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OK, we're ready. So, hello everyone. Welcome to the first online webinar session of the UK MLA series. My name is more and I'm part of me, our uh opening lecture centered around hematology is said to be contacted by Dr Liz Tilman. Uh Just before we start a reminder, feedback forms will be uh dispar following the conclusion of today's event, your insights are invaluable in helping us uh enhance the quality of our future events. If you need any clarification during today's lecture, you can always send a message in the chat. If you have any questions. Generally, you can always contact us through uh our social media or via email. That's all for me. Now, let's turn the floor over to doctors for today's lecture. Thank you very much and evening everybody and thank you very much for having me online. I'm still a very brief intro of myself. I'm Lisa. I'm a GP trainee currently based at Royal Free in London. Um We're gonna be doing some hematology cases where I'm very, definitely not a hematologist. Much more a generalist. So this is more kind of aimed at roughly what we would expect medical students to graduate knowing when they go for finals to be able to complete their final exams and go into foundation training. Um, feel free to write questions in the chat. Cos I don't think I can hear any of you and I'll try and answer as we go along. Um, we have five cases all centered on him. So we might as well start, we go to next slide then please. So start with case number one, we've got a 65 year old gentleman with a background of familial hypercholesterolemia hypertension. And there's been a referral sent from the GP due to high calcium levels, you do a little bit more digging and you can find out that he's also got some associated lower back pain and fatigue. So it's just sort of a small snippet that you might get in a UK um LA exam. So we're gonna go through blood test first. So next slide and then if you just have a look at those, I'll give you 20 seconds or so, just so you can see what stands out to you and start having to think about some differentials. Great. So if you go on to the next slide, we've highlighted the ones in red that are particularly concerning, but we can see that this patient is anemic. Um also hypercalcemic, a slightly raised ALP and has quite significant renal dysfunction. So the very high urea and creatinine if anybody feels like contributing. Yeah, exactly. AK I fantastic. Definitely. You're really worried. Actually, you don't really know what his baseline is from this set of blood. So, you're right. It could be a very significant first off renal impairment if we're thinking hematology. Does anyone have any ideas in terms of what we might be thinking, diagnosis wise to underlie this composition on the blood test of anemia, hypercalcemia and renal dysfunction. Yeah. Beautiful. Very nice, very nice. People are on it. Nice. So yeah, if we go to our next slide we have here, calcium elevation, renal dysfunction, anemia and bone pain. So that's all kind of, I remember that as a crab and that is quite a hallmark, especially in exams of multiple myeloma. So really at this point, any additional tests anybody wants to do to try and refute or confirm the diagnosis thinking you've just had a basic blood test from now. Anybody you wanna write anything in the chat for what they would do? Yeah, lovely. Got some really good stuff in there. Really good. I always think it's good to structure from basic to more complicated. So if we're thinking just first of all, we're just doing simple bedside stuff, they're anemic, who want to know why? So it's sensible to send off some iron studies of vitamin b12 or folate. Maybe um they've got this raging renal dysfunction. Is it an AK I, so we want to make sure that we're doing a urine dip um considering sending off the urinary protein creatinine ratios, considering whether they need an ultrasound of the renal tract as well. And then also additional bloods that we can send for our multiple myeloma. Things like serum protein electrophoresis, immunoglobulins, serum light chains. And you can also send off a urine sample for bent jones proteins. X-rays is also a very sensible choice. You would see potentially some lytic lesions which you can also see on act really what's gonna tell us the exact diagnosis is a bone marrow. So if we go to next slide, I think this patient has sent, they've set off some bits and pieces and we've got ap protein band. As you can see. Now, the immunoglobulins themselves are fine but there is selectively elevated Kappa light chains. So you can get suppression of immunoglobulins called an immuno paes. But here in this case of this patient, it was a Kappa light chain myeloma, which is the one which is monoclonal expansion of a capite chains. Go to your next slide. Like I was saying with the bone marrow, what you would see is a proliferation of plasma cells in there pictures just to remind you where those plasma cells come from. And the lineage bone marrow will also help us with phenotyping, which will then help us guide treatment. So next slide, a brief recap of what myeloma actually is. So you've got a malignant transformation of a terminally differentiated B cell. So it's a plasma cell right at the end of your lineage. Now, it can secrete paraproteins, light chains or both, which is why you get the different types and the primary site of proliferation is in your bone marrow, which is why you often get bone pain as one of the first symptoms and it's usually back. So lumbar spine. Now, if you only have one lesion, we call it a solitary plasmacytoma. But obviously, if you've got multiple, then you've got multiple myeloma. Next slide, we often think of multiple myeloma alongside two other conditions. The hematological conditions have got smoldering myeloma or MGUS, which is monoclonal gammopathy of undetermined significance. And the real way to tell which one is, which is by bone marrow. And that's mainly looking at the percentage of clonal cells in your bone marrow and the presence of end organ damage. You've got some basic diagnostic criteria here. Lovely. Next slide, please. So as we talked about, crab is a bit of a omic to remember many times of why these things happen. So you can get hypercalcemia because of bone demineralization. You've got a lot of bone breakdown and all these lytic lesions, renal dysfunction or AK I, as I said before, you, light chains often filter through the glomeruli and can significantly damage the renal tubules. You can get lots of infections, you can get an acquired hypogammaglobulinemia, which is a lack of normal antibodies, which means your body cannot mount the immune response that needs to. So people are especially at risk of infections from encapsulated organisms. Now, anemia is usually an impairment of hematopoiesis or crowding out to the bone marrow. You can get hyperviscosity syndrome. So things like headaches, visual changes because of the high levels of paraprotein in your blood, that just makes it that much more sticky. Now, what we were talking about before your x-rays, your CT S, you can get multiple osteolytic lesions causing pathological fractions fractures and which can also cause compression fractures, which obviously can then lead to different emergencies. Neurological emergencies. If they're in their spine, potentially things like corna. And I've got some pictures here. We go to the next one. Obviously, they're not. If you see pictures like this, it's not necessarily multiple myeloma, but you're significantly worried cos they're very osteolytic not of a soap bubble appearance is a bit of a classic buzzword again in exams, not good. Uh Next slide, general approach to management, really analgesia. They bone pain opioids is often good for bone pain, hypercalcemia, going through your fluids, loads and loads and loads of fluids at least 3 L in a day. Obviously, you're looking at the patient in front of you to see if they can take that much fluid, but they're going to be significantly dehydrated if they remain persistently hypercalcemic, then we consider bisphosphonates, making sure to monitor them to make sure they don't then go hypocalcemic instead. And then obviously, we're competing our work up to see exactly what type of myeloma it is and how we're gonna manage it. Next slide, please. So really, I mean, the guidelines will change though very dependent on the country. But induction chemotherapy is obviously the mainstay given that it is a cancer. And here we often use Velcade or revlimid um with a low dose dexamethasone alongside chemotherapy, we usually give prophylactic medications as well. So things like allopurinol, which is to prevent gout with a high cell turnover. Following chemotherapy, you get a big build up of uric acid. So the allopurinol helps prevent that and prevent gout. Acyclovir and cotrimoxazole are both used as prophylactic agents because you're at increased risk of infection when you're immunosuppressed and obviously, antiemetics are given cos having chemo is pretty grim. Good thing about multiple myeloma is it responds very, very well to treatment. Over 80% of patients respond well, however, despite there being good remission rates, over 90% of people will relapse and then will need retreatment. Unfortunately, but there's often something that people live with for years now, obviously, treatment or cure um could be potentially in the form of a stem cell transplant, which obviously comes with its own risks. It's a bit of a whistle stop toward multiple myeloma. If you've got any burning questions, please do pop in and chat throughout. Otherwise we will move on to a case two. So you have a 76 year old man where the background of osteoarthritis and rheumatoid arthritis, admitted with breathlessness, high grade fever initially, when he came into A&E was started on a 15 L non rebreather mask. However, that was weaned down, he was just on two or 3 L on the nasal cannula. He felt a lot lost a lot less tachypneic. Um but was only speaking in short sentences, he was COVID negative. We still test everyone who comes into A&E here for COVID and he had a background of just feeling, generally not himself, not that great, had lost a bit of weight and, and noticed some night sweats over the last couple of weeks, you get a call from the lab, cos the bloods you sent off are quite abnormal. So again, have a look and what is wrong? What kind of stands out? So if you move on to the next slide, have a look at those. What doesn't quite seem to match up? Yeah. Good thoughts. Very good thoughts. You're definitely right. I like everybody's keeping a broad mind. Remember this is hematology cases. Um But absolutely, it's good differential. So if we go on to the next slide, it is a bit bizarre really. In this case, obviously, they're anemic, they're thrombocytopenic. But here it's weird. So you've got loads and loads and loads of white blood cells, almost 200 per 10 to the nine in your per liter massively raised. But then when you look at your white cell differential, your neutrophils, your lymphocytes, your monocytes, they're fine. They're actually ok. So where are all of these, there are all these white blood cells um in response to the recent question? Yes, the session I think is recorded. Oh, good. So you've had lots of TB uh you've had some leukemia, some A MLS. So if you move on to the next slide, please, we do a blood film and you can see it's a, a manual differential. You're over 97% blasts, very high thrombocytopenia, our rods, neutropenia. Anybody else want to throw their hat in in terms of what they think it might be. Oh yeah. Nice. A ML probably probably a ML get a brief reminder. So we're going to the next slide in terms of how you categorize or classify your leukemias. So remember it, you classify them per lineage. So it's whether they're lymphoid or myeloid. So lymphoid are all your lymphocytic cells or B cells, your T cells and myeloid and then the other types of blood cells. And then the next way you classify it in is by the type or the age of the cells you see. So it's acute, if you see lots of blasts and then chronic of the more mature cells, usually it does kind of seem to be that the acute leukemias tend to present a lot faster in a much shorter time frame. And the chronic ones will kind of bubble along and then slowly build until you get symptoms within months or years, for example. So if you go on to the next slide, that's just broken down a little bit further. So here you can see first reclassifying according to lineage and on the next slide according to age. So blasts immature cells mature cells, you don't think chronic. So a little bit if you move on to the next slide, better, a cheat sheet again, it's not comprehensive. Really lovely. Our next slide again, thank you very much. There is a bit of a cheat sheet which won't be comprehensive, but it uses quite a lot of buzz words that they quite like to use in things like UK UK MLA exams. So in general, if you think about A ML versus A LL A ML is usually an slightly older population. So again, you've got your blasts on your bone marrow, so your all rods, your myeloperoxidase is staying positive. So there's some good buzzwords for exams. If you've got M three, then you're worried about an acute promyelocytic leukemia or A PML. These are very, very aggressive, they progress very rapidly. They often present very, very unwell. Once at that point, you need to be talking to hematology quite quickly and they need treatment with arsenic and retinoic acid. How often they end up going to itu as well because they're really quite unwell A L. On the contrary. So that's acute lymphoblastic leukemia is more in young people in Children usually have very very good response rates to treatment. Again, you've got lots of blasts. You can get at DT protein, your MPO staying negative in this case. And so usually not always. But if you got A B cell B cell A LL, then it's more associated with translocations in cells. And then at cell A LL is potentially associated with thymic mass in teenagers. In exam settings. Think about cll older people, a lymphocytosis. Again, you're not gonna have the blasts on your bone marrow, but you might have lots of smear cells and you can often get a positive d. Now in this, in CLL, you've got a risk of Richter's transformation. So roughly 2 to 10% of people actually um undergo richard trans formation where the CLL become a. So for example, a da diffuse large B cell lymphoma um and symptoms of this can include kind of worsening of the bee symptoms. So things like increased night sweats was weight, um weight loss fevers or new thrombocytopenias. And then they need work up again to find out what lymphoma they've transformed into and what it might be um treated with. And then CML is our last one. Again, more and older people, you get just a general leukocytosis. In this case, you get your Philadelphia chromosome, which is your T 922 fusion, which is BCR ABL gene, which is actually not too bad of a gene to have. Actually, if you are gonna have CML because it shows you've got tyrosine kinase activity, which means it responds super super well to imatinib, which is a tyrosine kinase inhibitor. Um but it's quite a good treatment for that. Um Like in CLL CML, you can transform and you can have a blast crisis where CML switches to A ML is much more aggressive and much harder to treat. In that case. Next slide please in general. No treating it with chemo. Um So really you want to in the different stages, induction, consolidation and maintenance, you can use radiotherapy. And again, bone marrow transplantation is a cure as long as they stay in remission. Lovely. Yeah, I can see in the chart someone's written in CML less than 20% blasts. Um I, yeah, I don't know if that's the exact cut off but it will be, it will be low. You'll have just a lot more of your more mature cells which are around. Great. We're gonna rattle three. So case three. Next slide, please. A 70 year old man background of GCA. Thanks Isabel. Perfect. Thank you. Um A scalp SCC and CMM L which is chronic myelomonocytic leukemia um presented with a fall. A CT head showed a small volume interventricular hemorrhage but didn't require any neurosurgical input. So again, some bloods for you. So if you go on to the next slide, you're gonna have a look at which ones are abnormal and why they might be. Yeah, nice. You've got an anemia. Again. If we go to the next slide, it's highlighted in red. But in general, we've got an anemia. We've got a leukocytosis and you've got an isolated, prolonged A PTT and slight thrombocytopenia. Now, I'm gonna tell you for this case, the anemia, the leukocytosis and the slight thrombocytopenia. They're all chronic, probably all related to the CM ML. Well, we're interested in here and what was new for this case was the isolated A PTT. So there's something wrong in the clotting. The I NR is fine, the PT is fine, fri frigen is fine. So we're gonna go back to our clotting cascade. You go to the next slide. I don't know if you need to remember it. But if you want to remember the numbers, at least in the intrinsic pathway, you can remember the fact 12 ends in an E 11 starts in an E ends in an N nine, starts with an N, ends in an E eight, starts with an E ends in at and then 10 starts with T NS and then an N. So that's if you want to remember the numbers an easy way to go through it. So in this case, A PTT is your intrinsic pathway PT is your extrinsic pathway, that's the form of tissue factor. So you go to the next slide. So in this case, if you've got an isolated A PTT rise, then you can be pretty sure it's just in the intrinsic pathway rather than the other bits of your plotting cascade. Uh Abby's asking to repeat, do you mean the A PTD is the intrinsic pathway? And PT is the extrinsic pathway. So the isolated A PTT, we think it's one of these red clotting factors that I've got something wrong because the common pathway itself is fine. So a possible diagnosis in this case, really, if we're going on to the next slide is a factor deficiency and one of the most common factor deficiencies is factor eight. Does anybody know what we always learn is a factor eight deficiency. A hereditary cause of a factor eight deficiency. Nice. Von Willebrand disease, I think is more related to Von Willebrand. Yeah. Good. A I like that. You've written hemophilia. A nice hemophilia B is factor nine. Beautiful, nice. Yeah, good. Um So for this lady, it was all new. So it's probably an acquired factor eight deficiency rather than anything that she's had going on for quite a long time. Um And with a history of her cm ML, it was probably paraneoplastic in origin. So kind of the next steps for her. I would try and find out whether she had something going on. Um looking at her bone film um and doing CT scans again to see if they could find any malignancy that was driving this new acquired factor Eight deficiency. If you go to the next slide, roughly, treatment is usually things like steroids and factor replacement. Obviously, if people have got hemophilia or form Willebrand, then you get repeated factor replacement throughout your entire life and that never really stops. Yeah. Good stuff. Very nice. Next slide we're getting there. Good, good, good. So case four of an 84 year old lady scleroderma D osteoarthritis and a past ti A have multiple falls this week. She was found by her poor family on the floor confused with a hematoma over her right eye. You go to the next slide, I can show you some bloods again. You have a look at those and see what's concerning to you. What are we worried about on those blood tests? Yeah. Beautiful. Definitely. Definitely. There's nothing wrong with all of it. Really, isn't it? At least this a little snapshot. Yeah. Good. So, if you move on to the next one, there's just a couple of high in the really? Yeah, they're all wrong. So, we've got a microcytic anemia and quite significant anemia. Really? With an HB of only 59. That's really quite low. Um, does anybody know some common causes for a microcytic anemia? Yeah, I am. Exactly. Exactly. Very classically microcytic anemias are related to iron. No, you're right. She does, she does have a raised white cell count. She does have a thrombocytosis and she does have a very mildly raised C RP as well. So, really, it might be related to the fall. But you'd also be wanting to screen her in this case for infection, especially since she was confused is she delirious? So you're doing that whole work up as well on the side, but we're just gonna focus on the anemia. So yeah, good. Go to the next slide is just highlighting in red. I think honestly, we've already moved um in terms of things you want to send off if you want to make sure you sent off your blood film, your hematinics. So your iron screens, your transferrin saturations, your vitamin b12, your folate to see what's going on. Now, in the acute setting, I don't know if you guys have ever had to prescribe on a paper chart before it or if you've all got fancy electronic systems. Um Here, we sort of have to prescribe on a chart. So if you wanna grab a piece of paper and feel like trying to just prescribing some red blood cells in the next 15 seconds or so, um just to do something a little bit more interactive and keep your brains busy. My current trust is all electronic, but my old trust was all paper still very good. So if you think about each red blood cell unit would probably increment your HB by about 10 g per liter. So if she's got an hp of 60 you're giving her at least one unit, potentially two. In terms of when you transfuse here, we often g have a cut off of 70 unless you've got acute coronary syndrome or ischemic heart disease, then usually it's a cut off of 80 to transfuse people. So she's well bless file. If you go to the next slide type in, what did roughly do? Um So really after every one or two units, you want to check their full blood count again with either a blood gas or a formal full blood count that you send to the lab to make sure they're incrementing properly. You wanna make sure you're monitoring for adverse effects. So things like Charley taco, any sort of bacterial reaction transfusion related reaction incompatibility. And if you're worried they are at a risk of overload and you can consider giving them a diuretic at the same time. So for example, low dose of frusemide just to make sure they're not fluid overloaded fab if you go to the next slide, rough timings of transfusion just in case you didn't know. So your red blood cells are usually transfused over about 2 to 3 hours might slow it down if they're frail, for example, quite small, um red blood cells do need to be completely transfused within four hours of being out of the fridge. So really, we don't usually give over more than three hours because you have to give the people porters time to go get the blood from the blood bank, bring it upstairs, get it all connected up to the patient. Platelets are a lot quicker. So it's only over about 20 to 30 minutes. But it's a similar thing that you want to make sure that you're monitoring them for any adverse signs and make sure they have good cross match. Of course, cos it's a never event otherwise. Lovely case five is a 62 year old lady. She had previous autoimmune thyroid disease, which is well controlled and she's got some new bruising and some new bleeding on brushing her teeth. So, on the next slide, you've got some bloods again, have a look at the bloods on the next one and let me know what stands out. Hm. Yeah, nice. So if you move on to the next slide, you just highlighted in red, you've got a thrombocytopenia. We got some good differentials coming up already. So you've got ICP has been said. Scurvy has been said, yeah, you're right if you've got a new thrombocytopenia. So you move to the next slide just for some pictures. Um I everybody's jumping on the ITP bandwagon. Um Don't forget everything else too. So if you've got a new thrombocytopenia, you want to make sure you're doing a full hemolytic screen, you want to screen for infections, you want to check the clotting and if you're an adult, it's always worth checking for HIV as well. A blood film will help because it will tell you if it's a true thrombocytopenia or if the platelets are just clumped and aggregated in the sample, which is just causing a false reading So really, when you're looking at thrombocytopenias, your main differentials are either related to reduced production of platelets. So, for example, in bone marrow failure. So, if you've got a cancer, for example of your bone marrow, the tumor has infiltrated and is suppressing it, then you can get thrombocytopenia there. You probably would as well have an anemia and a potentially a full on pancytopenia. Yeah, exactly. With your own plastic, um, or an increased destruction. So if you think of things like it, PTTP er D I chus. So hum Uremic syndrome or medications, so things like heparin can also cause thrombocytopenia. So actually this lady, if you just go on to the next slide, she had an immune thrombocytopenia. Um and generally they're classified into primary and secondary. So secondary can be due to something like a general infection somewhere else, any medication, um potentially a lymphoproliferative disease or another autoimmune disease like Lupus, for example. Um and it's when your body just makes antibodies against your platelet antigens and in general management is avoiding nsaids because that's obviously not gonna make your players work at all via the cox inhibitors, steroids and IV IG are the main ones. And obviously, if they're refractory to treatment and it keeps continuing, then they might consider splenectomy to stop the destruction with potentially riTUXimab for immunosuppression? It's also a chemotherapy agent. Lovely. Next slide question. Really. Do we transfuse? What do you guys think if you were an ITP patient with platelets of 35. Would you transfuse? I like it a nice mix. It's very nice. This is why I don't know where if, um, there's a hematology consultant actually sneaking in in the chat. Um, for me, at least for a trainee. Uh, the basic answer is ask hematology. Um, usually in itp, we generally don't transfuse. Um, just because it's an autoimmune process and the body will just destroy the new platelets coming in and may actually increase the rate of destruction. Um But obviously, it's incredibly complicated. If they've got ICP, they're bleeding. Um, they need surgery. Um One of the things that we can help guide us is by looking at the who bleeding grade to see, but it's very tricky. It might just be the need management with steroids really first. Um And see that it very much depends on the state of the patient. Absolutely. Yeah. Nice two. I think in general if they don't have itp, rough cut offs here are transfuse if it's below 50 they need a procedure transfuse if below 20 they're unwell or bleeding and below 10. Um, otherwise fine next slide. And this was something that was, um, that's a good question, Isabel. I don't know if ITP actually cos it's an immune process where the stem Isabel's asked whether stem cells might be able to help. Um, I would think because it's autoimmune. It's not your bone marrow. That's the problem. So, I don't think stem cells, a stem cell transplant would help. But I don't know if anybody else in the chat knows any more about it. Then please please feel free to share your opinion to be very grateful for um Lovely. OK. Fab. And then we can pop to the next slide. So a hit screen is not something I'd heard of until I actually started working and they're looking for something called heparin induced thrombocytopenia. So really, it's um again, immune mediated disorder where the heparin binds to the platelet factor four. So you've got low platelets because they're all being used up and you go to kind of like a hypercoagulable state. It's actually one of the most frequent types of drug induced thrombocytopenia. And we prescribe Heparin for all our inpatients as prophylaxis for clots. And we never really think about heparin induced thrombocytopenia. Um but it can, can occur after two weeks. Post heparin therapy has initiated and obviously the management is stop the heparin. And then you discuss with hematology to see if they need any reversible, any agents to reverse. But l you go um last thing really, if we go to the next slide, this is again, just a little bit of interaction. Um I don't know how many blood films you get in the exams. But if you have a quick look, see if you can match up the names, if not with the pictures, at least with what they might potentially be a sign of again, it's not specific to these diseases. Um but these signs are often seen in. So see if you can have a look, if you wanna type N out, just go for it. If you just wanna do it in your own time. Also. Fine. Nice. Yeah, hinds bodies and G six PD deficiency. Definitely. Yes. Some good. Again, if just for exams. Good buzzwords to know. Nice. Yeah. How are jolly bodies of hyposplenism? Good target cells I deficiency good. Also, poikilocytosis, aoc cytosis. Very nice, hereditary sperocytosis and spherocytes. Perfect. Yeah. Nice one. Schistocytes and maha are very nice. Very nice. Great. Yeah. Some of them are barn or which is always nice. Fab. Yes. If you go to the next slide, I think there are some lines connecting bits and pieces. Um I guess not all of them, but you've um spoken about most of it anyway. So you've got your target cells with your iron deficiency. Your hinds body is with a G six PD and see if you click forward another one, whether more lines come up or otherwise I've just forgotten to add the rest. Nope. OK. I forgot to add the rest. Go back on. That's absolutely fine. Um But I think you've covered them all. Really in the chat, which is great. Yeah. Really good. And your PG QA cells something like myelodysplasia, for example. So it's good. So the top picture is a target cell. Second picture is a how old Jolly body? Third picture is a s schistocyte. Fourth is a ph, a cell. It's like a blob white blood cell basically. And you've got Heinz Body. The second to last picture and the last picture is Spherocyte, which is beautiful. Yeah. Good. Nice fab. That's all I've really got, I think for you guys today. Bit of a whistle stop tour in terms of some more common hematology cases that they, I might see just on a general ward rather than a particularly hematology ward. Um If you've got any other questions, feel free to pop in the chat otherwise, thank you very much and have a wonderful evening. Really? Thank you Doc Doctor Liz for your informative and very helpful lecture. Thank you all for joining today. Let us know if you have any uh particular question in the chat. No, I think the whole thing is recorded. Andy. So it should all be on there, all slides, everything on there. So we encourage you to share your feedback by completing the feedback form that is gonna be sent to you shortly. And lastly, I would like to remind you about our upcoming event uh on cardiology, which will be presented by Doctor Jacobs uh on December on, on December 7th at the same time, if you don't have any other question. Thank you all again for joining. Thank you Doc Doctor Liz and goodbye.