SCCMPod-564 CCE: Endotoxin Activity and Precision Medicine in Septic Shock

Dr. Bulloch: Hello and welcome to the Society of Critical Care Medicine podcast. I'm your host, Marilyn Bulloch. Today, I'm speaking with Dr. John A. Kellum, MD, about the article Organ Failure, Endotoxin Activity, and Mortality in Septic Shock, published in the September 2025 issue of Critical Care Explorations. To access the full article, visit ccejournal.org. Dr. Kellum is a professor of and director for the Center for Critical Care Nephrology at the University of Pittsburgh in Pittsburgh, Pennsylvania. He's also vice chair for the Department of Critical Care Medicine. Welcome, Dr. Kellum. Before we start, do you have any disclosures to report?

Dr. Kellum: I do. And thank you, Marilyn. Spectral Medical, which is a small biotech company based in Toronto, was the sponsor of this study.

And as disclosed in the paper, I do serve as the chief medical officer for the company and in addition to my role at the university.

Dr. Bulloch: All right. Well, thank you for that disclosure, Dr. Kellum. Well, let's get started.

There was a lot of interesting information in your article, and I'm excited to hear your point of view from some of the thoughts that I had and I know many of our listeners will be as well. Let's start from the beginning for our listeners. Your study focuses on high endotoxin activity as a possible endotype for septic shock.

There's been a lot of discussion recently about a more targeted approach to sepsis and sepsis types. But for those who may be less familiar with sepsis endotypes, can you provide them just a brief background on how interest and awareness of this approach to sepsis came to be? I'm particularly interested in how you became interested in endotoxin activity.

Dr. Kellum: Sure. So I think there are sort of our two aspects of this question that really are, I think, vital to understanding why we think that a precision medicine approach, where we break this very diverse syndrome into parts and then try to target individual sort of subphenotypes, or you use the word endotype, which I think is appropriate here. And it really comes down to two things, really.

One is that, as we well know, there's enormous heterogeneity in the clinical outcomes and severity of even septic shock. I mean, we tend to think of septic shock, unlike all of sepsis, as a more serious syndrome, which of course it is and associated with much higher mortality. But even with patients with septic shock, there are patients that have a really uncomplicated course.

They need some supportive care in the ICU, in addition to their antibiotics and source control. But ultimately, they do pretty well without a lot of sequelae, and they have a fairly low risk of death. And then other patients seem to develop just multi-organ system failure and have a sort of a rapid spiral into a really a fatal situation.

And of course, we know that from the epidemiology of sepsis, that not only is sepsis more common in the extremes of age and patients with underlying severity of their immune response and being immunocompromised, etc., and that also impacts just how severe the septic shock is, if they indeed develop it. But there seems to be more going on than just that. And years ago, there was a lot of interest, I would say.

You know, when I trained in critical care a few years ago, back in the last century, indeed the last millennium, if you trained in the 90s, you were very much steeped in this idea of endotoxin being a critical driver of sepsis. And we've kind of forgotten a lot about endotoxin since then. That's not completely true, but we certainly don't focus on it the way we did sort of back in the 90s.

And there were some failed trials and using antibody therapies and other targeted therapies with drugs. And we just sort of moved on. And so I think there's a re-interest in looking at potential subphenotypes that are driven by mechanism, and that makes an endotype.

The term endotype refers to a subphenotype that is sort of mechanistically tied. And since endotoxin is a targetable mechanism of injury, of septic shock, then we would consider this an important potential source of enrichment that we would choose to identify patients with high levels of endotoxin and then target just those patients.

Dr. Bulloch: You bring up an interesting point because I trained in the early 2000s and you're right, even by then, I feel like a lot of the focus on endotoxin had maybe subsided. It certainly wasn't a big focus of my training. And I want to move something you mentioned just a minute ago about the phenotypes.

And there's four phenotypes, as you discussed in your paper, that differ in terms of prognosis, impact on organ function, and their response to treatment. You specifically mentioned that Delta has the highest mortality. I'm curious as to what extent we should worry or even be interested in the other three phenotypes.

Now, I'm not the expert here, but it seems to me there are interesting targets you mentioned based on the type of phenotype. Is that something you would agree with?

Dr. Kellum: Yeah, no, I think that's fair. And to give your listeners a little bit more background here, you know, you mentioned four phenotypes and that framework sort of comes from a paper that was published back in 2019 from our group led by Chris Seymour and Derek Angus and others. And the focus of that paper was to use some machine learning, kind of an artificial intelligence approach, if you will, at least a basic artificial intelligence approach where the analysis was really done to try to understand whether or not there were patterns of clinical features that existed on day one of hospital presentation with sepsis and septic shock, and to see whether or not you could differentiate patients into groups that had a very different mortality risk, but also a difference in their response to certain therapies. Early goal-directed therapy or drotrecogin alfa were two of the examples that were used in the paper.

Dr. Bulloch: Drotrecogin alfa brings back memories.

Dr. Kellum: Yeah, the old Eli Lilly drug that was the last therapy we had for for sepsis some years ago. And so what that study did was it found that the best solution to that problem from an artificial intelligence perspective was that a four phenotype or four subphenotype solution to the problem seemed to have the best fit for the data. And those were the four phenotypes that were given the alpha, beta, gamma, and delta phenotype.

And two of those phenotypes, the alpha and the beta phenotype, have really quite low hospital mortality, 2% for alpha and 5% for the beta phenotype. And so you could certainly argue that at least from a mortality perspective, that those patients have a pretty good prognosis and sort of focusing on, you know, the basic source control and antibiotics and not hurting them, right, with critical care, because we can hurt patients, you know, with our therapies as well is probably what we want to focus on for those patients. And then the other two phenotypes, the gamma and the delta phenotype, were associated with a much higher mortality, 13% for gamma, 32% for the delta phenotype.

And they had differences in terms of the proportion of patients that experienced different types of organ dysfunction. And most of the ARDS, for example, most of the lung injury was in the gamma phenotype, whereas the delta phenotype was more associated with acute kidney injury, hepatic dysfunction, endothelial dysfunction. And we became interested in that from an endotoxin perspective, because if you give an animal endotoxin, it of course develops multi-organ failure.

But in addition to rather severe shock, the preponderance of the injury is in those organs that are part of the delta phenotype, the AKI, the hepatic dysfunction, the endothelial dysfunction. And there's even been a case, a very unfortunate case of a human being that injected himself with a lethal dose, what surely would have been a lethal dose of salmonella endotoxin in an effort to, well, we're not exactly sure what his motivation was, but that individual presented a few hours later to critical care with, or at least to the emergency department with that same group of symptom complex, AKI, liver dysfunction, endothelial dysfunction, and interestingly, clear chest x-ray and a clear sensorium. So this delta phenotype that we see in association with endotoxemia is certainly interesting as a potential, not only in terms of precision medicine from a phenotype perspective, but now we have something to target specifically with therapy.

Dr. Bulloch: This is an interesting concept. I love learning about the advancement of diagnostics, and it's a great transition to your study, which was a prospective observational study. And you used a novel biomarker called the endotoxin activity assay, or the EAA, to detect endotoxin in the blood.

And I'll be honest, I understand that the EAA is a few decades old, but I'm in a community teaching hospital like many of our listeners, and we don't have this biomarker, at least not that I'm aware. It probably would be a send out of a send out if we wanted to even try to use it. I've done a lot of reading on it though, and it appears it can be really useful for things like antimicrobial stewardship, maybe directing resuscitation.

But for those who maybe don't have as much experience using this biomarker clinically, can you tell us how you maybe use it in practice if you do, and when you decide to order for a patient?

Dr. Kellum: Sure. I mean, you shouldn't feel too bad about not having it because no one really does. It's available in some research centers, but it's not clinically marketed.

The test was developed by a Canadian biotech company, the same company that we mentioned a moment ago, Spectral Diagnostics at the time, now Spectral Medical. And it was developed really as kind of an early warning test for sepsis. And it was one of the very first tests alongside tests like Procalcitonin, for example, to try to identify patients with high risk of developing sepsis.

And obviously, if you have a lot of endotoxin activity in your blood, you would be at increased risk for sepsis. The problem is, is that you can develop sepsis and septic shock without having endotoxin in your blood. And this paper that we're talking about now definitely shows that you can have low levels of endotoxin and still have septic shock.

So the test isn't very good at identifying people at risk for sepsis. What it's good at doing is identify patients that are at high risk for endotoxic septic shock. And the distinction is important because if we're going to use it to identify patients that have a high likelihood of responding to an anti-endotoxin therapy, then we really want to know that they have high levels of endotoxin in their blood.

The second part, if people who are listening to this, if they're also kind of looking at the paper, Figure 1 really sort of illustrates this quite well. There's two panels. The top panel of Figure 1 has the relationship between endotoxin activity and the SOFA score.

And you can see from that figure that patients that have a high level of endotoxin activity above 0.6, which is associated with a level of endotoxin that can be lethal and can certainly result in high morbidity as well. And this level of endotoxin, though, some patients don't develop organ failure and those patients have a very low risk of death. Only about 12% of those patients die, whereas patients that have a high level of SOFA, as an example of organ failure and a high level of endotoxin, those people meet the criteria for what we call endotoxic septic shock.

And those patients have a 60% mortality. And in Figure 2in that paper, there are some Kaplan-Meier curves for the 60-day mortality associated with having that pattern of high endotoxin together with organ failure versus having septic shock, but not having that pattern being in those other three quadrants. And you can see from that figure, the hazard ratio is four, which is obviously highly statistically significant.

Dr. Bulloch: Yeah, I found the information in the relationship between endotoxin activity and organ dysfunction very interesting, a little bit complex, to be honest. And I always try to think about how do we take this information and put it into practical circumstances? And you mentioned I shouldn't feel bad because not a lot of hospitals use this test clinically.

And you mentioned that it doesn't work really well as a predictor for sepsis. What do you think we could do in the clinical realm to make this test more useful for us and maybe bring it into use more often?

Dr. Kellum: Yeah, so I think the company chose not to market this test back several years ago because there was not a treatment for endotoxin, at least in North America. There are therapies that have been developed. And one therapy in particular is a therapy which uses an extracorporeal device to absorb endotoxin from the bloodstream.

And the Japanese invented this several years ago as well. It's used routinely, although not that commonly in Japan. They select patients that have a very high severity of illness to use this therapy.

And there's evidence that the therapy provides benefit. The evidence is largely limited to observational studies, propensity-matched large observational studies from registry data and things like that. The clinical trials have been less convincing.

But what we're hoping to do with this now is that we have the evidence we just talked about in the sense of this very high-risk group of patients that have not only high levels of endotoxin, but also evidence of organ failure. And those patients with a 60% mortality, you know, the opportunity to show benefit of the intervention in that group of patients is going to be much easier than in a group of patients that is kind of a mixture of low and high-risk patients, the low-risk patients diluting the signal, if you will. And so this concept of enrichment for the target and enrichment for the likelihood of benefit is where I think this project will go.

And we've recently completed a clinical trial called TIGRIS, which uses a Bayesian analysis to understand whether or not there's benefit for survival at both 28 days and at 90 days. And those results have been released in abstract form and have been presented at some meetings. And those results are positive with a posterior probability of benefit both at 28 days and at 90 days exceeding 95%.

But back to your question about what else we can do with EAA, I think you're right. I think if the test was developed today, there would be more interest potentially in utilizing it, not just to guide therapy, because the therapy, at least in the United States and Canada, isn't available yet. That absorption therapy with polymyxin B hemoabsorption isn't yet available.

But you still would presumably want to know if a patient had a 60% likelihood of death or a 12% likelihood of death. And you might do things differently for those patients. And so I think even as a prognostic tool, it probably has utility.

And had it been developed today, I think there might've been more of an interest in sort of applying it for that purpose.

Dr. Bulloch: I'm going to circle back to treatments in a minute because as a pharmacist, that's always something that's of interest to me. But before we get there, I saw some interesting information in there. Looking at the parameters, more of us are probably familiar with sepsis and thinking of how severe these patients are.

For instance, about 59% of the patients in your study had a lactate of greater than two, and only 20% were on the ventilator at baseline. Now, it may be due to the literature. It might be more of an emphasis from accreditation measures in the United States.

But it seems like we focus more on these variables, like lactate and the ventilator's disease severity. It did seem that a number of patients with an EAA of greater than 0.6, which is considered high, was similar to how many had high lactate. And 81% of those had endotoxic septic shock still.

I wonder if we're missing something. And back to your point of, would this be more useful today? Are we missing something valuable in assessing disease severity by not using the EAA?

Because if I just looked at the patient's baseline characteristics with their lactate levels, and how many were on the ventilator, it didn't seem that they were that bad.

Dr. Kellum: Yeah, no, I think, again, if you sort of go back to that Figure 1 that I started talking about, and for those listening to this who don't have that in front of them, I'll just sort of explain what it shows. But it has four quadrants, where we talked about the quadrant, which on the figure is in the upper right hand quadrant, which has a high level of endotoxin together with high organ failure. And some of those organ failures were kidney dysfunction, hepatic dysfunction, you know, the usual SOFA stuff, right?

You're on a ventilator with high PO2, FO2 ratio, etc, etc. And that got you in that quadrant with the high mortality. But what's interesting is there were some patients, not that many, but there were some patients that were in the upper left hand quadrant, in which they had high organ dysfunction by SOFA, but low levels of endotoxin, and they had a 0% mortality.

Now, it was not that many patients. So, you know, the confidence around that number is low. But they clearly had a much, much lower mortality than the patients that had organ failure that was in association with high levels of endotoxin.

So to your point, you know, again, knowing the difference between people who have a 60% mortality and patients that have a 0% mortality with sepsis, even though they have got organ failure would seem to be, as you said, something else in addition to the organ dysfunction that you're already measuring with things like, are you on a ventilator? And what's your PO2, FO2 ratio and things like that. So yeah, I do think there is value in understanding if endotoxin seems to be a driver of this process, because the mortality rate is much, much higher in that group of patients compared to the patients in which endotoxin is not a big factor.

Dr. Bulloch: Speaking of mortality, I wonder if you can talk just for a minute about the link you found between the delta phenotype and endotoxic septic shock.

Dr. Kellum: Sure. So given that background that we talked about at the beginning, in which patients or animal models in which have been exposed to endotoxin or that one unfortunate case of self-administration of a large dose of endotoxin, the type of organ failure patterns that emerged from that looked a lot like the delta phenotype. And so this idea that you see a patient who maybe has acute kidney injury, hepatic dysfunction and endothelial dysfunction, or we'll just say for the sake of argument, you know, two or three of those in the setting of septic shock, is that patient more likely to have endotoxic septic shock?

And the answer is yes. From these data, there was a much higher rate of endotoxic septic shock. About 60% of patients with the delta phenotype had endotoxic septic shock, whereas in patients without the delta phenotype and other phenotypes, it was much, much lower.

The problem though, is that the clinical phenotype or the sub phenotype, the delta phenotype or any of the other phenotypes, but focusing on the delta phenotype for a moment, obviously you could have hepatic dysfunction, endothelial dysfunction and acute kidney injury from other causes other than endotoxin. So it may not be that specific. And also if you've got healthy kidneys, you can actually have a lot of kidney damage before you develop kidney injury by creatinine and urine output.

So it may be that we're missing some patients at least early on. You also may have, you know, a drop in your platelet count from 300 to 150, which is significant, but probably doesn't get on the radar screen for most of us caring for patients. And so there's a possibility that there are some patients with, and maybe we didn't even measure, you know, liver dysfunction.

So there are certainly patients who probably do manifest some of these things that we don't actually measure very well is one thing. So there's a sensitivity question, but there's also a specificity issue with respect to the phenotype for selecting patients with endotoxic septic shock. And that is that it really comes down to the molecular biology.

So the fact is that endotoxin signals through toll-like receptor 4, but there are other ligands for toll-like receptor 4. And there are other toll-like receptors that activate the inflammasome in a very similar way. And so just because you have downstream evidence of inflammation doesn't mean that the cause was endotoxin.

You have to measure it. And then that brings us back to the utility of measuring endotoxin with an assay like the endotoxin activity assay. If you really need to know whether there's endotoxin in the blood, you really have to measure it.

Dr. Bulloch: You brought up an interesting point that sometimes people who are strong physiologic reserves at baseline, we may not notice something is going on until it's too late. And it seems that maybe waiting for organ dysfunction might limit reversibility. Is there anything we can do about that?

Dr. Kellum: Well, so that's a really important question. And I think that really kind of opens up a whole other area of interest in phenotyping and precision medicine. And the interest lies in developing new biomarkers and artificial intelligence and really ways of identifying these patients before they develop irreversible organ failure.

I mean, obviously, we know that someone who has a high level of endotoxin and is going into multi-system organ failure is going to have a much worse outcome than patients that are not going into multi-system organ failure. But it would be nice if we had some way of identifying those patients earlier. And that's where I think better diagnostics, not the diagnostic for the endotoxin per se, but the diagnostic for predicting organ dysfunction or an artificial intelligence approach or the combination of the two.

I mean, I think we forget that artificial intelligence isn't necessarily confined to simple clinical variables that we have access to today. It may also be trained on newer in vitro diagnostics as they become available. So I think there is a lot of interest in working through that.

There's another thing that's of interest that I think, and you see this maybe more in pediatrics than you do in adults, but I think it's only because we actually look for it in pediatrics. And that is there seems to be some genetic predisposition to the severe host response to endotoxin. So obviously we have enough endotoxin in our gut already to kill us.

And in fact, we have enough endotoxin if you could purify it and administer it to human beings, not that you would ever conceive of that, but if you were to do that, it would be enough to kill thousands of humans. And so there's quite a lot of endotoxin in the gut, obviously. And if it gets out into the bloodstream, it can cause a real catastrophe.

As a result, we've evolved to have mechanisms to deal with that, right? We have LPS binding protein. We have our HDL cholesterol binds the endotoxin.

It creates myceles around it and we remove it our liver. Complement activation has a role to play in terms of sopping up the endotoxin. Various other proteins may bind it as well.

And so we have countermeasures and some of us can tolerate at least transient high levels of endotoxin, whereas other patients really get into trouble acutely. And this might also be an avenue. If you knew, for example, that you were a hyper responder to endotoxin because of your genetic predisposition, you might have a very different perspective if you had high levels of endotoxin in your blood.

So there's that component as well. And in the future, we may have opportunities to leverage both the acute biologic response, but also the predisposition that patients may have.

Dr. Bulloch: When I hear things like that, I just think, wow, I wonder if I will still be practicing long enough to see those things come about and to come into play. And I don't know the answer to that question. I feel like some of the things I was promised when I was a student have yet to come to fruition and other things that I never could have imagined are here now.

Just be really complex to see this precision approach take root, hopefully before I retire. I don't know. I don't know how you feel about that.

Dr. Kellum: Well, I think I'll probably retire before you. So one of us may not get to see that in practice, although I think we're already seeing the very early signs of precision medicine. If you were to be a little bit more broad in your definition of precision medicine, we've been practicing precision medicine in some aspects of critical illness and medicine in general for some time.

Even just getting quantitative cultures and looking at the response to antibiotics to tailor our antibiotics to the very specific type of infection that someone has and the response that those organisms have to the antibiotics is a form of precision medicine. And I think this isn't Star Trek. I think this is very close to what we can deliver already.

I think when we start looking at delivering immunomodulation to patients based on their subphenotype and their genetics, that I is going to take a while to develop because it's very complex. But removing a toxin from the bloodstream when it matters, which is really kind of what this is all about, I think is a much easier proposition. And I think therapies that are focused on targeting bacterial toxins, that are focused on treating targetable or treatable traits that are less complex than the immune response may be something that you and I can expect to see as common practice in our lifetime.

Dr. Bulloch: You just stole my next question. As mentioned before, I'm a pharmacist and I love thinking about how can we use this data for drug discovery and development. I remember very clearly being in pharmacy school and one of my professors promised us one day that we would know all of the different types of the cytochrome enzymes and who is a fast acetylator and who is a slow metabolizer and we would use that.

And that's how we would dose medicines. That's how we discover new medicines. And I almost see your data rolling into a very similar picture for my colleagues in drug discovery.

What insight do you feel like your data gives them to developing novel therapies or maybe even repurposing old therapies?

Dr. Kellum: Well, if we turn the question around a little bit and because oftentimes it's easier to explain how things failed than it is to necessarily understand the clear pathway forward that will be because there'll be other curves in the road, right? There'll be other things that come up as we embark on these types of journeys that we haven't anticipated. But if you sort of ask the question, why did all of the anti-endotoxin therapy fail back in the nineties, right?

Why is it sort of relegated to the history books and not something that we can actually use in clinical practice today? Endotoxin removal with an extracorporeal device is really the only therapy that was developed in that era that continues to exist. All of the drug therapies had failed.

And it's interesting if you do kind of an autopsy on that program, there are various reasons why those drugs may have failed. One of the reasons may have been that they didn't have as much activity against endotoxin as people thought. And there's some evidence for that.

But I think a bigger one was that we made the mistake and it's forgivable because I think, you know, back in the nineties, really nobody had as good an understanding of this. Remember Bruce Spoiler didn't win the Nobel prize and it was Jules Hoffman until, you know, 2011 for work that was really done at the very end of the 1990s. And so early in the 1990s, when a lot of these endotoxin trials were done, people didn't even understand how endotoxin worked, you know, what receptors it signaled through, why it produced such high lethality.

And I think that what we failed to do in those trials was we failed to select patients who actually had high levels of endotoxin. And I keep up coming back to the talking about this Figure 1, people are going to be, so why does he keep talking about Figure 1? But I mean, that figure really shows quite nicely that it's really the minority of patients.

It's only about a quarter of the patients that kind of fall into, they all have septic shock by sepsis criteria, even sepsis three criteria that these patients have septic shock, but only about a quarter of really fall into this category of endotoxic septic shock, the treatable endotype. And this is not just a treatable endotype for polymyxin B hemoabsorption. It's a treatable endotype for anything where you want to target endotoxin and you want the readout to be mortality.

And so if you look at that, you come to the conclusion that, you know, nothing is going to work unless I enroll literally thousands and thousands of patients, you know, in a modestly sized clinical trial of a few hundred patients. I'm never going to see a treatment benefit if only a quarter of the patients have any chance of benefit. And I think that in terms of drug discovery, and not just drugs, but any treatment, but drug discovery for sure, if I treat patients based on a syndrome, and I characterize that syndrome by clinical features that are not specific for the endotype, then I run the risk of doing exactly what I think happened in the early days of anti-endotoxin therapy, and that is treat a lot of patients that had no chance of benefit, and therefore sort of threw the baby out with the bathwater, and there was no chance that those treatments would have been able to show benefit.

Dr. Bulloch: It's almost as if going forward, they need to take it through the lens of rare diseases, like we do with orphan drugs, and narrow our focus. At least that's how it appears to me from what you said.

Dr. Kellum: Well, so I very much agree with you, and I love that question, because I think, and I don't know how much more time we have, but I think in the remaining minutes, it is important to reflect on the ramifications of that reality, because I couldn't agree with you more. I think that's exactly what we're talking about with precision medicine, is we're taking a condition that is relatively common, but not that common, right? We take a, you know, not, sepsis is common, but it's not that common.

Only about a million, million and a half people a year develop a sepsis, and then of those, about a third or less than a third develop septic shock, right? So you've got maybe 450,000 people a year in the United States. That's kind of what the number that the CDC uses.

And if you take 450,000 and a third of those develop endotoxic septic shock, now you're down to 150,000 patients a year, which, you know, meets the criteria for an orphan disease. And so we've sub-segmented sepsis into different groups of patients. Maybe some of those segments are patients with, for example, the alpha and the beta phenotype, where we just say, look, standard therapy that we're providing today, good critical care, Surviving Sepsis Campaign guidelines, those things are all that patient needs.

And then you have maybe a third of patients, or 35% of patients that have the gamma and the delta phenotype, where you kind of say, well, those patients, despite good critical care and source control antibiotics, still have a high risk of death. What else can I do? And for those patients, you know, you have essentially a collection of orphan diseases, and this would be one of them, endotoxic septic shock, but there are others, and maybe there's four or five orphan diseases within that group that therapies could be developed for, but what are you gonna do for that?

We know it's difficult to develop therapies for small populations, because the market size is obviously quite small, and large pharmaceutical company knows that they're gonna have a really hard time to recoup their investment when there's really just a very small population of patients that they can ultimately treat.

Dr. Bulloch: Well, Dr. Kellum, I've got hope for you, because I feel like a good percentage of the new drugs that have come out in the past several years have been for rare diseases. So maybe somebody will hear this and take up the call to action and start working on some things. That would be amazing.

That is all the questions I had for you today, but before we close, I just wanna give you an opportunity to comment or say anything that we didn't have a chance to discuss today.

Dr. Kellum: No, it was incredibly thorough, and I definitely appreciate the opportunity to talk about these issues. I think where we sort of landed on the end was with some hope that segmenting the population of septic shock into treatable groups of patients, even though they're relatively rare subgroups, that there may be an opportunity for us to develop therapies or repurpose existing therapies to treat those patients. And I very much appreciate the opportunity to speak to this.

Dr. Bulloch: Well, and I thank you for being here with us today. I look forward to reading your next trial. I think you said it was the TIGRIS trial?

Dr. Kellum: Yeah, the TIGRIS trial. The manuscript is under review, and hopefully we'll find out the details sometime very soon.

Dr. Bulloch: All right, well, that's a coming attraction. This is going to conclude another episode of the Society of Critical Care Medicine podcast. If you're listening on your favorite podcast app and you liked what you heard, consider rating and leaving a review.

For the Society of Critical Care Medicine podcast, I'm Marilyn Bulloch.

Announcer: Marilyn N. Bulloch, PharmD, BCPS, FCCM, is an Associate Clinical Professor and Director of Strategic Operations at Auburn University Harrison School of Pharmacy. She is also an Adjunct Associate Professor in the Department of Family, Internal, and Rural Medicine at the University of Alabama in Tuscaloosa, Alabama, USA, and the University of Alabama Birmingham School of Medicine.

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