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Basic/Translational Science - 2024
Basic/Translational Science - 2024
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Well, good morning. I'm Joe Reppold. I'm a trauma critical care surgeon based in Portland, Maine at the Maine Medical Center, and I'm a professor at Tufts University in Boston. And my work in the research environment is focused on the mechanistic actions of TXA, which as probably many in the audience know, has reclaimed a very active life in the last 15 to 20 years. I've had the privilege of chairing the Basic and Translational Science Committee for the last year, and to follow up with Mary. Please feel free to join us. I think it's a very eclectic group. I am very indebted to Jamie Sturgill from the University of Kentucky for keeping me out of trouble for the last year, and we'd encourage any of you with any interest to join us. So what I opted to do for my little 15 minutes of fame is discuss a variety of articles from each month of the last year from the Journal of Critical Care Medicine. How do you move the slides? Left click, right. So I have no financial disclosures other than my lab is funded by the DoD. So January, hard to remember that a year ago this time, but this was an article that looked at alveolar biomarker profiles to subphenotypes, acute respiratory distress syndrome. And what they looked at was bronchoalveolar lavage fluid analysis of both hyper and hypo inflammatory markers. And what they really demonstrated was there was not a whole host of difference between the hyper and hypo inflammatory markers in the lavage fluid. My takeaway is that we really need to combine this with plasma analysis of biomarkers and see where the two may overlap to allow us to maybe subphenotype the different varieties of ARDS that we see. But it's a very well-written manuscript. It's incredibly detailed methodology and science. So I'd encourage you to read this particular one. February comes from a French meta-analysis that looked at early versus late tracheostomy in non-neurologically impacted patients. You know, as a trauma surgeon, head injury for us is kind of the bane of our existence. We can work out of the University of Pittsburgh a number of years ago that people with severe traumatic brain injury actually benefit from very early tracheostomy. And they were doing it in less than 72 hours. Our group in Portland has tried to replicate that. We may not hit the 72-hour mark, but we're usually done in the first week. In this particular article, which was a very large study, again, a meta-analysis, non-neurologically impaired patients, they didn't see any difference between doing it at 10 days or before 10 days or after 10 days. The question I have for these authors would be, where did 10 days come from? I think all of us have something in our back pockets of when we say we really should think about traching, you know, chronic ventilatory-dependent patients. Fourteen days historically has been the marker, but this group used 10 days. But what they really showed was there wasn't a darn bit of difference doing them early or late in terms of mortality. I think we would have expected that, but it's nice to see it in writing sometimes. So this is, again, another interesting article. This is one that should finally end this discussion for the foreseeable future, although somebody will publish something about it in the next week. The association between length of storage of transfused RBCs and outcomes in surgically critical patients, kind of right up my alley, so to speak. And this is a subgroup analysis of blood evaluation. This too comes from the French collaborative group, and there was no evidence that fresh red blood cells less than seven days made any difference in overall mortality or subset analysis morbidities compared to blood at 21 days of age. As I said, going back to my military experience, we went very early in 2008 to try to get blood products less than 14 days of age into the combat theater. It was a very difficult logistical challenge, as you can imagine. But we didn't demonstrate militarily with combat casualties that it made a difference, and this study confirms that. And this was a subset analysis, a much larger study called the ABLE study. And again, I hope this finally puts to rest, if you need blood, give them blood and use whatever the blood bank sends you. April was a cardiovascular subphenotypes in ARDS, and this looked at TTE and evidence of cardiac function based on four different phenotypes. They basically hyperdynamic, dilated RV but normal function, LV, normal function but hyperdynamic. And what they really demonstrated was those that had dilated RV and associated diminished RV function had the highest 90-day mortality. So this is interesting in the sense that if you look at that mortality number of 78%, that's pretty profound. And whether or not we can make an impact on that and change that outcome, I think, remains to be determined. But this too is an interesting article, and this is a study from India. Again, trying to get into personalized medicine for sepsis, and this is the diagnostic accuracies of monocyte distribution with versus procalcitonin and C-reactive protein. And this is a systemic review and meta-analysis. This comes from the group in Taiwan. And they basically said that MDW was as reliable a diagnostic marker for sepsis as was procalcitonin and CRP. Most of us realize that when we send a CBC, you get at least an automated MDW, and it certainly comes back quicker for us than a procalcitonin or a CRP level. So this, again, may be something to put in our toolbox. Again, the overall issue with all of these is what role they play in a given patient. And I think that's the ultimate holy grail for all of us, is to find the right marker for the right patient at the right time. This is another basic science, again, from the French. The immune profiling panel gene set identifies critically ill patients with low monocyte and antigen expression. This is part of the reanimation study based in France. Bottom line is the use of immune profiling via mass spectroscopy, and I'll caveat all this here, how many people can get mass spectroscopy at 2 o'clock in the morning? I would say no one, just to go out on a limb. But again, this is another attempt at personalized medicine. And my experience with sepsis, as a general and acute care surgeon, is you want to know what you're dealing with from a septic biomarker profile, if that's what you're going to use upfront. It's not doing us any good when we get it 48 to 72 hours or seven days later. That cat is already out of the bag, and you're down your treatment algorithm. But again, personalized medicine, another incredibly well-written scientific article. You get a little bleary-eyed reading this one. I just want to warn you on this upfront. But again, a very good article. This again is another from our Chinese colleagues, and looking at prolonged VVE ECMO. I think the take-home point is, for all of us, those of us who put people on VA ECMO, we have a, I'll give you our paradigm. In Portland, we say we have a big mechanical circulatory support program. Seven days. If you're on VA ECMO, and you're failing your RAMs, at seven days, we are having a very harsh conversation with patients' families, and really looking very quickly to remove them if they're not making significant progress. VVE ECMO is a totally different kettle of fish. The Japanese have kept people on VVE ECMO for well over a year, waiting for either lung repair or transplantation. I think the take-home point for this, for my perspective, is you need to have institutional guidelines of how you're dealing with VA and VVE ECMO patients. I think VA, we all probably have a process by which we live with. VVE is a totally different kettle of fish. And for us, we don't do lung transplantation in Portland. So longstanding VVE ECMO patients require us to find a source for potential transplant, whether that be Boston, and our other center of choice would be Duke. OK, this is another one that really needs to be put to bed. Don't give people vitamin C, please. Linus Pauling is turning in his grave somewhere. But we just really need to stop giving this stuff. If you remember, he won a Nobel Prize. He won two Nobel Prizes. He won the Physiology and Medicine, and he won the Peace Prize as well. But he was advocating 10,000 milligrams a day, which kept his surgical colleagues in good stead, because they all perforated their ulcers based on 10,000 milligrams a day of it. But poor Linus is turning in his grave. Don't give it to people. It's not good. I want to spend a few minutes on this by Tim Buckman. Error, fraud, and responsibility. If you read nothing else from the last year, you should read this article. This is a three-page editorial by a number of colleagues of Dr. Buckman's. But the issue of scientific misconduct is rising exponentially. I read an editorial in last week's issue of the journal Science stating the same thing. The Office of Research Integrity of the NIH is overwhelmed. They are underfunded, understaffed, but the complaints continue to follow in, or fall in. You may have read the news yesterday about the Dana-Farber Cancer Institute. Both the president and the chief operating officer, both physicians, work has been called into claim. There is an individual, a PhD in the UK, who's a molecular biologist, who kind of does this on the side. And there is substantial problems at the Dana-Farber, and they're retracting numerous articles for a whole host of researchers at the Dana-Farber Institute. Jamie and I were talking about ChatGBT, and as you know, it'll give you something on everything that you ask it. But remember the one thing it doesn't do, it doesn't do references well. And that's how people get caught. I was sharing with Jamie a story about a legal brief filed in New York City by an attorney who had ChatGBT write the brief. But all the references, the legal cases that were referenced, were made up. The computer just made it up. And the judge caught him, and he's in the process of being disbarred. So I don't think you'd want to be part of the ORI coming after you for any good reason. But this is a wonderfully well-written editorial by Tim, and I think it should be in all of your libraries. Again, another one that we should condemn. This is high-dose steroids for non-resolving ARDS in critically ill COVID-19 patients with dexamethasone. Don't give it. It doesn't work, and it's dangerous. And there was certainly increased mortality associated with the use of high-dose dexamethasone in this group of patients. So I think we should keep that in the back of our minds. Again, a bad drug used in the wrong situation. I had to have obligated to pick a pediatric article because I know nothing about children other than having a few. But this is a group in India that looked at multiple electrolyte solution versus saline bowls for resuscitation of pediatric septic shock patients. This was a very large study. But basically, this was a balanced crystalloid infusion resulted in a lower incidence of AKI and renal injury in children with sepsis. The bottom take-home line, though, was there was no difference in mortality. I'd leave it to the pediatricians and the PICU intensivists in the room to see if this is something they buy or not. But this was another well-done study by the groups in India. And last but not least is, again, the Cytosorb, the dialysis for inflammatory biomarkers in critically ill patients. This was, again, a review and meta-analysis of a variety of controlled trials. Basically, really, there was no consistent decrease in IL-6 or other inflammatory markers in the first five days of treatment. This is a very expensive technology that isn't ready for prime time. It's not to say it might not be ready in a few years or the indications for its use may be valuable at some point, but not yet. And with that, I will end and have given you the year in review. Thank you.
Video Summary
Joe Reppold, a trauma critical care surgeon, summarizes key studies from the Journal of Critical Care Medicine over the past year. He discusses various topics, including TXA's mechanisms, ARDS biomarkers, tracheostomy timing, and red blood cell storage duration. Key insights reveal no significant timing difference in tracheostomy outcomes and no mortality difference in using fresher blood. Cardiovascular subphenotypes in ARDS indicate high mortality linked to dilated RV. He stresses the unreliability of high-dose steroids for COVID-19 and experimental procedures like Cytosorb dialysis. Reppold emphasizes personalized medicine’s potential and warns against scientific misconduct.
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Year in Review | Year in Review: Research Section
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Year
2024
Keywords
trauma critical care
tracheostomy timing
ARDS biomarkers
personalized medicine
scientific misconduct
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