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 cognitive function, diet and exercise, intermittent vigorous exercise, bispecific antibodies, and weight loss, exercise and osteoarthritis pain.
Program notes:
0:43 New bispecific antibodies
1:44 Two arms that can be manipulated separately
2:44 Will antibodies be patient specific?
3:00 Vigorous intermittent lifestyle physical activity
4:00 The more VILPA the lower your risk
5:01 Also in exercisers
6:00 Osteoarthritis pain, exercise, and weight loss
7:00 Both groups experienced pain reduction
8:00 If it showed a benefit
8:18 Mindfulness training, exercise, and cognitive function
9:18 Hippocampal volume examined
10:20 Delay cognitive impairment?
11:28 End
Transcript:
Elizabeth: Do mindfulness and exercise have any impact on cognitive functioning in older adults?
Rick: What about diet and exercise in people that have knee pain from osteoarthritis?
Elizabeth: Can you just do things like take a quick flight of stairs and achieve some benefits?
Rick: And a new use of T cells to treat people that have refractory cancer.
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, where do you want to start?
Elizabeth: How about if we start with the New England Journal of Medicine? We’ve got a couple studies we are going to kind of treat together.
Rick: This is a new type of antibody. Here is what it does. It grabs onto the cancer cell with one arm and it grabs onto the T cell with the other arm, so it puts them in close proximity so the T cell can actually attack the cancer cell. These are called bispecific antibodies.
They have been tested in two types of cancer in individuals that had lymphoma or multiple myeloma. In both cases, these were individuals that had been refractory. They have recurrence of their cancer and sometimes they had a second line therapy. They were given these bispecific antibodies. About 40% of individuals had a complete response that is a cancer cure. In about 80% of these individuals, it was durable for at least a year. These are off the shelf. We can actually make these bispecific antibodies to specific cancers and to specific receptors.
Elizabeth: Right. Let’s just remind people about the architecture of a lot of antibodies where it kind of looks like a Y. It has two arms and we can manipulate those arms separately. We use this expression when we talk about generating antibodies — “raising antibodies.” Let’s talk about raising these antibodies and how onerous that is or isn’t, and how specific it is or isn’t.
Rick: We can get these antibodies very specific. This particular antibody for lymphoma attacks only the B cells — this is a B-cell lymphoma — and is very specific for grabbing T cells. This is a type of manufacturing process that years ago took a lot of effort, but now it’s fairly routine. It’s so routine that what we need to do is spend more time identifying receptors that are specific to a cancer and doesn’t have cross-reactivity.
For example, the multiple myeloma bispecific antibody, the receptor on the multiple myeloma cells is also present on the skin and also in the nails. One of the side effects are people develop a rash. We want to try to find receptors that are very specific to the cancer and that’s what we want to target the antibodies towards.
Elizabeth: We, of course, are learning that everybody’s cancer is unique. Will there be a day when we raise antibodies that will be specific to a patient?
Rick: Elizabeth, l think that is not far off.
Elizabeth: Something to look forward to.
Let’s turn from here to Nature Medicine and this is something that appeals to me: a study that takes a look at the association of wearable-device-measured vigorous intermittent lifestyle physical activity. Don’t you love that? Vigorous intermittent lifestyle physical activity and its association with mortality. Of course, they have an acronym that they use for that. It’s VILPA.
This is our study that’s fast becoming our favorite study, the U.K. Biobank study, yielding all sorts of very interesting information. The subset that they looked at in this case were 25,000+ non-exercisers about 62 years of age and slightly more women than men. Their average follow-up was just shy of 7 years and during that time 852 deaths.
This VILPA was inversely associated with all-cause mortality, cardiovascular disease, and cancer mortality. The more VILPA that you engaged in, the lower your risk of having any of these other outcomes.
The really interesting news is that it wasn’t intentional. “Hey, I’m going to carve out a couple hours and go to the gym.” This was really what I had initially said in the intro. Could you just go run up and down the stairs for 2 or 3 minutes and do that several times during the day? This is a pretty powerful reduction that we see in this study.
Rick: I must confess I was a little surprised at how significant the reduction was. You’re talking about 25% to 30% to 40% of reductions. These are bursts of activity, but you do it three or four or five times a day, and for the week that’s about 30-35 minutes. The next thing you know you’ve reduced mortality substantially.
But we’re talking about, “Let’s park your car at the end of the parking lot and walk fast to the store” or “Let’s walk up a flight of stairs instead of taking the elevator.” These very short bursts of activity, but done frequently throughout the week, really add up.
This improved mortality not only in non-exercisers, but did you notice they also did this analysis of people who were exercisers as well, and even in them it was also beneficial? That’s pretty profound.
Elizabeth: I like to think about doing this myself. Because as both of us are usually — when I’m on the unit I’m not of course desk bound, but at other times I am. I like to get up and actually stretch and move and do something a little bit different. I’m going to start intentionally doing these kinds of things. I’m thinking about stairs.
Rick: Yeah. Many of us take an elevator up one or two floors, so we could take the stairs. I walk to the clinic to see patients. It’s a block away. I could walk a little faster. All these activities really add up. They mean something even though they are short periods of time.
Elizabeth: Right. Then I would also just note that these folks all had a wearable device that could capture it. If you’re thinking of treating yourself for something for Christmas and you need that motivation, maybe this is the thing to get.
Rick: Yeah. This is the first time that a wearable device has actually examined VILPAs and how they are related or associated with mortality.
Elizabeth: On to your next one, sir, that’s in JAMA.
Rick: The number of people that have osteoarthritis is actually pretty staggering. From about the last decade, osteoarthritis affected approximately 240 million people worldwide. They live with their symptoms an average of 26 years.
One of the recommendations we oftentimes make to these individuals is let’s get you on a diet to reduce your weight and let’s get you on a regular exercise program with the intention that in fact that will improve their knee pain. This was a study that actually assessed whether that was the case or not.
They randomly took over 800 individuals to one of two arms: a diet and exercise intervention, or what’s called an attention control group, and they treated these people for 18 months. In the attention control group, they met for an hour over a several-month period to just give them some ideas about what they ought to do to lead a healthy lifestyle. It wasn’t directed toward diet and exercise. At the end of 18 months, was your knee pain better? Then they looked at a bunch of secondary measures — in fact, seven different secondary body measures — and here is what they found out.
About 80% completed the trial. In both groups, the pain in the knee went down similarly. The individuals that had the diet and exercise were no better off than those who had the attention control just to leading a healthy lifestyle. Even though they lost on average about 14 pounds or more, it may be that diet and exercise really isn’t any better. Despite the fact we’ve been recommending it, it really doesn’t provide any additional benefit.
Elizabeth: Hmm. I guess I’m struggling a little bit with this, because I would have thought that if you unweight that poor, painful joint you would end up with less pain. Could we also account for those with the idea that if we started earlier, we might have a better result?
Rick: I’m going to take a step back and say you and I suffer from the same thing. We have a bias. If you ask me would I have been enrolled in the study, I would say, “Well, of course not,” because we know that diet and exercise are beneficial in people with osteoarthritis. So part of our prejudice is, we feel like it is and when it doesn’t happen we have to find a reason. If it had showed a benefit, we just take it at face value. But this shows our own prejudice.
Now, could it be done differently? Absolutely. Would it be any different? It’s really hard to say.
Elizabeth: I definitely agree with that and I’m always finding out where those biases are in many different aspects of life. Sticking with JAMA then, let’s go to the Effects of Mindfulness Training and Exercise on Cognitive Function in Older Adults.
This study examined whether using these techniques, mindfulness-based stress reduction, exercise, or a combination of both, improved this cognitive function. This was a 2 × 2 study design. They had 585 adults between the ages of 65 and 84 with subjective cognitive concerns. I think this is a really important aspect of this study.
They randomized these folks to 60 minutes daily of meditation, which seems like a lot to me, exercise with aerobic, strength, and functional components with a target of 300 minutes weekly as a minimum, a combined exercise and mindfulness-based stress reduction, or a health education control group.
They carried on this study for 18 months and they had group-based classes and home practice. They looked at some measures that were objective. For example, hippocampal volume and dorsolateral prefrontal cortex thickness. They also did a bunch of neuropsychological testing.
What they found was that of these — they had 5 pre-specified secondary outcomes. None of them showed a significant improvement with any intervention compared with those not receiving the intervention. Those older adults who come to you with subjective cognitive concerns, exercise, mindfulness, and a combination really don’t seem to have much of an impact.
Rick: Were you surprised at this, Elizabeth?
Elizabeth: I was. I thought that there might have been an impact of this.
Rick: Yeah. I was surprised, too, because there are other studies that show that exercise might be beneficial, especially in people that have known cognitive impairment. But as you noted, these people didn’t have dementia. They didn’t have cognitive impairment. They were just worried about it as many of us are. As we enter our older years, we’re saying, “What can we do to delay the cognitive impairment?” If you don’t have any, it doesn’t look like mindfulness training and exercise helps delay it.
In our previous conversation, you said, “Well, if we applied exercise and diet earlier to osteoarthritis, would it help?” Well, this is a great example of if we apply exercise and mindfulness training earlier, before there is any cognitive impairment, it doesn’t help and it doesn’t appear to be helpful.
One of the measures they actually used was, they did MRI imaging of the brain to see if those areas of the brain that are associated with this cognitive impairment were any different in terms of their size. Eventually, the brain shrank. It didn’t really matter.
Elizabeth: We have to, of course, congratulate JAMA on publishing two negative studies.
Rick: Yeah. Oftentimes, negative studies don’t get published. But these are helpful because we have biases about these things. We need to know if things aren’t helpful we need to know and direct our attention somewhere else, so I agree with you. We report on both positive and negative studies, especially those things that we have control over.
Elizabeth: 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.
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