Bad Ideas, Good Outcomes, and Thin Melanomas

Welcome to season three of Derms on drugs, a video podcast brought to you by scholarship medicine the best education platform and dermatology and provided no cost to medical providers. Derms on drugs is we're cutting edge dermis in your miscommunity. Dr. Matt Zyres from Dr. Mottology in each week. I'm Dr. Maris and see buddy's Dr. Laura Ferris from the University of North Carolina and Dr. Tim Patton from the University of Pittsburgh and we use our 70 years of combined derm experience to discuss debate and dissect the hottest topics of dermatology is everything you need to know to be on the cutting edge of Derm and you actually have some fun listening. New episodes drop every Friday on scholarship medicine, Apple Podcasts, Spotify and other region podcasts, platforms and I highly recommend that you download this college medicine app to access the full podcast video archive, explore the best educational content in all of Derm real, pharma independent coverage of all of Dermatology supported by an amazing AI clinical consultant called Ask Simon. So this week we've got another one of our patented six pack episodes and we actually have Dr. Patton coming to us live from Italy and it turns out that when he's in Italy, he actually has better internet than he does whenever he's at home. It's kind of shocking. I just maybe maybe that means he needs a tech upgrade, but we'll see. But Dr. Patton, how was the trip to Italy? Did you just get you just got there last night? No, I've been here. Well, I can't remember. I got here on Sunday. What's today Monday? Yeah, we'll call it a morning. Sunday morning. Sunday morning. Sunday morning. Not last night. It's yesterday to the rest of us. Yeah, yeah. I left on left America on Saturday and got here Sunday morning. Where are you right now? Florence. Oh, have you been to Florence before? I have. Yeah. Okay. Because the Ferris have you been to Florence? I have not. I'm not a suff-- And the least sophisticated apparently. That's true. She's not been to-- For our listener, she has been to neither Venice nor Florence. So it's probably never even seen the needing tower of pizza. You know, that's the-- I will say, for any of our listeners, we've not been to Florence. Being in the same room as the statue of David, like, it feels like it's radiating some like this energy. It was really crazy. I like stood there for two hours and just was like, man, it was-- it was nuts. I don't know. Pat, did you experience anything like that when you went to see the statue of David? I haven't gone yet. It's on the schedule, but it hasn't-- haven't gone yet. Okay. All right. I felt that way with the Sistine Chapel. That kind of-- like I just got this vibe of like, man. Yeah. I agree. And I have been to Rome, those-- Oh, you don't have to make stuff up. Yeah, she's been-- well, she's been to the common parts of Italy. She's been to Rome, Texas. She probably had a-- she probably had a layover on her way to somewhere in Eastern Europe, the Sistine Chapel. Shoulders covered, knees covered, did it all. Okay. All right. Yeah. All right. Let's get into it here. Ferris, where do you got to lead us off? Okay. So today is Melanoma Monday for me, even though it is June already. Okay. But this is Melanoma Monday. So I am going to start with a paper that was in the BJD. And this is entitled "Impact of Clinical Pathologic Features on the Prognosis of Thin Melanomas, a retrospective cohort analysis, Beagles at all. Seminoff was the corresponding author. So what is this about? This is like, you know, we think of in Melanoma, no big deal, right? But, you know, sometimes that's not the case. There are those thin melanomas that are recurrent or metastatic. And so they looked at comparing non-recurrent versus recurrent melanomas or low versus high-risk thin melanoma. So all of these are melanomas of millimeter or thinner. Generally, they are stage one. They've been, you know, excised. And so these are the ones that you're like, okay, good. But interestingly, when you look at data, they, then, Melanomas, count for about 30% of Melanoma deaths. That's more because there's just lots of them, not because most 30% of them will kill you. But, you know, it's hard sometimes to know, you know, knowing that we can have, you know, metastatic Melanomas that are T1A, or that are stage one A or stage one B. You know, how can we get an inkling into which ones might be the bad actors without just treating them all as bad? Okay. So design, retrospective cohort story from mass general, brigham and the Dana Farber patients diagnosed between 2002-15, stage one A or B Melanoma, with a tumor thickness of a millimeter or less. That was biopsy-plus-excision. They looked at demographics, comorbidities, tumor features, recurrent status and type, and cause of death from EHR cancer registry. And so they were only considered non-recurrent. They only put, you know, patients in the non-recurrent bucket, if they had at least five years of follow-up. So, you know, recurrence, it could be shorter, non-recurrence was five years. And so what did this look like, this cohort size, 802 patients within Melanoma's 71 had recurrences, that's about 9%. And how did they look? They were a bit older, like you might expect 61 versus H57 for the non-recurrence. And sex distribution was pretty similar. What was predictive of recurrence in, you know, what were already thin melanomas? High-mitotic rate, that was, you know, a big one, odds ratio 1.28 per additional mitosis per millimeter squared. So that was one. The other one that's interesting was presence of tumor infiltrating lymphocytes. So my first thought was, yeah, yeah, you got tills. That's a better prognosis, not the case. So actually having tills was associated with a worse prognosis, odds ratio of 3.26. And then another one that we, you know, might expect, which is the absence of a radial growth phase. So, odds ratio of 7.52 if they saw no radial growth phase. For five year melanoma specific survival, being uninsured or self-paid, which is basically uninsured, was associated with kind of dramatically worse outcomes has a ratio of 29.5. Five year overall survival was linked to, you know, higher Charleston, comorbidity index, which is basically like, you know, taking into account all your other comorbidities. You're like Patent. Yeah, you probably have an already valid that's about to blow in any second. Exactly. Bad heart, you know, poorly traveled stuff like that. My exotic rate, higher my tonic rate also associated with worse overall survival, as well as that absence of the radio growth phase. I might think, okay, thin, less than a millimeter, you know, is that does that matter? So it didn't. So if they just said, well, let's consider point eight, you know, less than versus point eight or higher as the cut off. No difference if they could treat it as a continuous variable, you know, or you didn't matter. Within that one millimeter of thickness, it wasn't like there's thin, thin T ones or thick T ones, it was just no, it was really just the factors that we talked about. So radial growth phase, tills, be no radial growth phase, bad prognosis till tills present bad prognosis and then higher mytotic rate associated worth a worse prognosis. So what, what do we take away from this? So mytotic rate, like it makes sense. So if you start to see, you know, one mytosis, I don't worry. But when it's like five or six, I start to be a little bit concerned. The till thing was interesting, the author speculate that, you know, maybe these were sort of these exhausted non cytotoxic like regulatory T cells being present, they don't really have any data for that, that was speculation. And then the absence of the radial growth phase is kind of interesting. Like, I guess the way that I think about it is, you know, when we, I think a lot about, you know, melanoma screening and, you know, we always like, we kind of considered like, lots of thin melanomas is over diagnosis, but, you know, in a way, you know, what we're really trying to do with screening is to basically find those lesions, I think that maybe have a vertical growth phase and where we think we're going to like intervene just in time just before they get too deep and go back and excise those. So, you know, it would suggest that you can be all thin melanomas are not created equally. This would say about 9% of them if they really did this in a systematic sequential way and didn't sort of pick out cases, have some potential to, you know, have a bad outcome. So I guess when we're screening, we're really trying to find those 9% and intervene as quickly as possible before they metastasize. Maybe that's a way to think about it. First, what is your, so first, the immediate question that jumps to mind for me, this is exactly the group that people would normally be like, oh, these are the people that we should use castle for. You know, thin melanomas and blah blah blah. As we you and I you guys and I have changed from being a, we should use castle and everybody too. And we should never use castle. It's a terrible test. And eventually we'll do an episode just about castle and why I now think that. But so, so we argue about this castle change anything. Does any of this change anything for what, is this gonna play into any decisions you make? You know, I think that when you are having the, do we, you know, more frequent follow up maybe. Do we want to, you know, consider sentinel nodes? So, you know, when patients are on that border of being right around point eight, if they had more of these risk factors, I don't know what to make of the till. I'm gonna put that on the back burner in terms of what I'm gonna think. But, you know, I would say higher mitotic rate that's gonna push me toward, you know, saying sentinel nodes so that we have the ability to follow them a little bit more carefully. Absence of radial growth phase, that gets me a little bit more nervous. You know, maybe this will be somebody who I follow more carefully. I mean, we don't have prospective data to say, ah, what we need to do now is image you or send you when you're thinner, or, you know, anything else like that. Like it doesn't give me actionable data. But, you know, I guess what you could also say is, we don't, you know, maybe what we should be doing is like prospectively following, do the prospect of trial, you know, like you don't necessarily, gene expression profiling is just one thing to put into a model of deciding how high risk a patient is. You know, maybe we should look at what if we did this just with mitotic rate till, and, you know, absence of radial growth factor. Yeah, I don't know, I can't remember if they actually had like sentinel node positivity and things like that in here. I don't think that they looked at that, at that degree. So, okay. Interesting. Pat, do you have any takeaways on this? This is such a small target of patients though, isn't it? Like, anything you would-- It's small number, I mean, it's 800. That's not nothing. No, no, but what I'm saying is, if you come up with a plan to say, okay, you have more tills. And so, I'm going to change my how we follow you up. The-- most of the people that you follow up with, like, more tills are probably going to be okay. So, aren't you, like, just increasing everything to pick up? I smell like-- I can't see anything make, like, being cost effective or not without risk of overworking people who eventually don't go on to become anything. You know what I mean? Like, we're kind of getting to the point where, like, just keep doing what we do for these patients. It's unfortunate that this happens, but how are we going to change anything clinically? That's going to make a big difference. And not going to increase working up and following patients that actually are going to be okay, right? Yeah, I mean, I think that, again, it kind of goes into the decision making. And again, these are all in the patients. These are all the patients for whom you would fall under MCC guidelines into discuss and consider sentinel node biopsy. None of these are, like, 100% recommend. So these are all in that discuss and consider. So I think that being able to say, you know, you got to have things you consider. It's not just, I don't know, right? You say, why would we consider? It's sort of a bitchfair. I've never-- that's never occurred to me. People you should consider. We've got to have stuff you should consider. That's actually really useful. Yeah, I mean, consider isn't just like pontificated. Here's what you would take into consideration. Here are some high risk features. Or you don't have these. Or what-- I mean, there's a lot of things. What would you do if it were positive? What would you do if you're a negative? You're going to do the same thing than maybe don't do it procedure. OK. Well, that's used. Every once in a while, most of what you say, I'm just-- Yeah. Every once in a while, you get a good-- you do that a little, a little, a little, a little, a little. OK. All right, Pat, and what do you got? All right, my first six-packed paper from February, 2026, "Jad," and is titled "Biologic Therapy Plus," oral oxybutin and chloride, and hydrodinitis subrotea. We particularly valid therapy to moderate acute flares. Ooh. It was by Mollonali et al. It was a study performed at the Polytechnic Marca University right here in Italy, which is where I am. I'm not learning. Is it Halloween papers? I was going to do this other Italian one, and I couldn't access the journal. I traveled all the way to Italy. That was such a waste of money. I still couldn't access the journal. Your whole trip is now tax deductible, Pat. Yeah. Yeah. You get to stop over there. Get my tax lawyer on that. All right, yeah. So this group had an earlier paper evaluating oxydevenin as monotherapy in H.S. This paper is a similar study to the three. Ooh, ooh, ooh, ooh. It was at the monothec because there was one where they did antibiotics, somebody did antibiotics, and then they did oxybutinin at the end of the antibiotics, and it extended how long before people flared. Is that a difference? I'm not the study you're talking about. I don't know. I didn't open that study. I pulled it up on PubMed, and it was in 2023, J-E-D-D. That was it. And that was the title of the article. I didn't go into it. Yeah, yeah, I think that pretty. I'm one of the companies that I'm only reading Italian papers. Only Italian this week. Yeah. Yep, yep, yep. All right, so this was prospective study, 25 patients, and each group, group A, started at Aluminumab plus oxybutin. And group B started at Aluminumab alone. They didn't get into the dosing. I'm sure it was the standard H.S. dosing. At Aluminumab, that is. Oxybutinin was dosed five milligrams for the first week, seven and a half for the second, and then 10 milligrams for the duration of the study. Both groups were followed for 48 weeks. So valuations were done at baseline, 24 weeks, and 48 weeks by blinded evaluators. So it wasn't like a randomized double blind blah, blah, blah, but the evaluators, they didn't know what the patients were treated with. So that's pretty good. Table two kind of lays it out there. The improvements in the oxybutinin at Aluminumab group were statistically significantly better than the at Aluminumab alone. And multiple measured outcomes. My video went funny there. So mean IH4 scores, pain, pruritis scores, nodules, abscesses, DLQI, number, enderation of flares. Small numbers difference, but it was all statistically significant, favoring adding oxybutin into Aluminumab. So it seemed like oxybutinin helped. So maybe we start adding this on. What did you guys think? Almost was like-- I saw that paper briefly. What was there like mechanistic thought? You decreased sweating, even in patients who didn't have-- so the number of people that had hyperhydrosis versus nonhyperhydrosis was like the same. So whether the patients had hyperhydrosis, not hyperhydrosis, the oxybutinin still worked. But they still say that you sweat less. Sweat does contribute to the microbiome. We think microbi-- like bacteria has something to do, given the effectiveness of urtepanum. And so their theory is you're altering the microbiome by changing the amount of sweat on the skin. And that contributes to improvement. And people have done Botox, like regional Botox for HS. And there's kind of some efficacy with it. So I mean, then why not do what's that? Yeah, I mean, with like the HSX, we had the UNC guy on. I'm blanking. It's late in the middle. Chris Siet. Yeah. And then we talked to Dave Luey. When they-- when they had given their HS talks, I don't think they talk about sweating at all. I don't think they talk about Botox. I don't think they talk about oxybutinin. So is this real? I don't know. I don't know. I have 1,000% by it. 1,000% by it. We know it's-- It's a low-- it's a small study, very poorly controlled. That is all over it. It is all over it. All over it. Do you worry about oxybutinin and dementia? Oh, yes. So my question was going to be, should we be doing like a pyrolyte or oxybutinin in these people? Classical pyrolyte, there is no dementia risk because they're in crushed blood-brain barrier. But you might have to take it two or three times a day. But it makes-- and by the way, I am calling it right now. I am claiming that the title and dermatology of the king of low quality evidence. That is my-- That's what you are. That's what I want to be. The later-- Low quality evidence. And just the end of the world. That's what you are. Yeah. That's yes. But so great. I think it makes sense. We know that it's going to be related to not just apocrine glands, but sweating in general, because people get it in their areas that are non-classic apocrine areas. And so I think it's more of an occlusion disease. And I think that it's-- this makes sense to me. I'm going to start adding some glycopyralate on to people and see what happens. OK, here's my proposed clinical trial. If you want to design a small, not very well-designed, underpowered study, because I know you've loved-- Oh, quality. - Ew, quality. - How about Cue Brexaw wipes, glycopuralate wipes, kind of do like what insight did with topical rocks. And you do like take early stage disease, you wipe down one search white with Cue Brexaw wipes and see if you can prevent, you know, if you can treat earlier stage disease. - Here's even, so that's, I actually want to be the king of no evidence. Just low quality, even better no evidence. We should start compounding oxybutine and glycopyralate together with a topical jack. It'd be like, all that's, I think we just cured HS. - All right, don't worry, I was quit talking about it. We figured it out. - We're done, I'm in the disease. - You can't get compounded glycopyralate spray. - Yes, I know, she's throw some jack inhibitor in there, it's all done. - And compounded tofacitinib. Say you could do your glycopyralate, then ask him, no facitinib. - Right done, no, I'm not sure. - What are the karma middle man? Get it all compounded. - Just for all of our patients, for all of our listeners, can you imagine what kind of amazing treatment got? Patience got when the three of us were residents at the University of Pittsburgh, standing out in the hall. I don't know what to do for him. Do you know what to do? - I don't know what to do. And you guys were the ones who taught me. - Yeah. - Yeah, so scary. - So scary. We don't know anybody though. - That's what led to like photo-avaniac therapy for a patient with dairy is. - Oh, never forget it. - Yeah, I remember that. - That was an article about it. It was an article. - It was like a case in a impact factor, 0.2. - A low quality article, and that was like, yep, I'm signing you up. - So by that this was for anybody, who was listening before, this is the woman that Pat and I almost killed with the full body electron beam therapy for dairy. So I was desperate for like anything to do with this woman. So I photo-avaniac her neck. And then put her in the, you know, the thing, turned the light on, went to see another patient. I'm in the other room here in the patient. And I hear about here. (imitates car engine) And I'm like, what's going on in my heart? Help! Oh my God, help! 'Cause it was so pretty. - It was bad, yeah. That was maybe, that's not a good treatment. - No, no. - I know your heart was in the right place. - Yeah, I was trying to do anything that could work. I was also, I was also thought that patient for a while. So it is tough, but. - Yes. - All right, all right. Let's, let's, you guys got anything else you're going to mind? - Go on to yours. - All right, so I'm gonna do my more real one first. So this was an article out of China. And it was about, do you feel about facial air theme? And this was, to some extent, just another confirmation of what we already know. 'Cause I still hear people lecture and talk about this who just don't know what to talk about. So do Pilomem associated facial air theme? This was, so this title was Characteristics and Risk Factors who do Pilomem associated, head and neck dermatitis and patient with the top of your dermatitis. The basic takeaway, is it looked at a whole bunch of patients who ended up 130 patients who received Pilomem and some of them got, head and neck, the Pilomem facial air theme. Some of them did not. And what they found was that the two predictors were being over the age of 12 and having atop. So comorbid allergic rhinitis or an IgE that was above 1500. So those were the only two things they found that correlated with it and it confirms again for us what this, what the Pilomem facial air theme is. So we know head and neck atopic dermatitis for any of our listeners, head and neck atopic dermatitis. Whenever you have somebody who's, atopic dermatitis worst on their face, neck upper chest. Think areas that they get subarigne dermatitis. Those patients are allergic to malacezia. Might be, it's probably more IgE. It might be a little bit T cell, but those people are allergic to malacezia in addition to regular atopic dermat. And they do not do well on anything. So these are the patients who often will fail, motorbill biologics fail a jack, they fail everything. You put them on a little itchriconazole and they get better. You do itchriconazole 200 milligrams a day, till they're better, then once they're better, you do the itchriconazole, set it in Sunday only. Duplomate facial air theme is a variant of this. And so it's people who are, and we have data on this from some other studies that showed elevated specifically anti-malacezia IgE is associated with, it's the most predictive thing of duplomate facial air theme. And so it's see people over the internet of lying sensitivity to malacezia. When you put them on dupe, we get the immune shift towards TH17, TH17 is how you're writing reacts to malacezia, it's driving symptoms. And so you get this overlap AD, subderm picture, this is the middle of that facial air theme. Every one of those patients who has to pill them a facial air theme, you should assume that's what it is. You should put them on a triconazole. And then if they don't get better, then you think, okay, maybe this is Demodex, maybe this is contact germ, maybe this is something else. They're not all malacezia, but probably 80, 90% of them are. Okay, Matt, triconazole, not like fluconazole. So you can do fluconazole, but we have some literature on it. And it triconazole is substantially better. Not even by Matt's irons evidence standards. So there were like seven patients that somebody, they didn't get better on fluconazole and they switched them to it triconazole. So that is conclusive evidence. But mechanistically, mechanistically, right. So fluconazole is water soluble. That's why it's a good drug for mouth in vagina. It triconazole is lipid soluble. So it is a much better drug for the sub-derm spectrum of stuff. So it's the small amount of literature we have says it just better. And it's just gotten cheap, right? So it's not like it used to be where it was. - Yeah, it's interestingly hard to find sometimes. - Huh. - I just have this of a horrible tiniya case. And like I, which I think is multi-drug resistant, I cannot, it was like calling all over to farm and it was just a big, I guess I've got 30 pills. I've got the pharmacist called back and said, how about voraconazole? I was like, no, we're not gonna jump right to voraconazole. Maybe we'll just-- - Afo, Afotaracin, dee. - Afotaracin, yeah. - Afotaracin, yeah. - Yeah, I both of them. - I think you could call around and order itchriconazole. So yeah. - Big man, I have a question. So the IgE Malacesia, now one of the, like do be supposed to actually like work against class and switching. - Yes. - So what I think is happening, what I think is happening, the, I think the IgE is a marker that people probably also have T cells, 'cause we don't care. - There is some work looking at T cell reactivity to Malacesia and that has been shown in these patients as well. But there's a lot of commercial labs can do Malacesia, IgE, so we have a lot more data on it. I think it's just a marker of in general, like you are allergic to-- - The IgE could actually get better. But you have this. - The immune system is reactive to this. To Malacesia. - Okay. - Yeah. - All right. - All right, that's it. So yeah, but oh yeah, so to take away the things. So right then it was over the age of 12, because head and neck dermatitis always has its onset after puberty. So it's like once they would start to get acne that tells you now they have more sebums or they're malacesia. It can, it can have its onset anytime after puberty, but most commonly it's its onset during puberty. And then elevated IgE to tell you that they're at a topic and susceptible to developing allergy to Malacesia. All right. That's it. All right, Ferris, what's number two? - Okay, this is like the serious one. Not that the other one wasn't, but prevalent of familial melanoma genes and cancer risk among genomically ascertained individuals. This was recently in Jamaderm Goldstein at all. Okay, so this is kind of looking at this, you know, this comes up, people ask me all the time, when do you do genomic testing or, you know, genetic testing for patients with melanoma. And, you know, I always kind of say like, oh, if they've had three or more in base of melanomas and especially if the first one was before the age of 50 or there's three in the family or there's like, you know, melanoma, melanoma, pancreatic cancer. So that's kind of the answer I've always given. But they looked at this a little bit differently. So they looked at just, you know, they looked at patients, they didn't say, you have melanoma, we've tested you, here's what we found. They looked at, you know, over almost 700,000 people who had had their, you know, genome ascertained either through the UK Biobank or the GaiSinger My Code. And then they asked sort of the spark question, if you start with the genotype instead of the phenotype, what do you learn about the familial melanoma genes and their cancer risk? And they looked at melanoma risk, but then they also looked at sort of overall cancer. - So they looked at, they started with genome, found the people with the high-risk genes and then said, how many-- - Did I get melanoma? - Do they get melanoma? 'Cause we've never really been able to look at that before 'cause you just have to have a bunch of random people that you got at it. You got to do that. - Yeah, now that we've are doing that we can actually start to ask these questions. - Yeah, okay. Um, so the big eight major familial melanoma genes that they studied were, um, they were eight, they were back one CDK and two A CDK for MITF E 318 K, P, P, P, POP one, um, turf, two IP and turf promoter. Um, and so how did you just give away your password? I did. Yeah. Not shit. That's also the name of my next dog. But yeah, um, the combined pathologic variant prevalence was 0.5% in the my code and 0.9% in the UK biobank. Um, so, you know, that was basically at a population level, a little under 1%. So how many people had that's how many people had at least one of these had at least one of those. Um, interestingly, the most common one was MITF E 318 K. Um, and then the next most common was, um, well, so that was the most common, um, and then the next most common group were the CDK and two A, POP one, BAP one. And then a CD CDK for blah, blah, blah, those were the least common ones. So while like I was like MITF, I don't really think about that. Like I think a CDK and two A, you know, there are many more people who harbor this MITF mutation, but you can think of it as like having lower penetrance in terms of the absolute outcome. Um, okay, I can, if anybody is super interested, I'm going to give you the high level of what they do, because it's good like for us review fodder, because I know all my residents listen to me. Raptally. Okay, BAP one. Um, it's a DU, BIC would nice tumor suppressor gene CDK and two A encodes P 16, Inc. 4A and P 14 ARF, which are cell cycle checkpoint proteins. MITF is the, is a melanocyte master transcription factor in E 318K is a variant that's a moderate risk, allele sort of, you know, lower penetrance. POP one is in the shelter in complex of genes that protects telomeres, um, and um, ACD and turf to IP are also sheltering genes that help to maintain telomeres. And then the TERT promoter also is involved in telomere regulation. So lots of telomere related genes. Okay, that was where the basic science education ends. Um, okay, in both cohort, melanoma risk was increased primarily for the CD, CTK, CDK and two A, MITF, E 318K and POP one, um, gene mutations. And it was MITF and CDK and two A, um, carriers who developed melanoma significantly earlier than non-carrier. So, um, they do have a, you know, a capillary myocurbs and they show that they start separating in the fourth decade of life. Um, so that is kind of helpful because you're like, all right, if their family has, you know, MITF, E 318K or CDK and two A, think about starting screening, you know, more like fourth decade of life. So in their 30s, should you profil actively just remove all their skin? Yes, Matt. That's what you should give. I read that in a journal of, you know, it's something, uh, low quality evidence. I love quality. Durham. Now I just don't remove all their skin. BAP1 actually did not have a very, um, significant, uh, association, but there were fewer than 50 carriers per cohort. So it may have been, even though it's pretty big underpowered. Just look at that. My bias with BAP1 is I actually think that they carry a dot, they, they have these BAP1 associated, you know, epithelialoid, almost like spitsoid looking leotians. I think historically that the BAP1 or BAPOMAs had been called melanomas. And that's where a lot of that came in. I mean, I think there are still some melanomes in that population, but I think it seems higher because I think there's been misclassification of these spitsoid BAPOMAs. Okay. Broad or cancer spectrum important CDK and two A associated with melanoma pancreas, which we knew, but they also saw brain head and neck and, um, and at least one of the cohorts, uh, breast biliary tract and non melanoma skin cancer. Um, so that was kind of, um, interesting. The ones that held up after, you know, statistical correction where pancreas brain melanoma had neck biliary tract and non melanoma. So, you know, those were new, um, you know, think about, you know, those patients who have CDK and two A, they really are pretty high risk for cancer overall. MITF mutation associated with also kidney cancer, which has been talked about in the existing literature, but they also saw some associating with cervix nasal cavity middle ear and non melanoma skin cancer. Pot 1 associated with not just melanoma, but thyroid cancer and Hodgkin's lymphoma, and non Hodgkin's lymphoma and myeloma. So there is sort of this hematologic malignancy signal with pot 1 mutations. And then BAPOMA, they also saw a prostate cancer association. So I thought this was sort of interesting. It's like a way to look at this, um, you know, differently. The other thing that so takeaways, um, consider the place where they did see like higher rates of mutations are the group who got melanoma before the age of 40. So I've kind of said, like before the age of 50, but really consider this in patients who've had multiple primary melanomas and melanomas before the age of 40. And then care, like more care, ten-a-site carcinoma was kind of went along with that too. And then the other thing was that they used this like benchmark. There's this idea that, you know, when should we test for, you know, when should we do genetic tests? Like when our pre-test probability is greater than 2.5%. So they, this kind of met the match. So if you use the threshold of multiple primary melanoma is melanoma before the age of 40, then you do have sort of a leg to stand on the pre-test probability is 2.5% or greater. Have you guys ever sent a patient for gene testing? From I've never done this is not on my radar at all. Because, you know, if you, you would have to get like a good with all these different cancers. If a patient had one primary melanoma in a first degree relative with cervical cancer, is that like, no, oh my gosh, you could have, it's not enough? Yeah, they would have to have a primary melanoma before the age of 40 or multiple primary melanomas and particularly with one before the age of 40. So then, so have you ever sent anybody for genetic screening? I said yes, I send them to the genetic counselors to discuss. Okay. There's a lot of -- So you're not ordering the next gen sequencing yourself. You're like, go talk to genetic counselors, you had two primary and invasive, right? We're not talking in sight. Yeah, we're not talking about insight too. Invasive, particularly before the age of 40, you know, if you throw in, you know, family history, if there's something that looks like either BAP1 mutation or CDKN2A, I will, you know, dig into that a little bit more. The BAP1 thing in this study, like mesothelioma, I think, did not show up in this and like we know that's an association with BAP1 mutation. So I think it's a little underpowered to make dramatic conclusions. But yes, I will. I send them to genetic counselors. They talk to them and have the discussion about whether or not they want the testing. I will tell patients if they don't want to do it. Okay. If you've had, if you have an invasive melanoma, and a first degree relative with pancreatic, yes, send them. So sometimes it is only one melanoma, if a relative has another, but they go through and name all these cancers. So where do you draw, like pancreatic, yes, you, you suspicious for CDKN2A. So it is where there is a high, so like this is one study that picked up a signal. I'm not going to change sending to genetic. Okay. Okay. That's what I was confused about. I was like, so what are they telling us to, who are they telling us to refer these days? Now, it's really more before the age of 40. And that is more helpful than to me, than before the age of 50, right? That cuts out a group. So I think it is helpful and it's a discussion. And I tell patients like, even if you, you know, somebody's had four primary melanomas and they test negative for one of the genes. I'm like, I'm not going to, it doesn't really change what I'm going to do. Right? I know you're at risk. You've had multiple primary melanomas. You're going to keep seeing me. So they need to think about that. But I thought this was really the first time we've taken a huge population said, who identified who had the jet, people got tested, but people just had that and then follow them. Yeah. Yeah. I just, I was so confused by the end of it. I'm like, I guess we just refer anybody. But I think I got a little too excited here in Italy. And you can't just get 23 in me done. Now. Okay. That wasn't joking case. I love it when I say something that's supposed to be dumb and Ferris answers me very seriously. He may actually be seriously asking me this question. I need to take it seriously. Yeah. Yes. Yeah. It's not unreasonable. None unreasonable. All right. Let's go patent what you got. All right. October 2020. I, I'm so lazy here in Italy. I was jet lagged. I'm like, Matt, just give me two. papers and this was one 2020. Why the throwback? Because another paper came up that was about this topic. And so that I'd nugging into the literature like the one that came up recently was not that great. But this one, I was like, holy shit, I didn't know this. This is like super useful. So that title, Pintoxify lane for the prevention of post surgical Keyloid recurrence by Andrea Tan at all. Apparently Pintoxify lane has been shown to inhibit collagen formation and Keyloids and Sq. Reburetor and Morphea in vitro. But I don't ever remember reading about that. So whatever. So this was a retro. You know how we use it in lipodermatosclerosis sometimes. I think it's because of the anti-phibotic. Maybe. Maybe. This was a retrospective study done at UT Southwestern. All patients had Keyloid surgery followed by monthly intralesional injections of TAC 40 for six months. High risk group was also prescribed Pintoxify lane 400 milligrams TID for six months. What made you high risk? The surgeon was like, you're probably going to grow Keyloid. Because it was based on previous like number of Keyloid you had and maybe history recurrence and maybe family history. But the surgeon just kind of said, you're high risk and then you're not. So 67 Keyloids from 45 patients were surgically excised. They didn't go into detail there. Like, was it sutured? Was it like a shave excision? Was it left to secondary intent? They didn't go into the surgical details at all. The paper and I just said that. Was it shave? Was it elliptical? Was it left open to heal? Okay. 39 Keyloids were considered high risk and 28 Keyloids were considered low risk. So the 39 Keyloids, those guys got the Ptoxy filing and the 28 didn't and everybody got monthly interleasional TAC 40. There was a third group of patients that kind of came about during the study and these were the patients who the surgeon said, hi, risk, you're going to take Pintoxify lane and either they couldn't because like contraindicated pregnancy, bleeding disorder, whatever. And then there were also a few patients that couldn't take it for more than two weeks because they couldn't tolerate it, which is kind of odd because Ptoxy filing is like, I don't even, if somebody said, well, what are the risks of this medication? I'm like, I don't know. I don't think there are any. So these were patients that were considered high risk couldn't take it. So at the six month follow up, there were 19 Keyloids total in the high risk group that were left for analysis, six in the high risk control and nine that were left in the low risk control. So like half the Keyloids, like close to half of the Keyloids were lost to follow up. We have no idea what happened to them. So the authors calculated the percentage of recurrence using the denominator as the patients who weren't lost to follow up, which again was like close to half. So here are the numbers. The percentage of patients who have Keyloids that recurred the high risk control 66.7. There were only like six people in that group. The low risk control 22.2, they lost about 19 people to come up with that number. High risk treated, they lost about 14 people, but that was 10.5. So again, if you just went on the numbers that the author said 66.7 recurrence and the high risk that didn't get the toxic filing or couldn't tolerate it, the low risk control, the people that were low risk and didn't get any toxic filing recurrence 22.2 and the high risk treated 10.5. And then the ones who's Keyloid came back went to another dermatologist. Like the patients weren't randomized. Like if you look at the baseline differences, there are big differences like percentage of even men versus women and and easy and safe. So I don't I'm not going to suggest that people do this. I think a this is intriguing and I would say it's one of those studies where you say, ah, let's do a better study and really see if this pans out because Tintoxyfiling is just like the safest easiest. It's like oxybutin. It's giving my patients oxygen and and patoxyfiling because why not? You need to get them more X meds. So some oxybutin and some patoxyfiling more meds with X's in them. We'll do an episode where they are. I know what I was thinking as I was reprusing this article besides this is a crafty study. I was like, no, all right, it is interesting. Like we do Pintoxyfiling in like with dermatosclerosis. And I was like, well, what if it's the anti-fibrodic thing? And I was like, what about like CCCA? Right? Like that is a disease where I think it is driven by inappropriate fibrosis. Can we try it there? Can we have higher rates of key law information? Hmm. I don't know. But so the and let me throw in that the study that made me go back and search this up of Pintoxyfiling in key loids. One just came out that was a trinetic study. So again, now trinetics is too much in the in the mids between it could be low quality evidence. It could be decent evidence. I don't like that. I want just I want it low quality with no question. But this study they looked at people with coronary artery disease who are on Pintoxyfiling versus you know match controls who had coronary artery disease who were not on Pintoxyfiling and looked at over a long you know, very long period to follow up how many got diagnosed with the key loid. And the ones who were on Pintoxyfiling had a substantially lower probability of being diagnosed with a key loid while they were on the Pintoxyfiling. And so that was the that's what made me be like, well, let's go look at the so it's like good. It's now like an in Matt Zyrus world where you've got met now we've got a meta analysis. We've got two studies. Can't get the toxic file. We call that a meta analysis. Oh, oh, oh, all right. I'm on fire today. That is it. Right. So we got two studies now. That's enough. It's cheap. It's easy. Since it's tough, key loids are tough. I mean honestly, key loids are tough. It sucks, right? Yeah, I hate killers. I like the CCC. I'm going to do some search and later to see if there's any low quality of that. See if there's anything associated with that. Maybe you could come up with that you could do that. Try netics study, except you look at CCCA instead of key loids as your outcome. That seems I yeah, I can see it. I can see it. All right, move on to my last one. This was a study looking at one of my favorite topics recently for some reason because they've been publishing people have been publishing stuff about this more diaper dermatitis. And right, I was like to talk about diaper dermatitis because every, you know, it's it's got to can they come in to see us like, you know, lots of us who have used the big grandkids someday, there'll be kids. There's the whole thing. So this was the effect of open air of the effect of open to air frequency on diaper dermatitis recovery and maternal self efficacy in infants age zero to three months. They randomized control trial. So basically they took people who had mild diaper dermatitis, this was done in Turkey. And they randomized them to either get five minutes open to air every or six times a day or five minutes open to air 12 times a day. So either every two hours or every four hours, they were open to air for five minutes and just kind of, you know, lie in there with a little put a little, you know, some little something over there. So if they pee, it doesn't go everywhere. And it made a, and there was no other therapy. So they didn't do any zinc oxide. They didn't do any, like literally nothing else. It was just every two hours or every four hours. And the kids who they changed the diaper every two hours got better. They resolved completely in less than two days. And the kids who they did every four hours, it took over three days. So like three and a quarter on average. So it made a meaningful difference. The other thing that was interesting, they had a, it was a maternal self efficacy stagore, which I think was the basically like a do you feel like you're a good mother score. But it was a real like there were 10 questions and whatever and blah, blah, blah. But the ones who got randomized to the every two hours and they did do like an hour long training with them of like here, diaper dermatitis. And here's how you change a diaper and the whole thing so that they, you know, set the standards. The ones who got the every two hours, converted over four hours to have a more significant increase in maternal efficacy score, self efficacy score where they, you know, felt better about their mothering. Okay, is this open to air or is this just not sitting in your pee in your wet diaper? Could, could be either. But the main right, but it gives us a bit because this is actually not really been studied before. So it's a standard recommendation that whenever your kid has diaper dermatitis, you know, frequent diaper changes open to air, but it's never really been studied. And so this was the first, you know, you got to randomly, you got to choose some kind of of the control groups, they choose Joe's every four hours. So it now gives a very solid thing to be able to tell people, hey, there's a good study that showed if you, you know, do diaper change every two hours, leave him open to air for like five minutes to take the diaper off, wipe him down, just let it, you know, let the baby be kind of naked for five minutes, then put the new diaper on, do every two hours that works better than every four hours. I would let them run around naked outside. That would have been how I would have been. They were zero to three months old. Okay, never mind. Yeah, but kind of a mother are you guys are running around three months from about years. Right. So did they allow like what if the child had a horrible accident? You'd be like, well, you got three more hours. I need to follow through the call. Yeah, I saw. I think they were allowed to change in between. Well, and how did they control for who was because whenever they change in between that inly moping for five minutes? Oh, they didn't leave it open. So the open air was right. Right. And put it right back on. And then they didn't randomize to like change the diaper really quick versus leave him open for five like you're on the key four hour. I don't know. Yeah. You know what? I think it's just the more frequent diaper change. My kids like because I worked my whole life when my kids were little. So my kids were always in daycare. And daycare is like, you know, they're they have strict rules, right? Like if I were with them and be like, I you peed but we're at the store and like, you know, we're going to hang out or whatever. And I'm too lazy to go do it. But like they had a log and they had to have their diaper changed. It was every two or three hours. I can't remember. They had to mark it off in a log. They could never go more than three hours on diapers. My kids never had a diaper right. I think only would change my kid when it was like poop. Because you would smell it and you'd be like, oh, we need to change you. I don't think I ever thought, hey, they may have peed trying to change a diaper. My kids had diaper dermatitis like all throughout their babyhood. These things are, it's all coming together. It's all coming together. All coming together. And then it was that you know, and like they don't talk to me anymore. It's all. It's all. Yeah. I never had diaper rash and it was, I do attribute it to the frequent diaper changing that they received primarily at daycare, maybe somewhat with me. Ferris, I know we've talked about this before. Did you have any kids during, did you have any pregnancy? You get a kid during residency, right? Are you effing kidding me? You're asking me this question. Do you not, let me, I'm just going to share my experience of my having a kid during residency. She came in on fire. So the dirt regressive. I emailed you. Dear Dr. Zyrus, my chief resident, I wanted to let you know that I am pregnant. I am due in December of my first year. Dear Dr. Ferris, that's great news. You have six weeks of time away from residency. That will be all of your vacation, all of your CME. That's right. And all of your maternity leave. I was like, okay, so yeah, I took no CME, no vacation. I worked Saturday, Moes. In case I needed a C-section, and I had my six weeks of maternity leave, and then I came right back. Yep, see that's, I should have made you work extra. I'm sure if you don't remember this. It's like amazing. I'm still on friends with you at this point. I have, it's one of my strengths and weaknesses. I have no memory for episodes. Like what actually happened in my life? I have no idea at all. I can remember all kinds of stuff that I've read. What happens? No idea. None. Like pictures don't help. I can't remember anything. I see the picture. Oh, that looks like it was five percent. Yeah. Okay. Well, yeah. So, yes, I did. I had one child, and then I had my son when I started my two plus two year. Okay. Like so, yes. That was, I had him. And then I would bring him into lab with me, and I went back to work at two weeks after my time. At six weeks off with my daughter. And then, well, my first one I had like six weeks, then six weeks, and then about two weeks. It's a different world. It was. It was a different world. Very true. All right. Well, that's that's it for this week. I want to thank everybody for joining us. We hope you laughed a few times. We hope you learned a few things. But mostly we hope you're planning to join us next week. And until then, I'm Matt Zyrus. I'm Tim Patton. And I'm Laura Ferris, and we are Derms on drugs. [BLANK_AUDIO]