TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, 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 COVID and autoantibodies, MRI and prostate cancer biopsy, use of an antibody in graft versus host disease, and treatment of opioid use disorder among Medicaid beneficiaries.
0:41 Autoantibodies to the exoproteome
1:40 Collection of extracellular proteins
2:40 Antibody against interferon
4:47 Decreased overdiagnosis
5:46 Cost and availability of MRI
7:46 Additional substance use disorders
8:46 Quality measures suggest it may not be effective
9:46 What can we do to help in states that are struggling?
10:22 Common complication of stem cell transplant treatment
11:35 Use of inhibitor increased response rate
Elizabeth Tracey: What do we know about autoantibodies and severity of COVID-19 infection?
Rick Lange, MD: Can you use MRI to target prostate biopsy in people suspected of having cancer?
Elizabeth: What’s going on with the treatment of opioid use disorder among Medicaid beneficiaries?
Rick: And the treatment of a common complication in people that have had stem cell transplants.
Elizabeth: That’s what we’re talking about this week on TT HealthWatch, 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: I’m Rick Lange, president of Texas Tech University of Health Sciences Center in El Paso, where I’m also dean of the Paul L. Foster School of Medicine.
Elizabeth: [INAUDIBLE 00:00:41] if we turn to Nature first. This is our COVID material for this week. This is a study that took a look at these things that I called autoantibodies and does the presence of auto antibodies predict, which is the question I think is really important, how severe somebody’s COVID-19 infection might be.
I learned some things from this study. I didn’t know before about this thing called the high-throughput autoantibody discovery technique that they call rapid extracellular antigen profiling, REAP for short. They used this technique to screen a cohort of 194 people infected with SARS-CoV-2, 172 patients with COVID-19, and 22 healthcare workers with mild disease or asymptomatic infection.
They were looking for autoantibodies against 2,700 plus extracellular and secreted proteins. This was another point of education for me, this collection of extracellular and secreted proteins that we’re carrying around all the time, is something that’s called the exoproteome. I didn’t know that either.
The upshot of the whole thing is they found that patients with COVID-19 had marked increases and autoantibody reactivities compared to the uninfected individuals. They had a very high prevalence of those autoantibodies against proteins that are involved in modulating our immune response, especially as cytokines, chemokines, complement components, and cell-surface proteins.
Some of those particularly against type I interferons appeared to directly contribute to COVID-19 pathophysiology. I think that this is a really important technique and that is perhaps helping us maybe at some point being able to identify people who might experience more severe COVID-19 infection because many of these were preexisting.
Rick: Some of these antibodies existed before the person got infected and then some of these autoantibodies developed after the infection. As you noted, at least one of the autoantibodies that was against interferon was associated with the increased viral loads and also extended duration of hospital admission, indicating that it impairs the virologic clearance.
They looked at several corollary antibodies in a mouse model. It also increased disease severity. Some of the autoantibodies that targeted tissue seemed to be associated with some of the clinical manifestations. Some people are actually suggesting that the detection of autoantibodies could actually predict who are the long-haulers. They’re actually studying this across the pond to see whether in fact the presence of autoantibodies predicts who the long-haulers will be.
Elizabeth: Really interesting. Then the question, of course, is what are we going to do about it?
Rick: At this particular point, there isn’t any targeted therapeutic, but it’s not likely to be a single autoantibody. As you said, these were antibodies detected against almost 3,000 proteins outside the cell. Whether it ends up being predictive or therapeutic still remains to be seen.
Elizabeth: Let’s turn to the New England Journal of Medicine. Which of your two would you like to start with?
Rick: Let’s talk about the prostate cancer screening. Screening men in the general population by using the prostate-specific Antigen (PSA), leads to a high degree of overdiagnosis. Can you use MRI to help define individuals, who should be biopsied, to prevent overdiagnosis at the same time where you’re not missing clinically-significant disease?
This was a large study, over 12,750 men enrolled, of whom over 1,500 had elevated PSA, a PSA over 3. They randomized them into two groups, one is men who would just get biopsied and the other group they sent them for an MRI and they only got biopsied if there was MRI evidence of cancer. They used the MRI to target the biopsy.
Using the MRI did not change the ability to find clinically significant prostate cancer, but it did significantly decrease the overdiagnosis of it. Let me put some numbers to it. I’m going to quote directly from the article. “If you took 10,000 men ages 50 to 74 that had elevated PSA, using the MRI to target the biopsy would result in 409 fewer men undergoing a biopsy, 366 fewer biopsies with benign findings, and 88 fewer clinically insignificant cancers.” That means this would be a 48%, a 73%, and a 62% lower incidence of finding cancers that you wouldn’t do anything about.
Elizabeth: We’ve been talking a lot about the utility of MRI in this prostate cancer world. I think there is abundant evidence outside of this study that also points to the utility of MRI. Clearly in this biopsy regimen, where it’s registered against an ultrasound and then used to target where these cores are taken, the question I always come back to — there are two of them — or concerns are one is the cost of MRI and the other is the availability of MRI.
Rick: Yeah. The nice thing about this particular protocol is it’s done pretty quickly. The whole thing is done in about 15 minutes. What about the cost of MRI? You have to weigh that against the fact that you’d have a reduced biopsy rate and less overtreatment. That offers potential cost savings that are likely to offset the additional costs associated with MRI.
Elizabeth: I think that this issue I have heard raised before though about interpretation of these results and availability to men all around the country, and certainly around the world, is a real issue.
Rick: You’re right. You’re only as good as your reading, whether that’s an ultrasound or whether that’s an MRI, or, quite frankly, whether that’s even the pathologist as well.
Elizabeth: I suspect we’re going to see a lot more expansion of it and I hope it really turns out to be something that helps reduce unnecessary treatment.
Rick: Reducing unnecessary biopsy, unnecessary treatment, especially in the setting of prostate cancer, that’s really important.
Elizabeth: Let’s turn to JAMA now, something else that I think is really important too. We know that in parallel with the COVID-19 pandemic there has also been a huge increase in the number of overdose deaths nationally and a lot of those are due to heroin. This is a study that took a look at trends in the treatment of opioid use disorder and they used the Medicaid population to examine this issue.
They gathered data from 11 states and they had over a million Medicaid enrollees, 12 through 64 years of age, from 2014 through 2018, so pre-pandemic. They found that about 42% of Medicaid enrollees with opioid use disorder were 21 through 34 years of age, about half of them were female, and 76% plus were non-Hispanic Whites.
Over 50% of them were eligible through Medicaid expansion and another 50%, or maybe the same 50%, had additional substance use disorders besides their opioid use disorder. Those folks who were able to receive medication treatment for this increased from just under 48% in 2014 — that was the composite number, it varied a lot between these states — to 57% plus in 2018.
They used as a metric of, “Hey, are these people really getting good treatment?” Whether they got 180 days of continuous medications and found that that did not significantly change during this period. They also noted that non-Hispanic Black enrollees had lower opioid use disorder medication use than white enrollees, while pregnant women had higher use.
I think what this study points out is that even pre-pandemic it looked like trends were increasing while there was all this energy behind expanding use of the multitude, the four agents really in particular, that are used to help manage opioid use disorder, but that the quality measure suggests, at least to me, that maybe it’s not as effectively used as it might be.
Rick: You’re right, Elizabeth. There are two issues. One is extending its use because we know that opioid use had increased during that time period, but then extending it to other quality measures, making sure it’s used as appropriately and as effectively as possible.
Also doing other things: availability of counseling, they use urine drug testing to see whether there’s recidivism, and then finally even preventing co-prescribing benzodiazepines. There was more counseling offered, more urine testing done, and less prescribing of benzodiazepine, so there was some improvement.
I am at least heartened that there is an increase treatment of opioid use disorder, at least in these 11 states, but there are some states that had a dramatic increase in opioid use disorder treatment and other states that really had negligible amounts.
These are Medicaid patients. Medicaid represents about 40% of the treatment of opioid use disorders. In my opinion, this is just the initial information. Now we need to dig down a little bit further to say what can we do to help those individuals in states that are struggling with increasing availability to treat?
Elizabeth: Right. I absolutely agree with you. I think it’s especially urgent now to get our arms around this.
Rick: I was surprised that there wasn’t any difference between urban and rural access, the opioid use disorder medication. The issue with regard to pregnant women is kind of interesting. Those women are more likely to be screened for the disorder and more likely to be seen by a physician during the period when they’re pregnant, be exposed to medications that can treat their disorders.
Elizabeth: I agree. Let’s turn then to your final one, back to the New England Journal of Medicine.
Rick: I represented this as a common complication of people who had stem cell transplants. These are transplants that are given to individuals that have oftentimes hematologic or bone marrow types of cancers.
One of the more common complications is that the graft, the stem cells that are administered to the patient, often attack the organs of the patient. This is called graft versus host disease.
The primary treatment is the use of prednisone or steroids. Unfortunately, in approximately 50% of patients, the graft versus host disease becomes refractory to steroids, or actually dependent upon steroids, so they can’t get off. There are therapies that can be prescribed.
Second, there are about 10 of them that are commonly available. One of the ones that has received recent attention is the use of antibodies. It gets a particular pathway called the Janus Kinase or JAK 1, JAK 2 pathways. That’s called a JAK inhibitor and this is the medicine ruxolitinib.
To evaluate its effectiveness in preventing the inflammation in the graft versus host disease, they did a study in 329 patients and they looked at the overall response rate to ruxolitinib versus any of the other 10 therapies that the physician would normally use.
What they discovered is the use of the JAK inhibitor increased the response rate from 25% to 50%. It improved what’s called failure-free survival from about 6 months to more than 19 months.
It’s a very well tolerated medicine. The only side effects were anemia and thrombocytopenia decreased platelet count or decreased hematocrit, but most individuals were able to continue on the therapy.
Elizabeth: That’s really good news. How was this medicine administered?
Rick: It’s given orally twice a day and is currently available for treatment of hematologic disorders. It’s not a new medication, which is a new application.
Elizabeth: We love those kinds of things. I am wondering about the expansion of this into other places where this JAK pathway is important.
Rick: That’s a great question. Getting behind the basic biochemistry or the basic pathways to understand how these common complications occur and to be able to target therapy.
Elizabeth: On that positive note, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.
Rick: I’m Rick Lange. Y’all listen up and make healthy choices.