Lee C Rogers, DPM explains amniotic tissue products and their role in wound healing. Dr Rogers discusses the benefits of using amniotic tissue based products opposed to other cellular tissue based products.
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Release Date: 03/16/2018 Expiration Date: 12/31/2018
Lee Rogers, DPM
Amputation Prevention Centers of America
White Plains, NY
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TAPE STARTS - [00:00]
Lee Rogers: But I’ll start of myself with a talk on how amniotic tissue is changing the paradigm of wound healing. We're all familiar with, you know, probably every day in your clinic, a new company comes in with some new tissue, especially in the amniotic tissue world, you know, there's got to be at least 18 to 20 different companies that are in this space now, larger companies, it’s easy to bring an amniotic tissue to market, so even some smaller regional companies are popping up. But if you look at the tissue as a whole, that’s what I’m going to talk about, and how this is helping to change the paradigm in wound healing. So why is this even an issue and why are we talking about new products that are coming through? And one of the reasons is because of the very high cost in the diabetic foot. So the lower extremity accounts for roughly 33% of the total direct cost in diabetes in the United States. So, some of the data, more recent data, where we have four years worth of data is in 2007, $174 billion spent on diabetes, a third of that was due to the lower extremity complications of diabetes. But if you take people with diabetes and a foot ulcer, and you compare them to people with diabetes with no foot ulcer, but the similar complications, what you see is that the relative cost of care is greatly increased in the patients that have foot ulcers. So we have, on average, $26,000 a year, the spent on a patient with a foot ulcer versus $5,000 spent net year on a patient without a foot ulcer. And then if you look at why this is happening, diabetic foot ulcer patients had a more hospital days, six in a year on average versus one and a half to those without foot ulcers, and that carried on into year two, but they also had more emergency department visits. So, really, the last bit on why this is so important is because of the recurrence rate. Roughly 50% of those who have had a diabetic foot ulcer after it heals, roughly 50% will re-ulcerate within one year. So it’s really important to look at that when you’re considering everything in cost containments in what we're trying to accomplish. So, amniotic tissue fits into the paradigm of wound healing in a particular place, you know, we have to think about the whole algorithm when you start with infection, perfusion, offloading, debridement and it’s not until you have an adequate wound bed prepared in most cases where you’re thinking about what kind of tissue to use. Now, in some cases, you can use tissues to cover bone and tendon and we’ll talk about the differences in different tissues and how we can accomplish that and where amniotic tissue fits in. But it’s usually not until you’re all the way down to the level of a prepared wound bed in order to use this type of tissue. So if we look at amniotic tissue specifically, it’s been used and described in the clinical literature since 1910. There’s several in vivo studies, it’s been shown to be nonimmunogenic. If you think about one of the purposes of the amnion is to help separate the mother’s immune system from the fetus’s immune system, so there are no HLA receptors on either side, so you’re not going to get an immune response if you bury this tissue. So it’s not like transplanting a kidney or other human tissue, where you have to worry about rejection. This type of tissue would not have rejection. And it reduces inflammation, reduces scar tissue formation and it contains a lot of essential growth factors. And in fact, even when the amnion is damaged, it can repair itself. So, through amniocentesis or if there’s amniotic rupture, in some cases, it can repair itself because of all the growth factors that are present. So, what I would ask you to do is to think less about these types of tissues and these are in a broad category now by CMS and FDA will be following suit. You may have heard of the new acronym called CTP, Cellular and Tissue-based Products. And so, CMS is putting everything in this one bucket, so it doesn’t matter whether it’s alive or not alive, it’s all going to be categorized as a CTP, Cellular and Tissue-based Product. So instead of thinking about it like a graft like an autologous skin graft would heal a wound uniformly at the same time. What we see when we use tissue-based products is that it still heals the wound from the margins in, that’s secondary intention, it just heals them faster and that’s because of all the growth factors that are present. So, what I would encourage you to do is think about these tissues less like a graft and more like a pharmaceutical, where you’re placing growth factors on the wound and you want those growth factors to interact with receptors on the membranes in the cells that are present in order to get that wound to heal faster.
Now, if you don’t do a good job of debridement or there’s a lot of slough in the way or even an old graft that you kind of left, you know, sometimes the reps will tell you, “When you come back in a week, don’t do anything to the wound, it’s going to look bad but don’t just put another one on top of it.” And that's really the wrong thing to do in these particular cases, you want to debride that and have good clean wound bed with receptors that can actually interact with these growth factors you’re going to put on. So looking at different closure options, we have autologous skin grafts and we’ll look at the pros and cons of this, the pros and cons of other skin substitutes or CTPs and then amniotic tissue. But autologous skin grafts, these are things like either a split-thickness skin graft, as you can see here, harvest it from the thigh, could also be an epidermal graft. The pros are that they’re an autograft, which is really the standard of care for covering soft tissue defects. They have predictable healing, they’re generally a lot faster at healing than trying to heal secondary intention even with growth factors. The cons are that there is a cost associated with this mostly within the split-thickness skin graft group because of anesthesia that’s required, so there’s an operating room visit, so there is an added cost to this. There is donor site morbidity, although rare, almost nonexistent with epidermal grafts, but in split-thickness skin grafts, there is the risk of donor site morbidity, even though it's rare but when it happens, it can be problematic. And then there’s also the risk of an incomplete take, which you might consider a failure. However, I think that incomplete take in a patient, especially a comorbid patient, is not a failure as long as you’re getting some reduction in the wound area. So, let’s look at non-amniotic CTPs, so this would be things like Dermagraft, Apligraf, any of the ones that are nonamniotic because the talk is about how amniotic tissue is changing. So the non-amniotic CTPs, the pros are that some of these have living cells in them, there is PMA level evidence. The way that these things get cleared through the FDA, I think, is important but some of them don’t have to produce much data at all to get an approval, others have to go through a larger process to get approval. The PMA process is probably the most difficult process for this group of tissues and they have PMA level evidence to show that they work, which gives them a good history. Then the cons are there is an increased cost to these. There’s a lot of wastage, and I’ll show you a slide on how to calculate the amount of wastage and that actually increases the cost, because you’re wasting a lot based on what needs to be covered. There are some storage issues. If they’re frozen, having a freezer, if they’re not frozen, they have to be, you know, they only have a five-day shelf life. I don’t know if Bob [Phonetic] has any snow days down here, Bob, do you get snow days? No. You get the haboob days, right, with the big dust storms. But, in some parts of the country, you know, with snow days in clinics, there could be an issue with some of these products expiring while they’re out. And then another problem is that you can’t cover bone or tendon with these, it’s not FDA approved for covering bone or tendon. In those of us that have done it, it hasn’t worked that well for covering bone and tendon. So, when we look at amniotic tissue now, the pros are that these are an allograft. There’s no donor site morbidity because, obviously, there’s no donor site even though it’s human allograft. They’re sized appropriate, which will reduce the cost greatly. There are outcomes that have been published, in fact, there’s all book on amniotic tissue now on the outcomes and there are constantly new studies that are coming out including a new study that was just published a few days ago with Chuck Zelen as one of the authors looking at amniotic tissue and a randomized control trial showing its utility. They do have more growth factors versus host tissue, so even though we’re using autologous host tissue and that may be the standard, these tend to have a lot more variety of growth factors available in those cases. You can cover bone and tendon with this and bone and tendon exposure is a big problem especially in limb salvage, and so this is one option. Many times people are using negative pressure in combination with this in order to cover bone and tendon, and an incomplete take is not a failure because you don’t consider these to take like you would a split-thickness skin graft taking.
This is a sheet of growth factors that’s being applied to a wound and causing it to heal faster by secondary intention. So the cons in this group is that they still cost a lot of money, you know, there’s so many companies now, you can look at different companies and see what’s going to be the cheapest for you to get. There is some insurance coverage issues depending on which insurer, whether it’s private. Most government insurers are covering most of these now and that it does require multiple applications. Again, looking at the studies from different manufacturers, some applications as little as two to two and half, and others, you know, up to like eight applications in order to get complete closure. So, to mention size appropriateness, this is one of the big benefits of amniotic tissue especially over the other living Cellular and Tissue-based Products like Dermagraft and Apligraf. And it’s based on the median size of ulcers. So if we look in the United Sates at the median size of diabetic foot ulcer and a venous leg ulcer, the median size of a diabetic foot ulcer is about the size of a dime. And, we all remember the big ones, they come in, but if you look at the median size, what the median is, it’s about the size of a dime. The median size of a venous leg ulcer in the United States is about the size of a quarter. So, when you take those sizes and you put them into what is unfortunately through the PMA process, it can’t be changed. These sizes of grafts were approved by the FDA for Dermagraft and Apligraft, you see the square a Dermagraft and the circle as Apligraft. So if you take the median size, you see how much wastage you’re going to get and all of these cost a lot of money in order to do that. So instead, if you use what we have over here, which is a more sized appropriate graft, you can get something close to the size of the ulcer and these things are a lot, instead of being $1,700 or like $300 and there’s little wastage. So let’s look at a couple of cases, so one of the cases is using a peripatetic legalization. This is using in the hospital outpatient department. And we can see we have a patient here with a dorsal ulcer. This ulcer has been prepped and it’s ready for closure, so it’s granular, it's leveled with the surrounding skin, there’s no infection and vascular has been, profusion has been assured. So, in this particular case, I’m most experienced with Epofix. Can maybe somebody hit forward on this, you have videos not playing up here for some reason. Okay. So, this is the graft applied on the ulcer. This particular graft, you reconstitute with saline. Here’s one we gladder, you can already see that the margins have advanced. So this is what I’m saying you would want to debride this. Even though the wound is improving, you don’t have to do a big wide debridement, but you can at least take a curette and do a, what we call, a maintenance debridement and remove that tissue, that superficial, in order to get good wound based to have application of that next piece of tissue. Next piece of tissue applied, here’s another we gladder and then here’s the last week with the piece of tissue, and I didn’t debride this at this point because this looked to be epithelialized to me, so I left that alone until the graft is ready to come off, what you did here. So then, we use an electronic medical record that documents the different things that we did at different times. Patient came in this day, this was the first day we saw the patient, had the same patient here. First day, we saw her, we took her to the operating room, made her wound much bigger, she had a dehiscence so we made it bigger, put a VAC on it and you can see here, this pink X is VAC. The red carrot is debridement and this plus sign is Epofix. So we did a debridement and a VAC and got smaller, debridement and a VAC stay the same, so then we said, “Okay, now we’ll do debridement and Epofix much smaller, debridement and Epofix much smaller, debridement and Epofix, and this is the volume. Volume went to zero and then the nurses were just measuring the graft on top at this point until it was healed. So, looking at amniotic tissue to cover bone and tendon, this is one of the better uses of amniotic tissue in the operating room for limb salvage. David Pugach, who was my former fellow and not current partner, and I did this post presentation on case series of patients with exposed bone and exposed tendon.
But some of our cases look similar to this, lateral heel infection, wide debridement, partial resection of the calcaneus, here, you can see a little bit of calcaneus is exposed right there. So this has to be taken back and cleaned up. Infection is pretty much resolved, we’re ready to move on to the next step. So, we use a Versajet hydroscalpel on this particular case, debride the surrounding tissue and you can see the bone still here in the center. Here’s what it looks like after it’s cleaned, and now it’s ready to have a graft applied, so we applied the amniotic tissue here. We like to put VAC directly on top of this, the foam directly on top of, no interface. There are decisions that you have to make when you’re deciding on whether to use an interface or not. Interface is like silicone or Vaseline-impregnated gauze, anything that would interrupt the foam interaction with the wound, that would be an interface. Those interfaces are good for split-thickness skin grafts because you don’t want granulation tissue to form on your split-thickness skin graft, you want it to epithelialize. But when you want granulation tissue, you want the foam, which is black; it’s called GranuFoam, it’s GranuFoam for a reason, it granulates tissue. You want the foam to interact with the wound bed and to spark granulation tissue. So we put the foam directly on top of this and we leave it alone sometimes as long as seven days and don’t change it. And then they come back, and this is only one week later, had a lot of contraction on the margins. There’s still a deep space back here but no bone exposed anymore, so the bone is all covered. So, we can move on now to, you know, the goal was to cover the bone and tendon. We got the bone and tendon covered, now we move on to something else using a skin stretcher, stapling the anchors along the edges of the skin. These wire shoelaces through these anchors and then you twist this knob and it kind of pulls together like a core sitter shoelace almost. And then after three days, take them back to the operating room, suit ret closed, that gives you enough redundancy in the skin so you’re not worried about a dehiscence and then here it is after it’s healed. So here’s another case, this was the first time I’d seen this lady on this stage. She came to me referred because they could not heal this venous leg ulcer. And so you’re probably looking at that saying, “Well, it doesn’t look like a venous leg ulcer”, just the same thing I said. It’s necrotic tissue exposed tendon here and here, so it’s definitely not a venous leg ulcer, that’s not the characteristics of a venous leg ulcer. She, in fact, may have had some venous disease but really her etiology for ulcer was arterial. She was 89-year-old smoker, had an angioplasty done, really just in the SFA, which gave her enough tissue, enough perfusion to heal from that point forward, so did a nice debridement, VAC it. Now, we get still tendon exposed here, tendon exposed here, tendon here. So we’re not really ready to put a split-thickness skin graft on this yet and it still kind of looks sloughy. So we take back to the operating room, debride this off again with, I think, in this case, we use an ultrasonic debrider. And then you can see right here, there’s pieces of Epofix, in this case, covering these areas but we didn’t cover here because these areas look good, there’s no tendon or bone exposed, so why run up the bill and do that. I mean, if they took me to a better place for dinner, maybe I might put more graft, no, I’m just kidding. So we put the graft only where there’s exposed bone and exposed tendon, put VAC directly over the top of it, in this case, and no interface. And we get to a point where now it looks like this, so it’s hard to see on here because some of this is fibrosis but there’s tendon right here, really, and that’s about it. And so now, I say, “Okay, well, this is good enough”, sometimes the enemy of good is perfect, right? This is good enough, and if I keep waiting, it could get worse and I may not be able to put a split-thickness on it. So I decided to do a split-thickness at that point. So we put it on here and even if we healed everywhere but that spot, we still made it 98% smaller, so that was our rationale. So here we are watching it heal over the course of the next few, probably I think it was two months or so for this whole thing to heal until she is here and completely healed. So it works in a few ways, here’s the summary on how amniotic tissue is changing the paradigm in wound healing, is that one, we now have easy access to tissue, because these tissues can be stored and have long shelf lives and be shipped, and you have easy access to tissue because you can cover bone and tendon and use it for epithelialization.
There’s a wider applicability here so you don’t have to have multiple grafts at your disposal to use to perform more than one job. And then the last thing is that they end up being more cost effective, so there’s two parts of this, there’s cost and effective. They end up being more cost effective, one, because they have lot of data that shows that they can heal wounds, but two, they’re size appropriate so that you’re not having lot of wasting, which we call treating trash cans, you know, when you cut out the waste and you throw it in the garbage. So they end up being more cost effective in these cases, and this is really how it’s changing amniotic tissue as a whole, is changing the paradigm of wound healing. So I’ll leave you this quote from Will Rogers, and those of you that have heard me lecture before probably heard me use this quote because it’s one of my favorites. I’m not related to him that I know of, but he said, “Even if you’re on the right track, you get run over if you just sit there”, and that’s very true in dealing with people with a diabetic foot because you could be doing the right things but if you’re not doing them fast enough, then you’re going to get run over by that train, which is usually an infection and it’s going to come through and you have to start all over again, so.
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