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 Texas Tech Health El Paso, look at the top medical stories of the week.
This week’s topics include circular RNA to diagnose Alzheimer’s disease, a new agent for acute pain, trends in alcohol consumption in pregnant women, and diagnosing metabolic dysfunction-associated steatotic liver disease.
Program notes:
0:44 Novel agent for acute pain
1:44 After abdominal surgery and placebo, low, and high dose
2:46 Compared to placebo and opioids
3:19 Metabolic dysfunction-associated steatotic liver disease
4:19 Imaging with two techniques and plasma markers
5:19 Imaging and composite scores for staging
6:21 Identifying appropriate candidates for clinical trials
7:00 Alcohol consumption during pregnancy
8:00 Employed, tobacco use, and mental stress predicts
9:01 Never tested medicines for alcohol use in pregnant women
9:24 Early detection of Alzheimer’s disease with circular RNA
10:24 Can it identify those with the disease as well as those at risk
11:24 Almost 95% area under the curve
12:20 Use with tau it was even better
13:05 End
Transcript:
Elizabeth: Can circular RNA in blood help diagnose Alzheimer’s disease?
Rick: What do we know about the trends in alcohol consumption during pregnancy in the U.S.?
Elizabeth: How are we going to ultimately be able to diagnose non-alcoholic steatohepatitis known by a number of acronyms?
Rick: And early studies of a new medicine that may be effective for acute pain.
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 Health El Paso.
Elizabeth: Rick, I think everybody is interested in pain and in pain relief. And so I would like to turn first to the New England Journal of Medicine and talk about this novel medicine that may be helpful with that.
Rick: Typically, we reach for opioids to take care of acute pain, and of course they have side effects: nausea, vomiting, constipation, also the risk of abuse and addiction. When we compare them to the non-opioids analgesics, those non-opioids really have a marginal efficacy. It’s clear that those pain receptors have sodium channels in them, and if you can inhibit those, you can potentially provide new analgesia.
In 2025, there was a new agent approved by the FDA. There’s a related compound. It’s called LTG-001 — oral, it’s non-opioid, it’s much more potent, and it selectively inhibits the sodium channels — designed to deliver opioid-level analgesia without the side effects. How effective is it? And that’s what this phase IIb trial addressed.
Three hundred and forty-three individuals that had had abdominal surgery and randomized them to placebo, a low dose of this new agent, a high dose of this new agent — both given every 12 hours — or typical opioids every 6 hours. The new agent and the high dose was much more effective than placebo. And in fact, it was much more effective at the low dose. It seemed to be more effective than opioids. They were less likely to need additional intravenous opioids because they had breakthrough pain. The effect for this new agent was in less than 1 hour you had the peak effect, whereas for the oral opioids it took about 2 hours.
Elizabeth: How was the dosing interval determined? Because you said it was every 12 hours?
Rick: It is. So you give a loading dose up front, and then it’s dosed every 12 hours, both for the low-dose and the high-dose group.
Elizabeth: And you were going to refer to the side effects.
Rick: No major side effects. The individuals that took the newer agent were more likely to have fever (7% vs 2%) and a higher incidence of presyncope, that is lightheadedness, and that was 6% in the new agent versus 1% in the individuals that took placebo.
Elizabeth: You just said in individuals who took placebo. So this was not in comparison to the opioid?
Rick: It was. So the four arms — high dose, low dose, the opioids, and the placebo — there weren’t enough patients to provide a statistical analysis, the high dose versus the oxycodone in terms of pain relief. But we know that those that took the high dose were less likely to ask for intravenous medication.
Elizabeth: I guess we’re going to be seeing some more about this one.
Rick: We need something that can treat acute pain without the side effects. We’ll need to confirm it in phase III, larger trials.
Elizabeth: Let’s turn to Nature Medicine, this ongoing, what are we going to call this anyway? Metabolic-associated steatotic liver disease? Rather awkward acronyms that are being used to describe this condition in the liver that we’re seeing a lot more often and is frequently related to obesity. Right now, what do you do in order to assess whether someone has that? Well, you might have to do a liver biopsy. Invasive by definition, they require lots of specialized training. There’s a high potential for bleeding and pain subsequent to it. People don’t like it. They don’t want to have a needle stuck in their liver to determine whether they have this condition.
So this study is looking at non-invasive biomarkers for metabolic dysfunction-associated steatotic liver disease. This is a multicenter study that’s looking at the diagnostic accuracy of imaging using magnetic resonance elastography, which I was not familiar with, and something called FibroScan, which is a vibration-controlled transient elastography (VCTE), serum biomarkers, and composite scores for steatohepatitis and fibrosis. They also looked at folks who had cirrhosis.
Among their 357 participants, they had a variety of fibrosis stages, and not surprisingly, it was easiest to diagnose the cirrhosis, the more advanced disease. The magnetic resonance elastography was pretty good. Their serum biomarkers tended to outperform imaging for identifying at-risk people who might develop this condition, while the imaging techniques and composite scores were better for staging advanced cirrhosis. Their metric, which is the area under the curve, none of them are really especially fabulous except for the advanced conditions. To me, it looks like there’s a lot of work that’s left to be done, and there’s a compelling argument for why we probably need to keep doing that work because there’s so many more people who are developing this condition.
Rick: Yep, and it falls, I’m going to say, basically in four stages where you just have fat. There’s a stage where you have fat and people are at risk of developing inflammation. There’s those that have active inflammation, and they can actually have fibrosis as well, scarring. And then those that are at the end stage, those that are actually cirrhotic.
The reason why you want to be able to identify those four categories is once someone’s reached cirrhosis, the treatment for that is very different. People that just have fat but no inflammation, you’d like to be able to identify it because that’s related to obesity and diabetes, so we’d like to control those. Those in the middle that actually have some fibrosis, we now have a medication to treat those individuals. And as you mentioned, it looks like imaging, where it looks at the liver stiffness, is the best way of identifying those individuals that would receive therapy, and it’s much better than the serum markers.
Elizabeth: The authors also note that enrolling folks in clinical trials, being able to identify that they are appropriately staged in order to do that and to assess interventions, is also a pretty compelling reason. I learned something out of this study, which is that all of it, the fat deposition, the inflammation, the fibrosis, are not uniform throughout the liver. You can miss the diagnosis if you don’t do the biopsy in the proper place in the liver.
Rick: You’re absolutely right. So if we can do this in a non-invasive way, it’s preferable, and that’s why this study is so important.
Elizabeth: Let’s turn to JAMA.
Rick: One of the current trends in alcohol consumption during pregnancy in the U.S., prenatal alcohol exposure is a leading preventable cause of neurodevelopmental disability in kids. Until this study was published, we had estimates, but nothing that extended beyond 2020. This particular study examined both the trends and the correlates of current alcohol use, binge drinking, and heavy drinking among pregnant women in the U.S. from 2011 to 2024.
If you looked at non-pregnant women of reproductive age, current alcohol use, binge drinking, heavy drinking all remained relatively stable. But if you look at pregnant women, the current alcohol use increased from about 9% to about 15%. Binge drinking increased from about 2.5% to 5%, and very heavy drinking went from about 0.5% to about 2.5%.
Now, they did look at correlates, and current alcohol use was most prevalent among those who were older, college graduates, those that weren’t married or partnered, those that were employed, and those that had tobacco use and/or frequent mental distress. This is a preventable cause of neurodevelopmental issues in young kids and infants.
Elizabeth: Yikes, I had no idea. It sounds like the population that’s most at risk to make this choice are people who probably also have information relative to how dangerous it is for children.
Rick: Right. This report likely underestimates severity of it because this is self-reporting and there’s a stigma associated with it. The authors recommend, if we know there’s a co-occurrence of tobacco and alcohol use, maybe we should be screening for alcohol use and binge drinking in individuals we know that smoke. Also, screening people for mental distress. Very sad because we have the information at hand, and to see this continuing to increase is very concerning.
Elizabeth: It sure is. I’m wondering what is the utility of medicines, for example, or other interventions, either during pregnancy or in the postpartum period, for intervening in the use of alcohol.
Rick: Yep. Administering medicines typically used for alcohol use in pregnant women has never been tested. I’d say we need to start beforehand. We need to begin to address the range of behavioral health needs that these women of reproductive age, even before they become pregnant. Part of it’s information, and part of it is meeting the health needs of these young women.
Elizabeth: Finally, returning to Nature Medicine, this is a snapshot of a research briefing looking at early detection of Alzheimer’s disease using circular RNA from the blood.
Clearly, we are all searching for an accurate way to diagnose and stage Alzheimer’s disease without doing a lot of invasive things or having to do repeated imaging. There has been a lot of promise with that, and we’ve reported on a lot of biomarkers that are in the plasma that are specifically for amyloid and tau, and their predictive ability.
This is a brief report that’s looking at circular RNA, which is a highly stable, brain-enriched, non-coding RNA that crosses the blood-brain barrier and can be detected in the blood. These investigators were looking at whether a reproducible blood circular RNA signature can identify people with Alzheimer’s disease and Alzheimer’s disease pathology, predict the progression to symptomatic Alzheimer’s disease in cognitively unimpaired people, and be specific.
They did this RNA sequencing in a large, well-characterized discovery cohort of 1,221 people, 816 of whom were cognitively unimpaired, and 405 who had clinically diagnosed Alzheimer’s disease. They used three independent circular RNA callers — that’s a new term for me — to identify these robust reproducible circular RNA transcripts. Then they found a 34-transcript circular RNA signature that can predict individuals with clinical diagnosis of Alzheimer’s disease and those with that pathology before the clinical symptoms.
It showed high accuracy in that, again, area under the curve, almost 95% of that area, higher than the predictive ability of plasma tau or amyloid PET. Probably have to do this again in some more people. They also demonstrate that the circular RNA levels begin to diverge roughly 2 to 4 years before clinical symptom onset. If we develop something that’s going to be effective at intervention, it might give us a little bit more lead time.
Rick: We’d like to have blood tests that can predict ahead of time when someone might develop Alzheimer’s. We’d like to be able to determine someone who’s at risk, intervene to either stop it or to slow it down.
So this is a really exciting study. There’s not a whole lot of detail in here. It’s one of those things that was rapidly published. But as you mentioned, it looks like in a large group of individuals, they determined the circular RNA associated with Alzheimer’s dementia and then tested it in two large cohorts. And by the way, if you use that and tau blood test, it was even better at detecting. They also need to determine what are the processes in the brain that cause this particular circular RNA and whether these are potential therapeutic targets, because maybe we’re targeting the wrong thing. Maybe instead of targeting amyloid or tau, we need to be targeting whatever the product is of the circular RNAs.
Elizabeth: On that note then, that’s a look at this week’s medical headlines for Texas Tech. I’m Elizabeth Tracey.
Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.
