Chapters Transcript Video Should All Stages of Twin to Twin Transfusion Syndrome be Managed with Laser Surgery? thank you all for attending this webinar. Um As already mentioned, my name is Antonio Debo. I'm a professor with the University of South florida. I'm also the director of the fetal care center of Tampa Bay. I've been here for about six years now And if he took care center of Tampa Bay has been offering careful patients are high risk patients, especially those with conditions such as 20 twin transfusion syndrome for the last six years since I've been here. Um and I'm going to share with you some of the controversies regarding managing stage one. I really thank you for taking time from your family this evening to listen to this presentation. Next slide please. First, I want to declare that I have no disclosures to declare and also I'm not going to be discussing any products that are investigational or use of any of labour products during this presentation. Next line. So the objectives and what I aim to achieve in the next eyes really to look at an overview of 20 twin transfusion syndrome. We also want to map discuss the management options for 20 twin transfusion. About most of the focus is going to be on the controversy regarding management or treatment of stage 1.20 twin transmission singing next time as usual with most medical specialties are governing care here is that we should do no harm. So most of what I will be discussing here, we always have to balance the risk to the model and the risk to defeat us um against the goals or the advantages of what we're trying to achieve next light planes. So 20 twin transfusion syndrome affects about 15% of Monaco chorionic twin pregnancies. And despite this small amount of twins that it affects, it does contribute significantly to the total perinatal mortality among twins. Um up to 20% of perinatal mortality in twins is secondary to 20 twin transfusion syndrome. If untreated, you can have a mortality rate that approaches 100% in 2020 transmission center. Now there are other mobility's associated with this condition and the most significant is prematurity, Followed by neurodevelopmental delay that can call downstream as secondary to the complications of 22 in transition syndrome next life. So I'm going to start by looking at what, how we staged 20 twin transfusion syndrome. Um this is the staging that was published by Ruben Quintero when he was here in Tampa many, many years ago and up till death. This is still the standard uh staging that is used and during my presentation and we share some slides that have tried to question the validity of this staging system. However, up today, this is still what we we have and it's the best system we have. It also allows us to compare results of current studies with those that were published in the past. So I think this staging system has come to stay and will be very difficult to change. So Stage One is where you have poorly hydrangeas and ali guy dramas, police dramas in the recipient and oligarchy dramas in the uh in the donald, Stage two is where you start seeing signs of absence of the blood. It means you're not visualizing the fetal bladder and the donor. And in stage trees where you have Doppler Doppler abnormalities significant. Doppler abnormalities such as absent or reverse flow in your umbilical artery. Um in the recipient you may see cases of reversed a wave in the doctor's diagnosis. This will also make them fall into Stage three. I will also share with you a slide showing how other groups, such as the Cincinnati group, as well as a group from Children hospital in philadelphia have tried to modify Stage three using cardiac screening In stage four is where you have high drops of one or both fantasies. And stage five is where there's the demise of one fighters next life please. So the current management options available once we make a diagnosis of 20 twin transfusion syndrome include expectant management, which is watch and see. But as I mentioned, if you watch and do nothing, there could be mortality. That could be as high as 100 the next option with the pregnancy termination, especially in cases that happened very early in pregnancy. Um where we may not be able to offer the treatment options that I will discuss in this presentation. Now, radio frequency ablation is currently used mostly for Stage Four cases where you have high drops and you want to perform a term selective termination of the donor twin by using radio frequency ablation. A new reduction is the traditional treatment I was devised many years ago. It was initially device as a means of symptomatic relief for patients who have 20 twin transfusion syndrome. However, it became almost standard treatment until laser treatment came into them. Septa system is where you're going in and intentionally try to create a small hole in the membrane between the twins, thereby creating some channel from which its twin with polly hydrangeas can put some fluid to the twin, which Oliver hydro millions. It is rarely down the stairs. And then finally, laser photo coagulation is now the gold standard treatment. Initially it was done in a non selective fashion but currently is done mostly in a selective fashion, looking for only the vessels that our master moses between the donuts wayne and the recipient. Between next slide please. This is just a Cochrane review that was published many years ago. Looking at the outcome of uh 20 twin transfusion syndrome. Pregnancies that were managed by laser vessels are manual reduction. You can see that debt of both twins, which is dwell debt uh Can be reduced by laser by almost by 70%. Overall debt can be reduced by about 30%. So 0.71 is a relative risk. Whereas the Panetta that was also reduced by about 40%. No NATO. That was reduced by about 70%. And then long term neurological uh intact. A delivery six months after delivery was seen in about 66% of those who had laser compared with annual reduction. So there are some advantages with laser definite. So this next slide shows a stage based treatment algorithm that was popularized by the group in Cincinnati when tim crumble and was still uh the main sergeant there. And you can see here for between stage one, they were performing just annual reduction and then stages to two. Stages four were all offered laser and then radio frequency ablation was offered for stage four. And it also shows some of the investigations that we do in cases of 20 twin transfusion syndrome, including ultrasound as well as fetal echo. Um to for that characterizes stages. And this is the slide. I was referring to where I said there was some modification of stage three by the Cincinnati group as well as those from hospital of philadelphia. Here you have stage three, A three B and three C. Using what we called in my cardia performance uh index of the of the Beatles that's judged by fetal echocardiogram. Next night list. Now one, this is what we have. Once you do laser um you can see the schema they want to our right looking on the screen and just demonstrates the vessels that are connecting through the vascular Ecuador between the donor and the recipient. The larger placenta represents the recipient and the smaller part of the placenta represents the donor and the yellow box. Their shows and anastomosis, which is uh an arterial and venous anastomosis that you have to calculate with your laser. And on our left side on the screen you see the result of after laser coagulation of the type of example. We show there of an A. V. Uh anastomosis. You want to make sure that there's complete blanching of the vessel with your laser. And most of the time when we do these procedures, you 10 years complete blanching and then you come back to look at the vessel. You see some refilling occurring from the vessel and you have to re bus with your laser. Next slide please. So again, the current state of play is that most people would offer laser treatment for any case that is between stage 23 or four On stage Stage five cases. Next line Those in stage five. Next slide please. Those in stage five will be observed or some cases in stage five, make sure signs of fetal anemia, in which case you may have to trance. Use the surviving twin if you recall Stage five is when there's already death of one twin, but you may have a fetal anemia in the surviving twin, in which case you may have to offer transition in some cases next night, Stage one is where the controversy is whether should you just watch them or will they progress or should we offer laser for all of the cases of stage one and so most of the data we're presenting the next few slides have to do with management of stage one next light please. So the first thing we see with making a diagnosis of 2020 transmission syndrome is the discordance in amniotic fluid volume. So between 16 to 26 weeks gestation. We used a maximum vertical pocket M. V. P. Less than two to define our legal hydrangeas and greater than eight to define a polling hydra mias. And this is uh that no six station. That was a criteria that was established by Quintero since 1999 and has been used by more centers Next like Now there are people feel that there could be some pre clinical stages of 20 twin transfusion syndrome though where uh the these I'm not flu discordance may not necessarily be as category as defined in this life. May like, may not be less than two, or may not be greater than it. Next thing. However, before you make a conclusion that only go hydra mia's or poly hydra me a secondary to um uh in a twin is due to 20 twin transfusion syndrome. You want to rule out this differential diagnosis that are in the slides. So hopefully hydrangeas want to make sure you rule out diabetes. I saw immunization from other causes fetal infection or placenta, T. Mos. Whereas for our legal dramas, you want to make sure she's not ruptured. So there is no p prom, there are no congenital malformations and diabetes in severe cases may lead to legal dramas. I want to make sure there are no hypertensive disorders or it's not a severe case of fetal growth restriction, such as in selective intra uterine growth restriction. Next slide. So how did we come up with his uh definitions of our legal hydrangeas and pulling hydrangeas? Um it's interesting to look at this chart here, where he looks at amniotic fluid volume for gestational, starting from 16 weeks to 28 weeks. And you can see here that the 50% time it's constantly Um really above two And the 95th%ile is constantly less than eight. So this criteria of two and eight that we use in the diagnosis are really extreme. Uh numbers meaning that they are even more than greater than two standard deviations above where you would expect the fluid volume to be for each gestational age. Next line. So 20 weeks when we use uh this criteria of to an aid for making our diagnosis. How many cases of 20 twin transfusion syndrome are we going to detect on Miss Next Night? So review uh many years ago show that if you use this criteria, you can still miss up to 32% of 20 twin transfusion syndrome cases. And this was what I was referring to. When I said there are some atypical cases that may have shown some amniotic fluid discordance, but they may not necessarily meet the plastic definition of a legal aid romanians or poly hydra means that we use. So In in a story where they did some intervention just based on amniotic fluid discordance but not quite meeting the 2020 transition criteria. And About 14% of these cases had laser and about 2013% had annual reduction because they were more than 26 weeks gestation. And actually the survival rate in uh without laser was pretty high. Up 90-94%. I have any complications. Could be very high, especially in those who have laser and maybe as high as 46 next life. So, people have questioned whether there are, there are other ways we can evaluate the urine production or the amniotic fluid volume in cases of 20 twin transfusion syndrome. This was a study that was published by Yamamoto and colleagues in 2007, essentially, they were looking at using fetal urine production basically what you do. Yes, you do the blood er volume and then you watch it for some more time for hour or so and re measure the bladder volume. And there's a formula by which you can then George the urine output per hour if the urine output Uh hours less than uh one meal per are than us was considered to the uh severe cases of 20 twin transfusion syndrome. Interestingly in that study, in stage one T. T. T. S. Only 46% of cases had uh urine production. I was less than one mile per hour. About 100% of those in Stage two. Hard low urine production. Which makes sense because to make a definite diagnosis of Stage two, you have to have an absent bladder. So uh it makes sense. Stages three and four had a mixture almost 70 5- 78% of of a low urine production. Um however, because this system is very difficult to George, um it hasn't really gained much popularity. And and so we still stocked with using the two centimeter and the eight centimeters definition next right next. Like please. So I also mentioned uh the use of cardiac changes in defining or refining the staging of 20 twin transfusion syndrome. And interestingly, in cases of stage one where if you look at the recipients, you may find that up to 57% of them a show hypertrophic hypertrophy of the ventricles, especially left ventricle. I may see evidence of elevation in the Market Area Performance Index, which is an uh Eco index has used to value these cases of 20 train transfusion syndrome. This story was published from Cincinnati a few years ago. So in Stage one cases where you see this in Cincinnati, they will upgrade them to Stage three, A or B or C. Depending on the cardiac changes that they are saying. Next life. The Children's Hospital of philadelphia have their own current system for cardiac evaluation. And you can see here that depending on the stage. So in Stage One, you have very mild cardiac changes, which is C. V. One. But as a staging in 20 Twin gets higher, you start seeing cases with CV two and 73 4. And so in Stage four, most of them have more severe cardiac involvement. Next stage next site. So many years ago, enough net group meant to decide whether we need to modify the Quintero staging and the conclusion from that a consensus meeting was that there is insufficient data at that time to recommend revising or abandoning Quintero staging. And so most people still used on Terror Station and that's what we use in our center here in uh at U. S. F. And T. G. H. Um We are they also recommended to look at other things such as the cardiac indices and biochemical as well as ultrasound markers to see if they could have in further refining the stages of 20 twin transfusion syndrome. Next lay. So this is a conclusion from a review that was published many years ago by bribesville. Um basically, it says in the only randomized study that included sufficient cases to address the issue of survivor after primary treatment with either laser surgery or new reduction. Survivor rates were higher on mobility and the survivors were lower following selective laser at all stages compared with annual reduction. This was published by its ville, who was the one that really led the Euro fetal story, which is shown in the next slide next like place. So the Euro fetal study was performed again as they tried to say, Euro photos were all european centers, and it was the first and only randomized controlled trial that was published on um 20 twin transition management until a few years after that. And this is the study that really established laser as the gold standard from managing cases of 22 in transition syndrome. In that study, they found that for stages one and two, um using laser, you had 86% survival rate compared with 58% for annual reduction. And this was a statistically significant for stages three or four. When you combine them, Our daughter was higher survival rate with laser of 66%. This was just not statistically significant. Although when you add all the stages together in this randomized control trial, it did show that laser was superior to arm your reduction for treating a 2020 transmissions syndrome next life please. Now, one limitation in that story is that even though the table says state is one and two had a significant reduction, there were only six cases of stage one in the laser arm And there were only five cases of stage one in the annual reduction. Um and so most of the cases that it was based on was really stages to on stages trace cases and stage four only had one case each for each treatment. Um So this begs the question that there was not enough sample size in that study to really address the issue of whether laser to be used to treat cases of stage one uh versus annual reduction. Next slide. So in the absence of a randomized controlled trial, most people that are reporting the results from observation all story. This was a study that was by roberta and which looked at how patients performed following laser depending on whether it's uh the procedure was difficult or not. They also looked for the outcomes here were recurrent twin to twin transfusion syndrome. And the second outcome was taps, which is between anemia police item ian sequence. Um As as you can see the procedure was difficult. The incidents of uh recurrent T. T. T. S. Was about 64%. Um whereas the incidents of taps was also pretty high 23%. This should be considered in the background that most of the time we tell patients that the recurrence rate for 20 twin transfusion syndrome following laser is only about 10% and the incidence of taps following laser is usually about 4%, So this really shows how if you have a difficult laser case you can affect the outcomes. And yeah next slide please. Another group. These are three centers that reported their outcomes for stage one cases that were treated with laser. Again, these are not randomized controlled trials that were just observational studies. For example, the first study only looked at 10 cases of stage one that was treated with laser And the dwellers survival rate. There was about 90%. Uh When you look at the other outcome, which is called if it's at least one survivor which is a L or at least one survivor was about 100% in that study, which is pretty small but but very good result. Another study by huber and colleagues showed, they looked at 29 cases of stage 1, 2020 transition uh cases with Stage one and found that double survivor was about 76% whereas they had an at least one survivor in 93% of case and Smite from Los Angeles looked at 112 cases. This is pretty large And they showed 79% survivor of both photos. Post laser for stage one And 92%, survivor of at least one ft, toes following laser. So these were pretty good result. But the problem, as we all know which observational studies, they have a lot of uh confound ear's that can buy us the results. Uh And sometimes you have selection bias on who you perform laser on in stage one who you do not perform laser. So there was so limitations and you cannot use this to inform and guide management. Next slide please. So what about in natural history and natural history has put in court because uh with a natural history but we're looking at harm. If you observe cases of stage 1 2020 transition syndrome, what happens? You can see here that between 17 of really tend to about 40% of cases may progress if you observe them. Um and progression could be other progression to stay two or to a higher stage, in which case they may need laser or some form of treatment. And and they they below you can see that in these studies, people employ different types of treatments. Uh It wasn't just an annual reduction. Some people had selective reduction of one twin, some also had laser and others performed septal stunning. So it was very it is very difficult to look at this table and be able to recommend what the future treatment should be for cases of ST stage one T T. T. S. Um But if you look at the treatment depends on the survival rates, withdraw our survival. In all of these cases was about 54% to 77%. You can have at least one survivor here going as high as 97% any case reported by Wanna and colleagues. So the results were all over the place depend on the center from which is being reported. Um And most of these studies were very small, again limiting conclusions from them next life please, whatever. When you compare just laser with observation slash annual reduction. And there are three studies here uh put in the slides and again from different centers. So this was one of the series by Quintero a long time ago. I showed that for the laser group He had 75% over our survival, Whereas for the annual reduction group he had 95% overall survivor. Um interestingly the annual reduction patients in this in this study did better because even the neurologic intact group had 100% of them had no neurologic complication. Whereas the people had laser, it was only 86% had intact neurological outcome following a four stage one T. T. T. Yes. Um Wagner's group had results, I was a little bit different from that of uh of Quintero because here the survival overall survival rates were similar. But when you look at the neurologic outcome for laser in this series there was 100% intact Neurological status, whereas for our mural actually observation was a nurse group there, it was only 61%. However, you can see here that the observed group also had a very good survival rate, which is 87%. And again they hardly from Cincinnati showed again different groups. Their survival rate for observation was also as high as at 87%. They did not report a neurologic status of the of these patients. Uh However, these stories started making people to question that you could really watch these cases with Stage 1 20 twin transfusion syndrome and you can have outcomes with as good as 87% survivor without doing anything. Um And so there was a lot of plea for more undermines controlled trials to try and look at this sub next right wing. Um O'Donoghue kind of reported something similar again, showing that with annual reduction at least one survivor was about 81% versus 87% when you just observe them until nothing again, very encouraging from observing uh patients with stage one GTs. Next slide please. One other thing that study by Don O'Donoghue showed was looking at predictors of progression or regression in cases of 20 twin transfusion syndrome, trying to see their factors that could predict those who survived and those who progress. Um interestingly gestational asIA diagnosis was one of the factors the farm and and I must apologize because the P values there are less than 0.05, not greater than the recipients amniotic fluid volume or maximum vertical pocket. Was also a positive predictor. The number of artery to artery anastomosis were predictors. And then a small donor blood er was also a predictor of uh of progression. And then if the discordance in weight between the twins was greater than 25%. This also predicted those who progress compared with those who did not progress next. Like hi doctor a depot. We have a question. Yeah. What stage do you see most cases of twin to twin transfusion? So we tend to see most cases really at the moment at stage two or stage is three. Most of them. Um Most stage one people either most of the time suspect the doctors do not refer them to us because they're still watching them. But most of the cases that come to us are stages two and stages. Yeah. All right. And so this is a solid I was sent by Molina and colleagues and many years ago to members of the enough net international fee to medicine and surgery society and also to participants of the Euro photos T. T. T. S. Consortium. And basically they asked quite a lot of questions and uh one of the questions was what does the management recommendation that that you give for cases of stage one T. T. T. S. At 18 weeks. And you can see here in this survey that those people are not America most people will Of Observation for Stage one. And if If anything most of them we do annual reduction in 17% of cases In Europe. Similarly most of them will be observed. But if they want to do any procedure in stage one, they would do laser compared to America where it was eight and then other parts of the world. The numbers were pretty much similar to those from europe. Yeah, next slide please. The next question was what if the patient was symptomatic? So they had Polly hydra mia's complain of discomfort and the maximum vertical pocket was about 14 centimeters. What will you do? Most people in North America at that stage felt that we do annual reduction And the Europeans, most of them will do laser in that state 76%. Whereas those in other parts of the world will be like America and they would do a near reduction, knows case next life please. Then the other thing that sometimes confound us is when we see these cases with 22 in transition syndrome, they have a very short cervix and you start wondering if they have a risk of going into premature delivery. And the question becomes, what do you do if your patient has a short service? That's less than 1.5 cm. Most practitioners in North America and that's in that Seville and said they would offer um your reduction And the majority of them, about maybe 20% will do uh sir collage alone Instead of doing annual reduction. And then 5% we do both seek lodge and annual reduction in the setting of his short set. And only 10% of those in North America will do laser in those situations. And the Europeans were different in that 13% will do on your reduction by about 50% or more will do laser. And most of them will not do supplies Alors or if they do psychology will be in the certain of laser. So 27% of those in Europe will do laser and cirque lodge, even though the Cervix is shot. Uh and those from other parts of the world, they have almost similar to uh to the Europeans in this case, in that they did more laser and less annual reduction. And but when it comes to secular, majority of them will do sect large. Hello, next life. So again, this is again some conclusions from the half. Net um consensus statement and many years ago basically saying the options uh of management, a few under their inadequate data regarding Indications and efficacy of treatment for stage one um and embrace these options of expectant management and you're reductions that close to me and laser as treatment options that you can consider. But again, these were based on and non under my study. So they called for under my studies looking at these treatment options. Next slide please. So the Cochran database many years ago called for a Stage One on stage to be looked at particularly feeling that study that was published was not powered enough to uh to show any effect of uh of laser for those stages. So, they called for around my study for that stage. Again, similarly, there enough. Net called for a randomized controlled trials looking at not just uh treatment of stage one, but they also looked at other perinatal outcomes and infant mobility's uh to be included. And that we should extend the time of follow up to two years. As you can see from the previous slides, most of the neurological outcomes that people were looking at, where survival and neurological Intact status at six months of age next night thing. So, in recent meta analysis again combined all of the studies that have looked at stage based treatment outcomes showing that Stage one cases have a single survival of about 85%. And while survival of 70% this was published in a y journal this year and next slide please. And still in the same uh meta analysis, they showed that if you compare laser vessels expectant management vessels, annual reduction in treatment of stage one, that the outcomes are shown in this life. You can see the last two bars, the the slightly dark one and the darker ones are those with either at least one survival or at least uh showing some at least one survivor or double survival of twins following either laser or expectant management or a mere reduction. And for some reason this is not projecting well. And I apologize as you can see from the slide the survival rate though from they group their hard expectant, sorry, annual reduction seem to be higher vote for the dwell survival as well as at least one survived next line. So this was the state of play uh, many years ago. This is a review by a few authors, including Dog Wilson Greg, Ryan and Tony johnson basically saying that laser ablation is the gold standard of treatment for T. T. T. S. What still needs to be determined is when Those 20 train starts becomes an obstetrical and biological risk that were runs the risk of intervention. And that randomized control trials needed to answer all of the questions that were posed in the last few slides. And they again called for a randomized controlled trial. So the next line, This is the trial that has been done to really address this question of how do you treat stage 1? Do you want to do expectant management or laser treatment in this story? I'm your reduction was not one of the treatment answer was looked at. This story has just been published online and the full paper is not yet available. Um, so I'm just giving you what I'll call, like a condensed uh or abridged version of the of the findings. It was presented at the most recent issue of meeting. And on some of the details will be different ones. We read the food papers. It comes up however, this trial was started and Really almost seven years ago and has been going on with the mind of trying to recruit 200 plant patients. However, they had to stop the enrollment because after enrolling 117 patients, they found out it was very slow to get patients because most people were not sending their patients to be randomized for this study there Randomize 58 patients to expectant management and 59 to the immediate laser growth and The outcomes they found was that the intact survivor, as you can see here, the numbers are higher because we're talking about twins. So if you say 58 pregnancy, you're talking about 116 twins. So the intact survival rate was about 77% for the expectant management group And 78% for those who had laser. So this was not significantly different. And then obviously we know this story was on their power. Also, when you look at severe neurologic mobility, it's according about 4.6% of those in the expectant management group, On 2.6% of those who had blazer. Again, this was not significant statistic and the patients For the patients that were followed expectantly, about 41% of them remain stable, which a dwell intact survival Um at the age of six months. Um the take home from this was first of all, the study was not powered but there was really no difference and laser did not seem to improve the outcome of cases compared it expectant management. The second thing was that about 60% of cases who were in stage one actually did progress two, stages two or stage three or higher and eventually needed some form of intervention. Which is one of the drawback of this kind of study because you have to eventually analyze them in the group to which they were randomized following the principle of intention to treat analysis. So this in conclusion really, this shows that for stage one twin to twin transfusion syndrome, we still do not have any evidence that laser is better. So going forward, we're still left with observing them and if they progress they may need laser or if they do not progress than they just observe them throughout the pregnancy. So I'm going to stop here and take any questions and once again, thank you very much for spending your time with us this evening. Thank you. Excellent. We do have a couple of questions and while dr Adidas Debo takes time to answer these. If you have any other comments or anything you'd like to add, please use this time to type them into the chat box. So dr devo what's the time period? Sorry, what's the time period for which you can perform laser surgery? Yes, that's a very good question. Uh currently we perform surgery between 16 weeks and 27 weeks. I know some of my colleagues in Europe we involve stretch it to beyond 27 weeks. But Are those extreme suggest station allow age? Your risk of prematurity becomes so high that the balance becomes maybe it's better to just either think of managing them conservatively after 27 weeks. So For us we do it between 16 weeks and 26 and 6 7 tweets For 27 weeks. Yeah. Thank you. And another question When do you typically deliver after laser surgery? Yeah that is a very good question. Traditionally we've always advice delivery at around 32-33 weeks and one or two slides I showed earlier on showed that that was the gestational age that most people deliver this patient. Typically they will show you some signs or some reason why you may need to deliver them around that period or even earlier. However we've seen some patients that we've managed where the practitioners Either forgot what we advised and they left patients and watch them up to 36 weeks But beyond 30-34 weeks. I think we're really beginning to think that you you're playing with danger in that some other complications may come up. That will mess up all the good work you've done after your laser tree. Excellent. I don't see any other questions at this time. So I will like to say thank you for joining us everyone and thank you Doctor Debo for your time this evening. And just a reminder, I will email all attendees with directions on how to claim your cmi or CPU credits within the next couple of days. So thank you from everyone at T. G. H. And thank you Doctor Adobo. Any final words? No, thank you. And just remember at the fetal care center of Tampa Bay, is there to serve your patients? Um We have a policy or for like a one stop shop where we try to make our visits for our patients. Very comfortable and convenient. Uh Coordinator julie johnson. Just uh I think she just left the line but she's there and we can I can be reached anytime to help care for your patient. Thank you. Yes. Thank you again and have a good rest of your night, everyone. Thank you. Published June 7, 2021 Created by