Doc Discussions with Dr. Jason Edwards
THIS is the podcast you have been looking for! "Doc Discussions" are just what the title says they are: physicians from a wide range of specialties, talking about relevant, up-to-date medical topics, not to mention tips on habits to help you live your best life. Your host, Jason Edwards, MD, is a board-certified radiation oncologist with a PhD in cellular and integrative physiology at St. Luke's Hospital in St. Louis, Missouri. Dr. Edwards explores not only diseases but also suggests techniques to optimize mental and physical health for a long and good life. Real people. Real advice. Real good. This is Doc Discussions, with Dr. Jason Edwards!
Doc Discussions with Dr. Jason Edwards
From Crawfish to COVID: Tales from the Infectious Disease Frontline
What happens when a park ranger eats a raw crawfish on a dare? According to infectious disease specialist Dr. Matthew German, it can lead to a rare parasitic infection typically only seen in Tibet. This surprising case exemplifies why the most important qualities in medicine are persistence and doubt.
Dr. German joins oncologist Jason Edwards for a fascinating journey through the unexpected twists and turns of infectious disease diagnosis. With decades of experience treating everything from HIV to COVID-19, Dr. German shares how diseases often don't follow textbook descriptions, and why algorithms alone can't replace clinical judgment. "You have rules or guidelines, but they're not laws," he explains, emphasizing the dangers of pigeonholing diagnoses.
The conversation explores how non-infectious conditions frequently mimic infections, requiring doctors to maintain broad differential diagnoses. From autoimmune disorders like Familial Mediterranean Fever to immunotherapy side effects causing pituitary insufficiency, these medical mysteries demand both extensive knowledge and investigative persistence. Dr. German recounts his experience during the HIV epidemic's evolution - from the limited effectiveness of early AZT monotherapy to today's life-changing triple therapy regimens.
The physicians also tackle challenging topics including public mistrust in medicine, the complexities of doctor-patient communication across different educational backgrounds, and emerging threats like H5N1 avian influenza. Throughout their discussion, they return to a central theme: medical humility. Even brilliant doctors make mistakes when they become too certain of their diagnoses without considering alternatives.
Whether you're a healthcare professional, student, or simply fascinated by medical mysteries, this conversation offers valuable insights into how infectious disease specialists approach complex cases. The next time you hear hoofbeats, remember it might not be horses or zebras - sometimes it's a crawfish-borne parasite!
Hello, this is Jason Edwards. I'm here with Doc Discussions. This is my good friend, matthew German. Matt German is an infectious disease doctor here at St Luke's. He's highly respected and he treats a lot of patients with multiple different illnesses. Him and I share a lot of patients who've had HIV and have been immune, compromised and have cancer, but him and his colleagues are part of the infectious disease department here at St Luke's Hospital and if you're looking for an infectious disease doctor, you could find them at 314-205-6600. Matt, how are you doing today?
Speaker 2:I'm doing fine as far as I know.
Speaker 1:So my wife just went on a medical missions trip to Zimbabwe.
Speaker 2:Oh, wow.
Speaker 1:And as she came back she got sick and you know we were worried. Is this? You know measles, or you know it could be a slew of African-based diseases, and so it ended up being shigatoxin. But it made me think of you because you know you need a really smart doctor to kind of figure out what's going on with these cases.
Speaker 2:Well, I don't want my name associated with sugar toxin.
Speaker 1:And so you know, when people think of infectious disease doctors, they kind of think of a house MD. I think he was an ID doctor, Is that right?
Speaker 2:Generally, I get questioned about that.
Speaker 1:Yes, yeah, and it's probably annoying to some extent. No, no, no, I mean I'm that. Yes, yeah, and it's probably annoying to some extent. No, no, no, I mean I don't.
Speaker 2:I'm hard to annoy.
Speaker 1:Okay.
Speaker 2:Don't take that as a challenge, please.
Speaker 1:And so can you share like a more bizarre case or an unexpected case that you've encountered in your career.
Speaker 2:Well, I've encountered so many, but there are a few that stand out. But I will tell you that a lot of things that ID docs see aren't necessarily infections, because there's a lot of non-infectious diseases that mimic infections called in. We just have to keep an open mind. Unless it's completely obvious, like a big pneumonia or a big urinary tract infection, that's easy to diagnose. But a lot of times we're referred people who are just displaying either some fevers, white count or unexplainable symptoms and they think that maybe we can help solve it.
Speaker 1:Yeah, so what are some things, that kind of mimic infections that aren't?
Speaker 2:Well, I'll give you an example. I had a I'm going to say 53-year-old female, but I'm not sure, but she presented with intermittent fevers that would occur every few weeks to months. But she presented with intermittent fevers that would occur every few weeks to months, associated with other things like abdominal pain, and what she turned out to have ultimately was something called familial Mediterranean fever, which is an auto— well, it's an immunologic phenomena where there's certain checks and balances in the immune system and this one goes awry. So in general, the common symptoms would be intermittent fevers, abdominal pain.
Speaker 2:Sometimes they get a little bit of fluid in the abdomen. They get fluid in the chest sometimes, and it's a diagnosis. It gets fluid in the chest sometimes, and it's a diagnosis. We use genetics now, but it's also a diagnosis of exclusion. So often if you have people with fevers, you have to make sure they don't have other bacterial, viral, fungal causes before you can start looking in that direction for what we call autoinflammatory disorders. And there's like five or six of those that have been elucidated on, and Lord knows, with our gaining knowledge more about cytokines and immune system, that there may be others.
Speaker 1:Yeah, yeah, you know, I mean, as you're saying this, I think about the times that I've called infectious disease doctors and it's, you know the pathologist is known as the doctor's doctor, but for sure you guys are too. I mean, I think anytime I've got a hold of one of you guys that it, you know, it's I've been totally, you know, confused and really needed help, and it's it's good to know an infectious disease doctor.
Speaker 2:Well, thank you. It's always, you know, as with many other things, it's always good to keep an open mind and not pigeonhole yourself into well, it's got to be this or it's got to be that, because that's when we all start missing things.
Speaker 1:Yeah, you know, that reminds me a little bit of an aside. Something that really interests me are errors in human thinking, and there's, you know, there's books on this and it's a field of study, and whether it's biases or just ways that your mind can kind of lead you astray, yeah, and it's the same with all of us.
Speaker 2:I mean I myself and other, really very other bright and probably brighter infectious diseases than I have been fooled into thinking it's one thing and finding out it's another. However, I would say that it's persistence and doubt that cause us to find the right answers eventually.
Speaker 1:Yeah, yeah, medicine can be humbling and it's good to have humility, it's good to realize that you could be wrong. And that's science, right Questioning, examining.
Speaker 2:Right. So like, if I'm asked to do a consult and I'm not sure I know what's going on, I don't put down. I put down a very vague differential. So one way to look at it is if you get a fever of unknown origin and that's just, there's a definition, with documented fevers over a particular period of time and you have done an extensive workup including radiologic stuff, blood work and some other things that you don't have an answer, and then you can put it into the category of fever. On an origin.
Speaker 2:And then, once you've done that, that enters into an area where you tend to divide up the causes, and about a third of them are infectious, about a third of them are rheumatologic and about a third of them are neoplastic cancer. Sure of them are neoplastic cancer, and so that's when you start to widen your differential and start looking with other kinds of tests for what's causing this syndrome that this patient is presenting with.
Speaker 1:Yeah, so you have a kind of a method that you use, Right?
Speaker 2:I mean it's you know it's well described on how to proceed in that kind of situation. The problem is in my thoughts I've been doing this for a long time is that now a lot of places are using algorithms and not necessarily generated by AI, but algorithms that the hospital has decided on as how to proceed, and that kind of pigeonholes you in a way, because you know you don't check that box, but you check this box, so go down this way. But a lot of diseases don't read the textbooks, and so you have to be concerned. If you're following a pathway of investigation and it's not working, whatever intervention you're doing for the patient, then you got to go back and reconsider. Well, even though this is what's recommended, maybe that's not what's going on.
Speaker 1:Yeah yeah, you can get some curve balls sometimes. Oh yeah, and it's, it's good to. I guess it would be good to follow an algorithm. I mean, most people think medical algorithms are good things, but you should know why you're following it and the rationale behind it, because sometimes you have to. You know you have rules or guidelines, but they're they're not laws. I mean they're guidelines, exactly exactly.
Speaker 2:And with the HIV epidemic back when we had no known treatment and we were seeing a lot of different kinds of opportunistic infections or cancers that never occurred here at the rate they were occurring, that we had to kind of go outside the box and treat without there being much data. Yeah, so you know. And another example is the COVID epidemic where you know, we thought initially we'd be able to figure out the mechanism of what caused all of this as far as what was the virus doing to our systems. But you know, two, three years later we're still learning about this virus and what it can do, its short and long-term effects.
Speaker 1:Yeah, everything is more complex than you're initially going to anticipate. You know you don't want to underestimate the complexity of it.
Speaker 2:Right going to anticipate. You know you don't want to underestimate the complexity of it, right? Well, that's been my most frustrating experience with the general population is, at least in our country, a lot of people anticipate an immediate you know diagnosis and cure. So when you tell some people, well, these tests haven't come back positive like I thought they might, so we're just going to have to kind of change another direction, and then with certain illnesses, especially the rheumatologic illnesses, they don't necessarily present in a textbook way.
Speaker 2:So you might not have one symptom, that's classic. But you will develop that symptom, you know, in a month or two later or the same with a blood test. Perhaps it's not convincing that it's significant, and then you'll repeat it at a time later and oh yeah, this is really too high. This is what you have, kind of thing.
Speaker 1:Yeah, it takes a while for it to declare itself.
Speaker 2:Right, so it can be confusing.
Speaker 1:So you've kind of talked about bizarre and unexpected cases. What about your most difficult case? Can any cases come to mind?
Speaker 2:Well, let me go back to a case that would fit more in what you were saying. Before that, I had a gentleman that was referred to me by a very prominent pulmonologist because of an enlarging mass in their chest, and he was only 28 years old. He was a non-smoker.
Speaker 1:Anterior mediastinum.
Speaker 2:It was in the anterior Well, it was in the lung and the lymph nodes in the mediastinum and no reason to suspect that he had a neoplasm. And so he underwent a bronchoscopy and they did a biopsy and, as often happens, they got all this necrotic tissue. However, the culture grew an aspergillus, which is a fungal infection. Now the problem with these fungal infections is that the air surrounding you has got spores. So sometimes if you do a culture, you can put it on a special plate to culture for fungi, which is what aspergillus is. However, that can become seeded if they're not careful with a spore from the air or it could have gotten contaminated when they did the biopsy coming out. So this guy grew an Aspergillus, but Aspergillus doesn't usually cause invasive disease in a immunocompetent host. So tested him for all these immunodeficiencies. It was negative. There was nothing seen on path. But that was suspicious, but it's still.
Speaker 2:We had to treat him. So we started treating him and the mask continued to grow. I had asked him practically every question that I could ever think of to try to pin down what infection this could be. So he'd been to the Virgin Islands about a month prior. He didn't eat any sushi or raw food there, had an uneventful trip, just had a lot of drinking but no illnesses, and couldn't figure it out. Turned out he was a park ranger and was going out in the woods and a lot of things. So ultimately we opened up his.
Speaker 2:Well, yeah, they did a media sinuscope and got a big lymph node and on one slice of the lymph node they saw something that looked like a worm or just a parasite, let's put it that way.
Speaker 2:So, again under intense questioning, after this guy had gone through the bronchoscopy, he did remember that he was working with a bunch of his buddies in some forest here in Missouri and they had dared him to eat a raw crawfish out of the stream. Turned out to be a flatworm, which is known as Paragrysomyiasis I'm probably screwing up the pronunciation. It's seen mostly in Tibet, where they have a dish where they take crabs, dip them in alcohol, like maybe grain alcohol, and then you eat the crab. Well, there's a whole host of people that come down with it there and it turns out in North America we have our own subset of species of that type of organism that lives in crawfish here. Crazy, it was crazy. And then after that I could never eat crawfish and whenever I go down to a restaurant and they're having a crawfish boil, I just I see all these people downing them and I'm like I can't do this.
Speaker 1:Nuts, and the probability of that is just so, so rare.
Speaker 2:Well, it's so rare. And then it's also, you know, when you're treating somebody or trying to figure out how to treat somebody, it takes communication, and not everybody communicates in the same way or in the same level. Yeah, so there's a lot of variations in how people interpret what you are asking them and what answer they give you.
Speaker 1:Yeah.
Speaker 2:And also there's, you know, different educational levels. And also there's, you know different educational levels and, believe it or not, well, there's a lot of politicalization these days that can make a difference in what people will. One believe and two allow you to intervene. So I mean, I had people laugh in my face about the COVID-19 vaccine oh no, I'm not going to get it. And the reality of it is they're the ones who are at the highest risk for getting it and having a bad outcome. Yeah, but they were so convinced that they were getting some kind of microchip or something was going to happen that they just wouldn't take it.
Speaker 1:Yeah, I mean this has become a whole and we could. I don't want to go too far down this route because actually the last interview I did was about vaccine hesitancy, but it's, I think it's hard for people to have trust in institutions that they previously had trust in, and it's gotten more complicated for patients and it's gotten more complicated for doctors.
Speaker 2:Oh yeah, no, I mean, if you know exactly what you need to do, but the patient won't let you do it, I mean, do you just tell them to go away and good luck, which you don't want to do?
Speaker 1:Yeah, you need some. It takes a lot of people skills. You have that just because I know that you have an army of patients of every different kind of background who really love and respect you.
Speaker 2:Thank you.
Speaker 1:And a lot of mutual patients, because some of your patients, who are immune, compromised, end up getting cancer, and so that's how our paths kind of cross from time to time, and so that's how our paths kind of crossed from time to time. Have you ever dealt with any aside from COVID-19, any other?
Speaker 2:type of like outbreak or cluster of infections. Well, I was one of the doctors in the HIV epidemic, so I was in medical school just as AZT came about.
Speaker 1:Which is an amazing drug regimen right.
Speaker 2:Well, unfortunately, azt by itself, which they weren't aware of, it, was not enough to treat the HIV virus because of the high level of mutations and resistance of the high level of mutations and resistance. So there was a whole cohort, a whole group of people that got treated with AZT, which then caused a cascade of resistance to some future drugs. So eventually I would say around 1993, they figured out that one they had to use more than one drug and ultimately more than three drugs. And I happen to be lucky to have been doing my fellowship when the three-drug regimen came out and it made a huge difference.
Speaker 1:This is triple therapy. Is that what they call it? Yeah?
Speaker 2:Right, and now they've gotten so good that we can do double therapy.
Speaker 1:Okay, so there's some patients that you can do two instead of three.
Speaker 2:Right, but that was since the advent of the integrase inhibitors, which are now considered the backbone of your treatment for HIV, as opposed to when they first started the nukes, that these are drugs that mimic nucleic acids and would not nucleic acid, or, yeah well, pyrimidines or purines, the bases Right, and then they could wind up blocking certain active sites on some enzymes that the virus needs to replicate and prevent it from replicating. And the other thing about HIV, that was a springboard to treating malignancies, because it was, as far as I know, the first time they used X-ray crystallography to design drugs to fit into these active sites on various enzymes and block them. And so then they figured out they needed two or three, three at first, and now two.
Speaker 2:And it's become so potent that we rarely see any opportunistic infections anymore, unless people have ignored their symptoms to the point where they have a very low T-cell for a protracted period of time.
Speaker 1:Yeah, yeah, and you know what you were talking about earlier, like the Kaposi sarcoma, which is a really rare tumor, but when patients had HIV they would have that tumor, kind of an odd thing that came up. I just had one diagnosed as a poor guy who that came up.
Speaker 2:I just had one diagnosed. This is a poor guy who was just pretending not to be sick.
Speaker 1:Yeah.
Speaker 2:And he'd been sick for like a year and then he comes in with full-blown AIDS and he had Kaposi's sarcoma.
Speaker 1:Yeah, you might be seeing them because I referred him. Yeah, they're easy enough to take care of, for sure. Usually it's a pretty quick treatment and I've treated several of them across the years.
Speaker 2:Well, the one I had. I was thinking that he would respond to the antiretrovirals, which often will prevent it or cause it to regress. Yeah, because it's another virus that's not being controlled in your body that leads to the Kaposi sarcoma not being controlled in your body. That leads to the Kaposi sarcoma, which is a herpes virus type eight.
Speaker 1:Yeah, and where's it at on the body?
Speaker 2:Oh well, it's on his lower extremities.
Speaker 1:Yeah, and you can see it on the skin.
Speaker 2:Yeah, yeah, yeah, it's obvious when you see it. Yeah, that's my favorite place to treat because there's not much side effects on the lower extremities and so much side effects on the lower extremities and so, yeah, yeah, I've just I've seen people who've gotten radiation for other reasons down there and then unfortunately it can cause wounds that don't heal.
Speaker 1:yeah, so if you have like a regular sarcoma and especially if you treat the entire circumference of the leg, you know they can have lymphedema or for a regular sarcoma. A lot of times you're dealing with a surgical resection bed. That's already compromised.
Speaker 2:It's not normal tissue.
Speaker 1:The blood flow is not good, and then when you add radiation to it that's not good, but usually for a fresh tumor like that that's pretty radio sensitive. They typically take that one in stride. And so there are a few tumor types that I really enjoy treating because it's just there's not a lot of side effects and the patients do really well, and so we had one who had a plasma cytoma in his sternal area.
Speaker 2:What?
Speaker 1:an amazing. That was an amazing story because you know his whole story was really cool because I think he was about four weeks. I think at one point in like 92 or 93, they told him he had like four weeks to live and then I think he got on the triple therapy trial and you know is he's thriving live 30 years and he's a great guy.
Speaker 2:Yeah, no, no, he's doing great.
Speaker 1:Super, super cool. Um story, um. Are there any other? Um, um, uh, can you think of any other outbreaks that you've been involved with during your training?
Speaker 2:Well, so well, there was HIV Then I think it was 2011, we had the influenza pandemic.
Speaker 2:Yeah yeah, that was really rough because we were having people who were relatively young. We had one dentist, one ENT and I don't remember what the other one was, and they ended up staying in the ICU a minimum of four months up to six months. One required eight chest tubes at one point, the others multiple chest tubes, but not eight, and as a consequence of treating them, one developed disseminated aspergillosis. There you go. That went to his brain. Now he survived. The others two survived too, but they were not the same person that they had been prior to this infection, and at that time it was discovered that people who were moderately overweight were more at risk for severe disease. But then you try to explain to people that they're in their 30s. Then you try to explain to people that they're in their 30s. They have trouble comprehending that somebody in their 30s could get that ill. And the same thing happened with COVID. A lot of people were like, well, it's going to knock off the older population, but it's not going to touch me.
Speaker 1:Yeah, I mean so this kind of a whole other topic. But like what percentage of the population is moderately overweight? I mean it's a lot.
Speaker 2:Oh yeah, in the States it is a lot.
Speaker 1:Probably 70%.
Speaker 2:Although, with the advent of semaglutide, things are getting better. Yeah, the ozempic-type drugs?
Speaker 1:Yeah, for sure that seems to be effective and we'll I think kind of time will tell to see what's the long-term deal with that or not.
Speaker 2:Okay, I think that what's going to happen is it seems to have very little downside, with the exception of, initially, maybe some nausea. They talk about medullary thyroid cancer, but that was in rats and I don't know of any cases that have been tied to medullary thyroid cancer. So I think so far, after what's been out three years, now four years there has been very few side effects other than the nausea constipation, and a lot of people tolerate it.
Speaker 1:Yeah, some people have GI issues and have to get off of it, but for a lot of people tolerate it. Yeah, some people have GI issues and have to get off of it, but for a lot of patients, a good percentage respond to it, and so we'll see. I mean, it's definitely probably the biggest issue in health care right now is obesity and this seems like kind of maybe a wonder drug for it.
Speaker 2:So far.
Speaker 1:And so, yeah, personally, I'd like you know five or 10 years of history to and people are watching this for the longterm to see like how does this affect people for the long run. But it looks like it's promising so far and it looks like it's, from what I've heard it's actually cost effective. It actually saves money despite it being expensive. It saves money in overall healthcare because you care, because you have less heart attacks Right, I might be wrong on that.
Speaker 2:Well, at least they claim that with Lugovic. Now, as far as other things, it should be cost effective, as you said, for preventing dyslipidemia, heart attacks, diabetes and everything comes with that.
Speaker 1:Yeah, so Well, time will tell right. So, as good scientists, we should be optimistic but slightly skeptical. Right, Exactly, and so that's where I lie.
Speaker 2:How has the field of infectious diseases evolved during your career? Virus replication cascade to essentially stop the virus, stop regression of disease stop people from getting infections stop people from getting cancers that were associated with HIV. So now HIV patients can live probably almost equal, if not equal, if not better and I always say maybe better because as HIV doctors we've learned to follow the people very, very closely.
Speaker 1:Yeah, yeah, you know your patients very well on a personal level and kind of what makes them tick and whatnot, right?
Speaker 2:And then also, you know, we know when they're not acting the way they should be acting and we try to figure out and tease it out.
Speaker 1:Are you trying to tell me that humans don't act in a completely predictable linear fashion? Exactly.
Speaker 2:Including us doctors, by the way, for sure, for sure, yeah.
Speaker 1:And then it seems like another thing that, like you mentioned earlier, that we've had to deal with is public mistrust, and I think there's probably a lot of reasons for that.
Speaker 2:Well, there's also a stigma with certain diseases. You know, I never even realized, but I was listening to a program and there's ghosting people because they have difficult diseases such as HIV. But more recently, cancer patients are being ghosted by their friends and they had a whole series on people. Just kind of good luck.
Speaker 1:So define ghosting.
Speaker 2:Ghosting is a term for ignoring somebody that you might have known quite well, but you either emotionally don't want to deal with it or can't deal with it. And you kind of stop communicating with them. So from my understanding it's not such a rare phenomena.
Speaker 1:You know what I've seen when people I actually had this conversation with somebody this weekend who was newly diagnosed with cancer People who you would expect to be there for you you know, not all those people show up. A lot of them do, but not all of them but then there's people who you wouldn't expect to show up for you, who do yeah, and that's remarkable. I mean, um, it's, you do see some kind of heroes kind of come out of the woodwork and, um, you know, it could be a, it could be a stepdaughter, a former stepdaughter, you know who you haven't seen in a few years because of a divorce, who comes in and is helping her former stepdad out. I mean, I've seen that and it's like every day and that's remarkable.
Speaker 2:Well, I had a friend who was a chef we were acquaintances really but my friend who would go to the restaurant with me all the time. They became good friends and he got diagnosed with small cell of the lung.
Speaker 1:Yeah, tough cancer.
Speaker 2:Really tough cancer and you know she just took everything the bull by the horns, got him into a sightman, got him, went into the room and when she thought they weren't treating him well, she'd make a noise and get things done.
Speaker 1:Yeah, that's a move that works yeah.
Speaker 2:And she took them all as appointments and all that. Yeah, so there are a lot of people that do come to your support.
Speaker 1:Yeah, yeah, you do see kind of some disappointment, but also encouragement.
Speaker 2:Yeah.
Speaker 1:And you know I've heard it said that your friend group and your family can be like your immune system. You know, and I think that's a great analogy, a great frame that you know a lot of times, especially for some of these really tough treatments, I mean people just would not make it through if it weren't for, you know, their support system. And it's a really important thing to have for your health, your mental health, but also your physical health, when you're going through something tough.
Speaker 2:Yeah, and you just reminded me of also that being up the immune system in this situation. That's another thing that ID docs and internists and hematology and oncology doctors have to deal with, because with all the new immunotherapy, no matter what the mechanism you can get damage you know collaterally and that can present in really odd ways.
Speaker 2:Yeah, so I've had three patients who presented with pituitary insufficiency because the hypathesis was inflamed and wasn't working and they would come in with diabetes, insipidus, hypothyroidism and hypoadrenal. And you know this was at the time when it had first come out.
Speaker 1:Yeah.
Speaker 2:We're trying to figure out what the heck happened here.
Speaker 1:Yeah, yeah, you're right. I mean, the immune therapies are great because, I don't know, 70% of patients are symptom-free and doing wonderful and it's treating the cancer and they have virtually no side effects. And then, you know, 15% of patients can get pneumonitis and then the other 15% can get all sorts of weird, weird stuff.
Speaker 2:Right.
Speaker 1:And so you know, for those of you who don't know, that the hypothalamus, the anterior pituitary, is at the base of the brain and it's kind of where a lot of the hormones for your body originate, and one of those hormones is called antidiuretic hormone, and one of those hormones is called antidiuretic hormone and the or is it oxytocin?
Speaker 2:Or no is it ADH, adh.
Speaker 1:Yeah, adh and you can. That gland can kind of be obliterated and you can replace almost everything with supplemental hormones. But ADH, siadh is or ADH or diabetes, insipidus when you don't have ADH.
Speaker 2:that's really hard to deal with that reminds me of a really interesting case we had many years ago. A guy from India was visiting his family who happened to live in Newark, new Jersey, with profound dehydration and intravascular volume depletion, acute kidney injury, and so they gave him a lot of fluids. Things got better. Then he decided to visit some family here in St Louis. He came into this hospital profoundly dehydrated, hypotensive which means low blood pressure for those and looked for everything in the world septic. However, what happened was we started to realize that no matter how much fluid we put into this guy, he'd pee it out, and more fluid we put into this guy, he'd pee it out and more. So there was something not right about his way of conserving water. Finally figured out he had no thyroid hormone, had no cortisol, had no ADH. Did an MRI of his brain the pituitary Turned out he'd had tuberculosis involving his pituitary and it was no longer functioning. So that was another interesting case.
Speaker 1:Yeah, TB-induced panhypopituitarism.
Speaker 2:Yeah.
Speaker 1:And they call it diabetes insipidus, not because it has anything to do with diabetes, but because diabetics, when they're initially diagnosed, are urinating a lot, and when you don't have any antidiuretic hormone, you urinate a lot. Yeah, so it actually has no real relationship to diabetes.
Speaker 2:Yeah, I should have.
Speaker 1:No, no, no, but it's kind of a tricky tricky thing and it's been a long time since I've thought about the pituitary tricky thing and it's been a long time since I've thought about the pituitary, but but that kind of reminds me of um. We had some um India, a few Indian doctors who came over from India and were working in the ED where I went to medical school and the funny thing was um, for like every case that came in they were like, oh, but it's TB, because over there everything's TB. So so you know, not not a shocker that somebody from India, you know, would end up with TB. That's pretty common over there but not common here.
Speaker 2:But, however, you got to realize that they're coming into an environment where they don't have histoplasmosis, and histoplasmosis for the world can mimic TB.
Speaker 1:Is that right?
Speaker 2:Yeah, in certain ways yeah.
Speaker 1:And we have, and so histoplasmosis and blastomyces are fungi that are in the soil. Yeah, and the Ohio and Mississippi river valleys specifically, I think.
Speaker 2:Yeah Well, they tend to follow the I want to say the Starling route of migration but I'm not like the bird.
Speaker 2:Yeah, that was from medical, medical school, so don't take my word for it, but that's what I remember them telling me. But anyway, they love the soil here. It gets into your body through your lungs and then, depending on your immune response which has everything to do with how everything presents, uh you will get certain manifestations yeah, so everybody here does fine with it, and that's why a third of the people in St Louis will have a lung nodule in their lung.
Speaker 1:That's not cancer, right, right and so. But I guess at some point we develop an immunity to it. Yeah.
Speaker 2:It's a you. You develop a T cell immunity, which is a cell that kind of. Instead of lobbing immunoglobulins, which which are proteins that attach to various pathogens and signal your immune system to attack it, these attack them on their own More directly, more directly.
Speaker 1:And that's a cell that, when patients have HIV, is affected. Right.
Speaker 2:So then, with the tuberculosis and histo, you get granulomatous inflammation, and usually you keep it under control. However, if we give drugs that modify your immune system by lowering the effectiveness to help treat autoimmune diseases, they can reactivate. They can reactivate on your own because, for another reason perhaps, your immune system isn't functioning as well.
Speaker 2:For another reason perhaps your immune system isn't functioning as well. So an example would be tuberculosis in a patient with HIV. They could have been exposed when they were a kid to tuberculosis. Everything's working fine. You get your HIV. You don't realize it. Your immune system declines to the point where the TB reactivates. Once the TB reactivates, that's when you become infective and that's when the diagnosis is made.
Speaker 1:So that's nasty, that's crazy yeah.
Speaker 2:So it's very similar for TB and histo in that sense.
Speaker 1:You know I was talking, did you know Sid Devoraconda?
Speaker 1:He was a resident here but he became a medical oncologist at WashU and I think he's out in Seattle now, great guy. And so him and I were talking and he's seen a lot of patients and I'm busy so I see a lot of patients and I was telling him about a case where I saw this guy scan and I knew for sure it was just metastatic cancer, that he had just metastases everywhere in these bones. And I go talk to him and I say you know, it very much looks like you have metastasis. And then they got to get some biopsies to prove it. But you know, as soon as they get the biopsy I'm going to need to treat your spine with radiation because you've got these lesions on your vertebral bodies. And they got the biopsies and they came back as granulomas. And then they did more biopsies because it was like kind of hard to believe and it was just granulomas. And I asked him if he had ever seen a case like that, because I had only seen one and it just totally shocked me.
Speaker 1:And he said yeah, I've seen one case. What was the offending agent? You know what? I don't know. As soon as I saw it wasn't cancer, I kind of went on and said, hey, I think this is. You're probably better off than we thought you were. So what would the offending agents be?
Speaker 2:What would like your top couple picks be? Well, histo TB would be. Any kind of fungal infection can do it. I mean non-infectious things. Well, non-caseating granulose with sarcoid, but you know that would be unusual to see lytic lesions in the bone.
Speaker 1:Yeah, yeah, you see that in the heart and in the lung.
Speaker 2:You can see it in a lot of the lung is the primary place you can get neurosarcoidosis, sarcoidosis the heart I'm sure it could, but I'm not. That on top of how badly.
Speaker 1:you can get a cardiomyopathy with sarcoidosis, and how do they treat sarcoidosis?
Speaker 2:With steroids, steroids, yeah.
Speaker 1:And there's something that looks very similar to sarcoidosis. Is it like TB or something like that that you don't want to treat with steroids?
Speaker 2:So sarcoid causes non-caseating granuloma, which means it's a different histological picture than a caseating granuloma. Okay, so basically the granuloma turns to like a dry abscess. That's the best way to look at it.
Speaker 1:Okay.
Speaker 2:Like this kind of a real thick pussy-looking thing where, as opposed to the non-Caseyian granula, it just maintains the architecture of what you would see in sarcoid in a normal granula.
Speaker 1:Yeah, yeah, I just remember having to. Every once in a while. We'll see something like this in tumor board.
Speaker 2:It's not cancer.
Speaker 1:And it kind of reminds me of that Mark Twain quote it's not what you don't know, it's what you know for sure. That just ain't so.
Speaker 2:Exactly that was my whole point, about never pigeonholing yourself, because I can guarantee people have made lots of mistakes by saying, oh, this looks like this, we're going to treat it like this. It turns out to be something completely different.
Speaker 1:Yeah.
Speaker 2:And often you wouldn't be doing what you're doing. You'd be doing the opposite.
Speaker 1:Yeah, 19 times out of 20, right.
Speaker 2:Right. But again, no matter who you are as a doctor, no matter how good you are, you're going to end up doing it at least once or twice in your career.
Speaker 1:Yeah, people make mistakes, for sure. Have you used any AI as kind of a co-pilot?
Speaker 2:to help you?
Speaker 1:Yeah, no, what are your? What are your thoughts on?
Speaker 2:that Again, algorithms, so you can go to Google and use their AI and plug in your symptoms and you'll get a list. And then you go to your doctor and say I think I have this. It's like a menu. And you look at them and say, one, you don't fit the epidemiology. Two, nothing is backing this up. And three, please don't go to Google and.
Speaker 2:Dr Google, let us try to work on it in a logical way. I'm sure AI can give you a nice differential diagnosis, but a lot of people go to it and say, oh, I got this.
Speaker 1:Yeah, I would agree. Most of the time it's very rare for people to come up with the right diagnosis. If they knew what was important and what to put in the AI, they could come a lot closer. But you got to know what variables are important, like maybe where you've lived or where you currently live, or your age.
Speaker 2:Right.
Speaker 1:There's all these things that you wouldn't think would matter, but if you understand the disease process, they're super important. Or like have you eaten sushi Right?
Speaker 2:Or or like do you raise birds in the backyard?
Speaker 1:yeah, and then, and so yeah, why don't, why don't we, why don't we finish up on this one? So the the new, is it the h5n1?
Speaker 2:is kind of like the newest yeah, and it's it.
Speaker 1:It's a virus that is thought to be very deadly for humans, but it looks like it's mainly been passed from bird to bird or animal to animal and then, in some recent cases, from animal to human, and the fear is that it's going to become something that is passed from human to human, is that?
Speaker 2:accurate, yeah. So basically I look at it this way the two major flus are swine and bird. Okay, right now this one is mostly affecting birds and it's pretty lethal for the birds, but all other animals, including those fowl, are kind of like mixing chambers for their genetic material.
Speaker 1:Okay.
Speaker 2:So a lot of times when a virus infects an animal, it'll undergo mutations, and those mutations will either make it less likely to be able to affect other animals, because a lot of it has to do with the binding of the virus onto cells so that the genetic material of the virus can get into the cell.
Speaker 2:Remember, viruses are just entities that can't replicate without using a eukaryotes system to mutate mutate, so it gets into these mysclin vessels, whether it's a bird, swine now cow, now there's COVID in elk and deer, but every time it goes through a life cycle and reproduces, there's going to be a genetic change.
Speaker 2:So the thing about HIV and why it's been so hard to find a vaccine to treat and prevent it, is for every replication, or every 24 hours, there's a billion replications in the human body. I'm giving you a broad estimate. For every mutation, for every cycle, life cycle of the virus, one mutation occurs. So if you're having a billion different mutations occur daily in your body and you apply pressure by, say, putting them on an inadequate regimen so that some viruses can continue to replicate, eventually those viruses will become resistant to those two drugs. And then you have to remember that some of that resistance can cause decreased susceptibility or full resistance to other drugs we use for HIV. So that's why it's so important to use a strong regimen that the virus can't replicate on, because if you can't replicate you can't mutate.
Speaker 1:Yeah, and I guess if you're having a billion mutations, most of those can be mutations that just make no difference. But it only takes a couple of them to have a mutation in the bad part of the virus that makes it more virulent or more susceptible in the bad part of the virus that makes it more virulent or more susceptible.
Speaker 2:And that's what's going on with COVID, because we see that COVID in general this year is not as lethal as it had been, and it's a combination of things. We have better medications to treat it and we know how to treat it in a better way. It's a combination of suppressing the immune system, because a lot of the damage that's caused by the virus is not the virus itself but our immune response to it, and they're learning more and more about that. I mean, it's a combination of things.
Speaker 1:Yeah, but so back to the H5N1. And so is there a significant fear that that's going to kind of get worse and start to spread from human to human.
Speaker 2:I cannot predict 100%, but if it's like the way other viruses go, yes, it'll be more prevalent in humans, and once it gets a foothold in humans, then it's going to spread for sure. Then it's going to spread for sure.
Speaker 1:And hopefully so you can have. There's kind of two things you can look at how easily it spreads from human to human and then how bad of an impact it has on each human. And so hopefully, as its ability to spread from human to human increases, maybe its impact on each human maybe weakens. That would be a good thing.
Speaker 2:Right and fortunately I think the drugs that we have now, from my understanding of the very few people that have been studied, are still effective. But the whole problem is that if it keeps mutating it may mutate the proteins on the surface that will attach to different parts of your cells and get in. They may become more efficient.
Speaker 1:Yeah.
Speaker 2:And they also may develop resistance to the drugs and whatever mechanism that particular antiviral is using to stop the replication of the virus.
Speaker 1:Yeah, and here on Earth it's going to be a never-ending battle, as it has been up to this point, of our own immunity, protecting us versus vaccines or medications Right.
Speaker 2:And then the other thing is that when is it the virus that's? Is it the virus that's killing you, or is it your immune response to the virus that's killing you, or is it both?
Speaker 1:Yeah, and I remember in COVID early on that was kind of hard to figure out Do you use steroids? Do you not use steroids?
Speaker 2:to tamp down your immune response. Turns out that with COVID, steroids are our main stem of treatment. However, in flu at least in the 2011, if I'm getting the year correctly outbreak, they had worse outcomes when people got steroids.
Speaker 1:And so the virus was worse than the response to the virus, because the steroids tamped out their own response, so you could have a virus. That in itself isn't super harmful, but it just. It really amplifies your immune response and your immune response actually hurts you significantly, and that's when you want to use steroids, right?
Speaker 2:Right, and so the classic would be sepsis. You know, sepsis isn't necessarily the whole organism causing a problem. It's your immune system reacting to a protein that's on, or glycoprotein that's on that cell surface, sending off such a brisk immune response that you become so vasodilated, you can't maintain your blood pressure and you start hypoperfusing organs and they die and that's it. So that's very complicated.
Speaker 1:Matt, thanks so much for your time. It's always interesting talking to you. You're one of the most respected doctors at St Luke's. I really appreciate you coming on.
Speaker 2:My pleasure and thank you for having me.
Speaker 1:Thank you.