Episode Transcript
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Speaker 1 (00:00):
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Speaker 2 (00:35):
You're listening to
Veterinary Vertex, a podcast of
the AVMA Journals.
This episode we chat about howthe transfusion of rotococcal
hyperimmune plasma to newbornfoals does not markedly alter
serum electrolyte or proteinconcentrations, with our guests
Noah Cohen and Devin Volding.
Speaker 3 (00:55):
Welcome listeners.
I'm Editor-in-Chief LisaFortier, and I'm joined by
Associate Editor Sarah Wright.
Today we have Noah and Devinjoining us.
Thank you guys so much forcoming and talking about
rotococcus.
I'm not an internist as Noah is, but rotococcus has been a bane
of my existence as an equinesurgeon too.
So really great work you guysare doing and excited to bring
this to our listeners today.
Speaker 4 (01:17):
Thank you, we're so
excited to be here.
Speaker 5 (01:18):
Yeah, thank you so
much for letting us have a
chance to talk about what we'vedone.
Speaker 2 (01:23):
All right, let's trot
on over.
So, noah, your Jabma articlediscusses how the transfusion of
rhodococcus equi hyperimmuneplasma to foals does not appear
to have marked effects on serumconcentrations of electrolytes
or proteins, despite therelatively high sodium
concentrations in rhodococcusequi hyperimmune plasma.
Please share with our listenersthe background on this article.
Speaker 5 (01:46):
Great, yeah, thank
you for that question.
So the background I thinkprobably starts with rhodococcus
equi, which is a bacterium thatcauses pneumonia and foals
following inhalation of theorganism from their environment.
That pneumonia can be severe.
It has a worldwide distribution, as Dr Fourier alluded to.
It has extra-permanentdisorders including bone and
(02:10):
abdominal abscesses and things.
So pretty important clinicalproblem and unfortunately it's
not a vaccineytocl hyperimmuneplasma to prevent the disease in
foals.
(02:30):
The typical volume transfused tofoals is between 1 and 2 liters
For an average 50-kilogram foal.
We calculate that that expandstheir blood volume by somewhere
around 20 to 40 percent, expandstheir blood volume by somewhere
around 20 to 40% and we reallydon't know what the impact of
that volume expansion is onelectrolyte concentrations,
protein concentrations in foals.
(02:53):
There's a research abstract thatnever matured to peer-reviewed
publication that describesmarked variation in serum
electrolyte or, excuse me, inelectrolyte concentrations and
albumin concentrations incommercial plasma and that
raised concern amongst someexperts on what the impact might
(03:15):
be for foals when they'regetting those large volumes
transfused.
We know that foals are reallysusceptible to volume expansion
and to electrolyte derangementsand so legitimately there is
some concern.
Those concerns werecontradictory to what our
experience has been clinicallyhere on a limited basis and
anecdotally from veterinariansin practice, but we really
(03:39):
didn't know the answer to whatthe impact was on serum
electrolytes and proteinconcentrations following
transfusion of one or two litersof hyperimmune plasma.
Thanks to Dr Patti AuschwitzPatti Flores Auschwitz, excuse
me from Rudin-Riddle EquineHospital in Saratoga Springs, we
had some serum samplesavailable to us from Foles
(04:01):
before and after transfusion andthen we were also, through
generous support from a plasmamanufacturer, able to get some
plasma samples to testelectrolyte concentrations and
protein concentrations and itallowed us to address what we
think is an important clinicalquestion which had not been
(04:21):
considered.
Speaker 3 (04:23):
No, you might get to
answer this later, but you
already said there's no vaccineavailable.
How close are we to a vaccine?
I know you've spent a lot ofwaking hours in research studies
.
How close are we?
Speaker 5 (04:37):
Yes, I wish I could
say well, I can only speak for
our lab, I can't speak forothers.
So there are people working allover the world.
This organism was discovered asa cause of death in a foal in
Sweden over a hundred years agonow, 102 years ago since it was
first reported, and we stilldon't have a vaccine.
I think a vaccine's going to bedifficult to produce for many
(05:00):
reasons, but we are working onsome strategies.
We're hopeful, but I'm always,you know, kind of optimistic,
hopeful.
I'm hopeful that we're gettingclose, but so I can retire for
one thing, and so I'm hopefulthat in the next few years we
might have something to try.
Speaker 2 (05:20):
Okay.
Speaker 5 (05:20):
I think one of the
big challenges for vaccine
development is not just theproblems with developing a
vaccine for an intracellularpathogen like rhodococci sequi,
which is similar to themycobacterium tuberculosis.
People have been trying for along time to get a vaccine for
TB as well.
That's proved elusive.
But beyond that, I think alsoour expectations as
(05:42):
veterinarians sometimes iscomplete.
You know that a vaccine becompletely effective.
We use experimental models, weexpect it, and there's just
that's not how vaccines workthey are.
Some like measles are highlyeffective, but some like
influenza, tb, they're much lesseffective.
And so I think some of thelimitations also been
(06:05):
expectation that veterinarianshave for the efficacy of the
vaccine.
Speaker 3 (06:08):
Yeah, I'm guilty of
that.
You know, when you're lookingat spring shots and for the
horses, dentals and all theother things you're like, well,
if that's only 50% right, likeyou want something like rabies
that you know is going to work,so I can say I'm a little guilty
of that too.
But if I were raising foals andit was not 100% you know it's
such a devastating disease Ithink I'd be all over it.
Speaker 5 (06:31):
Yeah, I think that
partial protection so in my age,
influenza vaccine, I think isabout 11 or 12% effective, but
it's still important for me toget it and for others to get it.
That may protect me from youknow, from people my age, from
getting it.
So, yeah, I think that even ifwe can achieve partial
(06:51):
protection, which is kind ofwhat plasma does, it's only
partially effective, which iswhy some people have been not
convinced that it's useful.
It's because it's not 100%,it's not completely effective,
but it is when it's beenexamined it's not 100%, it's not
completely effective, but it iswhen it's been examined has
been for the most part notalways, but for the most part
been able to reduce theincidence of the disease.
(07:12):
Sarah, I'm sorry for thosedigressions.
Speaker 2 (07:16):
No, we welcome them.
This is a conversation.
It's important for ourlisteners too, so I appreciate
you sharing additional input andDevin what are some of the
important take-home messagesfrom this JAPMA article.
Speaker 4 (07:27):
Yeah.
So I think how Noah alreadystarted to say that since foals
are more susceptible to volumeexpansion and electrolyte
derangement, it kind of bringsup this question of is this
something that we should bemonitoring throughout plasma
transfusions, which is a verycommon procedure, especially for
foals out in the field, becauseare these potentially causing
this?
And from our work and what wedid in this population of
(07:49):
healthy foals, we're not seeingthis marked variation in
electrolyte derangements andonly small changes occurred.
In addition to that, therotococcal plasma that we did
test had very low levels ofvariation within it, so
hopefully this paper will helpreassure equine veterinarians
that using these products, atleast in healthy foals, should
(08:12):
cause very little change.
Speaker 3 (08:14):
Very cool, yeah.
As a surgeon, I don't eventhink about the electrolyte part
, right, it has nothing to dowith bones and joints, unless
they're going to be really sickunder anesthesia.
Noah, as an internist, whatsparked your research interest
in rhodococcus?
Did you have a foal that youcouldn't fix, or was it one of
your own animals?
What sparked this?
Speaker 5 (08:43):
this.
That's a great question.
I think back to my days as astudent and Dr Corinne Sweeney
was a teacher of mine.
She was a great teacher.
She taught us about our equinerhodococcus equifol pneumonia
and she was pretty inspirational.
But I saw lots of cases when Iwas in practice.
I saw cases here and thenreally I think what sparked my
interest in pursuing researchwas Dr Ron Martins who was here
(09:03):
at Texas A&M studying RodaKakasikwai, and his passion, his
enthusiasm, his energy justsort of, were pretty hard to
resist and drew me intocollaborating with him.
So that's probably where theinterest comes from,
longstanding but yeah, alongstanding interest.
Speaker 3 (09:24):
You've contributed so
much, devin.
You said to Sarah earlier whatare the important take-home
messages that maybe you don'tneed to be monitoring for these
electrolytes?
Don't be so afraid of it.
But always when we do thesestudies, there's something that
was like hmm, I didn't expectthat.
What was something that wassurprising from this article?
Speaker 4 (09:41):
Yeah, I don't think a
ton was that surprising to
either of us as we kind ofsuspected that there would be
very little change.
But I will say, out of all theelectrolytes and protein
parameters that we tested, Iwould have expected sodium to
have the most significantincrease, since sodium citrate
is used as its anticoagulant inthese plasma products and yes,
(10:01):
there was statistically asignificant increase in that.
However, clinically themagnitude of this effect was
pretty small.
I believe our median for sodiumincreased only by two
milliequivalents per liter,which is pretty small when you
think about it in clinicalpractice.
Speaker 3 (10:19):
Well, it's very small
, given what Noah in the
introductory statement thevolume expansion.
Speaker 5 (10:29):
Yeah, exactly yeah,
although the volume expansion
probably has a little bit of adilutional effect on that.
Sodium is my guess.
And then I think that it is anice example of the distinction
between statistical and clinicalsignificance.
Right, there's statisticalsignificance and clinical
importance, that, yes, theincrease was statistically
significant but looks to beclinically inconsequential.
These are healthy foals, ofcourse, but in healthy foals it
(10:53):
looks like this is safe and notsomething people need to be
concerned about.
Speaker 2 (10:59):
Amen the clinical
effect is more important than
the p-value.
Yeah, we need a poster thatsays that in our office.
So Nor.
What are the next steps forresearch in Rotor Kaka Sequai?
Speaker 5 (11:13):
Ooh, that's tough.
I'm going to answer from theperspective of a clinician
clinician-scientist.
I think if you asked amolecular microbiologist they'd
probably give you a differentset of answers.
But there are a lot of thingsthat need to be done.
So, from a diagnosticperspective, right now at most
breeding farms mostveterinarians make a presumptive
(11:34):
diagnosis of rhodococcuspneumonia because we don't have
a great non-invasive or simplediagnostic test.
So I think there's room forimprovement on the diagnostic
end and we're certainly workingon that.
Therapeutically, the macrolidesthat we use as the treatments of
choice for rhodococcus havesome limitations.
There are problems withresistance Macrolide rifampin
(11:56):
resistance has emerged and seemsto be disseminating as well as
the fact that there are sideeffects of those macrolides that
can be devastating to the foals.
So alternative antimicrobialsare much needed.
Transfusing you know this wholestudy started with the notion
that transfusing a large volumeof plasmas is challenging and
(12:19):
we're working on some conceptsfor monoclonal antibodies as
alternatives to plasmatransfusion.
But the golden ring, if youwill, of Rhodococcus research is
coming back to the question dowe have a vaccine and working
towards a vaccine?
I think that is probably themain goal that we have to strive
(12:39):
for.
But a vaccine won't becompletely effective.
So all of those other things Imentioned, you know, diagnostics
, treatment and even potentiallyimmunoprophylaxis or
immunotherapy, will be importantto pursue.
Speaker 2 (12:52):
And Devin.
Do you see a role for AI inthis area of research?
Speaker 4 (12:55):
So I'll start by
saying I am very far behind in
the role of AI research.
So I'll start by saying I amvery far behind in the role of
AI.
I just started using it forsome client comms and it has
helped speed some things up forlogging that for me, but in
general I'm pretty far behind inits use in everything.
Potentially, if it has somehelp with data organization in
the future, maybe, but as for Iknow sometimes people use it in
(13:16):
writing the paper and everythingand I just don't quite see use
for that yet.
But again, I am probably notthe best person to ask about
that.
Speaker 5 (13:24):
I'm also no expert,
but I'll throw out a couple of
things to consider that peopleare using AI to design
monoclonal antibodies, and so Ithink antibody design is one.
So I think antibody design isone and I suspect or I don't
(13:46):
suspect, I know that people areusing AI for vaccine, antigen
targeting strategies as well,but, like Devin, I bet
everything we do from diagnosisto disease management to health
management to records management.
Like Devin said, there's lotsof opportunities.
It's an enormously powerfultool.
Speaker 3 (14:02):
It's fascinating.
I was just at an AI symposiumat Cornell and one of the guest
speakers was talking about itsuse for remote in humans access
to care.
So they were having techniciansand other people go out in
remote in remote areas.
If you don't have accessimmediate access to care or
underserved communities,pregnant women at risk, they
(14:23):
don't know when their due dateis.
They don't know the fetalposition if they're going to
birth at home, so untrainedultrasoundographers basically
hold the ultrasound probe andthe machine learning algorithm
tells you how to scan theabdomen and then it comes back
and says the baby's in thisfetal position, your due date.
Is this Really amazing?
(14:46):
Yeah, like real tangible thingsthat can happen.
It's crazy, Like you said, thethings that we don't even think
about, how it can be used.
Speaker 5 (14:54):
Yeah, exactly.
Speaker 2 (14:56):
That's so cool, and
for those of you just joining us
, we're discussing the effectsof transfusion of rhodococcus
equi hyperimmune plasma on serumelectrolyte and protein
concentrations in neonatal foalswith our guests Noah and Devin.
Speaker 3 (15:11):
Noah, you've written
hundreds of articles and
chapters and have trained justas many people likely articles
and chapters and have trainedjust as many people likely what,
in your training, helps you?
And then how do you pass thaton to other people?
To conceptualize a project,finish the project and then get
this article written across thefinish line.
Speaker 5 (15:31):
Oh, wow, Okay, that's
yeah.
So I'll start by past training.
You know I was trained as aninternist, which I think helps
me to know the disease,understand the disease, ask the
clinically relevant questions.
My research training was inepidemiology, which helped me to
think about population-basedstudies, to work with
(15:51):
veterinarians in the field andcollaboratively, like Patty
Flores-Aschweid, to collectthese data.
And the other part of yourquestion was about well, how do
you encourage people to do thework and finish the work and I
(16:13):
wish I had more opportunity.
I wish I had opportunity to domore of that.
I wish I had more opportunity.
I wish I had opportunity to domore of that.
I miss having more graduatestudents and more residents
working with us.
I'd love to have many more, andI think that's just a skill
that I think people have tolearn for themselves to get
(16:34):
things done, to complete things.
I try to remodel that.
I'm not answering this querywell, so good thing we can edit
this.
I think it's important to justrole model that, to try and
encourage people to finish andto see the importance of not
just presenting an abstract butto actually bring it to fruition
(16:58):
so people can read it andassess for themselves.
I do try very hard to instillin trainees the importance of
reading the literature and notaccepting it at face value, but
to be able to have skills withcritical appraisal.
I think if I could do one thingover in my career, I probably
(17:19):
would have spent more timetraining people in critical
appraisal than I've been able to.
Speaker 2 (17:26):
Now, Noah and Devin.
This next set of questions isgoing to be really important for
our listeners, and the firstone is going to revolve around
the veterinarian's perspective.
So, Devin, what is one piece ofinformation the veterinarian
should know about rhodococcusequi?
Hyperimmune plasma transfusion.
Speaker 4 (17:42):
So previous studies
have already shown the
beneficiary of the response ofgiving two liters instead of one
liter of plasma, and I thinkit's important to veterinarians
to know that, despite claims ofvariability in these plasma sets
, we tested 90 different samplesof rotococcal plasma, 30 from
each year, and within these wehad very little variation
(18:02):
between them.
So I think that's superimportant for veterinarians to
know going forward.
Speaker 2 (18:06):
And on the other side
of the relationship, Noah,
what's one thing clients shouldknow about this topic.
Speaker 5 (18:11):
Yeah, I think for
clients and farm managers, it's
really important for them toknow that transfusing foals with
a volume of two liters doesn'tappear to be unsafe.
Safety is a complicated issue.
There's nothing that we do inlife that doesn't carry some
risk.
Whether it's taking an Advil,driving in our car to work,
(18:33):
transfusing a foal with plasma,there's always some risk to any
process.
But the risks appear to be low.
The products appear to be safeand they do appear to protect
foals against rotococcalpneumonia.
So I think it's reallyimportant that we're able to
reassure clients, who may haveheard from their veterinarians
(18:54):
that the practice may not besafe, that that's not the case.
Speaker 3 (18:59):
This could go on for
days, and I'm looking forward to
coming to visit Texas A&M andwe can talk more about
epidemiology and criticalappraisal literature and all
these fun things that wepontificate on as we get a
little bit on in our career.
And as we come to a close here,we like to ask a little bit
more of a personal question.
So for you, Devin first, if youcould have a superpower, what
(19:23):
would it be and why?
Speaker 4 (19:25):
Yeah.
So if I had a superpower, Ithink I would absolutely choose
teleportation, both for worklife and personal life.
Because for work life, thatwould be pretty nice to be able
to just show up when an ER showsup, and especially if you don't
get that 30 minute out callthat you want and a 2am call
shows up, it'd be nice to justpop on over and not have that
drive time.
And then for personal life too,because I think as
(19:47):
veterinarians we all do have togive up being at lots of big
events like weddings and variousholidays, because we are
supposed to be here for thepatients and everything, and
it's something that we accept.
But it would be pretty nice tobe able to just teleport back to
some of these events and be oncall at the same time and still
be here for our patients, ofcourse.
Speaker 3 (20:05):
It's a good point.
My oldest daughter is inmedical school and I was just
saying to her about so she'sstarting her fourth year of
medical school and just sayingto her, like you know, now you
really don't have your lifeanymore and you're going to have
to start missing unfortunatelymissing, as you were saying,
weddings and holidays, and yeah,medical professionals give up a
lot, but it's worth it.
(20:26):
All right, noah, and we need toknow how old you were and what
was the first concert that youattended.
I can't wait to hear this.
Speaker 5 (20:35):
My first concert was
a band called Led Zeppelin.
I don't know if you've heard ofthem A little-known rock band.
It's pretty amazing.
I got to see them in 1970 atthe Spectrum with my friend from
my friend's school named DanHicks and he took me to that
(20:55):
concert.
It was amazing.
Speaker 3 (20:57):
That's amazing.
I don't know anybody who's seenLed Zeppelin when they were.
You know, not this age of LedZeppelin.
That's really cool.
Speaker 5 (21:06):
It was pretty epic.
It was yeah.
Speaker 3 (21:12):
What was the cool
word, then?
What was the cool?
Speaker 5 (21:13):
word then what was
the cool word then?
Well, that's a good question.
How was it cool?
Yeah, cool was cool.
Oh gosh, yeah, I'm blanking onit now.
It was the thing that's in thatSimon and Garfunkel song that
people laugh about.
Oh, Groovy, groovy, groovy,groovy was still big.
Speaker 3 (21:39):
I still say groovy
all the time, I even put it in
emails.
And now Sarah sometimes is likegroovy.
Speaker 2 (21:46):
I can attest that's
true.
Speaker 5 (21:48):
I can attest that's
true.
Speaker 2 (21:51):
ACDC was just in
Chicago this weekend.
It's like oh, I did not go, butgood things Well.
Thank you so much, noah andDevin, for being here today and
for sharing your manuscript, too, with Javma.
Speaker 4 (22:03):
Thank you so much for
having us.
Speaker 5 (22:05):
Thank you.
Speaker 2 (22:07):
And to our listeners.
You can read Noah and Devin'sarticle in Javma.
I'm Sarah Wright with LisaFortier.
Be on the lookout for nextweek's episode and don't forget
to leave us a rating and reviewon Apple Podcasts or whatever
platform you listen to.