April 30, 2025 • 30 mins
Have you ever wondered who's behind those medical lab results that guide your treatment? Meet Dr. Jeff Melnick, St. Luke's Chief of Pathology and laboratory Medical Director, who pulls back the curtain on the fascinating world of "the doctor's doctor" in this eye-opening conversation.
Dr. Melnick reveals that pathology extends far beyond the familiar forensic work popularized by crime shows. With approximately 20 subspecialties spanning anatomic pathology (tissue examination) and clinical pathology (laboratory medicine), these physicians influence nearly every aspect of modern healthcare. While forensic pathology might capture public imagination, it represents the smallest slice of this diverse field.
The technological evolution of pathology presents a fascinating paradox. Core techniques like fixing tissue in formalin and staining with H&E remain largely unchanged after a century, forming the foundation of tissue diagnosis. Yet simultaneously, the field has been revolutionized by molecular pathology and genetic testing, enabling personalized medicine approaches that target specific mutations in individual patients' tumors. This precision has transformed cancer treatment, allowing oncologists to select therapies based on a tumor's genetic profile rather than just its tissue origin.
As laboratory Medical Director, Dr. Melnick serves as an essential bridge between laboratory staff and clinical providers. He describes his role as an "ombudsman" who translates between different professional languages, ensures quality testing protocols, and helps clinicians interpret complex results. Every hospital laboratory requires this medical leadership by law, though patients rarely realize a pathologist's involvement in their routine blood work.
The conversation touches on artificial intelligence's gradual impact on pathology, the scientific breakthroughs (like heat-resistant enzymes from Yellowstone hot springs) that enable modern testing techniques, and even the infamous Theranos scandal that promised revolutionary blood testing from a single drop. Through it all, Dr. Melnick emphasizes that the ultimate purpose remains doing what's best for patients: delivering high-quality diagnostic information at exactly the right time.
Join us for this illuminating glimpse into medicine's hidden experts who guide clinical decisions from behind the microscope. Subscribe to Doc Discussions for more conversations that reveal the fascinating intersections of science, medicine, and patient care.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:00):
Hello, this is Jason Edwards and this is Doc
Discussions.
I'm here with my good friendand pathologist, Dr Jeff Melnick
.
Dr Melnick is, like I said, apathologist, which is also known
as the doctor's doctor, Jeff,welcome.
Speaker 2 (00:15):
Thank you very much.
I'm excited to be here.
Speaker 1 (00:17):
Yeah, I am excited too.
I think in the lunchroom youand I have always had good
conversations, and so I thinkthis will be a nice episode for
everybody Super.
So I was reading aboutpathologists and I was surprised
to see that there are about 20subspecialties of pathology.
You may be less surprised bythat, but everybody knows the
(00:38):
forensic pathologist.
That's a big part.
But what are some othersubspecialties of pathology?
Speaker 2 (00:43):
That's a big part, but what are some other
subspecialties of pathology?
So yeah, a lot of times when alayperson asks me about
pathology, I tell them it's thescience behind a lot of medicine
.
Of course it doesn't touch toomuch on physiology, but it
touches on lots of other areas.
So within what we call theanatomic pathology arena you
have a lot of subspecialties byorgans or organ systems.
Speaker 1 (01:04):
So there's dermatopathology,
hematopathology.
Speaker 2 (01:09):
There are endocrine pathologists, gu, obgyn
pathologists certainlyneuropathology is its own field
and pulmonary pathology.
A lot of these subfields havetheir own separate boards.
Some of them do not, but thereare still like fellowship
(01:29):
training programs.
In them you get some sort ofcertificate but not an actual
separate board.
But a lot of the ones I nameddo have separate boards.
And then within the clinicalpathology area, which is sort of
more the wet lab, less thetissue area, and we can talk
about that more if you want, youhave pathologists that will
(01:49):
specialize in chemistry or inhematology.
You have coagulation peoplethat will focus.
Certainly.
Microbiology is a well-knownfield, transfusion medicine,
which is the whole area of bloodbanking, and these days
molecular pathology is a hugething.
Speaker 1 (02:07):
I think that's one thing people might not realize
is it's the pathologist who runsthe lab of the hospital.
It does the testing on theequipment for just your normal
day-to-day blood work.
Speaker 2 (02:18):
Yeah, that's correct.
I mean by law you have to havea medical director of a
laboratory, and pathology is thefield that specializes in that,
and it's hard to get the rightcredentials.
It's possible by other routes,but pathology is the most common
route.
Yeah, yeah, so we are sort ofbehind the scenes, often making
(02:44):
a lot of decisions, either thataffect testing in general or
about specific patients whenproblems arise.
Speaker 1 (02:52):
Yeah, and then there's the well-known forensic
pathology.
Speaker 2 (02:56):
Yeah, I didn't or maybe I did mention forensic
pathology.
It's probably the highestprofile field because of TV
programs like CSI and all that,but it's probably the smallest
field in all of pathology.
The forensic area is very, verysmall, very narrow niche.
Speaker 1 (03:15):
That people will specialize only in forensics,
yeah, and they go on to becomeyou know like, yeah, work for
the city or the county and I, um, I may have told you this, but
I thought at one point I wantedto become a pathologist.
So I did a few rotations inpathology and forensics.
Pathology was one of them andit was, I would say I had like
(03:37):
nightmares the first two weeksand then I felt like totally
comfortable with it the secondtwo weeks.
Um, but it was.
It was a fascinating experience, for sure.
Speaker 2 (03:48):
St Louis University, right here in town, runs a
program that's nationally known,that is, on stuff related to
death and dying.
Speaker 1 (03:57):
It's primarily not pathology people that attend it,
but I think it's run by thepathology department there At
least it used to be and lots ofpeople that are into being a
coroner, or sometimes firemenand law enforcement, will come
to this course and find out allthe morbid ways people have of
(04:19):
treating themselves themselvesand their bodies you, you, you
do get a a very interesting viewof life that you really can't
get in many other placesprobably police officers, you
know, see this side of you, knowsociety, but it's, it's,
there's kind of no, the very fewrealms where you you kind of
(04:40):
see what happens at the end ofpeople's lives and you're're
kind of told what the scenariois too around it sometimes.
Speaker 2 (04:48):
I agree.
So I mean coroners and so forth.
They often work very closelywith law enforcement in terms of
investigating the scene, andthey'll even go to court.
Speaker 1 (05:02):
I remember we went to court once.
Speaker 2 (05:06):
They actually have first access to the body.
Law enforcement can't touch ormove the body.
If there's I don't know theexact guidelines because, again,
not my area yeah, but um, untilthe um, until the pathologist
has given the clear, that kindof makes sense.
Speaker 1 (05:20):
Um, yeah, I do remember uh, working with the
lawyers and the police officersto try to kind of figure out.
I do remember working with thelawyers and the police officers
to try to kind of figure outwhat's going on with the cases.
And then you know you, in thatjob I remember you represent the
victim of the crime or what itmay be.
You know, when you go to courtyou know you're not for the
(05:43):
plaintiff or the defendant, youare advocating for the deceased.
In that.
Speaker 2 (05:49):
Yeah, well, or the truth I was going to say.
I think you're advocating forthe truth as you see it, based
on the facts that you uncover.
Speaker 1 (05:58):
Yeah.
Speaker 2 (05:59):
So I don't know if it's necessarily one side or the
other.
Speaker 1 (06:01):
Yeah, it's not one side.
You're nonpartisan, exactly,and so.
But yeah, you know it's whenyou think about these things,
just the breadth of medicine is,you know, pretty wide really
when you look at it, especiallywhen you I mean pathology,
especially so the advent of AI,or of this, artificial
(06:29):
intelligence.
Has that made its way intopathology?
Speaker 2 (06:40):
Well, there's a lot of interest in AI in the
pathology field, as, I think, inmany areas of medicine.
It's kind of limited so far, Ithink, in terms of what its
actual impact is.
We're still dealing inpathology a lot with digital
pathology, which, of course, hasmade huge inroads in the field
of radiology and has someapplications in pathology, but
(07:03):
perhaps going a lot slower thansome people would have thought.
I personally am not toosurprised, I agree with you by
the pace, but it's allowedpeople to do some things
remotely on certain types oftissues and specimens, to get
consults from afar, eveninternational if you want, by
(07:30):
showing images, rather thanhaving to send slides to someone
and wait for them to look atthem and write you back or call
you back.
In terms of AI, I mean, thereare a lot of possible
implications.
I think that a lot of theexcitement is the excitement in
medicine in general, which ismining the data, and a lot of
the data is in the lab and sothere's the possibility of
mining.
You know, the applicationswithin pathology or within
(07:53):
laboratory medicine are miningthat data to look for trends or
disease-specific implicationsthat we may not have previously
appreciated.
Speaker 1 (08:03):
Yeah, I've actually used it in my practice.
I have a commercially availableAI.
I use Claude Sonnet, 3.5 is theversion, but it's actually
pretty good.
I mean, it's actually prettygood you could put in.
Now I actually don't diagnosevery many things, but my wife
(08:24):
has, and she's a physician aswell, and you put in these
symptoms and you say, give me adifferential, and it'll kick out
kind of all the things that youwould expect, that an expert
would expect, and so it's notbad and it's only going to get
better, and so I think really itwill be more of a co-pilot.
It will be something that wouldassist you, but probably never
(08:49):
take over a radiologist or apathologist anytime soon is my
best guess.
Speaker 2 (08:57):
Yeah Well, and one also always has to be wary of
the databases on which it'strained.
You know whether they havebiases or blind spots.
Speaker 1 (09:06):
Yeah, and they do right.
They will have biases, theywill have blind spots.
Speaker 2 (09:10):
If they're reading other websites, then they're
just as blind as whoever createdthose websites.
Yeah, if they're readingliterature, they're just as
blind as whoever you knowpublished that literature.
Speaker 1 (09:31):
So that's what one has to be wary of.
Yeah, I think that, and humanshave biases, so that's what one
has to be wary of.
You know, by 2027 or or orsomething like that, and so well
, I guess time will tell.
It's a, it's an exciting time,and hopefully we can kind of
(09:53):
manage this technologyresponsibly.
You and I were talking about abook and Um and um, uh with this
.
Um, uh, it was, uh, ishmael, isthat right?
Speaker 2 (10:03):
That's correct.
Um by Daniel Quinn Ishmael.
I think it's about 20 years oldor so.
Yeah.
Speaker 1 (10:08):
Early nineties right 30 years old and I you know, if
you're like me, uh, 1991 seemslike it's like uh, nine years
ago right In my brain.
Um, but um.
But it was this, so I read asummary of it and it's this book
about kind of taking care ofthe world and technology and how
(10:29):
that impacts the world, and Ithought it was interesting and
there was a little bit of tie-in.
I mean there's, there's, Iwould say.
The technological advancementsin pathology have been
relatively slow, probably upuntil the last 10 years.
Right, I'm wrong as far as themolecular biology, as far as
(10:50):
staining slides and stuff likethat, but as far as like taking
a slide and making a section andlooking under a microscope,
that hasn't changed that much.
Speaker 2 (10:57):
Yeah, so the basis for anatomic pathology, which is
taking tissue sections, fixingthem almost always in formalin,
cutting very thin sections wecut usually at three microns
micron being a micrometer andthen staining them with H&E as
the core stain.
That's 80, 100-year-oldtechnology and that's still the
(11:20):
core for basically everything wedo.
And then we combine it with alot of special stains that have
been around for decadesimmunostaining that's been
around for 20 to 30 years now,but the menu continues to grow.
And then these days, combiningit with a lot of genetic studies
.
And so the trick is you knowwhat studies to do in what
(11:42):
situations, you know, given thatthere are limited resources of
money, if nothing else, the costof the test.
But yeah, so a lot of tumordiagnosis.
These days we're doing geneticstudies on either to properly
classify the tumor or to provideeither prognostic information
(12:04):
or therapeutic guidance for theoncologist because that's the
whole thrust of personalizedmedicine was to use therapeutic
approaches that are specific toa patient's individual tumor
instead of like a class of tumor.
Speaker 1 (12:22):
Yeah, not all breast cancers are the same.
Speaker 2 (12:23):
Pulmonary adenocarcinoma is too big of a
category or breast cancer ismuch too big of a category, but
rather to be able to subclassifyit and even down to specific
genetic mutations in a patient'sown tumor that can predict
either responsiveness to acertain drug or lack thereof.
Speaker 1 (12:42):
In the last 20 years that's been huge right.
Speaker 2 (12:45):
It has, you know, mushroomed in the last 20 years.
Speaker 1 (12:50):
I would imagine that the board study book for a
pathologist has gotten liketwice as thick over the past,
you know couple of decades.
Speaker 2 (12:58):
I really don't know, but you're probably right.
But I remember taking a list oflike translocations on the
plane to me as I flew down toTampa to take my boards and
cramming them on there.
So, yeah, it's probably quite abit larger now yeah.
Speaker 1 (13:13):
Yeah, I feel for the youngsters out there, and so
that kind of ties in with thisbook.
That's about technology.
Ties in with this book, that'sabout technology and they, they
kind of even, you know, go backlike through the agricultural
revolution, the industrialrevolutions and like what humans
have kind of done to the earthand and and kind of going
(13:33):
through the philosophy of thatthe book is sort of.
Speaker 2 (13:38):
The book Ishmael is sort of a discussion between a
kind of almost know-it-allteacher, who's actually a
gorilla, not a human being, anda student who's very open and
willing to learn and the gorilla.
The teacher is broadening hisperspective and opening him up
(14:01):
to blind spots that the gorillaclaims he's inherited as simply
by being a human being, by beinga homo sapien, and he doesn't
see the world the way it isaccording to nature, and so it
ties in a lot to the way, in hisviewpoint, human beings are
destroying the world anddestroying the environment, and
(14:24):
he claims that it's all going tobasically come back to bite us
one way or another.
We're going to pay for it.
Yeah, so it probably, in thescheme of things, was an early,
perhaps, view of what we'redoing to our environment.
Speaker 1 (14:41):
Yeah, you know, when I was, I read a few summaries of
this.
Actually, wikipedia had a nicesummary of it and so I wasn't
able to read the entire book,although there was a six-hour
audio version on YouTube.
But yeah, the and one of thelines was you may compete with
(15:04):
other animals, but you may notwage war against them.
And I thought that's you know,that's you know the agricultural
revolution.
You would look at fencing andcattle as they would probably
consider that waging war, or thegorilla would.
But I thought, you know,there's probably also this
disconnect between a person'sintellectual agreement after
reading the book and actualpractical action afterwards,
(15:27):
meaning that you might read thebook and say you know what, I
agree with that philosophy andthen go to McDonald's and get
like a, you know a value meal.
Speaker 2 (15:35):
And you still don't know.
You got to apply it to your ownlife or to your own community,
and you have a local communityand a national community and a
global community and stuff likethere.
So obviously it's a lot harderto translate it into action,
right yeah?
Speaker 1 (15:52):
Yeah, and I think we all have this cognitive
dissonance where we have thesebeliefs, but when those beliefs
are actually tested in reality,it just becomes kind of more
convenient to keep doing thesame old things, and everybody's
, you know, does that to anextent, I agree, but it's good
to at least kind of be aware ofthat.
Speaker 2 (16:09):
It is.
It's an eye-opening story.
The book it really is, yeah,and.
Speaker 1 (16:13):
I think any book that makes you kind of step back and
think about something,especially something that's a
blind spot, is a really coolthing.
I mean to say you know what.
I may have had that wrong.
Or you know when your beliefsare challenged and you have kind
of the maturity to change yourmind.
I think that can be a goodthing and you've probably
(16:36):
experienced this, as I have.
As you get older and hopefullymore wiser, you realize you kind
of know less and theprobability that you're wrong
actually goes up with the moreyou know.
Speaker 2 (16:48):
Yeah, I agree, it's humbling.
I think that's often what theycall wisdom.
Speaker 1 (16:53):
Yeah, yeah.
Speaker 2 (16:54):
It's the humility that comes with life.
Speaker 1 (16:56):
Yeah, I agree, and I think it's a good thing to have
some humility and realize Icould be wrong my position on
this.
I shouldn't be so entrenched.
Actually, before we started thepodcast, todd our producer here
, we were talking about Robert FKennedy and one of his quotes
was some people wake up in themorning and try to go to bed
(17:20):
believing the same thing theybelieved in the morning, and
some people are willing tochange their minds.
And I think it's good to bewilling to listen to others and,
you know, realize that youcould be wrong on something.
Speaker 2 (17:30):
Yeah, I agree, and Ishmael the book, I mean I would
recommend it.
It's a very unusual style ofnarration or presentation
because the teacher sometimesit's Socratic.
I mean probably his wholephilosophy could have been
summarized in a few pages.
I mean probably his wholephilosophy could have been
summarized in a few pages.
But you know he's trying tomake the student think about it
(17:52):
and then you as the reader arethinking about it as you go
along.
Yeah, and by Socratic you meanhe's asking questions to the
character.
He's asking questions to hisstudent, yeah, and in a lot of
ways, as you're reading the book, you're taking on the role of
his student and trying to answerthose questions, figuring out
what he wants you to figure out.
You know, thinking about whathe wants you to figure out.
Speaker 1 (18:14):
Yeah, that's fascinating.
Yeah, I think a lot of books dothat, where there's kind of a
central theme that you cansummarize, like you said, within
even a page and then it justkind of beats that, Fleshes it
out.
Yeah, I was going to say beatsit to death, but yeah, fleshes
it out is a better way to put it.
So, Jeff, what is your role inthe pathology department?
Speaker 2 (18:34):
So I'm the chief of the Department of Pathology and
I also serve in the role asmedical director of the
laboratory.
Medical director is required bylaw that there be a medical
director and in that role thereare kind of a whole number of
things to do.
(18:55):
There's the macro level interms of running the lab, so I
work very closely with ouradministrative director.
So I don't actually deal tooclosely with HR issues or the
financial issues, which is nice,but some medical directors in
some labs might end up having todo that if people own their own
(19:16):
lab, but not in a hospitalsetting like this.
But I'm involved in a lot ofthe macro decisions like what
type of equipment to buy, whattypes of methods should we be
looking to bring in.
Equipment decisions will impactwhat tests you can add in the
future, how you can configure,what kind of specimens you will
(19:38):
need to collect it, so how itintegrates in a larger picture.
I am responsible for theoverall quality of the running
of the lab, and that's by lawand in practice.
So overseeing the whole qualityassurance program, which
involves everything from youknow daily or multiple times a
(19:58):
day quality control what we callQC for a specific assay to all
kinds of process improvementinitiatives and then that kind
of ties into another role.
A lot of times I see myself asan ombudsman between the
laboratory staff and theprofessional caregivers, the
(20:21):
doctors and and other licensedcaregivers in the hospital.
To be someone who can translatefrom one set of language to the
other, understand the process,understand the needs of
physicians and caregivers andtranslate that into the way the
laboratory actually functionsand to try and understand, when
(20:44):
there are problems or friction,how we can make it better.
And all that has got theultimate goal of doing what's
best for the patient.
So trying to optimize patientcare, of course, keeping the
costs in mind, what's realisticand keeping the efficiency of
the process in mind as well, butultimately making sure we do
(21:08):
the best for the patient.
So we want high quality results, we want them in a timely
manner, we want them at theright time.
There are certain tests thatshouldn't be drawn in certain
situations because it doesn'tmean anything in an acute
setting.
It's based on, you know, achronic thing, so a lot of
coagulation risk factors, forexample, for thrombosis.
(21:30):
You don't want to draw an acutesetting of a thrombosis because
your whole coag system ismessed up.
Speaker 1 (21:38):
Yeah.
Speaker 2 (21:39):
And so it's not the right time to draw that, on the
other hand.
So that would be true of afunctional test, but on the
other hand, if it's agenetic-based test, you can draw
that at any time.
Their genes aren't changingwhen they're thrombosing.
So knowing things like that,right tests, right time, and
let's see what other roles.
(22:00):
Then there's individualinterpretations or problem
solving.
So physicians sometimes willorder a test because they read
that that's the next thing theyshould do, and then they don't
know how to interpret it.
Or they got a result that'soutside the simple plus minus
positive, negative that theywere expecting, and they don't
know what it means, and so theymight call me for help, guidance
(22:23):
on interpreting it.
Or they don't believe theresult.
So that kind of translates isthere some sort of interference?
So I have to learn about thepatient's history, look at other
lab results what was the acutesetting?
In order to try and find out ifthere's some limitation or some
interference that would give afalsely elevated or falsely
(22:46):
negative result.
And then advise is there analternative method?
You know, because a lot oftimes I mean, people order
things and there are multiplemethods on how to do it.
Yeah, so sometimes physiciansdon't even know exactly what
they want.
They just heard about somethingor read about something, but
they don't know whether theyneed, you know, an enzyme, a
(23:07):
measurement of the protein levelor the enzymatic activity or a
mutation in the gene for theenzyme?
Yeah, you know.
so, um it just, it has a name onit and and they just pull the
trigger so, um so, helpingpeople to decide what to do
about that or how to interpretthat, and sometimes, yeah, the
issues and one example is I.
Speaker 1 (23:28):
I remember when I would do floor work, which was a
long time ago, but they woulddraw blood and then we would say
, oh, there must have beenhemolysis.
Like when they drew the bloodsome of the red blood cells were
sheared, and so now you havesome um, differences in
potassium and things like that.
Speaker 2 (23:44):
That would be indicative of hemolysis or or,
you know, there's some reasonthat the sample's not true.
Or the specimen sat around toolong, yeah, glucose got consumed
, or it wasn't cooled properly,or the serum wasn't separated in
time or, like you said,hemolysis during drawing.
That's a really, really commonproblem and a problem we try and
(24:07):
monitor.
But like, people don't alwaysthink about the implications so
they want to have a rapid point,you know, very rapid test,
which means trying, may meanrunning it on whole blood.
So point of care tests arealways done on whole blood.
No one's separating the serumthere, you know.
So one potential drawback rightaway is you don't have an
(24:27):
opportunity to examine the bloodfor hemolysis, just a gross
hemolysis.
So that affects some assays andwhen people are running that
test on the whole blood, oftenat the point of care, they
forget about that limitation.
Speaker 1 (24:45):
So one thing that was in the news was this company,
theranos, where Elizabeth Holmeswas saying that she had this
product where she could take onedrop of blood and do all these
tests on, and I think PerkinElmer, a company that makes
machines that test blood I maybe saying the name wrong, but
threw up some red flags in order.
It's like there's no way thiscan be done and she ended up
(25:06):
being on Harvard's board ofdirectors and having all these
huge roles and then it came out.
It was all a sham.
Were you following this whenthat happened?
Speaker 2 (25:14):
So I didn't follow it really closely, but I knew
about it and saw headlines fromtime to time.
It's a wonderful dream, it's awonderful goal and maybe at some
point we'll do it.
I don't know if it'll be fromone drop of blood, but maybe
we'll be reaching to that point.
But the problem they had wasthey cut a lot of corners on
(25:36):
quality and they made falseclaims, yeah, and they didn't
follow a lot of FDA regulations.
They were so busy, I don't know, raising money.
Speaker 1 (25:47):
It was more of a sham .
It was more of a sham operation, right?
So that's what it turned out tobe, or it seemed, yeah.
Speaker 2 (25:52):
Well, that's certainly what the government
claimed, and she was convictedfor it.
So it was.
But you know, we can do a lotwith one drop of blood or one
piece of tissue in terms ofgenetics.
These days, we can examine forhundreds and even thousands of
different mutations byamplifying the RNA or using mRNA
(26:14):
to amplify.
So, again, if you're looking formutations in the genes, you're
usually looking at DNA.
But genes rearrange, you gettranslocations that result in a
fusion gene, and that's oftenbetter looked at by doing RT-PCR
instead of PCR on the RNA.
So, there again, there aresituations where we'll want to
(26:36):
examine the RNAs, the RNAproducts, the mRNA, instead of
the DNA, and so that again, thatgets forgotten a lot.
And if you want to do both,then that's even more and you
need two drops of blood insteadof one drop of blood.
And then there's a lot ofinterest in what we call
proteomics, which is like aprotein fingerprint of all the
(26:59):
proteins that are in your bloodor in a tissue and you can look
at fragments of proteins to seewhat's going on.
So that's reality in the fieldof microbiology.
But prokaryotic cells are a lotsimpler than eukaryotic cells
in our cells.
But, yeah, we do a lot ofbacterial identification now by
(27:23):
what's called MALDI, where youbasically it's a mass
spectrometry technique where youfragment the proteins that are
in a pure colony of thatbacterium and you do mass spec
on it and you get a charge andmass profiles of all the
(27:44):
fragments and then what you dois you match it to a huge
database and say okay, this onecomes out to be e coli and this
one comes out to be jasonedwards it has a characteristic
signature that, but you have tohave that huge database.
Speaker 1 (27:56):
Yeah very cool um you have to have that huge database
the one thing is I remember itwas like, uh, thermos aquaticus
or something like this was thethe uh enzyme, uh, that they
found in like these cauldrons inYellowstone.
That was this heat-resistantprotein, and that's what allowed
them to do reversetranscriptase PCR, and so it
(28:18):
heats up, it cools down, itheats up, it cools down, but
that enzyme stays the same.
But if somebody wouldn't havediscovered this bacteria in
these geysers, they would havenever had this enzyme to do this
technology, and so it's amazinghow these fields of science
kind of come together.
Speaker 2 (28:37):
Right, and that obviously was a huge scientific
breakthrough for someone torecognize that DNA polymerase or
associated enzymes were heatresistant, and that they were
heat resistant up to a levelthat would be required to
denature DNA and so thereforecould be used for PCR.
Speaker 1 (28:55):
Yeah, pretty cool.
Well, Jeff.
Thanks so much, buddy, it'sbeen a pleasure.
Speaker 2 (29:00):
Thank you.
Hello, this is Jason Edwards and this is Doc
Discussions.
I'm here with my good friendand pathologist, Dr Jeff Melnick
.
Dr Melnick is, like I said, apathologist, which is also known
as the doctor's doctor, Jeff,welcome.
Speaker 2 (00:15):
Thank you very much.
I'm excited to be here.
Speaker 1 (00:17):
Yeah, I am excited too.
I think in the lunchroom youand I have always had good
conversations, and so I thinkthis will be a nice episode for
everybody Super.
So I was reading aboutpathologists and I was surprised
to see that there are about 20subspecialties of pathology.
You may be less surprised bythat, but everybody knows the
(00:38):
forensic pathologist.
That's a big part.
But what are some othersubspecialties of pathology?
Speaker 2 (00:43):
That's a big part, but what are some other
subspecialties of pathology?
So yeah, a lot of times when alayperson asks me about
pathology, I tell them it's thescience behind a lot of medicine
.
Of course it doesn't touch toomuch on physiology, but it
touches on lots of other areas.
So within what we call theanatomic pathology arena you
have a lot of subspecialties byorgans or organ systems.
Speaker 1 (01:04):
So there's dermatopathology,
hematopathology.
Speaker 2 (01:09):
There are endocrine pathologists, gu, obgyn
pathologists certainlyneuropathology is its own field
and pulmonary pathology.
A lot of these subfields havetheir own separate boards.
Some of them do not, but thereare still like fellowship
(01:29):
training programs.
In them you get some sort ofcertificate but not an actual
separate board.
But a lot of the ones I nameddo have separate boards.
And then within the clinicalpathology area, which is sort of
more the wet lab, less thetissue area, and we can talk
about that more if you want, youhave pathologists that will
(01:49):
specialize in chemistry or inhematology.
You have coagulation peoplethat will focus.
Certainly.
Microbiology is a well-knownfield, transfusion medicine,
which is the whole area of bloodbanking, and these days
molecular pathology is a hugething.
Speaker 1 (02:07):
I think that's one thing people might not realize
is it's the pathologist who runsthe lab of the hospital.
It does the testing on theequipment for just your normal
day-to-day blood work.
Speaker 2 (02:18):
Yeah, that's correct.
I mean by law you have to havea medical director of a
laboratory, and pathology is thefield that specializes in that,
and it's hard to get the rightcredentials.
It's possible by other routes,but pathology is the most common
route.
Yeah, yeah, so we are sort ofbehind the scenes, often making
(02:44):
a lot of decisions, either thataffect testing in general or
about specific patients whenproblems arise.
Speaker 1 (02:52):
Yeah, and then there's the well-known forensic
pathology.
Speaker 2 (02:56):
Yeah, I didn't or maybe I did mention forensic
pathology.
It's probably the highestprofile field because of TV
programs like CSI and all that,but it's probably the smallest
field in all of pathology.
The forensic area is very, verysmall, very narrow niche.
Speaker 1 (03:15):
That people will specialize only in forensics,
yeah, and they go on to becomeyou know like, yeah, work for
the city or the county and I, um, I may have told you this, but
I thought at one point I wantedto become a pathologist.
So I did a few rotations inpathology and forensics.
Pathology was one of them andit was, I would say I had like
(03:37):
nightmares the first two weeksand then I felt like totally
comfortable with it the secondtwo weeks.
Um, but it was.
It was a fascinating experience, for sure.
Speaker 2 (03:48):
St Louis University, right here in town, runs a
program that's nationally known,that is, on stuff related to
death and dying.
Speaker 1 (03:57):
It's primarily not pathology people that attend it,
but I think it's run by thepathology department there At
least it used to be and lots ofpeople that are into being a
coroner, or sometimes firemenand law enforcement, will come
to this course and find out allthe morbid ways people have of
(04:19):
treating themselves themselvesand their bodies you, you, you
do get a a very interesting viewof life that you really can't
get in many other placesprobably police officers, you
know, see this side of you, knowsociety, but it's, it's,
there's kind of no, the very fewrealms where you you kind of
(04:40):
see what happens at the end ofpeople's lives and you're're
kind of told what the scenariois too around it sometimes.
Speaker 2 (04:48):
I agree.
So I mean coroners and so forth.
They often work very closelywith law enforcement in terms of
investigating the scene, andthey'll even go to court.
Speaker 1 (05:02):
I remember we went to court once.
Speaker 2 (05:06):
They actually have first access to the body.
Law enforcement can't touch ormove the body.
If there's I don't know theexact guidelines because, again,
not my area yeah, but um, untilthe um, until the pathologist
has given the clear, that kindof makes sense.
Speaker 1 (05:20):
Um, yeah, I do remember uh, working with the
lawyers and the police officersto try to kind of figure out.
I do remember working with thelawyers and the police officers
to try to kind of figure outwhat's going on with the cases.
And then you know you, in thatjob I remember you represent the
victim of the crime or what itmay be.
You know, when you go to courtyou know you're not for the
(05:43):
plaintiff or the defendant, youare advocating for the deceased.
In that.
Speaker 2 (05:49):
Yeah, well, or the truth I was going to say.
I think you're advocating forthe truth as you see it, based
on the facts that you uncover.
Speaker 1 (05:58):
Yeah.
Speaker 2 (05:59):
So I don't know if it's necessarily one side or the
other.
Speaker 1 (06:01):
Yeah, it's not one side.
You're nonpartisan, exactly,and so.
But yeah, you know it's whenyou think about these things,
just the breadth of medicine is,you know, pretty wide really
when you look at it, especiallywhen you I mean pathology,
especially so the advent of AI,or of this, artificial
(06:29):
intelligence.
Has that made its way intopathology?
Speaker 2 (06:40):
Well, there's a lot of interest in AI in the
pathology field, as, I think, inmany areas of medicine.
It's kind of limited so far, Ithink, in terms of what its
actual impact is.
We're still dealing inpathology a lot with digital
pathology, which, of course, hasmade huge inroads in the field
of radiology and has someapplications in pathology, but
(07:03):
perhaps going a lot slower thansome people would have thought.
I personally am not toosurprised, I agree with you by
the pace, but it's allowedpeople to do some things
remotely on certain types oftissues and specimens, to get
consults from afar, eveninternational if you want, by
(07:30):
showing images, rather thanhaving to send slides to someone
and wait for them to look atthem and write you back or call
you back.
In terms of AI, I mean, thereare a lot of possible
implications.
I think that a lot of theexcitement is the excitement in
medicine in general, which ismining the data, and a lot of
the data is in the lab and sothere's the possibility of
mining.
You know, the applicationswithin pathology or within
(07:53):
laboratory medicine are miningthat data to look for trends or
disease-specific implicationsthat we may not have previously
appreciated.
Speaker 1 (08:03):
Yeah, I've actually used it in my practice.
I have a commercially availableAI.
I use Claude Sonnet, 3.5 is theversion, but it's actually
pretty good.
I mean, it's actually prettygood you could put in.
Now I actually don't diagnosevery many things, but my wife
(08:24):
has, and she's a physician aswell, and you put in these
symptoms and you say, give me adifferential, and it'll kick out
kind of all the things that youwould expect, that an expert
would expect, and so it's notbad and it's only going to get
better, and so I think really itwill be more of a co-pilot.
It will be something that wouldassist you, but probably never
(08:49):
take over a radiologist or apathologist anytime soon is my
best guess.
Speaker 2 (08:57):
Yeah Well, and one also always has to be wary of
the databases on which it'strained.
You know whether they havebiases or blind spots.
Speaker 1 (09:06):
Yeah, and they do right.
They will have biases, theywill have blind spots.
Speaker 2 (09:10):
If they're reading other websites, then they're
just as blind as whoever createdthose websites.
Yeah, if they're readingliterature, they're just as
blind as whoever you knowpublished that literature.
Speaker 1 (09:31):
So that's what one has to be wary of.
Yeah, I think that, and humanshave biases, so that's what one
has to be wary of.
You know, by 2027 or or orsomething like that, and so well
, I guess time will tell.
It's a, it's an exciting time,and hopefully we can kind of
(09:53):
manage this technologyresponsibly.
You and I were talking about abook and Um and um, uh with this
.
Um, uh, it was, uh, ishmael, isthat right?
Speaker 2 (10:03):
That's correct.
Um by Daniel Quinn Ishmael.
I think it's about 20 years oldor so.
Yeah.
Speaker 1 (10:08):
Early nineties right 30 years old and I you know, if
you're like me, uh, 1991 seemslike it's like uh, nine years
ago right In my brain.
Um, but um.
But it was this, so I read asummary of it and it's this book
about kind of taking care ofthe world and technology and how
(10:29):
that impacts the world, and Ithought it was interesting and
there was a little bit of tie-in.
I mean there's, there's, Iwould say.
The technological advancementsin pathology have been
relatively slow, probably upuntil the last 10 years.
Right, I'm wrong as far as themolecular biology, as far as
(10:50):
staining slides and stuff likethat, but as far as like taking
a slide and making a section andlooking under a microscope,
that hasn't changed that much.
Speaker 2 (10:57):
Yeah, so the basis for anatomic pathology, which is
taking tissue sections, fixingthem almost always in formalin,
cutting very thin sections wecut usually at three microns
micron being a micrometer andthen staining them with H&E as
the core stain.
That's 80, 100-year-oldtechnology and that's still the
(11:20):
core for basically everything wedo.
And then we combine it with alot of special stains that have
been around for decadesimmunostaining that's been
around for 20 to 30 years now,but the menu continues to grow.
And then these days, combiningit with a lot of genetic studies
.
And so the trick is you knowwhat studies to do in what
(11:42):
situations, you know, given thatthere are limited resources of
money, if nothing else, the costof the test.
But yeah, so a lot of tumordiagnosis.
These days we're doing geneticstudies on either to properly
classify the tumor or to provideeither prognostic information
(12:04):
or therapeutic guidance for theoncologist because that's the
whole thrust of personalizedmedicine was to use therapeutic
approaches that are specific toa patient's individual tumor
instead of like a class of tumor.
Speaker 1 (12:22):
Yeah, not all breast cancers are the same.
Speaker 2 (12:23):
Pulmonary adenocarcinoma is too big of a
category or breast cancer ismuch too big of a category, but
rather to be able to subclassifyit and even down to specific
genetic mutations in a patient'sown tumor that can predict
either responsiveness to acertain drug or lack thereof.
Speaker 1 (12:42):
In the last 20 years that's been huge right.
Speaker 2 (12:45):
It has, you know, mushroomed in the last 20 years.
Speaker 1 (12:50):
I would imagine that the board study book for a
pathologist has gotten liketwice as thick over the past,
you know couple of decades.
Speaker 2 (12:58):
I really don't know, but you're probably right.
But I remember taking a list oflike translocations on the
plane to me as I flew down toTampa to take my boards and
cramming them on there.
So, yeah, it's probably quite abit larger now yeah.
Speaker 1 (13:13):
Yeah, I feel for the youngsters out there, and so
that kind of ties in with thisbook.
That's about technology.
Ties in with this book, that'sabout technology and they, they
kind of even, you know, go backlike through the agricultural
revolution, the industrialrevolutions and like what humans
have kind of done to the earthand and and kind of going
(13:33):
through the philosophy of thatthe book is sort of.
Speaker 2 (13:38):
The book Ishmael is sort of a discussion between a
kind of almost know-it-allteacher, who's actually a
gorilla, not a human being, anda student who's very open and
willing to learn and the gorilla.
The teacher is broadening hisperspective and opening him up
(14:01):
to blind spots that the gorillaclaims he's inherited as simply
by being a human being, by beinga homo sapien, and he doesn't
see the world the way it isaccording to nature, and so it
ties in a lot to the way, in hisviewpoint, human beings are
destroying the world anddestroying the environment, and
(14:24):
he claims that it's all going tobasically come back to bite us
one way or another.
We're going to pay for it.
Yeah, so it probably, in thescheme of things, was an early,
perhaps, view of what we'redoing to our environment.
Speaker 1 (14:41):
Yeah, you know, when I was, I read a few summaries of
this.
Actually, wikipedia had a nicesummary of it and so I wasn't
able to read the entire book,although there was a six-hour
audio version on YouTube.
But yeah, the and one of thelines was you may compete with
(15:04):
other animals, but you may notwage war against them.
And I thought that's you know,that's you know the agricultural
revolution.
You would look at fencing andcattle as they would probably
consider that waging war, or thegorilla would.
But I thought, you know,there's probably also this
disconnect between a person'sintellectual agreement after
reading the book and actualpractical action afterwards,
(15:27):
meaning that you might read thebook and say you know what, I
agree with that philosophy andthen go to McDonald's and get
like a, you know a value meal.
Speaker 2 (15:35):
And you still don't know.
You got to apply it to your ownlife or to your own community,
and you have a local communityand a national community and a
global community and stuff likethere.
So obviously it's a lot harderto translate it into action,
right yeah?
Speaker 1 (15:52):
Yeah, and I think we all have this cognitive
dissonance where we have thesebeliefs, but when those beliefs
are actually tested in reality,it just becomes kind of more
convenient to keep doing thesame old things, and everybody's
, you know, does that to anextent, I agree, but it's good
to at least kind of be aware ofthat.
Speaker 2 (16:09):
It is.
It's an eye-opening story.
The book it really is, yeah,and.
Speaker 1 (16:13):
I think any book that makes you kind of step back and
think about something,especially something that's a
blind spot, is a really coolthing.
I mean to say you know what.
I may have had that wrong.
Or you know when your beliefsare challenged and you have kind
of the maturity to change yourmind.
I think that can be a goodthing and you've probably
(16:36):
experienced this, as I have.
As you get older and hopefullymore wiser, you realize you kind
of know less and theprobability that you're wrong
actually goes up with the moreyou know.
Speaker 2 (16:48):
Yeah, I agree, it's humbling.
I think that's often what theycall wisdom.
Speaker 1 (16:53):
Yeah, yeah.
Speaker 2 (16:54):
It's the humility that comes with life.
Speaker 1 (16:56):
Yeah, I agree, and I think it's a good thing to have
some humility and realize Icould be wrong my position on
this.
I shouldn't be so entrenched.
Actually, before we started thepodcast, todd our producer here
, we were talking about Robert FKennedy and one of his quotes
was some people wake up in themorning and try to go to bed
(17:20):
believing the same thing theybelieved in the morning, and
some people are willing tochange their minds.
And I think it's good to bewilling to listen to others and,
you know, realize that youcould be wrong on something.
Speaker 2 (17:30):
Yeah, I agree, and Ishmael the book, I mean I would
recommend it.
It's a very unusual style ofnarration or presentation
because the teacher sometimesit's Socratic.
I mean probably his wholephilosophy could have been
summarized in a few pages.
I mean probably his wholephilosophy could have been
summarized in a few pages.
But you know he's trying tomake the student think about it
(17:52):
and then you as the reader arethinking about it as you go
along.
Yeah, and by Socratic you meanhe's asking questions to the
character.
He's asking questions to hisstudent, yeah, and in a lot of
ways, as you're reading the book, you're taking on the role of
his student and trying to answerthose questions, figuring out
what he wants you to figure out.
You know, thinking about whathe wants you to figure out.
Speaker 1 (18:14):
Yeah, that's fascinating.
Yeah, I think a lot of books dothat, where there's kind of a
central theme that you cansummarize, like you said, within
even a page and then it justkind of beats that, Fleshes it
out.
Yeah, I was going to say beatsit to death, but yeah, fleshes
it out is a better way to put it.
So, Jeff, what is your role inthe pathology department?
Speaker 2 (18:34):
So I'm the chief of the Department of Pathology and
I also serve in the role asmedical director of the
laboratory.
Medical director is required bylaw that there be a medical
director and in that role thereare kind of a whole number of
things to do.
(18:55):
There's the macro level interms of running the lab, so I
work very closely with ouradministrative director.
So I don't actually deal tooclosely with HR issues or the
financial issues, which is nice,but some medical directors in
some labs might end up having todo that if people own their own
(19:16):
lab, but not in a hospitalsetting like this.
But I'm involved in a lot ofthe macro decisions like what
type of equipment to buy, whattypes of methods should we be
looking to bring in.
Equipment decisions will impactwhat tests you can add in the
future, how you can configure,what kind of specimens you will
(19:38):
need to collect it, so how itintegrates in a larger picture.
I am responsible for theoverall quality of the running
of the lab, and that's by lawand in practice.
So overseeing the whole qualityassurance program, which
involves everything from youknow daily or multiple times a
(19:58):
day quality control what we callQC for a specific assay to all
kinds of process improvementinitiatives and then that kind
of ties into another role.
A lot of times I see myself asan ombudsman between the
laboratory staff and theprofessional caregivers, the
(20:21):
doctors and and other licensedcaregivers in the hospital.
To be someone who can translatefrom one set of language to the
other, understand the process,understand the needs of
physicians and caregivers andtranslate that into the way the
laboratory actually functionsand to try and understand, when
(20:44):
there are problems or friction,how we can make it better.
And all that has got theultimate goal of doing what's
best for the patient.
So trying to optimize patientcare, of course, keeping the
costs in mind, what's realisticand keeping the efficiency of
the process in mind as well, butultimately making sure we do
(21:08):
the best for the patient.
So we want high quality results, we want them in a timely
manner, we want them at theright time.
There are certain tests thatshouldn't be drawn in certain
situations because it doesn'tmean anything in an acute
setting.
It's based on, you know, achronic thing, so a lot of
coagulation risk factors, forexample, for thrombosis.
(21:30):
You don't want to draw an acutesetting of a thrombosis because
your whole coag system ismessed up.
Speaker 1 (21:38):
Yeah.
Speaker 2 (21:39):
And so it's not the right time to draw that, on the
other hand.
So that would be true of afunctional test, but on the
other hand, if it's agenetic-based test, you can draw
that at any time.
Their genes aren't changingwhen they're thrombosing.
So knowing things like that,right tests, right time, and
let's see what other roles.
(22:00):
Then there's individualinterpretations or problem
solving.
So physicians sometimes willorder a test because they read
that that's the next thing theyshould do, and then they don't
know how to interpret it.
Or they got a result that'soutside the simple plus minus
positive, negative that theywere expecting, and they don't
know what it means, and so theymight call me for help, guidance
(22:23):
on interpreting it.
Or they don't believe theresult.
So that kind of translates isthere some sort of interference?
So I have to learn about thepatient's history, look at other
lab results what was the acutesetting?
In order to try and find out ifthere's some limitation or some
interference that would give afalsely elevated or falsely
(22:46):
negative result.
And then advise is there analternative method?
You know, because a lot oftimes I mean, people order
things and there are multiplemethods on how to do it.
Yeah, so sometimes physiciansdon't even know exactly what
they want.
They just heard about somethingor read about something, but
they don't know whether theyneed, you know, an enzyme, a
(23:07):
measurement of the protein levelor the enzymatic activity or a
mutation in the gene for theenzyme?
Yeah, you know.
so, um it just, it has a name onit and and they just pull the
trigger so, um so, helpingpeople to decide what to do
about that or how to interpretthat, and sometimes, yeah, the
issues and one example is I.
Speaker 1 (23:28):
I remember when I would do floor work, which was a
long time ago, but they woulddraw blood and then we would say
, oh, there must have beenhemolysis.
Like when they drew the bloodsome of the red blood cells were
sheared, and so now you havesome um, differences in
potassium and things like that.
Speaker 2 (23:44):
That would be indicative of hemolysis or or,
you know, there's some reasonthat the sample's not true.
Or the specimen sat around toolong, yeah, glucose got consumed
, or it wasn't cooled properly,or the serum wasn't separated in
time or, like you said,hemolysis during drawing.
That's a really, really commonproblem and a problem we try and
(24:07):
monitor.
But like, people don't alwaysthink about the implications so
they want to have a rapid point,you know, very rapid test,
which means trying, may meanrunning it on whole blood.
So point of care tests arealways done on whole blood.
No one's separating the serumthere, you know.
So one potential drawback rightaway is you don't have an
(24:27):
opportunity to examine the bloodfor hemolysis, just a gross
hemolysis.
So that affects some assays andwhen people are running that
test on the whole blood, oftenat the point of care, they
forget about that limitation.
Speaker 1 (24:45):
So one thing that was in the news was this company,
theranos, where Elizabeth Holmeswas saying that she had this
product where she could take onedrop of blood and do all these
tests on, and I think PerkinElmer, a company that makes
machines that test blood I maybe saying the name wrong, but
threw up some red flags in order.
It's like there's no way thiscan be done and she ended up
(25:06):
being on Harvard's board ofdirectors and having all these
huge roles and then it came out.
It was all a sham.
Were you following this whenthat happened?
Speaker 2 (25:14):
So I didn't follow it really closely, but I knew
about it and saw headlines fromtime to time.
It's a wonderful dream, it's awonderful goal and maybe at some
point we'll do it.
I don't know if it'll be fromone drop of blood, but maybe
we'll be reaching to that point.
But the problem they had wasthey cut a lot of corners on
(25:36):
quality and they made falseclaims, yeah, and they didn't
follow a lot of FDA regulations.
They were so busy, I don't know, raising money.
Speaker 1 (25:47):
It was more of a sham .
It was more of a sham operation, right?
So that's what it turned out tobe, or it seemed, yeah.
Speaker 2 (25:52):
Well, that's certainly what the government
claimed, and she was convictedfor it.
So it was.
But you know, we can do a lotwith one drop of blood or one
piece of tissue in terms ofgenetics.
These days, we can examine forhundreds and even thousands of
different mutations byamplifying the RNA or using mRNA
(26:14):
to amplify.
So, again, if you're looking formutations in the genes, you're
usually looking at DNA.
But genes rearrange, you gettranslocations that result in a
fusion gene, and that's oftenbetter looked at by doing RT-PCR
instead of PCR on the RNA.
So, there again, there aresituations where we'll want to
(26:36):
examine the RNAs, the RNAproducts, the mRNA, instead of
the DNA, and so that again, thatgets forgotten a lot.
And if you want to do both,then that's even more and you
need two drops of blood insteadof one drop of blood.
And then there's a lot ofinterest in what we call
proteomics, which is like aprotein fingerprint of all the
(26:59):
proteins that are in your bloodor in a tissue and you can look
at fragments of proteins to seewhat's going on.
So that's reality in the fieldof microbiology.
But prokaryotic cells are a lotsimpler than eukaryotic cells
in our cells.
But, yeah, we do a lot ofbacterial identification now by
(27:23):
what's called MALDI, where youbasically it's a mass
spectrometry technique where youfragment the proteins that are
in a pure colony of thatbacterium and you do mass spec
on it and you get a charge andmass profiles of all the
(27:44):
fragments and then what you dois you match it to a huge
database and say okay, this onecomes out to be e coli and this
one comes out to be jasonedwards it has a characteristic
signature that, but you have tohave that huge database.
Speaker 1 (27:56):
Yeah very cool um you have to have that huge database
the one thing is I remember itwas like, uh, thermos aquaticus
or something like this was thethe uh enzyme, uh, that they
found in like these cauldrons inYellowstone.
That was this heat-resistantprotein, and that's what allowed
them to do reversetranscriptase PCR, and so it
(28:18):
heats up, it cools down, itheats up, it cools down, but
that enzyme stays the same.
But if somebody wouldn't havediscovered this bacteria in
these geysers, they would havenever had this enzyme to do this
technology, and so it's amazinghow these fields of science
kind of come together.
Speaker 2 (28:37):
Right, and that obviously was a huge scientific
breakthrough for someone torecognize that DNA polymerase or
associated enzymes were heatresistant, and that they were
heat resistant up to a levelthat would be required to
denature DNA and so thereforecould be used for PCR.
Speaker 1 (28:55):
Yeah, pretty cool.
Well, Jeff.
Thanks so much, buddy, it'sbeen a pleasure.
Speaker 2 (29:00):
Thank you.
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