Now the reason we didn't move yesterday down the level is because of so-called health advice. Man in charge of that is Director-General of Health, of course, Ashley Bloomfield is back with us. Morning to you. Morning. How are you, Mike? Well, thank you. Let me quote you, Michael Barnett of the Auckland Chamber. He goes, businesses have got no certainty or ability to plan. We still don't know the criteria and the rules to give us back our lives and livelihoods. What is it they're waiting for? No cases for an unknown number of days. Acceleration of testing. What? What's the answer to that? Well, just on that, I think there was quite a bit of certainty given in the announcements yesterday. There's certainty for outside of Auckland about a move down to Alert Level 1 early next week, a revision in particular of the Auckland situation around the maximum gathering size and signalling that probably a short period of time after that that Auckland needs to remain in Alert Level 2. In addition, of course, yesterday, the announcement based on some advice that I'd given around the relaxing of physical distancing requirements on public transport and on flights, because people are now using masks, which is great. And so that's then opened up, of course, many more domestic flights and also means people can now get asked about on public transport more easily. Exactly. But a review isn't certainty? Well, except that the reviews are happening every week and at the end of that discussion and cabinet, then there's an announcement made about what the... I think that's the part they're trying to say, Ashley. And you guys don't understand it because you're not in the private sector. A weakened business is a lifetime. Oh, look, absolutely understand the impact on business and on the wider community. And in fact, I'm part of a leadership team across government that includes the Secretary of the Treasury. We meet every day and talk about the economic and other issues. And so those are clearly an important input into our advice and into the government's decision-making. That 25% you came up with for the spread from Auckland. How do you do that? Well, that's the modelling done by Professor Sean Hendy and his team in Auckland and, yes, at the Auckland University. And in fact, what it showed is there's a difference between the North and South Island. So there's still, at the end of last week, about a 30% to 40% possibility of a case having been ceded outside of Auckland in the North Island. And it's still a 10% to 20% possibility in the South Island. That will continue to drop as the days go by, as we test and find no cases. But that was the state at the end of last week. And I think... Yeah, but how's it modelled, bro? I mean, it sounds like an invented number to me. Oh, look, a lot of the modelling papers are publicly available. But no, they put in a range of assumptions around the travel patterns, the number of cases in Auckland, the likelihood of people being infectious, the likelihood someone has travelled outside of Auckland who was infectious. And then that there's further spread there. So, look, they've been using this over the last few months to help. It's just one of the inputs that's helping form the decisions. Can we... What was materially different yesterday, as opposed to the previous decision, which is basically for Auckland gone nowhere? We seem to have a small number of cases, a bit of a tale, some tracing going on, but nothing fundamentally has changed. Are you saying that as long as we have this sort of scenario, we're in level 2.5, and that's just the way it is? On the contrary, actually, as long as we have this sort of scenario with small numbers of cases that we find quickly and can find all the contacts, then we will be in a position for Auckland to move down alert levels in due course. But we're only two weeks into that 2.5, where people have been travelling around a lot, both within Auckland and outside of Auckland. And it's just too soon to be able to say confidently that there haven't been other cases seated more widely in Auckland or outside of Auckland. And that, by the extra time in 2.5, was our recommendation. But when you take your two plus weeks, plus another week and a half, you're literally writing off a month every time you've got a handful of cases? Well, that's what we've done in this situation. That's the advice we've given. And I think... Yeah, but that's my question. Is this the way it's going to be? So every time you get a handful of cases and a bit of a tail, that's a month gone? No, not necessarily. And in this case, of course, we've added a number of new things. First of all, our contact tracing has shown that it's rapid and effective. Secondly, we've got the compulsory use of masks on public transport and flights. And that's having an impact. That's another thing in the toolbox. But just remember last time when we came down the levels, we had a number of days with no cases anywhere in the country before we moved down into Alert Level 1. It was well over two weeks. And in this situation, we are still getting cases, but we are confidently moving back down the levels and opening things up. Have you given up on the index case of the original Auckland cluster? Not given up at all. We're still very keen to find out where that might have come from. I'm sure you're keen, but where are you looking? Well, yes. So what we're confident of is that it wasn't a simmering infection in the community. It was just too long for that to have happened. So it must have come through the border somewhere. So we can now officially say the border leaked? Well, it must have been imported. The question is whether it happened by some sort of casual contact at the airport or at a port, or whether it happened in a managed isolation facility. And ESR is continuing to go through all the samples of those previous cases in managed isolation during July to genome sequence them and see if we get a match. So it will be important to see if we can find that. And once we do, we'll make that information available, of course. What do you think Shaun Hendy would model the chances of you being able to find it at? Oh, I'm not sure I haven't asked him that. Would it be close to zero? Yeah, I'm meeting him in the next day or two, so I can ask him that specifically. Oh, look, we're hunting, you know, it's like a police investigation, that's Mike. And we're just gradually working our way through it because we do want to find out. What about David Seymour's claim that the jet part worker, you haven't had a single positive test until you started testing people and then what do you know, you've got a positive test? Yeah, look, I think one of the things to point out is that there's a higher likelihood we will get an infected worker in managed isolation and or quarantine now than there was earlier because there are simply more people coming in who are infected. And remembering in the jet park are all our cases from the community. They are also housed in the jet park. So there are a large number of people in there who are infected, whereas previously there might have only been one or two or three each week. So the likelihood of transmission has increased, but that's why we have added in the weekly testing and why we're doing audits of the infection prevention and control regularly. Always a pleasure, Ashley Bloomfield, the Director-General of Health.


Welcome to the Texas Heart Institute Educational Programs featuring cardiology in the time of COVID-19 pandemic. The title of today's presentation is Cell Therapy to Modulate Inflammation. My name is Zvonemar Krazier. I'm an interventional cardiologist at the Texas Heart Institute and CHI Health Baylor St. Luke's Hospital. Joining me today is Dr. Stephanie Coulter. She's an assistant medical director at Texas Heart Institute and director at Center for Women's Heart and Vascular Health. And also she's a program director, Cardiovascular Disease Fellowship, as well as director of cardiology education. Joining us today is our special guest, Dr. Emerson Perrin, he's an interventional cardiologist at Texas Heart Institute and CHI Health St. Luke's Medical Center. He's also a medical director of Texas Heart Institute and medical director of cardiac cath lab here in Houston, Texas. Welcome Dr. Perrin. Thank you for being here. So we would like to know and get some information from you Emerson. What do we know about cell therapy? You have been involved in Texas Heart Institute cell therapy projects for many years. But now in the era of COVID, how can we use cell therapy to treat this serious condition? We've been working with cell therapy mainly for heart disease. We are the Texas Heart Institute and one of our main areas of focus has been heart failure. And we really started the first trials, lead the world in cell therapy for research for cell therapy in heart failure. We have three trials, one which is a phase three trial that are going to be unblinded this year. And so there's a lot of work going on there. Now the main focus at Texas Heart in terms of research is really innovation. And I'll get back to this, but there seems to be some very significant involvement of the heart in COVID infection. And there may be a role for cells in this. And I want to bring up the fact that innate immunity, which is the immunity that we're born with, the cells such as natural killer cells and monocytes go around and are sort of our first defense and army against something like if we catch COVID-19. And actually our innate immunity is what will dictate if we get the infection and we're home for a little bit and we do okay. Or if it's not that good, if we gradually go down, he'll have to go into the hospital and have complications. So cells are intimately involved in immunological defense. We are made of cells and so it's very important to consider the role that cell therapy might have in this disease. So here on this slide, when we think about why could these cells work? Well, there's many, many different kinds of cells and we've used different kinds of cells in cell therapy and a specific kind of cell or a mesenchymal cell. And this slide is from a publication of ours back in July of last year in circulation research and it demonstrates the actions of a particular cell. This is a proprietary cell called an MPC from Mesoblast. But the general properties of MSCs are possibly felt to be similar. So here you can see that an inflamed heart actually is something that gives off signals and that inflammation then acts upon these cells that we can treat people with. In turn, these inflammatory markers then transform the cell and have it then secrete certain substances. And you can see the representation of a M1 macrophage that is subsequently transformed into or polarized towards an M2 macrophage, which is a healing anti-inflammatory type of cell that instead of putting out pro-inflammatory cytokines and other things puts out healing and anti-inflammatory protein such as IL-10, PDGF, you see here, FGF2 and as opposed to the M1 type that secretes IL-6, TNF alpha, these things that we're used to seeing causing significant inflammation and are at the basis of, for example, in this case of chronic heart failure, but in general many diseases have this sort of underlying pathogenesis. And so the effects of these anti-inflammatory substances is great and it's not only local, but they can have an effect in, for example, the vasculature. I think this is a very important thing, being able to have an effect on endothelial health may be extremely important in these kinds of patients we're seeing. So recently, in last month, this was published in JAMA cardiology by a group in Wuhan in 416 patients and this is very interesting. I mentioned that I get back to the issue of cardiac involvement in COVID and they looked at these patients and the patients that were hospitalized, the ones that had cardiac injury and that's about 20% of patients, actually it was 19% of patients. And actually, if you had cardiac injury as defined by elevation and troponin, then your outcomes were significantly worse. So those patients with cardiac injury had a mortality of 51% versus those that didn't, they had a mortality of 4.5%. So this publication has been sort of a red flag and has really caught the attention of a lot of cardiologists around the world and really brought to the forefront that there may be cardiac involvement in COVID-19 or this may be a marker. So we don't really know to what extent the heart is involved, but we know that when we see these markers of cardiac involvement that these patients are at much higher risk of having complications. So Emerson, based on how we're watching the disease of COVID-19 make people ill, we're seeing patients, many patients, 80% that do well, that have minor symptoms that escape hospitalization altogether and then you see patients that have symptoms and fever and after five to 10 days have a sudden worsening in their respiratory state. When would you see and how would you use cell therapy in these patients with COVID-19 infections? Well, that's a very good question. I think the important part of the answer is that we want to, number one, identify those high risk patients and here's an example. For example, we can use troponin and patients that are troponin positive are at high risk even if they're not further down the road yet. It's a way to look at, in this study I showed you, people that were hospitalized and they have a positive troponin. So with a group of investigators around the country, we're working on putting together a trial and getting it funded and there'll be more on this. But to exactly identify then this group of patients where we can act early, identify the high risk patients and think of using immunomodulatory or anti-inflammatory cell therapy. In this case, cells like these mesenchymal cells to try to prevent or attenuate the reaction they can have maybe helping them with their hospital course and not going down the road of no return. Emerson, I think it's super entertaining because if you look at the way we've used the antiviral therapies in very sick patients, the results have been really very unsuccessful and not very, I don't know, I'm not that optimistic. Maybe I'm beginning to think that we're given the antivirals too late when the inflammatory response is hyped up too much and in fact maybe even the viral load in these patients have already started to decline and the immune system has taken a ravaging toll on the lung and that thinking outside the box, which is a unique skill set that Americans do to think about new ways to treat an unusual presentation of a disease that we're watching unfold in front of us. So how would you administer the treatment? Well, so this is sort of a fortuitous, very fortuitous and kind of an interesting thing. So back in the beginning of cell therapy, Josh Harris, the University of Miami, he did one of the first studies in heart attacks and using cell therapy and at that time he gave these kinds of cells MSCs and he gave them intravenously. Well, as we found out, giving intravenous cells is not a very efficient way to get them to the heart if you're having a heart attack and very interestingly these patients wound up, it didn't have a significant impact on their heart function but they all had improved significantly improved pulmonary function tests because when you give something IV the lungs act as a filter and these cells end up in the lungs. And so it is incredible that in the world of cardiology we go through all these things to try to inject these cells in the heart and it's kind of difficult to do but here we will be able to administer these cells intravenously very quickly. This is a 10, 20 minute infusion, very simple and these cells will go right where we want them to go and hopefully have an effect. I think that the lung parankuma is a place where the cells would definitely be challenged with local inflammation that they could then react to and respond to. So Emerson another very important question is I believe and maybe you can shed some light on it, where do the cells come from that you would administer to your patients? Yeah so the field in general, so we've been working on cell therapy for the heart for over 20 years and in generally progressed to using allogeneic cells so we're not doing a cell harvest procedure on the patient to get cells to give it back to them so that puts them and these patients with COVID are very sick and we don't want them to be having to go through anything extra. So an allogeneic cell procedure is very simple. You have one donor that can from which you can create many many cells and have a cell bank and so these cells exist and almost like a drug you do you pre-define a dose and then you could administer these cells very rapidly. So basically cells from a healthy young person that can be given to all the patients and it's important to mention in the trials that we've done in cardiac therapy that these cells these particularly these mesenchymal cells it's not like giving heart muscle cells that the immune system reacts to these these cells sort of fly under the radar of immunity and there's not a rejection kind of phenomenon going on when you administer them. So they're very well tolerated and the safety profile has been excellent when we use these kinds of cells in patients for heart purposes. Is this a safe treatment or will it hurt the patients in any way? Well you you never know right so I just can't affirm that it's safe. I can I can tell you that over a thousand patients have been studied with these kinds of cells in different trials around the world and so they've been found to be safe. We really don't have a reason to believe we would have any any issues. Again the immune logic issue does not seem to be a problem and we really haven't seen other safety issues so based on that I would think it would be a fairly safe treatment. I have a question Emerson do we have cells that are already harvested that could be used? Yes we do. You know the the fundamental property of a stem cell is cell renewal and so when you get cells they grow and so it's it's it's obviously it's not easy you have to know how to do this and but you can create a bank of cells from one donor where you could treat a thousand patients. So yes these cells exist. We've different groups and we're part of different groups of investigators around the country and so that we have deployed these kinds of cells treating other diseases recently for anthrocycline and induced cardiomyopathy or other cardiomyopathy so we have these treatments ready. So Emerson is this approach like one-time treatment or would it have to be done on multiple occasions in this particular scenario when you're talking about COVID patients? Well that's a that's a very interesting point because when you take medicine you take it every day or every some you know so many hours apart and you keep repeating the treatment when you take pills and usually medical therapy and historically now cell therapy has been usually one treatment and we give patients a one treatment and in many phase two signals we've seen some very significant signals in phase two trials you've seen very significant signals of that one treatment having a significant effect so you could think that you could treat them once but you could also you know so this is not a set in stone but you could treat them twice or maybe even three times and that's something that you know we do especially in this scenario really we don't answer is we don't know but we could do it once twice three times logistically you know you don't want to get in the way of the sort of housekeeping treatment of these patients that may need a lot of care and they may be very sick and and burdening the the the healthcare workers that are there at the bedside so you know we want to have something that is relatively easy to do. In which patients would you recommend administering this treatment? Well I think you know we've kind of already touched on this a little bit and so there's many approaches and you brought up Stephanie the issue of how sometimes treating patients later on the fire is raging and you know it's beyond the capabilities of trying to put it out so I think especially in inflammation the earlier the better so if we have a means to identify a high-risk patient and be able to treat him early before he's intubated before they're on ventilatory support that would be ideal and that's how we would like to approach this. Let me ask you and you have answered this in part but it's very intriguing to me to figure out who is the best candidate and what kind of tools or studies would you consider to screen those patients and to see which patient fits the best in this protocol and the reason that I'm mentioning this is because there is enough evidence now from experiences particularly from abroad from our colleagues from Italy and also from China that not all patients that have elevated troponin or even ST segment elevation have occluded coronary vessels as a matter of fact some of the researchers have found that up to 40% of patients that were thought to have a STEMI actually didn't have occluded vessel so it could be due to myocardial injury per se or microvascular being the primary cause for that or even pericarditis and so it's challenging to decide which patient therefore is the best candidate and I was thinking about an option of doing a cardiac maybe or coronary CT angiography and looking at your FFR and we do that routinely at our institution and you can immediately figure out who has true STEMI and who has some other causes and then maybe streamline your treatment depending on the findings well certainly the EKG can be confounding and as you just said there are many reports of EKGs that look like STEMI that really aren't that may represent microditis or perimicarditis we could think about using some different inflammatory markers certainly those need to be measured I think a simpler imaging modality is echocardiography that's widely available and in our cath lab discussions and with with investigators around the world actually it's felt that doing a quick look echo is a very good way to distinguish somebody who's having a true ischemic event such as a STEMI from somebody who's having a more generalized kind of phenomenon so I would think that definitely I would like to image these patients maybe echocardiography would be more approposed since it's exposes less people it's logistically simpler and and the images can are very reliable we can do a lot of measurements from these and I think you know Stephanie is an expert in this but we would be wanting to look at overall LV function as well as LV volumes and regional LV function we actually ordered I don't know if you know this Dr. Crazier but we ordered 40 of those small little handheld echocardiogram machines that we can put in a you know a condom sleeve of some port so we can take it into the room and image the patient without exposing our equipment to disease and really without having to transfer the patient which adds a complexity to spreading the virus within our hospital settings so there are other options and I think we've been trying to avoid taking them to radiology as much as possible okay let me ask you Emerson another very important thing is of course this is probably the most important question that I have when is this going to happen when can we expect that this trial will be initiated I wish my answer was tomorrow obviously we're in a huge rush to get something going there are several groups around the country that we're in touch with there are different cell protocols I wanted to make sure that we brought sort of sort of did an educational put an educational spotlight on cell therapy in this setting because I think it may have an important role so so back to your original question we are you know work work through the weekend we put together protocol we're looking at funding mechanisms and when different working with different investigators around the country and so I hope that we could follow this video with another video pretty soon maybe giving you details of a trial that we have put together with the different investigators on and and we can talk about exactly what we are doing so we are just being you can know for sure that we're in a very very big hurry to get this and bring something that we believe might play an important role in helping some of the patients that are at higher risk excellent Stephanie do you have any other question for Emerson no I do wonder if you could use your protocol somehow in conjunction with convalescent serum as a therapy for you know you get squashed the immune system and give them an antibody I have no idea but at this point we're looking for anything that can suppress the immune response or improve the outcomes in these patients because at this point being a medical professional watching as we have only really supportive care for critically ill people where the mortality in vented patients is in excess of 50% and all the studies that have been released to this point we're hopeful that we're adding you know improvement to people's life expectancy when we add people to the ventilator but I'm really worried and scared honestly that the therapies that we have to offer at this point are unfortunately not much better than we offered in 2019-18 during the flu epidemic the Spanish flu because all of our fancy science hasn't been put to good use at this point maybe because we're too early in the epidemic to have tried anything new but it doesn't appear that anything we're throwing at this virus is besides stay-at-home and social distancing is putting anything of an important into the into the mix so I entertain any courageous and creative ideas at this point to prevent this immune response which is so ravaging for which there's really no really good therapy so well science is the answer science is the answer and innovation is where we need to go and this could be one of the an application for self therapy that we were we have a lot of familiarity with it in and deploying this in this situation could be something that could have an impact we need to we need to find out if that's the case very interesting thank you so much yeah Emerson you've been leader in this field and I think with your leadership we can certainly expect that something positive will happen as far as this particular research project is concerned very near future and we thank you for your very valuable contribution to this Texas Heart Institute program in cardiology in the time of COVID-19 and beyond so we thank you also Stephanie for helping us in making this program happen and we will for those of you that have joined in see you very very very soon with our new and additional programs on COVID-19 in cardiology thank you very much thank you


So Rihanna, when people approach you and ask you, okay, the service design thing sounds awesome, I want to become the best service designer I can. What is the most important tip you'll give them? I think the most important tip I would give them is that they have to challenge, are willing and able to challenge the status quo. Do not say yes to me or whatever they work to for, because that's the hierarchy, but they remain independent in their fields, are able again to bring the outside world in and at the same time, because they interact very closely with the delivery team, they know that whatever they deliver is feasible to be a success. Was this a helpful tip? Let me know by clicking that thumbs up button down below. And if this is your first time here, I would love to have you to subscribe to the channel so we can keep bringing you more videos like this in the future.


Hi, this is Dr. Don. I'm going to take a couple of minutes and show you how to update packages. Remember the packages are an open source project and have a lot of individuals that are taking care of those packages and occasionally they will publish an update. Plastic Cloud doesn't automatically scan and look for everything that's updated. You have to manually update packages and I want to show you how to do that. This is the files window, the files pane I guess, the window pane down at the bottom. What you can do is click on packages and then click on update. And what it does, it goes through and it looks at the packages you have installed and it will tell you in this column the version that you have installed and in this column it will tell you the latest version that's available. You can see for most of these, these are, I don't use very much, it looks like there's a new version available. One package I'm interested in is called Infer and I'm going to look at it and you can see there I've got to install the version 1.0 but there's a new version 1.06. So I want to update that and what I'm going to do is just to click on that. First thing I'm going to do is select none to make sure I don't have any other packages. Theoretically you can select all and have every package updated but that may take you quite a while. So I like to do them one at a time and again I select none to make sure there's only the one I want. I'm going to select infer and then I'm going to install the update and it will ask you occasionally do you know that you need to restart R and down at the bottom do you want to restart? I usually restart once when I am updating packages and then I ignore the other do you want to restart messages unless I just have to force you. So I'm going to say yes, let's restart once. You can see it's restarting. And now down here you can see it's loading and it went through some comments, steps in the console window. We got back to our normal cursor and it's flashing so it's ready to go. Let's go back here and look at infer back in the packages. I'm going to scroll down and let's see where is it. There's infer and you can see now we've got version six. I want to show you one more that I know I need to update. I'm going to click update again and it's called tidyverse. That is a package we use a lot in this course and it has a lot of sub packages. I usually update it once you know every so often and it takes you know three or four minutes sometimes for tidyverse to update you've got to do some steps. So I'm going to say install updates, do you want to restart? I'm going to say yes one time, let it restart. Now I'm going to ignore the second time and just let it keep working. And you see a lot of red over here where it's doing things in the console. As I said there's a lot of sub packages in the tidyverse packages so this takes a while and I'm just going to pause it and let it run it may take a full minute or more. Okay it took about 30 seconds and you can see now we've got back to our start cursor. So I'm going to go over here back in the packages and scroll down and look in tidyverse and make sure it has been updated. Tidyverse one more. There's tidyverse we're the latest version 2.0. So that's all there is to it. I hope this helps. Thank you. Thank you. Bye. Bye. Bye.