Chinese Compound for MI?; Knee Pain Management

Derick Alison
Derick Alison
18 Min Read

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 a Chinese compound for heart attack, use of convalescent plasma in ventilated patients with COVID, management of knee pain, and a new colorectal cancer screening test.

0:37 Convalescent plasma in severe early COVID

1:36 Mortality of 35% versus 45% with placebo

2:35 Cocktail of antibodies?

3:30 Use of traditional Chinese medicine in MI

4:32 Followed for 1 year

5:32 Most commonly prescribed worldwide

6:32 Need to define active agent(s)

7:12 Treating knee pain

8:12 Knee replacement

9:12 For meniscal tears

10:07 New colorectal cancer screening test

11:07 12 month duration

12:07 Most start as polyps

13:12 End


Elizabeth: Can a Chinese herb help in folks who have one type of heart attack?

Rick: The evaluation and treatment of knee pain.

Elizabeth: A new multi-target stool RNA test for colorectal cancer screening.

Rick: And using convalescent plasma to treat individuals with COVID-19 who are on a ventilator.

Elizabeth: That’s what we’re taking 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: 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, of course, we’re going to turn right to the New England Journal of Medicine and take a look at this really perennial issue of the utility of convalescent plasma in folks with COVID-19.

Rick: Elizabeth, we have talked about this before. There have been some studies that suggest that it may be helpful and some that haven’t. Sometimes it’s applied to individuals with new onset COVID or more severe COVID and the convalescent plasma has been different as well.

This, I think, is one of the more rigorously done studies in which they use convalescent plasma — that is, plasma from individuals that have recently been infected with COVID-19 — to treat individuals that are severely affected. These are people that have acute respiratory distress syndrome and they are on a mechanical ventilator.

They used convalescent plasma that had a high titer of antibodies, 475 patients. They all received glucocorticoids, which is routine therapy, and half received convalescent plasma with an antibody titer that was at least 1:160. The other half received placebo. What they discovered was the mortality in the convalescent group was 35% at 4 weeks and 45% in those treated with placebo. The group that particularly benefited were those that received treatment within 48 hours.

Elizabeth: This issue, of course, [is] ongoing. I can’t even remember how many times we talked about it in the initial phases of the pandemic because it was one of the only tools in the armamentarium. What I’m wondering is, with analysis of the antibodies that are in this, is it possible to recreate this other than a convalescent plasma collection?

Rick: That’s been done already and people have received different types of antibodies, and that has been helpful. As you’re aware, as the COVID-19 virus evolves, sometimes those antibodies, which are very specific, aren’t as effective. The value of convalescent plasma is the antibodies are more heterogeneous and they are more likely to address the various types of COVID.

Elizabeth: What about if we develop, and I’m going to call it, a cocktail, even though I have been corrected in calling things cocktails. They imply “This is going to be a lot of fun” versus “This is going to be a rather serious treatment.” The other question I have is, do we have a complete analysis of convalescent plasma that might demonstrate that there are other factors that are in there outside of the antibodies that might also be impacting the course of the disease?

Rick: As you allude to, it’s heterogeneous, different antibodies and different factors.

Elizabeth: I just finally add this one thing, and that’s that at the beginning of any pandemic — and undoubtedly we are going to witness another one — this collection of convalescent plasma from those who are lucky enough to have survived the infection is probably a good strategy as we’re trying to develop other therapeutic agents.

Rick: Absolutely, because the convalescent plasma antibodies are evolving as the COVID-19 virus changes.

Elizabeth: Let’s talk about something else that impacts many, many people, in JAMA. This is the use of a traditional Chinese medicine compound that’s called Tongxinluo in folks who have had an ST-elevation myocardial infarction.

This was a powerful study in its structure in that it was randomized, double-blind, and placebo-controlled. These were folks who had a STEMI and they were treated within 24 hours of symptom onset from 124 hospitals in China. Patients were randomized 1:1 to receive either Tongxinluo or placebo orally for 12 months. Their loading dose was 2.08 grams after randomization. I mention that because of the side effects we’ll discuss in a second. Then they were also treated according to STEMI guideline direction in addition to this particular supplement.

Their primary endpoint was 30-day major adverse cardiac and cerebrovascular events that they abbreviate MACEs. These were a composite of cardiac death, MI, emergent coronary revascularization, and stroke. They followed these folks every 3 months to 1 year. Ultimately, they ended up with almost 4,000 people randomized half and half to the Tongxinluo and the placebo. The mean was age 61 years, 77% of whom were male.

What did they show? That, in fact, the supplement did reduce their major endpoint. The relative risk reduction was 36% for their primary MACE endpoint, 65% for recurring MIs, and a 23% lower rate of all-cause mortality that barely missed statistical significance at 1 year. Most of the adverse side effects were mainly related to stomach discomfort and nausea. At first blush, it looks like it might be a pretty powerful intervention and I know you’re about to poke holes in this, so let’s hear it.

Rick: Absolutely. First of all, I’m glad we’re doing randomized trials on what are considered traditional medications because they remain, I’m told, the most commonly prescribed therapeutic agents worldwide. There are almost 13,000 different traditional Chinese medicines. This particular one is extracted, concentrated, and freeze-dried from seven plant and five animal products including the dried bodies of cockroaches, centipedes, leeches, cicadas, and scorpions. Wow!

Where does this fit into our traditional treatment of what you call STEMIs or what we would call heart attacks? Well, first of all, this was all Chinese patients. Is it applicable to others that have a different genetic background or different lifestyles, or different cultures? We don’t know.

Secondly, this is a very low-risk population. In fact, over the course of the year, none of these individuals needed to have revascularization, which is very unusual in the United States. Usually about 20 or 30% do. In the United States, about 90% of people are given guideline therapy: beta-blockers, ACE inhibitors, and angiotensin receptor blockers, medications we know are beneficial. In this group of patients, only about a half or only a third of patients received those.

Ultimately, we’re going to need to define the active agent or agents in that extract that could be beneficial. It’s a study that poses a lot of questions and in my opinion doesn’t give a lot of answers yet.

Elizabeth: Especially when you look at the compounding of this stuff. It just seems like, really? That’s not to discount that there could be something in there that’s really active. It’s just that there is a lot of, what I’m going to call, a “yick” factor because it is that kind of crazy mixture and we’ve got a lot of trouble already with our FDA regulating what are categorized as supplements. It’s hard for me to imagine how something like this would be regulated.

Rick: Yep, and again it’s approved in China. What I don’t want people to do is hear about this in the news and try to get it online.

Elizabeth: Remaining in JAMA then, let’s take a look at, “Wow, what’s the best way to treat the knee?”

Rick: The authors took a look at the literature from the last 10 years looking at how to treat knee pain. They summarized, I think, in a really good way what the current evaluation of treatment of knee pain should be. Knee pain, which affects over 650 million people worldwide, is one of the most likely diagnoses in individuals over the age of 45 and somewhere between 10% to 15% visits are for knee pain. The most common causes are knee osteoarthritis, what’s called patellofemoral pain, and finally meniscal tears, usually medial meniscal tears.

Most of these could be diagnosed just on the basis of clinical information and an exam. They don’t usually require x-rays.

Treatment for these is usually not surgical therapy first. First-line management involves physical therapy, weight loss if the person is overweight, education, and self-management programs to empower patients to better manage their conditions. Even when individuals undergo a knee replacement, somewhere between 10% and 40% over the next 3 years will have recurrent knee pain. Conservative therapy is just as good or better than surgical therapy in most cases.

Elizabeth: When is it appropriate to go forward for either more sophisticated imaging or additional strategies for management?

Rick: For knee osteoarthritis, it usually has no more than 30 minutes of morning stiffness. If someone has prolonged joint stiffness, resting pain, they have calcium pyrophosphate crystalline deposition disease, there is rapidly progressive osteoarthritis, or there is a change in the clinical characteristics — those are circumstances that don’t usually fit into one of these three categories. They would indicate that further diagnostic evaluation — usually some labs and radiographic imaging — would be indicated.

Elizabeth: How about moving into either knee arthroscopy or knee replacement?

Rick: For osteoarthritis and for patellofemoral syndrome, knee arthroscopy isn’t particularly useful. For meniscal tears, one can undergo knee arthroscopy or knee replacement. If you can maintain the meniscus, people usually have a better outcome. For individuals in whom the meniscal tear is extensive or there is severe bone-on-bone rubbing, or severe pain that doesn’t respond, those are individuals in whom knee replacement might be considered.

Elizabeth: Any notions on future directions here? Because we’re reported on before things like stem cell injections and other strategies to kind of head off knee osteoarthritis.

Rick: Yeah. In fact, they looked at the studies that looked at putting plasma, purified plasma protein, in there or stem cells. The results really haven’t shown that it’s been very useful. There is still a lot more that we need to discover that would help hopefully identify areas we could regenerate synovium or cartilage, but at this particular time we don’t have anything.

Elizabeth: Sounds like conservative strategy first then.

Staying in JAMA, let’s finally turn to a phase III trial of, it sounds like, a test that’s going to soon be on the market. It’s a phase 3 clinical trial of a colorectal screening cancer test that’s abbreviated CRC-PREVENT, a blinded, prospective, cross-sectional study looking to support a premarket approval application for this particular class III medical device.

8,920 participants who all completed this, what they abbreviate, mt-sRNA test. It incorporated a commercially available, fecal immunochemical test (FIT), concentration of 8 RNA transcripts, and participant-reported smoking status. They collected stool samples from these folks. They completed a colonoscopy at their local endoscopy center. They compared these results from the tests, positive or negative, with index lesions observed on colonoscopy.

Over the course of 12 months, people 45 years and older were enrolled in this clinical trial. Their primary outcome included the sensitivity of this test for detecting colorectal cancer and advanced adenomas, and its specificity for no lesions on colonoscopy. Their mean age of these folks was 55. They had a fairly decent distribution of ethnicities.

Of course, out of all of these people, only 36 of them had colorectal cancer and 6.8% of them had advanced adenomas. This sensitivity for detecting colorectal cancer by the test was 94%, advanced adenomas 46%, and specificity for no lesions on colonoscopy 88%. It compares well with currently available tests for screening for colorectal cancer.

Rick: Colorectal cancer is the second deadliest cancer in the U.S., causing over 50,000 deaths. It can be prevented because most of the colorectal cancers start as polyps, or what you call adenomas. If we can detect the adenoma and remove it, we can prevent colorectal cancer. Or if we can detect it early, we can treat it before it becomes widespread.

The FIT test uses DNA detection of markers that would indicate either colorectal cancer or adenomas. This new test uses RNA. Here is the advantage of this particular test: colorectal cancer is showing up in individuals that are younger than previously seen. This particular test is sensitive and specific not only in those over the age of 50, but those between the ages of 45 and 50. The FIT test has never been tested in that patient population. We know that adenomas can’t be detected in that young group as well with FIT, but they can be with this particular test. I think that this will replace the FIT test.

Elizabeth: On that good-news note then, 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.

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