SCCM Resource Library-Translation Research in Clinical Nutrition: From Bed to Bench and Back Again

Video Transcription

Ladies and gentlemen, please welcome Dr. Beth Taylor. Good afternoon, it is my pleasure to introduce you to one of my international colleagues,  Dr. Zuden Puthacherry, who will present this year's William Shoemaker Memorial Lecture. Dr. Puthacherry graduated from Nottingham University in 1997.  He completed his training in respiratory general and intensive care between Bristol, Sydney, and London.  He currently serves as a clinical senior lecturer in intensive care medicine at the William Harvey Institute at the University of London.  He also serves as a consultant at the Royal London Adult Intensive Care Unit.  He co-chairs the UK National Post-Intensive Care Rehabilitative Collaboration, which is a multi-professional group similar to SCCM.  His research interests include muscle wasting, critical care nutrition, exercise, and acquired functional disability.  His research group has looked at these things through metabolism, physiology, basic science, and are currently involved in some Phase II trials.  Today, Dr. Puthacherry will present Translation Research Clinical Nutrition from Bed to Bedside and Back Again.  And as a special treat, he, along with some other nutrition experts, will be available at 2 p.m. today, Central Standard Time, for a live question and answer session.  Please join me in welcoming Dr. Zuden Puthacherry. Hello, everybody. I'd like to thank the organizers for the opportunity to give the William Shoemaker Lecture.  And I am so sorry that we can't do this in person, and I really hope that I'll be able to do this and interact with the crowd at SCCM again in the future when the pandemic is over.  The title of my lecture is Translational Research and Clinical Nutrition and Exercise from Bed to Bench and Back Again.  And I've snuck in the words and exercise because to me, as a muscle physiologist, I can't see how we can talk about nutrition without talking about exercise or exercise without talking about nutrition.  These are my disclosures. I work with all these companies in trying to develop interventions to prevent acute muscle wasting in the critically ill patient.  So traditionally, death, morbidity and economics were the only endpoints for trials.  But in reality, across the developed world, in modern intensive care units, critical care mortality is dropping.  If you're admitted to a modern intensive care unit, your mortality is only 20% on average.  So 80% of our patients are surviving. And in the coronavirus pandemic, 70% of our patients are surviving.  This is all coupled with a large number and an increasing number in critical care admissions for people who are critically ill.  So we're growing a large number of intensive care survivors. This survival is not without cost.  Almost 20 years ago, Margaret Herod showed that if you were of a working age, you admitted to intensive care with a critical illness and you survived, at one year, half of these people would not be returning to work.  A third of them would still need help with their activities of daily living. And she's gone on to show that this persists for up to five years.  This work has been repeated and validated over and over and over again.  And I just want to put out Jackie Washington's statement, which I think resonates with many of us, that actually survivorship will be the defining challenge of critical care in the 21st century.  And we know in February, in the deepest of winters that we're having over in Europe, and no doubt in the US, we have all this to come with our pandemic survivors.  So muscle wasting is the most common problem faced by patients with critical illness. Patients recognise this. Academics recognise this.  And in fact, if one looks at the data, muscle wasting, however you slice it, is the most common complication of critical illness.  However, we have no effective treatments because we lack a detailed understanding of the pathophysiology of muscle wasting.  And what I'm going to take you on now is the journey that we've gone through to try and understand this and intervene.  So in 2010, we put this framework forward and said, gosh, this is what happens to critically ill patients. So in health, you have a normal amount of muscle mass.  And as you become critically ill, you lose muscle mass rapidly. And sometimes you lose so much, you're functionally disabled. You're unable to perform your activities.  If you survive, and it's a long road back, then you may take you up to five years to recover.  And at that stage, much of work in the area was done here, trying to recover our patients' rehabilitation.  And we asked the question, should we not be working in this space over here? Preventing the time of functionally limiting, decreasing disability, getting our patients back to work.  But to do this, we needed to do two things. We needed to understand the pathophysiology of wasting and to develop tools for assessing wasting and recovery.  And this first section of my talk is going to be about the pathophysiology of muscle wasting. We put together the Muscle UK study cohort.  We recruited people who are critically ill but deemed likely to survive. You can see they are young, 54 years old. Apatitude scores are 23 and a half.  And we recruited them at the beginning of their critical illness. And we ended up recruiting survivors. 97% survived intensive care and 89% survived hospitals.  And we recruited 63 patients and did muscle biopsies in half of them on days 1 and day 7. And we looked at muscle mass using muscle ultrasound on days 1, 3, 7, and 10.  Paired these with muscle biopsies to look at the protein DNA ratio, histology to look at quality, and immunohistochemistry.  And this is what we started to see with muscle ultrasound. This is a picture of someone's muscle on the first day. We looked at rectus femoris cross-sectional area.  Rectus femoris is one of our most functional muscles. It's the muscle you need to get off that chair at the end of this talk.  The muscle you need to go to the toilet and to get off the toilet. It makes a difference to our patients. And it wastes away during critical illness. And this is what we see.  On the y-axis here is percentage change in muscle mass. And on the x-axis here is days from IC admission. And there's a loss of 17% of muscle mass in the first 10 days.  And we validated this against the fiber cross-sectional area and protein DNA ratio. Showing that this is a valid measure of muscle mass.  And we also showed that actually there was a differential in muscle mass wasting. Same y-axis, muscle mass loss. Same x-axis, days from IC admission.  But here you can see we're increasing illness severity. You see more and more muscle wasting.  So we showed that 2% of muscle loss we saw per day in people with greater than 2 organ failure. Leading to 20% muscle wasting in 10 days.  And is that increase of 46 organ failure, we were seeing 26 to 30% of muscle wasting over 10 days. This loss in quantity was associated with a loss in quality.  And we saw minor crosis occur in 40% of these cases. This is a picture of muscle histology. Showing healthy muscle on day 1 with the corresponding immunohistochemistry.  And by day 7 it was replaced by this. The shaggy necrotic tissue we found in 40% of our patients. And we saw a cellular infiltrate which stained positive for CD6 from macrophages.  So we saw necrosis with a macrophagic infiltrate in 40% of the cases. Which spilt over into the fascia giving us a fasciitis.  Which we also know impedes function and causes pain in people outside critical illness. There's no reason to think this won't happen within critical illness.  So why? Now we've seen what happens and we know what the landscape is. We then went on to look at muscle protein homeostasis.  So all the muscle in all organisms, human beings, animals, etc. Are balanced between muscle protein synthesis and muscle protein breakdown.  And there are many, many insults that our patients have to suffer in critical illness. And we needed to know how this balance was affected.  So in our experiments we dovetailed in stable isotope infusions of leucine and phenolalanate. To try and understand how much muscle was being made. And these aren't new techniques.  If you look at these citations of where they were first described. These citations are older than I am.  These are old techniques from sports and nutrition science that we brought into intensive care. And this is what we showed.  Patients on the first day of critical illness have the same levels of muscle protein synthesis. And this is new muscle being made. At the same rate as our fasted controls.  Despite the provision of adequate nutrition on the first day of critical illness. And this had a variable recovery over the next seven days.  So because muscle protein synthesis was depressed. Muscle protein breakdown was greater than muscle protein synthesis. Leading to a catabolic state.  Which continued for the first week of critical illness. We went on to look at signaling molecules. And rather than picking out individual signaling molecules.  We looked at all of these. And we demonstrated that the signaling molecule patterns using principal component analyses were exactly the same.  They corresponded what we saw in the isotope data. So we could be confident to say muscle protein synthesis was depressed.  And this seems to be the major problem in our critically ill patients. Not increased muscle protein breakdown. And lastly, we looked at the clinical correlates of muscle wasting.  And we found an inverse association with the PF ratio, bicarbonate and hemoglobin. So the worse your PF ratio, the more acidotic you were.  The lower your hemoglobin, the more muscle wasting you saw. And an association with the CRP and total protein delivered.  So the more inflamed you were, the more you wasted away. But also the more protein you gave patients, the more patients wasted away. We might come back to that discussion in a bit.  And when we use a logistic regression, we saw a similar pattern. So our summary point from this is about 2013-2014.  Muscle wasting in the critically ill occurs rapidly and early during the first week. Is most pronounced in multi-organ failure.  Is the result of decreased muscle protein synthesis and a net catabolic state. Is associated with age, acute lung injury and systemic acidosis.  And myo-necrosis is common and is associated with fasciitis and a macrophagic infiltrate. And that was stage 1 of the observational work. Now, muscle protein synthesis is depressed.  And this is a normal reaction. So critically ill patients are just human beings. And when our muscles are insulted, if you like,  the first reaction and the normal reaction is depressed muscle protein synthesis. What we saw in critically ill patients was confirmed by some work from the Karolinska Institute.  This is Lina Gammon-Grippenberg and Ola Rijak. They showed that muscle protein synthesis stayed depressed for the first 30 days.  3-0 days of critical illness before muscle protein breakdown became a problem. Now in clinical nutrition, there is this thing that people do. Where they say protein or energy.  Calories, protein, protein, energy. And they separate these things. But human beings don't do that. We use these things in conjunction.  And what we don't talk about is how the energy costs of muscle protein synthesis. And in your cells, between 40% and 60% of your ATP is used for muscle protein synthesis.  So quickly, glucose undergoes a 10-step process into pyruvate, into acetyl-CoA, into the Krebs cycle.  Which then generates ATP and components for the electron transport chain to generate more ATP.  There is a 5-step process by which fats are used to beta-oxidation to then produce acetyl-CoA.  In the critically ill patient, we know that hypoxia and inflammation are highly likely to occur. And this will lead to the Pasteur effect.  Where pyruvate can no longer be converted to acetyl-CoA. And you get diverted to lactate. So glucose doesn't produce the ATP that we need from it.  But that's okay because we have fat. And fat is much better at producing ATP. One molecule of glucose can produce 38 ATP. And one molecule of fat to about 125.  Unfortunately, what happens in critical illness, and we show this in our publication in Thorax. There is a decrease in mitochondrial beta-oxidation.  Leading to build-up of lipid within the tissues. Suggesting that we now have no ability to use glucose or fat to generate ATP. So if you take a standard 1 kcal feed.  We can't use the carbohydrate because of the Pasteur effect. We can't use fat because of loss of beta-oxidation.  And there is no human data to suggest that protein can be used for energy production. I'm happy to be challenged and discuss that. But all that work is from animal work.  No human work. And even if it could, most of those amino acids come in at the pyruvate level. And in the setting of hypoxia or inflammation, then they will be diverted to lactate.  As a result, this is what we see. There is a decrease in ATP content in the critically ill patient on the first day of critical illness.  Which most affects those in pre-existing chronic disease. Regardless of chronic disease status, over the next seven days, despite provision of nutrition,  there is a decrease in ATP content. Now, I've shown you that the use of substrates to generate ATP is reduced in critically ill patients.  And the question then is what happens to mitochondria? Well, there is a decrease of function of oxidative phosphorylation and of beta-oxidation within the mitochondria.  Affecting the Krebs cycle electrotransplant chain. But there is also a decrease in mitochondrial biogenesis.  So, biogenesis is the turnover and the replacement of old and damaged mitochondria with new mitochondria. It's like changing the batteries in your cell.  And unfortunately, in the critically ill patient, mitochondrial copy numbers, the ability to change new copy numbers, new mitochondria, decreases.  And all our markers of mitochondrial biogenesis decrease. So, not only do the mitochondria not work, we can't replace them well. That's not a great situation for biogenic failure.  So, the conclusion from our second stage of our observational work, was that a decline in intramuscular ATP content occurs in the first week, despite nutritional delivery.  And that's because biogenesis and beta-oxidation are decreased during critical illness. And fatty acids main part be biologically inert in critical illness. And this is a problem,  because when we feed people at the moment, both entrally and parentally, we assume that we can use fat and that there's a large energy contribution  from fat within our nutrition to our patients.  So the last observational thing was we developed a, we did a network analysis of all the factors that we thought we could find in muscle and in the clinical data  to why we had muscle wasting. And what this is like is a biochemical metabolic signature of acute muscle wasting in a critically ill patient.  So each of these nodes represents actual data, which we found in the skeletal muscle in clinical patients and change over time over seven days. And we used a clustering protocol  to see what clusters came out to try and understand how we might go forward.  And three clusters came out that were really interesting. So firstly, that there's a close relationship between impaired bioenergetic status,  biologic signaling signals, and decline in muscle mass, suggesting we need to address bioenergetic failure before we can address muscle mass loss. The intramuscular inflammation,  which is all these yellow dots, clusters really closely with anabolic signaling molecules, the purple dots, suggesting that actually this is what's impeding anabolic return.  And until we address inflammation, we're unlikely to get an increase in anabolism. And I showed you earlier on that beta-oxidation is decreased, fat's not being used,  and it's being built up in the muscle. Well, in this agnostic clustering analysis, the distance of these nodes from each other is really, really relevant. And here's where we are.  Here's all the nutritional fat, and miles over here is all the energy and muscle mass, showing in a separate analysis that the fatty acids delivered  are this nutritional part fruitful, has no direct indirect association with ATP synthesis or muscle mass, allowing us to conclude that there's a relationship  between impaired bioenergetic status and acute muscle wasting, but inflammation is associated with impaired anabolic recovery, and the lipid delivery is, in critical illness,  is unlikely bioenergetically inert.  That was the, this observational data, which took us a while to do, allowed us to go back to plan our bedside experiment and trials.  It then informed a large part of this new framework, which we started to put together. Well, this is more of a far greater conceptual framework of how we improve function  and return to work capacity of our patients. And my interest and the work I've shown you sits here, right at the bottom, altered protein hemiastasis,  bioenergetic failure, and inflammation, affecting the mechanisms of muscle wasting.  So looking first, right at the bottom, at bioenergetic failure and inflammation. And this really informed a new conceptual framework for me,  which my boss, Rupert Pearson, insisted I needed to put together  if I'm really going to go forward and try and solve this problem. And it covers data science, clinical trials, and methodology. And this is what we need to,  I think we need to solve to prevent and treat acquired functional disability. So looking first at clinical trials and interventions to maintain muscle mass,  well, we are currently in the middle of the alternative substrates in critical subjects, the ASICS trial, funded by the National Institute of Health Research in the UK,  where we are randomizing ventilated patients with multi-organ failure on the intensive care to a ketogenic diet or usual care. There have been many, many concerns  and difficulties with using ketogenic diets. This is a safety and feasibility study, so we can go on to do an efficacy study. And here you can see our recruitment rate,  which has been fantastic, except for the setting of the pandemic, where we've got the first wave here, back to recruitment, and the second wave is just here.  And we will be back into recruitment as fast as we can. And this is based on the biology that I showed you earlier on, where we have glucose being diverted to lactate  and a block of beta-oxidation. And so the generation of acetyl-acetone, beta-hydroxybutyrate, will feed into acetyl-CoA, go at the Krebs cycle,  going and generate ATP plus components for the electron transport chain, generating more ATP.  On the other side, we have information. Really soon, we hope to start the Iocyte ICU trial. And this is a US-UK phase two trial, funded by industry, by Faraday Pharmaceuticals,  using a reducing agent.  And we're looking to recruit patients with major trauma, with hemorrhagic shock, and they're going to be randomized either to the reducing agent, FDY 5301, or to usual care.  I'll say that I am the UK CI, Scott Brackenridge in Florida. Gainesville is the US PI. And we're really excited to be doing this trial in major trauma. We hope to do that soon.  And these reducing agents then will ameliorate the effects of intramuscular inflammation, that's the hypothesis, by absorbing reactive oxygen species,  decreasing the damage done by inflammation, and allowing anabolism to occur, and mitochondrial function to be regained.  If we take a step up the line to altered protein homeostasis, then this is the next stage that's informing our phase two trials. So Danny Bear at St. Thomas' in London  has just locked her database for her HMB ICU trial. And this is looking at the effect of beta-hydroxy-beta-amino-butyrate, which is a derivative of leucine  in preventing muscle wasting. So leucine is the essential amino acid that we really, really need to ingest to try and stimulate muscle protein synthesis.  However, you need 30 to 60 grams of this to have an effect. You need almost 10 times less HMB for this to occur, which is why that was her choice of supplementation.  She's leading on this trial, and we really hope to see some of the results very, very soon.  This is a really, really important, exciting trial led by Sue Birney, which is an Australian-United States collaboration looking at functional electrical stimulation  in an in-bed cycle to Fez ICU in mechanically ventilated patients. And patients are randomized to Fez ICU versus normal care and rehabilitation, and followed up with muscle wasting  and functional outcomes. I should remind you that if one compares interventions and exercise interventions in the critically ill patient, in the acute critical ill patient,  then this is some great work from Maastricht, where they show that actually Fez ICU, so functional electrical stimulation, is the only one to cause an increase in cardiac output,  unlike passive cycling and ergometry and normal electrical stimulation,  or passive range of movements. And so also the one that can actually deoxygenate hemoglobin over here, suggesting that there's oxygen uptake into the muscle, unlike all the others.  So it's the best exercise intervention that we have available. So I was really excited to be part of this collaboration.  Unfortunately, if one looks at the outcome measures, there was no difference in muscle mass and no difference in strength and physical function  in intensive care at the hospital discharge. Sue Burney from Melbourne, who led on the trial, was, I guess, cognizant enough to build in translational research  into the Fez ICU trial. And we will be hoping to see some of those data, which I hope we will explain the failure of this very interesting intervention  to produce a patient-centered outcome.  And lastly, our most recent trial, which was just published in CHEST was the effect of intermittent feeding versus acute muscle wasting. Ventilated, multi-organ failure patients  like to survive intensive care were randomized to six boluses a day, but all usual care. And the biological premise for this was to stimulate muscle photosynthesis,  in that if you feed someone continuously, either intimately or parentally, we know that muscle photosynthesis cannot be maintained. And at the one to two hour mark,  it starts to drop off. By feeding people intermittently, we hope to change this and therefore preserve muscle mass. However, this was not to be the case.  And we could not see a difference in our primary outcome between those fed continuously or intermittently. I'm gonna expand on this trial in another talk.  So I won't go into this in great detail, but other headlines might be that actually we saw a greater provision of nutrition, both protein and energy, using intermittent feeding.  And this overcame perhaps some of the process issues involved with feeding and nutritional delivery. So I would watch this space for intermittent feeding. It's not over yet.  And actually it addresses another part of my conceptual framework, which is the development of sustainable interventions in acute care rehabilitation.  Obviously, we need to deliver feed if we are gonna rehabilitate patients. It's pointless doing exercise if you don't have nutrition on board as well,  because exercise is a catabolic influence without nutrition. And I don't think I need to tell people this. It's just something we fail to recognize in our patients.  Doing all these clinical trials is great, but actually we need to be understanding subphenotypes and subgroups within the patient. This is really where data science  can really come into its own. And one of the things that we're very interested in is the urea to creatinine ratio, which if you look up on Wikipedia and ask the wrong people,  they will tell you this is a measure of dehydration. However, the urea to creatinine ratio has been used as a mark of catabolism for years. I actually can't find a source reference  because it's still being referenced in my, being commented on in books in the 1940s. But essentially what we have here is that the creatinine is merely a marker of muscle mass  as opposed to renal function.  And the urea is a marker of protein being driven into the urea cycle in the liver. So urea being a marker of protein not being used  and the creatinine being a marker of muscle wasting. So a raised urea creatinine ratio is catabolism because muscle is lost and protein is not being used  properly because of this combination of bioenergetic failure and inflammation.  Urea is also a surrogate marker for ammonia. Ammonia being one of the most toxic substances to mitochondria and to muscles. And urea is generated in an attempt  to get rid of circulating ammonia.  And so this is some work by Ryan Haynes, one of our PhD fellows, where they looked at the urea to creatinine ratio and they showed it to be a better biochemical signature  of catabolism and persistent critical illness than any of epidemiological markets,  allowing us to start to bring persistent critical illness research to the bedside now and start to look at it. And some of this work has been reproduced  by other groups around the world. We're seeing urea creatinine ratio as a good marker of persistent critical illness. So Ryan, and this is Ryan down here,  and Luke, one of our new research fellows, used these data science techniques and applied it to the intermittent versus continuous feeding study  to see whether we could understand what was going on, why we didn't, was there a benefit for instant feeding to protein metabolism wasn't obvious in muscle mass.  And this is what we saw. Blue here represents continuous feeding and red represents intermittent feeding, i.e. that in the end, continuous feeding  results in a rapid rise in urea to creatinine ratios and a higher urea to creatinine ratio, so more catabolism than our protein, than in intermittent feeding.  And if it was just about protein utilization, well, you'd expect the intermittent feeding data to be much, much higher because if you were intermittently fed,  you were more likely to get protein. So the conclusion of this data science, this reanalysis of our trial is that the extra protein delivered when delivered intermittently  is not diverted to ureogenesis. It's not wasted. It's most likely and potentially taken up by the tissues, giving us a further hypothesis to go back to look at protein trafficking  in critically ill patients when intermittently fed. So intermittent feeding may still have a benefit in protein trafficking, and that the next challenge will be  how we identify patients who can benefit from this, but also how we demonstrate this to be clinically useful.  But fundamental to data science, clinical trials, and development of interventions functionally has to be methodology. And this is really, really quite nascent.  It's like the boring side of research, but it's incredibly important because we can't do things otherwise. And it's worth noting that when one looks  at critically ill data and research out there, when one looks at randomized controlled trials, up to now, only two studies have used a functional outcome  as a primary outcome measure, and that's the intermittent feeding study and Danny's HMB study. So functional outcomes are not normally used for nutritional trials.  And in fact, they're very rarely used as secondary outcomes.  I'm going to finish off with some coronavirus work. So in the pandemic, the Intensive Care Society and the British Society of Rehabilitation Medicine put together a framework,  and we developed a outcome measure called the pickups tool to try and understand post-intensive care syndrome in the coronavirus, in our coronavirus patients.  And it was really interesting because it allowed us to examine the dependencies in patients with coronavirus and compare them to those patients without,  and having validated that we pulled out these data and we saw no difference in the post-intensive care syndrome in any of the domains that you see there  between COVID and non-COVID patients. We went on to do this in a network analysis to look at patterns. And we are happy to conclude from this robust data  using the pickups tool that a coronavirus patient is exactly the same as any other intensive care survivor when it comes to their needs post-critical illness.  I'm going to finish there. Just want to show you that I'm not the only person. Our group is not the only person in this field.  There are lots of people doing work in clinical nutrition and going from bed to bed, bed to bench, and back again, and including exercise. So Darren Halen and Dale Needham  are finishing up the NEXUS trial, which is exercise and nutrition. And Clark Files is also speaking somewhere here at SCCM.  He's going to talk about the Nesta Translational Research.  The Australians, Emma Ridley, is leading on a post-intensive care nutrition study, and they will again be Nesta Translational Research. And Peter Voldoff and Frankie Dusker  are also doing this in the Czech Republic, looking at FEZ, psycholigometry, and mitochondrial function. There are many, many others. Paul Wishmore is doing it.  Olav Rijaka is doing it. Everyone in the field is doing great research in clinical nutrition and exercise and trying to move forward to helping our patients.  In concluding these slides, very simply, binogenic failure, inflammation, and impaired muscle protein synthesis are likely targets for intervention to prevent muscle wasting.  Trial design, development, and phase two trials are now needed to move the field forward, and embedding translational research in prospective trials will accelerate our ability  to help our patients. Thank you very much.

Video Summary

Dr. Zuden Puthacherry gave a presentation titled "Translation Research Clinical Nutrition from Bed to Bedside and Back Again" for the William Shoemaker Memorial Lecture. In the lecture, he discussed the rapid and early occurrence of muscle wasting in critically ill patients, as well as the lack of effective treatments due to a limited understanding of the underlying pathophysiology. He presented findings from his research, which showed that muscle wasting is most pronounced in patients with multi-organ failure, and that it is associated with decreased muscle protein synthesis and a net catabolic state. He also highlighted the role of bioenergetic failure and inflammation in muscle wasting. Dr. Puthacherry discussed ongoing clinical trials aimed at addressing these factors, including studies on ketogenic diets, reducing agents, and intermittent feeding. He also emphasized the importance of incorporating functional outcomes into research, as well as the need for methodological advancements in the field. Overall, his lecture provided insights into the current understanding of muscle wasting in critical illness and highlighted potential avenues for future research and interventions to prevent and treat this condition.

Asset Subtitle

GI and Nutrition, Research, 2021

Asset Caption

The Society of Critical Care Medicine's Critical Care Congress features internationally renowned faculty and content sessions highlighting the most up-to-date, evidence-based developments in critical care medicine. This is a presentation from the 2021 Critical Care Congress held virtually from January 31-February 12, 2021.

Learning Objectives

Demonstrate how interventions in clinical nutrition need to align with the altered physiology and metabolism of critically ill patients
Relate how protein and energy delivery are linked and how separating these is useful for trials but not for patients
Illustrate how nutrition and exercise are closely linked, in both health and illness, and discuss whether one should include the other

William Shoemaker Memorial Lecture

Zudin Puthucheary

Meta Tag

Content Type Presentation

Knowledge Area Research

Knowledge Area GI and Nutrition

Knowledge Level Intermediate

Knowledge Level Advanced

Membership Level Select

Tag Nutrition

Tag Clinical Research Design

Year 2021

Keywords

muscle wasting

pathophysiology

multi-organ failure

muscle protein synthesis

clinical trials

ketogenic diets

intermittent feeding

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