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
Inside the Fight Against Foal Pneumonia
The battle against Rhodococcus equi, a devastating bacterial pneumonia in foals, continues to challenge equine veterinarians more than a century after its discovery. This fascinating conversation with Drs. Noah Cohen and Devynn Volding illuminates a previously unexplored aspect of a common preventive measure: the safety of hyperimmune plasma transfusions from an electrolyte perspective.
When veterinarians transfuse 1-2 liters of hyperimmune plasma into newborn foals, they're expanding the animal's blood volume by a staggering 20-40%. This significant intervention naturally raises questions about potential electrolyte imbalances, especially since foals are particularly susceptible to such disturbances. Through meticulous research involving sample collection from foals before and after transfusion, Drs. Cohen and Volding discovered reassuring news - the procedure causes minimal changes in electrolyte and protein concentrations, with even sodium (the electrolyte of greatest concern) showing only statistically but not clinically significant increases.
The researchers also tackle broader questions about Rhodococcus equi management, including the challenges of vaccine development, diagnostic limitations, and emerging antimicrobial resistance. Dr. Cohen provides valuable perspective on the realistic expectations for vaccine efficacy, noting that even partial protection (like that offered by human influenza vaccines) would represent significant progress. Their work exemplifies the critical distinction between statistical significance and clinical importance - a reminder that p-values don't always translate to meaningful differences in patient care.
Have you encountered Rhodococcus equi in your practice? This episode provides practical reassurance that hyperimmune plasma transfusions appear safe from an electrolyte perspective while offering insights into the future directions of research against this persistent equine pathogen. Subscribe to Veterinary Vertex for more clinically relevant conversations at the intersection of research and practice.
Open access JAVMA article: https://doi.org/10.2460/javma.25.02.0115
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Speaker 2:You're listening to Veterinary Vertex, a podcast of the AVMA Journals. This episode we chat about how the transfusion of rotococcal hyperimmune plasma to newborn foals does not markedly alter serum electrolyte or protein concentrations, with our guests Noah Cohen and Devin Volding.
Speaker 3:Welcome listeners. I'm Editor-in-Chief Lisa Fortier, and I'm joined by Associate Editor Sarah Wright. Today we have Noah and Devin joining us. Thank you guys so much for coming and talking about rotococcus. I'm not an internist as Noah is, but rotococcus has been a bane of my existence as an equine surgeon too. So really great work you guys are doing and excited to bring this to our listeners today.
Speaker 4:Thank you, we're so excited to be here.
Speaker 5:Yeah, thank you so much for letting us have a chance to talk about what we've done.
Speaker 2:All right, let's trot on over. So, noah, your Jabma article discusses how the transfusion of rhodococcus equi hyperimmune plasma to foals does not appear to have marked effects on serum concentrations of electrolytes or proteins, despite the relatively high sodium concentrations in rhodococcus equi hyperimmune plasma. Please share with our listeners the background on this article.
Speaker 5:Great, yeah, thank you for that question. So the background I think probably starts with rhodococcus equi, which is a bacterium that causes pneumonia and foals following inhalation of the organism from their environment. That pneumonia can be severe. It has a worldwide distribution, as Dr Fourier alluded to. It has extra-permanent disorders including bone and abdominal abscesses and things. So pretty important clinical problem and unfortunately it's not a vaccineytocl hyperimmune plasma to prevent the disease in foals.
Speaker 5:The typical volume transfused to foals is between 1 and 2 liters For an average 50-kilogram foal.
Speaker 5:We calculate that that expands their blood volume by somewhere around 20 to 40 percent, expands their blood volume by somewhere around 20 to 40% and we really don't know what the impact of that volume expansion is on electrolyte concentrations, protein concentrations in foals.
Speaker 5:There's a research abstract that never matured to peer-reviewed publication that describes marked variation in serum electrolyte or, excuse me, in electrolyte concentrations and albumin concentrations in commercial plasma and that raised concern amongst some experts on what the impact might be for foals when they're getting those large volumes transfused. We know that foals are really susceptible to volume expansion and to electrolyte derangements and so legitimately there is some concern. Those concerns were contradictory to what our experience has been clinically here on a limited basis and anecdotally from veterinarians in practice, but we really didn't know the answer to what the impact was on serum electrolytes and protein concentrations following transfusion of one or two liters of hyperimmune plasma. Thanks to Dr Patti Auschwitz Patti Flores Auschwitz, excuse me from Rudin-Riddle Equine Hospital in Saratoga Springs, we had some serum samples available to us from Foles before and after transfusion and then we were also, through generous support from a plasma manufacturer, able to get some plasma samples to test electrolyte concentrations and protein concentrations and it allowed us to address what we think is an important clinical question which had not been considered.
Speaker 3:No, you might get to answer this later, but you already said there's no vaccine available. How close are we to a vaccine? I know you've spent a lot of waking hours in research studies. How close are we?
Speaker 5:Yes, I wish I could say well, I can only speak for our lab, I can't speak for others. So there are people working all over the world. This organism was discovered as a cause of death in a foal in Sweden over a hundred years ago now, 102 years ago since it was first reported, and we still don't have a vaccine. I think a vaccine's going to be difficult to produce for many reasons, but we are working on some strategies. We're hopeful, but I'm always, you know, kind of optimistic, hopeful. I'm hopeful that we're getting close, but so I can retire for one thing, and so I'm hopeful that in the next few years we might have something to try.
Speaker 2:Okay.
Speaker 5:I think one of the big challenges for vaccine development is not just the problems with developing a vaccine for an intracellular pathogen like rhodococci sequi, which is similar to the mycobacterium tuberculosis. People have been trying for a long time to get a vaccine for TB as well. That's proved elusive. But beyond that, I think also our expectations as veterinarians sometimes is complete. You know that a vaccine be completely effective. We use experimental models, we expect it, and there's just that's not how vaccines work they are. Some like measles are highly effective, but some like influenza, tb, they're much less effective. And so I think some of the limitations also been expectation that veterinarians have for the efficacy of the vaccine.
Speaker 3:Yeah, I'm guilty of that. You know, when you're looking at spring shots and for the horses, dentals and all the other things you're like, well, if that's only 50% right, like you 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 and it was not 100% you know it's such a devastating disease I think I'd be all over it.
Speaker 5:Yeah, I think that partial protection so in my age, influenza vaccine, I think is about 11 or 12% effective, but it's still important for me to get it and for others to get it. That may protect me from you know, from people my age, from getting it. So, yeah, I think that even if we can achieve partial protection, which is kind of what plasma does, it's only partially effective, which is why 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 been examined it's not 100%, it's not completely effective, but it is when it's been examined has been for the most part not always, but for the most part been able to reduce the incidence of the disease. Sarah, I'm sorry for those digressions.
Speaker 2:No, we welcome them. This is a conversation. It's important for our listeners too, so I appreciate you sharing additional input and Devin what are some of the important take-home messages from this JAPMA article.
Speaker 4:Yeah. So I think how Noah already started to say that since foals are more susceptible to volume expansion and electrolyte derangement, it kind of brings up this question of is this something that we should be monitoring throughout plasma transfusions, which is a very common procedure, especially for foals out in the field, because are these potentially causing this? And from our work and what we did in this population of healthy foals, we're not seeing this marked variation in electrolyte derangements and only small changes occurred. In addition to that, the rotococcal plasma that we did test had very low levels of variation within it, so hopefully this paper will help reassure equine veterinarians that using these products, at least in healthy foals, should cause very little change.
Speaker 3:Very cool, yeah. As a surgeon, I don't even think about the electrolyte part, right, it has nothing to do with bones and joints, unless they're going to be really sick under anesthesia. Noah, as an internist, what sparked your research interest in rhodococcus? Did you have a foal that you couldn't fix, or was it one of your own animals? What sparked this?
Speaker 5:this. That's a great question. I think back to my days as a student and Dr Corinne Sweeney was a teacher of mine.
Speaker 5:She was a great teacher. She taught us about our equine rhodococcus equifol pneumonia and she was pretty inspirational. But I saw lots of cases when I was in practice. I saw cases here and then really I think what sparked my interest in pursuing research was Dr Ron Martins who was here at Texas A&M studying Roda Kakasikwai, and his passion, his enthusiasm, his energy just sort of, were pretty hard to resist and drew me into collaborating with him. So that's probably where the interest comes from, longstanding but yeah, a longstanding interest.
Speaker 3:You've contributed so much, devin. You said to Sarah earlier what are the important take-home messages that maybe you don't need to be monitoring for these electrolytes? Don't be so afraid of it. But always when we do these studies, there's something that was like hmm, I didn't expect that. What was something that was surprising from this article?
Speaker 4:Yeah, I don't think a ton was that surprising to either of us as we kind of suspected that there would be very little change. But I will say, out of all the electrolytes and protein parameters that we tested, I would have expected sodium to have the most significant increase, since sodium citrate is used as its anticoagulant in these plasma products and yes, there was statistically a significant increase in that. However, clinically the magnitude of this effect was pretty small. I believe our median for sodium increased only by two milliequivalents per liter, which is pretty small when you think about it in clinical practice.
Speaker 3:Well, it's very small, given what Noah in the introductory statement the volume expansion.
Speaker 5:Yeah, exactly yeah, although the volume expansion probably has a little bit of a dilutional effect on that. Sodium is my guess. And then I think that it is a nice example of the distinction between statistical and clinical significance. Right, there's statistical significance and clinical importance, that, yes, the increase was statistically significant but looks to be clinically inconsequential. These are healthy foals, of course, but in healthy foals it looks like this is safe and not something people need to be concerned about.
Speaker 2:Amen the clinical effect is more important than the p-value. Yeah, we need a poster that says that in our office. So Nor. What are the next steps for research in Rotor Kaka Sequai?
Speaker 5:Ooh, that's tough. I'm going to answer from the perspective of a clinician clinician-scientist. I think if you asked a molecular microbiologist they'd probably give you a different set of answers. But there are a lot of things that need to be done. So, from a diagnostic perspective, right now at most breeding farms most veterinarians make a presumptive diagnosis of rhodococcus pneumonia because we don't have a great non-invasive or simple diagnostic test. So I think there's room for improvement on the diagnostic end and we're certainly working on that.
Speaker 5:Therapeutically, the macrolides that we use as the treatments of choice for rhodococcus have some limitations. There are problems with resistance Macrolide rifampin resistance has emerged and seems to be disseminating as well as the fact that there are side effects of those macrolides that can be devastating to the foals. So alternative antimicrobials are much needed. Transfusing you know this whole study started with the notion that transfusing a large volume of plasmas is challenging and we're working on some concepts for monoclonal antibodies as alternatives to plasma transfusion. But the golden ring, if you will, of Rhodococcus research is coming back to the question do we have a vaccine and working towards a vaccine? I think that is probably the main goal that we have to strive for. But a vaccine won't be completely effective. So all of those other things I mentioned, you know, diagnostics, treatment and even potentially immunoprophylaxis or immunotherapy, will be important to pursue.
Speaker 2:And Devin. Do you see a role for AI in this area of research?
Speaker 4:So I'll start by saying I am very far behind in the role of AI research. So I'll start by saying I am very far behind in the role of AI. I just started using it for some client comms and it has helped speed some things up for logging that for me, but in general I'm pretty far behind in its use in everything. Potentially, if it has some help with data organization in the future, maybe, but as for I know sometimes people use it in writing the paper and everything and I just don't quite see use for that yet. But again, I am probably not the best person to ask about that.
Speaker 5:I'm also no expert, but I'll throw out a couple of things to consider that people are using AI to design monoclonal antibodies, and so I think antibody design is one. So I think antibody design is one and I suspect or I don't suspect, I know that people are using AI for vaccine, antigen targeting strategies as well, but, like Devin, I bet everything we do from diagnosis to disease management to health management to records management. Like Devin said, there's lots of opportunities. It's an enormously powerful tool.
Speaker 3:It's fascinating. I was just at an AI symposium at Cornell and one of the guest speakers was talking about its use for remote in humans access to care. So they were having technicians and other people go out in remote in remote areas. If you don't have access immediate access to care or underserved communities, pregnant women at risk, they don't know when their due date is. They don't know the fetal position if they're going to birth at home, so untrained ultrasoundographers basically hold the ultrasound probe and the machine learning algorithm tells you how to scan the abdomen and then it comes back and says the baby's in this fetal position, your due date. Is this Really amazing? Yeah, like real tangible things that can happen. It's crazy, Like you said, the things that we don't even think about, how it can be used.
Speaker 5:Yeah, exactly.
Speaker 2:That's so cool, and for those of you just joining us, we're discussing the effects of transfusion of rhodococcus equi hyperimmune plasma on serum electrolyte and protein concentrations in neonatal foals with our guests Noah and Devin.
Speaker 3:Noah, you've written hundreds of articles and chapters and have trained just as many people likely articles and chapters and have trained just as many people likely what, in your training, helps you? And then how do you pass that on to other people? To conceptualize a project, finish the project and then get this article written across the finish line.
Speaker 5:Oh, wow, Okay, that's yeah. So I'll start by past training. You know I was trained as an internist, which I think helps me to know the disease, understand the disease, ask the clinically relevant questions. My research training was in epidemiology, which helped me to think about population-based studies, to work with veterinarians in the field and collaboratively, like Patty Flores-Aschweid, to collect these data.
Speaker 5:And the other part of your question was about well, how do you encourage people to do the work and finish the work and I wish I had more opportunity. I wish I had opportunity to do more of that. I wish I had more opportunity. I wish I had opportunity to do more of that. I miss having more graduate students and more residents working with us. I'd love to have many more, and I think that's just a skill that I think people have to learn for themselves to get things done, to complete things.
Speaker 5:I try to remodel that. I'm not answering this query well, so good thing we can edit this. I think it's important to just role model that, to try and encourage people to finish and to see the importance of not just presenting an abstract but to actually bring it to fruition so people can read it and assess for themselves. I do try very hard to instill in trainees the importance of reading the literature and not accepting it at face value, but to be able to have skills with critical appraisal. I think if I could do one thing over in my career, I probably would have spent more time training people in critical appraisal than I've been able to.
Speaker 2:Now, Noah and Devin. This next set of questions is going to be really important for our listeners, and the first one is going to revolve around the veterinarian's perspective. So, Devin, what is one piece of information the veterinarian should know about rhodococcus equi? Hyperimmune plasma transfusion.
Speaker 4:So previous studies have already shown the beneficiary of the response of giving two liters instead of one liter of plasma, and I think it's important to veterinarians to know that, despite claims of variability in these plasma sets, we tested 90 different samples of rotococcal plasma, 30 from each year, and within these we had very little variation between them. So I think that's super important for veterinarians to know going forward.
Speaker 2:And on the other side of the relationship, Noah, what's one thing clients should know about this topic.
Speaker 5:Yeah, I think for clients and farm managers, it's really important for them to know that transfusing foals with a volume of two liters doesn't appear to be unsafe. Safety is a complicated issue. There's nothing that we do in life that doesn't carry some risk. Whether it's taking an Advil, driving in our car to work, 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 safe and they do appear to protect foals against rotococcal pneumonia. So I think it's really important that we're able to reassure clients, who may have heard from their veterinarians that the practice may not be safe, that that's not the case.
Speaker 3:This could go on for days, and I'm looking forward to coming to visit Texas A&M and we can talk more about epidemiology and critical appraisal literature and all these fun things that we pontificate 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 you could have a superpower, what would it be and why?
Speaker 4:Yeah. So if I had a superpower, I think I would absolutely choose teleportation, both for work life and personal life. Because for work life, that would be pretty nice to be able to just show up when an ER shows up, and especially if you don't get that 30 minute out call that you want and a 2am call shows up, it'd be nice to just pop on over and not have that drive time. And then for personal life too, because I think as veterinarians we all do have to give up being at lots of big events like weddings and various holidays, because we are supposed to be here for the patients and everything, and it's something that we accept. But it would be pretty nice to be able to just teleport back to some of these events and be on call at the same time and still be here for our patients, of course.
Speaker 3:It's a good point. My oldest daughter is in medical school and I was just saying to her about so she's starting her fourth year of medical school and just saying to her, like you know, now you really don't have your life anymore and you're going to have to start missing unfortunately missing, as you were saying, weddings and holidays, and yeah, medical professionals give up a lot, but it's worth it. All right, noah, and we need to know how old you were and what was the first concert that you attended. I can't wait to hear this.
Speaker 5:My first concert was a band called Led Zeppelin. I don't know if you've heard of them A little-known rock band. It's pretty amazing. I got to see them in 1970 at the Spectrum with my friend from my friend's school named Dan Hicks and he took me to that concert. It was amazing.
Speaker 3:That's amazing. I don't know anybody who's seen Led Zeppelin when they were. You know, not this age of Led Zeppelin. That's really cool.
Speaker 5:It was pretty epic. It was yeah.
Speaker 3:What was the cool word, then? What was the cool?
Speaker 5: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 on it now. It was the thing that's in that Simon and Garfunkel song that people laugh about. Oh, Groovy, groovy, groovy, groovy was still big.
Speaker 3:I still say groovy all the time, I even put it in emails. And now Sarah sometimes is like groovy.
Speaker 2:I can attest that's true.
Speaker 5:I can attest that's true.
Speaker 2:ACDC was just in Chicago this weekend. It's like oh, I did not go, but good things Well. Thank you so much, noah and Devin, for being here today and for sharing your manuscript, too, with Javma.
Speaker 4:Thank you so much for having us.
Speaker 5:Thank you.
Speaker 2:And to our listeners. You can read Noah and Devin's article in Javma. I'm Sarah Wright with Lisa Fortier. Be on the lookout for next week's episode and don't forget to leave us a rating and review on Apple Podcasts or whatever platform you listen to.
