October 23, 2025 • 27 mins
We sit down with Drs. Paul Freeman and Nick Jeffery to discuss a treatment for down dogs that’s changing outcomes and conversations: percutaneous intradiscal chondroitinase injections that act like chemical fenestration, reduce extruded disc material, and help non-ambulatory dogs recover without opening the spine.
We walk through the origin of the idea, the ethical hurdles, and the growing dataset behind safety and effectiveness. You’ll hear why deep pain–positive dogs with acute disc injuries often do as well with enzyme injections as with decompressive surgery, and how careful case selection can minimize risk. We get practical about inclusion criteria—currently focused on dogs under 15 kg, with French Bulldogs now included under close monitoring—and the technical realities of needle placement, imaging guidance, and when to add MRI. We also dig into the strategy of treating three to five disc levels to lower recurrence, and why this multi-level approach could outperform single-site surgery over the long term.
The conversation doesn’t dodge the hard calls. We compare large compressive lesions versus primarily contusive injuries, discuss when early surgery still makes sense, and share early experiences expanding to cervical cases with ultrasound and fluoroscopic checks. Looking ahead, we explore research priorities: defining time windows for chronic presentations, tracking recurrence across breeds, and building the evidence to place chondroitinase correctly in the treatment pathway. We even touch on how AI could one day use imaging data to predict which dogs need urgent decompression and which can safely recover with enzyme-first care.
If you’re an ER vet, GP, or neurologist looking to offer owners real choices, this is a grounded, data-informed guide to a less invasive option that can preserve mobility and reduce euthanasia driven by cost. Listen, share with your team, and help more “down dogs” stand again. Subscribe, leave a review, and tell us: where would you place chondroitinase in your spinal care protocol?
JAVMA article: https://doi.org/10.2460/javma.24.12.0790
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
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SPEAKER_02 (00:35):
You're listening to Veterinary Vertex, a podcast
that ADMA journals.
In this episode, we chat abouthow the percutaneous enzymatic
hemonucleolysis ofintravertebral discs appears
safe and effective with ourguests, Paul Freeman and Nick
Jeffrey.
SPEAKER_01 (00:54):
Welcome, listeners.
I'm editor-in-chief LisaFortier, and I'm joined by our
associate editor, Sarah Wright.
Today, as Sarah just said, wehave Paula Nick joining us.
Hey guys, thanks so much fortaking time out of your day to
be here with us.
SPEAKER_03 (01:07):
You're welcome.
It's good to be here.
SPEAKER_04 (01:09):
Yeah, it's great to be here.
Thank you.
SPEAKER_02 (01:11):
All right, let's dive right in.
So, Nick, your JAVMA articlediscusses the safety and
effectiveness of intradiscalchondroitinase injection as a
pragmatic treatment fornon-ambulatory paraparesis and
paraplegia in small dogs.
Please share with our listenersthe background on this article.
SPEAKER_04 (01:27):
Yeah, um, well, actually, it started with a
conversation that Paul and I haduh many years ago, uh,
discussing the recovery of withdogs that didn't have
decompressive surgery when theybecame parapheritic or
paraplegic uh following a discherniation.
And we were sort of going backthrough the history of the
(01:49):
surgeries that have been doneand realized that uh dogs that
had non-decompressive surgerydone had very good recovery
rates.
And so I've been sort of lookingaround for a way of doing like a
fenestration type of surgerythat was not surgical because as
soon as you do fenestration, assoon as you do open surgery,
(02:13):
then the obvious thing is youmight as well take out any
compressible material at thesame time.
And so it's difficult to make itto go back to doing
fenestrations as an alternative.
And so, really, the opportunitycame when this company that
produces chondroitase that I'vebeen talking to for a long time
were were talking to us aboutpossibilities of using this in
(02:35):
the spine, and uh it becameobvious that that it was a
possibility for doing anon-surgical penetration,
really, and that's reallybackground to it, I think.
SPEAKER_02 (02:47):
Yeah, I was really interested in this topic because
I know these are often sometimesheartbreaking cases too.
There's that big financialbarrier, right?
That big recovery barrier.
So this is definitely superinteresting of potentially we'll
see, maybe a game changer or twofor these cases.
SPEAKER_04 (03:01):
Yeah, it's uh we we both Paul and I have discussed
this as well, but you know,we're quite distressed about
hearing about animals that sortof become paraplegic or
paraphernic with uh discherniations or suspected disc
herniations, and we're gettingeuthanased.
Um and we thought we thoughtthat that because the owners
(03:22):
couldn't afford surgery, and sowe were thinking that that's uh
not really a very acceptable uhstate of affairs.
SPEAKER_02 (03:30):
And Nick, what are the important take-home messages
from this article?
SPEAKER_04 (03:35):
Uh well I think the the the big thing here is that
uh the results that we got fromthe percutaneous disc injections
were more or less the same assurgery.
Uh we I I say more or lessbecause the just statistically
speaking, the numbers of casesthat we've treated mean that we
(03:56):
can't be uh as precise about theyou know definition of success
as we can be pretty sure with uhthe results following surgery,
just because hundreds of caseshave been reported with surgery.
And we we've just we by now wehave done more than a hundred,
(04:18):
and so we're getting pretty sureabout the deep pain positive
cases.
The deep pain negative cases, wehave got much smaller numbers,
and so we can't quite be as sureabout the recovery rate for
those animals.
SPEAKER_01 (04:30):
That's fantastic numbers.
Paul, other than it sounds likea few conversations with Nick
over a few pints, uh, whatsparked your interest in the use
of chondroitinase uh forparapyratic and paraplegic,
especially in small dogs?
SPEAKER_03 (04:42):
Yeah, I mean, it actually goes back before uh the
conversation that Nick wastalking about and and the work
that we did um investigating theresults of fenestration, to be
honest.
I I've got uh uh things that Iwrote down and small
presentation that I made uhyears and years ago, uh, which
Nick won't even remember, but itwas when I was actually his
(05:04):
resident, believe it or not.
Um and uh and I had a case of auh a deep pain negative uh peek
and ease dog, Nick, actually,um, that whose hands couldn't
afford surgery and we managed itmedically and it actually
recovered.
And you know, it was a it wasone of those sort of, I don't
know, kind of light bulb momentsor whatever.
Uh, you know, and and I thinkeverybody who who operates on
(05:27):
these dogs regularly, which weall do, you know, as as
neurologists, neurosurgeons, wewe love doing the surgery
because it's is very satisfyingsurgery.
The dogs recover, you know, onceyou've done a few, it's pretty
straightforward, generallyspeaking.
Um, but I think everybody hasthis kind of question mark uh
after a lot of surgeries whereyou kind of come out and think,
(05:48):
well, did I actually achieveanything there?
You know, was that reallysomething that is actually going
to make a difference to thatdog's recovery?
And I and I think we've, youknow, we've discussed that a lot
over the years.
And and I think it was a case ofsort of, you know, wanting to to
try to um wanting to try to showthat these dogs can get better
(06:10):
and mostly do get better withoutsurgery, first of all, but then
thinking about um perhapssomething uh that we could offer
people who were not able toafford surgery, but who people
were being told needed surgeryas an alternative, because you
(06:32):
know, otherwise the alternativeis conservative management.
And and you know, we've we'vedone a lot of work on that.
We've shown that that generallyworks in most cases, actually,
but people are still very scaredof doing just conservative
management on paraplegic dogs,particularly.
Uh, and oh, you know, owners ofdogs are very scared.
And so actually being able tooffer something that is perhaps
(06:57):
more uh equivalent to surgeryand maybe has some advantages
over surgery as well.
Well, definitely has advantagesover surgery, but um, you know,
it when Nick sort of put it tome about the chondroitase, I was
instantly keen to be involved.
Um, and we had to sort of getover a few barriers in terms of
(07:19):
getting ethical approval to dothis kind of thing in the UK.
Um, but we managed to do that.
And uh, you know, um I was a fewmonths behind Nick getting
started, but you know, nowbetween the two of us, we've
done yeah, well over a hundreddogs.
And yeah, it's great.
I mean, it's it's it's reallytaken off now.
SPEAKER_01 (07:38):
That's really fantastic.
I think always uh, you know, yousaid well over a hundred dogs.
Every time we look back at ourown data, we're surprised um to
find things that we just didn'texpect.
What were some surprisingfindings uh from this article
and the data you accumulated?
SPEAKER_03 (07:52):
Yeah, surprising findings.
I mean, I don't think we weresurprised that the dogs were
covered, to be honest.
Um I think, you know, we we kindof expected that that would
happen.
You know, we were we were keento show that it was uh a
technique that was was doable.
I mean, I was pretty scared uhof doing the first one or two,
(08:14):
I'll I'll be honest with you,because uh, you know, I kind of
envisaged the possibility of ofnot being able to get the needle
into the discs and and you know,maybe causing some damage to
structures alongside.
And and but you know, the i wehaven't had any of that at all.
And I think maybe that's one ofthe perhaps surprising things
(08:35):
that we we don't appear to havehad really any complications in
this, Nick, do we?
Um that we're aware of at least.
SPEAKER_04 (08:41):
Yeah, I would agree with that.
I I you yeah, I I agree withPaul actually.
We I was thinking the same thingthat it might be very difficult
to position the needles, but itdoesn't seem to be as difficult
as you'd imagine.
Um I agree, yeah.
We I hadn't seen complicationsfrom doing it, of course.
Now I say that next one we'llget a competition, obviously.
(09:03):
Yeah.
I I it it I agree that it'sthat's surprising, yeah.
SPEAKER_02 (09:08):
Very cool.
Well, like I said, it's such acool topic and sounds like a
good, I guess, option for peopleto have in their toolkit, too,
especially for these owners,like you said, where surgery
might be too much of a financialconstraint for them.
So, what are the next steps forresearch into this topic?
SPEAKER_04 (09:21):
Yeah, I'd actually I'd I'd just like to come back a
little bit.
Yeah.
Paul mentioned about the uhconservative therapy, and I
think you know, there is quitegood evidence that conservative
therapy will work.
But uh, and Paul's done a greatstudy on that.
But uh the the the slight gap inhis study was the delay of time
(09:42):
before the dogs went into theconservative study for some of
the cases.
And so in uh in our study withthe chondroitinase, we've been
trying to fill that gap torestrict entry to being very
early on in the course because Ithink the big thing that
neurologists in particular areworried about with these cases
is that um they're gonna getworse.
(10:04):
You know, if you don't rush intodoing surgery, that they're
gonna get worse.
And I think that that creates alot of tension for the
neurologists and for the owner.
Um, and they the owners feelpressured to make a very quick
decision.
And so one of the things thatthat you know Paul and I have
discussed quite a lot again isthat the possibility of using
conjoitinase is the first linetreatment, and then you know,
(10:27):
cases that we imagine that somecases might not get fully
better, they might havepersistent pain, and then we
could take them to surgerylater.
Although I think so far we'veonly had like one or two out of
out of our 100 odd cases wherewe've felt that that was
necessary.
Is that is that correct, Paul?
SPEAKER_03 (10:46):
Yeah, yeah, it is correct.
Yeah, I I had one case where theowner, after three weeks, wasn't
seeing um uh a significantimprovement, let's say, and uh
found the money to uh to have anMRI scan and surgery.
Um and we we took that dog tosurgery and it did recover much
(11:08):
more quickly once it had beendecompressed.
And and I think, you know, as asNick said, one of the things
that we're kind of discussing abit and and thinking is that,
you know, that this might be abetter approach to a lot of
these dogs to to you know delaythe surgery for the ones that
don't recover.
SPEAKER_01 (11:26):
Paul, is there a or or Nick, is there a weight or a
size?
Everything in the title and themanuscript or small dogs, is
there a weight or a sizelimitation?
SPEAKER_03 (11:36):
Yeah, that's a that's a good question.
I mean, we've basically done,we've kept it to dogs under 15
kilos um at the moment.
That was the entry requirementfor the original trial.
Um now uh you know, we've atCambridge we've kind of started
to open it up.
Um, we're opening it up to dogsthat have been down for longer,
for instance.
Um I I think the big problemwith going for bigger dogs will
(12:00):
be getting the needles into thediscs.
You know, I think that it it'sthe the bigger the dog
potentially the more difficultthat will be.
But uh, you know, I think it'ssome uh if we had the right
case, let's say uh the ownerwith the dog that um needed that
approach, then I I think nowwe'd be willing to to give it a
(12:22):
try.
I'd be willing to give it a try.
I think Nick would be the same.
We were discussing the FrenchBulldogs um actually just this
week because uh we haven't doneany French Bulldogs in
Cambridge, but Nick was tellingme he's done a lot in Texas.
Um so that you know that's thenext sort of step for us, is is
you know, I've had loads ofinquiries from owners of French
(12:43):
Bulldogs um since this wentcrazy on social media.
So um, you know, they will becoming uh for sure.
SPEAKER_01 (12:51):
How about how many levels have you like set?
Like we're only doing one tostart two.
What do you advise orveterinarians to wanting to
start this?
SPEAKER_03 (13:00):
Well, you mean levels of numbers of disks that
we're treating?
Yeah.
So, you know, the original trialthat Nick devised and that we
both have followed with with thefirst uh cases, and and and uh
that is what we've published wasto treat four levels, four uh
disk spaces.
And part of the reason for thatwas that we're not we weren't
(13:21):
MRIing these dogs.
So we were basing where we weretreating them on the results of
the neurological examination.
Um, and you know, that was oneof the things that we always had
to explain to owners um and andone of the potential
limitations.
Um what we're doing now atCambridge is we're offering
people an MRI scan um alongsidetreatment so that we can
(13:44):
actually see precisely whichdisk has gone and target the
disk that's gone.
We've also got you know someinformation on uh the the the
disks, how they look, how theyappear on MRI in terms of their
level of degeneration andperhaps uh their risk of um
extrusion in the future.
So uh, you know, we're able toconsider which disks we're
(14:06):
targeting.
But I think I mean we're stillgenerally treating three, four,
or maybe five discs is is whatI'm saying to people now.
Um and you asked about futureresearch.
One of the things, sorry, I'mtaking over this, Nick.
One of the things that we havestarted looking at.
You can just mute me.
Uh one of the things that we'vecut back.
(14:29):
One of the things that we'vestarted looking at because it it
is recurrence.
Um, because you know, uh one ofthe things that people say about
surgical treatment is that dogsare less likely to have a
recurrence than withconservative treatment.
Well, A, we don't think that'snecessarily true.
Um B, it's probably only true ifthey're receiving multiple
(14:51):
fenestrations.
And so what we're kind of hopingis that by treating more than
one disc at a time, effectively,as Nick said, we're chemically
uh fenestrating the discs.
We would anticipate that therecurrence rate might be lower,
which will be another bigadvantage with this treatment
over standard surgery with youknow not doing multiple
(15:15):
fenestrations.
So um we're looking at that atthe moment.
That will be the the the next umproject, hopefully, that we're
um we'll publish.
SPEAKER_04 (15:24):
Yeah, I I for future things, uh I I can jump in there
as well.
So uh Paul's mentioned aboutdoing other breeds, and
certainly, yeah, we we'retreating French trees.
The original reason for for nottreating them was purely to do
with the respiratory problems.
And uh now that the owners areuh are are paying for the
(15:46):
treatment, we can explain tothem that if they have to stay
in the hospital, which sometimesthey do, um, if we treat them in
the afternoon, we sometimes keepthem overnight, but they'll go
into ICU so that they can bewatched.
But uh the reason for excludingthem before that is because we
were trying to keep the costsdown for us as well because we
were subsidizing what we weredoing.
But the French is uh beingcompletely fine about it.
(16:08):
One thing that Paul mentionedabout doing bigger dogs, that
the difficulty would be that insome Frenchies we're having to
use three and a half inch spinalneedles to be able to hit the
discs.
And so you can imagine if youwere doing a pit bull, uh that
you may have we may not actuallyjust have long enough spinal
needles, although, of course, wecould go up a gauge, but we
(16:28):
haven't got much experience withusing larger needles than 20
gauge, and the error that you'dmake in trying to hit those
discs because you're starting sofar away might make it more
difficult to do.
Um the the big progression thatwe're doing here in including
new cases is to treat necks now.
(16:49):
So we've started to um thereason was we had somebody come
in with a uh a dog with a neckproblem, pick and knees again as
it happens, that had beenparalyzed, unable to walk on on
all four legs for a long periodof time.
Theon has had the scan done andthen couldn't afford the
surgery.
And so we sort of likedesperately arranged for this to
(17:13):
be done as a compassionate use,and so we did treat the dog and
and it got better.
I mean, whether it's the whetherit's the chondrotonase or not,
you know, who knows?
But we it it did get better andquite quickly.
And so we then wrote the AUP tobe to be able to enable us to
recruit uh just neck dogs withchronic discs.
(17:34):
Um but we're gonna again, likePaul says, we're gonna have uh
an MRI to locate which discwe're treating, because we're
doing this with ultrasoundguidance uh along with the
radiologists, uh, because I'mnot very good at using
ultrasound, and so they positionthe needle very close, and then
I put it into the into the discbecause uh I know what it feels
(17:57):
like to get it in the rightplace, and we're checking it
with radio grips and things.
So it's a slightly more involvedprocess, but we're we're moving
into doing next as well.
Yeah.
SPEAKER_01 (18:07):
Sounds like you might need to collaborate with
your equine partners to findthose longer, stiffer needles to
get in there.
SPEAKER_04 (18:13):
Yeah, I know.
I yeah, I uh I have had someexperience of using a very long
needle, uh very long spinalneedles, but yeah, it's not
something we'd see me use.
SPEAKER_03 (18:24):
I think the just to to uh come back again uh with
one of the other areas thatwe're interested in, certainly
I'm getting a lot of interest,and I'm sure you are as well,
Nick, is is um you know howeffective this might be on more
chronic extrusions, because youknow, as as we said, we've
limited it to dogs that havebeen down for um uh 48 hours or
(18:46):
or less up to now.
And we're now starting to toopen it up to to dogs that have
been down longer.
And uh, you know, I I think itwill be very interesting to to
see what's the sort of timelimit in a sense.
You know, how long uh can a dischave been extruded before
chondroitinase is not likely tobe effective?
Um, because I think I I have thefeeling that it will be
(19:09):
effective for uh extrusions thathave been there definitely at
least a few weeks.
Yeah, but we could do with someevidence for that.
SPEAKER_02 (19:18):
Makes sense.
Very cool.
I think it's episode two is areally good reminder for our
first-line clinicians, like ourER clinicians, our GPs that are
seeing these down dogs, right?
Like at first clinicalpresentation, that there are a
lot of options and to reallypresent to owners the entire
picture and not just we need tocut ASAP or consider euthanasia.
So I think this is a really goodreminder, that audience.
SPEAKER_04 (19:40):
Yeah.
I think one of the things thatwe need to clarify with this
treatment is just its place in,you know, in the treatment on
Ethereum, as they like to say.
So the uh, you know, you've gotconservative therapy, got
surgery, and you I thinkconjoitinase is now another
realistic option.
And so we need to know where toplace that, you know, which dogs
(20:04):
you give which to and at whichstage.
Um, and so I I've got a feelingof how we can develop this in
the future, but we need moredata to know whether whether
what I'm thinking is is is thebest way of using it.
One of the things, for instance,is is the deep pain-negative
dogs.
We we see a quite a lot throughthis clinic, and some of them,
(20:28):
when you see them on the scan,they have a massive compression,
like huge compression.
Some of them don't, but some ofthem do have a huge compression.
And so my feeling is that someof those may be better treated
with surgery, you know, quickly.
Um, whereas the other ones thathave got mostly a contusive
injury where we've got longerperiods to try and disintegrate
(20:53):
the the extruded material, um,then the chase may be more
appropriate for those.
And so I we it'll take a whileto collect the data to know
whether that's the way thatwe're going, but I it's my sort
of feeling at the moment.
SPEAKER_02 (21:06):
And do you see a role for AI in this area of
research, Nick?
SPEAKER_04 (21:11):
Um Yeah, I saw that you put that on the list of
questions.
Um I guess I I the the the roleof AI here, I think, is in image
analysis, so that uh you knowwhat everybody wants to know is
what and neurologists really doneed to know this, like which
which cases need to have surgeryand when.
(21:35):
And you imagine that you couldcollect a lot of data, a lot of
imaging data, and then ask andand then tell the AI, you know,
what which ones got better andall this.
And hopefully they might betterwork out which ones need to be
treated quicker and that.
But I I I don't know that muchabout using AI, but my guess is
(21:57):
that you'd need thousands ofimages before you could um you
know reconcile that.
But I yeah, definitely for thefuture, yeah.
SPEAKER_01 (22:07):
Yeah, it's hard to know what the future of AI is.
It's very difficult to keep up.
SPEAKER_04 (22:12):
Yeah, right.
Yeah.
Yeah.
Every week you read somethingthat that tells you it's got
more potential than you thoughtit had, yeah.
SPEAKER_01 (22:18):
Yeah.
Well, this next set of questionswe ask are really important for
the listeners.
Uh, we'll start with Nick again.
What is the one piece ofinformation the veterinary team
should know about chondroitasefor presumed disc-associated
paresis and paraplegia?
SPEAKER_04 (22:33):
Uh but it's a very realistic treatment for a large
majority of animals that presentwith acute paraplegia.
Or small braid dogs that presentwith acute paraplegia, yeah.
SPEAKER_01 (22:46):
Very good.
And then, Paul, on the otherside of the same equation,
what's the one thing the clientshould know about this topic?
SPEAKER_03 (22:53):
I mean, it's almost the same answer, really.
Uh I I think um, you know, it'sthe fact that there is an
alternative to surgery.
You know, we're I think we'retrying to get this message out
more and more that surgery isnot the only treatment option,
uh, that it's probably not anemergency in the vast majority
(23:14):
of cases, um, you know, and tryand take away that kind of fear
and uh and anxiety that it thatit drives in owners of dogs and
also their vets, let's behonest.
Um, you know, it it really does.
And so I think the more thingsthat we can do and and publish
(23:36):
that try to dispel that,certainly the the less dogs will
end up being euthanized becausetheir owners haven't got the
money.
Um that's the that's the firstthing.
SPEAKER_02 (23:45):
So now we get to ask you some fun questions.
So, Paul, what is the oldest ormost interesting item on your
desk or in your desk drawer?
SPEAKER_03 (23:56):
That's uh yeah.
So I was thinking about this.
SPEAKER_01 (24:00):
Why does Nick laughing?
SPEAKER_03 (24:02):
I don't actually know why he's laughing because
you know what's on my desk.
He's probably got a good he'smaybe imagining what might be on
my desk.
SPEAKER_04 (24:12):
Yeah, and partly what's in my desk.
SPEAKER_03 (24:14):
There's a couple of there's a couple of things that
I was gonna say.
First of all, the thing that Ithink is the that I have on my
desk in my office at work, whichum uh is an extremely nice thing
to have, is just a little whitemarble Daxund statue.
I don't own a Daxon's, but theyhave supported Daxon Breed and
(24:36):
Breed Societies and charitieshave supported the work that um
both Nick and I have been doingfor a number of years, and and
really, especially my work inCambridge, that's for sure.
Um but this was a gift from uhan Italian uh veterinarian who
came and visited our departmenta few years ago, probably right
(24:56):
more or less at the beginning ofmy time at Cambridge, actually.
And when she left, she gave methis little white marble Daxon,
and it's a beautiful thing.
Um, it's apparently carved froma stone that's only available in
the area of Italy that she comesfrom.
So I kind of treasured it andit's it's really, really nice.
So that's the one thing.
The other thing I have, whichNick will also uh will know
(25:17):
about, I have a box full ofvertebrae from various species
that belonged to um aneurologist called Professor
Tony Palmer, uh, who I think isabout 98 years old now.
Um he still lives in Cambridge.
Uh he worked uh well he was uhhe was around a lot when uh Nick
(25:38):
was at Cambridge, I know.
Um he's a pathologist, reallyneuropathologist, and he's kind
of collected all these umartifacts and items.
And one of the things that I'vebeen able to do while I've been
at Cambridge is to pull all thisstuff together.
So I have this box of bonessitting on my desk, which um is
a is a reminder of kind of wherewe've come from, really.
SPEAKER_04 (25:59):
I I could add a funny story to that as well,
actually, that uh Tony Palmerleft those bones.
Uh he he found these horse bonesfrom a horse wobbler and left
them on my desk at Cambridge.
And at the time I had a dog thatcame in to work with me.
And uh I came back after goingto do a consultation or
something and found him eatingoak.
SPEAKER_01 (26:20):
I I could have predicted that as soon as you
said horse and dog.
I was like, oh no, this isn'tgoing to end well for the
wobbler neck.
SPEAKER_04 (26:28):
Yeah, so some of them have probably got bite
marks in.
SPEAKER_03 (26:30):
That's why a couple of them are a bit chewed, yeah.
SPEAKER_04 (26:32):
Yeah.
SPEAKER_02 (26:34):
I love that though.
Spoken like a true neurologist.
And then Nick, what's yourfavorite animal fact?
SPEAKER_04 (26:40):
Oh uh that all mammals have seven net vertebrae
apart from sloths.
SPEAKER_02 (26:49):
Very nice.
Another great neurofact.
Well, thank you both for beinghere today and for sharing your
article too with us.
We really appreciate it.
Like we said, I think it's gonnabe really cool info for our
listeners and readers.
SPEAKER_03 (27:01):
Thank you very much.
SPEAKER_04 (27:02):
Yeah, thank you for your interviewing us.
It's uh it's something we did weuh, you know, we're keen to sort
of develop this technique.
And so it's we're passionateabout it, Nick.
SPEAKER_03 (27:12):
We are.
SPEAKER_02 (27:13):
We can certainly tell.
And to our listeners, you canread Paul and Nick's article in
Japan.
I'm Sarah with Lisa Portier.
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.
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(00:21):
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SPEAKER_02 (00:35):
You're listening to Veterinary Vertex, a podcast
that ADMA journals.
In this episode, we chat abouthow the percutaneous enzymatic
hemonucleolysis ofintravertebral discs appears
safe and effective with ourguests, Paul Freeman and Nick
Jeffrey.
SPEAKER_01 (00:54):
Welcome, listeners.
I'm editor-in-chief LisaFortier, and I'm joined by our
associate editor, Sarah Wright.
Today, as Sarah just said, wehave Paula Nick joining us.
Hey guys, thanks so much fortaking time out of your day to
be here with us.
SPEAKER_03 (01:07):
You're welcome.
It's good to be here.
SPEAKER_04 (01:09):
Yeah, it's great to be here.
Thank you.
SPEAKER_02 (01:11):
All right, let's dive right in.
So, Nick, your JAVMA articlediscusses the safety and
effectiveness of intradiscalchondroitinase injection as a
pragmatic treatment fornon-ambulatory paraparesis and
paraplegia in small dogs.
Please share with our listenersthe background on this article.
SPEAKER_04 (01:27):
Yeah, um, well, actually, it started with a
conversation that Paul and I haduh many years ago, uh,
discussing the recovery of withdogs that didn't have
decompressive surgery when theybecame parapheritic or
paraplegic uh following a discherniation.
And we were sort of going backthrough the history of the
(01:49):
surgeries that have been doneand realized that uh dogs that
had non-decompressive surgerydone had very good recovery
rates.
And so I've been sort of lookingaround for a way of doing like a
fenestration type of surgerythat was not surgical because as
soon as you do fenestration, assoon as you do open surgery,
(02:13):
then the obvious thing is youmight as well take out any
compressible material at thesame time.
And so it's difficult to make itto go back to doing
fenestrations as an alternative.
And so, really, the opportunitycame when this company that
produces chondroitase that I'vebeen talking to for a long time
were were talking to us aboutpossibilities of using this in
(02:35):
the spine, and uh it becameobvious that that it was a
possibility for doing anon-surgical penetration,
really, and that's reallybackground to it, I think.
SPEAKER_02 (02:47):
Yeah, I was really interested in this topic because
I know these are often sometimesheartbreaking cases too.
There's that big financialbarrier, right?
That big recovery barrier.
So this is definitely superinteresting of potentially we'll
see, maybe a game changer or twofor these cases.
SPEAKER_04 (03:01):
Yeah, it's uh we we both Paul and I have discussed
this as well, but you know,we're quite distressed about
hearing about animals that sortof become paraplegic or
paraphernic with uh discherniations or suspected disc
herniations, and we're gettingeuthanased.
Um and we thought we thoughtthat that because the owners
(03:22):
couldn't afford surgery, and sowe were thinking that that's uh
not really a very acceptable uhstate of affairs.
SPEAKER_02 (03:30):
And Nick, what are the important take-home messages
from this article?
SPEAKER_04 (03:35):
Uh well I think the the the big thing here is that
uh the results that we got fromthe percutaneous disc injections
were more or less the same assurgery.
Uh we I I say more or lessbecause the just statistically
speaking, the numbers of casesthat we've treated mean that we
(03:56):
can't be uh as precise about theyou know definition of success
as we can be pretty sure with uhthe results following surgery,
just because hundreds of caseshave been reported with surgery.
And we we've just we by now wehave done more than a hundred,
(04:18):
and so we're getting pretty sureabout the deep pain positive
cases.
The deep pain negative cases, wehave got much smaller numbers,
and so we can't quite be as sureabout the recovery rate for
those animals.
SPEAKER_01 (04:30):
That's fantastic numbers.
Paul, other than it sounds likea few conversations with Nick
over a few pints, uh, whatsparked your interest in the use
of chondroitinase uh forparapyratic and paraplegic,
especially in small dogs?
SPEAKER_03 (04:42):
Yeah, I mean, it actually goes back before uh the
conversation that Nick wastalking about and and the work
that we did um investigating theresults of fenestration, to be
honest.
I I've got uh uh things that Iwrote down and small
presentation that I made uhyears and years ago, uh, which
Nick won't even remember, but itwas when I was actually his
(05:04):
resident, believe it or not.
Um and uh and I had a case of auh a deep pain negative uh peek
and ease dog, Nick, actually,um, that whose hands couldn't
afford surgery and we managed itmedically and it actually
recovered.
And you know, it was a it wasone of those sort of, I don't
know, kind of light bulb momentsor whatever.
Uh, you know, and and I thinkeverybody who who operates on
(05:27):
these dogs regularly, which weall do, you know, as as
neurologists, neurosurgeons, wewe love doing the surgery
because it's is very satisfyingsurgery.
The dogs recover, you know, onceyou've done a few, it's pretty
straightforward, generallyspeaking.
Um, but I think everybody hasthis kind of question mark uh
after a lot of surgeries whereyou kind of come out and think,
(05:48):
well, did I actually achieveanything there?
You know, was that reallysomething that is actually going
to make a difference to thatdog's recovery?
And I and I think we've, youknow, we've discussed that a lot
over the years.
And and I think it was a case ofsort of, you know, wanting to to
try to um wanting to try to showthat these dogs can get better
(06:10):
and mostly do get better withoutsurgery, first of all, but then
thinking about um perhapssomething uh that we could offer
people who were not able toafford surgery, but who people
were being told needed surgeryas an alternative, because you
(06:32):
know, otherwise the alternativeis conservative management.
And and you know, we've we'vedone a lot of work on that.
We've shown that that generallyworks in most cases, actually,
but people are still very scaredof doing just conservative
management on paraplegic dogs,particularly.
Uh, and oh, you know, owners ofdogs are very scared.
And so actually being able tooffer something that is perhaps
(06:57):
more uh equivalent to surgeryand maybe has some advantages
over surgery as well.
Well, definitely has advantagesover surgery, but um, you know,
it when Nick sort of put it tome about the chondroitase, I was
instantly keen to be involved.
Um, and we had to sort of getover a few barriers in terms of
(07:19):
getting ethical approval to dothis kind of thing in the UK.
Um, but we managed to do that.
And uh, you know, um I was a fewmonths behind Nick getting
started, but you know, nowbetween the two of us, we've
done yeah, well over a hundreddogs.
And yeah, it's great.
I mean, it's it's it's reallytaken off now.
SPEAKER_01 (07:38):
That's really fantastic.
I think always uh, you know, yousaid well over a hundred dogs.
Every time we look back at ourown data, we're surprised um to
find things that we just didn'texpect.
What were some surprisingfindings uh from this article
and the data you accumulated?
SPEAKER_03 (07:52):
Yeah, surprising findings.
I mean, I don't think we weresurprised that the dogs were
covered, to be honest.
Um I think, you know, we we kindof expected that that would
happen.
You know, we were we were keento show that it was uh a
technique that was was doable.
I mean, I was pretty scared uhof doing the first one or two,
(08:14):
I'll I'll be honest with you,because uh, you know, I kind of
envisaged the possibility of ofnot being able to get the needle
into the discs and and you know,maybe causing some damage to
structures alongside.
And and but you know, the i wehaven't had any of that at all.
And I think maybe that's one ofthe perhaps surprising things
(08:35):
that we we don't appear to havehad really any complications in
this, Nick, do we?
Um that we're aware of at least.
SPEAKER_04 (08:41):
Yeah, I would agree with that.
I I you yeah, I I agree withPaul actually.
We I was thinking the same thingthat it might be very difficult
to position the needles, but itdoesn't seem to be as difficult
as you'd imagine.
Um I agree, yeah.
We I hadn't seen complicationsfrom doing it, of course.
Now I say that next one we'llget a competition, obviously.
(09:03):
Yeah.
I I it it I agree that it'sthat's surprising, yeah.
SPEAKER_02 (09:08):
Very cool.
Well, like I said, it's such acool topic and sounds like a
good, I guess, option for peopleto have in their toolkit, too,
especially for these owners,like you said, where surgery
might be too much of a financialconstraint for them.
So, what are the next steps forresearch into this topic?
SPEAKER_04 (09:21):
Yeah, I'd actually I'd I'd just like to come back a
little bit.
Yeah.
Paul mentioned about the uhconservative therapy, and I
think you know, there is quitegood evidence that conservative
therapy will work.
But uh, and Paul's done a greatstudy on that.
But uh the the the slight gap inhis study was the delay of time
(09:42):
before the dogs went into theconservative study for some of
the cases.
And so in uh in our study withthe chondroitinase, we've been
trying to fill that gap torestrict entry to being very
early on in the course because Ithink the big thing that
neurologists in particular areworried about with these cases
is that um they're gonna getworse.
(10:04):
You know, if you don't rush intodoing surgery, that they're
gonna get worse.
And I think that that creates alot of tension for the
neurologists and for the owner.
Um, and they the owners feelpressured to make a very quick
decision.
And so one of the things thatthat you know Paul and I have
discussed quite a lot again isthat the possibility of using
conjoitinase is the first linetreatment, and then you know,
(10:27):
cases that we imagine that somecases might not get fully
better, they might havepersistent pain, and then we
could take them to surgerylater.
Although I think so far we'veonly had like one or two out of
out of our 100 odd cases wherewe've felt that that was
necessary.
Is that is that correct, Paul?
SPEAKER_03 (10:46):
Yeah, yeah, it is correct.
Yeah, I I had one case where theowner, after three weeks, wasn't
seeing um uh a significantimprovement, let's say, and uh
found the money to uh to have anMRI scan and surgery.
Um and we we took that dog tosurgery and it did recover much
(11:08):
more quickly once it had beendecompressed.
And and I think, you know, as asNick said, one of the things
that we're kind of discussing abit and and thinking is that,
you know, that this might be abetter approach to a lot of
these dogs to to you know delaythe surgery for the ones that
don't recover.
SPEAKER_01 (11:26):
Paul, is there a or or Nick, is there a weight or a
size?
Everything in the title and themanuscript or small dogs, is
there a weight or a sizelimitation?
SPEAKER_03 (11:36):
Yeah, that's a that's a good question.
I mean, we've basically done,we've kept it to dogs under 15
kilos um at the moment.
That was the entry requirementfor the original trial.
Um now uh you know, we've atCambridge we've kind of started
to open it up.
Um, we're opening it up to dogsthat have been down for longer,
for instance.
Um I I think the big problemwith going for bigger dogs will
(12:00):
be getting the needles into thediscs.
You know, I think that it it'sthe the bigger the dog
potentially the more difficultthat will be.
But uh, you know, I think it'ssome uh if we had the right
case, let's say uh the ownerwith the dog that um needed that
approach, then I I think nowwe'd be willing to to give it a
(12:22):
try.
I'd be willing to give it a try.
I think Nick would be the same.
We were discussing the FrenchBulldogs um actually just this
week because uh we haven't doneany French Bulldogs in
Cambridge, but Nick was tellingme he's done a lot in Texas.
Um so that you know that's thenext sort of step for us, is is
you know, I've had loads ofinquiries from owners of French
(12:43):
Bulldogs um since this wentcrazy on social media.
So um, you know, they will becoming uh for sure.
SPEAKER_01 (12:51):
How about how many levels have you like set?
Like we're only doing one tostart two.
What do you advise orveterinarians to wanting to
start this?
SPEAKER_03 (13:00):
Well, you mean levels of numbers of disks that
we're treating?
Yeah.
So, you know, the original trialthat Nick devised and that we
both have followed with with thefirst uh cases, and and and uh
that is what we've published wasto treat four levels, four uh
disk spaces.
And part of the reason for thatwas that we're not we weren't
(13:21):
MRIing these dogs.
So we were basing where we weretreating them on the results of
the neurological examination.
Um, and you know, that was oneof the things that we always had
to explain to owners um and andone of the potential
limitations.
Um what we're doing now atCambridge is we're offering
people an MRI scan um alongsidetreatment so that we can
(13:44):
actually see precisely whichdisk has gone and target the
disk that's gone.
We've also got you know someinformation on uh the the the
disks, how they look, how theyappear on MRI in terms of their
level of degeneration andperhaps uh their risk of um
extrusion in the future.
So uh, you know, we're able toconsider which disks we're
(14:06):
targeting.
But I think I mean we're stillgenerally treating three, four,
or maybe five discs is is whatI'm saying to people now.
Um and you asked about futureresearch.
One of the things, sorry, I'mtaking over this, Nick.
One of the things that we havestarted looking at.
You can just mute me.
Uh one of the things that we'vecut back.
(14:29):
One of the things that we'vestarted looking at because it it
is recurrence.
Um, because you know, uh one ofthe things that people say about
surgical treatment is that dogsare less likely to have a
recurrence than withconservative treatment.
Well, A, we don't think that'snecessarily true.
Um B, it's probably only true ifthey're receiving multiple
(14:51):
fenestrations.
And so what we're kind of hopingis that by treating more than
one disc at a time, effectively,as Nick said, we're chemically
uh fenestrating the discs.
We would anticipate that therecurrence rate might be lower,
which will be another bigadvantage with this treatment
over standard surgery with youknow not doing multiple
(15:15):
fenestrations.
So um we're looking at that atthe moment.
That will be the the the next umproject, hopefully, that we're
um we'll publish.
SPEAKER_04 (15:24):
Yeah, I I for future things, uh I I can jump in there
as well.
So uh Paul's mentioned aboutdoing other breeds, and
certainly, yeah, we we'retreating French trees.
The original reason for for nottreating them was purely to do
with the respiratory problems.
And uh now that the owners areuh are are paying for the
(15:46):
treatment, we can explain tothem that if they have to stay
in the hospital, which sometimesthey do, um, if we treat them in
the afternoon, we sometimes keepthem overnight, but they'll go
into ICU so that they can bewatched.
But uh the reason for excludingthem before that is because we
were trying to keep the costsdown for us as well because we
were subsidizing what we weredoing.
But the French is uh beingcompletely fine about it.
(16:08):
One thing that Paul mentionedabout doing bigger dogs, that
the difficulty would be that insome Frenchies we're having to
use three and a half inch spinalneedles to be able to hit the
discs.
And so you can imagine if youwere doing a pit bull, uh that
you may have we may not actuallyjust have long enough spinal
needles, although, of course, wecould go up a gauge, but we
(16:28):
haven't got much experience withusing larger needles than 20
gauge, and the error that you'dmake in trying to hit those
discs because you're starting sofar away might make it more
difficult to do.
Um the the big progression thatwe're doing here in including
new cases is to treat necks now.
(16:49):
So we've started to um thereason was we had somebody come
in with a uh a dog with a neckproblem, pick and knees again as
it happens, that had beenparalyzed, unable to walk on on
all four legs for a long periodof time.
Theon has had the scan done andthen couldn't afford the
surgery.
And so we sort of likedesperately arranged for this to
(17:13):
be done as a compassionate use,and so we did treat the dog and
and it got better.
I mean, whether it's the whetherit's the chondrotonase or not,
you know, who knows?
But we it it did get better andquite quickly.
And so we then wrote the AUP tobe to be able to enable us to
recruit uh just neck dogs withchronic discs.
(17:34):
Um but we're gonna again, likePaul says, we're gonna have uh
an MRI to locate which discwe're treating, because we're
doing this with ultrasoundguidance uh along with the
radiologists, uh, because I'mnot very good at using
ultrasound, and so they positionthe needle very close, and then
I put it into the into the discbecause uh I know what it feels
(17:57):
like to get it in the rightplace, and we're checking it
with radio grips and things.
So it's a slightly more involvedprocess, but we're we're moving
into doing next as well.
Yeah.
SPEAKER_01 (18:07):
Sounds like you might need to collaborate with
your equine partners to findthose longer, stiffer needles to
get in there.
SPEAKER_04 (18:13):
Yeah, I know.
I yeah, I uh I have had someexperience of using a very long
needle, uh very long spinalneedles, but yeah, it's not
something we'd see me use.
SPEAKER_03 (18:24):
I think the just to to uh come back again uh with
one of the other areas thatwe're interested in, certainly
I'm getting a lot of interest,and I'm sure you are as well,
Nick, is is um you know howeffective this might be on more
chronic extrusions, because youknow, as as we said, we've
limited it to dogs that havebeen down for um uh 48 hours or
(18:46):
or less up to now.
And we're now starting to toopen it up to to dogs that have
been down longer.
And uh, you know, I I think itwill be very interesting to to
see what's the sort of timelimit in a sense.
You know, how long uh can a dischave been extruded before
chondroitinase is not likely tobe effective?
Um, because I think I I have thefeeling that it will be
(19:09):
effective for uh extrusions thathave been there definitely at
least a few weeks.
Yeah, but we could do with someevidence for that.
SPEAKER_02 (19:18):
Makes sense.
Very cool.
I think it's episode two is areally good reminder for our
first-line clinicians, like ourER clinicians, our GPs that are
seeing these down dogs, right?
Like at first clinicalpresentation, that there are a
lot of options and to reallypresent to owners the entire
picture and not just we need tocut ASAP or consider euthanasia.
So I think this is a really goodreminder, that audience.
SPEAKER_04 (19:40):
Yeah.
I think one of the things thatwe need to clarify with this
treatment is just its place in,you know, in the treatment on
Ethereum, as they like to say.
So the uh, you know, you've gotconservative therapy, got
surgery, and you I thinkconjoitinase is now another
realistic option.
And so we need to know where toplace that, you know, which dogs
(20:04):
you give which to and at whichstage.
Um, and so I I've got a feelingof how we can develop this in
the future, but we need moredata to know whether whether
what I'm thinking is is is thebest way of using it.
One of the things, for instance,is is the deep pain-negative
dogs.
We we see a quite a lot throughthis clinic, and some of them,
(20:28):
when you see them on the scan,they have a massive compression,
like huge compression.
Some of them don't, but some ofthem do have a huge compression.
And so my feeling is that someof those may be better treated
with surgery, you know, quickly.
Um, whereas the other ones thathave got mostly a contusive
injury where we've got longerperiods to try and disintegrate
(20:53):
the the extruded material, um,then the chase may be more
appropriate for those.
And so I we it'll take a whileto collect the data to know
whether that's the way thatwe're going, but I it's my sort
of feeling at the moment.
SPEAKER_02 (21:06):
And do you see a role for AI in this area of
research, Nick?
SPEAKER_04 (21:11):
Um Yeah, I saw that you put that on the list of
questions.
Um I guess I I the the the roleof AI here, I think, is in image
analysis, so that uh you knowwhat everybody wants to know is
what and neurologists really doneed to know this, like which
which cases need to have surgeryand when.
(21:35):
And you imagine that you couldcollect a lot of data, a lot of
imaging data, and then ask andand then tell the AI, you know,
what which ones got better andall this.
And hopefully they might betterwork out which ones need to be
treated quicker and that.
But I I I don't know that muchabout using AI, but my guess is
(21:57):
that you'd need thousands ofimages before you could um you
know reconcile that.
But I yeah, definitely for thefuture, yeah.
SPEAKER_01 (22:07):
Yeah, it's hard to know what the future of AI is.
It's very difficult to keep up.
SPEAKER_04 (22:12):
Yeah, right.
Yeah.
Yeah.
Every week you read somethingthat that tells you it's got
more potential than you thoughtit had, yeah.
SPEAKER_01 (22:18):
Yeah.
Well, this next set of questionswe ask are really important for
the listeners.
Uh, we'll start with Nick again.
What is the one piece ofinformation the veterinary team
should know about chondroitasefor presumed disc-associated
paresis and paraplegia?
SPEAKER_04 (22:33):
Uh but it's a very realistic treatment for a large
majority of animals that presentwith acute paraplegia.
Or small braid dogs that presentwith acute paraplegia, yeah.
SPEAKER_01 (22:46):
Very good.
And then, Paul, on the otherside of the same equation,
what's the one thing the clientshould know about this topic?
SPEAKER_03 (22:53):
I mean, it's almost the same answer, really.
Uh I I think um, you know, it'sthe fact that there is an
alternative to surgery.
You know, we're I think we'retrying to get this message out
more and more that surgery isnot the only treatment option,
uh, that it's probably not anemergency in the vast majority
(23:14):
of cases, um, you know, and tryand take away that kind of fear
and uh and anxiety that it thatit drives in owners of dogs and
also their vets, let's behonest.
Um, you know, it it really does.
And so I think the more thingsthat we can do and and publish
(23:36):
that try to dispel that,certainly the the less dogs will
end up being euthanized becausetheir owners haven't got the
money.
Um that's the that's the firstthing.
SPEAKER_02 (23:45):
So now we get to ask you some fun questions.
So, Paul, what is the oldest ormost interesting item on your
desk or in your desk drawer?
SPEAKER_03 (23:56):
That's uh yeah.
So I was thinking about this.
SPEAKER_01 (24:00):
Why does Nick laughing?
SPEAKER_03 (24:02):
I don't actually know why he's laughing because
you know what's on my desk.
He's probably got a good he'smaybe imagining what might be on
my desk.
SPEAKER_04 (24:12):
Yeah, and partly what's in my desk.
SPEAKER_03 (24:14):
There's a couple of there's a couple of things that
I was gonna say.
First of all, the thing that Ithink is the that I have on my
desk in my office at work, whichum uh is an extremely nice thing
to have, is just a little whitemarble Daxund statue.
I don't own a Daxon's, but theyhave supported Daxon Breed and
(24:36):
Breed Societies and charitieshave supported the work that um
both Nick and I have been doingfor a number of years, and and
really, especially my work inCambridge, that's for sure.
Um but this was a gift from uhan Italian uh veterinarian who
came and visited our departmenta few years ago, probably right
(24:56):
more or less at the beginning ofmy time at Cambridge, actually.
And when she left, she gave methis little white marble Daxon,
and it's a beautiful thing.
Um, it's apparently carved froma stone that's only available in
the area of Italy that she comesfrom.
So I kind of treasured it andit's it's really, really nice.
So that's the one thing.
The other thing I have, whichNick will also uh will know
(25:17):
about, I have a box full ofvertebrae from various species
that belonged to um aneurologist called Professor
Tony Palmer, uh, who I think isabout 98 years old now.
Um he still lives in Cambridge.
Uh he worked uh well he was uhhe was around a lot when uh Nick
(25:38):
was at Cambridge, I know.
Um he's a pathologist, reallyneuropathologist, and he's kind
of collected all these umartifacts and items.
And one of the things that I'vebeen able to do while I've been
at Cambridge is to pull all thisstuff together.
So I have this box of bonessitting on my desk, which um is
a is a reminder of kind of wherewe've come from, really.
SPEAKER_04 (25:59):
I I could add a funny story to that as well,
actually, that uh Tony Palmerleft those bones.
Uh he he found these horse bonesfrom a horse wobbler and left
them on my desk at Cambridge.
And at the time I had a dog thatcame in to work with me.
And uh I came back after goingto do a consultation or
something and found him eatingoak.
SPEAKER_01 (26:20):
I I could have predicted that as soon as you
said horse and dog.
I was like, oh no, this isn'tgoing to end well for the
wobbler neck.
SPEAKER_04 (26:28):
Yeah, so some of them have probably got bite
marks in.
SPEAKER_03 (26:30):
That's why a couple of them are a bit chewed, yeah.
SPEAKER_04 (26:32):
Yeah.
SPEAKER_02 (26:34):
I love that though.
Spoken like a true neurologist.
And then Nick, what's yourfavorite animal fact?
SPEAKER_04 (26:40):
Oh uh that all mammals have seven net vertebrae
apart from sloths.
SPEAKER_02 (26:49):
Very nice.
Another great neurofact.
Well, thank you both for beinghere today and for sharing your
article too with us.
We really appreciate it.
Like we said, I think it's gonnabe really cool info for our
listeners and readers.
SPEAKER_03 (27:01):
Thank you very much.
SPEAKER_04 (27:02):
Yeah, thank you for your interviewing us.
It's uh it's something we did weuh, you know, we're keen to sort
of develop this technique.
And so it's we're passionateabout it, Nick.
SPEAKER_03 (27:12):
We are.
SPEAKER_02 (27:13):
We can certainly tell.
And to our listeners, you canread Paul and Nick's article in
Japan.
I'm Sarah with Lisa Portier.
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.
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