Michael S. Conte, MD, UCSF’s chief of vascular surgery, discusses the growing problem of PAD, subtleties of PAD signs, useful testing techniques, which patients to treat, therapeutic options, and how to educate your patients – especially diabetics – to safeguard their health.
thank you guys for the invitation. Um, I am, uh, at U C s f ast chief of vascular surgery, our division of Ask Your surgery. Um, sees patients at several locations, uh, in San Francisco, at Parnassus in the South Bay and San Mateo in the East Bay A to Berkeley. And we also have programs at San Francisco General Hospital at the VA Hospital as well. Um, so today I was asked to talk about one of the most common things we treat, which is peripheral artery disease, which is essentially atherosclerosis of the lower extremity arteries. And let's dive right in. So, by the way of objectives, just defining what it is. And it's public health importance, understanding the risk factors for PhD and its presentation in terms of clinical manifestations and the complications understanding a little bit about how was diagnosed and, in a very basic way, some of the broad strokes around how we choose different treatment options. I'm sure all of you are aware that peripheral artery disease is growing in the population as, uh, other cardiovascular er, um, syndrome. Zara's well, and alongside the aging of the world's population and the continued epidemic of diabetes we have seen across the globe and in every region in every socioeconomic strata purple heart disease increasing over the last couple of decades. This paper, published in The Lancet using different methodologies, suggested that over 200 million people now in the world likely have purple heart disease to some extent or another, and the rate of increase has been steady again based on diabetes and aging. So it's a major global health problem that has significant, uh, resource issues as well as disparities and care and outcomes. In the United States, it's often estimated that between 10 and 12 million Americans have Ph. D. And it's important to recognize that the diagnosis of P A D essentially carries a similar Afro sclerosis risk profile in terms of major adverse cardiovascular events to having coronary disease. UM, it clearly disproportionately affect certain populations, including minority populations and particularly African Americans and Hispanics, but also Pacific Islanders. It may in many cases be the first sign in a given patient that they have Afro cirrhosis or cardiovascular disease, and many studies have demonstrated that, um, it's not looked for it's under diagnosed and therefore undertreated and in general Once you have p a d. It has significant implications for both life and limb to to fall fold increased risk for heart attacks and strokes and can lead to significant disability and even in the worst case, major amputation, significant economic burden that continues to increase. And although we've done increasingly better job over the last decade in terms of developing specialized teams, there are still roughly 80,000 major amputations a year in the United States, and it's estimated that at least half of those could be preventable with earlier identification and treatment. So who's at risk for P. A. D. Um, based on the epidemiologic evidence, we can define who that population is, Um, and it's definitely related to age. So for those less than 50 years, really, it's patients who have diabetes and at least one additional risk factor, such as smoking, disip, anemia, hypertension or some other premature atherosclerosis condition. Anybody who's got a history of smoking your diabetes over age 50 and then anyone really over age 70 is at risk for getting Ph. D. And we'll talk a little bit about that. If you have a patient who's got like symptoms with exertion, suggestive of communication or complains of pain at rest in their lower limb or foot. If you have somebody who has an abnormal or a lower extremity pulse examination, which brings up the importance of doing a lower extremities, false examination on an annual exam, taking off the socks and looking at the feet, particularly in patients with these risk factors. And if you have someone who's already got a diagnosis of clinical cardiovascular atherosclerosis elsewhere, all of these patients should be in your mind as potentially at risk for having Ph. D. Strongest risk factor of all his age. This has been demonstrated in many studies. This slide is a summary of several large epidemiologic studies demonstrating the stepwise increase in the prevalence of P a. D. Based on FBI testing from those starting at age 42. Those greater than 70 years, uh, in the Indian Studying in the Partner Study, which we'll talk about a little bit more. You can see that once you get up to age 70 or have more than one risk factor, the prevalence could be in the range of 15 to 30%. Um, and the partner study, in fact, focused on this in primary care practice, a slight tight against where in this study, um, in a target population. Based on what I just showed you doing routine office based FBI screening. They identified 29% of patients within that group of over age 70 with a risk factor having previously undiagnosed PD. And what's important on this slide is that half of those patients Onley have Ph. D do not have other as in coronary or cerebral vascular disease. And these are the ones that are routinely missed, um, often in practice and are routinely undertreated in terms of cardio protective medications. It effects men and women differently based on age Earlier in life, women have a much lower prevalence, likely related to the hormonal effects. But they catch up later in life, such that today in our vascular practices and almost around the country, kind of routinely, if you look at Siris of patients getting surgery, it's often 40 to 50% female, so it's pretty even in terms of symptomatic disease. But the women do tend to be older than the men, often by 5 to 10 years, um, and so pretty common disease and octogenarians in general but previously not thought of as much in women and clearly quite prevalent. Diabetes is one of the most important risk factors, not only for having Ph. D, but for progression of disease. Um, patients who have diabetes and particularly those who have diabetes and are still smoking, are at the greatest risk for for progression to limb threatening complications of their Ph. D. You can see here that even impaired glucose tolerance in parts, a significant increased risk for P D. On then, overt diabetes, uh, nearly doubles the risk in an age match way. So what are the clinical presentations of PhD? Well importantly, most patients actually have no symptoms that they complain of and are entirely unaware of the disease. This may be because of diseases relatively mild or well compensated. Or it may be because they have other co morbidity ease that limit their activity or that they just are not active people. Most commonly, it's because of diseases relatively mild. When patients do present with symptoms, the most common symptom is pain in the legs while walking or Claude occassion. As things get more severe or may presented a more severe level, it may start to complain of rest, pain in the foot or evidence of limb threatening ischemia, which may show up as open source. That failed to hell for changes in color of the toes, including cyanosis and, you know, ultimately progressing to full thickness, skin loss or gangrene. Noninvasive testing plays a really important role in the evaluation and diagnosis of Ph. D. We can make the diagnosis of P 80 90% in one visit with a history and a simple A B I test, and we can usually quantify the severity of the disease, its location and its clinical stage within that same visit, with the addition of additional non invasive studies, the most common non invasive studies air based on ultrasound and ultrasound is very useful in lower extremity disease because we can easily monitor disease progression within the leg. It's a relatively superficial structures to image. There are no gas containing or Odysseus structures in the way of the ultrasound beam, so duplex ultrasound, which means the ability to directly imaged a plaque but also measure flow with Doppler, can be used to look at the abdominal aorta, the carotid lower extremity arteries. But importantly, physiologic studies where we measure pressures and can calculate profusion are actually quite important in addition to the anatomy. So these human dynamic measurements are based on measurement of pressures at different levels of the limb and most importantly, at the ankle and the toe and are used to derive indices such as the ankle breaking index in the toe breaking index, which I'll show you in a little bit. There are also other techniques that can be used to actually measure profusion down at the level of the foot and digits, including trans continuous socks. Symmetry. Another technique called skin profusion pressure. These are the most common sort of workhorse tools that are used in many practices and on Lee. If we think a patient has reached a level of symptom Atala Gee or signs that we're thinking about intervention, do we tend to proceed to get an atomic image ing of the disease? The FBI test is an office space test that is the screening test of choice to assess for the presence of purple heart disease and can also give us a pretty good idea of its severity. It's based on an inclusion pressure measured in the arm and measured at the ankle, which is kinesis plea done in an office setting. We typically in most vascular labs, have an automated system that can put cuffs on bilateral extremities and obtain these pressures in a systematic and quantitative way. And the way the FBI is calculated is the break. Your pressure or the denominator is the higher of the two armed pressures. And then, for each limb, one takes the higher of the two occlusion pressures, whether it's the door, Sallis Penis or the posterior tibial. Ah, higher of those two values is the numerator to obtain an A B for each limb. Typically, most of us who do not have significant P a d. A normal FBI is greater than one and up to 1.2 or so. Anything between nine and one is considered borderline, and under 0.9 is considered consistent with P. A. D. Um, it's important to note that ankle pressures can be falsely elevated, particularly in the setting of diabetes or renal disease or any severe calcification in the arteries that's sometimes easily detected because the pressure is not compressible it all. You can't actually measure it. It's non compressible, or sometimes if we can see that there's a mismatch between the inclusion pressure in the way form that suggests that the pressure inclusion pressure is incorrect. Um, there are gradations of abnormal in the A B that roughly correlate, usually with the severity of presentation. But patients who may have no symptoms at all across the whole range. Surprisingly, some patients may present with very vory bad FBI's, and they may not complain of anything because they're not active or because they just haven't had, um, they may not have any significant issues in their feet, But in general, patients who complain of Claude occassion are usually in the range of between 0.5 or 0.4 even and 0.9. And we don't really get to the more advanced stage of limb threatening disease until the baby is less than four. We also typically measure pressures in the digits, um, particularly because of the growth of the diabetes population and its effect on calcification and the tibial arteries. It's not infrequent that ankle pressures may be falsely elevated and toe pressure zehr generally mawr accurate for patients who present with more advanced problems, including wounds on their feet. It's the same concept, except there's a tiny little plus the mammography probe placed on the pulp of the digit there on the Alex and a tiny probe is inflated at the base of the digit to include the digital artery, and then it's deflated until you see the signal return. So it's really a cuff. Occlusion pressure at a at a digital level exercise. FBI testing can also be useful. Um, this could be very helpful to try to discriminate if exercise induced, like symptoms are related to P A D or possibly related to other things. And one of the most common other things that occurs in the same age group, his lumbar spine disease, which can also produce similar symptoms. We'll talk about that in a couple of minutes. Sometimes exercise testing is also useful when the resting FBI is normal, or point between 0.0.9 and one. But the symptoms are consistent with Claude occassion. In this case, it's kind of like performing a stress test for the lower extremities. You exercise the patient until they either get symptoms or they hit some mark. And if there is significant p A. D. And we re measure the A B. We would expect to see a significant drop and sometimes with a slow recovery. If we see that in the presence of symptoms at the same time, it's a pretty good indication that PDS to cause. Conversely, if we exercise the patient and they get pain and their A B is unchanged, it's a highly specific, uh, negative finding some other tests that are used occasionally, though less frequently now that also rely on non invasive recordings or pressure measurements using similar instrumentation, our segmental pressures and what's called Pulse Fi and recordings. Again, these air cuff based tests cuff based tests where multiple cups could be placed at different levels of the limb. And essentially, what they can tell you is where the stenosis or occlusion is by looking at the difference in the wave forms and the pressures at different levels. Um, so, for example, this is a pulse file and recording of a patient who has essentially normal way forms with which looked very much like direct arterial tracings on the right side of the screen, with a brisk upstroke and a democratic notch and a by phase IQ way form. Whereas on the left side of the screen. The way form is blunted, the acceleration is delayed and the amplitude is reduced. This is a patient who actually has a right iliac artery occlusion, and they're right leg is being fed by collaterals. We can tell this without even needing to do a C T scan. That that's what that's where the problem is going to be. Tests of profusion or sometimes used when ankle or toe pressures, or either not obtainable or the patient no longer has a digit or other other situations. TCP 02 or trans continue socks. Symmetry is a test we do in our outpatient setting. In some of those cases, it takes a bit longer to equip liberate, but essentially, these are tiny trance. Continuous oxygen probes that could be placed on multiple locations usually place one under control location, either on the arm or the trunk, and then we can put a couple on different parts of the ankle and foot. Um, this test can be useful. Like other tests, it has an S shaped curved in terms of its predictability for se surgical healing in the foot, meaning when it's really normal and the C C P 02 is greater than 40. Uh, there's a very high percentage that a surgical decision or wound will heal with that circulation. If it's less than 10 that's a very poor result. It's severe ischemia, and there's kind of a wide intermediate range between 20 and 40 or 50 where it's not all that predictive, but it's not normal. Similarly, skin profusion pressure is kind of an inclusion based test using a tiny laser Doppler probe. We don't actually use this test in our lab, but it is used in a number of outpatient labs. It gives you similar information, and there are similar threshold number of 30 millimeters of mercury, which is a common number for toe pressure. NTC Po to that seems to be kind of a threshold level for healing. I mentioned that duplex ultrasound is an easy to use noninvasive test. It's available in the outpatient setting. It's portable. Um, it's comfortable, and it allows us to image the lower extremity arteries very easily. We can usually map any areas of abnormality narrowing or occlusion from the groin, comin from a lottery literally, all the way down to the ankle. Um, and we can also usually tell the difference between a stenosis and say, an occlusion where the where the inclusion is located. And that may help us make some decisions about the options of patient might have for for treatment. Okay, so we mentioned first and foremost importance of diagnosing P. A. D is its relationship to cardiovascular events and actually immortality. So the A B, as I'm sure you know, is actually an independent predictor of all cause mortality. And in fact, it adds independent additive predictive value even to the Framingham risk score, for example, to predict cardiovascular events. And what this graph shows you is that, um, compared to people in the somewhat normal range between one and 1.3 that the risk of events actually increases on both ends. So as the disease gets more and more severe and the FBI goes down, the mortality rate goes up. But also, if you're vessels are extremely stiff or not, compressible on the right mortality rate goes up because that's also a sign of poor vascular health. Okay, so long term mortality in patients with Ph. D is impaired in a way that's essentially equivalent to having symptomatic coronary artery disease Andi. It does depend on also on the severity of the disease. But even patients with asymptomatic peripheral artery disease have a significantly reduced survival compared to age matched normal subjects. So that's why making the diagnosis, particularly in a patient who doesn't already have known coronary or cerebral vascular disease, is important because these patients, when identified, should be treated as though they have a coronary disease equivalent with anti platelet therapy and statins. Certainly, once you reach Symptomatic PD and more advanced litmus key MIA mortality rates go up significantly. In general, patients with Claude occassion have about a 5% mortality rate per year, whereas patients to reach the stage of critical or limb threatening ischemia have about double that mortality rate. At least half the patients that are diagnosed to have no symptoms at all. But it is important to know that, um, when patients complain about leg pain, they don't all give the classic story, which we'll talk about, you know, in the next couple of slides of intermittent communication that is brought on only when they exercise a certain distance. Rapidly relieved by rest and located in a major muscle group, a significant percentage of patients with P D have kind of a typical sounding leg pain symptoms that may not fit the classic pattern that would meet one of the questionnaire instruments that might be using epidemiologic studies and a small but important percentage present. With the most advanced stage of what we call CLT I, we can again established this diagnosis and which stage of the disease, usually in almost all cases, in a single off this visit combining a careful history of pulse exam and the non invasive studies. The most important thing we do in most of these patients when we diagnosed him, if they're not presenting with limb threat, is educate them. It's important to educate them about what it means to have Ph. D. That it means that you are an increased risk for heart attack and stroke, even though it's not the blockage in your leg arteries that's directly causing that, but that these diseases are linked. It's also important to tell patients who have mild disease, mild symptoms or no symptoms at all, that they're not in any urgent danger of losing their leg. In fact, the risk of amputation for patients with Claude Occassion is extremely low has been studied in many different ways, and it's in the order of 1% per year. So we tend to try to get patients to understand that this is a long term vascular health issue. Overall, if we follow patients with Claude occassion, about a quarter of them will ultimately complain of things Getting worse to appoint with a disability mandates a surgical intervention within several years on, of course, when we recognize them or advanced disease, particularly in patients with other risk factors like diabetes. That's a whole different scenario that requires us to mobilize and provide rapid intervention and treatment. Intermittent Claude Occassion as classically described as pain and a major muscle group of the leg that's brought on consistently with exercise in its classic situation. It's extremely predictable. Patients will say the same amount of time with the same amount of distance or the same distance down the street to the mailbox or the same hill. Every single time they do it, they're going to get it on then, typically, if they stop walking in rest for just a couple of minutes, it goes away. It is not generally brought on by just changing position standing up from a chair, getting out of a car or just standing still in the kitchen. You know, in a vertical position, without actually exercising those air farm or suggestive of spine disease. There's also a relationship between the level of the disease and where the complaint usually is such that it's usually one joint level below where the conclusion is to notices. So patients who have disease in their aorta iliac level will usually complain of hip, thigh or buttock symptoms. They may also have calf pain, but they complain more about the proximal disease, whereas patients disease in their superficial, formal or property lottery, which is more common, will complain of the classic calf pain, usually not more proximal. Not all leg pain or cloud occassion is PD. So again, the history really here is the key, um, patients whose complaints occur at rest, lying still in bed or in a chair, standing without actually exercising much more suggestive of neuropathy at some level, whether it's peripheral in the foot or ridiculous at the level of the spine. Of course, patients who are in their fifties sixties seventies and eighties have lots of other co morbidity ease of which osteoarthritis is quite common. Typically, arthritis pain gets a little bit better when you start moving, as opposed to getting worse. Restless leg syndrome or muscle cramps occurring at night are typically not from a vascular ideology, so their common complaints that it can occur in the same population and Venus diseases even more common than P a. D. It can cause, like paying just from swelling and Venus hypertension in the veins of the leg, usually relieved with simple elevation. So key features of PhD related leg pain. It's often described as cramping, aching, tightness, fatigue. It's in a muscle group. It's not at rest. It's exercise dependent. It's consistent on. We talked about, not changes in position, and it's usually quickly relieved by rest. Once diagnosed, our goals really fall into two groups. One is to is to address the limb itself or the disability that they're experiencing. But the bigger overall goal, of course, at all times is to reduce their cardiovascular event rate, try and decrease their likelihood of morbidity and mortality from heart attack and stroke. This comes down to smoking cessation, lifestyle, education and medical therapy. Every single time I see one of these patients in my office where you go through the same exact questions starting from smoking. Second, are you taking your medications? Or are you on the appropriate medications, which include any platelet therapy and a statin at a minimum? And then what's been going on in terms of your other cardiovascular issues? And then we go to focus on the leg so improving their ability to walk eyes to is the idea there is to just to improve their quality of life and reduce the disability, which they perceive, um, at a higher level. I view my number one job in these patients to do everything possible to prevent them from getting to that limb threatened state and avoid the chance of them seeing a major amputation their lifetime. So that's about thinking about prevention and progression on when they have those more severe stages of limb threat. The goals air really to heal the wounds reduced to pain and preserve a functional limb person. Foremost stop smoking, have a healthy diet, just like any other patient with atherosclerosis exercise as much as possible. We prefer to tell people to try 20 to 30 minutes of walking at least three times a week as a goal, and then blood pressure and glucose control medications to reduce cardiovascular events. We're not going to spend time talking about that. I know you're all aware of the data and the fact that very recently we've actually had some new randomized trials n p a d patients looking at, for example, River Rock, Saban and also looking at some of the new PCSK nine inhibitors, both of which were shown to actually reduce all cause events as well as limb related events and PhD patients. So it's actually an exciting time on the medical front and atherosclerosis, where we have some additional options to offer the PhD patients that have been shown to reduce their risk. What about treating the leg, though? Okay, so they're the medications. We don't have a lot that's new in terms of symptom reduction. Um, the best tested intervention short of doing an intervention on the blood vessels, is exercise. Supervised programs have been the best tested, but home exercise can also work to improve walking ability. And, you know, exercise studies typically show that would well selected participants people can increase their onset distance to communication by 50 to 100%. So losses all is an FDA approved drug is the only one we have in the US that specifically approved for the treatment of intermittent communication. Um, I find in my practice that it has variable effectiveness some patients to report improving their distance in time more modestly in general than with exercise, and some patients don't don't seem to have any result it all. We typically if we try it, um, ask Ask that people tried for a month, and it's generally, um, well tolerated. But some patients may complain of flushing headache or G I symptoms, and it's contraindicated in patients with heart failure important to recognize. And we always tell the patients that the ones with mild disease, even though you have a quote blockage in your artery, they don't need intervention. We don't just treat disease because it's there we treated to preserve function. However, patients with more advanced symptoms may certainly benefit from different types of interventions to open or bypass these arteries. The more advanced stage that certainly prompts more aggressive and urgent intervention is when Ph. D. Reaches a stage of limb threat, and this may present with pain. What we call a scheme IQ rest Pain, which is often described as a severe pain in the foot, 4 ft arts or toes, forces the patient to try to hang their foot over the bed at night. It's often very difficult to manage with pain medication alone because it's basically resting ischemia. Um, when things get to the level of tissue loss, one can see a pretty wide spectrum of wounds that may be associated with P A. D in varying degrees of ischemia. Many of these patients, because they also have diabetes, may also have neuropathy, which we'll talk about. But they may present with small wounds that just simply fail to heal or get bigger, or frank necrosis, which is gangrene. The more severe compromised circulation in these cases must be treated if amputation is going to be avoided. These patients are also at higher risk for cardiovascular events and mortality, So this is the highest risk population that we see in general. Um, from the standpoint of vascular intervention and vascular surgery, we think of P. A D by segments of disease and really three segments aorta iliac segment, or what we call inflow above the groin. Ephemeral pop a little disease between the groin and the knee and then tibial repeal disease or below the knee disease. And the reason these makes sense or are important is because, first of all, they tend to align with typical risk factors. Such a certain populations, like diabetes patients, tend to have more common disease below the knee, whereas pure smokers tend to have more common disease in the larger arteries. Um, in general disease of a single segment, usually only results include occassion, unless that diseases vory distal like in the Tibbles and pedals. Usually it takes disease in more than one segment to get to the more severe or critical level of ischemia. Yeah, treatment options, um, starts out, of course again, if we as we've already mentioned with the basics elements of optimal medical therapy, exercise, diet, lifestyle. When it gets to the point of needing to think about intervention, either for disability or for limb preservation, we essentially have both catheter based approaches and open surgical approaches to treat different types of inclusions in different locations based on their an atomic characteristics. Most current vascular surgeons and vascular specialists need to be Fassel, with both catheter based techniques and open surgery to understand all the options and what the best options might be for an individual patient. Most important thing is to pick the right treatment at the right time for the right patient and not a one size fits all mentality. Increasingly, particularly in vaster surgery, we work in hybrid Oh, our suites, where we have the option to do either purely per cutaneous, purely open or increasing what we call hybrid operations. What we may combine, for example, a decision in to do an endarterectomy or plaque removal with an upstream or downstream Angie plastic. Lots of useful reviews. This happens to be a review that we published in 2018 that if anyone is of interest to just it shows the kind of broad array of the interventions and also the expected outcomes, which vary based on the severity of disease in the top of type of treatment that's pursued we have seen over the last couple of decades, and increasing revolution and endovascular technologies, which has certainly given us many more options for minimally invasive treatment. And many patients, including various, uh, wires, catheters, stance balloons, within without drug coatings and plaque removal techniques. So now we have a really broad array of options, which, unfortunately fortunately has gives us a lot of choices. Unfortunately, as sort of outpaced the evidence, really, and and so sometimes we're trying to debate which treatment to use without the best available data. That's often based on giving patients different options and choices and trying to determine what's the most effective and safest approach. Just a couple of quick examples. This is an aorta Graham in a patient with severe Claude occassion you're seeing on the screen is the abdominal aorta and its beautification. And you can see this is the left iliac artery with a very severe, very calcified plaque at the origin of the left iliac artery, which is nearly completely included, which is causing very severe, very short distance communication symptoms. You can also see that thes lumbar arteries, which are usually very small branches of the aorta on the left side, is quite enlarged. It's providing collateral flow to the left leg through the pelvis. In a situation where this lesion has been present and worsening over time, this is very this type of lesion can be very nicely treated with a balloon expandable stent place in this case and giving you now nice and brisk flow in a normal contour. Um, here's, um, or extreme case where the narrowing is actually right at the bifurcation of the aorta and actually affects the flow to both legs by a very vory focal plaque with these huge collaterals in cases like this, we have to treat both both sides at the same time doing what's called the kissing balloon and stent technique, and you can see when those center deployed they're deployed simultaneously so that the plaque eyes not shifted from one leg towards the other. But it allows us to raise the Arctic verification and provide a resolution of this lesion. Here's, um, or extreme case of a patient whose aorta is included. These air large lumbar collaterals. This is a patient who would present with the sort of classic syndrome that used to be named after Larry sh Larisa syndrome. This is severe hip buttock and thigh Claude occasions, sometimes impotence in these patients with relying purely on collaterals when when the disease gets to this level of severe occlusion, although you might be able to treat it with stents, it becomes more likely that you would need to do open surgery and the kind of surgery you do for that are open bypasses from the aorta to both groins to replace that diseased artery with prosthetic graphs. And I mentioned that the more common, more current techniques that we use in hybrid or rooms where we can do both imaging per cattiness interventions and open surgery, they allow us to do things in one sitting that in the past we'd have to do in more than one intervention. So, for example, on this side doing an endarterectomy of the common from a lottery, which is sometimes needed for severe calcified plaque and then at the same time placing a stent in the iliac artery upstream to resolve lesions in two locations. On this side, a patient with a more severe blockage in their in their thigh artery and a narrowing in the iliac. We may place a stent and at the same time go ahead and do a fem pop bypass all in one, sitting in the O. R. To get, you know, the optimal outcome. Special concerns about diabetes, and this is where we're gonna end up is the more these patients where we already mentioned that diabetes markedly increases the risk of P a d, both for the patient's life and for the limb. But as far as the foot goes, it's really important to understand that perfect neuropathy creates a lot of problems in a diabetic foot. First of all, it takes away the gift of pain. So when you can't sense pain, you are prone to injury. Eso the impaired nerve function and also the impaired resistance to infection and diabetes combined to put them at risk for severe foot problems. It's absolutely mandatory that patients with diabetes play close attention to their feet that they wear proper shoes, inspect their feet and avoid injuries, and they get a foot exam if they have established Ph. D several times a year. These patients need close monitoring because early detection and treatment is the key to avoiding major problems. This problem is growing everywhere, but it's really growing also in California. It's no surprise because diabetes itself is growing dramatically in California, where more than 15 million adults are estimated to have pre diabetes or diabetes, and it's largely affecting our populations of color. When looked at a number of years ago, it was a striking rise in lower limb amputations in California by over 30% and it spans all district's particularly concentrated in the Central Valley. The diabetic foot is a problem because of these three fundamental issues the neuropathy, the vascular apathy and the immune apathy that together put the foot at risk for serious problems and wound breakdown. The neuropathy effects both sensory and motor and autonomic components. They lose protective sensation. They get weakened intrinsic foot muscles, which leads to deformities in their foot and promotes areas of high pressure. They also lose sweat, get dry skin, which tends to crack and break down. Repetitive and minor trauma over localized, bony prominence is set the patient up for wounds and ulceration, and once a wound is present, even mild or moderate ischemia can now become limiting, and the presence of infection greatly compounds the risk of amputation. This is a serious problem that still suffers from major educational issues across the public and also referring physicians and primary care physicians. There is a relatively low level of community awareness of when to refer these patients and who is at risk. In addition, did This whole area suffers a bit from inconsistent classifications schemes? No medical insurance staging systems. Often patients with these problems are referred and bounced around between multiple providers. A wound care center and endocrinologist, podiatrist and then maybe eventually a vascular specialists. And they go from one office to another, and not infrequently. They lose further, uh, tissue in between, or things get worse. Treatment approaches air quite variable, and quality is not standard. The absolute key is rapid recognition and treatment of patients who are at the highest level of risk, and we often say timeless tissue. These patients need attention quickly to resolve infection and restore blood flow, and then, even after they're treated and sometimes healed, they require surveillance because re interventions and recruit essence of symptoms is common from the vascular side. We have a lot of options now to treat increasingly complex disease, both with catheter based techniques as well as open bypass surgery, which we still dio in 30 to 40% of these patients, with the advanced presentations using preferably their staff in this vein and often to targets in the lower leg, ankle and foot the question really, that we are always working on is what should we try first? What's the best treatment strategy that's gonna be the most effective to heal the foot and actually prevented from further problem? And that's very individualized conversation. Yeah, almost 10 years ago now, we developed a center at UCSF to really try to focus the team approach to this problem, which really does require a team approach. UM, 2011. We had already been working with a dedicated group of podiatrist in San Francisco, and we decided to formalize this relationship into the CFCs UCSF Center. Fill in preservation, where we focus both inpatient and outpatient treatment with a dedicated team for patients with foot ulcers and advanced faster conditions. The goal of the center is not just to heal wounds and preserving extremity, but to preserve a functional extremity, and this requires expertise from multiple corners. Podiatry is critical to this effort. Vascular surgery, infectious disease, sometimes plastic surgery and certainly cardiology and other specialties for co morbid conditions. The secret sauce that we find here is to see the patients at the same time and make treatment decisions in a in a single setting rather than having patients bouncing between different offices and to have the Caribbean closely coordinated with same treatment team both outpatient inpatient as needed. Our Centers is, uh, provides rapid turnaround time for patients who are referred for either active ulcers or advanced symptoms. We see patients, UH, several times during the week, largely at the Parnassus campus. Um, but we can also see and assess these patients from a basic approach. At the other office settings that I mentioned in the South Bay and East Bay. We treat in that specific clinic and setting. We are treating all of these different ranges of foot and lower extremity problems. Diabetic foot ulcers, perfectly disease shark 0 ft, which is a difficult problem to treat, often requiring biomechanical stabilization and various other circulatory and lower extremity wound syndromes. So we've created this grid for referring physician practices to sort of highlight the acuity of the presentation and how quickly these patients should be seen. The patients who have active ulcers, any signs of spreading infection, any evidence of tissue loss or gangrene or have rest pain. When we get that call, we try to see them within 1 to 2 business days in our joint center at Parnassus optimally. Other patients who are presenting with lesser degrees we might see within the week. And then there are patients who really just are in the screening and preventive mode, who may be seen it one of the outer clinics or be followed by their local podiatrists and just communicating with us as needed. No.