Mayo Clinic experts discuss the probable causes of the COVID-19 associated rhino-orbital mucormycosis (“black fungus”) crisis in India, as well as therapeutic strategies for COVID-19 that can help to mitigate risks. In addition to medical and surgical treatment options, the role of monoclonal antibodies in high-risk patients are addressed.
Moderator: Amit K. Ghosh, M.D., M.B.A., consultant, Division of General Internal Medicine; professor of medicine
Featured Expert: Devyani Lal, M.D., dean of education, Mayo Clinic in Arizona; chair, Division of Rhinology, Mayo Clinic in Arizona; professor of otolaryngology
Featured Expert: Arun Kumar Agarwal, D.Sc., medical advisor, Innovation, Education and Clinical Excellence, Apollo Hospitals Group
Featured Expert: Alok Thakar, M.S., F.R.C.S., professor and chair, Department of Otolaryngology & Head-Neck Surgery, All India Institute of Medical Sciences, New Delhi
Featured Expert: Holenarasipur (Vik) R. Vikram, M.D., consultant, Division of Infectious Diseases, Mayo Clinic in Arizona; professor of medicine
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The views and perspectives shared in these resources are presented based on information available at the time of recording.
introduce themselves and the subject matter expertise. Sounds good. Yeah heading. Working objective. I can stop if you need me to. No, this is perfect. We've got this slide 13 we're looking at right now. Right Okay perfect. We got him off. Okay And I'm turning things over to dR goes right uh as you go down just before I think after this yeah I'll take over here and just introduce our first speaker. Why that's important. That's good. Okay So we're about three minutes out um so I'm just gonna bring it back to the beginning here. So is everybody okay? What's going to happen? Like I said if something happens where you're not able to advance just feel free to stay advance or next I will be able to advance for you. I will be trying to give each person access to advanced slides before we open up. Um uh Doctor did you want to try sharing your screen with the video As in what you want to do is just share on top of mind. It will actually replace my share. Ok. Sweet, ok, let's see. So the one thing I want you to do is right now I'm seeing your design views go up to where is the display settings and change it to swap view again? Spot display. If you can help not closing it after we do this that it would be best but if you want to swap displays, yep, that one, hang on, let me yeah the problem is I might want to go back and forth so I'll make sure that you know I'll swap it. Well what I want to do is um so let's stop, you're here. Let me do this. Let me uh stop your stop your share actually for you. I want you to try this one more time. Okay? Oh okay. Um try sharing again. There's just a trick that I do if I can get it to work. Okay? So right now we're in design mode. Okay so give me one second here so don't do anything. I'm going to stop your share. So now try to go to share again and try to find the power point presentation slide that's up and running right now in slide show mode, the one that's the large one you went to the it's showing the design mode on that one yet, so let's stop again. Don't do any try it again. Yeah I think I can just swap it. It takes 30 seconds. Most people are okay, we're good. There were good there. Now we see if you got one minute, one minute to wind up, understood. Alright, so I'm gonna switch it over to my screen and we're gonna open up Okay everybody sounds good and when dr goes introduces me, you will give me access to advance my slides. Right? That's correct. That's gonna go for all everyone. Perfect. Except for uh dr Andrea I'm placing that wrong but I know I'm in advance this. Here we go. Welcome on behalf of the Mayo Clinic School of continuous professional development. I'd like to welcome you to the black fungus and the indian subcontinent prevention and cure weapon. Are I'm Whitney Pruitt your host for today. This webinar is accredited by the A M A N A N C C and A oh A for 1.5 credits. Mhm. Here are the disclosures for this activity and we'd like to thank eli lilly and company for their support of this educational activity. Before we get started, we'll cover a few points. The first is how to clean credit. If you'd like to claim credit after the webinar, please visit c e dot mayo dot e D u forward slash Covid 0623 You'll need to log into the site and if this is your first time visiting, you will need to create an account profile After you've done this and logged in, you'll see an access code box. You'll want to type in today's code which is COVID 0623. This will allow you to access the course to complete a short evaluation and then you'll have the ability to download or save your certificate. This Lincoln code will be dropped into the chat box throughout today's webinar. The second item is how will facilitate questions. You'll see at the bottom of your screen, the chat and Q and a function. If you have any questions during this webinar for today's presenters, it's important that you drop them into the Q and a channel rather than the chat box. This will help to ensure that the panel can see your questions. There is also a helpful up vote button so be sure to upload the questions that you would like to see answered. If you are experiencing any technical issues during this webinar please use the chat feature to share so that our support team can assist. We'd like to introduce our moderators for today. Dr Ahmed Gosh is a consultant and professor of medicine within the division of General Internal Medicine at Mayo Clinic in Minnesota moderator. Dr Devyani Law is the Dean of Education in Arizona, Chair of the division of rhinology and professor of otolaryngology at Mayo Clinic in Arizona and now for our featured experts, Dr Aaron Kumar, Agarwal, Dr alec the car and Dr H R Vikram here are today's learning objectives which will be covered throughout the webinar. Finally, please register to attend our final segment of the monoclonal antibodies and other novel therapeutics in Covid 19 treatment webinar series which takes place on june 30th 2021 at 8:30 a.m. Central US time. With that, I'd like to turn things over to DR gosh, thank you Vicky. I first want to welcome all our attendees from all over the world at different time zones. Taking your time to attend this very important discussion today. Also want to thank our very distinguished panelists who are in different time zones uh in the in the west coast east coast as well as in India. Taking the time to present the expertise. Today, we are at a crossroad of history where really nothing had prepared us for the crisis that we found ourselves in uh India in particular did well last year. They had the first three cases. All three medical students come from Wuhan china On 23rd March last year when they got when they found out that the first cases were identified and India did well. It is september of last year when the cases speak and then they and the case is kind of uh play to down. However, uh, the whole thing, the tsunami of cases started on March 2021 when all of us saw an explosion of case in India led the world in the number of cases and a few days it was over. It exceeded over 400,000 cases of covid 19 as if that was not enough. Uh this resulted in a second crisis, what we call an unintended consequence of treatment management and the complexity of, of covid that we saw an outbreak which we have never seen in the world before of nuclear. My closest we are discussing today and I would like to invite our 1st 1st guest, dr Bill Graham who is a professor of infectious disease in Mayo Clinic Arizona, program director, vice chair of education, a very distinguished colleague, a very dear colleague of mine to discuss the risk factors and why Covid led to before my Croesus not to be trump. You can admit yourself have to become korean mute yourself. Thank you. Okay, can you hear me now? Yeah, sorry, I couldn't see my a mute button at the bottom for a second. Hello and welcome to all of you. Hope you can hear me and thank you for inviting me for this webinar today. What I would like to do in the next 10 minutes or so is to introduce uh McCormick Asus as a disease to the audience and then the rest of the conversation will follow And just click your most once and click one more time. There you go. The term McCormick oh sis has been used interchangeably with zika, maiko sis. The pathogens belong to the order mucus rallies. The most frequently reported pathogens within this order. Materials that cause disease in humans include a risible species, new car and like Tamia, among others. April feeder mice is has been a common species that has been described in India. The mucus rallies are ubiquitous in the environment, they are found in the soil, decaying organic matter, compost and in contaminated foods. The history pathology of patients with McCormick Asus reveal broad based ribbon like moles which are either causes accepted or non cept eight and branch at right angles, which is diagnostic for this pathogen. There are several different forms of music are my closest based on the part of the body and the tissues that they involved and the syndromes that they cause. Rhino orbital cerebral disease will be discussed in more detail in the coming minutes, which involves the sinuses, orbit and the brain in various combinations pulmonary disease. Uh cutaneous McCormick oh sis, which is often seen in both immuno competent and immuno suppressed hosts and as a result of trauma, either because of tsunamis, hurricanes, crush injuries, war trauma or burns with direct inoculation. Guess from the spinal McCormick Asus is often seen in immuno suppressed host as well as in premature neonatal who are on a few feet and who who are on broad spectrum antimicrobials and disseminated disease, which involves multiple organs via the bloodstream. There are several risk factors that have been described to cause my car. My closest diabetes militants either uncontrolled diabetes with without concurrent diabetic ketoacidosis is a major risk factor, especially for rhino orbital cerebral disease. Human logic malignancies and stem cell transplantation are the most common cause of McCormick oh sis in the immuno suppressed population and in the western countries, the main predisposition here is peron and severe neutropenia. Human logic malignancies, especially myelodysplastic syndromes and AML after induction, chemotherapy and stem cell transplantation before in graft mint and in the presence of graft versus host disease. Both are major risk factors. Solid organ transplantation can also lead to McCormick oh sis but less often about 10% of invasive mold infections or do them. You car in solid organ transplant recipients, especially after induction and during episodes of rejection. When the extent of immune suppression is enhanced, systemic steroids also increase the risk for McCormick oh sis in the presence of one of the other risk factors. For the most part, iron overload states also increase the risk because iron is an essential nutrient which increases violence and pathogenesis. City of mucus rallies, intravenous drug use can cause local disease. Or sometimes if the drug is contaminated can lead to disseminated infection, natural disastrous, as we discussed can lead to poor tania's disease. And there have also been healthcare associated outbreaks of McCormick Asus due to contaminated linen from contaminated tongue depressors, ivy, catheters and so forth. Now let's talk about the unprecedented epidemic of Covid associated McCormick Oh sis! And what are the potential risk factors that have led to such an outbreak? Especially in certain countries, including India, let's divide this into host factors, environmental factors and pathogen specific factors. If we talk about host factors, There is a baseline high incidents of my car, my closest in India and some of the studies from India have estimated the prevalence of my car, my closest in India to be about 70 times higher. Compared to global data. On top of this. There is an underlying, extremely high prevalence of diabetes in India. In a study that was published in Lancet Global Health in 2018 by the India state level deceased burden initiative, diabetes collaborators. There were about 26 million people with diabetes in India in 1990. Compared to 65 million in 2016 For every 100 overweight adults over 20 years, 38 had diabetes in India. The global averages 19 on top of this, there is a very high incidence of uncontrolled diabetes undiagnosed diabetes and prediabetes in the indian population. All of this has significant effects on the immune system. There are no beautiful defects for migration and chemo taxes, petition recognition, look side recruitment and there is suppression of cytokine production in the presence of uncontrolled diabetes. On top of these two major baseline risk factors have increased incidents of McCormick aosis as well as underlying high prevalence of diabetes in India covid 19 brought another major challenge which is excessive use of cortical steroids. Now the studies recommend Steroids in the setting of COVID-19 for hospitalized patients who require oxygen therapy or who are on mechanical ventilation. And in this specific scenario, the dose of steroids is six mg of dexamethasone or an equivalent corticosteroid For up to 10 days or less. However, what has happened is there are these criteria have been not. This criteria have not been followed ah As is recommended. In fact in the recovery trial in patients who did not require steroids. I'm sorry. In patients who did not require oxygen therapy or who were outpatients use of steroids had no benefit compared to placebo. And in fact those who received steroids had a higher mortality compared to those who did not mortality benefit was only seen with hospitalized patients requiring oxygen therapy. So in the inpatient setting, number of studies that have come out of India have described higher doses of steroids and parent duration of steroid therapy. On top of that, outpatient steroid use has been significant. Patients have been prescribed steroids when they are in the outpatient setting in an effort to try to prevent them from getting to the hospital as a prophylactic measure. In the absence of oxygen therapy. And in fact, use about patients, steroids can be more harmful because patients may not be monitoring there, blood sugars and they may not even realize that they have pre diabetes and street rights will push them over the edge. Other potential host factors that can contribute to covid associated McCormick oh sis include host factors such as being on broad spectrum empirical antibiotics, which will lead to loss of normal bacterial flora and selective colonization by East and malls acidosis, either from diabetic ketoacidosis or other forms of metabolic acidosis will lead to increase the availability of free iron within tissues and in plasma. And free iron is taken up by moles such as mucus rallies, which increases their pathogen. A city sided coin storm associated with covid also leads to increased risk of McCormick oh sis! Because of a combination of these entities, increased availability of free island as we discussed and enhanced expression of certain legans can also lead to increased risk of McCormick oh sis. How about environmental factors? There is a higher environmental presence of materials um in a certain climates including in India the soil and humidity favours growth of mucus rallies. There is also a potential for contaminated masks, humidifiers, ventilators and other hospital equipment, especially in the setting of a pandemic with lack of beds and also with overcrowding construction sites within the hospital are adjacent areas will also increase the risk of dissemination of soil moles with exposure to patients who have other risk factors, ventilation and air flow issues can also contribute. How about pathogen related risks for McCormick Asus. If you look at source kombi two, as we are aware, stars Kobe to leads to a higher incidence of tissue thrombosis and material damage and impaired local oxygenation as well as systemic hypoxia. All of these can facilitate growth and violence. Of uh new car lymphoma pina is something that accompanies covid infection which can also cause immune suppression and direct damage to pancreatic beta cells with is two mediated versus direct injury can also lead to worsening blood glucose levels. How about mucus rallies? Increased pathogenic city? Because of all of the above factors will lead to angio invasion with thrombosis of blood vessels, tissue necrosis and ah for the progression and rapid extension of the disease process. So to put this in perspective, I would like to draw your attention to a multi center epidemiologic study of coronavirus disease associated McCormick oasis in India. That was published, I had a print in emerging infectious diseases. This was a retrospective study from 16 medical centers, tertiary medical centers across India and this was conducted between September to December of 2020. So this was even before the second wave of COVID-19 infection, They studied 2 87 patients with McCormick coasts. Out of these, 65% were covid associated McCormick. Oh sis median age was about 54 years and 75% were meant More. McCormick closes cases was seen during the study period of September to December 2020 than in the corresponding period in 2019 When there were only 112 cases in the same institutions Underlying disease. In this cohort of patients with milk or my closest 63% had uncontrolled diabetes and it's important to note that 33% COVID was the only underlying disease that led to McCormick coasts. They did not have diabetes. However, in this population Up to 80% of them were receiving systemic steroids. The median time to covid Associated medical diagnosis was 18 days from presentation. So 84 are the vast majority of patients with Covid associated McCormick. Oh, sis had late onset disease which was defined as greater than eight days after Kobe diagnosis and 87% of later on said Covid associated McCormick Asus patients were receiving systemic steroids and this is interesting. The median cumulative dexamethasone equivalent dose was 84 mg of dexamethasone. So if you look at the maximum that's recommended would be six mg for 10 days. That would be 60 mg. And look at the range of steroids that was received 18 2300 mg of dexamethasone. Among these patients, 33 received an appropriate dose and duration of steroids. Another third street rights were not even indicated based on guidelines and the remaining third Street rights were indicated but the dose was inappropriately high in those who developed early Co uh Covid Associated McCormick oh sis. Which is defined as less than eight days after. Covid diagnosis. These patients more often had diabetic ketoacidosis at presentation. So here it was more uncontrolled diabetes with acidosis that probably put them at risk for McCormick oh sis. However, those who developed late Covid associated McCormick oh sis had a direct association with Street Art US. As we have discussed, mortality was about 38% at six weeks and 46% at 12 weeks. And this was identical between Covid associated McCormick Asus and non covid associated disease. Thank you. Doctor thank you Dr Vikram. I would now invite Professor of Global, who is former Professor of Excellence from E. N. T. And X. He was a previous Dean of Ma'am See uh he is hold so many titles and is currently a medical advisor for innovation and Education and clinical excellence at the Apollo Hospital. To discuss the epidemiology of nuclear Michaels is passed and forced. Covid 19 Dr Goran. Thank you. Thank you very much. Uh Professor I met my sincere thanks to uh Manoa original our Dean the journey you and Whitney for giving us this wonderful platform to express. I'll be talking about something about the number game in the past and what happened uh last 1.5 years and let me share with you that because Microsoft is nothing new, especially the topic of countries including subcontinent, indian subcontinent and India also. And if I can have the next late I would like to describe. Uh huh. Yes, you will recollect my colleagues uh ever since we were the student of TNT. And right from those days, the Maker Microcystis had been a focused area in certain part geographical distribution and there is a this PGA of chandigarh is one of the prestigious tertiary care centers who were described the because my closest when paris very few people were talking about it and there were numbers and there were numbers in such a way that perhaps we started thinking that the north of India or that particular part is having definitely a higher prevalence of maker marcoses as compared to south of India. But can I go to next slide, russell? Yes. This is the slide which is being published only a year back. And this was again the study which is the faculty is from pediatrician digger in a sweet journal. And this particular indicates that look the bigger micro C. Is nothing new to and dad worked countries, some of the countries they have mentioned here. But if I try to look into the indian subcontinent, they have given that of India as well as Pakistan. And this particular figure indicates that here comes that maximum number of the musical Microsoft I'm talking or past pre covid And that makes it the India has 70 time higher incidents of democracies with some of the countries It with some of the country it's 10-10 times higher. 20 times higher. But definitely Indian subcontinent has higher prevalence of economic process. And as the victim has already described that here comes the highest number of micro micro seeds and here comes the highest number of diabetes India is supposed known as diabetic capital. Can we go back just a minute? And that is why we can say that there is some sort of marriage witnessed these two. That is what we have to decide. And In last three months We had deported India has reported approximately 30,000. All little more. The exact numbers are not being declared. But whatever. Later the study we could do and the press statement that 30,000. So that makes that every 1000 patient with positive, make sure my uh positive of Covid perhaps had suffered with Michael microcystis. Next line, Yeah. And that is what has been described by. It was a press release from Health Ministry and definitely this was on seven June and now the number has increased and there is there seems to be a geographical distribution predominance in the state of um morass to and in north India in other bodies connector. Then we have the next thing whatever little telephonic survey I have done with the indian cities like and Bangladesh. What I realized that this big numbers in have personally interacted with my colleagues in New Delhi and Mumbai and Chennai and called Kolkata. There's no doubt that the big number of the the indian government has started Michael ward and number our big in numbers for examples in china So far they have treated approximately 700 plus indoor patients in one of the men after a center. The same is true in New Delhi years. So which my colleague dr Alan tucker will be taking on, there are few reference centers and big numbers are being treated. Same is true with Calcutta. But when I inquired about Bangladesh in Dhaka, the numbers are there. But I felt that those numbers are definitely less as compared to indian big towns the same. I tried to contact my colleague in Katmandu. Numbers are there, but far less. I read an article from Pakistan also, numbers are there, they are less semi sri Lanka and just and two hours back, I talked to one of my auntie colleague from Bhutan. He reported that there is not a single case of Michael Mukasey. Oh, my only worry is that why this particular jump over the number of numbers of meters has come to India and of course partly indian subcontinent. Vikram has given a very, very wide risk factors. But my worry is all this respect er, but my worry is that we have faced bigger micro sees during way too. one never know whether we are going to have faith three or not but if at all the We have three times how we are going to take us. I'm sure this particular platform of Mayo Arizona will definitely discuss the preventive aspect of it. That is the most important challenge as an administrator at the public health expert as a clinician for us to answer that is why I thought that represent these figures to you over. Do you want it? Thank you. Doctor Professor Gimbal. Uh dr lodges center chat to me, reminding to mention to all the audience that mu court does not happen in people with normal immune suppression. So the immuno suppression has to be knocked by some ways. Either steroids, diabetes on steroids or some other things transplant or something. You and I are exposed to sports of nuclear all the time. And we don't get it with mask without masks. But something which gets your immunity down uh will will enhance the chance of new car inviting. Now I'm inviting about I mean I mean may I have a couple of questions because I think that Dr Aggarwal led to some very pertinent points. So if we can back up one slide russell. So I think that this is an appropriate time if you go to why India. Right. Um I think that um I have wondered that as as a citizen that grew up in India uh and I really wanted to hone into this message because we have looked at the data from Dr Vikram and we have looked at the epidemiology from Dr other wall and I think there are certain cultural factors that might be pertinent to discuss here because it isn't just about um the prevalence of diabetes. I think the questions we need to ask and answer here is Um in the data that was shown uh 66% or two thirds of the individuals were given steroids at either an inappropriate indications or a prolonged duration of indication. And I think that in the indian public there is a lot of apprehension. I mean I got WhatsApp message from my sister that was forward and said don't go out and do the gardens, they soil and soil has fungus. So these are myths that need to be dispelled. Um And I think that the point that I wanted to ask, Dr Vikram is Dr Vikram you have a vast experience in co managing music or my closest have you seen cases of music or in people who are not immuno suppressed? That's a great question. Dr lal the answer is yes, but very infrequently. And as we alluded to earlier, it has mainly been in the scenario of direct inoculation or trauma. There have been some instances where it has happened in the setting of hospital outbreaks. There have been cases after a surgical procedures with direct inoculation. But once again, it is an extremely uncommon scenario with the mucus really species that we're talking about, that this would affect someone who has a code and quote, normal immune system. If that occurs, it is always good to look back to see if there are inherent defects in the immune system that would have led to such british position. Thank you. Thank you dr long. We need to we need to move to the next speaker, will come back in the question answer session is a very important question. Professor Tucker is the chief of auto rhinology in the premier institution of India aims India and he's at the stellar position and to see to see what's going on in the country. So back to you Dr tucker thank you Professor Gosh and of course thank you to Dr LA land to yourself for the invitation to be part of this. Very exciting where but now we have here. So yes uh Covid associated right now. Opportune miracle, my closest has been a major issue with us at this moment. And uh this curve here quite sort of shows to you as to what the situation has been with regard to Delhi. So in in in the red you see the number of cases of uh covid 19 per day over the past couple of months and you see that it beat it around 20 April and then blue you see the number of cases of medical micro so that were admitted that our inpatient facility and you can see very clearly that the two curves tend to sort of parallel each other. And of course there's a bit of a lag with the musical. My closest and mutual my closest came in at about a three week lad to what we found with Covid. So it uh So uh we have still did treated 200 patients that are in patients. And as was put forth by Dr. this is quite unprecedented. So now we did become aware that this was around the corner and that's about the about the end of May. Uh end up end of april, beginning of May where you see that arrow and we were sort of 41 for two reasons. They of course we have seen so much Covid and we have previously also seeing Covid Associated Medical, my closest but more so as to what had happened in other parts of India, primarily in Marash language Rod, where in the Covid we've had preceded us by about 4-6 weeks and in both instances they had seen a little bit of Milker. So what we did then itself, of course, at once we got to where we were, we flagged it to our colleagues. We did flag that we needed to get ample be deserved up and accumulated in the hospital. And we went on to organize ourselves in having a departmental meeting while putting forth a multi, the spirit clinical care team, putting forth communication of course, uh, to, to communicate with that team. And this team primarily had us entrepreneur ologists of course, the pulmonary american people and the anesthesiologist and of technologists. And this stream of course has gone bigger and bigger as as we have moved on with this uh experience. So, um, uh, as as has been said, this isn't something that was quite new to us. Every tertiary hospital, Portinari hospital has been aware and has been dealing with this and this is just to put things in perspective as to how we were pre covid. So pre covid, this is an experience put together by one of five trainees And this looks at a two-year period prior COVID 2017-2019 when we treated 25 patients in patients and the majority of them had diabetes. So as we do know uh that in the west and you're part of the world, much of mutual microservices because of patients who were treated for leukemias or have transplants and things of that sort. But in our part of the world this has generally been associated with uncontrolled diabetes and diabetic ketoacidosis. In this experience, pre covid we had a 36% mortality. And the point of this particular paper, what they see them certain correlated quite strongly with prognosis. This is something that is becoming fairly common knowledge. Now, I'll now take you back another 20 years to where we were. And sorry. And that this publication from ours was a was a prospective publication which which looked at Michael Michaels is over a two year period again. And we were fortunate to then actually get a good hang on. What were the earliest sentinel signs and symptoms? Which which oh, which would help for an early diagnosis. And basically what we had come up is to say that Perriello discoloration and often Perriello anesthesia, improbable anesthesia for early signs. Of course you can have gangrene. Gangrene is not necessarily an early signs, but these are early signs. And the students in good stead at this time when we had this epidemic with us because we were on the lookout for these kinds of things and patients who have had milka At that moment in time, 20 years ago, a mortality was 67%. And what we learned from this paper and the literature around that time, uh was that the maximum mortality was in week one and perhaps by focusing too much on surgery, surgery and surgery. We were not quite focusing enough on controlling the underlying immune compromise and getting the antifungal treatment in early and I would feel that the reason we have moved from a mortality of two thirds to one third is primarily because the focus has moved on from not just being on surgery alone to also looking at very actively controlling the underlying immuno compromised, which basically meant on most occasions treating the diabetes are treating the entrepreneur and early initiation of antifungal treatment. And the fact that like to zoom in and focus and be also became available at the same time and allowed us to push in far more doses of and focus and be then we could previously probably made a big difference in how we could cut down on the mentality. This is an experience with Covid associated nuclear. My closest three This explain this epidemic of free free this wave and this isn't the 1st 9, 10 months of the epidemic at our institution, where did we have created 16 patients with Covid associated right now because that will make the my closest and this again sort of reinforces the points that were made by dr victim a few minutes ago, which is to say that we found that the incidents had gone up about twice or ESP. So what would what we used to say in terms of this illness previously, but most of it was related to diabetes. Often it was associated a very mild covid 19. So asymptomatic or mild covid 19 And the mortality even in this experience was about the same 33%. The incidents, as was calculated by us based on this experience. And the incidents that have been calculated by the other paper quoted by DR victim again comes to about the 0.25% of in patients with Covid. So, so one in 400 patients with Covid will seem to be having Milker Micros is this is the past. What is in the present? We haven't quite worked out, but it does seem much more than this. So moving on from here, what we did, once we became aware that things were to happen to be set up a couple of documents to educate our uh patients with one of the alarming symptoms to watch out for, why was it happening? And then we also set up another similar documents for our colleagues to look at. I still work so sorry. So what were the checklist of sentinel science and symptoms that they should be watching out for in their patients? We moved under there to set up a guideline for intervention and the guideline for uh for a synoptic flow chart. And here in it sort of says that you need to suspect mucus if you have a patient with the high risk factors, the points that they've only raised up that you need a certain background for this disease to take up and then so you need the high risk factors. And if someone has poor placement control has been steroid with advent treated with steroids and presents with the early sentinel science. We've talked about you need to look at this diagnosis. We realized very early at a lot of these patients with Covid positive and presentation. In fact 85% of the patients and presentation before with positive. So the whole experience of treating these patients have been primarily an experience of treating patients who have been pulled with positive. And we set out as to how we will go about and make a diagnosis. So of course microbiology for swabs and assessment with radiology and blood sugar. But I'll just take it to a couple of slides and the experience as we went through this. So the initial thought was that we would do diagnosis by doing microbiology with with swabs which were initially done Who is blind nasal swabs. Similarly to how we do sampling for patients with covid RT PcR swabs. And that didn't quite turn out to be good enough because the Bohr these uh prostituted it was rather low and once the first four or five days it was pretty clear that blind nasal swabs weren't quite giving is good enough diagnostic yield. We moved on to the mucus screening clinic where obviously we need the whole gamut of of covid 19 precautions and PPS but we do site directed swaps and biopsies. And We now look at microbiology both by by smear examination and buy PCS. And this has pushed up our policy rate to 85 in terms of radiology. Another big challenge because the um are is ideal. Emma is not quite feasible when you have such a high number of cool with positive patients. So we moved very quickly to assessing these patients and the covid dedicated ct scanners that are around the hospital. And the covid dedicated city scanners with a special, uh, especially the sequence set up by a radiologist that the user spread bowlers single phase. So basically they sort of give the bullets in three phases. And the first phase looks at the pianist and the orbit and then another another, another another bowlers of steroid. It looks at the venus stays in the arterial phase. And you can do a full assessment of the pianist, the orbit, the cavernous sinus and the art plays with this uh, particular way of doing things. And this is done very well and has been useful to us. And I'm told us quite viral and radiology circles, we have had issues with the availability of after person be because once the number of cases goes are so dramatically, you can quite imagine that supply chains and are not quite geared for that kind of thing. So we have had some intermittent supplies that have to be uh things are now now now beat it out. Now. We do get the odd medicines quite okay, but they're having issues when we haven't quite been able to use as Madame for B as you would like. And so we have moved on from using amphibious are only and prime drug to using amphibious as the major drug, but also using fair amounts of physical assault. And there has been some amount of triaging of impetus in need. We're in patients in the early phase, first week and progressive symptoms or cNS involvement certainly get the emphasis in that is required. But patients who have come on to two g patients who have sort of had their surgery done and who are otherwise not showing any any obvious disease at that moment in time tend to get lesser answer person day. And we're also looking at moving on to doing Corsicana is all alone for for for the side of these patients. But some of these questions are not quite answered. There's also been some difficulty with regard to when we should be operating on these patients. As I said, we have come to a situation where we have realized years ago, a decade ago that to minimize mortality had to focus not only on surgery but also on getting early antifungal treatment in on this particular occasion. There is certainly concern about going in for surgery early because we know that surgery and anesthesia associated with Mortality and morbidity in patients with COVID-19 and this was bought out by very initial data with this illness. So generally we have not rushed in for surgery for the first a couple of days or even the first four or five days of the occupation being admitted. We have focused more on getting the diabetes sorted and getting the antifungal treatments in and surgery went safe, which basically means the surge is generally occurring at the end of week one rather than immediately. And we haven't quite thought that this is a problem. In fact I would say that patients were and we rushed in. I want quite right and this is experienced not quite with us but with many colleagues around that you have to be careful with the selection of patients for surgery with regard to what is the situation of covid but say for their patients and what is the situation of the underlying immunocompromised and diabetes Before you Russian for search. So I think I would leave there. But just to say that many uh many challenges remain. We have been through the first rush of patients. We have managed to control the disease in most situations, But there are challenges with a lot of people losing their ballots and their of its eyes. And this is about 25% for both. And of course we have experience with prostate antics and we have experience with free flaps and the next space is going to involve this. And there are other challenges challenges to whether how many patients can the hospital actually give and the person b as in patients or whether we need to move to daycare. Whether poster Canosa is going to be good enough for us uh as a treatment support. And and and of course looking at the psychosocial needs of these patients as time goes on. So, thank you for working progress. I think we have done well in the first uh in the last couple of weeks and getting a handle and and and controlling the lesson the large majority of our patients. But some challenges remain. So thank you. Thank you. Dr tucker. Um That was an excellent overview and you and I have had several discussions and written a paper on uh this issue. A couple of questions have popped up in the Q. And a box. Um and some of them pertain to whether Covid itself is causing mucosal erosion and invasion. Is that your experience or it's just more associated with diabetes and steroid use. So our experience, our experience over 200 patients, 189 and uncontrolled diabetes, their presentation. So that pretty much sums up the picture for you. Covid, it seems is certainly unmasking a fair bit of diabetes. It does happen. And as has been put forth already, uh steroids have been used overused Now as physicians were all judged by what appears to and what society is doing. And unfortunately to become the kind of standard out here for uh for having a very low threshold for a steroid prescription with regard to COVID-19. That has changed with this epidemic. And I think that's part of the reason why the epidemic of nuclear has suddenly sorted itself. There must be other issues which we haven't quite worked out yet. Right. And then the other question which has come forward is whether the use of contaminated oxygen has played a big role in this epidemic and what is your experience? So there is no case control of randomized. Of course, there's no case control data also, but in terms of observational data from our own series, this is unusual In our series of 200 patients are only 10 patients who have had oxygen outside of a hospital. Um of course, uh About 50% of patients had the oxygen, but only 10 our patients have had had oxygen outside of a hospital. It doesn't quite seem to be determinant dominant thing out there. And experts tell me that you can't quite expect supposed to be transmitted through humidified oxygen. In any case, I think the one of the things which rise across the EU car is known to have is an enzyme called ketone reluctance and that is the enzyme which allows us to thrive in situation of high blood sugar. It loves high blood sugar and acid environment. In fact, decay is a situation which also has high iron free iron where covid we're sorry, where musical tribes, so oxygen tubes and all that in an intact mucosa or an un intact nickels. And it's somebody who has a good immunity is not going to probably going to colonize, but it's not going to cause invasive new court to the point that we are seeing. So these are excellent points comes up in pandemics. But I also want to thank dr tucker for the amazing on the ground innovation you did with the Newport clinics. And we have and the immense amount of uh uh, catastrophically and and disturbances caused to these patients. You saw the woman with an eye and how she has to live the rest of her life. Uh, so that that is an amazing uh, generation on the run with ct scan. Another generation, they appear coming in. So if it's okay, Doctor Devyani, if you would need the medication management and here we would have a panel discussion. But we would start with Professor Devyani La who's uh whites dean of T. Wear several hats. She's a Dean of Education, She's the chair of rhinology and uh Merkel Nick Arizona and an extremely very well respected both in Mayo and outside of the United States and the U. S. And abroad. Dr lam would you step in and show some of the exciting videos uh that you have on what we expect to see when manny and d surgeon enters while you're doing that. I might bring into attention that which Doctor Vikram briefly mentioned. It's very difficult sometimes to swab and get culture, music or it's it's a very flimsy uh fungus in that sense. If I'm am I right dr Vikram in saying that it's very hard to kind of this culture new car from Nathan's webs. Yes, that's correct. And I will address that when we discuss diagnosis. Thank you. Thank you. Can you advance my slides please? Thank you. Yeah. Just so a couple of points over here just to reiterate and these are guidelines from the E. N. T. Society in India. And I see a lot of attendees are from India. Um I think the points to be made is the importance of nasal endoscopic examination fungus is ubiquitous, meaning that it's everywhere. If you swap my nose and have proper sensitive techniques you'll find fungus in my nose and dr go she's knows and dr tucker's those likely as well. So when you um and Dr tucker mentioned some of the early signs in our organization. If a patient is immune a compromise for example in the bone mary unit or um has uncontrolled ketoacidosis. The presence of unilateral symptoms, fever are early markers of uh nuclear. My closest now in other immuno compromised people. We look for the levels of absolute neutrophils accounts, which is usually not an issue with covid patients. So, um the CT scan, an endoscopic evaluation are actually complementary. So a city or ideally if you can do an MRI, which is contrast enhanced and when you see non contrast enhancing areas that should point you to the lack of oxygenation of blood supply in that area. But the endoscopic examination will actually show you more earlier signs of uh either mucosal ischemia or necrosis. And those should be biopsied. And those are high yield for looking for fungal elements. And if you have the capacity to do an immediate frozen section, that's best. And so late signs involved large s cars in the oral cavity, frozen globe violations, skin etcetera. Next slide. So, um I think the doctor Bikram will talk a little bit about this, so I'm going to skip over. But these guidelines are available next slide what I would really like to talk about and and some of our experts have already done this. Uh So I'm not gonna be labour this point. But reversal of immuno suppression in covid is very important. And the use of antifungal early on. And what dr tucker mentioned is you have to balance out the condition of the patient because they are severely ill. They have bad lungs, they may have thrombosis in their hearts, et cetera. They may be in keto acidosis, they may be uh in um renal failure. So it has to be balanced out between that and when it's safe to take. You should attempt to do that even in a really bad form in a new court cases I don't rush to surgery uh in in overnight situations unless I get an M. R. I. Et cetera when we have bone marrow transplant patients. Because that helps us assess the extent of disease and get the right team together. And sometimes it requires just more than E. N. T. Sometimes you may work with neurosurgeons. Certainly we don't do plastic reconstruction early on. We wait for the disease to get declared and then the defect to declare. And then we involve our theme ologists for early visual uh testing so that we know whether there is any ophthalmic artery thrombosis because you can have a good eye. But if you block thrombosis that can do so too. Next slide. So this is what new court looks like. And I think we call it black fungus because um it looks black and um the funded sports themselves are not black. So I am actually going to go ahead and share some videos here. Um and I would like to show that sometimes we can get by with endoscopic uh, strategies, but sometimes you have to go in with a lot of um, uh, tools like orbital exonerations, etcetera. So, can I go ahead and share my screen, yep. You were sharing? It looked like you were sharing the design view and that looks like, okay. All right, can you see it? We're in design me right view right now. So, if you want to go to the slide you want, is that good? That's good there. Yeah. All right. Let's go ahead. So, this is a case that we did with endoscopic techniques. And I'm gonna run through this. And what I'm trying to show is when you have deeper layers of invasion. Oftentimes the open approach will not actually allow or facilitate uh, access to all these deep areas and where I am going to target this uh surgery is actually in the base of skull at the area we call the terrible part in fostering inter temporal fossa. This is a scary noise sinus back of the nose, nasal hearings. Um And um if you if you don't find the areas of necrosis, for example, this is this area called the terrible palatine fossa which is way back um uh in the deep areas of the skull base. And um we have to find the fact that is actually necrotic and remove still bleeding tissue. Now that is the importance. You don't have to always remove things that are not necrotic. But what is necrotic needs to come out because the fungus um um thrombosis blood vessels, There's local acidosis creation of iron. So once you remove those things um and you get to vascular tissue that allows for the anti fungal is to premiere in there as well. So I will next go to my next slide which is actually um showing orbital equal narcosis. And um we were able to preserve the orbit even when there was no vision or um we did that for cosmetic reasons. Um this may or may not be possible in the Indian scenario. But in our scenario where we were working on diabetics and bone marrow transplant patients, we were able to preserve the orbit in about 75% with 50% having um preserve vision. So this is the right side. And this is actually the I and this gentleman we were able to preserve the eye. He had already thrombosis uh the thalamic arteries. So there was no functional vision. But by leaving the orbit you you actually don't have to do the construction. So this is actually showing debt tail muscle. Typically when we opened up the orbit for us etcetera. The muscles and nice and brown and red here. I'm just reading the orbit and removing all the d vascular tissue. So um I am going to stop sharing and if you could advance russell that would be great. Keep going. Mhm. Okay let's now go to Dr Vikram as slides. Unless anyone has comments or questions. I think we need to go back. Sorry about that. Uh One more slide. One more slide back and that's a blank slide right now. Yeah, well let me leave it there and then I can advance. If you can give me access I will do that one. Thank you. So before I talk about antifa be just a couple of words about a diagnosis of McCormick Asus. The microscopic diagnosis has been addressed for rhino arborio cerebral disease by dr tucker and Dr lal. Now, the other forms of economic losses, especially in immune suppressed host stem cell transplant patients and others any necrotic tissue either in the skin in the Because all areas sometimes in the gastrointestinal tract biopsy is always important to establish the diagnosis in patients with pulmonary disease, which is predominantly the most common in the absence of diabetes, patients present with either single or multiple pulmonary nodules, sometimes with the specific halo sign around the nodules or the reverse Hello sign. Which is supposed to be more specific for McCormick Asus. So any non regular disease in the lung, in the right immune suppressed host, but also benefit from a biopsy because the differential diagnosis is brought once tissues obtained, key to diagnosis will be history pathology and as we discussed, a musical will be uh ribbon like broad based positive spectator, non septet hi Fi. And the reason why history pathology sometimes Trump's culture is because only about 50% of cases will make or growing culture. The reason for that is my core is very delicate and even during the process of culture it might not survive. And a lot of times microbiology laboratories either homogenized or grind tissue, which is discouraged when you're looking for McCormick. Oh sis. There are no serum markers for the diagnosis of McCormick Asus for example, the bitter Diflucan as say in the blood is more for aspic pelosis invasive Canada isIS and other uh invasive fungal infections, but it is not positive in patients with McCormick. Oh sis. Therefore, if the bigger the Lucan is positive, it might indicate that the patient has dual or mixed invasive fungal infection. So let's uh talk about anti fungal therapy. There are only three effective antifungal against nuclear species. Effortless. and be formulations pose the Conason and I'd save your console. Other results do not have activity against my car. There are two major guidelines that Have addressed extensively the management of both diagnosis and treatment of Michael. My closest the first one is the European confederation of medical psychology, in cooperation with the my closest study group, education research consortium that was published in Lancet infectious diseases in 2019. And this is a global guideline with representation from the majority of the countries. And the second guideline was by dr santos, a handlebar from uh that was published in the Journal of Ophthalmology and the diagnosis of rhino orbit, a cerebral disease. So this is a busy slide, but the most important part of the discussion here is as soon as the diagnosis is suspected for McCormick. Asus, early surgical debridement is always helpful and for the reasons cited before to remove necrotic debris and allow amphotericin or other antifungal is to reach the area of active infection for in addition, as was stressed, we cannot stress this enough, cutting down immune suppression, stopping steroids and control of diabetes are key for effective management. So the drug of choice for my car. My closest is Lipid formulations of temperatures and be and there is no two ways about it. The dose should not be slowly escalated, but it should be started at 5-10 mg per kilogram from day one and should be continued as long as it's possible and the drug is available. Mhm. And if the person has pre existing renal compromise than either intravenous, I say the economy or post a console can be instituted However, in the setting of lack of availability of liposomes, elevators and be. But if either pose a kind of tolerance and kindness are available, those should be realized as the drugs of first choice, preferably intravenously so that there is no barriers to absorption of the drug and maximum doses are present in the serum for postcards. All the delayed release tablets are much better than all suspension because of much better absorption and that should be preferred for oral therapy. Conventional effort tourists and should be utilized only when either like Osama, left person or I see the consular post console are not available. And the reason for that is because of significant toxicity is associated with conventional amphotericin B and also because of infusion reactions, which might limit the duration of therapy that we can utilize. Now. How long do patients get treated? Well? That varies. But in general as long as possible use the drug of choice, which is like a normal person. Be and if there is adequate surgical debridement and the patient is responding both clinically and really graphically then treatment can be stepped down to either pose the console or maybe Conason orally. And this can be continued for the long run toxicities of antifungal briefly Africa's and be formulations can cause infusion reactions including fevers, chills and rigors. More so with conventional adventurism. Net For toxicity is the most significant risk factor and afters and formulations both conventional and lipid formulations can cause renal toxicity but it is significantly less with lipid formulations. Renal toxicity is reversible. Therefore, if the creatinine goes up, you can either hold the dose or decrease the dose of aphorism and resume the does after a few days electrolyte wasting, especially potassium and magnesium is almost universal with effortless and therapy and therefore this has to be carefully monitored. So that read me as another complications don't result. And there are several other toxicities which are not as common with regards to assault. Uh We're referring to both the council and I see the console with new car. Hepatic toxicity because of their hepatic clearance should be looked into cytochrome P 4 50 inhibition. All is also cytochrome P 4 50 inhibitors or drug drug interactions has to be carefully looked into. All is also lead to QT prolongation. Except I say we cancel which shortens Q. T. Interval duration of antifungal therapy as we discussed is based on several factors. There is no single recipe for all forms of McCormick oasis and it depends on the site of infection, extent of surgical resection and residual disease. Uh correction of underlying precipitating factors such as diabetes ketoacidosis, steroids and decreasing immune suppression and Tyler ability of antifungal therapy. Treatment should in general be continued until resolution of science and symptoms of infection and evidence of substantial radiographic improvement. So, with ongoing improvement, as we discussed, intravenous aphorism can be switched to either or post Conason. RscG Conason as ongoing uh continuation of therapy and total duration of therapy can sometimes people several weeks to months in some patients who have not shown adequate response to Libya Somalia fritters and be alone. We sometimes use a combination therapy with either put the candles on our savior kind of song. The data is not robust for using combination therapy but it has been utilized. Some centres including us had utilized a junked of therapies including uh a turnkey later differs Iraq's but uh a randomized trial mainly in uh leukemia and bone marrow transplant patients did not show improved survival with concurrent use of the first Iraq. So we are not doing that at the present time. Yeah, I think I will stop there with regards to the management of uh, McCormick Asus from an antifungal perspective, did you want me to continue with my slide on prevention? Uh dr victim to you uh finish the prevention slide and we can come back. Absolutely. This is one very important topic. Thank you. So, as far as prevention of Covid associated Michael. My closest I think we have touched upon a lot of these. Uh, here are some of my thoughts obviously first and foremost, uh if we can vaccinate the community, obviously, the vaccines available against Covid are extremely effective, especially to prevent severe disease. Hospitalization and death. And all of the vaccines have done an excellent job at this. And therefore as we increase the vaccination rates in all of our communities, the incidents of my car, my closest will hopefully also come down. We need to enforce and follow guidelines directed use of system a cortical steroids and we have stress this point enough and I won't belabor that intense blood glucose monitoring and management of known or newly diagnosed diabetes is also critical. And this is especially important in patients who are not in the hospital where we should also prevent use of steroids. We need to reverse both tissue hypoxia at the local level and the stomach hypoxia as well as acidosis because both of these contribute to Patrick's in the city of McCormick. Oh, sis aseptic precautions uh in the hospital with various equipment would probably also be a good practice, although a direct correlation with me or my closest has not been established. Personal and environmental hygiene. Likewise, we need to minimize and discontinue broad spectrum antibiotics. In patients with covid 19 associated pneumonia, The incidents of secondary bacterial infection is actually very small in patients with covid pneumonia. And we do not start broad spectrum antibiotics when patients are hospitalized with covid pneumonia, it seems to increase in incidents as patients spend more time in the hospital, especially if they need to be ventilated because these are secondary hospital acquired infections. But there is no benefit of using broad spectrum antibiotics in patients with covid 19 pneumonia following admission. And this might also help with preventing covid associated McCormick, oh sis. And lastly, if available, monoclonal antibodies uh Can be utilized for patients who are symptomatic and are in the outpatient setting but are considered at high risk for complications from COVID-19 as it has been shown to prevent hospitalization. And I know that this is uh difficult and it has just been showing some early signs of approval in India and there are several logistic challenges for administering monoclonal antibodies. But this is certainly one way to prevent hospitalization and severe covid. And these are some of the measures that I thought would be beneficial in preventing covid associated McCormick closest. Thank you. Thank you dr victor. Um That was an outstanding overview. Very thoughtfully done. We have um can we go back to the last slide um and um I'd like to now get our panelists on the screen. We have some questions with regard to covid. So uh some of the questions pertaining to the use of steroids when they are indicated and not let our experts, doctor Gao Xin uh Dr Vikram who are experts comment on that doctor, whatever you want to take it. Sure. so indication for steroids in patients with COVID-19, correct? Yes. So steroids, the The study that established the utility of steroids and patients with COVID-19 was the recovery trial in the UK. And based on this randomized trial, the benefit was seen in patients who are hospitalist and require either oxygen or mechanical ventilation With underlying COVID-19 infection and pneumonia. The mortality benefit was established only in this group of patients. However, when they also analyzed the group of people who were not hospitalized and who were not requiring oxygen, there was no mortality benefit. And in fact, there was a slight increase in mortality in patients who received steroids in the outpatient setting and in the absence of oxygen therapy and oxygen requirement and steroid use. The reason why they go together is because once you require oxygen, it indicates that the infection is in your lower respiratory tract. There is increased information and markers of inflammation are elevated and therefore using an anti inflammatory such as dexamethasone, there would be beneficial and there have been multiple other studies that were done but much smaller and other studies were abandoned after the recovery trial results came out and the does that is recommended is six mg of dexamethasone per day for up to 10 days. It is not that everyone has to get it for 10 days, it's up to 10 days but not beyond that. And if the patient's oxygenation improves and if they're ready to be discharged, they do not need to continue straight rights. Even if it's two or three days you can stop it. Thank you. And I think there were some comments on why this happened in India and I think that um for people that live in practice in India, we understand that prescriptions without a doctor's note are not difficult to get by. But by the same token, I think it was Dr. Aggarwal who in a pretty discussions mentioned that now there is a great hesitation amongst the public on when and when not to take steroids. So perhaps, you know, reiterating that following guidelines. Um and there are some indian guidelines put up by uh Dr tucker's group from AMES um as well on when to use steroids, when not to use steroids monitoring blood sugars, etcetera, deductible. She had a comment on that. My question is on why guidelines are made, guidelines are made in moments like this of chaos and uncertainty where there is radiation of literature and evidence. Um So different exports like Dr Tucker Dr Aggarwal and others like you, we sit around the table to look at the evidence and come up with a consensus statement guidelines are basically road maps, but you have to use your best judgment. What really happens in moments of uncertainty and chaos is a fear sets in and panic sets in which causes an emotional freeze. It kind of hijacked ceramic doll and everybody's running towards, okay, there's oxygen, there is no lack of oxygen. The shortage of oxygen shortage of medication. So people are buying these medications there, they really don't have a, even if they know the guidelines, they are in a position not to use the guidelines because of what's going around them. So there's so much noise in the system. So it's at this time when policymakers and leaders and dr randy galeria who's the director of aims and my senior from kindergarten, I see him frequently in the tv talking and reiterate a ring and it would need respected individuals like dr parker doctor when the pool area and others to come up and reinforce it, just like what Dr Vikram said, it's good to see what the pattern is, like amphotericin B and the other Antifungal dazzles. But then you run out of it, you don't have these medications and there is no real when it comes to a patient, you don't know whether you're going to give it for weeks or two months depends on the case. So there's so much variability, it causes panic among people and even the supply chain issues uh come into crisis and that is what the position is in the ground. It is not to criticize one or the other. This has happened through the history of pandemics everywhere. Um and so many medications. I saw a question come up and we can probably cover it on zinc used in India. It has been recommended. But the zinc in any way can prevent musical uh because iron of course is causing excessive iron is causing musical. So I have not seen any evidence to this fact. Dr vikram doctor Tucker, have you seen any evidence for the use of zinc? So zinc has been used and were used in India with the past uh last year or so, primarily with the presumption that this isn't a an immune modulating drugs which helps and probably overused. And certainly now there is some uh some some research ongoing that will try and answer this question as to whether zinc has uh going to see them levels, have anything to do with the epidemic of mucus that we have seen here. It's an open question. We should have an answer in a couple of months, I would think. And yes, it was sort of put forth as to what we should do for prevention. So I think there's been a great learning, I think the glucose put it away rightly when he said that there was a lot of panic with covid in the preceding four months. Um, oxygen uh did come to critical levels in a few cities, but not quite everywhere in the country. Nevertheless, we saw this kind of problem everywhere. I'm it does seem that uh that nuclear is no longer seen with the same intensity as it was seen in our city and other cities as the covid razor moves on from state to state. There are still parts of the country which are now having their covid ways so to say and have. Uh, but we nevertheless haven't seen the same intensity of nuclear on this occasion. So I think many doesn't happen learn. And I would sure over the next couple of months you would have answered more questions. That is this related to the virus variant? Is this related to something in the environment, The weather, Is this related to overuse a drink and things of that sort? I do hope he'll have some answers in a few months. Thank you. Doctor doctor if I may take a couple of minutes. So the issues inc and its uh immuno modulators. Three role. It's been studied for various infections and once again you're absolutely right. There is no hard data to suggest that it might prevent covid or later complications. And the National Institutes of Health NIH guidelines which are updated almost weekly or every other week here in the United States. Even the most recent guidelines at this point do the lack of data does not endorse zinc, vitamin C. Or other supplements to be used to prevent covid related complications. So that's when the second part is when we were talking about the enormous use of steroids in India and both in the inpatient and outpatient settings. So the inpatient setting I suppose is easier for clinicians to control once they're in the hospital as long as they are educated about when to use and when not to use fear rights, but based on the innumerable, a number of consultations through WhatsApp and other media that I got from my colleagues in India and others and relatives and friends, especially in the last few months. Uh I felt that it was more to do with the lack of resources and beds in the hospital and the fear and panic that ensued. So patients resorted to measures including use of steroids at home in an effort to prevent them from getting to the hospital or to be in a situation where they need a hospital. So unfortunately this led to increasing sugar levels even before they were hospitalized and set the stage for michael marcoses to sort of take over. And a lot of them presented with high sugars and even in the absence of diabetes now and the only other point I wanted to make was not just McCormick. Oh sis, we should also be careful and realize that there are other infections that high doses of steroids can also unmasked in. Certain patients. In the most important ones would be underlying chronic hepatitis B. That can reactivate with high dose steroids. Uh India has a high incidence of baseline exposure, stranger anxiety. So disseminated strangely these infections has been described with high dose the Street Rights. Likewise, mycobacterium, tuberculosis and herpes infections including herpes simplex on her disaster. All of these also need to be looked into when uh disproportionately in the street right is noted. Thank you. One of the things which came up Dr Vikram in one of the webinars. Dr Sachin joshi because the I think is the Dean of the indian College of Physicians mentioned that there was a lot of fear among people living in the community that if they have covid or if they come out with covid diagnosis, uh there is a stigma around their apartment complex and all that. So a lot of them did not come out with to get tested. They took steroids because when they're having these problems on their own, um and this was a difficult situation which led to a lot of complications down the line because they wanted to keep it to themselves and not come out. So there are many factors, everybody knows the evidence, evidence is clear, but uh this is expected human behavior which can happen because of fear and cultural issues. I'd like to take the next five minutes to address another topic that came up. And this is from dr Robbie Mayor. Um And this involves more intracranial thrombosis and um cerebral thrombosis etcetera. Um And I I can share my experience but I also like others to comment. And I'm going to actually share my screen and um share a video of a patient with cabinet sinus thrombosis. Because it's on a question. And the questions for the panelists is um that how often are you using um and traumatic you know and anti traumatic et cetera for patients with thrombosis. In my experience as as in this when you have a deep invasion of the uh the cabinet sinus etcetera. Some of these prom by will break and cause trouble, symbolic uh episodes. And in two of my patients I actually had middle needle trauma, middle cerebral artery thrombosis that resulted in minor strokes. So we do tend to put them on anti traumatic, but this is a case where um the entire cabinet sinus was thrombosis. The karate Audrey was thrombosis and this is actually on the right side. This is a solenoid sinus and um my neurosurgical colleague and I are working together to open the cabinet sinus after having cleared the orbital apex etcetera. Um And honestly this gentleman had severe immune uh irreversible immune problems and we can save his life. But I don't know whether anti tom biotic tom politics are going to work in a situation where everything is just from brasov in such a dense fashion. But certainly I think in patients that have video an artery thrombosis etcetera it might be helpful. So comments from any of the panelists on that. Sorry sir. Yes sir. Yes I agree with you there johnny wasn't the interest and sinus or any other was restructured. It totally thrombosis. But if the hardly had any role of any medical treatment and a good surgical intervention, a good department is the only solution dr tucker so progressive Trumbo's. This is certainly a very definite indication but non progressive thrombosis. I mean you really need to balance it out in the situation because in a situation where you're planning surgery that there's an open wound healing the secondary intention, you do need to be careful as to whether you want to use anticoagulants. So we do use them. We use them carefully. I am not not routinely. Yes. So um we have a few minutes left. Um I first of all wanted to take this opportunity to thank you all for being here today um and sharing each element of managing covid 19 and its associated uh devastating you quarrel my closest epidemic. We have some final conclusion slides that we prepared. Um and doctor goes, uh if you want to sign off on that and I do want to go ahead and invite you to our next webinar which will be on june 30th and this is actually about deployment um and the operational expertise required for deploying outpatient monoclonal antibody therapy. Um Please do register for that, but over to you Dr gosh, thank you Dr laura. So in conclusion, what we realized from the talk, which was given by our expert panel is that there is a high prevalence of covid associated medical microcystis in India because of high baseline prevalence of diabetes medicines and and excess use of slides. Can you get back to the slide just so can you get back to the slave yet? But I'm working out, sorry, it's something that happened on my cereal, it's back up um and excess use of steroids among other factors and we are still learning it and we will probably find more uh if I were to write the conclusion slides six months later from doctor Doctor's data, there would be some additional points as to what we have learned in the first bulleted point. An early diagnosis of Covid, a socialist medical micro sis requires the identification of the appropriate training orbital of cerebral symptoms history wise, which was mentioned and then the appropriate diagnostic. Usually it's an invasive test with the biopsy, as was shown toward excessive morbidity and mortality. And here the knowledge of the public educating them is very, very important. As was shown in the games data treatment of CAM uh really includes a team like team based approach with E. N. T. I. D. Ophthalmology, pharmacy policymakers for supply chain issue social workers and many other specialties plastic surgeons, among others and probably even priests and rabbis to comfort patients and their families. And finally the prevention strategies cannot be emphasized further the ability to use evidence based guidelines. Covid vaccinations. So even if you're diabetic and you don't have covid because of your taking the vaccination might help. And selected use of monoclonal antibody and selected outpatients. Yeah. Understanding the cost and the logistic use might be of benefit. Having that in conclusions. It's a humility with great humility uh with and encourage with what we are working towards is a problem which is solvable and it's getting under control. And I thank you all for taking your time at a very late time in India to listen to this our weapon or what do you dr love? Thank you dr um in coach. I think this panel was put together in basically a week and um I think that we continue to learn. But I take this one moment to thank all our colleagues in India. Whether they are otolaryngologist, whether you are community doctors, the population of patients that has come down sick in this pandemic is truly overwhelming and overall, you know, I am On what side with lots of my medical school friends, et cetera. And there is no one that has not gone to work because they wanted to stay at home. In fact, one of my colleagues who ended up with COVID-19 was impatient to get better and go back what you have done with a large number of very ill patients and relatively limited resources, given that so much has to be allocated to so many people. What you've done is truly stellar, commendable and and the time will come and I just wanted to be ahead of that time to just salute you all on the ground that are working so hard for for our patients. And I grew up in India, have family in India and I know that the future of medicine is very safe in your hands. I do want to thank you all for doing all that you do. And I like for Dr Aggarwal and Dr tucker to have the last word here because you are our heroes. And before they do that, before they have the last word uh Doctor Lol, I would like to 100%. I call your sentiments and feelings and thank you so much for giving me the opportunity to speak today. Thank you. Mhm. Yes, there were many I think, thank you very much for this particular platform. The only thing I want to say that every time we learned in last three months, a lot about second wave and last 1.5 months we learned a lot about Michael my process. I remember when it started coming as a log beautifully saw that there was a three week gap with the onset of second wave and the onset of patients reporting with me for my process. And that particular I will like to say opportunity to medical profession to understand, to learn as we like the way it was picked up. Even the media was also very proactive and the public has also picked up it so well that they have understood the various risk affected themselves. Of course the government is doing their best and we individually and the associations and it stood like all indian stood of Medical Sciences department of TNT are doing absolute public awareness but they have understood and the outcome is that our luck will agree with me that now the numbers have decreased right? So whatever we were getting 1.5 months back now, the number had victories all over India. So that is a good sign that uh public health approach is very important. Besides all the points, every one of you predict vikram and vaccination, diabetes control, availability of the latest medicine. Everything is very important. But more important is that there should be rational use of drugs. That is the most important. Key masses. Two our people through this platform. Hello. Yeah. Well I will say congratulations to all three of you really for putting this up because uh yes it's an important matter to discuss. Uh it's been a learning experience even here I think we have confronted some hard truths and voice them not not us but as a community, as a nation and I had a sort of come out with what could have been done better and as dr drug otherwise just said that this has been uh bruising experience. But nevertheless it is something that seems to be very much in the way in at this moment. Because lessons have been learned quickly. Lessons have been learned the hard way. But they've been learned quickly changes palpably. I do hope we don't see much of this against thank you and congratulations for making this happen because really disseminating this information and what we've been through is very very important. But I sent for others. Yes shouldn't happen again. Thank you dr tucker. And lastly I'd like to thank two people, Whitney Pruitt, who is our cmi specialist um and Russell who is our R. A. V. Specialist. But the person that I want to thank most at this time is Doctor Amit coach, who basically um I called one day and said can you do this? And he put together the slides, he was still putting together the slice last night and he was still putting it in this morning, and his um and he's so thorough and so good. So I want to thank you all and uh godspeed and be well, thank you, enjoy your day. Bye for now. Thank you. Thank you. Thank you very much. This was amazingly done. My job as a moderator is too make the speakers look the best they can. So, I was waiting for dr Aggarwal slide, which was so important, and Dr Vikram did at such a fantastic job of editing and what I thank you. Dr lal is your brilliant way of putting Q and A between the talk. That really made me calm down saying, okay, we are going to have a 30 minute Q and A. But it is interspersed because I was really worried about squeezing dr Vikram stock, which was so good the last part. But I didn't have to do it because you're brilliant. You kind of got that up front and so we got the portions we need and all the essential questions. That was really good. And the questions that came in were really good as well. So they helped highlight and um you know, I will say that um for the next seminar, I think we have another moderated uh dr Sharma, MS Anita Sharma. So that's going to talk about monoclonal antibodies etcetera. But vic, I know you've been through personal loss in this pandemic and um you spoke so beautifully with so much expertise and evidence and so that was just outstanding. And I meet you're moderating skills are amazing and I I am just blessed to work with a group like you all. And I would just say that it's uh it's just you know, we need to continue to work hard and can you to do what we can as an organization to help out with this pandemic all over as we get better in the United States, lessons learned and sharing them widely. No, it's uh it's it's this time where uh I don't think you can hide your expertise if you have it, please come forward. Dr Vikram and I, we have gone through so many slides, so many editing and I kind of gave him some clues on just put the data on the prevalence and he did a fantastic job digging. I'm sure he had to spend a lot of time doing pop met searches and calling people that really set the roll ball rolling. And Dr Aggarwal came up with some blockbuster slides today. Uh so because of the time difference you're sending at, your time is three o'clock in the morning for me here, but I did make out and then I'm sending it to dr lal and she's saying I can't see it in my ipad, whatever it is. Go forward. Yeah, I get the green light from the boss. I said okay go forward. And we have not had a discussion so that I think the half an hour, three Webinar discussion and Russell did a very good job of reviewing, going through all the slides that allowed Dr Aggarwal to pick in. I put that slide, why did you delete that slide? And those things were right and then dr lal beautifully put some of your slides to her discussion and it came out beautifully, this is what editing is all about. And uh I think this is what movie directors do flipping back and forth. But it came out very well and I think the brilliant thing came out with dr Vikram stressing I should start it. And he said the ball rolling very, very well. So I can't, no, thank you so much to all of you. Thanks mate for putting all the effort in editing the slides and this is a fantastic presentation and I'm so fortunate to be part of this. I appreciate it. Thank you. Have another meeting to go to. Uh thank you all. So great to see you. Uh Dr Aggarwal Dr tucker. So nice to meet you. I hope we can keep our conversation going. Certainly there. Absolutely. Take care. Thank you. Thank you Devyani. Thank you, become bye a look. And everybody, Whitney and Russell, you're welcome back to.