine. So I suppose during the secondary head injuries like wide range ischemia. It
1:25:04
is a significant role in it. Unfortunately, I haven't read too much about the role of xanthine oxidase in head injury, although it will be very interesting
1:25:15
And given that we know one of the major pathology in the head injury is a so excited toxicity. And if we do a reverse thinking, maybe excited to see, could be one of pathology in ischemia stroke as
1:25:26
well, since both leads to an ischemia of the brain tissue and at the same.
1:25:45
On the same line, we could also think about the role of sometimes oxidase in the brain injuries as well.
1:25:55
Yeah, the other thing is the similarity of hypothermia.
1:26:04
Is there any comparison or complementary treatment with hypothermia and all
1:26:11
of Pyranol for either stroke or any other brain injuries?
1:26:18
I suppose hypothermia is used to, as it comes to mechanisms to the
1:26:23
inflammatory process. I know it's been used before in cardiovascular disease. So
1:26:31
the thing we've done find oxidase, but it belongs to a family of enzymes called the zanphine, OXC,
1:26:38
dehydrogenase, enzymes, and so when they normal pathology. my understanding is that xanphine oxdays exist as the xanphine dehydrogenism enzymes and this itself does not lead to any release of a
1:26:57
reactive oxygen species and normally it does not contribute to the oxidative stress but some of research have found
1:27:12
that the xanphine oxdays expression actually elevates during an ischemic process especially during the reperfusion ischemic process and leading to increasing oxidative stress and so in terms of a
1:27:21
hypophonia
1:27:23
I'm not really sure about this relationship with any sort of reperfusion ischemic sort of mechanisms so I can't say
1:27:34
No, I'm not expecting you to say the rest, but because there have been some studies done particularly in neonatal head injuries with a combination of alopiginal or on top of them. Anyway, thank
1:27:45
you very much. That's a very interesting paper, so I was just wondering, you know, you can broaden the horizons towards a more, you know, wider pathology like TBIs, one of them. Okay, thank
1:27:57
you very much, Sally. Well done.
1:28:03
Lovely, and Sally, any other comments or anything from your end? I know it was amazing discussion, thank you all so much, yeah. Thank you very much, and that concludes this panel discussion.
1:28:16
Hi, welcome back everyone, so our next presentation is by Avila Aziz, and it's comparing person or surgical procedures and treatment of crowded arteries to losis. So no partial work to Avila,
1:28:28
we'll talk a little bit more about this So thank you for that introduction, Ayla. So my research was basically quite some poorly. I wanted to find out the best surgical procedure to treat a very
1:28:43
common issue. Corotid artery stenosis is one of the biggest causes for ischemic stroke, and that's a massive, massive causal mortality around the world now, such as superseded malignancies Sumar
1:28:56
research is
1:28:58
competing three main
1:29:02
procedures, carotid and artery rectomy, CEA,
1:29:07
carotid artery scenting, and trans-carotid artery revascularization.
1:29:14
Carotid and artery rectum has been around for a few years, now it's been about 50 years. It's quite an invasive procedure, but it's tried and tested and it still works and that's why it's kind of
1:29:23
first line for your risk-production procedures and the NHS, your step above that would be cross-artistry-stenting, which is a little bit newer and a little bit less invasive. But the new year one
1:29:37
that's not being bought to the UK is transcroted archery revascularization. So my research is basically just comparing three fundamental measures from these procedures as a literature review, which
1:29:52
would have been the mortality rate stroke rate and MI rate post procedure at 30 days. And it's quite simply showed that t-car or transcroted our reverse causation, had the lowest mortality rate,
1:30:08
the lowest growth rate out there to days, which was quite
1:30:15
interesting really, but not a surprise when you consider how brand-new it is. It's only currently been used in the USA for our trial basis. So yeah, that's really what my research was about.
1:30:33
Do you want me to just talk about like implications for practice? Oh, that would be beautiful. Please, by all means. So the implications for practice right now are low, to be honest, because as
1:30:46
though experimental procedure, the paper that I used in my and my research was only a single arm trial for the t-car, because it's such a new sort of procedure that they've not had chances around,
1:31:00
I randomized. try on it yet. So the implications are really for further research than anything else, to research this new procedure, to see if it's actually worth taking forward and bringing it to
1:31:14
the UK and implementing it in NHS as a viable option. And that's really what it's for. Interesting. I think I'd remember, can I ask first though? Yeah.
1:31:29
So it's interesting. I remember this kind of discussion during the postures. Now, one of the things, when you start off a new procedure is you're going to be super selective in what cases you do
1:31:45
and you're not taking any risk by doing complex studies. So how do you extrapolate that information or did you actually use very similar compared case controlled. when you were comparing with other
1:31:60
two procedures, which are much more commonly performed, much more, you know, in inverted common risk adverse, in a way, you know, you're taking higher risk with these procedures. So how did
1:32:12
you try to eliminate that kind of bias comparison? So, and all the papers had sort of similar based on characteristics of the participants within their study, but there were definitely differences
1:32:26
within the characteristics But I sort of looked at that. And that was one of the things that stuck out was that any cross-radaratory centing that paper in particular and the T-car paper, their
1:32:39
participants had a lot more patients with existing cardiac complications and the cross-radaratory centing paper, about 18 of their participants had had a previous MI. And so that's why I excluded
1:32:54
the MI figures from the results of my. I mean, it is there, but it's just not the main part of that talk about because, you know, if the participants do have higher MI rates previously, that
1:33:10
would reflect on that. So I wouldn't really say that was because of the T-Car, but that's sort of how I used it to compare the three. But generally speaking, the papers were competing sort of
1:33:25
moderate to severe stenosis and adult males, and majority of them, they were still relevant in the studies as well. The majority of them were white males. Were they
1:33:39
single operator for both procedures? For both procedures, what do you mean? I mean, single operator in the sense, you know, is it by a particular institute based or is it or a single surgeon or
1:33:54
an operator based?
1:33:58
The three papers are different. So for T-Car, that was a multi-center trial in America. So obviously different surgeons, but each of them had sort of
1:34:13
different standards for their surgeon recruitment requirements. I couldn't really find any particular surgical requirements for this growth in Interferectomy, 'cause that was a slightly older paper,
1:34:27
but it was sort of rigorous testing and qualification required for the T-car paper.
1:34:33
And you said about the complication and the safety issues, but what about the outcome? What was the outcome measure used, and was there a difference in the overall outcome? And what outcome
1:34:44
measures were used? So the outcome measures were like the mortality rate, stroke rate, MI rate, and
1:34:53
like cranial nerve injury post procedure Um That's kind of all I included in the trial. So all complications rather than, you know, neurological. Yeah, yeah. Okay, yeah, that's good. Thank
1:35:06
you very much. Thank you.
1:35:10
So, I must admit, I don't know much about T-Car at all, so this has all been very interesting for me. So just to pick up on that last point, so the really used echo measures, they were trying to
1:35:23
prove it was safe, so like at the kind of phase two trial But I guess, do you have any kind of longitudinal data? Is it as good as an indirect rate to me? Like, does it last as long or we've
1:35:34
saved a growth? Do we know that we have a sense of that yet? I don't know if that's a apologies, I don't know a lot about it, I don't know if that's a silly question. No, that's a really good
1:35:46
important question actually, because because indirect rate to me as an older procedure, we do have long data on it, and that's why it's still used, it's relatively safe long term.
1:36:02
and it's a similar sort of situation with a stinting. But because T-CART is so new, they've not actually had a chance to do a random-ass trial when I let alone long-term data. So that's why there's
1:36:09
only 30-D post-op data in that trial. And
1:36:16
there were a few participants that have fallen up to a year, but that's really it, to be honest. There's definitely not enough data on it to see, you know, implicated in practice, which is why I
1:36:27
said it doesn't award an implication practice, but implication before the research. So it looks promising. And is that someone taking up the grips involved in the study? Are they following these
1:36:39
patients up long, we should know ours or another? We now got an RCT set up, you know, how we're trying to move this forward. It sounds like it might be very clinically relevant, you know, and
1:36:50
so I'm just ingested to see how we're taking it on. I'm not sure, but that's honest. I don't actually know what. Who's in the movie or someone movie?
1:37:02
Hopefully, hopefully that was the point of the. Great. Thank you very much. Thank you.
1:37:09
Lovely. And I guess before we wrap up, any final comments or anything from yourself, Abdullah?
1:37:15
No,
1:37:20
that's so. Thank you very much. Appreciate your questions and your interest. Lovely. Thank you very much. And that concludes this panel recording
1:37:25
Hi, everyone. Welcome back to our panel discussion. Our next speaker is Avi Joti. And she'll be talking about her poster, recent advancements in robotic skull-based neurosurgery a review. I'll
1:37:37
hand over to you, Agi. Hi, thank you. So hi, everyone. So my project primarily focused on robotic surgery and its potential to overcome the limitations of an endoscopic endo-nasal surgical
1:37:49
approach. So for any mid-line skull topologies, endoscopic and unausal approach. is the current standard surgical approach. However, it has certain limitations such as constrained sino-nasal
1:38:01
corridor, a need for a second surgeon, the lack of sufficient dexterity to close large skull-based defects and so on. But robotic surgery could have become these limitations. So what I did was I
1:38:14
conducted a review with the AEMT to identify recent advancements in robotic skull-based neurosurgery And I chose studies from 2018 up till 2022. So a five-year time period and I used the Prisma
1:38:30
guidelines to generate six studies for data extraction. So ultimately the recent advancements in robotic surgery that were identified included
1:38:42
five robot. So they were concentric tube robot and robotic handles. The endoscopic robot, the micro continuum robot, The verses robotic system and also the semi-autonomous internet. robotic
1:38:55
system using the Raven to surgical system. So individually each of these robots had their own advantages and limitations. But as a whole, the advantages were improved performance, benefits in
1:39:11
lengthy interventions and deep corridors, and also higher dexterity and safety and also modularity And as a whole, the limitations were mostly requiring a redesign and also requiring validation of
1:39:26
their reliability. So to conclude, I did a review and I found out that there were five recent advancements in robotic neurosurgery and also my review pointed out the advantages and also the
1:39:40
limitations of these five systems.
1:39:44
Thank you.
1:39:49
Okay, I am happy for you to take the
1:39:55
Luteer Mr. Alejandro, I'm very interested in you. Just two questions, you know, I think this is a very rapidly evolving and developing field. So between the years to 18 and 22, where these
1:40:13
robots kind of sequentially identified over, they're all in the same era or generation So some of these robots, for example, the Raven 2 was in for quite a period before this, but what happened
1:40:23
was they sort of used the Raven 2, which was, which was previously here before 2018, and they added like a semi-autonomous system to it. So in terms of like modularity, they added a camera and an
1:40:34
endoscope and tried to make it semi-autonomous. So some of the systems were already there previously, but what they did was they modified it So in terms of like sequential-wise, there isn't a
1:40:45
sequential to it, so they were sort of there already. Because, you know, in anybody who's going to invest in a robot or an advanced, you know, engineering innovation, you're waiting for the
1:41:02
optimum time to purchase it because it's a huge investment. There are two issues here. One, when do we know you have peaked in technology, we never peaked in technology Secondly, how do you
1:41:15
identify a cost effectiveness and what your studies, have you studied, identified any aspect of this side, which is very, very important in UK medicine?
1:41:30
Right. Two questions, sorry, I've asked you in a row, but did you get the two questions? Yes, it was about cost and what is about cost effectiveness and one went to know when to buy. Right. So
1:41:43
I feel that because for most of the studies, they were mostly prototypes and they required, because they did also feedbacks from surgeons as well who use these robotic prototypes. And some of them
1:41:55
required a redesigning as well. So in terms of optimal timing to purchase it, I would feel that the ones which require redesigning, for example, the robotic handles, it's not time for them yet.
1:42:07
But I feel that they're sort of moving towards the direction where they're creating a proper system. So like my favorite one would be the semi-autonomous one because it's sort of integrating AI into
1:42:19
it and also using surgeons, knowledge as well, sort of combining both of them. But in terms of cost and optimal time, I feel like in terms of cost, I wouldn't much mention about cost. They did
1:42:34
compare the versus system and also the DaVinci system and mentioning that the versus system had a smaller footprint than the DaVinci system but not much, of course. So I'm thinking that for future
1:42:47
studies,
1:42:49
slightly larger scale studies comparing different robotic systems and ultimately identifying the best system available.
1:43:04
Okay, thank you very well then and a good thing to look at here. My question might be a bit more of a, I just want to ponder, all these advancements are great and when you were reflecting there
1:43:18
you thought that the best mechanism was one that could utilize like the surgeon's skills and I guess, I mean, this might be one from Mr. Alchandi as well, like robotics moving on safer practice is
1:43:27
good, but is there ever a body that we're going to de-scale the surgeons or is this always a good thing to bring robots into the operating theatre and as a lowly neurologist, I should just stay in
1:43:37
my lane.
1:43:40
Well, that's just interesting. I always feel that, you know, in medicine especially, it's important to have a human touch. So I feel that there's always a need for surgeons that and we do
1:43:52
require the surgeon to be in the operating theatre, but because in terms of technology, it has made our lives so much more easier in this last few decades. So I do feel that with integrating
1:44:04
artificial intelligence and combining the surgeons knowledge as well, that could
1:44:11
enhance patient safety in a long run. But of course, I'm not a professional in artificial intelligence and how it works as well. So I think there should be some sort of like a discussion between
1:44:26
like the computer scientists and also surgeons in the future, in terms of creating something better and something which could enhance patient safety as well. And also make the surgeon's lives so
1:44:38
much more easier.
1:44:42
Thank you. Thank you.
1:44:45
Lovely, actually, I have a question. Mr. Alchandi, do you have any experience with the expansion of robotics in neurosurgery in general, not just in skull base or any perceptions on it? So um.
1:44:59
Are you recording this? Because this is, yes, we have two robots in use in your research team. One is a da Vinci robot we use for
1:45:13
the DBS. So when you say robot, it's not doing a job of a surgeon, it's making it more accurate.
1:45:22
So the surgeon has to plan the target and everything. So we just, the robotic arm does it. So it is in a way replacing the
1:45:34
brain lab navigation. So instead of us adjusting the coordinates, the robotic arm does it. The second robot which we are trialing now and it's again for spine. It is similar to the navigation
1:45:50
system we used to put the screws in, but instead of us calculating the coordinates and It's got a robotic arm, which actually puts the screw in, and we just have to turn the screw. So at the
1:46:01
moment, it's not AI, it's not
1:46:06
doing its job, it's just guiding the surgeons. So surgeons are still doing the job and doing planning, trajectory and everything. So that's why I asked this question. There are different stages
1:46:16
of robotic advancements, you know, starting from a basic accuracy guidance to motor guidance, you know, where you reduce the tremors and movements to the third level, which is completely AI. So
1:46:33
surgeons just have to sit and watch and make sure that they don't make a mistake. So those levels, you know, that's a level. And where do we kind of feel comfortable from, you know, from what
1:46:46
Amy said about discoloring yourself and losing your job? to where the patient safety come into bed. So like Aggie said, it's the most important thing at the end of the day is patient safety. So if,
1:46:60
I think so, it's somewhere in the middle,
1:47:03
not completely AI, not just because of what we have in the brain lab and neuro navigation is,
1:47:10
it's not very different if you have a robotic to do the extra bit of, you know, it is in the corner, you can do it as else. So it could be somewhere in the middle, in laparoscopic surgeries, I
1:47:21
have seen people do it, it is actually where you have
1:47:27
the instruments being helped by surgeons. So you're actually finessing the movements as opposed to accuracy, which is what neurosurgeons, you know, use, yeah. Ah, it's really interesting
1:47:39
actually. And I guess I know Dr. Davidson in neurology, is there any drive for anything like this neural in the neurology field. Although, you know, and not just in terms of, I guess, robotics,
1:47:52
but in terms of any of these, this sort of future wave of, I guess, the next best thing of technology driven
1:48:00
topics, whether that be robotics or AI sort of thing. I mean, I think there certainly would be, I mean, I think, I mean, Mr. Alacandy offered the version, there's the one that we kind of work
1:48:12
closely with in the New Surgeons as DBS and Parkinson's and Intremers. So we often kind of take advantage of our neurosurgical colleagues in that respect to try to try and help with these things. So
1:48:25
I definitely, you know, we're going to see all kinds of, I guess, kind of joint working with the neurosurgents from, you know, as we move forward in neurology. And I think, you know, as
1:48:36
neurologists, we'd be quite happy to piggy back on to these things that come up
1:48:42
Absolutely. And I guess, Aggie, I guess a final question is, do you do you think from what you've seen, do you think it's the future?
1:48:51
Well, as whole, yes, I think it is sort of moving to it's there, like we are dependent, not depending, but we could potentially be depending on robots, how about like what
1:49:03
So,
1:49:06
I suppose in the future, there would be AI as well, and we are definitely moving towards that direction, but we're definitely not there yet. There's still room for improvement. So yes, we're
1:49:17
definitely moving towards that direction.
1:49:22
Fantastic. And any other final comments from yourself, I guess, before we wrap up No, but thank you for having me here. It's a pleasure. Wonderful. Thank you. And thank you, obviously, for
1:49:35
coming. It was a really interesting talk. Thank you.
1:49:38
And onto our next panelist is Rishi Arisha. who's going to be talking about his work, analyzing meningiomas in children, a rural Indian study. Over to you, Rishi. Well, thank you so much, Asan,
1:49:50
and thank you so much for the
1:49:53
committee for having me here. So my name is Rishi. I am a third geometrical student and I study at the University of Manchester. And today I'd like to just present my work which was done with the
1:50:04
aim of analyzing meningiomas and children. And so the way I'm
1:50:12
going to talk about this is first of all, I'm just going to give a brief introduction about meningiomas. And then afterwards, I'll talk about my work and possibly talk about some of the
1:50:23
implications that it might have. So I'm just going to start off with talking about meningiomas. So for many of the
1:50:29
viewers, this will be routine and it will be especially so for the - panel of specialist doctors today, but I'm just going to go through it for the sake of someone who might not be very familiar
1:50:40
with
1:50:43
meningiomas. So meningiomas, obviously, are one of the most common type of primary CNS tumors. They may originate from the arachnoid cells that are present on the inner surface of the dura. There
1:50:55
are many risk factors that can obviously increase the risk of developing these meningiomas, including things such as ionizing radiation to the skull and there have been other risk factors that have
1:51:07
been implicated as well, but obviously do require further research, things such as differences in sex hormones, diabetes, arterial hypertension, and possibly even mobile phone usage have been
1:51:20
implicated with meningiomas. Meningiomas by themselves are frequently asymptomatic. but sometimes they can have some symptoms, especially those are related with a mass effect. So for example,
1:51:33
causing some sort of neurological symptoms, possibly some seizures and headaches. And I'm gonna talk about that in my study as well. It's mainly, like the corner store, it's
1:51:45
the way it's mainly diagnosed is with the help of an MRI, although PET scans are, could be quite useful in diagnosing meningiomas According to
1:51:55
the World Health Organization classification, they divide into three different grades, grades one, two, and three, depending upon the characteristics. And the treatment is usually surgical. And
1:52:08
so with that being said, I'm just gonna talk a little bit about my work. So this work and the way I got involved with this actually is a bit special. So I actually reached out, I am of Indian
1:52:22
ethnicity so I do go back to India. every now and then to visit my family and live there. And so I came into contact with one of the neurosurgeons and it's quite an experienced neurosurgeon. He
1:52:34
actually works in a hospital and this is a government hospital. So the way healthcare works in India is you've got a private sector and you've got a government sector as well. And the private sector
1:52:47
is quite well-funded and they tend to have,
1:52:51
they tend to be much more, they tend to be what people use more. But the public sector, the government sector is where surgeons do work and it works, it's based on a free-for-all model. So it's
1:53:06
free at the point of care. So here's a surgeon who works in the public sector. So I got into a clash with him and I was actually fascinated to find out that meningiomas were being treated
1:53:21
in this part of India which is and the rural Southwest part of India. So then we got into contact and we decided to sort of analyze the pediatric meningumas to just look at, it's a bit like a case
1:53:35
series so like just looking retrospectively at the pediatric patients who came to the hospital and then analyzing them. So I'm just gonna go through my findings now. So pediatric meningumas by
1:53:48
themselves tend to be quite rare and this was quite surprising that I was, I was quite lucky that I was able to find some data on this, especially in India. So pediatric meningumas tend to be quite
1:53:59
rare and there has been some work on it that's been especially coming from the, that's quite established in the Western world really, but looking at the developing countries, there's really not
1:54:12
much out there. So, There was some work that was done in China a couple of years ago in which they analyzed about 32 pediatric patients with meningiomas. And quite recently, there was a piece of
1:54:24
work that came from Mumbai and India as well. But basically what we sort of try to do is just analyze these patients and divide them and analyze sort of characteristics that we found in these
1:54:38
patients. So I'm just gonna go through them now right now So
1:54:44
like I said, intracranial meningiomas in children often consider to be rare. And these tumors are anywhere from say 04 to 46 of all brain tumors in children. And like I said, as compared to the
1:54:59
thoroughly studied pattern of meningioma development in adults, pediatric
1:55:06
meningiomas tend to show differing developmental patterns. So one study that was actually conducted in the University of Iowa in the US said that pediatric men you must have more malignant.
1:55:13
histological subtypes, and they also tend to have greater rates of recurrence. So like I said, we just wanted to analyze the characteristics
1:55:22
and see what they show basically, and then just put out our research to the world so that it could potentially be useful. So I'm just gonna talk about it now. So this was like I said, a
1:55:31
retrospective study, and 26 about of analysis an was this
1:55:35
children presenting with meningiomas. And this was done, so the data over here was tracing all the way back into 1975 when they were first started to be recorded. This was done in a rural
1:55:48
government run hospital in Southwest in India.
1:55:52
So just talking a little bit about the patient characteristics. So the patients that were mentioned in this pediatric cohort was from as young as children that were one, to just say about a year old,
1:56:03
two patients who were about 17 years of age. Meningiomas tend to mainly have a female per respondent, So they tend to be quiet. They tend to be more prevalent in women as compared to men. However,
1:56:17
in this cohort that we found that it was quite surprising, it was slightly more prevalent in men as compared to women. So it was about 18 is to one. So slightly more common in men as compared to
1:56:28
women. About 23 of these meninger must happen in the posterior fossa, about 45 in the sphenoid, and about 21 in the tuberculum cellae, with the remaining developing in other regions for which the
1:56:44
precise location on data and subtype was not available.
1:56:49
Out of these 26 cases, about four patients actually tend to have atypical or malignant meningiomas.
1:56:59
The hospital data said that the complete tumor excision was actually achieving about 18 of patients, or whereas there was
1:57:10
mortality seen in about 3 of these patients. Now, one thing that this study tried to do was to try and follow up on these patients to see how they were doing. And as you can appreciate in a country
1:57:26
like India where the population is massive and with majority of these patients actually coming in from low socioeconomic backgrounds, it was quite difficult
1:57:42
to do that. So unfortunately, we were not able to follow up on these patients But we did find some information about one or two patients, and I'm just going to mention that here, but it might not
1:57:50
have much scientific benefit, but I'm just going to mention it. So we actually found out that one of our patients who was about 13 years of age when he had the surgery,
1:58:04
he actually had one of the anaplastic variant tubers, and he actually died because. He developed a cerebral hernia and he actually refused. But when it came back again, he actually refused
1:58:16
surgical treatment and he died because of cerebral hernia. I'm just going to discuss with all of that data being said, I'm just going to bring out a couple of, just going to discuss a few, a few
1:58:30
points, just sort of compare between adult meningiomers and what this study could potentially indicate.
1:58:38
Like I said, pediatric meningiomers tend to be relatively rare. And they're quite difficult to find. Like we said, in this study, it was more common in men as compared to women, but there is
1:58:51
often a female predispondent. So that was something we was quite surprised to find. Obviously, the sample size in this case was very, very small. So we can't say it with certainty.
1:59:04
We don't really know why this could have happened. Like we mentioned, sex hormones might be, potential risk for meningiomers, so possibly sex hormones could play a role in pediatric meningiomers.
1:59:18
So there was some interesting study that was done by rushing it out in the United States, and they basically mentioned that about 72 of pediatric meningiomers actually had a neurofibromatosis
1:59:36
as well, which was quite interesting. And obviously we weren't able to analyze that in our study.
1:59:46
So the symptoms that our patients mainly demonstrated were very nonspecific, headache was actually the most common symptom, and epilepsy was a common symptom as well. And
2:00:03
this was quite interesting, Because, like I said, Not much study has been done on this. So possibly this
2:00:21
could
2:00:30
sort of shed some light as to how many jumas, many present in children. And when these many jumas they develop, they can actually cause an increase in intracranial pressure and they can cause
2:00:31
obviously a local master factor and they can also cause some cranial nerve dysfunction especially in
2:00:34
nerves, in cranial nerves, two, three, four, six and seven as well.
2:00:40
Um, so, so, um, so that, that's, that's it from me. Um, so we, we always have a lot of limitation in the study. Um, the study was not, uh, it was not, it didn't have a very large sample
2:00:54
size. The data was very difficult to find and we didn't have much guidance when it came to, to, to, to, to, to, to, to, to sort of coming up with this abstract and this manuscript. But with
2:01:05
all of that being said, I think what this could, to potentially help with is just after that data pool, which is so limited to find, especially with regards to pediatric meningiomers coming from
2:01:18
developing countries. So that's it from me. Thank you so much.
2:01:28
Thank you very much. I think it's a big data compared to because it's such a rare tumor. So yeah, well done for that So my first thing is, I know you've said most of the meningiomers we see in
2:01:41
adults, which is much, much more common than the children, are they no meningiomers. They happen without a rhyme or reason. For kids, you correctly looked at primary causes, one of them is
2:01:56
the NF2, the family history. I know you can't, it's very unlikely you'll get gene testing done on these children, but family history is a good way of looking, did you look into that or was it
2:02:08
just?
2:02:10
No, so we did not look into the family history, we were just trying
2:02:17
to just mention in some of our discussions to look at some of the literatures already been out there and those points we mentioned, so we did not personally look into the family. The other thing is
2:02:26
radiation, so has any of these children been given radiation for things like teeny or you know, a little things like that, you know? Yeah, so this is something I forgot to mention, so no to none
2:02:40
of these children were actually given radiation, even with regards to the mening tumor treatment after surgery they were not given radiation or chemotherapy. And my final question is what proportion
2:02:54
of them were grade 2s and 3s, whereas in adults, you find almost 90 percent are grade 1s and only about 10 percent are 2s and 3s. So we weren't able
2:03:09
to buy them based on histological classification and this is a major limitation of our study and this is mainly because we weren't able to find accurate data and we didn't want to
2:03:21
sort of give out any assumptions but we weren't able to divide it based on the Simpson grading and to apologize for that. Not Simpson, I mean WHO. Anyway,
2:03:34
but still a very good paper because it's probably, you know, have you looked at literature? Are there enough other many papers which has got so many numbers of pediatric meningiomas? So there've
2:03:47
been some recent developments, some recent papers coming in. So like I said, there was some work coming out from China in which they had about 40 children. There was some recent paper coming in,
2:04:01
conducted in Mumbai in which they had around 16 patients. But like I said, these patients were dating back all the way to 1975. How many did you have? We had about 26. Yeah, that's a good number
2:04:15
Anyway, well done, pass it on to Dr. Davidson.
2:04:20
Yeah, no, really great, really interesting. So, cards on the table, I obviously know very little about meningiomas, I tend to find them when I scan people for other things and then refer them
2:04:31
to my surgical colleagues. So you mentioned about the NF2 stuff. So just out of interest, is that something that you screen for an all pediatric? in geomas or is that something you think that we
2:04:41
should be doing? If that's a common factor, you know, even without a family history, do you think we'd have a de novo hit rate that would be worthwhile thinking about something like that?
2:04:53
That's a very good question. So it could be possibly something that we could look into. Obviously, this was coming from a setting in which we sort of selected. And obviously, given in that sort
2:05:06
of setting, it will be very difficult. It's from a neurofibromatosis. And it could be, but coming onto the NHS, coming onto the UK and coming onto the developed part of the world, this,
2:05:19
obviously, the fact that it's related to NF2 wasn't something that we found out from our study. But it was something that was mentioned in a study, a very interesting study conducted at the
2:05:30
University of Iowa. So with that being said, where in those sort of settings in which the resources are available. I think that's a very, very interesting proposition to possibly look into
2:05:43
the relationship between NF2 and meningiomas and possibly that could be a way in which NF2s could be possibly screen for. But like I mentioned, this wasn't something I came from our study and I had
2:05:57
to apologize my knowledge on this is very limited. I don't need to apologize. You've done really great work, especially in what I imagine would have been challenging circumstances to collect the
2:06:07
data. So, and as you say, you've added knowledge to, you know, to have much knowledge about before, like it can only be a good thing. Never be sorry.
2:06:21
I guess actually, I've got a question about the practicalities of collecting such data, obviously given you mentioned it was in a public hospital, the data records went back to 1975. What was the,
2:06:32
this is just from a pure research point, the practicalities of trying to collect data like this from your point of view. So it was actually quite challenging. So just to give some insights, some
2:06:44
of these, so tracing up to maybe 10 years back, the data was actually shifted onto a sort of an EPR setting that you notice in the NHS. So there were digitalized records available. But before that,
2:07:01
most of these records were handwritten, and they were stored in thick piles of
2:07:08
books, and they were divided, because of which it was slightly easier for us. But this was data that was just collected and stored away in a bookshelf and possibly to be forgotten. But it was
2:07:24
quite good that we were able to get something out of it, at least, I believe.
2:07:32
Well, wait. And actually,
2:07:35
Jirek, again, just talking where the practicality is given that difficulty. Do you reckon from a research point of view, any might have potentially been missed given that difficulty of trying to
2:07:44
find these paper records? Yeah, that could also be a limitation or only to our study, but especially to, like I said, coming from resource-limited settings and especially looking years and years
2:07:58
back, like going almost 50 years back in time, where data obviously is very difficult to come from Many of these hospitals would not have even recorded the surgeries were carried out,
2:08:17
and especially coming from back back in those days, it was very difficult to even invalidate the credentials of the surgeons actually performing these surgeries, especially in those kind of settings.
2:08:30
So I would imagine that it's very difficult to find data regarding this, but
2:08:38
but to the best part of it is what we could find and we put out there really. Absolutely, no, thank you. And a really interesting discussion. And that wraps up this panel discussion recording.
2:08:51
Hi everyone, welcome back to our session. Our final speaker for today is Rishi Harisha. We'll be talking about his research analyzing the effectiveness of endoscopic endo-nasal approaches and the
2:09:03
surgical resection of tuberculum, salium, meningiomas. Juan, over to you
2:09:10
Rishi. Hi, thank you so much for having me. I'm very honored to be here in the presence
2:09:17
of such a committee in which there's a lot of expertise. So thank you so much for having me. My name is Rishi Harisha. I'm a third year medical student and I study at the University of Manchester
2:09:31
And I. So this was a systematic review that we conducted in order to look at the effectiveness of endoscopic endo-nasal approaches and how
2:09:42
they compare and how they sort of the data that we have with regards to the resection of tuberculosis and immunogenes. Now, I'm just gonna give a brief introduction about what these are, just for
2:09:58
someone who might not be versed with this So before I go into talking a little bit about the specifics, I'd like to just talk a little bit about why we decided to do this and how this was really done.
2:10:11
So this was a topic that was,
2:10:16
a systematic review that was conducted solely by medical students and there was no senior supervision that was involved in this. This was a topic that was suggested to us from one of our placement
2:10:27
supervisors and we decided to look into it in a bit more detail. So I'm just going to open up the data that I have now and just share it with you so if you can if you just plan with me for one second
2:10:38
please Um,
2:10:44
Okay, so just talking a little bit about what endoscopic endo-nasal approaches are. So when it comes to the
2:10:57
surgical resection of tuberculum-cellular meningiomas, like we said, tuberculum-cellular meningiomas are a distinctive group of meningiomas, they present in the supercellular space, and they have
2:10:58
attachment, deural attachment to the tuberculum cellae to the chiasmatic sulcus and to the diaphragm cellae as well. While traditionally these are actually removed through a wide variety of
2:11:20
microscopic transcranial approaches, recent applications
2:11:26
of concepts from endonasal sinus surgery where this concept actually originated from allowed neurosurgeons, especially those who are working with autolaryngologists to resex call-based tumors, and
2:11:39
obviously this could also work with regards to tubical and cellaminin tumors. Now, this has been a, I believe, and I'm not very well-versed with neurosurgery, but I think this has been a topic of
2:11:54
debate for quite some time along with your resurgence, because data which came from, there was quite a few systematic reviews published on this specific topic in
2:12:07
2013, in which the result, the data basically said that there was no significant approach for endoscopic end initial surgeries compared to your traditional transcranial approaches. However, data
2:12:22
coming from a couple of years ago, ranging from starting from 2018, I think there were some systematic reviews that were published, which mainly said that there was, in fact, a benefit to EEA's
2:12:34
as compared to a microscopic transcranial approach. So we just tried to explore that from a student perspective. And we tried to gave our input into the topic. So this is where the idea mainly came
2:12:46
from. So there have been many benefits that have been theorized for endoscopic endonasal approaches as compared to transcranial approaches.
2:12:57
Some of them, them actually being, you can actually avoid brain and optic nerve manipulation and retraction. You can actually deep-askillarize this cult-based blood supplied before the tumor
2:13:11
resection And surgeons, I think many people within this field actually believe that they have better outcomes. So we actually tried to explore that in a little bit more detail. So with all of that
2:13:25
being said, I'm just going to go into the specifics of
2:13:29
our work now. So this was a systematic review. And we mainly did this the search, we obviously came up with a search strategy, which was mainly looking at some terms. So the terms that we use
2:13:42
were typical in sedimenting jumas, endoscopic, intonated approaches, and translating approaches. And we did a preliminary search on MEDLINE and on MBase.
2:13:55
So I have the Prisma chart with me. We actually came up with around 211 papers out of which from both MEDLINE and MBase. And now around 58 of them were duplicates. And once we'd removed the
2:14:08
duplicates and once we'd actually assess the full articles for eligibility based upon the inclusionexcrusion criteria, which I'm going to talk about now, we came up to around eight papers. So that
2:14:20
was what we were able to include. I do appreciate that there have been other systematic reviews which have been more successful, which I've actually found on more papers, which are much more
2:14:30
extensive start strategy, but this is what we could do from this student perspective. So the eligibility of the studies for our paper, we actually focused on those papers
2:14:42
that talked about the interventions to increase cleaning uptake. We looked at RCTs, we looked at studies that talked about mainly the extent of reception, the visual improvement with this type of
2:14:53
surgery, the chance of all factory loss, and also about
2:14:59
CSF leakage and some other relevant parameters that we could find. So that was what was the methods of the study. Now, just talking to you a little bit about what we found and what we can share,
2:15:15
is that first you're just coming from a discussion point of view endoscopic skull-based surgeries. do actually have certain advantages. Like I mentioned, you can actually obviate your brain
2:15:27
structures and you can actually traverse any neurovascular structures as well. But we also found that there are certain disadvantages to EEAs as well. So I think some of the, and obviously I'm not
2:15:41
a neurosurgeon and I'm not very well versed in this field, but some of the stuff that we could find out that was mentioned by other people in this field actually said that the disadvantage of this
2:15:52
procedure was that there was a relatively restricted working space and
2:15:57
there was also dangers of inadequate thorough repair that would have done. And another major limitation was in terms of training doctors to actually perform these kind of surgeries. So I think there
2:16:12
is a significant amount of training that is required not only for neurosurgeons but also for auto-laringologists working this field. and training in terms of how to use an endoscopic sinus and how to
2:16:26
perform these kinds of surgeries.
2:16:29
And acquisition of these skills are actually slightly even more difficult for neurosurgeons as compared to
2:16:36
autolaryngologists with neurosurgeons rarely use endoscopes in other surgical procedures. So these were certain limitations and these are certain things that we found. These are certain things that
2:16:47
I can actually limit in terms of training and in terms of the availability of start to actually perform these surgeries. So just coming on to our outcomes and what we found out from our study, I'm
2:17:02
just going to summarize this very briefly is we found out the, in terms of total resection, the gross total resection in the endoscopic endo-nasal group was about anywhere from 65 to 92, whereas in
2:17:16
the transcranial.
2:17:19
and the trans-cranial cohort is about 74 to 92 percent, so slightly higher gross resection in the trans-cranial cohort as compared to the endoscopic cohort. However, we also found out that visual
2:17:33
improvement was actually higher for the
2:17:37
EEAs as compared to the traditional approaches. The cerebrospinal CSF leak was also slightly higher in your
2:17:46
trans-cranial approaches as compared to your endoscopic endo-nasal approach cohort. And intraoperative arterial injury was also higher in the trans-cranial approaches as compared to the endoscopic
2:17:59
endo-nasal approaches. So this was what we could find. But again, that being said, there have been lots of studies have been published with varying results with regards to this and varying
2:18:13
outcomes as well. So we do appreciate that the study might have not been done very comprehensively. And
2:18:21
there's been a lot of papers that we've missed. So there's a lot of limitations to this study. And the major limitation to this study was that we were not able to find an adequate supervision to
2:18:30
sort of guide us with this. But this is what we found from a student perspective. With that being said, one of the major things just to conclude that I would like to talk about is
2:18:41
from what we found at least, we found that EEAs could be, if not more successful than TCAAs, they could be equally as effective as TCAAs and obviously they're slightly less invasive as well. So
2:18:57
therefore, they could be considered as an alternative. And I'm not very well aware about how many surgeons and how many trainees actually learn this procedure, but it could be something that the
2:19:11
future. cohort of neurosurgeons and medical students going into neurosurgery could possibly benefit from. And there's been a constant drive into not only in neurosurgery, but
2:19:24
in all fields of medicine to move towards less invasive sort of surgical procedures. So this could be something that could be considered. And that's it from me. Thank you so much
2:19:40
Thank you, that was very good, very comprehensive.
2:19:46
So for now, okay, you know, you're going
2:19:56
to be in neurosurgeon, but before being in a neurosurgeon, you know, as a layman or a doctor, if you had the surgeon gives you the two options to have a tumor from yourself or your relative to be
2:20:03
taken on, which would you choose based on your understanding and studies stay. There's a very, very random question, but.
2:20:12
Have you made an abuse on this based on the study? So it would be the traditional trans-renal approach. Why would you do that? Is that because of surgeon skill or is it because of the technical
2:20:26
aspects of it? I'm not very well versed with the technical aspects of either two, but to the best of my knowledge, what I found at least is that the trans-renal approaches have been something that
2:20:38
have been tried and tested and performed for a very long period of time and with more data available, whereas endoscopic surgeries are relatively newer. And if I was a neurosurgeon, I believe that
2:20:53
I would be more well versed with the former. So that is what I would do. So what are the ways of
2:21:04
comparing or how would you mitigate this? with testing a time tested way of doing it was a new procedure which has come up and coming with new technology. How would you surgically compare and
2:21:23
identify the outcome and what are the mitigating factors in order to avoid these biases? Yeah, so that's a very good question. So just to put out that to the best of my knowledge, the way to
2:21:37
compare these things is quite difficult. But some of the ways you can do this is, first of all, to do, you know, a traditional study in which there is two different cohorts and then the
2:21:51
populations that actually go into these cohorts should have similar disease backgrounds, similar socioeconomic backgrounds, and then let's say group A undergoes, one procedure group B undergoes,
2:22:03
second procedure and then you look at certain outcomes from group A group B and then you compare the two. So that would be the way of analyzing them.
2:22:12
That's my knowledge. So that is what we try to do with - Yeah, I agree with that. But the problem with that is the endoscopic is a very rapidly expanding. So now 2013 is a totally different story
2:22:26
to 2022 or 2023 in terms of endoscopic surgery And,
2:22:34
you know, chronotomy for tuberculosis, LA. Manon-Jumas is a big undertaking and risk of seizures and driving other things. So, obviously, it depends on the surgeon you speak to, you know,
2:22:47
somebody might who's well versed in doing endoscopic surgery. But if you aren't asked me the same question about what I would choose, I probably choose the endoscopic approach. Right I'll pass it
2:23:00
on to Dr. King to get it
2:23:03
I'm going to bear that in mind, just in case I ever - No, no. The only problem with that is the CSF leak.
2:23:12
It's quite difficult to repair but CSF leaks. But the thing is that even with a transcriptional approach, you can get CSF leak. And then if that happens, you have to go back to the intelligence to
2:23:22
repair it through the nose. Right So it's not
2:23:31
as bad as getting seizures for the rest of life. You're not touching the brain. You're not letting the brain expose to hair. So that we end up just copy is better.
2:23:44
Interesting. I mean, it's all very interesting stuff. I'm learning a lot about neurosurgery tonight, which is very good for me When you were mentioning the kind of success rates in terms of
2:23:56
reception, the two procedures both kind of had 92. But then you just mentioned something that - This is me picking up on random bits and don't worry if you don't have an answer to this. But you
2:24:05
said that vision was better, with the
2:24:11
Indonesia approach. Did they say why? If the reception margins are the city, like did they offer any reasons why, like things like that would improve or is it just one of these? Yeah, so what we
2:24:26
mainly did was, in terms of this study, we weren't able to do a math analysis. So we just did a qualitative review of all of the papers that we could find. So we literally just did a very basic
2:24:41
pooling and then we just looked at the outcomes that paper A, B, C, D reported and then we just came up with final numbers. We weren't able to describe the nuances in detail and it is not
2:24:54
something that I'm biased with, I'm very sorry for that, I don't know, I could not answer that question why. But obviously, this is something that we want to pick up and we want to improve upon
2:25:06
before going somewhere with the Spanish script.
2:25:11
You've already, I know in yourself, but this is great work, especially when you haven't had any super, you've done this as a group of medical students, you've taken a subject that you're
2:25:21
interested in, you've researched it and you've come to present it It's like, be more proud of yourself. This is good stuff and it's a good foundation. You know, I think you should be pleased with
2:25:33
what you've achieved here.
2:25:35
So anyway, that's, me said my piece.
2:25:42
So any more questions?
2:25:45
No? Thank you very much for that, Rishi. That was really interesting work. And so that concludes the end of our final discussion sessions. Thank you very much for watching our series and we
2:25:56
really do hope you enjoyed the discussions that were involved. Thank you. Thank you. We hope you enjoy these presentations.
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