Guidance for Treating Children with Post-Acute Infection Syndromes: Special Series from The Cohen Center for Recovery from Complex Chronic Illnesses at Mount Sinai

Dr. Raven Baxter

Hi everyone. I'm Dr. Raven Baxter. I'm the host of this episode of Raise the Line and I'm a molecular biologist and director of science communication at the Cohen Center for Recovery from Complex Chronic Illness, or CORE, at the Icahn School of Medicine at Mount Sinai Hospital. At the center, we work to advance treatment and knowledge of long COVID, tick -borne and vector -borne illnesses, myalgic encephalomyelitis, chronic fatigue syndrome, and connective tissue disorders like hypermobile Ehlers -Danlos syndrome. 

This series of podcasts that we're doing is focused on post -acute infection syndromes, and those are characterized by persistent symptoms that last for months or even years after the initial infection has been treated. But we're still developing our understanding of these and how we should approach treatments and understanding all of the different clinical presentations of these syndromes. And so the part of the reason why this podcast exists is to help share the knowledge that exists in the science and healthcare communities and make progress in our understanding so that we can make sure our patients have a more comfortable journey to recovery. 

Today we have the pleasure of hosting Drs. Charlotte Mao and Lael Yonker. I am very excited about this. We're gonna be talking about some special populations and how to approach the treatment and understanding of these syndromes in that context. But before we get into that, I'd love to hear from you two. Who are you? What do you do? And I guess, how did you get started? 

Lael Yonker 

So my name is Dr. Lael Yonker. I'm a pediatric pulmonologist at Mass General Hospital in Boston, and I am the director of the Cystic Fibrosis Center. I split my time seeing patients and then not just with cystic fibrosis, but with other pulmonary diseases or respiratory diseases. I also spend time doing research trying to understand how the body responds to infections. 

My research pre -pandemic really focused on how the body responded to infections typical in cystic fibrosis, and now has expanded with COVID trying to understand specifically how kids respond to COVID. Both, you know, early on we were looking in the acute infection stage, and then when multi -system inflammatory syndrome came on, a really severe post -COVID illness, we were studying to see what was going on there. And now we're really interested in long COVID and trying to understand. So really I'm a translational researcher. I collect samples from patients, bring them back to the lab and try to understand what's driving disease and also try to find cures. So we do have a clinical trial underway as well. 

Dr. Raven Baxter 

Wow, that's very exciting work. Thank you. And Dr. Mao? 

Charlotte Mao 

Hi, I'm Charlotte Mao. I'm a pediatric infectious disease physician. I started my interest in Lyme disease when I was at Boston Children's Hospital. I was there for 25 years, although the original focus of my career was pediatric HIV clinical care and clinical research. About 20 years into that, I started also seeing patients at the general infectious disease clinic at Children's Hospital and found that Lyme disease was the single most common reason for which I was seeing kids at this referral clinic where pediatricians would refer their patients for a whole variety of infectious diseases. That is where I got an enormous education in Lyme disease. 

I then eventually went to Mass General Hospital, Pediatric Infectious Disease Division, but seeing patients at a multidisciplinary clinic for children and teenagers with complex Lyme disease and associated infections at the Dean Center for Tick Borne Illness, which is at Spaulding Rehabilitation Hospital in Boston, and continued to get an enormous education. Currently, I'm working with two foundations in the Lyme disease and associated infections arena. One is called Invisible International. It's very focused on physician education. And the other is Bay Area Lyme Foundation, which is one of the largest private funders of Lyme disease research in the US. 

Dr. Raven Baxter 

Thank you. So I sort of want to get back to basics on this episode a little bit because by this time -- this is the ninth episode of 10 in the series -- and by this time, we've talked about all of the various clinical manifestations of post -acute infection syndromes. We've talked about how to diagnose them and really what their drivers may be. But when we're looking in terms of pediatrics and pediatric research, what are some things that stand out about the pediatric side of this versus talking about this within an adult context? 

Lael Yonker 

I would say one of the biggest challenges is that adults are -- not all adults, but there are enough adults out there -- that are great advocates for themselves and they can articulate their symptoms really well. You just don't get that to the same degree in pediatrics. They have a harder time describing what their symptoms are so you might see a lot of different causes for symptoms manifest in the same way. So, it's hard to tease apart what's going on and it's harder to interpret what they're saying. 

It's harder for them to necessarily appreciate their symptoms to the same degree that an adult might advocate for themselves to have things followed up on or be able to request specific things. So it's more challenging for patients in that I think takes a lot of patience by the pediatrician, whether it's the primary care doctor or the subspecialist and also, you know, a little bit more conversation and really trying to dig into what's going on and, and what are their symptoms actually meaning and conversations with the family as well. So I think that's a big difference with pediatrics and adults. 

Charlotte Mao 

Yeah, I would agree with Dr. Yonker on that. With Lyme disease and complex Lyme disease, a lot of times the symptoms can be quite confusing. And you're relying, of course, on parents to provide a lot of the history. But one thing I did find is that it's always very important to ask the child themselves, because sometimes I would find that children would not report some certain symptoms to their parents and parents would sometimes be surprised at visits saying, “Oh, I'm hearing about this for the first time” and be a little bit embarrassed about it. And sometimes they thought that their child was hiding symptoms, maybe because they didn't want to go to the doctor. 

So, just as one example, peripheral neuropathy symptoms of tingling and numbness is often something that I find that children wouldn't necessarily report to their parents. But if you ask them at the visit on questioning, they will report it. So, that was one take -home lesson I always had, was to ask the child themselves. 

Dr. Raven Baxter 

Yeah, I mean, I guess I've never quite thought about -- since I've been a child – like how do kids think when you've only had so much of the human experience. Some things you might just think, hey, this is just a part of being human. My eyeball is supposed to be tingly sometimes or whatever that sensation is like. And I can imagine them just thinking it's a part of growing up when in reality, if you've never been asked, hey, is your eyeball tingly? you wouldn't say anything. So wow, yeah. 

You know, the overarching theme between all of these episodes has been listen to your patient, listen to your patient, but then also the notion of understanding what questions to ask your patient to get the full picture of their experience. So how do you communicate with children to pull out those pieces of information? And also what red flags might pop up if?I've been told in a previous recording we did that children have a unique vocabulary in how they describe things. So like, what questions do you ask the kids and what are some red flags of things you hear from them?

Lael Yonker 

I would say really the biggest questions are, are you participating in the sports that you normally participate in? Or are you missing school? Or have you stopped doing the activities that you really loved doing before? And so that really gives a sense of their impact and sort of how much is really affecting them because kids in general want to participate. If they've been wanting to participate before and something's changed, we need to figure out why. 

Charlotte Mao 

I think a message that I would really try to emphasize is that for post -acute infectious syndromes like Lyme disease, the symptoms are far wider than I think what's commonly thought of or communicated, such as fatigue, widespread musculoskeletal pain and cognitive difficulties or brain fog as it's sometimes called. But in fact, there's a whole panoply of symptoms that can be seen in acute Lyme disease that unfortunately aren't necessarily well delineated or sometimes not covered at all in standard paradigms of what kind of symptoms you think about Lyme disease. So of course, we always think about the skin, the rash of the tick bite that expands, the erythema migrans, heart involvement, neurologic involvement, joint involvement. 

But in fact, there are other organ systems that can be involved, gastrointestinal, psychiatric symptoms, neuropsychiatric symptoms. That is a big category. Ocular symptoms...they do get acknowledged some, but there's just a lot of manifestations that I found when I started actually seeing patients and being able to piece together some pattern recognition and then go back to the primary literature. I was surprised to find that a lot of these symptoms that I had no idea could potentially be related to Lyme disease were in fact reported either in case reports, case series, sometimes some select review articles. And so all those manifestations can also be in what's considered post -acute infection with Lyme disease. 

So really a very complete history, including a very complete review of systems, I think is exceedingly important with Lyme disease patients. And a lot of times patients, you know, or their parents, they won't even think of something as potentially being related to Lyme disease. So history is absolutely key. And having the time to take that history is key for these complex patients. When I was at the Dean Center for Tick Borne Illness, we had twice the amount of time as a standard visit. So two hours for a first visit for a patient and one hour for a follow -up visit because it does take a lot of time to tease out these histories. That would be my number one big message. 

Dr. Raven Baxter 

That's incredible. Wow. So I would like to know do children have greater or lesser risk for various post -acute infection syndromes and what does that look like? 

Charlotte Mao 

I would say in Lyme disease, there's not a lot of literature on post -acute infectious syndromes in children. In general, children, are the age group at highest risk for Lyme disease. If you look at data broken down by age groups, actually age five to nine is the peak incidence of Lyme disease. It's sort of a bimodal distribution and then later on age around 50, 55, there's another bump.

One explanation could be that children definitely are playing more in the grass, rolling around, etc. so they could have more exposure. In terms of post -acute infectious syndromes, I think that, as I said, there's less literature, but there's some feeling that maybe children don't have as high an incidence as you can see in adults. The figure that's cited for adults commonly, it'll be say 10 to 15 or 10 to 20 % will go on to have persistent symptoms. But when you actually look at the literature, there's pretty wide variation in what gets reported. And there's some good prospective studies where they report even figures around 36 % in adults. 

I haven't seen anything like that in children, a reported figure like that, but my personal thought is that an explanation for these post -acute infectious symptoms is probably what I like to call a “multiple hits” model. It's not just the acute infection that you were dealing with but other co -infections -- not necessarily ones even acquired at the same time -- they could have been preceding infections. Or maybe not even infections, say environmental toxic exposures. There's a lot of things that go into this multiple hits model and that maybe is why certain people go on to have persistent symptoms after their one identified acute infection. Maybe it is that children just being younger have not had the time to acquire as many of those multiple hits. That could be one explanation. 

Lael Yonker 

And for long COVID...COVID got a lot of attention for many reasons, but one of the most interesting things about COVID was it really impacted kids versus adults differently. And then we started to see MIS -C, this multi -system inflammatory syndrome in children. Thank goodness we don't see as much anymore. But kids would come into the hospital very sick just two weeks to two months after they had COVID. And it was mild, probably a mild COVID, like typical pediatric COVID, but they'd come in very sick, high fevers, sometimes severe cardiac injury. Many would end up in the ICU. But we didn't see that same phenomenon in adults. Sometimes we did. There were some adults, but it was more common in kids. So there's again, some sort of age discrepancy. 

For long COVID, which I think is along that sort of spectrum with MIS -C, sort of a more mild indolent version, a lot of the same symptoms are seen, but much more organs are involved, but to a milder degree. You know, it's hard to say because it's a newly recognized illness and so there are a bunch of different case series that seek out who has symptoms, but there's no diagnostic test for long COVID. You have to have these new symptoms that are either new or worsened within, you know, at least four weeks after having had COVID and they last. And it could be any of 200 plus symptoms have been described. So really the diagnosis of long COVID is very challenging. 

Often in my experience, it's the families who identify it because it's based on a very time -specific change and very vague symptoms. So parents are the ones who identify it. And the ranges, again...it's been reported that kids can have lasting symptoms after COVID in up to 25 % of kids. I think that is changing and maybe that was seen earlier in the pandemic. Now, certain symptoms can, you know, it ranges but anywhere from probably five to 10 % roughly can have these long lasting symptoms and it's probably about the same in adults as well. But again, the numbers of people who have had COVID – and essentially all of us have had COVID -- how many of us go on to have symptoms? I think it's hard to put a number on and I don't know that there's a huge difference between adults and kids as far as the risk of developing long COVID. 

Dr. Raven Baxter 

Thank you. And I wonder, interdisciplinary or multidisciplinary teams has also been a recurring thread in these episodes and developing that community to address these various symptoms and trying to find some roots and treatments. That's been something that's come up several times. And so does that pose a challenge in pediatrics? I'm asking as someone who's not a medical student or physician. Would you have to find a pediatric cardiologist to address heart issues? And does it make it a little harder for these parents to build that community because they're children? 

Lael Yonker 

I would say that within medical centers, there are strong pediatric communities. And generally, certainly at my institution, we all know each other and so it's easy to reach out. Often there are fewer pediatric subspecialists than adult subspecialists, for example, so you're often in the same clinic space or you meet in some way, shape or form regularly. So it's pretty easy to connect with other subspecialists. And pediatricians are generally nice people. We can reach out, even if it's outside of your institution, if there's an expert somewhere else across town or across the nation, it's easy enough to connect and to try to see. But certainly, multidisciplinary approaches are very important in these multi -organ post -infectious illnesses. 

Dr. Raven Baxter 

That's interesting. And so have you ever been like cold-contacted by a parent? 

Lael Yonker 

Oh, yeah.  

Dr. Raven Baxter 

Really? 

Lael Yonker 

Yeah. Yeah, all the time. But I do a lot of research as well, so I put my name out there and so people do email me a lot. I set up times to talk with them and sort of tell them about, you know, my clinical take and my research opportunities that we have. It's complicated and these kids are going through a lot and they're missing a lot of school and social interactions. And it's really -- especially for long COVID being such a new diagnosis -- we don't have treatments yet so research is the best I can offer, and people are happy to participate in any way in order to advance science so that their kid can feel better eventually. 

Charlotte Mao 

I likewise get contacted all the time by parents, maybe through friends who refer them or other physicians. Lyme disease is unfortunately a contested illness where patients often are diagnosed late or diagnoses are missed because symptoms aren't felt to be Lyme related. Doctors don't realize that a certain constellation of symptoms and signs could in fact be suggestive of Lyme disease and so patients and parents often don't know who to believe, maybe. They know that there's a lot of controversy in this field. 

They know that there are different, if you want to say, “camps” of clinicians who have differing views and they want some guidance as to where to turn and what to do for their child. 

Having been a physician who myself had my own views evolve in the course of seeing a lot of patients over a number of years, I feel I can communicate some of that...what led to my own education and provide some reinforcement to parents that they can trust their instincts. I think they know their child best and what's their baseline on what's different and that can be very reassuring and supportive for them, because it can be difficult when you don't know where to turn to or who to trust necessarily, because you're hearing that there's all these different views in the field. 

Dr. Raven Baxter 

I certainly want to get deeper into your experience with parents because I mean ultimately you have to communicate with two people about one person's health. So how do you navigate those conversations? What are some tips that you'd have for medical students? 

Charlotte Mao 

I'll say what I found initially when I was seeing patients. I had come into it thinking that maybe patients were looking for a diagnosis, like they wanted this Lyme diagnosis and thought that they had chronic Lyme, et cetera. And what I found was mostly that families were just really confused by this constellation of symptoms and they wanted an answer. It wasn't that they necessarily wanted Lyme, but they just really wanted to have an understanding of what was going on. And they knew that it wasn't... there's some sort of more pat explanations like, oh, the kid's having stress at school or things that just didn't really ring true to them. And they felt that there was something more. And that was a common theme that I would hear from parents that they really had to push their providers to consider Lyme. Sometimes even they had to demand or beg for testing to be done because it just wasn't considered a possibility and in fact, lo and behold, the patient ends up having a very positive Lyme test. 

Now, granted, you have to keep in mind – and I don't want to go too tangential -- but I just want to add that you can't necessarily say that a Lyme antibody test equates to Lyme disease because you can't just assume that those symptoms are due to Lyme disease because of that positive test. I wanted to add that corollary. But in fact, as I mentioned before, when I looked in the literature, I would find that there was support for some of these symptoms that I had no idea could be due to Lyme disease, could in fact be seen with it. And so I think it's mostly a matter of just being very comprehensive and very open to what both parent and child report as symptoms. And then knowing where to go deeper into certain symptoms to really tease out what might be going on. 

So just as one example -- I mentioned psychiatric symptoms often aren't recognized as being potentially due to Lyme disease -- another one is urinary voiding problems. That was something I had never heard about. There are in fact a number of reports in the literature of urinary voiding issues, sometimes in concert with GI symptoms like severe constipation and then difficulty voiding and it is felt to be related to basically an autonomic neuropathy involvement, dysfunction of the autonomic nervous system, which is responsible for more, if you want to say automatic bodily functions like heart rate and blood pressure and GI motility. 

So there can be certain clues that, you know, when you have a constellation of symptoms and signs, knowing where to dig further rather than just dismiss it as, ‘oh, it's something just random and not related to all these other things we're looking at.’ That would be, I guess, my main point in terms of talking to parents and children about their symptoms is really having a very good sense of all the different manifestations, possibly, of Lyme disease. 

I think it takes a lot of reading into the literature, including the historical literature. A lot of times early reports are some of the most detailed. When investigators were trying to figure out what is this disease and what is its manifestations, they gave some of the most beautiful clinical descriptions of patient cases. And frankly, even reading patients' accounts of their own cases can be very educational. I really appreciate it when patients took the time, even if it's a patient blog, they'll sometimes do beautiful clinical reports on their own, including their lab reports, including details of the banding pattern on their Lyme testing. I have to say, I was just enormously impressed with how educated some of these patients become when they are dealing with a contested disease and being able to communicate what their lived experience is. It can be enormously educational. 

Lael Yonker 

Yeah, I would agree with Dr. Mao. What you said and alluded to earlier is these families have gone through a long path and now they're coming to see you and they've likely seen other physicians before and had symptoms going on for a while. So you have to let them tell their story and let them get through it all before you start jumping with diagnoses or tests that you want to do. You might be forming a picture in your mind as you're going, ‘oh, that's making me think about we should look into this or we should look into this.’ But you have to like, have the self -control to make little notes to yourself and let the families -- and most often it's the parents who are recounting their child's experiences. 

Sometimes kids will jump in and I do like to engage them as well and ask them questions. I'll tell them like, ‘so this is going on?’ so that they're a part of it. But honestly, most of the conversation is with the parents and you just gotta let them tell their story and then start to troubleshoot together. 

It's really a conversation and I like to walk them through my mindset. “Here's what I hear that you're telling me and these are the symptoms that are most bothering you.” And also, since long COVID is so new, I say, “This is what we can do as a clinician. I can make sure we're not missing other diseases that can cause similar symptoms so we're not muddying the water or complicating things. And then we can focus on seeing what's underlying long COVID.”

Also, I offer the research arm too, where this is something that we hope to be able to learn more and we are learning more, but sort of trying to talk to the family and engaging the kids, as they're age appropriate able to. 

Dr. Raven Baxter 

I just learned so much in this episode. There was something that you said, Dr. Mao, and it was about dysautonomia. I've heard about ties between long COVID and dysautonomia, but I guess I didn't quite realize there’s a possible connection between Lyme disease and dysautonomia, which is very fascinating. Can you speak a little more on that? 

Charlotte Mao 

Yeah, I think there is definitely less known about autonomic nervous system involvement than say regular peripheral neuropathy in Lyme disease. But there are a number of reports, as I mentioned, that really are very suggestive of some type of autonomic neuropathy involvement going on. A lot of times, there are cases where the patient went on to have some more characteristic manifestation of Lyme disease, like they developed a Bell's palsy or something that was more recognizable that made the physicians then go on to test for Lyme disease. 

The mechanism, I think, is not clearly delineated. It's more reports of manifestations that are strongly suggestive of some type of dysautonomia going on, I would say, in addition to the things like GI motility and the urinary voiding issues, which sometimes seem to be a sensory type of issue where patients feel like maybe their bladder is full, but they can't void when they try to do it, or that they actually don't realize it's full and then they could have maybe overflowing continence. I've seen both of those kinds of issues. 

So in terms of other kinds of potential manifestations, POTS, which is postural orthostatic tachycardia syndrome, is also felt to be related to dysautonomia. That's something that is reported a lot by patients with Lyme disease, also Bartonella -- a common co -infection with Lyme disease -- and also in COVID patients, you can see that occurring. 

So, it does make me wonder what exactly is the mechanism, especially with long COVID? One of the proposed mechanisms is that there's activation or reactivation of previously latent infections, for instance, Epstein -Barr virus is one that's commonly mentioned. But I do think that both Lyme and Bartonella are infections that have to be considered as potentially being activated or reactivated, you know, basically a dormant or maybe minimally symptomatic Borrelia or Bartonella infection contributing to manifestations of long COVID, I think, is definitely a consideration. Just as one example. 

Another example is a sense of internal vibration is something that got reported in the COVID literature as a possible symptom in long COVID. And before COVID came along, that is a symptom that, anecdotally, a lot of Bartonella patients consider to be a Bartonella symptom and it's a very unusual symptom. Sometimes patients don't even want to report it because they think it sounds too weird or they're crazy. But it does make me wonder is it possible that Bartonella is getting activated by a SARS -CoV -2 infection? 

One of the places it's felt to reside is in the vascular endothelium, the lining of blood vessels. And, you know, we hear more and more about COVID being essentially a vascular disease. So, could disruption of the vascular endothelium actually be leading to, if you want to say release or activation of Bartonella? I think it's a very rational thought that should be looked into. Absolutely. 

Dr. Raven Baxter 

Mind blown. Well, I am almost completely recovered, I would say, from long COVID. But at the height of my illness, that was one of the most jarring sensations was that internal vibration. I could just feel it. I felt like my brain is just constantly like moving. It was hard to describe and I didn't want to say anything. So I'm just like, okay, this is too much. There's just too much going on. But that's very fascinating. 

On a previous episode, we heard from Dr. Ed Breitschwerdt, who does research with Bartonella. I'm just thinking about kids playing in the grass, even I played in the grass, you know, like rolling around. What's the likelihood of contracting these organisms? What is the likelihood that there are kids that have post -acute infection syndromes but don't know it because their symptoms aren't as severe so they never really think to bring it up or get it checked out and that developing into you know, adulthood illness? Like, is that a far -fetched thought? Does that sound like a conspiracy theory or something? 

Charlotte Mao 

No, I don't think it's a far -fetched thought at all. One thing that's important to know is that the rate of asymptomatic infection with these infections is really sizable with both Lyme and Bartonella and I would say especially with Bartonella. So especially in a Lyme endemic area, such as the Northeast, where we are, if you look at a healthy blood donor population, the rates of seropositivity to Lyme -- so showing exposure and infection at some point in the past, but without any symptoms -- can be quite high. Even like 8 % to 10 % often gets cited. 

But when you actually look at studies and the literature, it can even go up into -- this is for Lyme, for Borrelia – the 20 % range has even gotten reported up to that much...definitely in the teens. And then for Bartonella, if you look at studies around the world for Bartonella infection, I would say the US studies which tend to be older have somewhat lower rates. But again, this is a healthy blood donor population, or sometimes it might be asymptomatic family members of patients who were diagnosed with cat scratch disease, one of the most commonly recognized manifestations of Bartonellosis historically. And those rates can, again, be up into the teens percent, as low as maybe 4 % up into the teens or even 20s % percent. 

But if you look at the non -US studies, some of the rates are really high up into the 30s, 40s, 50s percent. A study of German university students of 30 %, or a study in Italian school children seen in an outpatient pediatric clinic, but with no symptoms that were felt to be related to Bartonella...that's the highest one I saw and it was 62 % I think. 

So you're talking about a very, common infection, it's almost like it's a part of our microbiome, if you want to say, in a lot of people that maybe will never cause any symptoms at all. But what is it that makes certain people develop symptomatic disease? And what are all the symptoms of that disease? I think Bartonella is definitely an area of emerging science. There's so much that is being learned about this organism and, you know, Dr. Breitschwerdt, who you mentioned, he is just an amazing researcher and clinician. He's a veterinarian, but he has contributed, I think, more than almost anyone to really elucidating and communicating the potential manifestations of Bartonella in both animals and humans. 

So basically, in terms of the question that you asked, no, I don't think that's crazy at all. I think this is a very common infection. And the question is, what is potentially making it cause symptomatic disease in some subset of people? My suspicion, personally, just from a clinical basis, is that SARS -CoV -2 is contributing to that. There are some interesting studies that have just started to come out reporting, you know, some evidence of basically Bartonella becoming manifest in the context of a SARS -CoV -2 infection. 

Lael Yonker 

As a pediatrician though, I wouldn't discourage kids from going out and rolling around in the grass! Do a tick check afterwards. 

Charlotte Mao 

Yeah, exactly. Tick checks, absolutely important. And there are many more insect vectors possible with Bartonella. It's actually contested in the literature whether ticks are competent vectors for transmission of Bartonella to humans, although it's been documented in all sorts of ticks all over the world. But there are many other vectors. Fleas and lice are sort of the classic ones that are thought of with Bartonella. Our pet animals have fleas and although body lice are historically the kind of lice that have been associated with Bartonella infection, there is some thought that head lice could potentially, also. Spider bites have been reported as a means of transmission. So many, many more vectors. 

I'll also mention animal bites. That's been reported as a means of transmission. So, you know, I love animals, but is it possible that saliva could be a fluid that has Bartonella in it? It has been documented by PCR testing in dog saliva. So, maybe we want to take care to have kids wash their hands and their faces after they let dogs lick them all over. 

Dr. Raven Baxter 

Well, I've learned so much. I am like 50 times smarter now. Thank you so much for your insights. I would love to leave the medical students with any words of wisdom that you may have for them before we sign off. 

Lael Yonker 

Sure. I would say to always keep an open mind when you're encountered with anything from common to uncommon presentations. Always keep an open mind. Always think about what the possibilities could be. Listen to your patients. If they have a gut feeling, listen to that and try to see if there's something there, but definitely keep an open mind. 

Charlotte Mao 

Yeah, that would be my big message, too. I would say my own education was really a lesson in both humility and respect. Humility in realizing that the things that I thought were true when I started...that there were some big gaps there. In retrospect, I told patients things that I wouldn't say now with the education I've received since. 

And respect for patients and their knowledge, their recognition of what's going on in their own body and that it's something more, if you want to say. I think not coming to preconceived conclusions, like Dr. Yonker said, but really listening with a very open mind because that's when you'll start picking up patterns here and there. 

A lot of these manifestations I described are certainly not typical. But when you take each of these atypical manifestations and you see common threads here and there, you know, if you keep that open mind, then you'll start cluing into things and then backing it up with reading very widely and deeply in the primary literature as much as you can. 

Dr. Raven Baxter 

Thank you both so much. I can't wait to circle back and work with you again. This has been extremely insightful, very inspiring, and I can't wait to hear what the medical students think when they hear it. The Icahn School of Medicine and CORE, thanks you for your time. And we will see everyone in the next episode, which is the final episode of our series. Bye.