Veterinary Vertex
Veterinary Vertex is a weekly podcast that takes you behind the scenes of the clinical and research discoveries published in the Journal of the American Veterinary Medical Association (JAVMA) and the American Journal of Veterinary Research (AJVR). Tune in to learn about cutting-edge veterinary research and gain in-depth insights you won’t find anywhere else. Come away with knowledge you can put to use in your own practice – along with a healthy dose of inspiration to remind you what you love about veterinary medicine.
Veterinary Vertex
Innovations in Equine Sepsis Treatment
Discover the future of equine health as we delve into sepsis treatment with Drs. Kallie Hobbs and Katie Sheats. Prepare to be captivated by their groundbreaking work, showcasing the potential of extracorporeal cytokine adsorption as a potential adjunct treatment for equine sepsis. Their commitment to restoring immune balance in horses has led to a successful ex vivo study, potentially paving the way for live applications and improving the treatment of the septic equine patient.
Open access article: https://doi.org/10.2460/ajvr.24.01.0022
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Speaker 2:You're listening to Veterinary Vertex, a podcast of the AVMA Journals. In this episode, we chat about hemabsorption extracorporeal therapy in horses with our guests Callie Hobbs and Katie Sheets.
Speaker 3:Welcome to Veterinary Vertex. I'm Editor-in-Chief Lisa Fortier, and I'm joined by Associate Editor Sarah Wright. Today we have Callie and Katie joining us. Callie and Katie, thank you so much for taking time out of your busy schedules to be with us here today.
Speaker 4:Thanks for the invitation. Thank you.
Speaker 2:All right, let's trot on over, callie. Your AJVR article discusses how heme adsorption extracorporeal therapy removes cytokines ex vivo and horses. Please share with our listeners the background on this study.
Speaker 5:Yeah, so we were actually really excited to be reached out to by the company Vet Rescue that actually produces these cartridges. So there's been evidence in humans that have cytokine storms, mostly in relation to COVID, that a product called Cytosorb is able to remove cytokines in those patients and then to restore immune balance. So they came to us asking if we thought this might be something useful in horses and foals, asking if we thought this might be something useful in horses and foals. So that was a little bit of the background of how we decided to kind of start at the beginning and first off make sure that it actually does filter cytokines and that it's safe, and want to move forward from there.
Speaker 2:Yeah, thank you. We really appreciate you sharing your research with our readers and now with our listeners too. And Katie, what were some of the pivotal findings from the study?
Speaker 4:The study that Callie just explained the background why we were interested found that in an ex vivo system so important to point out that this particular project was focused on sort of proof of concept and validating in an ex vivo model before we investigate this system in vivo in live horses. But this ex vivo system was able to demonstrate that filtration of whole blood from horses stimulated with LPS to have increased cytokines does remove significantly several different cytokines. So, as pointed out in the paper, il-10, il-5, il-8, tumor necrosis factor alpha and IL-1 beta were all significantly decreased by filtration. The other interesting finding was that it also significantly removed several drugs that we investigated, so specifically potassium, penicillin, genomycin and flunixin.
Speaker 3:Well, that's pretty fascinating. Implications are far reaching, not just to get over the sepsis but to avoid the dreaded laminitis and the associated complications. Yeah, really, and the associated complications yeah, really, really fascinating. And also, I think, a really great highlight for the collaboration with industry. A lot of times people are like, oh, industry sponsored that or industry is coming to do something, but that collaboration with researchers is really important. So, like Sarah said, thank you again for sharing that with AJVR and Katie. What sparked your research interest in sepsis?
Speaker 4:For me it was residency, so I did an internal medicine residency at NC State and the septic patients were my favorite. That's a strange thing to say, I know, but I just really appreciated the fact that sepsis is the immune system dysregulated. It's taking something it was designed to do respond to infection in a local area that is meant to defend the host in a local area that is meant to defend the host and then that process happening systemically is of detriment to the host, and so I always just was fascinated and wanted to understand that process better. I'm also a neutrophil biologist. My PhD really focused on neutrophils and neutrophils play a really big role in sepsis, so that added to my fascination.
Speaker 3:Wow, spoken like a true internist. As an equine orthopedic surgeon for 33 years, you could have that interest. Callie, this is a little bit self-serving for us, but why did you choose to submit this important manuscript to AJVR?
Speaker 5:So I guess for me, whenever I'm looking for him, what's the up and coming research? That's actually the resource that I go to first, and so, since this was so novel, I thought that AJVR would be the best place to go in order to get this out there, so that people would start at least thinking about hemoperfusion in horses, since I know the concept is a bit kind of overwhelming, I think, at first.
Speaker 3:It is a little bit overwhelming. Where do you see this going next? Where do you see this? Do you have plans to implement this in a real horse, a live horse?
Speaker 5:So we do. So that's actually. We are just finishing up our feasibility study. So we've completed it in three horses that are healthy, but then we also just finished a crossover with horses with LPS induced sepsis, that we filtered all six of those horses. And then, lastly, I had an opportunity in the clinic to filter a septic horse as well, which was a great experience, and actually was able to decrease some of his cytokines as well. Oh, that's so cool?
Speaker 3:Did you notice anything physically different about? Especially that? Well, the LPS, or the clinic horse.
Speaker 5:I did. So it's interesting in them that both clinically and in the LPS horses, that once they start going on the filter you'll see their fevers start decreasing. So, like the clinical horse, for instance, had a 105 fever but he also had acute kidney injury, so we couldn't give him a lot of kind of the common things we would give him, and during his filtration system his fever actually went down to 101, which was really impressive. And some of our LPS horses actually have a lot less severe colic signs than the sham horses.
Speaker 3:Oh, fascinating. I won't ask for any more spoiler alerts. Katie Kelly talked earlier about some of the pivotal findings of the manuscript or I guess you did, but always when we do research we're like wow, I didn't expect that. What were some of the most surprising findings from this study, katie?
Speaker 4:I think for me it was the awareness that I developed through this research of the potential applications of filtration hemabsorption beyond sepsis and specifically thinking about drug toxicities or different types of intoxications. And so we included the investigation of medications commonly used to treat sepsis because long-term we're interested in informing practical clinical application and use of this therapy if it comes out that the evidence supports its use. But really what that also demonstrates is other potential clinical applications and utility of filtration in horses. So it wouldn't. It's not necessarily a surprise, because the manufacturer does disclose what types of molecules and drugs bind the column, but this project helped me to really sort of see that as a potential additional application.
Speaker 3:Do you think there's any nefarious application for this technology? Like like horses, so they don't test positive.
Speaker 4:That's a really interesting question. I think the one thing that, just off the top of my head, will limit that nefarious use is the investment that is required to have the equipment, so the pumps and the special lines and catheters that allow for this type of filtration, as well as the personnel required to monitor it. So hopefully that will be a barrier to those types of uses. But I think you raise an important point to be cognizant of as this research moves forward.
Speaker 3:And I guess also I mean the really drugs that are banned banned, it sounds like this filtration system doesn't completely remove everything. It significantly reduces some things, so they might still be testable.
Speaker 4:Yeah, and so you bring up another part of how the system actually works, which is on a gradient, and so if you have elevated levels of a molecule, a drug, when you start filtration, it's only the things that are really in high concentration that will be removed most effectively and quickly. Once you reach lower concentrations, this type of column does not completely eliminate substances from the bloodstream, and so it's unlikely you could get to a zero concentration level. So that's right.
Speaker 3:Perfect Callie. What surprised you about the findings of your manuscript?
Speaker 5:I actually was as well kind of surprised about the drug profile. So I thought that it would remove cytokines, just because equine and human cytokines are so similar. But I was a little bit surprised that it removed aminoglycosides in the way that it did. Is that something on the human side that I think they're only getting like 50 percent removal, and we had much higher removal than that. So that was a bit kind of surprising to me. But, like you guys just talked about, it also opens up the door though for, like the horse that accidentally gets two or three doses of genomycin versus being in the clinic on fluids for six days that you may be able to do something kind of immediately for them.
Speaker 2:That's super interesting. I can see a lot of different applications for this in the future, potentially with different species. So thank you for sharing. And then, for those of you just joining us, we're discussing heme absorption extracorporeal therapy in horses with our guests Callie Hobbs and Katie Sheets. So, Katie, I know we discussed how you are a NutraFill expert, which I think is super cool. I've never met anyone who can say that before, but how did your advanced training prepare you to write this manuscripts?
Speaker 4:So I think the best part in terms of being prepared to write manuscripts is knowing the audience and the interests of the audience really well, and that's what we call it to. What we both kept center of focus as we were preparing to share this work with our veterinary community is really not just thinking about it from a laboratory, because it was an ex vivo system, but it wasn't just a laboratory experiment. It was for the purpose of hopefully one day impacting clinical practice and so I'd say, while there's multiple things that go into preparing you to write a manuscript, for me that was one of the more important parts of writing this particular manuscript was really thinking about the community and the veterinarians and the horses that we hope one day will benefit from this therapy.
Speaker 2:That's an excellent point. I think it's often overlooked too in scientific communication, because when you think about writing the manuscript, when you submit to a journal, you do have to think about who that audience is and who their readership is to ensure it has the biggest impact. I recently also turned a manuscript into a video where the audience was actually the general public, and that was super hard to like switch my mindset from people who might be clinical pathologists reading my research to the general public and making it applicable and important for them. So definitely a skill that I think is often underutilized. In. Now this next set of questions is going to be very important for our listeners. Callie, what is one piece of information the veterinarian should know before discussing heme absorption extracorporeal therapy in horses with a client?
Speaker 5:So I think that they have to be willing to explain to the client that it's not necessarily a one-time thing and it fixes the problem overall that these horses may require multiple treatments over several days and that also they have to sort of be all in that once they get started. It's not something that you can do one treatment and then stop, but it's something that if the horse requires two or three treatments that they need to be willing to keep going.
Speaker 2:And then Katie on the other side of the relationship. What's one thing clients should consider around hemoabsorption? Extracorporeal therapy in horses.
Speaker 4:It's a really interesting question because we're at an interesting point in this research on this particular therapeutic modality in horses, and so my first thought when asked that question is sort of a stay tuned sort of answer, which is that hopefully this is something promising. There have been very few big leaps in sepsis therapy and equine medicine, and it's been a long time since we've had something potentially new to offer, and so it's exciting to think about. Maybe this will be a new option, but it's also important to do the research and to understand the. They should also be willing to engage in the types of conversations with their treating veterinarians about the issues that Callie just brought up. Right, this is an experimental therapy at this stage and there has to be a lot of good communication about what's known and not known at this stage.
Speaker 3:Yeah, very exciting. It sounds like we're going to learn a lot more in the near future from you guys, and hopefully we'll learn it in JAVMA and AJVR as we wind down a little bit. Again, thank you. I've learned even more today talking with you guys than I did reading the manuscript, so thank you again for sharing it with AJVR and for joining us here today. Thank you so much for having us. This has been great. Yeah, thank you again. As we come to the close, we like to ask a very fun personal question. So, katie, for you, what is the oldest or the most interesting item on your desk or in your desk drawer?
Speaker 4:This is not particularly interesting, except for me. So I'm a mom and my oldest son turns 15 on Friday this week, and so I have his handprints on my desk. So I'm just feeling a little sentimental and nostalgic and I thought I'd share that.
Speaker 3:That's wonderful. You can't see because of a virtual background, but behind me I have all three of my kids' handprints framed from kindergarten. It's my favorite thing. So when I'm on all these Zoom calls, I can see their reflection in the back. So yeah, it's the best. Yeah, Callie, for you. When you do a puzzle, do you start with the inside pieces or are you an exterior border person?
Speaker 5:I am one of the crazy people that starts with the middle, because I think that's the hardest part, and by the end I think I'm bored enough with doing the puzzle that I need it to be just fairly easy for the border that's's very interesting.
Speaker 2:We had someone answer that question yesterday and their answer was the exterior. So everyone's different.
Speaker 1:And that person was a small animal surgeon, so I don't know if that matters or not.
Speaker 2:Very cool and just thank you again, callie and Katie. Like Lisa said, we just really appreciate you sharing your research with AJVR and also sharing it with this podcast too, so we can just increase its reach and impact.
Speaker 4:Thank you so much. This has been a great chance to chat about the research and just really want to commend Callie. This work has been part of her PhD and she's done a fabulous job.
Speaker 2:Not without a great mentor job, Not without a great mentor, and to our listeners. You can read Callie and Katie's article on AJVR online using your favorite search engine. I'm Sarah Wright with Lisa Fortier. We want to thank each of you for joining us on this episode of the Veterinary Vertex podcast. We love sharing cutting edge veterinary research with you and we want to hear from you. Be sure to leave us a rating and review on Apple Podcasts or whatever platform you listen to.
