~1

Well thanks John, it’s truly a pleasure. We started many, many years ago with Stankalish and Superbones at the Trade Winds Resort in Saint Petersburg. So it’s really a pleasure to be here with John and Karen Lamorsh, Rick Truder, Stan Kesh, everybody has put so much time in this meeting and you know, you think about the Bahamas and how much fun we have down here but really the educational component is so superb that we’re fortunate to have the educational portion in addition to the ability to have some fun with our families.

So without further a due, I’m going to spend a bit of time talking about wound bed preparation. As John mentioned, we have a pretty large research group, a full-time research coordinator and we do a lot of clinical trials in our facility. We’re both the North American Center for Limb Preparation and also Yale and Haven Hospital, Yale University School of Medicine.

~2

So what I want to do is take you through our approach to wound bed preparation and just talk about what do we see in wound healing? We hear so much about wound healing and preparation and how to get to that next step. And we know that the government, Medicare and all the insurance carriers are looking at cutting costs and looking at the sciences behind what we all do. So we’re going to have to continue to evolve and really identify what are the parameters involved with wound healing.

~3

So when we look at the wound healing and the cascade. This slide shows that the cascade is extensive and extremely comprehensive. But what part of this cascade do we have that really affects what we do as far as foot surgeries, wound bed preparation and wound reconstruction?

~4

So if we take a look at the ulcer healing and look at the parameters of what is involved with wound bed preparation, there are protocols that we follow as far as when is a wound ready for wound bed preparation and at what point do we use adjunct therapies to get to that standard.

So if we’re debriding a wound for a week, two weeks and five weeks and before you know it we’re three months into a debridement and the wound is still 3cm by 3cm. We’ve got a problem and we really understand at this point that patients require adequate perfusion, lack of infection and offloading but many of these folks meet those criteria. So if you’ve adequately offloaded that patient, you’ve debrided them, they do not have an infection and they’ve got adequate circulation; then at that point, at some point that wound should reduce in size. And there are now studies that really demonstrate those facts and those facts are quite simple. And I think that Peter Sheehan has done a number of studies that has helped us evaluate at what point do we do what we do as far as wound reconstruction?

And what he did is he looked at the ability of the four week healing rate to predict whether or not a wound would finally close and fully epitomize. And if you looked at the 203 patients and the ulcer size, if they didn’t reduce by 50% over that 4 week period, then those patients would not go on to healing. So a 15% reduction in wound area should be a reasonable goal over those two weeks.

Now what’s interesting, and I’ve had this discussion with several individuals in the past week or two, the LCD for Medicare in the northeast has really for debridement codes has evolved and is going to undergo some changes with the government. That is if you debride a wound every two weeks and you do not see a reduction in wound circumferdential area and depth, then you may not be paid for that additional debridement. So you’ve got to now show that the wound is undergoing some sequential epitheliumization in contraction. So not has the government really come on board, but the science and the ability to reimburse what we do is all coming together as one comprehensive unit.

~5

So when we look at 4% or 4 week reduction we want to see a good reduction in a period of time that leads to contraction of the wound. So if you look at the decision when we use adjunct therapy, you’ve got to think about advanced wound care and again, using the appropriate adjunct therapies, because if you look at this slide here 58% there was a 53% reduction area in week four. Those folks went on to heal, where to as if there wasn’t a reduction 9% went on to heal. So we know that if we don’t see sequential reduction of that wound volume, they’re not going to go on and heal, so we’ve got to think about some of the other therapies.

~6

So when we look at a wound, when is this wound ready for something?

~7

We see so many exhibitors at all these meetings talking about their products, but if you’ve got a wound bed that looks like this with fibrositis liquid action that wound is ready for nothing except debridement, an aggressive debridement and we’ll talk about some of those therapies. So if we’re going to use a growth factor, beioengineered skin or skin graft, we’re not going to have success if we have a wound that looks like this.

~8

Normal wound healing –

~9

And again, just to demonstrate this is an acute wound which is different from those chronic wounds that we see. And coagulation, inflammation, all these neutrophil functions, macrophage they all have to go through an appropriate cascade, but we know this acute wound which is a crushed injury from a garbage truck running over one of our firemen, this is a very different wound than the chronic wounds we see, both diabetic foot ulcerations, venousfacious aterial ulcerations and chronic ablating wounds.

~10

Again, just an example of a patient with a history of kidney and pancreas transplants that can’t mount an immune response with his very liquefied wound. That wound is ready for nothing except debridement and that patient went on to a below the knee amputation. So edema, perfusion all these affect what we see as chronic wounds, in addition to the subset of those dialysis patients which are the most difficult to heal.

~11

Let’s spend a few minutes talking about debridement.

~12

Because if we don’t adequately debridement we can’t use any therapies and those therapies will fail. So we’ve got a variety of different methods, for us surgical and sharp debridement is the most appropriate. Curettement wide, a blade of surgery, hydro-surgery, the ability to go ahead and really eliminate that bacteria bioburden, all those synthesis cells and produce a wound bed that is really ready for that next step.

~13

Goals of wound bed preparation.

~14

And the ability to get to this step. We all see these wounds that are stagnant and secesant, we want to produce a wound like this. Hypertropic granular tissue, you’ve got all your plate right growth factors fiberblast, tearatenasites, but you’ve got to ensure formation of good quality granulation tissue so that complete wound closure, either naturally by secondary intention or through adjunct therapies which is appropriate. Remember, the foot is a mechanical axis and there is certain areas we allow them to heal by secondary intention, like the dorsal of the foot medialaterial. But we try to prevent secondary intention under the weight bearing areas like the heel and the metatarsal head, so those are some areas we prepared for some adjunct therapy.

~15

So, wound bed therapy. What is wound bed preparation? It’s really the management of that wound to accelerate endogenous healing. You want to utilize the factors the patient has and to facilitate the effectiveness. So you want to debride, you want to make sure your quantity counts are less than 10 to the 5th, except for that fact is you have resistant bacterial strains such as MRSA and VRE you probably want less than 10 to the 3rd and you want to manage that moisture balance. We’ll talk about some of these therapies.

~16

Just think about we’ve got some companies out here exhibiting some biopsy techniques, and I know Brad Batotic talks about this and he gives great lectures, and that is when you have someone treating a wound like this, this not a wound. It’s a melantic melanoma. Please consider biopsies and differentials. I can’t tell you, we have two or three patients sent to us this year treated for wounds that do not have wounds. They truly have malignant tissue in that region.

~17

Staging of wound bed preparation, I included this because there really is a staging process. Vince Falanga who is a dermatologist, I think down in Miami, has come up with a nice wound bed preparation staging, and it’s really the assessment of the bed, how much exudates, how much neurosis and what do we do as far as evaluation of these wounds so that we can again, utilize the appropriate therapy?

~18

So global wound care – we travel quite a bit as John mentioned, we do a lot of surgery. I’ve traveled with John and Chris and we’ve been to a variety of countries all over Asia, Europe, and throughout the entire world looking at what are folks using. And they use everything. It’s amazing what folks use. But remember in the United States, FDA protocol, we’ve got three really approved products for diabetic foot ulcerations that are not 510K products, and that is Deragraft, Apligraf and Regranex. Those are your approved products, not to say we don’t have a lot of other very good products, but all the other products fall under the 510K products. So, once approved these 510K products reach the market but they don’t have the level one randomized trials, so it’s important to identify, again, especially with the change with the LCD’s in Medicare coverage, which products are covered and which codes are appropriate. Especially with all the post audit reviews that are going on with the government because they are really looking for money from a variety of areas.

~19

So adjunct therapies, it’s amazing what we have on our shelves. Everything from stem negative pressure therapy, pneumatic compression, lasers and there are newer technologies coming down the pipe, but we have adjunct therapies and we want to focus on a few of those as we go through this today.

~20

I think Andrew Boulton who’s extremely funny, has had also some great papers. And this paper in The New England Journal of Medicine, and this again, helps substantiate what Peter Sheehan stated, and that is really if you want to look at the clinical practice of what we do with respect to wounds, you’ve got to see reduction of that wound in the volume. And the failure to reduce the size of an ulcer after four weeks of treatment that includes appropriate debridement as we talked about pressure reduction, those wounds should probably be considered for some type of adjuvant therapy. With that being said, remember that in certain areas, especially ours, the LCD for using some adjunct therapies patients have had to fail six weeks of therapy. That is moist therapy, offloading and debridement. So you have to be cautious as to what your current LCD is.

~21

So Dave Steed who is a vascular surgeon in Pittsburg has also helped demonstrate what Andrew Boulton and Peter Sheehan have stated and that is the wound healing guidelines that were set in 2006, and if you look back to the consensus of the Boulton Conference which was in 1999, is now a long time ago, the ability to use adjuncts and the reason why we do is based on science. And that is the use of adjuncts should be employed and these therapies should be used if we don’t see reduction in wound volumes over time.

~22

So to mention silver, we hear so much about silver and adjunct therapies, I think it would be inappropriate to talk about adjunct therapies without mentioning silver. But remember, there are very few level one studies looking at the affect of silver on wounds. We know that in the lab it reduces bacterial reduction and really it’s a great antimicrobial agent for MRSA and VRE. And it really does kill microbes and it does help okay, but it is not something that is an active adjunct. So again, we use silver, we use all these products to get us to certain points, but we try to use these in different stages of the process.

~23

So if we take a look at additional studies, what we’ve done, we’ve done a pilot study trying to determine wound bed preparation. If we use something like PD Jeff Bata, does that help stimulate cells in the area so that it increases the area to take a skin graft? This was supposed to be present but Regranax was owned by Ortho McNeil, and then purchased by Johnson and Johnson, which is now owned by Sysagentics, but it showed that it does help a bit. But the pool was quite low, the end number was small. But again, just showing there are therapies we use to try to stimulate these cells.

~24

All of these products that you see up here, and again, some of these are a bit inexpensive like our skin bank at Yale, this is a sixty-five dollar piece of prior preserved skin that our PA’s take from the cadavers, all the way up through some of these fibroblast growth factors and dermograft and apligraf and pegra, all these are very interesting as far as wound preparation and adjunct therapies.

~25

I want to spend a little time on the products and the products that are approved as per the LCD Medicare covered insurance covered and those that are, that have undergone randomized controlled trials looking at the evidence of why we do what we do. And really human fibroblast-derived dermal substitutes I think have helped us quite a bit. So we have a wound at six weeks that has not reduced in size by 15 or 20%, then this is the time we use these therapies. And these fibroblast produced during the growth, the matrix proteins, the gags and all the other undifferinated and differentia products of growth factors and the keratinocytes. We want to deliver something to the wound that obliviously is not there and we want to stimulate that bed. So the provision of that epidermal layer with keratinocytes is not necessary, but we want to provide that dermal matrix. We want to activate that wound bed so that we can produce granulation tissue to either heal by secondary intention or to produce a wound bed for a flap or a skin graft.

~26

If we take a look at some of these studies, this is Bill Marston’s paper. Bill Marston is a vascular surgeon in the Carolinas. And this was in 03 and what he found was that if you looked at something like a fibroblast derma matrix product, the proportion of diabetic foot ulcers that healed by twelve weeks was 64% when compared to conventional therapy. So we understand that there is enough data out here and Jason Hemp has some papers that were published a while back, again, also demonstrating the effect of closure of wounds with using adjunct therapies.

~27

So let me take you through some of these examples. A patient with an open amputation, yes you can use a variety of therapies, in this case using products, in this case using something like derma graf to allow for closure. This is a wound that became stagnate in stage renal dialysis patient. After eight weeks the wound was still there. Sequential application, debridement we’ve got good secondary closure now, I don’t mind this dorsally because if I’ve got scar cut contractures here it’s not on a weight bearing area. I don’t have to be concerned about tissue loss and callous formation and ulceration.

~28

In this case, this is a patient that I would not skin graft because it’s in a weight bearing area. So sequential debridements, application again of fibroblast derma matrix products like dermagraf. And again, these are up to eight applications, weekly up to eight, if it heals at four weeks, its four applications. If it heals in eight weeks it’s an eight week application, if it doesn’t heal in eight weeks then we’ll transition to a hydrogel or some further moist wound therapy or what we would consider advanced moist wound therapy.



~29

This is a patient with an Achilles tendon wound. Wide resection, again, nocrosis continued tissue loss. We’re not seeing that wound contract over a period of time, as again, weekly applications are extremely helpful. And I’m not concerned about contracture here because I’ve excised the Achilles tendon and put the patient into a AFO.

~30

This is a nice case of a patient who had a significant infection. Diabetic, not in stage renal, I had to excet the extensor tendon. And wound bed preparation again, using a fibroblast derma matrix, applying until we’ve got good wound be preparation and now we’re employing multiple therapies. We’re using negative pressure therapy, we’ve using a vac, and we’ve got final contracture of the skin graft. And we thought we’d have to go back and do a fusion, but the short extensor was still intact and we were able to salvage that foot.

~31

Just some other quick examples. A patient that had undergone two distal resaprations, could not get the wound to heal, again, weekly applications until we’ve got full closure of those open trans metatarsal amputation wounds. And now we’ve been able to follow these folks because we’ve been using these products for a bit over two years now on a consistent basis.

~32

This is a gentleman who was in stage renal diabetic, stepped on a fish bone, necrotizing infection, wound bed preparation, skin graft and then the skin graft sloughed from the VRE. So again, back to some dermal matrix products, fibroblast and then application and we were able to salvage that foot. So again, I think adjunct therapies if a wound is not transitioning appropriately you’ve got to think about those.

~33

Negative pressure therapy, I think we’re all familiar with another excellent adjunct. There are enough papers on it.

~34

Role of debridement,

~35

you’ve got to make sure you adequately debride these wounds.

~36

Debridement reducing cellular senescence, sharp debridement, hydro surgery, they’re all extremely helpful.

~37

If you’ve got a nachrontic heel in stage renal patient I prefer a below the knee amputation. Think about these folks, what best suits them. Sometimes, we just published a paper on primary amputation can be considered a salvage procedure.

~38

Assess for infection, it’s extremely important.

~39

All really think about the studies that support why we debride wounds. This is from Dav Steed’s study.

~40

And really debridement techniques. Diabetic ulcer and time to heal, if you look at debridement, there is a reason why we debride, but the government now understands that if you’re going to debride you have to see reduction in that wound volume.

~41

So traditional debridements.

~42

We’ve got a variety of adjunct therapies here. This is how we use to debride wounds with a plusa vac and a valve bag.

~43

But you can use ultrasonic debridement techniques.

~44

You can use hydrosurgery techniques. There are a variety of methods that are available.

~45

That can be helpful for wounds themselves.

~46

[Blank screen]

~47

So in essence if we look at all the therapies, this patient had silver therapy, had VRE, MRSA, bioengineered tissues,

~48

skin graft. It took a lot to salvage this extremity,

~49

but we were able to do it.

~50

Same type of thing, negative therapy, stage procedure, salvage of the extremity.

~51

And a skin graft on a non-weight bearing area.

~52

So it really

~53

It takes quite a bit of work.

~54

Another veinus facius wound that required an antovalscuar procedure.

~55

Bioengineered tissue and finally a skin graft.

~56

So a puncture wound,

~57

negative pressure therapy. Application of a skin graft.

~58

And here we are now three years out.

~59

So we’re able to follow these folks for quite a while.

~60



~61

So diabetic foot ulceration costs, we talk about costs of these products. There was a study that was just produced in ostemy wound management in 2009. Just looking at the costs of using these products to salvage a limb, I think again, it supports itself. So there’s a reason why we make the decisions we do. We hope that the carriers will continue to reimburse because it is based upon true science and randomized controlled trails.

~62

So, in summary, we’ve got very little time. Wound transition , wound bed preparation, debridement techniques, offloading, time to closure, what do you remove and what do you add, you’ve got to look at your choices. We have some choices out there that are really supported well with respective therapy.

~63

And with that again, I’d like to thank John and all the folks here that have put together a super meeting.

Peter, I’d like to ask, I think we’ve made a lot of improvements as you’ve shown in technology and treatments, it seems like we’re lagging in the diagnostics to know when to use those, for instance you mentioned Dave Steed or growth factor data. What do you use as your indicators to use some of these products? If you just pick Regranx for instances, when do you put regranx in a prescription pad?

I think that’s a great question and the ability to determine what we use when is still truly troublesome for most of us. And that is when we look at these products when do we use them? A product like Regranx a platelet like growth factor, if we’ve adequately offloaded them, and again, we don’t see a reduction over a six week period we may add it. But I will tell you looking at the products like regranx, they can be helpful, but I don’t think they give us what we had initially seen in the trails, and that is the ability to truly epitheliumization most of these wounds. So our utilization of something like platelet like growth factor has been limited. We are looking at other ways to deliver the growth factors, and as you know John we have completed our gene activated matrix trial using an adnovectro virus to see if we can actually use an infected cell to up regulate. And we have seen some significant findings but yet the end numbers to some of the studies, I can’t get up here and say gene therapy right now is your answer, because it is not based upon the data we have. But we have found that some of these collagens and other advanced moist therapies have really shown to be very different than moist saline wethatro. We’ve got enough data for that. But I think that using adjunct therapies like derma graft and apligraf can be very helpful when you have a wound that is not transitioning. More often than not it’s the surgical decompression, and the problem I think that we have is identifying how much resistance in that wound impacts that outcome. Meaning what is happening with MSRA and VRE in your wounds and how much can that wound tolerate, because it is not 10 to the 5th because regular staff is a very different bug than MRSA. So I think the diagnostics not only will include what to use for a growth factor, but also what is the impact to that bacterial colonization in that wound and how much more elimination does it require.

~64

Meaningful Use Update 2010