TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.
This week's topics include keeping kidneys on ice, multivitamins for cognition, improving outcomes for small strokes, and non-alcoholic steatohepatitis (NASH) treatment.
1:36 After one year of intervention
2:36 Whether it really helps is unclear
3:36 So many are water soluble
5:26 Used more potent anti-platelet agent
6:26 If you detect a clot
7:00 Kidneys for transplant on ice or not
8:00 Put in normothermic machine perfusion device
9:00 Really doesn't improve viability
10:03 NASH treatment
11:10 Bariatric surgery used
Elizabeth: If you're an older adult, should you be taking a daily multivitamin?
Rick: Bariatric surgery versus lifestyle interventions in people with liver disease.
Elizabeth: Should we store kidneys for transplant on ice?
Rick: And can we improve the outcome in people with small strokes?
Elizabeth: That's what we're talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I'm Elizabeth Tracey, a Baltimore-based medical journalist.
Rick: And I'm Rick Lange, president of Texas Tech University Health Sciences Center in El Paso, where I'm also dean of the Paul L. Foster School of Medicine.
Elizabeth: Rick, how about if we turn first to the American Journal of Clinical Nutrition? This article got a tremendous amount of media attention. I just had to follow it up and find out why. This is actually a preprint and it's from a population of folks in a much larger study.
Basically, what they were looking at was, will a multivitamin, multi-mineral supplement help to preserve memory in older adults? This is part of this thing called the COSMOS Web study. This particular analysis includes 3,500+ older adults. They were randomly assigned to a daily multivitamin supplement or a placebo, and then they completed annually an internet-based battery of neuropsychological tests for 3 years.
Their prespecified primary outcome measure was a change in episodic memory. This was defined as immediate recall performance on one of their assessments called the ModRey test after 1 year of intervention. They looked at several secondary outcome measures also. They found that this daily multivitamin intervention did improve memory performance above placebo by the equivalent of 3.1 years of age-related memory change. That's a pretty powerful conclusion.
Rick: Elizabeth, I was pretty excited when I read about this because it's a routinely available multivitamin. But when I dug down deeper into the study, I'm a little bit more skeptical. Previous studies that have looked at multivitamins have looked at overall cognition over a longer period of time and have concluded that it doesn't really help. They picked one particular test, which they alleged looked at one specific area of the brain, that is the hippocampal gyrus, and then when you look at it here is what happened.
They showed that even in the placebo group the memory got better over the course of a year. That doesn't typically happen in people that age. Now, the memory recall was a little bit better in individuals that received the multivitamin, but it was really pretty minimal and whether there was any clinical significance or not is really unsure.
I think that the headlines were larger than the results of the study. I'm looking forward to seeing over a longer period of time and in a larger group of individuals whether this actually carries any weight. As you know, in this particular study they looked at other function 2 to 3 years later -- changes on performance in neuropsychologic tasks, novel optic recognition, executive function -- and there was really no change at all.
Elizabeth: I'm not persuaded either. I thought it was interesting that the daily multivitamin supplementation seemed to have an impact 1 year after the administration. Now, admittedly that was the interval during which they were actually doing the testing. The question that I would be interested in is, "Gosh, if we started looking at that immediately, like let's say once a month or so, would we see that there is some ramp up to this ostensible improvement?" Also, they make the assertion that it's inexpensive, it has few adverse side effects, and why not?
It's sort of the chicken-soup hypothesis, but as we've talked about before so many of these things are water-soluble, so we excrete them in urine. Then those that are fat-soluble sometimes build up to dangerous levels with regard to individual vitamins and minerals that are contained in these supplements. Right now I'm sort of like, "Hmm."
Rick: We've highlighted previous studies that looked at the American population, and the ingestion of daily multivitamins actually increased mortality by about 15%. Now, the other thing that's unique about this particular study was it was a web-based study, so participants had to meet the requirement to have a computer. They had to have computer skills and internet connectivity. They were more highly educated and they were mostly White participants as well. A biased population, a very minimal result, and even in the placebo group the memory got better. So I think we need additional data and a longer follow-up.
Elizabeth: Which of yours would you like to turn to, sir?
Rick: Can we improve treatment of smaller strokes? We know that if you give an agent that dissolves the clot or uses a device that extracts a large clot when people have clots in the large blood vessels in their brain, we can improve outcome if that's done early.
But there are many people who don't qualify for that. That is, they don't have blood clots in the large vessels -- sometimes it's the smaller vessel -- or they receive treatment and they have ongoing or worsening symptoms. So what these investigators did was to try and identify individuals that did not have occlusion of a large vessel and give them a more potent anti-platelet agent and compare that to what we would routinely do, and that's give aspirin.
This was conducted in China. There were about 1,200 patients that presented with a stroke -- but a relatively small stroke -- and they randomized them to receive either aspirin or this very potent anti-platelet agent called tirofiban. The outcome was very little or no symptoms at 90 days. The secondary outcome was functional independence at 90 days and the quality-of-life score.
What had they discovered was when they used the more potent anti-platelet agent is there was about 29% that had no or minimal symptoms at 90 days versus 22% with aspirin, so they herald that as a benefit.
A couple of caveats about this. One is again, it was conducted in China where actually very few people have access to some of the therapies we routinely have. There were very few individuals that had imaging to show that they didn't have occlusion of a large or medium vessel, and more importantly, the follow-up was conducted primarily by telephone. A study in which in my opinion, the methods say it wasn't a really very rigorous study, and the results are really fairly modest. By the way, it increases the risk of substantial bleeding.
Then when you looked at functional outcome at 90 days, did they have a better quality of life? The answer was no. I'm not sure it would have much relevance to the stroke patients in the United States.
Elizabeth: We need to mention, of course, that's in the New England Journal of Medicine. I guess one question I would have is, relative to these small and medium-sized kind of events, what can we do?
Rick: Well, Elizabeth, that's part of the problem in that if you detect a clot in a large or medium-sized vessel you can extract it with a device or give an agent that dissolves the clot. One of the concerns is if you dissolve it, does it go down into the smaller blood vessels and what do you do? We know that anti-platelet agents like aspirin are beneficial and this was an attempt to prove that a more potent anti-platelet agent was even better. Unfortunately, I'm not sure it does that. In fact, this agent has been used in other studies and it hasn't been beneficial. I'm concerned that the results of this study really aren't applicable to most of the individuals we see in the United States with small strokes.
Elizabeth: More work to be done, no doubt. Let's turn to Nature Medicine. This is this question of, "Gosh, should we put kidneys for transplant that are retrieved from deceased donors on ice, or should we use these things that are called normothermic machine perfusion devices?"
The reason this was of interest to me particularly is because I still remember hearing a talk a few years ago where surgeons who performed lung transplants regularly were extolling the virtues of normothermic machine perfusion, just talking about how they really improved the viability of the organs and seemed to be associated with better long-term outcomes.
There is no question, of course, that we have a dearth of kidneys for transplant and this is what causes them to be retrieved from people after circulatory death. Generally, they are stored on ice, but this renders them susceptible to cold ischemic injury before they actually are transplanted.
In this study, what they did was -- they didn't do this completely so it's kind of, that's one of the caveats that I found here -- they put them in these normothermic machine perfusion devices at some point prior to their transplantation, so that's this caveat. There were 338 kidneys that were allocated in this case and they said, "Does it make a difference in terms of a need for dialysis following transplantation?" Essentially they found that the outcome was the same.
Rick: When you put a kidney on ice, you try to slow the metabolism. Unfortunately it depletes the energy stores. Then when you put it into the body immediately, the kidney doesn't have their proper energy stores, and there are also some other chemicals or proteins that could prevent the kidney from functioning normally.
So what they did was they put it on ice to transport it from one place to the other, and then before they transplanted it, then they gave it 1 hour of normothermic perfusion to try to simulate what the normal circulation could do, with the hope that would make the graft more viable. As you mentioned, it doesn't.
With regard to the use of normothermic perfusion in other organs, it may have some benefit, for example, in liver transplantation, but this study suggests, at least the way it's used here, that it doesn't help with regard to kidney transplantation.
Elizabeth: I think it's important to note here also that this is a U.K. study and the authors talk about what they do there, their practice with regard to withdrawal of care and the harvesting of organs for transplantation. They talk about this thing, the agonal period, that's the time between withdrawal of treatment and circulatory arrest, and that those are likely to be really critical here. They were prolonged in the U.K. the way that they do it, and so they say already their practices may have influenced how well these kidneys were going to function in any case.
Rick: Absolutely. What you want to do is you want to transplant the kidneys as quickly as possible, you want to have them be underperfused or hypoxic for a minimal amount of time, and also to minimize the amount of time that they are placed in cold as well.
Elizabeth: Finally, then, let's turn to The Lancet, taking a look at nonalcoholic steatohepatitis.
Rick: What's called non-alcoholic fatty liver disease is the most common cause of chronic liver disease globally. It affects about half the people with type 2 diabetes and about 75% of people with obesity. The worsening condition of that is what's called non-alcoholic steatohepatitis where the liver cells are actually injured and then there's scarring or fibrosis. The unfortunate thing is that it leads to cirrhosis, liver failure, and cancer. With the increasing rise of obesity and type 2 diabetes, we're seeing a lot more NASH.
This is a study that looked at bariatric surgery versus lifestyle intervention in people with NASH as an attempt to resolve the steatohepatitis. Observational studies suggested that bariatric surgery could actually improve NASH.
They did a multicenter, randomized trial at 3 major hospitals in Italy, people 25 to 70 years old who were obese, either with or without type 2 diabetes, and they had confirmed NASH; they did a biopsy to confirm it. Then they randomized it to either bariatric surgery, with what's called a Roux-en-Y or a sleeve gastrectomy, or a lifestyle intervention. They looked at them in 1 year doing a repeat liver biopsy. What they discovered was that those had the bariatric surgery, about 70% of them had histological resolution of NASH without worsening fibrosis, as opposed to 20% in the lifestyle intervention group.
Elizabeth: I of course need to ask, what about BMI?
Rick: Elizabeth, that's the important thing. When you looked at individuals that had resolution, it was those that really had lost about 20% or more of their body weight. Few people did in the lifestyle intervention; that is, the average weight loss was about 5%, whereas with the bariatric surgery it was closer to about 30%.
Elizabeth: One thing that of course is of concern to me is that some NASH takes place in people who are of normal weight. I'm wondering about the impact of something like this in somebody who already is fine with regard to their BMI.
Rick: Elizabeth, it's a good question. This doesn't address that, because this is specifically limited to individuals that have obesity. Whether those procedures would be helpful in people without obesity is really unknown.
Elizabeth: We need something for those folks too. On that note then, that's a look at this week's medical headlines from Texas Tech. I'm Elizabeth Tracey.
Rick: And I'm Rick Lange. Y'all listen up and make healthy choices.