← Blood, Sweat and Smears - A Machaon Diagnostics Podcast
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- [00:06]
A
Hello and welcome to Blood, Sweat and Smears, a podcast produced by Macheon Diagnostics. In this podcast series, we will be discussing thrombosis and hemostasis from the perspective of our host benign hematologist and medical director of Macheon Diagnostics, Dr. Brad Lewis. Please remember to subscribe and leave a review.
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B
With that.
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A
I'll turn it over to Dr. Lewis. Brad, take it away.
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B
Hi, my name is Bjorn and I'm sitting in for Dr. Lewis for our series called Five Questions, where we pose five questions to physicians in and around the disease areas we work in. We hope you find these short interviews interesting and we hope these will age like fine wine. Today I'm joined by Dr. Xiaoping, who recently joined the Children's Hospital at Montefiore faculty as assistant professor in the Division of Genetics, Department of Pediatrics. She is co director of the newly formed New York center for Rare Diseases, which is part of Montefiore. So welcome and thank you for joining us.
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C
Dr. Pam thanks for having me, Bjorn. I'm so glad to be a part of your exciting podcast series and ready to answer any questions you want to send my way.
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B
That's great. We have five of them and here's the first one. Tell me about what you're building in Montefiore.
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C
Okay, this is a very multidimensional and layered question. So what we're doing at Montefiore is probably what people around the world are all trying to do right now for their patients, which is really to try to reconcile clinical with molecular medicine and also build end to end care for our patients. And what I mean by end to end care is really from the moment that patient walks into the clinic and you do your initial evaluation through all of the standard of care clinical things and then into all of the additional molecular studies and research based kinds of investigations that they may need through to any specific tailored therapies that might help with their specific disease concerns. So I think historically there's been a lot of, quite rightly so, medical, legal and, and infrastructure and logistical barriers that kind of make this process not the most streamlined. And I think at the New York center for Rare Disease, what we're really, really trying to do is make this a streamlined service for our patients because they already have to deal with so many logistical issues. I mean, you know, we're in the Bronx. It's one of, if not the most underserved of the communities from a socioeconomic perspective in all of America. And so there's a very, very strong burden as a strong what? Bruce McEwen would call Al static load already contributes to patients who have chronic rare disease. And so our goal is really to bring the best possible cutting edge science and clinical care to those patients who may not be able to otherwise access them. In doing so, to really learn lessons from this incredibly diverse population of patients that we may not otherwise be able to learn. So what that kind of looks like logistically for us right now is we are setting up extensive, you know, clinical infrastructure to be able to do deep phenotyping of different types. So not just labs, not just histopathology, not just detailed history taking, but certainly also with the use of the increasing arsenal of molecular and cellular tools that are clinically available, being able to sort of do more iterative longitudinal phenotyp phenotyping and also connecting that with upfront standard of care genomics and then transitioning to some of the more novel diagnostic technologies that I'm sure at this point many people have heard about, such as long read sequencing or optical genome mapping. Everyone may not need all of those things, but I think what we're hoping to do is sort of use strategies to be able to apply the correct tools to the correct patients in a very cost effective way. Another thing we're really, really hoping to do that I'm really excited about is some more de novo and pangenome assemblies, really to capture all of that missing diversity in our reference databases that we heretofore really haven't been able to do. Another thing that I'm really, really excited about as well is the ability to sort of establish functional downstream assays so that when we do have those candidate variants of interest that we think might be causing a patient's disease, we actually have the means to validate them, the means to sort of explore the mechanisms by which they cause disease and really informed tailored therapies for our patients.
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B
It sounds very exciting. I'm looking forward to seeing where that goes. Question number two. If you had to describe what you do as if it were a really good wine, what might that sound like?
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C
Okay, this is a much tougher question to answer because there are so many wines that could be used for this and, and I'm guessing that Bjorn, you're asking me this because we shared quite a few bottles now within it within a short time span. So I like to think of the wines that we don't typically engage with as much, I think, I guess you could say in a normal grocery store and wine shopping space, but are incredibly interesting wines that represent the places and the soul of, and the cultures they come from, and wines that have really astonished me, and given the kinds of complexity that have forced me to search for new vocabular when I'm thinking about wines, one region that has done that is certainly a lot of the islands in the Mediterranean basin. So Sicily, for example, the first bottle of Narella Masculaze, Narella Cappuccio I had from the area around Mount Etna was mind blowing. I mean, I could not. You know, there were moments when it threw out characteristics of Bordeaux, moments when it reminded me of great Burgundy from the most hallowed Pinot vineyards in France, moments when I could have guessed it was a Sangiovese from Tuscany. And yet it wasn't actually any of those things. You know, it had its own kind of character. And wines from Corsica do this for me as well. There's. There's this beautiful combination of feralness and Italian warmth and French elegance in those wines. And an additional genesis quoi that I think you can only get from sort of the. The meeting of the Mistral and the Sirocco winds and the meeting of granite and schist on that island. And then the third island I really want to highlight for our amazing wines is the island of Crete, which we're really just beginning to explore. And I'm really lucky that I'm friends with an amazing Greek wine importer whose name happens to be Dionysi, who introduced me to some of the wines from Satia years ago made from native grapes with beautiful names like Leotico and Mandalaria. And that is another island where, when I think about the lessons I've learned from those wines, those are the kinds of lessons I feel like I get from these cases, these undiagnosed patient cases. There's many, many ongoing layers of exploration and wonder. And you just feel so humbled at the generosity of the patients and what they sort of give to us and what they teach us and sort of allow us to do with their trust. And I feel that every time I have some of these lines as well.
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B
If anyone has a chance to share a bottle with Dr. Peng, one, let her order. And two, you're going to learn something. Our third question is, what's your favorite biomarker?
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C
Okay, this is so easy and a little bit unfair, and I apologize to all the other biomarkers out there in the world. But I have found, clinically, at least one of the biggest game changers for my clinical practice has been the ability to perform CD169 flow on monocytes as a surrogate readout for type 1 interferon activation. Historically, as many people probably know, it's been very, very difficult to interrogate for type 1 interferon activation. The normal serum cytokines that we're able to measure don't really give us that information. The type 1 interferons themselves are incredibly short lived and very difficult to measure in the blood. And so we've had to often sen research grade RNA based testing to very specific academic labs that are kindly willing to do this for us. And that is still available, but it does require more blood, it does require more time, and it is because it's research, you know, it's not something we can immediately put into a patient's chart for clinical actionability. A lot of Amazing doctors like Dr. Puili in Boston, Dr. Roshni Abraham and a number of other lab directors have sort of been able to implement this CD169 as a sort of readout. And CD169 is itself another furon target, as you might imagine. So using 1cc of blood in a purple top tube, I can now screen a lot of patients for this incredibly important inflammatory pathway to be aware of and for which we have targeted therapies like JAK inhibitors. So I feel like that's been an incredible game changer for a lot of my patients who have molecular diagnoses that lead to type 1 interferon activation, as well as for our patients who may not have monogenic disease but still have this as part of their overall genetically driven problems, like many patients, for example, who have lupus.
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B
Question number four. What is the most enjoyable part of your work?
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C
Okay, I probably can't say drinking wine with people like Bjorn. No, this is such a tough question to answer for me because there are so many enjoyable aspects of my work. It's probably easier to answer what is the least enjoyable part of my work, which is the bureaucracy and the logistics. But that's probably true of many fields, I have to say. It's the talking to the patients and that's probably a very generic answer, but I think I have to give a little bit of context for this. I grew up a latchkey kid, very, very much isolated. I spent a lot of time in museums and libraries and didn't really grow up talking to anyone. So I had virtually no social skills. Okay, so it's. I never thought of myself as being legitimately qualified to be a doctor because of the concern about the ability to even talk to human beings. And I have been incredibly lucky in my patient interactions. I feel like I really, really get along with my patients. They're such a joy to talk to. They all have such different personalities as you can imagine. But the ability to sort of communicate some very complicated seeming scientific and medical concepts in ways where people are, you know, having these aha moments where they kind of get it. Being able to feel that a patient feels supported from you, feels like their concerns are validated, even if you may not have all the answers for them at your fingertips. The feeling that, you know, you're sort of committed to this joint journey together and that they can appreciate and sense your empathy for them, that's been one of the most rewarding parts of my job.
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B
Yeah, one of the most enjoyable parts of my job is interacting with physicians. I don't get to talk to patients, but I do get to talk to physicians. And it's for many of those same reasons. All right, so question number five. Where do you fit into the medical picture? When do you get brought in? Who do you work with? What does that look like? Because I think it's fairly unique.
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C
Yes. And I guess even as a clinical geneticist, my role has been quite different, maybe from what many other clinical geneticists do. And it does very much depend on the institution and on the other providers who get initially involved. So as you probably know, people who practice clinical genetics really have had the specialization in metabolic genetics. Many of them are experts in what we call inborn areas of metabolism. And for those conditions, there's a clear sort of, I guess you could say, set of protocols for many of those diseases. And they get called up front to really help with life saving treatment and workup as needed. The involvement of clinical geneticists in genetically driven blood and immune disease has been probably much, much patchier. And historically was not a thing, I guess you could say. I can probably count on one hand the number of other genetics colleagues I know who are involved in the care of patients with genetically driven blood immune disease. You know, we're a very small community to begin with and we really all, you know, work together very well. But initially, a lot of times we would never get called, is kind of the honest answer. I can't tell you how many kids, even as a pediatrics resident that I worked with who would come into the pediatric ICU with what we call, you know, some kind of acute hyperinflammatory diathesis or other sort of potentially immune mediated problem. And genetics probably was one of the last services to be involved. And this was also true on the adult side as well, perhaps more so, because historically adult onset problems were not as recognized as potentially having a strong genetic driver. I think that is really, really changing now, certainly with the advent of a lot more upfront first line next generation sequencing, certainly with the recognition that immune diseases can affect people of all ages. And I've been very, very lucky at Johns Hopkins to have great colleagues who have sort of taken me into, I guess you could say, their diagnostic workup and planning. And so we're having these discussions up front much, much earlier. And we're having these discussions about patients who present with primary suspicion for immunodeficiency. So recurrent infections that are quite severe or life threatening. We're having these discussions more for patients who might have primary immunoregulatory or auto inflammatory conditions, which was a harder thing to recognize largely because we actually didn't have a lot of objective assays for some of these conditions until very recently. And again, I have to give so many kudos to the academic lab directors who've done so much to change that landscape for us so that now as geneticists, when we do send upfront genetic testing, we have a lot more information about what that patient's clinical immune system state looks like than we did previously when we were sort of just shooting in the dark using genomics. So I would say all over the map, sometimes I'm called very, very, very upfront, sometimes I'm called a little bit later in that person's course when they've sort of been refractory to a lot of the first line treatments tried or even, you know, first, second line treatments tried and the patient's not getting better. Sometimes they're diagnosed with something up front and really my role becomes one of counseling and sort of planning for long term management. And I think that's one of the great parts of my job, is that we are very, very versatile. We fill a lot of different roles. With some patients, I'm really the therapist and the genetic counselor much more than actively prescribing medications or doing anything. With other families, I'm more of like the quarterback. And so they're just trying to organize all of the different subspecialty providers who are providing care for that patient. And in other situations, I' really sort of, you know, on the front line trying to recommend and interpret, you know, different kinds of molecular diagnostic testing, whether it's genetic or cellular or functional.
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B
So yeah, great. Well, that's, that's our five questions. And now it's time for our bonus question. And that is, what is one thing, anything that you'd recommend?
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C
Oh, that is so tough. There's so many ways that one could go with this, huh? I'm going to give a very specific recommendation because I love to travel. And one of the things that I've recognized is quite difficult when you're traveling by yourself is drinking wine. So, you know, most places probably expect that you drink wine by the glass, and that kind of limits your options. If you're going to order more than wine Coin course, how do you choose all the wines to pair with that course? So I tend to like to travel besides for work in cities that have incredible wine cultures and people that I can learn a lot about wine from. And right now, two of those places are Turin and Madrid. And the wine I like to order most when I'm traveling is champagne. And the reason I like to order champagne is because historically, I think champagne has been thought of as just like a celebration wine. We drink from flutes, we toast, we move on with life. It's actually an incredible wine to pair with food. And when you have a grower champagne from a small artisanal producer, you know, you start off, it's a little bit more chilled, it's a little bit tighter and more closed. You get all of that sort of like palate opening acid and zest. And that goes really well with your opening course, your appetizer. As that champagne develops in your glass, you get more layers, you get more density, you get more texture, you get more complexity, and then it becomes incredible to pair with your subsequent courses. So if I had to pick a bottle of wine, 13 course meal, I would pick a bottle of champagne. And then the great thing is you don't have to drink it all. You can leave the rest of it for the kind restaurant staff who are putting up with you during that entire meal. So that's my recommendation. Travel well, buy yourself a bottle of champagne and enjoy your dinner.
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B
That sounds like very good advice. So thank you very much for your time here today, and I hope that we can share a bottle of champagne with our colleagues at the next nicer meeting where we had a bottle of champagne just recently. And yeah, thank you for your time. I look forward to what you build there at Montefiore.
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A
That's it for us here at Blood, Sweat and Smears, a podcast produced by Matrion Diagnostics, your reference lab, and CRO, specializing in thrombosis, hemostasis and rare disease. Thank you for listening. And if you have a question or comment or there's a topic you'd like Dr. Lewis to speak to, please send us an email to blood, sweat and smearsachondiagnostics.com that's M A C H A O N diagnostics.com you can follow Matrian at Twitter ationdx. Be sure to subscribe to Stay in the know Share this podcast with clinicians you think might appreciate it, and we hope you'll join us next time here at Blood, Sweat and Smears.