Extreme Temps and Particulate Matter in Fatal Heart Attacks; Impact of Thymectomy

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 the role of the thymus in adults, alpha-gal syndrome, AI and breast cancer screening, and extreme temperatures and particulate matter in fatal myocardial infarction.

Program notes:

0:36 Thymectomy in adults and its impact

1:36 Compared thymectomy versus not

2:36 Preoperative infection, cancer factored out

3:36 Keep in mind in cardiothoracic surgery

4:20 Extreme temperatures, particulate matter, and myocardial infarction death

5:23 Increased as much as 70%

6:23 Synergistic effects

7:19 Alpha-gal syndrome

8:20 Tests submitted from residences in the U.S.

9:20 Pork and beef, sometimes gelatin capsules

10:20 Diagnosis by allergist

10:30 Artificial intelligence (AI) and mammograms

11:30 Group that had AI reduced radiologist workload

12:30 Improves diagnosis

13:00 End

Transcript:

Elizabeth: What’s the point of the thymus in an adult?

Rick: Do extreme temperature events in particulate matter change the risk of dying from heart attack?

Elizabeth: What is alpha-gal syndrome and why is it increasing?

Rick: Using artificial intelligence to detect breast 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: 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, with your assent, I would like to start with the New England Journal of Medicine because the editorialist — here’s the spoiler alert — calls this paper seminal. It also was hugely educating for me. It’s called “Health Consequences of Thymus Removal in Adults.” As we’re aware, the thymus is a gland that in children is really important for the development of T cells, the T cell component of immunity.

It turns out that we’ve watched this thing, as we do lots of dissections and anatomy, in adults involute and become vestigial in most of us as we age. Everybody kind of thought for many years, wow, this thing isn’t really worth anything. If we slice and dice it when we’re in there anyway, especially during any kind of thoracic surgery, it’s not going to have much of an impact.

In this study, they looked at this routine removal of the thymus, which happens in a variety of surgical procedures, and then they evaluated the risk of death, cancer, and autoimmune disease among those patients who had undergone thymectomy as compared with a demographically matched group of controls, who also had similar cardiothoracic surgery, but their thymus was left intact. They had 1,146 patients who had undergone thymectomy and a matched control group, and this was their primary cohort.

Startlingly, at 5 years after surgery, all-cause mortality was higher in the thymectomy group — specifically 8.1% versus 2.8% in those folks who had the same kind of situation but didn’t have their thymus removed. Cancer, the thymectomy group, was 7.4% versus 3.7%.

They also looked at production of the CD4 and CD8 lymphocytes, the T cells and pro-inflammatory cytokines, and we’re also seeing that there are distinct changes with those. They factored out this issue of preoperative infection, cancer, or autoimmune disease and excluded that from their analysis, and they still found that this all-cause mortality was higher in the thymectomy group. Pretty amazing I think.

Rick: Elizabeth, it is. As you mentioned, we were always taught that the thymus was important when you’re a kid, and then it’s one of the first organs to atrophy. For our listeners to know, it just sits in the front of the chest wall. When people had cardiac surgery done, they just take the thymus out. Little did we know that it looks like it still plays an important part in immune regulation — perhaps the prevention of cancer, but certainly in preventing immune responses.

It doesn’t make very many T cells. The thought being that perhaps as T cells from other organs circulate through the thymus it somehow conditions them to be more self-tolerant, less likely to provoke autoimmune diseases and less likely to provoke inflammation based on this study. As you mentioned, this really is a seminal study.

Elizabeth: I think clearly this is going to be changing practice regarding removal of the thymus, vestigial or not, and I think it’s something people really need to keep in the front of their consciousness if they’re going to have cardiothoracic surgery.

Rick: Yeah. Most people wouldn’t be aware that the thymus is going to be removed, because it was just thought to be an atrophied organ, but this has implications for thoracic surgeries and cardiothoracic surgeons. Unless it needs to be taken out, don’t, because it still plays a role in regulating our immune system.

Elizabeth: Would you say that we need … this is a big study and it’s very carefully done. Do we need confirmatory studies on this?

Rick: Elizabeth, again, I think it’s a very good study. I think the evidence out there is pretty convincing. What we need to do now is to disseminate the information to the individuals that are most likely to be influenced, and those are the surgeons.

Elizabeth: Truly spoken. Which of your two would you like to go to?

Rick: Let’s talk a little bit about extreme temperature events, since the country seems to be embroiled in one or more. We know that extreme temperature events, whether it be extreme heat or cold, have been linked to the incidence of having heart attacks. They are increased, but no one is really asked whether it increases the risk of death from heart attack, and no one has really looked at how particulate matter can also affect events during extreme temperature.

What these authors did is they looked at over 200,000 deaths in a particular province in China that occurred over a 5-year period. They had very detailed data and they were able to look at whether there were any extreme temperature events, either extreme heat or cold, and also to look at the particulate matter during those particular times, and then look at whether it increased the risk of heart attack death in comparison to times that didn’t have extreme heat.

What they discovered is that the extreme heat could increase the risk of heart attack death by as much as 74%. Extreme cold could increase it by as much as 12%. By the way, the more extreme the temperature change or the longer the duration, the more likely it was to increase the risk of dying from a heart attack. If you throw in particulate matter, especially during excessive heat, it also had a synergistic effect.

In fact, they estimated that almost 3% of heart attack deaths were attributed to exposure to extreme temperature events and particulate matter. It’s more likely to occur in women and older adults who were more vulnerable to the extreme temperature events and the particulate matter.

Elizabeth: From the biological plausibility perspective, clearly those little particles get in there and they’re pro-inflammatory, so we have an increase in all those inflammatory factors. Outside of that, what would you say with respect to the myocardial infarction risk?

Rick: Not only does the particulate matter increase inflammation but also excessive heat does as well. It activates things in our blood vessels that may make blood more likely to coagulate, it increases blood flow, and for extreme cold it actually causes the blood vessels to constrict and the blood pressure to go up.

Furthermore, we know that it increases the risk of heart attacks in and of itself. We just really had looked to see whether it increases the risk of heart attack deaths and whether there were synergistic effects with particulate matter.

Elizabeth: Of course, this begs the question of what exactly we can do about this, because, for example, right now we have all these wildfires in Canada and here in the U.S. we’re enjoying not just heat, but a lot of particles.

Rick: They weren’t able to look to see whether adaptive behaviors were used, putting someone in air conditioning or staying indoors when there was a lot of particulate matter, so we really don’t know whether those things will actually affect this right or not. That’s the data that we need.

Elizabeth: And have a high index of suspicion when someone comes to the ED [emergency department] — especially a woman with oftentimes atypical symptoms of heart attack and have some suspicion that that might be taking place, I would add.

Rick: A good point, Elizabeth.

Elizabeth: Let’s turn to Morbidity and Mortality Weekly Report. This is a look at alpha-gal syndrome. This is a look at the geographic distribution of suspected alpha-gal syndrome cases in the U.S. between 2017 and 2022. Well, what is this anyway? This was the first time I ever heard about it. It’s an emerging, tick bite-associated, allergic condition and it is characterized by potentially life-threatening, IGE [immunoglobulin E]-mediated hypersensitivity to this sugar that’s called galactose-α-1,3-galactose. OK — they abbreviate that as alpha-gal.

This is found in most non-primate, mammalian meats and products derived from these mammals. They have variable symptoms and severity of, let’s call it AGS, and there is no treatment or cure that’s currently available. How often is this happening here domestically, and where is that happening?

They looked at this data for tests that were submitted from residences in the United States and these corresponded to just shy of 300,000 persons. Overall of those tests submitted, almost 31% received a positive test, and the number who got a positive test increased over this time period from 13,000-plus in 2017 to just shy of 19,000 in 2021 — largely occurring in southern Midwestern and mid-Atlantic U.S. states and probably going to have an increasing distribution as we experience warming and ticks are making their way.

By the way, the Lone Star tick is the culprit for the majority of this.

Rick: There are other ticks that have also been detected to be infected as well. What happens is people develop symptoms — hives or an itchy rash, nausea, vomiting, heartburn, diarrhea, cough, even anaphylaxis — about 2 to 6 hours after eating meat or dairy products. It’s pork and beef, but it can also occur with exposure to dairy products or even gelatin capsules — i.e., some of the medications we have because they have a meat protein in them. As you mentioned, there is no treatment; we just tried to prevent the tick bite.

This is important because it identifies about 110,000 cases over the last decade, which is probably an underestimate, because, first of all, the physician has to have a clue that that may be a possibility. About three fourths of physicians really don’t even know about AGS. It’s estimated as many as half a million individuals may have developed AGS over the last decade.

Elizabeth: We definitely, as you said, really need to increase the awareness. It was very interesting in a survey of healthcare providers in the U.S. that 42% had never heard of AGS and 35% reported that they were not too confident in their ability to diagnose it or to manage patients with the condition. That’s a rather daunting lack of knowledge.

Rick: It is. It’s usually diagnosed by an allergist, but a good primary care physician that takes a detailed history, a physical exam, you can actually obtain a blood test that looks for this specific antibody.

Elizabeth: Finally, let’s turn to the role of AI in mammograms.

Rick: We know that if you catch breast cancer early in its early stages, it’s more likely to be cured. Hence, we use mammograms. Over the course of years, physicians go through millions of mammograms looking to see abnormal breast tissue that might have a high suspicion for being breast cancer. What that means is that mammograms are oftentimes read by two radiologists because you just don’t want to miss it.

Well, the question is we know that artificial intelligence can do many of the tasks that we do. What these investigators did is they said can AI do just as good a job at detecting breast cancer as our routine of having two radiologists? They had 80,000 women. They first had the mammogram done. Half of them had AI read it. If it was considered to be low-risk, they just had one radiologist confirm that. If it was high risk, they had two radiologists look at it.

Here is what they discovered at the end of the study. The cancer detection risk was similar between both groups. The false-positive rate was similar. But what happened in the group that had AI is they were able to reduce the workload of the radiologists by about 44%.

Elizabeth: Clearly, the hard outcome here is do AI-read mammograms have the same reduction in death from breast cancer in two separate groups.

Rick: That’s a study that takes 10 or 15 years. They are looking at what’s called the interval cancer rate — i.e., if your first scan says it’s not there and then your subsequent follow-up scan says it’s there, that’s called an interval cancer, and you want to detect those. They oftentimes can be more aggressive. But then you go back and you say, “Gosh, was it there on the initial one and we just missed it?” That’s the study that will tell you whether the AI-generated reading is just as good as the radiology reading, or more importantly, is it better. That’s probably going to be the case.

Elizabeth: I think there is no question that we’re going to be using these kinds of tools in order to alleviate the workload on the healthcare workforce for sure, and also we’ve shown in other arenas that it actually improves the diagnosis.

Rick: It does because there is machine learning. You take the errors and basically you tell the machine you didn’t do that right and it has the ability to correct itself, so it continues to get better. Let’s take a step back and note that not all AI is the same.

Elizabeth: We’ll be seeing more about it, for sure. Let’s just mention this is in Lancet Oncology.

On that 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.

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