Update on Diagnosis and Management of Avascular Necrosis

June 13, 2024

Information

Presenter: Daniel Wiznia, MD and Rummana Aslam, MBBS

Meeting: GIM Grand Rounds

Host: General Internal Medicine

ID11780

To CiteDCA Citation Guide

00:02Go ahead and get things started while
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00:08For those of you who have not
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00:22And our goal is always to learn
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00:30And so, Tony, can you share our slides?
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01:04Today's noon conference will be
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01:12identity and patient care ownership.
01:14You'll remember that she is in
01:17academic hospital who presented our
01:20update on hospital medicine last year.
01:23Next slide, as you all know there
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01:33Next slide,
01:37we are excited to bring you Doctor Varty
01:41next time for a talk on advances in spine
01:44surgery for the primary care clinician.
01:46I don't know about you,
01:47but many people with spinal stenosis,
01:50many surgical decisions to to be made.
01:54So we're we're excited
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01:57OK, you can stop sharing our slides
02:00and we will let Doctor Wisnia and Dr.
02:03Oslam share theirs while I
02:06review their introductions.
02:08So I'm not going to go through
02:10them in in their entirety.
02:11You have it in your e-mail.
02:12But we're really delighted
02:14to have Doctor Wisnia and Dr.
02:17Oslam here with us today to
02:19talk to us about diagnosis and
02:22management of avascular necrosis.
02:25Dr.
02:25Wisnia,
02:26through various training at Yale
02:29and Weill Cornell and specialty
02:33fellowships at Institutes of
02:36Orthopedics and Sports Medicine,
02:39is now Associate Professor of
02:41Orthopedic Surgery and of Mechanical
02:44Engineering and Material Science who
02:46specializes in reconstructive surgery
02:49for the hip and knee and as well
02:53as revisions with a major clinical
02:55focus on AVN and osteonecrosis.
02:58Dr.
02:59Oslam comes to us through various
03:04different trainings but completed
03:06her fellowship in this area at Johns
03:09Hopkins and is now also Associate
03:12Professor of Orthopedics and the
03:15Director of Wound Care at Yale New
03:19Haven Health's Lawrence and Memorial
03:21Wound Care and Hyperbaric Medicine program.
03:25And we are thrilled to have you and
03:28I will turn the podium over to you.
03:30We used to do this in person and
03:32keep it real mellow and casual,
03:35so we still encourage people to do that.
03:38So people will pop things in the chat
03:40throughout your talk and as appropriate,
03:42I'll just interrupt you and ask you
03:44questions as if we were in a small
03:47conference room eating food and and
03:49just talking and learning together.
03:51So don't feel any pressure
03:52to to monitor the chat.
03:55Thank you.
03:57Thank you so much, Doctor Puglisi,
04:00for inviting us and having
04:03Doctor Aslam and I here.
04:06I'm Dan Wisnia.
04:08I'm an orthopedic surgeon and Doctor Aslam,
04:12she's a physical medicine
04:14rehabilitation specialist.
04:15We are gonna give you a talk today
04:19about what's new in avascular necrosis.
04:22So about two years ago,
04:26Doctor Aslam and I were at a departmental
04:29picnic talking about our passion.
04:33Mine in particular was
04:35treating a vascular necrosis,
04:37hers hyperbaric oxygen therapy.
04:39And the more we spoke,
04:42the more we realized we had a shared
04:44passion in which we could work together.
04:46And over the last two years,
04:48we've put together an assembled
04:52Yale's a vascular necrosis program.
04:54So we see a lot of patients with a
05:01vascular necrosis from across the
05:03country who come to Yale with a vascular
05:07necrosis primarily in their hips,
05:09but also in other joints.
05:11And we help them preserve their joints so
05:13that they don't need a joint replacement.
05:16And for those of you who are curious,
05:18you know, if you end up with a
05:20patient with a vascular necrosis,
05:22how would you refer them to our program?
05:25You'll go into EPIC in the
05:28chart in the order section,
05:31you can type in a,
05:33a VN or a vascular necrosis or
05:36osteonecrosis and then select
05:39the a vascular necrosis program.
05:41That will be the first in your list.
05:45And you can always feel free to e-mail us.
05:48You're never a bother,
05:49so always feel free to e-mail us as well.
05:55Now, a little bit of background about
05:59a vascular necrosis. What, what is it?
06:01So it's essentially an injury to the
06:05blood supply to the femoral head.
06:09And the femoral head, which is made of bone
06:13every day is remodeling. So as you walk,
06:16little micro fractures occur in the bone.
06:19And every day your body repairs those
06:22little cracks and it requires it,
06:25the bone to be alive.
06:27And when the blood supply is injured,
06:29the bone dies.
06:30Those cracks aren't able to heal.
06:32They propagate, they get bigger and
06:35then unfortunately the hip can collapse.
06:38And we do see this, I always tell, give
06:41the patients an analogy of a China plate.
06:43If you have a China plate,
06:47over time that China plate develops
06:49cracks and the cracks get bigger.
06:51And as the China plate ages,
06:52it then breaks.
06:54So it's really important for us to try
06:57to restore that blood supply to prevent
07:00the femoral head from collapsing.
07:03Over time,
07:04the name for a vascular necrosis has
07:09changed and some common names are
07:12osteonecrosis of the femoral head.
07:14That's primarily the term you'll see
07:16used in a lot of your pub Med searches,
07:20but also a historically ischemic necrosis.
07:24Subchondrially,
07:25vascular necrosis and aseptic necrosis
07:29have also been used in the United States.
07:34There's about 10 to 30,000 new cases
07:37that we're seeing every year and this
07:40is primarily in younger patients.
07:43So the patients who worsening with
07:47avascular necrosis can range from
07:49sometimes even in their teens
07:52to about 55 years old.
07:54And about 50 to 70% of them will
07:58go on and experience a hip collapse
08:01and need a hip replacement.
08:03And one thing that's really not
08:05well known is that 10% of all hip
08:07replacement due to a vascular necrosis.
08:12So when when we think of hip replacement,
08:15we think, well,
08:16that's because the cartilage has worn down,
08:18the patient has bone on bone arthritis.
08:21But actually 10% of all hip
08:23replacements are due to this disease.
08:25And it can be a very significant
08:28surgery for a young patient to have
08:31and then live with the potential
08:33risk and complications of the hip
08:36replacement for their entire adult life.
08:40What causes a vascular necrosis?
08:42The most common causes are trauma to the hip,
08:46alcohol abuse, high dose steroids.
08:50There is a correlation with COVID-19,
08:52which we'll talk about in a second.
08:54HIV,
08:55primarily the medication from HIV
08:58can be very toxic chemotherapy and
09:01then blood disgraces like sickle
09:04cell disease and clotting disorders.
09:08Now the thing that we really want to
09:11emphasize is that if we can catch a
09:15vascular necrosis early that it is
09:18possible to prevent or delay a hip collapse.
09:21So it's important that we catch these
09:24early because a hip replacement can actually.
09:29If you have a hip replacement at a young age,
09:31you may ultimately need a revision
09:33as the bearing surfaces wear out.
09:37And you could have a multitude of
09:40complications with the hip replacement,
09:41as I'm sure you've all have seen.
09:43And the best thing to do is
09:45try to avoid a hip replacement.
09:48And the therapies that we're
09:49going to talk to you about are
09:52relatively safe and a lot safer
09:54than having a hip replacement.
10:00So first I want to share with you a study
10:03in which this is a a big meta analysis.
10:07This meta analysis was looking to see how
10:12patients did with a total hip replacement.
10:16And they looked at patients who had
10:18a vascular necrosis and arthritis
10:20and they wanted to see the outcomes.
10:23How did these patients do after surgery?
10:26And they used national registry data.
10:29So this is really good dated.
10:30It's coming from countries like Australia
10:34and the United Kingdom that have really
10:37nice total joint replacement registries.
10:40And they found that AVN patients
10:44were 1.6 times more likely to have a
10:47revision after their hip replacement
10:49compared to patients who had arthritis
10:51who had a hip replacement.
10:53And they found that there is a higher
10:56risk of infection in these patients
10:58and also fracture around the implants.
11:01So this is something just to keep
11:03in mind that these patients even
11:05after they have the hip replacement
11:07have a higher risk of complication.
11:10Yeah. And I'm going to stop you
11:11there for a SEC. So question,
11:13what do you think that's from?
11:16So I mean, is it that this is a more
11:18systemic vascular process that we
11:20fail to realize as such and thus you
11:24have poor healing even around the,
11:26let's say, the implant,
11:27the site of the implant, etcetera?
11:30Or are there other factors at play?
11:34There's a few factors.
11:35One is these are younger patients.
11:38So you're having a 40 year old
11:40patient get a hip replacement compared
11:41to a 65 year old or 70 year old.
11:44So that younger patient is just
11:47going to be harder on the implant.
11:49They're going to be more active,
11:50they're going to engage in activities
11:53that maybe a 6570 year old wouldn't
11:56engage in that could lead to a fracture.
11:58The 2nd is that these patients
12:00have a lot of other comorbidities.
12:02You know, we went over the risk factors.
12:05They have HIV or a transplant or or
12:10sickle cell disease, alcohol abuse.
12:14So there's other reasons that that
12:17they're sicker that so they're
12:19higher risk for infections and
12:21that that that's another reason
12:23why they have more complications.
12:28So Doctor Asim and I have seen a lot of
12:33patients with a vascular necrosis who
12:37suffered of severe COVID-19 infections.
12:43And the reason for this is the relationship
12:48between COVID-19 hospitalization and
12:50being placed on high dose steroids.
12:53In this meta analysis,
12:55they looked at case reports, case series,
12:59they collected 104 patients who were
13:02diagnosed with avascular necrosis
13:04after being hospitalized for COVID-19.
13:07And they found that patients who had
13:11higher dose steroid use or prolonged use
13:14of steroids were at the highest risk of
13:17a developing a vascular necrosis. And
13:25this is not a reason not to give steroids.
13:29So I think the most important thing
13:32is steroids can be life saving.
13:33That if these patients
13:35hadn't received steroids,
13:36they may not have survived.
13:38So we're definitely not
13:40saying not to give steroids.
13:41There's many instances where you
13:43definitely have to 100% give steroids
13:47and if you think it's warranted,
13:50I wouldn't hesitate to follow the
13:54protocols that you currently follow.
13:56When you give a Medrol dose pack or
13:58if you or someones hospitalized and
14:00you're giving them high dose steroids,
14:02I think that is very reasonable
14:05because steroids have a lot of benefit,
14:09life saving benefit.
14:11But there is a correlation we're
14:14seeing in these COVID-19 patients
14:16who some of them were on steroids
14:17for a very long time,
14:19and we're seeing multifocally
14:20vascular necrosis in these patients.
14:25If you are interested in doing some reading,
14:28this is a terrific article
14:30written by one of my mentors,
14:33Doctor Lynn Jones at the Cleveland Clinic.
14:35It's a review article all about
14:37osteonecrosis of the femoral head.
14:39And we just want to share
14:41this article with you.
14:42So if you want some supplements
14:46reading after a talk,
14:48this article's available.
14:49So let's start with a case presentation.
14:53This is a typical patient that
14:55we'll see in the avascular Necros
14:58Avascular Necrosis program.
15:00A 29 year old female presents
15:02to our clinic with hip pain,
15:04complaining of three months of
15:06worsening groin pain and she was
15:08recently hospitalized about eight
15:10months ago with a severe asthma
15:12exacerbation in which she was given
15:14a course of high dose steroids.
15:17On exam she has groin pain and thigh
15:20pain and we obtained X-rays in the
15:24clinic and the X-rays are normal.
15:27This is very typical of a vascular necrosis.
15:30Early stage of vascular necrosis,
15:32you will not see signs of it on X-ray
15:35and that's why a lot of these cases are
15:38missed because patients get X-rays.
15:40The X-rays are normal and then for
15:44the work of it is delayed because
15:48because the X-rays are normal,
15:50folks don't pursue additional
15:53more advanced imaging.
15:56Well,
15:56Dan, let me just stop you there
15:58for a minute because if I'm the
16:00internist who this woman is coming to,
16:02which is the most classic place she would go,
16:06I'm not having AVN very high in my
16:08differential given that she just
16:10had a brief course of steroids.
16:12I tend to think of it more with
16:15prolonged steroid courses.
16:16Am I wrong in thinking about it like that?
16:18Is it, are you seeing this clinically
16:21even with brief burst treatments like
16:23an asthma exacerbation is Pred 40 for
16:26five days it are you seeing AVN and
16:29young people after a a course like that?
16:33So
16:34what we know is that there is a
16:38relationship between the length
16:40of the steroid use and the dose,
16:42but we also know that any amount of
16:46steroid use can lead to a vascular
16:49necrosis and certain patients are more
16:52prone to a vascular necrosis than others.
16:56So in fact, as an example,
16:58Doctor Asim and I have a have two
17:01brothers who each of them were
17:03put on a Medrol dose pack for
17:06back pain about a year ago.
17:09They both got AVN and we've
17:11done genetic testing,
17:13hematologic testing to try to figure out,
17:17you know, why would these two brothers,
17:20you know, with such a small
17:21amount of steroid use get AVN.
17:23So everyone,
17:24the way I think about it is everyone
17:27has a risk of AVN with steroid use.
17:30You know,
17:31there are some rheumatologic patients,
17:33they're on steroids every day
17:35for their entire lives and they
17:38never get AVN with other patients
17:40who they have one Medrol dose
17:42pack and they'll get AVN.
17:44So
17:44yeah, there's something genetic
17:46that we're not able or we don't
17:48know how to pick up on that can
17:51put people at differential risk.
17:52And so it sounds like even
17:54though it shouldn't be high,
17:56like very high on your list, this,
17:58this sort of scenario can lead to AVN
18:00and that's really helpful to know.
18:03I, I would definitely have it on the,
18:05on your differential diagnosis and
18:08some other potential diagnosis you
18:11should have on your list besides
18:14osteonecrosis of the femoral head would
18:17be a femoral neck stress fracture,
18:19a subchondral insufficiency fracture,
18:21a hip dysplasia.
18:23So labral pathology, early onset arthritis.
18:28And then sort of lower on the
18:29list would be septic arthritis.
18:31But if there's other,
18:32you really need to get a good history too.
18:36So if there's a history of other
18:38joints that are also painful,
18:40maybe a rheumatologic etiology that
18:43really comes down to getting a good HPI
18:49in terms of the work up,
18:50you want to get a good history.
18:52So Doctor Asim and I,
18:54we have a checklist that we go
18:56through of all the potential risk
18:58factors for avascular necrosis.
19:00So we really try to identify over the last
19:04few years if there were any potential risks.
19:08And then we want to understand the
19:10onset of the pain and where it is.
19:12And patients who have hip pain may have
19:14referred pain to the buttock or the knee.
19:16So if they're complaining
19:18of knee pain or pain,
19:19you have to really make certain you,
19:22you don't ignore the hip because
19:25I've had a few patients who
19:26come in saying my knee hurts,
19:28my knee hurts and I say,
19:30oh, by the way,
19:31your knee is hurting because
19:33you have hip avascular necrosis.
19:35So that's you always have to keep
19:37that in mind on physical exam.
19:40They're gonna have pain with thigh rotation.
19:42One classic sign is pain with a log
19:45roll where they're lying on their
19:47back and you rotate the leg and they
19:49have pain in their thigh and groin.
19:52And you'll start with X-rays.
19:54So you'll get X-rays of both hips.
19:56And then if the X-rays don't show anything,
19:58you'll move on to more advanced imaging.
20:01If you find a vascular necrosis in
20:05one joint and they're complaining
20:07of pain in other joints,
20:09that's when I would consider a skeletal
20:11survey and get X-rays of the knees,
20:14the ankles and the shoulders 'cause
20:16that's those are other joints in
20:19which we'll see a vascular necrosis
20:22in terms of which X-rays to order.
20:24So I would order these three X-rays.
20:27I would start with an AP pelvis.
20:29This allows us to see the hip
20:31joints and also the femoral heads.
20:34And then I would get dedicated
20:36AP right and left hips.
20:38This is where the X-rays focus right
20:41over the femoral head and we're able
20:44to identify if there's any signs
20:46of a vascular necrosis in the hip.
20:50And then we get a frog leg
20:52lateral right and left.
20:54And the value of this X-ray is
20:56that it allows us to get a 90°
20:59orthogonal view of the femoral head.
21:02Now in a bunch of patients,
21:05we will not see any signs
21:07of a vascular necrosis,
21:08especially in in AVN early on in the disease.
21:12So if the X-rays are negative,
21:14then you want to consider
21:17high resolution imaging.
21:19So first thing I tell everyone is before
21:22you rush and go ahead and order something,
21:25look in their chart and see if
21:27they've already had ACT scan
21:29or MRI over the last year.
21:31Because there are many times a
21:33patient has gone to the emergency
21:35room and the emergency room just
21:38reflect reflectively just gets ACT
21:40scan of the abdomen pelvis and
21:42we can see AVN on the CAT scan.
21:44And if it's already been done,
21:46there's no reason to repeat the the study.
21:50The gold standard is an MRI.
21:52So we'll get an MRI of the
21:54bilateral hips without
21:55contrast. You don't need contrast.
21:58And if they're not able to get an MRI,
22:01then you can get ACT pelvis without contrast.
22:05And this is what you'll see.
22:07You'll see edema in the femoral head.
22:09You'll see signs of a vascular necrosis
22:14where there isn't any perfusion.
22:15You'll see areas of dead bone.
22:19In this particular patient,
22:20we're able to tell that the
22:22femoral head does not collapse.
22:24We have a nice round femoral
22:26head to This patient is a great
22:28candidate for therapies to try to
22:31prevent femoral head collapse.
22:35So when a patient comes to
22:37our vascular necrosis program,
22:39we categorize them into two categories.
22:42Has your hip collapsed or not?
22:44If it hasn't collapsed,
22:45then you're a candidate for therapy
22:48such as medication, surgery,
22:51such as cord decompression in
22:54which we drill into the femoral
22:56head to remove some of that dead
22:58bone and then we will put some
23:00stem cells into the region and
23:04also hyperbaric oxygen therapy.
23:07But unfortunately,
23:07if the femal head has collapsed,
23:10then our only option is a hip replacement.
23:14We don't have a way to restore the
23:16femal head once that round spherical
23:19architecture has been destroyed.
23:21A
23:21couple questions here if you don't mind.
23:24One is what is the timing between
23:26taking a course of steroids and the
23:29development and symptoms of AVN?
23:30Is that predictable in any way?
23:35What I'll tell you is a lot of
23:38patients will say that during their
23:40course of treatment of the steroids,
23:43they will notice symptoms of joint pain.
23:49So it's likely the AVN is occurring
23:52as they're taking that medication.
23:55And then in terms of when during the
23:58course will the femoral head collapse,
24:00that timing is really hard to predict.
24:03It depends on the size of the
24:05lesion and where the lesion's
24:07located within the femoral head.
24:09So sometimes the lesion can be
24:11located in a more of a weight
24:13bearing region of the femoral head.
24:14That's higher risk of collapse.
24:16It's a larger lesion that's
24:18higher risk of collapse.
24:20Got it. That's helpful.
24:21And I think you said this,
24:23but just to confirm,
24:25if somebody already has existing
24:27significant hip arthritis away,
24:30will it be harder to
24:31see the AVN on imaging?
24:35It's a good question it it shouldn't be,
24:37but in patients who have underlying
24:41arthritis, they probably would not
24:43be a candidate for any of these
24:45preventative therapies for hip collapse.
24:48And we would probably recommend
24:51a hip replacement because if
24:53you have arthritis in the hip,
24:55then again, you know,
24:58what we're trying to preserve with
25:00these therapies is that round shape
25:02of the hip and the cartilage.
25:04But if you the cartilage is already damaged,
25:06it would most likely make sense not
25:10to do these preventative therapies.
25:13OK, And then one more and just humor
25:15me 'cause this one's a little bit
25:16out there and it's my own question,
25:18so I'll own that. But like, you know,
25:20this is an ischemic process.
25:22So if you have ischemia to the heart,
25:24we have a troponin that
25:26that can be our marker,
25:27our biomarker in addition to more
25:30rudimentary tests like an EKG.
25:32If you have ischemia to the gut,
25:34we have a lactate we can check as a marker of
25:37ischemia that can point us towards, you know,
25:40whether that process is, is occurring.
25:42Is there any such biomarker
25:44with ischemia to the bone?
25:46Because it seems like this imaging like
25:49it's like by the time the imaging changes,
25:51you already have some some
25:52big problems going on.
25:54You're not catching it early.
25:55It doesn't sound like with an X-ray per SE,
25:59probably something's happening before
26:00you can even see it on an X-ray.
26:04And so I wonder if there's work in the
26:06field on biomarkers of bone ischemia
26:08that can point you towards that.
26:12It's a great question.
26:14And there are certain biomarkers
26:16that can be elevated.
26:18These are markers that show
26:21osteoclast activity and they're
26:24just not sort of traditionally
26:28ordered or available in our lab.
26:31And, and, but there have been a bunch of
26:34papers looking at different biomarkers,
26:36different products of bone resorption
26:42that that in which you will see a spike,
26:45but I'm not aware of them being
26:50used for for a diagnostic purpose.
26:52Got it. Thank you.
26:56So in terms of medical
26:59therapies, there are certain
27:03there's certain comorbidities
27:04that place a patient at higher
27:07risk for avascular necrosis.
27:09So one are patients with thrombophilic
27:12or hypo forbidinolytic disorders.
27:15And there are some studies for this
27:19particular subset of patients that have
27:22found that Lovenox or heparin can be helpful.
27:27And there is another subset of patients
27:31with lipid metabolism disorders and
27:34hypercholesterol disorders in which
27:36statins have been found to be helpful.
27:40There are a number of studies looking at the
27:43use of bisphosphonates and bisphosphonates,
27:46specifically allodronate therapy.
27:48It's known to slow osteoclast activity
27:53and there's very strong evidence to
27:55show that it does slow the progression
27:58of the disease of avascular necrosis
28:00and it can also help with hip pain.
28:03So the bisphosphonates are a good
28:08medical therapy to consider,
28:10but not every patient is a candidate
28:12and they do have side effects and not
28:15every patient is really open to this.
28:17And the one thing about bisphosphonates is
28:20that while it it slows the progression,
28:23it doesn't help with angiogenesis,
28:25It doesn't help with revascularizing the hip.
28:29So it will delay the rate of progression,
28:32but it doesn't halt it.
28:37One particular surgery that has demonstrated
28:40a lot of effectiveness is cordee compression.
28:43So this is where we drill into the
28:46femoral head directly into the
28:49lesion and remove the dead bone.
28:52And the one big value of this surgery
28:55is that it reduces the swelling and
28:58pressure within the femoral head.
29:01So that provides some pain relief and also
29:04by reducing the pressure in the femoral head,
29:08helps with revascularization.
29:09The second thing is,
29:12is that a sclerotic margin of bone
29:15develops around the dead bone.
29:17This becomes very thick.
29:19And as a surgeon,
29:20I can tell you as I drill through it,
29:22it's almost like I'm drilling through rock.
29:24It is so thick and hard.
29:26And there's no way that new capillaries
29:28or blood vessels can cross that
29:31barrier into that region of dead bone.
29:33So the core decompression,
29:34another reason we do it is to
29:37provide a pathway for those new
29:39capillaries to grow into that region.
29:44There are many, many clinical studies
29:46that have been done over the years
29:48looking at core decompression.
29:501 challenge in comparing all these
29:52studies are that there's many different
29:55techniques drilling with the eight or
29:59nine different drill pins different
30:03removing certain amounts of bone.
30:06But they have all shown very good
30:10success with with smaller lesions
30:13and less advanced stage lesions
30:15and they really show a remarkable
30:18improvement with pain control and
30:20core decompression has been found to
30:23delay the need for hip replacement.
30:28One big question we had here at
30:30Yale is that if a patient has
30:32a core decompression surgery,
30:34does it then make their the hip replacement?
30:38If they need a hip replacement down the road,
30:40does it affect the outcome
30:42of that hip replacement?
30:44And what we demonstrated in the
30:48Journal of the American Association
30:50of Orthopedic Surgery is that if
30:52you have a cord decompression,
30:54it does not affect your outcome if
30:56you eventually go on to femoral head
30:58collapse and need a hip replacement.
31:00So that's a really reassuring finding
31:04to tell patients is that, you know,
31:07we're not closing any bridges or making
31:08if you need a hip replacement down the road,
31:11we're not increasing your
31:13risk of something happening.
31:16So according compression is very challenging
31:20because it's directed under fluoroscopy.
31:22So these are X-rays.
31:25So you try to see the lesion on X-ray.
31:28It's really hard.
31:29I don't know if you can see
31:31the lesion on this X-ray,
31:33but it's in, in my opinion,
31:34it's almost impossible to see on X-ray.
31:38So what traditionally is done is the surgeon,
31:42instead of just drilling in once,
31:43they'll drill in eight or nine times
31:46through different tracks to really
31:48ensure that they are hitting the lesion.
31:51But every time you drill
31:53through the femoral neck,
31:54you increase the risk of a hip fracture.
31:56So in the traditional sense,
31:58when these cord decompressions are done,
32:00most surgeons don't allow the patient
32:02to weight bear for three to six months
32:05because they're destabilizing the bone
32:07and they're removing so much bone.
32:12We also at Yale used stem cells.
32:15So what we'll do is we'll take bone
32:18marrow aspirate concentrate and then
32:19we'll spin it down with a special
32:21centrifuge system in the operating room.
32:24And then we'll give these stem cells back
32:27during the surgery through those drill tracks
32:30to supplement the core decompression surgery.
32:33And this procedure has a term,
32:36it's core decompression with adjuvants.
32:38And there's many different
32:39adjuvants on the market,
32:40bone marrow aspirate, concentrate,
32:43platelet risk rich plasma.
32:45There's even studies where they take
32:47patient stem cells and grow them in the
32:50lab for a few weeks and then and then
32:53inject those into the femoral head.
32:55But, but very good evidence has
32:59been demonstrated using these
33:01adjuvants and and improving the
33:03outcome of core decompression.
33:06One thing I want to emphasize is that a
33:10vascular necrosis has very different,
33:14very different in shapes and sizes.
33:18So these are four 3D models that we created
33:21on patients with avascular necrosis.
33:23And here you can see that some of
33:25the lesions are very small.
33:27Some of the lesions are very large.
33:30And this is just to emphasize that
33:32when you do a cardiac compression,
33:34you really need to customize the surgery
33:37for the patient and target the lesion.
33:40So we developed at Yale a 3D technique
33:44and we use computer navigation
33:47stereotactic techniques where we
33:49create the 3D model during the
33:52surgery and then we're able to guide
33:57during the surgery in 3D,
34:00our drill guide right into the lesion.
34:03In the panel A you can see the
34:06patients in the CT scanner and panel
34:09B you can see I'm holding a drill
34:13guide that has an optical array on
34:17it and the patient's thigh bone,
34:19the femur has an optical array.
34:21And then in 3D in the third panel,
34:23you can see that I'm able to move the
34:26drill guide and target the lesion directly.
34:30So with this technique, I'm usually
34:32able to do it with just one drill pass.
34:35And I'm not, I, I, I do not have to
34:39do eight or nine different drill paths.
34:40I'm able to do the surgery just
34:42with one drill path.
34:44And this is a technique that
34:46we developed here at Yale using
34:49our stereotactic techniques.
34:54And, and just quickly here,
34:57you can see we're drilling
34:58into the femoral head.
34:59We've targeted the lesion.
35:01We've deployed a flip cutter
35:03drill to remove the dead bone.
35:06We're inside the lesion,
35:08removing the dead bone,
35:09and then we're going to inject
35:12the stem cells into the lesion.
35:14Right now, I'm going to
35:15hand off to Doctor Aslam.
35:18Thank you, Doctor Bisniya.
35:20So I'm going to talk about my role in
35:23this program is providing hyperbaric
35:25oxygen therapy as an adjunct
35:28treatment to the procedure the doctor
35:30Viznia is doing for ABN patients.
35:33This is like a boost to what he does
35:36and I'll explain in the next few slides
35:40so you can advance the slide to that.
35:44Oxygen used in high concentrations
35:46of hyperoxia is actually a drug
35:50with many therapeutic effects and
35:52hyperbaric chamber is the dosing device.
35:56The definition of hyperbaric oxygen is
35:58not just hyperoxia, but it is hyperbaric.
36:01So it is 100% oxygen intermittently
36:04breathing by a patient breathing.
36:07So that's a systemic effect under
36:10pressure and the pressure that
36:13hyperbaric oxygen is defined at is at
36:17least 1.4 atmosphere absolute above
36:19sea level where one is at sea level.
36:23Most of the outpatient therapies
36:25that we provide with hyperbaric
36:27oxygen like wound healing,
36:29treating osteomyelitis,
36:30keeping radiation injuries is
36:32anywhere between 2 and 2.48 year
36:37absolute atmosphere pressures.
36:39That's the normal range and each
36:43patient would have about 30 treatments.
36:46That is five days a week for about 6
36:50weeks and each treatment is 2 hours in
36:55the chamber getting this 100% oxygen.
36:58With this therapy,
37:00the arterial PO2 raises to about
37:041000 to 1500 millimetres mercury,
37:06whereas this oxygen is not the
37:09oxygen bound to the hemoglobin.
37:11This is dissolved oxygen in your plasma.
37:14With that high pressure,
37:16this oxygen can diffuse out of the
37:18vascular system into ischemic tissues
37:20and in tissues we raise the high.
37:23We raise the oxygen tension to about
37:26300 to 400 millimetres AG with two
37:29to three atmosphere pressures of
37:32hyperbaric oxygen and that is the
37:35concentration where oxygen has
37:37the therapeutic effects.
37:38So oxy hyperbaric oxygen,
37:41the therapeutic effects are mostly through
37:48through you know generation of reactive
37:51species of oxygen and nitrogen and
37:54then these reactive oxygen and
37:57reactive nitrogen species will then
38:00lead to many signalling pathways which
38:02all have these therapeutic effects.
38:05So the biochemical pathways where hyperbaric
38:09oxygen improves neo vascularization
38:12or antibacterial effect of collagen
38:15synthesis and regulating inflammation,
38:18these are all biochemical pathways that
38:21have been established beyond, you know,
38:24with very good evidence for decades now.
38:27But what is now emerging is the
38:30mechanism of hyperbaric oxygen for
38:32avascular necrosis and how does it
38:34promote osteogenic process promotion,
38:36which I'll talk about in a few
38:38minutes next time please.
38:43So this is our oxygen hyperbaric
38:46chambers at the Lawrence and Memorial
38:48Wound and Hyperbaric Centre.
38:50These are monoplace chambers.
38:51These are more commonly used
38:54for outpatient therapies.
38:55There are multi place chambers which
38:58actually have many patients sitting
39:00in a big room and they actually wear
39:04hoods for the hyperbaric oxygen.
39:06Whereas in monoplace chambers
39:07which are very common in many
39:09hyperbaric outpatient centres,
39:11one patient goes into one chamber and
39:15stays there for about 90 minutes getting
39:19hyperbaric oxygen and next slide please.
39:22The patient lies on a stretcher.
39:25The stretcher,
39:25the top part of the stretcher
39:28goes directly into the chamber.
39:31The patient is given 100% oxygen, sorry,
39:34clothes that are safe for 100% oxygen.
39:37So they're 100% cotton and cotton sheets.
39:40These are all hyperbaric safe linen
39:43that goes in when the patient
39:45is in the door is closed.
39:47But there are all these diets and
39:49mechanisms to change pressure and be
39:52able to communicate with the patient.
39:54A hyperbaric physician is supposed to
39:56be in the center at all times when the
39:59patient is in the hyperbaric chamber.
40:01And a hyperbaric nurse and a
40:03technician is in the room at all times
40:05to communicate with the patients.
40:07Next slide, please.
40:09So I'm going to talk to you about
40:11a little bit about osteo radio
40:13necrosis of the mandible or ORN.
40:16This hyperbaric oxygen protocol
40:19for ORN was established like about.
40:22More than four decades ago by
40:24doctor Robert Marks and it's called
40:27the Marks protocol.
40:28The interesting thing is that
40:31the pathophysiology of ORN,
40:33how it affects the jawbone is actually
40:36an avascular necrosis which was
40:38established by Doctor Robert Marks
40:40like in 1980s that he established
40:43by by sampling bone from necrotic
40:47bone that they were no bacteria.
40:50So he said this is not an infectious process,
40:53this is essentially an avascular necrosis.
40:57Who gets this is patients who have
41:00radiation for head and neck cancers.
41:02They because of late effects of radiations,
41:05get fibrosis of blood vessels and
41:09develop this necrosis of the jawbone.
41:12The protocol that Doctor Marks came
41:15up with decades ago and it is actually
41:18the earliest use of hyperbaric oxygen
41:21and it is actually the most frequent
41:24use of hyperbaric oxygen that we see
41:27that we use in medicine today as well.
41:32So the protocol is 20 treatments
41:36of hyperbaric before the surgical
41:39treatment for the necrosis or the
41:41when the oral surgeon removes the
41:44necrotic bone and the decayed teeth.
41:46So you give 20 treatments before
41:48and the idea of those 20 treatments
41:50before is to condition the bone
41:52to decrease inflammation in,
41:54improve some neo vascularization
41:56so the bone can then withstand the
41:59trauma of the surgery, the wounding,
42:01as well as the metabolic need of
42:03the surgical intervention.
42:05And then you do the oral surgeon
42:07takes out the teeth,
42:09cleans out the bone and then you
42:10do 10 more treatments after that.
42:13So that has been an established
42:15protocol and then 10 more treatments
42:17after the surgical procedure is
42:19to heal the
42:20surgical bone and heal the bone.
42:22In my last 15 years of doing hyperbaric
42:26oxygen, this has been a very successful
42:29treatment of all ORN using this protocol
42:32and Doctor Marks has on many papers on this
42:36where they've shown complete resolution
42:38and really huge success of this procedure.
42:42Now the question that Dan and I were asking
42:45like if this is the same path of Physiology,
42:48so why isn't hyperbaric approved for AVN?
42:51And that is our mission now to get it
42:55approved for AVN because believe it or not,
42:57the European Council of Hyperbaric
42:59Medicine has included AVN and approved
43:01it for a condition treated that
43:05will benefit from hyperbaric oxygen.
43:06But we need large randomised controlled
43:09trials to get it approved here.
43:12But we do believe and this is our,
43:14our hypothesis or I think we have,
43:18we have done some cases that we think
43:20have suggested that the concurrent use of
43:23hyperbaric with core decompression that
43:25Doctor Viznia is doing with stem cells.
43:28This will all have a collaborative and
43:30enhanced effect on, on healing of this bone.
43:33Next slide please.
43:36So improved neo vascularization
43:38by hyperbaric is not only through
43:41angiogenesis, which is you know,
43:43takes a hyperbaric effect,
43:44endothelial cells and new blood
43:46vessels sprout in areas of ischemia,
43:48but also through vascular vascular genesis,
43:53which is basically de Novo
43:56synthesis from stem cells.
43:58So as I said, hyperbaric oxygen,
44:01the therapeutic effects are through reactive
44:04oxygen and reactive nitrogen species.
44:06But because hyperbaric oxygen is interrupted,
44:09so it's like daily for two hours and we
44:12do five days a week and interruption.
44:14This protocol has shown that hyperbaric
44:17oxygen will give enough oxidative stress
44:20to drive all these processes of neo
44:24vascularization and tissue regeneration,
44:26but it is not oxygen toxicity.
44:29So this is very important to understand
44:32about the mechanism of hyperbaric
44:34oxygen and its efficacy that the
44:36oxidative stress by hyperbaric oxygen
44:39is not synonymous with oxygen toxicity.
44:42Doctor Steven Palm has done extensive
44:45research on hyperbaric oxygen and
44:48shown that hyperbaric oxygen does
44:51mobilize stem cells from stem cells
44:54depot in the body from bone marrow,
44:57not only mobilizes them but enhances
45:00the recruitment of stem cells in
45:03ischemic tissues or areas of injury.
45:06Not only that,
45:07it also improves and stimulates
45:10the differentiation of pure pure
45:12reputant potent stem cells.
45:14So with Doctor Viznia putting
45:16the stem cells there,
45:18we believe that it is going to
45:20enhance a lot of effective stem cells,
45:22not only mobilizing the stem cells,
45:24but stimulating the stem cells that
45:26have been put there by Doctor Viznia
45:28so that they have their effect sooner.
45:30So the oxidative stress needs to hit 1A,
45:35which is hypoxia inducible
45:37factor stabilization,
45:38growth factor production.
45:40And there's a whole mechanism of
45:42many cytokines and growth factors
45:45that are affected.
45:47And these studies were done not only
45:49in mice but also in human volunteers
45:52and patients where samples were
45:54taken of blood at beginning of
45:56hyperbaric at 10 treatments 20 and 30.
45:58And they were shown that there was
46:01increasing stem cells circulating in
46:03the bodies. Doctor Kemporesi and Dr.
46:06Vizani have done extensive research
46:08and published widely and now have
46:11come up with these new indications of
46:14hyperbaric and have shown evidence
46:17that hyperbaric oxygen suppresses
46:19the activity of osteoclast.
46:21So in dead bone or ischemic bone,
46:24the osteoclasts are activated and there
46:26is more bone reduction than bone generation.
46:29So what hyperbaric does is
46:32it reverses this process.
46:34So it suppresses osteoclast
46:36differentiation and activation,
46:38it stimulates osteoblast differentiation,
46:41drives down the inflammation by decreasing
46:46amounts of TNF alpha Illinois 6.
46:49So it decreases the bone edema,
46:51it decreases pain.
46:52That way it tips the balance towards bone
46:55regeneration rather than bone resorption.
46:57But underlying mechanisms are
47:00still largely unclear as we are,
47:03and we hope to have more studies
47:05to elaborate on these effects.
47:07Next slide please.
47:09What are the side effects of hyperbaric?
47:11Basically,
47:12hyperbaric is one of the safest
47:14treatments in modern medicine.
47:16All the side effects that we see in
47:19our practice is they are temporary.
47:21So the most common are the
47:23patient can be claustrophobic,
47:25but once they get into these chambers,
47:27because their glass chambers is a person
47:30outside, they can watch TV outside.
47:33Most people are not claustrophobic
47:35like they would be in an MRI machine.
47:38Some oftentimes if they have
47:40significant claustrophobia,
47:41we give them a little anxiety
47:44medicine and they do fine.
47:47The other very common side effect
47:49which is also temporary can
47:50be middle year better trauma.
47:52So our our sinus squeeze because
47:54these cavities in our scalar airfield,
47:58airfield and can have the pressure if
48:02middle year starts bothering the patient,
48:05they can get a meeting guard and
48:06meet you by an ENT which equalizes
48:08pressure on both sides of the tympanic
48:11membrane and it's very comfortable.
48:13I've never had in my 20 years have
48:16anybody blow out the tympanic membrane.
48:19Those have been reported very,
48:21very rarely,
48:22but those have been in cases where you
48:24really have to increase the hyperbaric
48:27pressure for life saving emergencies
48:29like carbon monoxide poisoning.
48:31But again,
48:32are very rare and most patients
48:35do not even need a tympanic,
48:37you know, maryngotomy.
48:39They're fine by decongestant,
48:42you know, treatment by sprays.
48:45Progressive myopia sometimes happens.
48:47It's seen after many treatments
48:50like 20 or 30 treatments,
48:51but it gets reverted and gets normalized
48:54after we stop hyperbaric treatment.
48:57Any toxicity in the lungs,
49:00which can be like half or some
49:05inspirational burning or any CNS toxicity
49:08which we might think would happen with
49:12oxygen toxicity like seizures or nausea,
49:16vomiting.
49:16These are very,
49:17very rare.
49:18And these will happen after 100
49:21treatments or high pressures which
49:23are not really used in in any
49:26treatment protocols that we use.
49:28So it's very safe treatment.
49:31Next slide, please.
49:34This is an RCDA randomized controlled
49:36trial that was done by doctor Cam Borussi.
49:40When he compared this was a small trial,
49:42but it was very the evidence are very
49:46good with he took 20 patients and
49:50randomized them to either hyperbaric
49:53oxygen or just hyperbaric air.
49:55And these are patients of AVN stage two
49:59AVN and he did pain scores also did
50:06MRI imaging showed that after about
50:0920 treatments the pain got better.
50:11The range of mission got better between
50:1320 and 30 treatments and this is
50:16exactly what we are seeing with the
50:18patients that we have done so far.
50:21It is amazing that after 20 treatments
50:23these patients were walking with a
50:25cane and these are young patients
50:27were walking with a cane or limping.
50:29They come in without their cane in
50:31the centre and not limping anymore.
50:33So these are patients we get very
50:35attached to because they come every day
50:37and the staff gets attached to them.
50:39So when they come without a cane,
50:41you should see the excitement in
50:43the wound center.
50:43It's like, whoa, what happened here?
50:45Look at this patient now he's walking.
50:48So that we have noticing at
50:51about 20 treatment that happens.
50:53And in this trial they followed the
50:55patients for about one year and
50:58seven years with imaging and they
50:59found that none of them needed a hip
51:02replacement and there was complete
51:04resolution in at least seven patients
51:06of the ischemic necrosis.
51:08Now these did not have surgery,
51:10they were just treated with 30
51:13treatments of hyperbaric.
51:15Next slide,
51:16please.
51:17So we have come up with a protocol
51:19and we are still trying to design
51:22A protocol for our study.
51:23But most of these patients are coming
51:26from out of state and we just want
51:28to make sure that we have something
51:30that that is practical for them.
51:33And this is a protocol I came up
51:35with and with Doctor Viznia looking
51:38at the evidence,
51:39looking at the Marks protocol.
51:40Now where is Marks protocol is
51:44based on conditioning for 20
51:46treatments before the surgery.
51:48Now those surgeries are a little extensive,
51:50whereas Dr.
51:51Wisnia surgery is the patient
51:53is up and about and walking.
51:55It's so minimally invasive.
51:58And then he's putting stem cells.
51:59So we said,
52:00OK,
52:00let's just do about two weeks or
52:0310 treatments of conditioning,
52:05then do the core decompression because
52:08I felt the healing should happen
52:11after with the neo vascularization
52:13that we think is happening.
52:15So we are doing four weeks after.
52:18So far this is showing good results,
52:20but we are designing a clinical trial
52:23where we'll do different doses for
52:25hyperbaric to compare really what works.
52:28We don't know yet.
52:29Next slide please.
52:33So this is our program.
52:35Our mission is to provide integrated
52:37care to all avian patients.
52:39These are patients pre collapse
52:41and we hope to coordinate with
52:45other medical specialties.
52:47We want to catch them early.
52:49We want to minimize the risk of having
52:52them undergo hip replacement surgery.
52:54So, so far this is the program and it
52:58is Doctor Viznia's Co decompression.
53:00And then the hyperbaric is I've done
53:03under my supervision at the Lawrence
53:05and Memorial Munden Hyperbaric Center,
53:07which is part of the New Haven Health.
53:11And this is the core orthopaedic surgery team
53:16because we do have other joints
53:19with AVN, so happy to offer
53:22them hyperbaric if they need it.
53:25And Doctor Vizio, do you want to
53:28talk about the last slide, this one?
53:32Yes. So yeah, but we've been,
53:33we've been ramping up over the last
53:36year and we're now at the pace of
53:39doing about 60 core decompressions
53:42a year and dozens of hyperbaric
53:45oxygen therapy treatments at L&amp;M.
53:48And a few months ago,
53:50we had a patient with a vascular
53:52necrosis of their talus and we did
53:54the first total talus replacement in
53:56the health system for that patient.
54:02Again, if you need to get in touch with us,
54:05feel free to e-mail us.
54:07And you can always put an order in Epic.
54:10Just type in AVN or osteonecrosis
54:14or avascular necrosis and we'll
54:16try to help your patients.
54:19And if you have any questions at all,
54:22don't hesitate to reach out.
54:26Thank you. Thank you guys so much.
54:28Really interesting stuff in a topic
54:29we have not had in the past 10 years
54:32I've been directing this course.
54:34So really, really interesting to
54:36hear about what's going on at Yale.
54:38Certainly stuff we have I'd say
54:40more commonly in the outpatient is
54:42historically perhaps before your
54:44program was people on chronic pain
54:47medications for non operative AVN,
54:50which becomes quite a conundrum.
54:53And it's, it's really great to hear that
54:56there are other approaches going on now.
54:59A really great question in the chat by
55:02Doctor Banatowski asking can you talk
55:04briefly about how alendronate is both
55:06a potential cause of osteonecrosis
55:09and a treatment for osteonecrosis?
55:13It it's a great question because it's known
55:16to cause a vascular necrosis in the jaw.
55:19So why would you think it
55:21would help in the femoral head?
55:24Well, the architecture is different
55:27in terms of the blood supply.
55:30And in the femoral head,
55:32the epiphysis of the femoral head has a very,
55:35very poor blood supply.
55:37It's supplied by small little capillaries.
55:40You have to remember that the
55:42cartilage is not perfused at all.
55:44So you have small little capillaries
55:47that are very prone to injury.
55:50And the thought is,
55:53is that the the halodronate in that case
55:57is really preventing osteoclast activity.
56:01So just the progression of the collapse.
56:04Whereas in the jaw again you have
56:09different architecture and it's thought
56:12that the osteo the the reduction of
56:16osteoclast activity may be impacting the
56:19capillaries in that micro environment.
56:23We don't know specifically the mechanism of
56:27how the allodronate causes AVN in the jaw,
56:30but the way I would think about it is
56:32they are different micro environments
56:34that are perfused differently.
56:38That makes a lot of sense
56:40and is very helpful.
56:42Unless there are other questions,
56:44I don't see any in the chat right now.
56:46I just want to thank you
56:48for a fantastic talk.
56:49I think your your message went far and wide,
56:52so hopefully you will be
56:54getting some communication and,
56:56and it's great to know that you guys are
56:59here and this program is here as a resource.
57:01I think it's really intriguing.
57:03I'm still going to make a
57:04plug for the early biomarker.
57:06I think there's some,
57:07some work in the field to be
57:09done that I will not be leading,
57:10but I think it's really fascinating,
57:12right?
57:12Like we're treating everything
57:14at the way margin of once the
57:16the horse is out of the barn.
57:17It's I think it's a a fascinating
57:19and hard to diagnose condition
57:21and we will stay tuned.
57:23Thank you guys so much and
57:24hoping you have a great day.
57:26Thank you and thank you reaching
57:28out. Thank you so much
57:29and lots of thank yous in the chat.
57:32Thank you, thank you. Take
57:35care.