Ankle Arthritis 101: Evaluation & Treatment Options

Jorie:

Good evening everyone. And thank you for joining us at our first Florida Orthopaedic Institute Live Lecture series. My name is Jorie and I’m one of the physician liaisons here at FOI. I hope everyone’s having a nice evening and preparing for the upcoming holidays. Tonight, I’m so proud to present Dr. Evan Loewy, one of our foot and ankle surgeons who is board certified by the American Board of Orthopedic Surgery, as well as a member of the American Academy of Orthopedic Surgeons, the American Orthopedic Foot and Ankle Society, and the Florida Orthopedic Society. Dr. Loewy is also an assistant professor of orthopedic surgery at the University of South Florida. He sees patients at our North Tampa and our Brandon office. This evening, Dr. Loewy will be speaking about ankle arthritis. If you have any questions throughout the presentation, you can comment or ask directly on Zoom and I’ll be monitoring those questions. You can also send questions on our Instagram and Twitter at @fl_ortho.

Jorie:

At the end of the presentation, we’ll get to as many of those questions as possible. If at any time you don’t see slides moving or have trouble with the audio, try refreshing your browser. And lastly, we’ll be sending everyone a recorded link of the webinar in the following days. With that, I’m pleased to turn it over to the doctors, today’s speaker Dr. Evan Loewy.

Dr. Evan Loewy:

Thank you very much. So as she mentioned my name’s Evan Loewy. I’m a foot ankle orthopedic surgeon, and today I’m going to be talking about something near and dear to my heart, something I’m passionate about and that’s ankle arthritis. So I have no disclosures relevant to this talk. So in terms of ankle arthritis, but just to briefly kind of go over the basics of what we’re going to be talking about today, it’s very important for me when we’re going over something new with patients in terms of condition. I like to talk about the basics of that. And so we’re on this same page in terms of why we’re doing things and when and how, and all of those types. But I think it’s important for us to be on the same page for that, so we can have an educated discussion. So briefly going to talk about various points of ankle arthritis.

Dr. Evan Loewy:

So just to start, this is a normal ankle x-ray okay. This is an AP and the lateral. So this is the front and side view. So this would be the first if you’re facing me. Okay. In the x-ray, this is the inside part of the ankle, and that’s the outside part. This is the tibia or the shin bone. Okay. This is the fibula or the smaller bone on the outside of your ankle. Then this is the tails, so the bone that’s underneath. So this is your actual ankle joint here, and then important points on the others… On the side view. This is the profile view of the ankle joint itself. And then the most important things I’m going to be referencing are joints underneath and in front of the ankle. So that’s here and here. And then just briefly on the inside part of the ankle, there’s one ligament that has four components and that’s called the Deltoid ligament. And then on the outside part of the ankle or the lateral side, it’s three separate ligaments. So that’s here, here, and here.

Dr. Evan Loewy:

So a few things just talking about ankle arthritis, just kind of establishing this as an important condition. This is a study that looks at a self-reported physical function in patients that have ankle arthritis, showing that it’s equivalent to or worse than that, of patients that have end-stage renal disease on dialysis, congestive heart failure, or cervical radiculopathy or severe pain coming from the neck down the arm. So showing is just as big of a problem for these patients as those significant conditions. This looking at gait or walking mobility in patients that have ankle arthritis. And so it’s comparing it to the patients on their other side or the normal or unaffected side. And this is showing that basically the ankle arthritis side has decreased motion, decreased strength and decreased power. And it’s showing that patients in terms of step, they have decreased steps per day, and decreased Gait and affected Gait than population norms.

Dr. Evan Loewy:

This study showed the average number of steps per day for patients with end-stage ankle arthritis is equivalent to that of patients with hip and knee arthritis. So I’ll be referencing hip and knee arthritis as they’re much more common conditions. And this is just showing that it’s just as significant of a problem as those conditions are on patients. This is looking at the quality of life. So health-related quality of life. How much is this affecting your life in terms of the condition itself? So this is comparing patients with end-stage ankle arthritis, either going on ankle replacement or an ankle fusion, and comparing it to those patients that are going to a hip replacement for hip arthritis. And so both of these groups of patients scored well below the population norms on all factors of this scale. And there’s no difference between the two in terms of the physical component between patients with ankle arthritis and hip arthritis.

Dr. Evan Loewy:

And interestingly patients with ankle arthritis actually scored worse on the mental component of this score compared to hip arthritis. So those are the reasons why we kind of establish the baseline saying it’s just as important and just as significant and problematic as those more common conditions. Now we’re going to talk about what I think makes it so interesting and challenging and what makes it unique? Why is it different from those other conditions? And so first we’re going to talk about the age. So the average age of patients undergoing hip or knee replacement for arthritis is 68. For ankle arthritis, patients going to fusion replacement, it’s 55. So this is a much younger patient population on average, we’ll get into why that’s the case, but not to say one group of patients is more important than the other, but it’s different patients that have a different part of their life, different expectations, different desires, and therefore it’s something challenging in terms of treatment for those patients.

Dr. Evan Loewy:

Etiology. So the very common question is, all right, so I have this, but why do I have it? Where did it come from? And so with knee arthritis, the overwhelming majority of the time, probably close to 90%, if not higher, it’s primary osteoarthritis or just wear and tear. Then less than 10% of the time it’s post-traumatic or meaning it’s coming from an injury. Either one big injury or multiple small injuries. The opposite is true for ankle arthritis. The majority of the time, 70, 80, sometimes 90% reported the rate comes… Or the arthritis is coming from traumatic arthritis or again, one big injury or multiple small injuries. Pretty uncommon in terms of less than 10% of the time it’s primary osteoarthritis or wear and tear. So this is showing us okay, of those patients with posttraumatic ankle arthritis, well specifically what was the injury or injuries that led to it?

Dr. Evan Loewy:

And so this is showing about half the time, the central portion, the central bar, half the time it’s from a malleolar fracture, basically just a common ankle fracture. Okay. Ligament instability. So usually that’s more multiple small injuries or recurrent sprains. It’s about a fifth of the time or 20%. And then pilon or talus fractures, 20% of the time. Those are basically bigger injuries, higher energy. So fall from height or car accidents. And then on the far side, you’ll see basically years from that injury to needing ankle surgery for arthritis. And see in the ankle fractures, it’s less significant of an injury still significant, but about 25 years on average to needing their replacement. So arthritis continuously kind of gets worse and worse with time. Ligament instability is a little longer. And then pilon talus fractures are four years on average from the injury, needing reconstruction surgery. It’s much less common than hip and knee arthritis, usually talk to patients.

Dr. Evan Loewy:

Most people that are coming to see me, either have themselves or know someone, their direct family member, a friend, or multiple that have had hip or knee replacements. Not many people even know that an ankle or ankle replacement’s a thing. So knee arthritis is eight to 10 times more common than ankle arthritis. So last year in the US, over 650,000 knee replacements were done. Surgeries for ankle arthritis, so either a fusion or replacement, are less than 30,000. So significantly, a less common condition. And that brings with it very interesting challenges that we’re going to get into. So knee arthritis is 10 times more common, but surgery is 22 times more common. So not only is it a more common problem but surgery’s being done. So why is less surgery being done for ankle arthritis? It’s not a corresponding number.

Dr. Evan Loewy:

Something that makes it interesting as well is the complexity of the cases. Okay. So only 37%, a little over a third of patients having surgery for ankle arthritis have normal alignment. So we’ll get into that in a little bit, but basically, the side to side motion or if it’s tilting or if there are other issues from other fractures or things, only a third of them have normal alignment. Whereas the majority of the time in hip and knee replacements, it’s normal alignment. Okay. So major adjunct procedures are needed in 35 to 40% of ankle arthritis cases. And that’s really uncommonly needed in ankle… Or excuse me, in hip and knee arthritis. And so one thing you’ll hear me reference multiple times as we get more into this talk is, sometimes we have to change the tires or for instance, in ankle replacement, but a lot of times we also have to address the alignment. We can’t just change the tires if we don’t fix the alignment.

Dr. Evan Loewy:

Sometimes we have to do that in two different settings or two surgeries. Sometimes we can do it all at once, but again, more than half the time we have to address it in some capacity. So just kind of an example, we’ll get more into this, but just to kind of show some basics of this, right? This is a case example, not super uncommon in the sense of patients that have arthritis. So this is an example of a patient, a 56-year-old female had a triple arthrodesis or a fusion of those joints that I mentioned below and in front of the ankle. So she had that as a child for a club foot. Now, the way that they healed, the way her foot is moved around them, they’re in a bad position and they’re causing her to have ankle arthritis with deformity there as well. So lots of things going on here that we have to consider when we’re talking about treatment options. So we’ll get into that in a little bit, but here next line.

Dr. Evan Loewy:

So in terms of complexity as well, the postoperative course is very different. Okay. In of expectations of what we’d be getting into. So after hip and knee replacements, many of you probably know you can walk on the same day. You have very uncommon, have wound complications are rare, for instance. You don’t need a cast or a boot or brace anything after surgery. Pretty uncommon to need a reoperation. You start physical therapy on day one. And there are a lot of support programs and teaching programs out there. And then on the contrary, if we go to ankle surgery, so ankle replacement or fusion, usually, either way, we’re going to be no weight on your foot for four to six weeks after surgery. Skip down here. A lot of times you will need a cast or you will actually always, will either need a splint, and then a cast typically again for that four to six weeks, and then probably a boot after that. There’s a higher risk of reoperation than hip knee arthritis. We’ll get more into that, but not high but higher.

Dr. Evan Loewy:

You can’t start physical therapy until you’re out of the boot and you start walking on it, and it’s much less common to have educational programs. And so one thing too, and to get into in terms of wound complications, it’s not necessarily way more common to have a wound problem, but as you could imagine, it’s a bigger problem if you do have one. So if you imagine doing hip surgery on the side of your hip, if we have to go in and recreate, reclose the wound, there’s more tissue there than anybody, we can just push it together and get the wound closed. But on the front of your ankle, there’s not really a whole lot of extra tissue there. So it can be a bigger problem if we do have a problem.

Dr. Evan Loewy:

So, okay. That’s great. They’re different, but what does that mean? So taking it altogether, the long story short is, it’s just as big of a problem for patients as hip and knee replacements in terms of… Or excuse me, hip and knee arthritis in terms of quality of life and health adjustment. It’s probably a longer course of the disease. These patients have that for 25, 30 years of this condition getting worse and worse, affecting them. Usually, as we said, the average age for surgery is 55. So if we go 25 years back from that, the majority of your adult life, this is a significant problem for you and starts a lot earlier than hip and knee arthritis. And it’s a lot less common, but it’s more complex and it’s disproportionately less frequent from a surgical standpoint. So that kind of plays into a lot of these things as we go forward as well.

Dr. Evan Loewy:

Next slide, please. So again, I don’t want to get too far into the weeds with this, but just generally speaking, this is a classification scheme for patients with ankle arthritis. So there are four types. The basics are type one, is just straightforward. Ankle arthritis, the tires are worn out. There are no alignment issues, there are no other significant problems, and that’s the most basic situation. Then we go for instance, to type three, which are patients with significant alignment issues in addition to their ankle arthritis. And then, for instance, type fours, those are patients that have arthritis and the joints in front of or below, like we talked about before. The reason that’s important, we’ll get a little bit into it, but the reason that’s important is that, when you have an ankle fusion, it’s actually not a peg leg, which most people would think. You actually have pretty decent motion, still maintained through those joints in front of the ankle.

Dr. Evan Loewy:

And so most of the time, actually, if you have a patient that had an ankle fusion that’s well done and healed well, and they’re in sneakers, walking down the street, you probably wouldn’t be able to tell which side actually had surgery or not. But if that joint already has arthritis in it and it’s not working properly, to begin with, it’s going to be more painful. So in the past, we used to think that patients that are further on the side, that are more basic cases would probably be the ones for ankle replacements that are better suited for that. And people used to think, well, these big complex cases, the ankle replacements, even more complicated, we shouldn’t do that. Let’s just do it for the basic ones, those complicated ones, we just got to do a fusion. What we’re realizing is, is actually the opposite. Patients that have straightforward cases are probably better actual candidates for ankle fusions.

Dr. Evan Loewy:

As you can imagine, if we fuse the joint, that’s the ankle joint that puts extra on those other joints. If they’re already arthritic, like I said, then those are going to be problematic. We’re just shifting the problem. But if we do a replacement, then maybe that’s alleviated to some extent. So getting in terms of treatment options. So much like hip and knee arthritis, the mainstays are anti-inflammatories such as Aleve or Motrin, Advil, those types of things. And they do work well to some extent and for a period of time. Corticosteroid injections are certainly an option. They’re not as common for instance, in terms of knee arthritis, which they’re really a mainstay of non-operative treatment. A lot of times, because like we talked about, a lot of times, there’s a bigger deformity or there are other problems. And so even if we can get the inflammation down temporarily, it’s going to come right back because of those other issues, the alignment problems, and so forth. So they may not be as good of an option or as useful often, but we certainly do use them.

Dr. Evan Loewy:

Activity modification. That’s our fancy way of saying if it hurts, don’t do it. Bracing options, I’ll get into those are possibilities. And then a rocker bottom shoe I’ll show an example. But if you imagine the ankle is arthritic and it’s painful or decreased motion in that up and down the plane, then if we can use a rocker bottom shoe that kind of takes some of that motion from your ankle, it can be a little bit more functional and take away some of the pain. And so the next slide’s going to show us some awesome options for bracing. These are very high fashion, as you can see, easy to get on and off, and very functional. That’s not the case, but again, this is a rocker bottom type shoe.

Dr. Evan Loewy:

There are newer versions out there. This is one of the classic kind of original ones. I remember the commercials, but there are newer kinds of more fashionable options. But again, there are not a lot of tremendous options for these from a non-operative standpoint. And then once we start talking about operative options or surgery, how do we treat this with surgery? So there are four main ways of treating it. I’m going to focus on the top two because that’s the overwhelming majority of the time. That’s what we use, especially in our patient populations. Those are the two. So we’re going to do a fusion or a replacement. And so first, we’re going to talk about fusions. Next slide. So that’s the chart. Briefly, this is just a graph. This is from a few years ago from a study that was done from Medicare patient populations. Basically, that top line, or is the number of fusions that are done for replacement, the bottom lines replacements.

Dr. Evan Loewy:

And so with time, those numbers are going together. Again, there was a lot of hesitancy previously for doing replacements, for multiple different reasons. But as we’re getting better at them, the implants are getting better. We’re learning how to do them, and when to do them importantly, those numbers are coming closer together. And then the next slide. And so this is one of the reasons why we can do them more often and we’re getting better at them now. And so this is a company that I use, just in terms of… I think it’s an interesting slide, is a picture because it shows the different options that we have. So here, are some of the options. Those are minimal resection, minimal good bone, minimal deformity, younger patient, usually, those are the options we can do. Then the one, the InBone, the one that’s kind of second to the right, that’s usually patients that don’t have the good bone or they have a bigger deformity. That’s what I use.

Dr. Evan Loewy:

And then what’s really important is the last one on the right, the biggest one there that’s called envision. That’s a revision system, meaning replacing a replacement. So this is a pretty new system that’s available. And it’s the first one really out there for ankles. It’s important because a lot of times the biggest concern for people not wanting to do a replacement in the not-so-distant past is, okay, great, we replaced the ankle. Well, what happens when it goes bad? What do we do? We have a big hole and we don’t have any other options. Well, now we can replace the replacement. And this is a huge advance for us, an option. And then on the far left side, these are called prophecy guides. So this is a 3D printed guide that we make, that’s custom for the patient. And so if we go into the next slide, this is an example of what I get.

Dr. Evan Loewy:

So we’re going to do an ankle replacement. Typically we do a CT scan of your ankle, and then that’s sent to the company and they generate this… This program generates a guide or a plan for me and we go through it and make sure it basically allows me to pick what implant I want to put in, exactly how and where I want to put it. And then once we can confirm that, I know which size and exactly the positioning, it actually generates a 3D print, those little guides that I use during surgery to make sure I do your replacement surgery, exactly how I want it to be done. So away I kind of say it, is that the implants aren’t custom, but the surgery’s custom.

Dr. Evan Loewy:

So talking a little bit first, excuse me, about fusions. Okay. So the positives, everything’s positive and negatives. We have to weigh the risk and benefits. Okay. So the positives of an ankle fusion. It’s got a great track record. It’s the gold standard. We’ve been doing it for the longest amount of time. We have the most experience with it. It really is a great surgery when we need to do it, the union rate or the fusion success, or the actual healing of it is 93 to 97%, which is pretty good. There are not really any activity restrictions, meaning once it heals, there’s nothing that I’m going to tell you, you’re not allowed to do. There are maybe some things that you aren’t able to do because it’s fused, but you’re allowed to go do everything, go crazy, run, jump, jump out of airplanes, anything you want to do. And that’s a good option for a lot of patients that are younger and that may be a better option for them.

Dr. Evan Loewy:

The negatives are like we kind of got into it, it puts extra stress on those other joints. And so those can wear out with time, which I’m going to show a little bit about. But then also, if they already have arthritis, it can affect the option, because it’ll make more pain there. And then of course, even though it’s good mechanics still, and I said, it’s pretty normal, and do better than you would imagine, it’s still not normal. So this is a couple of things, a few studies on ankle fusions, just to give you a little background. So this is a long-term study and like most long-term studies in orthopedics, they come from Iowa. Take it what you will, but that’s where they come from. And 23 patients with posttraumatic arthritis that had no arthritis in the joints in front of overload. It’s very important.

Dr. Evan Loewy:

They had zero arthritis in those other joints before surgery. The average age fusion was 41. Okay. Very young patients. And the average follow-up is 22 years, which is pretty, pretty long for orthopedic studies. Okay. And then, the next slide here. This is again, a lot of numbers, but why don’t you focus on is the bottom box, okay, where the zero percents are. That’s looking at the other… The patient’s other foot in those joints in front of, or below the ankle. Basically, at most recent follow-up, they never had it to begin with, and they still don’t have arthritis in those joints on the x-ray. And then the top box is the patients that have the same side that they have the ankle fusion. So 91% of them in the joint underneath the ankle developed arthritis on the x-ray. That’s severe arthritis on x-ray, and then 56% are the ones in front. So they developed arthritis on x-ray.

Dr. Evan Loewy:

And then the next slide. Again, tons of numbers. And I don’t want you to get lost in the numbers, but just the important thing is, the left side, the left box, this is ipsilateral, that means the side that they had the surgery, the fusion on. And then the contralateral is the other side, right? So lots of numbers, but most importantly, there are more big numbers on the left and a lot of zeros on the right. So that’s basically just saying, that’s how much pain they had, essentially. How much disability they had from those joints. So the last slide said that they had arthritis a lot of the times on x-ray and this is just showing that it’s actually symptomatic arthritis. Okay. This is, I think is really a fascinating slide, fascinating information. So this is 28 patients that had ankle fusions that are highly satisfied.

Dr. Evan Loewy:

So they’re all extremely ecstatic. They’re very happy, they would do it again. They’re happy with their outcome. This is looking at the number of those 28 patients and the percentage of patients that have difficulty with these different activities, right? Walking on uneven ground, almost 80% had trouble with that. 75% or three and four of them had trouble with stairs. Okay. 71% trouble with pedals, right? 36% difficulty putting on boots. So you may look at this and say, wow, that sounds like a terrible surgery. These patients have a ton of trouble. I think it’s the opposite. These are all patients that are extremely happy. This is showing you how good of a surgery that is. It’s they have that big of a problem with basic activities, and daily living, but they’re still extremely happy with what happened because it’s such a successful surgery for getting rid of the pain.

Dr. Evan Loewy:

And that’s, what’s important from an expectation standpoint when you talk about an ankle fusion, it’s a salvage procedure. The number one goal is to get rid of the pain. We’re going to have to make some sacrifices to get rid of that pain, but sometimes that’s a necessary evil. And then the next slide. So now we’re going to talk about replacements. So some of the stuff’s the opposite, right? So better gait mechanics. We’re still maintaining some of that motion in that joint, or maybe even restoring motion. And so then you’re going to walk a little bit better, that in turn, we think we can’t necessarily say it definitively because we don’t have long term studies, really that show it yet. But it makes sense to say that there’s less arthritis in those joints in front of or below because we’re maintaining motion.

Dr. Evan Loewy:

The negatives, like we talked about higher complication rate or reoperation rate. So the CROCS that’s just a study that was done in Canada. A large study looked at comparing replacements and infusions. And so 30% of patients with replacements had reoperations and 14% of fusions had reoperations. Okay. That number with time, each time we have a study like that, that gap is narrowing. Again, as we have more repetitions, we have better implants, better technique, and better indications. That number is narrowing, okay. But sometimes that still is a true thing that we need to be aware of.

Dr. Evan Loewy:

Go to the next slide. So we’re going to talk about a couple of studies that we did actually, that I was lucky enough to be a part of, but so this is actually the star. This is a specific type of ankle replacement. This is one of the original three that was released in the US. So we have the longest-term data on it. And it’s actually the only of those original three that are still available today. And so we can go the next slide, sorry about the formatting issue there. But basically, this is a study that we did. I actually did here, when I was in training with one of my mentors on his patients, it was a part of the original study that was looking at the FDA study. We looked at these patients moving forward, basically, how long do the implants last? How well are the patients doing? And then do they need reoperations?

Dr. Evan Loewy:

And so, if you go to the next slide, it just talks about basically there were 140 patients, and at that time it was published a few years ago. It was the longest and largest, the largest… Excuse me. The largest and longest-term study on ankle replacements we’d ever been published in the United States to date. And so with that, we showed that at five years, 90% of patients still have the original implant in place, 82% at 10 years, and 77% at 15 years. So that’s when you say, Okay, well, great. We’ll do the replacement, but how long is it going to last? Am I going to need another surgery? So really to date, this is the best long-term data we have. And it’s certainly not where we want it to be, but it’s certainly reasonable and getting better, we think as the implants get better.

Dr. Evan Loewy:

And if you go to the next slide. So something that’s really important that we got out of the study, as well as it can. Like I kind of alluded to earlier, one of the concerns was, okay, great. We do the replacement, but what happens when it goes south. That we have a bigger problem than when we started with. So this, so we don’t really think so. Right? So this is what happens when patients had their failures. Okay. So we had to take out their replacement. What did we do with it? How do we manage it? So basically 80% of the time we were able to convert it to an ankle fusion or the surgery they would’ve had, initially, if we didn’t do the replacement or we did a revision replacement. So kept the replacement. So 80% of the time we were able to either do the same surgery or the one they would’ve had a way. And those were successful surgeries.

Dr. Evan Loewy:

And this was again, started in 1999 was the original, was the first surgery that was done for this study. And so, as I’ve mentioned, we’ve had this new revision system out, and we have better techniques. So I would argue if we redid this today, it probably would be even a greater number. So next, this is one that I mentioned earlier on the slide. This is one of the ones I use. And so this is called the Inbone 2. And this was actually during my fellowship. We did a study. And additionally, with that one, it was the largest and longest-term study for that specific implant that we had, and this implant… Then you go to the next slide. This was 126 patients.

Dr. Evan Loewy:

Those were first done in 2010, right? So that implant literally is only 11 years old. So we don’t have long-term data on it. So some of the time we can’t really answer exactly how long it’s going to last. But this study showed us in 75% of those patients, about half, we were able to get five years of follow-up. And the average age of surgery was about 62. So a little older than the average that I mentioned earlier, but nevertheless, around the same time.

Dr. Evan Loewy:

And if we go to the next one, we looked again, the same things. How long did it last? Did they need more surgery? And then the Coronal Plane Deformities, if they had a big deformity or alignment issue, did it maintain that? And then if you go to the next one shows, you see that five-year survival was about 92%. So a little bit higher than what we had for that other study. But again, we don’t have long-term study. We think that this is a better implant. Again, I can’t say that definitively, but we think for multiple different reasons, I think it’s a little bit better, some would argue that but nevertheless, we think we have better techniques and better technology. And again, so we think we’re going to have a little better outcomes maybe even than before. Interestingly too, with this, all the failures for this one that we had at least in this study were within two years of surgery.

Dr. Evan Loewy:

And so a lot, you may hear me say, if you ever see me in the clinic, that if you’re doing well at two years, you’re doing well at 10 years. And so we think that if you get past the first two years, is there going to be patients that had wound complications or other issues, infection, some of those things we don’t like to have, but that can happen. Maybe it was not the perfect surgery or something didn’t go well from that standpoint, still had pain from another source. Basically all those patients you get past the first two years, the alignment’s great, everything’s going to do. We think you’re going to continue to do well at least 10 years, if not after that. Additionally, an interesting thing from this study, only one of those failures that we had was actually really related to the implant itself. The other ones were those other issues that can happen with any surgery.

Dr. Evan Loewy:

And that was honestly also a technique issue. So we think this is a really good implant and we’re going to have to keep an eye on things moving forward, but we think we’re getting better implant survival. You can go to the next one. Just briefly, this is going to show that, 84% of the patients in this study where either type three are type four. So those bigger, bad or kind of more difficult cases and they still did very well. And so that’s why you could argue that even though their survival was the same, maybe these are harder patients, and so maybe then at the end of the day, it’s technically better, but either way we have good outcomes from this and good data moving forward. Go the next