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cool. No, uh, cause the recording, too. Good afternoon. My name's, um, Steven Marks. I'm professor of pediatric nephrology in transplantation at University College London. Great Ormond Street Institute of Child Health and Great Ormond Street Hospital for Children NHS Foundation Trust gives me great pleasure to talk to you today about protein, urea and, um, Hematuria. Hopefully, you can see the slides just now and then you can hear and see me. Well, if any problems, Hannah, will you let me know? Yeah, sure. As both of the small screen at the small screen and the main one are showing. So if you want to just have the main one. Is that Is that better? Yeah, that's the main one. Okay. Thank you. So it's It gives me great pleasure to speak to you today. I know you're Ukrainian medical students and others, some of whom around the world, so welcome to one and all. I'm going to start with some case presentations. Um, just to give you a flavor, I'm very happy to have audience participation. If you want to mute, I'll then talk about Does hematuria matter? Talk about the differences between microscopic or Frank Hematuria that you can see with the naked eye and microscopic hematuria when it's either positive and urine dipstick testing or in your microscopy when you see red cells and then a little bit about protein urea and trying to put it all together with some evidence based medicine. So let's start with some cases to illustrate some of the points. So a 12 year old boy is admitted with a four day history of severe left loin pain. He has a three week history of a febrile, now recurrent episodes of Frank macroscopic Hematuria. He's not been drinking as much recently, and when you examine him, he's got severe left loin, tenderness and investigations revealed. He's got a normal plasma Kratt and an albumin with a trace of protein area four plus of hematuria, and there's no cast seen on your microscopy. So what are people thinking with regards to this case? What could it be? So top on the list, I think with the loin pain and a fibril recurrent episodes of microscopic hematuria would be arino calculus. And here you can see on ultrasound evidence of renal calculus, and you can see what we call this acusticus shadowing, which I'm delineating here behind it, which is which is cast by the calculus itself. So the second case is a six month history. Um, in a three year old girl who's had again recurrent episodes of microscopic hematuria. They tend to be associated with previous vial upper respiratory tract infections she's otherwise eating and drinking normally without vomiting. And she's got no family or past medical history of note. She's got normal examination and investigations. She's got normal renal function, normal plasma creatinine, albumin. She's got no evidence of protein urea, but she's got three plus of hematuria without cast, and she has no evidence of calculi on ultrasound. So what are you thinking about? Another wise, healthy three year old girl with recurrent macroscopic hematuria? Well, the clue for this is that having precipitants with a viral upper respiratory tract infections, so this makes you think of Iga nephropathy so kind of a chronic presentation, somebody that you might likely see in an outpatient setting. And that leads us to the third case, who is a six year old girl who developed a viral operas virtue tract infection with a sore throat and cough three weeks ago, when both her parents and the youngest is who were also unwell with an upper is virtue tract infection. She then presents with the 48 hour history of vomiting and all those microscopic hematuria. There's actually features in direct question of Coca Cola colored urine, and that's associated with the 24 hour history of peri orbital edema. Oliguria, with less urine output and examination, reveals that she's hypovolemic. She's got evidence of peripheral edema. Her systolic BP is 1 30 millimeters of Mercury an investigation so that she's got renal dysfunction with an elevated plasma crackin of 100 and 50 micromoles per liter. She's hypoalbuminemic with an albumin of 22 g per liter and on urine dipstick. She's got three plus of protein urea three plus of hematuria with evidence of red cell casts. So this is more of an acute presentation. And in a patient such as this, the most likely scenario you're thinking about is a post infectious glomerulonephritis, and there's features of nephritic and Nephrotic syndrome. So, uh, Nephrotic Syndrome. So you've got the kidney and the sieve holes you can imagine are getting bigger. And that's resulting in the fact that protein has been lost in the urine, so three plus a protein urea here. And as a result of all of that loss of protein, the levels in the blood go down. So you get hyper proteinemia and hypoalbuminemia so low protein and albumin levels in the blood. And in addition to that, you get evidence of peripheral Adema. So the fluid is moving out into the interstitial spaces. And to try and to collaborate the oncotic pressure and that very often ca be associated with hypercholesterolemia or hyperlipidemia. And that's nephrotic syndrome. Whereas the features of Nephritic syndrome with microscopic hematuria hypertension secondary to fluid um, water retention with oliguria that's present, and an acute kidney injury with an elevator plasma crackin of 100 and 50 micro moles per liter. So does hematuria matter. Well, a simple way to think about it is, is it important? And should you investigate and the answer. If you've got evidence of blood that you see so microscopic hematuria, the answer is always yes. If, however, you've got microscopic immaterial, and if there's no protein urea, there's no hypertension, there's no Marino function. Then I would argue, in fact, you don't need to overly investigate. And why is that? Well, if you've got Frank Hematuria that you can see very often, there's a clear diagnosis. There's about a one in 500 prevalence, and the resolution varies. Microscopic, immaterial. The definition varies is a dipstick. Is a red cell seen on your own microscopy, and the prevalence can be up to eight times that of microscopic immaterial, and you'll find that nearly three quarters can resolve by six months. Excuse me. So if you've got recurrent episodes of microscopic hematuria, then you always have to investigate. Especially if there's evidence of protein urea always thinking about. Can you exclude a non guameri low cause? Is there something perhaps going on within the family? So getting a good family history looking at the genetics and the reason that I won worry if you've got microscopic hematuria is actually if you potentially label a child with the diagnosis that might have an impact on their future job insurance mortgage, so actually has quite a huge impact on their future life. And how can we be certain? Well, this shows that if you undertake percutaneously know biopsies for Children with recurrent microscopic or intermittent microscopic hematuria, you'll see that the majority of Children will have iga nephropathy or Alport syndrome. You'll also see there's quite a category, Um, about one in seven within basement membrane. You'll get a miscellaneous group, which is about one in five, where there might be some mesangium hypercellularity and the biopsy, and you'll see again that there's quite a subsection by one in seven who have a normal biopsy. So why does it matter? Well, what I'm trying to tell you is that although we have drugs on the horizon and one of my jobs as I lead our clinical research facility, we've got some drugs potentially, which may be able to have an impact on the long term outcome and prognosis of conditions such as all ports syndrome or thin basement membrane disease or even iga nephropathy. Unless you develop protein, urea, hypertension, a renal dysfunction, there is actually very little that we can do with the medications that we have at our armamentarium in 2022. So let's start a bit with macroscopic hematuria so frank blood that you can see with visual examination of the urine. And actually, if you take a liter of urine and you um prick your finger and you have one drop of blood which goes into the urine. You actually will find that the urine actually turns rose. So you need very small amounts of urine of blood in urine to be able to have microscopic you material. And indeed, microscopic hematuria may contain significant number of red blood cells. Now, obviously, you may get more severe blood, so you get red blood staining, even clots or heavy bleeding if there's been some trauma or coagulopathy. But actually cloudy urine, which can be due to federal pyelonephritis or an upper urinary tract infection with pyuria and associated with urinary tract infection, can also have microscopic hematuria. Also thinking about the development of nephrolithiasis arino calculus we discuss, but also even gravel. So if you've got associated calcium or you're eight cystine or struvite deposition, then that may result in blood being seen in the urine. But you may see blood when it's not actually blood. And why might that be? Well, we're using a lot more food additives, so I have seen Children, sometimes two or three a year who basically have food fads, eat a lot of beetroot, and that's about the only fruit, vegetable and their urine turn turns red. We also get that with their food colorings as well. But some drugs can do so. For example, rifampin Ethan, which can stain your tears red and stain your contact lenses. The same can happen in the urine and hemoglobinuria my globin. You're an inborn Ariza. Metabolism such as porphyria are very uncommon in Children, whereas urate crystals that we see in neon eights who are born especially to first time mothers who are breastfeeding. And this initial colostrum that comes in and they're dehydrated. They put out these urate crystals and very often in the nappy or the diaper. You'll see kind of orange tinge, which are these urate crystals and then laterally factitious hematuria what we used to call, uh, Munchausen syndrome by proxy. So this is where there is blood in the urine. But actually, it's not the blood of the patient from the urinary tract. This is somebody exogenously putting blood into the urine, and very often in these cases it can be a parent or a step parent trying to get attention from medical teams. And it's really important to involve the safeguarding teams as you undergo the investigation and make sure there's a chain of command so that any urine specimen, which leaves the room that you're consulting the child in and goes to the laboratory that you can verify. That's the urine sample. And then within that urine sample, you can speak to the laboratories with the social worker and safeguarding teams involved because you can ask for the blood group of the red cells within the urine to be analyzed, and it may be that it's different to the blood group of the patient. If not, you can potentially go on and do DNA studies as well. But the important is if you see blood in the urine, you always need to confirm the presence of red blood cells on your in microscopy as well. So here you can see, uh, renal calculus coming down and obstructing initially as it comes at the top. You can see it coming down, and there's obstruction of the P U junction or Pelvi Ureteric junction, and then the vehicle. You're a Terek Junction at the bottom. So here's the P. U. J Junction there. Here's the V. U J. Junction, and then, of course, you can have it within the urethra as well. Obviously, if you've got another kidney, which is doing normal function and you've got an obstruction in one kidney. So if you've got a contralateral kidney, which is functioning normally, then the child will have overall normal kidney function. And the timing of the microscopic hematuria is also important because if it's coming from the kidney, you have bleeding all the way throughout mature Ishan, whereas you get terminal hematuria if it's caused by the bladder or non specific, your arthritis. And if it's in the urethra them very often you have some bleeding, and then it will go away. So I don't make any apologies for Julian Go Finger, who published this? Um, as you can see over 45 years ago, I told her when I saw her recently and, um, as a editors of the New England Journal of Medicine and also uh, nephrologist at Boston Children's that there's not very much work has been done in this. But you can see here that nearly a half of proven or suspected cases of your new chats infection cause blood in the urine. The reverse is true. It's uncommon for microscopic hematuria to be due, but it's really important to check that you don't have a urinary tract infection. Another common cause is can be Pernal irritation, trauma, acute nephritis, coagulopathy, stones and tumor, as we mentioned earlier on. So why else might you have microscopic hematuria? Well, you can get exercise induced. So, um, what used to be called Marchi material? So if you go on a marathon, you can get start getting microscopic hematuria bit dehydrated as well. And so it's important, actually two or have ongoing rehydration throughout line pain. Hematuria syndrome can also be seen, as I said in the differential diagnosis of Nephrolithiasis. And you can get hemorrhagic cystitis from example from, um cyclophosphamide being metabolized and giving acrolein, which then can be toxic to the bladder and causing a hemorrhagic cystitis. Um, otherwise you can have hypercalciuria. And of course, the commonest cause of hypercalciuria and the developed world's just now is actually a high salt intake hyper uricosuria, but also very rarely bladder tumor, asthma, Lecco, play Kia and rhabdomyosarcoma. So to make it simple, I would tell you that if you've got microscopic hematuria without protein urea that investigations that you need to consider are a midstream sample of urine from microscopy, culture and sensitivity in an older child, um, urine Calcium Scranton ratio to exclude hypercalciuria and adopt a renal ultrasound checking if there's evidence of you know calculi, hydronephrosis and papillary to Crozes, especially in a patient who's got sick of cell anemia, we can see other causes, such as you thrown bladder abnormalities or a V malformations glomerulonephritis such as Lupus nephritis, IGA nephropathy, um, sickle cell disease we talked about and bacterial endocarditis. So the important thing in management is to confirm the presence of red blood cells and your microscopy and to send off a specimen to the laboratory. And you need to take a good history and physical examination, including checking the BP and taking a sample for a mystery and sample of urine and treating of this evidence of urinary tract infection. If the above is nonconfirmatory, the family history in your analysis, don't reveal anything. It's important to do further investigation, checking that you're not becoming anemic because of all the microscopic hematuria that there's no coagulopathy, no signs of inflammation or a post infectious glomerulonephritis, a urine dipstick culture albumin your rate and cost him to creatinine ratio. Although I've put down here abdominal lecturing, we very rarely do this nowadays because the only problem is potentially if you've got, um, renal Calculi, which is just at the junction of the V. U J. So as the ureters go into the bladder, you may not see the nephrolithiasis just as they enter. Remember, we want to know about the patient's if there's any evidence of renal dysfunction protein, urea, hypertension. So let's talk about microscopic hematuria. So this is when you've got dipstick positive for hematuria or you've got red cells which have seen in your microscopy. So as we know that your analysis, these dipsticks are convenient. They're widespread Lee used now. But you need to make sure you store them in a dry environment, especially the sheets and the strips, and you've got to make sure that the bottle is in date and has been stored correctly very often. Nowadays, you can have an automated result with a printout, and the reason is is that they're very, very sensitive because blood is detected by proxies like Axion it it takes very small quantities of blood, but a negative result does exclude hematuria equally well as well. To note is that protein you're is detected by Tetra promo final that are women demonstrates much better binding. So microscopic hematuria, maybe a symptomatic. So it may be a child who goes to a new general practitioner primary care physician, and the first thing to do is dip a urine to check. Everything is okay, but make sure that you do a good family screen. So if you've got protein urine hematuria, you definitely want to check that the mom and dad don't have that because if they had evidence, you'd want them to be investigated first. What you're wanting to do is see if you've got microscopic hematuria is to check, especially if there's no protein urea. You can wait and see if it resolves. It might have been an inter current infection if the child's got symptoms and are signs such as fever, lethargy, hypertension and um A. You're obviously going to investigate, as are those with urinary tract infections to exclude urinary tract infection with this surely urgency frequency and enuresis, but an inflammatory condition. Multi system condition. If you've got rash evidence of Purpura arthritis John distribution to stabled symptoms as well. But again, what the investigations were to keep it simple. It's the same. You want to do a midstream sample of urine for my cost, A culture and sensitivity. Are you in costume to creatinine ratio? Wanting an ultrasound for renal calculi and hydronephrosis is, and the question is, should we do a biopsy? We'll we're learning a lot more with genetic testing, and I think that will take the main four of future investigations. But the P the reason we undertake a biopsy historically is because to make a diagnosis to reassure the family to maybe say, okay, they don't need anything else done because we know what it is for help with genetic counseling and maybe avoid later investigations. But remember, it's an invasive procedure, and if there is a complication, then it may be for a biopsy that didn't need to happen. And there isn't any treatment specifically for the conditions unless the patient's develop hypertension, protein, urea or evidence of renal dysfunction. So let's look at some population studies. So if you take 100 and 60,000 Japanese Children annually who undergo a thorough school screening program, you'll detect here as you can see, um, about one in 500 having isolated microscopic hematuria and out of them you'll see that about 136 will have a symptomatic microscopic hematuria, and you'll see about 100 and 15 specific cause of microscopic hematuria. And if we look at this, what were the reasons? Well, many of them were isolated, and we're just picked up and you will see a distinct number 35%. About a third were either normal or was because of menstruation. You'll see that there's a small group then of less than 10% which is made up from Children who were having a pylon arthritis with or without reflux, evidence of hypercalciuria or investigations. For nephrolithiasis, a child with IGA vasculitis, there was three or h S p heinous on on purpose nephritis. But you would have got that information from the past medical history and detecting hydrogen froze is or polycystic kidney disease. Excuse me is very, very unusual and was overall long term outcome. But if you follow these patient's between six and 13 years, so a median of nearly 7.5 years you'll find that nobody developed hypertension or renal dysfunction, and only one patient developed mild protein urea. So this was a schema that I came up with when I was training in North America, looking to see what was it, the urine sediment By sending it off to the laboratory. If you don't have red blood cells, when you look at them under a microscope, it may be because the sample was left lying around in the red cells lies, but you need to think about is evidence of my globin urinary hemoglobinuria. But if there are red blood cells, you need to think about screening the family members. So starting off with the parents. And if you've got evidence of microscopic hematuria without protein urea, you need to think about A, as we said, doing those three tests with urine Carson to creatinine ratio, culture and sensitivity with microscopy and adopt a renal ultrasound. Once you start developing microscopic hematuria, you want to think about the Cosmo and adopted ultrasound might show evidence of hydronephrosis is of natural advices, but it may be that you've got evidence of post infectious or other cause of glomerulonephritis, and if you've got microscopic or microscopic hematuria with protein urea again you're going to really be thinking about glomerulonephritis and investigating more detailed with compliments, a any anchor immunoglobulins um, anti g b M antibody and considering a renal biopsy. So this is a schema showing that if you've proven you've got glomerulari hematuria without protein urea and you test members of the family. Um, and everybody else is fine, then you can reassure, and you don't necessarily need to perform a renal biopsy. If you start getting evidence of a family history or continues or ongoing microscopic you material, you may continue and continue thinking about doing a biopsy if you got a family. And I said, nobody in the last decade has persuaded me to undertake a biopsy when I've said, I don't think it's clinically warranted. But very often you want these patient's to be monitored as the hematuria persists. And what about if you develop protein urea? Well, the clinical evaluation is really important. So, for example, if you got an adolescent girl and they're menstruating, they've got microscopic hematuria protein area. You're wanting to take another sample mid cycle when they're not menstruating. If you've got evidence of a demand or hypertension, then that's much more likely that something clinically is going on, Um, and would want to be investigating further for nephrotic syndrome, plus or minus nephritic syndrome Protein Urea, as I said, is a bedside testing. You want to get their first urine of the day concentrated sample, but you might see that if you send and dipstick the urine during the day that there might be evidence of orthostatic protein urea. So this is a change in in the amount of protein urea coming out. And this is because, to be honest, if you've got a very significant glamour low cause of protein urea, then you'd expect that leakage to happen all the time. It might be worth thinking whether there's evidence of tubular protein urea as opposed to glomerular protein urea. And that's something which is more difficult to do in primary and secondary care. But testing for tubular protein urea by actually sending off for retinal binding protein or enemy know D gluc examine days to creatinine ratio is to see if they're abnormal, and usually if there is tubular protein urea, they're elevated into the thousands. But if you've got a nephrotic range proteinuria so dropping the albumin level less than 25 g per liter. There may be something to be said for considering doing a 24 hour urinary collection if there's complexities in collecting in other Children, but making sure you get an early morning urine sample for argument to creatinine ratio. When we look at the renal function, it's about checking the plasma crotan by estimated the glomerular filtration rate by using the modified Schwartz or seek it formulas and considering doing a percutaneous renal biopsy for those Children only where it's warranted. I put this slide up again. It depends on your individual laboratories, but show that the normal urine argument Scranton ratio is normally within single digits throughout childhood tends to be higher in the first week of life and within the first six months, where it can be up to 12.2 mg for minimal but worthwhile checking with your laboratory, checking their quality standards and making sure, um, that they've updated with regards to your child's specimen. So the idea with looking at the protein urea is to always look at the specific gravity to see how concentrated it is, you don't want a 1005 specific gravity so very dilute urine to be looking at for a patient when you think they might have significant protein urea if it wasn't investigated. But most patient's will have a trace one or two plus of protein urea. It's only when we get to a three plus of protein urea four plus that is likely to be pathological because we say that normal protein urea can be up to 60 mg per meter squared per day in arrested a federal child. So I touched on orthostatic protein urea. So this is protein urea during an upright position, so renal disease can give protein urea but tends to be, as I said every year and throughout the day and night over a 24 hour period. Orthostatic process your is most common in adolescent men. It can be transient, too variable in nature and normally is less than 2 g per day. And although this is previously a benign condition, if you undertake percutaneous renal biopsies, you can find up to about 45% having some subtle abnormalities of the Glomar ally and more than 8% having overt renal disease. So if you've got microscopic or microscopic hematuria with protein urine you're wanting to exclude a camera nephritis need to do these longer term investigations. As I said now, this is a red blood cell cast that you can see on your in microscopy, and you can see the features here. And when I trained in Newcastle in Toronto, we used to spin the urine when the patient came into It's an emergency and then look at it. If you saw this red blood cell cast, you would know that there was element of Premarin arthritis in this patient. So I tell Sean earlier that when we talk about Nephritic syndrome, we talked about hematuria protein urea oliguric, usually acute kidney injury with hypertension due to fluid overload. And obviously that situation can resolve pretty quickly, whereas with Nephrotic syndrome, we have a nephrotic range proteinuria with, uh, urine protein excretion of 40 mg per meter squared per hour and up to 1 g per meter squared per day. As a result of the protein, urea reduces the serum albumin levels below 25 g. When, later, and you get hypoalbuminemia, which is associated with the Dema and hyperlipidemia. If you've got mixed nephritic nephrotic syndrome, what could the Cosby Well, if you've got a nephritic syndrome, the most likely cause is a post infectious glomerulonephritis. If you've got a nephrotic syndrome, the most common reason is a minimal change nephrotic syndrome, whereas if you've got features of both, it is indeed a post infectious glomerulonephritis. And here's a schema saying that if you've got nephrotic range proteinuria. Um, considering if you've got, uh, Nephrotic syndrome but considering referral, if you've got abnormal features such as age above 10 years, evidence of systemic disease, hypertension or microscopic hematuria. And it's only in a small core of patient's that will actually be able to be discharged, um, if they have a normal urine albumin to creatine issue. So this was again in our book, the chapter that we did, showing that if you got dipstick test is positive for a protein on two occasions and you've got transient protein urine, it doesn't come up again, then you all you need to do is re evaluate at 12 months, whereas if you've got protein urea, which persists and orthostatic protein urea shows that you have, it's not orthostatic and a significant protein urea. You probably go on to look at 20 for our urine collection and thinking about the differences, as I mentioned between glomerular and tubular protein urea, where you might get like a Suria aminoaciduria, aminoacidemia, phosphaturia, renal, tubular acidosis or impaired urinary concentration. So how do we manage these patient's well modulating the protein urea is important, and we may use enemas suppression for active glomerulonephritis base inhibitors and angiotensin receptor blockers treat hypertension and protein urea with efferent arterial dilatations, reducing glomerular pressure. And we may commence an ace inhibitor such as lisinopril or enalapril 0.1 mg per kilogram per day. Or indeed, uh, angiotensin receptor blocker such as er, be certain or losartan, noting the side effects can be hypochelemia a renal dysfunction. So checking serum urea electrolytes one week after starting in two weeks, after any change in Doz and warning families that there may be the development of a non productive cough and that it is terra teratogenic, that's an important piece of information. But actually patient should be on the drug because we know fertility's reduced in patient's who have chronic kidney disease when they're planning for a family, hopefully as an adult and not as a child, because actually, if it takes you a few years to fall pregnant, then having three or four years without an ace inhibitor and angiotensin receptor blockade may promote the progression of the chronic kidney disease and the development of more fibro houses and reducing the renal function quicker, longer term. So putting this all together, where are we? Well, if you've got microscopic hematuria, think about if you've got recurrent and confirm red blood cells to check the timing during the urinary stream to help isolate the cause. And make sure you tailor make your investigations to exclude common conditions such as your new tract infections. And you know, calculi. If you've got microscopic immature, if it's continuous and confirmed red blood cells check family members and exclude protein, urine, hypertension, making sure you discuss with family the options of follow up versus biopsy. And, as I said mainly, we will do by biopsy in very rare cases nowadays, and most families will agree with us for follow up options. If you've got protein urea, always investigate if it's persistent and especially if it's not orthostatic, make sure you exclude nephrotic syndrome and glomerulonephritis, and with that I'm very happy to answer any questions. Thank you very much for your attention. So if MG wants to run mute, you can either give me your questions face to face, but also happy if you want to put it in the chat. Hopefully that's explained it well to you. As you know, we've got more and more dipstick testing of patient's, especially if they come from different centers just to do screening. There's a whole big debate about which Children and if all Children should have regular urine, dipstick and BP checks. Which, of course, is something which is adults we probably should get every year and has also put in, um two, if anybody's got any questions to add it into the chat. I'm also returning, um, for a few more times and so every other week to give updates on pediatric nephrology. So I'll be covering other topics such as acute kidney injury, chronic kidney disease, kidney transplantation, systemic Lupus erythematosus and Lupus nephritis. I see that some of you are in Kiev, so our thoughts are with you at the moment. I know it's been a difficult time for you, and our thoughts are with you and hoping that we can do something to end the situation in Ukraine. But I see some of you are also in London around the world. So sorry if it's it's Hannah. If there's no questions, can I just encourage everyone to fill in the feedback form? Um, and you can take a few minutes to do that, and then I'll post the certificate for this lecture at the end. So I was just going to say as well, Hannah. So you don't get your CBD certificate unless you do the feedback. It's a very simple questionnaire. Um, it's just if you just click on the link, it comes up in Google docks. And it's a very simple, quick form just to say that you've attended. And as a result of that, you'll end up getting your CPD certificate. Okay, if nothing further, then just want to thank you all for joining. And I look forward to seeing you all in future lectures. Thank you for your very kind comments in the in the chat as well. Thank you so much, Professor. That was superb. We really appreciate it. Thank you. And to everyone uh, participating. Please, please, please fill in the feedback forms. Thank you. Very much. Everyone have a good afternoon and a good evening. Take care. All the best. Thank you very much. Bye. Bye bye. Thank you. Um, everyone. If you're still people, you're still here. Please fill fill in the feedback form and then I'll post the certificate in the chat.